Miracle-dz/UniFAR-FTUs huggingface dataset:
Serine Antiproteinase Administration Preserves Innate Superoxide Dismutase Levels After Acid Aspiration and Hyperoxia but Does Not Decrease Lung Injury

Acute lung injury after acid aspiration and increased ambient oxygen result in significant oxidative damage to the lungs. Lung antioxidant levels are also reduced. Because levels of serine proteinases in the airspaces are also dramatically increased, we hypothesized that these enzymes play a role in degrading lung antioxidants. Rats were treated with a serine proteinase inhibitor, aprotinin, before pulmonary aspiration of acid in the presence of increased ambient oxygen (hyperoxia). Lung Cu/Zn and Mn superoxide dismutase (SOD) activity (by colorimetric assay) and Cu/Zn SOD immune reactive protein (enzyme-linked immunosorbent assay) were assayed. The effects of antiproteinase treatment on acute lung injury were also assessed. Total SOD, Cu/Zn SOD, and Cu/Zn SOD antigenic protein levels were decreased in animals after acid aspiration and hyperoxia. However, Mn SOD activity was unchanged. The decrease in Cu/Zn SOD was attenuated in animals, where serine proteinase activity was inhibited. However, antiproteinase treatment did not decrease acute pulmonary injury, as assessed by leakage of radiolabeled albumin into the lung (permeability index), arterial blood gases, and markers of acute inflammation (pulmonary myeloperoxidase activity, a surrogate neutrophilic marker, and inflammatory cytokine profiles). We conclude that production of serine proteinases play a major role in degrading Cu/Zn SOD, thereby decreasing pulmonary antioxidant capacity. However, the role this plays in the pathogenesis of the acute lung injury is not clear.
2-Aminoethyl Methylphosphonate, a Potent and Rapidly Acting Antagonist of GABAA-ρ1 Receptors

2-Aminoethyl methylphosphonate (2-AEMP), an analog of GABA, has been found to exhibit antagonist activity at GABAA-ρ1 (also known as ρ1 GABAC) receptors. The present study was undertaken to elucidate 2-AEMP's action and to test the activities of 2-AEMP analogs. Whole-cell patch-clamp techniques were used to record membrane currents in neuroblastoma cells stably transfected with human GABAA-ρ1 receptors. The action of 2-AEMP was compared with that of 1,2,5,6-tetrahydropyridin-4-yl methylphosphinic acid (TPMPA), a commonly used GABAA-ρ1 antagonist. With 10 μM GABA, 2-AEMP's IC50 (18 μM) differed by less than 2.5-fold from that of TPMPA (7 μM), and results obtained were consistent with a primarily competitive mode of inhibition by 2-AEMP. Terminating the presentation of 2-AEMP or TPMPA in the presence of GABA produced a release from inhibition. However, the rate of inhibition release upon the termination of 2-AEMP considerably exceeded that determined with termination of TPMPA. Moreover, when presented at concentrations near their respective IC50 values, the preincubation period associated with 2-AEMP's onset of inhibition was much shorter than that for TPMPA. Analogs of 2-AEMP possessing a benzyl or n-butyl rather than a methyl substituent at the phosphorus atom, as well as analogs bearing a C-methyl substituent on the aminoethyl side chain, exhibited reduced potency relative to 2-AEMP. Of these analogs, only (R)-2-aminopropyl methylphosphonate significantly diminished the response to 10 μM GABA. Structure-activity relationships are discussed in the context of molecular modeling of ligand binding to the antagonist binding site of the GABAA-ρ1 receptor.
Nodulating Competitiveness of a Nonmotile Tn7 Mutant of Bradyrhizobium japonicum in Nonsterile Soil

