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Retriever1400
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[Embolization of splenic artery aneurysms: Treatment of choice. About a case and review of the literature].
Splenic artery aneurysms constitute 60% of digestive artery aneurysms. They are often discovered incidentally and by imaging. Currently, endovascular treatment is considered the first-line treatment, as it is less invasive with less morbidity and mortality than surgery. An aggressive approach in their management is certainly justified because the overall mortality of ruptured splenic aneurysms is 25%. False splenic aneurysms have a greater potential for rupture than true aneurysms because they grow faster. Endovascular treatment is generally indicated for aneurysms larger than 2cm or with an increase in size of more than 0.5cm/year. Embolization is rarely associated with an infarction of the spleen due to the good supply of short gastric vessels. Embolization is performed using different materials including coils, which can be used alone or with other embolic agents. Post-embolization syndrome can be seen with persistent pain, fever and other systemic symptoms. Endovascular treatment compared to open surgery is associated with better quality of life and appears to be the most cost-effective strategy. Endovascular treatment and especially coil embolization are starting to be the standard treatment. Surgical and laparoscopic treatment are reserved for ruptured aneurysms which are burdened with significant mortality, especially in pregnant women. We report the case of a 66-year-old female patient in whom a splenic artery aneurysm was discovered incidentally during an ultrasound for an ovarian cyst.
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No pos
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Retriever1401
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The dominant influencing factors of desertification changes in the source region of Yellow River: Climate change or human activity?
Due to the combined effects of global warming and human activities, the ecological environment of the Yellow River source area has undergone profound changes and desertification has become increasingly prominent. In this study, an optimal desertification monitoring index based on feature space was proposed for the Yellow River source area, and constructed using Landsat images. Then, the spatial and temporal variation of desertification in the Yellow River source area and its driving mechanism were studied using Geodetector. The main conclusions are as follows: (1) The newly proposed feature space-based desertification monitoring index has good applicability in the study area. The best inversion accuracy of the point-to-point Albedo-NDVI feature space model was 88.4%. (2) Desertification in the eastern and southern regions of the Yellow River source area has a tendency to increase, while the desertification situation in the central region is relatively stable. (3) From 1995 to 2015, there was a significant improvement in desertification in the study area, as evidenced by a decrease in desertification intensity. (4) As the intensity of human disturbance increases, the influence of natural factors on desertification gradually diminishes. The interaction of natural and anthropogenic factors has greater explanatory power for desertification than that of individual natural or anthropogenic factors. The research results can be used as a reference for decision-making on desertification control in the Three-River Source Region.
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No pos
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No neg
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Retriever1402
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Feasibility of Poly (Vinyl Alcohol)/Poly (Diallyldimethylammonium Chloride) Polymeric Network Hydrogel as Draw Solute for Forward Osmosis Process.
Forward osmosis (FO) has been identified as an emerging technology for the concentration and crystallization of aqueous solutions at low temperatures. However, the application of the FO process has been limited due to the unavailability of a suitable draw solute. An ideal draw solute should be able to generate high osmotic pressure and must be easily regenerated with less reverse solute flux (RSF). Recently, hydrogels have attracted attention as a draw solution due to their high capacity to absorb water and low RSF. This study explores a poly (vinyl alcohol)/ poly (diallyldimethylammonium chloride) (PVA-polyDADMAC) polymeric network hydrogel as a draw solute in forward osmosis. A low-pressure reverse osmosis (RO) membrane was used in the FO process to study the performance of the hydrogel prepared in this study as a draw solution. The robust and straightforward gel synthesis method provides an extensive-scale application. The results indicate that incorporating cationic polyelectrolyte poly (diallyldimethylammonium chloride) into the polymeric network increases swelling capacity and osmotic pressure, thereby resulting in an average water flux of the PVA-polyDADMAC hydrogel (0.97 L m-2 h-1) that was 7.47 times higher than the PVA hydrogel during a 6 h FO process against a 5000 mg L-1 NaCl solution (as a feed solution). The effect of polymer and cross-linker composition on swelling capacity was studied to optimize the synthesized hydrogel composition. At 50 °C, the hydrogel releases nearly >70% of the water absorbed during the FO process at room temperatures, and water flux can be recovered by up to 86.6% of the initial flux after 12 hydrogel (draw solute) regenerations. Furthermore, this study suggests that incorporating cationic polyelectrolytes into the polymeric network enhances FO performances and lowers the actual energy requirements for (draw solute) regeneration. This study represents a significant step toward the commercial implementation of a hydrogel-driven FO system for the concentration of liquid-food extract.
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No pos
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No neg
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Retriever1403
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Early Experience with Bilateral Continuous Femoral Nerve Block and Single-Injection Spinal Anesthesia for Bilateral Total Knee Arthroplasty: A Case Series.
Objective
Total knee arthroplasty (TKA) is a commonly performed surgery in the United States, with demand for unilateral and simultaneous bilateral TKAs (BTKAs) expected to increase significantly over the coming decades. This study reports the authors' early experience in a consecutive series of simultaneous BTKAs performed under regional anesthesia and mild sedation.
Methods
In this retrospective case series, the authors examined all simultaneous BTKAs performed over two years by a single surgeon. Only patients receiving bilateral continuous femoral nerve blockade (CFNB) and single-injection sciatic nerve blockade in combination with single-injection subarachnoid block were included in the study. Of the 32 patients who underwent BTKAs during this period, 25 met the inclusion criteria. The patient's anesthesia records, physician notes, nursing notes, pharmacy records, and physical therapy records were then reviewed systematically to create a database of information.
Results
Only one of 25 patients required conversion to general anesthesia during surgery. There were no major perioperative complications. The average Defense and Veterans Pain Rating Scale score immediately postoperation was 0.6/10, and the average daily score remained below 3.5/10 throughout the hospital stay. The use of bilateral CFNB did not prevent patients from ambulating during physiotherapy.
Conclusions
This early retrospective case series suggests that it is feasible to effectively manage the postoperative pain associated with BTKA with staged bilateral CFNB and single-injection sciatic nerve blockage in combination with single-injection subarachnoid block as the sole anesthetic technique without negatively influencing early ambulation.
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No pos
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No neg
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Retriever1404
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[Preoperative evaluation, preparation and prognosis in depressed patients].
Depressed patients have some problems before, during and after anesthesia such as hypotension, and torsade de pointes during anesthesia, postoperative confusion, serotonin toxicity, increased intraoperative bleeding by selective serotonin reuptake inhibitors. Depressed patients treated by antidepressants have decreased plasma cortisol and interleukin-6 response to surgery and are more at risk for developing postoperative confusion, that is associated with abnormal cortisol response to surgery and more frequent in patients discontinued antidepressants 72 hours before surgery. Depressed patients treated by antidepressants have high postoperative pain score, that depend on their depressed state. A small-dose of ketamine improves postoperative depressive state and relieves postoperative pain in depressed patients and is a suitable anesthetic for depressed patients. As the anesthetic management in depressed patients is becoming increasingly, anesthesiologists should be familiar with medical illness, abnormal response to surgery in depressed patients and must learn their perioperative management.
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No pos
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Retriever1405
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Parathyroid hormone-related protein markedly potentiates depolarization-induced catecholamine release in PC12 cells via L-type voltage-sensitive Ca2+ channels.
PTH-related protein (PTHrP) is a normal product of many excitable cells of the nervous and endocrine systems. Functions of PTHrP in these tissues are, however, currently unknown. Prior study has suggested that a relationship exists between PTHrP and the L-type voltage-sensitive Ca2+ channel (L-VSCC). For example, in cerebellar granule neurons PTHrP gene transcription is regulated by Ca2+ influx specifically through this channel. Amino-terminal PTHrP products signal via the widely expressed PTH/PTHrP receptor, which is linked to both protein kinase A and C. These second messengers are known modulators of L-VSCC conductance. To determine whether PTHrP can modulate L-VSCC function, we studied catecholamine secretion in a PC 12 clone expressing the PTH/PTHrP receptor but not PTHrP. We found that PTHrP(1-36) (100 nM) to be an ineffective secretagogue for resting cells, but its presence markedly potentiates secretion to K+ depolarization. The PTHrP-augmented catecholamine secretion depends entirely upon L-VSCC Ca2+ influx and rapidly inactivates. Similar effects were produced by (Bu)2cAMP but not by carbachol. These observations support the hypothesis that PTHrP can regulate L-VSCC conductance. In the normal adrenal medulla that expresses both PTHrP and its receptor, PTHrP may act in an autocrine/paracrine fashion to modify catecholamine secretion.
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No pos
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Retriever1406
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Simultaneous interfacial rheology and microstructure measurement of densely aggregated particle laden interfaces using a modified double wall ring interfacial rheometer.
The study of particle laden interfaces has increased significantly due to the increasing industrial use of particle stabilized foams and Pickering emulsions, whose bulk rheology and stability are highly dependent on particle laden interface's interfacial rheology, which is a function of interfacial microstructure. To understand the physical mechanisms that dictate interfacial rheology of particle laden interfaces requires correlating rheology to microstructure. To achieve this goal, a double wall ring interfacial rheometer has been modified to allow real time, simultaneous interfacial visualization and shear rheology measurements. The development of this tool is outlined, and its ability to provide novel and unique measurements is demonstrated on a sample system. This tool has been used to examine the role of microstructure on the steady shear rheology of densely packed, aggregated particle laden interfaces at three surface concentrations. Through examination of the rheology and analysis of interfacial microstructure response to shear, a transition from shear thinning due to aggregated cluster breakup to yielding at a slip plane within the interface has been identified. Interestingly, it is found that aggregated interfaces transition to yielding well before they reached a jammed state. Furthermore, these systems undergo significant shear induced order when densely packed. These results indicate that the mechanics of these interfaces are not simply jammed or unjammed and that the interfacial rheology relationship with microstructure can give us significant insight into understanding how to engineer particle laden interfaces in the future. By examining both rheology and microstructure, the mechanisms that dictate observed rheology are now understood and can be used to predict and control the rheology of the interface.
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Retriever1407
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Large retroperitoneal sarcoma invading the inferior vena cava successfully resected. Technical notes of two cases.
Retroperitoneal sarcomas are rare neoplasms . They frequently reach a very large size and invade adjacent organs before they are detected. Involvent of the inferior vena cava is uncommon. Distant metastases are a late feature. The mainstay of treatment is compartmental resection and contiguous organ resection. We report two cases of right-sided massive primary retroperitoneal leiomyosarcoma in pauci symptomatic women. In both cases treatment consisted of radical surgery. En bloc resection of the tumor and surrounding tissues and organs as well as part of the right wall of the subrenal IVC. To close the wall defect direct suture repair was used resulting in a reduced caliber but no hemodynamic sequelae or endoluminal thrombi. All the resection margins, including the inferior vena cava wall, were negative. The postoperative course was unremarkable and caval blood flow was optimal. The current gold standard treatment for retroperitoneal sarcoma is en bloc multivisceral resectionresection. KEY WORDS: Peritoneal sarcoma, Surgery, Vena cava.
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Retriever1408
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Strategies to Advance Women: Career Insights From Senior Leadership Women in Professional Sport in Canada.
Women remain minimally represented in senior leadership roles in sport, despite increased female participation in both sport, sport management education programs, and in entry levels positions in the industry. Many women prematurely exit mid-level leadership positions in sport, or are often overlooked for senior leadership positions. To uncover the experiences and strategies of women who made it through the process, we interviewed all the women (N = 7) who now hold senior leadership positions with professional sport properties in Canada. Participants revealed they overcame real and perceived barriers, and they suggested women seeking senior leadership roles in the industry: (a) find, and later become role models, mentors, and sponsors; (b) create access to networks and opportunities; (c) strategically self-promote, and; (d) purposefully build a varied career portfolio. Recommendations for the industry and all those who work in the industry are presented with a goal to break the cycle and help ensure more equitable and inclusive leaders in the senior leadership ranks.
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No pos
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Retriever1409
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Functional integrity of the central and sympathetic nervous systems is a prerequisite for pressor and tachycardic effects of diphenyleneiodonium, a novel inhibitor of nitric oxide synthase.
The pressor and tachycardic effects of diphenyleneiodonium (DPI), a novel inhibitor of endothelial nitric oxide synthase with chemical structure different from those of NG-substituted Arg analogs, were studied in pentobarbital-anesthetized rats. Bolus injections of DPI (0.05-1.6 mg/kg i.v.) caused transient (1-2 min in duration) and dose-dependent increases in mean arterial pressure (MAP) with ED50 of 0.22 +/- 0.02 mg/kg and maximum effect (Emax) of 58 +/- 3 mm Hg, and heart rate (HR) with ED50 of 0.26 +/- 0.03 mg/kg and Emax of 60 +/- 5 beats/min. Pretreatments with tetrodotoxin, reserpine, guanethidine, mecamylamine, but not atropine, rauwolscine, captopril nor L-Arg, attenuated the MAP and HR responses to DPI. Phentolamine and prazosin attenuated the MAP but not HR response whereas propranolol attenuated the HR but not MAP response of DPI. Pithing abolished, whereas spinal cord transection reduced, the MAP and HR responses to DPI. Pithing did not alter the pressor response but blocked the reflex bradycardic response to NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. Bolus injection of a single dose of DPI (1.6 mg/kg i.v.) or NG-nitro-L-arginine increased MAP, but only DPI caused immediate and large increases (> 1 ng/ml) in plasma norepinephrine, epinephrine and moderate increase in dopamine; pretreatment with reserpine attenuated, whereas pithing abolished these increases. The increases in plasma norepinephrine and epinephrine by DPI were positively correlated to increases in MAP and HR. The results demonstrate that DPI, unlike NG-substituted Arg analogs, produces pressor and tachycardic effects via indirect activation of the sympathetic nervous system.
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Retriever1410
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Variables of importance in the Scientific Registry of Transplant Recipients database predictive of heart transplant waitlist mortality.
The prelisting variables essential for creating an accurate heart transplant allocation score based on survival are unknown. To identify these we studied mortality of adults on the active heart transplant waiting list in the Scientific Registry of Transplant Recipients database from January 1, 2004 to August 31, 2015. There were 33 069 candidates awaiting heart transplantation: 7681 UNOS Status 1A, 13 027 Status 1B, and 12 361 Status 2. During a median waitlist follow-up of 4.3 months, 5514 candidates died. Variables of importance for waitlist mortality were identified by machine learning using Random Survival Forests. Strong correlates predicting survival were estimated glomerular filtration rate (eGFR), serum albumin, extracorporeal membrane oxygenation, ventricular assist device, mechanical ventilation, peak oxygen capacity, hemodynamics, inotrope support, and type of heart disease with less predictive variables including antiarrhythmic agents, history of stroke, vascular disease, prior malignancy, and prior tobacco use. Complex interactions were identified such as an additive risk in mortality based on renal function and serum albumin, and sex-differences in mortality when eGFR >40 mL/min/1.73 m. Most predictive variables for waitlist mortality are in the current tiered allocation system except for eGFR and serum albumin which have an additive risk and complex interactions.
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Retriever1411
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Is It Safe To Use Frontofacial Monobloc Advancement and Cutting Guides on Adult Patients with Crouzon Syndrome? Introducing 2 Cases on 41- and 56-Year-Old Patients.
BACKGROUND
Patients with Crouzon syndrome are mainly treated in childhood by frontofacial monobloc advancement to avoid ophthalmic, neurologic, and maxillary complications. There is no reported case of surgery on adult patients with Crouzon syndrome in the literature. However, when faced with 2 cases of adult patients showing severe quality of life deterioration, our team decided to make an attempt using monobloc advancement technique.
CASE DESCRIPTION
Two women aged 41 and 56 presented with untreated Crouzon syndrome and suffered from exorbitism, intracranial hypertension with chronic headaches, and hypoplastic maxillary. We decided to perform frontofacial monobloc advancement with internal distraction despite their advanced age using planned surgery and cutting guides. Distraction began 7-10 days after surgery and was of 15 mm. Distractors were taken off at 6 months. Surgical treatment corrected chronic headaches, ocular symptoms due to exorbitism, and hypoplastic maxillary. Patients were satisfied with the functional and aesthetic results. We noticed that this heavy surgery was more difficult to bear by these adults than children.
