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1.
Artigo em Inglês | MEDLINE | ID: mdl-34886001

RESUMO

Diabetes and chronic kidney disease (CKD) are a major public health burden in low- and middle-income countries. This study aimed to explore factors associated with CKD in patients with type 2 diabetes (T2D) in Bangladesh. A cross-sectional study was conducted among 315 adults with T2D presenting at the outpatient department of Bangladesh Institute of Health Sciences (BIHS) hospital between July 2013 to December 2013. CKD was diagnosed based on the estimated glomerular filtration rate using the 'Modification of Diet in Renal Disease' equations and the presence of albuminuria estimated by the albumin-to-creatinine ratio. Multivariate logistic regression analysis was used to determine the factors associated with CKD. The overall prevalence of CKD among patients with T2D was 21.3%. In the unadjusted model, factors associated with CKD included age 40-49 years (OR: 5.7, 95% CI: 1.3-25.4), age 50-59 years (7.0, 1.6-39), age ≥60 years (7.6, 1.7-34), being female (2.2, 1.2-3.8), being hypertensive (1.9, 1.1-3.5), and household income between 10,001 and 20,000 Bangladeshi taka, BDT (2.9, 1.0-8.2) compared with income ≤10,000 BDT. However, after adjustment of other covariates, only the duration of hypertension and household income (10,001-20,000 BDT) remained statistically significant. There is a need to implement policies and programs for early detection and management of hypertension and CKD in T2D patients in Bangladesh.

2.
Nat Genet ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34837083

RESUMO

Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in 39,688 individuals, identifying 82 loci associated with ascending and 47 with descending thoracic aortic diameter, of which 14 loci overlapped. Transcriptome-wide analyses, rare-variant burden tests and human aortic single nucleus RNA sequencing prioritized genes including SVIL, which was strongly associated with descending aortic diameter. A polygenic score for ascending aortic diameter was associated with thoracic aortic aneurysm in 385,621 UK Biobank participants (hazard ratio = 1.43 per s.d., confidence interval 1.32-1.54, P = 3.3 × 10-20). Our results illustrate the potential for rapidly defining quantitative traits with deep learning, an approach that can be broadly applied to biomedical images.

3.
Curr Protoc ; 1(11): e291, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34748284

RESUMO

Genome editing of primary human cells with CRISPR-Cas9 is a powerful tool to study gene function. For many cell types, there are efficient protocols for editing with optimized plasmids for Cas9 and sgRNA expression. Vascular cells, however, remain refractory to plasmid-based delivery of CRISPR machinery for in vitro genome editing due to low transfection efficiency, poor expression of the Cas9 machinery, and toxic effects of the selection antibiotics. Here, we describe a method for high-efficiency editing of primary human vascular cells in vitro using nucleofection for direct delivery of sgRNA:Cas9-NLS ribonucleoprotein complexes. This method is more rapid and its high editing efficiency eliminates the need for additional selection steps. The edited cells can be employed in diverse applications, such as gene expression measurement or functional assays to assess various genetic perturbation effects in vitro. This method proves effective in vascular cells that are refractory to standard genome manipulation techniques using viral plasmid delivery. We anticipate that this technique will be applied to other non-vascular cell types that face similar barriers to efficient genome editing. © 2021 Wiley Periodicals LLC. Basic Protocol: CRISPR-Cas9 genome editing of primary human vascular cells in vitro.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Sistemas CRISPR-Cas/genética , Expressão Gênica , Humanos , Plasmídeos , Transfecção
4.
Artigo em Inglês | MEDLINE | ID: mdl-34757583

