Miracle-dz/UniFAR-FTUs huggingface dataset:
Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection

C-Tb, a novel Mycobacterium tuberculosis and 6-kDa early secretory antigenic target/10-kDa culture filtrate protein (ESAT-6/CFP-10)-specific skin test, has high specificity in bacille Calmette–Guerin-vaccinated healthy controls. However, the sensitivity of C-Tb has hitherto not been determined. The objective was to determine the sensitivity of C-Tb in patients with active tuberculosis (TB) in comparison with the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT). C-Tb and TST were randomly administered in a double-blinded fashion to one or the other forearm in 253 patients with active TB with or without HIV co-infection. QFT-GIT testing was performed prior to skin testing. Using a receiver operating characteristic curve-derived cut-point of 5 mm, C-Tb sensitivity was similar to QFT-GIT (73.9 (95% CI 67.8–79.3) versus 75.1 (95% CI 69.3–80.2)), and similar in HIV-infected and HIV-uninfected patients (76.7 (95% CI 69.0–83.3) versus 69.5 (95% CI 59.2–78.5)). However, sensitivity was significantly diminished in HIV-infected patients with CD4 counts <100 cells·mm–3. C-Tb and QFT-GIT combined had significantly higher sensitivity than C-Tb alone (p<0.0001). C-Tb was safe with no significant adverse events. The 5 mm cut-point corresponded to that found in the previously published specificity study (TESEC-04). C-Tb has similar sensitivity compared with QFT-GIT for the diagnosis of M. tuberculosis infection. Sensitivity was reduced only in HIV-infected patients with severe immunosuppression. Further studies in different settings are required to validate the proposed 5 mm cut-point. C-Tb has similar sensitivity compared with QFT-GIT for the diagnosis of M. tuberculosis infection http://ow.ly/TtFf6
CBCT for the assessment of second mesiobuccal (MB2) canals in maxillary molar teeth: effect of voxel size and presence of root filling.

AIM To compare detection of the second mesiobuccal (MB2) canal in maxillary molar teeth using cone-beam computed tomography (CBCT) with different voxel sizes against conventional radiographic examination when the MB1 was unprepared, prepared and filled. METHODOLOGY Radiographic examination and 0.2-, 0.25- and 0.3-mm CBCT (n = 89) were performed in 3 stages: S1, no first mesiobuccal (MB1) canal preparation or filling; S2, after MB1 preparation and filling; and S3, after MB1 root canal filling removal and canal repreparation. Images were analysed using the i-Cat software. After RE and CBCT acquisition in S3, all the samples were clarified to directly visualize the presence of the MB2 canal. All images were analysed by a blinded, previously calibrated examiner. Accuracy, specificity and sensitivity were compared using analysis of variance (P < 0.05 level of significance). RESULTS MB2 root canals were detected in 67% of the samples. Overall, radiographic examination was associated with lower mean accuracy values for detecting MB2 than CBCT regardless of the MB1 condition. The MB1 root canal condition did not influence MB2 detection in 0.2-mm voxel images. The presence of root fillings in the MB1 canals reduced the detection of MB2 canals, especially in the 0.3- and 0.25-mm voxel-size images (P < 0.05). CONCLUSION CBCT was associated with higher mean values of specificity and sensibility than radiographic examination for the detection of MB2 canals. When endodontic retreatment is necessary removal of the root filling prior to the CBCT examination eliminates artefacts, thereby permitting the use of the 0.3-mm voxel protocol that has good diagnostic performance and lower radiation dose.
Mucosally induced Immunological Tolerance, Regulatory T Cells and the Adjuvant Effect by Cholera Toxin B Subunit

