L-Carnitine counteracts in vitro fructose-induced hepatic steatosis through targeting oxidative stress markers

Purpose: Nonalcoholic fatty liver disease (NAFLD) is defined by excessive lipid accumulation in the liver and involves an ample spectrum of liver diseases, ranging from simple uncomplicated steatosis to cirrhosis and hepatocellular carcinoma. Accumulating evidence demonstrates that high fructose intake enhances NAFLD development and progression promoting inhibition of mitochondrial \u3b2-oxidation of long-chain fatty acids and oxidative damages. l-Carnitine (LC), involved in \u3b2-oxidation, has been used to reduce obesity caused by high-fat diet, which is beneficial to ameliorating fatty liver diseases. Moreover, in the recent years, various studies have established LC anti-oxidative proprieties. The objective of this study was to elucidate primarily the underlying anti-oxidative mechanisms of LC in an in vitro model of fructose-induced liver steatosis. Methods: Human hepatoma HepG2 cells were maintained in medium supplemented with LC (5 mM LC) with or without 5 mM fructose (F) for 48 h and 72 h. In control cells, LC or F was not added to medium. Fat deposition, anti-oxidative, and mitochondrial homeostasis were investigated. Results: LC supplementation decreased the intracellular lipid deposition enhancing AMPK activation. However, compound C (AMPK inhibitor-10 \u3bcM), significantly abolished LC benefits in F condition. Moreover, LC, increasing PGC1 \u3b1 expression, ameliorates mitochondrial damage-F induced. Above all, LC reduced ROS production and simultaneously increased protein content of antioxidant factors, SOD2 and Nrf2. Conclusion: Our data seemed to show that LC attenuate fructose-mediated lipid accumulation through AMPK activation. Moreover, LC counteracts mitochondrial damages and reactive oxygen species production restoring antioxidant cellular machine. These findings provide new insights into LC role as an AMPK activator and anti-oxidative molecule in NAFLD

Sex-differences in the longitudinal recovery of neuromuscular function in COVID-19 associated acute respiratory distress syndrome survivors

Introduction: Patients admitted to the intensive care unit (ICU) following severe acute respiratory syndrome 2 (SARS-CoV-2) infection may have muscle weakness up to 1 year or more following ICU discharge. However, females show greater muscle weakness than males, indicating greater neuromuscular impairment. The objective of this work was to assess sex differences in longitudinal physical functioning following ICU discharge for SARS-CoV-2 infection. Methods: We performed longitudinal assessment of physical functioning in two groups: 14 participants (7 males, 7 females) in the 3-to-6 month and 28 participants (14 males, 14 females) in the 6-to-12 month group following ICU discharge and assessed differences between the sexes. We examined self-reported fatigue, physical functioning, compound muscle action potential (CMAP) amplitude, maximal strength, and the neural drive to the tibialis anterior muscle. Results: We found no sex differences in the assessed parameters in the 3-to-6-month follow-up, indicating significant weakness in both sexes. Sex differences emerged in the 6-to-12-month follow-up. Specifically, females exhibited greater impairments in physical functioning, including lower strength, walking lower distances, and high neural input even 1 year following ICU-discharge. Discussion: Females infected by SARS-CoV-2 display significant impairments in functional recovery up to 1 year following ICU discharge. The effects of sex should be considered in post-COVID neurorehabilitation

Different circulating ghrelin responses to isoglucidic snack food in healthy individuals

The last decade has seen much debate on ghrelin as a potential target for treating obesity. Despite a close connection between snack food intake and obesity, snacking is controversially reviewed as a good habit in a healthy nutritional regimen. The aim of the study was to evaluate whether a different nutrient composition influences postprandial ghrelin levels and glucose increments induced by 6 isoglucidic snack food. 20 healthy individuals (10 M/10 F; BMI 23.1\ub10.5; age 33\ub10.67 years, mean and SE) from H San Raffaele Scientific Institute and Milan University were enrolled. The subjects underwent OGTT (50 g) and 6 isoglucidic test-meal loads to assess the ghrelin circulating levels and the area under glycemic curves induced by 6 commercial snacks. 3 h after hazelnut chocolate intake, ghrelin was significantly lower than with wafer chocolate intake (p<0.002). As a response to all snacks, the glycemic curves were not different even though hazelnut chocolate showed the lowest glycemic curve. Moreover, snack fat content was found to be inversely correlated to 3-h plasma ghrelin levels (p<0.0001; R2=0.77) and positively associated with satiety scores (p<0.02; R2=0.28). Also energy load was inversely correlated to 3-h plasma ghrelin (p<0.0001; R 2=0.73). Our results indicate that snack food administered in equivalent glucidic loads elicits postprandial ghrelin suppression and satiety ratings in different ways. Further studies are needed to elucidate the role of ghrelin as hunger-hormone in the regulation of energy balance

A simplified biventricular defibrillator with fixed long detection intervals reduces implantable cardioverter defibrillator (ICD) interventions and heart failure hospitalizations in patients with non-ischaemic cardiomyopathy implanted for primary prevention: the RELEVANT [Role of long dEtection window programming in patients with LEft VentriculAr dysfunction, Non-ischemic eTiology in primary prevention treated with a biventricular ICD] study

To investigate the efficacy and safety of a cardiac resynchronization therapy with cardioverter-defibrillator (CRT-D) device with simplified ventricular tachycardia management in patients with non-ischaemic heart failure (HF) and primary prevention implantable cardioverter defibrillator (ICD) indication

Benign thyroid nodules treatment using Percutaneous Laser Ablation (PLA) and Radiofrequency Ablation (RFA)

