Prevalence, correlates and common conditions associated with adolescent dietary supplement use: a cross-sectional survey in Bangladesh.

OBJECTIVE: There is a broad spectrum of dietary supplements (DS) and their accessibility worldwide. However, little is known about the prevalence of DS use among Bangladeshi adolescents. This study estimates the prevalence, correlates and common conditions related to DS use. DESIGN: A cross-sectional, convenient sampling strategy was adopted using an interviewer-administered, structured questionnaire. SETTING: Kurigram and Patuakhali districts of Bangladesh. PARTICIPANTS: 702 adolescents aged 10-19 years. RESULTS: The overall prevalence of DS use was 83 %. The majority of participants (93·4 %) agreed that DS were good for health, and 28·3 % reported general health and well-being as the reason for using DS. The most frequently used supplements were multivitamins (38·6 %) and Ca (37 %). DS use was more common among adolescents who had ≤5 siblings, good health status, no chronic diseases, a positive impression that DS are good for health and who had the tendency to encourage DS to others. DS use was also higher among those who received DS information from healthcare providers, professional literature, friends, family and relatives. CONCLUSIONS: The prevalence of DS use is relatively higher among Bangladeshi adolescents compared to Bangladeshi adults and adolescents from other countries, highlighting the inclination towards DS use. Guidelines for safe DS use for adolescents are warranted to control DS use and prevent adverse effects.

Angiotensin II-induced overexpression of sirtuin 1 contributes to enhanced expression of Giα proteins and hyperproliferation of vascular smooth muscle cells.

Angiotensin II (ANG II) plays an important role in the regulation of various physiological functions including proliferation, hypertrophy of vascular smooth muscle cells (VSMCs) through the overexpression of Giα proteins. Sirtuin 1 (Sirt1), a class III histone deacetylase and epigenetic regulator is implicated in a wide range of cellular functions, including migration and growth of VSMCs and in ANG II-induced hypertension. The present study was undertaken to examine the role of Sirt1 in ANG II-induced overexpression of Giα proteins and hyperproliferation of aortic VSMCs. We show that ANG II treatment of VSMCs increased the expression of Sirt1, which was attenuated by AT1 and AT2 receptor antagonists, losartan, and PD123319, respectively. In addition, the knockdown of Sirt1 by siRNA attenuated ANG II-induced overexpression of Giα-2 and Giα-3 proteins, hyperproliferation of VSMCs and the overexpression of cell cycle proteins, cyclin D1, Cdk4, and phosphorylated retinoblastoma proteins. Furthermore, ANG II-induced increased levels of superoxide anion (O2-) and NADPH oxidase activity and increased phosphorylation of ERK1/2 and Akt that are implicated in enhanced expression of Giα proteins and hyperproliferation of VSMCs were also attenuated to control levels by silencing of Sirt1. In addition, depletion of Sirt1 by siRNA also attenuated ANG II-induced enhanced phosphorylation of platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), and insulin-like growth factor receptor (IGFR) in VSMCs. In summary, our results demonstrate that ANG II increased the expression of Sirt1, which through oxidative stress, growth factor receptor-mediated mitogen-activated protein (MAP) kinase/Akt signaling pathway enhances the expression of Giα proteins and cell cycle proteins and results in the hyperproliferation of VSMCs.NEW & NOTEWORTHY ANG II regulates various physiological functions including proliferation of VSMCs through the overexpression of Giα proteins. Sirt1, a class III histone deacetylase, is implicated in several cellular functions, including VSMC growth and ANG II-induced hypertension. We showed for the first time that ANG II increased the expression of Sirt1, which through oxidative stress, growth factor receptor-mediated MAP kinase/Akt signaling pathway enhances the levels of Giα and cell cycle proteins resulting in the hyperproliferation of VSMCs.

Role of the JAK2/STAT3 pathway in angiotensin II-induced enhanced expression of Giα proteins and hyperproliferation of aortic vascular smooth muscle cells.

