Exposure to aircraft noise exacerbates cardiovascular and oxidative damage in three mouse models of diabetes.

Background: Epidemiology links noise to increased risk of metabolic diseases like diabetes and obesity. Translational studies in humans and experimental animals showed that noise causes reactive oxygen species (ROS)-mediated cardiovascular damage. The interaction between noise and diabetes, specifically potential additive adverse effects, remains to be determined.

Parent-reported genetic counselor adherence to the NSGC practice resource for communicating a potential prenatal diagnosis: Impact on the Down syndrome diagnosis experience.

In 2011, the National Society of Genetic Counselors (NSGC) published practice resources about communicating a prenatal or postnatal diagnosis of Down syndrome (DS). However, the impact of GC adherence to those recommendations on patient experiences has been unknown. The objective of this analysis was to investigate perceived GC adherence to professional recommendations for delivering a DS diagnosis and the impact on parental diagnosis experiences and the information and support offered.

Externalized histones fuel pulmonary fibrosis via a platelet-macrophage circuit of TGFβ1 and IL-27.

Externalized histones erupt from the nucleus as extracellular traps, are associated with several acute and chronic lung disorders, but their implications in the molecular pathogenesis of interstitial lung disease are incompletely defined. To investigate the role and molecular mechanisms of externalized histones within the immunologic networks of pulmonary fibrosis, we studied externalized histones in human and animal bronchoalveolar lavage (BAL) samples of lung fibrosis. Neutralizing anti-histone antibodies were administered in bleomycin-induced fibrosis of C57BL/6 J mice, and subsequent studies used conditional/constitutive knockout mouse strains for TGFβ and IL-27 signaling along with isolated platelets and cultured macrophages.

Promising Strategies for Teaching Augmentative and Alternative Communication in Inclusive Educational Settings: A Systematic Review.

Purpose: The purpose of this article was to conduct a systematic review of the literature on teaching or increasing the use of augmentative and alternative communication (AAC) by students with significant intellectual disabilities and complex communication needs (CCNs) within inclusive school settings.

Method: A systematic review of research literature from 1998 to 2022 was completed using multiple electronic databases, as well as citation chaining and cited author reference searches. Three hundred two articles were located with 17 meeting criteria for inclusion in this systematic review.

The impact of implicit and explicit bias about disabilities on parent experiences and information provided during prenatal screening and testing.

Background: Prenatal screening technology has consistently raised concerns regarding the conversations and information provided about disabilities, particularly given that research shows trauma related to negative prenatal screening and diagnosis experiences among parents of children with Down syndrome. OBJECTIVE: To determine what information obstetric medical providers (OB/MFMs) are most and least likely to provide when delivering prenatal screening/testing results about Down syndrome (DS), the subsequent impact of bias on prenatal screening experiences, and how these issues can be addressed through training, resources, and professional guidelines.

Methods: Online surveys were distributed to parents of children with DS born between 2016 and 2021 via local DS organizations and the national DS Diagnosis Network (April 2020-December 2021).

The role of acrolein for E-cigarette vapour condensate mediated activation of NADPH oxidase in cultured endothelial cells and macrophages.

Electronic cigarettes (E-cigarettes) have recently become a popular alternative to traditional tobacco cigarettes. Despite being marketed as a healthier alternative, increasing evidence shows that E-cigarette vapour could cause adverse health effects. It has been postulated that degradation products of E-cigarette liquid, mainly reactive aldehydes, are responsible for those effects.

Aircraft noise exposure induces pro-inflammatory vascular conditioning and amplifies vascular dysfunction and impairment of cardiac function after myocardial infarction.

Aims: Traffic noise may play an important role in the development and deterioration of ischaemic heart disease. Thus, we sought to determine the mechanisms of cardiovascular dysfunction and inflammation induced by aircraft noise in a mouse model of myocardial infarction (MI) and in humans with incident MI.

Methods And Results: C57BL/6J mice were exposed to noise alone (average sound pressure level 72 dB; peak level 85 dB) for up to 4 days, resulting in pro-inflammatory aortic gene expression in the myeloid cell adhesion/diapedesis pathways.

