Miracle-dz/UniFAR-FTUs huggingface dataset:
The US3 Protein of Pseudorabies Virus Drives Viral Passage across the Basement Membrane in Porcine Respiratory Mucosa Explants

ABSTRACT Passage of the basement membrane (BM), which forms a barrier between the epithelium and the underlying lamina propria, represents an important step in the early pathogenesis of different alphaherpesviruses. Rho GTPase signaling plays an important role in transmigration of cells across the BM during physiological and pathological processes. We reported earlier that the US3 protein kinase of the alphaherpesvirus pseudorabies virus (PRV) interferes with Rho GTPase signaling and causes a reorganization of the host cell cytoskeleton, which as a consequence, enhances viral cell-to-cell spread in epithelial cell cultures. Here, using an ex vivo system of porcine nasal respiratory mucosa explants that allows to study PRV invasion through the BM, we found that a PRV strain that lacks US3 expression (ΔUS3 PRV) showed a reduced spread in mucosal epithelium and was virtually unable to breach the BM, in contrast to isogenic wild-type (WT) or US3 rescue PRV strains. Interestingly, addition of IPA3, an inhibitor of p21-activated kinases that blocks the effects of US3 on the cytoskeleton, suppressed the ability of WT PRV to spread across the BM. In addition, artificial suppression of RhoA signaling using CPC3 (cell-permeable C3 transferase) to mimic the effects of US3 on Rho GTPase signaling, significantly increased passage of ΔUS3 PRV through the BM, whereas it did not significantly affect BM passage of WT or US3 rescue PRV. In conclusion, these data indicate that US3 plays an important role in PRV mucosal invasion across the BM, which involves its interference with Rho GTPase signaling. This is the first report describing an alphaherpesvirus protein that drives viral BM passage. IMPORTANCE Many viruses, including alphaherpesviruses, primarily replicate in epithelial cells of surface mucosae, such as the respiratory mucosa. Some of these viruses breach the basement membrane underlying these epithelial cells to reach underlying connective tissue and blood vessels and invade the host. Hence, epithelial spread and basement membrane passage represent crucial but still poorly understood early steps in (alphaherpes)virus pathogenesis. Here, using ex vivo porcine respiratory mucosa explants, we show that the conserved US3 protein of the porcine alphaherpesvirus pseudorabies virus (PRV) is critical for passage of PRV across the basement membrane and contributes to efficient viral epithelial spread. In addition, we show that US3-mediated viral epithelial spread and passage across the basement membrane depend at least in part on the ability of this viral protein to modulate cellular Rho GTPase signaling. This is the first report that identifies an alphaherpesvirus protein that drives viral basement membrane passage.
Acute bronchodilator responsiveness to tiotropium in postinfectious bronchiolitis obliterans in children.

BACKGROUND Patients with postinfectious bronchiolitis obliterans (PIBO) usually have severe airflow obstruction and respond poorly to β-adrenergic drugs. However, the bronchodilator response to an anticholinergic agent such as tiotropium bromide is not known. We studied the acute bronchodilator response to tiotropium for up to 24 h in children with PIBO using spirometric and plethysmographic criteria. METHODS A randomized, double-blind, placebo-controlled, crossover, prospective study was performed in patients with stable PIBO, 6 to 16 years of age. Standard spirometry and plethysmography were performed before and at 30, 60, 120, and 180 min and 24 h after inhalation of 18 μg of tiotropium or a placebo. After 7 to 14 days, the drugs were inverted, and the procedures were repeated. The changes in lung function parameters at each time point were compared with the baseline by analysis of variance and Tukey posttest, and the differences in all time points assessments vs baseline in tiotropium vs placebo groups were compared using the Friedman test. RESULTS A total of 30 patients were enrolled in the study (23 boys, seven girls; aged 10.9 ± 2.8 years) with baseline lung function values (% predicted) of FVC, FEV1, FEV1/FVC, forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), total lung capacity (TLC), residual volume (RV), RV/TLC, airway resistance (Raw), and specific airway conductance (sGaw) of 75 ± 15, 48 ± 14, 59 ± 11, 22 ± 11, 120 ± 19, 281 ± 101, 49 ± 13, 250 ± 65, and 23 ± 9, respectively. Statistically significant differences were observed after tiotropium inhalation in the following parameters compared with baseline: FVC at 60, 120, and 180 min and 24 h; FEV1 at 30, 60, 120, and 180 min; FEV1/FVC at 60, 120, and 180 min; FEF25%-75% at 60, 120, and 180 min; RV at 30, 60, 120, and 180 min; TLC at 30, 120, and 180 min; RV/TLC at 30, 60, 120, and 180 min; Raw at 30, 60, 120, and 180 min and 24 h; and sGaw at 30, 60, 120, and 180 min and 24 h. For the placebo group, no significant differences were observed in any lung function parameters at any time. The differences in the main functional measurements between the tiotropium and placebo groups were statistically significant. CONCLUSIONS Tiotropium acutely decreased airway obstruction and air trapping for up to 24 h in children with PIBO.
Translumbar Puncture for Retrograde Catheterization of a Kinked Left Renal Stent After Fenestrated Endograft Repair

