Knowledge, perceptions, attitudes, and barriers pertaining to genetic literacy among surgeons: a scoping review.

Background: The rapid evolution of genetic technologies and utilization of genetic information for clinical decision-making has necessitated increased surgeon participation in genetic counselling, testing, and appropriate referral of patients for genetic services, without formal training in genetics. We performed a scoping review to describe surgeons' knowledge, perceptions, attitudes, and barriers pertaining to genetic literacy in the management of patients who had confirmed cancer or who were potentially genetically at risk.

Methods: We conducted a scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews checklist.

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.

Feasibility Study and Clinical Impact of Incorporating Breast Tissue Density in High-Risk Breast Cancer Screening Assessment.

Breast tissue density (BTD) is known to increase the risk of breast cancer but is not routinely used in the risk assessment of the population-based High-Risk Ontario Breast Screening Program (HROBSP). This prospective, IRB-approved study assessed the feasibility and impact of incorporating breast tissue density (BTD) into the risk assessment of women referred to HROBSP who were not genetic mutation carriers. All consecutive women aged 40-69 years who met criteria for HROBSP assessment and referred to Genetics from 1 December 2020 to 31 July 2021 had their lifetime risk calculated with and without BTD using Tyrer-Cuzick model version 8 (IBISv8) to gauge overall impact.

Bridging clinical care and research in Ontario, Canada: Maximizing diagnoses from reanalysis of clinical exome sequencing data.

We examined the utility of clinical and research processes in the reanalysis of publicly-funded clinical exome sequencing data in Ontario, Canada. In partnership with eight sites, we recruited 287 families with suspected rare genetic diseases tested between 2014 and 2020. Data from seven laboratories was reanalyzed with the referring clinicians.

The early embryonic transcriptome of a Hawaiian Drosophila picture-wing fly shows evidence of altered gene expression and novel gene evolution.

A massive adaptive radiation on the Hawaiian archipelago has produced approximately one-quarter of the fly species in the family Drosophilidae. The Hawaiian Drosophila clade has long been recognized as a model system for the study of both the ecology of island endemics and the evolution of developmental mechanisms, but relatively few genomic and transcriptomic datasets are available for this group. We present here a differential expression analysis of the transcriptional profiles of two highly conserved embryonic stages in the Hawaiian picture-wing fly Drosophila grimshawi.

Feasibility of Electronic Health Record Assessment of 6 Pediatric Type 1 Diabetes Self-management Habits and Their Association With Glycemic Outcomes.

Importance: A low-burden electronic health record (EHR) workflow has been devised to systematize the collection and validation of 6 key diabetes self-management habits: (1) checks glucose at least 4 times/day or uses continuous glucose monitor (CGM); (2) gives at least 3 rapid-acting insulin boluses per day; (3) uses insulin pump; (4) delivers boluses before meals; (5) reviewed glucose data since last clinic visit, and (6) has changed insulin doses since the last clinic visit.

Objective: To describe the performance of these habits and examine their association with hemoglobin A1c (HbA1c) levels and time in range (TIR).

Design, Setting, And Participants: This cross-sectional study included individuals with known type 1 diabetes who were seen in a US pediatric diabetes clinic in 2019.

The expression of P-gp in leukemia cells is associated with cross-resistance to protein N-glycosylation inhibitor tunicamycin.

In P-gp-positive cell variants obtained from L1210 cells either by selection with vincristine (L1210/R) or by transfection with the human gene encoding P-gp (L1210/T), we have previously described cross-resistance to tunicamycin (TNM), a protein N-glycosylation inhibitor. Here we studied whether this cross-resistance also underlies P-gp-positive variants of human acute myeloid leukemia cells (AML) derived from SKM-1 and MOLM-13 cells (SKM-1/VCR, SKM-1/LEN, MOLM-13/VCR) by selection with vincristine (VCR) and lenalidomide (LEN). While SKM-1/LEN cells were P-gp positive, no P-gp was detected in MOLM-13/LEN cells.

Molecular changes induced by repeated restraint stress in the heart: the effect of oxytocin receptor antagonist atosiban.

Even though stress belongs to the most common lifestyle risk factors of cardiovascular diseases, there are only limited data on direct influence of stressors on the heart. The aim of the present study was to explore selected protein signaling pathways in response to repeated immobilization stress in the heart tissue. Effects of simultaneous treatment with atosiban, an oxytocin receptor antagonist, on stress-induced changes in the heart were also investigated.

[Risk factors for infective endocarditis in cardiac valve prosthesis patients].

Infective endocarditis (IM) of the artificial cardiac valve (ACV) constitutes one of severe postoperative complications and presents a total spectrum and number of observations, concerning infectioning of the implanted ACV or of the adjacent tissues, which have had occurred in various time postoperatively. Wide introduction in practical cardiosurgery have caused the raising of the IM of ACV occurrence rate from 16 to 45%. Basing on analysis of data of 276 patients there were studied up the factors and conditions, predisposing to occurrence of IM in ACV.

Static dielectric constants and molecular dipole distributions of liquid water and ice-Ih investigated by the PAW-PBE exchange-correlation functional.

The static dielectric constants, ε(s), of ice-Ih and liquid water were calculated using density functional theory with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional and the projector-augmented-wave (PAW) approach. Proton disordered ice configurations and uncorrelated liquid configurations were sampled with the electrostatic switching method using force fields specially designed to facilitate the ab initio free energy perturbation calculations. Our results indicate that PAW-PBE underestimates the ε(s) of both ice-Ih and liquid water but predicts the ratio of ice and water ε(s) in good agreement with experimental measurements.

