Protocol of a systematic review and network meta-analysis for the prevention and treatment of perinatal depression

Introduction Perinatal depression is common and can often lead to adverse health outcomes for mother and child. Multiple pharmacological and non-pharmacological treatments have been evaluated against usual care or placebo controls in meta-analyses for preventing and treating perinatal depression compared. It is not yet established which of these candidate treatments might be the optimal approach for prevention or treatment. Methods and analysis A systematic review and Bayesian network meta-analyses will be conducted. Eight electronic databases shall be searched for randomised controlled trials that have evaluated the effectiveness of treatments for prevention and/or treatment of perinatal depression. Screening of articles shall be conducted by two reviewers independently. One network meta-analysis shall evaluate the effectiveness of interventions in preventing depression during the perinatal period. A second network meta-analysis shall compare the effectiveness of treatments for depression symptoms in women with perinatal depression. Bayesian 95% credible intervals shall be used to estimate the pooled mean effect size of each treatment, and surface under cumulative ranking area will be used to rank the treatments\u27 effectiveness. Ethics and dissemination We shall report our findings so that healthcare providers can make informed decisions on what might be the optimal approach for addressing perinatal depression to prevent cases and improve outcomes in those suffering from depression through knowledge exchange workshops, international conference presentations and journal article publications. PROSPERO registration number CRD42020200081

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

The impact of blogging on Hong Kong primary school students’ bilingual reading literacy

This study looked at the types of blog consulted by 1,298 Primary 4 students in Hong Kong and whether such consultation influenced performance on standardised tests of Chinese and English reading comprehension. When students were asked if they consulted Chinese and English blogs, 42 % said they looked at Chinese blogs and 19% said they looked at English blogs. This difference was anticipated since Chinese is the mother tongue of most primary school students in Hong Kong and English is a second language. The themes of sites consulted were categorised into types: the Chinese blogs being able to be categorised into three types, and the English blogs into two. Boys and girls differed in their choice of Chinese and English blog topics and the strength of the students ’ Chinese and English reading proficiency clearly had some influence on the choice of blogs consulted. Factor analysis was used to group together types of blog and analysis of variance was applied to test differences in performance. With over half of the students saying they did not consult either Chinese or English blogs, it is unwise to draw weighty conclusions about the influence of blogging on reading standards. There was little evidence that regularly consulting the Internet was associated with high grades on either Chinese or English reading tests. Given the large number of students who said they had never consulted blogs, discussion of the analytical outcomes and conclusions are guarded but recommendations are offered

Transfer of Extracellular Vesicle-Associated-RNAs Induces Drug Resistance in ALK-Translocated Lung Adenocarcinoma

Anaplastic lymphoma kinase (ALK) translocation is an actionable mutation in lung adenocarcinoma. Nonetheless tumour consists of heterogeneous cell subpopulations with diverse phenotypes and genotypes, and cancer cells can actively release extracellular vesicles (EVs) to modulate the phenotype of other cells in the tumour microenvironment. We hypothesized that EVs derived from a drug-resistant subpopulation of cells could induce drug resistance in recipient cells. We have established ALK-translocated lung adenocarcinoma cell lines and subclones. The subclones have been characterized and the expression of EV-RNAs determined by quantitative polymerase chain reaction. The effects of EV transfer on drug resistance were examined in vitro. Serum EV-RNA was assayed serially in two patients prescribed ALK-tyrosine kinase inhibitor (ALK-TKI) treatment. We demonstrated that the EVs from an ALK-TKI-resistant subclone could induce drug resistance in the originally sensitive subclone. EV-RNA profiling revealed that miRNAs miR-21-5p and miR-486-3p, and lncRNAs MEG3 and XIST were differentially expressed in the EVs secreted by the resistant subclones. These circulating EV-RNA levels have been found to correlate with disease progression of EML4-ALK-translocated lung adenocarcinoma in patients prescribed ALK-TKI treatment. The results from this study suggest that EVs released by a drug-resistant subpopulation can induce drug resistance in other subpopulations and may sustain intratumoural heterogeneity

CC16 levels correlate with cigarette smoke exposure in bronchial epithelial cells and with lung function decline in smokers

Abstract Background Club cell protein-16 (CC16) expression has been associated with smoking-related lung function decline. The study hypothesis was that CC16 expression in both serum and bronchial epithelium is associated with lung function decline in smokers, and exposure to cigarette smoke will lead to reduction in CC16 expression in bronchial epithelial cells. Methods In a cohort of community-based male Chinese subjects recruited for lung function test in 2000, we reassessed their lung function ten years later and measured serum levels of CC16. CC16 expression was further assayed in bronchial epithelium from endobronchial biopsies taken from an independent cohort of subjects undergoing autofluorescence bronchoscopy, and tested for correlation between CC16 immunostaining intensity and lung function. In an in-vitro model, bronchial epithelial cells were exposed to cigarette smoke extract (CSE), and the expression levels of CC16 were measured in bronchial epithelial cells before and after exposure to CSE. Results There was a significant association between FEV1 decline and serum CC16 levels in smokers. Expression of CC16 in bronchial epithelium showed significant correlation with FEV1/FVC. Bronchial epithelial cells showed significant decrease in CC16 expression after exposure to CSE, followed by a subsequent rise in CC16 expression upon removal of CSE. Conclusions Results of these clinical and laboratory investigations suggested that low serum CC16 was associated with smoking-related decline in lung function, demonstrated the first time in a Chinese cohort. The data also lend support to the putative role of CC16 in protection against smoking-related bronchial epithelial damage. (Abstract word count: 243) US clinical trial registry NCT01185652, first posted 20 August, 2010

C–N Bond Cleavage of Anilines by a (Salen)ruthenium(VI) Nitrido Complex

We report experimental and computational studies of the facile oxidative C–N bond cleavage of anilines by a (salen)­ruthenium­(VI) nitrido complex. We provide evidence that the initial step involves nucleophilic attack of aniline at the nitrido ligand of the ruthenium complex, which is followed by proton and electron transfer to afford a (salen)­ruthenium­(II) diazonium intermediate. This intermediate then undergoes unimolecular decomposition to generate benzene and N₂