Thrombocytopenia 4 (THC4): Six novel families with mutations of the cytochrome c gene.

Thrombocytopenia 4 (THC4) is an autosomal-dominant thrombocytopenia caused by mutations in CYCS, the gene encoding cytochrome c (CYCS), a small haeme protein essential for electron transport in mitochondria and cell apoptosis. THC4 is considered an extremely rare condition since only a few patients have been reported so far. These subjects presented mild thrombocytopenia and no or mild bleeding tendency. In this study, we describe six Italian families with five different heterozygous missense CYCS variants: p.Gly42Ser and p.Tyr49His previously associated with THC4, and three novel variants (p.Ala52Thr, p.Arg92Gly, and p.Leu99Val), which have been classified as pathogenic by bioinformatics and segregation analyses. Moreover, we supported functional effects of p.Ala52Thr and p.Arg92Gly on oxidative growth and respiratory activity in a yeast model. The clinical characterization of the 22 affected individuals, the largest series of THC4 patients ever reported, showed that this disorder is characterized by mild-to-moderate thrombocytopenia, normal platelet size, and function, low risk of bleeding, and no additional clinical phenotypes associated with reduced platelet count. Finally, we describe a significant correlation between the region of CYCS affected by mutations and the extent of thrombocytopenia, which could reflect different degrees of impairment of CYCS functions caused by different pathogenetic variants.

Economic and social determinants of health care utilization during the first wave of COVID-19 pandemic among adults in Ghana: a population-based cross-sectional study.

BACKGROUND: The COVID-19 pandemic had socioeconomic effects in Africa. This study assessed the social and economic determinants of healthcare utilization during the first wave of COVID-19 among adults in Ghana. METHODS: Information about individuals residing in Ghana was derived from a survey conducted across multiple countries, aiming to evaluate the impact of the COVID-19 pandemic on the mental health and overall well-being of adults aged 18 and above. The dependent variable for the study was healthcare utilization (categorized as low or high). The independent variables were economic (such as financial loss, job loss, diminished wages, investment/retirement setbacks, and non-refunded travel cancellations) and social (including food scarcity, loss of financial support sources, housing instability, challenges affording food, clothing, shelter, electricity, utilities, and increased caregiving responsibilities for partners) determinants of health. A multinomial logistic regression was conducted to identify factors associated with healthcare utilization after adjusting for confounders (age, gender, access to medical insurance, COVID-19 status, educational background, employment, and marital status of the participants). RESULTS: The analysis included 364 responses. Individuals who encountered a loss of financial support (AOR: 9.58; 95% CI: 3.44-26.73; p < 0.001), a decrease or loss of wages (AOR: 7.44, 95% CI: 3.05-18.16, p < 0.001), experienced investment or retirement setbacks (AOR: 10.69, 95% CI: 2.60-43.88, p = 0.001), and expressed concerns about potential food shortages (AOR: 6.85, 95% CI: 2.49-18.84, p < 0.001) exhibited significantly higher odds of low healthcare utilization during the initial phase of the pandemic. Contrastingly, participants facing challenges in paying for basic needs demonstrated lower odds of low healthcare utilization compared to those who found it easy to cover basic expenses (AOR: 0.19, 95% CI: 0.06-0.67, p = 0.001). CONCLUSION: Economic and social factors were associated with low healthcare utilization in Ghana during the first wave of the pandemic. Investment or retirement loss and financial support loss during the pandemic had the largest effect on healthcare utilization. Further research is needed to understand the connection between concerns about food shortages, welfare losses during pandemics and healthcare utilization during pandemics in Ghana.

A multi-country survey on access to healthcare and treatment services among individuals with critical medical care needs during the first wave of the pandemic.

