Electron transfer in the respiratory chain at low salinity.

Recent studies have established that cellular electrostatic interactions are more influential than assumed previously. Here, we use cryo-EM and perform steady-state kinetic studies to investigate electrostatic interactions between cytochrome (cyt.) c and the complex (C) III-IV supercomplex from Saccharomyces cerevisiae at low salinity.

Crystal structure of NRAS Q61K with a ligand-induced pocket near switch II.

The RAS isoforms (KRAS, HRAS and NRAS) have distinct cancer type-specific profiles. NRAS mutations are the second most prevalent RAS mutations in skin and hematological malignancies. Although RAS proteins were considered undruggable for decades, isoform and mutation-specific investigations have produced successful RAS inhibitors that are either specific to certain mutants, isoforms (pan-KRAS) or target all RAS proteins (pan-RAS).

Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic Neurons.

The hypothalamus is a vital regulator of energy homeostasis. Orexigenic neuropeptide Y (NPY) neurons within the hypothalamus can stimulate feeding and suppress energy expenditure, and dysregulation of these neurons may contribute to obesity. We previously reported that bisphenol A (BPA), an endocrine disruptor with obesogenic properties, alters transcription in hypothalamic neurons by inducing oxidative stress.

Perivascular spaces mediate a relationship between diabetes and other cerebral small vessel disease markers in cerebrovascular and neurodegenerative diseases.

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together.

Elastin stabilization prevents impaired biomechanics in human pulmonary arteries and pulmonary hypertension in rats with left heart disease.

Pulmonary hypertension worsens outcome in left heart disease. Stiffening of the pulmonary artery may drive this pathology by increasing right ventricular dysfunction and lung vascular remodeling. Here we show increased stiffness of pulmonary arteries from patients with left heart disease that correlates with impaired pulmonary hemodynamics.

Is there a Difference in Interfragmentary Compression Strength Between Fully or Partially Threaded Screws? Results of an Experimental Biomechanical Pilot Study.

 This study assessed differences between fully- and partially-threaded screws in the initial interfragmentary compression strength. Our hypothesis was that there would be an increased loss in initial compression strength with the partially-threaded screw.  A 45-degree oblique fracture line was created in artificial bone samples.

Spirocyclic Iodonium Ylides for Fluorine-18 Radiolabeling of Non-Activated Arenes: From Concept to Clinical Research.

Positron emission tomography (PET) is a powerful imaging tool for drug discovery, clinical diagnosis, and monitoring of disease progression. Fluorine-18 is the most common radionuclide used for PET, but advances in radiotracer development have been limited by the historical lack of methodologies and precursors amenable to radiolabeling with fluorine-18. Radiolabeling of electron-rich (hetero)aromatic rings remains a long-standing challenge in the production of PET radiopharmaceuticals.

Comparison of the spread pattern of medial-to-lateral and lateral-to-medial rotator interval injections: A cadaveric study.

Objective: Rotator interval (RI) corticosteroid injections are used to alleviate pain associated with adhesive capsulitis, though the pattern of injectate spread remains unclear. The purpose of this anatomical study was to assess the staining patterns of intra-articular, intracapsular/extrasynovial, and pericapsular structures of the glenohumeral joint following medial-to-lateral and lateral-to-medial RI injections.

Design: Ten cadaveric specimens were injected with a methylene blue dye injectate: five using a medial-to-lateral RI injection technique and five using a lateral-to-medial RI injection technique.

The respiratory supercomplex from C. glutamicum.

Corynebacterium glutamicum is a preferentially aerobic gram-positive bacterium belonging to the phylum Actinobacteria, which also includes the pathogen Mycobacterium tuberculosis. In these bacteria, respiratory complexes III and IV form a CIIICIV supercomplex that catalyzes oxidation of menaquinol and reduction of dioxygen to water. We isolated the C.

Anti-vaccination attitudes are associated with less analytical and more intuitive reasoning.

Online anti-vaccination rhetoric has produced far reaching negative health consequences. Persons who endorse anti-vaccination attitudes may employ less analytical reasoning when problem solving. Considering limitations in previous research, we used an online web-based survey (n = 760; mean age = 47.

Exploring patient-provider interactions and the health system's responsiveness to street-connected children and youth in Kenya: a qualitative study.

Background: In Kenya, street-connected children and youth (SCY) have poor health outcomes and die prematurely due to preventable causes. This suggests they are not accessing or receiving adequately responsive healthcare to prevent morbidity and mortality. We sought to gain insight into the health systems responsiveness to SCY in Kenya through an in-depth exploration of SCY's and healthcare provider's reflections on their interactions with each other.

SUMOylation modulates the stability and function of PI3K-p110β.

Class I PI3K are heterodimers composed of a p85 regulatory subunit and a p110 catalytic subunit involved in multiple cellular functions. Recently, the catalytic subunit p110β has emerged as a class I PI3K isoform playing a major role in tumorigenesis. Understanding its regulation is crucial for the control of the PI3K pathway in p110β-driven cancers.

Supporting pharmacogenetic-guided opioid prescriptions for post-operative pain: The design, protocol and preliminary results of the OTP study.

