Gender differences in the association between adiposity and probable major depression: a cross-sectional study of 140,564 UK Biobank participants

<b>Background</b><p></p> Previous studies on the association between adiposity and mood disorder have produced contradictory results, and few have used measurements other than body mass index (BMI). We examined the association between probable major depression and several measurements of adiposity: BMI, waist circumference (WC), waist-hip-ratio (WHR), and body fat percentage (BF%).<p></p> <b>Methods</b><p></p> We conducted a cross-sectional study using baseline data on the sub-group of UK Biobank participants who were assessed for mood disorder. Multivariate logistic regression models were used, adjusting for potential confounders including: demographic and life-style factors, comorbidity and psychotropic medication.<p></p> <b>Results</b><p></p> Of the 140,564 eligible participants, evidence of probable major depression was reported by 30,145 (21.5%). The fully adjusted odds ratios (OR) for obese participants were 1.16 (95% confidence interval (CI) 1.12, 1.20) using BMI, 1.15 (95% CI 1.11, 1.19) using WC, 1.09 (95% CI 1.05, 1.13) using WHR and 1.18 (95% CI 1.12, 1.25) using BF% (all p <0.001). There was a significant interaction between adiposity and gender (p = 0.001). Overweight women were at increased risk of depression with a dose response relationship across the overweight (25.0-29.9 kg/m2), obese I (30.0-34.9 kg/m2), II (35.0-39.9 kg/m2) and III (≥40.0 kg/m2) categories; fully adjusted ORs 1.14, 1.20, 1.29 and 1.48, respectively (all p < 0.001). In contrast, only obese III men had significantly increased risk of depression (OR 1.29, 95% CI 1.08, 1.54, p = 0.006).<p></p> <b>Conclusion</b><p></p> Adiposity was associated with probable major depression, irrespective of the measurement used. The association was stronger in women than men. Physicians managing overweight and obese women should be alert to this increased risk

Detecting fake news and disinformation using artificial intelligence and machine learning to avoid supply chain disruptions

Fake news and disinformation (FNaD) are increasingly being circulated through various online and social networking platforms, causing widespread disruptions and influencing decision-making perceptions. Despite the growing importance of detecting fake news in politics, relatively limited research efforts have been made to develop artificial intelligence (AI) and machine learning (ML) oriented FNaD detection models suited to minimize supply chain disruptions (SCDs). Using a combination of AI and ML, and case studies based on data collected from Indonesia, Malaysia, and Pakistan, we developed a FNaD detection model aimed at preventing SCDs. This model based on multiple data sources has shown evidence of its effectiveness in managerial decision-making. Our study further contributes to the supply chain and AI-ML literature, provides practical insights, and points to future research directions

Capital Structure Dynamics of Shariah-Compliant vs Non-Compliant Firms: Evidence from Pakistan

Purpose This study aims to compare capital structure determinants' effect on the leverage levels of Shariah-compliant (SC) and noncompliant (NC) firms in Pakistan. This study also estimates and compares the capital structure adjustment speed for both firm types. Design/methodology/approach Based on the Karachi Meezan Index screening criterion, a balanced panel of 117 SC and 68 NC firms listed on the Pakistan Stock Exchange from 2008 to 2018 was constituted. This study used the generalized method of moments to identify the significant determinants of capital structure and estimate the speed of adjustment. In addition, the F-test was used to check whether the effect of the determinants on the leverage is same for SC and non-SC firms. Findings The authors found that different determinants affect both firm types' leverage levels (book and market) differently. The authors also found that the adjustment speed of SC firms toward their target leverage ratio is slower than their NC peers. Lastly, significant variation was observed in the results under different screening criteria. Research limitations/implications This study fills the literature gap by providing a comprehensive comparison of the capital structure decisions of the SC and non-SC firms. Because this study is limited to Pakistan, generalizability would be an issue. Practical implications This study will guide the management of SC and non-SC firms about which factors are reliably important in choosing their capital structure. The findings also call for bringing harmony in the different Shariah screening criteria being in practice. Originality/value To the best of the authors’ knowledge, this is the first comparative study that identifies the significant capital structure determinants for SC and NC firms and investigates their effect on the leverage of both firm types. By testing joint hypotheses of same relationship, this study seeks to determine if, because of Shariah restrictions, the capital structure determinants of SC firms are similar to NC firms or they exhibit different behavior. The authors also repeat their analysis using other prominent screening criteria to assess the consistency of their results