CONCLUSIONS
Adults with craniofacial malformations have a lower self-esteem, lower quality of life, and less satisfaction with their facial look as compared with individuals without facial malformations. There is also an increased risk of psychosocial problems. Despite postoperative difficulties and minor complications, our 2 patients were satisfied with the functional and aesthetic results. This led to the conclusion that surgically addressing adult patients with Crouzon syndrome via monobloc advancement is appropriate and secure when performed by a trained team.
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No pos
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Retriever1412
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[Effect of paracetamol on the microsomal oxidation, oxidative phosphorylation and liver mitochondria swelling in rats of various ages].
The effect of hepatotoxic dose of paracetamol (800 mg per kg, intraperitoneally, once a day during two days) on the system of microsomal oxidation, respiration, oxidative phosphorylation and high amplitude swelling of liver mitochondria was studied on 1-, 4- and 30-months old Wistar male rats. It has been shown, that paracetamol injection leads to the decrease of content of cytochrome P-450, to disorders of the function of monooxygenase system (the aminopyrine-N-demethylase and aniline hydroxylase activities were diminished), mitochondria macrostructure (the mitochondria high amplitude swelling time was decreased) and function (the respiratory control was decreased). These alterations have been observed to manifest to more extent in the liver of young rats as compared with old ones.
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No pos
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No neg
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Retriever1413
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The perceived social context of AIDS: study of inner-city sexually transmitted disease clinic patients.
The present study investigated perceptions of AIDS as a social problem relative to 10 other problems in a sample of 194 inner-city sexually transmitted disease (STD) clinic patients. Within-subjects analyses showed that AIDS was viewed as a more serious problem than housing, alcoholism, and child care, while AIDS was less of a problem than employment, drug abuse, crime, discrimination, and teen pregnancy, and no different from transportation and health care. Factor analysis was used to identify the interrelationships among social problems as perceived by STD patients. For men, factor analysis showed that AIDS was most closely related to crime, drug abuse, teen pregnancy, and discrimination, with these problems constituting the first factor and accounting for most of the variance in the analysis. Men also placed AIDS with alcoholism and child care on the third factor accounting for little variance. For women, however, AIDS clustered most closely with alcoholism and child care, accounting for a minimal amount of variance in the analysis. Results further showed that perceptions of social problems among women correlated with HIV-risk-related behaviors. The structural context of social problems, within which AIDS is embedded, is discussed with reference to HIV-AIDS-prevention interventions.
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No pos
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Retriever1414
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Solid-phase microextraction for the human biomonitoring of environmental chemicals: Current applications and future perspectives.
Sample preparation is one of the crucial steps in the analytical chemistry including human biomonitoring studies. Although there are several traditional approaches available, solid-phase microextraction is emerged as one of the pioneering techniques due to its simplicity, rapidness, wide applicability, and miniaturization of traditional sample preparation (e.g., use of less or no organic solvents). There are few earlier review articles available on the advancements in solid-phase microextraction and its use for the measurement of environmental chemicals in various types of environmental samples. However, a collective information on applicability and current usage of solid-phase microextraction for the human biomonitoring of environmental chemicals are scarce, nonetheless, rising demands on innovative analytical approaches for human biomonitoring studies. Hence, in this review article, we covered the application of solid-phase microextraction as extraction/purification methods for more than 15 classes of environmental chemicals to assess their respective exposure levels and associated health outcomes in various human population reported across the globe. Further, a detailed discussion on various types of matrix used, nature of coupled analytical instrumentations, and limitations and future perspectives of solid-phase microextraction for human biomonitoring studies is presented in this review.
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No pos
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Retriever1415
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Robust Finite-Time Stability for Uncertain Discrete-Time Stochastic Nonlinear Systems with Time-Varying Delay.
The main concern of this paper is finite-time stability (FTS) for uncertain discrete-time stochastic nonlinear systems (DSNSs) with time-varying delay (TVD) and multiplicative noise. First, a Lyapunov-Krasovskii function (LKF) is constructed, using the forward difference, and less conservative stability criteria are obtained. By solving a series of linear matrix inequalities (LMIs), some sufficient conditions for FTS of the stochastic system are found. Moreover, FTS is presented for a stochastic nominal system. Lastly, the validity and improvement of the proposed methods are shown with two simulation examples.
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No pos
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Retriever1416
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Effect of reduced glutathione supplementation on cryopreservation induced sperm cryoinjuries in Murrah bull semen.
The experiment was conducted to study cryopreservation induced sperm cryoinjuries and the protective effect of reduced Glutathione supplementation in Murrah bull semen. A total of 20 semen ejaculates were split into two parts after initial examination and were extended in glycerolated egg yolk TRIS diluter (Control group) and glycerolated egg yolk TRIS diluter + 0.5 mM reduced Glutathione (Treatment Group). The diluted semen samples were loaded into 0.25 ml French mini straw and sealing of straws were done. Thereafter, semen straws were kept for equilibration for 4 h at 5 °C and semen was frozen using a standard cryopreservation protocol in automatic biological freezer. Post-thaw analysis was performed after 24 h of semen storage in liquid nitrogen. Fresh and post-thaw sperm assessments included sperm motility, viability (SYBR-14/PI assay), mitochondrial function (JC-1/PI assay) and plasma membrane integrity (HOST). Cryopreservation of semen in liquid nitrogen induced a marked reduction in post-thaw sperm motility, viability, mitochondrial function and plasma membrane integrity and increased moribund type of sperm (SYBR-14/PI assay) in control group as compared to reduced glutathione treated group. There were significant (P < 0.05) cryo injuries in frozen-thawed spermatozoa following cryopreservation in buffalo bull semen. The supplementation of reduced glutathione in treatment group exhibited significantly (P < 0.05) lower cryoinjuries during cryopreservation and semen storage in liquid nitrogen. From the study it was concluded that, spermatozoa from Murrah bulls are susceptible to injuries due to cryopreservation in liquid nitrogen, but these cryo induced damage can be protected significantly (P < 0.05) by the use of reduced Glutathione.
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No pos
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Retriever1417
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Staphylococcal sepsis presenting as pulmonary embolism.
Deep vein thrombosis in children is rare and is often secondary to a predisposing condition. Staphylococcal sepsis following furunculosis and complicated by deep vein thrombosis and septic pulmonary emboli in a fourteen-yr-old boy is presented. He was managed successfully with antibiotics and anticoagulation.
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No pos
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No neg
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Retriever1418
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Additions to the genus Anthinus occurring in Minas Gerais and Goiás regions, Brazil, with description of five new species, one of them in the new related genus Catracca (Gastropoda, Eupulmonata, Strophocheilidae).
Four new species of the strophocheilid genus Anthinus are described from Brazil, being A. synchondrus from region of Unaí, Minas Gerais; A. vailanti from the region of Brasilândia de Minas, Minas Gerais; A. morenus from Paracatu region, Minas Gerais; and A. savanicus from Formosa region, Goiás. Another similar snail from Itacarambi, Minas Gerais, is described as a new genus and species: Catracca uhlei. All species are described conchologically and anatomically, with distinctions explored in almost all structures. For comparative purposes, a similar anatomical investigation on the Anthinus type species, A. multicolor, from Rio de Janeiro, is also performed. A detailed comparative analysis and discussion is provided, including taxonomic and initial phylogenetic inferences. The preliminary phylogenetic analysis is based on anatomically known species in the literature and in the presently study. A bulimulid, a simpulopsid and two dorcasiids are outgroups. The preliminary cladogram already shows a monophyletic Strophocheilidae (14 synapomorphies), divided into two also monophyletic subfamilies: Megalobuliminae (14 synapomorphies) and Strophocheilinae (5 synapomorphies). The new Catracca resulted as the most basal strophocheilid branch. Mirinaba and Anthinus were also supported as monophyletic (3 and 6 synapomorphies respectively. Register ZooBank: urn:lsid:zoobank.org:pub:FC4DD323-EF6A-404B-9755-F124F9DBB6D4.
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No pos
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Retriever1419
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Chemokine receptor CXCR4 oligomerization is disrupted selectively by the antagonist ligand IT1t.
CXCR4, a member of the family of chemokine-activated G protein-coupled receptors, is widely expressed in immune response cells. It is involved in both cancer development and progression as well as viral infection, notably by HIV-1. A variety of methods, including structural information, have suggested that the receptor may exist as a dimer or an oligomer. However, the mechanistic details surrounding receptor oligomerization and its potential dynamic regulation remain unclear. Using both biochemical and biophysical means, we confirm that CXCR4 can exist as a mixture of monomers, dimers, and higher-order oligomers in cell membranes and show that oligomeric structure becomes more complex as receptor expression levels increase. Mutations of CXCR4 residues located at a putative dimerization interface result in monomerization of the receptor. Additionally, binding of the CXCR4 antagonist IT1t-a small drug-like isothiourea derivative-rapidly destabilizes the oligomeric structure, whereas AMD3100, another well-characterized CXCR4 antagonist, does not. Although a mutation that regulates constitutive activity of CXCR4 also results in monomerization of the receptor, binding of IT1t to this variant promotes receptor dimerization. These results provide novel insights into the basal organization of CXCR4 and how antagonist ligands of different chemotypes differentially regulate its oligomerization state.
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No pos
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Retriever1420
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π-Stacking effects on the hydrogen bonding capacity of methyl 2-naphthoate.
π-stacking effects of fused two-ring system of methyl 2-naphthoate (MNP) with benzene derivatives on the CO group, as a hydrogen bond acceptor, has been investigated by the quantum mechanical calculations at the M06-2X/6-311++G(d,p) level of theory. All substituents enhance the stacking interactions relative to the unsubstituted case, where enhancement is higher for electron-withdrawing substituents (EWSs). The hydrogen bonding ability of lone pairs of O* atom of stacked MNP decreases in the presence of strong electron-withdrawing substituents (NO2, NO and CN). The hydrogen bond ability of CO group of MNP is related to the sum of local minima of electrostatic potentials (∑ESPs) observed between stacked rings. The charge transfer (CT) is lower in the presence of EWSs. The study also shows that the interaction energies (ΔE) are linearly dependent on the combination of the sum of electron densities calculated at the bond critical points (BCPs) between the rings (∑ρBCP) and the sum of electron charge densities calculated at the ring critical points (∑ρRCP). There are good relationships between the Hammett constant σmeta and the global minimum of electrostatic potential around the O* atom (Vmin), the sum of local minima of the electrostatic potentials obtained between stacked rings, and the results of natural population analysis (NPA). An excellent correlation was found between the ΔE values and a combination of the electrostatic (σmeta), resonance/induction (σpara) and dispersion/polarizibility (molar refractivity, MR) substituent constant terms.
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No pos
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Retriever1421
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A redox pathway leading to the alkylation of nucleic acids by doxorubicin and related anthracyclines: application to the design of antitumor drugs for resistant cancer.
Doxorubicin has been a constituent of antitumor drug protocols for a broad spectrum of cancers for more than two decades. Side effects and resistance continue to be important limitations. Drug targets responsible for both side effects and anti-tumor activity are cell membrane receptors, cell membrane lipids, nucleic acids and topoisomerase. Induction of oxidative stress is responsible for most if not all biological activity. An important consequence of oxidative stress is the production of formaldehyde which can subsequently be utilized by the drug for covalent bonding to nucleic acids and other targets as shown by in vitro experiments. Multidrug resistance mechanisms inhibit drug-induced DNA damage, drug uptake, and drug-induced oxidative stress. Synthetic anthracyclines conjugated to formaldehyde circumvent some if not all of the resistance mechanisms. Consequently, anthracycline-formaldehyde conjugates have potential for the treatment of resistant cancer.
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No pos
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Retriever1422
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Characterization of prednisone, prednisolone and their metabolites by gas chromatography-mass spectrometry.
Human urinary metabolites of the synthetic corticosteroids prednisone and prednisolone were detected in the course of gas chromatographic steroid profiling as methoxime-trimethylsilyl derivatives. Metabolites were provisionaly identified by combined gas chromatography-mass spectrometry. The major metabolites were 11-keto/11-hydroxy conversion products, 20-hydroxy and 4,5-dihydro analogues of the parent drugs. Cortisone, 6-hydroxy and fully saturated A-ring compounds were minor metabolites. Retention indices and mass spectral data are presented.
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Retriever1423
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Exome sequencing of oral leukoplakia and oral squamous cell carcinoma implicates DNA damage repair gene defects in malignant transformation.
OBJECTIVES
To map the genomic pathways of patients with oral leukoplakia (OLK) which transformed to cancer (progressive) and those which did not (non-progressive), and to compare their exomic profiles.
MATERIALS AND METHODS
Whole exome sequencing was performed on 42 sequential samples from five progressive and eight non-progressive patients. Association of genomic variant frequencies with progression or lesion severity were analysed by non-parametric tests (Kruskal-Wallis and Mann-Whitney-Wilcoxon) and multivariate sparse partial least squares discriminant analysis (sPLS-DA). Enrichment analysis was used to characterise the effect of mutations upon biological pathways. Confirmatory studies used qPCR and immunohistochemistry.
RESULTS
Using sPLS-DA, the variant frequency of a small number of genes could be used to classify the samples based on lesion severity or progressive status. Enrichment analysis showed that DNA damage repair gene related pathways were highly impacted in lesions which progressed to cancer. Multivariate analysis of a set of 148 DNA damage repair genes could be used to classify progressive lesions using mutation frequency. BRCA1, BRCA2 and other double strand break (DSB) repair Fanconi anaemia (FA)/BRCA pathway genes were prominent contributors to this classification.
CONCLUSION
Patients with progressive and non-progressive OLK can be differentiated using the frequency of exomic variants, particularly in DNA damage repair pathway genes. To our knowledge, this is the first report of FA/BRCA (DSB) pathway involvement in malignant transformation of OLK to oral squamous cell carcinoma (OSCC).
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No pos
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Retriever1424
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Management of the contralateral breast in patients with hereditary breast cancer.
Approximately 5% of all breast cancers arise on a background of one of the high-risk breast cancer genes (hereditary breast cancer and hereditary breast and ovarian cancer). An estimated 20% of cases arise in the presence of a less striking family history with later average age at onset and lower penetrance, familial breast cancer. For hereditary breast cancer, bilaterality is a recognized feature. Cancers often present at an early age with the contralateral risk high. This article explores the current state of knowledge regarding management options for women with hereditary breast cancer.
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No pos
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Retriever1425
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Confirmatory factor analysis of DSM-IV borderline, schizotypal, avoidant and obsessive-compulsive personality disorders: findings from the Collaborative Longitudinal Personality Disorders Study.
OBJECTIVE
To test the diagnostic constructs implied by DSM-IV Axis-II personality disorders by examining relationships between different combinations of DSM-IV criteria.
METHOD
Confirmatory factor analysis was used to test the borderline, schizotypal, avoidant and obsessive-compulsive personality disorder constructs in a large treatment-seeking sample (N= 668) from a multisite study. A model based on the three DSM-IV Axis II clusters was also tested. Both models were tested against a unitary 'generic' model constructed from four criteria sets combined.
RESULTS
Goodness-of-fit for both the three-cluster and four disorder models was significantly better than the unidimensional model, and the four-disorder model was significantly better than the three-cluster model. Results were replicated using data from 2-year follow-up obtained by interviewers blind to original Axis II diagnoses at baseline.
CONCLUSION
Support is provided for the DSM-IV disorder-level classification for schizotypal, borderline, avoidant and obsessive-compulsive personality disorders in a treatment-seeking sample.
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No pos
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No neg
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Retriever1426
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Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad.
The objective of this study was to investigate how joint specific biomechanical loading influences the functional development and phenotypic stability of cartilage grafts engineered in vitro using stem/progenitor cells isolated from different source tissues. Porcine bone marrow derived multipotent stromal cells (BMSCs) and infrapatellar fat pad derived multipotent stromal cells (FPSCs) were seeded in agarose hydrogels and cultured in chondrogenic medium, while simultaneously subjected to 10MPa of cyclic hydrostatic pressure (HP). To mimic the endochondral phenotype observed in vivo with cartilaginous tissues engineered using BMSCs, the culture media was additionally supplemented with hypertrophic factors, while the loss of phenotype observed in vivo with FPSCs was induced by withdrawing transforming growth factor (TGF)-β3 from the media. The application of HP was found to enhance the functional development of cartilaginous tissues engineered using both BMSCs and FPSCs. In addition, HP was found to suppress calcification of tissues engineered using BMSCs cultured in chondrogenic conditions and acted to maintain a chondrogenic phenotype in cartilaginous grafts engineered using FPSCs. The results of this study point to the importance of in vivo specific mechanical cues for determining the terminal phenotype of chondrogenically primed multipotent stromal cells. Furthermore, demonstrating that stem or progenitor cells will appropriately differentiate in response to such biophysical cues might also be considered as an additional functional assay for evaluating their therapeutic potential.
