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Representative examples of SVM separation score data selected from the 100 genes with the highest SVM scores using a random number generator. The x-axis shows the sample number; normal samples are on the left of each graph, tumour samples on the right separated by a red bar. The horizontal lines represent the means of the expression scores for the normal and tumour samples respectively.

Antibodies used and the conditions for immunohistochemistry.

The 5-year survival rate of esophageal cancer is less than 10% in developing countries, where more than 90% of these cancers are esophageal squamous cell carcinomas (ESCC). Endoscopic screening is undertaken in high incidence areas. Biomarker analysis could reduce the subjectivity associated with histologic assessment of dysplasia and thus improve diagnostic accuracy. The aims of this study were therefore to identify biomarkers for esophageal squamous dysplasia and carcinoma. A publicly available dataset was used to identify genes with differential expression in ESCC compared with normal esophagus. Each gene was ranked by a support vector machine separation score. Expression profiles were examined, before validation by qPCR and IHC. We found that 800 genes were overexpressed in ESCC compared with normal esophagus (P < 10−5). Of the top 50 genes, 33 were expressed in ESCC epithelium and not in normal esophagus epithelium or stroma using the Protein Atlas website. These were taken to qPCR validation, and 20 genes were significantly overexpressed in ESCC compared with normal esophagus (P < 0.05). TNFAIP3 and CHN1 showed differential expression with IHC. TNFAIP3 expression increased gradually through normal esophagus, mild, moderate and severe dysplasia, and SCC (P < 0.0001). CHN1 staining was rarely present in the top third of normal esophagus epithelium and extended progressively towards the surface in mild, moderate, and severe dysplasia, and SCC (P < 0.0001). Two novel promising biomarkers for ESCC were identified, TNFAIP3 and CHN1. CHN1 and TNFAIP3 may improve diagnostic accuracy of screening methods for ESCC. Cancer Prev Res; 9(7); 558–66. ©2016 AACR.

Abiotic stresses like heat, drought, and salinity are among the major threats to sustainable crop production. These stresses induce numerous adverse effects in plants by impairing biochemical, physiological and molecular processes, eventually affecting plant growth, development and productivity. The rising temperature is one of the major causes of heat stress in agriculture. The variation in temperature during crop development has led to devastating agricultural losses in terms of yield. To adapt and mitigate these effects, germplasm scientists and agronomists aim to develop heat-tolerant varieties or cultivars. These efforts generally include the identification of alleles responsible for heat tolerance and their introgression into breeding populations through conventional or biotechnological methods. However, heat tolerance is a very complex physio-biochemical response of plants governed by a number of genes positioned at different loci. The accumulation of various additive gene effects into a single genotype is an extremely tedious and time-consuming process in both plant breeding and biotechnology. Recent advancements in agricultural nanotechnology have raised expectations for sustainable productivity without altering the genetic make-up of plants. In this milieu, the application of biologically active nanoparticles (NPs) could be a novel approach to enhance heat tolerance in crops. Recently, the NPs from silver, silicon, titanium and selenium have been proven valuable for plants to combat heat stress by altering their physiological and biochemical responses. Due to nano-scale size and the high surface area along with their slow and steady release, the NPs exert positive effects in plants through their growth-promoting and antioxidant capabilities. In this review, various technologies used for NPs characterization and their applications in agriculture have been discussed. The review further elaborates the uptake mechanism of NPs and their translocation in different plant parts along with the factors affecting them. This article also describes the role of metal or metal oxide NPs, as well as nano, encapsulated plant growth regulators and signal molecules in heat stress tolerance. The review will provide an insight to the scientists working in the area of agricultural sciences to explore new NPs to encounter different types of biotic and abiotic stresses.

