Activity of the poly(A) binding protein MSUT2 determines susceptibility to pathological tau in the mammalian brain.

Brain lesions composed of pathological tau help to drive neurodegeneration in Alzheimer's disease (AD) and related tauopathies. Here, we identified the mammalian suppressor of tauopathy 2 () gene as a modifier of susceptibility to tau toxicity in two mouse models of tauopathy. Transgenic PS19 mice overexpressing tau, a model of AD, and lacking the gene exhibited decreased learning and memory deficits, reduced neurodegeneration, and reduced accumulation of pathological tau compared to PS19 tau transgenic mice expressing Conversely, overexpression in 4RTauTg2652 tau transgenic mice increased pathological tau deposition and promoted the neuroinflammatory response to pathological tau.

Optimizing efficiency and skill utilization: Analysis of genetic counselors' attitudes regarding delegation in a clinical setting.

This study assessed genetic counselors' (GCs) perceptions of delegation as a tool to increase workforce efficiency and help meet the current gap between the number of genetic service providers and the number of patients. GCs were recruited to participate via an online survey that assessed activities (categorized as typical genetic counseling, administrative, or professional development) performed by a clinical genetic counselor. Respondents indicated which activities represent their largest time consumers, their willingness to delegate these activities, and barriers to and perceived outcomes of delegation.

Screening for Lynch Syndrome by Immunohistochemistry of Mismatch Repair Proteins: Significance of Indeterminate Result and Correlation With Mutational Studies.

Context.—: Immunohistochemical expression of mismatch repair (MMR) protein is a well-accepted method for routine screening for Lynch syndrome with relatively high sensitivity and specificity. Occasionally, however, immunohistochemistry (IHC) can yield an equivocal result with poor reproducibility and the potential for misdiagnosis.

Public prescription drug plan coverage for antiretrovirals and the potential cost to people living with HIV in Canada: a descriptive study.

Background: Antiretrovirals are expensive and people living with HIV may experience a range of financial burdens when accessing these medications. Our aim was to describe the policy of all Canadian public drug insurance programs for antiretroviral drugs and illustrated how these policies might affect patients' annual out-of-pocket expenditures.

Methods: In December 2017, we reviewed public drug programs offering antiretroviral coverage in Canada using government websites to summarize eligibility criteria.

Genetic Counseling Assistants: an Integral Piece of the Evolving Genetic Counseling Service Delivery Model.

This study explores the potential impact of the genetic counseling assistant (GCA) position on the efficiency of the genetic counseling field, evaluates attitudes regarding expansion of the genetic counseling field to include the GCA, and presents data on GCA endeavors and GCA job tasks as reported by GCAs, certified genetic counselors (CGCs), and program directors (PDs). Data on GCA roles and attitudes toward different aspects of the GCA position were collected via surveys of CGCs who have worked with GCAs, PDs who have and have not had experience with GCAs in their programs, and GCAs. We analyzed responses from 63 individuals: 27 PDs, 22 CGCs, and 14 GCAs.

To stay or to go? Postretirement housing choices of single Baby Boomer women.

Single women of the Baby Boomer generation are often financially disadvantaged in the retirement planning process due to their lower accumulated savings compared to male retirees. This disadvantage impacts significant consumption decisions such as postretirement housing choices. This study uses the theory of planned behavior to examine how certainty in intentions influences preparing and planning for postretirement housing.

Prediction of Cancer Prevention: From Mammogram Screening to Identification of BRCA1/2 Mutation Carriers in Underserved Populations.

Background: The US Preventative Service Task Force recommends that physicians perform a genetic risk assessment to identify women at risk for BRCA1/2 mutations associated with hereditary breast and ovarian cancer (HBOC) syndrome. However, outcomes data after a diagnosis of HBOC syndrome especially in diverse populations, are minimal. Here we asked if genetic screening of high-risk underserved women identified in the mammogram population reduces cancer incidence.

