A local fingerprint for hydrophobicity and hydrophilicity: from methane to peptides

An important characteristic that determines the behavior of a solute in water is whether it is hydrophobic or hydrophilic. The traditional classification is based on chemical experience and heuristics. However, this does not reveal how the local environment modulates this important property. We present a local fingerprint for hydrophobicity and hydrophilicity inspired by the two body contribution to the entropy. This fingerprint is an inexpensive, quantitative and physically meaningful way of studying hydrophilicity and hydrophobicity that only requires as input the water-solute radial distribution functions. We apply our fingerprint to octanol, benzene and the 20 proteinogenic amino acids. Our measure of hydrophilicity is coherent with chemical experience and, moreover, it also shows how the character of an atom can change as its environment is changed. Lastly, we use the fingerprint as collective variable in a funnel metadynamics simulation of a host-guest system. The fingerprint serves as a desolvation collective variable that enhances transitions between the bound and unbound states

Relaxation processes in thiophene-based random copolymers

The relaxation dynamics of soluble polyalkylthiophenes obtained by the random copolymerisation of 3,4-dibutylthiophene and 3-butylthiophene monomers is investigated. In these systems, the effective conjugation length, the optical gap and the non-radiative decay rate are controlled by varying the content of disubstituted monomers, the steric hindrance of which induces a twisting angle between thiophene rings. Several indications are reported in favour of spectral diffusion of the photoexcitations. Migration processes mainly occur within a few tens of picoseconds

Ranger VII Flight Path and Its Determination from Tracking Data

Flight path and tracking study of Ranger VII LUNAR prob

Efficacy of biofeedback rehabilitation based on visual evoked potentials analysis in patients with advanced age-related macular degeneration

Age-related macular degeneration (AMD) is a progressive and degenerative disorder of the macula. In advanced stages, it is characterized by the formation of areas of geographic atrophy or fibrous scars in the central macula, which determines irreversible loss of central vision. These patients can benefit from visual rehabilitation programmes with acoustic "biofeedback" mechanisms that can instruct the patient to move fixation from the central degenerated macular area to an adjacent healthy area, with a reorganization of the primary visual cortex. In this prospective, comparative, non-randomized study we evaluated the efficacy of visual rehabilitation with an innovative acoustic biofeedback training system based on visual evoked potentials (VEP) real-time examination (Retimax Vision Trainer, CSO, Florence), in a series of patients with advanced AMD compared to a control group. Patients undergoing training were subjected to ten consecutive visual training sessions of 10min each, performed twice a week. Patients in the control group did not receive any training. VEP biofeedback rehabilitation seems to improve visual acuity, reading performances, contrast sensitivity, retinal fixation and sensitivity and quality of life in AMD patients

Cell death and impairment of glucose-stimulated insulin secretion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the beta-cell line INS-1E.

The aim of this research was to characterize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity on the insulin-secreting beta-cell line INS-1E. A sharp decline of cell survival (below 20%) was observed after 1 h exposure to TCDD concentrations between 12.5 and 25 nM. Ultrastructurally, beta-cell death was characterized by extensive degranulation, appearance of autophagic vacuoles, and peripheral nuclear condensation. Cytotoxic concentrations of TCDD rapidly induced a dose-dependent increase in intracellular calcium concentration. Blocking calcium entry by EGTA significantly decreased TCDD cytotoxicity. TCDD was also able to rapidly induce mitochondrial depolarization. Interestingly, 1 h exposition of INS-1E cells to very low TCDD concentrations (0.05-1 nM) dramatically impaired glucose-stimulated but not KCl-stimulated insulin secretion. In conclusion, our results clearly show that TCDD exerts a direct beta-cell cytotoxic effect at concentrations of 15-25 nM, but also markedly impairs glucose-stimulated insulin secretion at concentrations 20 times lower than these. On the basis of this latter observation we suggest that pancreatic beta-cells could be considered a specific and sensitive target for dioxin toxicity

Teaching geriatric medicine through gamification: a tool for enhancing postgraduate education in geriatric medicine

Background Polypharmacy is becoming increasingly common and all doctors must be prepared to manage it competently. Aims The aim of this project is to evaluate the feasibility and use of a novel gamification-based teaching intervention on polypharmacy among doctors undergoing advanced geriatric training. Among others, one of the learning goals for the students was to be able to describe the adherence to medication. Methods Electronic questionnaire sent to students of the third session “evidence-based medicine in geriatrics” of advanced postgraduate course in geriatrics of the European Academy for Medicine of Ageing. Results Most students reported issues with forgetting doses and remembering sufficiently to establish a medication routine due to busy schedules as well as social influences around medication taking. Reflecting on the challenges of the game, most students reported that their own prescribing practice was likely to change. Discussion and conclusion The current model of learning appears to be a feasible approach for postgraduate medical education or in other areas of healthcare such as nursing or physiotherapy. Learning through action and reflection promotes deeper thinking and can lead to behavioral change, in this case thus enhancing the attitudes and understanding regarding pharmacological issues associated with ageing. Recommendations for future research in medical education about medication adherence are outlined.publishedVersio

A Genome-Wide Association Study Using a Custom Genotyping Array Identifies Variants in GPR158 Associated with Reduced Energy Expenditure in American Indians

