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We assessed whether personal exposure to household air pollution [PM 2.5 and black carbon (BC)] is associated with lung functions (FEV 1 , FVC, and their ratio) in non-smoking adults in rural Bangladesh. We measured personal exposure to PM 2.5 using gravimetric analysis of PM 2.5 mass and BC by reflectance measurement between April 2016 and June 2019. The average 24-hour PM 2.5 and BC concentration was 141.0μgm -3 and 13.8μgm -3 for females, and 91.7 μgm -3 and 10.1 μgm -3 for males, respectively. A 1 μgm -3 increase in PM 2.5 resulted in a 0.02 ml reduction in FEV 1 , 0.43 ml reduction in FVC, and 0.004% reduction in FEV1/FVC. We also found a similar inverse relationship between BC and lung functions (9.6 ml decrease in FEV 1 and 18.5 ml decrease in FVC per 1μgm -3 increase in BC). A higher proportion of non-smoking biomass fuel users (50.1% of the females and 46.7% of the males) had restrictive patterns of lung function abnormalities, which need further exploration.

Household air pollution (HAP) arising from combustion of biomass fuel (BMF) is a leading cause of morbidity and mortality in low-income countries. Air pollution may stimulate pro-inflammatory responses by activating diverse immune cells and cyto/chemokine expression, thereby contributing to diseases. We aimed to study cellular immune responses among women chronically exposed to HAP through use of BMF for domestic cooking. Among 200 healthy, non-smoking women in rural Bangladesh, we assessed exposure to HAP by measuring particulate matter 2.5 (PM 2.5 ), black carbon (BC) and carbon monoxide (CO), through use of personal monitors RTI MicroPEM™ and Lascar CO logger respectively, for 48 h. Blood samples were collected following HAP exposure assessment and were analyzed for immunoprofiling by flow cytometry, plasma IgE by immunoassay analyzer and cyto/chemokine response from monocyte-derived-macrophages (MDM) and -dendritic cells (MDDC) by multiplex immunoassay. In multivariate linear regression model, a doubling of PM 2.5 was associated with small increments in immature/early B cells (CD19 + CD38 + ) and plasmablasts (CD19 + CD38 + CD27 + ). In contrast, a doubling of CO was associated with 1.20% reduction in CD19 + B lymphocytes (95% confidence interval (CI) = -2.36, -0.01). A doubling of PM 2.5 and BC each was associated with 3.12% (95%CI = -5.85, -0.38) and 4.07% (95%CI = -7.96, -0.17) decrements in memory B cells (CD19 + CD27 + ), respectively. Exposure to CO was associated with increased plasma IgE levels (beta(β) = 240.4, 95%CI = 3.06, 477.8). PM 2.5 and CO exposure was associated with increased MDM production of CXCL10 (β = 12287, 95%CI = 1038, 23536) and CCL5 (β = 835.7, 95%CI = 95.5, 1576), respectively. Conversely, BC exposure was associated with reduction in MDDC-produced CCL5 (β = -3583, 95%CI = -6358, -807.8) and TNF-α (β = -15521, 95%CI = -28968, -2074). Our findings suggest that chronic HAP exposure through BMF use adversely affects proportions of B lymphocytes, particularly memory B cells, plasma IgE levels and functions of antigen presenting cells in rural women., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

More than one third of world's population use biomass fuel for cooking that has been linked to an array of adverse health hazards including cardiovascular mortality and morbidity. As part of Bangladesh Global Environmental and Occupational Health (GEO Health) project, we assessed whether household air pollution (HAP) was associated with dysfunction in microvascular circulation (measured by reactive hyperemia index [RHI])., Methods: We measured exposure to HAP (particulate matter [PM2.5], carbon monoxide [CO], and black carbon [BC]) for 48 hours of 200 healthy nonsmoker adult females who used biomass fuel for cooking. Exposure to PM2.5 and BC were measured using personal monitor, RTI MicroPEM (RTI International, NC) with an internal filter that had been both pre- and post-weighed to capture the deposited pollutants concentration. Lascar CO logger was used to measure CO. Endothelial function was measured by forearm blood flow dilatation response to brachial artery occlusion using RHI based on peripheral artery tonometry. A low RHI score (<1.67) indicates impaired endothelial function., Results: Average 48 hours personal exposure to PM2.5 and BC were 144.15 μg/m 3 (SD 61.26) and 6.35 μg/m 3 (SD 2.18), respectively. Interquartile range for CO was 0.73 ppm (0.62-1.35 ppm). Mean logarithm of RHI (LnRHI) was 0.57 in current data. No statistically significant association was observed for LnRHI with PM2.5 (odds ratio [OR] = 0.97; 95% confidence interval [CI] = 0.92, 1.01; P = 0.16), BC (OR = 0.85; 95% CI = 0.72, 1.01; P = 0.07), and CO (OR = 0.89; 95% CI = 0.64, 1.25; P = 0.53) after adjusting for potential covariates., Conclusions: In conclusion, HAP was not associated with endothelial dysfunction among nonsmoking females in rural Bangladesh who used biomass fuel for cooking for years., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report. The results reported herein correspond to specific aims of grant U01TW010120 and U2R TW010122 to investigators (H.A. and M.Y.) from Fogarty International Center of the National Institutes of Health (NIH). This work was also supported by grant R24 ES028532 to investigator (H.A.) from NIH. Data and code can be obtained from corresponding author via email. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Sponsorships or competing interests that may be relevant to content are disclosed at the end of the article., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Introduction: Hypotonia is a common presentation that child neurologists encounter daily. The hypotonic neonate represents a diagnostic challenge as a lesion at any level in the neuro-axis may cause hypotonia. In this paper, we study the diagnostic yield of investigations commonly used as part of a hypotonia work-up., Methods: A 12-year retrospective cohort study was conducted at a tertiary care center in Saudi Arabia from 2007 to 2018. Final diagnoses, clinical presentations, laboratory tests, imaging and genetic studies were reviewed from the patient's electronic health records., Results: 164 patients were identified as fitting the inclusion criteria of the study. 50% had central hypotonia, 18% peripheral hypotonia and 32% mixed hypotonia. Molecular testing was performed for 82% (74) of patients. 65 Microarray studies were done; 27% abnormal and 9% diagnostic. 55 gene panels were done; 58% abnormal and 30% diagnostic. 53 single-gene tests were done; 57% abnormal and 40% diagnostic. 61 whole exome sequences were done; 72% positive and 59% diagnostic. 126 MRIs were reviewed; 56% abnormal and 33% contributed to the diagnosis., Conclusion: Molecular genetic testing is our recommended next step in the diagnosis of patients with hypotonia after careful phenotyping. Neuroimaging is helpful to guide further costly workup of patients with hypotonia., Competing Interests: None., (© 2020 The Authors.)

