Psychometric validation of the Bangla fear of COVID-19 Scale: confirmatory factor analysis and Rasch analysis

The recently developed Fear of COVID-19 Scale (FCV-19S) is a seven-item uni-dimensional scale that assesses the severity of fears of COVID-19. Given the rapid increase of COVID-19 cases in Bangladesh, we aimed to translate and validate the FCV-19S in Bangla. The forward-backward translation method was used to translate the English version of the questionnaire into Bangla. The reliability and validity properties of the Bangla FCV-19S were rigorously psychometrically evaluated (utilizing both confirmatory factor analysis and Rasch analysis) in relation to socio-demographic variables, national lockdown variables, and response to the Bangla Health Patient Questionnaire. The sample comprised 8550 Bangladeshi participants. The Cronbach α value for the Bangla FCV-19S was 0.871 indicating very good internal reliability. The results of the confirmatory factor analysis showed that the uni-dimensional factor structure of the FCV-19S fitted well with the data. The FCV-19S was significantly correlated with the nine-item Bangla Patient Health Questionnaire (PHQ-90) (r = 0.406,

Frustrated charge order and cooperative distortions in ScV6Sn6

Here we study the stability of charge order in the kagome metal ScV6Sn6. Synchrotron x-ray diffraction measurements reveal high-temperature, short-range charge correlations at the wave vectors along q=(1/3,1/3,1/2) whose inter-layer correlation lengths diverge upon cooling. At the charge order transition, this divergence is interrupted and long-range order freezes in along q=(1/3,1/3,1/3), as previously reported, while disorder enables the charge correlations to persist at the q=(1/3,1/3,1/2) wave vector down to the lowest temperatures measured. Both short-range and long-range charge correlations seemingly arise from the same instability and both are rapidly quenched upon the introduction of larger Y ions onto the Sc sites. Our results validate the theoretical prediction of the primary lattice instability at q=(1/3,1/3,1/2), and we present a heuristic picture for viewing the frustration of charge order in this compound

Ceibinin, a new positional isomer of mangiferin from the inflorescence of Ceiba pentandra (Bombacaceae), elicits similar antioxidant effect but no anti-inflammatory potential compared to mangiferin

Ceiba pentandra (L.) Gaertn. (Bombacaceae) is popular for the quality of its wood. However, its leaf, stem bark and root bark have been popular in ethnomedicine and, apart from the inflorescence, have been subject of extensive phytochemical investigations. In this study, two compounds were isolated from the crude methanol extract of the inflorescence. Through data from UV, NMR, MS, electrochemical studies, differential scanning calorimetry, and thermogravimetric analysis, the structures were elucidated as 3-C-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (1) and 2-C-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (mangiferin, 2). They were assessed for antioxidant efficacy (DCFDA assay) and for anti-inflammatory efficacy using the lipopolysaccharide (LPS)-induced inflammation model in the RAW 264.7 macrophages (nitrite levels quantified, using Griess Assay, as surrogate for nitric oxide (NO)). Compound 1 (named ceibinin) was established as a novel positional isomer of mangiferin (2). While both 1 and 2 were antioxidant against basal and hydrogen peroxide (100 μM)-induced oxidative stress (6.25 μg/ml abrogated peroxide-induced oxidative stress), ceibinin (1) demonstrated no anti-inflammatory potential, unlike mangiferin (2) which, as previously reported, showed anti-inflammatory effect. Our work reports a positional isomer of mangiferin for the first time in C. pentandra and demonstrates how such isomerism could underlie differences in biological activities and thus the potential for development into therapeutics

Microguards and micromessengers of the genome

The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as ‘transcription dynamics’. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term ‘microguarding’. An additional emerging role for miRNAs is as ‘micromessengers’—through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic

Birth preparedness and complication readiness (BPCR) among pregnant women in hard-to-reach areas in Bangladesh:BPCR in hard-to-reach areas of Bangladesh

