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Abstract Background Perianal fistulas (PF) affect one-third patients with Crohn’s disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. Methods An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn’s disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with

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.

Abstract Background Regardless of a proliferation of interest in reducing unsafe practices in healthcare, threats to patient safety (PS) remain high. Moreover, little attention has been paid towards the role of interprofessional education (IPE) in enhancing PS. This qualitative study was conducted to unfold the insights of the senior medical, dental and health sciences students at the University of Sharjah (UoS) in the United Arab Emirates (UAE) about PS in an online IPE-based workshop. Methods This inductive thematic analysis study was conducted on senior medical and health students at the Colleges of Medicine, Dental Medicine, Health Sciences, and Pharmacy of UoS. During an online workshop, students discussed plausible solutions for four real practice-based clinical scenarios with elements of unsafe healthcare practices. During the breakout rooms, the students exhibited high level of articulation and proactively participated in discussions. The data from the online workshop were transcribed and then coding, categorizing, and labelling of recurrent themes were carried out. Multiple individual deliberations, consolidation, incorporation of the identified preliminary themes, and merging and reorganizing sub-themes led to a final thematic framework. Results This work delved into the perspectives of 248 students regarding teamwork, communication, problem-solving, and other aspects concerning PS in interprofessional settings in an online workshop. The iterative process of data transcription, curating and qualitative analysis surfaced 32 codes. Later, the inductive themaric analysis yielded five themes with distinct yet interconnected nested subthemes in the context of PS in IPE settings. These themes of information sharing and grounding (problem-solving, social skills), maintaining communication (clinical reasoning, shared mental model), executing interprofessional activities (collaborative practice, collaboration scripts), professional cognitive abilities (cognitive maturity, metacognition), and negotiating professional identities (systematic change, socio-economic scaffolding) emerged as fundamental pillars for enhancing PS in healthcare. Conclusion Our study demonstrated the outcome of an innovative and team-based workshop which embedded PS within a scaffold of IPE environment. This research calls for incorporation of the emerging areas of clinical reasoning, problem solving, collaborative practice, and shared mental model into medical curricula for structured IPE in improving PS domains in medical education. These findings underscore the need for multifaceted dimensions of IPE imperatives for cultivating collaborative competence.

Abstract The gut microbiome plays a significant role in the development of Type 2 Diabetes Mellitus (T2DM), but the functional mechanisms behind this association merit deeper investigation. Here, we used the nanopore sequencing technology for metagenomic analyses to compare the gut microbiome of individuals with T2DM from the United Arab Emirates (n = 40) with that of control (n = 44). DMM enterotyping of the cohort resulted concordantly with previous results, in three dominant groups Bacteroides (K1), Firmicutes (K2), and Prevotella (K3) lineages. The diversity analysis revealed a high level of diversity in the Firmicutes group (K2) both in terms of species richness and evenness (Wilcoxon rank-sum test, p value

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.

Abstract Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this study, we investigated how diet changed the gut bacteriome, mycobiome and metabolome in people with and without type 2 Diabetes.1 Differential abundance testing determined that the metabolites Propionate, U8, and 2-Hydroxybutyrate were significantly lower, and 3-Hydroxyphenyl acetate was higher in the high fiber diet compared to low fiber diet in the healthy control group. Next, using multi-omics factor analysis (MOFA2), we attempted to uncover sources of variability that drive each of the different groups (bacterial, fungal, and metabolite) on all samples combined (control and DM II). Performing variance decomposition, ten latent factors were identified, and then each latent factor was tested for significant correlations with age, BMI, diet, and gender. Latent Factor1 was the most significantly correlated. Remarkably, the model revealed that the mycobiome explained most of the variance in the DM II group (12.5%) whereas bacteria explained most of the variance in the control group (64.2% vs. 10.4% in the DM II group). The latent Factor1 was significantly correlated with dietary intake (q 0.6). Alternatively, a linear regression model was fitted per disease group for each genus to visualize the relationship between the factor values and feature abundances, showing Xylose with positive weights and Propionate, U8, and 2-Hydroxybutyrate with negative weights. This data provides new information on the microbially derived changes that influence metabolic phenotypes in response to different diets and disease conditions in humans.

[This corrects the article DOI: 10.1371/journal.pone.0259588.].

