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High-altitude hypoxia (HH) causes a spectrum of pathophysiological effects, including headaches, gliovascular dysfunction, and cognitive slowing. Previous studies have shown arachidonic acid (AA) metabolism due to cyclooxygenase (COX) activity before clinical manifestations in many diseases. AA metabolites, including COXs and prostaglandin E2 (PGE2), are well known immunomodulators. However, the relative contribution of COX-2 and COX-1 isoforms in the downstream proinflammatory responses and cognitive deficit in HH remains unknown. In the present study, AA metabolism via the COX pathway was investigated in Sprague Dawley rats after 0, 1, 3, and 7 days of HH exposure. Furthermore, we investigated the inflammatory response and cell-type-specific induction of both COXs. Our data revealed that AA metabolites peaked on day 3 of HH exposure. Interestingly, we observed endothelial and microglial activation on day 1, accompanied by an increase in the levels of proinflammatory cytokines, followed by astrocyte activation on day 3. We showed that the increase in COX activity during HH culminated in a significant increase in hippocampal inflammation, concomitant with spatial memory impairment and neuronal injury at day 7 of HH. We showed HH induced distinct COX-1 expression in endothelial and microglial cells, whereas it induced COX-2 expression predominantly in neurons, endothelial cells, and astrocytes. Notably, our data showed that the inhibition of COX-1 using valeryl salicylate had a prominent role in containing hippocampal inflammation by reducing microglial activation. COX-2 inhibition using celecoxib, along with COX-1 inhibition, ameliorated spatial memory impairment, astrocyte activation, and neurodegeneration after HH exposure.

In this paper we propose a feature extraction algorithm for classifying Coronary Artery Disease (CAD) patients from Photoplethysmogram (PPG) signals. Several domain-independent features, representing inherent properties of a time series are explored in our study. These are combined with Heart Rate Variability (HRV) and other popularly used morphological PPG features. A statistical feature selection algorithm, based on Maximal Information Coefficient (MIC) is applied on MIMIC II dataset for ranking and choosing the optimum features. A second hospital dataset of different patient demography is used for performance evaluation. Results show that, Support Vector Machine (SVM) classifier, designed using the selected features yields average sensitivity and specificity of more than 0.8 in identifying CAD patients and also outperforms two recent prior art approaches when applied on the test dataset.

Fear memory is essential for survival, and its dysregulation leads to disorders. High altitude hypobaric hypoxia (HH) is known to induce cognitive decline. However, its effect on fear memory is still an enigma. We aimed to investigate the temporal effect of HH on fear conditioning and the underlying mechanism. Adult male Sprague-Dawley rats were trained for fear conditioning and exposed to simulated HH equivalent to 25,000 ft for different durations (1, 3, 7, 14 and 21 days). Subsequently, rats were tested for cued and contextual fear conditioning. Neuronal morphology, apoptosis and DNA fragmentation were studied in the medial prefrontal cortex (mPFC), hippocampus and basolateral amygdala (BLA). We observed significant deficit in cued and contextual fear acquisition (at 1, 3 and 7 days) and consolidation (cued at 1 and 3 days and contextual fear at 1, 3 and 7 days) under HH. HH exposure with retraining showed the earlier restoration of contextual fear memory. Further, we found a gradual increase in the number of pyknotic and apoptotic neurons together with the increase in DNA fragmentation in mPFC, hippocampus, and BLA up to 7 days of HH exposure. The present study concludes that HH exposure equivalent to 25,000 ft induced cued and contextual fear memory deficit (acquisition and consolidation) which is found to be correlated with the neurodegenerative changes in the limbic brain regions.

In this article, we propose a method to assess the clinical usability of fingertip Photoplethysmogram (PPG) waveform, collected from medical grade oximeter (train data) and smartphone (test data). We introduce a set of novel Signal Quality Indices (SQIs) to represent the noise characteristics of the PPG waveform. The SQIs are presented to a random forest classifier to discriminate between clean and noisy signals. The proposed method was evaluated on datasets annotated by four experts, resulting into a sensitivity and specificity of (92 ± 4.7 %, 95 ± 3 %) and (82.6 ± 4.6 %, 95.4 ± 3.1 %) on train and test data respectively. Further we applied the proposed method on PPG waveform of clinically proven control and disease population of Coronary Artery Disease (CAD), which resulted into (77 %, 77 %) of sensitivity and specificity respectively.

