Understanding Pathways to Health with Legacy of Caste among Sanitation Workers: An Eco-Social Approach

High levels of mortality and morbidity in sanitation workers can be attributable to the type of occupations they are engaged in, especially in India. Major diseases such as cardiac disorders, HIV and tuberculosis have an impact on their lives. Bacterial and viral infections are commonly observed among them. The nature of their work leads them towards alcoholism, smoking and unsafe sex. Overall, there is a better understanding of the physical environment to which the sanitation workers are exposed, but the psychosocial exposures to which the workers are thoroughly exposed needs a social approach while investigating social determinants. Thus the patterns of health, disease and well being of sanitation workers in biological sense can be explained in terms of social relations, in our case, caste, social environment and occupation. Caste is an important intrinsic feature which specifies the occupation allied to it. Sanitation workers are mostly ‘Dalits’ who stand in the lowest hierarchy in the Indian caste system. Due to the inter-generational transfer of occupation and stigma associated to the kind of occupation they are socially prohibited. This not only perpetuates into their social status but also in their economic terms of livelihoods. Literature reveals the dreadful nature of their socioeconomic status which further leads to consequences of exclusion and discrimination. The basic understanding of health and well being and how it is socially constructed through pathways influenced by social relations could be explained by the approach of eco-social framework. The eco-social approach explains embodiment, pathways of embodiment and cumulative interplay between exposures, susceptibility and resistance. The comprehending relations of the underlying determinant of caste still persist in the modern era plus the occupational hazards with their impact. This complex relation between caste, social environment and occupation with their pathways to health could be understood by this framework

Prevalence of 22q11.2 microdeletion in 146 patients with cardiac malformation in a referral hospital of North India

<p>Abstract</p> <p>Background</p> <p>The 22q11.2 microdeletion syndrome is a common condition that is associated with cardiac as well as extra-cardiac manifestations. Its prevalence and manifestations from north India has not been reported. This study was designed to determine the prevalence and ability of clinical criteria to predict 22q11.2 microdeletion.</p> <p>Methods</p> <p>A total of 146 cases of cardiac malformation requiring tertiary care at a teaching hospital were prospectively screened for 22q11.2 microdeletion using fluorescence in situ hybridization test. Detailed clinical information was obtained as per guidelines of Tobias, <it>et al </it>(1999).</p> <p>Results</p> <p>Nine out of 146 patients (6.16%) was found to have 22q11.2 microdeletion. All the positive patients showed the presence of extra-cardiac features of 22q11.2 microdeletion syndrome. None of the cases with isolated cardiac defect were positive for microdeletion.</p> <p>Conclusions</p> <p>It seems that 22q11.2 microdeletion syndrome is over-suspected in children with isolated congenital heart defects. Screening for 22q11.2 microdeletion should be considered in those cardiac malformation cases which have extra-cardiac manifestations in the form of facial dysmorphism and hypocalcaemia.</p

Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland

<p>Abstract</p> <p>Background</p> <p>The 22q11.2 microdeletion syndrome (22q11.2 deletion syndrome -22q11.2DS) refers to congenital abnormalities, including primarily heart defects and facial dysmorphy, thymic hypoplasia, cleft palate and hypocalcaemia. Microdeletion within chromosomal region 22q11.2 constitutes the molecular basis of this syndrome. The 22q11.2 microdeletion syndrome occurs in 1/4000 births. The aim of this study was to determine the frequency of 22q11.2 microdeletion in 87 children suffering from a congenital heart defect (conotruncal or non-conotruncal) coexisting with at least one additional 22q11.2DS feature and to carry out 22q11.2 microdeletion testing of the deleted children's parents. We also attempted to identify the most frequent heart defects in both groups and phenotypic traits of patients with microdeletion to determine selection criteria for at risk patients.</p> <p>Methods</p> <p>The analysis of microdeletions was conducted using fluorescence <it>in situ </it>hybridization (FISH) on metaphase chromosomes and interphase nuclei isolated from venous peripheral blood cultures. A molecular probe (Tuple) specific to the <it>HIRA (TUPLE1, DGCR1</it>) region at 22q11 was used for the hybridisation.</p> <p>Results</p> <p>Microdeletions of 22q11.2 region were detected in 13 children with a congenital heart defect (14.94% of the examined group). Microdeletion of 22q11.2 occurred in 20% and 11.54% of the conotruncal and non-conotruncal groups respectively. Tetralogy of Fallot was the most frequent heart defect in the first group of children with 22q11.2 microdeletion, while ventricular septal defect and atrial septal defect/ventricular septal defect were most frequent in the second group. The microdeletion was also detected in one of the parents of the deleted child (6.25%) without congenital heart defect, but with slight dysmorphism. In the remaining children, 22q11.2 microdeletion originated <it>de novo</it>.</p> <p>Conclusions</p> <p>Patients with 22q11.2DS exhibit wide spectrum of phenotypic characteristics, ranging from discreet to quite strong. The deletion was inherited by one child. Our study suggests that screening for 22q11.2 microdeletion should be performed in children with conotruncal and non-conotruncal heart defects and with at least one typical feature of 22q11.2DS as well as in the deleted children's parents.</p

