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The progression of gallbladder inflammatory lesions to invasive cancer remains poorly understood, necessitating research on biomarkers involved in this transition. This study aims to identify and validate proteins associated with this progression, offering insights into potential diagnostic biomarkers for gallbladder cancer (GBC). Label-free liquid chromatography assisted tandem mass spectrometry (LC-MS/MS) proteomics was performed on samples from 10 cases each of GBC and inflammatory lesions, with technical duplicates. Validation was conducted through the enzyme-linked immunosorbent assay (ELISA) using 80 samples (40 GBC and 40 inflammatory lesions). Bioinformatics tools analyzed protein-protein interaction (PPI) networks and pathways. Statistical correlations with clinicopathological variables were assessed. Prognostic evaluation utilized Kaplan–Meier survival analysis and Cox regression analyses. mRNA expressions were studied using real time-polymerase chain reaction (RT-PCR). Out of 5,714 proteins analyzed, 621 were differentially expressed. Three upregulated (the S100 calcium-binding protein P [S100P], polymeric immunoglobulin receptor [PIGR], and complement C1q-binding protein [C1QBP]) and two downregulated (transgelin [TAGLN] and calponin 1 [CNN1]) proteins showed significant expression. Pathway analysis implicated involvement of proteoglycans in cancer and glycosaminoglycan metabolism. Significant correlations were observed between protein concentrations and clinicopathological variables. Prognostic factors such as tumor size, lymph node metastasis, and preoperative bilirubin levels were associated with overall survival. Protein-based assays demonstrated higher resolution compared to mRNA analysis, suggesting their utility in GBC risk stratification. S100P, PIGR, C1QBP, TAGLN, and CNN1 emerge as potential protein-based biomarkers involved in the progression from gallbladder inflammatory lesions to invasive cancer. These findings hold promise for improved diagnostic and prognostic strategies in GBC management.

The Central Kerala coast in Southwest India serves as a valuable natural archive for studies of the Late Quaternary coastal evolution, palaeoclimate, and maritime trades. The coast is an archeologically and culturally significant region in South India, located in the mouth of the longest river in Kerala, the Periyar River. The riverbank of the Periyar at its mouth is believed to host the ancient port Muziris, whose remnants are found in the areas around where the Periyar River joins the Arabian Sea. Sea level oscillations and climate variabilities in the past have played a pivotal role in the destruction of the Muziris port. Recent excavations unearthed many artifacts from nearby areas of the river confluence; however, the exact location of the port remains unresolved. The present study is an attempt to trace out the coastal evolutionary processes and palaeoclimatic conditions that prevailed in the area during the Late Quaternary period using three drilled cores retrieved from this stretch of the coastal lands. A multi-proxy approach, combining geochemical, mineralogical, palynological, and geochronological tools was used in the study. The Holocene deposit in the study area is composed mainly of sand and clay-dominant sediments that fall within an age range of 1.1–8.1 cal kyr BP, whereas the underlying sedimentary sequence dates to a maximum of 31.5–37.9 cal kyr BP. The inorganic and organic elemental compositions, together with the textural and palynological attributes, indicate that Holocene sedimentation occurred here under fluctuating environmental conditions with significant changes in climate and sea level positions. The upper part of this section bears the signature of the humid depositional environment that prevailed during the Late Holocene when sand-dominated sediments were deposited and brought in under the influence of longshore drift. The sediments from the lower part of the section carry the signature of the Holocene transgression when deposition took place under submerged conditions with considerable marine influence but receiving significant terrestrial inputs. The study highlights the location of the historically significant lost ancient port of Muziris at Kodungallur near the mouth of the Periyar River. A three-fold evolutionary model proposed for the coastal segment revealed that the location of the Muziris port was part of the Periyar River near Kodungallur, as mentioned by the historians, and the settlement near Pattanam may be considered a satellite township of the ancient Muziris port.

Acinar cystic transformation (ACT) is a rare benign cystic lesion of the pancreas reported in elderly women. ACT can be easily confused with other cystic lesions of the pancreas, such as intraductal papillary neoplasm and serous and mucinous neoplasms, on imaging, especially when detected radiologically in a male patient as the index case. A preoperative histological examination can establish a diagnosis and avoid extensive surgical resection. We hereby report a case of ACT in a 69-year-old male patient that affected the body and tail region of the pancreas.

Background/Aims Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD). Methods Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. Results One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P

Background: Schwannomas are benign nerve sheath tumors that are extremely rare in the biliary tract. A comprehensive review of literature enumerated approximately 30 case reports of schwannoma in the biliary tract tree and porta hepatis region. Case Presentation: We report a case of a 40-year-old female who presented with abdominal pain. Imaging revealed a mass at the porta hepatis extending from the portal bifurcation till the hilum encasing the main portal vein and abutting the right portal vein. Differentials of carcinoma, lymphoma, and mesenchymal tumor were kept. Ultrasound-guided biopsy of the mass showed a benign nerve sheath tumor, immunopositive for S100. The histopathological evaluation of the excised mass confirmed the origin of mass in the common bile duct. Conclusions: Our case highlights that schwannomas, though benign, can mimic a carcinoma or lymphoma if present at a rare site such as bile ducts. An exhaustive clinical and radiological workup with diligent histopathological evaluation is mandatory in dealing with such rare cases as radical surgery and chemotherapy can be avoided in such patients.

One of the mechanisms shaping the pathophysiology during the infection of enteric pathogen Salmonella Typhimurium is host PTM machinery utilization by the pathogen encoded effectors. Salmonella Typhimurium (S. Tm) during infection in host cells thrives in a vacuolated compartment, Salmonella containing vacuole (SCV), which sequentially acquires host endosomal and lysosomal markers. Long tubular structures, called as Salmonella induced filaments (SIFs), are further generated by S. Tm, which are known to be required for SCV's nutrient acquisition, membrane maintenance and stability. A tightly coordinated interaction involving prominent effector SifA and various host adapters PLEKHM1, PLEKHM2 and Rab GTPases govern SCV integrity and SIF formation. Here, we report for the first time that the functional regulation of SifA is modulated by PTM SUMOylation at its 11th lysine. S. Tm expressing SUMOylation deficient lysine 11 mutants of SifA (SifAK11R) is defective in intracellular proliferation due to compromised SIF formation and enhanced lysosomal acidification. Furthermore, murine competitive index experiments reveal defective in vivo proliferation and weakened virulence of SifAK11R mutant. Concisely, our data reveal that SifAK11R mutant nearly behaves like a SifA knockout strain which impacts Rab9-MPR mediated lysosomal acidification pathway, the outcome of which culminates in reduced bacterial load in in vitro and in vivo infection model systems. Our results bring forth a novel pathogen-host crosstalk mechanism where the SUMOylation of effector SifA regulated S. Tm intracellular survival.

