Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of diabetes mellitus and hyperglycemia on the proliferation of human Tenon's capsule fibroblasts: Implications for wound healing after glaucoma drainage surgery

Glaucoma drainage surgery in diabetic patients is associated with a relatively poor prognosis due to increased scarring at the site of surgery, secondary to increased proliferation of human Tenon's capsule fibroblasts (hTCF). This is in marked contrast to diabetic wound healing at other sites, where it is generally impaired. The aim of this study was to determine why diabetics show an increased ocular scarring response in comparison to that found at other sites. Under normoglycemic conditions, hTCF isolated from diabetics showed a mean reduction in short‐term proliferation (95% CI) of 45 ± 12% compared with normal controls (p < 0.001). Under hyperglycemic conditions, proliferation of diabetic hTCF was reduced by 21 ± 11% (p < 0.01) compared with nondiabetic controls. When exposed to transforming growth factor‐β2 (1–10,000 pg/ml) and platelet‐derived growth factor‐BB (0.5–500 ng/ml) under both normo‐ and hyperglycemic conditions, there was a dose‐related increase in proliferation of both diabetic and nondiabetic controls. There was no significant difference in response to cytokine stimulation between the two groups at any of the cytokine concentrations used. Western blot analysis did not show any apparent difference in the expression of platelet‐derived growth factor receptor α, mitogen‐activated protein kinase/ERK2, or transforming growth factor‐β receptor II to account for the reduced proliferation of diabetic hTCF. These results suggest that hTCF behave in a manner similar to fibroblasts from other nonocular sites and that the increased proliferation and scarring response found in vivo may be secondary to the previously noted elevated cytokine concentrations in the aqueous and vitreous of diabetics.
Treatment of exogenous Candida endophthalmitis in rabbits with oral fluconazole

We investigated the efficacy of oral fluconazole, alone or in combination with oral flucytosine (5FC), in treating Candida endophthalmitis using a rabbit model. Albino rabbits were infected with an intravitreal inoculation of 1,000 CFU of susceptible Candida albicans and randomized 5 days later to receive treatment with oral fluconazole alone (80 mg/kg of body weight per day), a combination of fluconazole and 5FC (100 mg/kg/12 h), or no treatment. The treatment effect was assessed at 2 and 4 weeks after therapy by funduscopy, quantitative vitreous culture, and histopathology. Intravitreal levels of fluconazole, 2 to 24 h after the first dose, were measured to be > 10 times the MIC of the drug for C. albicans. Among rabbits treated with fluconazole for 2 weeks, 67% had a > 90% reduction in fungal load (P < 0.05) and 33% were sterile. After 4 weeks, all had a > 99% reduction in fungal load (P < 0.05) and 75% were sterile (P = 0.01). This treatment effect was unchanged 4 weeks after discontinuation of fluconazole. Among rabbits treated with fluconazole and 5FC for 2 weeks, 67% died during therapy. Among the surviving rabbits, 75% had a > 90% reduction in fungal load (P < 0.05) and 25% were sterile. We conclude that oral fluconazole may be useful for treatment of Candida endophthalmitis. Addition of 5FC was associated with high toxicity and minimal additional antifungal effect in our rabbit model.
Tobacco smoking and alcohol consumption as risk factors for glioma: a case-control study in Melbourne, Australia.

OBJECTIVE: To investigate possible associations between tobacco smoking and alcohol consumption and the risk of adult glioma. DESIGN: This was a population based, case-control study. Relative risks (RR) were estimated using logistic regression analysis. SETTING: Melbourne, Australia. PARTICIPANTS: These comprised 416 case subjects (166 women, 250 men), 66% of those eligible; and 422 control subjects (170 women, 252 men), 43.5% of those potentially eligible. RESULTS: There was no increase in risk of glioma with having ever smoked tobacco (RR 1.29, 95% CI 0.95, 1.75) for all subjects, adjusted for age, a reference date, and gender. There was a slight increase in risk for men (RR 1.64, 95% CI 1.1, 2.45), but not for women (RR 0.99, 95% CI 0.62, 1.62). For men, there was no increase in risk with increasing pack-years of cigarette smoking, but the risk was significantly increased in subjects who had smoked for less than 10 years. There was no increase in risk associated with having ever drunk alcohol for all subjects (RR 0.96, 95% CI 0.67, 1.37), women (RR 0.69, 95% CI 0.4, 1.15) or men (RR 1.40, 95% CI 0.81, 2.43). CONCLUSIONS: This study does not support an association between either tobacco smoking or alcohol consumption and glioma. The pattern of risk associated with tobacco smoking in men appears inconsistent with a causal role, and may be due to chance, response bias, or uncontrolled confounding.
A randomized controlled trial of telephone peer support's influence on breastfeeding duration in adolescent mothers.