Purpose: To describe a case of percutaneous retrograde left renal artery cannulation and restenting for severe distortion of a bridging stent diagnosed at the time of fenestrated endovascular aneurysm repair (FEVAR). Case Report: A 79-year-old man underwent 4-vessel FEVAR, during which completion angiography showed a good postoperative result, but cone beam computed tomography (CBCT) demonstrated severe distortion of the proximal part of the left renal stent. An antegrade or hybrid approach to recannulate the vessel was not possible due to the stent architecture and patient comorbidities. Contrast-enhanced CBCT was used to define the needle trajectory for a percutaneous translumbar approach. Fusion imaging software registered the planned needle track to the live fluoroscopy image. Respiratory motion compensation was used. Retrograde cannulation of the left renal artery was achieved; via a through-and-through wire with the left femoral artery, the left renal artery stent was relined using a covered stent. No deterioration of renal function was observed following the procedure. Contrast-enhanced duplex ultrasound demonstrated good flow in all target vessels without endoleak. Conclusion: Translumbar puncture and retrograde catheterization of a severely distorted left renal artery stent is possible during FEVAR using advanced imaging applications and can prevent target vessel loss.
Effect of Recent Contrast-Enhanced CT and Patient Age on Image Quality of Thyroid Scintigraphy

Purpose of the Report When thyroid scintigraphy (TS) is performed after contrast-enhanced CT (CE-CT), tracer uptake of 99mTcO4 in the thyroid gland can be inhibited by free iodide. Currently, it is recommended to postpone TS until 4 to 8 weeks after CE-CT, but few data exist to support this recommendation. The purpose was to investigate the effect of CE-CT and other variables for the diagnostic quality of TS. Patients and Methods This retrospective study included 196 patients subjected to TS less than 3 months after a CE-CT (median, 66 days). Patients with elevated thyroid-stimulating hormone (>4.5 mIU/L) or suspected thyroiditis were excluded. Logistic regression was used to calculate the probability of a TS of diagnostic quality with the variables days since CE-CT, age, thyroid-stimulating hormone, and kidney function (eGFR). Results Days since CT and age were highly significant (P < 0.001) predictors for diagnostic TS. The probability of diagnostic quality TS after CE-CT increased with time and reached approximately 70% to 80% 6 to 8 weeks after CE-CT. Analysis of age-specific populations showed age to be a strong independent factor. Conclusions Our findings are in consensus with the currently recommended interval of 6 to 8 weeks between CE-CT and TS. However, our results indicate that patient age should be taken into account, and we suggest the following delay from CE-CT to TS: 4 weeks for patients aged younger than 50 years, 6 weeks for patients aged 50 to 60 years, and 8 weeks for patients aged older than 60 years.
Butenafine hydrochloride: for the treatment of interdigital tinea pedis