Chronic inflammation in the gallbladder leading to persistent epithelium damage promotes invasive cancer. The study aimed to assess the prognostic value of PDL1 and CA19-9 markers in cancer/inflammatory lesions of the gallbladder. A total of 29 cases (19 cancer and 10 inflammatory) were included. The PDL1 protein concentration level and mRNA expression were assessed in the tissues’ lysates by ELISA and real-time PCR, respectively. PDL1 and CA19-9 concentration levels were compared and statistically related with clinico-pathological variables. The PDL1 protein level and its relative mRNA expression were correlated. Kaplan–Meir survival and Cox regression analyses were conducted for predicting prognosis. This study investigated the PDL1 and CA19-9 marker expression in both cancer and inflammatory cases of the gallbladder (p = 0.48 and p = 0.17 respectively). PDL1 protein expression was significantly associated with the hormonal profile of the cases (p = 0.04) at an optimum cut-off value of 13 pg/mL, while the CA19-9 marker expression was correlated with the status of liver metastasis (p = 0.0043) and size of the tumor (p = 0.004). A low PDL1 concentration was found when compared to the CA19-9 level among cancer cases (p = 0.12) and proportional in the inflammatory lesions (p = 0.63). A significant positive correlation was found between the PDL1 protein and its relative mRNA expressions in the inflammatory lesions (p = 0.029) when compared to cancer cases (p = 0.069). Our results showed that a protein-based assay for PDL1 expression would be more sensitive compared to RNA based assays for GBC risk stratifications. Overall survival was predicted with CA19-9 and PDL1 levels (p = 0.0074, p = 0.23, respectively). PDL1 and CA19-9 may act as a probable predictor of a poor prognosis in gallbladder cancer (GBC) cases.

Background: The causal association between IgA nephropathy (IgAN) and celiac disease (CeD) is based on their clinical coexistence. In this prospective study, we screened patients with IgAN for CeD and explored the utility of analysis of IgA anti-TG2 antibody deposits, for establishing a causal association. Methods: Biopsy-proven patients of IgAN were screened for serum IgA anti-tissue transglutaminase antibody (IgA anti-tTG Ab) titer and thereafter were invited to undergo endoscopic duodenal biopsy. Corresponding duodenal and kidney biopsies were subjected to IgA anti-TG2 antibody colocalization study using dual-color immunohistochemistry and immunofluorescence techniques. Additionally, kidney biopsies from 105 patients with IgAN who did not give consent for serology analysis, 30 non-IgA nephropathies, and 10 normal controls were also included. Dual-color-stained slides were interpreted based on stain distribution and intensity scores, and Pearson's index >0.3–1 on confocal imaging was considered significant. Results: Of a cohort of 151 patients with IgAN, 32 consented to undergo sero-screening and 5 of them had high serum anti-tTG Ab titer. Two out of the latter consented to endoscopic duodenal biopsies, in whom modified Marsh grade 3b changes were identified. Strong IgA anti-TG2 antibody deposits were noted in the kidney and duodenal biopsies of these patients. One patient out of non-consenting 105 patients with IgAN and 3 out of 30 patients with other non-IgA nephropathies also showed IgA anti-TG2 deposits. None of the healthy kidney tissues showed IgA anti-TG2 Ab deposits. Conclusions: Co-localized IgA anti-TG2 deposits in the kidney biopsies in patients with IgAN help to establish a pathogenic link with CeD. A small proportion of patients with IgAN have associated CeD.

The term hypercoordination refers to the extent of the coordination of an element by its normal value. In the hypercoordination sphere, the element can achieve planar and/or non-planar molecular shape. Hence, planar hypercoordinate carbon species violate two structural rules: (i) The highest coordination number of carbon is four and (ii) the tetrahedral orientation by the connected elements and/or groups. The unusual planar orientations are mostly stabilized by the electronic interactions of the central atom with the surrounding ligands. In this review article, we will talk about the current progress in the theoretical prediction of viable planar hypercoordinate carbon compounds. Primary knowledge of the planar hypercoordinate chemistry will lead to its forthcoming expansion. Experimental and theoretical interests in planar tetracoordinate carbon (ptC), planar pentacoordinate carbon (ppC), and planar hexacoordinate carbon (phC) are continued. The proposed electronic and mechanical strategies are helpful for the designing of the ptC compounds. Moreover, the 18-valence electron rule can guide the design of new ptC clusters computationally as well as experimentally. However, the counting of 18-valence electrons is not a requisite condition to contain a ptC in a cluster. Furthermore, this ptC idea is expanded to the probability of a greater coordination number of carbon in planar orientations. Unfortunately, until now, there are no such logical approaches to designing ppC, phC, or higher-coordinate carbon molecules/ions. There exist a few global minimum structures of phC clusters identified computationally, but none have been detected experimentally. All planar hypercoordinate carbon species in the global minima may be feasible in the gas phase.

Cronkhite–Canada syndrome is a rare non-hereditary disease characterized by gastrointestinal hamartomatous polyposis and protein-losing enteropathy. The presenting symptoms are onychodystrophy, skin pigmentation, alopecia, weight loss, and diarrhea. Diagnosis is suggested by a combination of clinical, imaging, and endoscopy findings, and histology is necessary for confirmation. Here we describe a case of a 54-year-old man presenting with watery diarrhea, colicky abdominal pain, nasal obstruction, and weight loss for 6 months. Endoscopy showed multiple polyps in the stomach, duodenum, and colon. These were seen on computed tomography (CT) enterography along with polyps in the small bowel. A final diagnosis was made after the biopsy.

We analyzed the features of the COVID-19 outbreak with temporal delay and stochastic influence using the SIRS epidemic model in this study. We investigate the local stability of each equilibrium point in terms of basic reproduction numbers. Hopf bifurcation is detected in the system, and a time delay is inserted in the transmission terms to represent the virus's incubation period. The spread of the novel COVID-19 strain to humans is influenced by environmental conditions such as mugginess, precipitation, and temperature. To explore the impact of environmental oscillations on the coronavirus, we employ white noise perturbations in the system. Finally, we examine the mathematical reenactments using MATLAB.