A nonmotile mutant of Bradyrhizobium japonicum serogroup 127 was generated by Tn7 mutagenesis and matched with the wild type against a common competitor in studies of soybean nodulation in nonsterile soil. The Tn7 mutant was very similar to the wild type in growth rate in culture, soybean lectin-binding ability, flagellar morphology, and nodulating capability, but it had a longer lag phase. Competing strains were distributed uniformly in soil in various ratios and at different population densities prior to planting. Mutant and wild type were equally prevalent in the seedling rhizosphere at about the time of nodule initiation, suggesting that motility conferred no advantage in rhizosphere colonization. Nodulation success of the Tn7 mutant was lower than that of the wild type under all test conditions. Differences were greatest at low soil populations of competitors and much less pronounced at initial populations of 107 g−1. The longer lag phase of the Tn7 mutant may have contributed to its decreased competitiveness, especially at the higher inoculation levels. The antibiotic and motility markers were stable, and the rifampin resistance derived from the parent did not affect adversely the competitiveness of the Tn7 mutant. We found motility to be of limited importance to the competitiveness of a strain in normal nonsterile soil, where the significance, if any, of this ability may be in migration at the immediate root surface in soils sparsely populated with rhizobial symbionts.
Early oral hydration: a novel regimen for management after elective cesarean section.

OBJECTIVE To compare early oral hydration versus the conventional intravenous fluid replacement after elective cesarean section. METHODS Two hundred women performed elective cesarean section were selected and randomized to: Regimen I (n = 100): early oral hydration (sips of fruit juices sweetened with honey once the women felt thirst immediately after the operation, then solid food 24 hours later, the amounts of juice or food were determined by the patient herself, i.e. she would regulate her physiological needs) versus regimen II (n = 100): conventional intravenous hydration (2-3 L of dextrose saline/24 hours and solid food thereafter). Biochemical, metabolic values, postoperative nausea and vomiting, propulsive bowel movements, tolerance of solid food, hospital stay and successful continuation of breast feeding were compared in both groups. RESULTS The two regimens were equally effective in maintaining fluid balance and normal plasma and urinary electrolytes without any observed differences in biochemical or metabolic values. The return of bowel sounds, first occurrence of flatus and tolerance of solid food were achieved in regimen I at time periods significantly shorter than those attained with regimen II (p < 0.0001). The incidence of nausea and vomiting, ileus and deep vein thrombosis was higher in regimen II than in regimen I but the difference is statistically insignificant (p > 0.05). Patients in regimen II were hospitalized for significantly longer times than those on regimen I (p < 0.0001). Successful continuation of breast feeding was significantly more in regimen I than in regimen II (p < 0.01). CONCLUSION Early oral hydration after elective cesarean section effectively maintained fluid balance and it was associated with rapid return of propulsive bowel movements, successful breast feeding, less side effects and shorter hospital stay than the conventional intravenous hydration. So, it should be used in most cases after elective cesarean section.
Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: implications for genetic testing.

AIM To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplification (MLPA). RESULTS Eighteen germline mutations (50%) were identified, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the definite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam I/II criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family. CONCLUSION Our study describes for the first time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population.
Mechanistic comparison of Bacillus subtilis 6S-1 and 6S-2 RNAs—commonalities and differences

Bacteria synthesize small regulatory RNAs known as 6S RNAs which bind to RNA polymerase and regulate transcription. This paper describes an analysis of two 6S RNAs produced in Bacillus subtilis. Although these two RNAs share many features, there are also distinct differences, the mechanistic implications of which are discussed.
Do Cash Holding and Corporate Governance Structure Matter for the Performance of Firms? Evidence from KMI 30- and KSE 100-Indexed Firms in Pakistan

The objective of the study is to investigate the combined impact of cash holding and corporate governance on the performance of non-financial firms. The sample consists of 30 Islamic-based firms from Karachi Meezan Index (KMI) 30 index and 42 non-Islamic firms from Karachi Stock Exchange (KSE) 100 index in Pakistan over the period of 2010–2014. The results show that corporate cash holding has negative and significant relationship with earnings per share and returns on assets (EPS and ROA), while it has a positive and statistically significant relationship with Tobin’s Q and market share price (TQ, MSP) in both KMI 30- and KSE 100-indexed firms. In addition, we find that the structure of corporate governance is poorly performed in KMI 30- and KSE 100-indexed firms. This poor governance structure leads to the firms dispelling cash quickly, which significantly reduces the performance of these firms. So the firms can increase their performance by establishing effective corporate governance structure.
Complications Following Therapeutic Bronchoscopy for Malignant Central Airway Obstruction: Results of the AQuIRE Registry.

