Assessment of Risk Factors for Development of Type-II Diabetes Mellitus Among Working Women in Berhampur, Orissa

Objectives:

1) Assess general health condition and anthropological parameters of the working women. 2) Identify prevalence of Type-II Diabetes among them. 3) Assess risk factors associated with development of diabetes. 4) Educate them about Life Style Modifications.

Materials and Methods:

A cross sectional study was carried out in six educational institutes. A total of 100 working women were selected as study population. During the two-month study period, Fasting Blood Sugar (FBS) was estimated to identify the diabetics and the Impaired Glucose Tolerance (IGT). Information from the study population was collected through pre-tested questionnaire using several anthropometric measurements.

Results:

Out of 100 women, 24 were having FBS compatible with IGT or diabetes. The incidence was highest in 46 to 55 yr age group. 75% of women with diabetes or IGT were in higher income group. Body Mass Index was more than 25 kg/m² in maximum (75%) women having diabetes or IGT. 92% women with diabetes or IGT had their Waist Hip Ratio ≥0.85. Moreover, orientation towards healthy life style modification to control diabetes and its prevention was poor among the study population.

Conclusion:

Prevalence of diabetes and IGT was higher among urban working women and is increasing with increase in age. Obesity plays a major role in development of Type 2 diabetes. Several long- and short-term steps should be taken for promotion of healthy life style modifications to prevent diabetes and emergence of its complications.     

A newly identified deletion of 970 bp at the alpha-globin locus that removes the promoter region of the alpha1 gene

The most common causes of alpha-thalassemia (thal) are deletions that remove a part, or one or both of the functional alpha-globin genes. These deletions cause diminished expression of the alpha-globin protein, which may result in relatively low hemoglobin (Hb) and/or mean corpuscular volume (MCV) values. We here report the identification of a 970 bp deletion in the alpha1-globin gene that encompasses the entire promoter region of the alpha1-globin gene and 26 bp encoding the 5' end of the mRNA. Thus, the affected alpha1-globin gene is prone to be nonfunctional. We therefore nominated the newly identified deletion allele alpha-alphaDelta970. The MCV values of four related carriers of the alpha-alphaDelta970 allele were slightly lowered, consistent with the presence of three functional alpha-globin genes.     

Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients

BACKGROUND: The contribution of ascorbate to urinary oxalate is controversial. The present study aimed to determine whether urinary oxalate and pH may be affected by vitamin C supplementation in calcium stone-forming patients. METHODS: Forty-seven adult calcium stone-forming patients received either 1 g (N=23) or 2 g (N=24) of vitamin C supplement for 3 days and 20 healthy subjects received 1 g. A 24-hour urine sample was obtained both before and after vitamin C for calcium, oxalate, magnesium, citrate, sodium, potassium, and creatinine determination. The Tiselius index was used as a calcium oxalate crystallization index. A spot fasting morning urine sample was also obtained to determine the urinary pH before and after vitamin C. RESULTS: Fasting urinary pH did not change after 1 g (5.8 +/- 0.6 vs. 5.8 +/- 0.7) or 2 g vitamin C (5.8 +/- 0.8 vs. 5.8 +/- 0.7). A significant increase in mean urinary oxalate was observed in calcium stone-forming patients receiving either 1 g (50 +/- 16 vs. 31 +/- 12 mg/24 hours) or 2 g (48 +/- 21 vs. 34 +/- 12 mg/24 hours) of vitamin C and in healthy subjects (25 +/- 12 vs. 39 +/- 13 mg/24 hours). A significant increase in mean Tiselius index was observed in calcium stone-forming patients after 1 g (1.43 +/- 0.70 vs. 0.92 +/- 0.65) or 2 g vitamin C (1.61 +/- 1.05 vs. 0.99 +/- 0.55) and in healthy subjects (1.50 +/- 0.69 vs. 0.91 +/- 0.46). Ancillary analyses of spot urine obtained after vitamin C were performed in 15 control subjects in vessels with or without ethylenediaminetetraacetic acid (EDTA) with no difference in urinary oxalate between them (28 +/- 23 vs. 26 +/- 21 mg/L), suggesting that the in vitro conversion of ascorbate to oxalate did not occur. CONCLUSION: These data suggest that vitamin C supplementation may increase urinary oxalate excretion and the risk of calcium oxalate crystallization in calcium stone-forming patients.     