Abstract Selective isolation of soil Actinobacteria was undertaken to isolate a new class of antibiotics and bioactive molecules. A Streptomyces sp. PSAA01 (= MTCC 13,157), isolated from soil of Eastern Himalaya foothill was cultivated on a large scale for the production of the antimicrobial SM02. It has been found that the maximum amount of SM02 produced while PSAA01 was grown in ISP-2 medium (pH 7.0) for 7 days at 30 °C in shaking (180 rpm) condition. A significant zone of inhibition against Staphylococcus aureus MTCC 96 has been found with the crude cell-free culture media (50 µL) of 7 days grown PSAA01. After the purification and chemical structural characterization, we found that SM02 is a new antimicrobial having 746 dalton molecular weight. The compound SM02 contains pyrimidine moiety in it and is produced by a species of Streptomyces and thus we have named this antibiotic pyrimidomycin. The antimicrobial spectrum of pyrimidomycin has been found to be restricted in Gram-positive organisms with a MIC of 12 µg/mL. SM02 was found active against Mycobacterium sp. and also multi-drug resistant Gram-positive bacteria with similar potency and found to disrupt the bacterial cell wall. Pyrimidomycin also showed significant impairment in the biofilm formation by S. aureus. Furthermore, pyrimidomycin showed synergy with the most used antibiotic like ampicillin, vancomycin and chloramphenicol. Pyrimidomycin did not have cytotoxicity towards human cell lines indicating its limited activity within bacteria.

Summary: A crypt autochthonous microbial population called crypt-associated microbiota (CAM) is localized intimately with gut regenerative and immune machinery. The present report utilizes laser capture microdissection coupled with 16S amplicon sequencing to characterize the CAM in patients with ulcerative colitis (UC) before and after fecal microbiota transplantation with anti-inflammatory diet (FMT-AID). Compositional differences in CAM and its interactions with mucosa-associated microbiota (MAM) were compared between the non-IBD controls and in patients with UC pre- and post-FMT (n = 26). Distinct from the MAM, CAM is dominated by aerobic members of Actinobacteria and Proteobacteria and exhibits resilience of diversity. CAM underwent UC-associated dysbiosis and demonstrated restoration post-FMT-AID. These FMT-restored CAM taxa correlated negatively with disease activity in patients with UC. The positive effects of FMT-AID extended further in refurbishing CAM-MAM interactions, which were obliterated in UC. These results encourage investigation into host-microbiome interactions established by CAM, to understand their role in disease pathophysiology.

Background/Aims Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. Methods Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. Results Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn’s disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn’s disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%. Conclusions Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.

Abstract Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.

Introduction: The etiopathogenesis of pelviureteric junction obstruction (PUJO) has been debated. Recently, the role of interstitial cells of Cajal-like cells (ICC-LC) has been studied and reported to be the cause of this functional obstruction. We studied the histopathology and ICC-LC density at PUJ and compared it with that of PUJ of the control group and distal ureteric margin of the study group. Methods: A prospective study was conducted which included PUJO patients in the study group and the renal tumor patients in the control group. Histopathological examination (muscle hypertrophy and fibrosis) and immunohistochemistry (ICC-LC density) were done. The muscle hypertrophy, fibrosis, and ICC-LC density at the PUJ in both the groups were compared. A similar comparison was performed between the findings at the PUJ and the distal margin in the study group. Results: The study and control groups included 37 PUJO patients and 13 Wilms tumor patients. The ICC-LC density at PUJ in the study group was significantly lower than that in the control group (P < 0.001) and that at the distal resected margin of the study group (P < 0.001). Significantly increased muscle hypertrophy (P < 0.001) and fibrosis (P = 0.002) were seen at PUJ in the study group compared to the control group. No significant association was noted between the ICC-LC density and muscle hypertrophy at PUJ and the distal resected margin in the study group. Conclusion: A significant decrease in the density of ICC-LC and increased fibrosis and muscle hypertrophy at PUJ in children with PUJO play a role in the etiopathogenesis of the disease.

PURPOSEGlobally, colorectal cancer (CRC) ranks third in terms of incidence and second in terms of mortality. A relatively low burden of CRC has been reported from low- and middle-income countries (LMIC), and there is a paucity of publications related to CRC from LMIC.PATIENTS AND METHODSA computerized comprehensive structured CRC clinical database was developed. All the patients with histopathologically proven CRC undergoing either curative and palliative multimodality management or surgical interventions between 2000 and 2019 were included in the study. A descriptive analysis of the demographic profile and clinical spectrum was performed.RESULTSA total of 970 patients of CRC were treated between 2000 and 2019. Of these, 401 patients (41.3%) had colon cancer and 569 (58.7%) had rectal cancer. The male-to-female ratio was 1.79:1. The mean age at presentation was 47.7 years. A total of 337 (34.7%) patients qualified as young CRC (≤ 40 years of age at diagnosis). The commonest symptom among patients with colon cancer was abdominal pain; 55.6% of patients had a right-sided primary tumor as compared with 42.2% with left-sided tumors. The commonest symptom among patients with rectal cancer was bleeding per rectum. The predominant location of the tumor was in the lower rectum (58%). Majority of patients with CRC presented with locally advanced stage II and III disease. The most common histologic subtype encountered for both colon and rectal cancers was adenocarcinoma (84.8% and 81.2%, respectively).CONCLUSIONThis study has revealed certain important findings related to CRC in LMIC including a higher burden of young colorectal cancer, a relatively higher proportion of rectal cancers in comparison with colon cancer, a high percentage of patients with low-rectal cancer, and advanced stage at presentation.

Abstract Background Carney’s triad is a rare syndrome comprising gastrointestinal stromal tumor, extra-adrenal paraganglioma, and pulmonary chondroma along with newer additions of adrenal adenoma and esophageal leiomyoma. The triad is completely manifest in only 25–30% cases, with most patients presenting with two out of three parts of the syndrome. Wild-type succinate-dehydrogenase-deficient gastric gastrointestinal stromal tumor forms the most common component of Carney’s triad and is usually multicentric and multifocal. It usually demonstrates indolent behavior and resistance to imatinib; hence, the management remains predominantly surgical. Pulmonary chondromas are commonly unilateral and multiple with slow-growing nature, which allows for conservative management. Adrenocortical adenomas are found in 20% of patients and are usually detected as incidentalomas. Case presentation A 49-year-old Asian male presented with upper gastrointestinal bleed and was diagnosed with multiple gastric succinate-dehydrogenase-deficient gastrointestinal stromal tumors. On evaluation, he was found to have left pulmonary chondroma and non-secretory adrenal adenoma, thus completing the Carney’s triad. He underwent surgery with sleeve gastrectomy and excision of the antral tumor nodule, while the adrenal and pulmonary tumors have been under close follow-up. Conclusion Literature regarding Carney’s triad is scarce, especially from the Indian setting. Our report aims to highlight the various manifestations of this syndrome with emphasis on management of wild-type succinate-dehydrogenase-deficient gastrointestinal stromal tumor. Radical gastric surgeries do not offer a survival advantage in this condition; hence, more conservative modalities of resection can be adopted.