BACKGROUND: Healthcare services were significantly interrupted during the early phase of the COVID-19 pandemic. The aim of the present study was to determine the associations between sociodemographic factors and healthcare access during the first wave of the COVID-19 pandemic among individuals with critical care needs. METHODS: This was a secondary analysis of the data of 5,156 participants recruited from 152 countries during the first wave of the COVID-19 pandemic. The dependent variables were self-reported difficulty of access to health care, challenges with obtaining medication, and the use of alternative medical services. The independent variables were age at last birthday; sex at birth, level of education, employment status and the macro-social vulnerability status. The confounding variable was the country income level. Three multivariable logistic regression analyses were conducted to determine the associations between the dependent variables and the independent variables after adjusting for the confounder. RESULTS: Difficulty accessing health care services and obtaining medications was experienced by 1922 (37.3%) and 3746 (72.7%) participants respectively. Also, 1433 (27.8%) used alternative medical care. Retirees (AOR:1.59), unemployed (AOR:1.198), people living with HIV (AOR:2.36) and at increased risk of COVID-19 (AOR:2.10), people who used drugs (AOR:1.83) and transacted sex (AOR:1.971) had significantly higher odds for reporting difficulty with access to health care. Males (AOR:1.23), respondents with secondary level of education (AOR:1.39), retirees (AOR:2.19), unemployed (AOR:1.47), people living with HIV (AOR:2.46), people who used drugs (AOR:1.79), transacted sex (AOR:2.71) and those who might be (AOR: 1.66) and were at (AOR: 2.3) increased risk of severe COVID-19 had significantly higher odds for reporting difficulty with access to medications. People who used drugs (AOR:2.093) transacted sex (AOR:1.639), who might be (AOR: 1.211) and were at (AOR: 1.511) increased risk of severe COVID-19, and who had difficulty accessing usual healthcare (AOR: 9.047) and obtaining medications (AOR:2.16) had significantly higher odds of reporting alternative medical care use. People living with HIV (AOR:0.562) had significantly lower odds of using alternative medical care. CONCLUSION: We identified populations who had challenges with access to healthcare and obtaining medications used alternative medical care except for people living with HIV. Priority attention should be given to alternative medical care use during future health pandemics.

A multi-country survey of the socio-demographic factors associated with adherence to COVID-19 preventive measures during the first wave of the COVID-19 pandemic.

BACKGROUND: Health behaviours are influenced by individual characteristics including age, gender, education and economic level. This study aimed to assess the associations between individual-level determinants and adherence to COVID-19 preventive measures. METHODS: We performed secondary analyses of international data collected using an online survey during the first wave of the COVID-19 pandemic between June and December 2020. The dependent variables were self-reported adherence to COVID-19 preventive measures (wearing of face masks, frequent washing/sanitizing of hands, physical distancing, working remotely). The independent variables were age, sex at birth (female vs male), having a chronic disease related elevated risk for severe COVID-19 (none/little, might be at increased risk, at increased risk), educational level completed (no formal education, primary, secondary vs college/university) and employment status (retiree, students, not employed vs employed). Four multivariate logistic regression analyses were conducted to determine the associations between the dependent variables and independent variables. Interaction terms with country-income level were tested in regressions to explore its moderating effect. RESULTS: Out of 16,866 respondents, 12,634 (74.9%) wore masks or face coverings, 12,336 (73.1%) washed or sanitized their hands frequently, 11,464 (68.0%) reported adherence to physical distancing and 5,646 (33.5%) worked remotely. In adjusted analyses, increased age, college/university education, employment, and having risks for severe COVID-19 were associated with significantly higher odds of adhering to COVID-19 preventive measures. Retirees and students had lower odds of adhering to COVID-19 prevention measures than employed individuals. Males had significantly lower odds of wearing face masks (AOR: 0.901), frequent washing/sanitizing hands (AOR: 0.774) and working remotely (AOR: 0.875) compared to females. Country-income level generally moderated the above relationships such that the associations disappeared in lower income countries. CONCLUSION: The study findings suggest that the individual socio-demographic factors-age, sex, employment status, education status and having a chronic disease - influence adherence to COVID-19 preventive measures. Findings further reiterate the need for health education and health promotion campaigns on preventive health measures to focus on subpopulations, such as younger males, students and retirees, that require targeted or unique messaging.

Associations between depression, fear of COVID-19 infection and students' self-care measures used during the first wave of the pandemic.

