Homologous recombination deficiency scar: mutations and beyond—implications for precision oncology

Homologous recombination deficiency (HRD) is a prevalent in approximately 17% of tumors and is associated with enhanced sensitivity to anticancer therapies inducing double-strand DNA breaks. Accurate detection of HRD would therefore allow improved patient selection and outcome of conventional and targeted anticancer therapies. However, current clinical assessment of HRD mainly relies on determining germline BRCA1/2 mutational status and is insufficient for adequate patient stratification as mechanisms of HRD occurrence extend beyond functional BRCA1/2 loss. HRD, regardless of BRCA1/2 status, is associated with specific forms of genomic and mutational signatures termed HRD scar. Detection of this HRD scar might therefore be a more reliable biomarker for HRD. This review discusses and compares different methods of assessing HRD and HRD scar, their advances into the clinic, and their potential implications for precision oncology

Workplace experience of radiographers: impact of structural and interpersonal interventions

PURPOSE: Within the framework of organisational development, an assessment of the workplace experience of radiographers (RGs) was conducted. The aims of this study were to develop structural and interpersonal interventions and to prove their effectiveness and feasibility. METHODS: A questionnaire consisting of work-related factors, e.g. time management and communication, and two validated instruments (Workplace Analysis Questionnaire, Effort-Reward Imbalance Scale) was distributed to all RGs (n = 33) at baseline (T1). Interventions were implemented and a follow-up survey (T2) was performed 18 months after the initial assessment. RESULTS: At T1, areas with highest dissatisfaction were communication and time management for ambulant patients (bad/very bad, 57% each). The interventions addressed adaptation of work plans, coaching in developing interpersonal and team leadership skills, and regular team meetings. The follow-up survey (T2) showed significantly improved communication and cooperation within the team and improved qualification opportunities, whereas no significant changes could be identified in time management and in the workplace-related scales 'effort' expended at work and 'reward' received in return for the effort. CONCLUSION: Motivating workplace experience is important for high-level service quality and for attracting well-qualified radiographers to work at a place and to stay in the team for a longer period

Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics

Item does not contain fulltextBACKGROUND: Mutations in complement factor H (CFH), factor I (CFI), factor B (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and autoantibodies against factor H (alphaFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (CFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS). METHODS: Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome. RESULTS: In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xalphaFH, of which five had CFHR1/3); four patients carried combined genetic defects or a mutation, together with alphaFH. In the majority (87%), disease onset was preceeded by a triggering event; in 25% of cases diarrhea was the presenting symptom. More than 50% had normal serum C3 levels at presentation. Relapses were seen in half of the patients, and there was renal graft failure in all except one case following transplant. CONCLUSIONS: Performing adequate DNA analysis is essential for treatment and positive outcome in children with aHUS. The impact of intensive initial therapy and renal replacement therapy, as well as the high risk of recurrence of aHUS in renal transplant, warrants further understanding of the pathogenesis, which will lead to better treatment options.01 augustus 201

Disparities in dialysis treatment and outcomes for Dutch and Belgian children with immigrant parents

BACKGROUND: In Belgium and the Netherlands, up to 40% of the children on dialysis are children with immigrant parents of non-Western European origin (non-Western). Concerns exist regarding whether these non-Western patients receive the same quality of care as children with parents of Western European origin (Western). We compared initial dialysis, post-initial treatment, and outcomes between non-Western and Western patients on dialysis. METHODS: All children <19 years old on chronic dialysis in the Netherlands and Belgium between September 2007 and May 2011 were included in the study. Non-Western patients were defined as children of whom one or both parents were born in non-Western countries. RESULTS: Seventy-nine of the 179 included patients (44%) were non-Western children. Compared to Western patients, non-Western patients more often were treated with hemodialysis (HD) instead of peritoneal dialysis (PD) as first dialysis mode (52 vs. 37%, p = 0.046). Before renal transplantation, non-Western patients were on dialysis for a median (range) of 30 (5-99) months, vs. 15 (0-66) months in Western patients (p = 0.007). Renal osteodystrophy was diagnosed in 34% of non-Western vs. 18% of Western patients (p = 0.028). The incidence rate ratio [95% confidence interval] for acute peritonitis was 2.44 [1.43-4.17] (p = 0.032) for non-Western compared to Western patients. CONCLUSIONS: There are important disparities between children on chronic dialysis with parents from Western European origin and those from non-Western European origin in the choice of modality, duration, and outcomes of dialysis therapy

Elevated Non-Esterified Fatty Acid Concentrations during Bovine Oocyte Maturation Compromise Early Embryo Physiology

