Analysis of factors influencing colostomy closure after low anterior resection for cancer rectum

Background: De-functioning colostomy or ileostomy is a procedure known worldwide as a protection measure to the rectal anatomises in low anterior resections and even some of anterior resections. Though the primary intention is a temporary one, many a times they end up in a permanent stoma. As the patients with stomas with attached bag appliances to their abdominal wall go through a lot of stress related to the quality of life and body image, they are always keen to get it closed as early as possible. Unfortunately, many factors come into play during and after the indexed surgery till the closure of stoma without any complication, prohibiting their early or even delayed closure.Methods: Authors here conducted a cohort study with retrospective data analysis and a prospective follow up patients in a tertiary care regional cancer centre from April 2011 to mid-June 2017. Statistical analysis was used by mean and percentage method.Results: Temporary colostomy was required in 88.37% of low anterior resections and some anterior resections. Most of those (92.11%) were transverse colostomy. Only 36.86% of those stomata were reversed. Four (10.83%) patients were dead by the end of the study. Twenty patients of stoma (52.63%) were not yet reversed and were deemed to continue with a permanent colostomy. This was found to be a very high figure as opposed to the literature of 9-25%. The reason behind this high figure was probably due to low general condition, lower socio-economic status, and low literacy prevailing in our patient population group. Moreover, the patient attendants and the surgeon himself also had played some role responsible for this situation.Conclusions: Patients should be told before initial rectal surgery that there is a risk of non-closure and possible complications associated with permanent stoma

Model Compression: Distilling Knowledge with Noise-based Regularization.

Deep Neural Networks give state-of-art results in all computer vision applications. This comes with the cost of high memory and computation requirement. In order to deploy State-of-art deep models in mobile devices, which have limited hardware resources, it is necessary to reduce both memory consumption and computation overhead of deep models. Shallow models t all these criteria but it gives poor accuracy while trained alone on training data set with hard labels. The only way to improve the performance of shallow networks is to train it with teacher-student algorithm where the shallow network is trained to mimic the response of a deeper and larger teacher network, which has high performance. The information passed from teacher to student is conveyed in the form of dark knowledge contained in the relative scores of outputs corresponding to other classes. In this work we show that adding random noise to teacher-student algorithm has good effect on the performance of shallow network. If we perturb the teacher output, which is used as target value for student network, we get improved performance. We argue that using randomly perturbed teacher output is equivalent to using multiple teachers to train a student. On CIFAR10 data set, our method gives 3.26% accuracy improvement over the baseline for a 3 layer shallow network

Lectins as possible candidates towards anti-microbial defense in silkworm, Bombyx mori L

Unlike vertebrates, insects do not have acquired immunity and therefore rely totally on innate immunity towards defense against invading microorganisms. Insect innate immunity consists of cellular and humoral reactions and both reactions work in concert in preventing insects acquiring infections. The most likely candidates for recognizing foreign material in insects are the lectins, which have already been shown to be important in mammalian innate immunity. Several reports of endogenous serum lectins having opsonic activity for invading pathogens have been circumstantiated in several insect specimens and therefore have been continuously explored for binding to wide range of microorganisms, obviating the necessity of antibodies in these animals. Silkworm, Bombyx mori L. is an important economic insect with unparalleled significance to the prosperity of weaker sections of the society and also has been promoted as a powerful laboratory model involving basic research in biology. It therefore merits immediate attention towards proper understanding of host-pathogen interactions, defensive mechanisms evolved in the host body in response to infection, anti-defensive molecules released by pathogen to suppress host immunity before reflecting on aspects of disease control. In this regard, lectins have been implicated as pattern recognition molecules serving as biosensors for detecting carbohydrate components on the microbial cells, thus triggering signaling cascade for immune activation. Understanding of such silkworm agglutinins, most specifically their binding specificities and pattern of recognition with identifiable gene families have been discussed towards establishment of its candidate role as immune defense molecules.Key words: Bombyx mori, lectins, innate immunity, carbohydrate-binding domains

