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Retriever900
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The dynamics of the vestibulo-ocular reflex after peripheral vestibular damage. I. Frequency-dependent asymmetry.
Accurate performance by the vestibulo-ocular reflex (VOR) is necessary to stabilize visual fixation during head movements. VOR performance is severely affected by peripheral vestibular damage; after one horizontal semicircular canal is plugged, the horizontal VOR is asymmetric and its amplitude is reduced. The VOR recovers partially. We investigated the limits of recovery by measuring the VOR's response to ipsilesional and contralesional rotation after unilateral peripheral damage in cats. We found that the VOR's response to rotation at high frequencies remained asymmetric after recovery was complete. When the stimulus was a pulse of head velocity comprising a dynamic overshoot followed by a plateau, gain was partially restored and symmetry completely restored within 30 days after the plug, but only for the plateau response. The overshoot in eye velocity remained asymmetric. The asymmetry was independent of stimulus velocity throughout the known linear velocity range of primary vestibular afferents. Sinusoidal rotation at 0.05-8 Hz revealed that, within this range, the persistent asymmetry was significant only at frequencies above 2 Hz. Asymmetry was independent of the peak head acceleration over the range of 50-500 degrees/s2. When both horizontal canals were plugged, a small residual VOR was observed, suggesting residual signal transduction by plugged semicircular canals. However, transduction by plugged canals could not explain the enhancement of the VOR gain, at high frequencies, for rotation away from the plugged side compared with rotation toward the plug. Also, the high-frequency asymmetry was present after recovery from a unilateral labyrinthectomy. These results suggest that high-frequency asymmetry after unilateral damage is not due to residual function in the plugged canal. The findings are discussed in the context of a bilateral model of the VOR that includes central filtering.
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No pos
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No neg
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Retriever901
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Points to consider for a validation study of iPS cell-derived cardiomyocytes using a multi-electrode array system.
Human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) provide a novel assay system to assess cardiac safety in drug development to overcome a problem of species difference in non-clinical testing during drug development. Using the multi-electrode array (MEA) platform, electrophysiological activities of iPS-CMs can be recorded easily to assess QT prolongation and proarrhythmic potential of drug candidates. Here we have established a standardized protocol to evaluate the possibility of iPS-CMs, and shared the protocol with an international consortium. To obtain reproducible and reliable experimental data from these cells, we determined the optimal experimental conditions, such as cell density, MEA coating, culture conditions, high-pass filter frequency, definition of early afterdepolarization or triggered activity, and calibration compounds. Based on the protocol, our validation study using 60 compounds is in progress. Thus, MEA-based experiments using iPS-CMs would be a standard testing method to evaluate QT prolongation and proarrhythmic potentials.
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No pos
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No neg
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Retriever902
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[The lacto-tampon concept. Determination and prevention of an increased risk for caries].
The lactobacillus count and buffer capacity (final pH) of whole stimulated saliva was assessed and related to the caries increment over the next 12 months in 327 teenagers. The caries increment was 3-4.5 times higher in children having a high lactobacillus count combined with a low buffer capacity, compared with other lacto-buffer combinations (P less than, 01-,001). The protective influence of a high buffer capacity seems to be stronger than the caries-promoting influence of high sugar consumption, indicated by a high lactobacillus count. On the one hand a low sugar consumption seems to have a decisive determining preventive effect even in children having impaired buffer systems. On the other hand a high sugar consumption strongly promotes caries when the buffer capacity is low. It is also demonstrated that consumption changes during a longitudinal study may impair the relationships between the salivary parameters, assessed at baseline, and the caries increment during the study.
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No pos
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No neg
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Retriever903
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Assessment of a Statewide Palliative Care Team Training Course: COMFORT Communication for Palliative Care Teams.
BACKGROUND
Despite increased attention to communication skill training in palliative care, few interprofessional training programs are available and little is known about the impact of such training.
OBJECTIVE
This study evaluated a communication curriculum offered to interprofessional palliative care teams and examined the longitudinal impact of training.
METHODS
Interprofessional, hospital-based palliative care team members were competitively selected to participate in a two-day training using the COMFORT(TM SM) (Communication, Orientation and options, Mindful communication, Family, Openings, Relating, Team) Communication for Palliative Care Teams curriculum. Course evaluation and goal assessment were tracked at six and nine months postcourse. Interprofessional palliative care team members (n = 58) representing 29 teams attended the course and completed course goals. Participants included 28 nurses, 16 social workers, 8 physicians, 5 chaplains, and one psychologist. Precourse surveys assessed participants' perceptions of institution-wide communication performance across the continuum of care and resources supporting optimum communication. Postcourse evaluations and goal progress monitoring were used to assess training effectiveness.
RESULTS
Participants reported moderate communication effectiveness in their institutions, with the weakest areas being during bereavement and survivorship care. Mean response to course evaluation across all participants was greater than 4 (scale of 1 = low to 5 = high). Participants taught an additional 962 providers and initiated institution-wide training for clinical staff, new hires, and volunteers. Team member training improved communication processes and increased attention to communication with family caregivers. Barriers to goal implementation included a lack of institutional support as evidenced in clinical caseloads and an absence of leadership and funding.
CONCLUSION
The COMFORT(TM SM) communication curriculum is effective palliative care communication training for interprofessional teams.
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No pos
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No neg
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Retriever904
|
[Determination of pyriminobac-methyl and bispyribac-sodium residues in rice by liquid chromatography-tandem mass spectrometry based on QuEChERS].
A method was developed for the determination of pyriminobac-methyl and bispyribac-sodium residues in rice by liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with modified QuEChERS. The samples were extracted with acidified acetonitrile, and then purified by octadecylsilane bonded silica (C18) adsorbents. The analytes were separated on a ZORBAX SB C18 column through a gradient elution using 0.1% (v/v) aqueous formic acid aqueous containing 5 mmol/L ammonium acetate and acetonitrile as mobile phases. Positive electrospray ionization (ESI+) was used. Qualitative work was performed using selected dynamic multiple reaction monitoring (dynamic MRM) mode. Quantization was performed using external standard method. The results showed good linearities of pyriminobac-methyl and bispyribac-sodium with correlation coefficients (r2) not less than 0.996. The limits of detection (LODs) of the method were 0.8 μ g/kg for pyriminobac-methyl, and 3 μ g/kg for bispyribac-sodium. The mean spiked recoveries of pyriminobac-methyl and bispyribac-sodium at three spiked levels were 76.6%-85.6% and 73.0%-86.7%, respectively, and the relative standard deviations (RSDs) of pyriminobac-methyl and bispyribac-sodium were 0.9%-3.4% and 1.2%-5.5%, respectively. This method is simple, rapid, sensitive, and suitable for the simultaneous determination of pyriminobac-methyl and bispyribac-sodium in rice.
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No pos
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No neg
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Retriever905
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[Prosthetic inguinal hernioplastics in day surgery. Which type of anesthesia? Our experience on 328 patients].
AIM
The aim of this paper is to compare local, spinal and general anesthesia with the tolerance of the patients as to pain and quality of life in the immediate postoperative period, and in the first week after the operation of prosthetic inguinal hernioplastics.
METHODS
Three hundred and fifty eight patients underwent inguinal hernioplastes in day surgery regimen. The patients were divided into three groups according to the type of anesthesia and with the help of a schedule given to them. The parameters of the immediate postoperative period, such as pain nausea, vomit, cephalalgia, diuresis and the parameters in the following seven days after the operation, such as mobility, activity, pain, dejection and analgesic therapy, were compared.
RESULTS
Collected data put into evidence a significative value, the mean pain value in the postoperative period, calculated on a numeric scale comprising numbers from 1 to 10. In patients who underwent a surgical procedure after a local anesthesia the mean pain value was 3.1. Comparison of postoperative symptoms highlights an asymptomatic condition in local or spinal anesthesia operated patients. Local anesthesia is generally more painful in the perioperative stage. Local anesthesia operated patients lament a longer duration of pain, in days, in the postoperative period and a longer administration of analgesics. No significance difference between mobility and quality of life has been noticed.
CONCLUSION
The results of our study demonstrate that the comparison among the three types of anesthesia operated in day surgery is well balanced, as it was clearly expressed by the patients of each group. Every group was satisfied with its own anesthesia protocol.
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No pos
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No neg
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Retriever906
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ANT1-mediated fatty acid-induced uncoupling as a target for improving myocellular insulin sensitivity.
AIMS/HYPOTHESIS
Dissipating energy via mitochondrial uncoupling has been suggested to contribute to enhanced insulin sensitivity. We hypothesised that skeletal muscle mitochondria of endurance-trained athletes have increased sensitivity for fatty acid (FA)-induced uncoupling, which is driven by the mitochondrial protein adenine nucleotide translocase 1 (ANT1).
METHODS
Capacity for FA-induced uncoupling was measured in endurance-trained male athletes (T) and sedentary young men (UT) in an observational study and also in isolated skeletal muscle mitochondria from Zucker diabetic fatty (ZDF) rats and C2C12 myotubes following small interfering RNA (siRNA)-mediated gene silencing of ANT1. Thus, fuelled by glutamate/succinate (fibres) or pyruvate (mitochondria and myotubes) and in the presence of oligomycin to block ATP synthesis, increasing levels of oleate (fibres) or palmitate (mitochondria and myotubes) were automatically titrated while respiration was monitored. Insulin sensitivity was measured by hyperinsulinaemic-euglycaemic clamp in humans and via insulin-stimulated glucose uptake in myotubes.
RESULTS
Skeletal muscle from the T group displayed increased sensitivity to FA-induced uncoupling (p = 0.011) compared with muscle from the UT group, and this was associated with elevated insulin sensitivity (p = 0.034). ANT1 expression was increased in T (p = 0.013). Mitochondria from ZDF rats displayed decreased sensitivity for FA-induced uncoupling (p = 0.008). This difference disappeared in the presence of the adenine nucleotide translocator inhibitor carboxyatractyloside. Partial knockdown of ANT1 in C2C12 myotubes decreased sensitivity to the FA-induced uncoupling (p = 0.008) and insulin-stimulated glucose uptake (p = 0.025) compared with controls.
CONCLUSIONS/INTERPRETATION
Increased sensitivity to FA-induced uncoupling is associated with enhanced insulin sensitivity and is affected by ANT1 activity in skeletal muscle. FA-induced mitochondrial uncoupling may help to preserve insulin sensitivity in the face of a high supply of FAs.
TRIAL REGISTRATION
www.trialregister.nl NTR2002.
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No pos
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No neg
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Retriever907
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Effect of a community-based Argentine tango dance program on functional balance and confidence in older adults.
Tango-dancing and walking programs are compared in nondemented seniors at risk for falls. Fallers (N = 30) age 62-91 were randomly assigned to a 10-wk (40 hr, 2 hr 2x/wk) tango class or walk group. The Activities-specific Balance Confidence (ABC) scale, sit-to-stand scores, and normal and fast walk were measured pre-, post-, and 1 month postintervention. Two-way repeated-measures ANOVAs indicated a significant main effect (p < .01) for time on all measures. Group and interaction effects for ABC led to improvement only in tango because of high baseline mean for the walk group. Clinical improvements measured using Established Populations for Epidemiologic Studies of the Elderly scoring were greater for the tango group. From these preliminary results it is suggested that although both interventions are effective activities for increasing strength and walk speed, tango might result in greater improvements than walking in balance skills and in walking speed in the 10-wk intervention. The study needs to be repeated with a greater sample size to determine the effectiveness of walking on fear of falling.
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No pos
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No neg
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Retriever908
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Transgenic Bt-producing Brassica napus: Plutella xylostella selection pressure and fitness of weedy relatives.
Release of transgenic insect-resistant crops creates the potential not only for the insect pest to evolve resistance but for the escape of transgenes that may confer novel or enhanced fitness-related traits through hybridization with their wild relatives. The differential response of diamondback moth (Plutella xylostella) populations in eastern and western Canada to Bt-producing (GT) Brassica napus and the potential for enhanced fitness of GT B. napus and weedy GT Brassica rapa x B. napus hybrid populations (F1, BC1, BC2) were studied. Comparative bioassays using neonates and 4th instars showed that GT B. napus and GT B. rapa x B. napus hybrids are lethal to larvae from both populations. No measurable plant fitness advantage (reproductive dry weight) was observed for GT B. napus (crop) and GT B. rapa x B. napus hybrid populations at low insect pressure (1 larva per leaf). At high insect densities (>10 larvae per leaf), vegetative plant weight was not significantly different for GT B. napus and non-GT B. napus, whereas reproductive plant weight and proportion of reproductive material were significantly higher in GT B. napus. Establishment of the Bt trait in wild B. rapa populations may also increase its competitive advantage under high insect pressure.
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No pos
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No neg
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Retriever909
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The intelligent use of digital tools and social media in practice management.
The Internet has fundamentally transformed the way patients and health-care providers communicate and interact. The use of digital tools and social media platforms, such as blogs, Facebook, Instagram, and Twitter, have empowered patients to expand their health-care knowledge and have provided practitioners with new ways to gain knowledge, lead discussions, promote causes, and build relationships with patients and other providers. In this article, we discuss the difference between digital communication, static one-way digital presence, and two-way social media connections. We also describe ways to establish and foster your digital profile, review the benefits and risks of engaging professionally in social media, and describe ways in which digital and social media tools may prove useful in both reimbursement and practice management.
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No pos
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No neg
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Retriever910
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Association of a rare variant with mismatch negativity in a region between KIAA0319 and DCDC2 in dyslexia.
It has been repeatedly shown that mismatch negativity (MMN), an event related potential measurement, reveals differences between dyslexic children and age-matched controls. MMN reflects the automatic detection of deviance between a stream of incoming sounds presented to the passive listener, and deficits in MMN (i.e. attenuated amplitudes) have been especially reported in dyslexia for detecting differences between speech sounds (e.g./ba/vs./da/). We performed an association analysis in 200 dyslexic children. This analysis focused on two MMN components, an early MMN (188-300 ms) and a late MMN (300-710 ms), and the dyslexia candidate genes KIAA0319 and DCDC2 on chromosome 6. Additionally, we imputed rare variants located in this region based on the 1000 genomes project. We identified four rare variants that were significantly associated with the late MMN component. For three of these variants, which were in high LD to each other, genotyping confirmed the association signal. Our results point to an association between late MMN and rare variants in a candidate gene region for dyslexia.
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No pos
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No neg
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Retriever911
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[Functional hypothalamic amenorrheas. II. Clinical aspects].
The most important causes of the functional hypothalamic amenorrhea (FHA), that are psychological stress, physical stress and weight loss, are associated with a decrease of the frequency of the LH secretory pulses and with a state of hypercortisolism. The slowing down of the LH pulse frequency is difficult to demonstrate in clinical practice. The classical symptoms of FHA which are low gonadotropin levels, and hypogonadism are not very specific. The diagnosis of FHA is therefore one of exclusion. Recent physiopathological studies have individualised new symptoms that are hypercortisolism, hypoprolactinaemia and an important increase in the night serum levels of melatonine, all of which could help to confirm the diagnosis. FHA is relatively frequent and its treatment with pulsatile GnRH administration or naltrexone is very successful.
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No pos
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No neg
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Retriever912
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Heart-to-Heart: promoting walking in rural women through motivational interviewing and group support.
BACKGROUND
Walking can significantly increase cardiorespiratory fitness and thereby reduce the incidence of heart disease in women. However, there is a paucity of research aimed at increasing walking in rural women, a high-risk group for heart disease and one for which exercise strategies may pose particular challenges.
PURPOSE
This study tested Heart-to-Heart (HTH), a 12-week walking program, designed to increase fitness through walking in rural women. Heart-to-Heart integrated individual-oriented strategies, including motivational interviewing, and group-based strategies, including team building.
METHODS
Forty-six rural women were randomized to either HTH or a comparison group. The primary outcome of cardiorespiratory fitness and secondary outcomes of self-efficacy and social support were measured preintervention and post-intervention. Group differences were analyzed with repeated-measures analysis of variance.