Co-exposure to urban particulate matter and aircraft noise adversely impacts the cerebro-pulmonary-cardiovascular axis in mice.

Worldwide, up to 8.8 million excess deaths/year have been attributed to air pollution, mainly due to the exposure to fine particulate matter (PM). Traffic-related noise is an additional contributor to global mortality and morbidity.

Perceived stress of individuals with disabilities in the United States during COVID-19.

Purpose/objective: This study was conducted to better understand how COVID-19 has impacted the stress, resiliency, and quality of life of people with disabilities near the height of the first surge of the COVID-19 pandemic in the summer of 2020.

Research Method/design: An online survey of 990 individuals who self-identified as having at least one disability in the United States was conducted.

Results: Quality of life, coping/resilience skills, number of identified disabilities, and age were all significantly related to perceived stress.

Direct Support Professionals: Stress and Resiliency Amidst the COVID-19 Pandemic.

This study reports on the results of an online survey of direct support professionals (DSPs) during the COVID-19 pandemic in June 2020 to measure their perceived quality of life, stressors, coping/resilience skills, and knowledge of health care rights directly related to the pandemic for the persons that they support. Specifically, we examined direct support workers' perceptions of their quality of life, levels of stress, and their self-reported resilience skills. We found that perceived stress was strongly correlated with both self-reported quality of life and resilience, but not with years of DSP experience.

The Role of KH-Type Splicing Regulatory Protein (KSRP) for Immune Functions and Tumorigenesis.

Post-transcriptional control of gene expression is one important mechanism that enables stringent and rapid modulation of cytokine, chemokines or growth factors expression, all relevant for immune or tumor cell function and communication. The RNA-binding protein KH-type splicing regulatory protein (KSRP) controls the mRNA stability of according genes by initiation of mRNA decay and inhibition of translation, and by enhancing the maturation of microRNAs. Therefore, KSRP plays a pivotal role in immune cell function and tumor progression.

A specific, non-immune system-related isoform of the human inducible nitric oxide synthase is expressed during differentiation of human stem cells into various cell types.

Background: NOS2 expression is mostly found in bacteria-exposed or cytokine-treated tissues and is mostly connected to innate immune reactions. There are three isoforms of NOS2 (NOS2-1 to -3). In RNA-seq data sets, analyzing inflammatory gene expression, only expression of the NOS2-1 mRNA isoform is detected.

Knockout of the KH-Type Splicing Regulatory Protein Drives Glomerulonephritis in MRL-Fas Mice.

KH-type splicing regulatory protein (KSRP) is an RNA-binding protein that promotes mRNA decay and thereby negatively regulates cytokine expression at the post-transcriptional level. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated cytokine expression causing multiple organ manifestations; MRL-Fas mice are an established mouse model to study lupus disease pathogenesis. To investigate the impact of KSRP on lupus disease progression, we generated KSRP-deficient MRL-Fas mice (MRL-Fas/KSRP mice).

Cyp2c44 epoxygenase-derived epoxyeicosatrienoic acids in vascular smooth muscle cells elicit vasoconstriction of the murine ophthalmic artery.

Cytochrome P450 (CYP) signalling pathway has been shown to play a vital role in the vasoreactivity of wild type mouse ophthalmic artery. In this study, we determined the expression, vascular responses and potential mechanisms of the CYP-derived arachidonic acid metabolites. The expression of murine CYP (Cyp2c44) and soluble epoxide hydrolase (sEH) in the wild type ophthalmic artery was determined with immunofluorescence, which showed predominant expression of Cyp2c44 in the vascular smooth muscle cells (VSMC), while sEH was found mainly in the endothelium of the wild type ophthalmic artery.

Deficiency of Antioxidative Paraoxonase 2 (Pon2) Leads to Increased Number of Phenotypic LT-HSCs and Disturbed Erythropoiesis.

