Miracle-dz/UniFAR-FTUs huggingface dataset:
17β‐Oestradiol Modulates Glucocorticoid, Neural and Behavioural Adaptations to Repeated Restraint Stress in Female Rats

Sex steroids have a role in modulating responses that extends beyond reproduction. The current study investigated the influence of the sex steroid 17β‐oestradiol on hypothalamic‐pituitary‐adrenal (HPA) and behavioural responses to acute or repeated restraint stress. Ovariectomized rats treated with 17β‐oestradiol or peanut oil via a subcutaneous silastic capsule were subjected to daily handling (non stressed), acute (single, 1 h) or daily (10 days, 1 h/day) restraint stress. Blood collected at the end of stress revealed that 17β‐oestradiol treatment augmented the corticosterone response to acute restraint. After daily exposure to restraint, the corticosterone response was noticeably diminished in untreated females but 17β‐oestradiol‐treated rats still showed an exaggerated response compared to castrated, untreated females. Brain tissue collected 3 h after the end of restraint was probed using isotopic in situ hybridization for corticotropin‐releasing factor (CRF) and vasopressin gene expression in the paraventricular nucleus (PVN) of the hypothalamus. 17β‐oestradiol treatment at the higher dose (120 µg/ml) decreased basal CRF mRNA. Stress caused an increase in CRF mRNA expression in 17β‐oestradiol‐treated rats but not in the vehicle group. Repeated restraint stress caused an increase in PVN parvocellular vasopressin gene expression, which was more pronounced in 17β‐oestradiol‐replaced rats. Animals were exposed to the elevated plus maze for 5 min as a test for anxiety. Non‐stressed control rats with or without 17β‐oestradiol replacement spent the same percentage amount of time exploring the open arms of the maze. Previous exposure to acute restraint stress caused a marked reduction in the time spent exploring the open arms, indicating an increase in anxiety levels in these rats; this effect was observed in both vehicle and 17β‐oestradiol‐treated rats. After repeated restraint stress, 17β‐oestradiol‐replaced rats spent as much time exploring the open arms of the maze as controls, indicating adaptation. By contrast, nonreplaced rats were still showing a significant reduction in open arm exploration after repeated restraint. The present study presents novel data showing that the HPA axis remains reactive to repeated stress in 17β‐oestradiol‐treated ovariectomized rats, but stress‐induced anxiety behaviour is reduced.
Management of insomnia in office-based practice. National prevalence and therapeutic patterns.

OBJECTIVES To identify the characteristics of patients who present to office-based physicians with complaints of insomnia, the physicians' diagnoses related to these complaints, and the use of prescription sleep medications. METHODS Based on 1989 and 1990 data from the National Ambulatory Medical Care Survey, with 3105 physicians participating (response rate, 74%). Participating physicians recorded data for a total of 81,853 patient visits. Patient characteristics, presenting complaint, diagnosis of condition, and pharmacologic therapy were included. RESULTS Annually, there are 3.3 million visits to office-based physicians for complaints of insomnia, 65% of which are to primary care specialists. Rates of insomnia visits are somewhat higher for middle-aged (45 to 64 years of age) women, and data for female insomniacs suggest a trend toward diagnoses of depression compared with other (somatic) diagnoses for men. The prescribing of long-acting sleep medications does not differ significantly by physician specialty, but it declines with increasing patient age. CONCLUSIONS Physician visits for insomnia account for only a small proportion of office visits but offer the opportunity for identification of underlying illnesses and for the prevention of associated problems. While some differences in diagnosis are associated with patient characteristics (possibly reflecting a bias in the workup), sleep medications appear to be prescribed appropriately, with a declining rate in the prescribing of long-acting medications for older patients.
Comparison of penile length at 6–24 months between children with unilateral cryptorchidism and a healthy normal cohort

Purpose Urologic diseases affected by testosterone can be associated with smaller penis size compared to the normal population. We sought to compare penile length in children with unilateral cryptorchidism and normative data from a cohort of healthy Korean boys. Materials and Methods This study was performed in 259 Korean boys (212, normal cohort; 47, cryptorchidism) aged 6–24 months, each of whom had been brought to an outpatient clinic at one of five tertiary hospitals (Gyeongsangnam-do Province) between April 2014 and June 2015. Penile length was measured via stretched penile length (SPL) and testicular size was measured using orchidometry (mL). Results SPL in children with cryptorchidism was significantly shorter compared to a cohort of healthy Korean boys aged 6–24 months (3.7±0.5 cm and 4.3±0.8 cm, p<0.001), although there were no differences with regard to height, body weight and contralateral testicular size between the two groups. According to the stratified ages (6–12, 12–18, and 18–24 months), SPL in children with cryptorchidism was persistently shorter at their ages than those without. Conclusions It might be that the penile length aged 6–24 months of children with unilateral cryptorchidism is shorter than that of a cohort of healthy Korean boys.
A Novel 111In-Labeled Anti–Prostate-Specific Membrane Antigen Nanobody for Targeted SPECT/CT Imaging of Prostate Cancer