Background Intra-tumour heterogeneity has been well-described in oesophageal adenocarcinoma and Barrett's oesophagus (BE) segments also consist of multiple clones (groups of cells which share mutations). In BE there is some suggestion that the number of individual genetic clones within the segment and the diversity of the segment can be predictors of progression to cancer. However, this was with pre- whole genome sequencing (WGS) methods. In this study we consider the detailed spatial maps of ten patients with different disease trajectories, using WGS, to determine the heterogeneity and correlate it with their progression. Methods We performed WGS (50x) on 35 high-quality, frozen, endoscopic biopsies taken spatially from ten cases (8 males, 2 females, median age 75 (range 31–83). This included 4 long-term non-dysplastic (ND) patients with long BE segments and 6 patients with dysplasia. We used the copy number and purity information (from Battenberg) and the somatic mutation clustering information (from DPClust) to infer the clonal and subclonal architecture of individual biopsies and looked at the spatial relationship between biopsies within the segment. Results In both ND and dysplastic BE we saw cells with unrelated patterns of mutations, or clones, implying completely separate origins for different parts of the segments. This suggests independent or parallel evolution. There was a higher burden of shared (truncal) mutations in the dysplastic biopsies (p=0.049), indicating a more recent clonal sweep with some clones being outcompeted. Dysplastic samples had more subclonal copy number aberrations and more clonal driver mutations. In addition, most of the driver gene alterations in the dysplastic trees occurred early, whereas CDKN2A, the p16 locus, was the only truncal mutation found on the ND clone trees. We did not find the number of clones or the diversity of the segment to differ between the two groups. Conclusions Each individual patient showed complex, distinct genomic features and evolutionary trajectories. Some cases arose from a single ancestral clone, while others had few shared mutational variants suggesting multiple clones. Importantly, in this sample of cases we did not see any trend that the clonal diversity or number of clones correlated with progression to cancer. This is different to previous studies and highlights the importance of multiple sampling to determine the propensity for cancer progression even if the samples look similar histologically.

There has been a steep rise in the incidence of mucormycosis in India during the second wave of COVID-19 infection. This outbreak has principally been attributed to uncontrolled diabetes mellitus and injudicious use of corticosteroids. However, many nondiabetics and those never on steroids have also suffered from this deadly disease recently. Thus, research is under the way to look for other offending factors. Mucormycosis is an opportunistic, potentially fatal, fungal infection caused by a group of saprophytic fungi belonging to family Mucoraceae. Rhino-orbito-cerebral mucormycosis is the most common reported type. The fungi are angioinvasive in nature, leading to thrombosis and rapid tissue necrosis. It also shows neurotropism. We have conducted current literature review using the electronic database of PubMed and recent mycology books, to analyze the possible risk factors, pathogenesis, clinical features, and management protocol of mucormycosis, giving special emphasis on the Indian data. Medline search was supplemented by the personal communication with some researchers, since the problem is of recent origin and publications are still in progress. Our personal experience and current data declared by, or orders issued by union health ministry or state ministries have also been referred to. A high index of suspicion is essential for the early detection as the initial signs and symptoms might go unnoticed as they are nonspecific. The diagnosis requires the sample collection by nasal and sinus endoscopy, direct microscopic examination under potassium hydroxide (KOH), culture, imaging, and molecular tools. Histopathology and KOH mount are the cornerstones for the confirmation of diagnosis. A combination of aggressive medical therapy and surgical debridement can improve the survival. Amphotericin B continues to be the drug of choice.

Prognostication in oesophageal cancer on the basis of preoperative variables is challenging. Many of the accepted predictors of survival are only derived after surgical treatment and may be influenced by neoadjuvant therapy. This study aims to explore the relationship between pre-treatment endoscopic tumour morphology and postoperative survival.Patients with endoscopic descriptions of tumours were identified from the prospectively managed databases including the OCCAMS database. Tumours were classified as exophytic, ulcerating or stenosing. Kaplan Meier survival analysis and multivariable Cox regression analyses were performed to determine hazard ratios (HR) with 95% confidence intervals.262 patients with oesophageal adenocarcinoma undergoing potentially curative resection were pooled from St Thomas' Hospital (161) and the OCCAMS database (101). There were 70 ulcerating, 114 exophytic and 78 stenosing oesophageal adenocarcinomas. Initial tumour staging was similar across all groups (T3/4 tumours 71.4%, 70.2%, 74.4%). Median survival was 55 months, 51 months and 36 months respectively (p 0.001). Rates of lymphovascular invasion (P = 0.0176), pathological nodal status (P = 0.0195) and pathological T stage (P = 0.0007) increased from ulcerating to exophytic to stenosing lesions. Resection margin positivity was 21.4% in ulcerating tumours compared to 54% in stenosing tumours (p 0.001). When compared to stenosing lesions, exophytic and ulcerating lesions demonstrated a significant survival advantage on multivariable analysis (HR 0.56 95% CI 0.31-0.93, HR 0.42 95% CI 0.21-0.82).This study demonstrates that endoscopic morphology may be an important pre-treatment prognostic factor in oesophageal cancer. Ulcerating, exophytic and stenosing tumours may represent different pathological processes and tumour biology.