Abstract Background Despite significant efforts to contain the Coronavirus Disease 2019 (COVID-19) pandemic through mass vaccination, numerous nations throughout the world have recorded breakout infections. The incidence and severity of COVID-19 breakthrough infections in the United Arab Emirates (UAE) remain unknown despite extensive COVID-19 vaccine coverage. The goal of this research is to establish the characteristics of COVID-19 breakthrough infections in the UAE’s vaccinated population. Methods Between February and March 2022, we conducted a descriptive cross-sectional study in the UAE with 1533 participants to examine the characteristics of COVID-19 breakthrough infection among the vaccinated population. Results The vaccination coverage was 97.97%, and the COVID-19 breakthrough infection rate was 32.1%, requiring hospitalization in 7.7% of cases. The bulk of the 492 COVID-19 breakthrough infections reported was among young adults (67%), with the majority experiencing mild to moderate symptoms (70.7%) or remaining asymptomatic (21.5%). Conclusions COVID-19 breakthrough infection were reported in younger age, male sex, non-healthcare professions, vaccination with inactivated whole virus vaccine (Sinopharm), and not receiving a booster dose. Information on breakthrough infection in the UAE might influence public health decisions and motivate measures such as providing additional booster doses of the vaccines to the people.

Background: Hepatitis B virus (HBV) infection is one of the major causes of chronic liver disease, which progresses from chronic hepatitis B (CHB) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Early detection and laboratory-based screening of hepatocellular carcinoma are still major challenges. This study was undertaken to determine whether the cancer hallmark gene signatures that are released into circulation as circulating tumour DNA (ctDNA) can be used as a liquid biopsy marker for screening, early detection, and prognosis of HCC.Methods: A total of 130 subjects, including HBV-HCC (n = 80), HBV-cirrhotic and non-cirrhotic (n = 35), and healthy (n = 15) controls, were evaluated for TP53 and beta-catenin (CTNNB1) gene hotspot mutations in ctDNA by Sanger-based cycle sequencing and droplet digital PCR (ddPCR) assays. Mutation detection frequency, percentage mutant fractions, and their association with tumour stage, mortality, and smoking habits were determined.Results: Sanger-based cycle sequencing was carried out for 32 HCC patients. Predict SNP Tools analysis indicated several pathogenic driver mutations in the ctDNA sequence, which include p.D228N, p.C229R, p.H233R, p.Y234D, p.S240T, p.G245S, and p.R249M for TP53 gene exon 7 and p.S33T for CTNNB1 gene exon 3. The TP53 c.746G>T (p.R249M) mutation was detected predominately (25% cases) by sequencing, but there was no dominant mutation at position c.747G>T (p.R249S) that was reported for HBV-HCC patients. A dual-probe ddPCR assay was developed to determine mutant and wild-type copy numbers of TP53 (p.R249M and p.R249S) and CTNNB1 (p.S45P) and their percentage mutant fraction in all 130 subjects. The TP53 R249M and CTNNB1 S45P mutations were detected in 31.25% and 26.25% of HCC patients, respectively, with a high mutant-to-wild-type fraction percentage (1.81% and 1.73%), which is significant as compared to cirrhotic and non-cirrhotic patients. Poor survival was observed in HCC patients with combined TP53 and CTNNB1 gene driver mutations. The TP53 R249M mutation was also significantly (p < 0.0001) associated with smoking habits (OR, 11.77; 95% CI, 3.219–36.20), but not the same for the TP53 R249S mutation.Conclusion: Screening of ctDNA TP53 and CTNNB1 gene mutations by ddPCR may be helpful for early detection and identifying the risk of HCC progression.

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.

Abstract Background In recent years, social networking sites (SNSs) have evolved beyond connection and networking to become a powerful instructional tool. There is still a dearth of knowledge on the professional use of SNSs for education particularly among students from diverse backgrounds. This study examined the extent and pattern of SNSs usage for education across six institutions and then conducted an interventional workshop to fortify and regulate the educational use of SNSs. Methods This multicenter study was done in two phases. In the first phase, an online cross-sectional survey using a validated inventory was administered to determine the prevalence, extent, and preferences of SNSs usage by undergraduate students in medicine, health sciences and dentistry across five centers. Later, the second phase of the study was undertaken in a 75-min guided live workshop about the appropriate use of SNSs in academia. Additionally, pre- and post-test surveys were conducted to assess the impact and outcome of workshop. Results Of the 1722 respondents, 1553 (90%) reported using SNSs with the frequency of once a month to three to five times per day for education and to stay in touch with others. Most students agreed with the benefits of SNSs for education mainly in terms of information gathering, networking and collaboration. Twitter, Instagram, and Pinterest were noted as the most preferred SNSs for education. Nevertheless, 63% perceived that proper instruction was required for the efficient use of SNSs. Following the guided workshop, there was a significant improvement in web technology understanding, digital professionalism, skills and knowledge on the productive use of SNSs. Students rated the efficient for conceptual learning, connection to community practice, e-portfolio, and collaborative learning as the top four major teaching and learning strategies, respectively, in the post-workshop survey. Conclusion Our study demonstrates that SNSs can be used as learning tools in medical education. However, SNSs usage should be regulated and guided for a more collegial and coherent learning climate in the digital realm. We urge medical educators to integrate SNSs into their courses for a technologically advanced and impactful curriculum.

