id
stringlengths 10
13
| query
stringlengths 52
8.83k
| pos
stringclasses 1
value | neg
stringclasses 1
value |
|---|---|---|---|
Retriever1500
|
An efficient ERP-based brain-computer interface using random set presentation and face familiarity.
Event-related potential (ERP)-based P300 spellers are commonly used in the field of brain-computer interfaces as an alternative channel of communication for people with severe neuro-muscular diseases. This study introduces a novel P300 based brain-computer interface (BCI) stimulus paradigm using a random set presentation pattern and exploiting the effects of face familiarity. The effect of face familiarity is widely studied in the cognitive neurosciences and has recently been addressed for the purpose of BCI. In this study we compare P300-based BCI performances of a conventional row-column (RC)-based paradigm with our approach that combines a random set presentation paradigm with (non-) self-face stimuli. Our experimental results indicate stronger deflections of the ERPs in response to face stimuli, which are further enhanced when using the self-face images, and thereby improving P300-based spelling performance. This lead to a significant reduction of stimulus sequences required for correct character classification. These findings demonstrate a promising new approach for improving the speed and thus fluency of BCI-enhanced communication with the widely used P300-based BCI setup.
|
No pos
|
No neg
|
Retriever1501
|
A cross-talk between integrin β4 and epidermal growth factor receptor induces gefitinib chemoresistance to gastric cancer.
BACKGROUND
Gastric cancer presents a major health burden worldwide. Therefore, many molecular targeting agents have been evaluated for treatment of gastric cancer. Gefitinib has shown anticancer activity against gastric cancer which work through inhibiting epidermal growth factor receptor (EGFR). However, the effect of gefitinib is limited due to its resistance. Therefore, understanding the mechanisms of gefitinib resistance is desperately needed to formulate novel strategies against gastric cancer. Here, we analyzed resistance mechanism from the crosstalk between EGFR and integrin β4.
METHODS
Integrin β4-expression vector or siRNA were used to analyze the functional effects of integrin β4 on chemoresistance of gastric cancer cells to gefitinib. EGFR and integrin β4 expression, proliferation and apoptosis of gastric cancer cells were assayed by indirect immunofluorescence, western blot, MTT and flow cytometry respectively. EGFR and integrin β4 expression were also assayed on patient samples.
RESULTS
It was found that the integrin β4 expression was increased in gefitinib-resistant gastric cell line. The upregulated integrin β4 expression was identified to promote gefitinib resistance and proliferation, and inhibit apoptosis, while downregulation of integrin β4 was to inhibit gefitinib resistance and proliferation, and induce apoptosis. Moreover, the overexpression of integrin β4 in SGC7901 cells resulted in the down-regulation of p-EGFR protein levels while down-regulation of integrin β4, significantly resulted in overexpression of p-EGFR. The results of western blot from patients also showed there was obvious negative correlation between p-EGFR and integrin β4 in gastric cancer patients.
CONCLUSION
Considering the above results, it is concluded that the interaction of EGFR and integrin β4 may change the sensitivity of gefitinib treatment.
|
No pos
|
No neg
|
Retriever1502
|
Male hormone replacement therapy including "andropause".
Adult onset male hypogonadism and the testosterone deficiency of the aging male often are under-recognized entities. The etiologies, presentation, and diagnosis of hypogonadism and andropause in the adult male are presented. The expected therapeutic goals, potential treatment risks, and management of androgen replacement therapy for the adult man are reviewed. The advantages and disadvantages of the various androgen delivery systems currently available and under investigation are discussed.
|
No pos
|
No neg
|
Retriever1503
|
Source-Sink Dynamics in Field-Grown Durum Wheat Under Contrasting Nitrogen Supplies: Key Role of Non-Foliar Organs During Grain Filling.
The integration of high-throughput phenotyping and metabolic approaches is a suitable strategy to study the genotype-by-environment interaction and identify novel traits for crop improvement from canopy to an organ level. Our aims were to study the phenotypic and metabolic traits that are related to grain yield and quality at canopy and organ levels, with a special focus on source-sink coordination under contrasting N supplies. Four modern durum wheat varieties with contrasting grain yield were grown in field conditions under two N fertilization levels in north-eastern Spain. We evaluated canopy vegetation indices taken throughout the growing season, physiological and metabolic traits in different photosynthetic organs (flag leaf blade, sheath, peduncle, awn, glume, and lemma) at anthesis and mid-grain filling stages, and agronomic and grain quality traits at harvest. Low N supply triggered an imbalance of C and N coordination at the whole plant level, leading to a reduction of grain yield and nutrient composition. The activities of key enzymes in C and N metabolism as well as the levels of photoassimilates showed that each organ plays an important role during grain filling, some with a higher photosynthetic capacity, others for nutrient storage for later stages of grain filling, or N assimilation and recycling. Interestingly, the enzyme activities and sucrose content of the ear organs were positively associated with grain yield and quality, suggesting, together with the regression models using isotope signatures, the potential contribution of these organs during grain filling. This study highlights the use of holistic approaches to the identification of novel targets to improve grain yield and quality in C3 cereals and the key role of non-foliar organs at late-growth stages.
|
No pos
|
No neg
|
Retriever1504
|
Somatic gene therapy in animal models of Parkinson's disease.
Gene therapy in Parkinson's disease (PD) emerged about 10 years ago but until now, no clinical trials are under way, because most approaches have failed to show long-term therapeutic effects in PD animal models and because safety concerns precluded the use in humans so far. This review tries to give an overview on the development of different strategies in gene therapy in PD animal models and point out new and possibly more successful directions, including the transplantation of neural precursor cells and pig tissue.
|
No pos
|
No neg
|
Retriever1505
|
Mediastinal seminoma in a patient with multiple endocrine neoplasia type 1.
A patient with multiple endocrine neoplasia type 1 (MEN1) developed a mediastinal seminoma. The patient was a 46-year-old man who presented with respiratory symptoms. A diagnosis of mediastinal seminoma was pathologically confirmed and a complete remission was achieved by chemotherapy. During his hospital stay, hyperparathyroidism and multiple pancreatic tumors associated with hypergastrinemia were found. A diagnosis of MEN1 was made genetically. Although patients with MEN1 manifest a variety of neoplastic disorders, no cases of concurrent seminoma and MEN1 have previously been reported. In addition, no etiological relationship between seminoma and MEN1 has yet been reported.
|
No pos
|
No neg
|
Retriever1506
|
α,ω-Reactive Building Blocks Based on a Dual Functional RAFT Agent for Thermal and Light-Induced Ligation.
A dual functional chain transfer agent (CTA) capable of highly efficient sequential thermal and photoinduced ligation, generating α,ω-functional polymers, is introduced. The newly designed CTA (1-(4-((2-formyl-3-methyl phenoxy)methyl)phenyl)ethyl (diethoxyphosphoryl)methane dithioate) fuses thermally triggered hetero Diels-Alder chemistry with rapid light-induced photoenol chemistry. The versatility of the CTA is exemplarily demonstrated via the preparation of an amphiphilic triblock quaterpolymer poly(isoprene-co-styrene)-block-poly(ethyl acrylate)-block-poly(ethylene oxide) (P(I-co-S)-b-PEA-b-PEO). Subsequent to the homopolymerization of ethyl acrylate (PEA), a Cp-functional poly(isoprene-co-styrene) (P(I-co-S)) is conjugated with the electron-deficient C═S double bond (dienophile) of the CTA end group, generating a P(I-co-S)-b-PEA diblock terpolymer. The triblock quaterpolymer P(I-co-S)-b-PEA-b-PEO is generated by photoligation of a macromolecular dienophile, i.e., the fumarate-terminated poly(ethylene oxide) (PEO-fum) to the photoenol-functional P(I-co-S)-b-PEA. The new dual functional ligation RAFT agent constitutes a technology platform for generating α,ω-reactive building blocks from one single chain transfer agent.
|
No pos
|
No neg
|
Retriever1507
|
Inhibition of mTORC1/P70S6K pathway by Metformin synergistically sensitizes Acute Myeloid Leukemia to Ara-C.
AIMS
Chemo-resistance still was the main obstacle for AML patients, more effective and less toxic forms of therapies were desperately needed. Metformin, a classic hypoglycemic drug for diabetes recently delivered us a new identity that it exerted anti-tumor activity through suppressing mTOR in various tumors. But the anti-tumor effect of metformin in AML was not clear.
METHODS
In this study, we used CCK8 assay and apoptosis assay to determine the anti-leukemia activity of metformin combined with AraC, and explore the mechanism of the joint role of Ara-C/metformin in AML. We finally used xenograft experiment in mice to determine the anti-leukemia effect of Ara-C/metformin in vivo.
KEY FINDINGS
We found that metformin could synergistically sensitize AML cells to Ara-C via inhibiting mTORC1/P70S6K pathway. In vivo experiment also verified metformin in aid of Ara-C caused an obviously synergistic anti-tumor effect.
SIGNIFICANCE
We firstly found the synergistic anti-tumor effect of Ara-C/metformin in AML through inhibiting mTORC1/P70S6K pathway.
|
No pos
|
No neg
|
Retriever1508
|
Microbial Community Structure Driven by a Volcanic Gradient in Glaciers of the Antarctic Archipelago South Shetland.
It has been demonstrated that the englacial ecosystem in volcanic environments is inhabited by active bacteria. To know whether this result could be extrapolated to other Antarctic glaciers and to study the populations of microeukaryotes in addition to those of bacteria, a study was performed using ice samples from eight glaciers in the South Shetland archipelago. The identification of microbial communities of bacteria and microeukaryotes using 16S rRNA and 18S rRNA high throughput sequencing showed a great diversity when compared with microbiomes of other Antarctic glaciers or frozen deserts. Even the composition of the microbial communities identified in the glaciers from the same island was different, which may be due to the isolation of microbial clusters within the ice. A gradient in the abundance and diversity of the microbial communities from the volcano (west to the east) was observed. Additionally, a significant correlation was found between the chemical conditions of the ice samples and the composition of the prokaryotic populations inhabiting them along the volcanic gradient. The bacteria that participate in the sulfur cycle were those that best fit this trend. Furthermore, on the eastern island, a clear influence of human contamination was observed on the glacier microbiome.
|
No pos
|
No neg
|
Retriever1509
|
Utility of Interphase FISH Panels for Routine Clinical Cytogenetic Evaluation of Chronic Lymphocytic Leukemia and Multiple Myeloma.
Specific genetic abnormalities are of prognostic significance for patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM); however, routine cytogenetic analysis usually provides normal results. We utilized two probe panels for interphase fluorescence in situ hybridization (FISH) studies to enhance the ability to detect genetic abnormalities in samples that were referred for routine cytogenetic studies for possible diagnoses of CLL or MM. The CLL panel consisted of probes for 11q22.3 (ATM gene), 13q14 (D13S319), the centromere of chromosome 12 (D12Z3) and 17p13.1 (P53 gene). The MM panel included probes for 14q32 (IgH gene) and/or t(11:14)(q13;q32) (BCL1/IgH), 13q14 (D13S319) and 17p13.1 (P53 gene). FISH detected clonal aberrations not identified by conventional cytogenetics in an additional 8 of 23 (35%) samples referred for possible CLL and 7 of 42 (17%) samples with possible MM. The prognostic significance of the aberrations identified ranged from favorable, to intermediate, to poor. Our studies indicate that many samples referred for routine cytogenetics testing for CLL and MM yield normal results for both conventional and FISH testing, likely due to lack of definitive diagnosis in a percentage of cases. However, FISH is more sensitive for the detection of clinically significant chromosome abnormalities and should be the testing methodology of choice for these disorders.
|
No pos
|
No neg
|
Retriever1510
|
Cores, microbial organelles possibly specific to group D streptococci.
A long, thin, approximately cylindrical core spans the interior of cells of 24-hr cultures of all group D streptococci that were examined, five strains of Streptococcus faecalis, single strains of S. faecalis subsp. zymogenes and S. durans, and three strains of Streptococcus spp. In one strain of S. faecalis, serial section electron microscopy showed that most cells possess a core. The core is 0.10 to 0.16 mum thick and consists of a matrix and an axial array of ribosomelike particles. It resembles one of two types of cores present in a stable protoplast form of one of the S. faecalis strains. Cores were not present in single strains of S. pyogenes (beta-hemolytic group A), S. agalactiae (group B), S. dysgalactiae (group C), S. equisimilis (group C), and S. mitis (viridans group) that were examined; nor were cores observed in single strains of Staphylococcus aureus, Escherichia coli, and Bacillus megaterium. Cores may be useful, therefore, in identification of group D streptococci. For preservation and rapid recognition of cores, a glutaraldehyde-osmium tetroxide sequence of fixation appears superior to the osmium tetroxide method often employed in processing bacteria for electron microscopy.
|
No pos
|
No neg
|
Retriever1511
|
Appraisal, coping, motivational factors and gender in vocational rehabilitation.
The applicability of a model of appraisal and coping was studied in vocational rehabilitation patients (n = 31:16 men, 15 women); the selection of patients aimed at obtaining a representative patient group for studying coordinated rehabilitation within various health care districts in southern Sweden. There were four phases of data collection and model adjustment. An initial, semi-structured interview concerned various key topics (program evaluation; causal attribution regarding the problem or disease; life-crises, threats, mobbing and unjust treatment; feeling of control; current situation; future; how the interview was experienced). The second phase involved a questionnaire study of hypochondriacal and depressive symptomatology, the third the analysis of patient records, and the fourth outcome data on sickness allowances and disability pensions at a 2-year follow-up. The results indicate the importance for rehabilitation of attending to motivational factors that influence the patients' coping strategies and appraisal, and to cultural (immigrant) and gender perspectives.
|
No pos
|
No neg
|
Retriever1512
|
How do neurons degenerate in prion diseases or transmissible spongiform encephalopathies (TSEs): neuronal autophagy revisited.
As in other neurodegenerative diseases such as Alzheimer's disease, neurons in prion diseases or transmissible spongiform encephalopathies (TSEs) die via programmed cell death of which the apoptotic process is relatively well characterized. A subcellular alteration linked to apoptosis is the formation of autophagic vacuoles, which we and others demonstrated in CJD- and scrapie-affected rodent brains. Autophagy may co-exist with apoptosis or may precede it and the process may be induced by apoptotic stimuli. Here, we extend these observations using different model of scrapie and CJD. Both scrapie models (the 263K and 22C-H) demonstrated autophagic vacuoles with the same frequency; hence, they will be described together. While the following changes had been observed simultaneously in different areas of the same sample, this description is organised as if it followed a sequence of events. First, a part of the neuronal cytoplasm was sequestrated by concentric arrays of membrane; that part of the cytoplasm closed by membranes appeared relatively normal but its density often appeared increased. Next, electron density of the central dramatically increased. Then, membranes proliferated within the cytoplasm in a labyrinth-like manner and an area sequestrated by these membranes enlarged and became more complex structure consisting of vacuoles, electron-dense area and areas of normally-looking cytoplasm connected with convoluted membranes. Finally, a large area of the cytoplasm was transformed into a collection of autophagic vacuoles of different sizes. Virtually identical alterations, albeit with much lower frequency, were seen in terminally ill CJD-affected hamsters.
|
No pos
|
No neg
|
Retriever1513
|
Self-Folded Three-Dimensional Graphene with a Tunable Shape and Conductivity.