Barrett's oesophagus with indefinite for dysplasia (BE-IND) is a subjective diagnosis with a low interobserver agreement (IOA) among pathologists and uncertain clinical implications. This study aimed to assess the utility of p53 immunohistochemistry (p53-IHC) in assessing BE-IND specimens.Archive endoscopic biopsies with a BE-IND diagnosis from two academic centres were analysed. First, haematoxylin and eosin-stained slides (HE) were reviewed by four expert gastrointestinal (GI) pathologists allocated into two groups (A and B). After a washout period of at least 8 weeks, HE slides were reassessed side-to-side with p53-IHC available. We compared the rate of changed diagnosis and the IOA for all BE grades before and after p53-IHC. We included 216 BE-IND specimens from 185 patients, 44.0 and 32.9% of which were confirmed after HE slide revision by groups A and B, respectively. More than half the cases were reclassified to a non-dysplastic BE (NDBE), while 5.6% of cases in group A and 7.4% in group B were reclassified to definite dysplasia. The IOA for NDBE, BE-IND, low-grade dysplasia (LGD) and high-grade dysplasia (HGD)/intramucosal cancer (IMC) was 0.31, 0.21, -0.03 and -0.02, respectively. Use of p53-IHC led to a40% reduction in BE-IND diagnoses (P 0.001) and increased IOA for all BE grades [κ = 0.46 (NDBE), 0.26 (BE-IND), 0.49 (LGD), 0.35 (HGD/IMC)]. An aberrant p53-IHC pattern significantly increased the likelihood of reclassifying BE-IND to definite dysplasia (odds ratio = 44.3, 95% confidence interval = 18.8-113.0).P53-IHC reduces the rate of BE-IND diagnoses and improves the IOA among pathologists when reporting BE with equivocal epithelial changes.

Background Barrett’s oesophagus (BE) is the main risk factor for the development of oesophageal adenocarcinoma (OAC), yet few patients ever go on to progress to cancer. The acquisition of events during the metaplasia-dysplasia-cancer sequence is poorly characterised. We present a large, unbiased, multi-omics analysis of a cross-sectional cohort of pre-cancer samples, with the aim of providing a comprehensive insight into the diversity and molecular changes driving the disease to cancer. Methods We generated and integrated the genomic (50x), transcriptomic and epigenomic (850K EPIC array) landscapes of snap-frozen endoscopic biopsies from 146 patients with a range of outcomes (27 long-standing non-dysplastic; 12 prior to progression to dysplasia; 14 low-grade; 25 high-grade; 21 intramucosal carcinoma; 47 cases of BE taken adjacent to OAC) and 642 person years of follow-up. All biopsies were reviewed independently by 3 pathologists and had associated annotation with detailed clinical information. Results The total number of structural variants (SV) captured the most variance between samples. Complex SVs and LINE-1 retrotransposon activity were observed even before dysplasia had developed and increased with progression. Increasing SV burden was associated with chromothripsis (12%, 18/146) and breakage-fusion bridges (BFBs; 8%, 13/146). In more than 50% of these, the BFBs were in chromosome 17, harbouring the oncogenes ERBB2 and CDK12, for which expression was significantly higher. With progression there was increased expression of genes related to cell-cycle checkpoint, DNA repair and chromosomal instability, and the epigenetic silencing of genes in WNT-signalling and cell-cycle pathways. Conclusions Genomic complexity occurs very early in the natural history of BE and increasing genomic instability appears to tip the balance towards cancer. This may inform the potential for progression to cancer beyond the clinically discernible phenotype. Efforts to better understand the triggers for chromosomal breakages and rearrangements that underly progression will aid clinical prediction and prevention strategies.