Abstract Background Medical schools have the obligation to direct their education toward addressing the priority health concerns of the societies that they serve. The purpose of this study was to evaluate the integration of the concepts and values of social accountability into the case scenarios that are used in a problem-based learning (PBL) curriculum at a medical school in the United Arab Emirates (UAE). Methods A validated “social accountability inventory for PBL” was used for examining 70 case scenarios in a problem-based learning (PBL) medical curriculum. Results The findings of the study showed that patient gender and age were included in all the 70 case scenarios. Vast majority of the case scenarios had successfully integrated the social accountably values in addressing the following: the major health problems or social health concerns of the UAE (73%), the social determinants of health (70%), the contextual integration of medical professionalism (87%), the evolving roles of doctors in the health system (79%), the healthcare referral system based on the case complexity (73%), the involvement of different stakeholders in healthcare (87%), psychosocial issues rather than only the disease-oriented issues (80%) and the values of health promotion/prevention (59%) cases. On the other hand, the case scenarios were deficient in integrating other social accountability values that related to the importance of treatment cost-effectiveness (91%), consideration of the underserved, disadvantaged or vulnerable populations in the society (89%), patient’s ethnicity (77%), multidisciplinary approach to patient management (67%), the socioeconomic statuses of patients (53%), the issues regarding the management of the health system (39%) respectively. There was variability in integrating the social accountability values in case scenarios across different units which are based on organ system. Conclusion Medical educators and healthcare leaders can use this valuable data to calibrate the curriculum content, especially when using a problem-based learning curriculum to integrate the values of social accountability such as relevance, quality, equity and cost-effectiveness to train the future generation of healthcare providers to be ready to address the ever-changing and diverse needs of the societies.

PURPOSEFor unresectable gallbladder cancer (GBC), gemcitabine and platinum is standard combination; however, outcome is poor. We conducted this study to find feasibility of modified flourouracil, oxaliplatin, and irinotecan in this group.MATERIALS AND METHODSWe conducted a prospective, phase II single-arm pilot study. Inclusion criteria were histologically proven GBC and Eastern Cooperative Oncology Group 0-1. Primary end points were overall response rates and overall survival. The following treatment was given: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and irinotecan 150 mg/m2, all once on day 1, fluorouracil 2,400 mg/m2 continuous intra-venous infusion over 46 hours repeated every 2 weeks, and maximum 12 doses, with primary granulocyte colony-stimulating factor prophylaxis.RESULTSBetween February 2019 and July 2020, 29 patients with unresectable GBC were enrolled. The median age was 52 years, and 18 were females. The Eastern Cooperative Oncology Group was 0 in 4. Five had bilirubin > normal, and 15 each had high serum alkaline phosphatase and carbohydrate antigen 19-9. Twenty-five patients had stage IV disease, and remaining unresectable locally advanced disease. A median of 8.5 cycles was given, and 11 completed treatment. Nine stopped chemotherapy because of progression, and one because of toxicity, and treatment is ongoing in three. Twenty-two required dose reduction. A treatment delay of 1-2 weeks was seen in 25 patients. Best response was complete response 1, partial response 13 (overall response rate 48.2%), and stable disease 9. Four patients with metastatic disease underwent R0 resection. As on cutoff date, nine are surviving (three without disease). Eighteen died of PD, and in two, cause was unknown. There was no toxic death. The median overall survival and progression-free survival were 309 and 252 days, respectively. Twenty-three patients experienced grade III or IV toxicity, and common were diarrhea (13), vomiting (12), and anemia (7).CONCLUSIONFirst-line modified flourouracil, oxaliplatin, and irinotecan is feasible in unresectable GBC with encouraging responses. Toxicities are higher but manageable. Higher response rates make this an option to explore in borderline resectable cases.