Three-dimensional (3D) graphene architectures are of great interest as applications in flexible electronics and biointerfaces. In this study, we demonstrate the facile formation of predetermined 3D polymeric microstructures simply by transferring monolayer graphene. The graphene adheres to the surface of polymeric films via noncovalent π-π stacking bonding and induces a sloped internal strain, leading to the self-rolling of 3D microscale architectures. Micropatterns and varied thicknesses of the 2D films prior to the self-rolling allows for control over the resulting 3D geometries. The strain then present on the hexagonal unit cell of the graphene produces a nonlinear electrical conductivity across the device. The driving force behind the self-folding process arises from the reconfiguration of the molecules within the crystalline materials. We believe that this effective and versatile way of realizing a 3D graphene structure is potentially applicable to alternative 2D layered materials as well as other flexible polymeric templates.
|
No pos
|
No neg
|
Retriever1514
|
Subtle but progressive cognitive deficits in the female tgHD hemizygote rat as demonstrated by operant SILT performance.
In accordance with the genetic nature of Huntington's disease (HD), transgenic and knock-in mouse models have been developed that have sought to recapitulate the key features of the human condition. To date, only a single rat model has been developed, the tgHD rat that carries 51 CAG repeats. The tgHD rat has many of the anatomical and behavioural characteristics of HD, including cognitive, emotional and motor abnormalities. To characterize this model further, hemizygous tgHD rats were tested on an operant serial implicit learning task (SILT), to determine whether these animals have an implicit learning deficit as reported in HD patients. The SILT utilises a predictable two-stage sequence of responding to two consecutive stimuli (S1 and S2) as a probe of implicit learning, embedded amongst many randomly presented two-stage sequences. The results suggest that the hemizygous tgHD rats have a mild but progressive cognitive deficit that is attentional in nature. Longitudinal responding to the S1 stimuli demonstrated deficits that progressed over time for both accuracy and reaction time measures, whereas responses to S2 stimuli were mild and stable over time. Whilst a significant effect of predictability over time was identified, analyses of the final time point alone, failed to demonstrate between group differences in their ability to utilise the predictable information at this time point, when differences between the groups should be at their most pronounced. The results suggest that the hemizygous tgHD rats have mild cognitive deficits that are attentional in nature, but no implicit learning deficit.
|
No pos
|
No neg
|
Retriever1515
|
Presentation of COVID-19 infection with bizarre behavior and encephalopathy: a case report.
BACKGROUND
Current studies show that patients with severe coronavirus disease 2019 (COVID-19) have neurological symptoms manifesting as acute cerebrovascular diseases, impaired consciousness, and skeletal muscle symptoms. Bizarre behavior is an unusual and unique presenting symptom of COVID-19 infection in our patient.
CASE PRESENTATION
We report a case of COVID-19 infection in a middle aged Iranian man without underlying disease who presented with bizarre behavior. Results of brain imaging were normal, but COVID-19 pneumonia was detected on chest computed tomography scan. Given the respiratory problem and positive polymerase chain reaction (PCR) test for COVID-19, treatment with hydroxychloroquine was administered, and after 2 days all of the symptoms resolved.
CONCLUSIONS
Encephalopathy and encephalitis may be a possible presentation of COVID-19. Clinicians and health care providers should consider the presence of COVID-19 with bizarre behavior during this COVID-19 pandemic.
|
No pos
|
No neg
|
Retriever1516
|
Lemierre's syndrome with bilateral empyema thoracis.
A 31-year-old patient is described with thrombophlebitis of the right jugular vein, and anerobic septicemia (Lemierre's syndrome). Multiple pulmonary abscesses and bilateral fibrinopurulent empyema were also present. Treatment included intravenous antibiotics, heparin, and video-assisted thoracoscopic debridement of pleural cavities. A favorable outcome was observed.
|
No pos
|
No neg
|
Retriever1517
|
Divergent responsiveness of the dentary and vertebral bone to a selective estrogen-receptor modulator (SERM) in the teleost Sparus auratus.
In teleosts the regulation of skeletal homeostasis and turnover by estrogen is poorly understood. For this reason raloxifene, a selective estrogen-receptor modulator (SERM), was administered to sea bream (Sparus auratus) and its effect on plasma calcium balance and transcript expression in dentary (dermal bone) and vertebra (perichondral bone) was studied. The concentration of total calcium or phosphorus in plasma was unchanged by raloxifene treatment for 6days. The activity of alkaline phosphatase (ALP) in dentary bone of raloxifene treated fish was significantly (p<0.05) higher than control fish but it was not changed in vertebral bone. Transcripts for estrogen receptor (ER) α were in very low abundance in the sea bream dentary and vertebra and were unchanged by raloxifene treatment. In contrast, raloxifene caused significant (p<0.05) up-regulation of the duplicate ERβ transcripts in the dentary but did not affect specific transcripts for osteoclast (TRAP), osteoblast (ALP, Runx2, osteonectin) or cartilage (IGF1, CILP2, FN1a). In the vertebra ERβb was not changed by raloxifene but ERβa was significantly (p<0.05) down-regulated as was the skeletal specific transcripts, TRAP, ALP, CILP2, FN1a. In summary, ERβs regulate estrogen sensitivity of the skeleton in sea bream, which responds in a non uniform manner. In common with mammals raloxifene appears to have an anti-resorptive role (in sea bream vertebra), but also an osteoblast stimulatory role, inducing ALP activity in the dentary of sea bream. Overall, the results indicate bone specific responsiveness to raloxifene in the sea bream. Further work will be required to understand the basis of bone responsiveness and the role of E(2) and ERs in teleost bone homeostasis.
|
No pos
|
No neg
|
Retriever1518
|
Relationships between psychosocial outcomes in adolescents who are obese and their parents during a multi-disciplinary family-based healthy lifestyle intervention: One-year follow-up of a waitlist controlled trial (Curtin University's Activity, Food and Attitudes Program).
BACKGROUND
Limited studies have investigated relationships in psychosocial outcomes between adolescents who are obese and their parents and how psychosocial outcomes change during participation in a physical activity and healthy eating intervention. This study examined both adolescent and parent psychosocial outcomes while participating in a one - year multi-disciplinary family-based intervention: Curtin University's Activity, Food, and Attitudes Program (CAFAP).
METHODS
Following a waitlist control period, the intervention was delivered to adolescent (n = 56, ages 11-16) and parent participants over 8 weeks, with one-year maintenance follow-up. Adolescent depression and quality of life, family functioning, and parent depression, anxiety, and stress were assessed at six time points: baseline and prior to intervention (e.g., waitlist control period), immediately following intervention, and at 3, 6, and 12 months post-intervention. Relationships between adolescent and parent psychosocial outcomes were assessed using Spearman correlations and changes in both adolescent and parent outcomes were assessed using linear mixed models. Changes in adolescent psychosocial outcomes were compared to changes in behavioural (physical activity and healthy eating) and physical (weight) outcomes using independent samples t-tests.
RESULTS
The majority of psychosocial outcomes were significantly correlated between adolescents and parents across the one-year follow-up. Adolescent depression, psychosocial and physical quality of life outcomes significantly improved before or following intervention and were maintained at 6-months or one-year follow-up. Parent symptoms of depression, anxiety, and stress were reduced during waitlist and primarily remained improved. Changes in adolescent psychosocial outcomes were shown to be partially associated with behavioural changes and independent of physical changes.
CONCLUSIONS
Adolescents in CAFAP improved psychosocial and physical quality of life and reversed the typical trajectory of depressive symptoms in adolescents who are obese during a one-year maintenance period. CAFAP was also effective at maintaining reductions in parent symptoms of depression, anxiety, and stress demonstrated during the waitlist period.
TRIAL REGISTRATION
The trial was registered with the Australian and New Zealand Clinical Trials Registry (No. 12611001187932 ).
|
No pos
|
No neg
|
Retriever1519
|
[Circadian studies with young and old rats (author's transl)].
8 and 28 months old, male Sprague-Dawley rats (36 animals in each group) were used to determine the rectal temperature, various organ weights (referred to the body weight and the brain weight), various blood parameters and the concentration of Ca and Mg in the plasma and the myocard as a function of the time of the day. The values were approximated to the function y = M + A cos (omega t + phi) (y = parameter value, M = mesor, mean value of the day, A = amplitude, omega = angular velocity, t = hour of the day, phi = acrophase, when y has its highest value). The approximations were significant at 6 out of 45 parameters in both groups (rectal) temperature, pancreas weight related to the body weight, leucocyte number/mm3, GPT, Mg and Ca/Mg in the plasma). 17 parameters could be approximated only at the young rats, 1 parameter only at the old animals. In some cases large age correlated alterations of the amplitude could be observed. The mesor changed only at the pancreas weight related to the body weight. The acrophase shifted only at the leucocyte number/mm3. These variations can lead to wrong interpretations when only mean values are used for age comparisons.
|
No pos
|
No neg
|
Retriever1520
|
Experimental granulomatous uveitis: an electron microscopic study of pigment containing giant cells.
An experimental granulomatous uveitis in the Brown Norway rat is characterized by large numbers of giant cells and epithelioid cells containing uveal pigment. Ultrastructurally, the epithelioid cells and the giant cells exhibited melanosomes and individual melanin granules in the absence of phagocytic membranes and compound pigment granules. These observations support the view that the pigment containing giant cells may develop from uveal melanocytes.
|
No pos
|
No neg
|
Retriever1521
|
Penetrating wounds of the neck and upper thorax.
During the past decade, a method utilizing individual case assessment has been employed in the treatment of 51 patients with penetrating wounds of the neck and upper thorax. Only those wounds penetrating the platysma are included. Thirty-five patients (68.6%) underwent neck exploration; 16 patients (31.4%) were managed nonoperatively. Overall, five patients died, four patients following operative treatment and one treated nonoperatively, for a mortality rate of 9.8%. In the nonoperative group, a mortality of 6.2% (one death) compares favorably with an operative mortality of 11.4% (four deaths). Ten patients (29%) in the neck exploration group exhibited significant later morbidity compared to seven patients (44%) in the patients not explored. Therefore the morbidity from a negative neck exploration was only 2% (one of 20 patients). The techniques for exploring the neck are discussed. Adequate surgical exposure is largely dependent on the possibility of vascular injury, the most common cause of death in this series.
|
No pos
|
No neg
|
Retriever1522
|
Sorbitol increases the growth inhibition of xylitol on Strep. mutans OMZ 176.
It was observed in a previous study that the growth of Streptococcus mutans strain OMZ 176 on sorbitol was inhibited by xylitol. The aim of the present study was to investigate the mechanisms involved in this inhibition. It was shown that the uptake of 14C-sorbitol was delayed when the cells had been pre-exposed to xylitol, and that the only labelled substance found intracellularly was sorbitol; no further metabolization occurred. This is in contrast with untreated normal cells, where sorbitol is taken up by a specific phosphotransferase system (pts). The 14C-xylitol metabolism of the cells was qualitatively unchanged in the presence of sorbitol; an intracellular accumulation of 14C-xylitol-phosphate (xylitol-P) and 14C-xylulose-phosphate (xylulose-P) was observed. However, a reduced uptake of xylitol was observed in the presence of sorbitol. Xylitol thus appears to change the pathway by which sorbitol is taken up by the cells. An inducible permease may replace the normal sorbitol pts when xylitol is present. No further metabolization of this intracellular sorbitol seemed to occur in the resting cell suspensions. It was furthermore observed that the presence of sorbitol enhanced the inhibitory potential of xylitol. The accumulation of intracellular sorbitol coincided with markedly increased xylulose-P/xylitol-P ratio. It may be speculated that, if xylulose-P were the major inhibitor of the glycolysis instead of xylitol-P, as previously assumed, an increased concentration of xylulose-P induced by sorbitol could explain that sorbitol enhances the inhibition potential of xylitol. It is not evident, however, how intracellular sorbitol could affect the xylulose-P/xylitol-P ratio.
|
No pos
|
No neg
|
Retriever1523
|
Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization.
Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3-17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways.
|
No pos
|
No neg
|
Retriever1524
|
Elavl3 regulates neuronal polarity through the alternative splicing of an embryo-specific exon in AnkyrinG.
Alternative splicing of RNAs diversifies the functionalities of proteins, and it is optimized for each cell type and each developmental stage. nElavl (composed of Elavl2, Elavl3, and Elavl4) proteins are the RNA-binding proteins that is specifically expressed in neurons, regulate the alternative splicing of target RNAs, and promote neuronal differentiation and maturation. Recent studies revealed that Elavl3 knockout (Elavl3-/-) mice completely lost the expression of nElavl proteins in the Purkinje cells and exhibited cerebellar dysfunction. Here, we found that the alternative splicing of AnkyrinG exon 34 was misregulated in the cerebella of Elavl3-/- mice. AnkyrinG is an essential factor for the formation of neuronal polarity and is required for normal neuronal functions. We revealed that exon 34 of AnkyrinG was normally included in immature neurons and was mostly excluded in mature neurons; however, it was included in the cerebella of Elavl3-/- mice even in adulthood. In the Purkinje cells of adult Elavl3-/- mice, the length of the AnkyrinG-positive region shortened and somatic organelles leaked into the axons. These results suggested that exon 34 of AnkyrinG is an embryonic-stage-preferential exon that should be excluded from mature neurons and that Elavl3 regulates neuronal polarity through alternative splicing of this exon.
|
No pos
|
No neg
|
Retriever1525
|
The occurrence of antibodies against Legionella pneumophila in patients with autoimmune rheumatic diseases.
INTRODUCTION
Patients with autoimmune rheumatic diseases are more susceptible to infection, owing to the underlying disease itself or to its treatment. Most commonly, infections affect the respiratory and urinary tracts. One of the etiological factors of infections in these patients is the bacteria of the genus Legionella.
OBJECTIVES
The aim of the study was to assess the prevalence of anti-Legionella pneumophila (L. pneumophila) antibodies in patients with autoimmune rheumatic diseases and to analyze individual and environmental risk factors for the development of Legionella infection in patients with positive antibody results.
PATIENTS AND METHODS
The study group consisted of 165 patients with autoimmune rheumatic diseases and 100 healthy subjects. Serum samples were tested for the presence of specific antibodies in the immunoglobulin (Ig) M and IgG classes against L. pneumophila serogroups 1 to 7 (SG 1-7) and the IgG class for serogroup 1 (SG 1).
RESULTS
Antibodies against L. pneumophila were found in 7 patients (4%): 5 cases with antibody positivity only in the IgG class and 2 cases with antibody positivity in both classes. In patients with positive IgG antibodies for SG 1-7, specific antibodies for L. pneumophila SG 1 were not detected. In the control group, positive results were obtained in 9 cases (9%): IgM positivity in 6 (6%) and IgG positivity in 3 (3%).
CONCLUSIONS
The frequency of antibodies to L. pneumophila in our patients is comparable to that in healthy individuals. L. pneumophila should be recognized as a potential pathogen in patients with autoimmune rheumatic diseases. Primary disease condition, immunosuppressive therapy, and other risk factors should not be ignored in these patients.
|
No pos
|
No neg
|
Retriever1526
|
Inactivation of T5 phage by cis-vaccenic acid, an antivirus substance from Rhodopseudomonas capsulata, and by unsaturated fatty acids and related alcohols.