BACKGROUND: COVID-19 lockdown resulted in the closure of schools with associated problems. The aim of this study was to determine the associations between depression, fear of contracting COVID-19 infection and the use of self-care measures by college students during the first wave of the COVID-19 pandemic. METHODS: This was a cross-sectional study that collected data from undergraduate and postgraduate college students 18 years and older from 152 countries between June and December 2020. Study participants were recruited through crowdsourcing using various social media platforms including Facebook, Twitter, and Instagram, WhatsApp groups and emails to participants in the collaborators' networks. The dependent variables were fear of contracting COVID-19 and depression while the independent variable was students' self-care measures. Multivariable logistic regression models were conducted to assess the associations between the dependent and independent variables. RESULTS: Of the 2840 respondents, 1305 (46.0%) had fears of contracting COVID-19 and 599 (21.1%) reported depression. The most common self-care measures were phone calls with friends/family (60.1%) and video chat (52.8%). Learning a new skill was significantly associated with higher odds of fear of contracting COVID-19 (AOR = 1.669) and lower odds of having depression (AOR = 0.684). Talking to friends/family through video chat (AOR = 0.809) was significantly associated with lower odds of feeling depressed while spending time with pets (AOR = 1.470) and taking breaks from the news/social media (AOR = 1.242) were significantly associated with higher odds of feeling depressed. Students from lower middle-income countries (AOR = 0.330) had significantly lower odds of feeling depressed than students from low-income countries. CONCLUSION: Self-care strategies involving social interactions were associated with less depression. Coping strategies with more cognitive demands may significantly reduce the risk of fear of COVID-19. Special attention needs to be given to students in low-income countries who have higher odds of depression during the pandemic than students from other countries.

Individual, familial and country-level factors associated with oral hygiene practices in children: an international survey.

BACKGROUND: Maintaining good oral hygiene is key to preventing dental caries and periodontal disease. Children and adolescents with good oral hygiene behaviours are likely to grow into adults with the same behaviours. This study assessed the frequency of using various oral hygiene methods among children and adolescents from different countries and individual, familial and country-level factors associated with the use of these methods. METHODS: A multi-country online survey collected data from caregivers of children in 2020-21 about children's use of oral hygiene methods including toothbrush, fluoridated toothpaste, mouthwash, dental floss and miswak using self-administered, close-ended questions. Adjusted multilevel logistic regression models were used to assess the relationship between each of the five oral hygiene methods (dependent variables) and the independent factors: sex, age, and history of dental visits (individual factors), mother's education and area of residence (familial factors) as well as country income and region (country-level factors). RESULTS: A total of 4766 parents/caregivers were included from 20 countries (77.4% Eastern Mediterranean-region and 41.6% lower middle income countries). The most frequent oral hygiene methods were using toothbrush and toothpaste (90% and 60.3%). The use of oral hygiene methods differed by age, sex and history of dental visits as well as mother's education and area of residence (P < 0.05). In addition, children from low income countries had significantly lower odds of using mouthwashes and dental floss than those from high income countries (AOR = 0.55, 95% CI 0.31, 0.98 and AOR = 0.34, 95% CI 0.12, 0.97) whereas children from the European region had higher odds of using mouthwash (AOR = 2.82, 95% CI 1.27, 6.26) and those from the region of the Americas had higher odds of using dental floss (AOR = 3.84, 95% CI 1.28, 11.52) than those from the Eastern Mediterranean region. CONCLUSIONS: The use of various oral hygiene methods is associated with individual, familial and country-level factors. Oral health promotion programs should be developed taking into account these influences.

Differences in COVID-19 Preventive Behavior and Food Insecurity by HIV Status in Nigeria.

The aim of the study was to assess if there were significant differences in the adoption of COVID-19 risk preventive behaviors and experience of food insecurity by people living with and without HIV in Nigeria. This was a cross-sectional study that recruited a convenience sample of 4471 (20.5% HIV positive) adults in Nigeria. Binary logistic regression analysis was conducted to test the associations between the explanatory variable (HIV positive and non-positive status) and the outcome variables-COVID-19 related behavior changes (physical distancing, isolation/quarantine, working remotely) and food insecurity (hungry but did not eat, cut the size of meals/skip meals) controlling for age, sex at birth, COVID-19 status, and medical status of respondents. Significantly fewer people living with HIV (PLWH) reported a positive COVID-19 test result; and had lower odds of practicing COVID-19 risk preventive behaviors. In comparison with those living without HIV, PLWH had higher odds of cutting meal sizes as a food security measure (AOR: 3.18; 95% CI 2.60-3.88) and lower odds of being hungry and not eating (AOR: 0.24; 95% CI 0.20-0.30). In conclusion, associations between HIV status, COVID-19 preventive behaviors and food security are highly complex and warrant further in-depth to unravel the incongruities identified.