BACKGROUND There are significant variations in how therapeutic bronchoscopy for malignant airway obstruction is performed. Relatively few studies have compared how these approaches affect the incidence of complications. METHODS We used the American College of Chest Physicians (CHEST) Quality Improvement Registry, Evaluation, and Education (AQuIRE) program registry to conduct a multicenter study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was the incidence of complications. Secondary outcomes were incidence of bleeding, hypoxemia, respiratory failure, adverse events, escalation in level of care, and 30-day mortality. RESULTS Fifteen centers performed 1,115 procedures on 947 patients. There were significant differences among centers in the type of anesthesia (moderate vs deep or general anesthesia, P < .001), use of rigid bronchoscopy (P < .001), type of ventilation (jet vs volume cycled, P < .001), and frequency of stent use (P < .001). The overall complication rate was 3.9%, but significant variation was found among centers (range, 0.9%-11.7%; P = .002). Risk factors for complications were urgent and emergent procedures, American Society of Anesthesiologists (ASA) score > 3, redo therapeutic bronchoscopy, and moderate sedation. The 30-day mortality was 14.8%; mortality varied among centers (range, 7.7%-20.2%, P = .02). Risk factors for 30-day mortality included Zubrod score > 1, ASA score > 3, intrinsic or mixed obstruction, and stent placement. CONCLUSIONS Use of moderate sedation and stents varies significantly among centers. These factors are associated with increased complications and 30-day mortality, respectively.
Isosilibinin inhibits advanced human prostate cancer growth in athymic nude mice: Comparison with silymarin and silibinin

Earlier studies have shown the cancer chemopreventive efficacy of silymarin and its semi‐purified constituent silibinin against prostate cancer (PCa), but the efficacy of other constituents of silymarin is largely unknown. In the present study, we assessed the in vivo growth inhibitory efficacy of one such constituent isosilibinin (a 50:50 mixture of isosilybin A and isosilybin B) in comparison with silymarin and silibinin in human PCa DU145 xenograft in athymic nude mice. Isosilibinin feeding (200 mg/kg body weight per day) significantly inhibited the growth of xenograft after 53 days of treatment (p ≤ 0.005), which was equally or slightly better effective than silymarin and silibinin, respectively. Treatment with isosilibinin, silymarin and silibinin was stopped after 53 days and tumor volume was measured till 77 days. After 24 days of treatments withdrawal, tumor volume remain decreased, however, it was statistically significant only with isosilibinin (p ≤ 0.05), suggesting its prolonged effect. Biomarker analysis showed that isosilibinin, silymarin and silibinin treatment for 53 days significantly inhibited the immunoreactivity for proliferating cell nuclear antigen (PCNA), microvessel density (CD31) and vascular endothelial growth factor along with significant increase in apoptotic cell population. The PCNA levels in tumors remained significantly low even after 24 days of treatments withdrawal. Western blot analysis of tumor tissue suggested that these flavonolignan formulations differentially alter the expression of cell cycle regulatory molecules, cyclins and Cdks. Overall, the results of present study suggest that isosilibinin has comparatively better efficacy against PCa and should be further analyzed for its clinical utility. © 2008 Wiley‐Liss, Inc.
Evaluation of the Impact of a Pharmacist‐Led Telehealth Clinic on Diabetes‐Related Goals of Therapy in a Veteran Population

Telemedicine has been offered as a way to ensure that all patients, including those who live in rural areas, have access to the same health care. This study was performed to evaluate the benefit of a real‐time, clinic‐based video telehealth (Clinical Video Telehealth [CVT]) program and the impact of a pharmacist‐led CVT clinic for chronic disease state management. The primary objective was to evaluate changes from baseline values, in veterans referred by primary care providers to this clinic.
Is non-linear frequency compression amplification beneficial to adults and children with hearing loss? A systematic review