Metabolic and immune-sensitive contacts between lipid droplets and endoplasmic reticulum reconstituted in vitro

Coordinated cell function requires a variety of subcellular organelles to exchange proteins and lipids across physical contacts that are also referred to as membrane contact sites. Such organelle-to-organelle contacts also evoke interest because they can appear in response to metabolic changes, immune activation, and possibly other stimuli. The microscopic size and complex, crowded geometry of these contacts, however, makes them difficult to visualize, manipulate, and understand inside cells. To address this shortcoming, we deposited endoplasmic reticulum (ER)-enriched microsomes purified from rat liver or from cultured cells on a coverslip in the form of a proteinaceous planar membrane. We visualized real-time lipid and protein exchange across contacts that form between this ER-mimicking membrane and lipid droplets (LDs) purified from the liver of rat. The high-throughput imaging possible in this geometry reveals that in vitro LD–ER contacts increase dramatically when the metabolic state is changed by feeding the animal and also when the immune system is activated. Contact formation in both cases requires Rab18 GTPase and phosphatidic acid, thus revealing common molecular targets operative in two very different biological pathways. An optical trap is used to demonstrate physical tethering of individual LDs to the ER-mimicking membrane and to estimate the strength of this tether. These methodologies can potentially be adapted to understand and target abnormal contact formation between different cellular organelles in the context of neurological and metabolic disorders or pathogen infection.

Lipid droplets (LDs) are triglyceride-rich cellular organelles that act as an energy depot, a reservoir for membrane biosynthesis, and a location where proteins are sequestered in response to specific stimuli (1–3). These functions require LDs to be dynamic, wherein the LDs exchange proteins and lipids with the endoplasmic reticulum (ER), mitochondria, peroxisomes, endosomes, and other organelles via physical contacts (4, 5). Abnormal LD–organelle interactions are implicated in neurological disease, metabolic disorder, fatty liver, and pathogen infection (5–7). Multispectral imaging showed that LD–ER contacts are the most promiscuous, with the ER contacting a majority of LDs (∼85%) irrespective of their location inside the cell (8). Accordingly, many researchers have used cell culture models to extract a wealth of information on the factors that sustain ER–LD contacts (1, 9–11). Most of these assays aim to understand the biogenesis of LDs, which is now well accepted to proceed through a triglyceride-rich, lens-like structure that expands in the ER lumen, eventually forming mature LDs on the cytosolic side of the ER lumen. Proteins such as seipin, sorting nexins (Snx14), and the NRZ-SNARE complex are required to sustain ER–LD contacts during these steps of LD-biogenesis (12–14).As an alternate line of investigation to these previous studies, we have attempted to address the physiologically relevant mechanisms that catabolize LDs inside mammalian liver to produce very-low-density lipoproteins (VLDL). We proposed that LD catabolism and ER–LD interactions are enhanced several-fold in the liver after feeding the animal (15, 16). Feeding stimulates insulin release, whereafter insulin activates the ARF1-GTPase and phospholipase-D to generate phosphatidic acid (PA) on the LD membrane. PA directly binds to kinesin-1 and recruits this motor to LDs. Kinesin induces rapid transport of LDs along microtubules to peripheral regions of the ER in hepatocytes, where ER–LD contacts likely form for catabolizing LDs and for delivering the resultant triglyceride to the ER lumen for assembling VLDL (15, 16). This entire pathway is toned down when insulin levels drop after fasting, causing ER–LD contacts to diminish and the liver to sequester LDs in a fasted state to protect other organs from lipotoxicity. Indeed, disrupting this homeostatic pathway caused massive accumulation of triglycerides in cardiac and skeletal tissue with potentially harmful consequences (15). In another exciting development, LDs were found to be a hub for immune activation in the liver, wherein the LDs could harbor and deliver antibacterial proteins for killing bacteria (3). It appeared to us that immune activation also promotes intimate ER–LD contacts in the liver (see supplementary figure 6 in ref. 3). We therefore wondered if LDs in liver cells first acquire antibacterial proteins from the ER via ER–LD contacts before these proteins can be used by the LDs to kill bacteria. Notably, this possibility was not explored by Bosch et al. (3). Two very different kinds of stimuli, namely feeding and immune activation, may therefore induce ER–LD contacts in the liver. Because the liver is a key player in lipid metabolism and systemic immune response, we saw an opportunity to understand how ER–LD contacts are modulated in the animal to serve physiologically important functions outside the well-understood and widely studied pathway of LD biogenesis.To address these questions, we developed an assay to deposit ER-enriched microsomes purified from rat liver, and also from cultured cells, on a coverslip in the form of an ER-mimicking planar membrane hereafter called the microsomal supported lipid bilayer (mSLB). We demonstrate that LDs purified from rat liver adhere to the mSLB via physical contacts, across which lipids and proteins are exchanged. Our results suggest formation of LD–mSLB fusion intermediates that mediate this exchange. In line with the above-discussed findings (3, 15), LD–mSLB contacts are dramatically enhanced after feeding or immune activation, thus bringing out their native-like nature and physiological relevance. Taking advantage of this in vitro assay, we show that the Rab18 GTPase and PA are common molecular players that engineer LD–mSLB contacts after feeding as well as after immune activation. This assay opens up possibilities to understand, in a controlled, in vitro environment, the molecular pathways that sustain LD–ER contacts in processes other than LD biogenesis. If adapted to other organelles, it may provide a tool to interrogate metabolic disorder, fatty liver, pathogen infection, and other human diseases arising out of abnormal organelle-to-organelle contact formation of diverse kinds.     