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: Hepatocellular carcinoma (HCC) occurs in the majority of patients with underlying chronic liver disease (CLD) of viral and non-viral etiologies, which requires screening for early HCC diagnosis. Liquid biopsy holds great promise now for early detection, prognosis, and assessment of response to cancer therapy. Cell-free DNA (cfDNA) as a liquid biopsy marker can be easily detected by a real-time quantitative PCR (RT-qPCR) assay for a change in its concentration, integrity, and fragmentation in cancer.Methods: Patients with HCC (n = 100), CLD (n = 100), and healthy (n = 30) controls were included in the study. The cfDNA was isolated from serum and real-time quantitative PCR (RT-qPCR) was carried out using primer pairs for large (>205 bp) and small (110 bp) fragments of repetitive elements (ALU and LINE1) and housekeeping genes (β-Actin and GAPDH). Total cfDNA concentrations and integrity index were determined by the absolute quantitation method (L/S ratio or cfDII-integrity). The cfDII as a measure of fragmentation was determined by comparative Ct (2–ΔΔCt) method of relative quantification (cfDII-fragmentation). Using a receiver operating characteristic (ROC) curve, cfDII-integrity and cfDII-fragmentation were used to differentiate HCC from CLD patients or healthy controls.Results: The total cfDNA concentrations in the sera of HCC (244 ng/ml) patients were significantly higher than those of CLD (33 ng/ml) patients and healthy (16.88 ng/ml) controls. HCC patients have shown poor DNA integrity or excess cfDNA fragmentation than CLD patients and healthy controls. The cfDII-integrity of GAPDH and ALU fragment significantly differentiate HCC from CLD at AUROC 0.72 and 0.67, respectively. The cfDII-fragmentation following normalization with cfDNA of healthy control has shown significant differential capabilities of HCC from CLD at AUROC 0.67 using GAPDH and 0.68 using the ALU element. The ROC curve of LINE1 and β-actin cfDII was not found significant for any of the above methods. The cfDII-fragmentation trend in HCC patients of different etiologies was similar indicating increased cfDNA fragmentation irrespective of its etiology.Conclusion: The cfDII measuring both DNA integrity (L/S ratio) and fragmentation of the Alu and GAPDH genes can differentiate HCC from CLD patients and healthy individuals.

Increased levels of 17-β estradiol (E2) due to pregnancy in young women or to hormonal replacement therapy in postmenopausal women have long been associated with an increased risk of yeast infections. Nevertheless, the effect underlying the role of E2 in Candida albicans infections is not well understood. To address this issue, functional, transcriptomic, and metabolomic analyses were performed on C. albicans cells subjected to temperature and serum induction in the presence or absence of E2. Increased filament formation was observed in E2 treated cells. Surprisingly, cells treated with a combination of E2 and serum showed decreased filament formation. Furthermore, the transcriptomic analysis revealed that serum and E2 treatment is associated with downregulated expression of genes involved in filamentation, including HWP1, ECE1, IHD1, MEP1, SOD5, and ALS3, in comparison with cells treated with serum or estrogen alone. Moreover, glucose transporter genes HGT20 and GCV2 were downregulated in cells receiving both serum and E2. Functional pathway enrichment analysis of the differentially expressed genes (DEGs) suggested major involvement of E2 signaling in several metabolic pathways and the biosynthesis of secondary metabolites. The metabolomic analysis determined differential secretion of 36 metabolites based on the different treatments’ conditions, including structural carbohydrates and fatty acids important for hyphal cell wall formation such as arabinonic acid, organicsugar acids, oleic acid, octadecanoic acid, 2-keto-D-gluconic acid, palmitic acid, and steriacstearic acid with an intriguing negative correlation between D-turanose and ergosterol under E2 treatment. In conclusion, these findings suggest that E2 signaling impacts the expression of several genes and the secretion of several metabolites that help regulate C. albicans morphogenesis and virulence.