Abstract Objective: To conduct a systematic review of the benefits of non-linear frequency compression (NLFC) in adults and children. Design: Ten databases were searched for studies comparing the effects of NLFC and conventional processing (CP) for the period January 2008 to September 2017. Study sample: Twelve articles were included in this review: four adults and school-aged only, one pre-school only and three with both adults and school-aged children. Results: A two-stage process was implemented to grade the evidence. The individual studies were graded based on their study type (from 1 = highest quality of evidence to 5 = the lowest quality) and then sub-graded based on their quality (“a” for “good quality” or “b” for “lesser quality”). All studies were awarded 4a, except the single pre-school study, which was awarded 2a. The overall evidence for each population was graded based on the quality, quantity and consistency of the studies. The body of evidence was rated as very low for both adults and school-aged children, but high for pre-school children. Conclusion: The low number (and quality) of studies means that evidence supporting the benefit from NLFC is inconclusive. Further high-quality RCTs are required to provide a conclusive answer to this question.
Apolipoprotein A-I Induces Translocation of Cholesterol, Phospholipid, and Caveolin-1 to Cytosol in Rat Astrocytes*

Intercellular cholesterol transport in the brain is carried by high density lipoprotein (HDL) generated in situ by cellular interaction with the apolipoprotein apoE, which is mainly synthesized by astrocytes, and with apoA-I secreted by cells such as endothelial cells. Rat astrocytes in fact generate HDL with extracellular apoA-I in addition to releasing HDL with endogenously synthesized apoE, seemingly by the same mechanism as the HDL assembly for systemic circulation. Relating to this reaction, apoA-I induced translocation of newly synthesized cholesterol and phospholipid to the cytosol prior to extracellular assembly of HDL, accompanied by an increase of caveolin-1 in the cytosol, activation of sterol regulatory element-binding protein, and enhancement of cholesterol synthesis. The lipid translocated into the cytosol was recovered in the fraction with a density of 1.09–1.16 g/ml as well as caveolin-1 and cyclophilin A. Cyclosporin A inhibited these apoA-I-mediated reactions and suppressed apoA-I-mediated cholesterol release. The findings suggest that such translocation of cholesterol and phospholipid into the cytosol is related to the apo A-I-mediated HDL assembly in astrocytes through functional association with caveolin-1 and a cyclosporin A-sensitive cyclophilin protein(s).
Cinacalcet in the treatment of persistent hyperparathyroidism after kidney transplantation.

BACKGROUND Secondary hyperparathyroidism persists in 30 - 50% of patients after a successful kidney transplant and it is the most frequent cause of hypercalcemia after transplant, contributing to graft loss and mortality. Several medical therapies have been studied for the treatment of this condition without clear benefit. Recently, interest has grown in the use of cinacalcet in kidney transplant recipients. METHODS We describe the efficacy of cinacalcet in 18 kidney transplant patients with persistent hyperparathyroidism and progressive hypercalcemia treated for a period of 12-months. We analyzed serum calcium, phosphorus and parathyroid hormone levels every 6 months, and cinacalcet was titrated if necessary. Statistical analysis was performed using ANOVA. RESULTS With therapy, all patients exhibited significant reduction in parathyroid hormone levels, from a mean value of 242.04 ± 105.82 pg/ml to a mean value of 145.62 ± 54.99 pg/ml (p < 0.001) 12 months later. In addition, serum calcium levels normalized during the study period, from 11.16 mg/d to 9.95 mg/dl (mean values) (p < 0.001). No significant change in serum creatinine was found in this group of patients. Cinacalcet was well tolerated, with no side effects documented. CONCLUSION This preliminary experience suggests that cinacalcet may be useful in the treatment of persistent hyperparathyroidism after kidney transplant. In addition, cinacalcet controlled hypercalcemia, which has well known adverse effects after transplant. This was accomplished with no evidence of declining kidney function or limiting side effects.
Role of temperament in early adolescent pure and co-occurring internalizing and externalizing problems using a bifactor model: Moderation by parenting and gender