Induction of peripheral immunological tolerance by mucosal administration of selected antigens (Ags) (‘oral tolerance’) is an attractive, yet medically little developed, approach to prevent or treat selected autoimmune or allergic disorders. A highly effective way to maximize oral tolerance induction for immunotherapeutic purposes is to administer the relevant Ag together with, and preferably linked to the non‐toxic B subunit protein of cholera toxin (CTB). Oral, nasal or sublingual administration of such Ag/CTB conjugates or gene fusion proteins have been found to induce tolerance with superior efficiency compared with administration of Ag alone, including the suppression of various autoimmune disorders and allergies in animal models. In a proof‐of‐concept clinical trial in patients with Behcet’s disease, this was extended with highly promising results to prevent relapse of autoimmune uveitis. Tolerization by mucosal Ag/CTB administration results in a strong increase in Ag‐specific regulatory CD4+ T cells, apparently via two separate pathways: one using B cells as APCs and leading to a strong expansion of Foxp3+ Treg cells which can both suppress and mediate apoptotic depletion of effector T cells, and one being B cell‐independent and associated with development of Foxp3‐ regulatory T cells that express membrane latency‐associated peptide and transforming growth factor (TGF‐β) and/or IL‐10. The ability of CTB to dramatically increase mucosal Ag uptake and presentation by different APCs through binding to GM1 ganglioside (which makes most B cells effective APCs irrespective of their Ag specificity), together with CTB‐mediated stimulation of TGF‐β and IL‐10 production and inhibition of IL‐6 formation may explain the dramatic potentiation of oral tolerance by mucosal Ags presented with CTB.
Relation Between Right Ventricular Function and Increased Right Ventricular [18F]Fluorodeoxyglucose Accumulation in Patients With Heart Failure

Background—Left heart failure is characterized by alterations in metabolic substrate utilization, and metabolic modulation may be a future strategy in the management of heart failure. Little is known about cardiac metabolism in the right ventricle and how it relates to other measures of right ventricular (RV) function. This study was designed to measure glucose metabolism in the right ventricle, as estimated by [18F]fluorodeoxyglucose (FDG) positron emission tomography imaging and to determine the relation between RV function and FDG uptake in patients with heart failure. Methods and Results—A total of 68 patients underwent cardiac [18F]FDG positron emission tomography scanning with measurement of RV FDG uptake as a standardized uptake value. Perfusion imaging was acquired at rest with rubidium-82 or [13N]ammonia. RV function was determined by equilibrium radionuclide ventriculography. Relative RV FDG uptake was determined as the ratio of RV to LV standardized uptake value. Fifty-five percent of these patients had ischemic cardiomyopathy. The mean LV and RV ejection fractions were 21±7% and 35±10%, respectively. There was a correlation between RV ejection fraction and the ratio of RV to LV FDG uptake whether the entire LV myocardium (r=−0.40, P<0.001) or LV free wall (r=−0.43, P<0.001) was used. This relation persisted in the subgroup with nonischemic cardiomyopathy (r=−0.37, P=0.04). RV FDG uptake was weakly related to increased RV systolic pressure but not related to LV size, function, or FDG uptake. The correlation between RV ejection fraction and RV/LV FDG was maintained after partial-volume correction (r=−0.68, P<0.001). Conclusions—RV dysfunction is associated with an increase in RV FDG uptake, the magnitude of which may be correlated with severity.
Clinical comparison of BACTEC 9240 plus aerobic/F resin bottles and the isolator aerobic culture system for detection of bloodstream infections

The Plus Aerobic/F resin bottle of the BACTEC 9240 automated blood culture system (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) was compared with aerobic culture of the Isolator system (Wampole Laboratories, Cranbury, N.J.) for the detection of bloodstream microorganisms from 6,145 blood cultures collected from adult patients with suspected septicemia. The BACTEC resin bottles were incubated for 7 days, and the sediment from the Isolator tube was inoculated to sheep blood and chocolate agars which were incubated for 72 h and to inhibitory mold, brain heart infusion, and Sabouraud agars which were incubated for 21 days. A total of 622 microorganisms were recovered from 583 blood cultures. The BACTEC resin bottle recovered statistically significantly more pathogens overall than the Isolator system (P = 0.0006). When individual pathogens isolated from either system for a 7-day study period were assessed, it was determined that the BACTEC resin bottle detected statistically significantly more isolates of Staphylococcus aureus (P = 0.0113) and coagulase-negative Staphylococcus spp. (P = 0.0029) than the Isolator system. The BACTEC resin bottle also detected statistically significantly more bloodstream infections (septic episodes) caused by coagulase-negative Staphylococcus spp. (P = 0.0146). The Isolator system recovered statistically significantly more contaminants overall (P < 0.0001), and among this group of microorganisms, recovered statistically significantly more Bacillus spp. (P < 0.0001), coagulase-negative Staphylococcus spp. (P < 0.0001), and viridans group Streptococcus spp. (P = 0.0156). The Isolator system detected statistically significantly more isolates of Histoplasma capsulatum (P = 0.004), but all of these isolates were detected at > or = 7 days of incubation of fungal plates, i.e., after the system to system comparison study period (7 days). In blood culture sets which produced growth of the same pathogen in both systems, there was a statistically significant difference in median time to detection for all pathogens combined favoring the BACTEC resin bottle over the Isolator tube (P < 0.05). When assessing individual microorganisms, the median times for detection of S. aureus, Enterococcus spp. , and Pseudomonas spp. were all statistically significantly less for the BACTEC system (P < 0.05). The BACTEC instrument had 79 (1.3%) false positive signals. The BACTEC system required less processing time than the Isolator system and eliminates the hands-on time for detection of positive cultures required with the Isolator system.
Safety and Effectiveness of Donepezil on Behavioral Symptoms in Patients With Alzheimer Disease