Alterations in the oral microbiota composition may influence mental health. However, linkages between compositional changes in the oral microbiota and their role in mental health among cigarette smokers remain largely unknown. In this study, we used shotgun metagenomics data for the oral microbiome of 105 participants. The data showed Bacteroidota, Fusobacteriota, Firmicutes, Proteobacteria, and Actinobacteria to be the most abundant phyla; Streptococcus, Haemophilus D, and Veillonella are the most abundant genera. Then, we clustered our subjects into avoidance and activation groups based on the behavioral activation for depression scale (BADS). Interestingly, the avoidance group exhibited a higher oral microbiome richness and diversity (alpha diversity). Differential abundance testing between BADS avoidance and activation groups showed the phyla Bacteroidota (effect size 0.5047, q = 0.0037), Campylobacterota (effect size 0.4012, q = 0.0276), Firmicutes A (effect size 0.3646, q = 0.0128), Firmicutes I (effect size 0.3581, q = 0.0268), and Fusobacteriota (effect size 0.6055, q = 0.0018) to be significantly increased in the avoidance group, but Verrucomicrobiota (effect size−0.6544, q = 0.0401), was found to be significantly decreased in the avoidance risk group. Network analysis of the 50 genera displaying the highest variation between both groups identified Campylobacter B, Centipeda, and Veillonella as hub nodes in the avoidance group. In contrast, Haemophilus and Streptococcus were identified as hub nodes in the activation group. Next, we investigated functional profiles of the oral microbiota based on BADS avoidance and activation groups and found Lysine degradations pathway was significantly enriched between both groups (ANCOM-BC, q = 0.0692). Altogether, we provide evidence for the presence of depression-related changes in the oral microbiota of smokers and possible functional contribution. The identified differences provide new information to enrich our understanding of oral microbiota-brain axis interplay and their potential impact on mental health.

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.

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.

Abstract Background In the current wave of educational reforms, understanding teaching styles of medical faculty can help modify instructional strategies for effective teaching. Few studies have probed distinctive teaching styles of medical faculty. We compared preferred teaching styles of faculty from seven medical schools in United Arab Emirates, the Netherlands, Saudi Arabia, Malaysia, Pakistan, and Sudan. Methods The validated Grasha-Riechmann teaching style inventory was administered online for data collection and used SPSS version 20.0 for statistical analysis. Results Of the 460 invitees, 248 responded (response rate; 54%). Delegator teaching style was most common with a highest median and mean of 2.38 and 2.45, respectively. There was a significant correlation between expert and authority teaching styles, correlation coefficient 0.62. Similarly, we found a significant correlation between authority teaching style and nature of curriculum, correlation coefficient 0.30. Multiple regression analysis showed that only authority teaching style and male gender had significant correlation. Interestingly, 117 (47%) teachers disagreed with the teaching philosophy of delivering course contents by strictly following learning outcomes. Female teachers (114/248) were more willing to negotiate with their students regarding how and what to teach in their course, while male teachers tended to allow more autonomy by allowing students to set their learning agenda. Conclusions This study showed that the medical teachers preferred delegator teacher style that promotes students’ collaboration and peer-to-peer learning. Most teachers are conscious of their teaching styles to motivate students for scientific curiosity. These findings can help medical educators to modify their teaching styles for effective learning.

Abstract Background Heavy tobacco smoking, a hallmark feature of lung cancer, is drastically predominant in Middle Eastern populations. The precise links between nicotine dependence and the functional contribution of the oral microbiota remain unknown in these populations. Methods We evaluated the composition and functional capabilities of oral microbiota with relation to cigarette smoking in 105 adults through shotgun metagenomics using buccal swabs. Results The oral microbiota composition in our study subjects was dominated by the phyla Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes, in addition to the genera Prevotella and Veillonella, similar to previously described westernized cohorts. Furthermore, the smoker's oral microbiota represented a significant abundance of Veillonella dispar, Leptotrichia spp. and Prevotella pleuritidis when compared to non-smokers. Within the smoking groups, differential relative abundance testing unveiled relative abundance of Streptobacillus hongkongensis, Fusobacterium massiliense, Prevotella bivia in high nicotine dependent compared to low nicotine dependent profiles based on Fagerström Test for Nicotine Dependence. Functional profiling showed marked differences between smokers and non-smokers. Smokers exhibited an enrichment of Tricarballylate utilization and Lactate racemization when compared to the non-smokers. According to their nicotine dependence, enrichment of Xanthosine utilization, p-Aminobenzoyl-Glutamate utilization, and multidrug efflux pump in Campylobacter jejuni biosynthesis modules were detected in the high nicotine dependent group. Conclusions These compositional and functional differences may provide critical insight on how variations in the oral microbiota could predispose to respiratory illnesses and smoke cessation relapse in cigarette smokers. In particular, the observed enrichment of Fusobacterium and Prevotella in the oral microbiota possibly suggests an intriguing linkage to gut and lung cancers.