Background: Long-term hematopoietic stem cells (LT-HSCs) reside in bone marrow niches with tightly controlled reactive oxygen species (ROS) levels. ROS increase results into LT-HSC differentiation and stem cell exhaustion. Paraoxonase 2 (PON2) has been shown to be important for ROS control.

Regulation of NOS expression in vascular diseases.

Nitric oxide synthases (NOS) are the major sources of nitric oxide (NO), a small bioactive molecule involved in the regulation of many cellular processes. One of the most prominent functions of NO is regulation of vasodilatation and thereby control of blood pressure. Most important for vascular tone is NOS3.

NOX2ko Mice Show Largely Increased Expression of a Mutated NOX2 mRNA Encoding an Inactive NOX2 Protein.

Background: The superoxide-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2 or gp91phox, the phagocytic isoform) was reported as a major source of oxidative stress in various human diseases. Genetic deletion is widely used to study the impact of NOX2-derived reactive oxygen species (ROS) on disease development and progression in various animal models. Here, we investigate why NOX2 knockout mice show no NOX2 activity but express NOX2 mRNA and protein.

Stakeholder perspectives on transition planning, implementation, and outcomes for students with autism spectrum disorder.

Little is known about factors impacting poor post-school outcomes for transition-age students with autism spectrum disorder. Guided by an implementation science framework that takes into account the multiple factors that influence transition outcomes, we sought to better understand the interdependent impacts of policy, organizational, provider, and individual factors that shape the transition planning process in schools, and the subsequent process through which transition plans are implemented as youth with autism spectrum disorder access services and gain employment after school. We conducted focus groups with individuals with autism spectrum disorder, parents, classroom teachers, school administrators, adult service providers, and state policymakers (10 groups,  = 40).

CNS myelin protein 36K regulates oligodendrocyte differentiation through Notch.

In contrast to humans and other mammals, zebrafish can successfully regenerate and remyelinate central nervous system (CNS) axons following injury. In addition to common myelin proteins found in mammalian myelin, 36K protein is a major component of teleost fish CNS myelin. Although 36K is one of the most abundant proteins in zebrafish brain, its function remains unknown.

Teaching medical students how to deliver diagnoses of Down syndrome: Utility of an educational tool.

Objective: This study assessed whether using an educational tool increased the knowledge and perceived comfort level of first-year medical students in giving a diagnosis of Down syndrome.

Method: A total of 295 students taking a genetics course completed a knowledge questionnaire and Situations Inventory (aimed at assessing comfort with sharing certain information), prior to and following use of Brighter Tomorrows, a web-based educational module on giving parents a diagnosis of Down syndrome.

Results: The pre-intervention mean on the knowledge survey was 3.

The RNA-Binding Protein KSRP Modulates Cytokine Expression of CD4 T Cells.

The KH-type splicing regulatory protein (KSRP) is a RNA-binding protein, which regulates the stability of many mRNAs encoding immune-relevant proteins. As KSRP regulates innate immune responses, for instance by the modulation of type I interferon mRNA stability, we were interested whether knockdown of the protein (KSRP) interferes with T cell activation and polarization. Polyclonally stimulated KSRP CD4 T cells proliferated at a higher extent and higher frequency and expressed the activation marker CD25 more than wild-type T cells.

Regulation of human inducible nitric oxide synthase expression by an upstream open reading frame.

The human inducible nitric oxide synthase (iNOS) gene contains an upstream open reading frame (uORF) in its 5'-untranslated region (5'-UTR) implying a translational regulation of iNOS expression. Transfection experiments in human DLD-1 cells revealed that the uORF although translatable seems not to inhibit the translation start at the bona fide ATG. Our data clearly show that human iNOS translation is cap-dependent and that the 5'-UTR of the iNOS mRNA contains no internal ribosome entry site.

The KH-type splicing regulatory protein (KSRP) regulates type III interferon expression post-transcriptionally.

Type III interferons (IFNs) are the latest members of the IFN family. They play an important role in immune defense mechanisms, especially in antiviral responses at mucosal sites. Moreover, they control inflammatory reactions by modulating neutrophil and dendritic cell functions.