PubTransformer

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prevention - Top 30 Publications

Hepatitis C Virus Testing for Case Identification in Persons Born during 1945-1965: Results from Three Randomized Controlled Trials.

CDC and U.S. Preventive Services Task Force recommend one-time hepatitis C virus (HCV) testing for persons born during 1945-1965 (birth cohort). However, few studies estimate the effect of birth cohort (BC) testing implementation on HCV diagnoses in primary care settings. We aimed to determine the probability of identifying HCV infections in primary care using targeted BC testing compared with usual care at three academic medical centers. From December 2012 to March 2014, each center compared one of three distinct interventions to usual care using an independently-designed randomized controlled trial. Across centers, BC patients with no clinical documentation of previous HCV testing or diagnosis were randomly assigned to receive a one-time offering of HCV antibody (anti-HCV) testing via one of three independent implementation strategies (repeated-mailing outreach, EMR-integrated provider best practice alert [BPA], and direct patient-solicitation) or assigned to receive usual care. We estimated model-adjusted risk ratios (aRR) of anti-HCV positive (anti-HCV+) identification using BC testing versus usual care. In the repeated-mailing trial, 8,992 patients (intervention=2,993; control=5,999) were included in the analysis. The intervention was eight times as likely to identify anti-HCV+ patients compared with control (aRR 8.0, 95%CI 2.8-23.0; adjusted probabilities: intervention=0.27%; control=0.03%). In the BPA trial, data from 14,475 patients (BC=8,928; control=5,547) were analyzed. The intervention was 2.6 times as likely to identify anti-HCV+ patients versus control (aRR 2.6, 95%CI 1.1-6.4; adjusted probabilities: intervention=0.29%; control=0.11%). In the patient-solicitation trial, 8,873 patients (BC=4,307; control=4,566) were analyzed. The intervention was five times as likely to identify anti-HCV+ patients compared with control (aRR 5.3, 95%CI 2.3-12.3; adjusted probabilities: intervention=0.68%; control=0.11%).

Inducing indel mutation in the SOX6 Gene by Zinc Finger Nuclease for gamma reactivation: An Approach towards Gene Therapy of Beta Thalassemia.

β-thalassemia is a common autosomal recessive disorder characterized by a deficiency in the synthesis of β-chains.Evidences show that increased HbF levels improve the symptoms in patients with β-thalassemia or sickle cell anemia. In this study, ZFN technology was applied to induce a mutation in the binding domain region of SOX6 to reactivate γ-globin expression. The sequences coding for ZFP arrays were designed and sub cloned in TDH plus as a transfer vector. The ZFN expression was confirmed using Western blot analysis. In the next step, using the site-directed mutagenesis strategy through the overlap PCR,a missense mutation (D64V) was induced in the catalytic domain of the integrase gene in the packaging plasmid and verified using DNA sequencing.Then, the integrase minus lentivirus containing ZFN cassette was packaged. Transduction of K562 cells with this virus was performed.Mutation detection assay was performed. The indel percentage of the cells transducted with lenti virus containing ZFN was 31%. After 5 days of erythroid differentiation with 15µg/ml cisplatin, the levels of γ-globin mRNA were 6-fold in the cells treated with ZFN compared to untreated cells. In the meantime, the measurement of HbF expression levels was carried out using hemoglobin electrophoresis and showed the same results. Integrase minus lentivirus can provide a useful tool for efficient transient gene expression and helps avoid disadvantages of gene targeting using the native virus.The ZFN strategy applied here to induce indel on SOX6 gene in adult erythroid progenitors may provide a method to activate fetal hemoglobin expression in individuals with β-thalassemia. This article is protected by copyright. All rights reserved.

A Critical Role for Donor-Derived IL-22 in Cutaneous Chronic GVHD.