We earlier showed that angiotensin (Ang) II-induced overexpression of Giα proteins contributes to the hyperproliferation of vascular smooth muscle cells (VSMC). In addition, the implication of the JAK2/STAT3 pathway in Ang II-induced hyperproliferation of VSMC has also been reported. However, the role of the JAK2/STAT3 pathway in Ang II-induced overexpression of Giα proteins and hyperproliferation of VSMC remains unexplored. In the present study, we show that inhibition or knockdown of the JAK2/STAT3 pathway by a specific inhibitor "cucurbitacin I" (CuI) or siRNAs attenuated Ang II-induced overexpression of Giα proteins and hyperproliferation of VSMC. In addition, the enhanced expression of cell cycle proteins induced by Ang II was also attenuated by CuI. Furthermore, Ang II-induced enhanced production of the superoxide anion (O2 -), H2O2, and NADPH oxidase activity, as well as the enhanced expression of NADPH oxidase subunits implicated in enhanced expression of Giα proteins and hyperproliferation, were also attenuated by inhibition of the JAK2/STAT3 pathway. On the other hand, Ang II-induced inhibition and augmentation of the levels of nitric oxide and peroxynitrite, respectively, in VSMC were restored to control levels by CuI. In summary, our results demonstrate that Ang II through the JAK2/STAT3 pathway increases nitroxidative stress, which contributes to the overexpression of Giα proteins and cell cycle proteins and the hyperproliferation of VSMC.

In utero exposures to electronic-cigarette aerosols impair the Wnt signaling during mouse lung development.

Currently, more than 9 million American adults, including women of childbearing age, use electronic-cigarettes (e-cigs). Further, the prevalence of maternal vaping now approaching 10% is similar to that of maternal smoking. Little, however, is known about the effects of fetal exposures to nicotine-rich e-cig aerosols on lung development. In this study, we assessed whether in utero exposures to e-cig aerosols compromised lung development in mice. A third-generation e-cig device was used to expose pregnant BALB/c mice by inhalation to 36 mg/mL of nicotine cinnamon-flavored e-cig aerosols for 14-31 days. This included exposures for either 12 days before mating plus during gestation (preconception groups) or only during gestation (prenatal groups). Respective control mice were exposed to filtered air. Subgroups of offspring were euthanized at birth or at 4 wk of age. Compared with respective air-exposed controls, both preconception and prenatal exposures to e-cig aerosols significantly decreased the offspring birth weight and body length. In the preconception group, 7 inflammation-related genes were downregulated, including 4 genes common to both dams and fetuses, denoting an e-cig immunosuppressive effect. Lung morphometry assessments of preconception e-cig-exposed offspring showed a significantly increased tissue fraction at birth. This result was supported by the downregulation of 75 lung genes involved in the Wnt signaling, which is essential to lung organogenesis. Thus, our data indicate that maternal vaping impairs pregnancy outcomes, alters fetal lung structure, and dysregulates the Wnt signaling. This study provides experimental evidence for future regulations of e-cig products for pregnant women and developmentally vulnerable populations.

Sub-ohm vaping increases the levels of carbonyls, is cytotoxic, and alters gene expression in human bronchial epithelial cells exposed at the air-liquid interface.