RESULTS
Women in HTH group had a greater improvement in cardiorespiratory fitness (P =.057) and in social support (P =.004) compared with women in the comparison group. Neither group of women experienced a change in exercise self-efficacy (P =.814).
CONCLUSIONS
HTH was effective in improving cardiorespiratory fitness in a sample of rural women. Further research is needed to refine HTH and determine the optimal approach in rural women to increase their walking.
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No pos
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No neg
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Retriever913
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[Study of the effects of utero-placental ischemia on the body and nervous system development in fetal rats].
OBJECTIVE
To discuss the effects of utero-placental ischemia on the body and nervous system development in fetal rats.
METHODS
By clamping the unilateral uterine artery of the rat, we produced a utero-placental ischemia model. The opposite uterus of the rat with normal uterine artery supply served as control. We compared the body weight, weight of brain, and the expression of growth associated protein-43 (GAP-43) mRNA in cerebral tissue by RT-PCR in the 13 day (group 1) and 17 day (group 2) old fetal rats respectively.
RESULTS
The body weight and weight of brain in group 1 were 3.2 g and 0.16 g respectively, significantly lower than those of control 1 of 3.6 g and 0.18 g respectively (P < 0.01, P < 0.05). The body weight and weight of brain in group 2 were 3.1 g and 0.16 g respectively, also significantly lower than those of control 2 of 3.72 g and 0.17 g respectively (P < 0.01, P < 0.05). The expression of GAP-43 mRNA in cerebral tissue of the group 1 (1.10) and its control (1.12) showed no obvious difference (P > 0.05). However, GAP-43 mRNA in cerebral tissue of the group 2 (1.06) was significantly decreased compared with that of its control (1.21) (P < 0.01).
CONCLUSION
Clamping the uterine artery can mimic intrauterine ischemia and produce FGR model. Intrauterine ischemia in the late stage of pregnancy may decrease the expression of GAP-43 mRNA, which might affect the development of nervous system in rats.
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No pos
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No neg
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Retriever914
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Stability of X chromosome differentiation in mouse embryos. Reversal may not be responsible for the extreme X-inactivation mosaicism in extraembryonic membranes.
By means of a double labeling method with H3-thymidine and 5-bromodeoxyuridine, it was found that the X chromosome showed no sign of change from an allocyclic to an isocyclic state, or vice vers in 6.5- and 7.5-day mouse embryos. Thus, reversal of allocycly may not account for the predominance of cells with the paternally derived X chromosome inactive in the yolk sac and the chorion of the mouse embryo.
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No pos
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No neg
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Retriever915
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Metastatic pathways in patients with cutaneous melanoma.
Metastasis represents the end product of an elaborate biological process, which is determined by a complex interplay between metastatic tumour cells, host factors and homoeostatic mechanisms. Cutaneous melanoma can metastasize haematogenously or lymphogenously. The three predominant models that endeavour to explain the patterns of melanoma progression are the stepwise spread model, the simultaneous spread model and the model of differential spread. The time course to the development of metastases differs between the different metastatic routes. There are several clinical and histopathological risk factors for the different metastatic pathways. In particular, patient sex and the anatomical location of the primary tumour influence patterns of disease progression. There is limited existing evidence regarding the relationship between tumour mutation status, other diagnostic and prognostic biomarkers and the metastatic pathways of primary cutaneous melanoma. This knowledge gap needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies.
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No pos
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No neg
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Retriever916
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[A study on the etiology and epidemiology of familial aggregation in arteriosclerotic cerebral infarction].
A case-control study including 214 pedigrees (109 cases and 105 controls) was carried out to explore the etiology of family aggregation of arteriosclerotic cerebral infarction in Yi-Xing city, March 1997. The results showed that the family member in both cases and control groups were comparable. The total prevalence rate of the first-degree relatives in cases was 5.12%, significantly higher than (1.63%) that noticed in controls, with chi 2 = 16.40 (P < 0.01). The same results was also found in their parents and siblings. Results from binominal distribution analysis showed that the number of cases in the families of arteriosclerotic cerebral infarction was significantly higher than the theortical range which indicated that there was significant familial aggregation in the occurance of arteriosclerotic cerebral infarction. Logistic regression model also showed that genetic factor was one of the most important risk factors in Xi-xing, Jiangsu. Dose-response was observed in this model. The heritability and the segregation ratio of arteriosclerotic cerebral infarction were the same as seen in other chronic diseases, such as coronary heart disease and esophageal cancer.
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No pos
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No neg
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Retriever917
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Effects of dietary Pediococcus acidilactici GY2 single or combined with Saccharomyces cerevisiae or/and β-glucan on the growth, innate immunity response and disease resistance of Macrobrachium rosenbergii.
One Pediococcus acidilactici strain, named PA-GY2 was isolated from the gut of cultured Macrobrachium rosenbergii. In order to better examine the potential scope and applicability of this strain in M. rosenbergii culture, based on the control diet, four experimental diets containing single or combined immunostimulants were produced by supplementing with yeast (Saccharomyces cerevisiae, SC) or/and β-glucan (G), then fed to the prawns (6.70 g ± 0.74) in five groups, which were named as group C (control group), P (PA-GY2), PS (PA-GY2 + SC, 1:1), PG (PA-GY2 + G) and PGS (PA-GY2 + SC + G), respectively. After a 60-day feeding trial, growth performance, feed utilization, immune response and disease resistance of prawns were evaluated in the present study. Results indicated that (1) The growth performance of the prawns in group PS and PGS were significantly improved. The prawns in group PGS presented the lowest feed coefficiency (FC), while prawns in group C presented the highest FC. (2) The protease activity was significantly improved by dietary immunostimulants supplementation, meanwhile, prawns in the group PS presented the highest lipase activity. (3) The highest total hemocyte count and respiratory burst activity were found in the group P and PG, respectively. The phagocytic index of the prawns in the group C was significantly lower than those in group P and PGS. (4) Dietary PA-GY2 single or combined with SC or/and β-glucan increased the immune related genes expression, including some antibacterial and antioxidant enzymes, while decreased the tumor necrosis factor-α gene expression, which led to the decreased cumulative mortality rate of prawns during the Aeromonas hydrophila challenge test. Based on the results of growth performance, digestive enzymes activity and immune response of M. rosenbergii, PA-GY2 supplementation, single or combined with SC or/and β-glucan could be suggested as promising immunostimulants in prawns farming.
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No pos
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No neg
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Retriever918
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A preliminary report of a strong genetic component for thought disorder in normals. A twin study.
Several authors have investigated the presence of thought disorder in psychiatric patients using different reliable methods. Under the hypothesis of a genetic predisposition to thought disorder, the degree and quality of thought disorder have also been studied in populations at a high risk for psychosis, in particular for schizophrenia. As a result, an increasing incidence of thought disorder was detected in relatives of schizophrenics. To account for the thought disorder also found in normal subjects, researchers propose that thought disorder exists in normal subjects on a continuum with schizophrenic patients. In the following report, we evaluated the inherited component of thought disorder in normal subjects, using a sample of 25 normal twin pairs, 16 monozygotic and 9 dizygotic twin pairs. We applied the Thought Disorder Index (TDI) to assess disordered thinking, genetic estimates were made with classical methods, controlling for environmental sources of variability where possible. Our findings suggest a strong additive genetic component for the global TDI rating variable, with a heritability estimate approaching 80-90%. New approaches in neuropsychology and neuropsychiatry-based on genetic methodologies should further define the cerebral physiology responsible for disordered thinking.
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No pos
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No neg
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Retriever919
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Preclinical Pharmacokinetics and First-in-Human Pharmacokinetics, Safety, and Tolerability of Velpatasvir, a Pangenotypic Hepatitis C Virus NS5A Inhibitor, in Healthy Subjects.
Preclinical characterization of velpatasvir (VEL; GS-5816), an inhibitor of the hepatitis C virus (HCV) NS5A protein, demonstrated that it has favorable in vitro and in vivo properties, including potent antiviral activity against hepatitis C virus genotype 1 to 6 replicons, good metabolic stability, low systemic clearance, and adequate bioavailability and physicochemical properties, to warrant clinical evaluation. The phase 1 (first-in-human) study evaluated the safety, tolerability, and pharmacokinetics of VEL in healthy human subjects following administration of single and multiple (n = 7) once-daily ascending doses and of VEL in the presence and absence of food. Following administration of single and multiple doses, VEL was safe and well tolerated when administered at up to 450 mg and when administered with food. The pharmacokinetic behavior of VEL observed in humans was generally in agreement with that seen during preclinical characterization. Following administration of multiple doses, VEL trough concentrations were significantly greater than the protein-adjusted half-maximal (50%) effective concentration of VEL against HCV genotype 1 to 6 replicons at all evaluated doses greater than 5 mg. The pharmacokinetics of VEL were not significantly affected by administration with food. Collectively, the results of this study support the further clinical investigation of VEL administered once daily as part of a regimen with other pangenotypic direct-acting antivirals for the treatment of HCV infection.
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No pos
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No neg
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Retriever920
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[Nitrate-Nitrogen Pollution Sources of an Underground River in Karst Agricultural Area Using 15N and 18O Isotope Technique].
The objectives of this study were to reveal the sources of nitrate and the ratio of karst in an agricultural basin based on a 15N and 18O isotope technique and quantitative calculation of the IsoSource model. From May to October 2017, six sampling points in the Qingmuguan river basin, Chongqing, were monitored every 24 d. Results showed that there was a great risk of nitrate pollution in the underground river system, because most NO3--N concentrations of the sampling points exceeded the threshold. Spatially, NO3--N concentrations in the underground river increased from upstream to downstream. Temporally, NO3--N concentrations of Fishpond and Yankou Ponor upstream and Jiangjia Spring downstream were impacted by agricultural fertilizer from May to June and fluctuated from June to September due to precipitation. With decreased agricultural activities, NO3--N concentrations gradually decreased after September. NO3--N concentrations were high in midstream soil water. Daluchi, in the middle and lower reaches, maintained relatively low NO3--N concentrations with stable fluctuations. Dual 15N and 18O isotopic compositions suggested that the upstream nitrates were derived from soil organic nitrogen and a mixture of manure and sewage. The midstream nitrates originated from soil organic nitrogen and NH4+ from fertilizer and rain. Nitrates in the middle and lower reaches were derived from the mixing of manure and sewage, soil organic nitrogen, and NH4+ from fertilizer and rain. Jiangjia Spring, the outlet of the underground river, was seriously polluted by nitrates. It is believed that soil organic nitrogen, NH4+ in fertilizer and rain, the mixing of manure and sewage, and NO3- in precipitation were the main nitrate sources in the outlet. Nitrate source contribution of the outlet was calculated with the IsoSource model. The calculation results showed that manure and sewage, soil organic nitrogen, NH4+ in fertilizer and rain, and NO3- in precipitation contributed 46.4%, 32.6%, 18.6%, and 2.4%, respectively.
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No pos
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No neg
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Retriever921
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Paediatric HIV management at primary care level: an evaluation of the integrated management of childhood illness (IMCI) guidelines for HIV.
BACKGROUND
Integrated Management of Childhood Illness (IMCI) is a WHO/UNICEF strategy to improve child survival in resource poor settings. South Africa adopted IMCI in 1997, and IMCI guidelines were adapted to include identification and management of HIV infected and exposed children. This study describes the validity of the IMCI/HIV algorithm when used by IMCI experts, the use of IMCI/HIV guidelines by IMCI trained health workers in routine clinical practice, and the burden of HIV among children under 5 years attending first level health facilities.
METHODS
Seventy seven randomly selected IMCI trained health workers were observed in 74 health facilities in two provinces of South Africa. Consultations were observed with 1357 sick children; each child was reassessed by an IMCI expert to confirm the correct findings. Consent was requested for HIV testing of all children who attended with a parent or legal guardian. Positive rapid HIV tests were confirmed with HIV PCR in children aged less than 18 months. HIV positive children had a CD4 count and HIV clinical staging done.
RESULTS
Of 1064 children with HIV results available, 76 (7.1% CI: 5.7% - 8.9%) children were confirmed HIV positive. IMCI experts using the HIV algorithm classified 54/76 (71.1% CI: 59.5%-80.9%) HIV positive children as suspected symptomatic HIV, and 15/22 remaining HIV positive children were identified as HIV exposed. Therefore, 69/76 (90.8% CI: 81.9-96.2) HIV infected children were identified by IMCI experts. No classification was made for HIV by observed health workers in 899/1357(66.2%) children.906/1243(72.9%) mothers had been tested previously for HIV, of whom 221(24.4%) reported testing positive. Of 221 children therefore identified as HIV exposed, only 78(35.3%) had been tested for HIV within routine services.
CONCLUSION
The HIV algorithm is a valid tool for identifying HIV infected and exposed children when correctly and comprehensively implemented. However, it is not being used by IMCI trained health workers in routine practise, leading to a failure to implement life saving interventions.
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No pos
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No neg
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Retriever922
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[Study on malaria vectors in malaria endemic areas of Tibet autonomous region].
The malaria situation in Tibet has been in an active status and the malaria incidence reached the second in China in 2010. Malaria vector prevention and control is one of the important methods for malaria control, while the malaria vectors are still unknown in Tibet. The author summarized the past researches on malaria vectors in Tibet, so as to provide the evidence for improving malaria control investigation in malaria endemic areas of Tibet, with hopes to provide useful vector message for other researcher.
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No pos
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No neg
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Retriever923
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In vivo regulation of glycolytic and gluconeogenic enzyme gene expression in newborn rat liver.
Glucagon and its second messenger, cAMP, are known to rapidly block expression of the L-type pyruvate kinase gene and to stimulate expression of phosphoenolpyruvate (PEP) carboxykinase gene in the liver in vivo. The respective roles, however, of hyperglucagonemia, insulinopenia, and carbohydrate deprivation in the inhibition of L-type pyruvate kinase gene expression during fasting are poorly understood. In addition, the long-term effects of physiological hyperglucagonemia on expression of the two genes are not known. In this study, we investigate the effects of long-term physiological hyperglucagonemia and insulinopenia induced by suckling (which provides a high-fat, low-carbohydrate diet) on expression of the two genes in the liver of normal newborn rats. We show that transcription of the L-type pyruvate kinase gene is inhibited at birth and remains low during the whole suckling period, whereas transcription of the PEP carboxykinase gene is maximal in the neonate, and then decreases despite very high levels of plasma glucagon during suckling. In contrast to the adult, however, in which L-type pyruvate kinase gene expression in the liver is blocked by cAMP and stimulated by carbohydrates, the regulation of L-type pyruvate kinase gene expression in the newborn undergoes a developmental maturation: the inhibitory effect of glucagon is never complete in developing rat liver and the stimulatory effect of glucose could not be detected during suckling, due to either hyperglucagonemia, immaturity of the gene regulatory system, or both.
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No pos
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No neg
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Retriever924
|
Connexin43 cardiac gap junction remodeling: lessons from genetically engineered murine models.
Sudden cardiac death is responsible for several hundred thousand deaths each year in the United States. Multiple lines of evidence suggest that perturbation of gap junction expression and function in the heart, or what has come to be known as cardiac gap junction remodeling, plays a key mechanistic role in the pathophysiology of clinically significant cardiac arrhythmias. Here we review recent studies from our laboratory using genetically engineered murine models to explore mechanisms implicated in pathologic gap junction remodeling and their proarrhythmic consequences, with a particular focus on aberrant posttranslational phosphorylation of connexin43.
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No pos
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No neg
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Retriever925
|
Hydroxyapatite Growth Inhibition Effect of Pellicle Statherin Peptides.
