Rational Design of Fe (μ-PR ) (L) Coordination Compounds Featuring Tailored Potential Inversion.

It was recently discovered that some redox proteins can thermodynamically and spatially split two incoming electrons towards different pathways, resulting in the one-electron reduction of two different substrates, featuring reduction potential respectively higher and lower than the parent reductant. This energy conversion process, referred to as electron bifurcation, is relevant not only from a biochemical perspective, but also for the ground-breaking applications that electron-bifurcating molecular devices could have in the field of energy conversion. Natural electron-bifurcating systems contain a two-electron redox centre featuring potential inversion (PI), i.

The employment discrimination experiences of younger and older Americans with cancer under Title I of the Americans with Disabilities Act.

Purpose: The goal of the research was to describe discrimination, both actual and perceived, that has occurred against younger individuals with cancer (i.e., 35 years of age and under) in comparison with older individuals with cancer (i.

Younger patients with Waldenström Macroglobulinemia exhibit low risk profile and excellent outcomes in the era of immunotherapy and targeted therapies.

We analyzed 160 young Waldenström Macroglobulinemia (WM) patients with a median age of 49 years (range 23-55 years), diagnosed between January 2000 and January 2019 in 14 Italian centers. At diagnosis, 70% of patients were asymptomatic. With a median follow-up of 5.

Manipulation of Dietary Amino Acids Prevents and Reverses Obesity in Mice Through Multiple Mechanisms That Modulate Energy Homeostasis.

Reduced activation of energy metabolism increases adiposity in humans and other mammals. Thus, exploring dietary and molecular mechanisms able to improve energy metabolism is of paramount medical importance because such mechanisms can be leveraged as a therapy for obesity and related disorders. Here, we show that a designer protein-deprived diet enriched in free essential amino acids can ) promote the brown fat thermogenic program and fatty acid oxidation, ) stimulate uncoupling protein 1 (UCP1)-independent respiration in subcutaneous white fat, ) change the gut microbiota composition, and ) prevent and reverse obesity and dysregulated glucose homeostasis in multiple mouse models, prolonging the healthy life span.

Conformal Avoidance of Normal Organs at Risk by Perfusion-Modulated Dose Sculpting in Tumor Single-Dose Radiation Therapy.

Purpose: Although 24 Gy single-dose radiation therapy (SDRT) renders >90% 5-year local relapse-free survival in human solid tumor lesions, SDRT delivery is not feasible in ∼50% of oligometastatic lesions owing to interference by dose/volume constraints of a serial organ at risk (OAR). Conformal OAR avoidance is based on a hypothetical model positing that the recently described SDRT biology specifically permits volumetric subdivision of the SDRT dose, such that high-intensity vascular drivers of SDRT lethality, generated within a major tumor subvolume exposed to a high 24 Gy dose (high-dose planning target volume [PTV), would equilibrate SDRT signaling intensity throughout the tumor interstitial space, rendering bystander radiosensitization of a minor subvolume (perfusion-modulated dose sculpting PTV [PTV]), dose-sculpted to meet a serial OAR dose/volume constraint. An engineered PTV may thus yield tumor ablation despite PMDS dose reduction and conformally avoiding OAR exposure to a toxic dose.

Effect of a standard schema of self-monitoring blood glucose in patients with poorly controlled, non-insulin-treated type 2 diabetes mellitus: A controlled longitudinal study.

The effect of self-monitoring of blood glucose (SMBG) on glycemic control with regard to non-insulin-treated Type 2 diabetes mellitus (NIT-Type 2 DM) is still a controversial topic. Against this backdrop, we sought to compare the effect of a continuous short-term SMBG schema with as-usual treatment, based on changes in oral antidiabetic treatment in patients with poorly controlled Type 2 DM. We reviewed 492 NIT-Type 2 DM record charts, selecting 27 patients, with poor glycemic control, who were thought to self-monitor their blood glucose levels (SMBG group).

A non-pharmacological therapeutic approach in the gut triggers distal metabolic rewiring capable of ameliorating diet-induced dysfunctions encompassed by metabolic syndrome.

Metabolic syndrome has increased at a worrisome level. Lifestyle changes are not sufficient to prevent and improve the adverse effects of obesity, thus novel interventions are necessary. The aim of this study was to investigate the use and metabolic outcomes of a non-pharmacological intervention in a high-fat diet (HFD) fed mouse model, capable of recapitulating key aspects of metabolic syndrome.

A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer.

: To evaluate the predictive value of F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). : Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured.

Dynamical Behavior and Conformational Selection Mechanism of the Intrinsically Disordered Sic1 Kinase-Inhibitor Domain.

Intrinsically Disordered Peptides and Proteins (IDPs) in solution can span a broad range of conformations that often are hard to characterize by both experimental and computational methods. However, obtaining a significant representation of the conformational space is important to understand mechanisms underlying protein functions such as partner recognition. In this work, we investigated the behavior of the Sic1 Kinase-Inhibitor Domain (KID) in solution by Molecular Dynamics (MD) simulations.

Initial Validation of GRASP: A Differential Diagnoses Algorithm for Children With Medical Complexity and an Unknown Source of Pain.