Butenafine, a derivative of benzylamine with potent fungicidal activity is a new generation of antimycotic compound that has shown to be extremely effective against experimentally-induced tinea pedis in the guinea-pig, a situation that resembles synergetic pathology similar to that of tinea pedis in humans. Butenafine, (N-4-tert-butylbenzyl-N-methyl-1-naphthalenemethyl-amine hydrochloride) with a chemical structure and mode of action similar to those of the allylamines, demonstrates superior fungicidal activity in vitro against dermatophytes and superior fungistatic activity toward Candida albicans than that of naftifine and terbinafine. In vitro, pharmacodynamic data has shown that the geometric mean of minimum inhibitory concentration values for butenafine were comparatively lower than those of naftifine and clotrimazole against clinical isolates for many dermatophytes. It inhibits sterol synthesis by blocking the squalene epoxidation stage in fungi. In phramacokinetic assessments butenafine achieves and maintains high concentrations and long retention time in skin, with associated anti-inflammatory activity in vivo. In controlled clinical trials when applied topically, butenafine appears to be well tolerated with a subjective mild burning sensation at the application site. There were no withdrawls from the study. Butenafine is sparingly soluble in water but readily soluble in methanol, ethanol, dichloromethane and chloroform. If incorporated properly in semisolid topical preparations, with a balanced vehicle, butenafine hydrochloride potentially exhibits as a promising alternative antimycotic agent for the treatment of tinea pedis.
Evidence That Plasma Leptin and Insulin Levels are Associated With Body Adiposity Via Different Mechanisms

OBJECTIVE Like insulin, the adipocyte hormone, leptin, circulates at levels proportionate to body adiposity. Because insulin may regulate leptin secretion, we sought to determine if plasma leptin levels are coupled to body adiposity via changes in circulating insulin levels or insulin sensitivity and whether leptin secretion from adipocytes is impaired in subjects with NIDDM. RESEARCH DESIGN AND METHODS We used multiple linear regression to analyze relationships between BMI (a measure of body adiposity) and fasting plasma levels of leptin and insulin in 98 nondiabetic human subjects (68 men/30 women) and 38 subjects with NIDDM (27 men/11 women). The insulin sensitivity index (S1) was also determined in a subset of nondiabetic subjects (n = 38). RESULTS Fasting plasma leptin concentrations were correlated to both BMI (r = 0.66, P = 0.0001) and fasting plasma insulin levels (r = 0.65, P = 0.0001) in nondiabetic men and women (r = 0.58, P = 0.0009 for BMI; r = 0.47, P = 0.01 for insulin). While the plasma leptin level was also inversely related to S1 (r = −0.35; P = 0.03), this association was dependent on BMI, whereas the association between insulin and S1 was not. Conversely, the relationship between plasma leptin and BMI was independent of S1, whereas that between insulin and BMI was dependent on S1. The relationship between plasma leptin levels and BMI did not differ significantly among NIDDM subjects from that observedin nondiabetic subjects. CONCLUSIONS We conclude that 1) body adiposity, sex, and the fasting insulin level are independently associated with plasma leptin level; 2) because NIDDM doesnot influence leptin levels, obesity associated with NIDDM is unlikely to result from impaired leptin secretion; and 3) insulin sensitivity contributes to the association between body adiposity and plasma levels of insulin, but not leptin. The mechanisms underlying the association between body adiposity and circulating levels of these two hormones, therefore, appear to bedifferent.
The use of anti-D immunoglobulins for rhesus prophylaxis: audit on knowledge and practices among obstetricians.

INTRODUCTION The development of anti-D antibodies results from foetomaternal sensitisation occurring in rhesus (Rh) negative blood group women who carry an Rh-positive foetus. Despite guidelines on Rh immunoprophylaxis, isoimmunisation continues to occur, suggesting that the guidelines are not being fully applied by obstetricians. This study aims to establish the adequacy of knowledge on Rh immunoprophylaxis among obstetricians and trainees in obstetrics and gynaecology in Singapore, and their usual practice in the care of an Rh-negative mother; and hence to audit their practice in accordance with evidence-based guidelines. METHODS An anonymous questionnaire survey auditing obstetricians' knowledge of guidelines on anti-D prophylaxis and their usual practice in the clinical setting. RESULTS The mean score achieved on the questionnaire was 75.9 percent. Many obstetricians did not know that anti-D immunoglobulins (Ig) should be given within 72 hours of a sensitising event for successful immunoprophylaxis. In clinical practice, all the obstetricians who participated in the questionnaire would offer anti-D Ig prophylaxis to Rh-negative women both antenatally and postnatally. However, only 12.7 percent of them would routinely perform a Kleihauer test in Rh-negative women following delivery. CONCLUSION The knowledge on anti-D prophylaxis among obstetricians can be improved. A continual system of education to raise awareness of evidence-based practices as well as clinical audit has been implemented to address this.
Effect of Diet and Exercise on Body Composition, Energy Intake and Leptin Levels in Overweight Women and Men

