Academic detailing to increase colorectal cancer screening by primary care practices in Appalachian Pennsylvania

<p>Abstract</p> <p>Background</p> <p>In the United States, colorectal cancer (CRC) is the third most frequently diagnosed cancer and second leading cause of cancer death. Screening is a primary method to prevent CRC, yet screening remains low in the U.S. and particularly in Appalachian Pennsylvania, a largely rural area with high rates of poverty, limited health care access, and increased CRC incidence and mortality rates. Receiving a physician recommendation for CRC screening is a primary predictor for patient adherence with screening guidelines. One strategy to disseminate practice-oriented interventions is academic detailing (AD), a method that transfers knowledge or methods to physicians, nurses or office staff through the visit(s) of a trained educator. The objective of this study was to determine acceptability and feasibility of AD among primary care practices in rural Appalachian Pennsylvania to increase CRC screening.</p> <p>Methods</p> <p>A multi-site, practice-based, intervention study with pre- and 6-month post-intervention review of randomly selected medical records, pre- and post-intervention surveys, as well as a post-intervention key informant interview was conducted. The primary outcome was the proportion of patients current with CRC screening recommendations and having received a CRC screening within the past year. Four practices received three separate AD visits to review four different learning modules.</p> <p>Results</p> <p>We reviewed 323 records pre-intervention and 301 post-intervention. The prevalence of being current with screening recommendation was 56% in the pre-intervention, and 60% in the post-intervention (p = 0. 29), while the prevalence of having been screened in the past year increased from 17% to 35% (p < 0.001). Colonoscopies were the most frequently performed screening test. Provider knowledge was improved and AD was reported to be an acceptable intervention for CRC performance improvement by the practices.</p> <p>Conclusions</p> <p>AD appears to be acceptable and feasible for primary care providers in rural Appalachia. A ceiling effect for CRC screening may have been a factor in no change in overall screening rates. While the study was not designed to test the efficacy of AD on CRC screening rates, our evidence suggests that AD is acceptable and may be efficacious in increasing recent CRC screening rates in Appalachian practices which could be tested through a randomized controlled study.</p

Genetic Structure of the Tiger Mosquito, Aedes albopictus, in Cameroon (Central Africa)

Background: Aedes albopictus (Skuse, 1884) (Diptera: Culicidae), a mosquito native to Asia, has recently invaded all five continents. In Central Africa it was first reported in the early 2000s, and has since been implicated in the emergence of arboviruses such as dengue and chikungunya in this region. Recent genetic studies of invasive species have shown that multiple introductions are a key factor for successful expansion in new areas. As a result, phenotypic characters such as vector competence and insecticide susceptibility may vary within invasive pest species, potentially affecting vector efficiency and pest management. Here we assessed the genetic variability and population genetics of Ae. albopictus isolates in Cameroon (Central Africa), thereby deducing their likely geographic origin. Methods and Results: Mosquitoes were sampled in 2007 in 12 localities in southern Cameroon and analyzed for polymorphism at six microsatellite loci and in two mitochondrial DNA regions (ND5 and COI). All the microsatellite markers were successfully amplified and were polymorphic, showing moderate genetic structureamong geographic populations (F-ST = 0.068, P<0.0001). Analysis of mtDNA sequences revealed four haplotypes each for the COI and ND5 genes, with a dominant haplotype shared by all Cameroonian samples. The weak genetic variation estimated from the mtDNA genes is consistent with the recent arrival of Ae. albopictus in Cameroon. Phylogeographic analysis based on COI polymorphism indicated that Ae. albopictus populations from Cameroon are related to tropical rather than temperate or subtropical outgroups. Conclusion: The moderate genetic diversity observed among Cameroonian Ae. albopictus isolates is in keeping with recent introduction and spread in this country. The genetic structure of natural populations points to multiple introductions from tropical regions

Predictive modelling of a novel anti-adhesion therapy to combat bacterial colonisation of burn wounds