PURPOSE Adolescent mothers breastfeed less often and for a shorter duration than adult mothers. This randomized controlled trial was designed to evaluate the effect of telephone peer support on breastfeeding duration among adolescents. METHODS Five adolescents who had previously breastfed were trained to provide peer support. Seventy-eight breastfeeding mothers were randomly assigned to an intervention group that received telephone calls from the peer support persons (n = 38) or to a control group that did not receive support (n = 40). An independent interviewer telephoned all new mothers weekly to document feeding patterns. Peer support persons, subjects, and the interviewer were all blinded to the research hypothesis and to group assignment. The primary outcome variable was "any breastfeeding" duration, i.e., the age at complete breastfeeding cessation. A secondary outcome variable was exclusive breastfeeding, i.e., the age at first introduction of any supplement. RESULTS "Any breastfeeding" duration did not differ significantly between the groups (median 75 days in the intervention group vs. 35 days in the control group, p = 0.26). Among the 13 intervention and 11 control mothers who were exclusively breastfeeding at the time of hospital discharge, the duration of exclusive breastfeeding was increased in the intervention group (median 35 days vs. 10 days, p = 0.004). CONCLUSIONS This study did not demonstrate a significant effect of peer support on "any breastfeeding" duration. In contrast, exclusive breastfeeding duration appeared to be extended by peer support. This latter finding would benefit from confirmation in future studies. However, unless better methods are developed for retaining peers, this is likely to be a labor-intensive approach to extending exclusive breastfeeding duration among adolescent mothers.
The Yeast Proprotein Convertase Encoded by YAP3 Is a Glycophosphatidylinositol-anchored Protein That Localizes to the Plasma Membrane (*)

The yeast YAP3 gene encodes an aspartyl endoprotease that cleaves precursor proteins at selected pairs of basic amino acids and after single arginine residues. Biosynthetic studies of this proprotein processing enzyme indicate that Yap3 is predominantly cell-associated and migrates as a 160-kDa protein on SDS-polyacrylamide gel electrophoresis. Nearly equal amounts of Yap3 are immunodetected in a-haploid, α-haploid, and a/α-diploid yeast, demonstrating that the expression of YAP3 is not mating type-specific. As shown by endoglycosidase H treatment, which drastically reduces both the estimated molecular mass and the heterogeneity of the protein on SDS-polyacrylamide gel electrophoresis (68 versus 160 kDa), the oligosaccharides N-linked to the protein are subjected to extensive outer chain mannosylation. Outer chain sugar mannosylation takes place in the Golgi apparatus and is commonly found on yeast secreted glycoproteins and/or cell wall mannoproteins. Treatment of the total yeast membranes with chemical agents known to disrupt protein-protein and protein-lipid interactions reveal that Yap3 is membrane-associated. Based upon the release of the membrane-bound form by bacterial phosphatidylinositol phospholipase C digestion and metabolic labeling of the protein with myo-[3H]inositol, Yap3 owes its association with the membrane to the addition of a glycophosphatidylinositol anchor. The cellular localization of Yap3 has been addressed by subcellular fractionation studies. In both differential centrifugation of intracellular organelles and sucrose density gradients, the bulk of Yap3 at steady state co-localizes with the plasma membrane azide-insensitive ATPase. Furthermore, consistent with the transport of Yap3 to the plasma membrane, the endoprotease sediments with secretory vesicles which accumulate at restrictive temperature in the late secretory mutant sec1-1. We therefore conclude that the endoprotease encoded by YAP3 is a glycophosphatidylinositol-anchored protein, which can process substrates both intracellularly and at the cell surface.
Nitric oxide‐induced adenosine inhibition of hippocampal synaptic transmission depends on adenosine kinase inhibition and is cyclic GMP independent

