Dominant ARL3-related retinitis pigmentosa

Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys).

Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure.

Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3.

Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa.     

The use of formal and informal knowledge sources in patients’ treatment decisions in secondary stroke prevention: qualitative study

Background There is robust empirical evidence to support clinical decision making in secondary stroke prevention after transient ischaemic attack (TIA) or recovered stroke. However, little attention has been paid to patients’ utilization of this evidence in coming to decisions about their treatment choices. Objective To examine the use of formal and informal knowledge by patients in making decisions about carotid endarterectomy (CEA) and medical treatment after TIA/recovered stroke. Setting and participants Twenty participants were recruited from an outpatient vascular surgical assessment clinic in England. Ten were receiving medical treatment alone, and 10 were undergoing CEA after TIA or recovered stroke. Method Twenty‐eight in‐depth qualitative interviews were conducted. An iterative approach was used whereby emergent themes were further explored in later interviews. Interviews were audiotaped, transcribed and coded. Results Participants gathered and utilized several types of knowledge in the process of making treatment decisions: Empirical knowledge (e.g. clinical trial findings); Pathophysiologic findings (e.g. results of clinical investigations); Experiential knowledge (e.g. personal experience of stroke); Goals and values (e.g. potential impact on family); System features (e.g. apparent urgency of treatment). Conclusions In addition to formal evidence, patients use other sources of informal or ‘non‐evidentiary’ knowledge to support their decisions about treatment after TIA or recovered stroke. To enable evidence‐based patient choice, health professionals need to appreciate the diverse types of evidence which patients use, to help them to access relevant and high‐quality evidence, to balance evidence from different sources and to make choices which are congruent with their values and expectations.     

Comparing midwife-led and doctor-led maternity care: a systematic review of reviews

sutcliffe k., caird j., kavanagh j., rees r., oliver k., dickson k., woodman j., barnett-paIge e. & thomas j. (2012)?Comparing midwife-led and doctor-led maternity care: a systematic review of reviews. Journal of Advanced Nursing68(11), 2376-2386. ABSTRACT: Aims. A report of a systematic review of reviews which examines the impact of having midwives-led maternity care for low-risk women, rather than physicians. Background. A rising birth rate, increasing complexity of births, and economic constraints pose difficulties for maternity services in the UK. Evidence about the most effective, cost-effective, and efficient ways to give maternity services is needed. Data sources. Searches were carried out in August-September 2009 of ten electronic databases, 16 key nursing and research websites, and reference lists of 56 relevant reviews. We also contacted 38 experts for information. No date restrictions were employed. Review methods. A narrative review of systematic reviews or 'meta review' was conducted using transparent and systematic procedures to limit bias at all stages. Systematic reviews that compared midwife-led care during pregnancy and birth with physician-led care were eligible for inclusion. Results. Three meta-analytic reviews were included. Midwife-led care for low-risk women was found to be better for a range of maternal outcomes, reduced the number of procedures in labour, and increased satisfaction with care. For some maternal, foetal, and neonatal outcomes reviews found no evidence that care led by midwives is different to that led by physicians. No adverse outcomes associated with midwife-led care were identified. Conclusions. For low-risk women, health and other benefits can result from having their maternity care led by midwives rather than physicians. Moreover, there appear to be no negative impacts on mothers and infants receiving midwife-led care.     

Too Much Sitting and Cardio-Metabolic Risk: An Update of Epidemiological Evidence

Sedentary behavior, as distinct from a lack of moderate-to-vigorous physical activity, is an emerging health risk behavior for the development of chronic diseases. Examples of sedentary behavior include sitting, watching television, using a computer, and driving a car. In this article, we define sedentary behavior; outline key concepts related to the physiology of sedentary behavior, review the recent evidence on the effects of prolonged sedentary behavior (or sitting) on the risk of cardio-metabolic disease and all cause mortality, and discuss the implications for current clinical practice. We found that most large scale studies on sedentary behavior were published in the last 5 years. There is moderately consistent evidence for an association between total sitting time and all-cause mortality, even when adjusted for or stratified by leisure time physical activity. Overall, we identified a compelling case for sitting reduction to be included in clinical preventive advice as a key component of ‘active living,’ where adults and children are encouraged to ‘move more and sit less’ across different settings and locations throughout the day.     