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10 -8 , in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.

Background: Millions of coastal inhabitants in Southeast Asia have been experiencing increasing sodium concentrations in their drinking-water sources, likely partially due to climate change. High (dietary) sodium intake has convincingly been proven to increase risk of hypertension; it remains unknown, however, whether consumption of sodium in drinking water could have similar effects on health., Objectives: We present the results of a cohort study in which we assessed the effects of drinking-water sodium (DWS) on blood pressure (BP) in coastal populations in Bangladesh., Methods: DWS, BP, and information on personal, lifestyle, and environmental factors were collected from 581 participants. We used generalized linear latent and mixed methods to model the effects of DWS on BP and assessed the associations between changes in DWS and BP when participants experienced changing sodium levels in water, switched from "conventional" ponds or tube wells to alternatives [managed aquifer recharge (MAR) and rainwater harvesting] that aimed to reduce sodium levels, or experienced a combination of these changes., Results: DWS concentrations were highly associated with BP after adjustments for confounding factors. Furthermore, for each 100 mg/L reduction in sodium in drinking water, systolic/diastolic BP was lower on average by 0.95/0.57 mmHg, and odds of hypertension were lower by 14%. However, MAR did not consistently lower sodium levels., Conclusions: DWS is an important source of daily sodium intake in salinity-affected areas and is a risk factor for hypertension. Considering the likely increasing trend in coastal salinity, prompt action is required. Because MAR showed variable effects, alternative technologies for providing reliable, safe, low-sodium fresh water should be developed alongside improvements in MAR and evaluated in "real-life" salinity-affected settings. https://doi.org/10.1289/EHP659.

Aims Darapladib, a potent inhibitor of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), has not reduced risk of cardiovascular disease outcomes in recent randomized trials. We aimed to test whether Lp-PLA 2 enzyme activity is causally relevant to coronary heart disease. Methods In 72,657 patients with coronary heart disease and 110,218 controls in 23 epidemiological studies, we genotyped five functional variants: four rare loss-of-function mutations (c.109+2T > C (rs142974898), Arg82His (rs144983904), Val279Phe (rs76863441), Gln287Ter (rs140020965)) and one common modest-impact variant (Val379Ala (rs1051931)) in PLA2G7, the gene encoding Lp-PLA 2 . We supplemented de-novo genotyping with information on a further 45,823 coronary heart disease patients and 88,680 controls in publicly available databases and other previous studies. We conducted a systematic review of randomized trials to compare effects of darapladib treatment on soluble Lp-PLA 2 activity, conventional cardiovascular risk factors, and coronary heart disease risk with corresponding effects of Lp-PLA 2 -lowering alleles. Results Lp-PLA 2 activity was decreased by 64% ( p = 2.4 × 10 -25 ) with carriage of any of the four loss-of-function variants, by 45% ( p < 10 -300 ) for every allele inherited at Val279Phe, and by 2.7% ( p = 1.9 × 10 -12 ) for every allele inherited at Val379Ala. Darapladib 160 mg once-daily reduced Lp-PLA 2 activity by 65% ( p < 10 -300 ). Causal risk ratios for coronary heart disease per 65% lower Lp-PLA 2 activity were: 0.95 (0.88-1.03) with Val279Phe; 0.92 (0.74-1.16) with carriage of any loss-of-function variant; 1.01 (0.68-1.51) with Val379Ala; and 0.95 (0.89-1.02) with darapladib treatment. Conclusions In a large-scale human genetic study, none of a series of Lp-PLA 2 -lowering alleles was related to coronary heart disease risk, suggesting that Lp-PLA 2 is unlikely to be a causal risk factor.

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Objectives: Famine exposure in utero can 'programme' an individual towards type 2 diabetes and obesity in later life. We sought to identify, (1) whether Bangladeshis exposed to famine during developmental life are programmed towards diabetes and obesity, (2) whether this programming was specific to gestational or postnatal exposure windows and (3) whether epigenetic differences were associated with famine exposure., Design: A historical cohort study was performed as part of a wider cross-sectional survey. Exposure to famine was defined through birth date and historical records and participants were selected according to: (A) exposure to famine in postnatal life, (B) exposure to famine during gestation and (C) unexposed., Setting: Matlab, a rural area in the Chittagong division of Bangladesh., Participants: Young adult men and women (n=190) recruited to a historical cohort study with a randomised subsample included in an epigenetic study (n=143)., Outcome Measures: Primary outcome measures of weight, body mass index and oral glucose tolerance tests (0 and 120 min glucose). Secondary outcome measures included DNA methylation using genome-wide and targeted analysis of metastable epialleles sensitive to maternal nutrition., Results: More young adults exposed to famine in gestation were underweight than those postnatally exposed or unexposed. In contrast, more young adults exposed to famine postnatally were overweight compared to those gestationally exposed or unexposed. Underweight adults exposed to famine in gestation in utero were hyperglycaemic following a glucose tolerance test, and those exposed postnatally had elevated fasting glucose, compared to those unexposed. Significant differences in DNA methylation at seven metastable epialleles (VTRNA2-1, PAX8, PRDM-9, near ZFP57, near BOLA, EXD3) known to vary with gestational famine exposure were identified., Conclusions: Famine exposure in developmental life programmed Bangladeshi offspring towards diabetes and obesity in adulthood but gestational and postnatal windows of exposure had variable effects on phenotype. DNA methylation differences were replicated at previously identified metastable epialleles sensitive to periconceptual famine exposure., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention., Competing Interests: Conflict of interests N. P. has received financial support from several pharmaceutical companies that manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees. S. K. has received Research Grant-Merck, Bayer, Aegerion; SAB-Catabasis, Regeneron Genetics Center, Merck, Celera; Equity-San Therapeutics, Catabasis; Consulting-Novartis, Aegerion, Bristol Myers-Squibb, Sanofi, AstraZeneca, Alnylam. P. Sever has received research awards from Pfizer Inc. A. Malarstig and M. Uria-Nickelsen are full time employees of Pfizer. D. Reily and M. Hoek are full time employees of Merck and co Inc. M.J. Caulfield is Chief Scientist for Genomics England a UK Government company. The authors declare no competing financial interest.