Reduced lymphocyte response to mitogens in patients with Bancroftian filariasis

Peripheral blood lymphocytes from patients with acute and chronic Wuchereria bancrofti infections responded poorly to concanavalin A, phytohaemagglutinin and pokeweed mitogen when cultured in heat-inactivated pooled normal serum. The lymphocyte response to mitogens in carriers of microfilariae (mff) were normal. The suppression of transformation to mitogens was not reversible by the removal of plastic adherent cells. Incubation with mitogens and the adult filarial worm antigen (BmA) did not alter the mitogen response either in control subjects or in filarial patients. The possible mechanism of immunosuppression is discussed.     

Multiscale neural signatures of major depressive,anxiety, and stress-related disorders

The extent of shared and distinct neural mechanisms underlying major depressive disorder (MDD), anxiety, and stress-related disorders is still unclear. We compared the neural signatures of these disorders in 5,405 UK Biobank patients and 21,727 healthy controls. We found the greatest case–control differences in resting-state functional connectivity and cortical thickness in MDD, followed by anxiety and stress-related disorders. Neural signatures for MDD and anxiety disorders were highly concordant, whereas stress-related disorders showed a distinct pattern. Controlling for cross-disorder genetic risk somewhat decreased the similarity between functional neural signatures of stress-related disorders and both MDD and anxiety disorders. Among cases and healthy controls, reduced within-network and increased between-network frontoparietal and default mode connectivity were associated with poorer cognitive performance (processing speed, attention, associative learning, and fluid intelligence). These results provide evidence for distinct neural circuit function impairments in MDD and anxiety disorders compared to stress disorders, yet cognitive impairment appears unrelated to diagnosis and varies with circuit function.