The antiviral extract from Rhodopseudomonas capsulata was purified and the predominant active component was defined as cis-vaccenic acid (Cl-8:1 delta 11) by gas-liquid chromatography and gas chromatography-mass spectrometry analyses. Antiviral activities of unsaturated fatty acids and related alcohols against T5 phage were also tested. Among them, linoelaidic acid, oleic acid, and petroselenyl alcohol inactivated 98%, 53%, 67% of T5 phage at the concentration of 50 micrograms/ml, respectively.
|
No pos
|
No neg
|
Retriever1527
|
Intravenous Recombinant Tissue Plasminogen Activator and Ischemic Stroke: Focused Update of 2010 Clinical Practice Advisory From the American Academy of Emergency Medicine.
BACKGROUND
Stroke treatment is a continuum that begins with the rapid identification of symptoms and treatment with transition to successful rehabilitation. Therapies for acute ischemic stroke (AIS) may vary based on anatomic location, interval from symptom onset, and coexisting health conditions. Successful therapy requires a seamless systematic approach with coordination from prehospital environment through acute management at medical facilities to disposition and long-term care of the patient. The emergency physician must balance the benefits and risks of alteplase recombinant tissue plasminogen activator (rtPA) for AIS management.
OBJECTIVE
We review the recent medical literature on the topic of AIS and assess intravenous rtPA for the following questions: 1) is there any applicable, new, high-quality evidence that the benefits of intravenous rtPA are justified in light of the harms associated with it, and 2) if so, does the evidence clarify which patients, if any, are most likely to benefit from the treatment.
METHODS
A MEDLINE literature search from January 2010 to October 2016 and limited to human studies written in English for articles with keywords of cerebrovascular accident and (thromboly* OR alteplase). Guideline statements and nonsystematic reviews were excluded. Studies targeting differences between specific populations (males vs. females) were excluded. Studies identified then underwent a structured review from which results could be evaluated.
RESULTS
Three hundred twenty-two papers on thrombolytic use were screened and nine appropriate articles were rigorously reviewed and recommendations given.
CONCLUSIONS
No new studies published between 2010 and 2016 meaningfully reduced uncertainty regarding our understanding of the benefits and harms of intravenous rtPA for AIS. Discussions regarding benefit and harm should occur for patients, and risk prediction scores may facilitate the conversation.
|
No pos
|
No neg
|
Retriever1528
|
Effect of ciliostatic factors from Pseudomonas aeruginosa on rabbit respiratory cilia.
Heat-stable factors released by Pseudomonas aeruginosa in culture supernatants inhibit functional cilia of rabbit tracheal epithelium. Chloroform extraction removed heat-stable factors from stationary-phase culture supernatants. The extracts contained at least seven components separable by thin-layer chromatography (TLC). Cilioinhibitory components were identified as a phenazine derivative, pyo compounds (2-alkyl-4-hydroxyquinolines), and a rhamnolipid, also known as a hemolysin. Fluorescence and absorption spectra, relative migration on TLC, staining characteristics, and gas chromatography were the basis for identification. Inhibitory concentrations of each active component were established by quantitative measures of percent motility and beat frequency. Corresponding damage to ciliary ultrastructure was examined by electron microscopy. The pyo compounds produced ciliostasis at concentrations of 50 micrograms/ml, but without obvious ultrastructural lesions. The phenazine derivative also inhibited ciliary motility and caused some membrane disruption, although at substantially greater concentrations of 400 micrograms/ml. Limited exposure of tracheal explants to the rhamnolipid resulted in ciliostasis which was associated with altered ciliary membranes. More extensive exposure to rhamnolipid was associated with removal of dynein arms from axonemes. Pyocyanin at a concentration of 0.5 mg/ml did not inhibit ciliary beating under our conditions. The data suggest that the pyo compounds are the most effective per weight ciliostatic factors released by P. aeruginosa and rhamnolipid is the most destructive of cilia ultrastructure. By interfering with normal ciliary function, these ciliostatic factors may enable P. aeruginosa to more easily colonize the respiratory tract.
|
No pos
|
No neg
|
Retriever1529
|
Drug transfer across the placenta. Considerations in treatment and research.
Using the pregnant woman as a means to medicate her fetus represents a new and exciting therapeutic approach in clinical pharmacology. In years to come, we will see an increase in the use of the currently accepted fetal therapies and an increase in the number of therapies available to the caregiver or clinician aimed at assisting the unborn child. The pharmacologist, through in vitro research that aids our understanding of the role of the placenta in fetal drug therapy, can contribute to the growth of this new field within the realm of obstetric medicine.
|
No pos
|
No neg
|
Retriever1530
|
Transcriptome analysis reveals the potential roles of long non-coding RNAs in feed efficiency of chicken.
Feed efficiency is an important economic trait and reduces the production costs per unit of animal product. Up to now, few studies have conducted transcriptome profiling of liver tissue in feed efficiency-divergent chickens (Ross vs native breeds). Also, molecular mechanisms contributing to differences in feed efficiency are not fully understood, especially in terms of long non-coding RNAs (lncRNAs). Hence, transcriptome profiles of liver tissue in commercial and native chicken breeds were analyzed. RNA-Seq data along with bioinformatics approaches were applied and a series of lncRNAs and target genes were identified. Furthermore, protein-protein interaction network construction, co-expression analysis, co-localization analysis of QTLs and functional enrichment analysis were used to functionally annotate the identified lncRNAs. In total, 2,290 lncRNAs were found (including 1,110 annotated, 593 known and 587 novel), of which 53 (including 39 known and 14 novel), were identified as differentially expressed genes between two breeds. The expression profile of lncRNAs was validated by RT-qPCR. The identified novel lncRNAs showed a number of characteristics similar to those of known lncRNAs. Target prediction analysis showed that these lncRNAs have the potential to act in cis or trans mode. Functional enrichment analysis of the predicted target genes revealed that they might affect the differences in feed efficiency of chicken by modulating genes associated with lipid metabolism, carbohydrate metabolism, growth, energy homeostasis and glucose metabolism. Some gene members of significant modules in the constructed co-expression networks were reported as important genes related to feed efficiency. Co-localization analysis of QTLs related to feed efficiency and the identified lncRNAs suggested several candidates to be involved in residual feed intake. The findings of this study provided valuable resources to further clarify the genetic basis of regulation of feed efficiency in chicken from the perspective of lncRNAs.
|
No pos
|
No neg
|
Retriever1531
|
[Evaluation of therapeutical appropriateness in psychiatric treatment of schizophrenia, by integrating computer data records with clinical audit results].
AIM
The aim is to evaluate prescriptive patterns of atypical antipsychotic drugs for the treatment of schizophrenia in the LHU Caserta in 2011-2013, and to indicate potentially inappropriate therapy; to plan or schedule corrective/preventive activities to support the continuous improvement of health services.
METHODS
Retrospective cohort study, based on integration of health records and clinical audit. The study was performed in the following steps: data retrieval and analysis; comparison of data with international literature; editing of the Diagnostic-Therapeutic Path. The analysis was performed by using the administrative database of drug prescriptions and treatment plans in the SANIARP portal, a web platform available to specialist facilities and private and public pharmacies of LHU Caserta. The subject of our analysis was to gain information about the diagnosis and treatment of users of atypical antipsychotics in the LHU of Caserta in the years 2011-2013.
RESULTS
We identified 2,768 patients with at least one prescription of atypical antipsychotics and diagnosis coded in the study period. Schizophrenia is the most frequent diagnosis (31.1%) and the most common drug in use is olanzapine (29.1%). About 70% of schizophrenics were on monotherapy with no change in drug, 23.6% were under polytherapy and 7.9% made a switch.
DISCUSSION AND CONCLUSION
Our findings were a starting point for editing Diagnostic and Therapeutic Paths aimed at raising the awareness of the scientific community about the appropriateness of diagnosis and treatment in schizophrenia. Pharmacological treatment of schizophrenia should be focused on improving the overall quality of life aimed at remission and possible recovery, although difficult.
|
No pos
|
No neg
|
Retriever1532
|
Heterologous Expression of Dehydration-Inducible MfbHLH145 of Myrothamnus flabellifoli Enhanced Drought and Salt Tolerance in Arabidopsis.
Myrothamnus flabellifolia is the only woody resurrection plant found in the world. It has a strong tolerance to drought and can survive long-term exposure to desiccated environments. However, few genes related to its drought tolerance have been functionally characterized and the molecular mechanisms underlying the stress tolerance of M. flabellifolia are largely unknown. In this study, we isolated a dehydration-inducible bHLH transcription factor gene MfbHLH145 from M. flabellifolia. Heterologous expression of MfbHLH145 enhanced the drought and salt tolerance of Arabidopsis. It can not only promote root system development under short-term stresses, but also improve growth performance under long-term treatments. Further investigation showed that MfbHLH145 contributes to enhanced leaf water retention capacity through the promotion of stomatal closure, increased osmolyte accumulation, and decreased stress-induced oxidative damage through an increase in antioxidant enzyme activities. These results suggest that MfbHLH145 may be involved in the positive regulation of stress responses in M. flabellifolia. This study provides insight into the molecular mechanism underlying the survival of M. flabellifolia in extreme dehydration conditions.
|
No pos
|
No neg
|
Retriever1533
|
Hyponatremia following mild/moderate subarachnoid hemorrhage is due to SIAD and glucocorticoid deficiency and not cerebral salt wasting.
CONTEXT
Hyponatremia is common after acute subarachnoid hemorrhage (SAH) but the etiology is unclear and there is a paucity of prospective data in the field. The cause of hyponatremia is variously attributed to the syndrome of inappropriate antidiuresis (SIAD), acute glucocorticoid insufficiency, and the cerebral salt wasting syndrome (CSWS).
OBJECTIVE
The objective was to prospectively determine the etiology of hyponatremia after SAH using sequential clinical examination and biochemical measurement of plasma cortisol, arginine vasopressin (AVP), and brain natriuretic peptide (BNP).
DESIGN
This was a prospective cohort study.
SETTING
The setting was the National Neurosurgery Centre in a tertiary referral centre in Dublin, Ireland.
PATIENTS
One hundred patients with acute nontraumatic aneurysmal SAH were recruited on presentation.
INTERVENTIONS
Clinical examination and basic biochemical evaluation were performed daily. Plasma cortisol at 0900 hours, AVP, and BNP concentrations were measured on days 1, 2, 3, 4, 6, 8, 10, and 12 following SAH. Those with 0900 hours plasma cortisol<300 nmol/L were empirically treated with iv hydrocortisone.
MAIN OUTCOME MEASURES
Plasma sodium concentration was recorded daily along with a variety of clinical and biochemical criteria. The cause of hyponatremia was determined clinically. Later measurement of plasma AVP and BNP concentrations enabled a firm biochemical diagnosis of the cause of hyponatremia to be made.
RESULTS
Forty-nine of 100 developed hyponatremia<135 mmol/L, including 14/100<130 mmol/L. The cause of hyponatremia, and determined by both clinical examination and biochemical hormone measurement, was SIAD in 36/49 (71.4%), acute glucocorticoid insufficiency in 4/49 (8.2%), incorrect iv fluids in 5/49 (10.2%), and hypovolemia in 5/49 (10.2%). There were no cases of CSWS.
CONCLUSIONS
The most common cause of hyponatremia after acute nontraumatic aneurysmal SAH is SIAD. Acute glucocorticoid insufficiency accounts for a small but significant number of cases. We found no cases of CSWS.
|
No pos
|
No neg
|
Retriever1534
|
Lermoyez syndrome revisited: 100-year mystery.
OBJECTIVE
This study revisited seven patients with Lermoyez syndrome over the past 25 years using an inner ear test battery to elucidate its mechanism.
METHODS
From 1992 to 2017, we have experienced 4096 patients with Meniere's disease (MD) and seven patients (5 males and 2 females, 8 ears) with Lermoyez syndrome. Two of the Lermoyez patients were elderly, aged 71 and 85 years. An inner ear test battery comprising audiometry, ocular and cervical vestibular-evoked myogenic potential (oVEMP and cVEMP) tests, and caloric test were performed.
RESULTS
Significant improvement of mean hearing levels (MHLs) was identified at low and middle frequencies after vertiginous attack, but not at high frequencies. Inner ear deficits in Lermoyez patients ran from abnormal hearing (100%) to abnormal cVEMP (43%), caloric (38%) and oVEMP (0) tests, exhibiting a significantly declining sequence. This declining sequence differed from that in MD.
CONCLUSIONS
Lermoyez syndrome is extremely rare, with prevalence relative to MD of 0.2%. The mechanism is considered as blockage in the ductus reuniens caused by dislodged saccular otoconia. Aging and trauma are two precipitating factors for the dislodged saccular otoconia, which may explain why Lermoyez syndrome occurs most frequently in males and some elderly.
|
No pos
|
No neg
|
Retriever1535
|
Thiazide-induced hypokalaemia; prevalence higher in women.
In 193 hypertensive patients taking bendrofluazide 5 mg daily, the mean serum potassium concentration was lower in women than in men (3.77 vs 3.99 mmol/l, P less than 0.001) and the prevalence of hypokalaemia (less than 3.5 mmol/l) was higher (25% vs 12%, P less than 0.05). This difference between the sexes was independent of age, body weight, renal function, the use of other antihypertensive drugs and compliance with treatment as judged by tablet counts. Severe hypokalaemia (less than 3.0 mmol/l) was uncommon and showed no difference between the sexes.
|
No pos
|
No neg
|
Retriever1536
|
[The sensory components in the regulation of human respiration under functional loads].
A relative constancy of breathing was shown under conditions of different grades resistance to respiration in 11 healthy subjects even when experiencing a respiratory discomfort. The data suggests that the sensation is due to afferents from the proprioreceptors of respiratory muscles. It is corroborated by the constant level of initial respiratory activity at the moment of refusal from continuation of the test.
|
No pos
|
No neg
|
Retriever1537
|
Exploring elements of interprofessional collaboration between pharmacists and physicians in medication review.
In medication review involving community pharmacists and physicians, there is an underlying assumption that if community pharmacists provide evidence based pharmacotherapeutic recommendations, physicians, in turn, will implement these recommendations. However, although in general medication review has been shown to improve the quality of medicine use, medication management plans arising from the medication review process are not always implemented. There is a need for better understanding of the factors that influence outcomes in medication review. The current paper will address some cultural and procedural factors that may assist in understanding outcomes in medication review using research into collaboration from areas outside the healthcare as a framework.
|
No pos
|
No neg
|
Retriever1538
|
Distinct iron isotopic signatures and supply from marine sediment dissolution.
Oceanic iron inputs must be traced and quantified to learn how they affect primary productivity and climate. Chemical reduction of iron in continental margin sediments provides a substantial dissolved flux to the oceans, which is isotopically lighter than the crust, and so may be distinguished in seawater from other sources, such as wind-blown dust. However, heavy iron isotopes measured in seawater have recently led to the proposition of another source of dissolved iron from 'non-reductive' dissolution of continental margins. Here we present the first pore water iron isotope data from a passive-tectonic and semi-arid ocean margin (South Africa), which reveals a smaller and isotopically heavier flux of dissolved iron to seawater than active-tectonic and dysoxic continental margins. These data provide in situ evidence of non-reductive iron dissolution from a continental margin, and further show that geological and hydro-climatic factors may affect the amount and isotopic composition of iron entering the ocean.
|
No pos
|
No neg
|
Retriever1539
|
[Apoptosis in chronic gastritis: correlation of glandular apoptosis with antigastric autoantibodies].
