Clinical Relevance of Gastroesophageal Cancer Associated SNPs for Oncologic Outcome After Curative Surgery.

Background: Gastric and esophageal cancers are malignant diseases with rising importance in Western countries. To improve oncologic outcome after surgery, it is essential to understand the relevance of germline mutations. The aim of the study was to identify and distinguish clinically relevant single-nucleotide polymorphisms (SNPs).

Participants' perceptions of a residency teaching certificate program: the quality, impact and benefits.

Background: Currently, there are no accreditation requirements for pharmacy resident teaching certificate programs (RTCPs) but rather suggested guidelines and documents for individual programs to follow. RTCP curriculums are often "handed-down" from past personnel and vary based on individual interpretation. Quality improvement may be overlooked when programs do not report to governing bodies.

Fasting blood glucose as a predictor of mortality: Lost in translation.

Aging leads to profound changes in glucose homeostasis, weight, and adiposity, which are considered good predictors of health and survival in humans. Direct evidence that these age-associated metabolic alterations are recapitulated in animal models is lacking, impeding progress to develop and test interventions that delay the onset of metabolic dysfunction and promote healthy aging and longevity. We compared longitudinal trajectories, rates of change, and mortality risks of fasting blood glucose, body weight, and fat mass in mice, nonhuman primates, and humans throughout their lifespans and found similar trajectories of body weight and fat in the three species.

Opioids in patients with COPD and refractory dyspnea: literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD).

Background: Refractory dyspnea or breathlessness is a common symptom in patients with advanced chronic obstructive pulmonary disease (COPD), with a high negative impact on quality of life (QoL). Low dosed opioids have been investigated for refractory dyspnea in COPD and other life-limiting conditions, and some positive effects were demonstrated. However, upon first assessment of the literature, the quality of evidence in COPD seemed low or inconclusive, and focused mainly on morphine which may have more side effects than other opioids such as fentanyl.

General health, healthcare costs and dental care use of elderly with a natural dentition, implant-retained overdenture or conventional denture: an 8-year cohort of Dutch elderly (aged 75 and over).

Background: Cross-sectional studies have shown that elderly with a natural dentition have better general health than edentulous elderly, but this has not been confirmed in studies with longitudinal design.

Methods: This prospective longitudinal study with a follow-up of 8 years aimed to assess differences in general health, healthcare costs and dental care use between elderly with a natural dentition and edentulous elderly wearing implant-retained or conventional dentures. Based on data of all national insurance claims for dental and medical care from Dutch elderly (aged ≥75 years) general health outcomes (chronic conditions, medication use), healthcare costs and dental care use could be assessed of three groups of elderly, viz.

Molecular Characterization of Limited Ulcerative Colitis Reveals Novel Biology and Predictors of Disease Extension.

Background And Aims: Disease extent varies in ulcerative colitis (UC) from proctitis to left-sided colitis to pancolitis and is a major prognostic factor. When the extent of UC is limited there is often a sharp demarcation between macroscopically involved and uninvolved areas and what defines this or subsequent extension is unknown. We characterized the demarcation site molecularly and determined genes associated with subsequent disease extension.

Resting-state functional connectivity and reading subskills in children.

Individual differences in reading ability have been linked to characteristics of functional connectivity in the brain in both children and adults. However, many previous studies have used single or composite measures of reading, leading to difficulty characterizing the role of functional connectivity in discrete subskills of reading. The present study addresses this issue using resting-state fMRI to examine how resting-state functional connectivity (RSFC) related to individual differences in children's reading subskills, including decoding, sight word reading, reading comprehension, and rapid automatized naming (RAN).

Improving healthcare for patients with HIV, tuberculosis and hepatitis C in eastern Europe: a review of current challenges and important next steps.

Objectives: In some eastern European countries, serious challenges exist to meet the HIV-, tuberculosis (TB)- and hepatitis-related target of the United Nations Sustainable Development Goals. Some of the highest incidence rates for HIV and the highest proportion of multi-drug-resistant (MDR) tuberculosis worldwide are found in the region. The purpose of this article is to review the challenges and important next steps to improve healthcare for people living with TB, HIV and hepatitis C (HCV) in eastern Europe.