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer (PCa) and a promising target for molecular imaging and therapy. Nanobodies (single-domain antibodies, VHH) are the smallest antibody-based fragments possessing ideal molecular imaging properties, such as high target specificity and rapid background clearance. We developed a novel anti-PSMA Nanobody (JVZ-007) for targeted imaging and therapy of PCa. Here, we report on the application of the 111In-radiolabeled Nanobody for SPECT/CT imaging of PCa. Methods: A Nanobody library was generated by immunization of a llama with 4 human PCa cell lines. Anti-PSMA Nanobodies were captured by biopanning on PSMA-overexpressing cells. JVZ-007 was selected for evaluation as an imaging probe. JVZ-007 was initially produced with a c-myc-hexahistidine (his) tag allowing purification and detection. The c-myc-his tag was subsequently replaced by a single cysteine at the C terminus, allowing site-specific conjugation of chelates for radiolabeling. JVZ-007-c-myc-his was conjugated to 2-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (p-SCN-DTPA) via the lysines, whereas JVZ-007-cys was conjugated to maleimide-DTPA via the C-terminal cysteine. PSMA targeting was analyzed in vitro by cell-binding experiments using flow cytometry, autoradiography, and internalization assays with various PCa cell lines and patient-derived xenografts (PDXs). The targeting properties of radiolabeled Nanobodies were evaluated in vivo in biodistribution and SPECT/CT imaging experiments, using nude mice bearing PSMA-positive PC-310 and PSMA-negative PC-3 tumors. Results: JVZ-007 was successfully conjugated to DTPA for radiolabeling with 111In at room temperature. 111In-JVZ007-c-myc-his and 111In-JVZ007-cys internalized in LNCaP cells and bound to PSMA-expressing PDXs and, importantly, not to PSMA-negative PDXs and human kidneys. Good tumor targeting and fast blood clearance were observed for 111In-JVZ-007-c-myc-his and 111In-JVZ-007-cys. Renal uptake of 111In-JVZ-007-c-myc-his was initially high but was efficiently reduced by coinjection of gelofusine and lysine. The replacement of the c-myc-his tag by the cysteine contributed to a further reduction of renal uptake without loss of targeting. PC-310 tumors were clearly visualized by SPECT/CT with both tracers, with low renal uptake (<4 percentage injected dose per gram) for 111In-JVZ-007-cys already at 3 h after injection. Conclusion: We developed an 111In-radiolabeled anti-PSMA Nanobody, showing good tumor targeting, low uptake in nontarget tissues, and low renal retention, allowing excellent SPECT/CT imaging of PCa within a few hours after injection.
Relationship between renalase and N-terminal pro-B-type natriuretic peptide (NT pro-BNP) in haemodialysis patients.

INTRODUCTION Our knowledge in the field of cause of deaths in dialysis patients is rapidly expanding, yet we still do not fully understand how renalase regulates the processes of cardiovascular disease developing in end-stage renal disease. Increased sympathetic nerve activity observed in chronic kidney diseases due to raised catecholamines in plasma results from the absence of renalase. Renalase synthesized and secreted by the kidneys participate in the regulation of sympathetic tone and blood pressure. A family of natriuretic peptides has been identified - NT pro-BNP - which seems to be the best predictor of clinical outcome and marker of extracellular fluid overload, as well as predicting mortality, irrespective of renal function. OBJECTIVE The aim of the presented study was to investigate renalase concentration and investigate associations between NT-proBNP, as well as analyzed parameters in haemodialysis patients. MATERIALS AND METHOD The study was conducted among residents of the municipality and neighbouring villages in the province of Lublin, central-eastern Poland. 49 male subjects on haemodialysis, aged 65.3 ± 14.2 years, median time on haemodialysis: 37.5 months, were included. All study subjects underwent haemodialysis 3 times a week. The mean concentration of renalase in the entire study population was 126.59 ± 32.63 ng/mL. The circulating levels of NT-proBNP was 813.64 ± 706.96 pg/mL. A significant inverse correlation was found between NT-proBNP and renalase plasma levels (R = -0.3, P = 0.03). CONCLUSIONS Inverse correlation between NT-proBNP and renalase plasma levels in haemodialysis patients were due to impaired kidney function, accompanied by increased sympathetic nerve activity, which have an impact on the development of hypertension and cardiovascular complications.
Ca2+‐independent hypoxic vasorelaxation in porcine coronary artery