In the course of time, chronic gastritis results in gastric atrophy. A typical example is type A-gastritis. Parietal cell antibodies lead to a loss of glands in the corpus mucosa. Atrophy is preceded by a preatrophic state (active type A-gastritis). Recently, gastric autoantibodies could also be detected in Helicobacter pylori induced type B-gastritis and could be specified as canalicular and luminal antibodies. The question of this study was whether apoptosis is responsible for the loss of gastric epithelium. Gastric biopsies from normal mucosa, type B-gastritis and active type A-gastritis were analysed for the presence of apoptosis using the TUNEL-method. Type B-gastritis was subdivided in cases without autoantibodies, with canalicular and luminal autoantibodies and with both types. In each case antrum- and corpus-mucosa was available and 200 cells of the foveolar as well as of the glands were counted. Normal mucosa showed only few apoptotic cells. The number of apoptosis was significantly elevated in all cases of type B-gastritis in the whole antrum and in the foveolar epithelium of the corpus. Active type A-gastritis revealed the highest number of apoptosis in the gastric glands of corpus mucosa. Subdividing type B-gastritis the most interesting result was the cases with canalicular antibodies had a similar high number of apoptosis in the corpus glands as active type A-gastritis. These cases were in this regard significantly different from cases of type B-gastritis without autoantibodies. The findings suggest that gastric atrophy might be the result of apoptosis in the gastric epithelium and that, possibly, different types of type B-gastritis lead to atrophy in different regions of the stomach.
|
No pos
|
No neg
|
Retriever1540
|
Combined PMD-PDL effects on BERs in simplified optical systems: an analytical approach.
A new analytical evaluation of polarization-induced error probability for optical systems consisting of both PMD and PDL is presented. Using a simplified model containing a lumped PMD-PDL fiber, an amplifier with ASE noise, an idealized optical filter, and an electrical filter with integrate-and-dump response, a closed-form of the probability density of the filtered current is obtained. This allows us to evaluate the BER affected by the PMD and PDL. Based on this, two polarization related effects, i.e., the PMD and PDL directional coupling and the polarization-induced intersymbol interference (ISI), are studied. We show that the PMD and PDL directional coupling can be strongest when the PMD vector perpendicularly correlates with both the PDL vector and the input signal polarization in the 3D Stokes space. Besides, its impact on bit-error-rate (BER) strongly depends on the PDL value. We also find that, for an optical system with realistic parameters, the impact of polarization-induced ISI on the BER is mostly caused by the two closest neighbors of the desired bit. Related with these two polarization effects is the PMD value fluctuation. Large PMD value variation can play an overwhelming role in impairing the optical performance.
|
No pos
|
No neg
|
Retriever1541
|
Serbia within the European context: An analysis of premature mortality.
BACKGROUND
Based on the global predictions majority of deaths will be collectively caused by cancer, cardiovascular diseases, and traffic accidents over the coming 25 years. In planning future national health policy actions, inter - regional assessments play an important role. The purpose of the study was to analyze similarities and differences in premature mortality between Serbia, EURO A, EURO B, and EURO C regions in 2000.
METHODS
Mortality and premature mortality patterns were analysed according to cause of death, by gender and seven age intervals. The study results are presented in relative (%) and absolute terms (age-specific and age-standardized death rates per 100,000 population, and age-standardized rates of years of life lost - YLL per 1,000). Direct standardization of rates was undertaken using the standard population of Europe. The inter-regional comparison was based on a calculation of differences in YLL structures and with a ratio of age-standardized YLL rates per 1,000. A multivariate generalized linear model was used to explore mortality of Serbia and Europe sub-regions with ln age-specific death rates. The dissimilarity was achieved with a p </= 0.05.
RESULTS
According to the mortality pattern, Serbia was similar to EURO B, but with a lower average YLL per death case. YLL patterns indicated similarities between Serbia and EURO A, while SRR YLL had similarities between Serbia and EURO B. Compared to all Europe sub-regions, Serbia had a major excess of premature mortality in neoplasms and diabetes mellitus. Serbia had lost more years of life than EURO A due to cardiovascular, genitourinary diseases, and intentional injuries. Yet, Serbia was not as burdened with communicable diseases and injuries as were EURO B and EURO C.
CONCLUSION
With a premature mortality pattern, Serbia is placed in the middle position of the Europe triangle. The main excess of YLL in Serbia was due to cardiovascular, malignant diseases, and diabetes mellitus. The results may be used for assessment of unacceptable social risks resulting from health inequalities. Within intentions to reduce an unfavourable premature mortality gap, it is necessary to reconsider certain local polices and practices as well as financial and human resources incorporated in the prevention of disease and injury burden.
|
No pos
|
No neg
|
Retriever1542
|
Maternal death surveillance and response in Tanzania: comprehensiveness of narrative summaries and action points from maternal death reviews.
BACKGROUND
Maternal deaths reviews are proposed as one strategy to address high maternal mortality in low and middle-income countries, including Tanzania. Review of maternal deaths relies on comprehensive documentation of medical records that can reveal the sequence of events leading to death. The World Health Organization's and the Tanzanian Maternal Death and Surveillance (MDSR) system propose the use of narrative summaries during maternal death reviews for discussing the case to categorize causes of death, identify gaps in care and recommend action plans to prevent deaths. Suggested action plans are recommended to be Specific, Measurable, Attainable, Relevant and Time bound (SMART). To identify gaps in documenting information and developing recommendations, comprehensiveness of written narrative summaries and action plans were assessed.
METHODS
A total of 76 facility maternal deaths that occurred in two regions in Southern Tanzania in 2018 were included for analysis. Using a prepared checklist from Tanzania 2015 MDSR guideline, we assessed comprehensiveness by presence or absence of items in four domains, each with several attributes. These were socio-demographic characteristics, antenatal care, referral information and events that occurred after admission. Less than 75% completeness of attributes in all domains was considered poor while 95% and above were good/comprehensive. Action plans were assessed by application of SMART criteria and according to the place of planned implementation (community, facility or higher level of health system).
RESULTS
Almost half of narrative summaries (49%) scored poor, and only1% scored good/comprehensive. Summaries missed key information such as demographic characteristics, time between diagnosis of complication and commencing treatment (65%), investigation results (47%), summary of case evolution (51%) and referral information (47%). A total of 285 action points were analysed. Most action points, 242(85%), recommended strategies to be implemented at health facilities and were mostly about service delivery, 120(42%). Only 42% (32/76) of the action points were deemed to be SMART.
CONCLUSIONS
Abstraction of information to prepare narrative summaries used in the MDSR system is inadequately done. Most recommendations were unspecific with a focus on improving quality of care in health facilities.
|
No pos
|
No neg
|
Retriever1543
|
Intravenous iron for critically ill children. Comparison of three dose regimens.
BACKGROUND
Anemia is extremely common among patients admitted to pediatric intensive care. Alternative treatments to transfusions such as intravenous iron must be considered. There are no published data for a prospective intravenous (IV) iron study focused in the critically ill children. The objective is to examine the safety and efficacy of intravenous iron sucrose infusion to manage anemia in pediatric critical care. A secondary objective is to examine the effect of different dose regimens of iron sucrose (3, 5, and 7 mg/kg dose).
PROCEDURE
Prospective investigation of intravenous iron sucrose utilization at a tertiary pediatric intensive care unit between October 2017 and November 2022.
RESULTS
In all 115 patients received a total of 616 infusions of IV iron. Transferrin saturation index (TSI) was the most common altered iron deficiency biomarker (91.8%). After IV iron treatment, hemoglobin showed a significant increase within a 30-day follow-up (9.2 vs. 11.6 g/dL, p < .001). There was also a significant improvement in TSI and serum iron (p < .001). Iron deficit replacement was higher in the 7 mg/kg dose group (94%) compared to 85.9% in the 5 mg/kg regimen and 77.5% in the lower dose group (p = .008), requiring less doses and a shorter time. Very few mild adverse reactions were reported (1.3% of infusions), with no differences between groups. The most frequent adverse effect was gastrointestinal in three cases. There were no anaphylaxis-like or other serious/life-threatening adverse effects.
CONCLUSIONS
This is the first study to evaluate intravenous iron therapy in pediatric critical care, providing preliminary evidence of safety and efficacy of IV iron sucrose. The 7 mg/kg dose regimen showed higher iron deficit replacement in a shorter time, which could be beneficial in critically ill children.
|
No pos
|
No neg
|
Retriever1544
|
Regional cerebral hypometabolism on 18F-FDG PET/CT scan in delirium is independent of acute illness and dementia.
INTRODUCTION
Delirium is associated with new onset dementia and accelerated cognitive decline; however, its pathophysiology remains unknown. Cerebral glucose metabolism previously seen in delirium may have been attributable to acute illness and/or dementia. We aimed to statistically map cerebral glucose metabolism attributable to delirium.
METHODS
We assessed cerebral glucose metabolism using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in sick, older patients with and without delirium, all without clinical dementia (N = 20). Strict exclusion criteria were adopted to minimize the effect of established confounders on FDG-PET.
RESULTS
Patients with delirium demonstrated hypometabolism in the bilateral thalami and right superior frontal, right posterior cingulate, right infero-lateral anterior temporal, and left superior parietal cortices. Regional hypometabolism correlated with delirium severity and performance on neuropsychological testing.
DISCUSSION
In patients with acute illness but without clinical dementia, delirium is accompanied by regional cerebral hypometabolism. While some hypometabolic regions may represent preclinical Alzheimer's disease (AD), thalamic hypometabolism is atypical of AD and consistent with the clinical features that are unique to delirium.
|
No pos
|
No neg
|
Retriever1545
|
D-lactic acidosis in neonatal ruminants.
Metabolic acidosis in calves with neonatal diarrhea was believed to be mainly caused by the loss of bicarbonate via the intestines or the formation of L-lactate during anaerobic glycolysis after tissue hypoperfusion in dehydrated calves. Because D-lactate was not considered to be of interest in human or veterinary medicine, routine diagnostic methods targeted the detection of L-lactate only. The development of stereospecific assays for the measurement of D-lactate facilitated research. This article summarizes the available information on D-lactic metabolic acidosis in neonatal ruminants.
|
No pos
|
No neg
|
Retriever1546
|
Dose errors in the near field of an HDR brachytherapy stepping source.
The dose rate at point P at 0.25 cm in water from the transverse bisector of a straight catheter with an active stepping source (Nucletron microSelectron HDR source) with a dwell length of 2 cm was calculated using Monte Carlo code MCNP 4.A. The source step sizes were 1 cm and 0.25 cm. The Monte Carlo (MC) results were used for comparison with the results calculated with the Nucletron brachytherapy planning system (BPS) formalism, first with BPS variants and then with its respective MC calculated radial dose function and anisotropy function. The dose differences at point P calculated using the BPS formalism and variants are +15.4% and +3.1% for the source step size of 1 cm and 0.25 cm respectively. This reduction in dose difference is caused by the increased importance of errors in the anisotropy function with the smaller step size, which counter the errors in the radial dose function. Using the MC calculated radial dose function and anisotropy function with the BPS formalism. 1% dose calculation accuracy can be achieved, even in the near field, with negligible extra demand on computation time.
|
No pos
|
No neg
|
Retriever1547
|
International Microsurgery Club: An Effective Online Collaboration System.
BACKGROUND
This study aimed to determine if International Microsurgery Club (IMC) is an effective online resource for microsurgeons worldwide, in providing an avenue for timely group discussions and advice regarding complicated cases, and an avenue for collaboration and information sharing.
METHODS
All posts on the IMC Facebook group from member 1 to 8,000 were analyzed according to inclusion criteria and categorized into three categories-case discussion, question, and information sharing. Posts were retrospectively analyzed for number of responses, time of responses, number of "likes," number of treatment options, time of day, and demographics of authors and responders.
RESULTS
A retrospective analysis of 531 cases showed an average response rate of 75.7% within 1 hour and as membership grew. The response rate stabilized averaging between 72.5 and 78% across all times of the day. An average of 11.8 microsurgeons was involved per case discussion, and 5.7 treatment options were provided per case.
CONCLUSION
IMC is shown to be an effective resource to allow microsurgeons to access timely advice from other microsurgeons without time and distance limitation, and to have interactive group discussions on complicated cases.
|
No pos
|
No neg
|
Retriever1548
|
Effect of once-daily fluticasone furoate/vilanterol versus vilanterol alone on bone mineral density in patients with COPD: a randomized, controlled trial.
BACKGROUND
The relationship between inhaled corticosteroids and bone mineral density (BMD) remains uncertain despite extensive research.
METHODS
This was an international, multicenter, randomized, double-blind, parallel-group, 3-year noninferiority study. Patients with chronic obstructive pulmonary disease (COPD) (⩾40 years of age; smoking history ⩾10 pack years) and at least one native hip evaluable for BMD were enrolled and randomized 1:1, stratified by sex, to treatment with vilanterol (VI) 25 µg or fluticasone furoate/vilanterol (FF/VI) 100 µg/25 µg. BMD measurements were taken via dual-energy X-ray absorptiometry every 6 months. The primary endpoint was assessment of the noninferiority of change from baseline in total hip BMD per year at the -1% noninferiority level. Change from baseline in BMD at the lumbar spine and BMD measurements by sex were secondary endpoints. Incidences of COPD exacerbations and bone fractures throughout the study were also recorded.
RESULTS
Of 283 randomized patients, 170 (60%) completed the study. Noninferiority was demonstrated for FF/VI versus VI with regards to change from baseline in total hip BMD per year, with changes of -0.27% and 0.18%, respectively, and a treatment difference of -0.46% per year [95% confidence interval (CI) -0.97 to 0.06]. The treatment difference for FF/VI versus VI regarding lumbar spine BMD was -0.51% per year (95% CI -1.11 to 0.10). COPD exacerbations and bone fracture rates were similar between treatment groups.
CONCLUSION
FF/VI showed noninferiority to VI for change from baseline in total hip BMD per year, when assessed at the -1% noninferiority margin in a combined sample of men and women with COPD.The reviews of this paper are available via the supplemental material section.
|
No pos
|
No neg
|
Retriever1549
|
The Glucan-Remodeling Enzyme Phr1p and the Chitin Synthase Chs1p Cooperate to Maintain Proper Nuclear Segregation and Cell Integrity in Candida albicans.
GH72 family of β-(1,3)-glucanosyltransferases is unique to fungi and is required for cell wall biogenesis, morphogenesis, virulence, and in some species is essential for life. Candida albicans PHR1 and PHR2 are pH-regulated genes that encode GH72 enzymes highly similar to Gas1p of Saccharomyces cerevisiae. PHR1 is expressed at pH ≥ 5.5 while PHR2 is transcribed at pH ≤ 5.5. Both are essential for C. albicans morphogenesis and virulence. During growth at neutral-alkaline pH, Phr1p-GFP preferentially localizes to sites of active cell wall formation as the incipient bud, the mother-daughter neck, the bud periphery, and concentrates in the septum at cytokinesis. We further investigated this latter localization. In chs3Δ cells, lacking the chitin of the chitin ring and lateral cell wall, Phr1p-GFP still concentrated along the thin line of the primary septum formed by chitin deposited by chitin synthase I (whose catalytic subunit is Chs1p) suggesting that it plays a role during formation of the secondary septa. RO-09-3143, a highly specific inhibitor of Chs1p activity, inhibits septum formation and blocks cell division. However, alternative septa are produced and are crucial for cell survival. Phr1p-GFP is excluded from such aberrant septa. Finally, we determined the effects of RO-09-3143 in cells lacking Phr1p. PHR1 null mutant was more susceptible to the drug than the wild type. The phr1Δ cells were larger, devoid of septa, and underwent endomitosis and cell death. Phr1p and Chs1p cooperate in maintaining cell integrity and in coupling morphogenesis with nuclear division in C. albicans.
|
No pos
|
No neg
|
Retriever1550
|
Biodegradable hybrid biopolymer film based on carboxy methyl cellulose and selenium nanoparticles with antifungal properties to enhance grapes shelf life.
