Activated Protein C Ameliorates Tubular Mitochondrial Reactive Oxygen Species and Inflammation in Diabetic Kidney Disease

Diabetic kidney disease (DKD) is an emerging pandemic, paralleling the worldwide increase in obesity and diabetes mellitus. DKD is now the most frequent cause of end-stage renal disease and is associated with an excessive risk of cardiovascular morbidity and mortality. DKD is a consequence of systemic endothelial dysfunction. The endothelial-dependent cytoprotective coagulation protease activated protein C (aPC) ameliorates glomerular damage in DKD, in part by reducing mitochondrial ROS generation in glomerular cells. Whether aPC reduces mitochondrial ROS generation in the tubular compartment remains unknown. Here, we conducted expression profiling of kidneys in diabetic mice (wild-type and mice with increased plasma levels of aPC, APChigh mice). The top induced pathways were related to metabolism and in particular to oxidoreductase activity. In tubular cells, aPC maintained the expression of genes related to the electron transport chain, PGC1-α expression, and mitochondrial mass. These effects were associated with reduced mitochondrial ROS generation. Likewise, NLRP3 inflammasome activation and sterile inflammation, which are known to be linked to excess ROS generation in DKD, were reduced in diabetic APChigh mice. Thus, aPC reduces mitochondrial ROS generation in tubular cells and dampens the associated renal sterile inflammation. These studies support approaches harnessing the cytoprotective effects of aPC in DKD

Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism

Procoagulant extracellular vesicles (EV) and platelet activation have been associated with gestational vascular complications. EV-induced platelet-mediated placental inflammasome activation has been shown to cause preeclampsia-like symptoms in mice. However, the effect of EV-mediated placental thrombo-inflammation on trophoblast differentiation remains unknown. Here, we identify that the EV-induced thrombo-inflammatory pathway modulates trophoblast morphology and differentiation. EVs and platelets reduce syncytiotrophoblast differentiation while increasing giant trophoblast and spongiotrophoblast including the glycogen-rich cells. These effects are platelet-dependent and mediated by the NLRP3 inflammasome. In humans, inflammasome activation was negatively correlated with trophoblast differentiation marker GCM1 and positively correlated with blood pressure. These data identify a crucial role of EV-induced placental thrombo-inflammation on altering trophoblast differentiation and suggest platelet activation or inflammasome activation as a therapeutic target in order to achieve successful placentation

Möjliggör rättvis smärthantering : Förstå könsbias i smärtbedömning och design för rättvis vård

The healthcare field, just like any industry which is driven by people, their interactions and decisions, is affected by the social norms and biases. Historically being centred around the average white male, the healthcare structure, systems and process are not equitable. Pain Management is not an exception either, and with pain’s subjective nature, the road to equitable care delivery is longer. Pain and gender have a complex relation, and pain being a universal shared experience sees several gender norms established around it. Women’s pain has been disregarded for a very long tagging it is as hysteria and attributing their physical pain to psychological reasons. With lesser research on the female body, women being seen as weaker and emotional gender, and often blurred understanding of sex and gender lead to delayed and improper pain management for women. The work presented in this study captures how these biases exist and affect both the actors’ (patients and healthcare professionals (HCPs)) behaviours and actions throughout the pain management journey thus leading to a down-streaming effect on the treatment delivered. Service design approach with qualitative research methods has been used in the project to bring out the factors, enablers and impact of the bias existing in the pain management process. The insights and findings are used to establish a clear understanding of the entire pain assessment process which is summarised as perception-communication-assessment model in the work, with a focus on both the main actors and their interaction. Based on the findings, concepts were designed to enable an equitable delivery that aims at changing the decisions and actions of the patients and HCPs for a more gender intentional process. Further evaluation led to a final solution space with a focus on patients’ understanding of their own pain and enabling clearer communication with HCP thus bringing more trust to the process.Sjukvårdsområdet, precis som alla branscher som drivs av människor, deras interaktioner och beslut, påverkas av sociala normer och fördomar. Historiskt sett är vårdstrukturen, system och processer inte rättvis, eftersom den är centrerad kring den genomsnittliga vita mannen. Smärtbehandling är inte ett undantag, och med smärtans subjektiva natur är vägen till rättvis vård längre. Smärta och kön har en komplex relation, och eftersom smärta är en universell delad upplevelse etableras flera könsnormer kring det. Kvinnors smärta har förbisetts under lång tid och då benämnts som hysteri och kvinnors fysiska smärta har tillskrivits psykologiska skäl. Med avsaknad av forskning om den kvinnliga kroppen där kvinnor ses som ett svagare och känslomässigt kön, och ofta med en suddig förståelse för kön har detta lett till felaktig smärtbehandling för kvinnor. Arbetet som presenteras i denna studie fångar hur dessa fördomar existerar och påverkar båda aktörernas (patienter och vårdpersonal (health care professionals, HCP)) beteenden och handlingar under hela smärtbehandlingsresan vilket leder till en nedströmseffekt på den behandling som levereras. En tjänstedesignansats med kvalitativa forskningsmetoder har använts i projektet för att få fram faktorerna, möjliggörarna och effekterna av den bias som finns i smärtbehandlingsprocessen. Insikterna och fynden används för att skapa en tydlig förståelse för hela smärtbedömningsprocessen som sammanfattas som perception-kommunikation-bedömningsmodell i arbetet, med fokus på båda huvudaktörerna och deras interaktion. Baserat på resultaten utformades koncept för att möjliggöra en rättvis smärtbedömningsprocess som syftar till att förändra patienters och hälsovårdares beslut och handlingar för en mer könsinriktad process. Ytterligare utvärdering ledde till ett slutgiltigt förslag med fokus på patienternas förståelse för sin egen smärta och möjliggör tydligare kommunikation med HCP vilket möjliggör mer förtroende till processen