Adenosine is an important inhibitory neuromodulator that regulates neuronal excitability. Several studies have shown that nitric oxide induces release of adenosine. Here we investigated the mechanism of this release. We studied the effects of nitric oxide on evoked field excitatory postsynaptic potentials (fEPSPs) recorded in the CA1 area of rat hippocampal slices. The nitric oxide donor 1,1‐diethyl‐2‐hydroxy‐2‐nitroso‐hydrazine sodium (DEA/NO; 100 µm) depressed the fEPSP by 77.6 ± 4.1%. This effect was abolished by the adenosine A1 antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX; 400 nm), indicating that the nitric oxide effect was mediated by adenosine accumulation. The DEA/NO effect was unaltered by the 5′‐ectonucleotidase inhibitor α,β‐methylene‐adenosine 5′‐diphosphate (AMP‐CP; 100 µm), indicating that extracellular adenosine did not derive from ATP or cAMP release. The guanylyl cyclase inhibitor 1H‐[1,2,4]oxadiazole[4,3‐a]quinoxaline‐1‐one (ODQ; 5 µm) did not affect nitric oxide depression of the fEPSPs, indicating that nitric oxide‐mediated adenosine release was not mediated through a cGMP signaling cascade. This conclusion was confirmed by the observation that 8‐(4‐chlorophenylthio)‐guanosine‐3′,5′‐cyclic monophosphate (8‐pCPT‐cGMP; 1 mm) reversibly depressed the fEPSP by 24.9 ± 4.5%, but this effect was not blocked by adenosine antagonists. Adenosine kinase inhibitor 5‐iodotubercidin (ITU; 7 µm) occluded the nitric oxide effects by 74%, suggesting that inhibition of adenosine kinase activity contributes to adenosine release. In conclusion, exogenous nitric oxide evokes adenosine release by a cGMP‐independent pathway. Intracellular cGMP elevation partially inhibits the fEPSP but not through adenosine release. Although a direct block of adenosine kinase by nitric oxide can not be excluded, the depression of adenosine kinase activity may be due to inhibition by its own substrate adenosine.
Identification of SPOR Domain Amino Acids Important for Septal Localization, Peptidoglycan Binding, and a Disulfide Bond in the Cell Division Protein FtsN

ABSTRACT SPOR domains are about 75 amino acids long and probably bind septal peptidoglycan during cell division. We mutagenized 33 amino acids with surface-exposed side chains in the SPOR domain from an Escherichia coli cell division protein named FtsN. The mutant SPOR domains were fused to Tat-targeted green fluorescent protein (TTGFP) and tested for septal localization in live E. coli cells. Lesions at the following 5 residues reduced septal localization by a factor of 3 or more: Q251, S254, W283, R285, and I313. All of these residues map to a β-sheet in the published solution structure of FtsNSPOR. Three of the mutant proteins (Q251E, S254E, and R285A mutants) were purified and found to be defective in binding to peptidoglycan sacculi in a cosedimentation assay. These results match closely with results from a previous study of the SPOR domain from DamX, even though these two SPOR domains share <20% amino acid identity. Taken together, these findings support the proposal that SPOR domains localize by binding to septal peptidoglycan and imply that the binding site is associated with the β-sheet. We also show that FtsNSPOR contains a disulfide bond between β-sheet residues C252 and C312. The disulfide bond contributes to protein stability, cell division, and peptidoglycan binding.
Partnership for Implementation of Evidence-Based Mental Health Practices in Rural Federally Qualified Health Centers: Theory and Methods