Symbols Are Special: An fMRI Adaptation Study of Symbolic, Nonsymbolic, and Non-Numerical Magnitude Processing in the Human Brain.

How are different formats of magnitudes represented in the human brain? We used functional magnetic resonance imaging adaptation to isolate representations of symbols, quantities, and physical size in 45 adults. Results indicate that the neural correlates supporting the passive processing of number symbols are largely dissociable from those supporting quantities and physical size, anatomically and representationally. Anatomically, passive processing of quantities and size correlate with activation in the right intraparietal sulcus, whereas symbolic number processing, compared with quantity processing, correlates with activation in the left inferior parietal lobule.

Thyroid disruption and oxidative stress in American kestrels following embryonic exposure to the alternative flame retardants, EHTBB and TBPH.

Brominated flame retardant chemicals, such as 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB) (CAS #: 183658-27-7) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) (CAS #: 26040-51-7), have been detected in avian tissues and eggs from remote regions. Exposure to EHTBB and TBPH has been shown to cause oxidative stress and altered thyroid function in rodents and fish, yet no controlled studies have examined potential adverse effects of exposure in birds. Because flame retardants have been detected in wild raptors, we used American kestrels (Falco sparverius) as a model raptor to determine whether in ovo exposure to EHTBB or TBPH affected growth, hatching success, oxidative stress, or thyroid function.

Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56CD57 natural killer (NK) cells and exhausted CD8 T cells.

Differences in Extracellular Vesicle Protein Cargo Are Dependent on Head and Neck Squamous Cell Carcinoma Cell of Origin and Human Papillomavirus Status.

To identify potential extracellular vesicle (EV) biomarkers in head and neck squamous cell carcinoma (HNSCC), we evaluated EV protein cargo and whole cell lysates (WCL) from HPV-positive and -negative HNSCC cell lines, as well as normal oral keratinocytes and HPV16-transformed cells. EVs were isolated from serum-depleted, conditioned cell culture media by polyethylene glycol (PEG) precipitation/ultracentrifugation. EV and WCL preparations were analyzed by LC-MS/MS.

Overexpression of the Autoimmune Risk Variant LYP-620W Fails to Restrain Human CD4 T Cell Activation.

A missense mutation (R620W) of protein tyrosine phosphatase nonreceptor type 22 (), which encodes lymphoid-tyrosine phosphatase (LYP), confers genetic risk for multiple autoimmune diseases including type 1 diabetes. LYP has been putatively demonstrated to attenuate proximal T and BCR signaling. However, limited data exist regarding expression within primary T cell subsets and the impact of the type 1 diabetes risk variant on human T cell activity.

Immunomodulatory Nanomedicine for the Treatment of Atherosclerosis.

Atherosclerosis is the main underlying cause of cardiovascular diseases (CVDs), which remain the number one contributor to mortality worldwide. Although current therapies can slow down disease progression, no treatment is available that can fully cure or reverse atherosclerosis. Nanomedicine, which is the application of nanotechnology in medicine, is an emerging field in the treatment of many pathologies, including CVDs.

The Jackson Laboratory Nathan Shock Center: impact of genetic diversity on aging.

Healthspan is a complex trait, influenced by many genes and environmental factors that accelerate or delay aging, reduce or increase disease risk, and extend or reduce lifespan. Thus, assessing the role of genetic variation in aging requires an experimental strategy capable of modeling the genetic and biological complexity of human populations. The goal of the The Jackson Laboratory Nathan Shock Center (JAX NSC) is to provide research resources and training for geroscience investigators that seek to understand the role of genetics and genetic diversity on the fundamental process of aging and diseases of human aging using the laboratory mouse as a model system.

Ab initio molecular dynamics with screened Lorentz forces. I. Calculation and atomic charge interpretation of Berry curvature.