As the development of new classes of antibiotics slows, bacterial resistance to existing antibiotics is becoming an increasing problem. A potential solution is to develop treatment strategies with an alternative mode of action. We consider one such strategy: anti-adhesion therapy. Whereas antibiotics act directly upon bacteria, either killing them or inhibiting their growth, anti-adhesion therapy impedes the binding of bacteria to host cells. This prevents bacteria from deploying their arsenal of virulence mechanisms, while simultaneously rendering them more susceptible to natural and artificial clearance. In this paper, we consider a particular form of anti-adhesion therapy, involving biomimetic multivalent adhesion molecule 7 coupled polystyrene microbeads, which competitively inhibit the binding of bacteria to host cells. We develop a mathematical model, formulated as a system of ordinary differential equations, to describe inhibitor treatment of a Pseudomonas aeruginosa burn wound infection in the rat. Benchmarking our model against in vivo data from an ongoing experimental programme, we use the model to explain bacteria population dynamics and to predict the efficacy of a range of treatment strategies, with the aim of improving treatment outcome. The model consists of two physical compartments: the host cells and the exudate. It is found that, when effective in reducing the bacterial burden, inhibitor treatment operates both by preventing bacteria from binding to the host cells and by reducing the flux of daughter cells from the host cells into the exudate. Our model predicts that inhibitor treatment cannot eliminate the bacterial burden when used in isolation; however, when combined with regular or continuous debridement of the exudate, elimination is theoretically possible. Lastly, we present ways to improve therapeutic efficacy, as predicted by our mathematical model

Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank

Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorate CZD/16/6 and the Scottish Funding Council HR03006. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z. YZ acknowledges support from China Scholarship Council. IJD is supported by the Centre for Cognitive Ageing and Cognitive Epidemiology which is funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). AMMcI and T-KC acknowledges support from the Dr Mortimer and Theresa Sackler Foundation. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. Ethics approval for the study was given by the NHS Tayside committee on research ethics (reference 05/S1401/8)Peer reviewedPublisher PD

Regulation of Brown Fat Adipogenesis by Protein Tyrosine Phosphatase 1B

Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of insulin signaling and energy balance, but its role in brown fat adipogenesis requires additional investigation.To precisely determine the role of PTP1B in adipogenesis, we established preadipocyte cell lines from wild type and PTP1B knockout (KO) mice. In addition, we reconstituted KO cells with wild type, substrate-trapping (D/A) and sumoylation-resistant (K/R) PTP1B mutants, then characterized differentiation and signaling in these cells. KO, D/A- and WT-reconstituted cells fully differentiated into mature adipocytes with KO and D/A cells exhibiting a trend for enhanced differentiation. In contrast, K/R cells exhibited marked attenuation in differentiation and lipid accumulation compared with WT cells. Expression of adipogenic markers PPARγ, C/EBPα, C/EBPδ, and PGC1α mirrored the differentiation pattern. In addition, the differentiation deficit in K/R cells could be reversed completely by the PPARγ activator troglitazone. PTP1B deficiency enhanced insulin receptor (IR) and insulin receptor substrate 1 (IRS1) tyrosyl phosphorylation, while K/R cells exhibited attenuated insulin-induced IR and IRS1 phosphorylation and glucose uptake compared with WT cells. In addition, substrate-trapping studies revealed that IRS1 is a substrate for PTP1B in brown adipocytes. Moreover, KO, D/A and K/R cells exhibited elevated AMPK and ACC phosphorylation compared with WT cells.These data indicate that PTP1B is a modulator of brown fat adipogenesis and suggest that adipocyte differentiation requires regulated expression of PTP1B

The effectiveness and cost-effectiveness of strength and balance Exergames to reduce falls risk for people aged 55 years and older in UK assisted living facilities: A multi-centre, cluster randomised controlled trial

