Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-acting injectable antipsychotics in the treatment of schizophrenia: their role in relapse prevention

Importance of the field: Antipsychotic medications are the cornerstone of treatment in schizophrenia, and a large body of data confirms the value of ongoing and continuous antipsychotic pharmacotherapy in controlling symptoms and preventing relapse. However, nonadherence with antipsychotic treatment is a significant issue, with estimates as high as 90%. Areas covered in this review: This review focuses on long-acting injectable (LAI) antipsychotics and their role in the treatment of schizophrenia. The existing literature, with an emphasis on clinical evidence, is assessed. This includes both reviews and specific trials that examine LAIs and compare them with oral agents, with measures ranging from relapse and rehospitalization to adherence. Both advantages and limitations (e.g., challenges in terms of dose titration and time to steady state) are examined. What the reader will gain: This overview serves as an update for clinicians wishing to understand LAIs better, including the newer second-generation antipsychotics (SGAs) with this formulation available, and their potential role in the long-term treatment of individuals with schizophrenia. Take home message: Despite identified advantages, LAIs are not used as widely as might be expected. It would seem that clinicians are at least partly responsible for this, influenced by our own misperceptions (e.g., that LAIs are not acceptable to patients) and, perhaps, misinformation (e.g., increased side effect risk). As clinicians, we may well be shortchanging LAIs if we position them as a treatment of last resort for the multi-episode, nonadherent, ‘revolving door’ patient, especially given recent evidence underscoring their potential benefits in first-episode patients. The search for new and more effective antipsychotics will continue, but we are reminded that suboptimal outcomes may have as much to do with nonadherence as inadequate treatments. Evidence has established that LAI antipsychotics demonstrate distinct benefits in this regard, and we would be remiss if we did not exploit this already available strategy. As well as additional research, we need to rethink how we position these agents in our treatment algorithms if we are to maximize their potential.
Transient Down-Regulation of Nucleoside Transporter 3 Gene Expression as a Drug Target in Leishmania major Using Antisense RNA Technology

Background: This study was aimed to silencing the Nucleoside transporter 3 (NT3) permease nucleobases involved in the salvage pathway of Leishmania in order to disrupt purine nucleotide uptake in the parasite and consequently, destruction of the parasite. Methods: Overall, 502 bp fragment of the NT3 gene sequence was designed to produce an antisense transcript upon entry of the vector into the parasite. The NT3 construct was transfected into L. major promastigotes and NT3 gene expression was studied in vivo and in vitro conditions. Results: Relative expression NT3 gene in transgenic Leishmania was decreased in tenth day. The percentages and the number of amastigotes infected macrophages with transgenic L. major were less than infected macrophages with wild-type strain. Our results in two groups of BALB/c female mice (wild-type strain and mutant, n=4 each group) were showed that size and number of ulcers in BALB/c mice infected with transgenic Leishmania promastigotes were less than the BALB/c mice infected with wild-type parasites. Conclusion: The results indicate the use of antisense RNA reduces of NT3 gene expression in L. major. More studies are required to obtain a new approach for treating Leishmania infection.
Explaining the Abundance of Ants in Lowland Tropical Rainforest Canopies

The extraordinary abundance of ants in tropical rainforest canopies has led to speculation that numerous arboreal ant taxa feed principally as “herbivores” of plant and insect exudates. Based on nitrogen (N) isotope ratios of plants, known herbivores, arthropod predators, and ants from Amazonia and Borneo, we find that many arboreal ant species obtain little N through predation and scavenging. Microsymbionts of ants and their hemipteran trophobionts might play key roles in the nutrition of taxa specializing on N-poor exudates. For plants, the combined costs of biotic defenses and herbivory by ants and tended Hemiptera are substantial, and forest losses to insect herbivores vastly exceed current estimates.
Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults.

Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors (NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus (HIV)-infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short-term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA (mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30-40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1-mo exposure in the stavudine-treated subjects compared with placebo (-0.8 +/- 0.5 vs. +0.7 +/- 0.3 mg.kg(-1). min(-1), P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine-treated group showed significant reduction in mtDNA/nuclear DNA (-52%, P = 0.005), with no change in placebo-treated subjects (+8%, P = 0.9). (31)P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures (r2 = 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity.
MicroRNA miR-155 Inhibits Bone Morphogenetic Protein (BMP) Signaling and BMP-Mediated Epstein-Barr Virus Reactivation

