Life Events as Risk Factors for Myocardial Infarction: A Pilot Case-control Study in Kolkata, India

This case-control study was conducted in the Cardiology Department of Medical College, Kolkata, India, during 2000-2001, to explore the link between stressful life events and subsequent myocardial infarction (MI). One hundred consecutive confirmed MI patients were selected as a case group. One hundred age-, sex- and income-matched controls were selected from visitors other than relatives who attended these patients. The subjects were interviewed and asked to rate 61 life events with a number between 0 and 20. They also noted which of these they had experienced in the last one year. The main exposure variables included life events as per E.S. Paykel, smoking, alcohol consumption, chewing of tobacco, marital status, literacy, employment, and monthly per-capita income. The results showed that an MI patient was likely to experience 4.16 stressful life events, which were twice as much as the control group (2.24). The total stress score was the highest for serious personal illness followed by illness of family members and unemployment for the MI patients. For the controls, conflict between husband and wife, death of friends, and personal illness had the highest total stress score. The mean stress score for the MI patients was 35.5 compared to 17.35 among the controls. The MI subjects were more likely to have experienced stressful life events than the controls

ASSESSMENT OF OCCUPATIONAL STRESSES AMONG POLICE OFFICERS WHO IMPART TEACHING IN POLICE TRAINING COLLEGE, WEST BENGAL

ABSTRACT According to the Anshel (2000) police work has been regarded as one of the stressful occupations in the world. Police force provides continuous service to the people. The police force has to serve around the clock for proper investigation, safety and justice. All police personnel have to prepare for responding efficiently and properly even for the unforeseen and unpredictable incidents. But only a few studies were carried out in India in ergonomic point of view. The present study was conducted to evaluate the psycho-physiological characteristics and occupational stress of police officers who were teaching in police training college as a teacher and have a huge experience of stress in police station jobs. Apart from questionnaire study, psychological study was conducted to evaluate occupational stresses of police officers. Data was analyzed into computer by using statistical software for SPSS version 16.0 for the analyzing mean, standard deviation, upper and lower limit, agglomeration schedule. Cluster analysis, factor analysis, correlation and multiple regressions. After analyzing the data it was found that high ratings for stressors were contact with criminals, lack of a modern system, boring daily duty, lack of resource etc. Study also revealed that many stressors were correlated to each other. Regression model showed that lack of modern system, negatives criticisms to police are responsible for heavy work load and stresses. On the contrary temptation for taking bribe is there to reduce the score of heavy work load and stresses

Life Events as Risk Factors for Myocardial Infarction: A Pilot Case-control Study in Kolkata, India

This case-control study was conducted in the Cardiology Department of Medical College, Kolkata, India, during 2000-2001, to explore the link between stressful life events and subsequent myocardial infarction (MI). One hundred consecutive confirmed MI patients were selected as a case group. One hundred age-, sex- and income-matched controls were selected from visitors other than relatives who attended these patients. The subjects were interviewed and asked to rate 61 life events with a number between 0 and 20. They also noted which of these they had experienced in the last one year. The main exposure variables included life events as per E.S. Paykel, smoking, alcohol consumption, chewing of tobacco, marital status, literacy, employment, and monthly per-capita income. The results showed that an MI patient was likely to experience 4.16 stressful life events, which were twice as much as the control group (2.24). The total stress score was the highest for serious personal illness followed by illness of family members and unemployment for the MI patients. For the controls, conflict between husband and wife, death of friends, and personal illness had the highest total stress score. The mean stress score for the MI patients was 35.5 compared to 17.35 among the controls. The MI subjects were more likely to have experienced stressful life events than the controls

NOTCH pathway inactivation reprograms stem-like oral cancer cells to JAK-STAT dependent state and provides the opportunity of synthetic lethality

Background: We have recently provided the evidence of interconvertible cellular states, driving non-genetic heterogeneity among stem-like oral cancer cells (oral-SLCCs). Here, NOTCH pathway-activity status is explored as one of the possible mechanisms behind this stochastic plasticity. Methods: Oral-SLCCs were enriched in 3D-spheroids. Constitutively-active and inactive status of NOTCH pathway was achieved by genetic or pharmacological approaches. RNA sequencing and real-time PCR was performed for gene expression studies. in vitro cytotoxicity assessments were performed by AlamarBlue assay and in vivo effects were studied by xenograft growth in zebrafish embryo. Results: We have observed stochastic plasticity in oral-SLCCs, spontaneously maintaining both NOTCH-active and inactive states. While cisplatin refraction was associated with post-treatment adaptation to the active-state of NOTCH pathway, oral-SLCCs with inactive NOTCH pathway status showed aggressive tumor growth and poor prognosis. RNAseq analysis clearly suggested the upregulation of JAK-STAT pathway in NOTCH pathway-inactive subset. The 3D-spheroids with lower NOTCH-activity status displayed significantly higher sensitivity to JAK-selective drugs, Ruxolitinib or Tofacitinib or siRNA mediated downregulation of tested partners STAT3/4. Oral-SLCCs were programmed to adapt the inactive status of NOTCH pathway by exposing to γ-secretase inhibitors, LY411575 or RO4929097, followed by targeting with JAK-inhibitors, Ruxolitinib or Tofacitinib. This approach resulted in a very significant inhibition in viability of 3D-spheroids as well as xenograft initiation in Zebrafish embryos. Conclusion: Study revealed for the first time that NOTCH pathway-inactive state exhibit activation of JAK-STAT pathways, as synthetic lethal pair. Therefore, co-inhibition of these pathway may serve as novel therapeutic strategy against aggressive oral cancer