Expression of mutant bone morphogenetic protein receptor II worsens pulmonary hypertension secondary to pulmonary fibrosis.

Pulmonary fibrosis is often complicated by pulmonary hypertension (PH), and previous studies have shown a potential link between bone morphogenetic protein receptor II (BMPR2) and PH secondary to pulmonary fibrosis. We exposed transgenic mice expressing mutant BMPR2 and control mice to repetitive intraperitoneal injections of bleomycin for 4 weeks. The duration of transgene activation was too short for mutant BMPR2 mice to develop spontaneous PH.

High copy wildtype human 1N4R tau expression promotes early pathological tauopathy accompanied by cognitive deficits without progressive neurofibrillary degeneration.

Introduction: Accumulation of insoluble conformationally altered hyperphosphorylated tau occurs as part of the pathogenic process in Alzheimer's disease (AD) and other tauopathies. In most AD subjects, wild-type (WT) tau aggregates and accumulates in neurofibrillary tangles and dystrophic neurites in the brain; however, in some familial tauopathy disorders, mutations in the gene encoding tau cause disease.

Results: We generated a mouse model, Tau4RTg2652, that expresses high levels of normal human tau in neurons resulting in the early stages of tau pathology.

Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic.

Despite the potential of whole-genome sequencing (WGS) to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with mutations (n = 176) and those without (n = 82). Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency < 1% in ESP6500) in 163 clinically-relevant genes suggested that WGS will provide useful clinical results.

Proactive case finding to improve concurrently curative and palliative care in patients with end-stage liver disease.

Background: Palliative care and preparation for liver transplantation are often perceived as conflicting for patients with end-stage liver disease (ESLD). We sought to improve both simultaneously through a case finding and care coordination quality improvement intervention.

Methods: We identified patients with cirrhosis using validated ICD-9 codes and screened them for ESLD by assessing medical records at a VA hospital for either a model for end-stage liver disease (MELD) ≥14 or a diagnosis of hepatocellular carcinoma (HCC) between October 2012 and January 2013.

Resistance to noise-induced hearing loss in 129S6 and MOLF mice: identification of independent, overlapping, and interacting chromosomal regions.

Noise-induced hearing loss (NIHL) is a prevalent health risk. Inbred mouse strains 129S6/SvEvTac (129S6) and MOLF/EiJ (MOLF) show strong NIHL resistance (NR) relative to CBA/CaJ (CBACa). In this study, we developed quantitative trait locus (QTL) maps for NR.

State of inertia: psychological preparation of single Australian and UK baby boomer women for retirement housing change.

The transition into retirement is an important life phase that presents significant challenges in respect to well-being, lifestyle, and consumption choices. This article examines the consumption context of housing after retirement, in particular for the low-resourced cohort of single baby boomer women. Utilizing an extended Theory of Planned Behavior model, we examine the relationship between intention and actual behavior, in this case financial advice seeking, as an important component of the psychological preparedness of single female baby boomer women.

An internal performance assessment of CancerGene Connect: an electronic tool to streamline, measure and improve the genetic counseling process.

CancerGene Connect (CGC) is a web-based program that combines the collection of family and medical history, cancer risk assessment, psychosocial assessment, report templates, a result tracking system, and a patient follow up system. The performance of CGC was assessed in several ways: pre-appointment completion data analyzed for demographic and health variables; a time study to assess overall time per case and to compare the data entry by the genetic counselor compared to the patient, and a measured quality assessment of the program via observation and interview of patients. Prior to their appointment, 52.

Engagement with Care, Substance Use, and Adherence to Therapy in HIV/AIDS.

Engagement with care for those living with HIV is aimed at establishing a strong relationship between patients and their health care provider and is often associated with greater adherence to therapy and treatment (Flickinger, Saha, Moore, and Beach, 2013). Substance use behaviors are linked with lower rates of engagement with care and medication adherence (Horvath, Carrico, Simoni, Boyer, Amico, and Petroli, 2013). This study is a secondary data analysis using a cross-sectional design from a larger randomized controlled trial (n = 775) that investigated the efficacy of a self-care symptom management manual for participants living with HIV.