Abstract Type 2 diabetes mellitus (T2DM) drastically affects the population of Middle East countries with an ever-increasing number of overweight and obese individuals. The precise links between T2DM and gut microbiome composition remain elusive in these populations. Here, we performed 16 S rRNA and ITS2- gene based microbial profiling of 50 stool samples from Emirati adults with or without T2DM. The four major enterotypes initially described in westernized cohorts were retrieved in this Emirati population. T2DM and non-T2DM healthy controls had different microbiome compositions, with an enrichment in Prevotella enterotype in non-T2DM controls whereas T2DM individuals had a higher proportion of the dysbiotic Bacteroides 2 enterotype. No significant differences in microbial diversity were observed in T2DM individuals after controlling for cofounding factors, contrasting with reports from westernized cohorts. Interestingly, fungal diversity was significantly decreased in Bacteroides 2 enterotype. Functional profiling from 16 S rRNA gene data showed marked differences between T2DM and non-T2DM controls, with an enrichment in amino acid degradation and LPS-related modules in T2DM individuals, whereas non-T2DM controls had increased abundance of carbohydrate degradation modules in concordance with enterotype composition. These differences provide an insight into gut microbiome composition in Emirati population and its potential role in the development of diabetes mellitus.

Mini-gastric bypass/one anastomosis gastric bypass (MGB/OAGB) is an emerging weight loss surgical procedure. There are serious concerns not only regarding the symptomatic biliary reflux into the stomach and the oesophagus but also the increased risk of malignancy after MGB/OAGB. A 54-year-old male, with a body mass index (BMI) of 46.1 kg/m2, underwent Robotic MGB at another centre on 22nd June 2016. His pre-operative upper gastrointestinal endoscopy was not done. He lost 58 kg within 18 months after the surgery and attained a BMI of 25.1 kg/m2. However, 2-year post-MGB, the patient had rapid weight loss of 19 kg with a decrease in BMI to 18.3 kg/m2 within a span of 2 months. He also developed progressive dysphagia and had recurrent episodes of non-bilious vomiting. His endoscopy showed eccentric ulcerated growth in lower oesophagus extending up to the gastro-oesophageal junction and biopsy reported adenocarcinoma of oesophagus. MGB/OAGB has a potential for bile reflux with increased chances of malignancy. Surveillance by endoscopy at regular intervals for all patients who have undergone MGB/OAGB might help in early detection of Barrett's oesophagus or carcinoma of oesophagus or stomach.

Candida albicans is the leading cause of life-threatening bloodstream candidiasis, especially among immunocompromised patients. The reversible morphological transition from yeast to hyphal filaments in response to host environmental cues facilitates C. albicans tissue invasion, immune evasion, and dissemination. Hence, it is widely considered that filamentation represents one of the major virulence properties in C. albicans. We have previously characterized Ppg1, a PP2A-type protein phosphatase that controls filament extension and virulence in C. albicans. This study conducted RNA sequencing analysis of samples obtained from C. albicans wild type and ppg1Δ/Δ strains grown under filament-inducing conditions. Overall, ppg1Δ/Δ strain showed 1448 upregulated and 710 downregulated genes, representing approximately one-third of the entire annotated C. albicans genome. Transcriptomic analysis identified significant downregulation of well-characterized genes linked to filamentation and virulence, such as ALS3, HWP1, ECE1, and RBT1. Expression analysis showed that essential genes involved in C. albicans central carbon metabolisms, including GDH3, GPD1, GPD2, RHR2, INO1, AAH1, and MET14 were among the top upregulated genes. Subsequent metabolomics analysis of C. albicans ppg1Δ/Δ strain revealed a negative enrichment of metabolites with carboxylic acid substituents and a positive enrichment of metabolites with pyranose substituents. Altogether, Ppg1 in vitro analysis revealed a link between metabolites substituents and filament formation controlled by a phosphatase to regulate morphogenesis and virulence.

Social accountability (SA) is an obligation for medical schools in meeting the priority health concerns of the communities they serve. To measure the integration of SA principles into medical curricula, suitable tools are needed. This study developed and validated an inventory to assess SA values within the existing case scenarios used in problem-based learning (PBL) curricula. The Delphi technique was employed to develop and validate the new inventory. The validation used expert opinion and calculated the content validity using content validity indices (CVIs). The initial draft (Draft 0) was formulated with 25 open-ended questions. Following expert evaluation, Draft 1 had 22 closed-ended questions and the mean ratings, according to the experts, were as follows: relevance, 3.33–4.83; importance (3.5–4.8); clarity (3.33–4.83); and simplicity (3:00–4.67). Draft 2 had 19 questions. After a further round of rating and analysis, a final draft was prepared, consisting of 17 items, with CVI scores ≥ 0.8 and 100% overall satisfaction. Using this inventory tool will help health professions schools to translate SA indicators into curricular activities by identifying the gaps in their PBL curricula. Deficiencies can be either in the type of case scenarios used or the triggers embedded in the individual case scenarios, subsequently leading to the development of PBL case scenarios that address real health social needs. A revision and rewriting of the problem case scenarios to incorporate SA will be the next step.