Graft-versus-host disease (GVHD) is the major cause of non-relapse morbidity and mortality after allogeneic stem cell transplant (allo-SCT). Prevention and treatment of GVHD remains inadequate and commonly leads to end-organ dysfunction and opportunistic infection. The role of IL-17 and IL-22 in GVHD remains uncertain, due to an apparent lack of lineage fidelity and variable and contextually determined protective and pathogenic effects. We demonstrate that donor T-cell-derived IL-22 significantly exacerbates cutaneous chronic GVHD, and that IL-22 is produced by highly inflammatory donor CD4(+) T-cells post-transplant. IL-22 and IL-17A derive from both independent and overlapping lineages, defined as Th22 and IL-22(+) Th17 cells. Donor Th22 and IL-22(+) Th17 share a similar IL-6-dependent developmental pathway and whilst Th22 arise independently of the IL-22(+) Th17 lineage, IL-17 signaling to donor Th22 directly promotes their development in allo-SCT. Importantly, while both IL-22 and IL-17 mediate skin GVHD, Th17-induced chronic GVHD can be attenuated by IL-22 inhibition in preclinical systems. In the clinic, high levels of both IL-17A and IL-22 expression are present in the skin of GVHD patients after allo-SCT. Together, these data demonstrate a key role for donor-derived IL-22 in chronic skin GVHD and confirm parallel but symbiotic developmental pathways of Th22 and Th17 differentiation. This article is protected by copyright. All rights reserved.

Stromal Cell-Derived Factor-1 Mediates Cardiac Allograft Tolerance Induced by Human Endometrial Regenerative Cell-Based Therapy.

Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells, and their therapeutic potential has been tested in the prevention of renal ischemic reperfusion injury, acute liver injury, ulcerative colitis, and immunosuppression. However, their potential in the induction of transplant tolerance has not been investigated. The present study was undertaken to investigate the efficacy of ERCs in inducing cardiac allograft tolerance and the function of stromal cell-derived factor-1 (SDF-1) in the ERC-mediated immunoregulation. The inhibitory efficacy of human ERCs in the presence or absence of rapamycin was examined in both mouse cardiac allograft models between BALB/c (H-2(d) ) donors and C57BL/6 (H-2(b) ) recipients and in vitro cocultured splenocytes. AMD3100 was used to inhibit the function of SDF-1. Intragraft antibody (IgG and IgM) deposition and immune cell (CD4(+) and CD8(+) ) infiltration were measured by immunohistochemical staining, and splenocyte phenotypes were determined by fluorescence-activated cell sorting analysis. The results showed that ERC-based therapy induced donor-specific allograft tolerance, and functionally inhibiting SDF-1 resulted in severe allograft rejection. The negative effects of inhibiting SDF-1 on allograft survival were correlated with increased levels of intragraft antibodies and infiltrating immune cells, and also with reduced levels of regulatory immune cells including MHC class II(low) CD86(low) CD40(low) dendritic cells, CD68(+) CD206(+) macrophages, CD4(+) CD25(+) Foxp3(+) T cells, and CD1d(high) CD5(high) CD83(low) IL-10(high) B cells both in vivo and in vitro. These data showed that human ERC-based therapy induces cardiac allograft tolerance in mice, which is associated with SDF-1 activity, suggesting that SDF-1 mediates the immunosuppression of ERC-based therapy for the induction of transplant tolerance. Stem Cells Translational Medicine 2017.

Donor derived Kaposi's sarcoma in a liver-kidney transplant recipient.

Human herpes virus 8 (HHV-8), also known as Kaposi's sarcoma associated herpesvirus (KSHV), is an oncogenic virus that can cause Kaposi's sarcoma (KS). KS can develop following organ transplantation through reactivation of the recipient's latent HHV-8 infection, or less commonly through donor-derived infection which has higher risk for severe illness and mortality. We describe a case of probable donor-derived KS in the recipient of a liver-kidney transplant. The donor had multiple risk factors for HHV-8 infection. The KS was successfully treated by switching immunosuppression from tacrolimus to sirolimus. With an increasing number of human immunodeficiency virus (HIV)-positive persons seeking organ transplantation and serving as organ donors for HIV-positive recipients, HHV-8 prevalence among donors and recipients will likely increase and with that the risk for post-transplant KS. Pre-determination of HHV-8 status can be useful when considering organ donors and recipients with risk factors, although there are currently no validated commercial tests for HHV-8 antibody screening. This article is protected by copyright. All rights reserved.

Different intervention strategies for preventing type 2 diabetes mellitus in China: A systematic review and network meta-analysis of randomized controlled trials.