ABSTRACT MicroRNA miR-155 is expressed at elevated levels in human cancers including cancers of the lung, breast, colon, and a subset of lymphoid malignancies. In B cells, miR-155 is induced by the oncogenic latency gene expression program of the human herpesvirus Epstein-Barr virus (EBV). Two other oncogenic herpesviruses, Kaposi's sarcoma-associated herpesvirus and Marek's disease virus, encode functional homologues of miR-155, suggesting a role for this microRNA in the biology and pathogenesis of these viruses. Bone morphogenetic protein (BMP) signaling is involved in an array of cellular processes, including differentiation, growth inhibition, and senescence, through context-dependent interactions with multiple signaling pathways. Alteration of this pathway contributes to a number of disease states including cancer. Here, we show that miR-155 targets the 3′ untranslated region of multiple components of the BMP signaling cascade, including SMAD1, SMAD5, HIVEP2, CEBPB, RUNX2, and MYO10. Targeting of these mediators results in the inhibition of BMP2-, BMP6-, and BMP7-induced ID3 expression as well as BMP-mediated EBV reactivation in the EBV-positive B-cell line, Mutu I. Further, miR-155 inhibits SMAD1 and SMAD5 expression in the lung epithelial cell line A549, it inhibits BMP-mediated induction of the cyclin-dependent kinase inhibitor p21, and it reverses BMP-mediated cell growth inhibition. These results suggest a role for miR-155 in controlling BMP-mediated cellular processes, in regulating BMP-induced EBV reactivation, and in the inhibition of antitumor effects of BMP signaling in normal and virus-infected cells.
Calcineurin/NFAT signaling in the β‐cell: From diabetes to new therapeutics

Pancreatic β‐cells in the islet of Langerhans produce the hormone insulin, which maintains blood glucose homeostasis. Perturbations in β‐cell function may lead to impairment of insulin production and secretion and the onset of diabetes mellitus. Several essential β‐cell factors have been identified that are required for normal β‐cell function, including six genes that when mutated give rise to inherited forms of diabetes known as Maturity Onset Diabetes of the Young (MODY). However, the intracellular signaling pathways that control expression of MODY and other factors continue to be revealed. Post‐transplant diabetes mellitus in patients taking the calcineurin inhibitors tacrolimus (FK506) or cyclosporin A indicates that calcineurin and its substrate the Nuclear Factor of Activated T‐cells (NFAT) may be required for β‐cell function. Here recent advances in our understanding of calcineurin and NFAT signaling in the β‐cell are reviewed. Novel therapeutic approaches for the treatment of diabetes are also discussed. BioEssays 29:1011–1021, 2007. © 2007 Wiley Periodicals, Inc.
Suicide by Self-Immolation in Durban, South Africa: A Five-Year Retrospective Review

Self-immolation is an uncommon method of suicide, and its occurrence in South Africa is thus far unknown. This study aimed to determine the prevalence of self-immolation deaths and to establish a profile of these cases and the circumstances under which this condition occurs. A 5-year (1996–2000) retrospective review at a mortuary in Durban, South Africa, was conducted. Data were obtained from the Department of Forensic Medicine, the Medical Research Council’s National Injury Mortality Surveillance System, and police and hospital records. During the study period, there were 12,339 nonnatural deaths, of which 696 (5.6%) were suicides. Self-immolation accounted for 69 (0.6%) of all nonnatural deaths and 69 (9.9%) of all suicides. The subjects had a mean age of 31.2 years and were predominantly female (76.8%) and black (81.2%). The mean burn surface area was 63.3%, and the mean injury severity score was 36.9. Accelerant use was documented in 53 (76.8%) of cases, and paraffin was preferred. All cases occurred indoors. The proportion of suicides due to self-immolation in our study is excessive when compared with international studies that report figures between 0.9% and 2.2% of suicides. Additional studies are necessary to further elucidate the reasons for this discrepancy.
Are Americans Receptive to Smokefree Bars?

Abstract It is not known whether the American public accepts smokefree bars and restaurants. Anticipating public displeasure with these ordinances, tobacco, liquor and restaurant industry trade associations have helped to stall efforts to pass laws curbing bar and restaurant smoking in the expectation that diminished patronage would inevitably result. This cross-sectional trend study uses data from the May 1993 and January 1999 Current Population Surveys, Tobacco Use Supplements to compare tobacco-control attitudes among American bar and restaurant workers, all other workers, smokers and nonsmokers (total n = 90,661). It was found that by 1999, smokefree workplaces were widely accepted by two-thirds of adults, with half favoring completely smokefree restaurants. Completely smokefree bars remained less popular, with nearly equal numbers (about 30%) preferring them or favoring unrestricted bar smoking. Even among bar and restaurant industry workers less than 10% favored unrestricted restaurant smoking. Greater acceptances of smokefree bars are now taking hold, especially in places like California, where acceptance rose 15% in six years. and 45% preferred them. Opponents to smokefree bars and restaurants may have underestimated the levels of support and growing acceptance of smokefree living areas now taking hold among the general public.
Intra-Arterial Thrombus Visualized on T2* Gradient Echo Imaging in Acute Ischemic Stroke