To demonstrate a Ca2+‐independent component of hypoxic vasorelaxation and to investigate its mechanism, we utilized permeabilized porcine coronary arteries, in which [Ca2+] could be clamped. Arteries permeabilized with β‐escin developed maximum force in response to free Ca2+ (6.6 μm), concomitant with a parallel increase in myosin regulatory light chain phosphorylation (MRLC‐Pi), from 0.183 ± 0.023 to 0.353 ± 0.019 MRLC‐Pi (total light chain)−1. Hypoxia resulted in a significant decrease in both force (–31.9 ± 4.1% prior developed force) and MRLC‐Pi (from 0.353 to 0.280 ± 0.023), despite constant [Ca2+] buffered by EGTA (4 mm). Forces developed in response to Ca2+ (6.6 μm), Ca2+ (0.2 μm) + GTPγS (1 mm), or in the absence of Ca2+ after treatment with ATPγS (1 mm), were of similar magnitude. Hypoxia also relaxed GTPγS contractures but importantly, arteries could not be relaxed after treatment with ATPγS. Permeabilization with Triton X‐100 for 60 min also abolished hypoxic relaxation. The blocking of hypoxic relaxation after ATPγS suggests that this Ca2+‐independent mechanism(s) may operate through alteration of MRLC‐Pi or of phosphorylation of the myosin binding subunit of myosin light chain phosphatase. Treatment with the Rho kinase inhibitor Y27632 (1 μm) relaxed GTPγS and Ca2+ contractures; but the latter required a higher concentration (10 μm) for consistent relaxation. Relaxations to N2 and/or Y27632 averaged 35% and were not additive or dependent on order. Our data suggest that the GTP‐mediated, Rho kinase‐coupled pathway merits further investigation as a potential site of this novel, Ca2+‐independent O2‐sensing mechanism. Importantly, these results unambiguously show that hypoxia‐induced vasorelaxation can occur in permeabilized arteries where the Ca2+ is clamped at a constant value.
Chromophore Interaction in Xanthorhodopsin—Retinal Dependence of Salinixanthin Binding †

Xanthorhodopsin is a light‐driven proton pump in the extremely halophilic bacterium Salinibacter ruber. Its unique feature is that besides retinal it has a carotenoid, salinixanthin, with a light harvesting function. Tight and specific binding of the carotenoid antenna is controlled by binding of the retinal. Addition of all‐trans retinal to xanthorhodopsin bleached with hydroxylamine restores not only the retinal chromophore absorption band, but causes sharpening of the salinixanthin bands reflecting its rigid binding by the protein. In this report we examine the correlation of the changes in the two chromophores during bleaching and reconstitution with native all‐trans retinal, artificial retinal analogs and retinol. Bleaching and reconstitution both appear to be multistage processes. The carotenoid absorption changes during bleaching occurred not only upon hydrolysis of the Schiff base but continued while the retinal was leaving its binding site. In the case of reconstitution, the 13‐desmethyl analog formed the protonated Schiff base slower than retinal, and provided the opportunity to observe changes in carotenoid binding at various stages. The characteristic sharpening of the carotenoid bands, indicative of its reduced conformational heterogeneity in the binding site, occurs when the retinal occupies the binding site but the covalent bond to Lys‐240 via a Schiff base is not yet formed. This is confirmed by the results for retinol reconstitution, where the Schiff base does not form but the carotenoid exhibits its characteristic spectral change from the binding.
Self-Efficacy and Perceived Exertion of Girls During Exercise

BackgroundAn important national goal in Healthy People 2010 is to reduce the high prevalence of sedentary lifestyles and resultant overweight and obesity among girls. ObjectivesThe purpose of the present study was threefold: (a) to determine if pre-exercise self-efficacy predicted girls’ perceptions of exertion during exercise, (b) to determine if these perceptions, in turn, influenced postexercise self-efficacy, and (c) to assess if exercise self-efficacy increased following completion of an exercise task. MethodsA sample of 103 girls, 8 to 17 years of age, pedaled 20 minutes on a cycle ergometer at 60% of their predetermined peak VO2 in a climatic chamber (90°F, 50% relative humidity). Ratings of perceived exertion were obtained every 4 minutes. Exercise self-efficacy was assessed before and after the exercise session. ResultsControlling for peak VO2 and percent body fat, pre-exercise efficacy exerted an independent effect on perception of exertion during exercise with girls high on pre-exercise self-efficacy reporting lower perceived exertion during exercise, than girls low on self-efficacy. Both pre-exercise efficacy and perceived exertion explained postexercise efficacy. Exercise self-efficacy increased significantly from pre- to postexercise. ConclusionsPre-exercise efficacy is an important factor influencing girls’ perceptions of exertion during exercise and their postexercise efficacy. Increased exercise self-efficacy of girls following successful completion of an exercise challenge suggests possible strategies to increase physical activity.
The Predictive Performance of a Pharmacokinetic Model for Manually Adjusted Infusion of Liquid Sevofluorane for Use with the Anesthetic-Conserving Device (AnaConDa): A Clinical Study