The dynamics of a molecule in a magnetic field is significantly different from its zero-field counterpart. One important difference in the presence of a field is the Lorentz force acting on the nuclei, which can be decomposed as the sum of the bare nuclear Lorentz force and a screening force due to the electrons. This screening force is calculated from the Berry curvature and can change the dynamics qualitatively.

Ab Initio molecular dynamics with screened Lorentz forces. II. Efficient propagators and rovibrational spectra in strong magnetic fields.

Strong magnetic fields have a large impact on the dynamics of molecules. In addition to the changes in the electronic structure, the nuclei are exposed to the Lorentz force with the magnetic field being screened by the electrons. In this work, we explore these effects using ab initio molecular dynamics simulations based on an effective Hamiltonian calculated at the Hartree-Fock level of theory.

A systematic review and meta-synthesis of qualitative studies that investigate the emotional experiences of staff working in homeless settings.

Homelessness is a pervasive issue in society, and government policies have highlighted the need to focus on the experience of front-line staff in homelessness settings. The aim of this meta-synthesis was to draw together the available research to further understanding of the experiences of staff working with homeless people. A systematic search was conducted across four electronic databases (ASSIA, PsycInfo, Sociological Abstracts and Web of Science) from the date of their inception.

Kinetics of Plasma Cytokines, Angiopoietin-2, and C-Reactive Protein in Dogs With Gastric Dilatation Volvulus.

The degree of systemic inflammation, reperfusion injury and endothelial activation are potentially important determinants of clinical outcomes in dogs with gastric dilatation volvulus (GDV). To evaluate plasma concentrations and kinetics of inflammatory markers in dogs with GDV over a time frame of 48 h, and to compare to healthy dogs. Prospective, observational cohort study in client-owned dogs with GDV.

Transcriptome signature of miRNA-26b KO mouse model suggests novel targets.

Background: MicroRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. One of the miRNAs that has been shown to play a role in various pathologies like cancer, neurological disorders and cardiovascular diseases is miRNA-26b. However, these studies only demonstrated rather ambiguous associations without revealing a causal relationship.

Lupus susceptibility gene Esrrg modulates regulatory T cells through mitochondrial metabolism.

Estrogen-related receptor γ (Esrrg) is a murine lupus susceptibility gene associated with T cell activation. Here, we report that Esrrg controls Tregs through mitochondria homeostasis. Esrrg deficiency impaired the maintenance and function of Tregs, leading to global T cell activation and autoimmunity in aged mice.

Pre-analytical stability of sorbitol dehydrogenase in equine heparinized plasma.

Sorbitol dehydrogenase (SDH) activity is one of the most sensitive and specific markers for hepatocellular injury in horses, but its reported lability makes it impractical for use in many clinical settings. To date, stability of SDH in equine samples has only been evaluated in a limited number of studies in serum samples of horses with activities within reference intervals. The objective of the study was to determine pre-analytical stability of equine SDH activity in heparinized plasma stored at different temperatures for up to 72 h.

Tyrosine Kinase Inhibitor Sunitinib Delays Platelet-Induced Coagulation: Additive Effects of Aspirin.

Background:  Sunitinib is a multitarget tyrosine kinase inhibitor (TKI) used for cancer treatment. In platelets, sunitinib affects collagen-induced activation under noncoagulating conditions. We investigated (1) the effects of sunitinib on thrombus formation induced by other TK-dependent receptors, and (2) the effects under coagulating conditions.

Synthesising the shifting terminology of community health: A critiquing review of agent-based approaches.

The field of community health promotion encompasses a wide range of approaches, including bottom-up approaches that recognise and build on the agency and strengths of communities to define and pursue their health goals. Momentum towards agent-based approaches to community health promotion has grown in recent years, and several related but distinct conceptual and methodological bodies of work have developed largely in isolation from each other. The lack of a cohesive collection of research, practice, and policy has made it difficult to learn from the innovations, best practices, and shortcomings of these approaches, which is exacerbated by the imprecise and inconsistent use of related terms.