Associations between COVID-19 testing status, non-communicable diseases and HIV status among residents of sub-Saharan Africa during the first wave of the pandemic.

BACKGROUND: This study determined if non-communicable disease status, HIV status, COVID-19 status and co-habiting were associated with COVID-19 test status in sub-Saharan Africa. METHODS: Data of 5945 respondents age 18-years-old and above from 31 countries in sub-Saharan Africa collected through an online survey conducted between June and December 2020, were extracted. The dependent variable was COVID-19 status (testing positive for COVID-19 and having symptoms of COVID-19 but not getting tested). The independent variables were non-communicable disease status (hypertension, diabetes, cancer, heart conditions, respiratory conditions, depression), HIV positive status, COVID-19 status (knowing a close friend who tested positive for COVID-19 and someone who died from COVID-19) and co-habiting (yes/no). Two binary logistic regression models developed to determine associations between the dependent and independent variables were adjusted for age, sex, employment, sub region and educational status. RESULTS: Having a close friend who tested positive for COVID-19 (AOR:6.747), knowing someone who died from COVID-19 infection (AOR:1.732), and living with other people (AOR:1.512) were significantly associated with higher odds of testing positive for COVID-19 infection, while living with HIV was associated with significantly lower odds of testing positive for COVID-19 infection (AOR:0.284). Also, respondents with respiratory conditions (AOR:2.487), self-reported depression (AOR:1.901), those who had a close friend who tested positive for COVID-19 infection (AOR:2.562) and who knew someone who died from COVID-19 infection (AOR:1.811) had significantly higher odds of having symptoms of COVID-19 infection but not getting tested. CONCLUSION: Non-communicable diseases seem not to increase the risk for COVID-19 positive test while cohabiting seems to reduce this risk. The likelihood that those who know someone who tested positive to or who died from COVID-19 not getting tested when symptomatic suggests there is poor contact tracing in the region. People with respiratory conditions and depression need support to get tested for COVID-19.

Factors associated with COVID-19 pandemic induced post-traumatic stress symptoms among adults living with and without HIV in Nigeria: a cross-sectional study.

BACKGROUND: Nigeria is a country with high risk for traumatic incidences, now aggravated by the COVID-19 pandemic. This study aimed to identify differences in COVID-19 related post-traumatic stress symptoms (PTSS) among people living and not living with HIV; to assess whether PTSS were associated with COVID-19 pandemic-related anger, loneliness, social isolation, and social support; and to determine the association between PTSS and use of COVID-19 prevention strategies. METHODS: The data of the 3761 respondents for this analysis was extracted from a cross-sectional online survey that collected information about mental health and wellness from a convenience sample of adults, 18 years and above, in Nigeria from July to December 2020. Information was collected on the study's dependent variable (PTSS), independent variables (self-reported COVID-19, HIV status, use of COVID-19 prevention strategies, perception of social isolation, access to emotional support, feelings of anger and loneliness), and potential confounder (age, sex at birth, employment status). A binary logistic regression model tested the associations between independent and dependent variables. RESULTS: Nearly half (47.5%) of the respondents had PTSS. People who had symptoms but were not tested (AOR = 2.20), felt socially isolated (AOR = 1.16), angry (AOR = 2.64), or lonely (AOR = 2.19) had significantly greater odds of reporting PTSS (p < 0.001). People living with HIV (AOR = 0.39), those who wore masks (AOR = 0.62) and those who had emotional support (AOR = 0.63), had lower odds of reporting PTSS (p < .05). CONCLUSION: The present study identified some multifaceted relationships between post-traumatic stress, HIV status, facemask use, anger, loneliness, social isolation, and access to emotional support during this protracted COVID-19 pandemic. These findings have implications for the future health of those affected, particularly for individuals living in Nigeria. Public health education should be incorporated in programs targeting prevention and prompt diagnosis and treatment for post-traumatic stress disorder at the community level.