The interindividual variability in opioid response is an issue that contributes to the ongoing opioid crisis. Current evidence suggests this variability can be attributed to genetic factors. The pharmacogenetics of Opioid Treatment for acute post-operative Pain (OTP) project was a prospective study that aimed to identify genetic markers associated with opioid treatment outcomes.

Barriers and facilitators for cervical cancer screening among adolescents and young people: a systematic review.

Background: Though cervical cancer is one of the leading causes of cancer-related death globally, its incidence is nearly entirely preventable. Young people have been an international priority for screening as this population has historically been under-screened. However, in both high-income and low-income countries, young people have not been screened appropriately according to country-specific guidelines.

Characterizing street-connected children and youths' social and health inequities in Kenya: a qualitative study.

Background: Street-connected children and youth (SCY) in Kenya disproportionately experience preventable morbidities and premature mortality. We theorize these health inequities are socially produced and result from systemic discrimination and a lack of human rights attainment. Therefore, we sought to identify and understand how SCY's social and health inequities in Kenya are produced, maintained, and shaped by structural and social determinants of health using the WHO conceptual framework on social determinants of health (SDH) and the Convention on the Rights of the Child (CRC) General Comment no.

Understanding perceptions of involving community pharmacy within an integrated care model: a qualitative study.

Background: Over the past several years, there has been more emphasis on integration within health care. Community pharmacy is often under-represented within integrated care models. This study explored stakeholder perceptions and enablers of including community pharmacy within an integrated care model.

Relationship between skin melanin index and nicotine pharmacokinetics in African American smokers.

Background: Blacks bear a disproportionate burden of smoking-related diseases and experience greater difficulty quitting smoking than Whites. Nicotine has a high affinity for melanin, and it has been hypothesized that melanin levels might influence nicotine pharmacokinetics and enhance dependence. The aim of this study was to evaluate the hypothesis that melanin affects nicotine disposition kinetics in humans.

Ethnic differences in prediabetes incidence among immigrants to Canada: a population-based cohort study.

Background: Prediabetes appears to be increasing worldwide. This study examined the incidence of prediabetes among immigrants to Canada of different ethnic origins and the age at which ethnic differences emerged.

Methods: We assembled a cohort of Ontario adults (≥ 20 years) with normoglycemia based on glucose testing performed between 2002 and 2011 through a single commercial laboratory database (N = 1,772,180).

What proportion of striatal D2 receptors are occupied by endogenous dopamine at baseline? A meta-analysis with implications for understanding antipsychotic occupancy.

Using molecular imaging techniques - positron emission tomography (PET) and single-photon emission computed tomography (SPECT) - in conjunction with an acute dopamine depletion challenge (alpha-methyl-para-tyrosine) it is possible to estimate endogenous dopamine levels occupying striatal dopamine D receptors (DR) in humans in vivo. However, it is unclear what proportion of striatal DR are occupied by endogenous dopamine under normal conditions. This is important since it has been suggested that in schizophrenia there may be a substantial proportion of striatal DR which are occupied by endogenous dopamine and not accessible by therapeutic doses of antipsychotics.

The epidemiology of HIV and other sexually transmitted infections in African, Caribbean and Black men in Toronto, Canada.

Background: African, Caribbean, and Black (Black) men account for 16.5% of new HIV diagnoses among men in Ontario. There is substantial evidence that sexually transmitted infections (STIs) are associated with increased likelihood of HIV infection; however, little is known regarding the prevalence of HIV/STI co-infections among Black men in Toronto.

Global Genetic Networks and the Genotype-to-Phenotype Relationship.

Genetic interactions identify combinations of genetic variants that impinge on phenotype. With whole-genome sequence information available for thousands of individuals within a species, a major outstanding issue concerns the interpretation of allelic combinations of genes underlying inherited traits. In this Review, we discuss how large-scale analyses in model systems have illuminated the general principles and phenotypic impact of genetic interactions.

Sodium Levels in Packaged Foods Sold in 14 Latin American and Caribbean Countries: A Food Label Analysis.

Population-wide sodium reduction is a cost-effective approach to address the adverse health effects associated with excess sodium consumption. Latin American and Caribbean (LAC) countries consume excess dietary sodium. Packaged foods are a major contributor to sodium intake and a target for sodium reduction interventions.

Correction to: Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial.

In contrast to statements made in the above paper, measurements of waist and hip circumference were in fact available.

Reproducible quantification of cardiac sympathetic innervation using graphical modeling of carbon-11-meta-hydroxyephedrine kinetics with dynamic PET-CT imaging.

Background: Graphical methods of radiotracer kinetic modeling in PET are ideal for parametric imaging and data quality assurance but can suffer from noise bias. This study compared the Logan and Multilinear Analysis-1 (MA1) graphical models to the standard one-tissue-compartment (1TC) model, including correction for partial-volume effects, in dynamic PET-CT studies of myocardial sympathetic innervation in the left ventricle (LV) using [C]HED.

Methods: Test and retest [C]HED PET imaging (47 ± 22 days apart) was performed in 18 subjects with heart failure symptoms.