The psychosocial impact of prostate cancer screening for BRCA1 and BRCA2 carriers.

Objectives: To report the long-term outcomes from a longitudinal psychosocial study that forms part of the 'Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls' (IMPACT) study. The IMPACT study is a multi-national study of targeted prostate cancer (PrCa) screening in individuals with a known germline pathogenic variant (GPV) in either the BReast CAncer gene 1 (BRCA1) or the BReast CAncer gene 2 (BRCA2).

Subjects And Methods: Participants enrolled in the IMPACT study were invited to complete a psychosocial questionnaire prior to each annual screening visit for a minimum of 5 years.

Pharmacological management of fragile X syndrome: a systematic review and narrative summary of the current evidence.

Introduction: Fragile X syndrome (FXS) is the most common inherited cause of Intellectual Disability. There is a broad phenotype that includes deficits in cognition and behavioral changes, alongside physical characteristics. Phenotype depends upon the level of mutation in the (fragile X messenger ribonucleoprotein 1) gene.

Identification and characterisation of a rare variant underlying hereditary non-alcoholic fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a complex trait with an estimated prevalence of 25% globally. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation, and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes.

Methods: Exome sequencing and genome comparisons were used to identify the likely causal variant.

Indocyanin Green Fluorescence Evaluation of Colonic Perfusion During Elective Open Abdominal Aortic Aneurysm Repair.

Objectives: Colonic ischaemia is a rare but devastating complication of open aortic aneurysm repair and is associated with high morbidity and a mortality of up to 50%. The aim of this study was to determine the safety and effectiveness of using indocyanin green florescence (ICG) to interrogate colonic perfusion intra-operatively.

Design: Prospective observational study.

Iliofemoral Polytetrafluoroethylene Graft Interposition: A Rescue Procedure in External Iliac Artery Dissection to Restore Lower Limb Revascularization and Salvage Kidney Transplant.

External iliac artery dissection is a catastrophic complication during kidney transplant surgery. We present a technically challenging case of external iliac artery dissection that occurred in severely atherosclerotic vessels of a high-risk patient receiving his third kidney transplant. The intimal dissection constituted by the upstream application of a vascular clamp during the preparatory dissection ofthe vessels and progressed rapidly along the iliofemoral axis.

Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes.

Background: Breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility.

Patients And Methods: We included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer.

Patients' perception of personal protective equipment during the SARS-Cov-2 pandemic.

Background: Since the outbreak of the coronavirus (SARS-Cov-2), wearing personal protective equipment (PPE) has become necessary. Patients' ability to recognize staff is disrupted impacting on the relationship between healthcare worker and patient.

Objective: Assess the patients' perspective of healthcare workers wearing PPE and its effect on communication.

Identification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspective.

The aim of this study was to assess the prevalence of germline variants in cancer-predisposing genes by either targeted (BRCA1/2) or multigene NGS panel in a high-risk Hereditary Breast and Ovarian Cancer (HBOC) cohort. Samples from 824 Caucasian probands were retrospectively collected and the impact of genetic diagnosis and genetic variants epidemiology in this cohort was evaluated. Performance of risk-reducing prophylactic measures, such as prophylactic mastectomy and/or prophylactic oophorectomy, was assessed through clinical follow-up of patients with a positive genetic result.

Evaluation of tumour surveillance protocols and outcomes in von Hippel-Lindau disease in a national health service.

Background: Von Hippel-Lindau (VHL) disease is an inherited tumour predisposition syndrome and a paradigm for the importance of early diagnosis and surveillance. However, there is limited information on the "real world" management of VHL disease.

Methods: A national audit of VHL disease in the United Kingdom.

Mutations in the ribosome biogenesis factor gene LTV1 are linked to LIPHAK syndrome, a novel poikiloderma-like disorder.

In the framework of the UK 100 000 Genomes Project, we investigated the genetic origin of a previously undescribed recessive dermatological condition, which we named LIPHAK (LTV1-associated Inflammatory Poikiloderma with Hair abnormalities and Acral Keratoses), in four affected individuals from two UK families of Pakistani and Indian origins, respectively. Our analysis showed that only one gene, LTV1, carried rare biallelic variants that were shared in all affected individuals, and specifically they bore the NM_032860.5:c.