Background/Aims Predictors of short-term outcome of intravenous (IV) steroid therapy in acute severe ulcerative colitis (ASUC) have been well described, but the impact of cytomegalovirus (CMV) infection as a predictor of outcome remains debatable. We investigated the role of quantitative CMV polymerase chain reaction (PCR) as a predictor of short-term outcome in patients with ASUC. Methods Consecutive patients with ASUC satisfying Truelove and Witts criteria hospitalized at All India Institute of Medical Sciences (AIIMS) from May 2016 to July 2019 were included; all received IV steroid. The primary outcome measure was steroid-failure defined as the need for rescue therapy (with ciclosporin or infliximab) or colectomy during admission. AIIMS’ index (ulcerative colitis index of severity >6 at day 1+fecal calprotectin >1,000 μg/g at day 3), with quantitative CMV PCR on biopsy samples obtained at initial sigmoidoscopy were correlated with the primary outcome. Results Thirty of 76 patients (39%) failed IV corticosteroids and 12 (16%) underwent surgery. Patients with steroid failure had a significantly higher mucosal CMV DNA than responders (3,454 copies/mg [0–2,700,000] vs. 116 copies/mg [0–27,220]; P2,000 copies/mg (odds ratio [OR], 10.2; 95% confidence interval [CI], 2.6–39.7; P2,000 copies/mg) independently predicts failure of IV corticosteroids and short-term risk of colectomy and it has an additional value to the established markers of disease severity in patients with ASUC.

Abstract Acute-on-Chronic Liver Failure (ACLF) is associated with innate immune dysfunction and high short-term mortality. Neutrophils have been identified to influence prognosis in ACLF. Neutrophil biology is under-evaluated in ACLF. Therefore, we investigated neutrophil-specific genes and their association with ACLF outcomes. This is an observational study. Enriched granulocytes, containing neutrophils, isolated from study participants in three groups- ACLF(n = 10), chronic liver disease (CLD, n = 4) and healthy controls (HC, n = 4), were analysed by microarray. Differentially expressed genes were identified and validated by qRT-PCR in an independent cohort of ACLF, CLD and HC (n = 30, 15 and 15 respectively). The association of confirmed overexpressed genes with ACLF 28-day non-survivors was investigated. The protein expression of selected neutrophil genes was confirmed using flow cytometry and IHC. Differential gene expression analysis showed 1140 downregulated and 928 upregulated genes for ACLF versus CLD and 2086 downregulated and 1091 upregulated genes for ACLF versus HC. Significant upregulation of neutrophilic inflammatory signatures were found in ACLF compared to CLD and HC. Neutrophil enriched genes ELANE, MPO and CD177 were highly upregulated in ACLF and their expression was higher in ACLF 28-day non-survivors. Elevated expression of CD177 protein on neutrophil surface in ACLF was confirmed by flow cytometry. IHC analysis in archival post mortem liver biopsies showed the presence of CD177+ neutrophils in the liver tissue of ACLF patients. Granulocyte genes ELANE, MPO and CD177 are highly overexpressed in ACLF neutrophils as compared to CLD or HC. Further, this three-gene signature is highly overexpressed in ACLF 28-day non-survivors.

Abstract Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has recently emerged as a viable management option for peritoneal surface malignancy (PSM). CRS and HIPEC is a complex, multidisciplinary and resource-intensive surgical procedure. It has a steep learning curve and is associated with significant morbidity and mortality. The expertise is mostly limited to few dedicated high-volume centers located in developed countries. We present a single institutional experience of 232 cases of CRS and HIPEC performed at a tertiary care cancer center in a low- and middle-income country (LMIC). Methods A multidisciplinary PSM program was initiated in 2015 at a high-volume public-sector tertiary care cancer center in North India catering largely to patients belonging to low- and middle-income groups. Perioperative protocols were developed, and a prospective structured database was created to capture data. All patients undergoing CRS and HIPEC between January 2015 and December 2020 were identified, and the data was retrospectively analyzed for clinical spectrum, surgical details, and perioperative morbidity and mortality. Results Two hundred and thirty-two patients underwent CRS and HIPEC during the study period. Epithelial ovarian carcinoma (56.5%) was the most common malignancy treated, followed by pseudomyxoma peritonei (18.5%), colorectal carcinoma (13.4%), and malignant mesothelioma (5.6%). Optimal CRS could be achieved in 94.4% of patients. Cisplatin and mitomycin were the most common drugs used for HIPEC. A total of 28.0% of patients had morbidity including deep vein thrombosis, subacute intestinal obstruction, sepsis, burst abdomen, lymphocele, urinoma, acute renal failure, and enterocutaneous fistula. The overall treatment-related mortality was 3.5%. Conclusions Results of the current study indicate that it is feasible to establish a successful CRS and HIPEC program for PSM in government-funded hospitals in LMIC facing resource constraints. The most common indication for CRS and HIPEC were carcinoma of the ovary followed by pseudomyxoma peritonei and colorectal carcinoma. Overall morbidity and mortality in the current series are comparable to global standards, reported from high-income countries. A protocol-based multidisciplinary team approach, optimal patient selection, and surgical expertise can help achieve optimal outcomes in government-funded hospitals in LMIC.

Mixed neuroendocrine non-neuroendocrine neoplasm (MiNeN) is a recently described entity of the esophagus in the latest (fifth) edition of WHO Classification of Digestive System Tumors. It is often a difficult pathological diagnosis, especially in small preoperative biopsies. We herein report a case of high-grade MiNeN of gastroesophageal junction diagnosed as a squamous cell carcinoma in preoperative biopsy and subsequently as a high-grade MiNeN in esophagogastrectomy specimen comprising areas of mucoepidermoid carcinoma and large-cell neuroendocrine carcinoma (NEC). This report accentuates the importance of deeper multisite preoperative biopsies as the management is completely different in a MiNeN from esophageal squamous cell carcinoma.