Hereditary lung cancer syndrome targets never smokers with germline EGFR gene T790M mutations.

Introduction: Hereditary lung cancer syndromes are rare, and T790M germline mutations of the epidermal growth factor receptor (EGFR) gene predispose to the development of lung cancer. The goal of this study was to determine the clinical features and smoking status of lung cancer cases and unaffected family members with this germline mutation and to estimate its incidence and penetrance.

Methods: We studied a family with germline T790M mutations over five generations (14 individuals) and combined our observations with data obtained from a literature search (15 individuals).

BMP pathway regulation of and by macrophages.

Pulmonary arterial hypertension (PAH) is a disease of progressively increasing pulmonary vascular resistance, associated with mutations of the type 2 receptor for the BMP pathway, BMPR2. The canonical signaling pathway for BMPR2 is through the SMAD family of transcription factors. BMPR2 is expressed in every cell type, but the impact of BMPR2 mutations affecting SMAD signaling, such as Bmpr2delx4+, had only previously been investigated in smooth muscle and endothelium.

The integration of next-generation sequencing panels in the clinical cancer genetics practice: an institutional experience.

Purpose: The advent of next-generation sequencing for cancer susceptibility genes holds promise for clinical genetics application, but the practical issues surrounding integration of this testing into the clinical setting have not been well addressed. This article describes the clinical experience of genetic counselors in an academic and community setting with next-generation sequencing cancer panels.

Methods: Between April 2012 and January 2013, 60 next-generation sequencing panels were ordered.

Hyperoxia synergizes with mutant bone morphogenic protein receptor 2 to cause metabolic stress, oxidant injury, and pulmonary hypertension.

Pulmonary arterial hypertension (PAH) has been associated with a number of different but interrelated pathogenic mechanisms. Metabolic and oxidative stresses have been shown to play important pathogenic roles in a variety of model systems. However, many of these relationships remain at the level of association.

Implementation of routine screening for Lynch syndrome in university and safety-net health system settings: successes and challenges.

Purpose: Routine screening for evidence of DNA mismatch repair abnormalities can identify colorectal cancer patients with Lynch syndrome, but impact in usual care settings requires study. After implementing routine screening at our university and safety-net health systems as usual practice, our aims were to determine outcomes, including screening process quality.

Methods: We conducted a retrospective cohort study from 1 May 2010 to 1 May 2011.

The impact of stressful life events, symptom status, and adherence concerns on quality of life in people living with HIV.

Studies concerning persons living with HIV (PLWH) report that stressful life events (SLEs) contribute to an exacerbation of symptoms and reduced antiretroviral (ARV) adherence and quality of life (QOL). Little is known about whether these findings are site-specific. Our study's aims were to characterize the type and frequency of SLEs for PLWH in Puerto Rico, South Africa, and the United States, and to assess the impact of SLEs by national site, symptoms, and ARV adherence concerns on QOL.

Genetic predisposition syndromes and their management.

Apart from BRCA1, BRCA2, and TP53, more than a dozen breast cancer susceptibility genes have been identified. Recognizing affected individuals depends on evaluation of cancer family history and recognition of certain phenotypic markers on physical examination. Genetic testing provides a powerful tool for individualized risk stratification.

Right ventricular systolic pressure measurements in combination with harvest of lung and immune tissue samples in mice.

The function of the right heart is to pump blood through the lungs, thus linking right heart physiology and pulmonary vascular physiology. Inflammation is a common modifier of heart and lung function, by elaborating cellular infiltration, production of cytokines and growth factors, and by initiating remodeling processes. Compared to the left ventricle, the right ventricle is a low-pressure pump that operates in a relatively narrow zone of pressure changes.