In our recent studies, we have shown that in vivo-acquired enamel pellicle is a sophisticated biological structure containing a significant portion of naturally occurring salivary peptides. From a functional aspect, the identification of peptides in the acquired enamel pellicle is of interest because many salivary proteins exhibit functional domains that maintain the activities of the native protein. Among the in vivo-acquired enamel pellicle peptides that have been newly identified, 5 peptides are derived from statherin. Here, we assessed the ability of these statherin pellicle peptides to inhibit hydroxyapatite crystal growth. In addition, atomistic molecular dynamics (MD) simulations were performed to better understand the underlying physical mechanisms of hydroxyapatite growth inhibition. A microplate colorimetric assay was used to quantify hydroxyapatite growth. Statherin protein, 5 statherin-derived peptides, and a peptide lacking phosphate at residues 2 and 3 were analyzed. Statherin peptide phosphorylated on residues 2 and 3 indicated a significant inhibitory effect when compared with the 5 other peptides (P < 0.05). MD simulations showed a strong affinity and fast adsorption to hydroxyapatite for phosphopeptides, whereas unphosphorylated peptides interacted weakly with the hydroxyapatite. Our data suggest that the presence of a covalently linked phosphate group (at residues 2 and 3) in statherin peptides modulates the effect of hydroxyapatite growth inhibition. This study provides a mechanism to account for the composition and function of acquired enamel pellicle statherin peptides that will contribute as a base for the development of biologically stable and functional synthetic peptides for therapeutic use against dental caries and/or periodontal disease.
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No pos
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No neg
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Retriever926
|
Patterns of weight change after treatment for bulimia nervosa.
OBJECTIVE
The current study examined changes in weight and body mass index (BMI) at 5-year follow-up among women treated for bulimia nervosa.
METHOD
The study comprised 80 women who had participated in a randomized clinical trial evaluating cognitive-behavior therapy for bulimia nervosa. The women had attended assessments at posttreatment and at 5-year follow-up while not pregnant.
RESULTS
Changes in mean weight and BMI between posttreatment and 5-year follow-up were small in absolute terms and were not statistically significant. However, by the 5-year follow-up, approximately one half of the participants had either lost (31%) or gained (18%) 5 or more kilograms or were underweight (31%) or overweight (24%) as defined by BMI. Univariate analyses suggest that it is the patients who gain weight over the follow-up that are distinctive. Patients who gained weight over the follow-up were more likely to have commenced menstruation at a younger age, to have a lifetime history of being heavier, and to have been heavier and more dissatisfied with their body at pretreatment, posttreatment, and at 5-year follow-up.
CONCLUSION
Five years after treatment for bulimia nervosa, approximately one half of the participants had changed substantially in weight. For those who had changed, weight loss was more common than weight gain.
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No pos
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No neg
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Retriever927
|
SARS-CoV-2 vaccination does not induce relapses of patients with inflammatory bowel disease.
BACKGROUND
Vaccination against SARS-CoV-2 is a promising strategy to protect immunocompromised IBD patients from a severe course of COVID-19. As these patients were excluded from initial clinical vaccination trials, patients frequently express concerns regarding the safety of these vaccines, especially whether vaccination might trigger IBD flares ("hit-and-run-hypothesis").
METHODS
In order to assess the risk of an IBD flare after vaccination against SARS-CoV-2, an anonymous survey was performed at five German IBD centers and one patient organization (Deutsche Morbus Crohn/Colitis ulcerosa Vereinigung (DCCV) e.V.) in August and October 2021.
RESULTS
The questionnaire was answered by 914 patients, 781 of whom reported a previous vaccination against SARS-CoV-2 (85.4%). Vaccination against SARS-CoV-2 was not associated with an increased risk of IBD flares (p=0.319) or unscheduled visits to the IBD physician (p=0.848). Furthermore, typical symptoms of an IBD flare including abdominal pain, increases in stool frequency, or rectal bleeding were not influenced by the vaccination.
CONCLUSION
Vaccination against SARS-CoV-2 is safe in IBD patients. These results may help to reduce fears regarding the vaccination in IBD patients. Our results can help to reduce fears in IBD patients regarding the SARS-CoV-2 vaccine. A close communication between patients and physicians before and after the vaccination may be beneficial.
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No pos
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No neg
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Retriever928
|
Hydrogen sulfide maintains dental pulp stem cell function via TRPV1-mediated calcium influx.
Hydrogen sulfide (H2S), an endogenous gasotransmitter, mediated a variety of biological processes through multiple signaling pathways, and aberrant H2S metabolism has been associated with mesenchymal stem cell (MSC) dysfunction. Here we employed the small interfering RNA treatment for cystathionine β-synthase (CBS), cystathionine γ-lyase, the main enzymes to synthesize H2S, and CBS-knockout mice to analyze the effect of H2S on dental pulp homeostasis. We showed that H2S deficiency attenuated dental pulp stem cell (DPSC) osteogenic/dentinogenic differentiation in vitro and in vivo with enhanced cell proliferation. Mechanically, H2S facilitated the transient receptor potential action channel subfamily V member 1-mediated calcium (Ca2+) influx, which subsequently activated the β-catenin pathway. While H2S deficiency decreased Ca2+, resulting in glycogen synthase kinase-3β-mediated β-catenin degradation, which controls proliferation and differentiation of DPSCs. Consistently, H2S-deficient mice displayed disturbed pattern of dental pulp and less dentin formation. In this study, we identified a previously unknown mechanism by which H2S regulates DPSC lineage determination and dental pulp homeostasis.
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No pos
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No neg
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Retriever929
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Comparative Network Analysis of Patients with Non-Small Cell Lung Cancer and Smokers for Representing Potential Therapeutic Targets.
Cigarette smoking is the leading cause of lung cancer worldwide. In this study, we evaluated the serum autoantibody (AAb) repertoires of non-small cell lung cancer (NSCLC) patients and smokers (SM), leading to the identification of overactivated pathways and hubs involved in the pathogenesis of NSCLC. Surface- and solution-phase biopanning were performed on immunoglobulin G purified from the sera of NSCLC and SM groups. In total, 20 NSCLC- and 12 SM-specific peptides were detected, which were used to generate NSCLC and SM protein datasets. NSCLC- and SM-related proteins were visualized using STRING and Gephi, and their modules were analyzed using Enrichr. By integrating the overrepresented pathways such as pathways in cancer, epithelial growth factor receptor, c-Met, interleukin-4 (IL-4) and IL-6 signaling pathways, along with a set of proteins (e.g. phospholipase D (PLD), IL-4 receptor, IL-17 receptor, laminins, collagens, and mucins) into the PLD pathway and inflammatory cytokines network as the most critical events in both groups, two super networks were made to elucidate new aspects of NSCLC pathogenesis and to determine the influence of cigarette smoking on tumour formation. Taken together, assessment of the AAb repertoires using a systems biology approach can delineate the hidden events involved in various disorders.
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No pos
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No neg
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Retriever930
|
Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs.
Follicular helper T (Tfh) cells are necessary for germinal center B cell maturation during primary immune responses; however, the T cells that promote humoral recall responses via memory B cells are less well defined. In this article, we characterize a human tonsillar CD4+ T cell subset with this function. These cells are similar to Tfh cells in terms of expression of the chemokine receptor CXCR5 and the inhibitory receptor PD-1, IL-21 secretion, and expression of the transcription factor BCL6; however, unlike Tfh cells that are located within the B cell follicle and germinal center, they reside at the border of the T cell zone and the B cell follicle in proximity to memory B cells, a position dictated by their unique chemokine receptor expression. They promote memory B cells to produce Abs via CD40L, IL-10, and IL-21. Our results reveal a unique extrafollicular CD4+ T cell subset in human tonsils, which specialize in promoting T cell-dependent humoral recall responses.
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No pos
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No neg
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Retriever931
|
Sex-related changes in cardiac function following myocardial infarction in mice.
Recent awareness of cardiovascular diseases as a number one killer of the middle-aged women has prompted interest in sex differences leading to heart failure (HF). Therefore, we evaluated cardiac function in female and male mice following myocardial infarction (MI) using the Millar pressure-volume (P-V) conductance system in vivo, at time points corresponding to early (2 wk), late compensatory hypertrophy (4 wk), and decompensation (10 wk) to HF. A significant deterioration of the load dependent and independent hemodynamic measurements occurred in both female and male mice during the early phase of hypertrophy. Later, compensatory hypertrophy was marked by a normalization of volumes to control levels in females compared with males. The most notable differences between sexes occurred in the measurements of cardiac contractility during the decompensation to HF. In females, there was a significant improvement in contractility compared with males, which was apparent in the load-independent measurements of preload recruitable stroke work (10 wk post-MI, female=48.7+/-8.0 vs. male=25.2+/-1.8 mmHg, P<0.05) and maximum dP/dt vs. maximum end-diastolic volume (10 wk post-MI, female=359+/-58 vs. male=149+/-28 mmHg.s(-1).microl(-1), P<0.05). Despite these differences, there were no differences in the heart weight to body weight ratio and infarct size between the sexes. These data demonstrate that compensatory hypertrophy is associated with an improvement in contractility and a delayed decompensation to HF in females. However, compensatory hypertrophy in males appears to be undermined by a steady decline in contractility associated with decompensation to HF.
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No pos
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No neg
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Retriever932
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Morphological characteristics of Aspergillus fumigatus strains isolated from patient samples.
The Aspergillus fumigatus group splits into the anamorphic A. fumigatus series and the teleomorphic Neosartorya fischeri series. The species A. fumigatus Fresenius is the most common species within the A. fumigatus series. Forty-seven clinical isolates out of the A. fumigatus group were obtained from patients with diseases such as localized and invasive aspergilloses or allergic disorders due to Aspergillus and were mainly isolated from respiratory secretions. Isolates were studied concerning macro- and micromorphological parameters. All isolates were shown to be isolates of the species A. fumigatus Fresenius. In general, the macro- and micromorphological variability between the different isolates was low. Four isolates (DSM 10661, DSM 10662, DSM 10705, DSM 11069) showed significant differences towards the type strain A. fumigatus Fresenius ATCC 1022; one of these isolates was highly atypical (DSM 10705).
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No pos
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No neg
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Retriever933
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Frequent overexpression of ErbB--receptor family members in brain metastases of non-small cell lung cancer patients.
The ErbB receptor family has been implicated in brain metastases (BM) formation in various cancer types and specific targeted therapies are available. We investigated the overexpression of EGFR, HER2 and HER3 in BM of non-small cell lung cancer (NSCLC) patients to get a better insight on pathobiology of BM and potential drugable targets. We performed immunohistochemical analysis of EGFR, HER2 and HER3 on tissue microarrays of 131 NSCLC-BM. Fifty-one of 131 (38.9%) specimens were considered as positive for EGFR overexpression, 12/131 (9.2%) for HER2 and 27/131 (20.6%) for HER3 respectively. Sixty-nine of 131 (52.7%) of the cases showed overexpression of at least one marker. Four of 131 (3.1%) were positive for all three markers. Strong correlation was observed between HER2 and HER3 overexpression (p = 0.009; Chi-square test after Bonferroni-Holmes correction). No statistically significant correlation of EGFR, HER2 or HER3 overexpression with clinico-pathological parameters including overall survival times was observed. We observed overexpression of ErbB receptor family members, which represent established therapeutic targets in various primary tumours, in approximately half of NSCLC-BM. Further studies should investigate the role of the ErbB pathway in development of and as a therapeutic target in BM of NSCLC patients.
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No pos
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No neg
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Retriever934
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Employment of detergent-tag/solute interactions in capillary electrophoresis of neutral polysaccharides.
Neutral and inherently immobile polysaccharides are induced to migrate in an electric field through interactions with a detergent added to the electrophoretic electrolyte buffer. Before analysis the polysaccharides are converted to fluorescent derivatives to enable detection, but choice of a tag can also be utilized for modulation of the electrophoretic mobility. Three cases are discussed and exemplified, namely detergent-solute, detergent-solute+tag, and detergent-tag interactions. Anionic as well as cationic surfactants were exploited along with different derivatization reagents. Depending on the approach chosen, different kinds of information about sample composition and distribution(s) can be obtained, including degree of substitution, distribution of molecular weight (obtained in free solution without sieving media) and polymer conformation. A shift in polymer conformation upon a change in solvent composition can be monitored.
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No pos
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No neg
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Retriever935
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Characterization of early-onset motor deficits in the Pink1-/- mouse model of Parkinson disease.
In Parkinson disease (PD), a complex neurodegenerative disorder that affects nearly 10 million people worldwide, motor skills are significantly impaired. However, onset and progression of motor deficits and the neural correlates of these deficits are poorly understood. We used a genetic mouse model of PD (Pink1-/-), with phenotypic similarities to human PD, to investigate the manifestation of early-onset sensorimotor deficits. We hypothesized this mouse model would show early vocalization and gross motor dysfunction that would be progressive in nature. Pink1-/- mice, compared to wild type (WT) controls, were evaluated at 2, 3, 4, 5, and 6 months of age. To quantify deficit progression, ultrasonic vocalizations and spontaneous locomotor activity (cylinder test and pole test) were analyzed. Although somewhat variable, in general, Pink1-/- mice produced significantly more simple calls with reduced intensity as well as a larger percentage of cycle calls compared to WT counterparts. However, there were no significant differences in duration, bandwidth, or peak frequency for any of the ultrasonic call types between genotypes. Pink1-/- mice showed a significant impairment in limb motor skills with fewer hindlimb steps, forelimb steps, and rears and lands in the cylinder test compared to WT. Additionally, Pink1-/- mice took significantly longer to turn and traverse during the pole test. Immunohistochemical staining showed no significant difference in the number of tyrosine hydroxylase (TH) positive cells in the substantia nigra or density of TH staining in the striatum between genotypes. These data suggest the Pink1-/- mouse model may be instrumental in defining early motor biomarkers of PD in the absence of nigrostriatal dopamine loss.
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No pos
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No neg
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Retriever936
|
Polarization dependent resonant x-ray emission spectroscopy of D2O and H2O water: assignment of the local molecular orbital symmetry.
The polarization dependence of the split two peaks in the lone-pair region in the x-ray emission spectra has been determined at several different excitation energies for both D(2)O and H(2)O water. In contrast to predictions based on a narrow range of local water structures where the two peaks would be of different molecular orbital symmetry and arise from, respectively, intact and dissociated molecules, we show that the two peaks in the lone-pair region are both of lone-pair 1b(1) orbital symmetry. The results support the interpretation that the two peaks appear due to fluctuations between two distinct different main structural environments.
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No pos
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No neg
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Retriever937
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Interaction of Fapp1 with Arf1 and PI4P at a membrane surface: an example of coincidence detection.
Interactions among ADP-ribosylation factors (ARFs), various adaptor proteins, and membrane lipids are essential for intracellular vesicle transport of a variety of cellular materials. Here, we present nuclear magnetic resonance (NMR)-based information on the nature of the interaction of yeast Arf1 (yArf1) and the pleckstrin homology (PH) domain of four-phosphate-adaptor protein 1 (Fapp1) as it occurs at a model membrane surface. Interactions favor a model in which Fapp1 is partially embedded in the membrane and interacts with a membrane-associated Arf1 molecule primarily through contacts between residues in switch I of Arf1 and regions near and under the solution exposed C-terminal extension of the PH domain. The Arf1 binding site on Fapp1-PH is distinct from a positively charged phosphatidylinositol-4-phosphate (PI4P) binding site. A structural model is constructed that supports coincidence detection of both activated ARF and PI4P as a mechanism facilitating Fapp1 recruitment to membranes.
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No pos
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No neg
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Retriever938
|
Immunometabolism, Micronutrients, and Bariatric Surgery: The Use of Transcriptomics and Microbiota-Targeted Therapies.
BACKGROUND
Obesity is associated with the gut microbiota and decreased micronutrient status. Bariatric surgery is a recommended therapy for obesity. It can positively affect the composition of the gut bacteria but also disrupt absorption of nutrients. Low levels of micronutrients can affect metabolic processes, like glycolysis, TCA cycle, and oxidative phosphorylation, that are associated with the immune system also known as immunometabolism.