In the current study, cellulose was extracted from sugarcane bagasse and further converted into carboxy methyl cellulose. The morphological, chemical, and structural characterization of synthesizeed carboxy methyl cellulose was performed. Further, the biopolymer was fabricated with mycogenic selenium nanoparticles and used to develop the biofilms. The developed biofilms were examined for the fruit shelf life stability, antifungal activity, and biodegradation potential. The results revealed that grapefruits wrapped with biofilms showed enhanced shelf life of fruit at all storage time intervals. The study also witnesses the antifungal activity of biofilms with a remarkable inhibitory action on the spores of Fusarium and Sclerospora graminicola phytopathogens. Lastly, the biofilms were significantly degradable in the soil within two weeks of incubation. Thus, the developed biofilms exhibit multifaceted properties that can be used as an alternative to synthetic plastics for fruit packaging and also helps in protecting against fungal contaminants during storage with naturally degradable potential.
|
No pos
|
No neg
|
Retriever1551
|
Crystal structure and Hirshfeld surface analysis of (Z)-6-[(2-hy-droxy-4-methyl-anilino)-methyl-idene]-4-methyl-cyclo-hexa-2,4-dien-1-one.
The title compound, C15H15NO2, is a Schiff base that exists in the keto-enamine tautomeric form and adopts a Z configuration. The mol-ecule is almost planar, with the two phenyl rings twisted relative to each other by 9.60 (18)°. There is an intra-molecular N-H⋯O hydrogen bond present forming an S(6) ring motif. In the crystal, pairs of O-H⋯O hydrogen bonds link adjacent mol-ecules into inversion dimers with an R 2 2(18) ring motif. The dimers are linked by very weak π-π inter-actions, forming layers parallel to (01). Hirshfeld surface analysis, two-dimensional fingerprint plots and the mol-ecular electrostatic potential surfaces were used to analyse the inter-molecular inter-actions, indicating that the most important contributions for the crystal packing are from H⋯H (55.2%), C⋯H/H⋯C (22.3%) and O⋯H/H⋯O (13.6%) inter-actions.
|
No pos
|
No neg
|
Retriever1552
|
[Stem cells and therapeutic cloning, medical perspectives under discussion].
Innovative biotechnical progress over the past few years regards stem cells and therapeutic cloning, which open promising medical horizons for many presently incurable diseases. THE CURRENT DEBATE: The research work in France has been stalled because of the prohibitions listed in the so-called "bioethical" laws of 1994. The ongoing revision of these laws is based on a certain number of ethical questions and launches a disputable parlementary debate. Other than reproductive cloning and research on the embryo, the possibilities provided by stem cells and therapeutic cloning should be emphasized and the different positions advanced specified, showing an evolution in the laws in France. ABUSIVE LEGISLATIVE PROHIBITIONS: The proposed law, which maintains the prohibition for research on the embryo, with a 5-Year dispensation, and which explicitly prohibits therapeutic cloning, is not in keeping with the widening of in this field expected by research teams. Many scientists and physicians, supported by patients' associations, are aware of the importance of therapeutic progress attached to such research. They should not be stalled in their studies by the prohibitions maintained in the new law.
|
No pos
|
No neg
|
Retriever1553
|
New Multiresponsive Chromic Soft Materials: Dynamic Interconversion of Short 2,7-Dicyanomethylenecarbazole-Based Biradicaloid and the Corresponding Cyclophane Tetramer.
This work reports on a quinodimethane-type molecule, 2,7-dicyanomethylene-9-(2-ethylhexyl)carbazole (1), one of the shortest π-conjugated biradicaloids reported to be stable in solution under ambient conditions. This carbazole-based quinoidal precursor is able to form a macrocyclic σ-bonded tetramer (2). The resolved single-crystal X-ray structure of tetramer 2 shows that four molecules of 1 are linked together through four long (CN)2 C-C(CN)2 bonds (1.631 Å) resulting from coupling of the unpaired electrons in biradicaloid 1. Dynamic interconversion between monomer 1 and cyclophane tetramer 2 is achieved by reversible cleavage and recovery of the four (CN)2 C-C(CN)2 bonds upon soft external stimuli (light absorption, temperature and pressure), which is accompanied by significant color changes. These novel photo-, thermo-, and mechanochromic properties expand the versatility of π-conjugated biradicaloid compounds as novel functional materials that, in combination with spin chemistry and dynamic covalent chemistry, can be relevant in molecular machines, sensors, and switches.
|
No pos
|
No neg
|
Retriever1554
|
Stability of risk factors for cardiovascular diseases in Portuguese children and adolescents from the Porto area.
An important aspect of preventive medicine is to identify subjects at risk as soon as possible, so preventive strategies can be introduced at early ages. The justification for this strategy is twofold: firstly, the assumption that children maintain a particular high value of a risk factor for disease throughout life; and secondly, the assumption that lowering the level of the risk factor in early life will have a greater impact on the disease than will risk factor changes in later life. In epidemiology the analysis of such factors over time is referred to as tracking. Tracking analysis has been applied to risk factors for cardiovascular diseases (CVD) in pediatric years. The aims of this study were: I) to analyze the stability of biological risk factors [high blood pressure (BP), high percentage of fat mass (%FM) and high total cholesterol (TC)] and lifestyle risk factors [low physical activity index (PAI)] in isolation; and II) to analyze the stability of zero, one, two or three biological risk factors. There were two evaluations in 692 children and adolescents (325 boys and 367 girls), aged between 8 and 15 years. The quartiles, adjusted for age and gender, were the criterion used to identify subjects with biological risk factors (fourth quartile) and with lifestyle risk factors (first quartile) for CVD. The stability was calculated through the relative frequency of subjects who maintained or changed quartile between the two evaluations. There is stability for biological risk factors as well as for behavioral and/or lifestyle risk factors. However, the highest stability is seen in biological risk factors.
|
No pos
|
No neg
|
Retriever1555
|
Suicide on the Isle of Wight: A Case-study of 35 Suicides among Mental Health Service Users Between 2006 and 2008.
AIMS
To identify the sociodemographic, clinical and service delivery risk factors for suicide in psychiatric patients in a limited geographic area.
METHOD
A retrospective case study of 35 patients who died as a result of suicide between January 2006 and December 2008.
RESULTS
Male gender, unemployment, living alone, basic education and significant life events were identified as sociodemographic factors. A history of previous psychiatric admission, previous suicide attempt, suffering from depression, co-morbidity of another psychiatric disorder (mainly stress-related symptoms and alcoholism), and contacting the services prior to suicide were found as typical clinical factors. Hanging was the most common method of suicide in both men and women. Most men died in spring and summer, while the majority of females died in autumn.
CLINICAL IMPLICATIONS
As in similar studies, mental disorders could be identified as the strongest risk factor for suicide. Almost 70% of suicides were conducted by people suffering from a mental disorder. Treating mental disorders and identifying certain sociodemographic and clinical characteristics of people suffering from mental disorders and addressing them is the key in suicide prevention strategies.
|
No pos
|
No neg
|
Retriever1556
|
Role of cytokine in malignant T-cell metabolism and subsequent alternation in T-cell tumor microenvironment.
T cells are an important component of adaptive immunity and T-cell-derived lymphomas are very complex due to many functional sub-types and functional elasticity of T-cells. As with other tumors, tissues specific factors are crucial in the development of T-cell lymphomas. In addition to neoplastic cells, T- cell lymphomas consist of a tumor micro-environment composed of normal cells and stroma. Numerous studies established the qualitative and quantitative differences between the tumor microenvironment and normal cell surroundings. Interaction between the various component of the tumor microenvironment is crucial since tumor cells can change the microenvironment and vice versa. In normal T-cell development, T-cells must respond to various stimulants deferentially and during these courses of adaptation. T-cells undergo various metabolic alterations. From the stage of quiescence to attention of fully active form T-cells undergoes various stage in terms of metabolic activity. Predominantly quiescent T-cells have ATP-generating metabolism while during the proliferative stage, their metabolism tilted towards the growth-promoting pathways. In addition to this, a functionally different subset of T-cells requires to activate the different metabolic pathways, and consequently, this regulation of the metabolic pathway control activation and function of T-cells. So, it is obvious that dynamic, and well-regulated metabolic pathways are important for the normal functioning of T-cells and their interaction with the microenvironment. There are various cell signaling mechanisms of metabolism are involved in this regulation and more and more studies have suggested the involvement of additional signaling in the development of the overall metabolic phenotype of T cells. These important signaling mediators include cytokines and hormones. The impact and role of these mediators especially the cytokines on the interplay between T-cell metabolism and the interaction of T-cells with their micro-environments in the context of T-cells lymphomas are discussed in this review article.
|
No pos
|
No neg
|
Retriever1557
|
FDG-PET in Follicular Lymphoma Management.
18-Fluoro-deoxyglucose positron emission tomography/computerised tomography (FDG PET/CT) is commonly used in the management of patients with lymphomas and is recommended for both initial staging and response assessment after treatment in patients with diffuse large B-cell lymphoma and Hodgkin lymphoma. Despite the FDG avidity of follicular lymphoma (FL), FDG PET/CT is not yet applied in standard clinical practice for patients with FL. However, FDG PET/CT is more accurate than conventional imaging for initial staging, often prompting significant management change, and allows noninvasive characterization to guide assessment of high-grade transformation. For restaging, FDG PET/CT assists in distinguishing between scar tissue and viable tumors in residual masses and a positive PET after induction treatment would seem to predict a shorter progression-free survival.
|
No pos
|
No neg
|
Retriever1558
|
Temozolomide treatment of pituitary carcinomas and atypical adenomas: systematic review of case reports.
BACKGROUND
Pituitary carcinomas (PC) and atypical pituitary adenomas (APA) are rare variants of pituitary tumors for which no evidence-based treatment currently exists. We sought to determine whether temozolomide represents an effective chemotherapeutic option for patients with PC and APA.
METHODS
A systematic review was performed using all published cases of PC and APA treated with temozolomide, and for which information on treatment regimen, clinical response, and survival could be identified. The primary goal of this analysis was to describe overall survival and progression-free survival among PC and APA patients after temozolomide treatment. Secondary goals included assessment of response rate and biomarkers of response.
RESULTS
We identified 57 cases and obtained follow-up data on 54 patients (31 APA and 23 PC) for analysis. Estimates of 5-year progression-free survival and overall survival were 21.9% and 57.4% for patients with APA and 36.1% and 56.2% for patients with PC. Among those who responded to temozolomide, overall survival was marginally statistically significantly greater for patients on long-term temozolomide therapy compared with those who were not (5-year overall survival 91.7% vs 54.1%, P = .08); Progression-free survival results were similar but not statistically significant. The objective response rate was 48.4% for patients with APA and 65.2% for patients with PC. Stable disease occurred in 29% of APA and 17.4% of PC patients. Neither histology nor expression of Ki-67 correlated with response; however, negative O6-methylguanine-DNA methyltransferase staining was strongly related to response to temozolomide in patients with APA (P < .001).
CONCLUSIONS
Temozolomide is an effective treatment of both PC and APA, and long-term treatment can be considered for particularly aggressive cases.
|
No pos
|
No neg
|
Retriever1559
|
Network motifs modulate druggability of cellular targets.
Druggability refers to the capacity of a cellular target to be modulated by a small-molecule drug. To date, druggability is mainly studied by focusing on direct binding interactions between a drug and its target. However, druggability is impacted by cellular networks connected to a drug target. Here, we use computational approaches to reveal basic principles of network motifs that modulate druggability. Through quantitative analysis, we find that inhibiting self-positive feedback loop is a more robust and effective treatment strategy than inhibiting other regulations, and adding direct regulations to a drug-target generally reduces its druggability. The findings are explained through analytical solution of the motifs. Furthermore, we find that a consensus topology of highly druggable motifs consists of a negative feedback loop without any positive feedback loops, and consensus motifs with low druggability have multiple positive direct regulations and positive feedback loops. Based on the discovered principles, we predict potential genetic targets in Escherichia coli that have either high or low druggability based on their network context. Our work establishes the foundation toward identifying and predicting druggable targets based on their network topology.
|
No pos
|
No neg
|
Retriever1560
|
Fascial Tc-99m MDP uptake in eosinophilic fasciitis as demonstrated by SPECT.
BACKGROUND
The presence of bone-seeking radiopharmaceutical uptake in extraskeletal tissues of the lower or upper extremities may indirectly reflect the presence of active inflammatory lesions in patients in whom systemic disease is suspected.
MATERIALS AND METHODS
The authors present the case of a 26-year-old woman who had mixed signs of scleroderma and cosinophilic fasciitis, in whom misleading findings on planar bone scintigraphy suggested diffuse muscular tracer uptake in the lower extremities.
RESULTS
However, using additional SPECT imaging of the pelvis and thighs, it was shown that the soft tissue radioactivity was clearly restricted to the fascia overlying the muscles. The fascial localization of the inflammation was confirmed by biopsy.
CONCLUSION
SPECT imaging was proven useful in indicating the exact localization of an active inflammatory process in the muscle fascia.
|
No pos
|
No neg
|
Retriever1561
|
Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats.
The study investigated the mechanism by which glycine protects against increased circulating nonesterified fatty acids (NEFA), fat cell size, intra-abdominal fat accumulation, and blood pressure (BP) induced in male Wistar rats by sucrose ingestion. The addition of 1% glycine to the drinking water containing 30% sucrose, for 4 wk, markedly reduced high BP in sucrose-fed rats (SFR) (122.3 +/- 5.6 vs. 147.6 +/- 5.4 mmHg in SFR without glycine, P < 0.001). Decreases in plasma triglyceride (TG) levels (0.9 +/- 0.3 vs. 1.4 +/- 0.3 mM, P < 0.001), intra-abdominal fat (6.8 +/- 2.16 vs. 14.8 +/- 4.0 g, P < 0.01), and adipose cell size were observed in SFR treated with glycine compared with SFR without treatment. Total NEFA concentration in the plasma of SFR was significantly decreased by glycine intake (0.64 +/- 0.08 vs. 1.11 +/- 0.09 mM in SFR without glycine, P < 0.001). In control animals, glycine decreased glucose, TGs, and total NEFA but without reaching significance. In SFR treated with glycine, mitochondrial respiration, as an indicator of the rate of fat oxidation, showed an increase in the state IV oxidation rate of the beta-oxidation substrates octanoic acid and palmitoyl carnitine. This suggests an enhancement of hepatic fatty acid metabolism, i.e., in their transport, activation, or beta-oxidation. These findings imply that the protection by glycine against elevated BP might be attributed to its effect in increasing fatty acid oxidation, reducing intra-abdominal fat accumulation and circulating NEFA, which have been proposed as links between obesity and hypertension.
|
No pos
|
No neg
|
Retriever1562
|
Involvement of heme in the degradation of iron-regulatory protein 2.