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No pos
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No neg
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Retriever1427
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Birth size and arterial compliance in young adults.
Impaired fetal growth may cause reduced compliance of the aorta and other large arteries, and predispose an individual to higher blood pressure in later life. We found that neither low birth size nor interaction between birth size and adult size were associated with arterial pulse-wave velocity in men and women aged 25 years.
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No pos
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No neg
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Retriever1428
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Blood-brain barrier opening in a large animal model using closed-loop microbubble cavitation-based feedback control of focused ultrasound sonication.
Focused ultrasound (FUS) in combination with microbubbles has been established as a promising technique for noninvasive and localized Blood-brain barrier (BBB) opening. Real-time passive cavitation detection (PCD)-based feedback control of the FUS sonication is critical to ensure effective BBB opening without causing hemorrhage. This study evaluated the performance of a closed-loop feedback controller in a porcine model. Calibration of the baseline cavitation level was performed for each targeted brain location by a FUS sonication in the presence of intravenously injected microbubbles at a low acoustic pressure without inducing BBB opening. The target cavitation level (TCL) was defined for each target based on the baseline cavitation level. FUS treatment was then performed under real-time PCD-based feedback controller to maintain the cavitation level at the TCL. After FUS treatment, contrast-enhanced MRI and ex vivo histological staining were performed to evaluate the BBB permeability and safety. Safe and effective BBB opening was achieved with the BBB opening volume increased from 3.8 ± 0.7 to 53.6 ± 23.3 mm3 as the TCL was increased from 0.25 to 1 dB. This study validated that effective and safe FUS-induced BBB opening in a large animal model can be achieved with closed-loop feedback control of the FUS sonication.
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No pos
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No neg
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Retriever1429
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Endothelial dysfunction of hindquarter resistance vessels in experimental heart failure.
Local vascular alterations may contribute to increased peripheral vasoconstriction in chronic heart failure. To test whether endothelial dysfunction might be involved, the effect of acetylcholine, nitroglycerin, and NG-monomethyl-L-arginine (L-NMMA) was investigated in a constant-flow perfused hindquarter of rats with and without chronic heart failure (CHF) due to myocardial infarction. Changes in perfusion pressure were measured as an index of changes in hindlimb vascular resistance. The endothelium-dependent vasodilator effect of acetylcholine was significantly reduced in rats with large infarcts (greater than 40% of the left ventricle). However, the endothelium-independent vasodilator effect of nitroglycerin and the vasoconstrictor effect of L-NMMA were similar for infarct and normal animals. The vasodilator response to acetylcholine was partially inhibited by pretreatment with L-NMMA. Thus the basal release of nitric oxide from hindquarter resistance vessels is preserved in CHF. However, the endothelium-mediated dilation in response to acetylcholine is attenuated, in part, due to a depressed stimulated release of nitric oxide. The latter mechanism might be involved in the impaired vasodilatory capacity in the peripheral circulation in CHF, e.g., during exercise.
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No pos
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No neg
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Retriever1430
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Comprehensive Analyses of the Bacterial Population in Non-Healing Claw Lesions of Dairy Cattle.
Non-healing claw lesions (NHCLs) are a newly characterized disorder affecting the deep dermis of the hoof in dairy cattle. Although NHCLs are thought to be associated with bovine digital dermatitis (BDD), their precise etiology is not yet understood. To investigate the bacterial populations present in each type of NHCL (toe necrosis: TN, non-healing white line disease: nhWLD, and a non-healing sole ulcer: nhSU), and the newly added entity non-healing verrucous-like lesions (nhVLL), 16S rRNA-based metagenomic analysis with next-generation sequencing (NGS) was employed. Twelve cases of NHCLs (3 TN, 3 nhWLD, 4 nhSU, and 2 nhVLL) were collected from five dairy farms in two prefectures in Japan. Three samples of healthy hoof dermis collected from two farms and a slaughterhouse were used as controls. Furthermore, culture-dependent and -independent approaches were conducted for detecting Treponema species and Fusobacterium necrophorum. As reported in BDD, Treponema species and F. necrophorum were detected frequently from NHCLs by PCR and immunohistochemistry, but NGS showed that these bacterial genera were not predominant in NHCLs. The predominant bacterial genera in NHCLs differed among the lesions examined, suggesting that Treponema species present predominantly in BDD were not predominant in NHCLs and that the bacterial population in NHCLs may vary among individual cattle and/or farms.
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No pos
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No neg
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Retriever1431
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Interpretation of genomic data: questions and answers.
Using a question and answer format we describe important aspects of using genomic technologies in cancer research. The main challenges are not managing the mass of data, but rather the design, analysis, and accurate reporting of studies that result in increased biological knowledge and medical utility. Many analysis issues address the use of expression microarrays but are also applicable to other whole genome assays. Microarray-based clinical investigations have generated both unrealistic hype and excessive skepticism. Genomic technologies are tremendously powerful and will play instrumental roles in elucidating the mechanisms of oncogenesis and in bringing on an era of predictive medicine in which treatments are tailored to individual tumors. Achieving these goals involves challenges in rethinking many paradigms for the conduct of basic and clinical cancer research and for the organization of interdisciplinary collaboration.
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No pos
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No neg
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Retriever1432
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Theoretical investigation of the SO(2+) dication and the photo-double ionization spectrum of SO.
Highly correlated ab initio methods were used in order to generate the potential energy curves of the electronic states of the SO(2+) dication and of the electronic ground state of the neutral SO molecule. These curves were used to predict the spectroscopic properties of this dication and to perform forward calculations of the double photoionization spectrum of SO. In light of spin-orbit calculations, the metastability of this doubly charged ion is discussed: for instance, the rovibrational levels of the X (1)Sigma(+) and A (3)Sigma(+) states are found to present relatively long lifetimes. In contrast, the other electronic excited states should predissociate to form S(+) and O(+) in their electronic ground states. The simulated spectrum shows structures due to transitions between the v=0 vibrational level of SO (X (3)Sigma(-)) and the vibrational levels below the barrier maximum of 11 of the calculated electronic states. The 2 (1)Sigma(+) electronic state of SO(2+) received further treatment: in addition to vibrational bands due to the below barrier energy levels of this electronic state, at least nine continuum resonances were predicted which are responsible for the special shape of the spectrum in this energy region. This work is predictive in nature and should stimulate future experimental investigations dealing with this dication.
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No pos
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No neg
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Retriever1433
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CD8 T cell priming by B lymphocytes is CD4 help dependent.
While it is generally accepted that B lymphocytes can present antigen and activate CD4 T cells, priming of CD8 T cells by B lymphocytes remains controversial. Recently, we showed that mice injected with genetically programmed B lymphocytes generate antigen specific CD4 and CD8 T cell responses in vivo that could also be induced in mice lacking functional dendritic cells. To gain further insights into the requirements for T cell priming by antigen-presenting B lymphocytes, in vitro experiments were performed using ovalbumin (OVA) and OVA-specific TCR-transgenic CD4 and CD8 T cells. We found that while B lymphocytes can directly prime CD4 T cells, the activation of CD8 T cells requires T cell help. Transfer experiments show that help can either be contact dependent or be mediated by soluble factors in the supernatants of activated OVA-specific CD4 T cells. Furthermore, the effect of activated CD4 T cells can be replaced by soluble recombinant IL-4. Collectively, the data show the existence of different requirements for priming of CD4 and CD8 T cells and point to the previously unappreciated fact that the induction of CD8 T cell responses by B lymphocytes requires T cell help.
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No pos
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No neg
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Retriever1434
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The power of the Heterogenous Stock rat founder strains in modeling metabolic disease.
Metabolic diseases are a host of complex conditions, including obesity, diabetes mellitus, and metabolic syndrome. Endocrine control systems (e.g., adrenals, thyroid, gonads) are causally linked to metabolic health outcomes. N/NIH Heterogeneous Stock (HS) rats are a genetically heterogeneous outbred population developed for genetic studies of complex traits. Genetic mapping studies in adult HS rats identified loci associated with cardiometabolic risks, such as glucose intolerance, insulin resistance, and increased BMI. This study determined underappreciated metabolic health traits and the associated endocrine glands within available substrains of the HS rat founders. We hypothesize that the genetic diversity of the HS rat founder strains causes a range of endocrine health conditions contributing to the diversity of cardiometabolic disease risks. ACI/EurMcwi, BN/NHsdMcwi, BUF/MnaMcwi, F344/StmMcwi, M520/NRrrcMcwi, and WKY/NCrl rats of both sexes were studied from birth until 13 weeks-of-age. Birth weight was recorded, body weight was measured weekly, metabolic characteristics were assessed, and blood and tissues were collected. Our data show wide variation in endocrine traits and metabolic health states in ACI, BN, BUF, F344, M520, and WKY rat strains. This is the first report to compare birth weight, resting metabolic rate, endocrine gland weight, hypothalamic-pituitary-thyroid axis hormones, and brown adipose tissue weight in these rat strains. Importantly, this work unveils new potential for the HS rat population to model early life adversity and adrenal and thyroid pathophysiology. The HS population likely inherited risk alleles for these strain-specific traits, making the HS rat a powerful model to investigate interventions on endocrine and metabolic health.
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No pos
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No neg
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Retriever1435
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Ovarian endocrine disruption underlies premature reproductive senescence following environmentally relevant chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin.
The aryl hydrocarbon receptor (AHR) mediates the effects of many endocrine disruptors and contributes to the loss of fertility in polluted environments. While previous work has focused on mechanisms of short-term endocrine disruption and ovotoxicity in response to AHR ligands, we have shown recently that chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces premature reproductive senescence in female rats without depletion of ovarian follicular reserves. In the current study, premature reproductive senescence was induced using a range of low-dose exposure to TCDD (0, 1, 5, 50, and 200 ng kg(-1) wk(-1)) beginning in utero and continuing until the transition to reproductive senescence. Doses of 50 and 200 ng TCDD kg(-1) wk(-1) delayed the age at vaginal opening and accelerated the loss of normal reproductive cyclicity with age without depletion of follicular reserves. Serum estradiol concentrations were decreased in a dose-dependent fashion (> or = 5 ng kg(-1) wk(-1)) across the estrous cycle in perisenescent rats still displaying normal cyclic vaginal cytology. Serum FSH, LH, and progesterone profiles were unchanged by TCDD. The loss of reproductive cyclicity following chronic exposure to TCDD was not accompanied by decreased responsiveness to GnRH. Ovarian endocrine disruption is the predominant functional change preceding the premature reproductive senescence induced by chronic exposure to low doses of the AHR-specific ligand TCDD.
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No pos
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No neg
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Retriever1436
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Murine B cell proliferation and protection from apoptosis with an antibody against a 105-kD molecule: unresponsiveness of X-linked immunodeficient B cells.
We established a novel monoclonal antibody, RP/14, that can protect B cells from apoptosis induced by irradiation or dexamethasone. A molecule recognized by RP/14 (the RP antigen) was expressed on B cells with B220bright, IgMdull, and IgDbright. Immunoprecipitation experiments revealed that RP/14 recognized a monomeric protein with an approximate molecular mass of 105 kD. Stimulation of B cells with RP/14 for 48 h induced B cell proliferation and blastogenesis. In contrast to B cells of wild-type mice, X-linked immunodeficient (XID) B cells did not proliferate upon stimulation with RP/14, although the RP antigen was expressed to the same extent as that of wild-type B cells. These results suggest that the RP antigen-mediated signaling pathway is important for rescuing B cells from apoptosis and is deficient in XID B cells.
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No pos
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No neg
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Retriever1437
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Comparison between ensilage and fungal pretreatment for storage of giant reed and subsequent methane production.
Ensilage and fungal pretreatment of giant reed harvested from August through December were compared based on their effects on feedstock preservation, glucose yield, and subsequent methane production via anaerobic digestion (AD). Compared to fungal pretreatment, ensilage obtained lower total solids (<1.2%) and cellulose (<3.5%) losses, and comparable hemicellulose degradation, except for giant reed harvested in August. Ensilage increased glucose and methane yields by 7-15% and 4-14%, respectively, for giant reed harvested from August through December. Fungal pretreatment failed for giant reed harvested in August and October with reduced glucose yields, and was effective for that harvested in November and December, with about 20% increases in glucose yield. However, hydrocarbon losses during fungal pretreatment offset the increased glucose yield, resulting in decreased methane yields by AD. In summary, ensilage was found to be more suitable than fungal pretreatment for giant reed storage and its methane production via AD.
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No pos
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No neg
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Retriever1438
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Genitourinary sarcoidosis: An essential review for the practicing clinician.
INTRODUCTION
Sarcoidosis is a multisystem disease that commonly involves the lungs, but may also present with extrapulmonary manifestations. Genitourinary (GU) tract involvement has been traditionally thought to be rare, but that view may underestimate the true prevalence of the disease due to the often, silent presentation thereof.
METHODS
The literature pertaining to sarcoidosis from the general systemic point of view, etiology and therapy and with regard to specific organs was reviewed by identifying key words in a PubMed search. That material with special relevance to the Indian experience was emphasized.
RESULTS
There are a number of isolated case reports in the literature describing symptomatic and asymptomatic GU tract sarcoidosis. The world literature associated with the generalized syndrome was reviewed and summarized. Specific aspects of GU involvement are presented for each organ of the GU tract.
CONCLUSIONS
It is critical for the practicing clinician to have a working knowledge of the clinical manifestations of this disease as it involves the GU tract, as well as to be able to distinguish it from tuberculosis and the various malignancies that affect this organ system.
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No pos
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No neg
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Retriever1439
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Science, Medicine and the Creation of a 'Healthy' Soviet Cinema.
Cinema had long been hailed by Bolshevik party leaders as a crucial ally of the Soviet mass enlightenment project. By the mid-1920s, however, Soviet psychologists, educators and practitioners of 'child science' (pedology) were pointing to the grave effects that the consumption of commercial cinema was exerting on the physical, mental and moral health of Soviet young people. Diagnosing an epidemic of 'film mania', specialists battled to curtail the NEP-era practices of film production and demonstration that had rendered cinema 'toxic' to children. Campaigns to 'healthify' Soviet cinema, first manifesting in the organization of child-friendly screenings and forms of 'cultural enlightenment work', soon extended to attempts to develop a new children's film repertoire based on the results of psycho-physiological viewer studies. A vast variety of pedological research institutions established during the late 1920s and early 1930s began to experimentally test cinema's effects on children with the view of assisting the production of films that could cultivate a sound mind and body. Tracing a link between the findings of pedological viewer studies and the 'healthy' cinema championed in the 1930s, this article sheds light on the vital role played by medical and scientific expertise in shaping Stalinist culture.
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No pos
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No neg
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Retriever1440
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Effects of 4-aminopyridine on neuromuscular transmission.
4-Aminopyridine (4-AP) powerfully increases transmitter release from motor nerve terminals of rat and frog skeletal muscle in response to single nerve impulses. The drug also enhances transmitter release during repetitive nerve activity but, at D-tubocurarine-blocked endplates, only the first impulses cause increased transmitter release at stimulation frequencies at or above 50 Hz. At magnesium- and botulinum-poisoned endplates, 4-AP potentiates transmitter release at every stimulus during tetanic nerve stimulation and restores neuromuscular transmission. Spontaneous transmitter release in the rat is not affected by the drug, but at some frog endplates miniature endplate potential (mepp) frequency increases. The drug has no post-synaptic action, as evidenced by its lack of effect on amplitude or time course of mepps. Decreasing the temperature from 37 to 15 degrees C does not abolish the effect of 4-AP on neuromuscular transmission. In the presence of 4-AP, single nerve impulses produce repetitive spontaneous activity in the nerve terminal of the frog nerve-muscle preparation. Experiments on the mode of action of 4-AP suggest that the drug increases transmitter release by enhancing the influx of calcium ions during depolarization of the nerve terminal.