RESUMO

INTRODUCTION: Bangladesh has experienced a rising trend in hypertension in recent years and women are suffering from this non-communicable disease more than men. About one-fifth of the adult population is suffering from hypertension and almost three-fifth of them are undiagnosed. AIM: This study aims to assess the prevalence and determinants of undiagnosed hypertension and to examine the extent of socioeconomic inequalities in undiagnosed hypertension among adult Bangladeshi population (≥ 18 years). METHODS: This study used nationally representative Bangladesh Demographic and Health Survey 2017-18 data. Undiagnosed hypertension was defined as having systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg and was never told by the health professionals to lower/control blood pressure. Multiple logistic regression analysis was performed to assess factors associated with undiagnosed hypertension. Further, socioeconomic inequalities in the prevalence of undiagnosed hypertension were estimated using Concentration Index. RESULTS: Out of total 3196 hypertensive adults, half (50.1%) were undiagnosed. In the adjusted model, older age, overweight/obesity, female gender, richest wealth quintiles had lower odds of being undiagnosed. Overall concentration index showed that poor patients were disproportionately affected by undiagnosed hypertension (Concentration Index: - 0.103, Standard Error (SE) of Concentration Index: 0.024; P value < 0.001). The poor(Q1)-to-rich(Q5) ratio of 1.3 also demonstrates that poorest hypertensive Bangladeshi adults have higher prevalence of undiagnosed hypertension than their richest counterparts. CONCLUSION: Awareness building program should be targeted towards adults belong to poor wealth quintiles for checking blood pressure regularly. Hypertension should be diagnosed and treated to prevent further complications.

5.
Implement Sci Commun ; 2(1): 115, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34625121

RESUMO

BACKGROUND: Kangaroo mother care (KMC) is a proven low-cost intervention to prevent neonatal mortality of pre-term and low birth weight babies and is very relevant to Bangladesh. KMC provides thermal regulation and thus directly avert neonatal mortality. KMC includes early, continuous, and prolonged skin-to-skin contact between an infant and caregiver, exclusive breastfeeding, early discharge from the hospital, and post-discharge follow-up. The purpose of this study was to investigate the fidelity of this intervention's implementation according to national guidelines across all tiers of government (public) health facilities of Bangladesh. METHODS: We adopted a triangulation mixed-methods approach of both quantitative and qualitative components in this research to support and explain the information obtained from quantitative observation with the help of qualitative interviews on the fidelity of KMC practice. We used an observation checklist to find the fidelity of KMC practice and used semi-structured guidelines to explain and understand the moderators of fidelity through key informant interviews and in-depth interviews. We undertook eight facility visits in four districts, observed twenty-three neonates and their caregivers during KMC practice at those facilities, and conducted twenty-seven key informant interviews with facility managers, health care providers, and five in-depth interviews with caregivers. Extracted information was triangulated and arranged under the themes of the fidelity framework. RESULTS: Despite being a low-cost intervention, findings exhibit some adherence to the national guideline with several gaps in practice. Leadership played a critical role in ensuring the KMC practice. Specific components of KMC practice, like duration, nutrition maintenance, discharge criteria, and follow-up, were not consistent as recommended. Infrastructure, human resources, developmental partner support, and the demand-side and supply-side responsiveness played a critical role in enacting this human-centric approach's fidelity. The observed interruption found in the implementation process posed threats to achieve the intended outcome as these caused violations of the basic principles of KMC. CONCLUSIONS: The study findings will help find ways to effectively deliver this intervention so that fidelity of practice is maintained, enhancing KMC services' quality and advocating towards the successful scale-up of this program.

