Investors Dilemma

The case shows an ethical dilemma with Angel investor Arthur Vandelay. His Angel fund has the choice to invest in two different businesses. One was started by a Stanford MBA who may have obtained the idea for the business unethically. The other is run by a hardworking man from Pittsburgh who needs this money to keep his business alive and provide for his family. The Stanford MBA clearly has the better business and Vandelay is the deciding vote. He faces a dilemma on whether to invest with his head or go with his heart

Lactobacillus Cell Surface Proteins Involved in Interaction with Mucus and Extracellular Matrix Components

The gut microbiota is a complex microbial ecosystem where bacteria, through mutual interactions, cooperate in maintaining of wellbeing and health. Lactobacilli are among the most important constituents of human and animal intestinal microbiota and include many probiotic strains. Their presence ensures protection from invasion of pathogens, as well as stimulation of the immune system and protection of the intestinal flora, often exerted through the ability to interact with mucus and extracellular matrix components. The main factors responsible for mediating adhesion of pathogens and commensals to the gut are cell surface proteins that recognize host targets, as mucus layer and extracellular matrix proteins. In the last years, several adhesins have been reported to be involved in lactobacilli–host interaction often miming the same mechanism used by pathogens

Hepatosplenic T-Cell Lymphoma Mimicking Acute Onset of Cholestatic Hepatitis in a Young Immunocompetent Man: A Case Report

We herein report a case of hepatosplenic T-cell lymphoma (HSTCL) incidentally found in a 30-year-old man who came to the emergency department after an ankle trauma. At admission, laboratory tests revealed abnormal liver enzymes and pancytopenia, and imaging showed mild hepatosplenomegaly. During hospitalization, the patient's clinical condition worsened rapidly, with a concomitant increase in cholestatic enzymes, severe jaundice, and the worsening of pancytopenia. Causes of liver injury, including many infectious diseases, were explored until the diagnosis of HSTCL was made by liver and bone marrow biopsies. Subsequently, the patient underwent six cycles of chemotherapy with a CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone or prednisolone) regimen and one with Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) but, despite this aggressive treatment, died due to disease progression 2 months after diagnosis. This rare disease should be considered in the diagnostic workup of acute cholestatic hepatitis presenting with concomitant hepatosplenomegaly and cytopenia

Meta-analysis: Post-COVID-19 functional dyspepsia and irritable bowel syndrome

Introduction: The burden of post-COVID-19 functional dyspepsia (FD) and irritable bowel syndrome (IBS) remains unclear. The aim of this meta-analysis was to estimate the rate of post-COVID-19 FD and IBS. Methods: MEDLINE, Scopus and Embase were searched through 17 December 2022. Studies reporting the incidence of FD and/or IBS in COVID-19 survivors and controls (without COVID-19), when available, according to the Rome criteria, were included. Estimated incidence with 95% confidence intervals (CI) was pooled. The odds ratio (OR) with 95% confidence intervals (CI) was pooled; heterogeneity was expressed as I2. Results: Ten studies met the inclusion criteria and were included in the analysis. Overall, four studies including 1199 COVID-19 patients were considered for FD. Post-COVID-19 FD was reported by 72 patients (4%, 95% CI: 3%–5% and I2 0%). The pooled OR for FD development (three studies) in post-COVID-19 patients compared to controls was 8.07 (95% CI: 0.84–77.87, p = 0.071 and I2 = 67.9%). Overall, 10 studies including 2763 COVID-19 patients were considered for IBS. Post-COVID-19 IBS was reported by 195 patients (12%, 95% CI: 8%–16%, I2 95.6% and Egger's p = 0.002 test). The pooled OR for IBS development (four studies) in COVID-19 patients compared to controls was 6.27 (95% CI: 0.88–44.76, p = 0.067 and I2 = 81.4%); considering only studies with a prospective COVID-19 cohort (three studies), the pooled OR was 12.92 (95% CI: 3.58–46.60, p < 0.001 and I2 = 0%). Conclusions: COVID-19 survivors were found to be at risk for IBS development compared to controls. No definitive data are available for FD

Green roof seasonal variation: comparison of the hydrologic behavior of a thick and a thin extensive system in New York City