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No pos
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No neg
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Retriever1441
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PERK-mediated induction of microRNA-483 disrupts cellular ATP homeostasis during the unfolded protein response.
Endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR), which reduces levels of misfolded proteins. However, if ER homeostasis is not restored and the UPR remains chronically activated, cells undergo apoptosis. The UPR regulator, PKR-like endoplasmic reticulum kinase (PERK), plays an important role in promoting cell death when persistently activated; however, the underlying mechanisms are poorly understood. Here, we profiled the microRNA (miRNA) transcriptome in human cells exposed to ER stress and identified miRNAs that are selectively induced by PERK signaling. We found that expression of a PERK-induced miRNA, miR-483, promotes apoptosis in human cells. miR-483 induction was mediated by a transcription factor downstream of PERK, activating transcription factor 4 (ATF4), but not by the CHOP transcription factor. We identified the creatine kinase brain-type (CKB) gene, encoding an enzyme that maintains cellular ATP reserves through phosphocreatine production, as being repressed during the UPR and targeted by miR-483. We found that ER stress, selective PERK activation, and CKB knockdown all decrease cellular ATP levels, leading to increased vulnerability to ER stress-induced cell death. Our findings identify miR-483 as a downstream target of the PERK branch of the UPR. We propose that disruption of cellular ATP homeostasis through miR-483-mediated CKB silencing promotes ER stress-induced apoptosis.
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No pos
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No neg
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Retriever1442
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Development of a Maternal and Child mHealth Intervention With Aboriginal and Torres Strait Islander Mothers: Co-design Approach.
BACKGROUND
Despite their growing popularity, there are very few mobile health (mHealth) interventions for Aboriginal and Torres Strait Islander people that are culturally safe and evidence based. A co-design approach is considered a suitable methodology for developing health interventions with Aboriginal and Torres Strait Islander people.
OBJECTIVE
The aim of this study was to co-design an mHealth intervention to improve health knowledge, health behaviors, and access to health services for women caring for young Aboriginal and Torres Strait Islander children.
METHODS
Aboriginal researchers led engagement and recruitment with health services and participants in 3 Aboriginal and Torres Strait Islander communities in New South Wales, Australia. Focus groups and interviews were facilitated by researchers and an app developer to gather information on 3 predetermined themes: design characteristics, content modules, and features and functions. Findings from the co-design led to the development of an intervention prototype. Theories of health behavior change were used to underpin intervention components. Existing publicly available evidence-based information was used to develop content. Governance was provided by an Aboriginal advisory group.
RESULTS
In total, 31 mothers and 11 health professionals participated in 8 co-design focus groups and 12 interviews from June 2019 to September 2019. The 6 design characteristics identified as important were credibility, Aboriginal and Torres Strait Islander designs and cultural safety, family centeredness, supportive, simple to use, and confidential. The content includes 6 modules for women's health: Smoke-free families, Safe drinking, Feeling good, Women's business, Eating, and Exercising. The content also includes 6 modules for children's health: Breathing well; Sleeping; Milestones; Feeding and eating; Vaccinations and medicines; and Ears, eyes, and teeth. In addition, 6 technology features and functions were identified: content feed, social connection, reminders, rewards, communication with health professionals, and use of videos.
CONCLUSIONS
An mHealth intervention that included app, Facebook page, and SMS text messaging modalities was developed based on the co-design findings. The intervention incorporates health behavior change theory, evidence-based information, and the preferences of Aboriginal and Torres Strait Islander women and health professionals. A pilot study is now needed to assess the acceptability and feasibility of the intervention.
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No pos
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No neg
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Retriever1443
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[Identification of Corydalis yanhusuo,C. turtschaninovii,C. decumbens by allele-specific PCR].
To establish a DNA molecular markers method for identification of Corydalis yanhusuo,C. turtschaninovii and C. decumbens,the mat K,trn G and psb A-trn H sequences of 56 samples from 14 species of C. yanhusuo,C. turtschaninovii,C. decumbens and their related species were obtained by sequencing. The SNP loci were obtained by Bio Edit 7. 2. 2 software. The primers for AS-PCR identification were designed based on the mutation sites,and the conditions of PCR were optimized to identify C. yanhusuo,C. turtschaninovii,and C. decumbens according to the specific bands. The results showed that the amount of template( 0. 6-1 200 ng)and annealing temperature( 42-60 ℃) had little influence on the amplification results,and the number of cycles had much influence on the amplification results. When the number of cycles was 20,the specific bands of 297 bp( mat K),353 bp( trn G) and 544 bp( mat K) were amplified from C. yanhusuo,C. turtschaninovii and C. decumbens,respectively. The method established in this study had a minimum detection limit of 6 ng for C. yanhusuo,60 ng for C. decumbens and less than 0. 6 ng for C. turtschaninovii. Thus,the allelespecific PCR method established in the research can specifically identify C. yanhusuo,C. turtschaninovii,and C. decumbens.
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No pos
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No neg
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Retriever1444
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Association of left atrial volume index and all-cause mortality in patients referred for routine cardiovascular magnetic resonance: a multicenter study.
BACKGROUND
Routine cine cardiovascular magnetic resonance (CMR) allows for the measurement of left atrial (LA) volumes. Normal reference values for LA volumes have been published based on a group of European individuals without known cardiovascular disease (CVD) but not on one of similar United States (US) based volunteers. Furthermore, the association between grades of LA dilatation by CMR and outcomes has not been established. We aimed to assess the relationship between grades of LA dilatation measured on CMR based on US volunteers without known CVD and all-cause mortality in a large, multicenter cohort of patients referred for a clinically indicated CMR scan.
METHOD
We identified 85 healthy US subjects to determine normal reference LA volumes using the biplane area-length method and indexed for body surface area (LAVi). Clinical CMR reports of patients with LA volume measures (n = 11,613) were obtained. Data analysis was performed on a cloud-based system for consecutive CMR exams performed at three geographically distinct US medical centers from August 2008 through August 2017. We identified 10,890 eligible cases. We categorized patients into 4 groups based on LAVi partitions derived from US normal reference values: Normal (21-52 ml/m2), Mild (52-62 ml/m2), Moderate (63-73 ml/m2) and Severe (> 73 ml/m2). Mortality data were ascertained for the patient group using electronic health records and social security death index. Cox proportional hazard risk models were used to derive hazard ratios for measuring association of LA enlargement and all-cause mortality.
RESULTS
The distribution of LAVi from healthy subjects without known CVD was 36.3 ± 7.8 mL/m2. In clinical patients, enlarged LA was associated with older age, atrial fibrillation, hypertension, heart failure, inpatient status and biventricular dilatation. The median follow-up duration was 48.9 (IQR 32.1-71.2) months. On univariate analyses, mild [Hazard Ratio (HR) 1.35 (95% Confidence Interval [CI] 1.11 to 1.65], moderate [HR 1.51 (95% CI 1.22 to 1.88)] and severe LA enlargement [HR 2.14 (95% CI 1.81 to 2.53)] were significant predictors of death. After adjustment for significant covariates, moderate [HR 1.45 (95% CI 1.1 to 1.89)] and severe LA enlargement [HR 1.64 (95% CI 1.29 to 2.08)] remained independent predictors of death.
CONCLUSION
LAVi determined on routine cine-CMR is independently associated with all-cause mortality in patients undergoing a clinically indicated CMR.
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No pos
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No neg
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Retriever1445
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LPWAN Key Exchange: A Centralised Lightweight Approach.
The Internet of Things (IoT) is one of the fastest emerging technologies in the industry. It includes diverse applications with different requirements to provide services to users. Secure, low-powered, and long-range transmissions are some of the most vital requirements in developing IoT applications. IoT uses several communication technologies to fulfill transmission requirements. However, Low Powered Wide Area Networks (LPWAN) transmission standards have been gaining attention because of their exceptional low-powered and long-distance transmission capabilities. The features of LPWAN transmission standards make them a perfect candidate for IoT applications. However, the current LPWAN standards lack state-of-the-art security mechanism s because of the limitations of the IoT devices in energy and computational capacity. Most of the LPWAN standards, such as Sigfox, NB-IoT, and Weightless, use static keys for node authentication and encryption. LoRaWAN is the only LPWAN technology providing session key mechanisms for better security. However, the session key mechanism is vulnerable to replay attacks. In this paper, we propose a centralized lightweight session key mechanism for LPWAN standards using the Blom-Yang key agreement (BYka) mechanism. The security of the session key mechanism is tested using the security verification tool Scyther. In addition, an energy consumption model is implemented on the LoRaWAN protocol using the NS3 simulator to verify the energy depletion in a LoRaWAN node because of the proposed session key mechanisms. The proposed session key is also verified on the Mininet-WiFi emulator for its correctness. The analysis demonstrates that the proposed session key mechanism uses a fewer number of transmissions than the existing session key mechanisms in LPWAN and provides mechanisms against replay attacks that are possible in current LPWAN session key schemes.
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No pos
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No neg
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Retriever1446
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Alcohol vehicles in tests for non-immunological immediate contact reactions.
In a search for vehicles that might enhance the sensitivity of human skin tests for nonimmunological immediate contact reactions, benzoic acid was tested in 17 liquid vehicles on 16 medical students using the open application test method on the upper back. The results were read visually and the change in blood flow was measured using a laser-Doppler flowmeter 20, 40 and 60 min after application of the test substances. 2-propyl alcohol (isopropanol), ethyl alcohol (ethanol), 1,2-propylene glycol and water were mixed to form alcohol, alcohol/water, alcohol/alcohol, alcohol/propylene glycol and propylene glycol/water vehicles. The reactions were stronger in the alcohol/water vehicles than in the alcohols as such. The addition of 25% propylene glycol to isopropanol and ethanol had the greatest enhancing effect on the reactions. Ethanol has been the most popular liquid vehicle in tests for non-immunological immediate contact reactions, but at least with benzoic acid, stronger reactions can be elicited if alcohol/propylene glycol or alcohol/water mixture are used.
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No pos
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No neg
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Retriever1447
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[Sex differences in congenital heart disease].
Gender influences the clinical presentation and the management of some acquired cardiovascular diseases, such as coronary artery disease, resulting in different outcomes. Differences between women and men are also noticed in congenital heart disease. They are mainly related to the prevalence and severity of some congenital heart defects at birth, and in adulthood to the prognosis, incidence of Eisenmenger syndrome and risks of pregnancy. The role of gender on the risk of operative mortality of congenital heart surgery remains debated.
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No pos
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No neg
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Retriever1448
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Selective cyclooxygenase inhibitors increase paclitaxel sensitivity in taxane-resistant ovarian cancer by suppressing P-glycoprotein expression.
OBJECTIVE
The purpose of this study was to investigate whether selective cyclooxygenase (COX) inhibitors promote paclitaxel-induced apoptosis in taxane-resistant ovarian cancer cells by suppressing MDR1/P-glycoprotein (P-gp) expression.
METHODS
Taxane-resistant ovarian cancer cells were cultured with paclitaxel alone or combined with a selective COX inhibitors. The expression patterns of MDR1/P-gp and the ability of COX inhibitors to inhibit growth of taxane-resistant ovarian cancer cells were measured. The efficacy of prostaglandin E2 (PGE2) supplementation was measured to evaluate the mechanisms involved in suppressing MDR1 gene expression.
RESULTS
P-gp was upregulated in taxane-resistant ovarian cancer cells compared to paired paclitaxel-sensitive ovarian cancer cells. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that selective COX inhibitors significantly enhanced the cytotoxic effects of paclitaxel in taxane-resistant ovarian cancer cells via a prostaglandin-independent mechanism. These increased apoptotic effects were further verified by measuring an increased percentage of cells in sub-G1 stage using flow cytometry. Selective COX inhibitors suppressed MDR1 and P-gp expression. Moreover, combined treatment with paclitaxel and selective COX inhibitors increased poly (ADP-ribose) polymerase (PARP) cleavage in taxane-resistant ovarian cancer cells.
CONCLUSION
Selective COX inhibitors significantly promote paclitaxel-induced cell death in taxane-resistant ovarian cancer cells in a prostaglandin-independent manner. COX inhibitors could be potent therapeutic tools to promote paclitaxel sensitization of taxane-resistant ovarian cancers by suppressing MDR1/P-gp, which is responsible for the efflux of chemotherapeutic agents.
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No pos
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No neg
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Retriever1449
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Effect of micro- and nanoscale topography on the adhesion of bacterial cells to solid surfaces.
Attachment and biofilm formation by bacterial pathogens on surfaces in natural, industrial, and hospital settings lead to infections and illnesses and even death. Minimizing bacterial attachment to surfaces using controlled topography could reduce the spreading of pathogens and, thus, the incidence of illnesses and subsequent human and financial losses. In this context, the attachment of key microorganisms, including Escherichia coli, Listeria innocua, and Pseudomonas fluorescens, to silica and alumina surfaces with micron and nanoscale topography was investigated. The results suggest that orientation of the attached cells occurs preferentially such as to maximize their contact area with the surface. Moreover, the bacterial cells exhibited different morphologies, including different number and size of cellular appendages, depending on the topographical details of the surface to which they attached. This suggests that bacteria may utilize different mechanisms of attachment in response to surface topography. These results are important for the design of novel microbe-repellant materials.
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No pos
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No neg
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Retriever1450
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More than additive effects on liver triglyceride accumulation by combinations of steatotic and non-steatotic pesticides in HepaRG cells.
The liver is constantly exposed to mixtures of hepatotoxic compounds, such as food contaminants and pesticides. Dose addition is regularly assumed for mixtures in risk assessment, which however might not be sufficiently protective in case of synergistic effects. Especially the prediction of combination effects of substances which do not share a common adverse outcome (AO) might be problematic. In this study, the focus was on the endpoint liver triglyceride accumulation in vitro, an indicator of hepatic fatty acid changes. The hepatotoxic compounds difenoconazole, propiconazole and tebuconazole were chosen which cause hepatic fatty acid changes in vivo, whereas fludioxonil was chosen as a hepatotoxic substance not causing fatty acid changes. Triglyceride accumulation was analyzed for combinations of steatotic and non-steatotic pesticides in human HepaRG hepatocarcinoma cells. Investigations revealed a potentiation of triglyceride accumulation by mixtures of the steatotic compounds with the non-steatotic fludioxonil, as compared to the single compounds. Mathematical modeling of combination effects indicated more than additive effects for the tested combinations if the method by Chou was applied, and a decrease in EC50 values of the steatotic compounds when applied in mixtures. Use of an adverse outcome pathway (AOP)-driven testing strategy for liver steatosis showed interactions of the test compounds with the nuclear receptors AHR, CAR and PXR, as well as a downregulation of ACOX2. An ACOX2-dependent mechanism underlying the observed mixture effect could not be verified using a siRNA approach. By contrast, a toxicokinetic interaction was identified including an inhibition of the metabolic enzyme CYP3A4 by fludioxonil and a decreased metabolic conversion of the CYP3A4 substrate difenoconazole when used in mixture experiments. In conclusion, an interaction by a steatotic and a non-steatotic compound at the toxicokinetic level on the endpoint triglyceride accumulation in vitro was described.
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No pos
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No neg
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Retriever1451
|
Unusual coordination mode of tetradentate Schiff base cobalt(III) complexes.
Contrary to the stereotype, Jacobsen's catalyst, chiral (salcy)Co(III)OAc adopts an unusual binding mode. The tetradentate {ONNO} ligand does not form a square plane but wraps cobalt in a cis-β fashion while acetate is chelating.
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No pos
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No neg
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Retriever1452
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Competing risks of death in women treated with adjuvant aromatase inhibitors for early breast cancer on NCIC CTG MA.27.