Leishmania Promastigote Membrane Antigen-Based Enzyme-Linked Immunosorbent Assay and Immunoblotting for Differential Diagnosis of Indian Post-Kala-Azar Dermal Leishmaniasis

Diagnosis of post-kala-azar dermal leishmaniasis (PKDL), caused by Leishmania donovani, is difficult, as the dermal lesions are of several types and resemble those caused by other skin diseases, especially leprosy. Since the disease generally appears very late after the clinical cure of kala-azar in India, it is also difficult to correlate PKDL with a previous exposure to L. donovani. Very few attempts have been made so far to diagnose PKDL serologically, and the diagnostic methods vary in their sensitivities and specificities. Diagnosis of PKDL through sophisticated PCR methods, although highly sensitive, has limited practical use. We have developed a serodiagnostic method using an enzyme-linked immunosorbent assay to detect specific immunoglobulin (Ig) isotypes and IgG subclass antibodies in the sera of Indian PKDL patients. Our assay, which uses L. donovani promastigote membrane antigens, was 100% sensitive for the detection of IgG and 96.7% specific for the detection of IgG and IgG1. Optical density values for individual patients, however, demonstrated wide variations. Western blot analysis based on IgG reactivity could differentiate patients with PKDL from control subjects, which included patients with leprosy, patients from areas where kala-azar is endemic, and healthy subjects, by the detection of polypeptides of 67, 72, and 120 kDa. The recognition patterns of the majority of serum samples from patients with PKDL were also distinct from those of the serum samples from patients with visceral leishmaniasis (VL), at least for a 31-kDa polypeptide. To further differentiate patients with PKDL from those with active and cured VL, we analyzed the specific titers of the Ig isotypes and IgG subclasses. High levels of IgG, IgG1, IgG2, and IgG3 antibodies significantly differentiated patients with PKDL from patients cured of VL. The absence of antileishmanial IgE and IgG4 in patients with PKDL differentiated these patients from those with active VL. These results imply intrinsic differences in the antibodies generated in the sera from patients with PKDL and VL

NSAID targets SIRT3 to trigger mitochondrial dysfunction and gastric cancer cell death

Summary: Gastric cancer (GC) is a deadly malignancy that demands effective therapeutic intervention capitalizing unique drug target/s. Here, we report that indomethacin, a cyclooxygenase non-selective non-steroidal anti-inflammatory drug, arrests GC cell growth by targeting mitochondrial deacetylase Sirtuin 3 (SIRT3). Interaction study revealed that indomethacin competitively inhibited SIRT3 by binding to nicotinamide adenine dinucleotide (NAD)-binding site. The Cancer Genome Atlas data meta-analysis indicated poor prognosis associated with high SIRT3 expression in GC. Further, transcriptome sequencing data of human gastric adenocarcinoma cells revealed that indomethacin treatment severely downregulated SIRT3. Indomethacin-induced SIRT3 downregulation augmented SOD2 and OGG1 acetylation, leading to mitochondrial redox dyshomeostasis, mtDNA damage, respiratory chain failure, bioenergetic crisis, mitochondrial fragmentation, and apoptosis via blocking the AMPK/PGC1α/SIRT3 axis. Indomethacin also downregulated SIRT3 regulators ERRα and PGC1α. Further, SIRT3 knockdown aggravated indomethacin-induced mitochondrial dysfunction as well as blocked cell-cycle progression to increase cell death. Thus, we reveal how indomethacin induces GC cell death by disrupting SIRT3 signaling

Increased levels of interleukin‐10 and IgG3 are hallmarks of Indian Post–kala-azar dermal leishmaniasis

Background. Post-kala-azar dermal leishmaniasis (PKDL), an established sequela of visceral leishmaniasis (VL), is proposed to facilitate anthroponotic transmission of VL, especially during interepidemic periods. Immunopathological mechanisms responsible for Indian PKDL are still poorly defined. Methods. Our study attempted to characterize the immune profiles of patients with PKDL or VL relative to that of healthy control subjects by immunophenotyping, intracellular cytokine staining of peripheral blood mononuclear cells, and enzyme-linked immunosorbent assay for serum cytokines and immunoglobulin G (IgG) subclasses. Results. Patients with PKDL had significantly raised percentages of peripheral CD3+CD8+ cells compared with control subjects, a difference that persisted after cure. Patients with PKDL showed an intact response to phytohemagglutinin, with the percentages of lymphocytes expressing interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-10 being comparable to those in control subjects. Patients with VL had decreased IFN-γ and IL-2 expression, which was restored after cure, and increased IL-10 expression, which persisted after cure. In their response to Leishmania donovani antigen, patients with PKDL showed a 9.6-fold increase in the percentage of IL-10-expressing CD3+CD8+ lymphocytes compared with control subjects, and this percentage decreased with treatment. Patients with PKDL had raised levels of IgG3 and IgG1 (surrogate markers for IL-10), concomitant with increased serum levels of IL-10. Conclusions. IL-10-producing CD3+CD8+ lymphocytes are important protagonists in the immunopathogenesis of Indian PKDL

Growth of Germanium Thin Films on Sapphire Using Molecular Beam Epitaxy

Germanium films were grown on c-plane sapphire with a 10 nm AlAs buffer layer using molecular beam epitaxy. The effects of Ge film thickness on the surface morphology and crystal structure were investigated using ex situ characterization techniques. The nucleation of Ge proceeds by forming (111) oriented three-dimensional islands with two rotational twin domains about the growth axis. The boundaries between the twin grains are the origin of the 0.2% strain and tilt grains. The transition to a single-grain orientation reduces the strain and results in a better-quality Ge buffer. Understanding the role of thickness on material quality during the Ge(111)/Al2O3(0001) epitaxy is vital for achieving device quality when using group IV material on the sapphire platform