METHODS
MEDLINE, PUBMED, and Google Scholar were searched. Articles involving gut microbiome, micronutrient deficiency, gut-targeted therapies, transcriptome analysis, micronutrient supplementation, and bariatric surgery were included.
RESULTS
Studies show that micronutrients play a pivotal role in the intestinal immune system and regulating immunometabolism. Research demonstrates that gut-targeting therapies may improve the microbiome health for bariatric surgery populations. There is limited research that examines the role of micronutrients in modulating the gut microbiota among the bariatric surgery population.
CONCLUSIONS
Investigations are needed to understand the influence that micronutrient deficiencies have on the gut, particularly immunometabolism. Nutritional transcriptomics shows great potential in providing this type of analysis to develop gut-modulating therapies as well as more personalized nutrition recommendations for bariatric surgery patients.
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No pos
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No neg
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Retriever939
|
Effect of infection control measures on the frequency of diarrheal episodes in child care: a randomized, controlled trial.
BACKGROUND
Diarrheal infections are common in children who attend child care, and preventing transmission of disease in this setting depends on actions by child care staff. We set out to discover whether transmission of gastrointestinal infections in child care could be reduced by improved infection control procedures.
METHODS
We performed a cluster randomized, controlled trial of an infection control intervention conducted in child care centers for 1 city in Australia. The intervention was training of child care staff about transmission of infection and handwashing and focused on both staff and child behavior. Implementation of the intervention was recorded by an observer. Illness was measured by parent report in telephone interviews every 2 weeks.
RESULTS
There were 311 child-years of surveillance for diarrheal episodes. The rate of episodes of diarrhea was 1.9 per child-year in intervention centers and 2.7 per child-year in control centers. Multivariable analysis showed that diarrheal episodes were significantly reduced in intervention center children by 50%. However, the impact of the intervention was confined to children over 24 months of age. For those centers in which children's compliance with handwashing was high, diarrheal episodes were reduced by 66%.
CONCLUSIONS
This trial supports education about infection control, for staff and children in child care, as a means of reducing transmission of diarrhea. Reduction in episodes of diarrhea in children in child care was limited to children over 24 months of age.
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No pos
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No neg
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Retriever940
|
Selective functional inhibition of a tumor-derived p53 mutant by cytosolic chaperones identified using split-YFP in budding yeast.
Life requires the oligomerization of individual proteins into higher-order assemblies. In order to form functional oligomers, monomers must adopt appropriate 3D structures. Molecular chaperones transiently bind nascent or misfolded proteins to promote proper folding. Single missense mutations frequently cause disease by perturbing folding despite chaperone engagement. A misfolded mutant capable of oligomerizing with wild-type proteins can dominantly poison oligomer function. We previously found evidence that human-disease-linked mutations in Saccharomyces cerevisiae septin proteins slow folding and attract chaperones, resulting in a kinetic delay in oligomerization that prevents the mutant from interfering with wild-type function. Here, we build upon our septin studies to develop a new approach for identifying chaperone interactions in living cells, and use it to expand our understanding of chaperone involvement, kinetic folding delays, and oligomerization in the recessive behavior of tumor-derived mutants of the tumor suppressor p53. We find evidence of increased binding of several cytosolic chaperones to a recessive, misfolding-prone mutant, p53(V272M). Similar to our septin results, chaperone overexpression inhibits the function of p53(V272M) with minimal effect on the wild type. Unlike mutant septins, p53(V272M) is not kinetically delayed under conditions in which it is functional. Instead, it interacts with wild-type p53 but this interaction is temperature sensitive. At high temperatures or upon chaperone overexpression, p53(V272M) is excluded from the nucleus and cannot function or perturb wild-type function. Hsp90 inhibition liberates mutant p53 to enter the nucleus. These findings provide new insights into the effects of missense mutations.
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No pos
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No neg
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Retriever941
|
Montelukast and Nightmares: Further Characterisation Using Data from VigiBase.
INTRODUCTION
Montelukast is a medicine indicated for use in asthma. Psychiatric disorders including nightmares have not been described in clinical trials but during recent years have been included in the product information as having been reported post-marketing, without further description of the events. Previous descriptions in the scientific literature were based on limited numbers of reports or lacked detailed case information.
OBJECTIVE
The study aim was to further characterise post-marketing adverse drug reactions for nightmares, suspected to be induced by montelukast, to facilitate safer use of the medicine by providing additional information to patients and healthcare professionals.
METHODS
We clinically reviewed reports of nightmares with montelukast present in VigiBase, World Health Organization's global database of suspected adverse reactions to medicinal products, developed and maintained by the Uppsala Monitoring Centre, until 3 May, 2020.
RESULTS
There were 1118 reports of nightmares with montelukast in VigiBase, which provided valuable descriptions of the nightmares as well as information about the impact on the daily lives, with many cases describing a severe impact of the nightmares. About half of the reports were classified as serious. Two thirds concerned children, with the largest age group represented being children aged 5-10 years. In most cases, the nightmares disappeared upon discontinuation of the drug but for some patients it took a long time until the nightmares ceased.
CONCLUSIONS
The nature and potential severity of this adverse drug reaction, as described in these reports, present important knowledge for patients and healthcare providers that could help reduce drug-induced harm. This study highlights the value of post-marketing reports for further characterisation of known adverse drug reactions. The benefit-risk balance should be continuously monitored while patients are taking montelukast.
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No pos
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No neg
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Retriever942
|
Paroxysmal nocturnal hemoglobinuria: significant association with specific HLA-A, -B, -C, and -DR alleles in an Italian population.
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the expansion of a PIG-A mutated hematopoietic stem cell. An immune-mediated origin has been suggested for this disease. Because HLA genes represent a susceptibility factor for autoimmunity, we investigated HLA genotype in 42 Italian PNH patients compared with 301 control subjects of the same ethnic origin. A significantly increased frequency of the HLA class I alleles A*0201 (p < 0.05), B*1402 (p < 0.001), and Cw*0802 (p < 0.005), and of the HLA class II DRB1*1501 (p < 0.01) with the linked DQB1*0602 (p </= 0.05) and DRB1*01 (p </= 0.05) with the linked DQB1*0501 (p </= 0.01) alleles, has been observed. Notably, a fourfold increase of the haplotype B*1402, Cw*0802 (p < 0.0005) and a 15-fold increase of the Mediterranean haplotype A*33, B*1402, Cw*0802, DRB1*0102, DQB1*0501 (p < 0.005) was also revealed. This association may provide new insights into the autoimmune pathogenesis of PNH.
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No pos
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No neg
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Retriever943
|
MicroRNA: biogenetic and functional mechanisms and involvements in cell differentiation and cancer.
MicroRNAs (miRNAs) are endogenous small noncoding RNAs (20-23 nucleotides) that negatively regulate the gene expressions at the posttranscriptional level by base pairing to the 3' untranslated region of target messenger RNAs. Hundreds of miRNAs have been identified in humans and evolutionarily conserved from plants to animals. It is revealed that miRNAs regulate various physiological and pathological pathways such as cell differentiation, cell proliferation, and tumoriogenesis. By the computational analysis, it is predicted that 30% of protein-encoding genes are regulated by miRNAs. In this review, we discuss recent remarkable advances in the miRNA biogenetic and functional mechanisms and the involvements of miRNAs in cell differentiation, especially in hematopoietic lineages, and cancer. These evidences offer the possibility that miRNAs would be potentially useful for drug discovery.
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No pos
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No neg
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Retriever944
|
Positive rolandic sharp waves in preterm infants with periventricular leukomalacia: their relation to background electroencephalographic abnormalities.
The aim of this study was to clarify the significance of positive rolandic sharp waves (PRS) in preterm infants with periventricular leukomalacia (PVL) and their relation to background electroencephalographic (EEG) abnormalities. We retrospectively evaluated EEG findings of 93 preterm infants; 31 infants in the PVL group and 62 in the control group. PVL was diagnosed on the basis of ultrasonographic findings. We evaluated the EEG within 3 weeks of life in this study. PRS were defined as sharp transients of positive polarity appearing in the rolandic regions with an amplitude of more than 100 microV, sharply differentiated from the background activities. The number of PRS per minute was calculated over each record. PRS were defined as present when their frequency was beyond 0.1 per minute. PRS were observed in 14 (45%) and disorganized patterns in 27 (87%) of 31 infants in the PVL group, but both were not recognized in any infants in the control group. PRS were always associated with disorganized patterns. In the first EEG, PRS were absent in 8 of 11 infants with more than two recordings, although at least one of acute or chronic stage EEG abnormalities were already present. PRS were observed in 9 of 10 infants with severe diplegia, in 5 of 11 infants with moderate diplegia and none in 10 infants with mild diplegia. The average age of the first appearance of PRS was 7.6 days. The average age of the first appearance of periventricular echodensity and cyst was 4.2 days and 21.1 days, respectively. In conclusion, PRS are related to severe deep white matter injury and could be an early marker of severe PVL. PRS appeared in combination with disorganized patterns and were considered to be incorporated into chronic-stage EEG abnormalities. Detailed evaluation of background EEG activities can be helpful in detecting PVL with a high sensitivity from the early neonatal period.
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No pos
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No neg
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Retriever945
|
Rift Valley fever trasmission dynamics described by compartmental models.
Rift Valley fever (RVF) is one of the most important zoonotic Transboundary Animal Diseases able to cross international borders and cause devastating effect on animal health and food security. Climate changes and the presence of competent vectors in the most of the current RVF-free temperate countries strongly support the inclusion of RVF virus (RVFV) among the most significant emerging viral threats for public and animal health. The transmission of RVFV is driven by complex eco-climatic factors making the epidemiology of RVF infection difficult to study and to understand. Mathematical, statistical and spatial models are often used to explain the mechanisms underlying these biological processes, providing new and effective tools to plan measures for public health protection. In this paper we performed a systematic literature review on RVF published papers with the aim of identifying and describing the most recent papers developing compartmental models for the study of RVFV transmission dynamics.
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No pos
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No neg
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Retriever946
|
Short report: Schistosoma mansoni miracidia are killed by the defense system of an Argentine strain of Biomphalaria straminea.
Biomphalaria straminea snails from Argentina fail to shed cercariae even if exposed to high doses of Schistosoma mansoni EC miracidia. Alternative explanations for this failure are that miracidia are unable to penetrate the snail's epithelium or that the miracidia are killed by the snail's defense system. To discriminate between these 2 possibilities, B. straminea snails were individually exposed to increasing doses of miracidia. Susceptible B. glabrata were used as controls. Exposed snails were fixed 12 hr after exposure, and histological sections of the whole specimens were examined. Miracidia were seen to penetrate the epithelium of B. straminea and B. glabrata at similar rates (14.7%), independent of the exposure level. Regardless of the miracidial dose, 94% of the penetrating miracidia appeared encapsulated by the B. straminea defense system, whereas in B. glabrata, only 42% of the miracidia underwent encapsulation. These results show that resistance of B. straminea to S. mansoni EC strain is due to an efficient defense system that destroys miracidia once they have penetrated.
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No pos
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No neg
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Retriever947
|
Co-localization of corticotropin-releasing factor and vasopressin in median eminence neurosecretory vesicles.
Vasopressin (VP) potentiates the effect of corticotropin-releasing factor (CRF) on the secretion of adrenocorticotropic hormone (ACTH) from anterior pituitary cells in vitro, and both CRF and VP have been found in portal blood. These data support the hypothesis that VP acts synergistically with CRF to cause the secretion of ACTH in vivo but the origin of the CRF and VP, and the physiology of their release, have not been precisely defined. Parvocellular cell bodies in the paraventricular nucleus (PVN) which project to the external zone of the median eminence can be stained for both CRF and VP after adrenalectomy, and there is light microscopic immunocytochemical evidence that neurophysin (NP) may be located within some of the CRF-containing axons. Electron microscopic immunocytochemical studies have demonstrated the presence of CRF, VP and its 'carrier' protein, VP-associated neurophysin (NP-VP) in 100-nm neurosecretory vesicles (NSVs) in axons terminating near the portal capillary plexus in the external zone of the median eminence. If these peptides are extensively co-localized in the same NSVs in the median eminence, then coordinate secretion of CRF and VP in vivo is obligatory, at least in some physiological circumstances. We demonstrate in this report, using post-embedding electron microscopic immunocytochemistry on serial ultrathin sections, that CRF, VP and NP-VP are contained not only in the same axons and terminals, but in the same 100-nm NSVs in the median eminence of both normal and adrenalectomized rats. In addition, in the normal rat median eminence 44% of the CRF-positive axons and terminals stained strongly for VP and NP-VP, whereas in the adrenalectomized rat virtually all the CRF-positive structures in the median eminence showed strong staining for VP and NP-VP, indicating a transformation of one subpopulation of CRF-positive axons and terminals by adrenalectomy.
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No pos
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No neg
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Retriever948
|
Mesenchymal stem cells: a promising tool for targeted gene therapy of endometriosis.
Endometriosis is a leading, benign gynecological disorder around the world. Last few years have witnessed tremendous growth in the field of endometriosis and endometrial stem-cell research. Despite advancements in the biology and pathology of endometriosis, disease recurrence is still an enigma. Gene therapy holds promise in treating many pathologic conditions including endometriosis. Mesenchymal stem cells (MSCs) serve as ideal candidates for regenerative medicine and cell-based therapies. Owing to their specificity to the endometrium, residing endometrial MSC populations could be utilized as ideal candidates for targeting endometrial disorders. Recently, we demonstrated their flexibility for gene transduction using adenoviral vectors. The review highlights the potential of endometrial MSCs in devising targeted gene therapies for endometriosis.
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No pos
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No neg
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Retriever949
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piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism.
piRNAs, a class of small non-coding RNAs associated with PIWI proteins, have broad functions in germline development, transposon silencing, and epigenetic regulation. In diverse organisms, a subset of piRNAs derived from repeat sequences are produced via the interplay between two PIWI proteins. This mechanism, termed "ping-pong" cycle, operates among the PIWI proteins of the primordial mouse testis; however, its involvement in postnatal testes remains elusive. Here we show that adult testicular piRNAs are produced independent of the ping-pong mechanism. We identified and characterized large populations of piRNAs in the adult and postnatal developing testes associated with MILI and MIWI, the only PIWI proteins detectable in these testes. No interaction between MILI and MIWI or sequence feature for the ping-pong mechanism among their piRNAs was detected in the adult testis. The majority of MILI- and MIWI-associated piRNAs originate from the same DNA strands within the same loci. Both populations of piRNAs are biased for 5' Uracil but not for Adenine on the 10th nucleotide position, and display no complementarity. Furthermore, in Miwi mutants, MILI-associated piRNAs are not downregulated, but instead upregulated. These results indicate that the adult testicular piRNAs are predominantly, if not exclusively, produced by a primary processing mechanism instead of the ping-pong mechanism. In this primary pathway, biogenesis of MILI- and MIWI-associated piRNAs may compete for the same precursors; the types of piRNAs produced tend to be non-selectively dictated by the available precursors in the cell; and precursors with introns tend to be spliced before processed into piRNAs.
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No pos
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No neg
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Retriever950
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Measuring the financial productivity of physician assistants.
The first formal physician assistant (PA) program began at Duke University 25 years ago, write David M.S., and Kenneth Harbert, M.H.A., PA-C. Since then, PAs have become widely utilized in the medical field, yet little has been done to measure their financial contribution. The authors provide a methodology and framework for groups to measure the financial productivity of their PAs.
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No pos
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No neg
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Retriever951
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Evaluation of cardiotoxicity in Amazonian fish Bryconops caudomaculatus by acute exposure to aluminium in an acidic environment.