Killer immunoglobulin-like receptor (KIR) gene shows a high degree of polymorphism. Natural killer cell receptor gets activated once they bind to self-human leukocyte antigens (HLAs) with specific ligand. KIR gene and HLA ligand incompatibility due to the presence/absence of KIR in the recipient and the corresponding HLA ligand in the allograft may impact graft survival in solid organ transplantation. This study evaluates the effect of matches between KIR genes and known HLA ligands. KIR genotypes were determined using sequence specific primer polymerase chain reaction. Presence of certain KIR in a recipient, where the donor lacked the corresponding HLA ligand was considered a mismatch. The allograft was considered matched when both KIR receptor and HLA alloantigen reveald compatibility among recipient and donor. The data revealed better survival among individuals with matched inhibitory KIR receptors and their corresponding HLA ligands (KIR2DL2/DL3-HLAC2, KIR3DL1-HLABw4). On the contrary, no adverse effect was seen for matched activating KIR receptors and their corresponding HLA ligands. One of the activating gene KIR2DS4 showed risk (P = 0.0413, odds ratio = 1.91, 95% confidence interval = 1.02-3.57) association with renal allograft rejection. We conclude that the presence of inhibitory KIR gene leads to better survival; whereas activating motifs show no significant role in renal allograft survival.

We aimed to investigate the glial cells activation as a potential mechanism involved in the sleep deprivation (SD) induced cognitive impairment through changes in inflammatory cytokines. We analyzed the spatial memory, inflammatory cytokine levels, and gliosis during SD. SD induced spatial memory impairment, imbalance of inflammatory (increased pro- and decreased anti-) cytokines in both hippocampus and plasma in association with glial cells activation in the hippocampus of sleep-deprived rats were observed. Further analysis of the data presented a correlation between spatial memory impairment and activated microglia induced increased pro-inflammatory cytokines after 48h of SD.

Introduction Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors (KIR) expressed on surface of natural killer cells and CD28 null T-cells which are present in synovial membrane of RA. The present study has evaluated associations of KIR genes with RA among North Indian population from Uttar Pradesh. Materials and methods KIR genotypes were determined in 100 RA cases and 100 healthy controls using sequence specific primer polymerase chain reaction (PCR-SSP) method. Results RA cases positive for KIR3DS1 (OR = 1.17, p-value = 0.0498) and KIR2DS2 (OR = 2.21, p-value = 0.0120) showed risk associations. While, KIR2DL2 (OR = 0.40, p-value = 0.0026), KIR2DL3 (OR = 0.44, p-value = 0.0283) and KIR3DL1 (OR = 0.32, p-value = 0.0012) showed protective associations. Increased incidence of BB genotype (45%) was revealed among cases. Risk association was noted against telomeric region (OR = 2.12, p = 0.0120) genes for RA. Pair-wise linkage disequilibrium (LD) analysis among RA cases revealed KIR2DS1-2DL1 (D′ = 0.83, r2 = 0.36), KIR3DL1-3DS1 (D′ = 1, r2 = 0.58) and KIR2DL1-2DL2 (D′ = 1, r2 = 0.61) to be in significant LD. KIR3DS1 and KIR2DS3 genes showed significant risk associations among RA patients with extra-articular manifestations (OR = 5.14, p-value = 0.0018; OR = 3.79, p-value = 0.0106) and in limited range of motion in affected joints (OR = 14.91, p-value = 0.0001; OR = 2.95, p-value = 0.0126). Conclusion The KIR activating genes have risk association with RA in the present study.

Introduction NK cell function is regulated by cell surface inhibitory and activating receptors including the C-type lectin receptors and Killer Immunoglobulin-like receptors (KIR). The effect of immune modulating cytokines produced by NK cells in the pathogenesis of end stage renal disease (ESRD) remained intriguing. In this regard the present study assesses the combinatorial association of KIR gene content and KIR receptor–HLA ligand in the North Indian ESRD patients. Material and methods KIR gene polymorphism as a susceptible marker in ESRD among 512 patients and 512 ethnically matched controls was analyzed. PCR-SSP based genotyping for KIR gene content and HLA-A, B, C typing was carried out. Results Significant difference in frequencies of KIR2DS1–HLA-C2 ( p ⩽ 0.0001, OR = 1.98, CI = 1.50–2.61), KIR2DS2–HLAC1 ( p ⩽ 0.0001, OR = 1.87, CI = 1.42–2.46), KIR3DS1–HLA-Bw4 ( p = 0.0038, OR = 1.46, CI = 1.13–1.88) combinations for ESRD was found. In the combinatorial analysis Bw4 + /3DL1 − /3DS1 + ( p ⩽ 0.0001, OR = 4.90, CI = 2.75–8.71) and C1 + /2DL2 − /2DL3 − /2DS2 + /2DS3 + ( p = 0.0037, OR = 2.50, CI = 1.35–4.63) showed risk association. KIR3DS1 was observed to be susceptible for all four primary kidney disease groups. Conclusion NK cell de-regulation due to HLA ligand binding KIR receptors may be involved in the patho-physiology of ESRD. Upon analyzing the data in this context it was found that C2/C2 donor might improve the clinical outcome of patients having C2 ligands.

