Hepatokine ITIH3 protects against hepatic steatosis by downregulating mitochondrial bioenergetics and de novo lipogenesis.

Recent studies demonstrate that liver secretory proteins, also known as hepatokines, regulate normal development, obesity, and simple steatosis to non-alcoholic steatohepatitis (NASH) progression. Using a panel of ∼100 diverse inbred strains of mice and a cohort of bariatric surgery patients, we found that one such hepatokine, inter-trypsin inhibitor heavy chain 3 (ITIH3), was progressively lower in severe non-alcoholic fatty liver disease (NAFLD) disease states highlighting an inverse relationship between Itih3/ITIH3 expression and NAFLD severity. Follow-up animal and cell culture models demonstrated that hepatic ITIH3 overexpression lowered liver triglyceride and lipid droplet accumulation, respectively. Conversely, ITIH3 knockdown in mice increased the liver triglyceride in two independent NAFLD models. Mechanistically, ITIH3 reduced mitochondrial respiration and this, in turn, reduced liver triglycerides, via downregulated de novo lipogenesis. This was accompanied by increased STAT1 signaling and Stat3 expression, both of which are known to protect against NAFLD/NASH. Our findings indicate hepatokine ITIH3 as a potential biomarker and/or treatment for NAFLD.

Cultivating compassion in medicine: a toolkit for medical students to improve self-kindness and enhance clinical care.

BACKGROUND: Compassionate care lies at the foundation of good patient care and is a quality that patients and providers continue to value in the fast-paced setting of contemporary medicine. Compassion is often discussed superficially in medical school curricula, but the practical aspect of learning this skill is often not taught using a formal framework. In the present work, the authors present an 8-session curriculum with a mindfulness-based approach to compassion that addresses this need. It is hypothesized that students in this curriculum will improve in their levels of compassion based on validated scales. METHODS: The curriculum was delivered to fourth-year medical students at Renaissance School of Medicine at Stony Brook University who had just completed their clerkship year. It was developed as a customizable set of modules that could be delivered in various ways. The students were taught with evidence-based cognitive exercises followed by group discussions and written reflections based on compassion-focused thematic questions. All students completed a pre- and post-Self-Compassion Scale, Compassion Scale, and Toronto Mindfulness Scale. Students in this course were compared with students in different courses about non-clinical topics delivered at the same time. Wilcoxon Signed Rank tests and Mann Whitney U tests were used to assess potential associations between pre- and post-survey responses for the validated scales and subscales. RESULTS: 17 fourth-year medical students completed pre- and post-course tests, 11 participated in the compassion curriculum while 6 participated from the other courses. Before any of the courses began, all students performed similarly on the pre-test across all scales. The students in the compassion curriculum demonstrated a significant increase in their total Self-Compassion score by 8.7 [95% CI 4.3 to 13.2] points (p = 0.008), total Compassion score by 6.0 [95% CI 1.4 to 10.6] points (p = 0.012), and the curiosity component of the Toronto Mindfulness Scale by 4.4 [95% CI 1.0 to 7.7] points (p = 0.012). There was no statistically significant difference between pre- and post-tests among the non-compassion curriculum students in the aforementioned scales (p = 0.461, p = 0.144, p = 0.785, respectively). CONCLUSIONS: Our results indicate that the students in our course developed an enhanced ability to engage in self-compassion, to understand the shared human experience, and to be motivated to act to alleviate suffering. Regardless of a program's existing compassion education, this customizable model allows for easy integration into a medical student's crowded curriculum. Furthermore, although teaching compassion early and often in a clinician's training is desirable, our study that targeted fourth-year medical students suggests an additional benefit of rekindling the loss of compassion well described in a medical student's clinical years.

Knowledge, Attitude and Practices Towards Dengue Fever Among Slum Dwellers: A Case Study in Dhaka City, Bangladesh.