PCR-SSCP and Sequencing of CXCR2 Receptor Gene in Vrindavani Cattle

Genetic markers associated with inflammatory responses during mastitis could aid in the selection of diseased cattle. One potential marker is CXCR2, a chemokine receptor required for neutrophil migration to infection sites. The objective of this experiment was to identify genetic polymorphism of CXCR2 gene and associate it with subclinical and clinical mastitis. Ninety five Vrindavani crossbred cows (42-mastitis tolerant and 53-clinical mastitis) that completed at least two full lactations were taken for study. Blood of selected crossbred cows was collected, and genomic DNA was isolated by phenol chloroform method. The DNA of good quality having OD ratio (260/280 nm) between 1.7-1.9 were used for further analysis. PCR-SSCP technique was used to reveal the polymorphism in 269bp fragments of CXCR2 gene. The 269 bp fragment of CXCR2 gene was found to be monomorphic in all the DNA samples of crossbred cows

P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages

Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is endemic in different parts of the globe. The host macrophages are identified as the major cellular reservoirs of CHIKV during infection and this virus triggers robust TNF production in the host macrophages, which might be a key mediator of virus induced inflammation. However, the molecular mechanism underneath TNF induction is not understood yet. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV to address the above-mentioned question. It was observed that CHIKV induces both p38 and JNK phosphorylation in macrophages in a time-dependent manner and p-p38 inhibitor, SB203580 is effective in reducing infection even at lower concentration as compared to the p-JNK inhibitor, SP600125. However, inhibition of p-p38 and p-JNK decreased CHIKV induced TNF production in the host macrophages. Moreover, CHIKV induced macrophage derived TNF was found to facilitate TCR driven T cell activation. Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. Further, it was demonstrated that CHIKV mediated TNF production in the macrophages is dependent on p38 and JNK MAPK pathways linking p-c-jun transcription factor. Interestingly, it was found that CHIKV nsP2 interacts with both p-p38 and p-JNK MAPKs in the macrophages. This observation was supported by the in silico protein-protein docking analysis which illustrates the specific amino acids responsible for the nsP2-MAPKs interactions. A strong polar interaction was predicted between Thr-180 (within the phosphorylation lip) of p38 and Gln-273 of nsP2, whereas, no such polar interaction was predicted for the phosphorylation lip of JNK which indicates the differential roles of p-p38 and p-JNK during CHIKV infection in the host macrophages. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. Hence, this information might shed light in rationale-based drug designing strategies toward a possible control measure of CHIKV infection in future

TLR4 is one of the receptors for Chikungunya virus envelope protein E2 and regulates virus induced pro-inflammatory responses in host macrophages

Toll like receptor 4 (TLR4), a pathogen-associated molecular pattern (PAMP) receptor, is known to exert inflammation in various cases of microbial infection, cancer and autoimmune disorders. However, any such involvement of TLR4 in Chikungunya virus (CHIKV) infection is yet to be explored. Accordingly, the role of TLR4 was investigated towards CHIKV infection and modulation of host immune responses in the current study using mice macrophage cell line RAW264.7, primary macrophage cells of different origins and in vivo mice model. The findings suggest that TLR4 inhibition using TAK-242 (a specific pharmacological inhibitor) reduces viral copy number as well as reduces the CHIKV-E2 protein level significantly using p38 and JNK-MAPK pathways. Moreover, this led to reduced expression of macrophage activation markers like CD14, CD86, MHC-II and pro-inflammatory cytokines (TNF, IL-6, MCP-1) significantly in both the mouse primary macrophages and RAW264.7 cell line, in vitro. Additionally, TAK-242-directed TLR4 inhibition demonstrated a significant reduction of percent E2-positive cells, viral titre and TNF expression in hPBMC-derived macrophages, in vitro. These observations were further validated in TLR4-knockout (KO) RAW cells. Furthermore, the interaction between CHIKV-E2 and TLR4 was demonstrated by immuno-precipitation studies, in vitro and supported by molecular docking analysis, in silico. TLR4-dependent viral entry was further validated by an anti-TLR4 antibody-mediated blocking experiment. It was noticed that TLR4 is necessary for the early events of viral infection, especially during the attachment and entry stages. Interestingly, it was also observed that TLR4 is not involved in the post-entry stages of CHIKV infection in host macrophages. The administration of TAK-242 decreased CHIKV infection significantly by reducing disease manifestations, improving survivability (around 75%) and reducing inflammation in mice model. Collectively, for the first time, this study reports TLR4 as one of the novel receptors to facilitate the attachment and entry of CHIKV in host macrophages, the TLR4-CHIKV-E2 interactions are essential for efficient viral entry and modulation of infection-induced pro-inflammatory responses in host macrophages, which might have translational implication for designing future therapeutics to regulate the CHIKV infection