Background: MR signal loss related to arterial thrombosis leading to vascular susceptibility artifacts (VSA) has recently been reported on gradient echo images. The time course and sensitivity of VSA in acute stroke patients has been scarcely investigated. The aim of this study was to assess the frequency and course of VSA in acute stroke patients, to compare its sensitivity to distinct features of arterial occlusion as detected on FLAIR images or on CT scan. Methods: Twenty-nine patients were scanned from 45 min to 6 h after stroke onset using identical MR parameters. All had an acute ischemic lesion identified on diffusion-weighted images, 25 had an occlusion of MCA or PCA confirmed by magnetic resonance angiography. Results: VSA was detected in 22/25 patients having an occluded artery at the time of MRI examination. Flair disclosed a hyperintense vessel in all of these 25 cases, but CT scan revealed a hyperdense artery in only 15 cases. Follow-up studies showed that VSA can vanish or disappear after partial recanalization. When the artery remains occluded, VSA can decrease, disappear or increase in the next hours, possibly related to structural modifications of the thrombus with time. Most occlusions were due to cardiac and arterial emboli or to intracranial extension of carotid occlusion. Conclusions: VSA are frequent in the first hours of MCA or PCA occlusion in acute stroke patients. The sensitivity of VSA appears lower than the arterial hyperintensity on FLAIR images but higher than the hyperdense artery sign on CT scan. The extent and intensity of VSA can change with recanalization or structural modifications of the thrombus.
Sugarcane Bagasse Hydrolysis Enhancement by Microwave-Assisted Sulfolane Pretreatment

Sugarcane bagasse is the major by-product of the sugarcane industry and, due to its abundant availability, it has been extensively studied for lignocellulosic bioconversion in the production of bioethanol and other value-added commercial products. In the study presented herein, a combined pretreatment using sulfolane, TiO2 and alkali microwave irradiation (MW-A) was assessed for the dissolution of lignin prior to enzymatic saccharification of holocellulose. Total reducing sugars (TRS) and saccharinic acid yields were investigated. The increase in NaOH concentration up to 5% and in temperature from 120 °C to 140 °C were found to have a positive influence on both yields. While increasing the reaction time from 5 to 60 min only led to an increase in TRS yield <2%, a reaction time of 30 min almost doubled the saccharinic acids production. TRS yields and saccharinic acid production were approximately 5% and 33% higher when the sulfolane-TiO2 reaction medium was used, as compared to MW-A in water, reaching up to 64.8% and 15.24 g/L of saccharinic acids, respectively. The proposed MW-A pretreatment may hold promise for industrial applications, given the good TRS yields obtained, and the associated enzyme and time/energy savings. The use of sulfolane-TiO2 reaction medium is encouraged if saccharinic acids are to be recovered too.
Differential lipid metabolism in monocytes and macrophages: influence of cholesterol loading[S]

The influence of the hypercholesterolemia associated with atherosclerosis on monocytes is poorly understood. Monocytes are exposed to high concentrations of lipids, particularly cholesterol and lysophosphatidylcholine (lyso-PC). Indeed, in line with recent reports, we found that monocytes accumulate cholesteryl esters (CEs) in hypercholesterolemic mice, demonstrating the need for studies that analyze the effects of lipid accumulation on monocytes. Here we analyze the effects of cholesterol and lyso-PC loading in human monocytes and macrophages. We found that cholesterol acyltransferase and CE hydrolase activities are lower in monocytes. Monocytes also showed a different expression profile of cholesterol influx and efflux genes in response to lipid loading and a different pattern of lyso-PC metabolism. In monocytes, increased levels of CE slowed the conversion of lyso-PC into PC. Interestingly, although macrophages accumulated glycerophosphocholine, phosphocholine was the main water-soluble choline metabolite being generated in monocytes, suggesting a role for mono- and diacylglycerol in the chemoattractability of these cells. In summary, monocytes and macrophages show significant differences in lipid metabolism and gene expression profiles in response to lipid loading. These findings provide new insights into the mechanisms of atherosclerosis and suggest potentials for targeting monocyte chemotactic properties not only in atherosclerosis but also in other diseases.
Comparison of two cohorts of women who expulsed either a copper‐intrauterine device or a levonorgestrel‐releasing intrauterine system

To assess if there is a difference in the characteristics of the women who expelled a copper‐intrauterine device (TCu‐IUD) or the levonorgestrel‐releasing intrauterine system (LNG‐IUS) and the frequency of expulsions over different periods of observation.
Effect of dose on pharmacokinetics and serum bactericidal activity of mezlocillin

