33 research outputs found

    Multimorbidity in South Asian adults: prevalence, risk factors and mortality.

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    Background: We report the prevalence, risk factors and mortality associated with multimorbidity in urban South Asian adults. Methods: Hypertension, diabetes, heart disease, stroke and chronic kidney disease were measured at baseline in a sample of 16 287 adults ages ≥20 years in Delhi, Chennai and Karachi in 2010-11 followed for an average of 38 months. Multimorbidity was defined as having ≥2 chronic conditions at baseline. We identified correlates of multimorbidity at baseline using multinomial logistic models, and we assessed the prospective association between multimorbidity and mortality using Cox proportional hazards models. Results: The adjusted prevalence of multimorbidity was 9.4%; multimorbidity was highest in adults who were aged ≥60 years (37%), consumed alcohol (12.3%), body mass index ≥25 m/kg2 (14.1%), high waist circumference (17.1%) and had family history of a chronic condition (12.4%). Compared with adults with no chronic conditions, the fully adjusted relative hazard of death was twice as high in adults with two morbidities (hazard ratio [HR] = 2.3; 95% confidence interval [CI]: 1.6, 3.3) and thrice as high in adults with ≥3 morbidities (HR = 3.1; 95% CI: 1.9, 5.1). Conclusion: Multimorbidity affects nearly 1 in 10 urban South Asians, and each additional morbidity carries a progressively higher risk of death. Identifying locally appropriate strategies for prevention and coordinated management of multimorbidity will benefit population health in the region

    Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression

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    Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.−69G>A, c.−69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted. Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. Nanopore sequencing confirmed the lower transcription of the TMEM216 c.−69G>T allele in blood-derived RNA from a heterozygous carrier, and reduced expression was further recapitulated by qPCR, using both leukocytes-derived RNA of c.−69G>T homozygotes and total RNA from genome-edited hTERT-RPE1 cells carrying homozygous TMEM216 c.−69G>A. In conclusion, these variants explain a significant proportion of unsolved cases, specifically in individuals of African ancestry, suggesting that reduced TMEM216 expression might lead to abnormal ciliogenesis and photoreceptor degeneration

    Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression

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    Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted. Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. Nanopore sequencing confirmed the lower transcription of the TMEM216 c.-69G>T allele in blood-derived RNA from a heterozygous carrier, and reduced expression was further recapitulated by qPCR, using both leukocytes-derived RNA of c.-69G>T homozygotes and total RNA from genome-edited hTERT-RPE1 cells carrying homozygous TMEM216 c.-69G>A. In conclusion, these variants explain a significant proportion of unsolved cases, specifically in individuals of African ancestry, suggesting that reduced TMEM216 expression might lead to abnormal ciliogenesis and photoreceptor degeneration

    Programmed Cellular Necrosis Mediated by the Pore-Forming α-Toxin from Clostridium septicum

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    Programmed necrosis is a mechanism of cell death that has been described for neuronal excitotoxicity and ischemia/reperfusion injury, but has not been extensively studied in the context of exposure to bacterial exotoxins. The α-toxin of Clostridium septicum is a β-barrel pore-forming toxin and a potent cytotoxin; however, the mechanism by which it induces cell death has not been elucidated in detail. We report that α-toxin formed Ca2+-permeable pores in murine myoblast cells, leading to an increase in intracellular Ca2+ levels. This Ca2+ influx did not induce apoptosis, as has been described for other small pore-forming toxins, but a cascade of events consistent with programmed necrosis. Ca2+ influx was associated with calpain activation and release of cathepsins from lysosomes. We also observed deregulation of mitochondrial activity, leading to increased ROS levels, and dramatically reduced levels of ATP. Finally, the immunostimulatory histone binding protein HMGB1 was found to be released from the nuclei of α-toxin-treated cells. Collectively, these data show that α-toxin initiates a multifaceted necrotic cell death response that is consistent with its essential role in C. septicum-mediated myonecrosis and sepsis. We postulate that cellular intoxication with pore-forming toxins may be a major mechanism by which programmed necrosis is induced

    Validity and reliability of subjective methods to assess sedentary behaviour in adults: a systematic review and meta-analysis.