Iron-regulatory proteins (IRPs) recognize and bind to specific RNA structures called iron-responsive elements. Mediation of these binding interactions by iron and iron-containing compounds regulates several post-transcriptional events relevant to iron metabolism. There are two known IRPs, IRP1 and IRP2, both of which can respond to iron fluxes in the cell. There is ample evidence that IRP1 is converted by iron to cytoplasmic aconitase in vivo. It has also been shown that, under certain conditions, a significant fraction of IRP1 is degraded in cells exposed to iron or heme. Studies have shown that the degradation of IRP1 that is induced by iron can be inhibited by either desferrioxamine mesylate (an iron chelator) or succinyl acetone (an inhibitor of heme synthesis), whereas the degradation induced by heme cannot. This suggests that heme rather than iron is responsible for this degradation. Several laboratories have shown that IRP2 is also degraded in cells treated with iron salts. We now show evidence suggesting that this IRP2 degradation may be mediated by heme. Thus, in experiments analogous to those used previously to study IRP1, we find that IRP2 is degraded in rabbit fibroblast cells exposed to heme or iron salts. However, as shown earlier with IRP1, both desferrioxamine mesylate and succinyl acetone will inhibit the degradation of IRP2 induced by iron but not that induced by heme.
|
No pos
|
No neg
|
Retriever1563
|
[Pathological anatomy of the heart in myopathies and infantile muscular atrophies].
In progressive muscular dystrophy, the heart is always affected and presents characteristic histological lesions: irregular, diffuse and intense rearrangements predominantly in the left ventricle, the septum and conductive tissue, consisting of wide, poorly vascularized fibrous bands, that are destructive but without an inflammatory aspect. The remaining myocardium is dystrophic with degeneration of the fibers (hyalin, atrophic or hypertrophic) with irregular nuclei. Plaques of adipose tissue are found under the epicardium within the heart wall. Sometimes, a fibrous thickening of the intracoronary arteries is observed without modification of the intima, but vascular lesions are not systematically seen. In congenital muscular dystrophy, cardiomyopathy certainly exists, but there is no histological description. Half of the patients suffering from myopathy with intracytoplasmic inclusions also have dystrophic and fibrotic cardiac involvement. Congenital myopathies may have their own specific cardiomyopathy, as in central core myopathy, nemaline (rod) myopathy and especially myotubular myopathy, where involvement is common. Werdnig-Hoffmann disease types I and II do not affect the heart. In contrast, several cases of fibrotic lesions have been described in KugelbergWelander disease.
|
No pos
|
No neg
|
Retriever1564
|
Flow cytometric analysis of within-strain variation in polysaccharide expression by Bacteroides fragilis by use of murine monoclonal antibodies.
The reactivity of four different monoclonal antibodies (MAbs) with populations of Bacteroides fragilis NCTC 9343, enriched by density gradient centrifugation for a large capsule, small capsule and electron-dense layer (EDL) only visible by electronmicroscopy, was examined. The MAbs reacted strongly with polysaccharides present in both the large capsule- and EDL-enriched populations but not in the small capsule-enriched populations. The pattern of labelling was determined by immunoblotting, immunofluorescence and immuno-electronmicroscopy, and flow cytometry. The MAbs labelled cell membrane-associated epitopes in the large capsule- and EDL-enriched populations and cell-free material in the EDL population. By immunoblotting, ladders of repeating polysaccharide subunits were evident in the EDL population but not in the large capsule population. The proportion of cells labelled within each population was determined by flow cytometry. The reactivity of another MAb with the small capsule population was confirmed by flow cytometry. A qualitative indication of epitope expression was obtained by examination of the flow cytometric profiles. Differential expression of the same saccharide epitope was observed both between and within structurally distinct B. fragilis populations. The MAbs were species-specific and cross-reacted with several recent clinical isolates. These polysaccharides may be relevant to the virulence of B. fragilis.
|
No pos
|
No neg
|
Retriever1565
|
Personal values and meaning in the use of methamphetamine among HIV-positive men who have sex with men.
Our aim with this qualitative study was to understand the role of personal values, meaning, and impact of drug use among HIV-positive men who have sex with men (MSM) who struggle with methamphetamine use. Participants were 22 MSM recruited from an ethnically diverse county in the San Francisco Bay area of California. Grounded theory was used to analyze the data collected in individual interviews. Emergent constructs of context, meaning, and perceived impact were identified and are described in a theoretical narrative format. The importance of broadening our understanding of HIV and methamphetamine addiction and their interaction is highlighted. This study contributes to the understanding of the complexity of methamphetamine use within the specific population of MSM living with HIV/ AIDS, and suggests possible directions for addressing important maintaining factors like adaptive use and enhancing factors that could contribute to an individual's ability to make better choices based on meaning and personal values.
|
No pos
|
No neg
|
Retriever1566
|
Oncogenic KRAS signaling drives evasion of innate immune surveillance in lung adenocarcinoma by activating CD47.
KRAS is one of the most frequently activated oncogenes in human cancers. While the role of KRAS mutation in tumorigenesis and tumor maintenance has been extensively studied, the relationship between KRAS and the tumor immune microenvironment is not fully understood. Herein, we identified a novel role of KRAS in driving tumor evasion from innate immune surveillance. In lung adenocarcinoma patient samples and Kras-driven genetic mouse models of lung cancer, mutant KRAS activated the expression of cluster of differentiation 47 (CD47), an antiphagocytic signal in cancer cells, leading to decreased phagocytosis of cancer cells by macrophages. Mechanistically, mutant KRAS activated PI3K-STAT3 signaling, which restrained miR-34a expression and relieved the post-transcriptional repression of miR-34a on CD47. In three independent lung cancer patient cohorts, KRAS mutation status positively correlated with CD47 expression. Therapeutically, disruption of the KRAS-CD47 signaling axis with KRAS siRNA, the KRASG12C inhibitor AMG 510 or miR-34a mimic suppressed CD47 expression, enhanced the phagocytic capacity of macrophages and restored innate immune surveillance. Our results revealed a direct mechanistic link between active KRAS and innate immune evasion and identified CD47 as a major effector underlying KRAS-mediated immunosuppressive tumor microenvironment.
|
No pos
|
No neg
|
Retriever1567
|
Differential expression of crown gall tumor markers in transformants obtained after in vitro Agrobacterium tumefaciens-induced transformation of cell wall regenerating protoplasts derived from Nicotiana tabacum.
To obtain transformation of plant cells, we incubated 3-day-old cell wall-regenerating protoplasts from tobacco with Agrobacterium tumefaciens harboring tumor-inducing plasmids. Putative transformed tobacco cells were selected by phytohormone autotrophic growth and were shown to be transformed by the detection of the tumor cell specific enzymes lysopine dehydrogenase or nopaline dehydrogenase. This was substantiated by the detection, in transformed tumor tissues, of DNA sequences homologous to sequences in the tumor-inducing plasmid. Segregation of tumor markers has been observed among the transformants and it is suggested that this happened during the initiation of the transformation. The stable character of the transformed state was shown by the retention of tumor markers in subcloning of primary transformants under nonselective conditions. Suppression of the neoplastic state of transformants could take place, resulting in the development of transformed shoots. Indications were obtained for the inheritance of tumor markers through meiosis from seedlings obtained from seeds of flowering transformed plants that still expressed nopaline synthesis.
|
No pos
|
No neg
|
Retriever1568
|
Effects of denervation on the glomus cell membrane.
Trophic influences of the carotid nerve (CN) on carotid body (CB) glomus cells were studied by comparing the membrane potential (Em), input resistance (Ro) and voltage noise (Erms) of normal and 3-31-day denervated cells had more negative Ems. Higher Ros were recorded at 3 and 6 days. Erms sharply increased at 3 days, returned to normal at 6-15 days and was below normal at 31 days. A transmitter (ACh) and NaCN, producing histotoxic anoxia, were used for stimulation. These substances either depolarized or hyperpolarized innervated cells and increased or decreased voltage noise. Denervation selectively changed these patterns but only for a short time. ACh preferentially depolarized the cells, only at 3 days, whereas its effects on noise did not change. The Em responses to NaCN remained unaltered although at 3-6 days noise increases were smaller and depressions exaggerated. Possible reasons for these effects are discussed.
|
No pos
|
No neg
|
Retriever1569
|
Autonomic regulation in response to stress: The influence of anticipatory emotion regulation strategies and trait rumination.
According to the neurocognitive framework for regulation expectation, adaptively regulating emotions in anticipation of a stressful event should help individuals deal with the stressor itself. The goal of this study was twofold: first, the authors compared the influence of adaptive versus maladaptive anticipatory emotion regulation (ER) on the autonomic system during anticipation of, confrontation with, and recovery from a stressor; second, they explored whether trait rumination moderated this relationship. The authors collected data from 56 healthy female undergraduates during a public speaking task. The task involved 4 phases: baseline, anticipatory ER, stressor, and recovery. Participants were assigned to 1 of 2 anticipatory ER instructions (reappraisal or catastrophizing). Heart rate variability (HRV) indexed autonomic regulation. Results confirmed that HRV was higher in the reappraisal than in the catastrophizing group (over all time points, except for baseline). Trait rumination levels moderated the effect of anticipatory ER strategy on HRV during the stressor phase. Specifically, whereas for low ruminators reappraisal (versus catastrophizing) in the anticipation phase led to higher HRV when confronted to the stressor, high ruminators demonstrated lower HRV in that same condition. To conclude, over all participants, using reappraisal during the anticipation phase allowed participants to better cope with stress. However, only low, but not high ruminators could profit from the beneficial effect of anticipatory reappraisal on autonomic regulation. Even though further research is needed, this study suggests that, in female undergraduates, the tendency to ruminate is associated with abnormal anticipatory ER that might hinder an adaptive response to a stressor. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
|
No pos
|
No neg
|
Retriever1570
|
Blindness as a complication of Le Fort osteotomies: role of atypical fracture patterns and distortion of the optic canal.
Blindness in patients suffering maxillofacial trauma is usually caused by optic nerve or optic canal injuries. It is, however, an uncommon complication of facial trauma, with a reported incidence of only 3 to 5 percent. This incidence drops dramatically when fractures are performed in the controlled situation of orthognathic surgery. Given the rarity of ophthalmic complications after traumatic Le Fort I injuries, it is not surprising that few cases have been reported after orthognathic surgery. In this article, three cases of visual loss or skull base injury after elective Le Fort I osteotomy are described. All of these cases were presumably straightforward surgically and were performed by experienced surgeons. The literature is reviewed and the pathomechanics of each injury are experimentally explored in a cadaver model. To determine the presence of increased pressure on the optic nerve, optic canal deformation, or fractures extending to the skull base, two separate experiments were devised. In the first experiment, a pressure transduction system was used to document any significant forces that may be directly transmitted to the contents of the optic canal during pterygomaxillary separation. Then tested was the hypothesis that a stepped or tapered osteotomy will allow for a more predictable pterygomaxillary fracture. One of five cadaver specimens in group 1 demonstrated a transient increase in the right optic canal pressure during down-fracture of the maxilla. This change was less than 10 mmHg, and its duration was less than 5 seconds. The canal pressure returned to baseline with the completion of the fracture. In group 2, there was no documented pressure change with either osteotomy technique. Of note, in group 2, all specimens undergoing standard Le Fort osteotomy demonstrated uncontrolled propagation of the fracture lines superiorly in the pterygoid bones. The uncontrolled and unpredictable nature of pterygomaxillary disjunction may result in the extension of fractures to the skull base or the generation of deforming forces to the optic canal may compress or injure the optic nerve and its circulation. It is proposed that a stepped or tapered osteotomy will generate a more controlled pterygomaxillary separation during orthognathic surgery and may reduce the risk of devastating ophthalmologic complications.
|
No pos
|
No neg
|
Retriever1571
|
Rp diastereomeric analogs of cAMP inhibit both cAMP- and cGMP-induced dilation of hamster mesenteric small arteries.
Cross talk between the adenosine (3',5'-cyclic monophosphate) (cAMP) and the guanosine (3',5'-cyclic monophosphate) (cGMP) signalling pathways in vascular smooth muscle may occur such that cAMP may act through cGMP-dependent protein kinase rather than cAMP-dependent protein kinase to induce relaxation of this tissue. Therefore, it was hypothesized that due to this crosstalk, competitive antagonists of cAMP may not show much selectivity in inhibition of cAMP- or cGMP-induced vasodilation. To test this hypothesis, the effects of Rp-diastereomeric phosphorothioate derivatives of cAMP, putative competitive antagonists of cAMP at cAMP-dependent protein kinase, were assessed on vasodilation induced by Sp-phosphorothioate derivatives of cAMP, dibutyryl cAMP, 8-Br cGMP and sodium nitroprusside. Hamster mesenteric arteries (200-400 microns i.d.) were cannulated and pressurized to 75 mm Hg and constricted to approximately 50% of maximum with 1 mumol/l phenylephrine. Vasodilators were then added in cumulative fashion and diameter responses recorded in the absence and presence of (Rp)-adenosine (3',5'-cyclic monophosphorothioate) (Rp cAMPs) or (Rp)-8-(parachlorophenylthio) adenosine (3',5'-cyclic monophosphorothioate) (Rp 8CPT cAMPs). Rp cAMPs (0.1-0.5 mmol/l) inhibited dilations induced by the cAMP agonists, (Sp)-adenosine (3',5'-cyclic monophosphorothioate) (Sp cAMPs) and dibutyryl cAMP, but also inhibited dilations induced by 8-Br cGMP and sodium nitroprusside (p < 0.05 and n > 4 for all). In a more detailed study we found that Rp 8CPT cAMPs against Sp 8CPT cAMPs (3.6 +/- 1.2) was similar to the pA2 for Rp 8CPT cAMPs against 8-Br cGMP (4.1 +/- 1.2) (p > 0.05, d.f. = 37). These data support the hypothesis that both cAMP and cGMP act through a common protein kinase to cause vasodilation and urge caution in the use of Rp-diastereomeric analogs of cyclic nucleotides to dissect out specific signal transduction pathways in blood vessels.
|
No pos
|
No neg
|
Retriever1572
|
Cytokine-induced increases in endothelial permeability occur after adhesion molecule expression.
BACKGROUND
Transmigration of neutrophils (PMNs) through endothelial cell tight junctions is a critical stage in the tissue injury of ischemia-reperfusion (I/R). Although cytokines are released in I/R, it is unclear whether cytokines directly increase permeability or this phenomenon requires both expression of cell adhesion molecules and PMN adhesion-activation.
METHODS
We exposed confluent monolayers of human umbilical vein endothelial cells to physiologic concentrations of interleukin-1 (10 pg/ml) and tumor necrosis factor-alpha (10 pg/ml) in the absence of PMNs. Tight junction permeability was quantified with both transendothelial electrical resistance and albumin flux, whereas expression of endothelial-leukocyte adhesion molecule-1 was measured by flow cytometry (t test p < 0.05).
RESULTS
Stimulation with tumor necrosis factor-alpha or interleukin-1 produced maximal transendothelial electrical resistance decreases at 12 hours with return to baseline at 24 hours. Increases in albumin flux began at 6 hours, with maximum effects at 24 hours. These changes occurred soon after maximal expression of endothelial-leukocyte adhesion molecule-1 at 4 hours.
CONCLUSIONS
Cytokines induced increases in both cell adhesion molecule expression and endothelial permeability. This sequence of events is consistent with direct cytokine effects on cytoarchitecture, because it occurred without the adhesion-activation of PMNs.
|
No pos
|
No neg
|
Retriever1573
|
A Multicenter Study on Long-Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death.