Aluminium (Al) is soluble in acidic waters and may become toxic to organisms. In this study, the acute effects of two Al concentrations were evaluated in the Amazonian fish Bryconops caudomaculatus. Antioxidant responses and lipid damage were assessed in gills, liver and muscle, along with the electrocardiography (ECG) and characterization of cardiac complex and wave intervals. Fish were essayed as follows: two control groups at neutral and acidic pH and two exposure groups at acidic pH (0.3 mg/L and 3.0 mg/L Al). Water samples were collected at 0h, 24h and 48h, for chloride (Cl-), fluoride (F-) and sulphate (SO42-) ion analyses, while total Al was quantified in muscle. Concentrations of Cl- and SO42- were constant over time whereas F- was not detected. Total Al concentrations in water and muscle were concentration-dependent. Antioxidant responses, total antioxidant capacity against peroxyl radicals (ACAP) and glutathione S-transferase were not triggered in fish tissues exposed to 0.3 mg/L Al; however, fish exposed to 3.0 mg/L Al presented increased and reduced ACAP in gills and liver, respectively. No changes in lipoperoxidation levels occurred among groups. Fish exposed to 0.3 mg/L Al showed prolonged intervals in ECG as a reflection of low heart rate (HR), with sinus bradycardia. Moreover, there was a marked prolongation of the PQ interval (time between the atrial activity and the start of ventricular activity), indicating interference on the cardiac cell automaticity. Fish exposed to the highest concentration of Al showed reduced wave intervals as a consequence of increased HR, with sinus arrhythmia, while ECG tracings did not present P waves (atrial contraction), indicating an atrioventricular blockade. In conclusion, 48h exposure sufficed to cause cardiotoxicity in B. caudomaculatus at either Al concentration. However, as oxidative stress was not observed, such cardiac alterations seem to be reversible under the experimental conditions established herein.
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No pos
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No neg
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Retriever952
|
A novel wide-field neuron with branches in the lamina of the Drosophila visual system expresses myoinhibitory peptide and may be associated with the clock.
Although neuropeptides are widespread throughout the central nervous system of the fruifly Drosophila, no records exist of peptidergic neurons in the first synaptic region of the visual system, the lamina. Here, we describe a novel type of neuron that has wide-field tangential arborizations just distal to the lamina neuropil and that expresses myoinhibitory peptide (MIP). The cell bodies of these neurons, designated lateral MIP-immunoreactive optic lobe (LMIo) neurons, lie anteriorly at the base of the medulla of the optic lobe. The LMIo neurons also arborize in several layers of the medulla and in the dorso-lateral and lateral protocerebrum. Since the LMIo resemble LN(v) clock neurons, we have investigated the relationships between these two sets of neurons by combining MIP-immunolabeling with markers for two of the clock genes, viz., Cryptochrome and Timeless, or with antisera to two peptides expressed in clock neurons, viz., pigment-dispersing factor and ion transport peptide. LMIo neurons do not co-express any of these clock neuron markers. However, branches of LMIo and clock neurons overlap in several regions. Furthermore, the varicose lamina branches of LMIo neurons superimpose those of two large bilateral serotonergic neurons. The close apposition of the terminations of MIP- and serotonin-producing neurons distal to the lamina suggests that they have the same peripheral targets. Our data indicate that the LMIo neurons are not bona fide clock neurons, but they may be associated with the clock system and regulate signaling peripherally in the visual system.
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No pos
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No neg
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Retriever953
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Rational Design of a Red-Emissive Fluorophore with AIE and ESIPT Characteristics and Its Application in Light-Up Sensing of Esterase.
The development of red fluorophores with efficient solid-state emission is still challenging. Herein, a red fluorophore 1 with aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) characteristics is rationally designed and facilely synthesized by attaching an electron-donor diethylamine and an electron-acceptor maleonitrile group to salicyladazine. In contrast to many red fluorophores which undergo serious aggregation-caused quenching (ACQ), compound 1 emits bright red fluorescence (λem = 650 nm, ΦF = 24.3%) in the solid state with a large Stokes shift of 174 nm. Interestingly, control compounds 2 and 3, which have similar structures as 1, exhibit obvious aggregation-caused quenching (ACQ) characteristics. The difference in the crystal structures of 1, 2, and 3 reveals that the interplanar spacing among molecules plays a decisive role in realizing the AIE characteristics of 1. Moreover, when the hydroxyl group of 1 was substituted by an esterase reactive acetoxyl, a fluorescence light-up probe 4 was developed for sensing of esterase based on the selective reaction between 4 and esterase to generate the AIE and ESIPT active molecule 1. The linear range for in vitro quantification of esterase is 0.01-0.15 U/mL with a detection limit of 0.005 U/mL. Probe 4 was also successfully applied to image esterase in mitochondria of living cells.
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No pos
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No neg
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Retriever954
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Long non-coding RNA TMPO-AS1 facilitates the progression of colorectal cancer cells via sponging miR-98-5p to upregulate BCAT1 expression.
BACKGROUND AND AIM
Colorectal cancer, as a common malignant carcinoma in the gastrointestinal tract, has a high mortality globally. However, the specific molecular mechanisms of long non-coding RNA (lncRNA) thymopoietin antisense transcript 1 (TMPO-AS1) in colorectal cancer were unclear.
METHODS
We tested the expression level of TMPO-AS1 via qRT-PCR in colorectal cancer cells, while the protein levels of branched chain amino acid transaminase 1 (BCAT1) and the stemness-related proteins were evaluated by western blot analysis. Colony formation, EdU staining, TUNEL, flow cytometry, and sphere formation assays were to assess the biological behaviors of colorectal cancer cells. Then, luciferase reporter, RIP, and RNA pull down assay were applied for confirming the combination between microRNA-98-5p (miR-98-5p) and TMPO-AS1/BCAT1.
RESULTS
TMPO-AS1 was aberrantly expressed at high levels in colorectal cancer cells. Silenced TMPO-AS1 restrained cell proliferation and stemness and promoted apoptosis oppositely, while overexpressing TMPO-AS1 exerted the adverse effects. Furthermore, miR-98-5p was proven to a target of TMPO-AS1 inhibit cell progression in colorectal cancer. Additionally, BCAT1 was proved to enhance cell progression as the target of miR-98-5p, and it offset the effect of silenced TMPO-AS1 on colorectal cancer cells.
CONCLUSION
TMPO-AS1 promotes the progression of colorectal cancer cells via sponging miR-98-5p to upregulate BCAT1 expression.
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No pos
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No neg
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Retriever955
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Safety of deep sedation in the endoscopy suite.
PURPOSE OF REVIEW
As the complexity of endoscopic procedures increases, the use of propofol and the desire for deep sedation are becoming more common in the endoscopy suite. This review explores sedation depth, agents used for sedation, recommended monitoring, and adverse event risks that occur during sedation for endoscopy.
RECENT FINDINGS
The sedation provider for endoscopy varies by practice location and with regulatory requirements. As increasingly deep levels of sedation are used in this setting, the need for all providers to have training in the ability to rescue patients from sedation-related side effects is paramount. Propofol has an important role for prolonged and uncomfortable endoscopic interventions and has a strong safety record in the endoscopy suite. Vital signs monitoring is recommended during all endoscopy sedation, and there is emerging interest in advanced monitoring (e.g., capnography, processed electroencephalogram, respiratory monitoring) in this setting. The reported rate of adverse events during endoscopy sedation varies widely; however, advanced age and increasing American Society of Anesthesiologists physical status score are consistently associated with increased risk. Whether anesthesiologist-administered sedation is safer than non-anesthesiologist-administered sedation remains controversial.
SUMMARY
This review provides some guidance to providers who administer sedation in the endoscopy suite and is intended to improve the safety of patients. The recommendations are based on best available evidence and expert opinion.
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No pos
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No neg
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Retriever956
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Vagococcus fluvialis as a causative pathogen of bloodstream and decubitus ulcer infection: Case report and systematic review of the literature.
BACKGROUND
Vagococcal infections are uncommon in humans; there are limited studies on the clinical manifestations, the optimal methods for identifications, and antimicrobial susceptibility testing for vagococcal infections. Here, we have reported a case of Vagococcus fluvialis-induced bacteremia and decubitus ulcer and have systematically reviewed other reported Vagococcus infections.
CASE PRESENTATION
A 74-year-old man presented to our emergency department with muscle weakness on his left extremities, dysarthria, and altered mental status along with fever for the past 4 days. Physical examination revealed a decubitus ulcer with foul smelling and yellowish exudative pus on his left chest wall and abdomen, forearm, thigh, and lower leg. He was empirically treated with 2.25 mg of piperacillin/tazobactam every 8 hours and 0.5 g of vancomycin every 24 hours intravenously (IV) for his decubitus ulcer. Vagococcus fluvialis was detected in both aerobic and anaerobic blood cultures (upon admission) using the VITEC 2 GP ID card (bioMérieux) and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). We continued the mentioned IV antimicrobial therapies for 4 weeks following which the patient was transferred to a long-term care facility for further rehabilitation.
CONCLUSIONS
To our best knowledge, this is the first literature review of Vagococcus infections in humans. Since it is challenging to distinguish Vagococcus from Enterococcus by a conventional method due to the similarity of its biochemical properties to those of Enterococcus, based on our literature review, 16S rRNA sequencing or analysis of bacterial protein profile using MALDI-TOF MS may be useful for the precise identification.
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No pos
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No neg
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Retriever957
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Hypoxia affects sex differentiation and development, leading to a male-dominated population in zebrafish (Danio rerio).
Hypoxia is affecting thousands of square kilometers of water and has caused declines in fish populations and major changes in aquatic communities worldwide. For the first time, we report that hypoxia can affect sex differentiation and sex development of zebrafish (Danio rerio), leading to a male-biased population in the F1 generation (74.4% +/- 1.7% males in the hypoxic groups versus 61.9% +/- 1.6% males in the normoxic groups, n = 5; p < 0.05, chi2 test). The increase in males was associated with downregulations of various genes controlling the synthesis of sex hormones (i.e., 3beta-HSD, CYP11A, CYP19A, and CYP19B) as well as an increase in the testosterone/estradiol ratio. The male-dominated populations caused by hypoxia will have reduced reproductive success, thereby threatening the sustainability of natural fish populations.
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No pos
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No neg
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Retriever958
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Degradation of Reactive Brilliant Red X-3B by zero-valent iron/activated carbon system in the presence of microwave irradiation.
Reactive Brilliant Red X-3B in aqueous solution could be degraded rapidly by zero-valent iron/activated carbon in the presence of microwave irradiation (ZVI/AC/MW). From the analysis of ultraviolet-visible adsorption, chemical oxygen demand, total organic carbon, infrared spectra and capillary electrophoresis, we found the degradation was complete and no intermediates remained in the final solution treated for 2 min. Considering the many advantages including high degradation ratios, short reaction time, low costs, no intermediates and no secondary pollution, this method might be fit for dealing with various azo dye wastewaters on a large scale.
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No pos
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No neg
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Retriever959
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Characterization of Saccharomyces cerevisiae mutants supersensitive to aminoglycoside antibiotics.
We describe mutants of Saccharomyces cerevisiae that are more sensitive than the wild type to the aminoglycoside antibiotics G418, hygromycin B, destomycin A, and gentamicin X2. In addition, the mutants are sensitive to apramycin, kanamycin B, lividomycin A, neamine, neomycin, paromomycin, and tobramycin--antibiotics which do not inhibit wild-type strains. Mapping studies suggest that supersensitivity is caused by mutations in at least three genes, denoted AGS1, AGS2, and AGS3 (for aminoglycoside antibiotic sensitivity). Mutations in all three genes are required for highest antibiotic sensitivity; ags1 ags2 double mutants have intermediate antibiotic sensitivity. AGS1 was mapped 8 centimorgans distal from LEU2 on chromosome III. Analyses of yeast strains transformed with vectors carrying antibiotic resistance genes revealed that G418, gentamicin X2, kanamycin B, lividomycin A, neamine, and paromomycin are inactivated by the Tn903 phosphotransferase and that destomycin A is inactivated by the hygromycin B phosphotransferase. ags strains are improved host strains for vectors carrying the phosphotransferase genes because a wide spectrum of aminoglycoside antibiotics can be used to select for plasmid maintenance.
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No pos
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No neg
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Retriever960
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Deep-sea Ophiuroidea (Echinodermata) from the Danish Galathea II Expedition, 1950-52, with taxonomic revisions.
The brittle star samples collected by the Danish cruise 'Galathea II' (1950-52) had not been studied completely. We examined the remaining deep-sea samples (400 m) and present the species inventory, discussing taxonomic issues in relation to recent phylogenetic data. About 235 samples were examined, over 9,300 individuals, from 67 species and 74 sampling localities, at depths of 425-5340 m. The species complex Amphiophiura bullata (Thomson, 1877) is morphologically not well separated, but molecular data suggest at least two clades. We propose to apply A. bullata for Atlantic and Australian populations and A. convexa (Lyman, 1878) for the North Pacific clade. We consider A. bullata pacifica Litvinova, 1971 conspecific with A. convexa. Ophiuroglypha irrorata (Lyman, 1878) and its subspecies are a polyphyletic group with unclear morphological boundaries. We propose to transfer Ophiura ossiculata (Koehler, 1908), Ophiura plana (Lütken Mortensen, 1899) and Ophiura scomba Paterson, 1985 to Ophiuroglypha. Silax Fell, 1962, until now synonymised with Amphioplus Verrill, 1899, is proposed as a valid genus with the species S. verrilli (Lyman, 1879), S. consors (Koehler, 1908), S. daleus (Lyman, 1879), S. patulus (Lyman, 1879) and S. magnificus (Koehler, 1907). Triplodia Turner Hallen, 2011 (a replacement name for Triodia A. M. Clark, 1970, due to homonymy) is synonymised with Silax, and possible specimens of its type species Triodia abdita A. M. Clark, 1970 are analysed. The species limits of Ophiacantha cosmica Lyman, 1879 and Ophiacantha pacifica Lütken Mortensen, 1899 could not be confirmed morphologically, but published molecular data suggest two clades. We propose to apply O. pacifica to the Northern/Central Pacific population and O. cosmica to the Southern Pacific/Antarctic population.
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No pos
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No neg
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Retriever961
|
Histologic features of stromogenic carcinoma of the prostate (carcinomas with reactive stroma grade 3).
Prostatic carcinoma, like many other carcinomas, generates a stromal reaction. This phenomenon is well established in the scientific literature. The normal parenchymal smooth muscle phenotype switches to a myofibroblastic phenotype in response to the presence of cancer cells, with an expansion of the extracellular matrix compartment. The amount of reactive stroma is a predictor of biochemical recurrence in both radical prostatectomies and biopsies. It is a predictor of prostate cancer-specific death in prostatectomies. The aim of this study is to improve our histologic understanding of reactive stroma in prostate cancer and to determine the histologic features of the malignant epithelium found in stromogenic carcinomas or carcinomas with reactive stromal grade 3. Tissue microarrays of 800 patients and hematoxylin and eosin-stained sections of 120 radical prostatectomies, previously determined to contain a high proportion of areas with stromogenic carcinoma, were evaluated and findings systematically recorded. We identified 3 histologic patterns of reactive stroma: extracellular matrix-rich, cellular variant and edematous/myxoid variant. The most common pattern of carcinoma in stromogenic areas is of the acinar type with angulated glands and periglandular halos. The nuclei are enlarged, opened, with prominent nucleoli. Luminal borders are undulated, and amorphous pink secretion is often seen. Perineural invasion is frequently identified. Because of the clinical relevance, identification and quantification of areas with high reactive stromal grade by pathologists and reproducibility of our findings by others become essential. We believe that with the previously proposed grading system and the present morphologic description, both can be achieved.
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No pos
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No neg
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Retriever962
|
N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease.