The objective of this study was to evaluate the prevalence and treatment responsiveness of neuropsychiatric symptoms in patients with mild to moderately severe Alzheimer disease recruited in a naturalistic treatment setting in Spain. All the patients, who matched the prescribing recommendations for donepezil and were able to participate in the study, received donepezil (5 to 10 mg/d) for 6 months. The primary outcome measure was the incidence of adverse events. Secondary outcome measures were neuropsychiatric function measured by the Neuropsychiatric Inventory (NPI), the Mini-Mental State Evaluation, and caregiver burden measured by the Zarit scale. Five hundred and twenty-nine patients were included of which 455 completed the study. The mean baseline NPI score was 19.1. Sixty-five patients (12.3%) experienced an adverse event. The most frequent adverse events were diarrhea and agitation (<2%). Seventeen patients (3%) presented with a neuropsychiatric adverse event and 11 (2%) patients presented with a neurologic adverse event over the course of the study. NPI scores improved by 34.4% over the course of the study, with all items showing a statistically significant improvement. Mini-Mental State Evaluation scores and Zarit caregiver burden scores also improved by 1.27 points and 5.9 points, respectively. This study showed a low incidence of adverse events accompanied by an improvement in the neuropsychiatric and cognitive functions in patients with mild to moderately severe Alzheimer disease treated with donepezil in a community setting in Spain. Donepezil also reduced caregiver burden.
Mutation of Drosophila focal adhesion kinase induces bang‐sensitive behavior and disrupts glial function, axonal conduction and synaptic transmission

The role of the conserved focal adhesion kinase (FAK) family of protein tyrosine kinases in the development and physiological functions of the CNS has long been an area of interest among neuroscientists. In this report, we observe that Drosophila mutants lacking Fak56 exhibit a decreased lifespan, accompanied by a bang‐sensitive phenotype, which is characterized by sensitivity to mechanical and high‐frequency electrical stimulation. Fak56 mutant animals display lower thresholds and higher rates of seizures in response to electroconvulsive stimuli. Direct measurements of action potential conduction in larval segmental nerves demonstrate a slowed propagation speed and failure during high‐frequency nerve stimulation. In addition, neuromuscular junctions in Fak56 mutant animals display transmission blockade during high‐frequency activity as a result of action potential failure. Endogenous Fak56 protein is abundant in glial cells ensheathing the axon bundles, and structural alterations of segmental nerve bundles can be observed in mutants. Manipulation of Fak56 function specifically in glial cells also disrupts action potential conduction and neurotransmission, suggesting a glial component in the Fak56 bang‐sensitive phenotype. Furthermore, we show that increased intracellular calcium levels result in the dephosphorylation of endogenous Fak56 protein in Drosophila cell lines, in parallel with our observations of highly variable synaptic potentials at a higher Ca2+ level in Fak56 mutant larvae. Together these findings suggest that modulation of Fak56 function is important for action potential propagation and Ca2+‐regulated neuromuscular transmission in vivo.
Neurological mechanism of Xiaochaihutang's antidepressant‐like effects to socially isolated adult rats