The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one-to-one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long-term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool.
|
No pos
|
No neg
|
Retriever1574
|
Vertebrate proteins related to Drosophila Naked Cuticle bind Dishevelled and antagonize Wnt signaling.
Wnt signals control cell fate decisions and orchestrate cell behavior in metazoan animals. In the fruit fly Drosophila, embryos defective in signaling mediated by the Wnt protein Wingless (Wg) exhibit severe segmentation defects. The Drosophila segment polarity gene naked cuticle (nkd) encodes an EF hand protein that regulates early Wg activity by acting as an inducible antagonist. Nkd antagonizes Wg via a direct interaction with the Wnt signaling component Dishevelled (Dsh). Here we describe two mouse and human proteins, Nkd1 and Nkd2, related to fly Nkd. The most conserved region among the fly and vertebrate proteins, the EFX domain, includes the putative EF hand and flanking sequences. EFX corresponds to a minimal domain required for fly or vertebrate Nkd to interact with the basic/PDZ domains of fly Dsh or vertebrate Dvl proteins in the yeast two-hybrid assay. During mouse development, nkd1 and nkd2 are expressed in multiple tissues in partially overlapping, gradient-like patterns, some of which correlate with known patterns of Wnt activity. Mouse Nkd1 can block Wnt1-mediated, but not beta-catenin-mediated, activation of a Wnt-dependent reporter construct in mammalian cell culture. Misexpression of mouse nkd1 in Drosophila antagonizes Wg function. The data suggest that the vertebrate Nkd-related proteins, similar to their fly counterpart, may act as inducible antagonists of Wnt signals.
|
No pos
|
No neg
|
Retriever1575
|
Sequential strand displacement beacon for detection of DNA coverage on functionalized gold nanoparticles.
Functionalizing nanomaterials for diverse analytical, biomedical, and therapeutic applications requires determination of surface coverage (or density) of DNA on nanomaterials. We describe a sequential strand displacement beacon assay that is able to quantify specific DNA sequences conjugated or coconjugated onto gold nanoparticles (AuNPs). Unlike the conventional fluorescence assay that requires the target DNA to be fluorescently labeled, the sequential strand displacement beacon method is able to quantify multiple unlabeled DNA oligonucleotides using a single (universal) strand displacement beacon. This unique feature is achieved by introducing two short unlabeled DNA probes for each specific DNA sequence and by performing sequential DNA strand displacement reactions. Varying the relative amounts of the specific DNA sequences and spacing DNA sequences during their coconjugation onto AuNPs results in different densities of the specific DNA on AuNP, ranging from 90 to 230 DNA molecules per AuNP. Results obtained from our sequential strand displacement beacon assay are consistent with those obtained from the conventional fluorescence assays. However, labeling of DNA with some fluorescent dyes, e.g., tetramethylrhodamine, alters DNA density on AuNP. The strand displacement strategy overcomes this problem by obviating direct labeling of the target DNA. This method has broad potential to facilitate more efficient design and characterization of novel multifunctional materials for diverse applications.
|
No pos
|
No neg
|
Retriever1576
|
L-type calcium channel: Clarifying the "oxygen sensing hypothesis".
The heart is able to respond acutely to changes in oxygen tension. Since ion channels can respond rapidly to stimuli, the "ion channel oxygen sensing hypothesis" has been proposed to explain acute adaptation of cells to changes in oxygen demand. However the exact mechanism for oxygen sensing continues to be debated. Mitochondria consume the lion's share of oxygen in the heart, fuelling the production of ATP that drives excitation and contraction. Mitochondria also produce reactive oxygen species that are capable of altering the redox state of proteins. The cardiac L-type calcium channel is responsible for maintaining excitation and contraction. Recently, the reactive cysteine on the cardiac L-type calcium channel was identified. These data clarified that the channel does not respond directly to changes in oxygen tension, but rather responds to cellular redox state. This leads to acute alterations in cell signalling responsible for the development of arrhythmias and pathology.
|
No pos
|
No neg
|
Retriever1577
|
Injection and electroporation of plasmid DNA into human cortical organoids.
Pluripotent stem cell-derived human cortical organoids allow for the analysis of stem cell behavior and neurogenesis in neural tissues. Delivery of plasmid DNA into organoids permits visualization of individual cells, characterization of cellular components, and manipulation of gene expression. We describe a protocol to transfect cells inside organoids with plasmid DNA using micro-injection and electroporation, allowing for DNA delivery to cells within cortical units. This protocol was optimized for cortical organoids; however, it may be adapted to other organoid models. For complete details on the use and execution of this protocol, please refer to Denoth-Lippuner et al. (2021).
|
No pos
|
No neg
|
Retriever1578
|
Association of TNF -1031 C/C as a potential protection marker for leprosy development in Amazonas state patients, Brazil.
Polymorphisms present in the TNF promoter region has shown to influence the gene transcription. Leprosy displays different clinical manifestations according to the immune responses of the individual infected with Mycobacterium leprae. In this study, we evaluated the single nucleotide polymorphisms (SNPs) -238 G/A (rs361525), -308 G/A (rs1800629), -857 C/T (rs1799724), -863 A/C (rs1800630) and -1031 T/C (rs1799964) in the promoter region of the TNF to see whether these SNPs influence host-susceptibility to leprosy and the different clinical manifestation. Nucleotide sequencing was performed with DNA samples from 108 leprosy patients and 253 control subjects. An association between -1031 C/C genotype and protection from leprosy was observed when leprosy patients were compared to controls (OR 0.11; 95% CI=0.01-0.82; p=0.012). The -857 C/T genotype may be associated with susceptibility to leprosy (OR=1.81; 95% CI=1.09-3.00; p=0.028). Similar genotype and allele frequencies for the SNPs -308 G/A and -238 G/A were observed between leprosy patients and control subjects. Altogether, TNF polymorphisms in the promoter region may be predictive of leprosy outcome.
|
No pos
|
No neg
|
Retriever1579
|
UV-B induced changes in antioxidant enzymes and their isoforms in cucumber (Cucumis sativus L.) cotyledons.
To assess the role of antioxidant defense system on exposure to ultra-violet-B (UV-B) radiation, the activities of antioxidant enzymes superoxide dismutase (SOD), ascorbic acid peroxidase (APX), glutathione reductase (GR) and guaiacol peroxidase (GPX), as well as the level of antioxidants ascorbic acid (AA) and alpha-tocopherol were monitored in cucumber (Cucumis sativus L. var long green) cotyledons. UV-B enhanced the activity of antioxidant enzymes as well as AA content, but decreased the level of alpha-tocopherol. Significant increase was observed in the activities of SOD and GPX. Analysis of isoforms of antioxidant enzymes by native-PAGE and activity staining revealed three isoforms of GPX in unexposed dark-grown cotyledons (control), and their intensity was enhanced by UV-B exposure. In addition, four new isoforms of GPX were observed in cotyledons after UV-B exposure. Although no new isoforms were observed for the other antioxidant enzymes, the activities of their existing isoforms were enhanced by UV-B.
|
No pos
|
No neg
|
Retriever1580
|
Delayed onset of congenital hereditary endothelial dystrophy due to compound heterozygous SLC4A11 mutations.
BACKGROUND
Congenital hereditary endothelial dystrophy (CHED) is an autosomal recessive disorder characterized by bilateral, symmetrical, noninflammatory corneal clouding (edema) present at birth or shortly thereafter. This study reports on an unusual delayed presentation of CHED with compound heterozygous SLC4A11 mutations.
MATERIALS AND METHODS
A 45-year-old female, presenting with bilateral decreased vision since childhood that deteriorated in the last 5 years, was evaluated to rule out trauma, viral illness, chemical injury, glaucoma, and corneal endothelial dystrophies. Tear sample was sent for herpes simplex viral (HSV) antigen testing. Genomic DNA from peripheral blood was screened for mutations in all exons of SLC4A11 by direct sequencing. Full-thickness penetrating keratoplasty was done and corneal button was sent for histopathological examination.
RESULTS
Slit-lamp findings revealed bilateral diffuse corneal edema and left eye spheroidal degeneration with scarring. Increased corneal thickness (762 μm and 854 μm in the right and left eyes, respectively), normal intraocular pressure (12 mmHg and 16 mmHg in the right and left eyes, respectively), inconclusive confocal scan, and specular microscopy, near normal tear film parameters, were the other clinical features. HSV-polymerase chain reaction was negative. Histopathological examination revealed markedly thickened Descemet's membrane with subepithelial spheroidal degeneration. SLC4A11 screening showed a novel variant p.Ser415Asn, reported mutation p.Cys386Arg and two polymorphisms, all in the heterozygous state and not identified in 100 controls.
CONCLUSIONS
The study shows, for the first time, compound heterozygous SLC4A11 mutations impair protein function leading to delayed onset of the disease.
|
No pos
|
No neg
|
Retriever1581
|
Hidden blood loss and the risk factors after posterior lumbar fusion surgery: A retrospective study.
Hidden blood loss (HBL) plays an important role in perioperative rehabilitation of patients underwent posterior lumbar fusion surgery. This study was to calculate the volume of HBL and evaluate the risk factors among patients after posterior lumbar fusion surgery.A retrospective analysis was made on the clinical data of 143 patients underwent posterior lumbar fusion surgery from March 2017 to December 2017. Recording preoperative and postoperative hematocrit to calculate HBL according to Gross formula and analyzing its related factors including age, sex, height, weight, body mass index (BMI), surgery levels, surgical time, surgery types, duration of symptoms, disorder type, specific gravity of urine (SGU), plasma albumin (ALB), glomerular filtration rate (GFR), glucose (GLU), drainage volume, hypertension. Risk factors were further analyzed by multivariate linear regression analysis and t test.Eighty-six males and 57 females, mean age 52.7 ± 11.4 years, mean height 162 ± 7.0, mean weight 61.5 ± 9.4, were included in this study. The HBL was 449 ± 191 mL, with a percentage of 44.2% ± 16.6% in the total perioperative blood loss. Multivariate linear regression analysis revealed that patients with higher BMI (P = .026), PLIF procedures (P = .040), and more surgical time (P = .018) had a greater amount of HBL. Whereas age (P = 0.713), sex (P = .276), surgery levels (P = .921), duration of symptoms (P = .801), disorder type (P = .511), SGU (P = .183), ALB (P = .478), GFR (P = .139), GLU (P = .423), hypertension (P = .337) were not statistically significant differences with HBL.HBL is a large proportion of total blood loss in patients after posterior lumbar fusion surgery. BMI >24 kg/m, PLIF procedures, and more surgical time are risk factors of HBL. Whereas age, sex, surgery levels, duration of symptoms, disorder type, SGU, ALB, GFR, GLU, hypertension were not associated with HBL.
|
No pos
|
No neg
|
Retriever1582
|
Nobiletin Mitigates D-Galactose-Induced Memory Impairment via Improving Hippocampal Neurogenesis in Mice.
Memory impairment is a characteristic of brain aging, and it is associated with a decrease in neurogenesis. Therefore, enhancing neurogenesis is a potential method for mitigating brain aging. Nobiletin (NOB) is a natural polymethoxylated flavonoid derived from citrus peels. It acts as an antioxidant, enhances anti-inflammation, and displays neuroprotective properties. However, the mechanism of NOB on brain aging has not been elucidated. In this study, D-galactose-induced aging mice were treated with NOB (100 mg/kg/day) for 10 weeks. NOB administration attenuated D-galactose-induced memory impairment and restored hippocampal neurogenesis, including the number of newborn neurons and neural stem cells in mice. Furthermore, it downregulated the pro-inflammatory mediators IL-1 β, IL-6, and pP65 (by 42.2%, 22.9%, and 46.4% of those in the D-galactose treated group, respectively) in the hippocampus and blocked microglia and astrocyte activation. In vitro, NOB inhibited D-galactose-induced inflammatory responses in BV2 cells, and the conditioned medium prepared from NOB- and D-galactose-co-treated BV2 cells elevated the viability (90.3% of control) and differential ability (94.9% of control) of C17.2 cells, compared to the D-galactose-treated group alone. It was concluded that NOB could restore memory impairment via the improvement of neurogenesis by ameliorating neuroinflammation in the hippocampus. Overall, NOB is a potential candidate neurogenesis enhancer for improving brain function.
|
No pos
|
No neg
|
Retriever1583
|
The clinical features of cataplexy: a questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency.
BACKGROUND
Narcolepsy is often not recognized or accurately diagnosed. This may be due to the fact that cataplexy, a core symptom which is virtually 100% specific, can-in practice-only be diagnosed based on the patient's history. However, the current definition of cataplexy is not very precise and the common distinction between "typical" and "atypical" cataplexy is not well codified.
METHODS
We aimed to provide a detailed description of the phenotypic variability of cataplexy. We included 109 patients with a definite history of cataplexy and a proven hypocretin-1 deficiency. The questionnaire contained 37 items to broadly cover the clinical aspects of cataplexy, including triggers, pattern and duration of muscle weakness, associated aspects such as sensory phenomena, and limitations in daily life due to cataplexy.
RESULTS
"Laughing" only listed in place 11th of most frequent triggers. "Laughing excitedly" was much more potent, showing that a certain intensity of the emotion is important for a "cataplectogenic" effect. Anger was the highest ranking "non-humorous" trigger, followed by "unexpectedly meeting someone well known." About 60% of patients also had spontaneous cataplectic attacks. Forty-five percent of patients experienced both partial and complete attacks and 30% only partial cataplexy. Fifteen percent of complete attacks were reported to last longer than 2 min. An abrupt return of muscle function was an important feature. The jaw and the face were most often involved in partial attacks, even more than the knee or the leg.
CONCLUSIONS
Cataplexy presents with a large phenotypical diversity, so the current "typical" versus "atypical" distinction may be difficult to hold. We propose that grading cataplexy with different levels of diagnostic confidence may be more useful.
|
No pos
|
No neg
|
Retriever1584
|
Physical activity guidelines for preschoolers: a call for research to inform public health policy.
There are many challenges in developing evidence-based physical activity guidelines for preschoolers that can ensure health benefits for children. Guidelines for the preschool years have recently been developed in several countries, but there are notable inconsistencies in the amount of physical activity regarded as sufficient for this age group. Given the currently high prevalence of childhood obesity, there is an urgent need for evidence-based studies to inform the development of community-targeted programs to ensure healthy levels of physical activity in young children. Our article outlines the global recommendations for physical activity for children ≤ 5 years of age. We identify gaps in the literature and suggest recommendations for future research and public health policy.
|
No pos
|
No neg
|
Retriever1585
|
Synthesis of Ynones via N-Iodosuccinimide-Mediated Oxidation of Propargyl Alcohols under Mild Conditions.
A convenient and mild approach for the construction of ynones via N-iodosuccinimide (NIS)-mediated oxidation of propargyl alcohols has been described. This reaction could furnish the ynone products with a diversity of functional groups in moderate to excellent yields, and the flexibility of this method was demonstrated by the gram-scale experiment and further transformation.
|
No pos
|
No neg
|
Retriever1586
|
The natural history and pathogenesis of HIV infection.