Elevated concentrations of serum non-esterified fatty acids (NEFA), associated with maternal disorders such as obesity and type II diabetes, alter the ovarian follicular micro-environment and have been associated with subfertility arising from reduced oocyte developmental competence. We have asked whether elevated NEFA concentrations during oocyte maturation affect the development and physiology of zygotes formed from such oocytes, using the cow as a model. The zygotes were grown to blastocysts, which were evaluated for their quality in terms of cell number, apoptosis, expression of key genes, amino acid turnover and oxidative metabolism. Oocyte maturation under elevated NEFA concentrations resulted in blastocysts with significantly lower cell number, increased apoptotic cell ratio and altered mRNA abundance of DNMT3A, IGF2R and SLC2A1. In addition, the blastocysts displayed reduced oxygen, pyruvate and glucose consumption, up-regulated lactate consumption and higher amino acid metabolism. These data indicate that exposure of maturing oocytes to elevated NEFA concentrations has a negative impact on fertility not only through a reduction in oocyte developmental capacity but through compromised early embryo quality, viability and metabolism

Health-care and home-care utilization among frail elderly persons in Belgium

BACKGROUND: The patterns of health- and home-care utilization among Belgian frail elderly persons living at home with varying socio-economic status are currently unknown. METHODS: In this cross-sectional study based on a representative sample of 4777 elderly participants (&gt;/=65 years) in the Belgian Health Interview Survey the prevalence of frailty, as determined by items referring to the Fried phenotype, was estimated according to age, gender, comorbidity, place of residence, survey year, living situation and socio-economic status. Differing health-care utilization [contacts with a general practitioner (GP), specialist and emergency department; and hospital admission) and home-care utilization (home nursing, home help and meals-on-wheels] patterns among the frail, prefrail and robust subpopulations were examined. RESULTS: Overall, 9.3% respondents (426) were classified as frail, 30.7% (1636) as prefrail and 60.0% (2715) as robust. Frailty was associated with age, gender, comorbidity, region, survey year and socio-economic status. The frail and prefrail groups were more likely than the robust to contact a GP, a specialist or an emergency department and were more likely to be admitted to hospital, independent of age, gender, comorbidity, survey year, living situation, region and socio-economic status. They were also more likely to appeal to home nursing, home help and meals-on-wheels than the robust participants. CONCLUSION: Even after adjustment for potential confounders, including age, gender and comorbidity, frailty among Belgian elderly persons is associated with their socio-economic status and is strongly associated with their health- and home-care utilization</p

Pharmacokinetics of Oral Rebaudioside A in Patients with Type 2 Diabetes Mellitus and Its Effects on Glucose Homeostasis: A Placebo-Controlled Crossover Trial

Background and&nbsp;Objectives Rebaudioside A, a steviol glycoside, is deglycosylated by intestinal microflora prior to the absorption of steviol and conjugation to steviol glucuronide. While glucose-lowering properties are observed for rebaudioside A in mice, they have been attributed to the metabolites steviol and steviol glucuronide. We aimed to characterize the pharmacokinetic and pharmacodynamic properties of rebaudioside A and its metabolites in patients with early-onset type 2 diabetes mellitus (T2DM). Methods This randomized, placebo-controlled, open-label, two-way crossover trial was performed in subjects with T2DM on metformin or no therapy at the University Hospitals Leuven, Belgium. Following oral rebaudioside A (3 g), plasma concentrations of rebaudioside A, steviol and steviol glucuronide were determined. The effect on glucose homeostasis was examined by an oral glucose tolerance test (OGTT) performed 19 h following rebaudioside A administration, i.e. the presumed time of maximal steviol and steviol glucuronide concentrations. The primary pharmacodynamic endpoint was the difference in area under the blood glucose concentration–time curve during the first 2 h of the OGTT (AUCGlucose(0–2h)) for rebaudioside A vs.&nbsp;placebo. Results In total, 30 subjects [63.5 (57.8–69.0) years&nbsp;of age, 86.7% male] completed the trial. Rebaudioside A was detected as early as 1 h after administration in nearly all subjects. As expected, steviol and steviol glucuronide reached their maximal concentrations at 19.5 h following rebaudioside A administration. Rebaudioside A did not lower the AUCGlucose(0–2h)&nbsp;compared to placebo (−&nbsp;0.7 (95% CI −&nbsp;22.3; 20.9) h·mg/dL,&nbsp;P&nbsp;= 0.95). Insulin and C-peptide concentrations were also comparable between both conditions (P&nbsp;&gt;&nbsp;0.05). Conclusion Rebaudioside A is readily absorbed after oral administration and metabolized to steviol and steviol glucuronide. However, no effect on glucose nor insulin or C-peptide excursion was observed during the OGTT at the time of maximal metabolite concentrations. Thus, no antidiabetic properties of rebaudioside A could be observed in patients with T2DM after single oral&nbsp;use.</p