6.
Circ Genom Precis Med ; 14(5): e003399, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34592835

RESUMO

BACKGROUND: Corin is a protease expressed in cardiomyocytes that plays a key role in salt handling and intravascular volume homeostasis via activation of natriuretic peptides. It is unknown if Corin loss-of-function (LOF) is causally associated with risk of coronary artery disease (CAD). METHODS: We analyzed all coding CORIN variants in an Italian case-control study of CAD. We functionally tested all 64 rare missense mutations in Western Blot and Mass Spectroscopy assays for proatrial natriuretic peptide cleavage. An expanded rare variant association analysis for Corin LOF mutations was conducted in whole exome sequencing data from 37 799 CAD cases and 212 184 controls. RESULTS: We observed LOF variants in CORIN in 8 of 1803 (0.4%) CAD cases versus 0 of 1725 controls (P, 0.007). Of 64 rare missense variants profiled, 21 (33%) demonstrated <30% of wild-type activity and were deemed damaging in the 2 functional assays for Corin activity. In a rare variant association study that aggregated rare LOF and functionally validated damaging missense variants from the Italian study, we observed no association with CAD-21 of 1803 CAD cases versus 12 of 1725 controls with adjusted odds ratio of 1.61 ([95% CI, 0.79-3.29]; P=0.17). In the expanded sequencing dataset, there was no relationship between rare LOF variants with CAD was also observed (odds ratio, 1.15 [95% CI, 0.89-1.49]; P=0.30). Consistent with the genetic analysis, we observed no relationship between circulating Corin concentrations with incident CAD events among 4744 participants of a prospective cohort study-sex-stratified hazard ratio per SD increment of 0.96 ([95% CI, 0.87-1.07], P=0.48). CONCLUSIONS: Functional testing of missense mutations improved the accuracy of rare variant association analysis. Despite compelling pathophysiology and a preliminary observation suggesting association, we observed no relationship between rare damaging variants in CORIN or circulating Corin concentrations with risk of CAD.

7.
Nucl Med Commun ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34678831

RESUMO

OBJECTIVE: Treatment of chondrosarcomas is grade based; intralesional curettage for grade 1 and resection for grade 2 or more. Currently used methods to determine grades before surgery are not highly accurate and create a dilemma for the surgeon. We have used a PET-CT combined with imaging to answer the following study questions: (1) Does SUVmax value from an 18F-FDG PET/CT correlate with the grade of chondrosarcoma? (2) Can a cutoff SUVmax value be used to differentiate between various grades of chondroid neoplasms with sufficient sensitivity and specificity? (3) Does SUVmax guide the clinician and add value to radiology in offering histologic grade-dependent management? METHODS: SUVmax values of patients with suspected chondrosarcoma were retrospectively correlated with the final histology grade for the operated patients. Radiologic parameters and radiology aggressiveness scores (RAS) were reevaluated and tabulated. RESULTS: Totally 104 patients with chondroid tumors underwent 18F-FDG PET/CT assessment. In total 73 had tissue diagnosis available as a pretreatment investigation. Spearman correlation indicated that there was a significant positive association between SUVmax and the final histology grading of chondroid tumors (correlation coefficient = 0.743; P < 0.01). SUVmax cutoff of 13.3 was 88.9% sensitive and 100% specific for diagnosing dedifferentiated chondrosarcomas. An RAS cutoff value of 3 or more could diagnose IHGCS with a sensitivity of 80.7% and specificity of 93.75%. Adding an SUVmax cutoff of 3.6 improves the sensitivity to 89.5%. CONCLUSION: SUVmax value can reliably help diagnose dedifferentiated chondrosarcoma and when added to the radiology score can improve the accuracy of grading chondrosarcoma.

8.
Endocrinol Diabetes Metab ; 4(4): e00285, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34505412

RESUMO

INTRODUCTION: The prevalence of gestational diabetes mellitus (GDM) is increasing in developing countries including the South Asian Nations. The current study aimed to examine the association of GDM with adverse pregnancy outcomes from foetal and maternal perspectives in South Asia. METHODS: A systematic review was conducted including primary studies published since January 2020 from South Asian countries. Following electronic databases were searched to locate the articles: MEDLINE, EMBASE and EMCARE. Data were extracted using a customized extraction tool and methodological quality of the included studies was assessed using modified Effective Public Health Practice Project (EPHPP) quality assessment tool. Narrative synthesis was performed as statistical pooling was not possible due to the heterogeneous nature of the studies. RESULTS: Eight studies were included in the review. Overall, the review found a positive correlation between GDM and adverse foetal outcomes such as macrosomia, neonatal hyperglycaemia, intrauterine growth retardation (IUGR), stillbirths and low birthweight (LBW), but the findings were not conclusive. GDM was also positively associated with preeclampsia but the association between GDM and C-section delivery was not conclusive. CONCLUSION: Policymakers, public health practitioners and researchers in South Asia should take in to account the link between GDM and adverse pregnancy outcomes while designing interventions to promote maternal health in South Asia. Researchers should focus on conducting longitudinal studies in future to clearly understand the epidemiology and pathobiology of this issue.