Purpose – During any crisis situation like a pandemic, war or natural disaster, online/blended learning could meet the academic needs of the learners in a bigger way. The use of information and communication technology (ICT)-based technologies has converted the entire teaching pedagogy to a learner centred pedagogy, following which the skills of using technology are to be seen as the most essential qualifications on the part of both the teachers/educators and learners. Therefore, the purpose of this paper is to understand the perceptions of the teachers and learners regarding the use of online/blended learning modes in teaching learning transactions. Another purpose of the paper being to find out the prospects and challenges of providing online/blended learning in a country like India, particularly during and in post-Covid-19 situations. Design/methodology/approach – The academic analytics approach was used for the study. A structured questionnaire was designed in Google Forms covering the perceptions of the teachers and learners in different Indian universities and colleges regarding online/blended services and analysis was done using Google Analytics. Further, analysis of the data received had been done by using simple statistical tool like percentage. Findings – Blended learning could be the solution for providing education in the context of the 21st century India. However, unlike in case of the conventional education, open education has widened the scope of learning adhering to the motto – “Bring your own device” to learn. The extensive use of open educational resources, massive open online courses, social media and meeting apps during the Covid-19 lockdown, has opened up the minds of the knowledge-hungry people, further enabling them to receive the necessary educational inputs, training and skills even during the current pandemic situation. This is going to have a big impact in the ways of educational transactions in the days to come. Research limitations/implications – The discussions in the paper are limited to a study of representative states of India, and it is a general study only. The sample size was limited to only 120 as the response rate was significantly low compared to the number of addressees to whom the questionnaire was sent. Practical implications – This study will help in understanding the present state of online/blended learning in a country like India. The use of online learning was no doubt intensified by the sudden outbreak of the Covid-19 Pandemic. However, the study will also help in preparing a roadmap, at the policy level, regarding the beneficial use of online/blended teaching learning models both by the teachers and learners during any future crisis-like situations in a country like India. Social implications – Through this paper, a new social constructivism has been visualised to know the acceptability of online/blended learning opportunities on the part of the teachers and learners across India. If that social constructivism can actually be realised through the benefits of online learning, India might emerge as one of the important leaders of education in the coming days. To that extent, the Covid-19 pandemic can be seen as a blessing in disguise. Originality/value – It is important to examine the perceptions of both teachers and learners on the use of online learning in their regular curriculum transactions most particularly when the whole world is facing the brunt of the Covid-19 pandemic, which has adversely affected millions of learners across the world. The paper is original because it explores the current state of online/blended learning in a developing country like India to provide a practical and realistic vision of a new way of learning in the post-Covid-19 situations.

Abstract Early-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

Isolated renal mucormycosis is rare in children. A case of 3-month-old infant presenting with right-sided flank lump and fever is being reported. Investigations revealed a nonfunctioning right kidney with intrarenal abscesses and a low percent-frequency of T-cells. He made an uneventful recovery following surgery and systemic antifungal therapy. Compared to the other forms of deep mucormycosis, a review of literature suggests favorable prognosis in children with isolated renal involvement.

Background: Aggressive pancreatobiliary tumors often require oxaliplatin-based therapies, instead of standard gemcitabine-based therapy and biomarker studies at diagnosis to decide the appropriate therapeutic regimen. The ribonucleotide Reductase catalytic subunit M1 (RRM1) and excision repair cross-complementing gene-1 (ERCC1) are related to DNA synthesis and repair and essential in this regard. However, apart from the therapeutic benefit, their prognostic implication is controversial. Methods: In this retrospective study, paraffin-embedded tissue from 51 cases of pancreatic cancer and 29 cases of cholangiocarcinoma were evaluated for RRM1 and ERCC1 expression by immunohistochemical technique along with 18 control pancreatic and biliary tissues. The semiquantitatively H score was calculated based on stain distribution and stain intensities. Results: Both RRM1 and ERCC1 expression were high in tumor epithelium than in controls (RRM1: the difference was statistically significant in cholangiocarcinoma (P = 0.008); ERCC1: the difference was statistically significant both in pancreatic and cholangiocarcinoma (P < 0.05)]. However, no correlation was noted between RRM1 and ERCC1-low and high tumors with histological markers of prognosis and overall survival in these patients. Conclusions: The present study adds further evidence against the controversy that if RRM1 and ERCC1 expression in pancreatic and biliary carcinomas have any prognostic significance apart from their proven therapeutic benefits in these tumors.

The Indian Association of Pathologists and Microbiologists (IAPM) and Indian Society of Gastroenterology (ISG) decided to make a joint consensus recommendation for handling, processing, and interpretation of SI biopsies for the diagnosis and management of celiac disease (CD) recognizing the inhomogeneous practice of biopsy sampling, orientation, processing, and interpretation. A modified Delphi process was used to develop this consensus document containing a total of 42 statements and recommendations, which were generated by sharing the document draft, incorporating expert's opinion, followed by three cycles of electronic voting as well as a full-day face-to-face virtual ZOOM meeting and review of supporting literature. Of the 42 statements, 7 statements are on small intestinal (SI) biopsy in suspected patients of CD, site and the number of biopsies; 7 on handling, fixative, orientation, processing, and sectioning in pathology laboratories; 2 on histological orientation; 13 statements on histological interpretation and histological grading; 3 on the assessment of follow-up biopsies; 2 statements on gluten-free diet (GFD)-nonresponsive CD; 4 on challenges in the diagnosis of CD; 2 statements each on pathology reporting protocol and training and infrastructure in this area. The goal of this guideline document is to formulate a uniform protocol agreed upon both by the experienced pathologists and gastroenterologists to standardize the practice, improve the yield of small bowel biopsy interpretation, patients' compliance, overall management in CD, and generate unified data for patient care and research in the related field.

Background: Both noncirrhotic portal fibrosis (NCPF) and extrahepatic portal venous obstruction (EHPVO) are important causes of noncirrhotic portal hypertension (PH) in the Asian region. In this study, we analyzed the histopathological changes of liver needle-core biopsies from patients with NCPF and EHPVO. Patients and Methods: The patients were diagnosed as per the Asia Pacific Association for the Study of Liver (APASL) criteria. Minimum adequacy criteria for liver core biopsies were defined, and finally, 69 liver biopsies from patients with NCPF and 100 liver biopsies from patients with EHPVO were analyzed. All histological parameters were predefined, and three experienced pathologists analyzed the biopsies after reaching consensus. Institute ethics committee clearance was taken. Results: Although some histological features were overlapping, phlebosclerosis of intra-hepatic branches of the portal vein (PV), periportal aberrant vascular channels, remnant portal tracts, and hepatic fibrosis beyond the portal tracts without the formation of complete hepatic nodules (P < 0.001 for all) were common histological characteristics of NCPF on core-needle liver biopsies; while maintained lobular architecture, nonspecific dilatation of PV branches, absence of intra-hepatic PV phlebosclerosis, aberrant vascular channels, and significant fibrosis were characteristics of EHPVO. Conclusions: Despite the considerable histological overlap between NCPF and EHPVO, careful histological evaluation, supplemented by clinical features, radiological and biochemical findings can help in making a conclusive diagnosis. Patients with NCPF and EHPVO with clinical jaundice show transaminitis, high serum alkaline phosphatase level, more variceal bleed, and histological evidences of nodular regenerative hyperplasia.

