Sudden cardiac death in South India: Incidence, risk factors and pathology.

BACKGROUND: Sudden cardiac death (SCD) is a major cause of mortality secondary to coronary artery disease (CAD) in the industrialized societies. Although South Asians have a high prevalence of CAD, the frequency and underlying pathology of SCD among this population are unknown. METHODS: Medical records of consecutive patients presenting with unexplained sudden death (USD) in a tertiary care center were reviewed. Patients with trauma, violent deaths, positive toxicology and non-cardiac pathology were excluded to determine sudden cardiac death (SCD). Cardiac pathological findings were analyzed by autopsy. SCD rate was estimated based on census and government vital statistics for the years studied. RESULTS: During a two year period, 223 patients (mean age 55 + 10 yrs, 78.9% male, body mass index 26 + 4, 60% smokers, 39% known CAD, 46% hypertension, 43% diabetes) presented to hospital with USD. SCD was attributed to myocardial infarction (MI) in 87% of cases; 69% were acute (96% anterior MI); 76% were small/moderate infarct and 9.9% of the cohort had normal hearts. Based on official municipal vital statistics, the SCD rate in those >35 yrs of age was estimated as 39.7/100,000 with male/female ratio of 4.6. CONCLUSIONS: SCD in this south Indian city occurred predominantly in men of relatively young age and was most frequently associated with small or moderate-sized acute MI. Improved health care access, preventive measures and enhanced emergency management may reduce SCD from acute MI in this locale.

Pesticides and human diabetes: a link worth exploring?

It is no exaggeration to claim that the 'diabetes epidemic' has become a 'runaway train' causing huge health and economic consequences, especially in the developing nations. Traditionally, the risk factors for diabetes have largely focused on genetics and lifestyle. Great emphasis is placed on lifestyle measures and finding novel pharmacological treatment options to combat diabetes, but there is increasing evidence linking environmental pollutants, especially pesticides, to the development of insulin resistance and Type 2 diabetes. Pesticide use has increased dramatically worldwide and the effects of pesticides on glucose metabolism are too significant for a possible diabetogenic link to be dismissed. The aim of this review article was to assess the links between pesticides and human diabetes with the goal of stimulating further research in this area.

Methyl (2Z)-2-bromo-methyl-3-(2,4-dichloro-phen-yl)prop-2-enoate.

In the title compound C11H9BrCl2O2, which represents the Z isomer, the methyl-acrylate moiety is essentially planar within 0.039 (2) Šand has an extended trans configuration. The benzene ring makes a dihedral angle of 28.3 (1)° with the mean plane of the methyl-acrylate moiety. The crystal packing is characterized by C-H⋯O hydrogen bonding and halogen-halogen inter-actions [Cl⋯Cl = 3.486 (3) Å], resulting in the formation of R 2 (2)(11) ring motifs and connecting the mol-ecules into chains propagating along the b axis.

Methyl (2Z)-2-bromo-meth-yl-3-(3-chloro-phen-yl)prop-2-enoate.

There are two independent mol-ecules (A and B) in the asymmetric unit of the title compound C11H10BrClO2, which represents the Z isomer. The methyl-acrylate moieties are essentially planar, within 0.084 (2) and 0.027 (5) Šin mol-ecules A and B, respectively. The benzene ring makes dihedral angles of 13.17 (7) and 27.89 (9)° with the methyl-acrylate moiety in mol-ecules A and B, respectively. The methyl-bromide moiety is almost orthogonal to the benzene ring, making dihedral angles of 81.46 (16)° in mol-ecule A and 79.61 (16)° in mol-ecule B. The methyl-acrylate moiety exhibits an extended trans conformation in both mol-ecules. In the crystal, pairs of C-H⋯O hydrogen bonds result in the formation of quasi-centrosymmetric R 2 (2)(14) AB dimers.

Cognitive Function in Early Onset Type 1 Diabetes in Children.

