CHANGES IN URINARY MONOAMINE METABOLITES WITH ANTIPSYCHOTIC TREATMENT IN SCHIZOPHRENIA

Objective: Monoamine neurotransmitters have been considered important mediators of schizophrenia pathology and antipsychotic drug action. Thisstudy examines the level of monoamine metabolites, homovanillic acid (HVA), 5-hydroxy indole acetic acid (5-HIAA), and vanillylmandelic acid (VMA),monoamine metabolites of major neurotransmitters dopamine, serotonin and norepinephrine, respectively in urine of patients with schizophrenia ascompared to normal controls and the change in monoamine metabolites with antipsychotic treatment.Methods: Thirty-four drug-free patients with schizophrenia diagnosed with Diagnostic and Statistical Manual of Mental Disorders Fourth Edition(DSM-IV) criteria and 15 normal controls were taken for the study. Patients were assessed for psychopathology using positive and negative syndromescale (PANSS) scale at baseline and 4 weeks after the treatment. Urinary monoamine metabolites (HVA, 5-HIAA, and VMA) were measured before andafter 4 weeks of treatment using high-performance liquid chromatography.Results: There was a trend toward higher levels of HVA and VMA in the patients as compared to controls. There was a trend toward reduction in 5-HIAAlevels with treatment in patients with schizophrenia. No correlation was found between the levels of monoamine metabolites and psychopathology.Significant positive correlation was found between 5-HIAA with VMA and HVA.Conclusion: The present study indicates that noninvasive measurement of monoamine metabolites in urine may be of value in differentiating patientswith schizophrenia from controls.Keywords: Monoamine, Homovanillic acid, 5-Hydroxy indole acetic acid, Vanillyl mandelic acid, Schizophrenia.Â

Improved lung function and patient-reported outcomes with co-suspension delivery technology glycopyrrolate/formoterol fumarate metered dose inhaler in COPD:a randomized Phase III study conducted in Asia, Europe, and the USA

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Novel Topical Microbicides Through Combinatorial Strategies

Purpose Developing microbicides for topical epithelial applications is extremely challenging, as evidenced by the scarcity of approved products even after decades of research. Chemical enhancers, including surfactants, are known to be effective antimicrobial agents but are typically toxic towards epithelial cells. Here, we report on the discovery of unique surfactant formulations with improved safety and efficacy profile for epithelial applications, via a combination of high throughput screening techniques. Methods Over three-hundred formulations derived from nine surfactants were screened for antibacterial properties against E. coli in vitro. A subset of these formulations showed high antibacterial activity and was screened for cytotoxicity in vitro. Formulations showing high antibacterial activity and reduced cytotoxicity compared to their individual components were tested for efficacy against B. thailendensis, a model for melioidosis-causing B. pseudomallei. Results Lead formulations showed lower toxicity towards epidermal keratinocytes, with LC50 values up to 3.5-fold higher than their component surfactants, while maintaining antibacterial efficacy against B. thailendensis. Conclusions Our results demonstrate that such a combinatorial screening approach can be used for designing safe and potent microbicides for epithelial applications

Comparison of MRI- and TRUS-Informed Prostate Biopsy for Prostate Cancer Diagnosis in Biopsy-Naive Men: A Systematic Review and Meta-Analysis.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) with informed targeted biopsies (TGBX) has changed the paradigm of prostate cancer (PCa) diagnosis. Randomized studies have demonstrated a diagnostic benefit of Clinically significant (CS) for TGBX compared to standard systematic biopsies (SBX). We aimed to evaluate whether mpMRI-informed TGBX has superior diagnosis rates of any-, CS-, high-grade (HG)-, and clinically insignificant (CI)-PCa compared to SBX in biopsy-naive men. METHODS: Data was searched in Medline, Embase, Web of Science, and Evidence-based medicine reviews-Cochrane Database of systematic reviews from database inception until 2019. Studies were selected by two authors independently, with disagreements resolved by consensus with a third author. Overall 1951 unique references were identified, and 100 manuscripts underwent full-text review. Data were pooled using random-effects models. The meta-analysis is reported according to the PRISMA statement. The study protocol is registered with PROSPERO (CRD42019128468). RESULTS: Overall 29 studies (13,845 patients) were analyzed. Compared to SBX, use of mpMRI-informed TGBX was associated with a 15% higher rate of any PCa diagnosis (95% CI 10-20%, p\u3c0.00001). This relationship was not affected by the study methodology (p=0.11). Diagnosis of CS and HG PCa were more common in the mpMRI-informed TGBX group (risk difference of 11%, 95% CI 0-20%, p=0.05, and 2%, 95% CI 1-4%; p=0.005, respectively) while there was no difference in diagnosis of CI PCa (risk difference of 0, 95% CI -3-3%, p=0.96). Notably, the exclusion of SBX in the mpMRI-informed TGBX arm significantly modified the association between a mpMRI strategy and lower rates of CI PCa diagnosis (p=0.01) without affecting the diagnosis rates of CS- or HG-PCa. CONCLUSIONS: In comparison to SBX, a mpMRI-informed TGBX strategy results in a significantly higher diagnosis rate of any-, CS-, and HG-PCa. Excluding SBX from mpMRI-informed TGBX was associated with decreased rates of CI-PCa diagnosis without affecting diagnosis of CS- or HG-PCa

Who Is Treating Periprosthetic Femur Fractures? An Analysis of the Periprosthetic Research Consortium

Background: Periprosthetic femur fractures (PPFFs) following total hip arthroplasty (THA) have increased in the past decade as the demand for primary surgery continues to grow. Although there is now more evidence to describe the treatment of Vancouver B fractures, there is still limited knowledge regarding factors that cause surgeons to perform either an open reduction and internal fixation (ORIF) or revision THA (rTHA). The purpose of this study was to determine what type of surgeons treat Vancouver B PPFFs at 11 major academic institutions and if there are trends in treatment decision-making regarding the use of ORIF or rTHA based on surgical training or patient factors. Methods: This multicenter retrospective study evaluated patients surgically treated for Vancouver B PPFF after THA between 2014 and 2019. Patients from 11 academic centers located in the United States were included in this study. Surgical outcomes and patient demographics were evaluated based on surgeon training, surgical treatment type, and institution. Results: Presence of Vancouver B2 (odds ratio [OR]: 0.02, P \u3c .001) or B3 (OR: 0.04, P \u3c .001) fractures were independent risk factors for treatment with rTHA. Treatment by a trauma (OR: 12.49, P \u3c .001) or other-specified surgeon (OR: 13.63, P \u3c .001) were independent risk factors for ORIF repair of Vancouver B fractures. There were no differences in outcomes based on surgeon subspecialty training. Conclusions: This study showed the trends in surgeons who surgically manage Vancouver B fractures at 11 major academic institutions and highlighted that regardless of surgical training or surgical treatment type, postoperative outcomes following management of PPFF were similar

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030