Different strategies are increasingly used for early intervention on prediabetes in China, but the effects of these strategies on incident diabetes have not yet been confirmed. This study was to systematically assess the effects of different strategies on preventing diabetes, aimed at Chinese prediabetic subjects. Seven electronic databases were searched to identify eligible trials published from inception to Sep 20, 2016. Randomized controlled trials with a minimum follow-up duration of 6 months were included. Standard pairwise meta-analysis with a random-effects model and network meta-analysis with a frequentist framework were performed. Sixty-three studies with 11 intervention strategies were included. Compared with placebo, all strategies, except for lipid-affecting drugs and sitagliptin, reduced the incident diabetes with different levels of effectiveness, ranging from 0.18 (95%CI 0.12, 0.27) to 0.39 (95%CI 0.20, 0.75). Ranking probability analysis indicated that metformin and β-cell simulating drugs reduced the risk of diabetes most, with probabilities of 87.4 and 81%, respectively. Ethnicity and cultural factors should be considered for diabetes prevention. However, most of the included trials were of poor methodological quality; the results should be interpreted with caution.

Advancements in the design and scalable production of viral gene transfer vectors.

The last 10 years have seen a rapid expansion in the use of viral gene transfer vectors, with approved therapies and late stage clinical trials underway for the treatment of genetic disorders, and multiple forms of cancer, as well as prevention of infectious diseases through vaccination. With this increased interest and widespread adoption of viral vectors by clinicians and biopharmaceutical industries, there is an imperative to engineer safer and more efficacious vectors, and develop robust, scalable and cost-effective production platforms for industrialization. This review will focus on major innovations in viral vector design and production systems for three of the most widely used viral vectors: Adenovirus, Adeno-Associated Virus, and Lentivirus. This article is protected by copyright. All rights reserved.

Genetics and Epigenetics of Autism (Review).

Autism is a developmental disorder that starts before age 3, and children with autism has impairment in both social interaction and communication, and has restricted, repetitive and stereotyped patterns of behavior, interests and activities. There is a strong heritable component of autism and autism spectrum disorder as studies have shown that parents who have a child with ASD have a 2-18% chance of having a second child with ASD. Since the prevalence of autism and autism spectrum disorders have been increasing during the last 3 decades, much research has been carried out to understand the etiology, so as to develop novel preventive and treatment strategies. This review aims at summarizing the latest research studies related to autism and autism spectrum disorder, focusing not only on the genetics but also some epigenetic findings of autism/autism spectrum disorder. Some promising areas of research using transgenic/knockout animals and some ideas related to potential novel treatment and prevention strategies will be discussed.

Gaps in African swine fever: Analysis and priorities.

African swine fever (ASF) causes greater sanitary, social and economic impacts on swine herds than many other swine diseases. Although ASF was first described in 1921 and it has affected more than fifty countries in Africa, Europe and South America, several key issues about its pathogenesis, immune evasion and epidemiology remain uncertain. This article reviews the main characteristics of the causative virus, its molecular epidemiology, natural hosts, clinical features, epidemiology and control worldwide. It also identifies and prioritizes gaps in ASF from a horizontal point of view encompassing fields including molecular biology, epidemiology, prevention, diagnosis and vaccine development. The purpose of this review is to promote ASF research and enhance its control.

Knowledge gaps that hamper prevention and control of Mycobacterium avium subspecies paratuberculosis infection.

In the last decades, many regional and country-wide control programmes for Johne's disease (JD) were developed due to associated economic losses, or because of a possible association with Crohn's disease. These control programmes were often not successful, partly because management protocols were not followed, including the introduction of infected replacement cattle, because tests to identify infected animals were unreliable, and uptake by farmers was not high enough because of a perceived low return on investment. In the absence of a cure or effective commercial vaccines, control of JD is currently primarily based on herd management strategies to avoid infection of cattle and restrict within-farm and farm-to-farm transmission. Although JD control programmes have been implemented in most developed countries, lessons learned from JD prevention and control programmes are underreported. Also, JD control programmes are typically evaluated in a limited number of herds and the duration of the study is less than 5 year, making it difficult to adequately assess the efficacy of control programmes. In this manuscript, we identify the most important gaps in knowledge hampering JD prevention and control programmes, including vaccination and diagnostics. Secondly, we discuss directions that research should take to address those knowledge gaps.

