Effectiveness analysis of antipsychotics in schizophrenia using psychometric scales: an observational study

Background: Schizophrenia is a commonest and one of the well known psychiatric disorders. Life expectancy of a patient with schizophrenia may be 20 to 30 years shorter than the general population. Long term antipsychotic therapy is usually required for the management of schizophrenia. It is not currently possible to predict which antipsychotic may be optimal for a given patient because there are still many debates about effectiveness and efficacy of atypical drugs over first generation antipsychotics. So, our aim is to assess the effectiveness of various antipsychotics by using various psychometric scales, which will be helpful to bring out better treatment options for schizophrenia patients.Methods: This was an observational questionnaire based study, conducted on patients of inpatient and outpatient Department of Psychiatry and Department of Pharmacology at VIMSAR, Burla, for a period of 24 months (September 2015 to August 2017). Patients of schizophrenia aged 18 years or above were subjected to clinical global impression – severity scale (CGI-S) and clinical global impression – improvement scale (CGI-I) questionnaire after taking informed consent. Then scores were calculated using non parametric test with Graph pad Prism version 6.0.Results: Out of the 90 cases, majority (60) of patients belonged to the middle (25 to 45 yrs) age group followed by 20 younger (45 yrs) patients. Both scales showed significant improvement with atypical antipsychotics as compared to first generation antipsychotics.Conclusions: Based on these findings, we can conclude that atypical antipsychotics are more effective than first generation antipsychotics. But further studies are needed to assist clinicians in making optimum treatment decisions

Salinity Ingress in Phreatic Aquifer of Coastal Maharashtra State, India

Maharashtra is a coastal state on the west coast of India where six out of thirty five districts, namely Palghar, Thane, Raigad, Ratnagiri, Sindhudurg and Greater Mumbai are maritime. Being coastal area, the immediate effect of high groundwater development is sea water intrusion. Hence, an analysis was carried out to decipher the extent of salinity intrusion of the shallow coastal aquifer in the coastal Maharashtra. The study was conducted with the objective to assess the extent of contamination of groundwater in the phreatic aquifers in the tidal backwater limits and adjacent to coast and estuaries. Geochemical characteristics, extent of salinity intrusion, drinking and irrigation suitability of the groundwater of the area were also assessed. Total 162 ground water samples from coastal part of Maharashtra were subjected to chemical analysis for 15 basic parameters during the month of May 2017. In order to differentiate and confirm the sea water intrusion, various ionic ratios like Ca:Mg, Na:Cl, Cl:CO3 + HCO3, were computed. Wilcox Diagram, EC Vs Cl plots, Pipers Trilinear diagram etc were also plotted for the interpretation of the results. Groundwater in the study area is mildly alkaline with pH range of 6.9 to 9.0 and electrical conductivity range from 61 to 29370 μS/cm. In general, water quality is good and suitable for domestic and irrigation uses. Though salinity can be imparted to groundwater in many ways, in the current study area it is mainly due to sea water ingress and waste water including industrial effluents. From the analysis it is found that about 2 to 10 km area from the coast and the inland tidal backwaters are affected from salinity intrusion. Over-exploitation of groundwater, low seaward freshwater flow in rivers etc are the major reasons for sea water ingression. Regulation of groundwater development in the coastal area and adjacent to estuaries, maintaining adequate stream flow and stopping of river bed sand mining, construction of tidal regulators at suitable places and creating fresh water barrier through rainwater harvesting and groundwater recharge are essential to control further sea water intrusion in the area

Innate adaptive immune cell dynamics in tonsillar tissues during chronic SIV infection

HIV-infected patients are at higher risk of developing oral mucosal infection and Epstein–Barr virus (EBV)-associated B cell malignancies. However, the potential role of oral immunity in the pathogenesis of oral lesions is unknown. Tonsils are oral-pharyngeal mucosal-associated lymphoid tissues that play an important role in oral mucosal immunity. In this study, we investigated the changes of innate and adaptive immune cells in macaque tonsils during chronic SIV infection. We found significantly higher frequencies of classical monocytes, CD3+CD56+ (NKT-like) cells, CD3+CD4+CD8+ (DP), and CD161+ CD4 T cells in tonsils from chronic infected compared to naïve animals. On the contrary, intermediate monocytes and CD3+CD4-CD8- (DN) cells were lower in chronic SIV-infected macaques. We further confirmed a recently described small B-cell subset, NKB cells, were higher during chronic infection. Furthermore, both adaptive and innate cells showed significantly higher TNF-α and cytotoxic marker CD107a, while IL-22 production was significantly reduced in innate and adaptive immune cells in chronic SIV-infected animals. A dramatic reduction of IFN-γ production by innate immune cells might indicate enhanced susceptibility to EBV infection and potential transformation of B cells in the tonsils. In summary, our observation shows that the SIV-associated immune responses are distinct in the tonsils compared to other mucosal tissues. Our data extends our understanding of the oral innate immune system during SIV infection and could aid future studies in evaluating the role of tonsillar immune cells during HIV-associated oral mucosal infections

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Association of Cytokine Gene Polymorphisms in Patients with Chronic Obstructive Pulmonary Disease

