Distal thoracic oesophageal perforation secondary to blunt trauma: Case report

BACKGROUND: Traumatic perforation of the distal oesophagus due to blunt trauma is a very rare condition and is still associated with a significant morbidity and mortality. This is further exacerbated by delayed diagnosis and management as symptoms and signs are often masked by or ascribed to more common blunt thoracic injuries. CASE REPORT: We present a case of a distal oesophageal perforation, secondary to a fall from a third storey window, which was masked by concomitant thoracic injuries and missed on both computed tomography imaging and laparotomy. The delay in his diagnosis significantly worsened the patient's recovery by allowing the development of an overwhelming chest sepsis that contributed to his death. CONCLUSION: Early identification of an intrathoracic oesophageal perforation requires deliberate consideration and is essential to ensure a favorable outcome. Treatment should be individualised taking into account the nature of the oesophageal defect, time elapsed from injury and the patient's general condition

Synthesis of novel tetrapeptides as potential ACE inhibitors

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Current Scenario of Molecular Diagnostics in Indian Healthcare Sector

After successfully accomplishing the Human genome project and opening new avenues for genome based diagnostics and therapy in healthcare sector, development of personalized medicine and advancing molecular diagnostics has been the prime agenda of scientists all-round the globe. Molecular diagnostics has made possible the diagnosis of the previously undetected viral nucleic acids, early access of data to doctors, a deeper understanding of the disease cause, treatment dose and success of the treatment depending upon the case. It has provided an immense scope of novel and more sophisticated biotechnology and biomedical tools to be employed in the sector procreating a new interdisciplinary field. The gene based testing in all fields has flourished in leaps and bounds after the prediction of >5% in 2005. Here we discuss the current scenario, scope and limitations of the Molecular diagnostics in terms of its significance in public health care

A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases

A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.</p

Essential Role of PSM/SH2-B Variants in Insulin Receptor Catalytic Activation and the Resulting Cellular Responses

The positive regulatory role of PSM/SH2-B downstream of various mitogenic receptor tyrosine kinases or gene disruption experiments in mice support a role of PSM in the regulation of insulin action. Here, four alternative PSM splice variants and individual functional domains were compared for their role in the regulation of specific metabolic insulin responses. We found that individual PSM variants in 3T3-L1 adipocytes potentiated insulin-mediated glucose and amino acid transport, glycogenesis, lipogenesis, and key components in the metabolic insulin response including p70 S6 kinase, glycogen synthase, glycogen synthase kinase 3 (GSK3), Akt, CbI, and IRS-1. Highest activity was consistently observed for PSM alpha, followed by beta, delta, and gamma with decreasing activity. In contrast, dominant-negative peptide mimetics of the PSM Pro-rich, pleckstrin homology (PH), or src homology 2 (SH2) domains inhibited any tested insulin response. Potentiation of the insulin response originated at the insulin receptor (IR) kinase level by PSM variant-specific regulation of the K(m) (ATP) whereas the V(max) remained unaffected. IR catalytic activation was inhibited by peptide mimetics of the PSM SH2 or dimerization domain (DD). Either peptide should disrupt the complex of a PSM dimer linked to IR via SH2 domains as proposed for PSM activation of tyrosine kinase JAK2. Either peptide abolished downstream insulin responses indistinguishable from PSM siRNA knockdown. Our results implicate an essential role of the PSM variants in the activation of the IR kinase and the resulting metabolic insulin response. PSM variants act as internal IR ligands that in addition to potentiating the insulin response stimulate IR catalytic activation even in the absence of insulin

Smoking Rationalisation, Tobacco Dependence and Intention to Quit Among Indian Adults and Adolescents

Introduction: Unfortunately, indicators of tobacco dependence are present even after low levels of exposure in young smokers. Early emergence of these signal risk for subsequent chronic smoking and nicotine dependence is negatively associated with cessation in young adults. One important yet understudied modifiable predictor of intention to quit among smokers is smoking rationalization. Smokers often subscribe to smoking rationalisation beliefs, also known as self-exempting beliefs, to justify or rationalize their smoking behaviors. Smoking rationalizations can predict a lack of intention to quit. Objective: To assess the correlation between smoking rationalisation, tobacco dependence and intention to quit among Indian adults and adults. Methodology: A cross-sectional pilot study was carried out among 18–60-year-old subjects. Data were collected for tobacco dependence, smoking rationalisation and intention to quit (no/yes) by structured interview. Data were analysed using IBM SPSS statistics for windows, version 16 (IBM Corp, Armork, NY.) The independent t-test and one way ANOVA and binary logistic regression were performed for inferential statistics. Results: Smokers with no intention to quit and high tobacco dependence scores had significantly higher smoking rationalisation than those to quit and low dependence scores. Logistic regression models demonstrated that all types of rationalisation beliefs were consistently inversely associated with the intention to quit and low tobacco dependence. Conclusion: Findings suggest that smoking rationalisation plays an important role in the lack of intention to quit among Indian smokers. Future interventions should tackle smoking rationalisation beliefs as a strategy to promote smoking cessation

Chlorhexidine chip and tetracycline fibers as adjunct to scaling and root planing - A clinical study

Aim: Prevention of periodontal disease progression is the primary goal of periodontal therapy. When conventional therapy is found inadequate to attain periodontal health in chronic periodontitis, local antimicrobial agents have been used as adjunct to scaling and root planing, producing encouraging results. Hence, a study was undertaken to evaluate clinically, the newly released sustained drugs, PerioCol TM-CG (Chlorhexidine - CHX- chip) with Periodontal Plus AB TM (Tetracycline fibers). Methods: Patients were allocated in 3 experimental treatment groups, Group A- SRP + CHX Chip, Group B- SRP + Tetracycline fibers, and Group C- SRP alone (control group). Forty-five sites in 14 patients (9 females and 5 males) with chronic periodontitis (5-8mm probing depth), were evaluated clinically for probing depth (PD) and relative attachment level (RAL). Results: All the treatment groups were found to be efficacious in the treatment of periodontal disease as demonstrated by improvement in PD and RAL. Conclusion: Combination of SRP + CHX chip (Group A) resulted in added benefits compared to the other two treatment groups

cdg557 5712..5722

contributed equally to this work To understand the traf®cking of endocytosed hemoglobin (Hb) in Leishmania, we investigated the characteristics of in vitro fusion between endosomes containing biotinylated Hb (BHb) and avidin±horse-radish peroxidase (AHRP). We showed that early endosome fusion in Leishmania is temperature and cytosol dependent and is inhibited by ATP depletion, ATPgS, GTPgS and N-ethylmaleimide treatment. The Rab5 homolog from Leishmania donovani, LdRab5, was cloned and expressed. Our results showed that homotypic fusion between the early endosomes in Leishmania is Rab5 dependent. Early endosomes containing BHb fused ef®ciently with late endosomes in a process regulated by Rab7, whereas no fusion between early and late endosomes was detected usinḡ uid phase markers. Pre-treatment of early endosomes containing BHb with monoclonal antibody speci®c for the C-terminus of the Hb receptor (HbR) or the addition of the C-terminal cytoplasmic fragment of the HbR speci®cally inhibited the fusion with late endosomes, suggesting that signal(s) mediated through the HbR cytoplasmic tail promotes the fusion of early endosomes containing Hb with late endosomes