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    BACKGROUND: Subjective measures of sedentary behaviour (SB) (i.e. questionnaires and diaries/logs) are widely implemented, and can be useful for capturing type and context of SBs. However, little is known about comparative validity and reliability. The aim of this systematic review and meta-analysis was to: 1) identify subjective methods to assess overall, domain- and behaviour-specific SB, and 2) examine the validity and reliability of these methods. METHODS: The databases MEDLINE, EMBASE and SPORTDiscus were searched up to March 2020. Inclusion criteria were: 1) assessment of SB, 2) evaluation of subjective measurement tools, 3) being performed in healthy adults, 4) manuscript written in English, and 5) paper was peer-reviewed. Data of validity and/or reliability measurements was extracted from included studies and a meta-analysis using random effects was performed to assess the pooled correlation coefficients of the validity. RESULTS: The systematic search resulted in 2423 hits. After excluding duplicates and screening on title and abstract, 82 studies were included with 75 self-reported measurement tools. There was wide variability in the measurement properties and quality of the studies. The criterion validity varied between poor-to-excellent (correlation coefficient [R] range - 0.01- 0.90) with logs/diaries (R = 0.63 [95%CI 0.48-0.78]) showing higher criterion validity compared to questionnaires (R = 0.35 [95%CI 0.32-0.39]). Furthermore, correlation coefficients of single- and multiple-item questionnaires were comparable (1-item R = 0.34; 2-to-9-items R = 0.35; ≥10-items R = 0.37). The reliability of SB measures was moderate-to-good, with the quality of these studies being mostly fair-to-good. CONCLUSION: Logs and diaries are recommended to validly and reliably assess self-reported SB. However, due to time and resources constraints, 1-item questionnaires may be preferred to subjectively assess SB in large-scale observations when showing similar validity and reliability compared to longer questionnaires. REGISTRATION NUMBER: CRD42018105994

    Specific Factors, Unemployment, and Immiserizing Growth in a Small Open Economy

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    The economic rationale of import-substituting strategy of development pursued by the majority of the developing countries has long been questioned. Apart from the familiar argument that tariff tends to discourage exports and hence, can be viewed as an export tax, there is the immiserization argument proposed by Professor Johnson. Within the framework of a two-factor two-commodity model, Johnson has shown that a small tariff-imposing country may suffer a welfare loss from an increase in the stock of resources or technological change if the growth is biased in favor of the importable sector so that it tends to magnify the distortion in production caused by the tariff. The purpose of this paper is to examine the possibility of Johnson-type immiserizing growth for the developing countries characterized by massive unemployment

    Controlled Delivery of Bioactive Molecules for the Treatment of Chronic Wounds

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    A cut or break on the surface of the skin is usually referred to as a wound. Any wound has a potential to heal by itself through a complex cascade of events. However, some wounds show delayed healing due to their underlying physiology and are referred to as chronic wounds like diabetic ulcers, venous ulcers, pressure ulcers and chronic infected ulcers. Extensive care has to be taken for the management of chronic wounds and these have become a major concern in the current medical scenario. The use of bioactive molecules or in other words the molecules that can actively interact with the wound environment and help in wound healing are gaining much importance. The incorporation of bioactive molecules into a suitable matrix system which not only provide a controlled release of the molecules, but also enable better exudate management is desired to overcome the shortcomings of the conventional treatment modalities. A major problem associated with chronic wounds is that they are easily prone to infections. In such cases, the topical delivery of antibiotics helps eliminate infection. However, the continuous use of high dose of antibiotics has led to the development of multi drug resistant bacterial strains. To overcome these issues, other broad-spectrum antimicrobial agents like antiseptics, metallic nanoparticles and antimicrobial peptides are being adopted nowadays. Growth factors play a major role in the wound healing cascade, thus topical delivery of growth factor from a suitable matrix is an interesting strategy. The delivery of nucleic acids with the aid of suitable vectors for either silencing a particular gene or over expressing a gene of interest is also being investigated nowadays. This review is an attempt to draw light over some of the recent approaches adopted for the treatment of chronic wounds using bioactive molecules like antibiotics, antiseptics, metallic nanoparticles or ions, growth factors and nucleic acids
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