De novo small bowel adenocarcinoma (SBA) in the terminal ileum is the least common of the SBA types. However, its highest prevalence is found in the presence of Crohn’s disease (CD). As patients with SBA and CD present with similar symptoms, there is a high chance of misdiagnosing SBA as CD. This can lead to delay in proper diagnosis and can affect prognosis. In this article, we discuss two cases of de novo SBA mimicking CD, in the absence of CD, on conventional CT, CT enteroclysis and magnetic resonance imaging (MRI) enteroclysis. Moreover, it underlines the importance of suspecting SBA in cases where there is a lack of response to long-term medical treatment.

Invasive pulmonary aspergillosis (IPA) is mainly caused by Aspergillus fumigatus and other Aspergillus species. Galactomannan (GM) is a polysaccharide antigen that exists primarily in the cell walls of Aspergillus species. GM may be released into the blood and other body fluids even in the early stages of Aspergillus invasion; therefore, detection of the GM antigen level can be useful in making an early diagnosis of IPA.

ImportanceWith worldwide emergence of recalcitrant and resistant dermatophytosis, itraconazole is increasingly being used as the first-line drug for treatment of tinea corporis/cruris (TCC). Apparent inadequacy with low doses has led to empirical use of higher doses and antifungal combinations.ObjectiveTo compare cure rates, treatment durations, safety profiles, and relapse rates of itraconazole 100, 200, and 400 mg/d for the treatment of TCC.Design, Setting, and ParticipantsThis double-blind randomized clinical trial included adult patients with treatment-naive TCC involving at least 5% body surface area. Patients were recruited from the dermatology outpatient department of a tertiary care hospital in New Delhi, India between March 1, 2020, and August 31, 2021.InterventionsPatients were randomized to 1 of the 3 treatment groups. Biweekly blinded assessments were performed until cure or treatment failure. Posttreatment follow-up of at least 8 weeks was conducted to detect relapses.Main Outcome and MeasuresCure rates, treatment durations, safety profiles, and relapse rates were assessed. Secondary outcomes included comparison of rapidity of clinical response and cost-effectiveness between groups.ResultsOf the 149 patients assessed, the mean (SD) age was 34.3 (12.2) years, 69 patients (46.4%) were women, and 80 patients (53.6%) were men. The difference in cure rate between the 100- and 200-mg groups was statistically nonsignificant (hazard ratio [HR], 1.44; 95% CI, 0.91-2.30; P = .12), while the difference between the 100- and 400-mg groups (HR, 2.87; 95% CI, 1.78-4.62; P P = .002) was statistically significant. Mean (SD) treatment durations were statistically significantly different between the 100- and 400-mg groups (7.7 [4.7] weeks vs 5.2 [2.6] weeks; P = .03) and between the 200- and 400-mg groups (7.2 [3.8] weeks vs 5.2 [2.6] weeks; P = .004), but the difference between the 100- and 200-mg groups was not statistically significant. A total of 55 patients (47.4%) relapsed after treatment. Relapse rates were comparable across groups. No patient discontinued treatment due to adverse effects. Treatment with the 200-mg dose incurred a 63% higher cost and 400 mg a 120% higher cost over 100 mg in achieving cure.Conclusions and RelevanceIn this randomized clinical trial, high overall efficacy was observed among the 3 itraconazole doses for treatment of TCC, but with prolonged treatment durations and considerable relapse rates. Treatment with the 200- and 100-mg doses did not differ significantly in efficacy or treatment durations, while 400 mg scored over the other 2 on these outcomes. Considerable additional cost is incurred in achieving cure with the 200- and 400-mg doses.Trial RegistrationClinical Trials Registry of India Identifier: CTRI/2020/03/024326

Enteric protozoa usually cause severe morbidity and mortality in humans. Protozoal infections contribute to the high burden of infectious diseases. Despite recent advances in the epidemiology, diagnostic tool, molecular biology, and treatment of protozoan illnesses, gaps in knowledge still exist; hence, protozoal infections require further research. We are describing here some important enteric protozoal infections along with the immune dysfunction produced by them. Genus- 1. Entamoeba; 2. Giardia; 3. Cryptosporidium; 4. Cyclospora; 5. Cystoisospora; 6. Dientamoeba; 7. Blastocystis; 8. Balantidium.