Porcine circovirus-like virus P1 in cattle, goats and rabbits in China.

Porcine circovirus-like virus P1, a novel single-stranded circular DNA virus, is a potential causative agent of post-weaning multisystemic wasting syndrome in swine. In this study, we detected P1 strains in serum samples from cattle, goats and rabbits suffering different clinical symptoms, in Jiangsu Province, China. We sequenced the whole genomes of six P1 strains, which showed 99.4%-100% nucleotide sequence similarity and were closely related to other porcine-origin P1 isolates. The sequences of six non-porcine-origin P1 viruses were most closely phylogenetically related to other porcine-origin P1 sequences. Therefore, the P1 virus has a wide host range in China.

Efficacy of a Work Disability Prevention Program for People with Rheumatic and Musculoskeletal Conditions: The Work It Study Trial.

Work disability rates are high among people with rheumatic and musculoskeletal conditions. Effective disability preventive programs are needed. We examined the efficacy of a modified vocational rehabilitation approach delivered by trained occupational therapists and physical therapists on work limitation and work loss over two years among people with rheumatic and musculoskeletal conditions.

2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

The Voting Panel recommended oral bisphosphonates as a first choice and parenteral bisphosphonates as a second choice after comparing data about absolute fracture reduction, harms (toxicity and inconvenience of daily injections), and costs. Drs. Maricic, Deal, Dore, and Laster cite the randomized trial of alendronate versus teriparatide in glucocorticoid-treated patients that reported incident fractures as a secondary outcome. This trial found a lower risk of clinical vertebral fractures in the teriparatide compared to alendronate treated patients (0% vs. 2.4% [n=4/169], p=0.037) but no difference in the risk of nonvertebral fracture (7.5% vs. 7.0%, p=0.843) (1). This article is protected by copyright. All rights reserved.

Comment on 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

We have read the recently published 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (1), and applaud the committee's efforts, but have a number of areas of disagreement. Our main concern is that in adults at high risk for fracture, oral and then parenteral bisphosphonates are recommended over teriparatide in selecting drug therapy. This represents a departure from the 2010 ACR GIO Guidelines (2) which avoided rating bisphosphonates (either oral or parenteral) preferentially over teriparatide. This article is protected by copyright. All rights reserved.

The association between specific types of childhood adversity and attenuated psychotic symptoms in a community sample.

This study aimed to examine the relationship between types of childhood adversity and attenuated psychotic symptoms in a general population sample, and to determine the predictive role of other psychosocial factors such as resilience, coping style and social support.

Sedentary behavior and physical activity levels in people with schizophrenia, bipolar disorder and major depressive disorder: a global systematic review and meta-analysis.

People with severe mental illness (schizophrenia, bipolar disorder or major depressive disorder) die up to 15 years prematurely due to chronic somatic comorbidities. Sedentary behavior and low physical activity are independent yet modifiable risk factors for cardiovascular disease and premature mortality in these people. A comprehensive meta-analysis exploring these risk factors is lacking in this vulnerable population. We conducted a meta-analysis investigating sedentary behavior and physical activity levels and their correlates in people with severe mental illness. Major electronic databases were searched from inception up to April 2017 for articles measuring sedentary behavior and/or physical activity with a self-report questionnaire or an objective measure (e.g., accelerometer). Random effects meta-analyses and meta-regression analyses were conducted. Sixty-nine studies were included (N=35,682; 39.5% male; mean age 43.0 years). People with severe mental illness spent on average 476.0 min per day (95% CI: 407.3-545.4) being sedentary during waking hours, and were significantly more sedentary than age- and gender-matched healthy controls (p=0.003). Their mean amount of moderate or vigorous physical activity was 38.4 min per day (95% CI: 32.0-44.8), being significantly lower than that of healthy controls (p=0.002 for moderate activity, p<0.001 for vigorous activity). People with severe mental illness were significantly less likely than matched healthy controls to meet physical activity guidelines (odds ratio = 1.5; 95% CI: 1.1-2.0, p<0.001, I(2) =95.8). Lower physical activity levels and non-compliance with physical activity guidelines were associated with male gender, being single, unemployment, fewer years of education, higher body mass index, longer illness duration, antidepressant and antipsychotic medication use, lower cardiorespiratory fitness and a diagnosis of schizophrenia. People with bipolar disorder were the most physically active, yet spent most time being sedentary. Geographical differences were detected, and inpatients were more active than outpatients and those living in the community. Given the established health benefits of physical activity and its low levels in people with severe mental illness, future interventions specifically targeting the prevention of physical inactivity and sedentary behavior are warranted in this population.