IntroductionWorldwide gastric cancer is the 5th most commonly diagnosed cancer and the leading cause of gastrointestinal cancer-related deaths. Alone surgery provides long-term survival improvements in 20% of the patients with local advanced gastric cancer. The results can be improved considering multimodal management including chemotherapy and radiotherapy. However, in low middle-income countries like India, multimodal management is challenging. Herein, we evaluated the experience of multimodal management of gastric cancer and the long-term outcome.MethodsRetrospective analysis of the data of 372 patients was done from a prospectively maintained computerized database from 1994 to 2021. Records were analyzed for demographic details, treatment patterns, recurrences, and long-term outcomes (DFS and OS). Statistical analysis was done with the package SPSS version 26 (IBM Corp, Chicago, Illinois, USA).ResultsThis study included 372 patients. The mean age of the patients was 54.07. A total of 307 patients (82.5%) were operated upfront, 45 (12%) received NACT, and 20 (5.5%) underwent the palliative procedure. A total of 53.2% underwent curative resection. R0 resection rate was achieved in 95% of patients. A total of 72.58% of patients required adjuvant treatment, and the majority of the patients underwent chemoradiotherapy. The most common site of metastasis was the liver. Median follow-up was 50.16 months. The 3-year disease-free survival and overall survival were 36.28% and 67.8%, and the 5-year disease-free survival and overall survival were 30.15% and 37.7%, respectively.ConclusionOur study suggested that multimodal management is required in locally advanced gastric cancer to achieve good long-term outcomes. The treatment sequence can be tailored based on the available resources.

Gluten ataxia is a rare immune-mediated neurological disorder caused by the ingestion of gluten. The diagnosis is not straightforward as antibodies are present in only up to 38% of patients, but often at lower titers. The symptoms of ataxia may be mild at the onset but lead to permanent damage if remain untreated. It is characterized by damage to the cerebellum however, the pathophysiology of the disease is not clearly understood. The present study investigated the neurochemical profile of vermis and right cerebellum and structural changes in various brain regions of patients with gluten ataxia (n = 6, age range 40–65 years) and compared it with healthy controls (n = 10, 40–55 years). Volumetric 3-D T1 and T1-weighted magnetic resonance imaging (MRI) in the three planes (axial, coronal, and sagittal) of the whole brain and single-voxel 1H- magnetic resonance spectroscopy (MRS) of the vermis and right cerebellum were acquired on 3 T human MR scanner. The metabolite concentrations were estimated using LC Model (6.1–4A) while brain volumes were estimated using the online tool volBrain pipeline and CERES and corrected for partial volumes. The levels of neuro-metabolites (N-acetyl aspartate + N-acetyl aspartate glutamate, glycerophosphocholine + phosphocholine, and total creatine) were found to be significantly lower in vermis, while N-acetyl aspartate + N-acetyl aspartate glutamate and glycerophosphocholine + phosphocholine was lower in cerebellum regions in the patients with gluten ataxia compared to healthy controls. A significant reduction in the white matter of (total brain, cerebellum, and cerebrum); reduction in the volumes of cerebellum lobe (X) and thalamus while lateral ventricles were increased in the patients with gluten ataxia compared to healthy controls. The reduced neuronal metabolites along with structural changes in the brain suggested neuronal degeneration in the patients with gluten ataxia. Our preliminary findings may be useful in understanding the gluten-induced cerebral damage and indicated that MRI and MRS may serve as a non-invasive useful tool in the early diagnosis, thereby enabling better management of these patients.

Introduction: Acute Encephalitis Syndrome (AES) is a group of neurologic manifestation caused by wide range of microbes, chemicals and toxins. Japanese Encephalitis Virus (JEV) is the major cause of AES in India. Isolation of aetiological agent in AES cases presents a fundamental challenge to prevention and management. Lack of study on AES in the paediatric population of Tripura prompted the authors to take up this study. Aim: To determine the clinical profile and short term outcome of children with AES from Tripura, India. Materials and Methods: This hospital-based cross-sectional observational study was conducted from November 2017 to April 2019 in the Department of Paediatrics at Agartala Government Medical College (AGMC), Tripura, India. Total 100 children, from 1 month to 12 years of age, fulfilling definition of AES were enrolled in the study. All the cases were managed as per institutional treatment protocol and were followed-up at one and three months following discharge. Case record, patient profile records and reports of investigations were the study tools. Chi-square test and Fisher’s-exact test were used as per applicability to test the significance of difference of proportions using Statistical Package for the Social Sciences (SPSS) version 15.0. The difference was considered significant for a p-value

Implantation in humans is a multistep process that involves apposition, adhesion, and invasion of the developing blastocyst into the receptive maternal endometrium. Though significant volume of research in this direction has identified important players orchestrating this delicate process, there are still gaps in our understanding of all the sequence of events during embryo implantation. Also, the early pregnancy-related complications that lead to fetal loss and miscarriage often occur in this critical window of implantation, which is primarily defined as the time when the maternal endometrium is supposed to be most receptive to the free blastocyst that emerges out from the zona pellucida. Studies in humans and rodents have identified several mediators like folliculin, LIF, IL11Rα, splicing factor SC35, etc. to be essential for early implantation. Trophoblasts, that form the outer epithelial layer of the blastocyst, participate in the formation of the placenta. During placentation, invasive extravillous trophoblasts (EVTs), migrate into the endometrium, and a transient epithelial to mesenchymal transition (EMT) and remodel the uterine arteries for blood and nutrient exchange.

Treatment of tuberculosis needs to be taken for several weeks, despite good potency of drugs in vitro. Here, the authors show that mesenchymal stem cells can harbor Mycobacterium tuberculosis providing a niche for evasion of anti-bacterial drugs and cytokines.

Purpose – Lifelong learning needs to be visualized as the milestone for generating a progressive and knowledge society. Because it is through lifelong learning that one can continuously upgrade one's knowledge and acquire the relevant skills for getting livelihood opportunities. Moreover, for ensuring a sustainable and advanced society in the 21st century industrial setup, people are desirous to receive a global form of learning as they tend to follow the principle, that is, “earning while learning”. In this context, the various types of online courses, Massive Open Online Courses (MOOCs) and Open Educational Resources (OERs) provide myriad opportunities to the people by introducing them to a global form of learning. Against this background, the introduction of MOOCs in India for providing lifelong learning opportunities might work in a big way. However, to what extent, can MOOCs promote the idea of lifelong learning in a vast country like India needs to be discussed in greater detail. Design/methodology/approach – While writing the paper, descriptive research methodology has been used. The sources such as Report of Census 2011, Human Development Report 2016, 2018, Economic Survey 2016 are also consulted. Analysis has been done based on the data extracted from the secondary source of information. Findings – The literature review made in the paper implies that the educational institutes across India may adopt some of the good national and international practices for transforming the society and produce some need-based MOOCs under the SWAYAM platform with regard to providing opportunities of lifelong learning. Thus, the courses run through SWAYAM should help in achieving the three cardinal principles of the Indian Education – access, equity and quality. However, there are many challenges to be met while the adoption and development of MOOCs for the purpose of lifelong learning in India are taken into consideration. The current modes and popularity of digitally offered education in India thus need to be justified. Research limitations/implications – The discussions made in the paper are limited to a reference to the Indian MOOCs particularly under SWAYAM, and it is a general study only. Practical implications – It is important to note that a new kind of transformation is currently being initiated across the world by encouraging more and more online interventions in the field of education. In fact, various studies are also being conducted on the implementation of online courses across the world, particularly in the developed countries where more than 70% education is delivered online. However, in a country like India, the practical utility or the implementation of the online courses such as MOOCs is not so popular even at present, and it is only limited to a small section of the society. The University Grants Commission (UGC) with a view to promoting CBCS as well as Credit Transfer made 20% course delivery through MOOCs mandatory in Indian higher education. However, the CBCS system itself has several loopholes considered in the Indian context, as it was launched without sufficient ground work, and no one seems to have a clear idea of its implementation method. The UGC's move was to introduce a system of education that would help in bringing parity of Indian higher education with Western or European higher education systems. This paper shall try to imply how the Indian MOOCs should be used in providing lifelong learning opportunities to the people of the country. Social implications – This paper refers to a new social constructivism initiated through MOOCs, where a learner can directly interact with the people in the community, share their own ideas and thoughts and collectively undertake new researches. This is sure to transform the Indian society in the days to come, although a study on the usefulness of the existing MOOCs is of utmost necessity Originality/value – This paper reiterates the necessity of a detailed study of the available MOOCs in India based on the findings of the common problems and challenges of MOOCs development and implementations that need to be resolved first. Then the paper provides an analysis of this situation so that one could develop or adopt a MOOC in order to meet one's need of lifelong learning in a country like India.