Objective: Chronic obstructive pulmonary disease (COPD) is a major health problem. The disease is driven by abnormal inflammatory reactions in response to inhaled particles and fumes. Therefore, inflammatory mediators are postulated to be of distinct importance. Keeping in view of the above facts; we investigate the role of polymorphisms of cytokine genes in the genetic predisposition of COPD.Methods: In this present case-control study, the allele and genotype distributions of IL1B, IL1RN, TNF-α, and IL4 were studied in COPD patients (N=204) and healthy individuals (N=208). Genomic DNA was obtained by whole blood and genotyping was carried out by a polymerase chain reaction (PCR) based Restriction Fragment Length Polymorphism technique.Results: Genotype IL1RN*2/IL1RN*2 was identified as protective for male COPD, its frequency being 8.7% in COPD patients and 14.6% in healthy subjects (p=0.017; OR=0.53), but IL1RN*1/IL1RN*2 turned out to be a risk factor for females COPD. No significant differences were found between the groups of COPD patients and healthy subjects concerning the genotype frequencies of the polymorphisms T (-511) C of IL1B and 70bp VNTR of IL-4. Genotype GA of the TNF-α polymorphism G (-308) A was more common in the COPD patients than in the controls (20.5% vs.14.4%; p=0.107), and allele A was significantly associated with COPD patients (p=0.023; OR=0.65).Conclusion: IL-1RN *2 allele appears to be significantly associated with the COPD female patients and TNF-α-308A allele is a risk factor for the development of COPD

Evaluation of Groundwater Quality and its Suitability Assessment for Drinking and Agriculture purposes in Vidarbha Region of Maharashtra, India

Water is an excellent solvent and can contain lots of dissolved chemicals. Since groundwater moves through rocks and subsurface soil, it has a lot of opportunity to dissolve substances as it moves. For that reason, groundwater will often have more dissolved substances than surface water will. To assess the groundwater quality of the Vidarbha Region of Maharashtra State, the present study was conducted in the month of May 2019. Total 345 groundwater samples were collected from all the eleven districts of the Vidarbha region and analysed for 11 water quality indicative parameters viz. pH, Electrical Conductance, Total Dissolved Solids, Total hardness, Sodium, Potassium, Total Alkalinity, Chloride, Sulphate, Nitrate and Fluoride. Selected chemical indices were also calculated viz. Calcium Hardness, Sodium Absorption Ratio, Residual Sodium Carbonate, Soluble Sodium Percentage, Permeability Index and Kelly’s Ratio. More than 95 percent of the ground water samples were found to be fit for drinking, irrigation and other purposes

Comparison of CD3e Antibody and CD3e-sZAP Immunotoxin Treatment in Mice Identifies sZAP as the Main Driver of Vascular Leakage

Anti-CD3-epsilon (CD3e) monoclonal antibodies (mAbs) and CD3e immunotoxins (ITs) are promising targeted therapy options for various T-cell disorders. Despite significant advances in mAb and IT engineering, vascular leakage syndrome (VLS) remains a major dose-limiting toxicity for ITs and has been poorly characterized for recent “engineered” mAbs. This study undertakes a direct comparison of non-mitogenic CD3e-mAb (145-2C11 with Fc-silentTM murine IgG1: S-CD3e-mAb) and a new murine-version CD3e-IT (saporin–streptavidin (sZAP) conjugated with S-CD3e-mAb: S-CD3e-IT) and identifies their distinct toxicity profiles in mice. As expected, the two agents showed different modes of action on T cells, with S-CD3e-mAb inducing nearly complete modulation of CD3e on the cell surface, while S-CD3e-IT depleted the cells. S-CD3e-IT significantly increased the infiltration of polymorphonuclear leukocytes (PMNs) into the tissue parenchyma of the spleen and lungs, a sign of increased vascular permeability. By contrast, S-CD3e-mAbs-treated mice showed no notable signs of vascular leakage. Treatment with control ITs (sZAP conjugated with Fc-silent isotype antibodies) induced significant vascular leakage without causing T-cell deaths. These results demonstrate that the toxin portion of S-CD3e-IT, not the CD3e-binding portion (S-CD3e-mAb), is the main driver of vascular leakage, thus clarifying the molecular target for improving safety profiles in CD3e-IT therapy

Pseudomonas aeruginosa pulmonary infection results in S100A8/A9-dependent cardiac dysfunction.

Pseudomonas aeruginosa (P.a.) infection accounts for nearly 20% of all cases of hospital acquired pneumonia with mortality rates >30%. P.a. infection induces a robust inflammatory response, which ideally enhances bacterial clearance. Unfortunately, excessive inflammation can also have negative effects, and often leads to cardiac dysfunction with associated morbidity and mortality. However, it remains unclear how P.a. lung infection causes cardiac dysfunction. Using a murine pneumonia model, we found that P.a. infection of the lungs led to severe cardiac left ventricular dysfunction and electrical abnormalities. More specifically, we found that neutrophil recruitment and release of S100A8/A9 in the lungs activates the TLR4/RAGE signaling pathways, which in turn enhance systemic inflammation and subsequent cardiac dysfunction. Paradoxically, global deletion of S100A8/A9 did not improve but aggravated cardiac dysfunction and mortality likely due to uncontrolled bacterial burden in the lungs and heart. Our results indicate that P.a. infection induced release of S100A8/9 is double-edged, providing increased risk for cardiac dysfunction yet limiting P.a. growth