9.
Clin Hypertens ; 27(1): 17, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465390

RESUMO

BACKGROUND: The prevalence of hypertension is increasing in Bangladesh, however, few recent studies investigated the proportion of people and factors associated with prevalence, awareness, and control of this condition in this country. This study investigated these among Bangladeshi adults. METHODS: Using Bangladesh Demographic and Health Survey 2017-18 data, a cross-sectional study was conducted. Multilevel logistic regression analysis was employed after descriptive analysis and prevalence estimation. RESULTS: Among 12,926 persons (mean age: 40 years, 57% women), the prevalence of hypertension was 27.4% (n = 3551), it was 28.4 and 26.2% among females and males, respectively. Among hypertensive people, about 42.4% (n = 1508) people were aware of having it, 48.7% among females and 33.5% among males. Of the 1313 people who were taking antihypertensive medication, only 33.8% (n = 443) had controlled hypertension, 34.7 and 31.7% among females and males, respectively. Among the studied factors associated with hypertension, people with older age, female gender, overweight/obesity, diabetes, richer wealth quintiles, and residence in some administrative divisions had higher odds of hypertension (p < 0.05). However, the odds of awareness was lower among younger people, males, and people without overweight/obesity, diabetes, or richer wealth quintiles. Odds of controlled hypertension was also lower among people with older age and higher among college-educated people. CONCLUSION: This study identified several important factors associated with prevalence, awareness, and control of hypertension. It is important to address these factors with nationwide prevention and control programs.

11.
Genet Med ; 23(12): 2352-2359, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34446925

RESUMO

PURPOSE: Recent reports of individuals with cytoplasmic transfer RNA (tRNA) synthetase-related disorders have identified cases with phenotypic variability from the index presentations. We sought to assess phenotypic variability in individuals with AARS1-related disease. METHODS: A cross-sectional survey was performed on individuals with biallelic variants in AARS1. Clinical data, neuroimaging, and genetic testing results were reviewed. Alanyl tRNA synthetase (AlaRS) activity was measured in available fibroblasts. RESULTS: We identified 11 affected individuals. Two phenotypic presentations emerged, one with early infantile-onset disease resembling the index cases of AARS1-related epileptic encephalopathy with deficient myelination (n = 7). The second (n = 4) was a later-onset disorder, where disease onset occurred after the first year of life and was characterized on neuroimaging by a progressive posterior predominant leukoencephalopathy evolving to include the frontal white matter. AlaRS activity was significantly reduced in five affected individuals with both early infantile-onset and late-onset phenotypes. CONCLUSION: We suggest that variants in AARS1 result in a broader clinical spectrum than previously appreciated. The predominant form results in early infantile-onset disease with epileptic encephalopathy and deficient myelination. However, a subgroup of affected individuals manifests with late-onset disease and similarly rapid progressive clinical decline. Longitudinal imaging and clinical follow-up will be valuable in understanding factors affecting disease progression and outcome.