OBJECTIVES: To assess cognitive function and factors affecting it in Indian children with early-onset type 1 diabetes (T1D) (less than 6 y). METHODS: This cross-sectional, single-centre study recruited children diagnosed with T1D before 6 y of age and having a disease duration of at least 2 y, as cases. Controls were age- and sex-matched apparently healthy children or siblings. Children with birth asphyxia, intellectual disability, syndromic children, or pre-existing psychiatric illness were excluded. Enrolled children underwent cognitive assessment using Malin's Intelligence Scale for Indian Children (MISIC), and scores in various subtests were compared between cases and controls. RESULTS: A total of 60 children were enrolled in each group. When compared to controls, cases had significantly lower scores on most subtests, verbal, performance and overall Intelligence Quotient (IQ- 100.62 ± 3.26 vs. 103.23 ± 1.22). HbA1c >9%, severe hypoglycemia and lesser duration since the last diabetic ketoacidosis (DKA) episode significantly correlated with lower neurocognitive scores. CONCLUSIONS: Children with early onset T1D showed significant deficits in various cognitive domains and IQ. Poor glycemic control, higher glycemic variability and exposure to severe hypoglycemia are risk factors for poor cognitive outcomes in these children. Further longitudinal studies could potentially aid in a finer understanding of factors affecting cognitive functioning in T1D children in developing countries.

Pathogenomic Signature and Aberrant Neurogenic Events in Experimental Cerebral Ischemic Stroke: A Neurotranscriptomic-Based Implication for Dementia.

BACKGROUND: Cerebral ischemic stroke is caused due to neurovascular damage or thrombosis, leading to neuronal dysfunction, neuroinflammation, neurodegeneration, and regenerative failure responsible for neurological deficits and dementia. The valid therapeutic targets against cerebral stroke remain obscure. Thus, insight into neuropathomechanisms resulting from the aberrant expression of genes appears to be crucial. OBJECTIVE: In this study, we have elucidated how neurogenesis-related genes are altered in experimental stroke brains from the available transcriptome profiles in correlation with transcriptome profiles of human postmortem stroke brain tissues. METHODS: The transcriptome datasets available on the middle cerebral artery occlusion (MCAo) rat brains were obtained from the Gene Expression Omnibus, National Center for Biotechnology Information. Of the available datasets, 97 samples were subjected to the meta-analysis using the network analyst tool followed by Cytoscape-based enrichment mapping analysis. The key differentially expressed genes (DEGs) were validated and compared with transcriptome profiling of human stroke brains. RESULTS: Results revealed 939 genes are differently expressed in the brains of the MCAo rat model of stroke, in which 30 genes are key markers of neural stem cells, and regulators of neurogenic processes. Its convergence with DEGs from human stroke brains has revealed common targets. CONCLUSION: This study has established a panel of highly important DEGs to signify the potential therapeutic targets for neuroregenerative strategy against pathogenic events associated with cerebral stroke. The outcome of the findings can be translated to mitigate neuroregeneration failure seen in various neurological and metabolic disease manifestations with neurocognitive impairments.

(2S,5S,6R)-5-(4-Methyl-phen-yl)-3-phenyl-4,8-dioxa-3-aza-tricyclo-[7.4.0.0]trideca-1(13),9,11-triene-6-carbonitrile.

In the title compound, C(24)H(20)N(2)O(2), the six-membered pyran ring adopts a half-chair conformation with one C atom deviating from the mean plane of the remaining ring atoms by 0.654 (6) Å. The five-membered isoxazole ring adopts an N-envelope conformation with the N atom displaced by 0.742 (5) Šfrom the mean plane formed by the remaining ring atoms. The carbonitrile side chain is almost linear, with a C-C-N angle of 178.6 (5)°. The crystal packing is stabilized by inter-molecular C-H⋯N inter-actions, through bifurcated acceptor hydrogen bonds formed between the carbonitrile N atom and two alternate C atoms in the unsubstituted benzene ring. The mol-ecular structure and crystal packing are further stabilized by intra-molecular and inter-molecular C-H⋯π inter-actions.

Metamorphic In(0.20)Ga(0.80)As p-i-n photodetectors grown on GaAs substrates for near infrared applications.

The growth and performance of top-illuminated metamorphic In(0.20)Ga(0.80)As p-i-n photodetectors grown on GaAs substrates using a step-graded In(x)Ga(1-x)As buffer is reported. The p-i-n photodetectors display a low room-temperature reverse bias dark current density of ~1.4×10(-7) A/cm(2) at -2 V. Responsivity and specific detectivity values of 0.72 A/W, 2.3×10(12) cm·Hz(1/2)/W and 0.69 A/W, 2.2×10(12) cm·Hz(1/2)/W are achieved for Yb:YAG (1030 nm) and Nd:YAG (1064 nm) laser wavelengths at -2 V, respectively. A high theoretical bandwidth-responsivity product of 0.21 GHz·A/W was estimated at 1064 nm. Device performance metrics for these GaAs substrate-based detectors compare favorably with those based on InP technology due to the close tuning of the detector bandgap to the target wavelengths, despite the presence of a residual threading dislocation density. This work demonstrates the great potential for high performance metamorphic near-infrared InGaAs detectors with optimally tuned bandgaps, which can be grown on GaAs substrates, for a wide variety of applications.