An innovative approach was developed to solve the problem of setup planning, which is the most critical problem in process planning for discrete metal parts. Setup planning is the act of preparing detailed work instructions for setting up a part. The major objective of this research is to improve the performance of CAPP systems by developing a systematic approach to generate practical setup plans based on tolerance analysis. A comprehensive literature review on tolerance control in CAPP was conducted. It was found that tolerance chart analysis, a traditional tolerance control technique, is reactive in nature and can be greatly improved by solving the problem of setup planning. In order to develop a theoretically sound foundation for tolerance analysis-based setup planning, the problem of tolerance stack up in NC machining was analyzed in terms of manufacturing error analysis. Guidelines for setup planning were then developed based on the analysis. To systematically solve the setup planning problem, a graph theoretical setup planning algorithm for rotational parts was then developed for automated and integrated setup planning and fixture design. Its efficiency and effectiveness evaluated. The result is promising. The algorithms were then computerized. A setup planning program was developed under the Microsoft Windows environment using C.

Recently smartphones are used every area in day-to-day life. Smartphones comes with several built-in sensors like gyroscope, accelerometer etc., along with powerful processing units. There exist various frameworks which use mobile as sensing device and mobile sensors as data extractor and process extracted data to calculate various parameter. This processing unit can be resided either in mobile side or cloud side, which provides flexibility to the researcher/developer to reduce computation time by migrating processing unit and transferring data to the cloud side. This may create problem of packet dropping or network issue while transferring data to the cloud. To overcome network issue, we propose a common framework which maintains trade-off between network overhead and processing time. The key feature of proposed framework is dividing processing unit into mobile and cloud side, sends raw data to cloud after preprocessing at mobile side. This will take very low processing time and reduce raw data size, which reduces number of packets to send to the cloud. We investigate feasibility of our proposed framework by implementing and testing with several collaborative sensing applications and comparing with the existing framework. Our result shows promising result by trading off between on-board processing and network overhead across all the solutions we had tested.

Mobile smartphones have revolutionized the concept of mobile phones as different apps are built to offer various interesting applications in healthcare, gaming, etc. rather than using the phone only for voice services. The application developers take advantage of onboard sensors, web connectivity and powerful processing units of the smartphones to develop such interesting apps. In this paper, we present an interesting approach where direct acoustic coupling technique is employed to quickly and conveniently convert the smartphones into high quality digital stethoscope by using an ultra-low cost attachment. The design consideration primarily focused on affordability, simplicity and use-friendly aspects into account. The motivation of this work is to enable the heart patients to send their heart sound to doctor's chamber/ hospitals from their home instead of travelling all the way to hospitals/clinics. This is particularly useful in poor or developing countries where there is scarcity of healthcare centers and patients have to travel a long distance to visit the clinic. The situation becomes more serious in case of patients who went through heart surgery and requires follow up visits or for elderly population requiring routine checkups. For both the cases, in many instances, doctors primarily listen to the heart sound to prescribe further actions. Our solution can greatly help such situations and in many cases it can completely eliminate the travel. In addition, since data can also be recorded and saved, this opens up possibility for statistical analysis to further aid the diagnosis / monitoring. Thus, our solution can serve as a viable tool in connected health use cases for heart patients for needy geography.

We assessed the prevalence of post-kala-azar dermal leishmaniasis (PKDL), a late cutaneous manifestation of visceral leishmaniasis (VL), in 16 VL-endemic communities in Bihar, India. The prevalence of confirmed PKDL cases was 4.4 per 10 000 individuals and 7.8 if probable cases were also considered. The clinical history and treatment of the post-kala-azar dermal leishmaniasis cases are discussed.

Genes encoding KIR receptors are clustered in one of the most variable regions of the human genome. KIR gene frequencies vary in worldwide populations and reveal high probability of individuals differing in their gene content.This study aimed to investigate KIR diversity among the northern Indian population who share features with either Western Eurasian or East Asian populations. It sought to decipher how northern Indians are associated phylogenetically with global populations whilst also focusing on differentiation of populations.This paper studied 867 northern Indians using PCR-SSP. Gene and genotypic frequencies were calculated, using statistical analyses. Findings were compared against 76 global populations of differing ethnicities.This northern Indian population shared characteristics with Western Eurasian or Asian Indian populations, as is evident from genetic distance, clustered heatmap, phylogenetic assessment and principal component analysis. The findings are consistent with the demographic history of northern India, including specific features, such as presence of comparatively high KIR B-haplotype as compared to A-haplotype.KIR frequencies and profiles of northern Indians were more similar to Western Eurasians, Africans and Asian Indians. This may suggest that KIR genes are under constant evolutionary pressures and selection, which may be linked to different invading pathogens.

OBJECTIVE: To assess the prevalence of Post-kala-azar dermal leishmaniasis (PKDL) in 16 visceral leishmaniasis-endemic communities in Bihar, India. METHODS: Three-stage house-to-house survey of 2020 households to identify and confirm PKDL cases. RESULTS: The prevalence of confirmed PKDL cases was 4.4 per 10 000 individuals and 7.8 if probable cases were also considered. The clinical history and treatment of the PKDL cases are discussed in detail. CONCLUSION: PKDL can develop in visceral leishmaniasis patients treated with different anti-leishmanial drugs. Migration of PKDL cases to other villages may expand visceral leishmaniasis-affected areas.