Huntington's disease (HD) is a neurodegenerative disorder, involving psychiatric, cognitive and motor symptoms, caused by a CAG-repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Oxidative stress and excitotoxicity have previously been implicated in the pathogenesis of HD. We hypothesized that N-acetylcysteine (NAC) may reduce both excitotoxicity and oxidative stress through its actions on glutamate reuptake and antioxidant capacity. The R6/1 transgenic mouse model of HD was used to investigate the effects of NAC on HD pathology. It was found that chronic NAC administration delayed the onset and progression of motor deficits in R6/1 mice, while having an antidepressant-like effect on both R6/1 and wild-type mice. A deficit in the astrocytic glutamate transporter protein, GLT-1, was found in R6/1 mice. However, this deficit was not ameliorated by NAC, implying that the therapeutic effect of NAC is not due to rescue of the GLT-1 deficit and associated glutamate-induced excitotoxicity. Assessment of mitochondrial function in the striatum and cortex revealed that R6/1 mice show reduced mitochondrial respiratory capacity specific to the striatum. This deficit was rescued by chronic treatment with NAC. There was a selective increase in markers of oxidative damage in mitochondria, which was rescued by NAC. In conclusion, NAC is able to delay the onset of motor deficits in the R6/1 model of Huntington's disease and it may do so by ameliorating mitochondrial dysfunction. Thus, NAC shows promise as a potential therapeutic agent in HD. Furthermore, our data suggest that NAC may also have broader antidepressant efficacy.
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No pos
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No neg
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Retriever963
|
Escherichia coli associated with childhood diarrheas.
We studied 2,246 episodes of childhood diarrhea over a 2-year period in a general hospital serving a population of about one million on the island of Hong Kong. Rotavirus (24%) and nontyphoid salmonellas (23%) were the most common causal agents, followed by Campylobacter sp. (9%). Rotavirus occurred largely during winter, whereas salmonellas and Campylobacter sp. occurred more commonly during summer and autumn, respectively. Enterotoxigenic Escherichia coli was rarely isolated (1%), and the isolates were clonally diverse. A small percentage (2.8%) of E. coli had serological specificities commonly associated with enteropathogenic E. coli, but only two of the isolates were also positive for HEp-2 adhesive factor. Pure or heavy and predominant growth of E. coli was obtained in repeated stool cultures of 432 (19%) of these episodes, which did not yield any of the above-mentioned pathogens. Although associated with diarrhea, these E. coli isolates possess neither the pathogenic attributes of enterotoxigenic E. coli nor the properties commonly associated with enteropathogenic E. coli. Enteroinvasive E. coli and enterohemorrhagic E. coli were considered unlikely causes on clinical grounds.
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No pos
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No neg
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Retriever964
|
Cathepsin A protein from the accessory sex gland of the Chinese mitten crab (Eriocheir sinensis) plays a key role in spermatophore digestion.
Accessory sex gland (ASG) secretory proteins of the Chinese mitten crab (Eriocheir sinensis) can effectively digest the spermatophore wall. In order to identify which proteins participate in spermatophore wall digestion, a 50-kDa protein secreted from the ASG was purified to homogeneity by a series of isolation steps, including ammonium sulfate fractionation, Sephadex G-25 S gel-filtration, ion exchange chromatography on a DEAE-Sephacel column and Sephacryl S-200 gel-filtration. The purified protein was effective in spermatophore wall rupture, and the subsequent HPLC-ESI-MS/MS shotgun analysis showed the digestive protein to be cathepsin A (cathA). This finding was also confirmed by Western blot analysis and a cathA inhibitor digestion experiment. ELISA analysis showed that cathA enzymatic activity from ASG secretions increased during its purification process. Furthermore, enzymatic activity was significantly higher in the mating period of E. sinensis parallel to the latest developmental stage of the gland. Moreover, analysis from a cathA inhibitor that inhibits spermatophore wall digestion showed that cathA is the main enzyme involved. Hence, we first report the characterization of cathA from the ASG, which might play a key role in digesting the spermatophore wall of E. sinensis.
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No pos
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No neg
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Retriever965
|
[Non-immunologic factor: immunosuppressive drug-induced nephrotoxicity].
Immunosuppressant-induced nephrotoxicity contributes to kidney graft loss in the long-term as one of the non-immunologic factors. We previously reported that correction of cyclosporine A (CsA)-induced hypomagnesemia reduced chronic CsA nephrotoxicity. This study was conducted to elucidate the mechanism of the beneficial effects of magnesium (Mg) on CsA nephrotoxicity and examine the role of the renin-angiotensin system in this mechanism. We particularly focused on CsA-induced interstitial mononuclear cell infiltration. CsA (15 mg/kg/day, s.c.) was administered daily to rats maintained on low sodium diets for 7, 14 and 28 days. The inhibitory effects of Mg supplementation and those of angiotensin converting enzyme inhibitor (ACEI) were compared for renal function, renal histology, mononuclear cell infiltration and gene expression profile. CsA lowered creatinine clearance and developed characteristic tubulointerstitial fibrosis that were mostly evident at day 28. CsA-induced impairment of renal function was ameliorated by Mg supplementation but not by ACEI. Monocyte/macrophage infiltration preceded the renal fibrosis and increased progressively with the duration of CsA administration. CsA markedly upregulated the expression of chemoattractant proteins, osteopontin and monocyte chemoattractant protein-1, concomitantly. These changes were markedly attenuated by Mg but only slightly by ACEI. CsA also promoted expression of fibrogenic molecules and extracellular matrices that were markedly attenuated by Mg but only slightly by ACEI. Similarly, CsA-induced tubulointestitial fibrosis was almost completely abolished by Mg supplementation but only partially attenuated by ACEI. These results suggested that Mg supplementation abolished CsA-induced precedent inflammatory cell influx possibly via inhibition of expression of chemoattractants and consequently suppressed tubulointerstitial fibrosis. In this beneficial mechanism, factors independent of renin-angiotensin system seem to be mainly involved.
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No pos
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No neg
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Retriever966
|
Parents' emotion socialization beliefs moderate relations between parent and patient coping, but not sibling coping, with pediatric cancer.
OBJECTIVE
This study evaluated (a) differences in parents' emotion socialization (ES) beliefs for patients/siblings, (b) whether parents' ES beliefs predict patient/sibling coping, and (c) whether parents' ES beliefs moderate links between parent and patient/sibling coping with pediatric cancer.
METHOD
This was a cross-sectional, questionnaire-based study of 134 pediatric cancer patients, their caregiver, and their nearest-age sibling. Participants could complete measures themselves via paper-and-pencil or telephone, or researchers could read questions aloud.
RESULTS
Parents' ES beliefs differed for patients/siblings. ES beliefs did not directly predict patient/sibling coping but did moderate relations between parent and patient coping.
CONCLUSIONS
Despite extent literature promoting universal emotion coaching ES, our study indicates that ES beliefs might have a complex relation with parent coping in predicting patient coping.
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No pos
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No neg
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Retriever967
|
The Protective Effect of Oxitard on Sperm Function and Antioxidant Status in Rats Exposed to Swimming Stress.
BACKGROUND
Infertility is a significant public health issue, but its impact on quality of life and treatment efficacy is limited. Modern medicine lacks safe and effective drugs for male infertility, while traditional medicine has explored herbal extracts like Oxitard, which contains multiple extracts and oils. This study aimed to investigate the effects of Oxitard on male rats exposed to swimming (SW) stress.
METHODS
Albino rats weighing 220-250 g were divided into five groups: control, SW stress, and SW treated with Oxitard at low, medium, and high doses of 250, 500, and 750 mg/kg/day, respectively. The rats were subjected to SW stress for 15 days and then assessed for body weight, reproductive organ weight, testosterone, antioxidant status, sperm function, and histological changes in the testes, seminal vesicles, and vas deferens.
RESULTS
The results showed that SW stress significantly reduced body weight, seminal vesicle weight, testosterone levels, superoxide dismutase (SOD), catalase (CAT), sperm count, sperm motility, sperm viability, and significantly increased malondialdehyde (MDA) levels. The testes of the SW-stress group rats also showed a significant decrease in spermatogenesis and the number of seminiferous tubules containing sperm. In contrast, treatment with Oxitard, especially at the highest dose, demonstrated potent free radical scavenging activity, recovering antioxidant status, and sperm function.
CONCLUSION
SW stress led to decreased sperm function, antioxidant status, and increased lipid peroxidation (LPO) in male rats. Oxitard treatment, particularly in high doses, showed a potential role as a free radical scavenger in treating oxidative stress (OS)-associated male infertility. Further studies are needed to investigate the individual components of Oxitard and conduct clinical trials in human subjects.
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No pos
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No neg
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Retriever968
|
Hollow Porous CoO@Reduced Graphene Oxide Self-Supporting Flexible Membrane for High Performance Lithium-Ion Storage.
We report an environment-friendly preparation method of rGO-based flexible self-supporting membrane electrodes, combining Co-MOF with graphene oxide and quickly preparing a hollow CoO@rGO flexible self-supporting membrane composite with a porous structure. This unique hollow porous structure can shorten the ion transport path and provide more active sites for lithium ions. The high conductivity of reduced graphene oxide further facilitates the rapid charge transfer and provides sufficient buffer space for the hollow Co-MOF nanocubes during the charging process. We evaluated its electrochemical performance in a coin cell, which showed good rate capability and cycling stability. The CoO@rGO flexible electrode maintains a high specific capacity of 1103 mAh g-1 after 600 cycles at 1.0 A g-1. The high capacity of prepared material is attributed to the synergistic effect of the hollow porous structure and the 3D reduced graphene oxide network. This would be considered a promising new strategy for synthesizing hollow porous-structured rGO-based self-supported flexible electrodes.
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No pos
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No neg
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Retriever969
|
Pre- and intraoperative transcranial Doppler: prediction and surveillance of tolerance to carotid clamping.
We report 91 patients (mean age 70 years) operated upon, prospectively for a total of 100 carotid revascularizations (nine bilateral). Eighty-five of these patients had pre-, intra-, and postoperative transcranial Doppler investigations. Preoperatively, these 85 patients (92 procedures) were classified into two groups based on the results of their Doppler examinations: Group A (65 patients, 72 procedures), those who did not require an intraoperative indwelling shunt and Group B (20 patients, 20 procedures), those who did. The shunt was inserted only when the mean stump (back) pressure was less than 50 mmHg after cross-clamping. Group A all had satisfactory collaterality with a functional anterior and one or two posterior communicating arteries. Group B had no communicating arteries (anterior or posterior) identified by transcranial Doppler. In 17 of 20 patients in this group, the stump pressure was less than 50 mmHg and a shunt was placed. The overall prediction based on Doppler examination of whether or not patients would need a shunt during operation for the two groups A and B (i.e., 92 procedures) was correct in 95.6% (88/92) of cases. Moreover, six hemodynamically significant stenoses (four in the cavernous portion, two in the middle cerebral artery) were disclosed. Sensitivity and specificity of transcranial Doppler as correlated with arteriographic findings were 70 and 90%. Preoperative transcranial Doppler can measure the velocities of the principal cerebral arteries and the collateral capacity of the circle of Willis, and can forecast tolerance to carotid cross-clamping. Intraoperatively, the velocity of flow in the middle carotid artery was correlated with stump pressure, which allowed for surveillance of the shunt.
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No pos
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No neg
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Retriever970
|
Detection of altered extracellular matrix in surface layers of unstable carotid plaque: an optical spectroscopy, birefringence and microarray genetic analysis.
Erosion and rupture of surface layers in atherosclerotic plaque can cause heart attack and stroke; however, changes in luminal surface composition are incompletely defined. Laser-induced fluorescence spectroscopy (LIFS), with limited tissue penetration, was used to investigate the surface of unstable carotid plaque and correlated with microscopy, birefringence and gene expression. Arterial matrix collagens I, III and elastin were assessed in unstable plaques (n = 25) and reference left internal mammary arteries (LIMA, n = 10). LIFS in addition to selective histological staining with picrosirius red, Movat pentachrome and immunostaining revealed decreased elastin and increased collagen I and III (P < 0.05) in carotid plaque when compared with LIMA. Within plaque, collagen I was elevated in the internal carotid region versus the common carotid region. Polarized light microscopy detected layers of aligned collagen and associated mechanical rigidity of the fibrous cap. Microarray analysis of three carotid and three LIMA specimens confirmed up-regulation of collagen I, III and IV, lysyl oxidase and MMP-12. In conclusion, LIFS analysis coupled with microscopy revealed marked regional differences in collagen I, III and elastin in surface layers of carotid plaque; indicative of plaque instability. Birefringence measurements demonstrated mechanical rigidity and weakening of the fibrous cap with complementary changes in ECM gene expression.
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No pos
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No neg
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Retriever971
|
Isolated right ventricular cardiomyopathy in a dog.
Right-sided heart failure was diagnosed in a young dog with clinical and pathologic features of isolated right ventricular cardiomyopathy. This disorder, also referred to as right ventricular dysplasia, is an infrequent cause of heart failure and sudden death in people. Echocardiography of this dog revealed right ventricular and right atrial dilatation and severe right ventricular systolic dysfunction. Left ventricular size and function were normal. Electrocardiography revealed ventricular bigeminy. The configuration of the ectopic beats was similar to that seen with left bundle branch block. The dog died suddenly, and histologic examination of the heart revealed fibroadipose replacement of right atrial and right ventricular myocardium.
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No pos
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No neg
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Retriever972
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Superparamagnetic iron oxide nanoparticle uptake alters M2 macrophage phenotype, iron metabolism, migration and invasion.
Superparamagnetic iron oxide nanoparticles (SPIONs) have shown promise as contrast agents and nanocarriers for drug delivery. Their impact on M2-polarised macrophages has nonetheless not been well studied. Here we explored the effects of SPIONs coated with dimercaptosuccinic acid, aminopropyl silane or aminodextran in two M2 macrophage models (murine primary IL-4-activated bone marrow-derived macrophages and human M2-like differentiated THP-1 cells). All SPIONs were internalised and no cell toxicity was observed. SPION treatment produced reactive oxygen species and activated the extracellular signal-regulated kinase and AKT pathways. After 24-h SPION incubation, M2 macrophages switched their iron metabolism towards an iron-replete state. SPION treatment in both M2 macrophage models altered their M2 activation profiles, promoted IL-10 production, and stimulated protease-dependent invasion. These results highlight the need to evaluate the interactions between SPIONs and cells to take full advantage of the intrinsic properties of these nanoparticles in biological systems.
FROM THE CLINICAL EDITOR
Superparamagnetic iron oxide nanoparticles (SPIONs) have been used as an MRI contrast agent in many experimental studies. The authors here investigated the effects of these nanoparticles on M2 macrophages after cellular uptake. The findings of cell activation further enhanced our current knowledge on the interaction of SPIONS with macrophages.
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No pos
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No neg
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Retriever973
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The impact of portopulmonary hypertension on intraoperative right ventricular function of living donor liver transplant recipients.
BACKGROUND
Portopulmonary hypertension (PPH) burdens a right ventricle (RV) already exposed to physiologic stress during liver transplantation. The magnitude of the impact of PPH on RV function, especially early reperfusion, has not been evaluated adequately by prospective controlled trials. In this study, we prospectively quantified the impact of PPH on the RV function in living donor liver transplant recipients.
METHODS
Twenty patients undergoing living donor liver transplant were stratified based on mean pulmonary artery pressure (mPAP) into a control group (mPAP <25 mm Hg) and a PPH group (mPAP ≥25 mm Hg). Standard anesthetic technique and monitoring were used. Fiberoptic pulmonary artery catheters enabled to measure RV ejection fraction (RVEF) were used. Hemodynamics were recorded after induction of anesthesia, the end of hepatectomy, before portal unclamping, 5 and 30 minutes after reperfusion, and at skin closure.
RESULTS
The PPH group had significantly lower RVEF, stroke volume, and higher central venous pressure and RV end-diastolic volume index after portal unclamping versus the controls. Pulmonary vascular resistance index and mPAP were significantly higher throughout the operation in the PPH group, but RV stroke work index did not differ significantly between groups. RVEF was significantly reduced in the PPH group after reperfusion compared with baseline, but the control group did not experience such a reduction.
CONCLUSIONS
Mild to moderate PPH was associated with reduced RVEF during liver transplantation, especially after reperfusion, likely because of a reduced RV contractile reserve in PPH patients. This reduction in RVEF was clinically well tolerated by patients with mild to moderate PPH.