Socioeconomic status (SES) is a risk factor for cardiovascular disease (CVD) and either low or high heart rate variability (HRV) at rest has been shown to predict cardiovascular morbidity and mortality. The study investigated the extent HRV features can predict SES. Four hundred and twenty eight people were randomly selected from the commercial districts (high SES) and slum areas (low SES) within Dhaka city. Demographic, clinical, and HRV features were recorded. Of the clinical variables age, waist circumference and diastolic blood pressure (p<;0.01) were significantly different. HRV feature extraction from heart rate recordings were analyzed using Kubios software. Age corrected results showed that high frequency power (Median (IQR): 112.1 (85.6) ms 2 vs. 96.8 (97.6) ms 2 , p=0.02) and the correlation dimension (0.78 (0.82) vs. 0.51 (1.20), p<;0.0002) were significantly lower in the low SES group, whilst the high frequency peak was significantly higher (0.1500 (0.0004) Hz vs. 0.1503 (0.0066) Hz, p<;0.0001). Our results show that although the high SES group had a more sedentary behavior, the low SES group had a higher risk of cardiac arrhythmia even though they were generally younger with normal blood pressure and waist circumference.

Background: Type 2 diabetes and pre-diabetes are an increasing pandemic globally and often remain undiagnosed long after onset in low-income settings. The objective of this study is to assess the determinants and prevalence of undiagnosed diabetes and pre-diabetes among adults in Bangladesh., Methods: In an exploratory study, we performed oral glucose tolerance test on 1243 adults ≥20 years of age from urban Mirpur, Dhaka (n = 518) and rural Matlab, Chandpur (n = 725) who had never been diagnosed with diabetes or pre-diabetes. We collected data on socioeconomic, demographic, past medical history, physical activity, and measured weight, height, waist and hip circumferences, and blood pressure. Risk factors associated with undiagnosed diabetes and pre-diabetes were examined using a multiple logistic regression model., Results: Overall prevalence of diabetes and pre-diabetes was 6.6 % (95 % CI 5.3, 8.1) and 16.6 % (14.5, 18.7) respectively, with both being significantly higher in urban than rural populations (diabetes 12.2 % vs 2.6 % respectively, p < 0.000; pre-diabetes 21.2 % vs 13.2 %, p < 0.001). After adjustment the variables, urban residence (OR 2.5 [95 % CI 1.02, 5.9]), age group 40-59 y (2.9 [1.7-5.2]), ≥60 y (8.1 [2.8-23.8]), overweight (2.2 [1.3-3.9]), abdominal obesity (3.3 [1.8-6.0]) and high WHR 5.6 (2.7-11.9) were all significant predictors of diabetes. Significant predictors of pre-diabetes included age group 40-59 (1.6 [1.1-2.2]), female sex (1.5 [1.0-2.2]), abdominal obesity (1.7 [1.2-2.4]) and high WHR (1.6 [1.2-2.3])., Conclusion: Both overweight and abdominal obesity contribute to the hidden public health threat of undiagnosed diabetes and pre-diabetes. Awareness raising and screening of high risk groups combined with a tailored approach are essential for halting the epidemic of diabetes and pre-diabetes in Bangladesh.

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant)., (Copyright © 2016, American Association for the Advancement of Science.)

Background: Currently available tools for assessing high cardiovascular risk (HCR) often require measurements not available in resource-limited settings in low- and middle-income countries (LMIC). There is a need to assess HCR using a pragmatic evidence-based approach., Objectives: This study sought to report the prevalence of HCR in 10 LMIC areas in Africa, Asia, and South America and to investigate the profiles and correlates of HCR., Methods: Cross-sectional analysis using data from the National Heart, Lung, and Blood Institute-UnitedHealth Group Centers of Excellence. HCR was defined as history of heart disease/heart attack, history of stroke, older age (≥50 years for men and ≥60 for women) with history of diabetes, or older age with systolic blood pressure ≥160 mm Hg. Prevalence estimates were standardized to the World Health Organization's World Standard Population., Results: A total of 37,067 subjects ages ≥35 years were included; 53.7% were women and mean age was 53.5 ± 12.1 years. The overall age-standardized prevalence of HCR was 15.4% (95% confidence interval: 15.0% to 15.7%), ranging from 8.3% (India, Bangalore) to 23.4% (Bangladesh). Among men, the prevalence was 1.7% for the younger age group (35 to 49 years) and 29.1% for the older group (≥50); among women, 3.8% for the younger group (35 to 59 years) and 40.7% for the older group (≥60). Among the older group, measured systolic blood pressure ≥160 mm Hg (with or without other conditions) was the most common criterion for having HCR, followed by diabetes. The proportion of having met more than 1 criterion was nearly 20%. Age, education, and body mass index were significantly associated with HCR. Cross-site differences existed and were attenuated after adjusting for age, sex, education, smoking, and body mass index., Conclusions: The prevalence of HCR in 10 LMIC areas was generally high. This study provides a starting point to define targeted populations that may benefit from interventions combining both primary and secondary prevention strategies., (Copyright © 2016 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)

