Crohn's Disease Associated with Sweet's Syndrome and Sjögren's Syndrome Treated with Infliximab

The association of Crohn's disease (CD) and Sweet's syndrome is rare and the presence of Sjögren's syndrome in Crohn's disease is even rarer, with only three reports found in the literature. We describe two cases of Crohn's disease associated with Sweet's syndrome, one of which is the first case of CD and Sweet's concomitantly associated with Sjögren's syndrome. Both cases responded rapidly to Infliximab therapy with complete resolution of the skin lesions

Antagonistic Potentiality of Trichoderma harzianum Against Cladosporium spherospermum, Aspergillus niger and Fusarium oxysporum

Many species of genus Trichoderma are used as an important source of biological agents. The potential efficacy of Trichoderma harzianum against the pathogenic fungi like Cladosporium spherospermum, Aspergillus niger and Fusarium oxysporum was evaluated on the fungal growth by culture pattern in which radial growth extension rates of two categories of fungal colonies were analyzed. All the fungal species were isolated from the rhizosphere of Juglans regia L. and cultured on the separate sterilized potato dextrose agar (Hi Media). Antagonism of T. harzianum was observed when all the fungal isolates were grown on the same PDA petri-plate in vitro by using the dual culture techniques. Trichoderma harzianum had a discernible inhibitory effect on the growth of pathogens in dual culture. The mycelial growth of pathogenic isolates was noticeably constrained after a period of 10 days at the temperature of 250C and pH of 5.6. T. harzianum caused the maximum growth inhibition in A. niger (75%) followed by C. spherospermum (72.2%) and F. oxysporum (25%) at the specific temperature and pH, which justifies that T. harzianum is a promising biological agent for restricting the wilt and other fungal diseases. Keywords; Trichoderma harzianum, pathogenic fungi, antagonism, radial growt

Arterial blood gas levels in high altitude Kashmiri population, India

Background: The valley of Kashmir lies at an average height of 1730 m above the sea level with a barometric pressure of 624 mmHg. The fall in atmospheric pressure at higher altitude decreases the partial pressure of inspired oxygen and hence the driving pressure for gas exchange in the lungs. At sea level the normal range of PaCO2 is 35 mmHg to 45 mmHg and at 1500m above sea level (barometric pressure 634 mmHg), the predicted normal PaO2 in a healthy young adult is approximately 80 mmHg; this contrasts with a value close to 95 mmHg at sea level. On these grounds this study was undertaken to formulate normal ABG values for this place as it lies at a higher altitude.Methods: The study was undertaken to measure "arterial blood gases" (ABG) in ethnic Kashmiri population and consisted of a sample of one hundred healthy Kashmiri subjects of either sex after proper inclusion and exclusion by spirometrically measuring Vital Capacity and Forced expiratory volume in one second/Forced vital capacity (Fev1/FVC). A modified Allen's test was performed to check for adequate collateral circulation ruling out Ischemia.Results: The average mean PaO2 of 78.51 ± 4.40 mmHg and the average mean PaCO2 of 33.37 ± 2.38 mmHg was obtained of the volunteers of both the sexes. The average mean pH of males (7.43 ± 0.02) was significantly lower than the mean pH of females (7.45 ± 0.021).Conclusions: The present study might provide useful base line normal values of Arterial Blood Gases for the local population and will be beneficial to the clinicians.

A Decade of Mighty Lipophagy: What We Know and What Facts We Need to Know?

From Hindawi via Jisc Publications RouterHistory: publication-year 2021, received 2021-02-22, rev-recd 2021-09-30, accepted 2021-10-15, pub-print 2021-11-05, archival-date 2021-11-05Publication status: PublishedLipids are integral cellular components that act as substrates for energy provision, signaling molecules, and essential constituents of biological membranes along with a variety of other biological functions. Despite their significance, lipid accumulation may result in lipotoxicity, impair autophagy, and lysosomal function that may lead to certain diseases and metabolic syndromes like obesity and even cell death. Therefore, these lipids are continuously recycled and redistributed by the process of selective autophagy specifically termed as lipophagy. This selective form of autophagy employs lysosomes for the maintenance of cellular lipid homeostasis. In this review, we have reviewed the current literature about how lipid droplets (LDs) are recruited towards lysosomes, cross-talk between a variety of autophagy receptors present on LD surface and lysosomes, and lipid hydrolysis by lysosomal enzymes. In addition to it, we have tried to answer most of the possible questions related to lipophagy regulation at different levels. Moreover, in the last part of this review, we have discussed some of the pathological states due to the accumulation of these LDs and their possible treatments under the light of currently available findings

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

BACKGROUND Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. METHODS In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. FINDINGS Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). INTERPRETATION Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes. FUNDING Intercept Pharmaceuticals

Trust but verify: the effect of religiosity and social conformity on verification of content shared via social media

Purpose: This study aims to understand the patterns of content-sharing behaviour on major social media platforms by young adult users with reference to how these sharing patterns are influenced by two main sociocultural factors in their lives, religiosity and social conformity. Design/methodology/approach: Online surveys including both the ATSCI test for social conformity as well as the Hoge test for religiosity were filled out by 590 participants. In-depth interviews with six participants representative of the same population were conducted to deepen analysis of key variables explored in the surveys. The design of the interviews was semi-structured, whereby the focus was to achieve a general overview of participants\u27 intentions and habits regarding sharing information via social media. Findings: The findings show a significant positive impact of religiosity and social conformity on users\u27 sharing intention which, in turn, affects their inclination towards verifying the content they share. Social implications: The authors\u27 findings emphasise how users bear the onus of correcting the online information space. It paves the way for future research by recognising the value of independent corroboration amongst users. Originality/value: This study lends key support to the growing body of research on social media use in societies in which shared religious and cultural values tend to clearly impact everyday social interaction

Interfacial shear strength and tensile properties of injection-molded, short- and long-glass fiber-reinforced polyamide 6,6 composites

Injection-molded short- and long-glass fiber/polyamide 6,6 composites were subjected to tensile tests. To measure the effectiveness of the fibers in reinforcing the composites, a computational approach was employed to compute the fiber-matrix ISS, orientation factor, reinforcement efficiency, tensile-, and fiber length-related properties. Although the LFCs showed great improvement in fiber characteristics compared to the SFCs, enhancement in tensile properties was small, which is believed to be due to the larger fiber diameter. Kelly-Tyson model provides good approximation for the computation of ISS and tensile-related properties