Xiaochaihutang (XCHT) has antidepressant effects in multiple animal models of depression in our previous studies. But the antidepressant effects and exact mechanisms of XCHT in a rat model of chronic social isolation stress (CSIS) have never been studied. We therefore aimed to investigate the effects of XCHT on depressive/anxiety‐related behaviours of CSIS‐exposed rats and understand the neurological mechanism involving neurogenesis.
MiR-497 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting VEGFA and AEG-1

Hepatocellular carcinoma (HCC) is a worldwide malignance and displays marked vascular abnormalities and active metastasis. MicroRNAs (miRNAs) have been shown to play important roles in regulating tumor properties in cancer, however, whether miR-497 contributes to HCC angiogenesis or metastasis remains unclear. In this study, we found that miR-497 was significantly down-regulated in HCC tissue samples and cell lines. Gain-of-function and loss-of-function studies revealed that miR-497 could repress both the pro-angiogenic and metastatic ability of HCC cells. Subsequent investigations disclosed that miR-497 directly inhibited the 3′-untranslated regions (UTRs) of vascular endothelial growth factor A (VEGFA) and astrocyte elevated gene-1 (AEG-1). Furthermore, overexpression of these targets antagonized the function of miR-497. Based on nude mouse models, we demonstrated that overexpression of miR-497 significantly repressed microvessel densities in xenograft tumors and reduced pulmonary metastasis. In conclusion, our findings indicate that miR-497 downregulation contributes to angiogenesis and metastasis in HCC.
Protective effect of administration of Withania somifera against bromobenzene induced nephrotoxicity and mitochondrial oxidative stress in rats

Abstract Background: The present study was conducted to elucidate the protective role of Withania somnifera against bromobenzene induced nephrotoxicity and mitochondrial dysfunction in rats. Methods: In this study, Wistar albino rats of either sex were divided into six groups consisting of six animals each. The first one was control, those in group II received bromobenzene (10 mmol/kg, intragastric intubation) once, but group III and IV animals received W. somnifera (250 and 500 mg/kg, orally), respectively for 8 days followed by bromobenzene once on the 8th day and silymarin (100 mg/kg, orally) was given for 8 days to group V animals and then bromobenzene on the last day. Group VI animals received only W. somnifera (500 mg/kg) for 8 days. Results: The levels of renal lipid peroxidation, lysosomal enzymes and glycoprotein were increased significantly (p < 0.05) in the bromobenzene alone treated rats and antioxidant status and mitochondrial enzymes were found to be decreased, when compared to the control group. The levels of kidney functional markers (urea, uric acid and creatinine) were also found to be abnormal in serum of bromobenzene alone treated rats. On the other hand, administration of W. somnifera (250 and 500 mg/kg) along with bromobenzene offered a significant dose-dependent protection to the biochemical alterations as observed in the bromobenzene alone treated rats, which was also evidenced by histopathology. Conclusion: Thus, the oral administration of W. somnifera significantly protected against the bromobenzene induced nephrotoxicity and renal mitochondrial dysfunction in rats.
Mindsets That Promote Resilience: When Students Believe That Personal Characteristics Can Be Developed

Because challenges are ubiquitous, resilience is essential for success in school and in life. In this article we review research demonstrating the impact of students’ mindsets on their resilience in the face of academic and social challenges. We show that students who believe (or are taught) that intellectual abilities are qualities that can be developed (as opposed to qualities that are fixed) tend to show higher achievement across challenging school transitions and greater course completion rates in challenging math courses. New research also shows that believing (or being taught) that social attributes can be developed can lower adolescents’ aggression and stress in response to peer victimization or exclusion, and result in enhanced school performance. We conclude by discussing why psychological interventions that change students’ mindsets are effective and what educators can do to foster these mindsets and create resilience in educational settings.
Sonographically Guided Percutaneous Needle Tenotomy for the Treatment of Chronic Tendinosis

