Explaining the uptake of paediatric guidelines in a Kenyan tertiary hospital--mixed methods research.

BACKGROUND: Evidence-based standards for management of the seriously sick child have existed for decades, yet their translation in clinical practice is a challenge. The context and organization of institutions are known determinants of successful translation, however, research using adequate methodologies to explain the dynamic nature of these determinants in the quality-of-care improvement process is rarely performed. METHODS: We conducted mixed methods research in a tertiary hospital in a low-income country to explore the uptake of locally adapted paediatric guidelines. The quantitative component was an uncontrolled before and after intervention study that included an exploration of the intervention dose-effect relationship. The qualitative component was an ethnographic research based on the theoretical perspective of participatory action research. Interpretive integration was employed to derive meta-inferences that provided a more complete picture of the overall study results that reflect the complexity and the multifaceted ontology of the phenomenon studied. RESULTS: The improvement in health workers' performance in relation to the intensity of the intervention was not linear and was characterized by improved and occasionally declining performance. Possible root causes of this performance variability included challenges in keeping knowledge and clinical skills updated, inadequate commitment of the staff to continued improvement, limited exposure to positive professional role models, poor teamwork, failure to maintain professional integrity and mal-adaptation to institutional pressures. CONCLUSION: Implementation of best-practices is a complex process that is largely unpredictable, attributed to the complexity of contextual factors operating predominantly at professional and organizational levels. There is no simple solution to implementation of best-practices. Tackling root causes of inadequate knowledge translation in this tertiary care setting will require long-term planning, with emphasis on promotion of professional ethics and values and establishing an organizational framework that enhances positive aspects of professionalism. This study has significant implications for the quality of training in medical institutions and the development of hospital leadership

Five Glutathione S-Transferase Gene Variants in 23,452 Cases of Lung Cancer and 30,397 Controls: Meta-Analysis of 130 Studies

BACKGROUND: Glutathione S-transferases (GSTs) are known to abolish or reduce the activities of intracellular enzymes that help detoxify environmental carcinogens, such as those found in tobacco smoke. It has been suggested that polymorphisms in the GST genes are risk factors for lung cancer, but a large number of studies have reported apparently conflicting results. METHODS AND FINDINGS: Literature-based meta-analysis was supplemented by tabular data from investigators of all relevant studies of five GST polymorphisms ( GSTM1 null, GSTT1 null, I105V, and A114V polymorphisms in the GSTP1 genes, and GSTM3 intron 6 polymorphism) available before August, 2005, with investigation of potential sources of heterogeneity. Included in the present meta-analysis were 130 studies, involving a total of 23,452 lung cancer cases and 30,397 controls. In a combined analysis, the relative risks for lung cancer of the GSTM1 null and GSTT1 null polymorphisms were 1.18 (95% confidence interval [CI]: 1.14–1.23) and 1.09 (95% CI: 1.02–1.16), respectively, but in the larger studies they were only 1.04 (95% CI: 0.95–1.14) and 0.99 (95% CI: 0.86–1.11), respectively. In addition to size of study, ethnic background was a significant source of heterogeneity among studies of the GSTM1 null genotype, with possibly weaker associations in studies of individuals of European continental ancestry. Combined analyses of studies of the 105V, 114V, and GSTM3*B variants showed no significant overall associations with lung cancer, yielding per-allele relative risks of 1.04 (95% CI: 0.99–1.09), 1.15 (95% CI: 0.95–1.39), and 1.05 (95% CI: 0.89–1.23), respectively. CONCLUSIONS: The risk of lung cancer is not strongly associated with the I105V and A114V polymorphisms in the GSTP1 gene or with GSTM3 intron 6 polymorphism. Given the non-significant associations in the larger studies, the relevance of the weakly positive overall associations with the GSTM1 null and the GSTT1 null polymorphisms is uncertain. As lung cancer has important environmental causes, understanding any genetic contribution to it in general populations will require the conduct of particularly large and comprehensive studies

The role of ergonomic saddle seats and magnification loupes in the prevention of musculoskeletal disorders. A systematic review.

OBJECTIVES: Musculoskeletal disorders affect a high percentage of dentists, dental hygienists and therapists. Static and awkward working postures are considered as major risk factors. Proper seat selection and use of magnification loupes are promoted for their ergonomic benefits. The aim of this review was to evaluate the existing empirical evidence on the effect of the above interventions on (i) correction of poor posture and (ii) reduction in musculoskeletal pain. METHODS: The review was conducted according to the PRISMA guidelines. The review protocol was registered with PROSPERO (CRD42017058580). The Medline via Ovid, CINHAL via EBSCO, Web of Science, OpenGrey and EThOS electronic databases were searched. Prospective experimental studies were considered for inclusion. The Effective Public Health Practice Project Quality Assessment Tool (EPHPP) was used to assess the methodological quality of the included studies. RESULTS: Eight studies were included in the review. Four investigated the effect of loupes on posture and musculoskeletal pain, 4 the effect of the saddle seats on posture and one of the latter explored the combined effect of magnification and use of saddle seats on posture. CONCLUSIONS: Based on a limited number of studies, the use of ergonomic saddle seats and dental loupes leads to improved working postures. The use of loupes appears to relieve shoulder, arm and hand pain. However, their effect on neck pain is scarce. None of the studies reported on the effect of the saddle seats on musculoskeletal pain. Future well-powered prospective longitudinal studies are deemed necessary to confirm the conclusions of this review