This article discusses the use of the sternohyoid muscle for facial reanimation. The report outlines the rationale for use, the technical aspects of flap harvest, and early clinical outcomes. The utility of the flap and its comparative attributes relative to the gracilis flap are discussed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Immunosuppressed patients have higher rates of cutaneous squamous cell carcinoma of the head and neck., Objective: This study reviews the effect of immune status on disease characteristics and treatment outcomes., Methods: Patients with cutaneous squamous cell carcinoma of the head and neck treated with surgery and postoperative radiotherapy between 2000 and 2011 were included. Immunosuppressed patients underwent prior organ transplantation or chemotherapy. Baseline variables were compared using χ(2) and unpaired t tests. Overall survival and disease-free survival were calculated using the Kaplan-Meier method., Results: In this study of 59 patients, 38 (64%) were immunocompetent and 21 (36%) were immunosuppressed. Most patients had recurrent tumors (63%) and node-positive disease (61%), which were well balanced between the groups. Poorly differentiated tumors (62% vs 21%; P = .009), lymphovascular invasion (29% vs 11%; P = .08), and extracapsular extension (57% vs 41%; P = .09) were more frequent in the immunosuppressed group. Two-year disease-free survival (45% vs 62%) and 2-year overall survival (36% vs 67%) were inferior for immunosuppressed patients., Limitations: Limitations include single institution, retrospective study with small sample size, and potential referral bias., Conclusions: Immunosuppressed patients with cutaneous squamous cell carcinoma of the head and neck more frequently present with high-risk pathologic features and inferior outcomes. Early multidisciplinary assessment and alternate management strategies merit prospective investigation., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

During recent decades, Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases. Coronary heart disease (CHD), with myocardial infarction (MI) as its main manifestation, is a major cause of death in the country. However, there is limited reliable evidence about its determinants in this population. The Bangladesh Risk of Acute Vascular Events (BRAVE) study is an epidemiological bioresource established to examine environmental, genetic, lifestyle and biochemical determinants of CHD among the Bangladeshi population. By early 2015, the ongoing BRAVE study had recruited over 5000 confirmed first-ever MI cases, and over 5000 controls "frequency-matched" by age and sex. For each participant, information has been recorded on demographic factors, lifestyle, socioeconomic, clinical, and anthropometric characteristics. A 12-lead electrocardiogram has been recorded. Biological samples have been collected and stored, including extracted DNA, plasma, serum and whole blood. Additionally, for the 3000 cases and 3000 controls initially recruited, genotyping has been done using the CardioMetabochip+ and the Exome+ arrays. The mean age (standard deviation) of MI cases is 53 (10) years, with 88 % of cases being male and 46 % aged 50 years or younger. The median interval between reported onset of symptoms and hospital admission is 5 h. Initial analyses indicate that Bangladeshis are genetically distinct from major non-South Asian ethnicities, as well as distinct from other South Asian ethnicities. The BRAVE study is well-placed to serve as a powerful resource to investigate current and future hypotheses relating to environmental, biochemical and genetic causes of CHD in an important but under-studied South Asian population.

Aims: To investigate the clinical features of patients with type 2 diabetes on oral medication and determine the complications and risk factors in these patients., Methods: A cross-sectional was conducted among 515 patients with type 2 diabetes at the outpatient clinics of Bangladesh Institute of Health Science (BIHS) hospital from September to December 2013. We collected data on socio-economic characteristics, clinical status, risk factors, complications, anthropometric measurements and blood tests. Univariate and multivariate logistic regression was performed to identify risk factors associated with diabetes complications., Results: The mean(±SD) age of the participants was 50.0(±10.1) years and 15.3% were less than 40 years. The mean HbA1c was 8.3(±2.1). Only 28.7% of the participants achieved targets for HbA1c. The overall prevalence of hypertension, obesity and dyslipidemia was 57.5%, 62.6% and 72.7%, respectively. Eye problems were the most common complication (68.9%) followed by chronic kidney diseases (21.3%) and cardiovascular diseases (11.8%). There were significant associations between the complications and age, duration of diabetes and duration of hypertension. In the multivariate analysis adjusting for other confounding variables, only systolic blood pressure was found to be significantly associated with complications [OR 0.809, 95% CI 0.666-0.981 (p-value 0.031)]., Conclusion: Results of the study confirm that even under best clinical settings a great majority Bangladeshi adults with type 2 diabetes have uncontrolled diabetes and a high prevalence of risk factors that might contribute to early development of complications. Early screening of high risk groups and proper management of diabetes is recommended to avoid early complications., (Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Rationale: There is a paucity of population-based data on COPD prevalence and its determinants in Bangladesh., Objective: To measure COPD prevalence and socioeconomic and lifestyle determinants among ≥40 years Bangladeshi adults., Methods: In a cross-sectional study, we measured lung function of 3744 randomly selected adults ≥40 years from rural and urban areas in Bangladesh, using a handheld spirometer. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as post-bronchodilator ratio of Forced Expiratory Volume in 1st second (FEV1) to Forced Vital Capacity (FVC) < 0.7. In addition, COPD was also assessed by the lower limit of normal (LLN) threshold defined as lower fifth percentile for the predicted FEV1/FVC., Results: The prevalence of COPD was 13.5% by GOLD criteria and 10.3% by LLN criteria. Prevalence of COPD was higher among rural than urban residents and in males than females. More than half of the COPD cases were stage II COPD by both criteria. Milder cases (Stages I and II) were over estimated by the GOLD fixed criteria, but more severe cases (Stages III and IV) were similarly classified. In multiple logistic regression analysis, older age, male sex, illiteracy, underweight, history of smoking (both current and former), history of asthma and solid fuel use were significant predictors of COPD., Conclusion: COPD is a highly prevalent and grossly underdiagnosed public health problem in Bangladeshi adults aged 40 years or older. Illiteracy, smoking and biomass fuel burning are modifiable determinants of COPD.

