BackgroundFor antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events.MethodsIn a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART.FindingsA total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar.InterpretationEarly initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability.Trial registrationCTRI/2011/12/002260

Background Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin. Methods In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD). Results Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.

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Background: Postmortem interval estimation is an important tool in forensic medicine. Estimating time since death is extremely important in cases where there is doubt about the period of death. After death, many changes occur in a regular sequence and can be used to arrive at an approximate time since death. When a post-mortem is conducted, doctor conducting the post-mortem examination has to give his opinion about post-mortem interval i.e. the probable time that elapsed between death and post-mortem examination even in cases of decomposed dead bodies. While giving this opinion, we always think we should have some other dependable methods to be more accurate in answering this question. Algor mortis, Rigor mortis, and Livor mortis have been the basis for ascertaining the post-mortem interval collectively. Among them, Rigor Mortis is an important indicator of post-mortem interval. Although it is a dependable tool for estimating post-mortem interval, it is influenced by many endogenous and exogenous factors like nature of death, nature of the body, temperature, humidity etc. Time of death is almost always asked by investigating authorities to connect the crime with criminals. Determining the death time has always been a topic of keen interest amongst forensic pathologists from its inception to date. Many workers in forensic medicine have tried to investigate to determine the time of death based on post mortem findings. To date, it is still an important and fascinating criterion to ascertain the time since death. With this study, we aimed to demonstrate the intricacies of Rigor Mortis with fluctuating temperature and humidity of the local region. We planned to estimate and compare the post-mortem interval based on Rigor Mortis in different body muscles. Materials and Methods: This study was conducted in the Department of Forensic Medicine and Toxicology at G.G.S. Medical College, Faridkot after taking clearance from the institutional ethics committee. Thirty medico-legal autopsy cases were included in the study where the exact time of death was known and included only hospital deaths. The relatives of the deceased were explained the purpose and nature of the study and provided with the patient information sheet and informed consent was taken. The details of the cases were noted from the hospital bed head ticket, relative interview and the police inquest papers. The exact temperature and humidity were noted at the start of autopsy using a digital hygrometer. Results: A total of 30 cases were observed out of which males outnumbered the females by approximately 3:1. Maximum cases consisted of Roadside Accidents (43.3%) followed by poisoning, assault and hanging, in that order. The average temperatures during the study months varied from a maximum of 41.3°C (June) to a minimum of 33.7°C (July). The average humidity varied from a maximum of 62.6% (July) to a minimum of 29.3% (May). The average temperatures during the study months varied from a maximum of 41.3°C (June) and a minimum of 33.7°C (July). The average humidity during the study months varied from a maximum of 62.6 % (July) and a minimum of 29.3% (May). Fully established Rigor Mortis was observed at a minimum of 10 hours and a maximum of 29 hours in May and June.

Background: Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin.Methods: In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSCs) derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSCs-derived EVs. Lung tissue was subjected to histological analysis using hematoxylin and eosin staining, alcian blue-periodic acid Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t-test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median±standard deviation (SD).Results: Both, transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, as well as a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions: In conclusion, we show that hUC-MSCs-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free based therapy for the treatment of COPD.