Möjliggör rättvis smärthantering : Förstå könsbias i smärtbedömning och design för rättvis vård

The healthcare field, just like any industry which is driven by people, their interactions and decisions, is affected by the social norms and biases. Historically being centred around the average white male, the healthcare structure, systems and process are not equitable. Pain Management is not an exception either, and with pain’s subjective nature, the road to equitable care delivery is longer. Pain and gender have a complex relation, and pain being a universal shared experience sees several gender norms established around it. Women’s pain has been disregarded for a very long tagging it is as hysteria and attributing their physical pain to psychological reasons. With lesser research on the female body, women being seen as weaker and emotional gender, and often blurred understanding of sex and gender lead to delayed and improper pain management for women. The work presented in this study captures how these biases exist and affect both the actors’ (patients and healthcare professionals (HCPs)) behaviours and actions throughout the pain management journey thus leading to a down-streaming effect on the treatment delivered. Service design approach with qualitative research methods has been used in the project to bring out the factors, enablers and impact of the bias existing in the pain management process. The insights and findings are used to establish a clear understanding of the entire pain assessment process which is summarised as perception-communication-assessment model in the work, with a focus on both the main actors and their interaction. Based on the findings, concepts were designed to enable an equitable delivery that aims at changing the decisions and actions of the patients and HCPs for a more gender intentional process. Further evaluation led to a final solution space with a focus on patients’ understanding of their own pain and enabling clearer communication with HCP thus bringing more trust to the process.Sjukvårdsområdet, precis som alla branscher som drivs av människor, deras interaktioner och beslut, påverkas av sociala normer och fördomar. Historiskt sett är vårdstrukturen, system och processer inte rättvis, eftersom den är centrerad kring den genomsnittliga vita mannen. Smärtbehandling är inte ett undantag, och med smärtans subjektiva natur är vägen till rättvis vård längre. Smärta och kön har en komplex relation, och eftersom smärta är en universell delad upplevelse etableras flera könsnormer kring det. Kvinnors smärta har förbisetts under lång tid och då benämnts som hysteri och kvinnors fysiska smärta har tillskrivits psykologiska skäl. Med avsaknad av forskning om den kvinnliga kroppen där kvinnor ses som ett svagare och känslomässigt kön, och ofta med en suddig förståelse för kön har detta lett till felaktig smärtbehandling för kvinnor. Arbetet som presenteras i denna studie fångar hur dessa fördomar existerar och påverkar båda aktörernas (patienter och vårdpersonal (health care professionals, HCP)) beteenden och handlingar under hela smärtbehandlingsresan vilket leder till en nedströmseffekt på den behandling som levereras. En tjänstedesignansats med kvalitativa forskningsmetoder har använts i projektet för att få fram faktorerna, möjliggörarna och effekterna av den bias som finns i smärtbehandlingsprocessen. Insikterna och fynden används för att skapa en tydlig förståelse för hela smärtbedömningsprocessen som sammanfattas som perception-kommunikation-bedömningsmodell i arbetet, med fokus på båda huvudaktörerna och deras interaktion. Baserat på resultaten utformades koncept för att möjliggöra en rättvis smärtbedömningsprocess som syftar till att förändra patienters och hälsovårdares beslut och handlingar för en mer könsinriktad process. Ytterligare utvärdering ledde till ett slutgiltigt förslag med fokus på patienternas förståelse för sin egen smärta och möjliggör tydligare kommunikation med HCP vilket möjliggör mer förtroende till processen

Template security analysis of multimodal biometric frameworks based on fingerprint and hand geometry

Biometric systems are automatic tools used to provide authentication during various applications of modern computing. In this work, three different design frameworks for multimodal biometric systems based on fingerprint and hand geometry modalities are proposed. An analysis is also presented to diagnose various types of template security issues in the proposed system. Fuzzy analytic hierarchy process (FAHP) is applied with five decision parameters on all the designs and framework 1 is found to be better in terms of template data security, templates fusion and computational efficiency. It is noticed that template data security before storage in database is a challenging task. An important observation is that a template may be secured at feature fusion level and an indexing technique may be used to improve the size of secured templates