Objectives: To assess the effect of awareness and advice to seek care on blood pressure (BP) control among patients with hypertension in Bangladesh., Design: Longitudinal study., Setting: The study was carried out in icddr,b surveillance sites at rural Matlab in Chandpur district and semi-urban Kamalapur in Dhaka, Bangladesh., Participants: Randomly selected men and non-pregnant women aged 20 years or older without any acute illness or history of any vascular events such as stroke or acute myocardial infarction., Main Outcome Measure: Hypertension was defined as systolic BP (SBP) ≥140 and/or diastolic BP (DBP) ≥90 mm Hg or as self-reported hypertension under medication. We advised patients to seek care from a qualified provider and to adopt a healthy lifestyle. We compared changes in BP from baseline to follow-up at around 6 months., Results: Overall, 17.1% (n=287) of participants had hypertension at baseline with significantly higher prevalence in the semi-urban than in the rural population (23.6% vs 10.8%; p<0.001); half were unaware of their condition. At follow-up, 83% (n=204) reported a visit to any healthcare provider. In the semi-urban area, a higher proportion of patients visited medically qualified practitioners than in the rural area (76.7% vs 36.6%, p<0.000). SBP (-3.3±20.7 mm Hg; p<0.01) and DBP (-2.0±13.0 mm Hg; p<0.02) were lower at follow-up. Those who visited medically qualified practitioners had significant SBP (-3.9±22.4 mm Hg; p<0.03) and DBP (-2.7±14.1 mm Hg; p<0.02) reduction. BP reduction did not reach statistical significance among those visiting a pharmacist or their village doctors. Overall, half of the patients with hypertension achieved the BP control goal (BP<140/90 mm Hg)., Conclusions: Awareness and simple health messages increase provider visit, reduce blood pressure and improve BP control in hypertensive Bangladeshis. Longer-term follow-up is required to verify the sustainability., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Mobile phone technologies including SMS (short message service) have been used to improve the delivery of health services in many countries. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. The aim of this study therefore is to measure the impact of a mobile phone SMS service on treatment success of newly diagnosed type 2 diabetes in an urban area of Bangladesh., Methods/design: This is a single-centred randomized controlled intervention trial (prospective) comparing standard-of-care with standard-of-care plus a mobile phone-based SMS intervention for 6 months. A total of 216 participants with newly diagnosed type 2 diabetes will be recruited. Data will be collected at the outpatient department of Bangladesh Institute of Health Science (BIHS) hospital at baseline and after 6 months. The primary outcome measure will be change in HbA1c between baseline and 6 months. The secondary outcome measures are self-reported medication adherence, clinic attendance, self-reported adoption of healthy behaviours, diabetes knowledge, quality of life and cost effectiveness of the SMS intervention. The inclusion criteria will be as follows: diagnosed as patients with type 2 diabetes by the BIHS physician, using oral medication therapy, living in Dhaka city, registered with the BIHS hospital, using a mobile phone, willing to return for follow up after 6 months and providing written informed consent. Participants will be allocated to control and intervention arms after recruitment using a randomization software. Data will be collected on socio-demographic and economic information, mobile phone use and habits, knowledge of prevention, management and complications of diabetes, self-perceived quality of life assessment, self-reported diseases, medical history, family history of diseases, medication history, medication adherence, health seeking behaviour, tobacco use, physical activity, diet, mental health status, life events and disability, anthropometric measurements of weight, height, blood pressure and blood tests for HbA1c., Discussion: Mobile phone SMS services have the potential to communicate with diabetes patients and to build awareness about the disease, improve self-management and avoid complications also in resource-limited setting. If this intervention proves to be efficient and cost-effective in the current trial, large-scale implementation could be undertaken., Trial Registration: DRKS00005188 .

Background: Poor adherence has been identified as the main cause of failure to control hypertension. Poor adherence to antihypertensive treatment is a significant cardiovascular risk factor, which often remains unrecognized. There are no previous studies that examined adherence with antihypertensive medication or the characteristics of the non-adherent patients in Bangladesh., Objective: This paper aims to describe hypertension and factors affecting adherence to treatment among hypertensive persons in rural Bangladesh., Design: The study population included 29,960 men and women aged 25 years and older from three rural demographic surveillance sites of the International Center for Diarrheal Disease Research, Bangladesh (icddr,b): Matlab, Abhoynagar, and Mirsarai. Data was collected by a cross-sectional design on diagnostic provider, initial, and current treatment. Discontinuation of medication at the time of interview was defined as non-adherence to treatment., Results: The prevalence of hypertension was 13.67%. Qualified providers diagnosed only 53.5% of the hypertension (MBBS doctors 46.1 and specialized doctors 7.4%). Among the unqualified providers, village doctors diagnosed 40.7%, and others (nurse, health worker, paramedic, homeopath, spiritual healer, and pharmacy man) each diagnosed less than 5%. Of those who started treatment upon being diagnosed with hypertension, 26% discontinued the use of medication. Age, sex, education, wealth, and type of provider were independently associated with non-adherence to medication. More men discontinued the treatment than women (odds ratio [OR] 1.74, confidence interval [CI] 1.48-2.04). Non-adherence was greater when hypertension was diagnosed by unqualified providers (OR 1.52, CI 1.31-1.77). Hypertensive patients of older age, least poor quintile, and higher education were less likely to be non-adherent. Patients with cardiovascular comorbidity were also less likely to be non-adherent to antihypertensive medication (OR 0.79, CI 0.64-0.97)., Conclusions: Although village doctors diagnose 40% of hypertension, their treatments are associated with a higher rate of non-adherence to medication. The hypertension care practices of the village doctors should be explored by additional research. More emphasis should be placed on men, young people, and people with low education. Health programs focused on education regarding the importance of taking continuous antihypertensive medication is now of utmost importance.

Objective: We aimed to determine the timing and size of the cognitive deficit associated with poverty in the first 5 years of life and to examine the role of parental characteristics, pre- and postnatal growth, and stimulation in the home in Bangladeshi children. We hypothesized that the effect of poverty on cognition begins in infancy and is mainly mediated by these factors., Methods: We enrolled 2853 singletons, a subsample from a pregnancy supplementation trial in a poor rural area. We assessed mental development at 7, 18, and 64 months; anthropometry at birth, 12, 24, and 64 months; home stimulation at 18 and 64 months; and family's socioeconomic background. In multiple regression analyses, we examined the effect of poverty at birth on IQ at 64 months and the extent that other factors mediated the effect., Results: A mean cognitive deficit of 0.2 (95% confidence interval -0.4 to -0.02) z scores between the first and fifth wealth quintiles was apparent at 7 months and increased to 1.2 (95% confidence interval -1.3 to -1.0) z scores of IQ by 64 months. Parental education, pre- and postnatal growth in length, and home stimulation mediated 86% of the effects of poverty on IQ and had independent effects. Growth in the first 2 years had larger effects than later growth. Home stimulation had effects throughout the period., Conclusions: Effects of poverty on children's cognition are mostly mediated through parental education, birth size, growth in the first 24 months, and home stimulation in the first 5 years., (Copyright © 2014 by the American Academy of Pediatrics.)