BACKGROUND: Exposure to electronic-cigarette (e-cig) aerosols induces potentially fatal e-cig or vaping-associated lung injury (EVALI). The cellular and molecular mechanisms underlying these effects, however, are unknown. We used an air-liquid interface (ALI) in vitro model to determine the influence of two design characteristics of third-generation tank-style e-cig devices-resistance and voltage-on (1) e-cig aerosol composition and (2) cellular toxicity. METHODS: Human bronchial epithelial cells (H292) were exposed to either butter-flavored or cinnamon-flavored e-cig aerosols at the ALI in a Vitrocell exposure system connected to a third-generation e-cig device. Exposures were conducted following a standard vaping topography profile for 2 h per day, for 1 or 3 consecutive days. 24 h after ALI exposures cellular and molecular outcomes were assessed. RESULTS: We found that butter-flavored e-cig aerosol produced under 'sub-ohm' conditions (< 0.5 Ω) contains high levels of carbonyls (7-15 µg/puff), including formaldehyde, acetaldehyde and acrolein. E-cig aerosol produced under regular vaping conditions (resistance > 1 Ω and voltage > 4.5 V), contains lower carbonyl levels (< 2 µg/puff). We also found that the levels of carbonyls produced in the cinnamon-flavored e-cig aerosols were much lower than that of the butter-flavored aerosols. H292 cells exposed to butter-flavored or cinnamon-flavored e-cig aerosol at the ALI under 'sub-ohm' conditions for 1 or 3 days displayed significant cytotoxicity, decreased tight junction integrity, increased reactive oxygen species production, and dysregulated gene expression related to biotransformation, inflammation and oxidative stress (OS). Additionally, the cinnamon-flavored e-cig aerosol induced pro-oxidant effects as evidenced by increases in 8-hydroxy-2-deoxyguanosine protein levels. Moreover, we confirmed the involvement of OS as a toxicity process for cinnamon-flavored e-cig aerosol by pre-treating the cells with N-acetyl cysteine (NAC), an antioxidant that prevented the cells from the OS-mediated damage induced by the e-cig aerosol. CONCLUSION: The production of high levels of carbonyls may be flavor specific. Overall, inhaling e-cig aerosols produced under 'sub-ohm' conditions is detrimental to lung epithelial cells, potentially via mechanisms associated with OS. This information could help policymakers take the necessary steps to prevent the manufacturing of sub-ohm atomizers for e-cig devices.

Cell-specific toxicity of short-term JUUL aerosol exposure to human bronchial epithelial cells and murine macrophages exposed at the air-liquid interface.

BACKGROUD: JUUL, an electronic nicotine delivery system (ENDS), which first appeared on the US market in 2015, controled more than 75% of the US ENDS sales in 2018. JUUL-type devices are currently the most commonly used form of ENDS among youth in the US. In contrast to free-base nicotine contained in cigarettes and other ENDS, JUUL contains high levels of nicotine salt (35 or 59 mg/mL), whose cellular and molecular effects on lung cells are largely unknown. In the present study, we evaluated the in vitro toxicity of JUUL crème brûlée-flavored aerosols on 2 types of human bronchial epithelial cell lines (BEAS-2B, H292) and a murine macrophage cell line (RAW 264.7). METHODS: Human lung epithelial cells and murine macrophages were exposed to JUUL crème brûlée-flavored aerosols at the air-liquid interface (ALI) for 1-h followed by a 24-h recovery period. Membrane integrity, cytotoxicity, extracellular release of nitrogen species and reactive oxygen species, cellular morphology and gene expression were assessed. RESULTS: Crème brûlée-flavored aerosol contained elevated concentrations of benzoic acid (86.9 µg/puff), a well-established respiratory irritant. In BEAS-2B cells, crème brûlée-flavored aerosol decreased cell viability (≥ 50%) and increased nitric oxide (NO) production (≥ 30%), as well as iNOS gene expression. Crème brûlée-flavored aerosol did not affect the viability of either H292 cells or RAW macrophages, but increased the production of reactive oxygen species (ROS) by ≥ 20% in both cell types. While crème brûlée-flavored aerosol did not alter NO levels in H292 cells, RAW macrophages exposed to crème brûlée-flavored aerosol displayed decreased NO (≥ 50%) and down-regulation of the iNOS gene, possibly due to increased ROS. Additionally, crème brûlée-flavored aerosol dysregulated the expression of several genes related to biotransformation, inflammation and airway remodeling, including CYP1A1, IL-6, and MMP12 in all 3 cell lines. CONCLUSION: Our results indicate that crème brûlée-flavored aerosol causes cell-specific toxicity to lung cells. This study contributes to providing scientific evidence towards regulation of nicotine salt-based products.

Sodium nitroprusside attenuates hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats through the inhibition of overexpression of AT1 receptor, cell cycle proteins, and c-Src/growth factor receptor signaling pathways.