Background & Aims Colorectal cancer (CRC) is thought to arise when the cumulative mutational burden within colonic crypts exceeds a certain threshold that leads to clonal expansion and ultimately neoplastic transformation. Therefore, quantification of the fixation and subsequent expansion of somatic mutations in normal epithelium is key to understanding colorectal cancer initiation. The aim of the present study was to determine how advantaged expansions can be accommodated in the human colon. Methods Immunohistochemistry was used to visualize loss of the cancer driver KDM6A in formalin-fixed paraffin-embedded (FFPE) normal human colonic epithelium. Combining microscopy with neural network-based image analysis, we determined the frequencies of KDM6A-mutant crypts and fission/fusion intermediates as well as the spatial distribution of clones. Mathematical modeling then defined the dynamics of their fixation and expansion. Results Interpretation of the age-related behavior of KDM6A-negative clones revealed significant competitive advantage in intracrypt dynamics as well as a 5-fold increase in crypt fission rate. This was not accompanied by an increase in crypt fusion. Mathematical modeling of crypt spacing identifies evidence for a crypt diffusion process. We define the threshold fission rate at which diffusion fails to accommodate new crypts, which can be exceeded by KRAS activating mutations. Conclusions Advantaged gene mutations in KDM6A expand dramatically by crypt fission but not fusion. The crypt diffusion process enables accommodation of the additional crypts up to a threshold value, beyond which polyp growth may occur. The fission rate associated with KRAS mutations offers a potential explanation for KRAS-initiated polyps., Graphical abstract

Funder: Biomedical Research Centre; Id: http://dx.doi.org/10.13039/100014461, AIMS: Barrett's oesophagus with indefinite for dysplasia (BE-IND) is a subjective diagnosis with a low interobserver agreement (IOA) among pathologists and uncertain clinical implications. This study aimed to assess the utility of p53 immunohistochemistry (p53-IHC) in assessing BE-IND specimens. METHODS AND RESULTS: Archive endoscopic biopsies with a BE-IND diagnosis from two academic centres were analysed. First, haematoxylin and eosin-stained slides (H&E) were reviewed by four expert gastrointestinal (GI) pathologists allocated into two groups (A and B). After a washout period of at least 8 weeks, H&E slides were reassessed side-to-side with p53-IHC available. We compared the rate of changed diagnosis and the IOA for all BE grades before and after p53-IHC. We included 216 BE-IND specimens from 185 patients, 44.0 and 32.9% of which were confirmed after H&E slide revision by groups A and B, respectively. More than half the cases were reclassified to a non-dysplastic BE (NDBE), while 5.6% of cases in group A and 7.4% in group B were reclassified to definite dysplasia. The IOA for NDBE, BE-IND, low-grade dysplasia (LGD) and high-grade dysplasia (HGD)/intramucosal cancer (IMC) was 0.31, 0.21, -0.03 and -0.02, respectively. Use of p53-IHC led to a >40% reduction in BE-IND diagnoses (P < 0.001) and increased IOA for all BE grades [κ = 0.46 (NDBE), 0.26 (BE-IND), 0.49 (LGD), 0.35 (HGD/IMC)]. An aberrant p53-IHC pattern significantly increased the likelihood of reclassifying BE-IND to definite dysplasia (odds ratio = 44.3, 95% confidence interval = 18.8-113.0). CONCLUSION: P53-IHC reduces the rate of BE-IND diagnoses and improves the IOA among pathologists when reporting BE with equivocal epithelial changes.