Pima Indians living in Arizona have a high prevalence of obesity, and we have previously shown that a relatively lower energy expenditure (EE) predicts weight and fat mass gain in this population. EE is a familial trait (heritability = 0.52); therefore, in the current study, we aimed to identify genetic variants that affect EE and thereby influence BMI and body fatness in Pima Indians. Genotypic data from 491,265 variants were analyzed for association with resting metabolic rate (RMR) and 24-h EE assessed in a whole-room calorimeter in 507 and 419 Pima Indians, respectively. Variants associated with both measures of EE were analyzed for association with maximum BMI and percent body fat (PFAT) in 5,870 and 912 Pima Indians, respectively. rs11014566 nominally associated with both measures of EE and both measures of adiposity in Pima Indians, where the G allele (frequency: Pima Indians = 0.60, Europeans <0.01) associated with lower 24-h EE ( = -33 kcal/day per copy), lower RMR ( = -31 kcal/day), higher BMI ( = +0.6 kg/m(2)), and higher PFAT ( = +0.9%). However, the association of rs11014566 with BMI did not directionally replicate when assessed in other ethnic groups. rs11014566 tags rs144895904, which affected promoter function in an in vitro luciferase assay. These variants map to GPR158, which is highly expressed in the brain and interacts with two other genes (RGS7 and CACNA1B) known to affect obesity in knockout mice. Our results suggest that common ethnic-specific variation in GPR158 may influence EE; however, its role in weight gain remains controversial, as it either had no association with BMI or associated with BMI but in the opposite direction in other ethnic groups

Patients with MEN1 are at an increased risk for venous thromboembolism VTE risk in MEN1

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder predisposing to the development of multiple functional and non-functional neuroendocrine tumors (NETs). Only uncommon MEN1-associated functional NETs such as glucagonomas (&lt;1%) and ACTH-producing tumors (&lt;5%) are known to be associated with hypercoagulability. It is unknown if patients with MEN1 generally have increased risk of VTE. Methods: We queried a prospective natural history study of germline mutation positive MEN1 patients (n=286) between 1991-2019 for all lifetime events of VTE. Search terms were: DVT, thromb, embol, PE, pulmonary embolism, clot, hematology consult, anticoagulant, coumadin, lovenox, xarelto, warfarin, aspirin, rivaroxaban and apixaban. Incidence rates were calculated accounting for age and sex. Comparison was made to published incidence rates in healthy populations, different types of cancer, and Cushing's syndrome. Results: Thirty-six subjects (median age 45 years, range 16-75) experienced a VTE event, yielding a prevalence rate of 12.9%. The age-sex adjusted incidence rate of VTE is 9.11 per 1,000 patient-years, with a sex-adjusted lifetime incidence rate of 2.81 per 1,000 patient-years. MEN1-associated lifetime incidence rates are ~two-fold higher than the estimated annual incidence rate in the general population and are comparable to known risk in the setting of various types of cancer. Approximately 80% were diagnosed with pancreatic NETs, of which 24% were insulinomas. Fourteen patients (42%) experienced peri-operative VTE events. Conclusions: MEN1 patients have an increased risk of VTE. Further mechanistic investigation and validation from other MEN1 cohorts are needed to confirm the increased prevalence of VTE in MEN1

Acute Hypoglycemia Induces Retinal Cell Death in Mouse

BACKGROUND: Glucose is the most important metabolic substrate of the retina and maintenance of normoglycemia is an essential challenge for diabetic patients. Glycemic excursions could lead to cardiovascular disease, nephropathy, neuropathy and retinopathy. A vast body of literature exists on hyperglycemia namely in the field of diabetic retinopathy, but very little is known about the deleterious effect of hypoglycemia. Therefore, we decided to study the role of acute hypoglycemia in mouse retina. METHODOLOGY/PRINCIPAL FINDINGS: To test effects of hypoglycemia, we performed a 5-hour hyperinsulinemic/hypoglycemic clamp; to exclude an effect of insulin, we made a hyperinsulinemic/euglycemic clamp as control. We then isolated retinas from each group at different time-points after the clamp to analyze cells apoptosis and genes regulation. In parallel, we used 661W photoreceptor cells to confirm in vivo results. We showed herein that hypoglycemia induced retinal cell death in mouse via caspase 3 activation. We then tested the mRNA expression of glutathione transferase omega 1 (Gsto1) and glutathione peroxidase 3 (Gpx3), two genes involved in glutathione (GSH) homeostasis. The expression of both genes was up-regulated by low glucose, leading to a decrease of reduced glutathione (GSH). In vitro experiments confirmed the low-glucose induction of 661W cell death via superoxide production and activation of caspase 3, which was concomitant with a decrease of GSH content. Moreover, decrease of GSH content by inhibition with buthionine sulphoximine (BSO) at high glucose induced apoptosis, while complementation with extracellular glutathione ethyl ester (GSHee) at low glucose restored GSH level and reduced apoptosis. CONCLUSIONS/SIGNIFICANCE: We showed, for the first time, that acute insulin-induced hypoglycemia leads to caspase 3-dependant retinal cell death with a predominant role of GSH content