Segmental ileal dilatation is an uncommon cause of neonatal intestinal obstruction. This report highlights a rare combination of abnormal distribution of muscles in the muscularis propria and partial loss of interstitial cells of Cajal as causative factors for segmental intestinal dilatation.

Oral inflammatory myofibroblastic tumor (IMT) is extremely rare and its manifestation as generalized gingival enlargement (GGE) has never been reported. We are reporting the case of 50-year-old female patient presenting with recurrent GGE for 4 years. Panoramic radiograph revealed severe bone loss in posterior sextants and root resorption in some teeth. Initial incisional biopsy was suggestive of chronic inflammatory infiltrate with fibrocollagenous tissue. Definitive treatment comprised of surgical excision of the enlarged gingiva with a tapering dose of steroid therapy. Histopathological and immunohistochemical examination from a repeat biopsy of deeper tissues was suggestive IMT. No recurrence was found at 2 years follow up. Recurrent GGE with advanced bone loss and external root resorption should raise the suspicion of a locally aggressive lesion. Dentists should be aware of oral IMT and include it in differential diagnosis of gingival enlargements for comprehensive management to avoid recurrence of the lesion.

The pancreatic neuroendocrine tumors (PanNETs) most commonly present as solid neoplasms; however, very rarely, they may present primarily as cystic neoplasms. Most of the cystic PanNETs are non-secreting tumors, and the radiological features are not well defined. Hence pre-operative diagnosis is usually challenging and the tumors are misdiagnosed as mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, serous cystic neoplasms, solid pseudopapillary neoplasms, and non-neoplastic cysts. However, the management depends on the accurate diagnosis of these cystic lesions, which poses a dilemma. Herein, we report the case of a cystic PanNET in the tail of the pancreas, which was clinically and radiologically misdiagnosed as a mucinous cystic neoplasm. This case is reported to highlight this issue to the medical community regarding the diagnostic difficulty in such rare non-functioning pancreatic neuroendocrine tumors.

Background/Aims The existing histological classifications for the interpretation of small intestinal biopsies are based on qualitative parameters with high intraobserver and interobserver variations. We have developed and propose a quantitative histological classification system for the assessment of intestinal mucosal biopsies. Methods We performed a computer-assisted quantitative histological assessment of digital images of duodenal biopsies from 137 controls and 124 patients with celiac disease (CeD) (derivation cohort). From the receiver-operating curve analysis, followed by multivariate and logistic regression analyses, we identified parameters for differentiating control biopsies from those of the patients with CeD. We repeated the quantitative histological analysis in a validation cohort (105 controls and 120 patients with CeD). On the basis of the results, we propose a quantitative histological classification system. The new classification was compared with the existing histological classifications for interobserver and intraobserver agreements by a group of qualified pathologists. Results Among the histological parameters, intraepithelial lymphocyte count of ≥25/100 epithelial cells, adjusted villous height fold change of ≤0.7, and crypt depth-to-villous height ratio of ≥0.5 showed good discriminative power between the mucosal biopsies from the patients with CeD and those from the controls, with 90.3% sensitivity, 93.5% specificity, and 96.2% area under the curve. Among the existing histological classifications, our quantitative histological classification showed the highest intraobserver (69.7%–85.03%) and interobserver (24.6%–71.5%) agreements. Conclusions Quantitative assessment increases the reliability of the histological assessment of mucosal biopsies in patients with CeD. Such a classification system may be used for clinical trials in patients with CeD.

X-linked lissencephaly, absent corpus callosum, and epilepsy of neonatal onset with ambiguous genitalia comprises the XLAG syndrome and only 15 cases have been reported in literature. Due to its rarity, the exact clinical course and outcome are not known. Exact associations of this disease are also elusive. Hereby we are reporting this extremely rare entity and we searched the English literature extensively to get consolidated knowledge regarding this entity that would help the readers. Pre-natal radiological work-up can detect these malformations, which should be followed by medical termination, counseling and karyotyping. Till date the longest survival noted was 4 years only.

Calotropis procera, a latex producing plant is known to possess medicinal properties including its beneficial effect in gastrointestinal disorders. The anti-inflammatory effect of its latex in various experimental models is noteworthy and in light of this the present study was carried out with an objective to evaluate its efficacy in ulcerative colitis, an inflammatory condition of the colon. Colitis was induced in rats by acetic acid and the rats were divided into four groups where one group served as experimental control and the other groups were treated with two doses of methanol extract of dried latex of C. procera (MeDL; 50 and 150 mg/kg) and mesalazine (MSZ; 300 mg/kg). The study also included normal control (NC) group for comparison of various parameters related to colon like macroscopic changes, ulcer score, adherent mucus content, weight/length ratio, small intestinal transit, oxidative stress and inflammatory markers, tissue histology and immunoreactivity of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor kappa beta (NFκB) subunit p65. Treatment of colitic rats with MeDL produced a significant reduction in colonic mucosal damage as revealed by macroscopic and microscopic evaluation and normalization of tissue levels of oxidative stress markers and pro-inflammatory mediators. The protection afforded by MeDL was also evident from its restorative effect on tissue histology and expression of COX-2, iNOS and NFκB(p65). This study shows that by targeting oxidative stress and NFκB(p65) mediated pro-inflammatory signaling, the latex of C. procera affords protection in colitis and its effect was comparable to that of mesalazine. This study suggests that latex of C. procera could serve as a promising therapeutic option for treating inflammatory conditions of the colon.