Is self-reported depression, HIV status, COVID-19 health risk profile and SARS-CoV-2 exposure associated with difficulty in adhering to COVID-19 prevention measures among residents in West Africa?

BACKGROUND: The aim of this study was to determine whether self-reported depression, coronavirus disease of 2019 (COVID-19) health risk profile, HIV status, and SARS-CoV-2 exposure were associated with the use of COVID-19 prevention measures. METHODS: This survey collected data electronically between June 29 and December 31, 2020 from a convenient sample of 5050 adults 18 years and above living in 12 West African countries. The dependent variables were: social distancing, working remotely, difficulty obtaining face masks and difficulty washing hands often. The independent variables were self-reported depression, having a health risk for COVID-19 (high, moderate and little/no risk), living with HIV and COVID-19 status (SARS-CoV-2 positive tests, having COVID-19 symptoms but not getting tested, having a close friend who tested positive for SARS-CoV-2 and knowing someone who died from COVID-19). Four binary logistic regression models were developed to model the associations between the dependent and independent variables, adjusting for socio-demographic variables (age, gender, educational status, employment status and living status). RESULTS: There were 2412 (47.8%) male participants and the mean (standard deviation) age was 36.94 (11.47) years. Respondents who reported depression had higher odds of working remotely (AOR: 1.341), and having difficulty obtaining face masks (AOR: 1.923;) and washing hands often (AOR: 1.263). People living with HIV had significantly lower odds of having difficulty washing hands often (AOR: 0.483). Respondents with moderate health risk for COVID-19 had significantly higher odds of social distancing (AOR: 1.144) and those with high health risk had difficulty obtaining face masks (AOR: 1.910). Respondents who had a close friend who tested positive for SARS-CoV-2 (AOR: 1.132) and knew someone who died of COVID-19 (AOR: 1.094) had significantly higher odds of social distancing. Those who tested positive for SARS-CoV-2 had significantly lower odds of social distancing (AOR: 0.629) and working remotely (AOR: 0.713). Those who had symptoms of COVID-19 but did not get tested had significantly lower odds of social distancing (AOR: 0.783) but significantly higher odds of working remotely (AOR: 1.277). CONCLUSIONS: The study signifies a disparity in the access to and use of COVID-19 preventative measures that is allied to the health and COVID-19 status of residents in West Africa. Present findings point to risk compensation behaviours in explaining this outcome.

Computational investigation of Moringa oleifera phytochemicals targeting EGFR: molecular docking, molecular dynamics simulation and density functional theory studies.

Epidermal growth factor receptor (EGFR) is a prominent target for anticancer therapy due to its role in activating several cell signaling cascades. Clinically approved EGFR inhibitors are reported to show treatment resistance and toxicity, this study, therefore, investigates Moringa oleifera phytochemicals to find potent and safe anti-EGFR compounds. For that, phytochemicals were screened based on drug-likeness and molecular docking analysis followed by molecular dynamics simulation, density functional theory analysis and ADMET analysis to identify the effective inhibitors of EGFR tyrosine kinase (EGFR-TK) domain. Known EGFR-TK inhibitors (1-4 generations) were used as control. Among 146 phytochemicals, 136 compounds showed drug-likeness, of which Delta 7-Avenasterol was the most potential EGFR-TK inhibitor with a binding energy of -9.2 kcal/mol followed by 24-Methylenecholesterol (-9.1 kcal/mol), Campesterol (-9.0 kcal/mol) and Ellagic acid (-9.0 kcal/mol). In comparison, the highest binding affinity from control drugs was displayed by Rociletinib (-9.0 kcal/mol). The molecular dynamics simulation (100 ns) exhibited the structural stability of native EGFR-TK and protein-inhibitor complexes. Further, MM/PBSA computed the binding free energies of protein complex with Delta 7-Avenasterol, 24-Methylenecholesterol, Campesterol and Ellagic acid as -154.559 ± 18.591 kJ/mol, -139.176 ± 19.236 kJ/mol, -136.212 ± 17.598 kJ/mol and -139.513 ± 23.832 kJ/mol, respectively. Non-polar interactions were the major contributors to these energies. The density functional theory analysis also established the stability of these inhibitor compounds. ADMET analysis depicted acceptable outcomes for all top phytochemicals without displaying any toxicity. In conclusion, this report has identified promising EGFR-TK inhibitors to treat several cancers that can be further investigated through laboratory and clinical tests.