Correlation of Vitamin D3, Insulin-Like Growth Factor 1 and Insulin Resistance in Pre-Diabetes and Newly Diagnosed Type 2 Diabetes

Background: Vitamin D deficiency is implicated in the pathogenesis of diabetes mellitus, and more importantly, in the progression of 'pre-diabetes' to overt diabetes mellitus. Alterations in circulating insulin-like growth factor 1 (IGF-1) levels to defects in insulin secretion from beta cells. IGF-1 increases 1,25(OH)D level in vitro by stimulating 1α-hydroxylase expression. Interaction between vitamin D and the IGF-1 system provides an explanation of why hypovitaminosis D levels lead to Insulin resistance. This study aims to find the role of vitamin D and IGF-1 in pre-diabetic individuals and their role in the progression of pre-diabetes to clinically overt diabetes mellitus. Methods: The observational study was done in the Department of Medicine and Department of Biochemistry, ABVIMS & PGIMER, Dr. RML Hospital, New Delhi, after Ethical approval from the institutional review board (IRB). Ninety study participants were enrolled, which included 30 pre-diabetics, 30 newly diagnosed type-2 diabetics, and 30 healthy controls. Results: Vitamin D levels decreased as the insulin resistance (homeostatic model assessment for insulin resistance [HOMA-IR] score) increased and this negative correlation between vitamin D levels and HOMA-IR was significant in pre-diabetic (p = 0.001) and the newly diagnosed diabetics group (p = 0.011), but not in the controls group (p = 0.067). Whereas, vitamin D and IGF-1 levels showed a similar positive correlation when compared amongst the three groups. The positive association between vitamin D and IGF-1 was statistically significant (p = 0.0012). Conclusions: Thus, vitamin D and IGF-1 levels should be measured in all individuals with dysglycemia, whether pre-diabetic or overt type 2 diabetic. And, if vitamin D insufficiency/deficiency is found, it should be corrected adequately in these patients. Although, a large population-based study is needed for the same

Hydrochemical assessment of groundwater quality in the Narmada River Basin (Central India)

This study details the hydrochemical characterization and human health risk assessment of groundwater in the Narmada River Basin. The study was performed based on data collected from 305 groundwater sample stations in the Narmada River Basin. Hydrochemical evaluation illustrated that cationic ions in the upper and middle Narmada Basin were dominated by Ca2+; however, in the lower basin it was dominated by Na+ ions. Similarly, anionic ions were dominated by HCO3− throughout the basin. A Chadha plot drawn from the collected data inferred that most groundwater belonged to the recharge water category (Ca-Mg-HCO3 type). Base-exchange indices of the collected data confirmed the presence of Na+-SO42− type of groundwater. Meteoric genesis indices indicated deep meteoric percolation groundwater. Further, Gibbs plots categorized groundwater samples in the rock dominated section, while chloro-alkaline indices confirmed direct as well as reverse ion-exchange reactions governing groundwater quality. Water Quality Index values showed that groundwater ranged from excellent to very poor. Human health risk of the Narmada River confirmed the non-carcinogenic risk for Nitrate (NO3−) and Fluoride (F−) ions. However, several indices justified that groundwater was ideal for irrigation. However, groundwater treatment is recommended before direct consumption such as drinking. HIGHLIGHTS Both reverse and direct ion exchange reactions and rock weathering govern the groundwater quality.; Dominance of Na+-SO42− type and deep meteoric percolation types of groundwater.; The Water Quality Index (WQI) ranges from excellent to very poor categories.; A non-carcinogenic risk due to nitrate and fluoride contamination was confirmed.

In-vitro cancer cell cytotoxicity and alpha amylase inhibition effect of seven tropical fruit residues

Objective: To determine quantitative phytochemical, anticancer and antidiabetic effect of seven Indian tropical fruit residues. Methods: In-vitro cytotoxic activity (IC50) was evaluated against cervical cancer cells (HeLa), breast cancer cells (MCF-7), hepatocellular carcinoma cells (HepG-2) and bone sarcoma cells (MG-63) and alpha amylase inhibition assay was used for antidiabetic activity. Results: Results of phytochemical analysis revealed that all residues contained remarkable amount of alkaloid, saponin, tannin and flavonoid. Notable cancer cell growth inhibition was observed for the extract from Carissa carandas pomace and Litchi sinensis seeds with IC50 values ranged from 56.72 to 89.24 μg/mL. Alpha amylase inhibition assay was measured at six different concentrations (5, 10, 25, 50, 100 and 200 mg/mL) by using different solvent extract. Results showed that Carissa carandas possessed best activity with IC50 value as 29.66 mg/mL followed by other residues in methanol extract. Conclusions: Study suggests that these fruit residues demonstrate promising antidiabetic and anticancer activity that substantiated its ethno medicinal use and may provide new molecules for the treatment of these diseases