Evaluation of the diagnostic accuracy of exome sequencing and its impact on diagnostic thinking for patients with rare disease in a publicly funded health care system: A prospective cohort study.

Purpose: To evaluate the diagnostic utility of publicly funded clinical exome sequencing (ES) for patients with suspected rare genetic diseases.

Methods: We prospectively enrolled 297 probands who met eligibility criteria and received ES across 5 sites in Ontario, Canada, and extracted data from medical records and clinician surveys. Using the Fryback and Thornbury Efficacy Framework, we assessed diagnostic accuracy by examining laboratory interpretation of results and assessed diagnostic thinking by examining the clinical interpretation of results and whether clinical-molecular diagnoses would have been achieved via alternative hypothetical molecular tests.

Differential Effects of Remdesivir and Lumacaftor on Homomeric and Heteromeric hERG Channels.

The encodes for the pore-forming subunit of the channel that conducts the rapidly activating delayed K current (I) in the heart. The hERG channel is important for cardiac repolarization, and reduction of its expression in the plasma membrane due to mutations causes long QT syndrome type 2 (LQT2). As such, promoting hERG membrane expression is a strategy to rescue mutant channel function.

The athletic work force: Sport as a key to employment for people with intellectual disabilities?

Background: People with disabilities are employed at lower rates than non-disabled individuals and, among people with disabilities, those with intellectual disabilities have most difficulty finding and keeping employment. The reasons for the low labour participation among people with intellectual disabilities are many. Sport participation has a number of positive effects for the individual, and it is reasonable to hypothesise that sport participation favours labour-force participation for individuals with intellectual disabilities.

Complications of red cell exchange for anemia management in patients with transfusion-dependent thalassemia.

Background: In the Rare Blood Disorders clinic at the University of Alberta in Edmonton, red cell exchange (RCE) was utilized in transfusion-dependent thalassemia (TDT) patients with severe iron overload despite oral chelation and no access to iron infusion pumps for parenteral chelation. It was hypothesized that RCE would be less iron loading compared to simple transfusion. The purpose of this study is to document observations of the potential risks and benefits of RCE in TDT patients.

Geographic disparities in the care and outcomes in adult chronic immune thrombocytopenia.

Introduction: Despite expert-based recommendations, real-world adherence to immune thrombocytopenia (ITP) guidelines is unclear. The impact of geographic and socioeconomic disparities on the quality of care and outcomes is unknown. We sought to determine the association between geographic remoteness and material deprivation on ITP care and outcomes.

Employees Perceptions of Job Insecurity and Performance: A Qualitative Approach.

The purpose of this article is to understand the experience of workers' perceptions of job insecurity and its relation to performance. To this end, we conducted semi-structured interviews with 38 workers in the retail, services, education, financial, construction, and pharmaceutical industries in Chile. Using content analysis based on workers' accounts of their own experience, we identified two main categories: (a) the experience of job insecurity viewed in relation to the context of the COVID-19 pandemic and emotional aspects of job insecurity, and (b) the relation between job insecurity and performance.

Treatment patterns and outcomes of second-line rituximab and thrombopoietin receptor agonists in adult immune thrombocytopenia: A Canadian retrospective cohort study.

Background: The optimal choice of second-line treatment for immune thrombocytopenia (ITP) is unclear. Guidelines recommend either rituximab, splenectomy, or thrombopoietin receptor agonists (TPO-RA). There is, however, scarce data comparing treatment patterns, outcomes and resource utilization across second-line treatments.

Frequency and utility of bone marrow examination in relapsed/refractory immune thrombocytopenia.

Background: The diagnosis of immune thrombocytopenia (ITP) is one of exclusion. Although guidelines recommend against routine bone marrow examination (BME) at time of ITP diagnosis, the role of BME in relapsed/refractory ITP is unclear.

Objectives: To examine the frequency and predictors of BME in relapsed/refractory ITP.

Experiences of job demand and control: A study of first line managers in for-profit psychiatric and addiction care.

Background: The complex position of a first line manager is characterized by heavy workload and contradictory demands. Little is known about how first line managers experience demand and control in their work.

Objectives: The aim of this study was to explore experiences of demand and control among first line managers within psychiatric and addiction care.

The Importance of Belonging to a Context: A Nurse-Led Lifestyle Intervention for Adult Persons with ADHD.

Living with attention deficit hyperactivity disorder (ADHD) and mental illness involves an increased risk of lifestyle-related diseases. Although there are several ways to provide support to adult persons with ADHD, there is a lack of non-medical strategies for this purpose. This study explore how adult persons with ADHD with mental illness experienced taking part in a nurse-led lifestyle intervention.

A nurse-led lifestyle intervention for adult persons with attention-deficit/hyperactivity disorder (ADHD) in Sweden.

Attention-deficit/hyperactivity disorder (ADHD) is associated with lifestyle-related diseases. Therefore, a nurse-led lifestyle intervention including interpersonal relationships, health education and cognitive support was developed to facilitate healthier lifestyle habits. The aim was to develop a lifestyle intervention and investigate its impact on mental and physical health The 52-week intervention included 35 adults with ADHD.