Colorectal cancer is thought to arise when the mutational burden of the clonal population of stem cells within a colonic crypt exceeds a certain threshold. Therefore, quantification of the fixation and subsequent expansion of somatic mutations in histologically normal epithelium is key to understanding colorectal cancer initiation. Here, using immunohistochemistry, loss of the histone demethylase KDM6A in normal human colonic epithelium is visualised. Interpretation of the age-related behaviour of KDM6A-negative clones revealed significant competitive advantage in intra-crypt dynamics. Further, subsequent clonal expansion into multi-crypt patches was quantified to reveal a significant 5-fold increase in crypt fission rate. To accomodate the local accumulation of new crypts, the role of crypt fusion was considered. However, no compensatory increase in fusion rate was found. Instead, evidence for crypt diffusion is presented and proposed as a means of accommodating clonal expansions. The threshold fission rate at which diffusion fails to accommodate new crypts, and which may promote polyp growth, is defined.

BACKGROUND & AIMS: Esophageal adenocarcinomas (EACs) are heterogeneous and often preceded by Barrett's esophagus (BE). Many genomic changes have been associated with development of BE and EAC, but little is known about epigenetic alterations. We performed epigenetic analyses of BE and EAC tissues and combined these data with transcriptome and genomic data to identify mechanisms that control gene expression and genome integrity.METHODS: In a retrospective cohort study, we collected tissue samples and clinical data from 150 BE and 285 EAC cases from the Oesophageal Cancer Classification and Molecular Stratification consortium in the United Kingdom. We analyzed methylation profiles of all BE and EAC tissues and assigned them to subgroups using non-negative matrix factorization with k-means clustering. Data from whole-genome sequencing and transcriptome studies were then incorporated; we performed integrative methylation and RNA-sequencing analyses to identify genes that were suppressed with increased methylation in promoter regions. Levels of different immune cell types were computed using single-sample gene set enrichment methods. We derived 8 organoids from 8 EAC tissues and tested their sensitivity to different drugs.RESULTS: BE and EAC samples shared genome-wide methylation features, compared with normal tissues (esophageal, gastric, and duodenum; controls) from the same patients and grouped into 4 subtypes. Subtype 1 was characterized by DNA hypermethylation with a high mutation burden and multiple mutations in genes in cell cycle and receptor tyrosine signaling pathways. Subtype 2 was characterized by a gene expression pattern associated with metabolic processes (ATP synthesis and fatty acid oxidation) and lack methylation at specific binding sites for transcription factors; 83% of samples of this subtype were BE and 17% were EAC. The third subtype did not have changes in methylation pattern, compared with control tissue, but had a gene expression pattern that indicated immune cell infiltration; this tumor type was associated with the shortest time of patient survival. The fourth subtype was characterized by DNA hypomethylation associated with structure rearrangements, copy number alterations, with preferential amplification of CCNE1 (cells with this gene amplification have been reported to be sensitive to CDK2 inhibitors). Organoids with reduced levels of MGMT and CHFR expression were sensitive to temozolomide and taxane drugs.CONCLUSIONS: In a comprehensive integrated analysis of methylation, transcriptome, and genome profiles of more than 400 BE and EAC tissues, along with clinical data, we identified 4 subtypes that were associated with patient outcomes and potential responses to therapy.

Background: Previous published literature has shown that there is no significant difference between outcomes of culture positive and culture negative infective keratitis. This study was done to find the outcome in cases of indeterminate keratitis in our institute. Purpose was to highlight the fate of indeterminate microbial keratitis.Methods: Patients presenting to cornea services of ABVIMS and Dr. RML hospital from February 2017 to April 2021 were evaluated for demographic and microbiological assessment, clinical presentation and management.Results: The 188 out of 310 cases were microbiologically positive. No organism could be detected in 122 cases. Clinical prognosis is worse in cases of indeterminate keratitis.Conclusions: Cases with indeterminate microbial keratitis do not show timely and appropriate response which leads to spread of infection resulting in more complications and less CDVA.