We recently showed that sodium nitroprusside (SNP), a NO donor, attenuated hypertension in spontaneously hypertensive rats (SHR). Since hypertension is associated with enhanced proliferation and hypertrophy of vascular smooth muscle cells (VSMC), the present study examines whether in vivo treatment of SHR with SNP could also inhibit the augmented proliferation of VSMC and explore the signaling mechanisms. Treatment of 8 week old SHR and Wistar Kyoto rats with SNP twice a week for 2 weeks inhibited the enhanced proliferation of VSMC from SHR, the enhanced expression of angiotensin II type 1 (AT1) receptor, and enhanced activation of c-Src and growth factor receptors and ERK1/2 signaling pathways. In addition, SNP also inhibited the overexpression of cell cycle proteins including cyclins D1, Cdk4, and phosphorylated pRB and restored the downregulated Cdk inhibitors p21Cip1 and p27Kip1 expression towards control levels. Furthermore, SNP-induced inhibition of enhanced levels of the AT1 receptor and enhanced proliferation was reversed by L-NAME, an inhibitor of nitric oxide synthase. These results suggest that the SNP-induced antiproliferative effect may be mediated through the inhibition of enhanced expression of the AT1 receptor, cell cycle proteins and activation of c-Src, growth factor receptors, and MAP kinase signaling.

Natriuretic peptide receptor-C activation attenuates angiotensin II-induced enhanced oxidative stress and hyperproliferation of aortic vascular smooth muscle cells.

We showed previously that natriuretic peptide receptor-C (NPR-C) agonist, C-ANP4-23, attenuated the enhanced expression of Giα proteins in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) through the inhibition of enhanced oxidative stress. Since the enhanced levels of endogenous angiotensin II (Ang II) contribute to the overexpression of Giα proteins and augmented oxidative stress in VSMC from SHR, the present study was undertaken to investigate if C-ANP4-23 could also attenuate angiotensin II (Ang II)-induced oxidative stress and associated signaling. Ang II treatment of aortic VSMC augmented the levels of superoxide anion (O2-), NADPH oxidase activity, and the expression of NADPH oxidase subunits and C-ANP4-23 treatment attenuated all these to control levels. In addition, Ang II-induced enhanced levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyl content were also attenuated toward control levels by C-ANP4-23 treatment. On the other hand, Ang II inhibited the levels of nitric oxide (NO) and augmented the levels of peroxynitrite (OONO-) in VSMC which were restored to control levels by C-ANP4-23 treatment. Furthermore, C-ANP4-23 treatment attenuated Ang II-induced enhanced expression of Giα proteins, phosphorylation of p38, JNK, and ERK 1,2 as well as hyperproliferation of VSMC as determined by DNA synthesis, and metabolic activity. These results indicate that C-ANP4-23, via the activation of NPR-C, attenuates Ang II-induced enhanced nitroxidative stress, overexpression of Giα proteins, increased activation of the p38/JNK/ERK 1,2 signaling pathways, and hyperproliferation of VSMC. It may be suggested that C-ANP4-23 could be used as a therapeutic agent in the treatment of vascular remodeling associated with hypertension and atherosclerosis.

Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle cells through the transactivation of growth factor receptors.

We previously showed that augmented levels of endogenous angiotensin II (AngII) contribute to vascular smooth muscle cell (VSMC) hypertrophy through the transactivation of growth factor receptors in spontaneously hypertensive rats. Resveratrol (RV), a polyphenolic component of red wine, has also been shown to attenuate AngII-evoked VSMC hypertrophy; however, the molecular mechanism mediating this response is obscure. The present study was therefore undertaken to examine whether RV could prevent AngII-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. AngII treatment of VSMC enhanced the protein synthesis that was attenuated towards control levels by RV pretreatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also inhibited enhanced levels of superoxide anion, NADPH oxidase activity, increased expression of NADPH oxidase subunits, and phosphorylation of c-Src, EGF-R, PDGE-R, ERK1/2, and AKT1/2. In conclusion, these results indicate that RV attenuates AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling. We suggest that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.