12.
BMJ Open ; 11(8): e045547, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380718

RESUMO

OBJECTIVE: This study aimed to assess the possible relationship between television viewing and overweight and obesity among Timorese women of reproductive age. METHODS: This cross-sectional study analysed the Timor-Leste Demographic and Health Survey 2016 dataset. A weighted sample of 11 398 Timorese women aged 15-49 years was chosen using a two-stage stratified random sampling technique. Asian criteria-based body mass index (BMI) cut-offs were used to define overweight (BMI 23.0 to <27.5 kg/m2) and obesity (BMI ≥27.5 kg/m2). Frequency of TV viewing was categorised into three groups: (1) not at all, (2) less than once a week and (3) at least once a week. Multilevel ordered logistic regression was performed to identify the correlates of overweight and obesity. Both crude and adjusted odds ratios (AOR) along with a 95% CI were calculated to show the strength of association. RESULTS: Among 11 398 respondents, 19.4% were overweight or obese (overweight: 15.7% and obese: 3.8%). Although about half of the respondents reportedly did not watch TV at all, just over two-thirds watched TV at least once a week. Women who watched TV at least once a week were found to have 1.3 times the odds of being overweight or obese compared with those who never watched TV (AOR: 1.3, 95% CI: 1.1 to 1.5; p<0.001). However, when stratified by settlement type, the statistical significance stood for the rural women only (AOR: 1.5, 95% CI: 1.2 to 1.8; p<0.001), after adjusting for the covariates. CONCLUSION: Watching TV at least once a week was found to be a significant correlate of overweight and obesity in rural Timorese women of reproductive age. Further studies need to be undertaken to assess physical activity, sedentary and dietary patterns to clarify the possible mechanism through which TV viewing may influence BMI in those groups.


Assuntos
Sobrepeso , Televisão , Índice de Massa Corporal , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Prevalência , Fatores de Risco , Timor-Leste
13.
Antioxidants (Basel) ; 10(8)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34439506

RESUMO

Both pro- and antiatherosclerotic effects have been ascribed to dietary peroxidized lipids. Confusion on the role of peroxidized lipids in atherosclerotic cardiovascular disease is punctuated by a lack of understanding regarding the metabolic fate and potential physiological effects of dietary peroxidized lipids and their decomposition products. This study sought to determine the metabolic fate and physiological ramifications of 13-hydroperoxyoctadecadienoic acid (13-HPODE) and 13-HODE (13-hydroxyoctadecadienoic acid) supplementation in intestinal and hepatic cell lines, as well as any effects resulting from 13-HPODE or 13-HODE degradation products. In the presence of Caco-2 cells, 13-HPODE was rapidly reduced to 13-HODE. Upon entering the cell, 13-HODE appears to undergo decomposition, followed by esterification. Moreover, 13-HPODE undergoes autodecomposition to produce aldehydes such as 9-oxononanoic acid (9-ONA). Results indicate that 9-ONA was oxidized to azelaic acid (AzA) rapidly in cell culture media, but AzA was poorly absorbed by intestinal cells and remained detectable in cell culture media for up to 18 h. An increased apolipoprotein A1 (ApoA1) secretion was observed in Caco-2 cells in the presence of 13-HPODE, 9-ONA, and AzA, whereas such induction was not observed in HepG2 cells. However, 13-HPODE treatments suppressed paraoxonase 1 (PON1) activity, suggesting the induction of ApoA1 secretion by 13-HPODE may not represent functional high-density lipoprotein (HDL) capable of reducing oxidative stress. Alternatively, AzA induced both ApoA1 secretion and PON1 activity while suppressing ApoB secretion in differentiated Caco-2 cells but not in HepG2. These results suggest oxidation of 9-ONA to AzA might be an important phenomenon, resulting in the accumulation of potentially beneficial dietary peroxidized lipid-derived aldehydes.