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No pos
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No neg
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Retriever974
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Assessing creatinine clearance from modification of diet in renal disease study equations in the ADEMEX cohort: limitations and potential applications.
BACKGROUND AND OBJECTIVES
Twenty-four-hour urine and dialysate collections provide accepted means to assess adequacy in peritoneal dialysis (PD). Recent publications suggest that creatinine clearance (CrCl) estimated from the Modification of Diet in Renal Disease (MDRD) equations (eCrCl) accurately approximates measured CrCl (mCrCl) derived from 24-hour collections of urine and dialysate and might serve as an alternative means to assess small-solute clearance and adequacy in PD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Post hoc analysis of data from patients enrolled in ADEMEX was used to assess agreement between mCrCl and eCrCl derived by four- and six-variable MDRD equations (4V-MDRDE and 6V-MDRDE, respectively). Additionally, associations among mCrCl, eCrCl, and survival were determined.
RESULTS
Acceptable precision was observed between mCrCl and 4V-MDRDE-eCrCl and 6V-MDRDE-eCrCl for the entire cohort. Precision was markedly diminished when analysis was limited to functionally anuric patients with mCrCl < 12 ml/min per 1.73 m². Although there was no association between survival and mCrCl, for every 1-ml/min per 1.73 m² increase in 4V- and 6V-MDRDE-eCrCl, there was a 6% and 4% increase in risk of death, respectively. There was a negative association between MDRDE-eCrCl and creatinine appearance rates, suggesting MDRDE-eCrCl is significantly confounded by individual differences in muscle mass.
CONCLUSIONS
MDRDE-eCrCl provides demographically comparable values to 24-hour urine and dialysate collections across the ADEMEX cohort. However, MDRDEs should not be used to assess small-solute removal or adequacy in individual PD patients or to predict outcome in any cohort of patients over narrow ranges of limited clearance.
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No pos
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No neg
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Retriever975
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[A transcultural study of personality in Mexican and English children].
The Junior Eysenck Personality Questionnaire (EPQ-J) was translated into Spanish and was completed by 436 boys and 405 girls from various schools from the southern area of Mexico City, aged 12.12 +/- 1.91 and 11.93 +/- 1.94 years, respectively. The aims of the study were firstly, to show that the factors of psychoticism (P), extraversion (E), neuroticism (N) and social desirability (L) were present and measurable in Mexico. Secondly, to present a valid scoring key for this country, with appropriate items and reasonably high alpha reliabilities. Finally, to make comparisons between Mexican and English children, using only items in common to both scoring keys. Results showed that factor comparisons ranged from 0.91 to 0.99. Sex differences were the usual ones found in most cross-cultural studies, i.e. boys scoring higher than girls on P and E, but lower on N and L. Cross-cultural comparisons found that Mexican children scored higher on E and L than their English counterparts, but lower (for girls only) on N. The four factors were deemed to be measurable in Mexico as well as in England.
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No pos
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No neg
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Retriever976
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[Combined transscleral and transpupillary thermotherapy in large vasoproliferative retinal tumors].
Three cases (two patients) of large vasoproliferative retinal tumor treatment by an original method, which includes intraoperative non-contact transscleral thermotherapy and subsequent transpupillary thermotherapy, are described. Positive anatomical results were achieved in all three cases.
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No pos
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No neg
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Retriever977
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Characterization of the variable region in the class 1 integron of antimicrobial-resistant Escherichia coli isolated from surface water.
Fecal bacteria are considered to be a potential reservoir of antimicrobial resistance genes in the aquatic environment and could horizontally transfer these genes to autochthonous bacteria when carried on transferable and/or mobile genetic elements. Such circulation of resistance genes constitutes a latent public health hazard. The aim of this study was to characterize the variable region of the class 1 integron and relate its genetic content to resistance patterns observed in antimicrobial-resistant Escherichia coli isolated from the surface waters of Patos Lagoon, Southern Brazil. Genetic diversity of the isolates and presence of the qacEΔ1 gene, which confers resistance to quaternary ammonium compounds, were also investigated. A total of 27 isolates were analyzed. The variable region harbored dfrA17, dfrA1 and dfrA12 genes, which confer resistance to trimethoprim, and aadA1, aadA5 and aadA22 genes that encode resistance to streptomycin/spectinomycin. Most of the isolates were considered resistant to quaternary ammonium compounds and all of them carried the qacEΔ1 gene at the 3' conserved segment of the integron. ERIC-PCR analyses of E. coli isolates that presented the integrons showed great genetic diversity, indicating diverse sources of contamination in this environment. These results suggest that fecal bacteria with class 1 integrons in aquatic environments are potentially important reservoirs of antibiotic-resistance genes and may transfer these elements to other bacteria that are capable of infecting humans.
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No pos
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No neg
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Retriever978
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[Vaso-occlusion of the pulmonary artery].
Vaso-occlusion of the pulmonary artery is an angiographic technique which involves the voluntary and precise obstruction, temporary or permanent, performed at the end of diagnostic studies or therapeutic studies on one or several branches of the pulmonary artery. The diagnostic indications are touched on briefly at the end of this review because they are older and better known than the therapeutic indications. The latter has developed in less than 10 years and concerns first and foremost two pathologies: hemoptysis and arterio-venous aneurysms of the lung. The erosive pseudo-aneurysm of the pulmonary artery complicating parenchymatous necrosis above all of infections or tumours should be sought in certain situations and treated by vascular occlusion. The pulmonary arteriovenous aneurysms may equally be treated by selective obstruction of their afferent pedicles by metal spirals or detachable balls. This technique, in sacrificing the minimum of pulmonary parenchyma, should be considered according to each case as a possible supplement or replacement for surgery.
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No pos
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No neg
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Retriever979
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Increased release of tumour cells by collagenase at acid pH: a possible mechanism for metastasis.
The ability of collagenase to disaggregate a solid metastasizing lymphosarcoma has been shown to considerably increase with reducing environmental pH. It is suggested that this effect may be operating in vivo to release cells from a primary tumour.
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No pos
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No neg
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Retriever980
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Distribution of glycoproteins with beta-N-acetylgalactosaminylated N-linked sugar chains among bovine tissues.
Only a small number of glycoproteins has been reported to contain N-linked sugar chains with GalNAcbeta1-->4GlcNAc structure. Our previous studies showed that most glycoproteins from bovine milk fat globule membranes contain beta-N-acetylgalactosaminylated N-linked sugar chains [Sato et al., J. Biochem. 114 (1993) 890-900]. In order to study how widely this glycosylation occurs, lectin blot analysis of membrane glycoproteins from 12 bovine tissues was performed using Wistaria floribunda agglutinin (WFA), which interacts with oligosaccharides terminating with N-acetylgalactosamine. The WFA-positive bands were detected in samples from most tissues except for intestine although the number and reactivity of bands to lectin varied among the tissues. Upon pretreatment of blotted filters with Bacillus beta-N-acetylgalactosaminidase or N-glycanase, no lectin binding was observed. WFA-agarose column chromatography of oligosaccharides released by hydrazinolysis from membrane glycoproteins of bovine tissues except for intestine revealed that a few to 18% of the released oligosaccharides bind and are eluted from the column with 100 mM N-acetylgalactosamine. These results indicate that many glycoproteins from a variety of bovine tissues contain N-linked sugar chains with GalNAcbeta1-->4GlcNAc structure, suggesting a wider occurrence of this glycosylation in bovine tissues.
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No pos
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No neg
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Retriever981
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Research ethics and the use of visual images in research with people with intellectual disability.
The aim of this paper is to encourage debate about the use of creative visual approaches in intellectual disability research and discussion about Internet publication of photographs. Image-based research with people with intellectual disability is explored within the contexts of tighter ethical regulation of social research, increased interest in the use of visual methodologies, and rapid escalation in the numbers of digital images posted on the World Wide Web. Concern is raised about the possibility that tighter ethical regulation of social research, combined with the multitude of ethical issues raised by the use of image-based approaches may be discouraging the use of creative visual approaches in intellectual disability research. Inclusion in research through the use of accessible research methods is also an ethical issue, particularly in relation to those people who have hitherto been underrepresented in research. Visual approaches which have the potential to include people with profound and multiple intellectual disabilities are also discussed.
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No pos
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No neg
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Retriever982
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Discrepancy of coronal morphology between mandibular condyle and fossa is related to pathogenesis of anterior disk displacement of the temporomandibular joint.
OBJECTIVE
To evaluate whether morphological discrepancy between the mandibular condyle and fossa of the temporomandibular joint (TMJ) is related to disk displacement on magnetic resonance imaging (MRI).
STUDY DESIGN
This study included 61 patients with unilateral internal derangement based on both MRI and clinical examination. Coronal morphologies of the condyle and fossa were divided into four groups based on Öberg's classification. According to the coronal morphology of the condyle and fossa, all joints were dichotomized into either harmonized group or a discrepancy group (e.g., angled condyle and concave fossa). The incidence of discrepancy and the relationship of the discrepancy to other findings on MRI were statistically evaluated.
RESULTS
The discrepancy had a significantly higher incidence on the affected side. The discrepancy correlated with incidence of disk deformity on the affected side.
CONCLUSION
Morphological discrepancy between the condyle and fossa is related to development of anterior disk displacement in the TMJ.
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No pos
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No neg
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Retriever983
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Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: a genomic and molecular study.
Activation of telomerase can be observed in almost all human tumor histotypes and detection of the urinary telomerase activities is useful for the diagnosis and surveillance of bladder cancer. In this study, we screened, by Sanger sequencing, 302 patients with various urogenital cancers for somatic mutations in the promoter of the telomerase reverse transcriptase (TERT) gene and determined the clinical relevance of TERT promoter mutations in urogenital cancer. In vitro assays were also performed to evaluate the functional influence of the discovered mutations. We found that the frequencies of somatic mutations in the TERT promoter varied substantially between different types of urogenital tumors (range: 0-63.7%), with urothelial carcinomas showing the highest mutation frequency and prostate cancer showing no mutation. The mutations upregulated the expression of TERT and enhanced the invasiveness of the tumor cells. The mutations were more prevalent in older patients with invasive diseases and advanced tumor stages, and were associated with significantly shorter survival time. Moreover, we also observed a significant co-occurrence of mutations between the TERT promoter and the tumor protein 51/retinoblastoma1 (TP53/RB1) signaling pathway. Hence, TERT promoter mutations may serve as important markers for the differential diagnosis and surveillance of urogenital tumors.
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No pos
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No neg
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Retriever984
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Assessment of hormone refractory prostate cancer.
OBJECTIVES
To define guidelines for the assessment of treatment in patients with hormone-refractory prostate cancer (HRPC).
METHODS
In the light of modern research, and taking new treatment options into account, the Committee essays to specify different categories of patients entering clinical trials, and to define response criteria and those endpoints that are relevant in phase III studies and in short-term follow-up.
RESULTS
HRPC comprises a range of disease states with varying responsiveness to therapy and length of survival. Patients with progression as evaluated by increasing prostate-specific antigen (PSA) values alone have a more favorable prognosis than those presenting with increasing tumor spread. In the assessment of these patients, the modes of previous therapy and the kind of tumor progression must be taken into account. The benefit of treatment of HRPC is often modest. While duration of survival remains the main and ultimate endpoint, the means of measuring short-term responsiveness to therapy are limited. A minority of patients have measurable tumor lesions. Decrease of PSA or other biochemical tumor markers may indicate depression of the tumor activity, but is not always associated with prolongation of survival. A variety of new treatments in HRPC are being investigated. They affect measurable tumor parameters in different ways.
CONCLUSIONS
When a new agent is to be tested, it is important to measure all possible parameters before deciding which particular ones are appropriate for future investigations of this agent. In symptomatic patients, evaluation of subjective parameters, for example, relief of pain or improvement of performance status, is often the most reliable measure of treatment effect. However, these parameters should be clearly defined.
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No pos
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No neg
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Retriever985
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UV-254 degradation of nicotine in natural waters and leachates produced from cigarette butts and heat-not-burn tobacco products.
Nicotine is an important emerging contaminant widely detected in water resources. The main nicotine sources are human excretions from users and leaching from discarded tobacco product waste, which represents the most commonly littered item in urban areas and coasts. In this study, the UV254 photolytical fate of nicotine in natural water and leachates produced from conventional cigarettes (CCs) and the new generation heat-not-burn (HnBs) tobacco products is examined for the first time. The effect of UV254 irradiation on nicotine depletion in ultrapure water was initially studied. The reaction was pseudo first-order with respect to nicotine concentration at low concentrations and shifted to lower order at higher concentrations, an effect associated to absorption saturation. Although nicotine removal was fast, only 9.5% of the total organic carbon was removed after irradiation due to the formation of by-products. The chemical structures of six photo-products were derived by means of liquid and gas chromatography coupled to mass spectrometry. The photodegradation kinetics was found to depend on pH and faster kinetics were recorded when the monoprotonated form of nicotine was dominant (pH = 5-8). The presence of humic acids was found to slightly delay kinetics as they competed with nicotine for lamp irradiance, whereas the presence of salt had no effect on the direct photolysis of nicotine. Direct photolysis studies were also performed using natural waters. Compared to ultra-pure water, photodegradation was found to proceed slightly slower in river water, in similar kinetics in seawater, and relatively faster in rain water. The later was assumed to be due to the lower pH compared to the rest of the natural water tested. Leachates from used HnBs and smoked CCs were also submitted to UV254 irradiation and direct photolysis was found to proceed fast despite the high complexity of these matrices. Nonetheless, the total organic carbon in the system remained the same after irradiation due to the abundance of organics and photo-products formed. We take advantage of the present investigations and report the leaching behavior of nicotine from HnBs and CCs. Among others, we found that in HnBs ~70% of the total and bioavailable nicotine content remains in the tobacco sticks after operation and this percentage drops to 15% in CCs due to the reduction in mass after smoking. This finding demonstrated the importance of properly disposing tobacco product waste to prevent nicotine leaching in water bodies.
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No pos
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No neg
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Retriever986
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The Disease Burden of Atopic Dermatitis.
Recent studies have shed light on the nature of the burden of atopic dermatitis. Analysis of observational data has revealed the effect of atopic dermatitis in diverse areas such as work productivity, physical activity, mood, and risk of comorbidities beyond other atopic conditions. Studies on adults with moderate to severe disease show that the symptoms and consequences of atopic dermatitis affect many aspects of their lives. A clearer understanding of the burden for patients can inform open, sensitive discussions about goals of therapy. Semin Cutan Med Surg 36(supp4):S92-S94.
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No pos
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No neg
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Retriever987
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QSPR/QSAR: State-of-Art, Weirdness, the Future.
Ability of quantitative structure-property/activity relationships (QSPRs/QSARs) to serve for epistemological processes in natural sciences is discussed. Some weirdness of QSPR/QSAR state-of-art is listed. There are some contradictions in the research results in this area. Sometimes, these should be classified as paradoxes or weirdness. These points are often ignored. Here, these are listed and briefly commented. In addition, hypotheses on the future evolution of the QSPR/QSAR theory and practice are suggested. In particular, the possibility of extending of the QSPR/QSAR problematic by searching for the "statistical similarity" of different endpoints is suggested and illustrated by an example for relatively "distanced each from other" endpoints, namely (i) mutagenicity, (ii) anticancer activity, and (iii) blood-brain barrier.
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No pos
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No neg
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Retriever988
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Establishment, Differentiation, Electroporation and Nuclear Transfer of Porcine Mesenchymal Stem Cells.