Objectives: This study intends to evaluate Dhaka city slum dwellers' responses to Dengue fever (DF). Methods: 745 individuals participated in a KAP survey that was pre-tested. Face-to-face interviews were performed to obtain data. Python with RStudio was used for data management and analysis. The multiple regression models were applied when applicable. Results: 50% of respondents were aware of the deadly effects of DF, its common symptoms, and its infectious nature. However, many were unaware that DF could be asymptomatic, a previously infected person could have DF again, and the virus could be passed to a fetus. Individuals agreed that their families, communities, and authorities should monitor and maintain their environment to prevent Aedes mosquito breeding. However, overall 60% of the study group had inadequate preventative measures. Many participants lacked necessary practices such as taking additional measures (cleaning and covering the water storage) and monitoring potential breeding places. Education and types of media for DF information were shown to promote DF prevention practices. Conclusion: Slum dwellers lack awareness and preventative activities that put them at risk for DF. Authorities must improve dengue surveillance. The findings suggest efficient knowledge distribution, community stimulation, and ongoing monitoring of preventative efforts to reduce DF. A multidisciplinary approach is needed to alter dwellers' behavior since DF control can be done by raising the population's level of life. People and communities must perform competently to eliminate vector breeding sites.

Bilateral microsporidial keratoconjunctivitis in a clinically healthy female receiving intravitreal steroid injections: Associations and potential risk factors.

Purpose: To present a unique case of bilateral microsporidial keratoconjunctivitis in a clinically healthy female receiving intravitreal steroid injections, and explore several associations and potential risk factors. Observations: A 75-year-old woman with chronic idiopathic anterior uveitis was receiving regular intravitreal steroid in both eyes for secondary cystoid macular edema. Flare-ups of iritis were usually treated with topical non-steroidal anti-inflammatory drops, but in the left eye the patient also received a few limited courses of topical corticosteroid. The patient regularly instilled topical cyclosporine 0.05% for dry eyes. She was otherwise clinically healthy but had low serum Immunoglobulin (Ig) M levels. There was no history of trauma or exposure to contamination. In her course of treatment, she developed a bilateral punctate keratitis. Corneal scrapings were diagnostic of Microsporidia. Topical voriconazole and moxifloxacin, as well as corneal debridement, were effective in resolving the infection. Conclusions and importance: We propose that the factors and associations described in this case--intravitreal steroid, topical steroid, topical cyclosporine, and IgM deficiency--contributed variably to create relative, local, immunologic suppression in our patient. Among these potential risk factors, we believe that intravitreal steroid exposure may be prominent. In aggregate, they facilitated development of her opportunistic microsporidial corneal infection. Eye care specialists should have a high index of suspicion for microsporidial keratitis, if they observe an atypical chronic punctate keratitis in patients with similar clinical associations.

TRAP transporter TakP: a key player in the resistance against selenite-induced oxidative stress in Rhodobacter sphaeroides.

Almost one-third of all proteins require metal ions as an essential component in key biological processes and approximately half of all enzymes are associated with one or more metal ions. The naturally occurring selenium is very toxic at higher levels, but few bacteria can reduce it into the less toxic insoluble elemental selenium. Selenium is required for the synthesis of selenocysteine, an essential residue involved in the active sites of various enzymes. The purple non-sulphur bacteria, Rhodobacter sphaeroidesis demonstrated for its selenite reduction capacity. The exact mechanism of selenite toxicity is unknown but it reacts with glutathione to form selenodiglutathione, producing the highly toxic compounds namely, H2O2and O2-. A R. sphaeroidesstrain with mutated takP gene, a member of the TRAP (tripartite ATP-independent periplasmic) family of transporter, was reported to be showing more resistance towards selenite in the growth medium but the reason for the resistance is unknown. TRAP transporters are the best-studied family of substrate-binding protein and in our previous study it was confirmed that the gene takP in R. sphaeroides is down-regulated by a small non-coding RNA SorY, providing more resistance to the bacterium against the oxidative stress. By comparative growth analysis and sensitivity assays in the presence of 2 mM selenite, it was observed that the SorY knockout strain is more sensitive to selenite while overexpression of the sRNA conferred more resistance to the bacterium like the takP mutant strain. TakP is involved in the import of malate into the cell, which under oxidative stress needs to be down-regulated to limit malate flux into the cell. Limited malate flux leads to metabolic rearrangements in the cell to avoid excessive generation of prooxidant NADH and facilitate constant generation of antioxidant NADPH. In the presence and absence of selenite, a drastic increase in the NADPH and decrease in the NADH levels are reported respectively. Accumulation of metallic selenium in the cytoplasm was detected via atomic absorption spectrophotometer and our analysis clearly demonstrated the presence of more selenium in the electron micrographs of the SorY knockout strain compared to the takP mutant grown under dark semi-aerobic growth conditions in the presence of selenite. Hence based on our analysis, it is confirmed that lack of TakP transporter led to reduced selenite influx into the cytoplasm, relieving cells with limited generation of ROS, eventually exhibiting more resistance against selenite-induced oxidative stress.