Minding the gap: health and social care provider perceptions of parental communication and Black-Canadian youths’ sexual health

Abstract

Health and social care providers’ perceptions of Black-Canadian parent-youth sexual health communication has important implications for addressing knowledge gaps in the provision of services to young people and their parents. Providers’ perceptions are crucial as they often act as advisers in tailoring programmes or services to the perceived needs of parents and youth. To understand these perceptions, 17 semi-structured in-depth interviews were conducted with providers who worked with African, Caribbean or Black (ACB) parents and youth in Toronto, Ontario, Canada. Critical Race Theory was used to help guide the interpretation of findings. The findings revealed providers believed that many parents were unlikely to explicitly discuss sexual health or HIV prevention with young people. Additionally, providers perceived that the content of and approach to parent-youth sexual health communication differed between African and Caribbean clients. Moreover, providers believed that both parents’ and young people’s sex and gender impacted the quality, content and style of sexual health communication and had important implications for programme development. Overall, findings suggest a need for understanding the development of providers’ perceptions of this communication, ways to address these perceptions and further parent-provider collaboration to promote Black youths’ sexual health.     

No difference in clinical progression between patients infected with the predominant human immunodeficiency virus type 1 circulating recombinant form (CRF) 02_AG strain and patients not infected with CRF02_AG,in Western and West-Central Africa: a four-year prospective multicenter study

To compare human immunodeficiency virus (HIV) type 1 disease progression in patients infected by the predominant strain circulating recombinant form (CRF) 02_AG in western and west-central Africa and in patients infected by other strains, a prospective multicenter cohort study was conducted in Cameroon and Senegal. Among the 335 patients, a broad HIV-1 group M subtype diversity was observed in the envelope V3-V5 region, but strain CRF02_AG predominated in both Cameroon and Senegal (61.2% and 62.9%, respectively; P<.8). Multivariate analyses showed no difference between patients infected by CRF02 strains and those infected by other strains in terms of survival (adjusted hazards ratio [HR], 1.16; 95% confidence interval [CI], 0.76-1.78; P=.5), clinical disease progression (HR, 0.79; 95% CI, 0.50-1.25; P=.3), or square root CD4 cell decline (regression coefficient, -0.01; 95% CI, -0.82 to 0.81; P=.9). This study suggests that the predominance of HIV-1 CRF02_AG strain in western and west-central Africa should have no major clinical consequences.     

Malaria-associated cytokine changes in the placenta of women with pre-term deliveries in Yaounde, Cameroon

The prevalence of pre-term deliveries (PTDs) is increased in women who become infected with Plasmodium falciparum during pregnancy. Because prematurity is a risk factor for newborns, it is important to identify conditions that contribute to malaria-associated PTDs. Plasmodium falciparum-infected erythrocytes sequester in the placenta and attract activated mononuclear cells that secrete pro-inflammatory cytokines. Increased inflammatory cytokine levels in other microbial infections are associated with PTDs. To determine if such is the case in women with placental malaria, concentrations of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), and IL-10 were measured in placental plasma of 391 malaria-infected and -uninfected Cameroonian women with premature and full-term deliveries. Risk factors for malaria-associated PTDs included peripheral and placental parasitemias greater than 1%, maternal anemia, elevated IL-10 levels, and low TNF-alpha:IL-10 ratios due to over-expression of IL-10. Alterations in cytokine levels may contribute to PTDs through the induction of anemia and/or altering cellular immune responses required for eliminating placental parasites.