Histomorphological evaluation of colon lesions

Background: Both macroscopic and microscopic appearance helps in identification of the colon lesion which supports in the treatment of the patient in a better way. The authors were aimed at the prevalence of various colon lesions site wise distribution of various neoplastic and non-neoplastic lesions of the patients and to compare the distribution according to their age, sex and site.Methods: A retrospective study was designed to study of various intestinal biopsies sent for histopathological examination at Department of Pathology, N.H.L. Municipal Medical College and V.S. Hospital, Ahmedabad, from January 2015 to December 2016 for period of 2 years. The study was based on the histomorphological evaluation of colon lesions received during the study period.Results: A male preponderance was seen in the incidence of tumors irrespective of tumor type and site of tumor and M:F ratio was 1.64:1. In the large intestine, adenocarcinomas were the commonest malignant tumor. 46 cases (62.61%) were reported. The highest occurrence of appendicitis is in the 2nd and 3rd decade.Conclusions: The study revealed that various types of lesions in large intestine along with the age group and gender affected more. Male patients were majorly affected. Morphological identification helped to diagnose the type of lesion for early diagnosis. This study focuses the role of histopathological identification in early diagnosis of the disease so that the survival rates in such cases will be increased

Diabetic foot resulting in amputation: our experience

Background: The aim of our study was to early diagnosis of diabetic foot so that the complications can be prevented, to control the systemic infection and prevent the complications, to study the effectiveness of regular dressing in diabetic foot so as to prevent the local spread of infection and the ulcer and to conclude that early diagnosis, care and proper meticulous treatment of diabetic foot can prevent amputation. Methods: The present study was prospective, observational and longitudinal. Protocol of the procedure was formed along with Performa, Patient Information Sheet, Informed Consent Form and approval from Ethical Committee. The present study was carried out in surgery department of C.U Shah medical college, Surendranagar; Gujarat state. The study was carried out from 1st August 2011 to 30th September 2013. A total of one hundred patients admitted in surgery ward with diabetes type 1 or 2 with ulcer on foot having grade 1 or 2 of Wagner’s classification without any other co morbid condition. These patients undergo daily dressing with various dressing solutions according to their ulcer characteristics. All the patients given diet/oral hypoglycaemic drug/insulin for control of diabetes. Antibiotics given according to the infective status of the patients. Patients were either completely treated, went under skin grafting or ended up with amputation were recorded.Results: Of 100 cases studied, youngest patient was 32 years and oldest was 80 years of age. Highest number of cases was found in the age group 61-70 years (30%). Of the 100 cases studied in this series 36 (36%) patient were having Wagner’s class 1 ulcer and 64 (64%) patient having class 2 ulcers. Of 100 cases, various surgical treatment given to the patients according to the ulcer. In that 65(65%) debridement, 20 (20%) Incision & drainage, 10 (10%) STG, 5 (5%) fasciotomy. Most of the patients were undergone basic surgical procedure which is debridement on the 7th day follow up, out of 100 cases 70 patients came for follow up. Out of 70, all patients having healing ulcer. Out of 70 patients, 15(21.43%) patients were underwent STG on 15th day and other 55 (71.57%) patients having healing ulcer advised daily dressing with follow up after 1 week. Out of 30 patients, 3 (10%) patients underwent amputation on 7th day of follow up. On the 15th day new 5 (16.67%) patients underwent amputations, so total number of amputation done till date was 8 (26.67%). On 21st day, new 7 (23.34%) patients were underwent amputations and total number of amputations till date were 15 (50%). On 30th day, new 15 (50%) patients underwent amputations.Conclusions: Foot ulceration in diabetic patients is a resource consuming, disabling morbidity that often is the first step towards lower extremity amputation. Prevention is the best treatment.

Usefulness of gene expression profiling of bronchoalveolar lavage cells in acute lung allograft rejection.

BackgroundChronic lung allograft dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Because effective therapies are lacking, early identification and mitigation of risk factors is a pragmatic approach to improve outcomes. Acute cellular rejection (ACR) is the most pervasive risk factor for CLAD, but diagnosis requires transbronchial biopsy, which carries risks. We hypothesized that gene expression in the bronchoalveolar lavage (BAL) cell pellet (CP) could replace biopsy and inform on mechanisms of CLAD.MethodsWe performed RNA sequencing on BAL CPs from 219 lung transplant recipients with A-grade ACR (n = 61), lymphocytic bronchiolitis (n = 58), infection (n = 41), or no rejection/infection (n = 59). Differential gene expression was based on absolute fold difference >2.0 and Benjamini-adjusted p-value ≤0.05. We used the Database for Annotation, Visualization and Integrated Discovery Bioinformatics Resource for pathway analyses. For classifier modeling, samples were randomly split into training (n = 154) and testing sets (n = 65). A logistic regression model using recursive feature elimination and 5-fold cross-validation was trained to optimize area under the curve (AUC).ResultsDifferential gene expression identified 72 genes. Enriched pathways included T-cell receptor signaling, natural killer cell-mediated cytotoxicity, and cytokine-cytokine receptor interaction. A 4-gene model (AUC = 0.72) and classification threshold defined in the training set exhibited fair performance in the testing set; accuracy was 76%, specificity 82%, and sensitivity 60%. In addition, classification as ACR was associated with worse CLAD-free survival (hazard ratio = 2.42; 95% confidence interval = 1.29-4.53).ConclusionsBAL CP gene expression during ACR is enriched for immune response pathways and shows promise as a diagnostic tool for ACR, especially ACR that is a precursor of CLAD

Gene Expression Profiling of Bronchoalveolar Lavage Cells Preceding a Clinical Diagnosis of Chronic Lung Allograft Dysfunction.

BackgroundChronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects.MethodsIn a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n = 9) and CLAD free (n = 8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression analysis, based on an absolute fold change (incipient CLAD vs no CLAD) >2.0 and an unadjusted p-value ≤0.05, generated a candidate list containing 55 differentially expressed probe sets (51 up-regulated, 4 down-regulated).ResultsThe cell pellets in incipient CLAD cases were skewed toward immune response pathways, dominated by genes related to recruitment, retention, activation and proliferation of cytotoxic lymphocytes (CD8+ T-cells and natural killer cells). Both hierarchical clustering and a supervised machine learning tool were able to correctly categorize most samples (82.3% and 94.1% respectively) into incipient CLAD and CLAD-free categories.ConclusionsThese findings suggest that a pathobiology, similar to AR, precedes a clinical diagnosis of CLAD. A larger prospective investigation of the BAL cell pellet transcriptome as a biomarker for CLAD risk stratification is warranted

Medicinal chemistry advances in targeting class I histone deacetylases

Histone deacetylases (HDACs) are a class of zinc (Zn)-dependent metalloenzymes that are responsible for epigenetic modifications. HDACs are largely associated with histone proteins that regulate gene expression at the DNA level. This tight regulation is controlled by acetylation [via histone acetyl transferases (HATs)] and deacetylation (via HDACs) of histone and non-histone proteins that alter the coiling state of DNA, thus impacting gene expression as a downstream effect. For the last two decades, HDACs have been studied extensively and indicated in a range of diseases where HDAC dysregulation has been strongly correlated with disease emergence and progression—most prominently, cancer, neurodegenerative diseases, HIV, and inflammatory diseases. The involvement of HDACs as regulators in these biochemical pathways established them as an attractive therapeutic target. This review summarizes the drug development efforts exerted to create HDAC inhibitors (HDACis), specifically class I HDACs, with a focus on the medicinal chemistry, structural design, and pharmacology aspects of these inhibitors

Developing the Next Generation of Entrepreneurs: Giving Students the Opportunity to Gain Experience and Thrive

Higher Education Institutions (HEIs) have increasingly utilized experiential approaches in business education; however, some researchers have suggested that further research is required to investigate the effectiveness and student reaction to such approaches. The aim of this study is to determine the impact of an experiential learning approach on the perceived development of entrepreneurial traits and to measure the level of both student engagement and satisfaction. The approach was designed and tested during a Higher National Diploma (HND) entrepreneurship module in a British HEI. Traditional taught sessions were blended with applied activities that required students to utilize the skills they learned to complete steps of the activities, which increased in length and complexity. Results found both a high level of student satisfaction and engagement and the belief that the module’s experiential approach had, in many instances, helped to develop entrepreneurial traits. Successful practice and modifications are discussed

Will the Snow Balls Ever Melt?

Resident case conference

SHIVGAMI : Simplifying tHe titanIc blastx process using aVailable GAthering of coMputational unIts

Assembling novel genomes from scratch is a never ending process unless and until the homo sapiens cover all the living organisms! On top of that, this denovo approach is employed by RNASeq and Metagenomics analysis. Functional identification of the scaffolds or transcripts from such drafted assemblies is a substantial step routinely employes a well-known BlastX program which facilitates a user to search DNA query against NCBI-Protein (NR:~120Gb) database. In spite of having multicore-processing option, blastX is an elongated process for the bulk of lengthy Queryinputs. Tremendous efforts are constantly being applied to solve this problem by increasing computational power, GPU-Based computing, Cloud computing and Hadoop based approach which ultimately requires gigantic cost in terms of money and processing. To address this issue, here we have come up with SHIVGAMI, which automates the entire process using perl and shell scripts, which divide, distribute and process the input FASTA sequences as per the CPU-cores availability amongst the computational units individually. Linux operating system, NR database and blastX program installations are prerequisites for each system.  The beauty of this stand-alone automation program SHIVGAMI is it requires the LAN connection exactly twice: During ‘query distribution’ and at the time of ‘proces completion’. In initial phase, it divides the fasta sequences according to the individual computer's core-capability. Then it will evenly distribute all the data along with small automation scripts which will run the blastX process to the respective computational unit and send back the results file to the master computer. The master computer finally combines and compiles the files into a single result. This simple automation converts a computer lab into a GRID without investment of any software, hardware and man-power. In short, SHIVGAMI is a time and cost savior tool for all users starting from commercial firm to a common man, utilises the "Little Drops of Water make a Mighty Ocean" concept without any requirement of parallel processing. The automation and compilation of SHIVGAMI is under process and will be freely available shortly to the users