Background: It is hypothesized that the duodenal mucosal damage in patients with celiac disease (CeD) is caused by the mucosa-infiltrating lymphoid cells. This study aimed to analyze the immune effective and regulatory T (Treg) cells in duodenal biopsies from treatment-naive adult patients with CeD having different histological grades and controls. Patients and Methods: Dual-color immunohistochemical staining was done in a total of 234 duodenal biopsies, including 132 controls and 102 adult patients with CeD using CD20, CD3:CD4, CD3:CD8, CD4:FoxP3, CD8:FoxP3, and TCRαβ:TCRγδ antibodies. The density of these lymphoid cells in lamina propria and mucosal epithelium was compared between controls and CeD, with different modified Marsh grades. Results: Densities of CD4+ T cells in lamina propria and CD8+γδ intraepithelial lymphocytes (IELs) were significantly more in biopsies from patients with CeD, than in controls. An increasing linear pattern of IELs, CD3+ T cells, and CD20+ B cells was observed with increasing grades of villous abnormalities. Although CD8+ FoxP3+ Treg cells were significantly more in biopsies from patients with CeD, there was no significant difference in CD4+ FoxP3+ Treg cell infiltrate between both the groups. Conclusion: Our finding in this observational study generates interest to study the local intestinal mucosal immunity in CeD in detail. A study to prove the failure of CD4+ FoxP3+ Treg cell recruitment in CeD and its direct functional impact may yield valuable information regarding loss of mucosal tolerance.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400–705) than controls (900, IQR: 667–1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390–620) vs. 427 µm (IQR: 348–569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Density functional theory (DFT) based computation is performed on the endohedrally encapsulated Li3 cluster inside the B40 and C60 cages namely, Li3@B40 and Li3@C60. For both these systems, the Li-Li bond lengths are shorter than that in the free Li3 cluster. Due to confinement, the Li-Li vibrational frequencies increase in both the systems as compared to that in the free Li3 cluster. Thermodynamically, the formation of these two systems is spontaneous in nature as predicted by the negative values of Gibbs’ free energy changes (ΔG). For both the systems one non-nuclear attractor (NNA) is present on the middle of the Li3 cluster which is predicted and confirmed by the electron density analysis. The NNA population and the percentage localization of electron density at the NNA of the Li3@C60 system are higher than that in the Li3@B40 system. At the NNA the values of the Laplacian of electron density are negative and an electron localization function basin is present at the center of the Li3 cluster for localized electrons. Both systems show large values of nonlinear optical properties (NLO). Both the Li3 encapsulated endohedral systems behave as electrides. Electrides have low work function and hence have a great potential in catalytic activity toward the activation of small molecules (such as CO2, N2). Even some electrides have greater catalytic activity than some well-studied metal-loaded catalysts. As the systems under study behave as electrides, they have the power to show catalytic activity and can be used in catalyzing the activation of small molecules.

Background/AimsClassical M1 macrophage activation exhibits an inflammatory phenotype while alternative M2 macrophage activation exhibits an anti-inflammatory phenotype. We aimed to determine whether there are discriminant patterns of macrophage polarization in Crohn's disease (CD) and intestinal tuberculosis (iTB).MethodsColonic mucosal biopsies from 29 patients with iTB, 50 with CD, and 19 controls were examined. Dual colored immunohistochemistry was performed for iNOS/CD68 (an M1φ marker) and CD163/CD68 (an M2φ marker), and the ratio of M1φ to M2φ was assessed. To establish the innate nature of macrophage polarization, we analyzed the extent of mitochondrial depolarization, a key marker of inflammatory responses, in monocyte-derived macrophages obtained from CD and iTB patients, following interferon-γ treatment.ResultsM1φ polarization was more prominent in CD biopsies (P=0.002) than in iTB (P=0.2) and control biopsies. In granuloma-positive biopsies, including those in CD, M1φ predominance was significant (P=0.001). In iTB, the densities of M1φ did not differ between granuloma-positive and granuloma-negative biopsies (P=0.1). Interestingly, higher M1φ polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients.ConclusionsProinflammatory M1φ polarization was more common in colonic mucosa of CD patients, especially in the presence of mucosal granulomas. Further characterization of the innate immune system could help in clarifying the pathology of iTB and CD.

Background/AimsAberrant crypt foci (ACF) are early microscopic lesions of the colonic mucosa, which can be detected by magnified chromoendoscopy. Herein, we have investigated whether ACF identified in different clinical groups can be differentiated based on their characteristics.MethodsMacroscopically unremarkable mucosal flaps were collected from 270 fresh colectomies and divided into 3 clinical groups: colorectal carcinoma (group A), disease controls having known pre-neoplastic potential (group Bc), and disease controls without risk of carcinoma development (group Bn). Topographic and histologic analysis, immunohistochemistry, and molecular studies (high-resolution melt curve analysis, real-time polymerase chain reaction, and Sanger sequencing) were conducted for certain neoplasia-associated markers.ResultsACF were seen in 107 cases, out of which 72 were left colonic ACF and 35 right colonic ACF (67.2% vs. 32.7%, P=0.02). The overall density of left colonic ACF was 0.97/cm, which was greater than the right colonic ACF density of 0.81/cm. Hypercrinia was present in 41 out of 72 left colonic ACF and in 14 out of 35 right colonic ACF (P=0.01). Immunohistochemical expression of p53 was also greater in left colonic ACF than in right colonic ACF (60.5% vs. 38.2%, P=0.03). However, ACF identified among the 3 clinical groups did not show any distinguishing topographic, histological, or genetic changes.ConclusionsLeft colonic ACF appear to be high-risk based on their morphological and prototypic tumor marker signature. ACF identified in different clinical groups do not show significant genotypic or topographic differences. Further detailed genetic studies are required to elucidate them further.

Abstract Background Herein, for the first time, we report aberrant expression of membrane-associated RING-CH8 (MARCH8) in human esophageal squamous cell carcinoma. MARCH8 is a member of the recently discovered MARCH family of really interesting new genes (RING) E3 ligases. Though initial studies primarily focused on its immunomodulatory role, the newly discovered targets of this E3 ligase point towards its possible role in other biological processes such as embryogenesis and inhibition of apoptosis. However, its relevance in cancers is yet to be elucidated. Methods We carried out quantitative real time PCR and immunohistochemistry to examine the levels of MARCH8 mRNA and protein in esophageal squamous cell carcinoma tissues. The role of MARCH8 in esophageal cancer cells was evaluated by cell proliferation, clonogenic and migration/invasion assays and flow cytometry with MARCH8 gene knockdown. Results Significantly increased expression of MARCH8 mRNA was found in esophageal squamous cell carcinoma as compared to distant matched non-malignant tissues (p = 0.024, AUC = 0.654). Immunohistochemical analysis revealed overexpression of MARCH8 protein in 86% of esophageal squamous cell carcinoma tissues (p