14.
Chest ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34298007

RESUMO

BACKGROUND: Traditional hookah smoking has grown quickly to become a global tobacco epidemic. More recently, electronic hookahs (e-hookahs)-vaped through traditional water pipes-were introduced as healthier alternatives to combustible hookah. With combustible tobacco smoking, oxidative stress, inflammation, and vascular stiffness are key components in the development and progression of atherosclerosis. The comparable effects of hookah are unknown. RESEARCH QUESTION: What is the differential acute effect of e-hookah vaping vs combustible hookah smoking on oxidation, inflammation, and arterial stiffness? STUDY DESIGN AND METHODS: In a randomized crossover design study, among a cohort of 17 healthy young adult chronic hookah smokers, we investigated the effect of e-hookah vaping and hookah smoking on measures of conduit arterial stiffness, including carotid-femoral pulse wave velocity (PWV), augmentation index-corrected for heart rate before and after a 30-min exposure session. We assessed a panel of circulating biomarkers indicative of inflammation and oxidants and measured plasma nicotine and exhaled carbon monoxide (CO) levels before and after the sessions. RESULTS: e-Hookah vaping tended to lead to a larger acute increase in PWV than hookah smoking (mean ± SE: e-hookah, +0.74 ± 0.12 m/s; combustible hookah, +0.57 ± 0.14 m/s [P < .05 for both]), indicative of large artery stiffening. Compared with baseline, only e-hookah vaping induced an acute increase in augmentation index (e-hookah, +5.58 ± 1.54% [P = .004]; combustible hookah, +2.87 ± 2.12% [P = not significant]). These vascular changes were accompanied by elevation of the proinflammatory biomarkers high-sensitivity C-reactive protein, fibrinogen, and tumor necrosis factor α after vaping (all P < .05). No changes in biomarkers of inflammation and oxidants were observed after smoking. Compared with baseline, exhaled CO levels were higher after smoking than after vaping (+36.81 ± 6.70 parts per million vs -0.38 ± 0.22 parts per million; P < .001), whereas plasma nicotine concentrations were comparable (+6.14 ± 1.03 ng/mL vs +5.24 ± 0.96 ng/mL; P = .478). INTERPRETATION: Although advertised to be "safe," flavored e-hookah vaping exerts injurious effects on the vasculature that are, at least in part, mediated by inflammation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03690427; URL: www.clinicaltrials.gov.

15.
Indian J Plast Surg ; 54(2): 114-117, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34305339

RESUMO

Background Authors describe a novel procedure in a group of patients for prepuce reconstruction, ensuring complete glans penis coverage who had either been circumcised in childhood or had congenitally short prepuce. Methods Case records of all cases done by the novel method which involved penile degloving and maintenance of neoprepuce, with the help of de-epithelization of glans penis and a few key sutures performed over the period from January 2010 to December 2019 were reviewed retrospectively. A total of 46 patients, 32 had congenitally short prepuce and 14 had previous circumcision. Results All the patients had complete glans penis coverage. None of the patients had complications like urinary infection, meatal stenosis, collection in neoprepucial sac, balanitis, or posthitis. The mean followup was 23.24 months in 37 patients. Nine lost to followup. Conclusions The procedure is simple, gives reliable results, and is customized to the needs of the patients. It does not interfere with penile erections.

16.
BMJ Open ; 11(7): e050493, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330863

RESUMO

AIMS: Overweight and obesity (OWOB) is a modifiable risk factor for both hypertension and diabetes. However, the association between OWOB and diabetes among Bangladeshi adults and how hypertension may mediate this relationship are not well explored. This study aimed to examine (1) whether OWOB is independently associated with diabetes among Bangladeshi adults, (2) whether this association is mediated by hypertension, and (3) the effect modification by wealth status and place of residence in the relationships. RESEARCH DESIGN AND METHODS: We used data of 9305 adults aged ≥18 years from the most recent nationally representative cross-sectional study of Bangladesh Demographic and Health Survey 2017-2018. Design-based logistic regression was used to assess the association between OWOB and diabetes, and counterfactual framework-based weighting approach was used to evaluate the mediation effect of hypertension in the OWOB-diabetes relationship. We used stratified analyses for the effect modifications. RESULTS: The prevalence of OWOB, diabetes and hypertension was 48.5%, 11.7% and 30.3%, respectively. We observed a significant association between OWOB and diabetes and a mediating role of hypertension in the OWOB-diabetes association. The odds of diabetes was 51% higher among adults with OWOB than those without OWOB (adjusted OR: 1.51, 95% CI 1.29 to 1.77). We observed that 18.64% (95% CI 9.84% to 34.07%) of the total effect of OWOB on the higher odds of diabetes was mediated through hypertension, and the mediation effect was higher among adults from non-poor households and from both rural and urban areas. CONCLUSIONS: Adult OWOB status is independently associated with diabetes in Bangladesh, and hypertension mediates this association. Therefore, prevention policies should target adults with both OWOB and hypertension, particularly those from non-poor households and from both rural and urban areas, to reduce the growing burden of diabetes and its associated risk.