P-glycoprotein depresses cisplatin sensitivity in L1210 cells by inhibiting cisplatin-induced caspase-3 activation.

Multidrug resistance (MDR) is a phenomenon in which cells become resistant to cytostatic drugs and other substances with diverse chemical structures and cytotoxicity mechanisms. The most often observed molecular mechanism for MDR includes high levels of P-glycoprotein (P-gp)--an ABCB1 member of the ABC drug transporter family. Overexpression of P-gp in neoplastic tissue is an obstacle to chemotherapeutic treatment.

Structural basis of C-terminal β-amyloid peptide binding by the antibody ponezumab for the treatment of Alzheimer's disease.

Alzheimer's disease, the most common cause of dementia in the elderly and characterized by the deposition and accumulation of plaques, is composed in part of β-amyloid (Aβ) peptides, loss of neurons, and the accumulation of neurofibrillary tangles. Here, we describe ponezumab, a humanized monoclonal antibody, and show how it binds specifically to the carboxyl (C)-terminus of Aβ40. Ponezumab can label Aβ that is deposited in brain parenchyma found in sections from Alzheimer's disease casualties and in transgenic mouse models that overexpress Aβ.

Increased nuchal translucency thickness: a potential indicator for Ritscher-Schinzel syndrome.

Objective: The Ritscher-Schinzel syndrome (RSS), also known as the 3C syndrome, is an autosomal recessive disorder classically comprising craniofacial, cerebellar and cardiac defects. The underlying molecular etiology remains unknown; therefore, prenatal diagnosis of recurrences depends on identification of the associated structural anomalies on second trimester ultrasound examination. Identification of recurrences using first-trimester ultrasound has not been reported previously.

Stem cell research: cloning, therapy and scientific fraud.

Stem cell research has generated intense excitement, awareness, and debate. Events in the 2005-2006 saw the rise and fall of a South Korean scientist who had claimed to be the first to clone a human embryonic stem cell line. From celebration of the potential use of stem cells in the treatment of human disease to disciplinary action taken against the disgraced scientists, the drama has unfolded throughout the world media.

Structure of the ESCRT-II endosomal trafficking complex.

The multivesicular-body (MVB) pathway delivers transmembrane proteins and lipids to the lumen of the endosome. The multivesicular-body sorting pathway has crucial roles in growth-factor-receptor downregulation, developmental signalling, regulation of the immune response and the budding of certain enveloped viruses such as human immunodeficiency virus. Ubiquitination is a signal for sorting into the MVB pathway, which also requires the functions of three protein complexes, termed ESCRT-I, -II and -III (endosomal sorting complex required for transport).

NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway.

The target-derived neurotrophic factor "nerve growth factor" (NGF) signals through TrkA to promote the survival, differentiation, and maintenance of neurons. How the NGF signal in axon terminals is conveyed to the cell body is unknown. The "signaling endosome hypothesis" envisions that NGF-TrkA complexes are internalized at the axon terminal and retrogradely transported to the cell body.

Distinctive Swann blood group genotypes: molecular investigations.

Background And Objectives: Phenotypically, Sw(a+) erythrocytes have been classified as either 700:4,41 or 700:4,-41. Since anti-700.4, in particular, and sometimes anti-700.

Incorporation of fatty acids into phosphatidylcholine is reduced during storage of human erythrocytes: evidence for distinct lysophosphatidylcholine acyltransferases.

The incorporation of [1-14C]palmitic or [1-14C]oleic acid into phosphatidylcholine and the effect on blood group antigen expression were examined in human erythrocytes stored at 4 degrees C for 0-3 weeks. Blood drawn into EDTA was obtained by venepuncture from healthy volunteers. A 50% suspension of washed erythrocytes was incubated in buffer containing [1-14C]fatty acid for up to 60 min at 37 degrees C with moderate shaking.

Cardiolipin remodeling in a Chinese hamster lung fibroblast cell line deficient in oxidative energy production.

The metabolism of cardiolipin was investigated in a Chinese hamster lung fibroblast cell line CCL16-B2 deficient in oxidative energy metabolism and its parental cell line CCL16-B1. Mitochondrial enzyme activities involved in de novo cardiolipin biosynthesis were elevated in CCL16-B2 cells compared with CCL16-B1 cells, indicating initially an elevation in cardiolipin biosynthesis. Content of all phospholipids, including cardiolipin and its precursors, and high energy nucleotides were unaltered in CCL16-B2 cells compared to CCL16-B1 cells.

[The extracorporeal connection of a donor spleen in the treatment of anaerobic sepsis].

In 12 patients with anaerobic sepsis, extracorporeal connection of donor spleen, its sections and transfusion of perfusates of xenospleen were used in the complex treatment. A positive result--reduction of intoxication, improvement of general state, normalization of immunologic indices--has been obtained.

[Use of ultraviolet irradiation of the blood in the complex treatment of peritonitis].

According to the data of tetrasolium nitroblue test and titer of the blood serum antibodies to the most frequently cultured microflora in complex treatment of 27 patients with diffuse purulent peritonitis, it was established, that the use of ultraviolet irradiation of the blood stimulated the specific and non-specific organism resistance.