Staging in bipolar disorder: from theoretical framework to clinical utility.

Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage-specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage-specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at-risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative-type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper are to: a) explore the current level of evidence supporting the descriptive staging of the syndromal pattern of bipolar disorder; b) describe preliminary attempts at validation; c) make recommendations for the direction of further studies; and d) provide a distillation of the potential clinical implications of staging in bipolar disorder within a broader transdiagnostic framework.

Estimating treatment coverage for people with substance use disorders: an analysis of data from the World Mental Health Surveys.

Substance use is a major cause of disability globally. This has been recognized in the recent United Nations Sustainable Development Goals (SDGs), in which treatment coverage for substance use disorders is identified as one of the indicators. There have been no estimates of this treatment coverage cross-nationally, making it difficult to know what is the baseline for that SDG target. Here we report data from the World Health Organization (WHO)'s World Mental Health Surveys (WMHS), based on representative community household surveys in 26 countries. We assessed the 12-month prevalence of substance use disorders (alcohol or drug abuse/dependence); the proportion of people with these disorders who were aware that they needed treatment and who wished to receive care; the proportion of those seeking care who received it; and the proportion of such treatment that met minimal standards for treatment quality ("minimally adequate treatment"). Among the 70,880 participants, 2.6% met 12-month criteria for substance use disorders; the prevalence was higher in upper-middle income (3.3%) than in high-income (2.6%) and low/lower-middle income (2.0%) countries. Overall, 39.1% of those with 12-month substance use disorders recognized a treatment need; this recognition was more common in high-income (43.1%) than in upper-middle (35.6%) and low/lower-middle income (31.5%) countries. Among those who recognized treatment need, 61.3% made at least one visit to a service provider, and 29.5% of the latter received minimally adequate treatment exposure (35.3% in high, 20.3% in upper-middle, and 8.6% in low/lower-middle income countries). Overall, only 7.1% of those with past-year substance use disorders received minimally adequate treatment: 10.3% in high income, 4.3% in upper-middle income and 1.0% in low/lower-middle income countries. These data suggest that only a small minority of people with substance use disorders receive even minimally adequate treatment. At least three barriers are involved: awareness/perceived treatment need, accessing treatment once a need is recognized, and compliance (on the part of both provider and client) to obtain adequate treatment. Various factors are likely to be involved in each of these three barriers, all of which need to be addressed to improve treatment coverage of substance use disorders. These data provide a baseline for the global monitoring of progress of treatment coverage for these disorders as an indicator within the SDGs.

Improving outcomes of first-episode psychosis: an overview.

Outcomes of psychotic disorders are associated with high personal, familiar, societal and clinical burden. There is thus an urgent clinical and societal need for improving those outcomes. Recent advances in research knowledge have opened new opportunities for ameliorating outcomes of psychosis during its early clinical stages. This paper critically reviews these opportunities, summarizing the state-of-the-art knowledge and focusing on recent discoveries and future avenues for first episode research and clinical interventions. Candidate targets for primary universal prevention of psychosis at the population level are discussed. Potentials offered by primary selective prevention in asymptomatic subgroups (stage 0) are presented. Achievements of primary selected prevention in individuals at clinical high risk for psychosis (stage 1) are summarized, along with challenges and limitations of its implementation in clinical practice. Early intervention and secondary prevention strategies at the time of a first episode of psychosis (stage 2) are critically discussed, with a particular focus on minimizing the duration of untreated psychosis, improving treatment response, increasing patients' satisfaction with treatment, reducing illicit substance abuse and preventing relapses. Early intervention and tertiary prevention strategies at the time of an incomplete recovery (stage 3) are further discussed, in particular with respect to addressing treatment resistance, improving well-being and social skills with reduction of burden on the family, treatment of comorbid substance use, and prevention of multiple relapses and disease progression. In conclusion, to improve outcomes of a complex, heterogeneous syndrome such as psychosis, it is necessary to globally adopt complex models integrating a clinical staging framework and coordinated specialty care programmes that offer pre-emptive interventions to high-risk groups identified across the early stages of the disorder. Only a systematic implementation of these models of care in the national health care systems will render these strategies accessible to the 23 million people worldwide suffering from the most severe psychiatric disorders.