Berberine ameliorates the progression of primary sclerosing cholangitis by activating farnesoid X receptor.

Primary sclerosing cholangitis (PSC) is a rare cholestatic disease characterized by biliary infiltration, hepatic fibrosis and bile duct destruction. To date, treatment options for PSC are very limited. Therefore, the current study is aimed to investigate the therapeutic potential of berberine (BBR) against PSC. The disease was induced by feeding the mice with 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC) for four weeks. The serum biochemistry and liver histology were analyzed. Furthermore, the expression of farnesoid X receptor (FXR) was also evaluated by real-time PCR. The results indicated that berberine prevents the progression of PSC by modulating the expression of FXR which ultimately regulates other genes (including Cyp7A1 and BSEP) thus maintaining bile acids homeostasis. Furthermore, the docking analysis showed that berberine interacts with the binding pocket of FXR to activate the protein thus acting as an FXR agonist. In conclusion, data indicate that berberine protects the liver from PSC-related injury. This effect might be due to the modulation of FXR activity.

Repurposing FDA approved drugs against monkeypox virus DNA dependent RNA polymerase: virtual screening, normal mode analysis and molecular dynamics simulation studies.

Zoonotic monkeypox disease, caused by the double-stranded DNA monkeypox virus, has become a global concern. Due to the absence of a specific small molecule drug for the disease, this report aims to identify potential inhibitor drugs for monkeypox. This study explores a drug repurposing strategy using virtual screening to evaluate 1615 FDA approved drugs against the monkeypox virus DNA dependent RNA polymerase subunit A6R. Normal mode analysis and molecular dynamics simulation assessed the flexibility and stability of the target protein in complex with the top screened drugs. The analysis identified Nilotinib (ZINC000006716957), Conivaptan (ZINC000012503187), and Ponatinib (ZINC000036701290) as the most potential RNA polymerase inhibitors with binding energies of - 7.5 kcal/mol. These drugs mainly established hydrogen bonds and hydrophobic interactions with the protein active sites, including LEU95, LEU90, PRO96, MET110, and VAL113, and residues nearby. Normal mode analysis and molecular dynamics simulation confirmed the stability of interactions between the top drugs and the protein. In conclusion, we have discovered promising drugs that can potentially control the monkeypox virus and should be further explored through experimental assays and clinical trials to assess their actual activity against the disease. The findings of this study could lay the foundation for screening repurposed compounds as possible antiviral treatments against various highly pathogenic viruses.

Socio-economic factors associated with post-traumatic stress symptoms among adolescents and young people during the first wave of the COVID-19 pandemic.

This study assessed the association between sociodemographic factors and post-traumatic stress symptoms (PTSS) among 18-24-year-olds during the first wave of the COVID-19 pandemic. This was a secondary analysis of data from 4508 individuals collected through an online survey conducted between June and January 2021. PTSS was measured as a dependent variable using the checklist for post-traumatic stress disorder in civilians. Age, birth sex, sexual, level of education, access to emotional and social support, and emotional distress were the independent variables. A multivariate logistic regression analysis was conducted to determine the associations between the dependent and independent variables while controlling for the country related confounding variables. Females (AOR:2.023), sexual minority individuals (AOR:1.868), those who did not disclose their sexual identify (AOR:1.476), those with poor access to emotional and social support (AOR:4.699) and individuals with no formal education (AOR:13.908), and only primary level education (AOR:4.521) had higher odds of PTSS. The study highlights the multifaceted nature of PTSS during the pandemic and suggests the importance of promoting access of young people, especially females, sexual minority individuals and those with low educational status, to emotional/social support to mitigate the probability of PTSS, especially among sexual minority individuals.

In-silico prediction of TGF-ß1 non-synonymous variants and their impact on binding affinity to Fresolimumab.