Socio-Economic Drivers of Renewable Energy: Empirical Evidence from BRICS

There is a need to implement efficient strategies to mitigate the challenges of climate change and income inequalities in developing countries. Several studies have been conducted to address the relationship among different econometric and environmental indicators of renewable energy (RE) but overlooked the relationship between RE and income inequalities. This study investigates the influence of the distribution of income on the RE in Brazil, Russia, China, and South Africa (BRICS) between 1988 and 2017. The econometric (economic growth and trade), environmental, and institutional parameters are also integrated into the model. The outcomes reveal that reduced inequality in income distribution increases the consumption of RE. In contrast, CO2 emissions have a positive correlation with RE. The governments should implement environmentally friendly policies and increase the consumption of renewable energy in the future with regards to reducing environmental pollution. Furthermore, findings from the study indicate a positive effect on the reduction of corruption in renewable energy. This shows that institutional quality can affect the uptake of renewable energy. The study further identified that growth in a country’s economy decreases RE consumption, suggesting that these countries prefer fossil fuels to gain economic growth. The Granger causality results show that a bidirectional causality exists between income inequality and RE consumption. Bidirectional causality is observed between income distribution and CO2 emissions. The results from this study are important for policymakers to achieve sustainable development because fair income distribution and environmental quality are considered as two key factors for sustainable development. Strong institutions and control on corruption can bring sound social and economic gains. Therefore, fair distribution of income and strong institutional policies can increase RE consumption to achieve a clean environment. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Can Financial Institutional Deepening and Renewable Energy Consumption Lower CO2 Emissions in G-10 Countries: Fresh Evidence from Advanced Methodologies

To tackle the challenges associated with global warming and climate change, several countries set their targets to lower carbon emissions in accordance with COP21 (Paris Conference). Even though studies highlighted the different aspects that contribute to environmental degradation, there still exists the scarcity of adequate research that emphasizes the environmental implications of financial institutional deepening, renewable energy consumption (REC), and technology innova-tions. Therefore, this study investigated the significance of financial institutional deepening, REC, gross domestic product (GDP), imports, exports, and technology innovations to achieve sustaina-bility in G-10 countries, namely The Netherlands, Germany, France, Switzerland, United Kingdom, Sweden, Japan, Belgium, Canada, and Italy from 1990 to 2020. The results obtained from cross-sec-tionally augmented autoregressive distributed lag (CS-ARDL) and the dynamic common correlated effects mean group (DCCEMG) models reveal that financial institutional deepening and imports positively impact CO2 emissions (CO2e) both in the long and short run. A 1% increase in financial institutional deepening and import will increase CO2e by 0.5403% and 0.2942% in the short run and 0.2980% and 0.1479% in the long run levels, respectively. Contrary to this, REC, GDP, exports, and technology innovations improve environmental quality in these countries. The Dumitrescu & Hur-lin causality test shows bidirectional causality between imports and CO2e, GDP and CO2e, exports and CO2e, and financial institutional deepening and CO2e, compared to unidirectional causality from technology innovations to CO2e and from REC to CO2e. Apart from this, the outcomes suggest that policymakers in G-10 countries have to consider their financial markets and firms to revise their current environmental policies. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This research work does not get any funding from any organization

Association of adiposity and mental health functioning across the lifespan:Findings from understanding society (The UK household longitudinal study)

Background: Evidence on the adiposity-mental health associations is mixed, with studies finding positive, negative or no associations, and less is known about how these associations may vary by age. Objective: To examine the association of adiposity -body mass index (BMI), waist circumference (WC) and percentage body fat (BF%)- with mental health functioning across the adult lifespan. Methods: Data from 11,257 participants (aged 18+) of Understanding Society: the UK Household Longitudinal Study (waves 2 and 3, 5/2010-7/2013) were employed. Regressions of mental health functioning, assessed by the Mental Component Summary (MCS-12) and the General Health Questionnaire (GHQ-12), on adiposity measures (continuous or dichotomous indicators) were estimated adjusted for covariates. Polynomial age-adiposity interactions were estimated. Results: Higher adiposity was associated with poorer mental health functioning. This emerged in the 30s, increased up to mid-40s (all central adiposity and obesity-BF% measures) or early 50s (all BMI measures) and then decreased with age. Underlying physical health generally accounted for these associations except for central adiposity, where associations remained statistically significant from the mid-30s to50s. Cardiovascular, followed by arthritis and endocrine, conditions played the greatest role in attenuating the associations under investigation. Conclusions: We found strong age-specific patterns in the adiposity-mental health functioning association that varied across adiposity measures. Underlying physical health had the dominant role in attenuating these associations. Policy makers and health professionals should target increased adiposity, mainly central adiposity, as it is a risk factor for poor mental health functioning in those aged between mid-30s to 50 years