Mucormycosis is a rare necrotizing angioinvasive infection caused by fungi of the class Zygomycetes (order Mucorales). It predominantly occurs in immunocompromised/ predisposed individuals. Recent surge in its incidence in healthy individuals has emphasized the need to reconsider our age-old presumption of 'mucormycosis as a classical opportunistic infection'. Apophysomyces elegans has emerged as a pathogen causing invasive Rhino-Orbitocerebral Mucormycosis (ROCM), mostly in immunocompetent individuals. Mostly resistant to commonly used azoles and echinocandins, management of A elegans associated ROCM solely depends on radical debridement and Amphotericin B. Recent reports of Amphotericin B resistant A elegans strains is disturbing. Till date only 12 cases of ROCM in immunocompetent/ otherwise healthy individuals attributable to A elegans has been reported. Our main objective is to delineate the clinical characteristics and treatment outcome of immunocompentent/ otherwise healthy individuals suffering from A elegans caused ROCM. We also report four new cases of A. elagans caused ROCM. J Microbiol Infect Dis 2017; 7(4):207-212

History A 30-year-old man presented to the emergency department with epigastric pain. He was vomiting and in distress, and he had a history of thalassemia. Physical examination findings were unremarkable. Pertinent blood results were a hemoglobin level of 10.5 g/dL (6.52 mmol/L) (normal range, 13.5-18.0 g/dL [8.38-11.17 mmol/L]) and a bilirubin level of 62 µmol/L (normal range, 3-17 µmol/L). The remaining hematologic and biochemical results were normal. Aortic dissection was suspected clinically, so the patient was referred for imaging. Unenhanced and arterial phase computed tomographic (CT) images were acquired initially. Ultrasonography (US) (images not shown) and magnetic resonance (MR) imaging were performed subsequently. Because of the imaging findings, the patient was referred for surgery.

Background: Hospital-associated infections are a major cause of patient morbidity and mortality. Microbiological contamination of air in the operation theaters (OTs) and Intensive care units (ICUs) is a major risk factor for surgical site and other hospital-associated infections. The aim of the study was to determine the microbial contamination of air in the OTs and ICUs of a tertiary care hospital in north India. Methods: The study was conducted in the department of microbiology, Dr. RML hospital & PGIMER, New Delhi. Air samples were collected from 9 OTs and 4 ICUs by settle plate method between January 2017–June 2018. Bacterial species were isolated and identified by conventional methods. Results: A total of 630 samples were collected from environment of various OTs and ICUs. Out of these, 130 (20%) plates showed bacterial growth and yielded 380 isolates. Emergency OT and ECS OT showed highest bacterial CFU per plate. The most common isolate was Bacillus species 472 (75%) followed by micrococcus 352(56%), Staphylococcus aureus 6 (1%). Conclusion: Routine surveillance of OT and ICU air in conventional OTs where there is no control on air quality, meticulous cleaning and strict adherence to OT and ICU protocol are essential steps for the prevention of hospital acquired infections. Further, the hospitals need to develop and implement processes for good infection control practices

Spontaneous rupture of the non-labouring uterus leading to maternal collapse is a relatively rare occurrence in obstetrics

Background Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20–30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. Methods Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. Results A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal–external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). Conclusion The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients., Early recurrence after surgery for adenocarcinoma of the oesophagus is common. A risk prediction model was derived using modern machine learning methods that accurately predicts risk of early recurrence using postoperative pathology. Machine learning may help

Introduction: Healthcare associated infections (HCAIs) pose a significant risk to patient's health with increasing morbidity and mortality. A large portion of HCAI can be prevented by hand hygiene, but adherence to hand hygiene has been found to be very low. Methodolgy: This study was conducted to assess the rate of hand hygiene compliance during 'my five moments of hand hygiene' as per the WHO guidelines in our intensive care units and to implement multimodal intervention strategies to improve hand hygiene compliance. Results: The average compliance amongst all HCWs in both ICUs was 45.7% before sensitisation which increased to 85.4% after sensitisation using multimodal strategies. Conclusion: Multimodal Intervention strategies such as the one we employed had a good impact in improving compliance in our ICU and these improvements can be easily duplicated in healthcare settings across the country.