Objective: To investigate the effect of diet alone (D), exercise alone (E), and a combination of diet and exercise (DE) on body weight, body composition, energy intake, blood pressure, serum lipid and leptin levels, and fitness levels in mildly obese sedentary women and men. Design: The three interventions were compared in a randomized longitudinal study design. The exercise programs were supervised for six months, after which participants in E and DE were provided with exercise equipment to take home. Subjects: 90 adult overweight women and men (age: 44.2 ± 7.2 years; BMI = 30.5 ± 2.7 kg/m2). Measurements: Body weight, body composition, waist and hip circumferences, blood pressure, serum lipid levels, and fitness levels were evaluated at 0, 3, 6, 9, and 12 months. Serum leptin concentrations were measured at 0 and 6 months only. Results: At 6 and 9 months in women, and 9 months in men, DE demonstrated a significant loss of body weight compared to both D and E (p < 0.05). Serum leptin levels significantly decreased from baseline to 6 months in women in D (p = 0.05) and DE (p = 0.0003) and men in E (p = 0.038). At one year, no significant differences existed among groups in any of the measures. Conclusion: A combination of diet and exercise resulted in a significant decrease in body weight in women and men; but this decrease was not maintained at one year follow-up. Serum leptin concentrations showed significant within-group decreases, but were not different among groups. A supervised diet and exercise program is effective for weight loss; however, once intensive participant-investigator and participant-participant contact is discontinued, weight regain ensures.
Diabetes trends in Europe

Estimates and projections suggest an epidemic expansion of diabetes incidence and prevalence in Europe. To evaluate trends in type 1 and type 2 diabetes in seven European countries (Finland, Denmark, the UK, Germany, France, Spain, and Italy), a variety of information is available, including population‐based studies on small or large cohorts of subjects representative of the general population in a particular country, European co‐operative studies, and sales figures for insulin and oral hypoglycemic agents that allow extrapolation of the number of pharmacologically treated diabetic patients. The incidence of type 1 diabetes in young people is increasing in most European countries, as is its prevalence in all age groups. Type 2 diabetes is the major contributor to the epidemic rise in diabetes. From 1995 to 1999, the prevalence of type 2 diabetes increased considerably, particularly in the UK, Germany, and France. Costs of ambulatory and in‐hospital diabetic care (including antidiabetic, antihypertensive, and hypolipidemic agents) have increased even more rapidly than has the number of affected patients. Diabetes trends in Europe are alarming; health care professionals involved in diabetes care must be made aware of these detrimental trends, and health care delivery to patients with diabetes must be improved. Copyright © 2002 John Wiley & Sons, Ltd.
Determinants of bank profitability before, during and after the financial crisis

© 2018, Emerald Publishing Limited. Purpose: The purpose of this paper is to report the results of an investigation into the relationship between bank-specific, macroeconomic factors and bank profitability before (1999-2006), during (2007-2009), and after (2010-2013) the financial crisis. Design/methodology/approach: Using the Economic Community of West African States’ bank panel data from 1999 to 2013, the paper used fixed effect models. The panel model includes bank-specific determinants (size, cost management, and liquidity), industry level, and macroeconomic variables. Findings: Panel data analyses results show that there is a significant relationship between bank-specific determinants (size, cost management, and liquidity) and bank profitability (ROA) before, during, and after the financial crisis. However, the relationships between other bank-specific (capital strength, credit risk, and market power), macroeconomic (gross domestic product and inflation) determinants are sensitive to both periods of analysis (before, during, and after financial crisis) and bank profitability measure used (ROA or NIM). Originality/value: Overall, these results suggest that the financial crisis did not affect the relationships between some bank-specific determinants and bank profitability.
Secretion of brain‐derived neurotrophic factor from brain microvascular endothelial cells