Baseline patient and tumor characteristics differentially affected type of death in the MA.17 placebo-controlled letrozole trial where cardiovascular death was not separately identified. The MA.27 trial allowed competing risks analysis of breast cancer (BC), cardiovascular, and other type (OT) of death. MA.27 was a phase III adjuvant breast cancer trial of exemestane versus anastrozole. Effects of baseline patient and tumor characteristics were tested for whether factors were associated with (1) all cause mortality and (2) cause-specific mortality. We also fit step-wise forward cause-specific-adjusted models. 7576 women (median age 64 years; 5417 (72 %) < 70 years and 2159 (28 %) ≥ 70 years) were enrolled and followed for median 4.1 years. The 432 deaths comprised 187 (43 %) BC, 66 (15 %) cardiovascular, and 179 (41 %) OT. Five baseline factors were differentially associated with type of death. Older patients had greater BC (p = 0.03), cardiovascular (p < 0.001), and other types (p < 0.001) of mortality. Patients with pre-existing cardiovascular history had worse cardiovascular mortality (p < 0.001); those with worse ECOG performance status had worse OT mortality (p < 0.001). Patients with T1 tumors (p < 0.001) and progesterone receptor positive had less BC mortality (p < 0.001). Fewer BC deaths occurred with node-negative disease (p < 0.001), estrogen receptor-positive tumors (p = 0.001), and without adjuvant chemotherapy (p = 0.005); worse cardiovascular mortality (p = 0.01), with trastuzumab; worse OT mortality, for non-whites (p = 0.03) and without adjuvant radiotherapy (p = 0.003). Overall, 57 % of deaths in MA.27 AI-treated patients were non-breast cancer related. Baseline patient and tumor characteristics differentially affected type of death with women 70 or older experiencing more non-breast cancer death.
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No pos
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No neg
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Retriever1453
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[Bacteria of the genus Aeromonas and their role in aquaculture].
Bacteria of genus Aeromonas are constant components of microbiota of fresh reservoirs where they, together with other microorganisms, play the part of natural biofilter and promote water self-purification. They are necessarily present in normal microflora of hydrobionts inhabiting fresh reservoirs. The greatest attention is paid by the researchers to Aeromonas and biotrophs in connection with epizootics in aquaculture which have become more frequent, in particular, under fish breeding. That is why the review is, to more extent, concerned in the works of this trend made by the foreign and home researchers for the last decade.
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No pos
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No neg
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Retriever1454
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Polluted porpoises: Generational transfer of organic contaminants in harbour porpoises from the southern North Sea.
Persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and hexachlorobenzene (HCB), bioaccumulate in marine ecosystems. Top predators contain high levels of POPs in their lipid-rich tissues, which may result in adverse effects on their reproductive, immune and endocrine functions. Harbour porpoises (Phocoena phocoena) are among the smallest of cetaceans and live under high metabolic demand, making them particularly vulnerable to environmental pressures. Using samples from individuals of all maturity classes and sexes stranded along the southern North Sea (n = 121), we show the generational transfer of PCBs, PBDEs and HCB from adults to foetuses. Porpoise placentas contained 1.3-8.2 mg/kg lipid weight (lw) Sum-17PCB, <dl-0.08 mg/kg lw Sum-17PBDE and 0.14-0.16 mg/kg lw HCB, which were similar to concentrations in foetus blubber. Contaminant levels increased significantly after birth through suckling. Milk samples contained 0.20-33.8 mg/kg lw Sum-17PCB, 0.002-0.51 mg/kg lw Sum-17PBDE and 0.03-0.21 mg/kg lw HCB. Especially lower halogenated and more toxic contaminants were transferred to calves, exposing them to high levels of contaminants early in life. Of all animals included in this study, 38.5% had PCB concentrations exceeding a threshold level for negative health effects (>9 mg/kg lw). This was particularly true for adult males (92.3% >9 mg/kg lw), while adult females had relatively low PCB levels (10.5% >9 mg/kg lw) due to offloading. Nutritional stress led to higher offloading in the milk, causing a greater potential for toxicity in calves of nutritionally stressed females. No correlation between PCB concentration and parasite infestation was detected, although the probability of a porpoise dying due to infectious disease or debilitation increased with increasing PCB concentrations. Despite current regulations to reduce pollution, these results provide further evidence of potential health effects of POPs on harbour porpoises of the southern North Sea, which may consequently increase their susceptibility to other pressures.
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No pos
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No neg
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Retriever1455
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African-American girls' dietary intake while watching television.
OBJECTIVE
Television viewing has been associated with childhood obesity, although the mechanisms that link television viewing to higher BMI have not been established. Therefore, our objectives, in this report, were to describe the amount and types of foods that African-American girls consume while watching television and to examine the associations between African-American girls' BMI and the food they consume while watching television.
RESEARCH METHODS AND PROCEDURES
Data were collected from 210 8- to 10-year-old African-American girls at four field centers by trained and certified nutritionists. Two nonconsecutive 24-hour dietary recalls were collected from each girl. For each eating episode reported, the girls were asked if they had been watching television while eating. Height and weight were collected using standard methods and used to calculate BMI.
RESULTS
The data were analyzed separately by field center. The proportion of average daily energy intake that the girls consumed while watching television ranged from 26.9% to 35.0%. At all field centers, 40% to 50% of evening meals were consumed while watching television. None of the Spearman correlations between girls' BMI and the amount and type of foods consumed while watching television or at other times during the day were statistically significant (p > 0.05).
DISCUSSION
This research revealed that a significant proportion of African-American girls' daily energy intake is consumed while watching television. Interventions that target reductions in food consumption while watching television or reducing television viewing may be effective strategies to decrease children's energy intakes. These results support a need for research to test the efficacy of these approaches.
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No pos
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No neg
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Retriever1456
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Enkephalinergic synaptic axon terminals on serotoninergic neurons in the dorsal raphe nucleus of the rat: an electron microscopic study by the double immunostaining method.
Met-enkephalinergic synaptic axon terminals on serotoninergic neurons in the dorsal raphe nucleus of the rat were observed with double immunostaining at the electron microscopic level. Met-enkephalin-like immunoreactive axon terminals were found to make asymmetrical or symmetrical synaptic contacts with serotonin-like immunoreactive nerve cell bodies and dendrites. The findings suggest that opioid-containing neurons modulate serotoninergic neurons through synapses in the dorsal raphe nucleus.
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No pos
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No neg
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Retriever1457
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Artificial insemination: can appropriate stimulation improve success rates?
Studies of other animal species suggest that stimulation during copulation has important effects on the probability of conception. Thus appropriate stimulation during artificial insemination may improve rates of conception.
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No pos
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No neg
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Retriever1458
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Ultrasound classification of breast masses using a comprehensive Nakagami imaging and machine learning framework.
In this study we investigate the potential of parametric images formed from ultrasound B-mode scans using the Nakagami distribution for non-invasive classification of breast lesions and characterization of breast tissue. Through a sliding window technique, we generated seven types of Nakagami images for each patient scan in our dataset using basic and as well as derived parameters of the Nakagami distribution. To determine the suitable window size for image generation, we conducted an empirical analysis using 4 windows, which includes 3 column windows of lengths 0.1875 mm, 0.45 mm and 0.75 mm and widths of 0.002 mm, along with the standard square window with sides equal to three times the pulse length of incident ultrasound. From the parametric image sets generated using each window, we extracted a total of 72 features that consisted of morphometric, elemental and hybrid features. To our knowledge no other literature has conducted such a comprehensive analysis of Nakagami parametric images for the classification of breast lesions. Feature selection was performed to find the most useful subset of features from each of the parametric image sets for the classification of breast cancer. Analyzing the classification accuracy and Area under the Receiver Operating Characteristic (ROC) Curve (AUC) of the selected feature subsets, we determined that the selected features acquired from Nakagami parametric images generated using a column window of length 0.75 mm provides the best results for characterization of breast lesions. This optimal feature set provided a classification accuracy of 93.08%, an AUC of 0.9712, a False Negative Rate (FNR) of 0%, and a very low False Positive Rate (FPR) of 8.65%. Our results indicate that the high accuracy of such a procedure may assist in the diagnosis of breast cancer by helping to reduce false positive diagnoses.
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No pos
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No neg
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Retriever1459
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IL-23 promotes growth and proliferation in human squamous cell carcinoma of the oral cavity.
Interleukin (IL)-23 is a heterodimeric cytokine, comprising IL-12p40 and the cloned IL-23-specific p19 subunit, was identified as a cancer-associated cytokine in a recent study. Like IL-12, IL-23 is expressed predominantly by activated dendritic cells and phagocytic cells. These cytokines antagonistically regulate local inflammatory responses in the tumor microenvironment and infiltration by intraepithelial lymphocytes. We have previously demonstrated the expression of IL-23 and its receptors in human oral squamous cell carcinoma (HOSCC) cell lines and tissue. Hence, this study investigated whether IL-23 has a role in the growth and proliferation of oral cancer cells by examining the expression kinetics of IL-23 and NF-kappaB activity, in vitro and in vivo. IL-23, which constitutively expressed in oral cancer, was enhanced by TNF-alpha and IL-23. IL-23 promotes cell proliferation in oral cancer and enhances the transport of nuclear factor-kappaB (NF-kappaB p65, RelA) to the nucleus in HSC-3 cells. Furthermore, luciferase reporter assay showed that IL-23 strongly induces RelA activity, and confirmed this finding by knockdown of IL-23 using RNA interference. Although RelA activity was down-regulated by anti-human IL-23p19 polyclonal antibody, used to neutralize the activity of IL-23, apoptosis was not induced. Immunohistochemistry revealed a weak IL-23 immunoreactivity in the cytoplasm of inflammatory infiltrating cells and in the cancer cells derived from 14 of 40 cases (35%) of oral SCC. In contrast, strong RelA immunoreactivity was observed in 30 of 40 cases of SCC (75%), especially consistent with IL-23 positive cells in SCC tissues. These data suggest that IL-23 up-regulates the growth and cell proliferation of oral cancer by promoting the nuclear transactivation of RelA.
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No pos
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No neg
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Retriever1460
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Usefulness of Mean Platelet Volume-to-Lymphocyte Ratio for Predicting Angiographic No-Reflow and Short-Term Prognosis After Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction.
Primary percutaneous coronary intervention (pPCI) is associated with improved prognosis in patients with ST-segment elevation myocardial infarction (STEMI). However, no-reflow phenomenon limits the benefit of revascularization and predicts adverse outcomes. The specific mechanism for its occurrence is still not entirely clear, and it is believed at present that platelet activation and inflammation play a pivotal role in developing no-reflow. Both increased mean platelet volume (MPV), which is a platelet activation marker, and lymphopenia, which is an inflammation marker, have been linked to adverse events and poor prognosis after STEMI. Recently, MPV-to-lymphocyte ratio (MPVLR) has emerged as a novel marker of poor short- and long-term prognosis in diabetic patients with STEMI who underwent pPCI. In this study, we aimed to investigate whether MPVLR predicts angiographic no-reflow and in-hospital mortality in all STEMI patients. From January 2014 to January 2017, a total of 1,206 patients who underwent pPCI, admitted within 12 hours from symptom onset, were enrolled and divided into 2 groups based on the final thrombolysis in myocardial infarction (TIMI) flow grading. No-reflow was defined as post-pPCI TIMI grade 0, 1, and 2 flows and normal-reflow was defined as TIMI 3 flow. The incidence of no-reflow was 16.1% (n = 198). The MPVLR values were higher in no-reflow group than in normal-reflow group (p <0.001). In multivariate analysis, MPVLR was an independent predictor of angiographic no-reflow. Furthermore, in multivariable Cox regression models adjusted for potential confounders, MPVLR was independently and positively associated with the hazard of 30-day all-cause mortality. In conclusion, the MPVLR was a strong independent predictor for angiographic no-reflow and short-term mortality in patients with STEMI who underwent pPCI.
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No pos
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No neg
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Retriever1461
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Electrochemical deposition of high density gold nanoparticles on indium/tin oxide electrode for fabrication of biosensors.
High density gold nanoparticles (GNPs) on indium tin oxide (ITO) film coated glass have been prepared by one-step electrochemical deposition from KAu(CN)2 in phosphate buffer (pH 8.0) solution. The resulting electrode surface was characterized by scanning electron microscopy (SEM), UV-vis spectroscopy, X-ray diffraction (XRD) and electrochemical method. Experimental results revealed that the number density of the nanoparticles was increased by the negative shift of the applied potential, while the coverage of the deposited GNPs on ITO substrate surface was also increased by means of the increasing deposition cycles. The presence of GNPs with high coverage improved the electrochemical response of Fe(CN)6 (3-/4-). This high coverage GNP/ITO substrate was applied to immobilization superoxide dismutase (SOD) for fabrication of electrochemical biosensors. The direct electron transfer between enzyme and electrode was realized, and the electrochemical performance of the SOD electrode was improved with the high coverage of GNPs. The biosensor exhibited a rapid and high response to superoxide anion.
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No pos
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No neg
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Retriever1462
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Vasopressin-induced neurotrophism in cultured neurons of the cerebral cortex: dependency on calcium signaling and protein kinase C activity.
Neuronal process outgrowth has been postulated to be one of the fundamental steps involved in neuronal development. To test whether vasopressin can influence neuronal development by acting on the outgrowth of neuronal processes, we determined the neurotrophic action of the memory-enhancing peptide, vasopressin, in neurons derived from the cerebral cortex, a site of integrative cognitive function and long-term memory. Exposure to V(1) receptor agonist significantly increased multiple features of nerve cell morphology, including neurite length, number of branches, branch length, number of branch bifurcation points and number of microspikes. The dose-response profile of V(1) receptor agonist-induced neurotrophism exhibited a biphasic function, with lower concentrations inducing a significant increase while higher concentrations generally induced no significant effect. The neurotrophic effect of V(1) receptor activation did not require growth factors present in serum. Analysis of the regional selectivity of the vasopressin-induced neurotrophic effect revealed significant V(1) receptor agonist-induced neurotrophism in occipital and parietal neurons, whereas frontal and temporal neurons were unresponsive. Results of experiments to determine the mechanism of vasopressin-induced neurotrophism demonstrated that vasopressin-induced neurotrophism is dependent on V(1)a receptor activation, requires L-type calcium channel activation and activation of both pathways of the phosphatidylinositol signaling cascade, inositol trisphosphate and protein kinase C. These studies are the first to describe a functional cellular response for vasopressin in the cerebral cortex. The findings are discussed with respect to their implications for understanding the role of vasopressin-induced neurotrophism, the associated signaling pathways required for this response, and the ability of vasopressin to enhance memory function.
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No pos
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No neg
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Retriever1463
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The effects of low density lipoprotein and high density lipoprotein on phosphoinositide hydrolysis in bovine aortic endothelial cells.
Low density lipoprotein (LDL) and high density lipoprotein (HDL3) were tested for their ability to induce inositol phospholipid turnover and inositol phosphate production in bovine aortic endothelial cells (BAEC). The production of inositol phosphates following hydrolysis of the phosphoinositides was demonstrated by two methods; release of [3H]inositol phosphates after labelling with [3H]myo-inositol and by a direct binding assay for inositol 1,4,5-trisphosphate (InsP3). Acute exposure to LDL induced InsP3 release at low concentrations of the lipoprotein within the physiological range of LDL in tissues. HDL3 did not cause any release of the inositol phosphates. Pre-incubation of BAEC with HDL3 suppressed bradykinin- and LDL-induced inositol phosphate production in BAEC in a concentration-dependent manner. It is concluded that LDL acutely stimulates phosphoinositide breakdown and that pre-incubation of cells with HDL3 inhibits this effect. The mechanism responsible for these effects remains to be elucidated.
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No pos
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No neg
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Retriever1464
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A two-stage genome scan for schizophrenia susceptibility genes in 196 affected sibling pairs.
We undertook a systematic search for linkage in 196 affected sibling pairs (ASPs) with DSMIV schizophrenia. In stage 1 we typed 97 ASPs with 229 microsatellite markers at an average inter-marker distance of 17.26 cM. Multipoint affected sib pair analysis identified seven regions with a maximum lod score (MLS) at or above the level associated with a nominal pointwise significance of 5%, on chromosomes 2q, 4p, 10q, 15q, 18p, 20q and Xcen. In stage 2 we genotyped a further 54 markers in 196 ASPs together with parents and unaffected siblings. This allowed the regions identified in stage 1 to be typed at an average spacing of 5.15 cM, while the region of interest on chromosome 2 was typed to 9.55 cM. Analysis was performed on the whole data set. Simulation studies suggested that we would expect one multipoint MLS of 1.5 per genome scan in the absence of linkage. An MLS of 3 would be expected only once in every 20 genome scans and thus corresponds to a genome-wide significance of 0.05. We obtained three multipoint MLSs >1.5 and, on this basis, the results on chromosomes 4p, 18q and Xcen can be considered suggestive. However, none approached a genome-wide significance of 0. 05. The power of this study was >0.95 to detect a susceptibility locus of lambda(s)= 3 with a genome-wide significance of 0.05, but only 0.70 to detect a locus of lambda(s)= 2. Our results suggest that common genes of major effect (lambda(s)> 3) are unlikely to exist for schizophrenia.