The clinical diagnosis of cutaneous tuberculosis (CT) was based on criteria of reinfection and reactivation. Laboratory tests are mandatory but have limitations, thus demanding continuous innovation. In our study, we took punch biopsies from lesions on 48 patients. Half of these biopsies underwent histopathologic investigation, and the other half were analysed using the BACT Alert 3D system, the Amplified

The linkages of oral health with the holistic health of an individual are now well-established. Nevertheless, marginalizing oral health continues to pose a challenge in the public health scenario globally and especially in developing countries. Maternal and fetal health have been regarded as pivotal yardsticks of development in all civil societies. The oral cavity acts as a route of entry for various microorganisms into the body and oral lesions are easily detectable. Thus, early intervention is possible and morbidity in the vulnerable populations can be reduced.

Background & Aims: Most patients with esophageal adenocarcinoma (EAC) present with de novo tumors. Although this could be due to inadequate screening strategies, the precise reason for this observation is not clear. We compared survival of patients with prevalent EAC with and without synchronous Barrett esophagus (BE) with intestinal metaplasia (IM) at the time of EAC diagnosis. Methods: Clinical data were studied using Cox proportional hazards regression to evaluate the effect of synchronous BE-IM on EAC survival independent of age, sex, TNM stage, and tumor location. We analyzed data from a cohort of patients with EAC from the Mayo Clinic (n=411; 203 with BE and IM) and a multicenter cohort from the United Kingdom (n=1417; 638 with BE and IM). Results: In the Mayo cohort, BE with IM had a reduced risk of death compared to patients without BE and IM (hazard ratio [HR] 0.44; 95% CI, 0.34–0.57; PConclusion: Two types of EAC can be characterized based on the presence or absence of BE. These findings could increase our understanding the etiology of EAC, and be used in management and prognosis of patients.

Large-scale cancer genome studies suggest that tumors are driven by somatic copy number alterations (SCNAs) or single-nucleotide variants (SNVs). Due to the low-cost, the clinical use of genomics assays is biased towards targeted gene panels, which identify SNVs. There is a need for a comparably low-cost and simple assay for high-resolution SCNA profiling. Here we present our method, conliga, which infers SCNA profiles from a low-cost and simple assay.

This study was designed to identify significant differences in gene expression profiles of human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinomas (OPSCC) and to better understand the functional and biological effects of HPV infection in the premalignant pathway. Twenty-four consecutive patients with locally advanced primary OPSCC were included in a prospective clinical trial. Fresh tissue samples (tumor vs. matched normal epithelium) were subjected to whole transcriptome analysis and the results validated on the same cohort with RT-quantitative real-time PCR. In a separate retrospective cohort of 27 OPSCC patients, laser capture microdissection of formalin-fixed, paraffin-embedded tissue allowed RNA extraction from adjacent regions of normal epithelium, carcinoma in situ (premalignant) and invasive SCC tissue. The majority of patients showed evidence of high-risk HPV16 positivity (80.4%). Predictable fold changes of RNA expression in HPV-associated disease included multiple transcripts within the p53 oncogenic pathway (e.g. CDKN2A/CCND1). Other candidate transcripts found to have altered levels of expression in this study have not previously been established (SFRP1, CRCT1, DLG2, SYCP2, and CRNN). Of these, SYCP2 showed the most consistent fold change from baseline in premalignant tissue; aberrant expression of this protein may contribute to genetic instability during HPV-associated cancer development. If further corroborated, this data may contribute to the development of a non-invasive screening tool. This study is registered with the UK Clinical Research Network (ref.: 11945).

Continual evolution of cancer on a microscopic scale makes accurate clinical assessment challenging. The highly varied and unpredictable patient outcomes in esophageal adenocarcinoma (EAC) prompted us to question conventional modes of metastatic spread. Whole genome sequencing and phylogenetic analysis of 396 samples across 18 EAC cases demonstrated contemporaneous polyclonal seeding from the primary to multiple disparate sites at a single time-point in 90% cases- so-called clonal diaspora. The age-dependent trinucleotide signature was rarely observed post diaspora supporting a near-synchronous metastatic seeding process. Clustering of lymph nodes and distant metastases (n=250) demonstrated that samples sharing a common clonal origin were widely dispersed spatially. Metastatic subclones at autopsy were present in the primary tumor at diagnosis, and in blood samples at earlier time-points. This is consistent with our hypothesis that metastasis occurs at a single time-point and has far-reaching implications of our understanding of metastatic progression, clinical staging and patient management.