Lipopolysaccharide augments the uptake of oxidized LDL by up-regulating lectin-like oxidized LDL receptor-1 in macrophages.

There is a growing body of evidence supporting an intimate association of immune activation with the pathogenesis of cardiovascular diseases, including atherosclerosis. Uptake of oxidized low-density lipoprotein (oxLDL) through scavenging receptors promotes the formation of mature lipid-laden macrophages, which subsequently leads to exacerbation of regional inflammation and atherosclerotic plaque formation. In this study, we first examined changes in the mRNA level of the lectin-like oxLDL receptor-1 (LOX-1) in the mouse macrophage cell line RAW264.7 and the human PMA-induced macrophage cell line THP-1 after LPS stimulation. LPS significantly up-regulated LOX-1 mRNA in RAW264.7 cells; LOX-1 cell-surface protein expression was also increased. Flow cytometry and fluorescence microscopy analyses showed that cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with LPS stimulation. The augmented uptake of Dil-oxLDL was almost completely abrogated by treatment with an anti-LOX-1 antibody. Of note, knockdown of Erk1/2 resulted in a significant reduction of LPS-induced LOX-1 up-regulation. Treatment with U0126, a specific inhibitor of MEK, significantly suppressed LPS-induced expression of LOX-1 at both the mRNA and protein levels. Furthermore, LOX-1 promoter activity was significantly augmented by LPS stimulation; this augmentation was prevented by U0126 treatment. Similar results were also observed in human PMA-induced THP-1 macrophages. Taken together, our results indicate that LPS up-regulates LOX-1, at least in part through activation of the Erk1/2 signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of TLR4-mediated aberrant LOX-1 signaling in the pathogenesis of atherosclerosis.

Self-Medication Practices among Adult Population in Bangladesh: A Cross-Sectional Study.

BACKGROUND: The practice of self-medication (SM) is common worldwide and is an important component of medical self-care. However, improper practice can be dangerous. This study aimed to estimate the prevalence of SM and the factors associated with it among Bangladeshi adults. METHODS: A cross-sectional survey was conducted between April and June 2021 among Bangladeshi adults (aged > 19 years) using convenient sampling. A total of 1320 subjects were collected through face-to-face interviews using a standardized questionnaire. Multivariable logistic regression analysis was used to identify factors associated with the practice of SM. RESULTS: Overall, 41% of adults in our survey reported SMP. The most common illnesses that prompted SM were common cold/flu (66.4%), gastric problems (65%), and headache (64.4%). The most frequent reasons for SM were to get better-perceived quality of care (30.6%), perceiving SM without side effects (23.3%), and saving time with effectiveness (14.56%). Potential risk factors included 10 years (AOR = 1.91; 95% CI: 1.04-3.50) and >12 years of schooling (AOR = 5.03; 95% CI: 2.27-11.15), being a businessman (AOR = 4.64; 95% CI: 1.74-12.37), having ≤6 family members (AOR = 2.13; 95% CI: 1.40-3.24), being a member of a social group (AOR = 1.53; 95% CI: 1.10-2.12), a health status check after every six months (AOR = 1.52; 95% CI: 1.08-2.13), and current ill-health (AOR = 1.41; 95% CI: 1.06-1.87). Protective factors identified included ≤30 years of age (AOR = 0.40; 95% CI: 0.17-0.93), and practice of modern (AOR = 0.39; 95% CI: 0.22-0.69) and herbal (AOR = 0.45; 95% CI: 0.21-0.97) treatment modality. CONCLUSION: More than one-third of the study participants reported practicing SM. Increasing the community's awareness of the adverse outcomes of SM and not just the average experience might sway individuals away from SM, and implementing strict jurisdiction could be a way to minimize inappropriate SM.

Arsenic trioxide prevents nitric oxide production in lipopolysaccharide -stimulated RAW 264.7 by inhibiting a TRIF-dependent pathway.