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No pos
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No neg
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Retriever1465
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Insights into the hallmarks of human nucleus pulposus cells with particular reference to cell viability, phagocytic potential and long process formation.
OBJECTIVE
As a main cellular component within the disc, nucleus pulposus (NP) cells play important roles in disc physiology. However, little is known on the biologic hallmarks of human NP cells. Therefore, the present study aimed to address the features of human NP cells.
METHODS
Human NP samples were collected from normal cadavers, patients with scoliosis and disc degeneration as normal, disease control and degenerative NP, respectively. The NP samples were studied using transmission electron microscopy and TUNEL assay. Pre-digested NP samples were studied using flow cytometry with PI/Annexin V staining.
RESULTS
Both control and degenerative human NP consisted of mainly viable cells with a variety of morphology. Both necrosis and apoptosis were noted in human NP as forms of cell death with increased apoptosis in degenerative NP, which was further confirmed by the TUNEL assay. Phagocytic NP cells had the hallmarks of both stationary macrophages with lysosomes and NP cells with the endoplasmic reticulum. Annulus fibrosus cells have similar morphologic characteristics with NP cells in terms of cell nest, phagocytosis and intracellular organs. Moreover, NP cells with long processes existed in degenerative and scoliotic NP rather than normal NP. When cultured in glucose-free medium, NP cells developed long and thin processes.
CONCLUSION
Human degenerative NP consists of primarily viable cells. We present direct and in vivo evidence that both human annulus fibrosus and NP cells have phagocytic potential. Moreover, NP cells with long processes exist in both scoliotic and degenerative NP with lack of glucose as one of the possible underlying mechanisms.
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No pos
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No neg
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Retriever1466
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Log-normal distribution of pulse amplitudes due to Raman cross talk in wavelength division multiplexing soliton transmission.
The effect of delayed Raman response on soliton collisions in wavelength division multiplexing (WDM) transmission systems is investigated. Taking into account the stochastic nature of pulse sequences in different frequency channels and the Raman-induced cross talk, it is shown that the soliton amplitude is a random variable with a log-normal distribution. Moreover, the Raman-induced self-frequency shift and cross-frequency shift are also random variables with log-normal-like distributions. These results imply that fluctuations in soliton amplitude and frequency induced by soliton collisions in the presence of delayed Raman response play an important role in massive WDM transmission.
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No pos
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No neg
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Retriever1467
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Crystal structure of 2-[(di-chloro-methane)sulfon-yl]pyridine.
The asymmetric unit of the title compound, C6H5Cl2NO2S, contains two mol-ecules with similar conformations (r.m.s. overlay fit for the non-H atoms = 0.067 Å). Atoms attached to the pendent Csp (3)-S bond are arranged in a staggered conformation with one of the Cl atoms anti to the C atom in the aromatic ring [C-S-C-Cl torsion angles = 178.41 (11) and -176.70 (13)°]. In the crystal, mol-ecules are linked by C-H⋯N and C-H⋯O hydrogen bonds, generating a three-dimensional network, and weak aromatic π-π stacking is also observed [centroid-centroid separation = 3.8902 (17) Å].
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No pos
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No neg
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Retriever1468
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Comparison of the release of endogenous and of 3H-acetylcholine from slices of rat cerebral cortex.
A comparison of the release of endogenous and of tritiated acetylcholine (3H-ACh) was performed in eserinized slices of rat cerebral cortex labelled in vitro in the presence of 0.43 microM tityustoxin (TsTX), a scorpion venom known to increase the overflow of endogenous acetylcholine. The endogenous and the radioactive ACh were spontaneously released into the organ bath. At the moment when the spontaneous efflux had levelled off, the endogenous ACh collected during 1 min accounted for 1.03 +/- 0.14% of the tissue content and a similar value (0.80 +/- 0.26%) was found for 3H-ACh. The basal outflow as well as the tissue retention of ACh and of 3H-ACh were not modified by exposure to the scorpion venom. In the presence of 20 mM KCl for 1 min, the overflow of both radioactive and endogenous ACh was increased up to approximately 100% above basal levels and this K+-evoked release was almost doubled under the action of TsTX. The results presented are compatible with the view that no major functional differences exist in the rat cortex between responses of pools storing 3H-ACh synthesized from 3H-choline and those storing ACh formed from endogenous substrate.
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No pos
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No neg
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Retriever1469
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Effect of castration on prostaglandin-mediated changes in membrane potential and prostaglandin synthesis in guinea-pig seminal vesicle tissue.
Arachidonic acid stimulated an increase in transmural electrical potential difference (p.d.) in guinea-pig seminal vesicle tissue in vitro. Pretreatment with indomethacin abolished this response. Indomethacin pretreatment did not prevent the p.d. from increasing in response to theophylline. Changes in p.d. in response to arachidonic acid were greatly attenuated, and the response to theophylline was abolished in seminal vesicle tissue taken from castrated guinea-pigs. Seminal vesicles, aorta and ileum taken from castrated guinea-pigs synthesized and released more prostaglandins than did those from control animals. It is concluded that the effects of arachidonic acid on p.d. are mediated by its metabolism to prostaglandins; the inability of seminal vesicles from castrated animals to respond to arachidonic acid is not a result of a decrease in prostaglandin production, but is more likely a result of other degenerative changes attendant upon castration; and androgens appear to have some regulatory function on prostaglandin synthesis in a variety of tissues.
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No pos
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No neg
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Retriever1470
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Bilateral sudden deafness as a prodrome of anterior inferior cerebellar artery infarction.
BACKGROUND
Acute ischemic stroke in the distribution of the anterior inferior cerebellar artery is known to be associated with hearing loss, facial weakness, ataxia, nystagmus, and hypalgesia. There have been few reports on bilateral deafness and vertebrobasilar occlusive disease. Furthermore, previous reports have not emphasized the inner ear as a localization of bilateral deafness.
OBJECTIVE
To describe the presentation of acute ischemic stroke in the distribution of the anterior inferior cerebellar artery as sudden bilateral hearing loss with minimal associated signs.
DESIGN AND SETTING
Case report and tertiary care hospital.
PATIENT
A 66-year-old man with diabetes mellitus developed sudden bilateral deafness, unilateral tinnitus, and vertigo 7 days before the onset of dysarthria, facial weakness, and ataxia. T2-weighted magnetic resonance imaging scans showed hyperintensities in the right lateral pons and right middle cerebral peduncle and a possible abnormality of the left middle cerebellar peduncle. A magnetic resonance angiogram showed moderately severe stenosis of the distal vertebral artery and middle third of the basilar artery. The patient's right limb coordination and gait improved steadily over several weeks, but there was no improvement in hearing in his right ear.
CONCLUSIONS
The relatively isolated onset of deafness as well as the severity and persistence of the hearing loss led us to conclude that the hearing loss in this case was likely due to prominent hypoperfusion of the internal auditory artery, with labyrinthine infarction as the earliest event. Vertebrobasilar occlusive disease should be considered in the differential diagnosis of sudden bilateral deafness.
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No pos
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No neg
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Retriever1471
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Improved overall survival is associated with adjuvant chemotherapy after definitive concurrent chemoradiotherapy for N3 nasopharyngeal cancer.
Concurrent chemoradiotherapy is the established treatment for locally advanced nasopharyngeal carcinoma (NPC). However, there is no evidence supporting routine adjuvant chemotherapy. We aimed to demonstrate the effect of adjuvant chemotherapy on survival and distant metastasis in high-risk N3 NPC patients. We linked the Taiwan Cancer Registry and Cause of Death database to obtain data. Clinical N3 NPC patients were divided as those receiving definitive concurrent chemoradiotherapy (CCRT) with adjuvant 5-fluorouracil and platinum (PF) chemotherapy and those receiving no chemotherapy after CCRT. Patients receiving neoadjuvant chemotherapy were excluded. We compared overall survival, disease-free survival, local control, and distant metastasis in both groups using Cox proportional hazards regression analysis. Propensity-score matching was also performed to evaluate the independent effect of adjuvant PF in a matched cohort with similar baseline characteristics. We included 431 patients (152 and 279 patients in the adjuvant PF and observation groups, respectively). Median follow-up was 4.3 years. The 5-year overall survival were 69.1% and 57.4% in the adjuvant PF chemotherapy and observation groups, respectively (p = 0.02). Adjuvant PF chemotherapy was associated with a lower risk of death (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.43-0.84; p = 0.003), even after adjusting for baseline prognostic factors (HR 0.61, 95% CI 0.43-0.86; p = 0.005). Distant metastasis-free survival at 12 months was higher in the adjuvant PF chemotherapy group than in the observation group (98% vs 84.8%; p < 0.001). After adjusting for baseline prognostic factors, adjuvant PF chemotherapy was associated with freedom from distant metastasis (HR 0.11, 95% CI 0.02-0.46; p = 0.003). Adjuvant chemotherapy was also associated with a decreased risk of death (HR 0.59, 95% CI 0.41-0.85, p = 0.004) in a propensity score-matched cohort. Prospective evaluation of adjuvant PF chemotherapy in N3 NPC patients treated with definitive CCRT is warranted because adjuvant PF chemotherapy was associated with improved overall survival and decreased risk of distant metastasis.
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No pos
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No neg
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Retriever1472
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New Imaging Tools to Analyze Mitochondrial Morphology in Caenorhabditis elegans.
Mitochondria are highly dynamic organelles that constantly fuse and divide. This process is essential as several neurodegenerative diseases have been associated with defects in mitochondrial fusion or fission. Several tools have been developed over the years to visualize mitochondria in organisms such as Caenorhabditis elegans. Combining these tools with the powerful genetics of C. elegans has led to the discovery of new regulators of mitochondrial morphology. In this chapter, we present additional tools to further characterize mitochondrial morphology as well as regulators of mitochondrial morphology. Specifically, we introduce a photoactivatable mitoGFP (PAmitoGFP) that allows to investigate the connectivity of complex mitochondrial networks. In addition, we describe an immunostaining protocol that enables localization studies of these newly identified regulators of mitochondrial morphology.
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No pos
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No neg
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Retriever1473
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Risk perception in context: the Savannah River Site Stakeholder Study.
Environmental managers are increasingly charged with involving the public in the development and modification of policies regarding risks to human health and the environment. Involving the public in environmental decision making first requires a broad understanding of how and why the public perceives various risks. The Savannah River Stakeholder Study was conducted with the purpose of investigating individual, economic, and social characteristics of risk perceptions among those living near the Savannah River Nuclear Weapons Site. A number of factors were found to impact risk perceptions among those living near the site. One's estimated proximity to the site and relative river location surfaced as strong determinants of risk perceptions among SRS residents. Additionally, living in a quality neighborhood and demonstrating a willingness to accept health risks for economic gain strongly abated heightened risk perceptions.
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No pos
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No neg
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Retriever1474
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Temperature-induced greening of Chlorella vulgaris. The role of the cellular energy balance and zeaxanthin-dependent nonphotochemical quenching.
When cells of the green alga Chlorella vulgaris Beij. are transferred from growth at 5 degrees C and an irradiance of 150 micromol photons m(-2) s(-1) to 27 degrees C and the same irradiance, they undergo what is normally considered a high-light to low-light phenotypic change. This involves a 3-fold increase in cellular chlorophyll content with a concomitant increase in light-harvesting complex polypeptide levels. This process appears to occur in response to the cellular capacity to utilize the products of photosynthesis, with the redox state of the plastoquinone pool sensing the cellular energy balance. The phenotypic adjustment can be enhanced or blocked using chemical inhibitors that modulate the redox state of the plastoquinone pool. The functional changes in the photosynthetic apparatus that occurred during the high-light to low-light acclimation were examined with special consideration paid to the paradox that 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU)-treated cells, with non-functional photosystem II (PSII), accumulate light-harvesting polypeptides. At the structural and basic functional levels, the light-harvesting complex of the cells treated with DCMU was indistinguishable from that of the untreated, control cells. To examine how PSII was protected in the DCMU-treated cells, we measured the content of xanthophyll-cycle pigments. It appeared that a zeaxanthin-dependent nonphotochemical quenching process was involved in PSII protection during greening in the presence of DCMU. Metabolic inhibitors of mitochondrial respiration were used to examine how the change in cellular energy balance regulates the greening process. Apparently, the mitochondrion acts to supply energy to the chloroplast during greening, and inhibition of mitochondrial respiration diminishes chlorophyll accumulation apparently through an increase in the redox state of the plastoquinone pool.
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No pos
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No neg
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Retriever1475
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Influence of different surface treatments on the short-term bond strength and durability between a zirconia post and a composite resin core material.
STATEMENT OF PROBLEM
Reliable bonding between zirconia posts and composite resin core materials is difficult to achieve because of the smooth surface texture and lack of silica content of zirconia posts.
PURPOSE
The purpose of this study was to evaluate the effect of different surface treatments on the short-term bond strength and durability between a zirconia post and a composite resin core material.
MATERIAL AND METHODS
Eighty zirconia posts were divided into 4 groups (n=20). Specimens received 1 of 4 different surface treatments: group AIRB, airborne-particle abrasion; group TSC-SIL, tribochemical silica coating (CoJet system) and silanization (ESPE Sil); group AIRB-BSIL, airborne-particle abrasion and MDP-containing primer (Clearfil SE Bond Primer)/silane coupling agent (Clearfil Porcelain Bond Activator) mixture application; and group TSC-BSIL, tribochemical silica coating and MDP-containing primer/silane coupling agent mixture application. Average surface roughness (Ra) of zirconia posts produced by airborne-particle abrasion or silica coating was measured using an optical profilometer. Composite resin core foundations (Build-it FR) were formed using transparent acrylic resin tubes (12mm in length and 7mm in diameter). Each group was further divided into 2 subgroups of 10 specimens and stored in distilled water at 37 degrees C, either for 24 hours or for 150 days with 37,500 thermal cycles between 5 degrees C and 55 degrees C, with a dwell time of 30 seconds. Following water storage, the specimens were sectioned perpendicular to the bonded interface into 2-mm-thick post-and-core specimens under water cooling. Push-out tests were performed with a universal testing machine at a crosshead speed of 0.5mm/min. Debonded post surfaces were examined with SEM. Data were analyzed with 1- and 2-way ANOVA and Tukey multiple comparison tests (alpha=0.05).
RESULTS
No significant differences were detected between the Ra values of airborne-particle-abraded and silica-coated specimens (P=.781). The short-term mean bond strengths for group TSC-BSIL (27.1 +/- 3.2 MPa) and TSC-SIL (25.2 +/- 2.4 MPa) were statistically higher (P<.001) than AIRB-BSIL (23.3 +/- 2.2 MPa). The relatively high bond strengths for groups TSC-BSIL and TSC-SIL decreased significantly after 150 days of water storage to 13.5 +/- 1.6 and 11.8 +/- 1.2 MPa, respectively (P<.001). Durable bonding was obtained only in group AIRB-BSIL (21.8 +/- 2.7 MPa), which was also the only group demonstrating predominantly cohesive failures in the core material after long-term water storage.
CONCLUSIONS
Data suggest that the short-term high bond strength obtained with a silane coupling agent or MPD-containing primer/silane coupling agent mixture to silica-coated zirconia posts was decreased with water storage and thermal cycling, whereas a durable bond could be obtained when an MPD-containing primer/silane coupling agent mixture was applied to the airborne-particle-abraded post surface.
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No pos
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No neg
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Retriever1476
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Anti-inflammatory properties of lipid oxidation products.