On Time: A Qualitative Study of Swedish Students', Parents' and Teachers' Views on School Attendance, with a Focus on Tardiness.

Tardiness is a common problem in many schools. It can be understood as an individual risk for future problematic behavior leading to absenteeism, school dropout, exclusion and later health problems. Tardiness can also be examined in relation to a broader social-ecological perspective on health.

Interaction of Treponema pallidum, the syphilis spirochete, with human platelets.

Extracellular bacteria that spread via the vasculature employ invasive mechanisms that mirror those of metastatic tumor cells, including intravasation into the bloodstream and survival during hematogenous dissemination, arrestation despite blood flow, and extravasation into distant tissue sites. Several invasive bacteria have been shown to exploit normal platelet function during infection. Due to their inherent ability to interact with and influence other cell types, platelets play a critical role in alteration of endothelial barrier permeability, and their role in cancer metastasis has been well established.

Traffic safety behaviour among young people in different residential settings: the use of seat belts, bicycle helmets, and reflectors by young people in Sweden.

This study examines if, and how, the size of the community in which people live may contribute to explaining differences in traffic safety behaviour (self-reported behaviour regarding the use of seat belts, bicycle helmets and reflectors) among young people in Sweden. The study is based on a Swedish nationwide traffic safety survey with a net sample of 2854 respondents aged 16-25. Ordered logit regressions were performed, and place of residence is shown to have an impact on traffic safety behaviour.

Density of tumour stroma is correlated to outcome after adoptive transfer of CD4+ and CD8+ T cells in a murine mammary carcinoma model.

Adoptive immunotherapy shows promise for the treatment of cancer; however, partial or mixed responses remain common outcomes due to the heterogeneity of tumours. We studied three murine mammary tumour lines that express an ovalbumin-tagged version of HER-2/neu and reproducibly undergo complete regression (CR), partial regression (PR), or progressive disease (PD) after adoptive transfer of ovalbumin-specific CD8(+) (OT-I) and CD4(+) (OT-II) T cells. The three tumour lines were implanted in immunocompetent C57Bl/6 host mice, and established tumours were treated by adoptive transfer of naive OT-I and OT-II T cells.

Mammary tumors with diverse immunological phenotypes show differing sensitivity to adoptively transferred CD8+ T cells lacking the Cbl-b gene.

We tested the efficacy of CD8+ T cells lacking the Cbl-b gene against a panel of mammary tumor lines with different intrinsic sensitivities to T cells. Mice bearing established tumors expressing an ovalbumin-tagged version of HER-2/neu underwent adoptive transfer with Cbl-b-replete or -null CD8+ T cells from OT-I T cell receptor transgenic donor mice. In general, Cbl-b-null OT-I cells showed enhanced expansion, persistence, and capacity for tumor infiltration.

CD8+ T cells induce complete regression of advanced ovarian cancers by an interleukin (IL)-2/IL-15 dependent mechanism.

Purpose: In vitro studies suggest that ovarian cancer evades immune rejection by fostering an immunosuppressive environment within the peritoneum; however, the functional responses of ovarian cancer-specific T cells have not been directly investigated in vivo. Therefore, we developed a new murine model to enable tracking of tumor-specific CD8(+) T-cell responses to advanced ovarian tumors.

Experimental Design: The ovarian tumor cell line ID8 was transfected to stably express an epitope-tagged version of HER-2/neu (designated Neu(OT-I/OT-II)).

Spontaneous mammary tumors differ widely in their inherent sensitivity to adoptively transferred T cells.

Immunotherapy of cancer can lead to the selection of antigen loss variants, which provides strong rationale to target oncogenes that are essential for tumor growth or viability. To investigate this concept, we tagged the HER2/neu oncogene with epitopes from ovalbumin to confer recognition by T-cell receptor transgenic CD8(+) (OT-I) and CD4(+) (OT-II) T cells. Transgenic mice expressing neu(OT-I/OT-II) developed mammary adenocarcinomas at 6 to 10 months of age.

Detection and quantification of roundup ready soy in foods by conventional and real-time polymerase chain reaction.

Transgenic soybean line GTS-40-3-2, marketed under the trade name Roundup Ready (RR) soy, was developed by Monsanto (USA) to allow for the use of glyphosate, the active ingredient of the herbicide Roundup, as a weed control agent. RR soy was first approved in Canada for environmental release and for feed products in 1995 and later for food products in 1996 and is widely grown in Canada. Consumer concern issues have resulted in proposed labeling regulations in Canada for foods derived from genetically engineered crops.

Reliable detection and identification of genetically modified maize, soybean, and canola by multiplex PCR analysis.

Multiplex PCR procedures were developed for simultaneously detecting multiple target sequences in genetically modified (GM) soybean (Roundup Ready), maize (event 176, Bt11, Mon810, T14/25), and canola (GT73, HCN92/28, MS8/RF3, Oxy 235). Internal control targets (invertase gene in corn, lectin and beta-actin genes in soybean, and cruciferin gene in canola) were included as appropriate to assess the efficiency of all reactions, thereby eliminating any false negatives. Primer combinations that allowed the identification of specific lines were used.