Objective. Initial reports have shown percutaneous sonographically guided needle tenotomy without corticosteroid injection to be effective for the treatment of tennis elbow. The purpose of this study was to determine the effectiveness of this procedure with various tendons throughout the body. Methods. Fourteen tendons in 13 patients were identified as having a greater than 6‐month history of clinical presentation consistent with tendinopathy that had failed treatment with physical therapy. All patients were treated with sonographically guided percutaneous tenotomy using a 22‐gauge needle and a local anesthetic. A visual analog scale (VAS) pain score measurement was obtained before the procedure and at 4‐ and 12‐week follow‐up appointments. All complications were recorded. Results. The 14 tendons in this study included patellar (5), Achilles (4), proximal gluteus medius (1), proximal iliotibial tract (1), proximal hamstring (1), common extensor elbow (1), and proximal rectus femoris (1). The composite VAS score was significantly lower at both 4 weeks (mean ± SEM, 2.4 ± 0.7) and 12 weeks (2.2 ± 0.7) compared with the baseline (5.8 ± 0.6; P < .001). No complications or morbidity occurred. Conclusions. Sonographically guided percutaneous tenotomy of tendinosis was effective in improving patient symptoms without complications. Further investigation with additional patients and comparisons to alternative treatments is needed to validate these preliminary results.
Negligible Senescence during Reproductive Dormancy in Drosophila melanogaster

Some endemic Drosophila overwinter in a state of adult reproductive diapause where egg maturation is arrested in previtellogenic stages. When maintained at cool temperatures, adult Drosophila melanogaster enter reproductive dormancy, that is, diapause or diapause‐like quiescence. The ability to survive for extended periods is a typical feature of diapause syndromes. In adults this somatic persistence may involve reduced or slowed senescence. Here we assess whether reproductively dormant D. melanogaster age at slow rates. Adults were exposed to dormancy‐inducing conditions for 3, 6, or 9 wk. After this period, demographic parameters were measured under normal conditions and compared to the demography of newly eclosed cohorts. The age‐specific mortality rates of postdormancy adults were essentially identical to the mortality rates of newly eclosed, young flies. Postdormancy reproduction, in contrast, declined with the duration of the treatment; somatic survival during dormancy may tradeoff with later reproduction. Adults in reproductive dormancy were highly resistant to heat and to oxidative stress. Suppressed synthesis of juvenile hormone is known to regulate reproductive diapause of many insects. Treatment of dormant D. melanogaster with a juvenile hormone analog restored vitellogenesis, suppressed stress resistance, and increased demographic senescence. We conclude that D. melanogaster age at slow rates as part of their reproductive dormancy syndrome; the data do not agree with an alternative hypothesis based on heat‐dependent “rate of living. ” We suggest that low temperature reduces neuroendocrine function, which in turn slows senescence as a function of altered stress response, nutrient reallocation, and metabolism.
Spleen Size Predicts Resistance of Rainbow Trout to Flavobacterium psychrophilum Challenge12

Selective breeding of animals for increased innate resistance offers an attractive strategy to control disease in agriculture. However, this approach is limited by an incomplete knowledge of the heritability, duration, and mechanism(s) of resistance, as well as the impact of selection on the immune response to unrelated pathogens. Herein, as part of a rainbow trout broodstock improvement program, we evaluated factors involved in resistance against a bacterial disease agent, Flavobacterium psychrophilum. In 2005, 71 full-sibling crosses, weighing an average of 2.4 g, were screened, and resistant and susceptible crosses were identified. Naive cohorts were evaluated at 10 and 800 g in size, and most maintained their original relative resistant or susceptible phenotypes, indicating that these traits were stable as size increased >300-fold. During the course of these studies, we observed that the normalized spleen weights of the resistant fish crosses were greater than those of the susceptible fish crosses. To test for direct association, we determined the spleen-somatic index of 103 fish crosses; created high, medium, and low spleen-index groups; and determined survival following challenge with F. psychrophilum or Yersinia ruckeri. Consistent with our previous observations, trout with larger spleen indices were significantly more resistant to F. psychrophilum challenge; however, this result was pathogen-specific, as there was no correlation of spleen size with survival following Y. ruckeri challenge. To our knowledge, this is the first report of a positive association between spleen size and disease resistance in a teleost fish. Further evaluation of spleen index as an indirect measure of disease resistance is warranted.