3-(3-Chloro-phen-yl)-1-methyl-3,3a,4,9b-tetra-hydro-1H-chromeno[4,3-c]isoxazole-3a-carbonitrile.

In the title compound, C(18)H(15)ClN(2)O(2), the five-membered isoxazole ring adopts an envelope conformation [the deviation of the N atom is 0.3154 (15) Å] and the six-membered pyran ring adopts a half-chair conformation. The mean plane through all atoms of the isoxazole ring forms dihedral angles of 47.98 (8)° with the mean plane of the chromene ring system and 75.10 (9)° with the chloro-benzene ring.

1-Methyl-3-(2-methyl-phen-yl)-3,3a,4,9b-tetra-hydro-1H-chromeno[4,3-c][1,2]oxazole-3a-carbonitrile.

In the title compound, C(19)H(18)N(2)O(2), the five-membered isoxazole ring adopts an envelope conformation and the deviation of the N atom from the mean plane of the isoxazole ring is -0.3256 (11) Å. The pyran ring adopts a half-chair conformation. The isoxazole ring forms dihedral angles of 44.07 (7) and 84.23 (7)° with the pyran and methyl-benzene rings, respectively. The mol-ecular structure is stabilized by weak C-H⋯π inter-actions.

(E)-2-(2-Formyl-phen-oxy-meth-yl)-3-phenyl-prop-2-ene-nitrile.

In the title compound, C(17)H(13)NO(2), the dihedral angle between the benzene and the phenyl ring is 65.92 (7)°. The carbonitrile side chain is almost linear, the C-C-N angle being 175.55 (14)°. The crystal structure is stabilized by inter-molecular C-H⋯O inter-actions.

Methyl rac-(2R,11S,12R)-12-(2-chloro-phen-yl)-22-oxo-9,13,21-trioxapenta-cyclo-[12.8.0.0.0.0]docosa-1(14),3,5,7,15(20),16,18-hepta-ene-11-carboxyl-ate.

In the title compound C(27)H(19)ClO(6), the coumarin ring system is not exactly planar, with a dihedral angle of 4.12 (7)° between its benzene and lactone rings. The cis-fused pyran rings adopt half-chair conformations. The carbometh-oxy and chloro-phenyl groups are in a trans configuration. The crystal packing is stabilized by inter-molecular C-H⋯O interactions, which produce a centrosymmetric R(2) (2)(14) dimer and two centrosymmetric R(2) (2)(18) dimers connecting the mol-ecules in a two-dimensional fashion.

Individualization of exosuit assistance based on measured muscle dynamics during versatile walking.

Variability in human walking depends on individual physiology, environment, and walking task. Consequently, in the field of wearable robotics, there is a clear need for customizing assistance to the user and task. Here, we developed a muscle-based assistance (MBA) strategy wherein exosuit assistance was derived from direct measurements of individuals' muscle dynamics during specific tasks. We recorded individuals' soleus muscle dynamics using ultrasonographic imaging during multiple walking speeds and inclines. From these prerecorded images, we estimated the force produced by the soleus through inefficient concentric contraction and designed the exosuit assistance profile to be proportional to that estimated force. We evaluated this approach with a bilateral ankle exosuit at each measured walking task. Compared with not wearing a device, the MBA ankle exosuit significantly reduced metabolic demand by an average of 15.9, 9.7, and 8.9% for level walking at 1.25, 1.5, and 1.75 meters second−1, respectively, and 7.8% at 1.25 meters second−1 at 5.71° incline while applying lower assistance levels than in existing literature. In an additional study (n = 2), we showed for multiple walking tasks that the MBA profile outperforms other bioinspired strategies and the average profile from a previous optimization study. Last, we show the feasibility of online assistance generation in a mobile version for overground outdoor walking. This muscle-based approach enables relatively rapid (~10 seconds) generation of individualized low-force assistance profiles that provide metabolic benefit. This approach may help support the adoption of wearable robotics in real-world, dynamic locomotor tasks by enabling comfortable, tailored, and adaptive assistance.

Decoding information on COVID-19: Ontological approach towards design possible therapeutics.