Major depressive disorder (MDD) and anxiety disorders (i.e., generalized anxiety disorder and panic disorder without agoraphobia) are highly comorbid psychiatric disorders (1–3), with shared epidemiologic, developmental, and genetic features (4, 5), and are among the leading causes of disability worldwide (6). Depression and anxiety are often triggered by stressful life events, thus sharing the etiology of stress-related disorders that are defined by occurrence of a severe stressor or trauma (7). More specifically, posttraumatic stress disorder (PTSD) is characterized by hyperarousal states during recurring flashbacks to the stressful event, while stress adjustment disorder is characterized by depressive symptoms in response to a severe stressor (7). Unlike MDD and anxiety disorders, which are recurrent or chronic, stress adjustment disorder resolves within 6 mo after termination of the stressor. While considerable neurobiological research has been conducted at a disorder-specific level, few studies have investigated a broad spectrum of MDD, anxiety, and stress disorders to examine shared and distinct neural correlates.Task-based functional MRI (fMRI) findings point to disrupted emotional processing and executive dysfunction, exemplified by disrupted cognitive control (8, 9), across a variety of disorders, including but not limited to MDD and anxiety disorders. Similarly, gray matter reductions have been shown in the insular and anterior cingulate cortices across mood, anxiety, and other disorders (10, 11). Many of these similarities in brain structure have been shown to be partially attributable to similarities in common variant architectures (12), encouraging the consideration of genetic risk measures in studies of intermediate imaging phenotypes for psychiatric illness. Polygenic liability for psychiatric disorders can be quantified using polygenic risk scores (PRSs), which are predictive of disease progression (13) and often transdiagnostically informative (14, 15). Therefore, parsing transdiagnostic phenotypes that capture the shared and distinct genetic, neurobiological, and cognitive basis of symptoms presenting across disorders could have utility in improving psychiatric nosology (16).Inferior prefrontal and insular cortex, the inferior parietal lobule, and the putamen are hypoactivated in task-based fMRI paradigms across MDD, anxiety disorders, and stress-related disorders (17), implicating inhibitory control and salience processing as shared neural phenotypes underlying these disorders. Impairments in executive functions such as inhibitory control over emotional reactivity and negative mood may capture a transdiagnostic dimension of psychopathology (18, 19). Executive function is also impaired by anxiety, which reduces cognitive flexibility, working memory (20), and attentional control (21). While some evidence also supports executive dysfunction in PTSD (22, 23), psychological theories of posttraumatic stress typically emphasize the effects of the traumatic event on memory (24, 25). Executive dysfunction may be linked to both dysregulated mood in MDD and heightened emotional reactivity in anxiety disorders (26) and thus provides a promising transdiagnostic treatment target.Here we leveraged multimodal data from the UK Biobank to determine unique and shared features of brain structure and function in MDD, anxiety disorders (ANX), and stress-related disorders (STR), as well as the relationship of such neuroimaging measures to several aspects of cognitive function across these disorders. The UK Biobank includes midlife and older adults and is thus also suitable for investigating cognition in the context of aging with and without MDD, anxiety, and stress-related disorders. We selected trail making performance (27), digit–symbol substitution (28), fluid intelligence (29), and paired associate learning (PAL) (30) to measure key domains of cognitive function, expecting executive function and processing speed impairments in MDD and anxiety disorders and memory deficits in stress-related disorders. We used second-order statistical comparisons to investigate genetic and environmental contributions to disorder similarity. We expected to find default mode and frontostriatal connectivity differences in MDD (31) and anxiety disorders (32, 33), resulting in shared neural signatures. We also hypothesized reduced cortical thickness of the frontoparietal regions in both MDD and anxiety disorders (34–36) and a separate neural signature of stress-related disorders focused on the hippocampal regions (37). Given varying degrees of shared genetic liability for our selected disorders and our interest in disentangling their overlapping vs. discrete neural signatures, we anticipated that controlling for disease-specific PRS would impact the correlation of cross-disorder neural signatures, providing insight into nature vs. nurture components of these intermediate phenotypes. Finally, we expected connectivity of frontoparietal (FPN), attention, and default mode networks (DMN) to underlie cognitive performance across disorders.