Background: Falls are the leading cause of fatal and non-fatal unintentional injuries in older people. The use of Exergames (active, gamified video-based exercises) is a possible innovative, community-based approach. This study aimed to determine the effectiveness of a tailored OTAGO/FaME based strength and balance Exergame programme for improving balance, maintaining function and reducing falls risk in older people. Methods: A two-arm cluster randomised controlled trial recruiting adults aged 55 years and older living in 18 assisted-living (sheltered housing) facilities (clusters) in the UK. Standard care (physiotherapy advice and leaflet) was compared to a tailored 12-week strength and balance Exergame programme, supported by physiotherapists or trained assistants. Complete-case analysis (intention to treat) was used to compare Berg Balance Scale (BBS) at baseline and at 12 weeks. Secondary outcomes included: fear of falling, mobility, falls risk, pain, mood, fatigue, cognition, healthcare utilisation and health-related quality of life; self-reported physical activity and falls. Results: Eighteen clusters were randomised (9 to each arm) with 56 participants allocated to the intervention and 50 to the control (78% female, mean age 78 years). Fourteen participants withdrew over the 12 weeks (both arms), mainly for ill health. There was an adjusted mean improvement in balance (BBS) of 6.2 (95% CI 2.4 to 10.0), reduced fear of falling (p=0.007) and pain (p=0.02) in Exergame group. Mean attendance at sessions was 69% (mean exercising time of 33 minutes/week). 24% of control group and 20% of Exergame group fell over trial period. The change in falls rates significantly favoured the intervention (incident rate ratio 0.31 (95% CI 0.16 to 0.62, p=0.001)). The point estimate of the incremental cost effectiveness ratio (ICER) was £15,209.80 per QALY. Using 10,000 bootstrap replications, at the lower bound of the NICE threshold of £20,000 per QALY, there was a 61% probability of Exergames being cost-effective, rising to 73% at the upper bound of £30,000 per QALY. Conclusions: Exergames, as delivered in this trial, improve balance, pain and fear of falling and are a cost-effective fall prevention strategy in assisted living facilities for people aged 55 years or older

Ginseng administration protects skeletal muscle from oxidative stress induced by acute exercise in rats

Enzymatic activity was analyzed in the soleus, gastrocnemius (red and white) and plantaris muscles of acutely exercised rats after long-term administration of Panax ginseng extract in order to evaluate the protective role of ginseng against skeletal muscle oxidation. Ginseng extract (3, 10, 100, or 500 mg/kg) was administered orally for three months to male Wistar rats weighing 200 ± 50 g before exercise and to non-exercised rats (N = 8/group). The results showed a membrane stabilizing capacity of the extract since mitochondrial function measured on the basis of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities was reduced, on average, by 20% (P < 0.05) after exercise but the activities remained unchanged in animals treated with a ginseng dose of 100 mg/kg. Glutathione status did not show significant changes after exercise or treatment. Lipid peroxidation, measured on the basis of malondialdehyde levels, was significantly higher in all muscles after exercise, and again was reduced by about 74% (P < 0.05) by the use of ginseng extract. The administration of ginseng extract was able to protect muscle from exercise-induced oxidative stress irrespective of fiber type

Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations.

The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms-intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1r mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1r mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r rodents. Csf1r mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals

A comparison of methods for temporal analysis of aoristic crime

Objectives: To test the accuracy of various methods previously proposed (and one new method) to estimate offence times where the actual time of the event is not known. Methods: For 303 thefts of pedal cycles from railway stations, the actual offence time was determined from closed-circuit television and the resulting temporal distribution compared against commonly-used estimated distributions using circular statistics and analysis of residuals. Results: Aoristic analysis and allocation of a random time to each offence allow accurate estimation of peak offence times. Commonly-used deterministic methods were found to be inaccurate and to produce misleading results. Conclusions: It is important that analysts use the most accurate methods for temporal distribution approximation to ensure any resource decisions made on the basis of peak times are reliable