To date, no effective preventive or curative medical interventions exist against COVID-19, caused by Severe Acute Respiratory Syndrome corona virus 2 (SARS CoV-2). The available interventions are only supportive and palliative in nature. Popular among the emerging explanations for the mortality from COVID-19 is "cytokine storm", attributed to the body's aggressive immune response to this novel pathogen. In less than a year the disease has spread to almost all countries, though the mortality rates have varied significantly from country to country based on factors such as the demographical mix of the population, prevalence of comorbidities, as well as prior exposure to viruses from the corona family. This review examines the current literature on mortality rates across the globe, explores the possible reasons, thereby decoding variations. COVID-19 researchers have noted unique characteristics in the structural and host-pathogen interaction and identified several possible target proteins and sites that could exhibit control over the entry of SARS CoV-2 into the host, which this paper reviews in detail. Identification of new targets, both in the virus and the host, may accelerate the search for effective vaccines and curative drugs against COVID-19. Further, the ontological approach of this review is likely to provide insights for researchers to anticipate and be ready for future mutant viruses that may emerge in future.

Search for secondary osteoporosis: are Z scores useful predictors?

AIM: To determine whether Z scores can be used to predict the likelihood of patients having a secondary cause of low bone mineral density. METHODS: A retrospective cross sectional study was conducted among 136 consecutive patients with osteoporosis at Ninewells Hospital, Dundee, UK, between 1998-2002. RESULTS: 20.5% of female patients in this study were identified with previously unrecognised contributors to the low bone mineral density. In women, at a Z score cut-off of -1, the sensitivity of detecting a secondary cause for osteoporosis is 87.5% with a positive predictive value of 29.2%. CONCLUSION: In women, a Z score of -1 would identify a majority of patients with a secondary cause for low bone mineral density and identifies patients who would especially benefit from a thorough history and clinical examination.

Hepatoprotective and curative properties of Kombucha tea against carbon tetrachloride-induced toxicity.

Kombucha tea (KT) is sugared black tea fermented with a symbiotic culture of acetic acid bacteria and yeasts, which is said to be tea fungus. KT is claimed to have various beneficial effects on human health, but there is very little scientific evidence available in the literature. In the present study, KT along with black tea (BT) and black tea manufactured with tea fungus enzymes (enzyme-processed tea, ET) was evaluated for hepatoprotective and curative properties against CCl4-induced toxicity, using male albino rats as an experimental model by analyzing aspartate transaminase, alanine transaminase, and alkaline phosphatase in plasma and malondialdehyde content in plasma and liver tissues. Histopathological analysis of liver tissue was also included. Results showed that BT, ET, and KT have the potential to revert the CCl4-induced hepatotoxicity. Among the three types of teas tried, KT was found to be more efficient than BT and ET. Antioxidant molecules produced during the fermentation period could be the reason for the efficient hepatoprotective and curative properties of KT against CCI4-induced hepatotoxicity.

Nitrate removal using Brevundimonas diminuta MTCC 8486 from ground water.

Brevundimonas diminuta MTCC 8486, isolated from marine soil of coastal area of Trivandrum, Kerala, was used for biological removal of nitrate from ground water collected from Kar village of Pali district, Rajasthan. The organism was found to be resistance for nitrate up to 10,000 mg L(-1). The optimum growth conditions for biological removal of nitrate were established in batch culture. The effect of carbon sources on nitrate removal was investigated using mineral salt medium (MSM) containing 500 mg L(-1) of nitrate to select the most effective carbon source. Among glucose and starch as carbon source, glucose at 1% concentration increased the growth (182+/-8.24 x 10(4) CFU mL(-1)) and induced maximum nitrate reduction (86.4%) at 72 h. The ground water collected from Kar village, Pali district of Rajasthan containing 460+/-5.92 mg L(-1) of nitrate was subjected to three different treatment processes in pilot scale (T1 to T3). Higher removal of nitrate was observed in T2 process (88%) supplemented with 1% glucose. The system was scaled up to 10 L pilot scale treatment plant. At 72 h the nitrate removal was observed to be 95% in pilot scale plant. The residual nitrate level (23+/-0.41 mg L(-1)) in pilot scale treatment process was found to be below the permissible limit of WHO.