TGF-ß1 is a potent immunoregulatory cytokine that plays diverse roles in development, bone healing, fibrosis, and cancer. However, characterizing TGF-ß1 gene variants is challenging because the structural and functional consequences of these variants are still undetermined. In this study, we aimed to perform an in-silico analysis of TGF-ß1 non-synonymous variants and their pathogenic effects on the TGF-ß1 protein. A total of 10,252 TGF-ß1 SNPs were collected from the NCBI dbSNP database and in-silico tools (SIFT, PROVEAN, Mutation Taster, ClinVar, PolyPhen-2, CScape, MutPred, and ConSurf) were used. The in-silico predicted potential variants were further investigated for their binding to the TGF-ß1 targeting drug "Fresolimumab". Molecular docking was performed using HADDOCK and confirmed by PRODIGY and PDBsum. The in-silico analysis predicted four potential TGF-ß1 nsSNPs: E47G in the LAP domain of the propeptide and I22T, L28F, and E35D in the mature TGF-ß1 peptide. HADDOCK and molecular dynamics simulations revealed that the I22T and E35D variants have higher binding affinity for Fresolimumab as compared to the wild type and L28F variants. Molecular dynamics simulations (100 ns) and principal component analysis showed that TGF-ß1 variants influenced the protein structure and caused variations in the internal dynamics of protein complexes with the antibody. Among them, the E35D variant significantly destabilized the TGF-ß1 protein structure, resulting in rearrangement in the binding site and affecting the interactions with the Fresolimumab. This study identified four variants that can affect the TGF-ß1 protein structure and result in functional consequences such as impaired response to Fresolimumab.Communicated by Ramaswamy H. Sarma.

A computational and bioinformatic analysis of ACE2: an elucidation of its dual role in COVID-19 pathology and finding its associated partners as potential therapeutic targets.

Despite the continued global spread of the current COVID-19 pandemic, the nonavailability of a vaccine or targeted drug against this disease is still prevailing. The most established mechanism of viral entry into the body is considered to be via angiotensin-converting enzyme 2 (ACE2) acting as a receptor for viral spike protein thereby facilitating its entry in the cell. However, ACE2 is also involved in providing the protection from severe pathological changes. This article provides a computational and bioinformatics-based analysis of ACE2 with an objective of providing further insight into the earnest efforts to determine its true position in COVID-19 pathology. The results of this study show that ACE2 has strikingly low expression in healthy human lung tissue and was absent from the list of differentially expressed genes. However, when transcription factors were analyzed, we found a significant upregulation of FOS and downregulation of FOXO4 and FOXP2. Moreover, the miRNA prediction analysis revealed that miR-1246, whose upregulation has been experimentally established to be a cause of acute respiratory distress syndrome (ARDS), was found to be targeting the coding DNA sequence (CDS) of ACE2. This study presents a wide range of potentially important transcription factors as well as miRNA targets associated with ACE2 which can be potentially used for drug designing amid this challenging pandemic situation.Communicated by Ramaswamy H. Sarma.

Impact of the COVID-19 pandemic on student' sleep patterns, sexual activity, screen use, and food intake: A global survey.

BACKGROUND: The education sector experienced substantial impacts during the COVID-19 pandemic resulting from worldwide restrictions. PURPOSE: To examine differences in the sleep patterns, sexual activity, screen use, and food intake of students and non-students during the COVID-19 pandemic. METHODS: This was a global cross-sectional study conducted in the second half of 2020 using multiple social media platforms to recruit study participants globally. A close-ended questionnaire was administered anonymously in English, French, Spanish, Portuguese, and Arabic to adults ages 18 and older. The outcome variables considered in analyses were changes in sleep pattern, sexual activity, screen use, and food intake. The explanatory variable was student status categorized as students vs. non-student. T-test, chi-square, and Mann Whitney U tests were used to assess differences between student and non-student populations. One logistic regression model was built for each outcome variable. Country of residence and country income level were included in the adjusted models. RESULTS: There were 17,008 participants of which 3,793 (22.3%) were students. Of the total sample, 4,889 (28.7%) reported changes in sleep, 4,642 (31.8%) reported increases in sexual activity, 10,278 (70.7%) reported increases in screen use, and 5,662 (40.2%) reported increases in food intake during the pandemic. Compared to non-students, students had significantly higher odds of reporting changes in sleep (AOR = 1.52), increases in sexual activity (AOR = 1.79), and increases in screen use (AOR = 1.36) but lower odds of reporting increase in food intake (AOR = 0.87). CONCLUSION: Students displayed higher risk of experiencing changes in sleep, sexual behavior, and screen use during the COVID-19 pandemic. This has the potential to lead to broader adverse effects on students' overall wellbeing. The findings and implications raise further obligations on the education sector to put extra-curricular support systems in place that address COVID-19 related behavior changes that have the potential to adversely impact students' wellbeing.