Supervised Treatment in Outpatients for Schizophrenia Plus (STOPS+): Protocol for a cluster randomised trial of a community-based intervention to improve treatment adherence and reduce the treatment gap for schizophrenia in Pakistan

Introduction: There is a significant treatment gap, with only a few community-based services for people with schizophrenia in Low- and Middle-Income countries. Poor treatment adherence in schizophrenia is associated with poorer health outcomes, suicide attempts and death. We previously reported the effectiveness of STOPS (Supervised Treatment in Outpatients for Schizophrenia) for improving treatment adherence in patients with schizophrenia. However, STOPS was evaluated in a tertiary care setting with no primary care involvement, limiting its generalisability to the wider at-risk population. We aim to evaluate the effectiveness of STOPS+ in scaling up the primary care treatment of schizophrenia to a real-world setting. Methods and analysis: The effectiveness of the STOPS+ intervention in improving the level of functioning and medication adherence in patients with schizophrenia in Pakistan will be evaluated using a cluster randomised controlled trial design. We aim to recruit 526 participants from 24 Primary Health Care Centres (PHCs) randomly allocated in 1:1 ratio to STOPS+ intervention and Enhanced Treatment as Usual (ETAU) arms. Participants will be followed-up for 12 months post recruitment. The sample size is estimated for two outcomes (i) The primary clinical outcome is level of functioning, measured using the Global Assessment of Functioning (GAF) scale, and (ii) the primary process outcome is adherence to treatment regimen measured using a validated measure. An intention-to-treat approach will be used for the primary analysis. Ethics and Dissemination: Ethical approval has been obtained from Keele University Ethical Review Panel (ref: MH-190017) and Khyber Medical University Ethical Review Board (ref: DIR-KMU-EB/ST/000648). The results of the STOPS+ trial will be reported in peer reviewed journals and academic conferences and disseminated to local stakeholders and policy makers

In silico modeling of the specific inhibitory potential of thiophene-2,3-dihydro-1,5-benzothiazepine against BChE in the formation of β-amyloid plaques associated with Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease, known to be associated with the gradual loss of memory, is characterized by low concentration of acetylcholine in the hippocampus and cortex part of the brain. Inhibition of acetylcholinesterase has successfully been used as a drug target to treat Alzheimer's disease but drug resistance shown by butyrylcholinesterase remains a matter of concern in treating Alzheimer's disease. Apart from the many other reasons for Alzheimer's disease, its association with the genesis of fibrils by β-amyloid plaques is closely related to the increased activity of butyrylcholinesterase. Although few data are available on the inhibition of butyrylcholinesterase, studies have shown that that butyrylcholinesterase is a genetically validated drug target and its selective inhibition reduces the formation of β-amyloid plaques.</p> <p>Rationale</p> <p>We previously reported the inhibition of cholinesterases by 2,3-dihydro-1, 5-benzothiazepines, and considered this class of compounds as promising inhibitors for the cure of Alzheimer's disease. One compound from the same series, when substituted with a hydroxy group at C-3 in ring A and 2-thienyl moiety as ring B, showed greater activity against butyrylcholinesterase than to acetylcholinesterase. To provide insight into the binding mode of this compound (Compound A), molecular docking in combination with molecular dynamics simulation of 5000 ps in an explicit solvent system was carried out for both cholinesterases.</p> <p>Conclusion</p> <p>Molecular docking studies revealed that the potential of Compound A to inhibit cholinesterases was attributable to the cumulative effects of strong hydrogen bonds, cationic-π, π-π interactions and hydrophobic interactions. A comparison of the docking results of Compound A against both cholinesterases showed that amino acid residues in different sub-sites were engaged to stabilize the docked complex. The relatively high affinity of Compound A for butyrylcholinesterase was due to the additional hydrophobic interaction between the 2-thiophene moiety of Compound A and Ile69. The involvement of one catalytic triad residue (His438) of butyrylcholinesterase with the 3'-hydroxy group on ring A increases the selectivity of Compound A. C-C bond rotation around ring A also stabilizes and enhances the interaction of Compound A with butyrylcholinesterase. Furthermore, the classical network of hydrogen bonding interactions as formed by the catalytic triad of butyrylcholinesterase is disturbed by Compound A. This study may open a new avenue for structure-based drug design for Alzheimer's disease by considering the 3D-pharmacophoric features of the complex responsible for discriminating these two closely-related cholinesterases.</p

Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes

Abstract Background Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO). Methods IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot. Results IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase. Conclusion This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions.</p