Time-dependent effect of oligomeric amyloid-ß (1-42)-induced hippocampal neurodegeneration in rat model of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is characterized with an abnormal deposition of insoluble amyloid-beta (Aß) peptide plaques, tangles formation and synaptic dysfunction. These result in impaired functioning of neuronal circuits and alter the behavioral response owing to activation of neurotransmitter receptors. Recently, it has been implicated that Aß influences N-methyl d-aspartate (NMDA) receptor activation in AD; however, the molecular mechanism underlying remains unclear. Thus, emerged specific aim to study the time-course effect of oligomeric Aß(1-42) (oAß1-42) on the mRNA expression of genes encoding NMDA and acetylcholine receptors in the rat model of AD. METHODS:  Aggregated forms of synthetic Aß peptides were injected bilaterally into the intrahippocampal region of rat brain using stereotaxic surgery. Behavioral analysis was performed using eight-arm Radial Arm Maze task at the end of experimental period. Euthanized rat brain hippocampal tissue was used to study the mRNA expression of glutamatergic and cholinergic receptor using semiquantitative reverse transcription-polymerase chain reaction. RESULTS: oAß1-42 decreased the gene expression level of α7-nicotinic acetylcholine receptor and increased the mRNA expression of NMDA receptor 2A, and -2B subunits. In particular, oAß1-42 aggregates increased the retention time and altered the behavioral response in rats after 15 days of injection. Further, amyloid-ß1-42 are highly expressed in 15 days after postinjection in hippocampus of adult rats. CONCLUSION: Acute exposure of oAß1-42 modulated differential gene expression of glutamatergic and cholinergic receptors in hippocampus of adult rats and is duration dependent reflecting changes in hippocampal circuitry system underlying learning and memory impairments. ABBREVIATIONS: AD: Alzheimer's disease, Aß: amyloid-ß; oAß1-42: oligomeric amyloid-ß 1-42 full length peptide; CAM: calmodulin; CNS: central nervous system; CR: Congo red; DG: dentate gyrus; EC: entorhinal cortex; HFIP: 1,1,1,3,3,3-hexafluoro-2-propanol; IBO: ibotenic acid; NMDA: N-methyl d-aspartate; NMDAR: N-methyl d-aspartate receptor; NR2A: N-methyl d-aspartate receptor 2A; NR2B: N-methyl d-aspartate receptor 2B; ACh: acetylcholine; α7-nAChR: α7-nicotinic acetylcholine receptor; PBS: phosphate buffered saline; RAM: Radial Arm Maze; ThT: thioflavin T.

TGF-ß-induced fibrotic stress increases G-quadruplex formation in human fibroblasts.

Scar formation after wound healing is a major medical problem. A better understanding of the dynamic nuclear architecture of the genome during wound healing could provide insights into the underlying pathophysiology and enable novel therapeutic strategies. Here, we demonstrate that TGF-ß-induced fibrotic stress increases formation of the dynamic secondary DNA structures called G-quadruplexes in skin fibroblasts, which is coincident with increased expression of collagen 1. This G-quadruplex formation is attenuated by a small molecule inhibitor of intracellular Ca2+ influx and an anti-fibrotic compound. In addition, we identify G-quadruplex-forming sequences in the promoter region of COL1A1, which encodes collagen 1, and confirm their ability to form G-quadruplex structures under physiologically relevant conditions. Our findings reveal a link between G-quadruplexes and scar formation that may lead to novel therapeutic interventions.

Determination of kinetic constants of hybrid textile wastewater treatment system.

The present study is related to treatment of textile wastewater in microaerophilic-aerobic hybrid reactor. The study showed the effectiveness of biological treatment of wastewater involving appropriate microorganism and suitable reactors. COD and color were reduced to 82-94%, and 99% respectively for textile wastewater. The reactor was operated at highest loading of 16.4 g COD g l(-1)d(-1) and obtained 80% COD and 72% color removal. Biokinetic models were applied to data obtained from experimental studies in continuously operated hybrid reactor. Treatment efficiencies of the reactor were investigated at different hydraulic retention times (2.3-9.1d) and organic loading rates (2.6-16.4 g COD l(-1)d(-1)). Second-order and a Stover-Kincannon models were best fitted to the hybrid column reactor. The second-order substrate removal rate constant (k(2(S))) was found as 41.44 d(-1) for hybrid reactor. Applying the modified Stover-Kincannon model to the hybrid reactor, the maximum removal rate constant (U(max)) and saturation value constant (K(B)) were found to be 212 g l(-1)d(-1) and 22.89 g l(-1)d(-1), respectively.