Background: Mental disorders constitute a major public health problem globally with higher burden in low and middle-income countries. In Bangladesh, systematically-collected data on mental disorders are scarce and this leaves the extent of the problem not so well defined. We reviewed the literature on mental health disorders in Bangladesh to summarize the available data and identify evidence gaps., Methods: We identified relevant literature on mental disorders within Bangladesh published between 1975 and October, 2013 through a systematic and comprehensive search. Relevant information from the selected articles was extracted and presented in tables., Results: We identified 32 articles which met our pre-defined eligibility criteria. The reported prevalence of mental disorders varied from 6.5 to 31.0% among adults and from 13.4 to 22.9% among children. Some awareness regarding mental health disorders exists at community level. There is a negative attitude towards treatment of those affected and treatment is not a priority in health care delivery. Mental health services are concentrated around tertiary care hospitals in big cities and absent in primary care., Conclusions: The burden of mental disorders is high in Bangladesh, yet a largely unrecognized and under-researched area. To improve the mental health services in Bangladesh, further well-designed epidemiological and clinical research are needed.

Background: Non-communicable diseases are a threat to human health and economic development of low-income countries. Hypertension (HT) and chronic obstructive pulmonary disease (COPD) are two major causes of deaths, worldwide. This study assesses the health status, health-care seeking, and health provider responses among patients with these conditions., Methods: The study carried out population-based cross-sectional survey in a rural and an urban surveillance area in Bangladesh. It interviewed all patients identified with HT and COPD at home using a structured questionnaire on the health consequences, healthcare-seeking behaviours, and coping strategies. Qualitative techniques identified key factors relating to the behaviours of patients and providers., Results: COPD and HT correlate with lower activities of daily living (ADL) scores. The odds ratio (OR) for ADL scores in the combied conditions are high (OR: 3.04, p < 0.05) as compared to hypertension. Financial crises occur significantly more frequently among COPD patients in the urban site as compared to those in rural ares (12.5% vs. 2.4%, p < 0.01). Self-treatment at the onset is common. Seeking care from trained providers is higher in urban settings and is higher for HT. Referral for both COPD and hypertension was inadequate until the disease severity increased., Conclusions: COPD and HT significantly are associated with lower ADL scores and financial problems. Public-sector primary healthcare facilities should be better organised to address both conditions with the aim to reduce household poverty.

Background: The burden of chronic kidney disease (CKD) will rise in parallel with the growing prevalence of type two diabetes mellitus in South Asia but is understudied. Using a cross-sectional survey of adults living in a middle-income neighborhood of Dhaka, Bangladesh, we tested the hypothesis that the prevalence of CKD in this group would approach that of the U.S. and would be strongly associated with insulin resistance., Methods: We enrolled 402 eligible adults (>30 years old) after performing a multi-stage random selection procedure. We administered a questionnaire, and collected fasting serum samples and urine samples. We used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate, and sex-specific cut offs for albuminuria: > 1.9 mg/mmol (17 mg/g) for men, and >2.8 mg/mmol (25 mg/g) for women. We assessed health-related quality of life using the Medical Outcomes Study Short Form-12 (SF-12)., Results: A total of 357 (89%) participants with serum samples comprised the analytic cohort. Mean age of was 49.5 (± 12.7) years. Chronic kidney disease was evident in 94 (26%). Of the participants with CKD, 58 (62%) had albuminuria only. A participant with insulin resistance had a 3.6-fold increase in odds of CKD (95% confidence interval 2.1 to 6.4). Participants with stage three or more advanced CKD reported a decrement in the Physical Health Composite score of the SF-12, compared with participants without CKD., Conclusion: We found an alarmingly high prevalence of CKD--particularly CKD associated with insulin resistance-in middle-income, urban Bangladeshis.

Objectives/hypothesis: Patients undergoing laryngopharyngectomy with extensive pharyngeal mucosal resection or those failing chemoradiation protocols are commonly reconstructed using free tissue transfer. Radial forearm free flaps (RFFFs) and anterolateral thigh free flaps (ALTs) are two of the most commonly used free flaps for laryngopharyngectomy reconstruction. It has been suggested that alaryngeal tracheoesophageal prosthesis (TEP) speech outcomes in patients undergoing ALT reconstruction may be inferior due to the possibly bulkier neopharynx. We report the results of patients treated with ALT and RFFF with regard to postoperative TEP voice outcomes., Study Design: Retrospective cohort study., Methods: We identified 42 consecutive patients who were treated with total laryngopharyngectomy and free flap reconstruction utilizing either RFFFs (20 patients) or ALTs (22 patients) between April 2001 and August 2010. Evaluations with statistical analysis of standard TEP speech outcome measures (maximal sustained phonation, fluent count, syllable count) and qualitative variables were conducted., Results: Patient demographics were similar between the RFFF and ALT groups, and 95% and 91% of RFFF and ALT patients received radiation therapy, respectively. Subjective voice quality did not significantly differ between the groups. Differences in outcomes of intelligibility, maximal sustained phonation time, maximum number of syllables, and fluent count, as evaluated by a single speech pathologist, were not statistically significant between RFFF and ALT patients. There was no difference in postoperative complications., Conclusions: These data indicate that reconstruction of laryngopharyngectomy defects using either the ALT or RFFF technique can produce similarly acceptable TEP voice results., Level of Evidence: 2b., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Obesity and overweight in children and adolescents is an emerging public health concern alongside under-nutrition in low and middle income countries. Our aim was to conduct a scoping review of literature to ascertain what is known about childhood and adolescent overweight and/or obesity in Bangladesh., Method: Using the scoping review based on York methodology, a comprehensive search of published academic articles, conference proceedings and grey literature was carried out through PubMed, BanglaJOL, Google and Google scholar limited to English-written papers. We summarized prevalence, risk factors and health outcomes of obesity/overweight in young children and adolescents aged between 0 to 19 years old in Bangladesh and highlighted use of different reference standards to measure childhood obesity., Results: In total 21 studies met the inclusion criteria. Nearly all of the reviewed articles used data from cross sectional studies, while only two used case-control design. Overall thirteen studies (62%) were primary research and eight (38%) included secondary data. Studies indicated an increasing trend in childhood obesity over time. Prevalence ranged from less than 1% to 17.9% based on different reference standards, with higher percentage amongst urban children across different age groups and sexes., Conclusion: This review demonstrated paucity of comprehensive literature on childhood obesity in Bangladesh, which might be explored through population-based prospective studies based on strong methodology and uniform reference standards. Sustainable and scalable preventative measures targeting high risk groups are required to avoid further rise.