BACKGROUND: The Anesthetic-Conserving Device (AnaConDa) can be used to administer inhaled anesthetics using an intensive care unit (ICU) ventilator. We evaluated the predictive performance of a simple manually adjusted pump infusion scheme, for infusion of liquid sevoflurane to the AnaConDa. METHODS: We studied 50 ICU patients who received sevoflurane via the AnaConDa. They were randomly divided into three groups. A 6-h infusion of liquid anesthetic was adjusted according to the infusion scheme to a target end-tidal sevoflurane concentration of 1% (Group 1%, n = 15) and 1.5% (Group 1.5%, n = 15). The initial rate was adjusted to reach the target concentration in 10 min and then the infusion was reduced to the first hour maintenance rate and readjusted once each hour afterwards. The actual concentrations were measured in the breathing circuit and compared with the target values. In the third group (n = 20) we used the model to increase and decrease the target concentration (±0.3%) for 3 h and evaluated the actual change in concentration achieved. The ability of the infusion scheme to provide the target concentration was quantified by calculating the performance error (PE). Infusion scheme performance was evaluated in terms of accuracy (median absolute PE, MDAPE) and bias (median PE, MDPE). RESULTS: Performance parameters (mean ± sd, %) were for 1%, 1.5%, increase of concentration by 0.3% and decrease of concentration by 0.3% groups, respectively: MDAPE 5.3 ± 5.5, 2.6 ± 4.0, 5.0 ± 5.6, 5.5 ± 5.4; MDPE −5.3 ± 5.5, −2.3 ± 4.1, −0.1 ± 7.1, 0.2 ± 5.4. No significant differences were found between means of all performance parameters when the 1% and 1.5% groups were compared. CONCLUSIONS: There is an excellent 6-h predictive performance of a simplified pharmacokinetic model for manually adjusted infusion of liquid sevoflurane when using the AnaConDa to deliver sevoflurane to ICU patients.
Validation of some pathophysiological mechanisms of the CKD progression theory and outcome prediction in IgA nephropathy.

BACKGROUND The "remnant kidney" chronic kidney disease (CKD) progression theory based on hemodynamic, proteinuric and inflammatory mechanisms consequent to nephron loss has not been confirmed in a human disease. The aim of this study was to evaluate whether some of these mechanisms are present in IgA nephropathy (IgAN) and predict functional outcome. METHODS In 132 IgAN patients (68 untreated, 64 angiotensin-converting enzyme inhibitor [ACEi]-treated) fractional excretion of IgG (FEIgG) and α1-microglobulin, proteinuria/day and β-NAG excretion were divided by percentage of nonglobally sclerotic glomeruli ("surviving glomeruli" [SG]) to assess the effective glomerular loss and tubular load of proteins in surviving nephrons. Proteinuric markers were compared between 4 SG groups: group 1: ≤50%; group 2: >50% and <80%; group 3: ≥80% and <100%; and group 4: 100%. The outcome prediction (estimated glomerular filtration rate [eGFR] improvement and stability, progression) was assessed comparing low- and high-risk groups for each marker. RESULTS Proteinuric markers showed increasing values in parallel with reduction of percentages of SG (p<0.0001). FEIgG/SG, 40-fold higher in patients with SG ≤50% vs. SG=100% (0.00040 ± 0.00039 vs. 0.00001 ± 0.00002, p<0.0001), was the most powerful outcome predictor: in ACEi-untreated patients, FEIgG/SG less or greater than 0.00010 predicted eGFR improvement and stability (88% vs. 12%, p<0.0001) and end-stage renal disease (ESRD) + eGFR reduction ≥50% (2% vs. 87.5%, p<0.0001); ACEi treatment reduced ESRD+eGFR reduction ≥50%: 36% vs. 87.5% (p=0.002). In patients with FEIgG/SG <0.00010 the eGFR increase is significantly higher in ACEi-treated for ≥70 months versus ACEi-untreated with follow up ≥70 months (+35% ± 23% vs. +13% ± 8%, p=0.004). CONCLUSIONS In IgAN, progressive nephron loss is associated with an increase of proteinuric markers of glomerular and tubular damage. FEIgG/SG is the best outcome predictor. These data represent the first validation in a human disease of some pathophysiological mechanisms of CKD progression theory.
Total intravenous anaesthesia in horses using medetomidine and propofol.