Arsenic trioxide (ATO) is one of the most potent drugs in cancer chemotherapy, and is highly effective in treating both newly diagnosed and relapse patients with acute promyelocytic leukemia (APL). Despite a number of reports regarding the molecular mechanisms by which ATO promotes anti-tumor or pro-apoptotic activity in hematological and other solid malignancies, the effects of ATO on immune responses remain poorly understood. To further understand and clarify the effects of ATO on immune responses, we sought to examine whether ATO affects the production of nitric oxide (NO) in a lipopolysaccharide (LPS)-stimulated mouse macrophage cell line, RAW 264.7. Arsenic trioxide was found to prevent NO production in a dose-dependent manner. Arsenic trioxide significantly inhibited the increase in inducible nitric oxide synthase (iNOS) at both the mRNA and protein levels. Furthermore, our analyses revealed that the inhibitory effect of ATO on iNOS expression was ascribed to the prevention of IRF3 phosphorylation, interferon (IFN)-ß expression, and STAT1 phosphorylation, but not the prevention of the MyD88-dependent pathway. Taken together, our results indicate that ATO prevents NO production by inhibiting the TIR-domain-containing adaptor protein inducing IFN-ß (TRIF)-dependent pathway, thus highlighting an anti-inflammatory property of ATO in innate immunity.

Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells.

Although chronic arsenic exposure is a well-known risk factor for cardiovascular diseases, including atherosclerosis, the molecular mechanism underlying arsenic-induced atherosclerosis remains obscure. Therefore, this study aimed to elucidate this molecular mechanism. We examined changes in the mRNA level of the lectin-like oxidized LDL (oxLDL) receptor (LOX-1) in a mouse aortic endothelial cell line, END-D, after sodium arsenite (SA) treatment. SA treatment significantly upregulated LOX-1 mRNA expression; this finding was also verified at the protein expression level. Flow cytometry and fluorescence microscopy analyses showed that the cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with SA treatment. In addition, an anti-LOX-1 antibody completely abrogated the augmented uptake of Dil-oxLDL. We observed that SA increased the levels of the phosphorylated forms of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB)/p65. SA-induced upregulation of LOX-1 protein expression was clearly prevented by treatment with an antioxidant, N-acetylcysteine (NAC), or an NF-κB inhibitor, caffeic acid phenethylester (CAPE). Furthermore, SA-augmented uptake of Dil-oxLDL was also prevented by treatment with NAC or CAPE. Taken together, our results indicate that arsenic upregulates LOX-1 expression through the reactive oxygen species-mediated NF-κB signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of the aberrant LOX-1 signaling pathway in the pathogenesis of arsenic-induced atherosclerosis.

Prevalence and factors associated with depression, anxiety, and stress among people with disabilities during COVID-19 pandemic in Bangladesh: A cross-sectional study.

BACKGROUND: The COVID-19 pandemic has had a profound impact on the mental health of individuals across various populations. People with disabilities (PWDs) are particularly vulnerable to these effects, yet there is a lack of studies investigating the mental health of PWDs in Bangladesh. This study aims to investigate the prevalence of and factors associated with depression, anxiety, and stress among PWDs during the COVID-19 pandemic in Bangladesh. METHODS: Data was collected through interviews with 391 PWDs between December 2020 and February 2021. Demographic information, clinical characteristics, and scores from the Depression, Anxiety, and Stress Scale (DASS-21) were obtained. Chi-square tests and logistic regression analyses were conducted to examine the relationship between psychological measures and potential risk factors. RESULTS: The prevalence was found to be 65.7% for depression, 78.5% for anxiety, and 61.4% for stress, respectively. Several factors were identified as associated with these mental health issues, including gender (male), marital status (being married), low education levels, multiple impairments, comorbid medical illnesses, poor sleep quality, rural residency, hearing disability, disability onset later in life, and testing positive for COVID-19. CONCLUSIONS: The prevalence was found to be 65.7% for depression, 78.5% for anxiety, and 61.4% for stress, respectively. Several factors were identified as associated with these mental health issues, including gender (male), marital status (being married), low education levels, multiple impairments, comorbid medical illnesses, poor sleep quality, rural residency, hearing disability, disability onset later in life, and testing positive for COVID-19.

Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic.

Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose-response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions.

Assessment of the long-term transcriptional activity of a 550-bp-long human ß-actin promoter region.

ß-actin (ACTB) is one of the genes expressed most abundantly and ubiquitously in human non-muscular tissues. Here, we investigated the long-term activity of a 550-bp-long human ACTB promoter region in human cells in comparison with other commonly used constitutive promoters. We first constructed plasmid vectors expressing enhanced green fluorescent protein (GFP) driven by one of the 5 promoters, human ACTB, human elongation factor-1α (EF1α), cytomegalovirus early enhancer/chicken ß-actin (CAG), cytomegalovirus (CMV), and herpes simplex virus thymidine kinase, and transfected them into multiple human somatic cell lines. Stable transfectants were maintained for 45 days, and GFP signals from the cells were quantified by fluorescence flow cytometry. GFP signals driven by the human ACTB and the CMV promoters were also compared over time for up to 60 days following transfection. We observed robust, prolonged transcriptional activity with the human ACTB promoter that is comparable to the human EF1α and the CAG promoters and significantly more stable than the CMV promoter.

Trends and determinants of taking tetanus toxoid vaccine among women during last pregnancy in Bangladesh: Country representative survey from 2006 to 2019.

BACKGROUND: Tetanus occurring during pregnancy is still an important cause of maternal and neonatal mortality in developing countries. This study estimated the trend of tetanus toxoid (TT) immunization coverage from 2006 to 2019 in Bangladesh, considering socio-demographic, socio-economic, and geospatial characteristics. METHODS: The dataset used in this study was extracted from Multiple Indicator Cluster Surveys (2006, 2012-13, and 2019) including 28,734 women aged between 15-49 years. Data analysis was performed using cross-tabulation and logistic regression methods. Further, the spatial distribution of TT immunization coverage was also depicted. RESULTS: The trend of TT immunization (81.8% in 2006 to 49.3% in 2019) and that of taking adequate doses of TT (67.1% in 2006 to 49.9% in 2019) has gradually decreased throughout the study period. Among the administrative districts, North and South-West regions had lower coverage, and South and West regions had relatively higher coverage of both TT immunization and that of adequate doses. Antenatal TT immunization (any dosage, inadequate or adequate) was significantly associated with lower age (AOR = 3.13, 1.55-6.34), higher education (AOR = 1.20, 1.03-1.40), living in urban areas (AOR = 1.17, 1.03-1.34), having immunization card (AOR = 5.19, 4.50-5.98), using government facilities for birth (AOR = 1.41, 1.06-1.88), and receiving antenatal care (ANC) (AOR = 1.51, 1.35-1.69). In addition, living in urban areas (AOR = 1.31, 1.10-1.55), having immunization cards (AOR = 1.62, 1.36-1.92), and choosing others' homes for birth (AOR = 1.37, 1.07-1.74) were significantly associated with adequate TT immunization. However, higher education (AOR = 0.57, 0.44-0.74), having poor wealth index (AOR = 0.65, 0.50-0.83), and receiving ANC (AOR = 0.76, 0.63-0.92) had lower likelihood of taking adequate TT immunization. CONCLUSIONS: The gradual decline in the TT immunization rate in the present study suggests the presence of variable rates and unequal access to TT immunization, demanding more effective public health programs focusing on high-risk groups to ensure adequate TT immunization.

Suicidal ideation among people with disabilities during the COVID-19 pandemic in Bangladesh: prevalence and associated factors.