Background: Gallbladder carcinoma (GBC) exhibits poor prognosis due to its detection at an advanced stage. Upregulation of lysosomal cysteine proteases cathepsin L (CTSL) and cathepsin B (CTSB) has been implicated in several tumorigenic processes. However, no such information in GBC was available. Therefore, the present study was planned to investigate the expression and clinical significance of these cathepsins in GBC.Methods: Activities of CTSL and CTSB were assayed in the gallbladder (GB) tissues obtained from GBC patients (n = 43) and control subjects (n = 69). Protein and mRNA levels were quantified using immunohistochemistry and real-time PCR (qPCR), respectively. Finally, serum levels of CTSL and CTSB were estimated by ELISA. Receiver operating characteristic (ROC) curve analysis was used for the assessment of sensitivity, specificity, and diagnostic accuracy of these cysteine cathepsins in GBC. The association of combined CTSL and CTSB activity with overall survival was assessed using Kaplan Meier survival analysis.Results: The expression and activity of both CTSL and CTSB were significantly increased (p < 0.050) in tumors of GBC patients as compared to controls. Enzymatic activity of CTSL+B and CTSB exhibited a strong positive association with tumor stage and lymph node involvement in GBC (p < 0.050). Interestingly, the elevated activity of combined CTSL+B was also associated with increased mortality in these patients. Furthermore, significantly enhanced levels of serum CTSL and CTSB were also observed in GBC (p < 0.050) as compared to controls. ROC analysis revealed high diagnostic significance of serum CTSB and CTSL for distinguishing GBC patients from controls with an area under the curve (AUC) of 82 and 77%, respectively.Conclusion: This study, for the first time, demonstrates the clinical significance of CTSL and CTSB overexpression in GBC. Our findings may help improve the clinical management of this carcinoma.

Background/AimsTruelove and Witts criteria have been used to define acute severe colitis since the 1950s. However, hemoglobin (an additional criterion of the definition) levels in the general population in developing countries are lower than in the population of developed countries. We aimed to determine the relevance of Truelove and Witts criteria in the Indian population.MethodsConsecutive patients with acute severe colitis satisfying the Truelove and Witts criteria, hospitalized at a single center between April 2015 and December 2016 were included. All patients received intravenous corticosteroids and 16 required colectomy. The hemoglobin levels at admission were subsequently excluded from the classification criteria, and the effect this had on the criteria for diagnosis was determined.ResultsOut of 61 patients of acute severe colitis diagnosed according to the original Truelove and Witts criteria, 12 patients (20%) had 1 additional criterion, 33 (54%) had 2 additional criteria and 16 (26%) had 3 or more additional criteria in addition to 6 or more blood stained stools on admission. On excluding hemoglobin as an additional criterion from the Truelove and Witts definition, all patients still met the criteria for acute severe colitis.ConclusionsTruelove and Witts criteria can be used to define acute severe colitis in India, despite lower mean hemoglobin in the native population.

Background/Aims: Patients with small bowel strictures have varied etiologies, including malignancy. Little data are available on the demographic profiles and etiologies of small bowel strictures in patients who undergo surgery because of intestinal obstruction but do not have a definitive pre-operative diagnosis.Methods: Retrospective data were analyzed for all patients operated between January 2000 and October 2014 for small bowel strictures without mass lesions and a definite diagnosis after imaging and endoscopic examinations. Demographic parameters, imaging, endoscopic, and histological data were extracted from the medical records. Univariate and multivariate analyses were conducted to identify factors that could differentiate between intestinal tuberculosis (ITB) and Crohn's disease (CD) and between malignant and benign strictures.Results: Of the 7,425 reviewed medical records, 89 met the inclusion criteria. The most common site of strictures was the proximal small intestine (41.5%). The most common histological diagnoses in patients with small bowel strictures were ITB (26.9%), CD (23.5%), non-specific strictures (20.2%), malignancy (15.5%), ischemia (10.1%), and other complications (3.4%). Patients with malignant strictures were older than patients with benign etiologies (47.6±15.9 years vs. 37.4±16.4 years, P=0.03) and age >50 years had a specificity for malignant etiology of 80%. Only 7.1% of the patients with malignant strictures had more than 1 stricture and 64% had proximally located strictures. Diarrhea was the only factor that predicted the diagnosis of CD 6.5 (95% confidence interval, 1.10–38.25; P=0.038) compared with the diagnosis of ITB.Conclusions: Malignancy was the cause of small bowel strictures in approximately 16% patients, especially among older patients with a single stricture in the proximal location. Empirical therapy should be avoided and the threshold for surgical resection is low in these patients.