OBJECTIVE To examine the clinical suitability of medetomidine-propofol infusions for total intravenous anaesthesia in horses. ANIMALS Fifty client-owned horses of mixed breed, age [mean +/- SD (range)] 6.6 +/- 4.4 (0.04-18) years, mass 478 +/- 168.3 (80-700) kg presented for a range of operations requiring general anaesthesia. MATERIALS AND METHODS Pre-anaesthetic medication was intravenous (IV) medetomidine 7 mug kg(-1). Anaesthesia was induced with IV ketamine (2 mg kg(-1)) and diazepam (0.02 mg kg(-1)). After endotracheal intubation, O2 was delivered (FiO2 > 0.85). Positive pressure ventilation was initiated if breath-holding in excess of 1 minute occurred. Anaesthesia was maintained with a constant rate medetomidine infusion (3.5 microg kg(-1) hour(-1)) and propofol infused IV to effect (initial dose 0.1 mg kg(-1) minute(-1)). Heart (HR) respiratory (fr) and propofol administration rates, and systemic arterial blood pressures were recorded at 5-minute intervals. Arterial blood gas (O2 and CO2) tensions and pH values were recorded every 15 minutes. Ten minutes after ending medetomidine-propofol infusion, medetomidine (2 microg kg(-1); IV) was given. Cardiopulmonary data were analysed using descriptive statistical techniques. RESULTS Thirty-three orthopaedic, seven integumentary and 10 elective abdominal operations were performed. Cardiopulmonary data, presented as range of mean individual (and absolute individual minimum and maximum values) were: HR: 28.0-39.2 (16-88) beats minute(-1); mean arterial blood pressure: 74.0-132.5 (42-189) mmHg; PaO2: 22.1-42.9 (4.9-67.8) kPa; [166-322 (37-508) mmHg], PaCO2: 6.7-8.1 (4.2-11.8) kPa [50-61 (32-88) mmHg] and pH 7.35-7.39 (7.15-7.48). Positive pressure ventilation was required in 23 horses. In three horses, HR values below 20 beats minute(-1) were treated with 20 microg kg(-1) atropine (IV). Mean propofol infusion rates were 98-108 microg kg(-1) minute(-1). During anaesthesia, movement occurring in 14 horses was controlled with thiopental. Duration of anaesthesia was 111.6 +/- 41.4 (46-225) minutes. Recovery in all horses was uneventful and completed within 42.2 +/- 19.8 (12-98) minutes. CONCLUSIONS AND CLINICAL RELEVANCE Medetomidine-propofol infusion produces adequate conditions for a range of surgical procedures. Cardiovascular function was adequate, as no pressor agents were required. Positive pressure ventilation was required in 23 horses.
Hyperoxia Inhibits Oxidant-induced Apoptosis in Lung Epithelial Cells*

It has previously been shown that hyperoxia induces nonapoptotic cell death in cultured lung epithelial cells, whereas hydrogen peroxide (H2O2) and paraquat cause apoptosis. To test whether pathways leading to oxidative apoptosis in epithelial cells are sensitive to molecular O2, A549 cells were exposed to 95% O2 prior to exposure to lethal concentrations of H2O2. The extent of H2O2-induced apoptosis was significantly reduced in cells preexposed to hyperoxia compared with room-air controls. Preexposure of the hyperoxia-resistant HeLa-80 cell line to 80% O2 also inhibited oxidant-induced apoptosis, suggesting that this inhibition is not due to O2toxicity. Because hyperoxia generates reactive oxygen species and activates the redox-sensitive transcription factor nuclear factor κB (NF-κB), the role of antioxidant enzymes and NF-κB were examined in this inhibitory process. The onset of inhibition appeared to be directly related to the degradation of IκB and subsequent activation of NF-κB (either by hyperoxia or TNF-α), whereas no significant up-regulation of endogenous antioxidant enzyme activities was found. In addition, suppression of NF-κB activities by transfecting A549 cells with a dominant-negative mutant construct of IκB significantly augmented the extent of H2O2-induced apoptosis. These data suggest that hyperoxia inhibits oxidant-induced apoptosis and that this inhibition is mediated by NF-κB.