Assuntos
Diabetes Mellitus , Hipertensão , Adolescente , Adulto , Bangladesh/epidemiologia , Estudos Transversais , Diabetes Mellitus/epidemiologia , Humanos , Hipertensão/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Prevalência , Fatores de Risco
17.
Environ Sci Pollut Res Int ; 28(47): 67814-67821, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34268688

RESUMO

Household air pollution from cooking fuel may have adverse health effects, particularly among women from countries like Bangladesh, where women participate in most household cooking activities. However, little is known about how cooking fuel influences adult women's blood pressure (BP) status in Bangladesh. This study assessed the association between household cooking fuel and women's BP in Bangladesh. Data of 6543 women (aged ≥18 years) from the latest nationally representative Bangladesh Demographic and health survey 2017-18 were used in this study. This survey collected data on various variables, including women's BP and cooking fuel. Multivariable regression models were used for this evaluation. About 82.3% of women were living in households using solid cooking fuel. Women's average systolic BP (SBP) and diastolic BP (DBP) were 121.5 mmHg and 80.7 mmHg, respectively, and 25% had elevated BP. Women residing in a household using solid fuel had significantly higher SBP (ß 3.76 mmHg, 95 confidence interval (CI) 2.00, 5.51) and DBP (ß 1.17 mmHg, 95% CI 0.17, 2.18) relative to women from households using clean fuel. The odds of elevated BP was 58% higher (adjusted odds ratio, 1.58, 95% CI 1.19, 2.11) among women residing in households using solid fuels compared to their counterparts. Usage of solid cooking fuel was predominantly high and negatively impacted women's BP status in Bangladesh. In addition to other lifestyle change interventions, improved cooking facilities and clean cooking fuel provision and monitoring could be important initiatives to reduce the burden of elevated BP among women.

19.
Sci Signal ; 14(686)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103421

RESUMO

Cancer cells have differential metabolic dependencies compared to their nonmalignant counterparts. However, few metabolism-targeting compounds have been successful in clinical trials. Here, we investigated the metabolic vulnerabilities of triple-negative breast cancer (TNBC), particularly those metabolic perturbations that increased mitochondrial apoptotic priming and sensitivity to BH3 mimetics (drugs that antagonize antiapoptotic proteins). We used high-throughput dynamic BH3 profiling (HT-DBP) to screen a library of metabolism-perturbing small molecules, which revealed inhibitors of the enzyme nicotinamide phosphoribosyltransferase (NAMPT) as top candidates. In some TNBC cells but not in nonmalignant cells, NAMPT inhibitors increased overall apoptotic priming and induced dependencies on specific antiapoptotic BCL-2 family members. Treatment of TNBC cells with NAMPT inhibitors sensitized them to subsequent treatment with BH3 mimetics. The combination of a NAMPT inhibitor (FK866) and an MCL-1 antagonist (S63845) reduced tumor growth in a TNBC patient-derived xenograft model in vivo. We found that NAMPT inhibition reduced NAD+ concentrations below a critical threshold that resulted in depletion of adenine, which was the metabolic trigger that primed TNBC cells for apoptosis. These findings demonstrate a close interaction between metabolic and mitochondrial apoptotic signaling pathways and reveal that exploitation of a tumor-specific metabolic vulnerability can sensitize some TNBC to BH3 mimetics.

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