The limited success of somatic cell nuclear transfer (SCNT) is largely attributed to defects in epigenetic reprogramming of the donor genome. Donor cell types with distinct potential competence may offer different epigenetic flexibility for subsequent genome reprogramming in SCNT. Stem cells possibly enable their genomes to be more readily reprogrammed than differentiated cells. To improve the efficiency of cloning, porcine mesenchymal stem cells (pMSCs) were isolated and well identified by 6-channel flow cytometry and differentiation assays and were used as donors in SCNT. Compared with porcine embryonic fibroblasts (pEFs), our results showed that pMSCs markedly enhanced cloned embryo development in terms of cleavage and blastocyst formation (p < 0.05). To enhance the epigenetic flexibility of pMSCs, classical reprogramming factors (RFs) were transfected by electroporation, and we achieved optimization with ectopic expression of RFs in pMSCs. Our results suggest that the epigenetic status of donor cells has an improvement on genome reprogramming, and multipotent pMSCs favoured subsequent embryonic development.
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No pos
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No neg
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Retriever989
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An unusual case of bilateral virilizing adrenal adenoma co-secreting androgens and cortisol.
We report the case of a 68-year-old woman presenting with clinical and biochemical evidence of hyperandrogenism. Imaging studies revealed the presence of a bilateral adrenal tumor. Although there was a predominant secretion of androgens, autonomous production of cortisol was also evidenced on the basis of an inversion of the circadian rhythm of plasma cortisol and an absence of cortisol suppression by dexamethasone. The functional status of both tumors was demonstrated by an iodocholesterol scintigraphy and by an adrenal vein catheterization. Surgical excision of both adrenal tumors was performed and histological examination disclosed no criteria of malignancy. The patient still remains disease-free 3 years after surgery. To our knowledge, this is the second report of the bilateral occurrence of a virilizing adrenal tumor and the first in which the functional characteristics of the tumors are detailed.
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No pos
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No neg
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Retriever990
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Point mutation affecting processing of the ornithine aminotransferase precursor protein in gyrate atrophy.
A generalized deficiency of the mitochondrial enzyme, ornithine aminotransferase (OAT) is the inborn error in gyrate atrophy, an autosomal recessive degenerative disease of the choroid and retina of the eye that leads to blindness. Southern analysis, using the OAT cDNA probe, of the OAT gene in a gyrate atrophy patient whose level of OAT protein is markedly decreased indicated the functional gene to be grossly intact. Northern analysis of his OAT mRNA demonstrated only half the normal level of OAT message, suggesting expression of only one of the two alleles of the OAT gene. A functional assay of the expressed OAT mRNA by in vitro translation and immunoprecipitation with anti-human OAT antibody indicated synthesis of an OAT protein from the message. The expressed message was cloned and sequenced and was shown to contain a single base change from C to T, resulting in an amino acid codon change from CAT (histidine) to TAT (tyrosine) at position 319 in the translated OAT protein. The mutant and normal OAT precursors were synthesized using transcriptional expression clones of OAT and in vitro translation of the expressed mRNA and tested in an in vitro mitochondrial transport/processing system. The results indicate that the mutant OAT precursor from the gyrate atrophy patient can be transported to the mitochondria but is minimally processed there, which would lead to degradation of the labile precursor and loss of OAT activity as phenotypically observed.
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No pos
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No neg
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Retriever991
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Steady-state pharmacokinetics of diltiazem and hydrochlorothiazide administered alone and in combination.
Diltiazem and hydrochlorothiazide are widely used to treat cardiovascular disease, often in combination. The purpose of this investigation was to determine whether a drug-drug pharmacokinetic interaction exists between diltiazem and hydrochlorothiazide. In a randomized, crossover, open study, multiple doses of diltiazem (60 mg four times daily for 21 doses) and hydrochlorothiazide (25 mg twice daily for 11 doses) were administered alone and in combination on three separate occasions to 20 healthy male volunteers. Trough and serial blood samples were collected and plasma was assayed for diltiazem, hydrochlorothiazide, and diltiazem metabolites (desacetyldiltiazem and N-desmethyldiltiazem) using HPLC. Total urine was also collected and quantified for hydrochlorothiazide. Coadministered hydrochlorothiazide did not significantly (p > 0.05) alter diltiazem (alone versus combination) steady-state maximum plasma concentration (Css(max); 145 versus 158 ng mL(-1), respectively), time to maximum plasma concentration (t(max); 3.0 versus 2.8 h, respectively); area under the plasma concentration-time curve (AUCss; 688 versus 771 ng x h mL(-1)), oral clearance (Cl(oral); 96.2 versus 88.0 L h(-1)), or elimination half-life (t(1/2); 5.2 versus 5.2 h). Similarly, administration of diltiazem did not significantly (p > 0.05) influence hydrochlorothiazide (alone versus combination) Css(max) (221 versus 288 ng mL(-1)), t(max) (1.8 versus 2.0 h), AUCss (1194 versus 1247 ng x h mL(-1)), Cl(oral) (22.4 versus 21.2 L h(-1)); t(1/2) (9.8 versus 9.6 h), or renal Cl (15.5 versus 15.2 L h(-1)). In conclusion, a clinically significant pharmacokinetic interaction between diltiazem and hydrochlorothiazide does not exist.
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No pos
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No neg
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Retriever992
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Diffuse alveolar hemorrhage: diagnosing it and finding the cause.
Diffuse alveolar hemorrhage is an acute, life-threatening event, and repeated episodes can lead to organizing pneumonia, collagen deposition in small airways, and, ultimately, fibrosis. Among the many conditions it can accompany are Wegener granulomatosis, microscopic polyangiitis, Goodpasture syndrome, connective tissue disorders, antiphospholipid antibody syndrome, infectious or toxic exposures, and neoplastic conditions. Its many causes and presentations pose an important challenge to the clinician.
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No pos
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No neg
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Retriever993
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The Effect of Age, Gender and Comorbidities Upon SARS-CoV-2 Spike Antibody Induction After Two Doses of Sinopharm Vaccine and the Effect of a Pfizer/BioNtech Booster Vaccine.
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 emerged in China in 2019 and has since travelled the world infecting millions. SARS-CoV-2 causes Corona Virus Disease (COVID-19), that has to date taken over 4 million lives. The Kingdom of Bahrain's vaccine roll-out has consisted of Sinopharm's BBIBP-CorV (Sinopharm) and Pfizer/BioNtech's BNT162b2 (Pfizer/BioNtech). Testing for SARS-CoV-2 anti-Spike (S) antibodies is a useful technique in estimating an individual's immune protection against the infection. In this study we evaluated S antibody levels by electro-chemiluminescence immunoassay in 379 individuals double vaccinated with Sinopharm and 15 of whom were given a booster with the Pfizer/BioNtech vaccine. Among our double vaccinated cohort, we found a spectrum of S antibody levels. Indeed, we found that a significant proportion of individuals with low S antibody levels had clinical conditions, which were mainly immune-related disorders. Furthermore, a significant proportion of individuals with low S antibody levels were above 50 years of age. Finally, we observed a significant increase in S antibody levels after the Pfizer/BioNtech booster was administered. These findings reveal that while a large proportion of Sinopharm vaccinated individuals did not develop high levels of antibodies against the S protein, a booster dose of the Pfizer/BioNtech vaccine significantly enhances S antibody levels, revealing this "triple dose" vaccination strategy as a useful method of ensuring protective immunity against SARS-CoV-2.
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No pos
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No neg
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Retriever994
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Computer-assisted multistep chemoenzymatic retrosynthesis using a chemical synthesis planner.
Chemoenzymatic synthesis methods use organic and enzyme chemistry to synthesize a desired small molecule. Complementing organic synthesis with enzyme-catalyzed selective transformations under mild conditions enables more sustainable and synthetically efficient chemical manufacturing. Here, we present a multistep retrosynthesis search algorithm to facilitate chemoenzymatic synthesis of pharmaceutical compounds, specialty chemicals, commodity chemicals, and monomers. First, we employ the synthesis planner ASKCOS to plan multistep syntheses starting from commercially available materials. Then, we identify transformations that can be catalyzed by enzymes using a small database of biocatalytic reaction rules previously curated for RetroBioCat, a computer-aided synthesis planning tool for biocatalytic cascades. Enzymatic suggestions captured by the approach include ones capable of reducing the number of synthetic steps. We successfully plan chemoenzymatic routes for active pharmaceutical ingredients or their intermediates (e.g., Sitagliptin, Rivastigmine, and Ephedrine), commodity chemicals (e.g., acrylamide and glycolic acid), and specialty chemicals (e.g., S-Metalochlor and Vanillin), in a retrospective fashion. In addition to recovering published routes, the algorithm proposes many sensible alternative pathways. Our approach provides a chemoenzymatic synthesis planning strategy by identifying synthetic transformations that could be candidates for enzyme catalysis.
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No pos
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No neg
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Retriever995
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Regulation of mitochondrial protein synthesis by cytoplasmic proteins.
Isolated yeast mitochondria, which synthesize identifiable polypeptides identical to those made in vivo, have been used in an invitro system to study cytoplasmic control of mitochondrial protein synthesis. It has been found that protein synthesis in isolated mitochondria is dependent on an endogenous pool of cytoplasmically synthesized proteins present within mitochondria at the time of isolation, that protein synthesis ceases apparently when this pool of proteins is depleted, and that a cytoplasmic extract can restore protein synthesis in depleted mitochondria. By use of depleted mitochondria to assay for stimulatory factors it has been found that the bulk of the stimulatory activity in the cytoplasm is of a protein nature and resides predominantly in the postpolysomal supernatant. At least one cytoplasmic stimulatory protein appears to exert a specific effect on the synthesis of subunits I-III of cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1).
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No pos
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No neg
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Retriever996
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Mislabeling of cases, specimens, blocks, and slides: a college of american pathologists study of 136 institutions.
CONTEXT
Accurate specimen labeling is a major patient-safety initiative by the Joint Commission and the College of American Pathologists. Inadequate specimen labels have led to patient injury from wrong patient diagnosis, wrong side treatment, and delay in diagnosis.
OBJECTIVES
To quantify the rates of mislabeled cases, specimens, blocks, and slides and to identify the sources of error and the ways in which errors are detected.
DESIGN
In this voluntary-subscription Q-Probes study, participants prospectively reviewed surgical pathology cases for 8 weeks or until 30 errors (mislabeled cases, specimens, blocks, and slides) were identified. Information collected on each labeling error included the work location where the defect occurred, what was mislabeled, the number of items affected, the point of detection, and the consequences of the mislabeling error, along with institutional demographics and practice. The rates of mislabeled cases, specimens, blocks, and slides were tested for association with institutional demographics and practice variables.
RESULTS
Of the 136 institutions providing information on a total of 1811 mislabeling occurrences, the overall mislabeling rates per 1000 were 1.1 cases, 1.0 specimen, 1.7 blocks, and 1.1 slides. Of all mislabeling events, 27.1% were cases, 19.8% specimens, 25.5% blocks, and 27.7% slides. The work locations at which the errors occurred were 20.9% before accessioning, 12.4% at accessioning, 21.7% at block labeling, 10.2% during gross pathology, and 30.4% at tissue cutting. Errors were typically detected in the first or second steps immediately following the error. Lower mislabeled slide rates were associated with continuous individual case accessioning and use of formal checks at accessioning. Routinely including a statement in the gross description that the specimen is labeled with the patient's name and is properly identified was also associated with lower rates of specimen mislabeling. The errors were corrected before reports were issued 96.7% of the time; for 3.2% of errors, a corrected report was issued. In 1.3% of error occurrences, participants gauged that patient care was affected.
CONCLUSIONS
This study quantified mislabeling rates across 136 institutions of cases (0.11%), specimens (0.1%), blocks (0.17%), and slides (0.11%). Errors in labeling appear nearly equally throughout the system of accessioning, gross pathology processing, and tissue cutting. Errors are typically detected in the immediate steps after the errors occurred, reinforcing the need for quality checks throughout the system.
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No pos
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No neg
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Retriever997
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Tranilast attenuates TGF-β1-induced epithelial-mesenchymal transition in the NRK-52E cells.
We previously reported that tranilast can halt the pathogenesis of chronic cyclosporine nephrotoxicity in rats via the transforming growth factor-β (TGF-β) /Smad pathway, an important signaling system involved in epithelial-mesenchymal transition (EMT), but the exact underlying cellular mechanisms are not yet clear. Thus, by selecting TGF-β1-induced normal rat kidney proximal tubular epithelial cells (NRK-52E) as a model, we demonstrated potential modifying effect of tranilast on EMT-induced by TGF-β1 in vitro. NRK-52E cells were incubated with the blank vehicle (Dulbecco's modified Eagle's medium and F-12 (DMEM/F12) added with 10% fetal bovine serum (FBS)), 10 ng/ml TGF-β1 alone or together with 100, 200 or 400μM tranilast for 48 h after incubation in medium containing 1% FBS for 24 h. Cell morphological changes were observed to confirm occurrence of EMT. Protein expressions of two typical markers of EMT, E-cadherin and α-smooth muscle actin (α-SMA), were assessed by western blotting and flow cytometry, respectively. Our results showed that TGF-β1 induced spindle-like morphological transition, the loss of E-cadherin protein and upregulation of expression of α-SMA. However, the TGF-β1-produced changes in cellular morphology, E-cadherin and α-SMA were inversed by tranlilast in concentration-dependent manner. Our findings indicate that tranilast can directly inhibit EMT. Thus, it may be implied that regulation of EMT be the target to prevent renal tubulointerstitial fibrosis.
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No pos
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No neg
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Retriever998
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Satellite tracking reveals novel migratory patterns and the importance of seamounts for endangered South Pacific humpback whales.
The humpback whale population of New Caledonia appears to display a novel migratory pattern characterized by multiple directions, long migratory paths and frequent pauses over seamounts and other shallow geographical features. Using satellite-monitored radio tags, we tracked 34 whales for between 5 and 110 days, travelling between 270 and 8540 km on their southward migration from a breeding ground in southern New Caledonia. Mean migration speed was 3.53±2.22 km h(-1), while movements within the breeding ground averaged 2.01±1.63 km h(-1). The tag data demonstrate that seamounts play an important role as offshore habitats for this species. Whales displayed an intensive use of oceanic seamounts both in the breeding season and on migration. Seamounts probably serve multiple and important roles as breeding locations, resting areas, navigational landmarks or even supplemental feeding grounds for this species, which can be viewed as a transient component of the seamount communities. Satellite telemetry suggests that seamounts represent an overlooked cryptic habitat for the species. The frequent use by humpback whales of such remote locations has important implications for conservation and management.
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No pos
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No neg
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Retriever999
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Pre-exposure to 50 Hz magnetic fields modifies menadione-induced genotoxic effects in human SH-SY5Y neuroblastoma cells.
BACKGROUND
Extremely low frequency (ELF) magnetic fields (MF) are generated by power lines and various electric appliances. They have been classified as possibly carcinogenic by the International Agency for Research on Cancer, but a mechanistic explanation for carcinogenic effects is lacking. A previous study in our laboratory showed that pre-exposure to ELF MF altered cancer-relevant cellular responses (cell cycle arrest, apoptosis) to menadione-induced DNA damage, but it did not include endpoints measuring actual genetic damage. In the present study, we examined whether pre-exposure to ELF MF affects chemically induced DNA damage level, DNA repair rate, or micronucleus frequency in human SH-SY5Y neuroblastoma cells.
METHODOLOGY/PRINCIPAL FINDINGS
Exposure to 50 Hz MF was conducted at 100 µT for 24 hours, followed by chemical exposure for 3 hours. The chemicals used for inducing DNA damage and subsequent micronucleus formation were menadione and methyl methanesulphonate (MMS). Pre-treatment with MF enhanced menadione-induced DNA damage, DNA repair rate, and micronucleus formation in human SH-SY5Y neuroblastoma cells. Although the results with MMS indicated similar effects, the differences were not statistically significant. No effects were observed after MF exposure alone.
CONCLUSIONS
The results confirm our previous findings showing that pre-exposure to MFs as low as 100 µT alters cellular responses to menadione, and show that increased genotoxicity results from such interaction. The present findings also indicate that complementary data at several chronological points may be critical for understanding the MF effects on DNA damage, repair, and post-repair integrity of the genome.
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No pos
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No neg
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