Pseudoaneurysmogastric fistula is a rare consequence of pseudoaneurysms occurring in the vicinity of stomach. They are the result of pseudoaneurysms eroding into the stomach, and represent a life threatening emergency. Urgent surgical intervention is often necessary to salvage the patient. Data regarding the presentation and management of this condition is sparse. Herein, we present our experience with four cases of pseudoaneurysmogastric fistula, their clinical context, presentation, management and outcomes. We attempt to outline an algorithm for the diagnosis and management of this unusual complication.

Helicobacter pylori (H. pylori) is known to colonize gastric mucosa, induce inflammation, and alter gastric microbiota resulting in a spectrum of gastric diseases. Likewise, changes in gut microbiota have recently been linked with various metabolic and inflammatory diseases. While extensive number of studies were published examining the relationship between H. pylori and gastric microbiota, little is known about the impact of H. pylori on downstream gut microbiota. In this study, we performed 16 S rRNA and ITS2-based microbial profiling analysis of 60 stool samples from adult individuals. Remarkably, the gut microbiota of H. pylori infected individuals was shown to be increased of members belonging to Succinivibrio, Coriobacteriaceae, Enterococcaceae, and Rikenellaceae. Moreover, gut microbiota of H. pylori infected individuals was shown to have increased abundance of Candida glabrata and other unclassified Fungi. These results links possible role for H. pylori-associated changes in the gut microbiota in intestinal mucosal barrier disruption and early stage colorectal carcinoma deployment. Altogether, the identified differences in bacterial and fungal composition provides important information that may eventually lead to the development of novel biomarkers and more effective management strategies.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

INTRODUCTION: Professionalism is an essential theme in both undergraduate and postgraduate medical education. The current study aimed to assess the preclerkship medical students' perception on medical professionalism. METHODS: A cross-sectional qualitative study using the critical incident technique was conducted at the University of Sharjah in the United Arab Emirates (UAE). An online survey was sent to 300 medical students (years 1–3). Participants were asked to describe an official doctor–patient encounter that they have experienced in a health-care setting and to highlight the professional behaviors in that encounter. They were then requested to list the top five characteristics of a professional doctor. Thirty (10%) medical students responded to the study; only 13 reported real incidents. The responses were independently reviewed by the authors. The descriptions of the professional attitudes were grouped according to the six domains of professionalism defined by the American Board of Internal Medicine (ABIM) Physicians Charter and then plotted against the nine domains of medical professionalism published in the UAE Consensus Statement. RESULTS: The most common professional behaviors reported were patience, honesty, respect, and patient care. The participants addressed all six domains of professionalism described by the ABIM physicians charter (altruism, accountability, duty , excellence, honor and integrity, and respect for others) and all the domains of medical professionalism published in the UAE Consensus Statement, except for “commitment to advocacy” and “commitment to education” domains. CONCLUSION: Preclerkship medical students had an insight about the professional behaviors needed from doctors before formal teaching about professionalism in the curriculum.

Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder, with increased risk of developing benign and malignant tumors of the gastrointestinal tract (GIT). However, the synchronous presence of multiple GIT stromal tumors and duodenal submucosal somatostatinoma, like in this 50-year-old female NF-1 patient, is very rare. She presented with hematemesis, malena, along with multiple neurofibromas all over the body. Thorough radiological and peroperative work-up revealed multiple ulcerated submucosal and serosal nodules in the proximal small intestine. Histological work-up revealed diagnosis of a duodenal submucosal somatostatinoma with multifocal serosal gastrointestinal stromal tumors. This case is being reported to highlight the rare coincidence of multiple GIT tumors in an NF-1 patient.

Transhiatal herniation of abdominal organs after oesophageal resection and reconstruction is rare and sparsely described in the literature. The commonest organ to herniate is the colon. Pancreatic herniation has been reported twice before. We report a case of postoesophagectomy transhiatal pancreatic herniation in an asymptomatic patient.

A case of unilobar Caroli′s disease in an 8-year-old girl treated with left hepatectomy is reported here.