Background: Diabetes affects both individuals and their families and has an impact on economic and social development of a country. Information on the availability, cost, and quality of medical care for diabetes is mostly not available for many low- and middle-income countries including Bangladesh. Complications from diabetes, which can be devastating, could largely be prevented by wider use of several inexpensive generic medicines, simple tests and monitoring and can be a cost saving intervention. This study will provide an in-depth and comprehensive picture of social and economic impacts of diabetes in Bangladesh and propose clear recommendations for improving prevention and management of diabetes. The objectives of the study are: 1) To study the association between diabetes and other health problems and its social impacts. 2) To estimate the economic impact of diabetes including total direct and indirect costs. 3) To measure the impact of diabetes on quality of life among diabetes patients in Bangladesh. 4) To study the impact of diabetes on the health care system, Methods: This is a case-control study comparing cases with type 2 diabetes to controls without diabetes matched on age, sex and place of residence. 564 cases and 564 controls will be selected from the outpatient department of a tertiary hospital in Dhaka, Bangladesh. Data on socioeconomic status, health utility index, direct and indirect costs for diabetes, medication adherence, quality of life, treatment satisfaction, diet, physical activity, mental state examination, weight, height, hip and waist circumference, blood pressure, pulse, medication history, laboratory data and physical examination will be conducted., Outcome Measures: The primary outcome measures will be association between diabetes and other health problems, cost of diabetes, impact of diabetes on quality of life and secondary outcome measures are impact of diabetes on healthcare systems in Bangladesh., Discussion: This study will provide an in-depth and comprehensive picture of social and economic impacts of diabetics in Bangladesh and propose clear recommendations for improving prevention and management of diabetics. It will help to develop programs and policies for better management of Diabetics and cost effective strategies in Bangladesh context.

Objective: To directly estimate how much smoking contributes to cause-specific mortality in Bangladesh., Methods: A case-control study was conducted with surveillance data from Matlab, a rural subdistrict. Cases (n = 2213) and controls (n = 261) were men aged 25 to 69 years who had died between 2003 and 2010 from smoking-related and non-smoking-related causes, respectively. Cause-specific odds ratios (ORs) were calculated for "ever-smokers" versus "never-smokers", with adjustment for education, tobacco chewing status and age. Smoking-attributable deaths among cases, national attributable fractions and cumulative probability of surviving from 25 to 69 years of age among ever-smokers and never-smokers were also calculated., Findings: The fraction of ever-smokers was about 84% among cases and 73% among controls (OR: 1.7; 99% confidence interval, CI: 1.1-2.5). ORs were highest for cancers and lower for respiratory, vascular and other diseases. A dose-response relationship was noted between age at smoking initiation and daily number of cigarettes or bidis smoked and the risk of death. Among 25-year-old Bangladeshi men, 32% of ever-smokers will die before reaching 70 years of age, compared with 19% of never-smokers. In 2010, about 25% of all deaths observed in Bangladeshi men aged 25 to 69 years (i.e. 42,000 deaths) were attributable to smoking., Conclusion: Smoking causes about 25% of all deaths in Bangladeshi men aged 25 to 69 years and an average loss of seven years of life per smoker. Without a substantial increase in smoking cessation rates, which are low among Bangladeshi men, smoking-attributable deaths in Bangladesh are likely to increase.

This article describes the challenges of facial reconstruction and the role of facial transplantation in certain facial defects and injuries. This information is of value to surgeons assessing facial injuries with massive soft tissue loss or injury., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited., Methods: This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7-17 years. Children with in utero and early life arsenic exposure were compared with children exposed to less than 10 µg/l in utero and throughout childhood. Because most children drank the same water as their mother had drunk during pregnancy, we could not assess only in utero or only childhood exposure., Results: Children exposed in utero to more than 500 µg/l of arsenic were more than eight times more likely to report wheezing when not having a cold [odds ratio (OR) = 8.41, 95% confidence interval (CI): 1.66-42.6, P < 0.01] and more than three times more likely to report shortness of breath when walking on level ground (OR = 3.86, 95% CI: 1.09-13.7, P = 0.02) and when walking fast or climbing (OR = 3.19, 95% CI: 1.22-8.32, P < 0.01]. However, there was little evidence of reduced lung function in either exposure category., Conclusions: Children with high in utero and early life arsenic exposure had marked increases in several chronic respiratory symptoms, which could be due to in utero exposure or to early life exposure, or to both. Our findings suggest that arsenic in water has early pulmonary effects and that respiratory symptoms are a better marker of early life arsenic toxicity than changes in lung function measured by spirometry.