Arabidopsis AtVPS15 is essential for pollen development and germination through modulating phosphatidylinositol 3-phosphate formation

Arabidopsis thaliana phosphatidylinositol 3-kinase (AtVPS34) functions in the development and germination of pollen by catalyzing the biosynthesis of phosphatidylinositol 3-phosphate (PI3P). In yeast, Vps15p is required for the membrane targeting and activity of Vps34. The expression of Arabidopsis thaliana VPS15 (AtVPS15), an ortholog of yeast Vps15, is mainly detected in pollen grains and pollen tubes. To determine its role in pollen development and pollen tube growth, we attempted to isolate the T-DNA insertion mutants of AtVPS15; however, homozygous lines of atvps15 were not obtained from the progeny of atvps15/+ heterozygotes. Genetic analysis revealed that the abnormal segregation is due to the failure of transmission of the atvps15 allele through pollen. Most pollen grains from the atvps15/+ genotype are viable, with normal exine structure and nuclei, but some mature pollen grains are characterized with unusual large vacuoles that are not observed in pollen grains from the wild AtVPS15 genotype. The germination ratio of pollen from the atvps15/+ genotype is about half when compared to that from the wild AtVPS15 genotype. When supplied with PI3P, in vitro pollen germination of the atvps15/+ genotype is greatly improved. Presumably, AtVPS15 functions in pollen development and germination by regulating PI3P biosynthesis in Arabidopsis

Mediterranean Jellyfish Venoms: A Review on Scyphomedusae

The production of natural toxins is an interesting aspect, which characterizes the physiology and the ecology of a number of marine species that use them for defence/offence purposes. Cnidarians are of particular concern from this point of view; their venoms are contained in specialized structures–the nematocysts–which, after mechanical or chemical stimulation, inject the venom in the prey or in the attacker. Cnidarian stinging is a serious health problem for humans in the zones where extremely venomous jellyfish or anemones are common, such as in temperate and tropical oceanic waters and particularly along several Pacific coasts, and severe cases of envenomation, including also lethal cases mainly induced by cubomedusae, were reported. On the contrary, in the Mediterranean region the problem of jellyfish stings is quite modest, even though they can have anyhow an impact on public health and be of importance from the ecological and economic point of view owing to the implications on ecosystems and on some human activities such as tourism, bathing and fishing. This paper reviews the knowledge about the various aspects related to the occurrence and the stinging of the Mediterranean scyphozoan jellyfish as well as the activity of their venoms

Dietary Protein and Blood Pressure: A Systematic Review

Background - Elevated blood pressure (BP), which is a major risk factor for cardiovascular disease, is highly prevalent worldwide. Recently, interest has grown in the role of dietary protein in human BP. We performed a systematic review of all published scientific literature on dietary protein, including protein from various sources, in relation to human BP. Methodology/Principal Findings - We performed a MEDLINE search and a manual search to identify English language studies on the association between protein and blood pressure, published before June 2010. A total of 46 papers met the inclusion criteria. Most observational studies showed no association or an inverse association between total dietary protein and BP or incident hypertension. Results of biomarker studies and randomized controlled trials indicated a beneficial effect of protein on BP. This beneficial effect may be mainly driven by plant protein, according to results in observational studies. Data on protein from specific sources (e.g. from fish, dairy, grain, soy, and nut) were scarce. There was some evidence that BP in people with elevated BP and/or older age could be more sensitive to dietary protein. Conclusions/Significance - In conclusion, evidence suggests a small beneficial effect of protein on BP, especially for plant protein. A blood pressure lowering effect of protein may have important public health implications. However, this warrants further investigation in randomized controlled trials. Furthermore, more data are needed on protein from specific sources in relation to BP, and on the protein-BP relation in population subgroup

Clinical classification of cancer cachexia:phenotypic correlates in human skeletal muscle

Aim – To relate muscle phenotype to a range of current diagnostic criteria for cancer cachexia Methods – 41 patients with resectable upper gastrointestinal (GI) or pancreatic cancer underwent characterisation for cachexia based on weight-loss (WL) and / or low muscularity (LM). Four diagnostic criteria were used >5%WL, >10% WL, LM, and LM + >2%WL. Patients underwent biopsy of the rectus muscle. Analysis included immunohistochemistry for fibre size and type, protein and nucleic acid concentration, and Western blots for markers of autophagy, SMAD signalling, and inflammation. Results – Compared with non-cachectic cancer patients, if patients were classified by LM or LM + >2%WL, mean muscle fibre diameter was significantly reduced (p = 0.02 and p = 0.001) repectively. No difference in fibre diameter was observed if patients were classified with WL alone. Regardless of classification, there was no difference in fibre number or proportion of fibre type across all myosin heavy chain isoforms. Mean muscle protein content was reduced and the ratio of RNA/DNA decreased if patients were classified by either >5% WL or LM + >2%WL. Compared with non-cachectic patients, when patients were classified according to >5% WL, SMAD3 protein levels were increased (p=0.022) and with >10% WL, beclin (p = 0.05) and ATG5 (p = 0.01) protein levels were also increased. There were no differences in pNFkB or pSTAT3 levels across any of the groups. Conclusions – Whereas fibre type is not targeted selectively, muscle fibre size, biochemical composition and pathway phenotype can vary according to whether the criteria for cachexia include both a measure of low muscularity and weight loss