Infection with human immunodeficiency virus (HIV) results in progressive deterioration of the cell-mediated immune system characterized by T-helper-cell dysfunction and loss in the face of signs of generalized immune-system activation. The final stage of HIV disease, AIDS, has a myriad of opportunistic infections and malignancies as its hallmarks. The causal relationship between HIV and this complex disease pattern is clear but the mechanisms by which it occurs are not well understood. There are a number of new developments in our understanding of the natural history of HIV infection from a laboratory standpoint. Our review of this information raises further questions as to the validity of the conventional "cytopathic" model and all its direct descendants. In response to these conflicts, we have developed and present an alternative hypothesis in which AIDS pathogenesis, in all its manifestations, is seen as the outcome of one central process, excess immune activation generated by the interaction of virus with the CD4 receptor. The implications of this hypothesis on therapy of HIV infections are discussed.
|
No pos
|
No neg
|
Retriever1587
|
A simple two-step protocol for the purification of human pancreatic beta cells.
AIMS/HYPOTHESIS
Isolated pure human beta cells would be helpful for a number of research purposes. However, lack of beta cell-specific surface antigens has been a major problem. We aimed to develop a simple method for human beta cell isolation based on the initial elimination of ductal cells by their expression of carbohydrate antigen 19-9 (CA19-9), followed by positive selection of beta cells by their expression of polysialic acid-neural cell adhesion molecule (PSA-NCAM).
METHODS
Cell type-specific expression of CA19-9, NCAM and PSA-NCAM was studied in sections of adult human pancreas and in cultured primary endocrine and exocrine cells. Dispersed human islet cells were purified in two steps, after 4 days of suspension culture, by binding to magnetic microbeads coupled to antibodies against CA19-9 and PSA-NCAM.
RESULTS
NCAM expression was detected in ducts and islets in the human pancreas. In contrast, PSA-NCAM immunoreactivity was detected only in islets. PSA-NCAM staining in dispersed cells revealed that the marker is expressed in all endocrine cell types, but not in duct cells. Purification of dispersed islet cells using PSA-NCAM microbeads alone did not completely eliminate contaminating duct cells. However, elimination of the duct cells by CA19-9 microbeads followed by positive sorting of the PSA-NCAM-positive cells in five consecutive islet preparations resulted in 90 to 98% pure endocrine cells, of which 89 to 97% were beta cells.
CONCLUSIONS/INTERPRETATION
We describe a simple and reproducible method for purification of viable human pancreatic beta cells devoid of exocrine acini and ducts.
|
No pos
|
No neg
|
Retriever1588
|
[Gastrointestinal hemorrhage after removal of brain tumors].
The diagnosis of gastrointestinal bleeding after the removal of a brain tumor is very difficult due to the severity of the state of the patients. Treatment of the bleeding is effective only in influencing both its source and the higher vegetative centers.
|
No pos
|
No neg
|
Retriever1589
|
Pharmacological effects of ephedrine alkaloids on human alpha(1)- and alpha(2)-adrenergic receptor subtypes.
Ephedra species of plants have both beneficial and adverse effects primarily associated with the presence of ephedrine alkaloids. Few reports have appeared that examine the direct actions of ephedrine alkaloids on human subtypes of adrenergic receptors (ARs). In the present study, ephedrine alkaloids were evaluated for their binding affinities on human alpha(1A)-, alpha(1B)-, alpha(1D)-, alpha(2A)-, alpha(2B)-, and alpha(2C)-AR subtypes expressed in HEK and Chinese hamster ovary cells. Cell-based reporter gene assays were used to establish functional activity of ephedrine alkaloids at alpha(1A)-, alpha(2A)-, and alpha(2C)-ARs. The data showed that ephedrine alkaloids did not activate alpha(1)- and alpha(2)-ARs and that they antagonized the agonist-mediated effects of phenylephrine and medetomidine on alpha(1)- and alpha(2)-ARs, respectively. As in the binding studies, 1R,2R- and 1R,2S-ephedrine showed greater functional antagonist activity than the 1S,2R- and 1S,2S-isomers. The rank order of affinity for the isomers was 1R,2R > 1R,2S > 1S,2R > 1S,2S. The rank order of potencies of alkaloids containing a 1R,2S-configuration was norephedrine > or = ephedrine >> N-methylephedrine. These studies have demonstrated that orientation of the beta-hydroxyl group on the ethylamino side chain and the state of N-methyl substitution are important for alpha-AR binding and functional activity of the ephedrine alkaloids. In conclusion, the ephedrine isomers and analogs studied did not exhibit any direct agonist activity and were found to possess moderate antagonist activities on cloned human alpha-ARs. The blockade of presynaptic alpha(2A)- and alpha(2C)-ARs may have a pharmacological role in the direct actions of Ephedra alkaloids.
|
No pos
|
No neg
|
Retriever1590
|
US daily temperature records past, present, and future.
Observed temperature extremes over the continental United States can be represented by the ratio of daily record high temperatures to daily record low minimum temperatures, and this ratio has increased to a value of about 2 to 1, averaged over the first decade of the 21st century, albeit with large interannual variability. Two different versions of a global coupled climate model (CCSM4), as well as 23 other coupled model intercomparison project phase 5 (CMIP5) models, show larger values of this ratio than observations, mainly as a result of greater numbers of record highs since the 1980s compared with observations. This is partly because of the "warm 1930s" in the observations, which made it more difficult to set record highs later in the century, and partly because of a trend toward less rainfall and reduced evapotranspiration in the model versions compared with observations. We compute future projections of this ratio on the basis of its estimated dependence on mean temperature increase, which we find robustly at play in both observations and simulations. The use of this relation also has the advantage of removing dependence of a projection on a specific scenario. An empirical projection of the ratio of record highs to record lows is obtained from the nonlinear relationship in observations from 1930 to 2015, thus correcting downward the likely biased future projections of the model. For example, for a 3 °C warming in US temperatures, the ratio of record highs to lows is projected to be ∼15 ± 8 compared to the present average ratio of just over 2.
|
No pos
|
No neg
|
Retriever1591
|
Vaccine-associated "wild-type" measles.
Measles is the most contagious of the childhood exanthems and is the leading cause of vaccine-preventable deaths in children, mostly in developing countries. The prodromal stage, consisting of high fever and the triad of cough, coryza, and conjunctivitis, is followed by a caudal progressing rash over a period of 2 to 3 days. With a worldwide vaccination program in place, mortality and morbidity have decreased substantially. Receipt of the live attenuated vaccine generally causes no or only mild side effects such as a low-grade fever and a subtle rash. We report a 1-year-old boy who, 10 days after vaccination, developed vaccine measles which was clinically indistinguishable from the natural disease. Vaccine virus was detected by polymerase chain reaction in the patient's nasopharyngeal secretions.
|
No pos
|
No neg
|
Retriever1592
|
Physiology and metabolism of Northern krill (Meganyctiphanes norvegica Sars).
Advances in our understanding of the physiology and metabolism of Northern krill, Meganyctiphanes norvegica have been sporadic but significant. Despite problems with keeping M. norvegica in good condition in the laboratory, those who have tried, and succeeded, have contributed to a better knowledge of krill biology and challenged our understanding of some basic biological processes. Most recent work has been concentrated in the fields of digestive physiology, lipid biochemistry, respiration and anaerobiosis, metabolic properties, and pollutants. M. norvegica is capable of digesting an opportunistic, omnivorous diet, showing some digestive enzyme polymorphism and high levels of enzyme activity, the latter varying with season. It also seems capable of digesting cellulose and hemicelluloses, for example, laminarin. The biochemical composition of krill is relatively well known with some recent extensive work focusing on the previously little studied lipid and fatty acid composition, particularly with reference to reproduction, overwintering energy storage and as a nutrition marker. A high aerobic metabolism (but poor anaerobic capacity) is characteristic of M. norvegica, and how this is affected by temperature, low O(2), and season has attracted some attention, particularly in the context of diel vertical migration (DVM) across pronounced pycnoclines. Despite determining high metabolic turnover rates and a high physiological plasticity for this species, we know little of the regulative potential of metabolites, particularly their modulative effect on enzyme activity. Certainly a modest ability to maintain aerobic metabolism when encountering hypoxia, and little or no ability to osmoregulate in hyposaline conditions, does not prevent DVM in adults of this species. The ability to maintain aerobic metabolism develops early in ontogeny at about furcilia III (i.e. concurrent with first DVM behaviour). The respiratory pigment of M. norvegica, haemocyanin, has a low O(2) affinity and high temperature sensitivity (although temperature has the opposite effect on O(2) binding than found for nearly every other haemocyanin). Also surprising is the apparent use of haemocyanin as an energy source/store. While recent work has focused on physiological effects, the ecophysiological effects of transuric elements and trace metals, the effects of pollution generally are widely understudied.
|
No pos
|
No neg
|
Retriever1593
|
[Tuberculoid leprosy revealed by active ulcerative colitis: a case report].
Leprosy is endemic in Senegal. In 2011, there were 73 new cases reported in Dakar. The circumstances of discovery are often dermatologic or neurologic. Few case reports describe an association with chronic inflammatory colitis, probably fortuitous. We report the case of a 30-year-old woman who had a tuberculoid leprosy revealed by active ulcerative colitis. Treatment according to the WHO protocol of leprosy, combined with corticosteroids and then methotrexate, resulted in healing of the leprosy and remission of the colitis.
|
No pos
|
No neg
|
Retriever1594
|
Survey of patient satisfaction in adult psychiatric outpatient clinics.
A client satisfaction survey was undertaken in two adult psychiatric outpatient clinics. The anonymous self-report questionnaire covering demographic, setting and satisfaction with service variables was endorsed by 203 participants. The mean age of the subjects was 42.5 +/- 19 years, with a small majority (58.6%) of females. Overall satisfaction with psychiatric care was high (79.8%). None of the demographic or setting variables correlated significantly with satisfaction. Psychoeducation was significantly correlated with level of satisfaction with services. These findings further emphasize the importance of psychoeducation by service providers in mental health.
|
No pos
|
No neg
|
Retriever1595
|
Effects of a denture adhesive on masticatory functions for complete denture wearers--consideration for the condition of denture-bearing tissues--.
The purpose of this study was to examine effects of a denture adhesive on masticatory functions for complete denture wearers considering the condition of denture-bearing tissues. Sixteen edentulous subjects wearing well-fitting complete dentures volunteered to participate in this study. According to the condition of denture-bearing tissues, subjects were divided into two groups; "good group" and "poor group". Maximum biting forces, masticatory performance, and electromyography of the masseter muscle during mastication were recorded with and without a denture adhesive. Durations of chewing burst and cycle, and coefficients of variation for these variables were calculated using electromyography recordings. Data were analyzed by using two-way repeated-measured ANOVA and paired t-test in order to assess the effect of the use of a denture adhesive. The use of the denture adhesive increased maximum biting force and provided rhythmic masseter muscle activity during mastication for both groups. Masticatory performance was improved and duration of chewing burst was decreased only for "poor group". It was concluded that the effects of the denture adhesive on masticatory functions were observed overall for both groups, and more significant for denture wearers with poor denture-bearing tissues than with good denture-bearing tissues.
|
No pos
|
No neg
|
Retriever1596
|
Reducing the frequency of errors in medicine using information technology.
BACKGROUND
Increasing data suggest that error in medicine is frequent and results in substantial harm. The recent Institute of Medicine report (LT Kohn, JM Corrigan, MS Donaldson, eds: To Err Is Human: Building a Safer Health System. Washington, DC: National Academy Press, 1999) described the magnitude of the problem, and the public interest in this issue, which was already large, has grown.
GOAL
The goal of this white paper is to describe how the frequency and consequences of errors in medical care can be reduced (although in some instances they are potentiated) by the use of information technology in the provision of care, and to make general and specific recommendations regarding error reduction through the use of information technology.
RESULTS
General recommendations are to implement clinical decision support judiciously; to consider consequent actions when designing systems; to test existing systems to ensure they actually catch errors that injure patients; to promote adoption of standards for data and systems; to develop systems that communicate with each other; to use systems in new ways; to measure and prevent adverse consequences; to make existing quality structures meaningful; and to improve regulation and remove disincentives for vendors to provide clinical decision support. Specific recommendations are to implement provider order entry systems, especially computerized prescribing; to implement bar-coding for medications, blood, devices, and patients; and to utilize modern electronic systems to communicate key pieces of asynchronous data such as markedly abnormal laboratory values.
CONCLUSIONS
Appropriate increases in the use of information technology in health care- especially the introduction of clinical decision support and better linkages in and among systems, resulting in process simplification-could result in substantial improvement in patient safety.
|
No pos
|
No neg
|
Retriever1597
|
Biologics in asthma management - Are we out of breath yet?
The biologics authorized for the add-on therapy of severe asthma are monoclonal antibodies (mAbs). Before they are considered for therapy intensification, the patient's asthma endotype is determined on the basis of phenotypic characteristics. So far, 5 biologics are available that target the signaling pathways of the "TH2-high" asthma endotype, in which cytokines of the inflammation cascade mediated by type 2 T-helper cells are upregulated. The corresponding phenotype of this inflammatory endotype is severe eosinophilic asthma, with elevated eosinophils, immunoglobulin E, and fractional exhaled nitric oxide (FeNO). In contrast, the heterogeneous "TH2-low" endotype is not yet sufficiently understood. Frequently described in this variant is an increase of sputum neutrophils and an increased expression of the TH17-mediated interleukin-17 signaling pathway. There are numerous biologics currently in clinical trials, the thymic stromal lymphopoietin (TSLP) mAbs in particular have shown promising results independent of the asthma phenotype.
|
No pos
|
No neg
|
Retriever1598
|
Actin-dependent vacuolar occupancy of the cell determines auxin-induced growth repression.
The cytoskeleton is an early attribute of cellular life, and its main components are composed of conserved proteins. The actin cytoskeleton has a direct impact on the control of cell size in animal cells, but its mechanistic contribution to cellular growth in plants remains largely elusive. Here, we reveal a role of actin in regulating cell size in plants. The actin cytoskeleton shows proximity to vacuoles, and the phytohormone auxin not only controls the organization of actin filaments but also impacts vacuolar morphogenesis in an actin-dependent manner. Pharmacological and genetic interference with the actin-myosin system abolishes the effect of auxin on vacuoles and thus disrupts its negative influence on cellular growth. SEM-based 3D nanometer-resolution imaging of the vacuoles revealed that auxin controls the constriction and luminal size of the vacuole. We show that this actin-dependent mechanism controls the relative vacuolar occupancy of the cell, thus suggesting an unanticipated mechanism for cytosol homeostasis during cellular growth.
|
No pos
|
No neg
|
Retriever1599
|
Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA.
A gene vector consisting of nanodiamond, polyglycerol, and basic polypeptide (ND-PG-BPP) has been designed, synthesized, and characterized. The ND-PG-BPP was synthesized by PG functionalization of ND through ring-opening polymerization of glycidol on the ND surface, multistep organic transformations (-OH → -OTs (tosylate) → -N3) in the PG layer, and click conjugation of the basic polypeptides (Arg8, Lys8 or His8) terminated with propargyl glycine. The ND-PG-BPP exhibited good dispersibility in water (>1.0 mg/mL) and positive zeta potential ranging from +14.2 mV to +44.1 mV at neutral pH in Milli-Q water. It was confirmed by gel retardation assay that ND-PG-Arg8 and ND-PG-Lys8 with higher zeta potential hybridized with plasmid DNA (pDNA) through electrostatic attraction, making them promising as nonviral vectors for gene delivery.
|
No pos
|
No neg
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.