Purpose: To evaluate the reduction over time of benign thyroid nodules treated using percutaneous laser ablation (PLA) and radiofrequency ablation (RFA) by the same equipe. Materials and methods: Ninety patients (age 55.6\u2009\ub1\u200914.1 years) underwent ablation for benign thyroid nodule causing compression/aesthetic dissatisfaction from 2011. Fifty-nine (age 55.8\u2009\ub1\u200914.1 years) underwent RFA and 31 (age 55.2\u2009\ub1\u200914.2 years) PLA, ultrasound guided. Technical success, complications, duration of ablation and treatment, energy deployed, volumetric percentage reduction at 1, 6 and 12 months were derived. A regression model for longitudinal measurements was used with random intercept and random slope. Values are expressed as mean\u2009\ub1\u2009standard deviation or N (%). Results: Technical success was always obtained. No major complications occurred. Mean ablation time was 30.1\u2009\ub1\u200913.8 vs. 13.9\u2009\ub1\u20095.9\u2009min (p\u2009<\u2009.0001) and mean energy deployment was 5422.3\u2009\ub1\u20092484.5 J vs. 34 662.7\u2009\ub1\u200915 812.3 J in PLA vs. RFA group. Mean volume reduced from 20.3\u2009\ub1\u200916.4\u2009ml to 13.17\u2009\ub1\u200910.74\u2009ml (42%\u2009\ub1\u200917% reduction) at 1st month, 8.7\u2009\ub1\u20097.4\u2009ml (60%\u2009\ub1\u200915% reduction) at 6th month and 7.1\u2009\ub1\u20097.7\u2009ml (70%%\u2009\ub1\u200916% reduction) at 12th month, in PLA group, and from 32.7\u2009\ub1\u200919.5\u2009ml to 17.2\u2009\ub1\u200912.9\u2009ml (51%\ub115% reduction) at 1st month, 12.8\u2009\ub1\u20099.6\u2009ml (64\u2009\ub1\u200914% reduction) at 6th month and 9.9\u2009\ub1\u20099.2\u2009ml (74%\u2009\ub1\u200914% reduction) at 12th month in RFA group. No difference in time course of the relative volume reduction between the two techniques was found. Conclusions: RFA and PLA are similarly feasible, safe and effective in treating benign thyroid nodules when performed by the same equipe. RFA is faster than PLA but require significantly higher energy

Developing surrogate markers for predicting antibiotic resistance "hot spots" in rivers where limited data are available

Pinpointing environmental antibiotic resistance (AR) hot spots in low-and middle-income countries (LMICs) is hindered by a lack of available and comparable AR monitoring data relevant to such settings. Addressing this problem, we performed a comprehensive spatial and seasonal assessment of water quality and AR conditions in a Malaysian river catchment to identify potential "simple"surrogates that mirror elevated AR. We screened for resistant coliforms, 22 antibiotics, 287 AR genes and integrons, and routine water quality parameters, covering absolute concentrations and mass loadings. To understand relationships, we introduced standardized "effect sizes"(Cohen's D) for AR monitoring to improve comparability of field studies. Overall, water quality generally declined and environmental AR levels increased as one moved down the catchment without major seasonal variations, except total antibiotic concentrations that were higher in the dry season (Cohen's D > 0.8, P < 0.05). Among simple surrogates, dissolved oxygen (DO) most strongly correlated (inversely) with total AR gene concentrations (Spearman's ρ 0.81, P < 0.05). We suspect this results from minimally treated sewage inputs, which also contain AR bacteria and genes, depleting DO in the most impacted reaches. Thus, although DO is not a measure of AR, lower DO levels reflect wastewater inputs, flagging possible AR hot spots. DO measurement is inexpensive, already monitored in many catchments, and exists in many numerical water quality models (e.g., oxygen sag curves). Therefore, we propose combining DO data and prospective modeling to guide local interventions, especially in LMIC rivers with limited data

MONITORING DIFFERENT PARAMETERS DURING 3 WEEKS WALKING IN A TYPE 1 DIABETIC PATIENT WITH INSULIN PUMP AND CMGS

The purpose of this project is monitoring different parameters in a T1DM patient using an insulin pump with a Continuous Glucose Monitoring System (CGMS) performing a 3 weeks walking exercise (700 km). In a 40 years old T1DM patient we evaluated body composition by bioelectrical impedance analysis, continuously monitored the glycemic profile for 3 weeks via CGMS, and evaluated the energy expenditure 3 days each week during the walking. We registered a decrease in total body weight (PRE=83.5 to POST=81.1 kg) and fat mass (PRE=12.2 to POST=8.9 kg), and an increase in fat free mass plus water (PRE=71.3 to POST=72.9 kg). The CGMS data showed a 9 % decrease in the average glucose concentration comparing the first week (W1=133 mg/dl) to the third week (W3=121 mg/dl). The average daily insulin decrease by 12 % was (W1=38, to W3=33.5 IU), resulted from the sum of average daily basal insulin (W1=16.2 to W3=12.6 IU) and average daily insulin bolus (W1=21.8 to W3=20.9 IU). The % in which glucose level stayed on target [between 80 - 160 mg/dl] increase by 7% (W1 = 57 to W3= 64 %) and decrease by 8 % during hyperglycemia (W1=26 to W3 18%). Data showed that an aerobic exercise performed for 3 weeks can improve the glucose profile and the other metabolic parameters in a T1DM patient. A simple walking exercise without engaging in any risky high intensity -physical activity can have overall beneficial effects on health in a T1DM patients