Objectives: Identifying the source of pain for children with medical complexity (MC) is challenging. The purpose of this study was the initial validation of a tool to guide the medical evaluation for identifying the source of pain in children with MC by using differential diagnoses. The tool is entitled Guidelines for Ruling Out and Assessing Source of Pain (GRASP).

Long-term effects on growth of an energy-enhanced parenteral nutrition in preterm newborn: A quasi-experimental study.

Aim: To assess the best energy intake in Parenteral Nutrition (PN) for preterm newborns, considering both possible benefits for growth and risk of complications.

Methods: Quasi-experimental study comparing two cohorts of newborns, receiving Energy-Enhanced vs. Standard PN (Cohort A, from 1st January 2015 to 31 January 2016 and Cohort B from 1st February 2016 to 31 March 2017; respectively) after implementation of a change in the PN protocol.

Emergency management in epidermolysis bullosa: consensus clinical recommendations from the European reference network for rare skin diseases.

Epidermolysis bullosa (EB) comprises a group of genetic disorders with the hallmark of fragility of the skin and mucosal surfaces. The severity of different types of EB varies markedly as does the occurrence of extra-cutaneous involvement and complications. A number of emergency situations may occur in the context of EB including obstruction to oral intake from oral or esophageal blisters or scarring, acute airway obstruction, acute urinary retention, sepsis and corneal erosions.

Long-term outcome of patients with ST-segment elevation myocardial infarction treated with low-dose intracoronary thrombolysis during primary percutaneous coronary intervention: the 5-year results of the DISSOLUTION Trial.

We tested the hypothesis that adjunctive thrombolysis at time of primary percutaneous coronary intervention (PCI) may affect favourably the long-term outcome of patients with ST elevation myocardial infarction (STEMI). To this end, we undertook a substudy of the DISSOLUTION (Delivery of thrombolytIcs before thrombectomy in patientS with ST-segment elevatiOn myocardiaL infarction Undergoing primary percuTaneous coronary interventION) trial. A total of 95 patients were randomized to local delivery of urokinase (n = 48) or placebo (n = 47).

Development of Pyrazolo[3,4-]pyrimidine Kinase Inhibitors as Potential Clinical Candidates for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor. Residual cells at the tumor margin are responsible for up to 85% of GBM recurrences after standard treatment. Despite this evidence, the identification of compounds active on this cell population is still an underexplored field.

Personalized medicine and circadian rhythms: Opportunities for modern society.

Circadian rhythms govern physiology and metabolism, leading to controlled homeostasis. We discuss the impact of circadian rhythms on society and the challenges for the imminent future of personalized medicine.

Expression study of candidate miRNAs and evaluation of their potential use as biomarkers of diabetic neuropathy.

To evaluate the expression of candidate miRNAs in relation to diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). The expression of six candidate miRNAs has been evaluated in 49 Type 2 diabetes patients with neurological evaluation. A higher expression of miR-128a was seen in patients with DPN compared with those without DPN (p = 0.

Work Personality, Core Self-evaluation and Perceived Career Barriers in Young Adult Central Nervous System Cancer Survivors.

Purpose: The purpose of this study is to examine the relationship between work personality, core self-evaluation (CSE), and perceived internal and external barriers to employment in a group of young adult CNS survivors.

Methods: The participants consisted of 110 young adult survivors of pediatric central nervous system (CNS) tumors aged between 18 and 30 years old (M = 23.05, SD = 3.

The large subunit of the regulatory [NiFe]-hydrogenase from - a minimal hydrogenase?

Chemically synthesized compounds that are capable of facilitating the reversible splitting of dihydrogen into protons and electrons are rare in chemists' portfolio. The corresponding biocatalysts - hydrogenases - are, however, abundant in the microbial world. [NiFe]-hydrogenases represent a major subclass and display a bipartite architecture, composed of a large subunit, hosting the catalytic NiFe(CO)(CN) cofactor, and a small subunit whose iron-sulfur clusters are responsible for electron transfer.

Mitochondrial DNA Copy Number in Peripheral Blood Is Reduced in Type 2 Diabetes Patients with Polyneuropathy and Associated with a Gene Polymorphism.

Our aim was to evaluate in a cohort of 125 Italian patients with type 2 diabetes (T2D), who underwent neurological evaluation, the possible differences in the number of mitochondrial DNA copies (mtDNA) comparing positive and negative patients for cardiovascular autonomic neuropathy (CAN) or diabetic peripheral neuropathy (DPN) and comparing them with healthy controls. We also investigated a possible correlation of the number of mtDNA copies with the polymorphism rs3746444 of the . T2D patients show a decrease in the number of mtDNA copies compared to healthy controls ( = 2 × 10).

A conceptual framework to promote career development for vocational rehabilitation consumers with traumatic brain injuries.

The purpose of this article is to describe the Illinois Work and Well-being Model (ILW2M), a multi-domain framework for conceptualizing the employment development of people with traumatic brain injuries (TBIs). The model emphasizes the interaction of contextual and career development domains to improve participation in the areas of work, society, community, and home. A brief discussion of potential implications regarding vocational rehabilitation research and service is offered with the overall goal of reinforcing employment development as the foundation of vocational rehabilitation services for adults with TBIs.