Factors Associated With Experiences of Fear, Anxiety, Depression, and Changes in Sleep Pattern During the COVID-19 Pandemic Among Adults in Nigeria: A Cross-Sectional Study.

Background: Multiple facets of the pandemic can be a source of fear, depression, anxiety and can cause changes in sleep patterns. The aim of this study was to identify health profiles and the COVID-19 pandemic related factors associated with fear, depression, anxiety and changes in sleep pattern in adults in Nigeria. Methods: The data for this analysis was extracted from a cross-sectional online survey that collected information about mental health and well-ness from a convenience sample of adults 18 years and above resident in Nigeria from July to December 2020. Study participants were asked to complete an anonymous, closed-ended online questionnaire that solicited information on sociodemographic profile, health profiles (high, moderate and low COVID-19 infection risk profile) including HIV status, COVID-19 status, and self-reported experiences of fear, anxiety, depression and changes in sleep patterns. Results: In total, 4,439 participants with mean age of 38.3 (±11.6) years responded to the survey. Factors associated with higher odds of having COVID-19 related fear were health risk (p < 0.05); living with HIV (AOR: 3.88; 95% CI: 3.22-4.69); having COVID-19 symptoms but not tested (AOR: 1.61; 95% CI: 1.30-1.99); having a friend who tested positive to COVID-19 (AOR: 1.28; 95% CI: 1.07-1.53) and knowing someone who died from COVID-19 (AOR: 1.43; 95% CI: 1.24-1.65). The odds of feeling anxious was significantly higher for those with moderate or low health risk profile (p < 0.05); living with HIV (AOR: 1.64; 95% CI: 1.32-2.04); had a friend who tested positive for COVID-19 (AOR: 1.35; 95% CI: 1.08-1.68) or knew someone who died from COVID-19 (AOR: 1.53; 95% CI: 1.28-1.84). The odds of feeling depressed was significantly higher for those with health risk profile (p < 0.05); living with HIV (AOR: 2.49; 95% CI: 1.89-3.28); and respondents who had COVID-19 symptoms but had not taken a test (AOR: 1.41; 95% CI: 1.02-1.94). Factors associated with higher odds of having sleep pattern changes were having moderate and low health risk profiles (p < 0.05). Conclusion: The study findings suggest that the pandemic may cause fear, anxiety, depression and changes in sleep patterns differently for people with different health profile, HIV status and COVID-19 status.

Factors Associated with Financial Security, Food Security and Quality of Daily Lives of Residents in Nigeria during the First Wave of the COVID-19 Pandemic.

An online survey was conducted to identify factors associated with financial insecurity, food insecurity and poor quality of daily lives of adults in Nigeria during the first wave of the COVID-19 pandemic. The associations between the outcome (experience of financial loss, changes in food intake and impact of the pandemic on daily lives) and the explanatory (age, sex, education level, anxiety, depression, HIV status) variables were determined using logistic regression analysis. Of the 4439 respondents, 2487 (56.0%) were financially insecure, 907 (20.4%) decreased food intake and 4029 (90.8%) had their daily life negatively impacted. Males (AOR:0.84), people who felt depressed (AOR:0.62) and people living with HIV -PLHIV- (AOR:0.70) had significantly lower odds of financial insecurity. Older respondents (AOR:1.01) had significantly higher odds of financial insecurity. Those depressed (AOR:0.62) and PLHIV (AOR:0.55) had significantly lower odds of reporting decreased food intake. Respondents who felt anxious (AOR:0.07), depressed (AOR: 0.48) and who were PLHIV (AOR:0.68) had significantly lower odds of reporting a negative impact of the pandemic on their daily lives. We concluded the study findings may reflect a complex relationship between financial insecurity, food insecurity, poor quality of life, mental health, and socioeconomic status of adults living in Nigeria during the COVID-19 pandemic.