Birth preparedness and complication readiness aims to reduce delays in care seeking, promote skilled birth attendance, and facility deliveries. Little is known about birth preparedness practices among populations living in hard-to-reach areas in Bangladesh.To describe levels of birth preparedness and complication readiness among recently delivered women, identify determinants of being better prepared for birth, and assess the impact of greater birth preparedness on maternal and neonatal health practices.A cross-sectional survey with 2,897 recently delivered women was undertaken in 2012 as part of an evaluation trial done in five hard-to-reach districts in rural Bangladesh. Mothers were considered well prepared for birth if they adopted two or more of the four birth preparedness components. Descriptive statistics and multivariable logistic regression were used for analysis.Less than a quarter (24.5%) of women were considered well prepared for birth. Predictors of being well-prepared included: husband's education (OR = 1.3; CI: 1.1-1.7), district of residence, exposure to media in the form of reading a newspaper (OR = 2.2; CI: 1.2-3.9), receiving home visit by a health worker during pregnancy (OR = 1.5; CI: 1.2-1.8), and receiving at least 3 antenatal care visits from a qualified provider (OR = 1.4; CI: 1.0-1.9). Well-prepared women were more likely to deliver at a health facility (OR = 2.4; CI: 1.9-3.1), use a skilled birth attendant (OR = 2.4, CI: 1.9-3.1), practice clean cord care (OR = 1.3, CI: 1.0-1.5), receive post-natal care from a trained provider within two days of birth for themselves (OR = 2.6, CI: 2.0-3.2) or their newborn (OR = 2.6, CI: 2.1-3.3), and seek care for delivery complications (OR = 1.8, CI: 1.3-2.6).Greater emphasis on BPCR interventions tailored for hard to reach areas is needed to improve skilled birth attendance, care seeking for complications and essential newborn care and facilitate reductions in maternal and neonatal mortality in low performing districts in Bangladesh

Antimicrobial and antioxidant activity of kaempferol rhamnoside derivatives from Bryophyllum pinnatum

Abstract Background Bryophyllum pinnatum (Lank.) Oken (Crassulaceae) is a perennial succulent herb widely used in traditional medicine to treat many ailments. Its wide range of uses in folk medicine justifies its being called "life plant" or "resurrection plant", prompting researchers' interest. We describe here the isolation and structure elucidation of antimicrobial and/or antioxidant components from the EtOAc extract of B. pinnatum. Results The methanol extract displayed both antimicrobial activities with minimum inhibitory concentration (MIC) values ranging from 32 to 512 μg/ml and antioxidant property with an IC50 value of 52.48 μg/ml. Its partition enhanced the antimicrobial activity in EtOAc extract (MIC = 16-128 μg/ml) and reduced it in hexane extract (MIC = 256-1024 μg/ml). In addition, this process reduced the antioxidant activity in EtOAc and hexane extracts with IC50 values of 78.11 and 90.04 μg/ml respectively. Fractionation of EtOAc extract gave seven kaempferol rhamnosides, including; kaempferitrin (1), kaempferol 3-O-α-L-(2-acetyl)rhamnopyranoside-7-O-α-L-rhamnopyranoside (2), kaempferol 3-O-α-L-(3-acetyl)rhamnopyranoside-7-O-α-L-rhamnopyranoside (3), kaempferol 3-O-α-L-(4-acetyl)rhamnopyranoside-7-O-α-L-rhamnopyranoside (4), kaempferol 3-O-α-D- glucopyranoside-7-O-α-L-rhamnopyranoside (5), afzelin (6) and α-rhamnoisorobin (7). All these compounds, except 6 were isolated from this plant for the first time. Compound 7 was the most active, with MIC values ranging from 1 to 2 μg/ml and its antioxidant activity (IC50 = 0.71 μg/ml) was higher than that of the reference drug (IC50 = 0.96 μg/ml). Conclusion These findings demonstrate that Bryophyllum pinnatum and some of its isolated compounds have interesting antimicrobial and antioxidant properties, and therefore confirming the traditional use of B. pinnatum in the treatment of infectious and free radical damages.</p

Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism

Gemcitabine (GEM, 2′,2′-difluorodeoxycytidine) is currently used in advanced pancreatic adenocarcinoma, with a response rate of < 20%. The purpose of our work was to improve GEM activity by addition of cannabinoids. Here, we show that GEM induces both cannabinoid receptor-1 (CB1) and cannabinoid receptor-2 (CB2) receptors by an NF-κB-dependent mechanism and that its association with cannabinoids synergistically inhibits pancreatic adenocarcinoma cell growth and increases reactive oxygen species (ROS) induced by single treatments. The antiproliferative synergism is prevented by the radical scavenger N-acetyl--cysteine and by the specific NF-κB inhibitor BAY 11-7085, demonstrating that the induction of ROS by GEM/cannabinoids and of NF-κB by GEM is required for this effect. In addition, we report that neither apoptotic nor cytostatic mechanisms are responsible for the synergistic cell growth inhibition, which is strictly associated with the enhancement of endoplasmic reticulum stress and autophagic cell death. Noteworthy, the antiproliferative synergism is stronger in GEM-resistant pancreatic cancer cell lines compared with GEM-sensitive pancreatic cancer cell lines. The combined treatment strongly inhibits growth of human pancreatic tumor cells xenografted in nude mice without apparent toxic effects. These findings support a key role of the ROS-dependent activation of an autophagic program in the synergistic growth inhibition induced by GEM/cannabinoid combination in human pancreatic cancer cells

Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening

There is significant need to identify novel prostate cancer drug targets because current hormone therapies eventually fail, leading to a drug-resistant and fatal disease termed castration-resistant prostate cancer. To functionally identify genes that, when silenced, decrease prostate cancer cell proliferation or induce cell death in combination with antiandrogens, we employed an RNA interference-based short hairpin RNA barcode screen in LNCaP human prostate cancer cells. We identified and validated four candidate genes (AKT1, PSMC1, STRADA, and TTK) that impaired growth when silenced in androgen receptor positive prostate cancer cells and enhanced the antiproliferative effects of antiandrogens. Inhibition of AKT with a pharmacologic inhibitor also induced apoptosis when combined with antiandrogens, consistent with recent evidence for PI3K and AR pathway crosstalk in prostate cancer cells. Recovery of hairpins targeting a known prostate cancer pathway validates the utility of shRNA library screening in prostate cancer as a broad strategy to identify new candidate drug targets

Cyclin-dependent kinase 5 mediates pleiotrophin-induced endothelial cell migration

Pleiotrophin (PTN) stimulates endothelial cell migration through binding to receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and ανβ3 integrin. Screening for proteins that interact with RPTPβ/ζ and potentially regulate PTN signaling, through mass spectrometry analysis, identified cyclin-dependent kinase 5 (CDK5) activator p35 among the proteins displaying high sequence coverage. Interaction of p35 with the serine/threonine kinase CDK5 leads to CDK5 activation, known to be implicated in cell migration. Protein immunoprecipitation and proximity ligation assays verified p35-RPTPβ/ζ interaction and revealed the molecular association of CDK5 and RPTPβ/ζ. In endothelial cells, PTN activates CDK5 in an RPTPβ/ζ- and phosphoinositide 3-kinase (PI3K)-dependent manner. On the other hand, c-Src, ανβ3 and ERK1/2 do not mediate the PTN-induced CDK5 activation. Pharmacological and genetic inhibition of CDK5 abolished PTN-induced endothelial cell migration, suggesting that CDK5 mediates PTN stimulatory effect. A new pyrrolo[2,3-α]carbazole derivative previously identified as a CDK1 inhibitor, was found to suppress CDK5 activity and eliminate PTN stimulatory effect on cell migration, warranting its further evaluation as a new CDK5 inhibitor. Collectively, our data reveal that CDK5 is activated by PTN, in an RPTPβ/ζ-dependent manner, regulates PTN-induced cell migration and is an attractive target for the inhibition of PTN pro-angiogenic properties

Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

Background Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma. Methodology/Principal Findings Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, and FGFR1–is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition. Conclusions/Significance These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.Novartis Pharmaceuticals CorporationAmerican Lung AssociationUniting Against Lung CancerSara Thomas Monopoli FundSeaman FoundationIndia. Dept. of BiotechnologyNational Lung Cancer Partnershi