Extended Cohort for E-health, Environment and DNA (EXCEED) COVID-19 focus.

New data collection in established longitudinal population studies provides an opportunity for studying the risk factors and sequelae of the novel coronavirus disease 2019 (COVID-19), plus the indirect impacts of the COVID-19 pandemic on wellbeing. The Extended Cohort for E-health, Environment and DNA (EXCEED) cohort is a population-based cohort (N>11,000), recruited from 2013 in Leicester, Leicestershire and Rutland. EXCEED includes consent for electronic healthcare record (EHR) linkage, spirometry, genomic data, and questionnaire data.

Assessing BRCA1 activity in DNA damage repair using human induced pluripotent stem cells as an approach to assist classification of BRCA1 variants of uncertain significance.

Establishing a universally applicable protocol to assess the impact of BRCA1 variants of uncertain significance (VUS) expression is a problem which has yet to be resolved despite major progresses have been made. The numerous difficulties which must be overcome include the choices of cellular models and functional assays. We hypothesised that the use of induced pluripotent stem (iPS) cells might facilitate the standardisation of protocols for classification, and could better model the disease process.

An interprofessional activity involving pharmacy and physician assistant students aimed at reinforcing the patient care process.

Background: Pharmacy students should have the opportunity to practice applying the Pharmacists' Patient Care Process (PPCP) in an interprofessional environment. The purpose of this study was to compare the change in students' confidence in their ability to complete the five steps of the PPCP before and after participation in an interprofessional activity involving physician assistant (PA) students.

Interprofessional Education Activity: Second-year pharmacy students and second-year PA students completed an activity in teams of six (four pharmacy and two PA students per team) in which they applied the PPCP to a patient case to create a plan of care.

Sexual Motivation and Sexual Reward in Male Rats are Attenuated by the Gonadotropin-Releasing Hormone Receptor Antagonist Degarelix.

Background: Preclinical studies that have examined the effects of androgen deprivation therapies (ADTs) on sexual outcomes have either relied on a surgical castration model of ADTs or have largely focused on consummatory sexual behaviors.

Aim: The aim of this study was to examine the effects of a single administration of the gonadotropin-releasing hormone receptor antagonist, degarelix, on sexual incentive motivation (SIM), sexual reward, consummatory sexual behaviors, anxiety-like behavior, and androgen receptor signaling in male rats, and to determine if sexual stimulation attenuates the effects of degarelix on SIM.

Methods: Male rats were treated with degarelix, or vehicle, and half of the rats in each condition were briefly exposed to a sexually receptive female immediately before SIM trials (experiment 1).

Telomere Instability in Lynch Syndrome Families Leads to Some Shorter Telomeres in Carriers.

Lynch syndrome (LS) is an inherited predisposition to early onset of various cancers, caused by mutation in a DNA mismatch repair (MMR) gene. In heterozygous MMR carriers, somatic mutation, loss or silencing of the wild type allele increases the mutation rate, facilitating the initiation of MMR-defective cancers. These cancers are characterized by instability at short tandem repeats (STRs) and in telomeric DNA.

Report of a Delphi exercise to inform the design of a research programme on screening for thoracic aortic disease.

Objectives: To inform the design of a clinical trial of a targeted screening programme for relatives of individuals affected by thoracic aortic disease, we performed a consensus exercise as to the acceptability of screening, the optimal sequence and choice of tests, long-term patient management, and choice of trial design.

Methods: Working with the Aortic Dissection Awareness UK & Ireland patient association, we performed a Delphi exercise with clinical experts, patients, and carers, consisting of three rounds of consultation followed by a final multi-stakeholder face-to-face workshop.

Results: Thirty-five experts and 84 members of the public took part in the surveys, with 164 patients and clinicians attending the final workshop.

Prostate Cancer Risk by BRCA2 Genomic Regions.

A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3') wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a prospective cohort study of 447 male BRCA2 PV carriers recruited in the UK and Ireland from 1998 to 2016, we estimated standardised incidence ratios (SIRs) compared with population incidences and assessed variation in risk by PV location.