Oxidative modification of lipids occurs during inflammatory processes and leads to the formation and accumulation of biologically active lipid oxidation products that induce specific cellular reactions. These reactions lead to a modulation of the inflammatory process and may determine the fate and outcome of the body's reaction in acute inflammation during host defense. The processes by which oxidized lipids may play an important role include resolution of inflammation involving apoptosis, chronic inflammatory processes, and innate and adaptive immune responses. The classical view of lipid oxidation products is that they can induce and propagate chronic inflammatory reactions. However, evidence is accumulating that cells and tissues respond towards these oxidatively formed stress signals also by activation of anti-inflammatory processes. These include defense strategies such as (a) induction of signaling pathways leading to the upregulation of anti-inflammatory genes, (b) inhibition of signaling pathways coupled to the expression of proinflammatory genes, and (c) preventing the interaction of proinflammatory bacterial products with host cells. This contribution summarizes recent findings on the anti-inflammatory action of oxidized lipoproteins and lipid oxidation products. We discuss confirmed and suggested mechanisms as well as the (patho)physiological significance of these findings.
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No pos
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No neg
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Retriever1477
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Occurrence of Escherichia coli in feces of psittacine birds.
The feces of 125 psittacine birds, representing 12 species, were cultured on selective media to determine the presence of Escherichia coli. Only 13.6% (17) of the birds yielded E. coli.
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No pos
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No neg
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Retriever1478
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Does the treatment of gastroesophageal reflux disease (GERD) meet patients' needs? A survey-based study.
OBJECTIVE
Symptoms of gastroesophageal reflux disease (GERD) affect approximately 20% of people on a weekly basis. A number of different therapies are prescribed to control the disease. This survey-based study was carried out to assess patients' and physicians' perceptions of GERD and its treatment.
METHODS
Randomly selected general practitioners (GPs) from five countries (USA, UK, Japan, Germany and France) took part in a faceto-face interview, using a standard questionnaire, concerning the last four GERD patients (those taking GERD medication) who had consulted them and who consented to be interviewed. Those patients were then interviewed via telephone, also using a standard questionnaire.
RESULTS
Completed questionnaires were available for 927 of the 1044 patients who were identified. The mean length of time that patients suffered GERD symptoms prior to consultation was more than 1.5 years, with 52.3% of those consulting a GP stating the reason they sought medical attention was that 'symptoms were too uncomfortable to bear'. Only 36% of patients receiving prescription therapy reported that they were currently asymptomatic; 20.5% of patients were also taking at least one over-the-counter (OTC) medication.
CONCLUSIONS
In the primary care setting, many patients receiving GERD therapy do not have fully controlled symptoms. It is recommended that GPs question patients routinely about persistent symptoms on therapy, and OTC use, in order that effective treatment choices are made in the management of GERD.
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No pos
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No neg
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Retriever1479
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Patterns of Local and Systemic Cytokines in Bacterial Meningitis and its Relation with Severity and Long-Term Sequelae.
Bacterial meningitis (BM) is a pyogenic infection present in the subarachnoid space, potentially fatal and frequently associated with neurological sequelae. During BM, cytokines (CTs) are locally produced. We sought to determine the CTs' clinical role as disease severity predictors in adults, which is not completely clear. Using a bead-based flow cytometric assay, levels of six CTs were determined in cerebrospinal fluid (CSF) and plasma from 18 adult BM patients and 19 uninfected controls. Long-term neurological sequelae were evaluated using the Glasgow Outcome Scale (GOS). All evaluated CTs were higher in CSF than in plasma, and the levels of CSF interleukin (IL)-6, IL-8, IL-10, IL-1β, and tumor necrosis factor-α and plasma IL-10 and IL-12p70 were significantly higher in patients with severe sepsis than with sepsis, suggesting an association with clinical severity. There was a strong negative correlation between CSF IL-6 and plasma IL-12p70 with GOS score, supporting the possible role of these CTs in the development of neurological long-term sequelae. These findings could be helpful to identify candidates to receive neuroprotective treatments and early physiotherapy schemes.
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No pos
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No neg
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Retriever1480
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Dynamic Balance of Excitation and Inhibition in Human and Monkey Neocortex.
Balance of excitation and inhibition is a fundamental feature of in vivo network activity and is important for its computations. However, its presence in the neocortex of higher mammals is not well established. We investigated the dynamics of excitation and inhibition using dense multielectrode recordings in humans and monkeys. We found that in all states of the wake-sleep cycle, excitatory and inhibitory ensembles are well balanced, and co-fluctuate with slight instantaneous deviations from perfect balance, mostly in slow-wave sleep. Remarkably, these correlated fluctuations are seen for many different temporal scales. The similarity of these computational features with a network model of self-generated balanced states suggests that such balanced activity is essentially generated by recurrent activity in the local network and is not due to external inputs. Finally, we find that this balance breaks down during seizures, where the temporal correlation of excitatory and inhibitory populations is disrupted. These results show that balanced activity is a feature of normal brain activity, and break down of the balance could be an important factor to define pathological states.
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No pos
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No neg
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Retriever1481
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Motility and phototaxis of Gonium, the simplest differentiated colonial alga.
Green algae of the Volvocine lineage, spanning from unicellular Chlamydomonas to vastly larger Volvox, are models for the study of the evolution of multicellularity, flagellar dynamics, and developmental processes. Phototactic steering in these organisms occurs without a central nervous system, driven solely by the response of individual cells. All such algae spin about a body-fixed axis as they swim; directional photosensors on each cell thus receive periodic signals when that axis is not aligned with the light. The flagella of Chlamydomonas and Volvox both exhibit an adaptive response to such signals in a manner that allows for accurate phototaxis, but in the former the two flagella have distinct responses, while the thousands of flagella on the surface of spherical Volvox colonies have essentially identical behavior. The planar 16-cell species Gonium pectorale thus presents a conundrum, for its central 4 cells have a Chlamydomonas-like beat that provide propulsion normal to the plane, while its 12 peripheral cells generate rotation around the normal through a Volvox-like beat. Here we combine experiment, theory, and computations to reveal how Gonium, perhaps the simplest differentiated colonial organism, achieves phototaxis. High-resolution cell tracking, particle image velocimetry of flagellar driven flows, and high-speed imaging of flagella on micropipette-held colonies show how, in the context of a recently introduced model for Chlamydomonas phototaxis, an adaptive response of the peripheral cells alone leads to photoreorientation of the entire colony. The analysis also highlights the importance of local variations in flagellar beat dynamics within a given colony, which can lead to enhanced reorientation dynamics.
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No pos
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No neg
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Retriever1482
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Effects of familial hypothyroidism and subtotal surgical nephrectomy on gentamicin pharmacokinetics in beagle dogs.
Gentamicin serum pharmacokinetics were studied in normal, subtotally nephrectomized, and familial hypothyroid beagle dogs. Length of the gamma phase was not affected by subtotal nephrectomy but was shorter or almost nonexistent in hypothyroid dogs.
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No pos
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No neg
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Retriever1483
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Surgical Aspects of Ovarian Tissue Removal and Ovarian Tissue Transplantation for Fertility Preservation.
Introduction: The removal of ovarian tissue prior to starting oncologic treatment and the subsequent transplantation of this tissue after completing therapy have become increasingly important surgical fertility-preserving techniques. The aim of this review was to investigate the different surgical techniques used for this method reported in the literature to date and to discuss the advantages and disadvantages of the respective techniques. Review: A search was done in MEDLINE using a defined algorithm to find studies published between January 2004 and December 2015. All study designs were included in our review if they contained statements on the surgical technique used. We found 16 publications (8 retrospective cohort studies, 6 case reports and 2 systematic reviews) with a total of 1898 female patients which reported on the surgical technique used for ovarian biopsy and 15 publications (7 retrospective cohort studies, 6 case reports and 2 systematic reviews) with a total of 455 women which mentioned the surgical technique used for ovarian transplantation. Different surgical techniques can be used both for ovarian biopsy and for the transplantation of ovarian tissue. A number of different surgical routes have been used, and the amount of tissue extracted, the instruments used, the treatment of the ovary, the transplantation site, the blood supply to the transplanted ovarian tissue and the procedure used for simultaneous surgical interventions vary. Conclusion: In future, one of the tasks will be to establish a standard surgical method for ovarian extraction and transplantation which will have a low rate of complications and a high pregnancy and birth rate while ensuring that the transplanted tissue is fully functional.
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No pos
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No neg
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Retriever1484
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In Utero Exposure to Histological Chorioamnionitis Primes the Exometabolomic Profiles of Preterm CD4+ T Lymphocytes.
Histological chorioamnionitis (HCA) is an intrauterine inflammatory condition that increases the risk for preterm birth, death, and disability because of persistent systemic and localized inflammation. The immunological mechanisms sustaining this response in the preterm newborn remain unclear. We sought to determine the consequences of HCA exposure on the fetal CD4+ T lymphocyte exometabolome. We cultured naive CD4+ T lymphocytes from HCA-positive and -negative preterm infants matched for gestational age, sex, race, prenatal steroid exposure, and delivery mode. We collected conditioned media samples before and after a 6-h in vitro activation of naive CD4+ T lymphocytes with soluble staphylococcal enterotoxin B and anti-CD28. We analyzed samples by ultraperformance liquid chromatography ion mobility-mass spectrometry. We determined the impact of HCA on the CD4+ T lymphocyte exometabolome and identified potential biomarker metabolites by multivariate statistical analyses. We discovered that: 1) CD4+ T lymphocytes exposed to HCA exhibit divergent exometabolomic profiles in both naive and activated states; 2) ∼30% of detected metabolites differentially expressed in response to activation were unique to HCA-positive CD4+ T lymphocytes; 3) metabolic pathways associated with glutathione detoxification and tryptophan degradation were altered in HCA-positive CD4+ T lymphocytes; and 4) flow cytometry and cytokine analyses suggested a bias toward a TH1-biased immune response in HCA-positive samples. HCA exposure primes the neonatal adaptive immune processes by inducing changes to the exometabolomic profile of fetal CD4+ T lymphocytes. These exometabolomic changes may link HCA exposure to TH1 polarization of the neonatal adaptive immune response.
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No pos
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No neg
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Retriever1485
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Principles-based medical informatics for success--how Hong Kong built one of the world's largest integrated longitudinal electronic patient records.
Since 1994, the Hospital Authority has been developing and deploying clinical applications at its constituent 41 hospitals and 121 clinics. The Clinical Management System (CMS) is now used by over 4000 doctors and 20000 other clinicians on a daily basis to order, document and review care. The territory-wide Electronic Patient Record (ePR) has given clinicians an integrated, longitudinal, lifelong view of a patient's record. Today the CMS and ePR form an essential clinical and management tool to the Hospital Authority. The CMS handles two million clinical transactions per day, and the ePR has over 6TB of data covering 57 million episodes for 7.9 million patients. This paper describes how the HA has taken a principles-based approach to Medical Informatics to achieve its success in the enterprise-wide deployment and deep utilization of a comprehensive clinical information system.
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No pos
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No neg
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Retriever1486
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[Interaction of derivatives of 3-(indol-3-yl)propionic, nicotinic, and 1-nitroanthraquinone-2-carboxylic acid with pyrimidine nucleosides and their 5'-amino-5'-deoxy analogs].
The reaction of 5'-amino-2',5'-dideoxyuridine and 5'-amino-5'-deoxy-2',3'-O-ethoxymethyliden-6- azauridine with 3-(3-indolyl)propionic or 1-nitroanthraquinon-2-carboxylic acids in THF in the presence of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) resulted in the corresponding amide derivatives. The reaction conditions of the standard procedure for the removal of the O-alkylidene protecting group turned out to be too severe for the 5'-N-acylamide derivatives of 6-azauridine. 5'-Deoxy-5'-[3-(3-indolyl)propionyl-amino]-6-azauridine was synthesized from 5'-amino-5'-deoxy-6-azauridine and 3-(3-indolyl)propionic acid in THF in the presence of EEDQ. A reaction between 5'-O-tosyl-2',3'-O-ethoxymethyliden-6-azauridine and 3-aminopropanol gave 3-(3-hydroxypropylamino)-2-(2',3'-O-ethoxymethylidene-beta- D-ribofuranosyl)-as-triazine-5(2H)-one, the structure of which was confirmed also by synthesis from O2,5'-anhydronucleoside and 3-aminopropanol followed by further chemical transformations. A reaction of 3-(3-hydroxypropylamino) derivative obtained with nicotinoyl chloride prepared in situ, or with 1-nirtoanthraquinon-2-carboxylic acid in the presence of DCC with subsequent deprotection, afforded 3-[(3-pyridin-3-ylcarboxy)propylamino]- or 3-[3-(1-nitroanthraquinon-2-carboxy)propylamino]-2-beta-D-ribof ura nosyl-as- triazine-5(2H)-one, respectively. Structures of the nucleosides prepared were examined by 1H NMR spectroscopy. 2',5'-Dideoxy-5'-[(1-nitroanthraquinon-2-carbonyl)amino]uridine at a 10(-4) M concentration was shown to inhibit thymidine incorporation into cell DNA (CE50 10(-5) M) by 72%.
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No pos
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No neg
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Retriever1487
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Rapid discovery of a novel series of Abl kinase inhibitors by application of an integrated microfluidic synthesis and screening platform.
Drug discovery faces economic and scientific imperatives to deliver lead molecules rapidly and efficiently. Using traditional paradigms the molecular design, synthesis, and screening loops enforce a significant time delay leading to inefficient use of data in the iterative molecular design process. Here, we report the application of a flow technology platform integrating the key elements of structure-activity relationship (SAR) generation to the discovery of novel Abl kinase inhibitors. The platform utilizes flow chemistry for rapid in-line synthesis, automated purification, and analysis coupled with bioassay. The combination of activity prediction using Random-Forest regression with chemical space sampling algorithms allows the construction of an activity model that refines itself after every iteration of synthesis and biological result. Within just 21 compounds, the automated process identified a novel template and hinge binding motif with pIC50 > 8 against Abl kinase--both wild type and clinically relevant mutants. Integrated microfluidic synthesis and screening coupled with machine learning design have the potential to greatly reduce the time and cost of drug discovery within the hit-to-lead and lead optimization phases.
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No pos
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No neg
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Retriever1488
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Exploring the lived experience of gay men with prostate cancer: A phenomenological study.
PURPOSE
Gay men with prostate cancer are an 'invisible species' in the research literature despite concerns that the impact of treatment may be more profound and in some ways unique compared to heterosexual men. The aim of this research is to explore the lived experience of gay men with prostate cancer.
METHOD
In-depth interviews were recorded and transcribed verbatim from a purposive sample of eight gay men treated for prostate cancer in Ireland. A qualitative methodological approach employing Giorgi's descriptive phenomenological method was used to collect and analyse data.
FINDINGS
Three key aspects emerged representing the essence of the participants lived experience; The experience of diagnosis, treatment decision making, and the impact of treatment, with sub-themes of shock of diagnosis, the generalist nature of information, sexual side effects and incontinence, and masculinity and gay identity. Secondly, the experience of the healthcare service with sub-themes of sexual orientation disclosure and communication with the healthcare team; and thirdly, sources of support and means of coping which included significant others, family & friends, cancer support groups, and gay resources and support services.
CONCLUSION
Gay men with prostate cancer have unmet information and supportive care needs throughout their prostate cancer journey, especially related to the impact of sexual dysfunction and associated rehabilitation, negatively impacting their quality of life. Issues associated with heteronormativity, minority stress, and stigma may influence how gay men interact with the health service, or how they perceive the delivery of care. Healthcare education providers should update prostate cancer education programmes accordingly.
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No pos
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No neg
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Retriever1489
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Cervical spinal dural fistulas leading to remote thoracolumbar myelopathy: A diagnostic pitfall.
PURPOSE OF REVIEW
Spinal dural arteriovenous fistulas (SDAVFs) are abnormal connections between 1 or more radiculomeningeal arteries and a single radiculomedullary vein draining into the perimedullary venous system. SDAVFs present in older patients with a progressive myelopathy caused by diffuse spinal venous hypertension. The discrepancy between the focal nature of the arteriovenous shunt and the extent of the induced myelopathy is a classic feature of SDAVFs related to the coexistence of diffuse spinal venous drainage impairment.
RECENT FINDINGS
We describe 3 cases of cervical SDAVFs (at C1, C4, and C7) presenting with a myelopathy that spared the cervical spinal cord and, in 2 instances, the upper thoracic cord. This is to our knowledge the first observations of cervical SDAVFs with MRI showing absent or subtle flow voids and presenting remote thoracolumbar myelopathy without cervical cord involvement.