Abstract We contribute to the literature on the relations of temperament to externalizing and internalizing problems by considering parental emotional expressivity and child gender as moderators of such relations and examining prediction of pure and co-occurring problem behaviors during early to middle adolescence using bifactor models (which provide unique and continuous factors for pure and co-occurring internalizing and externalizing problems). Parents and teachers reported on children's (4.5- to 8-year-olds; N = 214) and early adolescents’ (6 years later; N = 168) effortful control, impulsivity, anger, sadness, and problem behaviors. Parental emotional expressivity was measured observationally and with parents’ self-reports. Early-adolescents’ pure externalizing and co-occurring problems shared childhood and/or early-adolescent risk factors of low effortful control, high impulsivity, and high anger. Lower childhood and early-adolescent impulsivity and higher early-adolescent sadness predicted early-adolescents’ pure internalizing. Childhood positive parental emotional expressivity more consistently related to early-adolescents’ lower pure externalizing compared to co-occurring problems and pure internalizing. Lower effortful control predicted changes in externalizing (pure and co-occurring) over 6 years, but only when parental positive expressivity was low. Higher impulsivity predicted co-occurring problems only for boys. Findings highlight the probable complex developmental pathways to adolescent pure and co-occurring externalizing and internalizing problems.
A more physiological alternative to total fundoplication for the surgical correction of resistant gastro‐oesophageal reflux

The incidence of mechanical complications associated with the Nissen fundoplication has prompted evaluation of an anti‐reflux procedure designed to be simpler and more physiological, and encompassing a broader view of the many factors involved in the anti‐reflux mechanism. Preliminary assessment of the first 100 patients with a mean follow‐up of 3–5 years showed symptomatic improvement in 96 per cent and complete relief in 85 per cent. A further 100 patients were studied using formal symptom scoring, endoscopy, manometry and pH monitoring performed before operation and 3 months after operation. Similar clinical results were accompanied by improvement in endoscopic oesophagitis in 95 per cent, complete healing in 74 per cent and restoration of the pH profile to physiological levels in 84 per cent. Troublesome mechanical complications comprised a 2 per cent incidence of dysphagia, but there was no gas bloat or inability to belch or vomit, which may relate to the restoration of lower oesophageal sphincter characteristics close to those of 30 asymptomatic controls. The procedure is simpler to perform than total fundoplication, is well tolerated and is applicable to patients with reflux stricture and impaired oesophageal body motility. The results of this study support the hypotheses that effective reflux control can be achieved without total fundoplication by attention to several factors of known relevance to the anti‐reflux mechanism, and that restoration of characteristics of the lower oesophageal sphincter close to physiological levels results in a lower incidence of mechanical complications.
Calcineurin–Rcan1 Interaction Contributes to Stem Cell Factor–Mediated Mast Cell Activation

The receptor for stem cell factor (SCF) is expressed on mast cells and hematopoietic progenitors. SCF-induced signaling pathways remain incompletely defined. In this study, we identified calcineurin and regulator of calcineurin 1 (Rcan1) as novel components in SCF signaling. Calcineurin activity was induced in SCF-stimulated primary mouse and human mast cells. NFAT was activated by SCF in bone marrow–derived mast cells (BMMCs) and mouse bone marrow cells, which contain hematopoietic progenitors. SCF-mediated activation also induced expression of Rcan1 in BMMCs. Rcan1-deficient BMMCs showed increased calcineurin activity and enhanced transcriptional activity of NF-κB and NFAT, resulting in increased IL-6 and TNF production following SCF stimulation. These results suggest that Rcan1 suppresses SCF-induced activation of calcineurin and NF-κB. We further demonstrated that SCF-induced Rcan1 expression is dependent on the transcription factor early growth response 1 (Egr1). Interestingly, SCF-induced Egr1 was also suppressed by Rcan1, suggesting a negative regulatory loop between Egr1 and Rcan1. Together, our findings revealed that calcineurin contributes to SCF-induced signaling, leading to NFAT activation, which, together with NF-κB and Egr1, is suppressed by Rcan1. Considering the wide range of biological functions of SCF, these novel regulatory mechanisms in SCF signaling may have broad implications.