The cerebral microvasculature has recently been identified as a source of factors that can influence the generation and survival of neurons, including brain‐derived neurotrophic factor (BDNF). However, relatively little is known about signals that regulate secretion of endothelial cell derived BDNF. To approach this issue the present study examined BDNF secretion from brain endothelial cells in response to reduced oxygen availability (hypoxia), using the mouse brain microvascular endothelial cell line, bEnd.3. We found that exposure of bEnd.3 cells to either sustained or intermittent hypoxia (IH) stimulates BDNF expression and release and that IH is the more potent stimulus. IH‐induced BDNF release can be partially inhibited by either N‐acetyl‐l‐cysteine, a scavenger of reactive oxygen species, or by the stable superoxide dismutase mimetic manganese(III)tetrakis1‐methyl‐4‐pyridylporphyrin, indicating that oxyradical formation contributes to enhanced secretion of BDNF. In addition, we found that IH‐induced BDNF release requires Ca2+ mobilization from internal stores through ryanodine‐ and inositol (1,4,5‐triphosphate) IP3 receptors and is completely blocked by SKF 96365, a nonselective inhibitor of transient receptor potential (TRP) channels. These data demonstrate that bEnd.3 cells respond to oxidative stress by increasing BDNF secretion and, in addition, highlight TRP channels as potential therapeutic targets for enhancing BDNF availability from the cerebral microvasculature.
The Impact of the Reformation on the Economic Development of Western Europe

The Protestant Reformation is a vivid example of how religious transformation could set in motion institutional changes, leading to profound consequences for economic and political development. Although economists and other social scientists agree that there is a strong relation between the Reformation and economic growth, there is an active discussion as to what are the causal pathways connecting Protestantism to long-run economic success. We discuss the causal pathways that received substantial empirical support in academic literature. Some of them, such as “work ethic” and entrepreneurial spirit of Protestants, were originally suggested by Max Weber, while others, such as religious freedom and education, are deeply grounded in economic theory. More recently, other causal pathways have been suggested, such as social ethic, civil society, and institutional changes. We bring our view of these pathways.
Structure-activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae.

BACKGROUND Dengue fever is a severe public health problem for several countries. In order to find effective larvicides to aid control programs, the structure-activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae were evaluated. Additionally, the composition and larvicidal activity of Syzygium aromaticum essential oil was assessed. RESULTS Four compounds representing 99.05% of S. aromaticum essential oil have been identified. The essential oil was active against Ae. aegypti larvae (LC(50) = 62.3 and 77.0 ppm, field-collected and Rockefeller larvae respectively). The larvicidal activity of eugenol, the major compound of the essential oil, was further evaluated (LC(50) = 93.3 and 71.9 ppm, field-collected and Rockefeller larvae respectively). The larvicidal activity and structure-activity relationships of synthetic derivatives of eugenol were also assessed. The larvicidal activity of the derivatives varied between 62.3 and 1614.9 ppm. Oxidation of eugenol allylic bond to a primary alcohol and removal of the phenolic proton resulted in decreased potency. However, oxidation of the same double bond in 1-benzoate-2-methoxy-4-(2-propen-1-yl)-phenol resulted in increased potency. CONCLUSION Structural characteristics were identified that may contribute to the understanding of the larvicidal activity of phenylpropanoids. The present approach may help future work in the search for larvicidal compounds.
Laser and incisional myringotomy in otitis media with effusion-a comparative study.

BACKGROUND Otitis media with effusion (OME) or middle ear effusion (MEE) is a common cause of hearing difficulty in children. MEE must be detected early and managed properly to prevent conductive hearing loss in children. It was aimed to compare results of laser myringotomy and conventional myringotomy in terms of hearing improvement, recurrence of MEE and time to put ventilation tube. METHODS This randomized control trial was conducted from February 2012 to April 2014. Children of 4 years age or older with MEE were included in the study. These children were investigated with Pure tone audiometry (PTA) and tympanometry to confirm conductive hearing loss. X-Ray nasopharynx lateral view was performed for adenoids. Sixty-six patients were randomly assigned in to 2 groups, (1) treated with laser myringotomy and (2) treated with classical myringotomy. The ears were evaluated for MEE, for presence of perforation and level of hearing. RESULTS A total of 98 ears in 66 patients underwent intervention. Middle ear effusion cleared in 44 out of 48 ears with laser myringotomy (LM) as compared to34 out of 50 ears with incisional myringotomy. The perforation was still patent in 36 ears treated with LM while it was found closed in all 50 ears with conventional myringotomy after 2 weeks. The hearing level improved with LM by 10-15 dB after first 3 months. CONCLUSION The aim of management in otitis media with effusion is ventilation of tympanic cavity. Laser myringotomy is a best alternative to conventional one. It also has comparable results with ventilation tubes (VT). The ears with refractory or recurrent MEE should have VT insertion.