SUMMARY
A considerable distance may separate low-flow spinal arteriovenous fistulas from the spinal cord damage they produce. These observations emphasize the importance of performing a complete spinal angiogram when investigating a vascular myelopathy of any location and extent.
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No pos
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No neg
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Retriever1490
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Is the regulation of apoptosis altered in smooth muscle cells of adult spontaneously hypertensive rats?
Whereas the protein product of the Bcl-2 gene inhibits apoptosis, the protein product of the Bax gene acts as a promoter of apoptosis. To gain insight into the regulation of apoptosis in vascular smooth muscle cells in arterial hypertension, we investigated the expression of the proteins Bcl-2 and Bax in small intramyocardial arteries of 36-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In addition, 16-week-old SHR were treated for 20 weeks with the angiotensin-converting enzyme inhibitor quinapril and killed at 36 weeks of age. We measured the percentages of smooth muscle cells expressing these proteins using monoclonal antibodies and the avidin-biotin immunoperoxidase method. Compared with WKY, untreated SHR exhibited increased (P<.001) Bcl-2 expression and similar Bax expression. Values of Bcl-2 measured in quinapril-treated SHR were significantly lower than values measured in untreated SHR and similar to values measured in WKY. Quinapril-treated SHR showed higher (P<.001) Bax expression than WKY and untreated SHR. Bcl-2 expression was directly correlated with systolic pressure. Inverse correlations were found between the expression of Bax and the activities of both cardiac and circulating angiotensin-converting enzyme. These findings suggest that smooth muscle cell apoptosis might be inhibited in small arteries of adult SHR as a consequence of an excess of the protein Bcl-2. In addition, our results suggest that chronic angiotensin-converting enzyme inhibition might restore the susceptibility to apoptosis in these cells through stimulation of the protein Bax.
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No pos
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No neg
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Retriever1491
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Six-month continuous intraputamenal infusion toxicity study of recombinant methionyl human glial cell line-derived neurotrophic factor (r-metHuGDNF) in rhesus monkeys.
Recombinant human glial cell line-derived neurotrophic factor (r-metHuGDNF) is a potent neuronal growth and survival factor that has been considered for clinical use in the treatment of Parkinson's disease (PD). Here we present results of a 6-month toxicology study in rhesus monkeys conducted to support clinical evaluation of chronic intraputamenal infusion of r-metHuGDNF for PD. Monkeys (6-9/sex/group) were treated with 0 (vehicle), 15, 30, or 100 micro g/day r-metHuGDNF by continuous unilateral intraputamenal infusion (150 micro l/day flow rate) for 6 months; a subset of animals (2-3/sex/group) underwent a subsequent 3-month treatment-free recovery period. Notable observations included reduced food consumption and body weight at 100 micro g/day and meningeal thickening underlying the medulla oblongata and/or overlying various spinal cord segments at 30 and 100 micro g/day. In addition, multifocal cerebellar Purkinje cell loss (with associated atrophy of the molecular layer and, in some cases, granule cell loss) was observed in 4 monkeys in the 100-micro g/day group. This cerebellar finding has not been observed in previous nonclinical studies evaluating r-metHuGDNF. The small number of affected animals precludes definitive conclusions regarding the pathogenesis of the cerebellar lesion, but the data support an association with r-metHuGDNF treatment.
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No pos
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No neg
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Retriever1492
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Anticholinergics improve fibreoptic intubating conditions during general anaesthesia.
PURPOSE
To determine if anticholinergic agents improve fibreoptic intubating conditions and to compare the efficacy and side effects of glycopyrrolate and hyoscine.
METHODS
Eighty ASA I adults undergoing elective wisdom tooth extraction were randomly allocated to receive 0.4 mg hyoscine hydrobromide po, 0.4 mg hyoscine hydrobromide im, 0.4 mg glycopyrrolate im or no anticholinergic, one hour pre-operatively. All underwent nasal fibreoptic intubation under general anaesthesia. The time taken to pass the fibreoptic scope was noted and visual analogue scores (VAS) were recorded for clarity of visual field and post-operative sore throat, dry mouth and nausea.
RESULTS
The time to intubation was not different among the four groups (Kruschal-Wallis P = 0.07). The clarity of visual field was improved in all three anticholinergic groups (Kruschal-Wallis P = 0.006), but there was no difference among the three groups (median VAS control 6.4, glycopyrrolate 8.0, oral hyoscine 7.9, im hyoscine 7.7). There was no difference in post-operative side effects among any of the groups at both 30 min and four hours.
CONCLUSION
The addition of an anticholinergic produced better visual conditions for intubation but had no effect on the incidence of post-operative sore throat, dry mouth and nausea.
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No pos
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No neg
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Retriever1493
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Self-renewal and differentiation of stem cells in a biopotential murine leukemia: an in vitro model for differentiation therapy.
PGM-2 is a variant of the transplantable PGM-1 leukemia of strain C3H/HeJ. Freshly explanted cells had lymphoid morphology with a CD5+ CD45R (B220)- IgM- phenotype. They were not viable in unstimulated cultures, but formed IgM+ lymphoid colonies in response to interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-7, and Steel factor, and macrophage colonies in response to IL-3. IL-3-stimulated colonies had no recloning potential, but colonies from IL-7 cultures gave rise to large numbers of secondary macrophage colonies in IL-3-stimulated cultures and secondary lymphoid colonies in IL-7-stimulated cultures. The latter ones could be serially transferred in vitro for several months, and formed typical PGM-2 tumors in vivo. IL-7-stimulated colonies could therefore be used to measure leukemic stem cells in vitro. Supramaximal IL-3 stimulation (2,500 U/mL) of suspension cultures was followed by an increase in overall cell numbers and a disappearance of leukemic stem cells, compatible with differentiation induction. This could not be counteracted by simultaneous stimulation with IL-7. However, lower IL-3 concentrations (500 U/mL) induced an expansion of the stem cell pool, possibly by facilitating density-dependent autostimulatory mechanisms involving endogenous production of IL-7. The system described is a simple in vitro model for differentiation therapy. It shows that leukemic stem cells can be induced by hematopoietic growth factors to undergo terminal differentiation, but the concentrations required for differentiation induction in stem cells are much higher than those required for other biologic effects. Submaximal stimulation may favor expansion rather than repression of the leukemic cell population.
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No pos
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No neg
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Retriever1494
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Amino acid analysis of dried blood spots for diagnosis of phenylketonuria using capillary electrophoresis-mass spectrometry equipped with a sheathless electrospray ionization interface.
We describe a capillary electrophoresis-mass spectrometry (CE-MS) method for newborn screening of a representative amino acid metabolic disease, namely, phenylketonuria (PKU). Underivatized phenylalanine and tyrosine in a dried blood spot (DBS) were simultaneously determined by CE-MS equipped with an ionophore membrane-packed sheathless electrospray ionization interface, which was developed by our group. The method was optimized for rapid determination of the underivatized amino acids, phenylalanine and tyrosine extracted from a DBS. Under the optimized conditions, the limit of detection of phenylalanine and tyrosine (signal-to-noise ratio, 3) was 0.03 and 0.07 mg/L in DBS, respectively, with a CE run time of less than 3 min. For repeated runs of a sample, coefficients of variation (CVs) for migration time were less than 3.7%, whereas CVs for the area ratio under the curve were 2.1 and 2.9% for 20 consecutive runs of 49.5 mg/kg Phe and 36.2 mg/kg Tyr, respectively. However, the relative standard deviations of intra- and interday assays for DBS samples were <6.2 and <5.8%, respectively, which were substantially due to sample extraction from DBS. The analytical method was applied to real clinical samples of Korean neonates, and results were compared with those of conventional methods for PKU diagnosis, which required reference analytical methods such as isotope dilution CE-MS or high-performance liquid chromatography-mass spectrometry for quality assurance of the conventional kit-based assays. The distinct advantages of high sensitivity and extremely low sample volume, as well as a simple, easy, and economic sample pretreatment, were demonstrated for the proposed method.
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No pos
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No neg
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Retriever1495
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The somatising effect of clinical consultation: what patients and doctors say and do not say when patients present medically unexplained physical symptoms.
Patients with symptoms that doctors cannot explain by physical disease are common in primary care. That they receive disproportionate amounts of physical intervention, which is largely ineffective and sometimes iatrogenic, is usually attributed to patients' belief that they are physically diseased, their denial of psychological difficulties, and their demand for physical intervention. The evidence for this view has mainly been doctors' subjective reports. By observing what patients and doctors say in consultation, we tested hypotheses arising from recent qualitative evidence. In particular, that physical intervention is proposed more often by general practitioners (GPs) than by patients, that most patients indicate psychosocial needs, and that GPs offer little effective explanation or empathy. Consultations of 420 consecutive patients identified by British GPs as presenting medically unexplained symptoms (MUS) were audio-recorded, transcribed and coded, utterance-by-utterance, using a specially developed coding scheme based on the previous qualitative analyses of these kinds of consultation. Physical intervention was, as predicted, proposed more often by GPs than patients. Also as predicted, almost all patients provided cues concerning psychosocial difficulties or their need for explanation. Although, contrary to prediction, most GPs did provide explanations other than physical disease, most also suggested physical disease. Few GPs empathised. The findings suggest that the explanation for the high level of physical intervention for MUS lies in GPs' responses rather than patients' demands, and we propose that explanations for 'somatisation' should be sought in doctor-patient interaction rather than in patients' psychopathology.
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No pos
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No neg
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Retriever1496
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Combined depletion of cell cycle and transcriptional cyclin-dependent kinase activities induces apoptosis in cancer cells.
Selective cyclin-dependent kinase (cdk) 2 inhibition is readily compensated. However, reduced cdk2 activity may have antiproliferative effects in concert with other family members. Here, inducible RNA interference was used to codeplete cdk2 and cdk1 from NCI-H1299 non-small cell lung cancer and U2OS osteosarcoma cells, and effects were compared with those mediated by depletion of either cdk alone. Depletion of cdk2 slowed G1 progression of NCI-H1299 cells and depletion of cdk1 slowed G2-M progression in both cell lines, with associated endoreduplication in U2OS cells. However, compared with the incomplete cell cycle blocks produced by individual depletion, combined depletion had substantial consequences, with G2-M arrest predominating in NCI-H1299 cells and apoptosis the primary outcome in U2OS cells. In U2OS cells, combined depletion affected RNA polymerase II expression and phosphorylation, causing decreased expression of the antiapoptotic proteins Mcl-1 and X-linked inhibitor of apoptosis (XIAP), effects usually mediated by inhibition of the transcriptional cdk9. These events do not occur after individual depletion of cdk2 and cdk1, suggesting that reduction of cdk2, cdk1, and RNA polymerase II activities all contribute to apoptosis in U2OS cells. The limited cell death induced by combined depletion in NCI-H1299 cells was significantly increased by codepletion of cdk9 or XIAP or by simultaneous treatment with the cdk9 inhibitor flavopiridol. These results show the potency of concomitant compromise of cell cycle and transcriptional cdk activities and may guide the selection of clinical drug candidates.
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No pos
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No neg
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Retriever1497
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Thromboembolic complications after cardioversion of acute atrial fibrillation: the FinCV (Finnish CardioVersion) study.
OBJECTIVES
This study sought to explore the incidence and risk factors of thromboembolic complications after cardioversion of acute atrial fibrillation.
BACKGROUND
Anticoagulation therapy is currently recommended after cardioversion of acute atrial fibrillation in patients with risk factors for stroke, but the implementation of these new consensus-based guidelines has been slow.
METHODS
A total of 7,660 cardioversions were performed in 3,143 consecutive patients with atrial fibrillation lasting <48 h in 3 hospitals. For this analysis, embolic complications were evaluated during the 30 days after 5,116 successful cardioversions in 2,481 patients with neither oral anticoagulation nor peri-procedural heparin therapy.
RESULTS
There were 38 (0.7%; 95% confidence interval [CI]: 0.5% to 1.0%) definite thromboembolic events (31 strokes) within 30 days (median 2 days, mean 4.6 days) after cardioversion. In addition, 4 patients suffered transient ischemic attack after cardioversion. Age (odds ratio [OR]: 1.05; 95% CI: 1.02 to 1.08), female sex (OR: 2.1; 95% CI: 1.1 to 4.0), heart failure (OR: 2.9; 95% CI: 1.1 to 7.2), and diabetes (OR: 2.3; 95% CI: 1.1 to 4.9) were the independent predictors of definite embolic events. Classification tree analysis showed that the highest risk of thromboembolism (9.8%) was observed among patients with heart failure and diabetes, whereas patients with no heart failure and age <60 years had the lowest risk of thromboembolism (0.2%).
CONCLUSIONS
The incidence of post-cardioversion thromboembolic complications is high in certain subgroups of patients when no anticoagulation is used after cardioversion of acute atrial fibrillation. (Safety of Cardioversion of Acute Atrial Fibrillation [FinCV]; NCT01380574).
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No pos
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No neg
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Retriever1498
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The assembly of the CAAT-box binding complex at a photosynthesis gene promoter is regulated by light, cytokinin, and the stage of the plastids.
A functionally important region in the promoter of the spinach photosynthesis gene AtpC, which encodes the subunit gamma of the chloroplast ATP synthase, is located immediately upstream of the CAAT-box. A single nucleotide exchange in this region (AAAATTCAAT --> AAGATCAAT) uncouples the expression of an AtpC promoter::uidA gene fusion from the regulation by light, cytokinin, and functional plastids and results in a high constitutive expression of the reporter gene. By screening an Arabidopsis thaliana expression library with a double-stranded wild-type oligonucleotide from this promoter region, we have isolated cDNAs from Arabidopsis libraries that code for plant homologs of the CAAT-box binding factor (CBF)-C. Binding occurs only in the presence of nuclear extracts, consistent with reports from metazoa CBFs that the subunits A and B in addition to C are required for the formation of the CBF-DNA complex. At least eight genes with homologies to CBF-C are present in the Arabidopsis genome; one of them exhibits striking similarities to the gene for the human global transcriptional repressor Drap1. In gel mobility shift assays, low binding activity of CBF to the wild-type AtpC promoter sequence was observed with nuclear extracts from tissue with low AtpC expression levels, i.e. extracts from etiolated and photobleached seedlings, whereas high binding activity was detectable with extracts from tissues with high AtpC expression levels, i.e. extracts from light-grown seedlings and etiolated seedlings treated with cytokinin. Binding to the mutant sequence, which directs constitutive high level uidA expression in vivo, is significantly stronger than to the wild-type sequence. The data are consistent with the idea that the assembly of CBF at the AtpC promoter is regulated in response to light and cytokinin and that the low level of expression in etiolated and photobleached material is caused by an inhibitory effect. The structure/function relationships of the Arabidopsis CBFs are discussed in relation to their regulatory function in AtpC gene expression.
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No pos
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No neg
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Retriever1499
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The C-terminal extension of Saccharomyces cerevisiae Hsp104 plays a role in oligomer assembly.
The Saccharomyces cerevisiae protein Hsp104, a member of the Hsp100/Clp AAA+ family of ATPases, and its orthologues in plants (Hsp101) and bacteria (ClpB) function to disaggregate and refold thermally denatured proteins following heat shock and play important roles in thermotolerance. The primary sequences of fungal Hsp104's contain a largely acidic C-terminal extension not present in bacterial ClpB's. In this work, deletion mutants were used to determine the role this extension plays in Hsp104 structure and function. Elimination of the C-terminal tetrapeptide DDLD diminishes binding of the tetratricopeptide repeat domain cochaperone Cpr7 but is dispensable for Hsp104-mediated thermotolerance. The acidic region of the extension is also dispensable for thermotolerance and for the stimulation of Hsp104 ATPase activity by poly-l-lysine, but its truncation results in an oligomerization defect and reduced ATPase activity in vitro. Finally, sequence alignments reveal that the C-terminal extension contains a sequence (VLPNH) that is conserved in fungal Hsp104's but not in other orthologues. Hsp104 lacking the entire C-terminal extension including the VLPNH region does not assemble and has very low ATPase activity. In the presence of a molecular crowding agent the ATPase activities of mutants with longer truncations are partially restored possibly through enhanced oligomer formation. However, elimination of the whole C-terminal extension results in an Hsp104 molecule which is unable to assemble and becomes aggregation prone at high temperature, highlighting a novel structural role for this region.
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No pos
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No neg
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