Mezlocillin is subject to dose-dependent pharmacokinetics. Previous studies have examined the pharmacokinetic but not the pharmacodynamic aspects of this effect. The pharmacokinetic disposition of mezlocillin was determined in eight healthy volunteers in a randomized, crossover fashion after single infusions of 50 and 80 mg of mezlocillin per kg of body weight. Plasma and urine were assayed with a specific high-pressure liquid chromatography assay and analyzed by noncompartmental methods. Pharmacodynamic (bactericidal) effects were evaluated from serial serum bactericidal titers obtained after each dose by using the area under the bactericidal activity curve method. The mean mezlocillin total body clearance decreased from 203.6 +/- 36.2 ml/min after the 50-mg/kg dose to 171.7 +/- 42.1 ml/min after the 80-mg/kg dose (P, 0.01). The decreased clearance was reflected by a decrease in nonrenal clearance only (108.9 +/- 20.0 to 77.9 +/- 23.5 ml/min, respectively; P, 0.001). Mean areas under the curve for concentration in plasma versus time normalized to the 50-mg/kg dose were 314 +/- 73 and 375 +/- 64 micrograms X h/ml for the low and high doses, respectively (P, 0.01). No significant changes were observed in the steady-state volume of distribution or elimination half-life. Mean areas under the bactericidal activity curve were 100 +/- 77 and 244 +/- 143 for the 50- and 80-mg/kg doses, respectively. The decrease in mezlocillin clearance and the disproportionate increase in the area under the curve for concentration in plasma versus time, coupled with the observed prolonged bactericidal effects of the 80-mg/kg dose, lend support for administration of mezlocillin at a higher dose less frequently (e.g., 5 g every 8 h). Clinical trials with the higher-dose regimen are warranted to validate these observations.
If you build it will they come? Factors influencing rural primary pupils' urination and defecation practices at school in western Kenya

There is a need for a more comprehensive understanding of sanitation behaviors and determinants in the school setting to mitigate health risks, improve sanitation practices and programs, and maximize educational and health impacts. We conducted qualitative research with pupils and teachers in western Kenya to understand where pupils urinate and defecate and what factors influence location selection. Despite the availability of gender-separated latrines at all schools, pupils listed numerous locations for urination and defecation. Several physical environmental, social, and individual factors influence pupils9 selection of where to urinate and defecate. Physical environment factors include condition, safety, privacy, accessibility, and availability of facilities; social factors include norms, expectations, and responsibility; and individual factors include experience, routine, risk perception, and personal needs. Students simultaneously weigh several competing factors to determine where to go. The factors that facilitate or hinder latrine use need to be taken into consideration during design, construction, operation and maintenance, if healthy habits are to be formed and sustained.
Online Social and Professional Support for Smokers Trying to Quit: An Exploration of First Time Posts From 2562 Members

Background Both intratreatment and extratreatment social support are associated with increased rates of smoking cessation. Internet-based social support groups have the capability of connecting widely dispersed groups of people trying to quit smoking, making social support available 24 hours a day, seven days a week, at minimal cost. However, to date there has been little research to guide development of this particular feature of Web-assisted tobacco interventions (WATIs). Objective Our objectives were to compare the characteristics of smokers who post in an online smoking cessation support group with smokers who do not post, conduct a qualitative analysis of discussion board content, and determine the time it takes for new users to receive feedback from existing members or moderators. Methods Data were collected from StopSmokingCenter.net version 5.0, a WATI equipped with an online social support network moderated by trained program health educators that was operational from November 6, 2004, to May 15, 2007. Demographic and smoking characteristics for both users and nonusers of the online social support network were analyzed, and qualitative analyses were conducted to explore themes in message content. Posting patterns and their frequency were also analyzed. Results During the study period, 16,764 individuals registered; of these, 70% (11,723) reported being American. The mean age of registrants was 38.9 years and 65% (10,965) were female. The mean number of cigarettes smoked was 20.6 per day. The mean score for the 41% (6849) of users who completed the Fagerström Test for Nicotine Dependence was 5.6. Of all registered members, 15% (2562) made at least one post in the online social support network; 25% of first posts received a response from another member within 12 minutes, 50% within 29 minutes. The most frequent first posts were from recent quitters who were struggling with their quit attempts, and most responses were from members who had quit for a month or more. Differences in demographic and smoking characteristics between members who posted on the support group board at least once and those who did not post were statistically but not clinically significant. Conclusions Peer responses to new users were rapid, indicating that online social support networks may be particularly beneficial to smokers requiring more immediate assistance with their cessation attempt. This function may be especially advantageous for relapse prevention. Accessing this kind of rapid in-person support from a professional would take an inordinate amount of time and money. Further research regarding the effectiveness of WATIs with online social support networks is required to better understand the contribution of this feature to cessation, for both active users (posters) and passive users (“lurkers”) alike.