Importance: Neuromuscular reanimation of the face provides the correct specific neural functional input and thereby prevents synkinesis. Unfortunately, this ideal situation is rarely encountered in the clinical setting., Objectives: To assess the technical feasibility of and define the surgical procedure for harvesting the sternohyoid muscle as a novel free flap for use in facial reanimation indications., Design, Setting, and Participants: Fresh, postmortem, nonfixed cadavers were used to define the anatomy and perform the flap harvest procedures. Twenty-four flap harvests were performed. Angiography was performed on the pedicle of the harvested flaps to assess potential flap perfusion. Adenosine triphosphatase staining was performed on the muscle specimens to establish fiber type., Main Outcome Measures: The harvest technique, pedicle (arterial or venous), nerve length, and flap geometry parameters were characterized., Results: The sternohyoid muscle was found to be reliably vascularized by the superior thyroid artery in all cases with an appropriate arterial and venous pedicle for vascular anastomosis. The mean arterial (5.5 cm) and venous (5.9 cm) pedicle lengths are comparable with gracilis flaps. The mean motor nerve length was 10.7 cm. The inclusion of the hyoid bone allows rigid fixation, and the muscle size, fiber type, and volume profiles all compare favorably to the gracilis flap for use in the indication of facial reanimation. Mock surgical procedures were performed to define inset parameters. This flap potentially allows single-stage cross-facial neurorrhaphies to be performed., Conclusions and Relevance: This is the first article, to our knowledge, of the sternohyoid muscle as a potential donor site for free-tissue transfer. This muscle has a predictable vascular pedicle and neural innervation along with size and fiber type parameters that make it an ideal potential free flap for facial reanimation., Level of Evidence: NA.

Upper airway manifestations, particularly sinonasal manifestations, are encountered frequently in granulomatosis with polyangiitis (GPA). Nasal endoscopy often reveals crusting, friable erythematous mucosa, and granulation. Up to 25% of patients may have a "saddle-nose" deformity as cartilage destruction worsens. Treatment is often complicated by loss of mucociliary function and necrosis, leading to refractory symptoms. Culture-directed antibiotics, topical antibiotic and saline irrigations, and occasional debridement of adherent crusts can reduce the frequency of sinonasal exacerbations and improve obstructive symptoms. Surgery should be reserved for patients unresponsive to maximal medical therapy. Saddle-nose reconstruction is possible in highly selected patients and can improve nasal breathing and resolve anosmia. Up to 20% of patients with GPA have subglottic stenosis; patients with respiratory symptoms should undergo laryngoscopy to assess the presence of subglottic narrowing. Although systemic manifestations of GPA are managed by immunosuppressive therapy, most patients with subglottic stenosis of GPA require surgical management (ie, endoscopic dilation, endoscopic or laser excision, surgical resection followed by reconstruction).

Objective: After nerve injury, an exaggerated neuroinflammatory process may hinder neuron regeneration and recovery. Immunomodulation using glucocorticoids may therefore improve facial nerve injury outcomes. This study aims to examine the effect of both local and systemic dexamethasone administration on facial nerve functional recovery after axotomy in a rat model., Study Design: Randomized, placebo-controlled, blinded animal study. Setting Animal laboratory., Subjects and Methods: Seventy-four Wistar rats underwent facial nerve axotomy with immediate neurorrhaphy. Rats were randomly assigned a postoperative group: control (no therapy); systemic dexamethasone 0.5, 1, 5, or 10 mg/kg for 3 administrations; or topically applied dexamethasone at 2 or 4 mg/mL. Blinded, standardized facial assessments and nerve conduction studies (NCS) were performed. Gross facial motion assessments were corroborated with vibrissae frequency video analysis., Results: At 8 weeks, rats receiving systemic dexamethasone at 5 mg/kg attained greater eye blink closure (P = .004) and vibrissae motion (P = .012) compared with controls. Systemic dexamethasone at 0.5, 1, and 10 mg/kg and intraoperative topical application of dexamethasone at 2 or 4 mg/mL did not produce a significant improvement in facial motion compared with controls. Nerve conduction studies show a trend of increased return of compound muscle action potential amplitude levels compared with baseline among rats that received systemic dexamethasone 5 mg/kg but do not achieve statistical significance., Conclusion: In a rat facial nerve axotomy model, high-dose systemic dexamethasone therapy may improve functional recovery when administered in the immediate period following neurorrhaphy.

Background: Indoor air pollution (IAP) due to solid fuel use is a major risk factor of respiratory and cardiovascular mortality and morbidity. Rural Matlab in Bangladesh has been partly supplied with natural gas since the early 1990s, which offered a natural experiment to investigate the long-term impact of IAP on cardiopulmonary mortality., Objective: This study sought to compare adult cardiopulmonary mortality in relation to household fuel type as a surrogate for exposure to indoor air pollution., Study Design: This was a retrospective cohort study. We identified all households in 11 villages in Matlab, Bangladesh, and categorized them as either supplied with natural gas or using solid fuel for cooking or heating since January 1, 2001. Cause-specific mortality data including cardiopulmonary deaths were obtained through verbal autopsy as part of a permanent surveillance. Person-years (PYs) of exposure were computed from baseline until the event. Subjects with missing information on cause of death, outward migration, or on fuel type were excluded. Event rates for each fuel category were calculated as well as the relative risk of dying with 95% confidence intervals (CI)., Setting: Rural Matlab, Bangladesh., Patients: Adults 18 years of age or older., Outcome Measure: Death from cardiopulmonary diseases over a 10-year period., Findings: In total, 946 cardiopulmonary deaths occurred with 884 in the solid-fuel and 62 in the gas-supplied households (n=7,565 and n=508, respectively) over the 10-year period. Cardiopulmonary death rate was 6.2 per 1,000 PYs in the solid-fuel group and 5.3 per 1,000 PYs in people living in households using gas. Mortality due to cardiovascular event was 5.1 and 4.8 per 1,000 PY in people from the solid-fuel and gas-supplied households, respectively, and the incident rate ratio was 1.07 (95% CI: 0.82 to 1.41). Mortality due to respiratory disease was 1.2 and 0.5 per 1,000 PYs in the solid-fuel and gas-supplied groups, respectively, and the incident rate ratio was 2.26 (95% CI: 1.02 to 4.99)., Interpretation: Household solid-fuel use is associated with increased respiratory mortality and nonsignificantly increased risk of cardiovascular mortality. Reduction of exposure to pollution due to in-household solid-fuel use is likely to improve survival in Bangladeshi and similar populations., (Copyright © 2012 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)