BACKGROUND: Evidence from pandemic and pre-pandemic studies conducted globally indicates that people with disabilities (PWDs) have a higher risk for suicidality. However, none of these studies has assessed suicidality among PWDs in Bangladesh. AIMS: The purpose of this study was to determine the prevalence of and factors associated with suicidal ideation among PWDs during the COVID-19 pandemic in Bangladesh. METHOD: Using a snowball sampling technique, a cross-sectional survey was conducted from February to April 2021 among PWDs from six districts in the northern region of Bangladesh. Information related to sociodemographic factors, clinical characteristics, behavioural factors and suicidal ideation was collected. Chi-squared test and logistic regression were used to describe the data and explain the relationship of factors associated with suicidal ideation. RESULTS: The prevalence of COVID-19-related past-year suicidal ideation was 23.9%. The factors associated with suicidal ideation included: age above 35 years, being female, acquiring a disability later in life, lack of sleep and current substance use. In addition, higher education appeared to be a protective factor against suicidal ideation. CONCLUSIONS: This study highlighted that PWDs had an increased risk of suicide; that is, one-fourth of them had past-year suicidal ideation. This may have been because of COVID-19-related restrictions and stressors. Thus, the government and policy makers need to pay more attention to developing effective suicide assessment, treatment and management strategies, especially for at-risk groups, to minimise the impact of the COVID-19 outbreak.

Knowledge, Attitudes, and Practices towards COVID-19 among Pregnant Women in Northern Bangladesh: A Community-Based Cross-Sectional Study.

Background: COVID-19, caused by SARS-CoV-2, remains a global public health concern despite the availability of effective antiviral treatment against multiple strains. Studies have shown that pregnant women are more susceptible to COVID-19 due to altered physiology and immunological features. Therefore, this study was designed to investigate pregnant women's knowledge, attitudes, and practice (KAP) to prevent COVID-19 and determine the factors associated with KAP. Methods: A community-based cross-sectional study was conducted among 425 pregnant women in Northern Bangladesh. The samples were obtained using a simple random sampling technique from 5 April to 15 June 2020. The data were collected by face-to-face survey with a structured and pre-tested questionnaire and analyzed using SPSS version 25. Bivariable and multivariable logistic regression analyses were performed, and p-values < 0.05 at 95% CI were considered statistically significant. Results: Overall, the score of KAP among the respondents was 47.76%, 49.41%, and 56.24%, respectively. Participants' area of residence, educational status of the husband, and antenatal care (ANC) visit were significantly associated with the level of knowledge, whereas age, educational status of the husband, number of living children, and knowledge were significant predictors of attitude. The knowledge of COVID-19 was the only predictor associated with the practice. Conclusion: Our study shows that almost half of the participants had poor knowledge, a negative attitude, and poor practices regarding COVID-19. Additional health education programs by healthcare professionals and different media, coordinated and combined efforts of government and individuals' participation will be required to fight the spread of the infection.

Sirtuin1 contributes to the overexpression of Giα proteins and hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats.

BACKGROUND: We earlier demonstrated that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit the overexpression of Giα proteins and hyperproliferation that is attributed to the enhanced levels of endogenous angiotensin II (Ang II). In addition, the implication of Sirtuin1 (Sirt1) a histone deacetylase class III family in Ang II-induced hypertension has also been shown. We recently demonstrated that Ang II increased the expression of Sirt1 in aortic VSMC that contributed to the overexpression of Giα proteins. However, whether Sirt1 is overexpressed in VSMC from SHR and is linked to the enhanced expression of Giα proteins and hyperproliferation remains unexplored. METHOD AND RESULTS: In the present study, we show that Sirt1 is upregulated in VSMC from SHR and this upregulation was attenuated by AT1 receptor antagonist losartan. In addition, the inhibition or knockdown of Sirt1 by specific inhibitors EX 527 and NAM and/or siRNA attenuated the enhanced expression of Giα proteins, cell cycle proteins and hyperproliferation of VSMC from SHR. Furthermore, the enhanced levels of reactive oxygen species (ROS), hydrogen peroxide and NADPH oxidase subunits NOX2 and p47phox, increased phosphorylation of EGFR, ERK1/2 and AKT displayed by VSMC from SHR were also attenuated by knocking down of Sirt1 by siRNA. CONCLUSION: In summary, our results demonstrate that Sirt1 is overexpressed in VSMC from SHR which through augmenting oxidative stress contributes to the enhanced expression of Giα proteins, cell cycle proteins and resultant hyperproliferation of VSMC.