Background: Mental health and substance abuse are among the most commonly reported reasons for visits to Federally Qualified Health Centers (CHCs), yet only 6.5% of encounters are with on-site behavioral health specialists. Rural CHCs are significantly less likely to have on-site behavioral specialists than urban CHCs. Because of this lack of mental health specialists in rural areas, the most promising approach to improving mental health outcomes is to help rural primary care (PC) providers deliver evidence-based practices (EBPs). Despite the scope of these problems, no research has developed an effective implementation strategy for facilitating the adoption of mental health EBPs for rural CHCs. We sought to describe the conceptual components of an implementation partnership that focuses on the adaption and adoption of mental health EBPs by rural CHCs in Arkansas.Methods: We present a conceptual model that integrates seven separate frameworks: (1) Jones and Wells' Evidence-Based Community Partnership Model, (2) Kitson's Promoting Action on Research Implementation in Health Services (PARiHS) implementation framework, (3) Sackett's definition of evidence-based medicine, (4) Glisson's organizational social context model, (5) Rubenstein's Evidence-Based Quality Improvement (EBQI) facilitation process, (6) Glasgow's RE-AIM evaluation approach, and (7) Naylor's concept of shared decision making.Conclusions: By integrating these frameworks into a meaningful conceptual model, we hope to develop a successful implementation partnership between an academic health center and small rural CHCs to improve mental health outcomes. Findings from this implementation partnership should have relevance to hundreds of clinics and millions of patients, and could help promote the sustained adoption of EBPs across rural America.
Improved Obstetric Outcomes and Few Maternal Toxicities Are Associated With Antiretroviral Therapy, Including Highly Active Antiretroviral Therapy During Pregnancy

Data from 2543 HIV-infected women were analyzed to correlate antiretroviral therapy (ART) used during pregnancy with maternal and pregnancy outcomes. ART was analyzed according to class of agents used and according to monotherapy versus combination ART containing neither protease inhibitors (PIs) nor nonnucleoside reverse transcriptase inhibitors versus highly active ART. Timing of ART was classified according to early (recorded at or before 25-week gestation study visit) and late (recorded at 32-week gestation or delivery visit) use. Maternal outcomes assessed included hematologic, gastrointestinal, neurologic, renal, and dermatologic complications; gestational diabetes; lactic acidosis; and death. Adverse pregnancy outcomes assessed included hypertensive complications; pre-term labor or rupture of membranes; preterm delivery (PTD); low birth weight; and stillbirth. Logistic regression analyses controlling for multiple covariates revealed ART to be independently associated with few maternal complications: ART use was associated with anemia (odds ratio [OR] = 1.6, 95% confidence interval [CI]: 1.1-2.4), and late use of ART was associated with gestational diabetes (OR = 3.5, 95% CI: 1.2-10.1). Logistic regression analyses revealed an increase in PTD at <37 weeks for 10 women with late use of ART not containing zidovudine (ZDV; OR = 7.9, 95% CI: 1.4-44.6) and a decrease in adverse pregnancy outcomes as follows: late use of ART containing ZDV was associated with decreased risk for stillbirth and PTD at <37 weeks (OR = 0.06, 95% CI: 0.02-0.18; OR = 0.5, 95% CI: 0.3-0.8, respectively), and ART containing nucleoside reverse transcriptase inhibitors but not ZDV during early and late pregnancy was associated with decreased risk for PTD at <32 weeks (OR = 0.3, 95% CI: 0.2-0.7). Benefits of ART continue to outweigh observed risks.
Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus

Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections and play an important role in mucosal immunity. However, the role of MAIT cells remains enigmatic in autoimmune diseases. In this study, we examined the level and function of MAIT cells in patients with rheumatic diseases. MAIT cell, cytokine, and programmed death-1 (PD-1) levels were measured by flow cytometry. Circulating MAIT cell levels were significantly reduced in systemic lupus erythematosus (SLE) and rheumatoid arthritis patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets, and significantly correlated with disease activity, such as SLE disease activity index and 28-joint disease activity score. Interestingly, MAIT cell frequency was significantly correlated with NKT cell frequency in SLE patients. IFN-γ production in MAIT cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca2+/calcineurin/NFAT1 signaling pathway. In SLE patients, MAIT cells were poorly activated by α-galactosylceramide–stimulated NKT cells, thereby showing the dysfunction between MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In rheumatoid arthritis patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood. Our study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression. These abnormalities possibly contribute to dysregulated mucosal immunity in SLE.
Caring for Depressed and Suicidal Older Patients: A Survey of Physicians and Nurse Practitioners