Green roofs have been utilized for urban stormwater management due to their ability to capture rainwater locally. Studies of the most common type, extensive green roofs, have demonstrated that green roofs can retain significant amounts of stormwater, but have also shown variation in seasonal performance. The purpose of this study is to determine how time of year impacts the hydrologic performance of extensive green roofs considering the covariates of antecedent dry weather period (ADWP), potential evapotranspiration (ET0) and storm event size. To do this, nearly four years of monitoring data from two full-scale extensive green roofs (with differing substrate depths of 100 mm and 31 mm) are analyzed. The annual performance is then modeled using a common empirical relationship between rainfall and green roof runoff, with the addition of Julian day in one approach, ET0 in another, and both ADWP and ET0 in a third approach. Together the monitoring and modeling results confirm that stormwater retention is highest in warmer months, the green roofs retain more rainfall with longer ADWPs, and the seasonal variations in behavior are more pronounced for the roof with the thinner media than the roof with the deeper media. Overall, the ability of seasonal accounting to improve stormwater retention modeling is demonstrated; modification of the empirical model to include ADWP, and ET0 improves the model R 2 from 0.944 to 0.975 for the thinner roof, and from 0.866 to 0.870 for the deeper roof. Furthermore, estimating the runoff with the empirical approach was shown to be more accurate then using a water balance model, with model R 2 of 0.944 and 0.866 compared to 0.975 and 0.866 for the thinner and deeper roof, respectively. This finding is attributed to the difficulty of accurately parameterizing the water balance model

Smad2-dependent glycosaminoglycan elongation in aortic valve interstitial cells enhances binding of LDL to proteoglycans

Calcific aortic valve disease is a progressive condition that shares some common pathogenic features with atherosclerosis. Transforming growth factor-ß1 is a recognized mediator of atherosclerosis and is expressed in aortic valve lesions. Transforming growth factor-ß1 stimulates glycosaminoglycan elongation of proteoglycans that is associated with increased lipid binding. We investigated the presence of transforming growth factor-ß1 and downstream signaling intermediates in diseased human aortic valves and the effects of activated transforming growth factor-ß1 receptor signaling on aortic valve interstitial cell proteoglycan synthesis and lipid binding as a possible mechanism for the initiation of the early lesion of calcific aortic valve disease

Surface displaced alfa-enolase of Lactobacillus plantarum is a fibronectin binding protein.

BACKGROUND: Lactic acid bacteria of the genus Lactobacillus and Bifidobacterium are one of the most important health promoting groups of the human intestinal microbiota. Their protective role within the gut consists in out competing invading pathogens for ecological niches and metabolic substrates. Among the features necessary to provide health benefits, commensal microorganisms must have the ability to adhere to human intestinal cells and consequently to colonize the gut. Studies on mechanisms mediating adhesion of lactobacilli to human intestinal cells showed that factors involved in the interaction vary mostly among different species and strains, mainly regarding interaction between bacterial adhesins and extracellular matrix or mucus proteins. We have investigated the adhesive properties of Lactobacillus plantarum, a member of the human microbiota of healthy individuals. RESULTS: We show the identification of a Lactobacillus plantarum LM3 cell surface protein (48 kDa), which specifically binds to human fibronectin (Fn), an extracellular matrix protein. By means of mass spectrometric analysis this protein was identified as the product of the L. plantarum enoA1 gene, coding the EnoA1 alfa-enolase. Surface localization of EnoA1 was proved by immune electron microscopy. In the mutant strain LM3-CC1, carrying the enoA1 null mutation, the 48 kDa adhesin was not anymore detectable neither by anti-enolase Western blot nor by Fn-overlay immunoblotting assay. Moreover, by an adhesion assay we show that LM3-CC1 cells bind to fibronectin-coated surfaces less efficiently than wild type cells, thus demonstrating the significance of the surface displaced EnoA1 protein for the L. plantarum LM3 adhesion to fibronectin. CONCLUSION: Adhesion to host tissues represents a crucial early step in the colonization process of either pathogens or commensal bacteria. We demonstrated the involvement of the L. plantarum Eno A1 alfa-enolase in Fn-binding, by studying LM3 and LM3-CC1 surface proteins. Isolation of LM3-CC1 strain was possible for the presence of expressed enoA2 gene in the L. plantarum genome, giving the possibility, for the first time to our knowledge, to quantitatively compare adhesion of wild type and mutant strain, and to assess doubtless the role of L. plantarum Eno A1 as a fibronectin binding protein

Non-celiac gluten sensitivity in the context of functional gastrointestinal disorders

Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut–brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut–brain interaction