Condições de iluminação em ambiente de escritório : influência no conforto visual

Mestrado em Ergonomia na Segurança no TrabalhoCom o aumento da população laboral na actividade de escritório surge a necessidade de adequar estes espaços ao homem de forma a tornar o ambiente de trabalho motivante, e a melhorar o desempenho laboral. A adequada iluminação do posto de trabalho é um importante factor que contribui directamente para a segurança, saúde, bem-estar e conforto do trabalhador. As condições de iluminação condicionam a percepção do trabalhador face ao conforto visual, que se traduz em fadiga visual, stress e esforço físico. Este estudo pretendeu identificar condições anómalas e avaliar as condições de iluminação que influenciam o conforto visual dos trabalhadores em ambientes de escritório. A amostra do estudo é constituída por 143 indivíduos do sector administrativo, de 3 empresas. Os instrumentos usados para recolha de informação foram questionário, checklist, luxímetro e máquina fotográfica. Para tratar os dados foi usado o SPSS, versão 18. Efectuou-se análise descritiva, análise de inferência estatística sendo aplicados os testes de Kruskal-Wallis e de comparações múltiplas. Para a medição da iluminância e a uniformidade foram seguidas as normas europeias EN 12464 (2002), DIN 5035 (1990) e ISO 8995 (2002). Os resultados do estudo revelam desconforto visual (fadiga visual, irritabilidade ocular, dores de cabeça, dores musculares, dificuldade de concentração e de SVC) relacionado com o tempo de trabalho em computador sem pausas, com valores de iluminância inferiores aos valores recomendados e com a existência de brilhos e reflexos.With increasing population in the labor office activity comes the need to adapt these workplaces to man in order to make the work environment motivating, and improve task performance. Adequate lighting of the workplace is an important factor that directly contributes to the health, well-being and worker comfort. The lighting conditions affect the perception of the worker towards visual comfort, which results in eyestrain, stress and physical exertion. This study aims to identify anomalous conditions and evaluate the lighting conditions that influence the visual comfort of workers in office environments. The study sample is composed of 143 individuals from three companies, of the administrative sector. The data collection instruments were a questionnaire, a checklist, a light meter and a camera. To process the data SPSS software, version 18 was used. A descriptive analysis and a statistical inference analysis were carried and Kruskal-Wallis tests and multiple comparisons tests were applied. For measuring the illuminance and uniformity European standards EN 12464 (2002), DIN 5035 (1990) and ISO 8995 (2002) were followed. The study results revealed visual discomfort (eyestrain, irritated eyes, headaches, muscle aches and Computer Visual Syndrome) related to working time with computer without breaks, with illuminance below the recommended values and with the existence of glare and reflections

Clinical outcomes of DCD type V liver transplantation: donation after euthanasia

Introduction: Due to shortage of donor organs, physicians and surgeons are forced to accept livers from donation after circulatory death (DCD) donors. One special group of DCD organs are those obtained after euthanasia (DCD type V). To create more awareness on the possibility of organ donation after euthanasia, it is important to evaluate the results of transplantation with this type of graft. The aim of our study was to evaluate the outcome of DCD type V liver transplantation (LT) in the Netherlands and Belgium. Methods: All DCD type V LT performed until 2018 in all three Dutch LT centers and four out of six Belgian LT centers, were included in this study. Grafts that have been preserved with machine perfusion were excluded. Continuous data are expressed as median (IQR), categorical data as number (percentage). Results: Until 2018, 44 DCD type V LT have been performed. Five cases in which the liver was preserved by machine perfusion were excluded. Median age of donor and recipient was 51 years (42–58) and 56 years (48–64), respectively. A neurological disease was the most common underlying disease in donors requesting euthanasia, followed by psychiatric disorders. Median time between administration of the euthanatics and cold perfusion was 19 min (14–25). Peak AST and ALT levels in the recipients were 904 U/l (586–2,478) and 709 U/l (448– 1,841) respectively. One-, three- and five-year patient survival was 90%, 83% and 83%, respectively (figure 1). Five patients (13%) required a retransplantation, due to PNF (n = 1), HAT (n = 1) or post-transplant cholangiopathy (n = 3), the majority within the first year after the prior LT. Conclusion: Liver transplantations with grafts from donors who underwent euthanasia yield satisfying results during the relatively short follow up period that is currently available. Comparison of these results with DCD type III LT and donation after brain death (DBD) LT is currently ongoing