Long-living optical gain induced by solvent viscosity in a push-pull molecule

The combination of continuum and ultrafast pump-probe spectroscopy with DFT and TDDFT calculations, in viscous and non-viscous environments, is effective in unraveling important features of the twisted intramolecular charge transfer mechanism in a new push-pull molecule that possesses aggregation induced emission properties. Long-living optical gain is found when this mechanism is inhibited, highlighting the importance of the environment rigidity in the design of materials for photonic applications

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

Immunosuppressive therapy in pancreas and islet transplant : Need for simultaneous assessment of insulin sensitivity and secretion

Diabetes mellitus is a metabolic disease possi- ble to treat via pancreas/islet transplantation but most immunosuppressive drugs are diabeto- genic. In this letter, we review current up to date methods to assess insulin action and secretion (using the surrogate indexes) suggesting their use in large studies in populations of pancreas/ islets transplanted patients

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

Potential therapeutic role of L-carnitine in skeletal muscle oxidative stress and atrophy conditions

The targeting of nutraceutical treatment to skeletal muscle damage is an emerging area of research, driven by the need for new therapies for a range of muscle-associated diseases. L-Carnitine (CARN) is an essential nutrient and plays a key role in mitochondrial \u3b2-oxidation and in the ubiquitin-proteasome system regulation. As a dietary supplement to improve athletic performance, CARN has been studied for its potential to enhance \u3b2-oxidation. However, CARN effects on myogenesis, mitochondrial activity, and hypertrophy process are not completely elucidated. This in vitro study aims to investigate CARN role on skeletal muscle remodeling, differentiation process, and myotubes formation. We analyzed muscle differentiation and morphological features in C2C12 myoblasts exposed to 5 mM CARN. Our results showed that CARN was able to accelerate C2C12 myotubes formation and induce morphological changes, characterizing the start of hypertrophy process. In addition, CARN improved AKT activation and downstream cellular signaling pathways involved in skeletal muscle atrophy process prevention. Also, CARN positively regulated the pathways involved in oxidative stress defense. In this work, we provide an interesting novel mechanism of the potential therapeutic use of CARN to treat pathological conditions characterized by skeletal muscle morphological and functional impairment, oxidative stress production, and atrophy process in aging

Autoimmune polyendocrine syndrome 3 onset with severe ketoacidosis in a 74-year-old woman

Type 1 diabetes mellitus (T1D), autoimmune thyroid disease, and autoimmune gastritis often occur together forming the so-called autoimmune polyendocrine syndrome type 3 (APS3). We here report a clinical case of a 74-year-old woman who presented for the first time with severe hyperglycemia and ketoacidosis diagnosed as T1D. Further clinical investigations revealed concomitant severe hypothyroidism with autoimmune thyroid disease and severe cobalamin deficiency due to chronic atrophic gastritis. The diagnosis of type 1 diabetes mellitus was confirmed by the detection of autoantibodies against glutamic acid decarboxylase 65, islet cell antibodies, and anti-insulin autoantibodies. Anti-thyroperoxidase, anti-thyroglobulin, and anti-gastric parietal cell antibodies were also clearly positive. The case emphasized that new onset diabetic ketoacidosis, hypothyroidism, and cobalamin deficiency may simultaneously occur, and one disease can mask the features of the other, thereby making diagnosis difficult. It is noteworthy that an APS3 acute episode occurred in an asymptomatic elder woman for any autoimmune diseases

Plasma Citrulline : a New Marker of Gut Epithelium Alteration in Obese Patients?

Objectives: In the last decade gut microbial diversity was associated with the pathogenesis of obesity in humans. Plasma citrulline was a simple and accurate biomarker for the severity of intestinal failure and was associated with short bowel syndrome and alteration of gut permeability, being developed as an alternative to D-xylose tolerance test for the diagnosis of an abnormal small intestinal absorption of nutrients. This study was performed to ascertain whether obesity might be associated with dysregulation of epithelial gut function. Methods: Fifteen obese individuals (5 M/10 F; BMI 37.4 \ub1 6.1 Kg/m2; 42 \ub1 6 yrs) and 15 healthy gender- and age-matched controls (6 M/9 F BMI: 22.7 \ub1 2.1 Kg/m2; 39 \ub1 7 yrs) underwent D-xylose load (25 g) and plasma citrulline, plasma insulin, glucose and lipid profile testing. Results: Plasma citrulline was significantly lower in the obese group (p = 0.045) with respect to controls, whilst total cholesterol, LDL and tryglicerides concentration, insulin level and HOMA-IR were significantly higher in obese patients. In contrast, after D-xylose load no difference in serum xylose was found between the two groups (p = ns). Conclusions: Obese patients show a decreased citrulline concentration with respect to lean subjects. Since citrulline is a known marker of intestinal health, alterations in the gut epithelium are likely to be associated with the obesity syndrome. We propose to measure citrulline level in obese patients on a routine basis

Pheochromocytoma in Congenital Cyanotic Heart Disease

Studies on genome-wide transcription patterns have shown that many genetic alterations implicated in pheochromocytoma-paraganglioma (P-PGL) syndromes cluster in a common cellular pathway leading to aberrant activation of molecular response to hypoxia in normoxic conditions (the pseudohypoxia hypothesis). Several cases of P-PGL have been reported in patients with cyanotic congenital heart disease (CCHD). Patients affected with CCHD have an increased likelihood of P-PGL compared to those affected with noncyanotic congenital heart disease. One widely supported hypothesis is that chronic hypoxia represents the determining factor supporting this increased risk. We report the case of a 23-year-old woman affected with congenital tricuspid atresia surgically by the Fontan procedure. The patient was admitted to hospital with hypertensive crisis and dyspnea. Chest computed tomography revealed, incidentally, a 6-cm mass in the left adrenal lodge. Increased levels of noradrenaline (NA) and its metabolites were detected (plasma NA 5003.7 mu g/ml, n.v.< 480; urinary NA 1059.5 mu g/24 h, n.v.< 85.5; urinary metanephrine 489 mu g/24 h, n.v.< 320). The patient did not report any additional symptom related to catecholamine excess. The left adrenal tumor showed abnormal accumulation when 131I-metaiodobenzylguanidine scintigraphy was performed. A 18F-fluorodeoxyglucose positron emission tomography showed no significant metabolic activity in the left adrenal gland but intense uptake in the supra and subdiaphragmatic brown adipose tissue, probably due to noradrenergic-stimulated glucose uptake. The patient underwent left open adrenalectomy after preconditioning with alpha-and beta-blockers and histopathological examination confirmed the diagnosis of pheochromocytoma (Ki-67<5%). Screening for germline mutations did not show any genes mutation (investigated mutations: RET, TMEM127, MAX, SDHD, SDHC, SDHB, SDHAF2, SDHA, andVHL). Clinicians shouldconsider P-PGLwhenan-unexplained clinical deterioration occurs in CCHD patients, even in the absence of typical paroxysmal symptoms

The Case for Perspicuous Programming

This essay examines the nature of programs, classifies the traditional or enigmatic styles of programming, distinguishing template, prose and literate styles; notes the contrast between batch programs and interactive programs; and highlights the advantages of giving priority in developing interactive programs to the online documentation, and proposes that this documentation should be the principal target of development, with the executable program code being regarded of secondary and consequent