Objective: This study sought to describe patterns of mental health care for depressed and suicidal geriatric patients by primary care physicians (MDs) and nurse practitioners (NPs). Methods: A probability sample of 300 Illinois MDs from the AMA Physician Masterfile and a national sample of 595 NPs from the American Academy of Nurse Practitioners were surveyed. Sixty-three percent of MDs and 61 percent of NPs responded regarding their approaches to assessing, treating, and referring older adult patients who were depressed or suicidal. Respondents rated their confidence in assessing and treating depression and suicidality and identified barriers to mental health treatment in a primary care setting. Results: Both similarities and differences were found among MDs and NPs in their patterns of managing depressed and suicidal older adults. NPs used more varied approaches in assessing, treating, and referring their geriatric patients with mental health problems. MDs relied more heavily on psychotropic medications for the treatment of depression and on psychiatrists when referring suicidal older patients. NPs were more likely than MDs to note lack of training and referral resources as barriers to treating depression of older patients. NPs rated their training in geriatric mental health more favorably than MDs. Conclusions: In terms of assessment of depression, preferred treatment approaches, the use of referral resources, and perceived barriers to mental health care, there appears to be a greater orientation towards a psychosocial approach among NPs. Primary care MDs and NPs often have different perspectives that in combination could enhance the mental health care of geriatric patients.
FLAME STRUCTURE OF CL-20 STUDIED BY PROBING MOLECULAR BEAM MASS SPECTROMETRY

Introduction Hexanitrohexaazaizowurzitan (HNIW or CL-20) is a cage nitramine, which was synthesized quite recently. CL-20 is one of the new high energy materials (HEMs). At present time investigations of CL-20 as an ingredient of rocket propellants are conducted all over the world. For the first time CL-20 was synthesized by Nielsen in 1987 [1]. In literature the first information on synthesis of compounds from class of polycyclic nitramines appeared in 1991 [2]. Detailed description of synthesis and main characteristics of CL-20 were presented significantly later (in 1997-1998) in Refs. [3, 4]. Data presented in literature are devoted to measurements of CL-20 burning rate [5, 6], issues of its thermal stability and thermal decomposition [1, 7-12]. However in literature there are completely absent data on chemical structure of CL-20 flame. The only investigation on thermal structure of CL-20 flame is presented in Ref. [5]. Main products of thermal decomposition of CL-20 at temperature conditions close to those in combustion wave are NO2 and NO [7]. Increase of temperature leads to decrease of NO2/NO ratio, i.e. to more preferable formation of NO. Other decomposition products, which form in small amounts, are CO, HCN, N2O and CO2. At lower temperatures main decompositions products are N2, CO2, CO and N2O [8]. Analysis of literature data on thermal decomposition of CL-20 has shown that chemical processes in the condensed phase are strongly dependent on experimental conditions, and therefore these data can not be used as a basis for understanding of chemistry involved in self-sustained combustion of CL-20. The main goal of present work was to study chemical structure of CL-20 flame at pressures of 0.1-0.5 MPa using probing molecular beam mass spectrometry.
Cardiovascular effects of N-butylscopolammonium bromide and xylazine in horses.

REASONS FOR PERFORMING STUDY N-butylscopolammonium bromide (NBB) and xylazine are commonly used medications for the treatment of spasmodic colic and other forms of abdominal pain in horses. Both NBB and xylazine exert significant effects on the cardiovascular system and other vital systems of horses. OBJECTIVE To evaluate the effects of i.v. administration of NBB, xylazine, and the combination of NBB and xylazine on heart rate, other commonly measured physiological parameters, cardiac rhythm and blood pressure. METHODS Six mature horses of mixed breed were used. In a random cross-over design, each horse was given 0.3 mg/kg bwt of NBB i.v. , 0.25 mg/kg bwt xylazine i.v. , and a combination of 0.3 mg/kg bwt NBB and 0.25 mg/kg bwt xylazine. Heart rate, physiological parameters, cardiac rhythm and indirect blood pressure were recorded at timed intervals before and 60 min following administration. RESULTS Heart rate and blood pressure were significantly elevated immediately following administration of NBB or NBB with xylazine. Administration of NBB with xylazine resulted in significantly greater initial and peak blood pressure values than with NBB alone. Administration of xylazine resulted in a decrease in heart rate, with an initial increase in blood pressure followed by a decrease in blood pressure. Sinus tachycardia was seen with NBB, and NBB and xylazine administration. First and second degree atrioventricular block was identified with xylazine administration. Ventricular tachycardia was identified in one horse following NBB and xylazine administration. CONCLUSIONS Results of this study suggest that the effects of administration of NBB alone or in combination with xylazine to horses with colic, especially to those with systemic cardiovascular compromise, should be considered carefully to assess condition and predict prognosis accurately, and to avoid potential adverse effects.