Genes in the Ureteric Budding Pathway: Association Study on Vesico-Ureteral Reflux Patients

Vesico-ureteral reflux (VUR) is the retrograde passage of urine from the bladder to the urinary tract and causes 8.5% of end-stage renal disease in children. It is a complex genetic developmental disorder, in which ectopic embryonal ureteric budding is implicated in the pathogenesis. VUR is part of the spectrum of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). We performed an extensive association study for primary VUR using a two-stage, case-control design, investigating 44 candidate genes in the ureteric budding pathway in 409 Dutch VUR patients. The 44 genes were selected from the literature and a set of 567 single nucleotide polymorphisms (SNPs) capturing their genetic variation was genotyped in 207 cases and 554 controls. The 14 SNPs with p<0.005 were included in a follow-up study in 202 cases and 892 controls. Of the total cohort, ∼50% showed a clear-cut primary VUR phenotype and ∼25% had both a duplex collecting system and VUR. We also looked for association in these two extreme phenotype groups. None of the SNPs reached a significant p-value. Common genetic variants in four genes (GREM1, EYA1, ROBO2 and UPK3A) show a trend towards association with the development of primary VUR (GREM1, EYA1, ROBO2) or duplex collecting system (EYA1 and UPK3A). SNPs in three genes (TGFB1, GNB3 and VEGFA) have been shown to be associated with VUR in other populations. Only the result of rs1800469 in TGFB1 hinted at association in our study. This is the first extensive study of common variants in the genes of the ureteric budding pathway and the genetic susceptibility to primary VUR

GPs' perspectives of type 2 diabetes patients' adherence to treatment: A qualitative analysis of barriers and solutions

BACKGROUND: The problem of poor compliance/adherence to prescribed treatments is very complex. Health professionals are rarely being asked how they handle the patient's (poor) therapy compliance/adherence. In this study, we examine explicitly the physicians' expectations of their diabetes patients' compliance/adherence. The objectives of our study were: (1) to elicit problems physicians encounter with type 2 diabetes patients' adherence to treatment recommendations; (2) to search for solutions and (3) to discover escape mechanisms in case of frustration. METHODS: In a descriptive qualitative study, we explored the thoughts and feelings of general practitioners (GPs) on patients' compliance/adherence. Forty interested GPs could be recruited for focus group participation. Five open ended questions were derived on the one hand from a similar qualitative study on compliance/adherence in patients living with type 2 diabetes and on the other hand from the results of a comprehensive review of recent literature on compliance/adherence. A well-trained diabetes nurse guided the GPs through the focus group sessions while an observer was attentive for non-verbal communication and interactions between participants. All focus groups were audio taped and transcribed for content analysis. Two researchers independently performed the initial coding. A first draft with results was sent to all participants for agreement on content and comprehensiveness. RESULTS: General practitioners experience problems with the patient's deficient knowledge and the fact they minimize the consequences of having and living with diabetes. It appears that great confidence in modern medical science does not stimulate many changes in life style. Doctors tend to be frustrated because their patients do not achieve the common Evidence Based Medicine (EBM) objectives, i.e. on health behavior and metabolic control. Relevant solutions, derived from qualitative studies, for better compliance/adherence seem to be communication, tailored and shared care. GPs felt that a structured consultation and follow-up in a multidisciplinary team might help to increase compliance/adherence. It was recognized that the GP's efforts do not always meet the patients' health expectations. This initiates GPs' frustration and leads to a paternalistic attitude, which may induce anxiety in the patient. GPs often assume that the best methods to increase compliance/adherence are shocking the patients, putting pressure on them and threatening to refer them to hospital. CONCLUSION: GPs identified a number of problems with compliance/adherence and suggested solutions to improve it. GPs need communication skills to cope with patients' expectations and evidence based goals in a tailored approach to diabetes care

Effect of Part-time Practice on Patient Outcomes

Primary care physicians are spending fewer hours in direct patient care, yet it is not known whether reduced hours are associated with differences in patient outcomes. OBJECTIVE: To determine whether patient outcomes vary with physicians' clinic hours. DESIGN: Cross-sectional retrospective design assessing primary care practices in 1998. SETTING: All 25 outpatient-clinics of a single medical group in western Washington. PARTICIPANTS: One hundred ninety-four family practitioners and general internists, 80% of whom were part-time, who provided ambulatory primary care services to specified HMO patient panels. Physician appointment hours ranged from 10 to 35 per week (30% to 100% of full time). MEASUREMENTS: Twenty-three measures of individual primary care physician performance collected in an administrative database were aggregated into 4 outcome measures: cancer screening, diabetic management, patient satisfaction, and ambulatory costs. Multivariate regression on each of the 4 outcomes controlled for characteristics of physicians (administrative role, gender, seniority) and patient panels (size, case mix, age, gender). MAIN RESULTS: While the effects were small, part-time physicians had significantly higher rates for cancer screening (4% higher, P = .001), diabetic management (3% higher, P = .033), and for patient satisfaction (3% higher, P = .035). After controlling for potential confounders, there was no significant association with patient satisfaction ( P = .212) or ambulatory costs ( P = .323). CONCLUSIONS: Primary care physicians working fewer clinical hours were associated with higher quality performance than were physicians working longer hours, but with patient satisfaction and ambulatory costs similar to those of physicians working longer hours. The trend toward part-time clinical practice by primary care physicians may occur without harm to patient outcomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73810/1/j.1525-1497.2003.20401.x.pd

DNA methylation-based classification of central nervous system tumours

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challengingwith substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

The evolution of living beings started with prokaryotes and in interaction with prokaryotes

In natural world, no organism exists in absolute isolation, and thus every organism must interact with the environment and other organisms. Next-generation sequencing technologies are increasingly revealing that most of the cells in the environment resist cultivation in the laboratory and several prokaryotic divisions have no known cultivated representatives. Based on this, we hypothesize that species that live together in the same ecosystem are more or less dependent upon each other and are very large in diversity and number, outnumbering those that can be isolated in single-strain laboratory culture. In natural environments, bacteria and archaea interact with other organisms (viruses, protists, fungi, animals, plants, and human) in complex ecological networks, resulting in positive, negative, or no effect on one or another of the interacting partners. These interactions are sources of ecological forces such as competitive exclusion, niche partitioning, ecological adaptation, or horizontal gene transfers, which shape the biological evolution. In this chapter, we review the biological interactions involving prokaryotes in natural ecosystems, including plant, animal, and human microbiota, and give an overview of the insights into the evolution of living beings. We conclude that studies of biological interactions, including multipartite interactions, are sources of novel knowledge related to the biodiversity of living things, the functioning of ecosystems, the evolution of the cellular world, and the ecosystem services to the living beings