Evaluating protein cross-linking as a therapeutic strategy to stabilize SOD1 variants in a mouse model of familial ALS

Mutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS) cases. A shared effect of these mutations is that SOD1, which is normally a stable dimer, dissociates into toxic monomers that seed toxic aggregates. Considerable research effort has been devoted to developing compounds that stabilize the dimer of fALS SOD1 variants, but unfortunately, this has not yet resulted in a treatment. We hypothesized that cyclic thiosulfinate cross-linkers, which selectively target a rare, 2 cysteine-containing motif, can stabilize fALS-causing SOD1 variants in vivo. We created a library of chemically diverse cyclic thiosulfinates and determined structure-cross-linking-activity relationships. A pre-lead compound, “S-XL6,” was selected based upon its cross-linking rate and drug-like properties. Co-crystallographic structure clearly establishes the binding of S-XL6 at Cys 111 bridging the monomers and stabilizing the SOD1 dimer. Biophysical studies reveal that the degree of stabilization afforded by S-XL6 (up to 24°C) is unprecedented for fALS, and to our knowledge, for any protein target of any kinetic stabilizer. Gene silencing and protein degrading therapeutic approaches require careful dose titration to balance the benefit of diminished fALS SOD1 expression with the toxic loss-of-enzymatic function. We show that S-XL6 does not share this liability because it rescues the activity of fALS SOD1 variants. No pharmacological agent has been proven to bind to SOD1 in vivo. Here, using a fALS mouse model, we demonstrate oral bioavailability; rapid engagement of SOD1G93A by S-XL6 that increases SOD1G93A’s in vivo half-life; and that S-XL6 crosses the blood–brain barrier. S-XL6 demonstrated a degree of selectivity by avoiding off-target binding to plasma proteins. Taken together, our results indicate that cyclic thiosulfinate-mediated SOD1 stabilization should receive further attention as a potential therapeutic approach for fALS

Calibration and application of a sediment accumulation rate model-A case study

A mechanistic mass balance model for sediment accumulation rate (SAR) that accommodates the dry density and burial velocity of solids and the depth dependency of porosity was tested and applied to Onondaga Lake, New York, for a 130-year period. The modeling for this case study is supported by a rich history of multiple anthropogenic drivers and coupled date horizons from the paleolimnological record, characterization of physical attributes of the sediments, and long-term monitoring of the water column and lake inputs. The consistency of predictions of SAR and measurements of downward flux of suspended particulate material (DFSPM) from a long-term sediment trap program was also evaluated. The model was demonstrated to perform well in simulating the lake\u27s history of SAR, which was supported by 10 different depth-date horizons. This history for 100 years was regulated by the production of soda-ash at an adjoining industry, which enhanced autochthonous formation and deposition of calcium carbonate (CaCO3), proportional to the level of production of this chemical. The SAR was extraordinarily high (~5 kg m-2 yr-1) during the 40 years of peak soda-ash production. An abrupt, more than 2-fold decrease in SAR occurred when the industry closed. The contemporary SAR remains relatively high as a result of multiple drivers but is serving to enhance burial of contaminants, including mercury, as part of an ongoing rehabilitation program. A high level of consistency (within 30%) between the contemporary SAR and an annual estimate of DFSPM was documented. The utility of the model was demonstrated through applications that depict the amount of deposits contributed by the industry, the effect of compaction on burial velocity, the dilution effect of the high SAR values on the paleolimnological record, and the resolution of sediment diagenesis kinetics