Nanomaterials in the Prevention, Diagnosis, and Treatment of Mycobacterium Tuberculosis Infections.

Despite the tremendous advancements that have been made in biomedical research, Mycobacterium tuberculosis (TB) still remains one of the top 10 causes of death worldwide, outpacing the Human Immunodeficiency Virus as a leading cause of death from an infectious disease. In the light of such significant disease burden, tremendous efforts have been made worldwide to stem this burgeoning spread of disease. The use of nanomaterials in TB management has increased in the past decade, particularly in the areas of early TB detection, prevention, and treatment. Nanomaterials have been proven to be efficacious in the rapid and accurate detection of TB pathogens. Novel nanocarriers have also shown tremendous promise in improving drug delivery, potentially enhancing drug concentrations in target organs while at the same time, reducing treatment frequency. In addition, the engineering of antigen nanocarriers represents an exciting front in TB research, potentially paving the way for the successful development of a new class of effective TB vaccines. This article discusses epidemiology and pathogenesis of TB infections, current TB therapeutics, advanced nanomaterials for anti-TB drug delivery, and TB vaccines. In addition, challenges and future perspectives in developing safe and effective nanomaterials in TB diagnosis and therapy are also presented.

Effect of socioeconomic status on stage at diagnosis of lung cancer in a hospital-based multicenter retrospective clinical epidemiological study in China, 2005-2014.

There is inconsistent evidence of associations between socioeconomic status (SES) and lung cancer stage in non-Chinese populations up to now. We set out to determine how SES affects stage at diagnosis at both individual and area levels, from a hospital-based multicenter 10-year (2005-2014) retrospective clinical epidemiological study of 7184 primary lung cancer patients in mainland China. Individual-level SES data were measured based on two indicators from case report forms of the study: an individual's education and occupation. Seven census indicator variables were used as surrogates for the area-level SES with principal component analysis (PCA). Multivariate analysis was undertaken using binary logistic regressions and multinomial logit model to describe the association and explore the effect across tertiles on stage after adjusting for demographic variables. There was a significant stepwise gradient of effect across different stages in the highest tertile of area-level SES, comparing with the lowest tertile of area-level SES (ORs, 0.77, 0.67, and 0.29 for stage II, III, and IV). Patients with higher education were less likely to have stage IV lung cancer, comparing with the illiterate group (ORs, 0.52, 0.63, 0.71, 0.64 for primary school, middle school, high school, college degree or above subgroup, respectively). Findings suggest that the most socioeconomically deprived areas may be associated with a higher risk of advanced-stage lung cancer, and increasing educational level may be correlated with a lower risk to be diagnosed at advanced stage in both men and women.

Islet neuropeptide Y receptors are functionally conserved and novel targets for the preservation of beta-cell mass.

Two unmet therapeutic strategies for diabetes treatment are prevention of beta-cell death and stimulation of beta-cell replication. Our aim was to characterise the role of Neuropeptide Y receptors in the control of beta-cell mass.

MicroRNA-192 as a specific biomarker for the early diagnosis of diabetic kidney disease.

To evaluate the diagnostic value of microRNA as biomarkers in patients with diabetic kidney disease (DKD).

Rural veterinarian's perception and practices in terms of biosecurity across three European countries.

The implementation of biosecurity measures in the animal health and production context is quite broad and aims at limiting the risk of introduction and spread of diseases. Veterinarians play a major role in biosecurity as key informants on the subject for cattle holders, key players in terms of disease prevention/control and eradication programs, as well as key risk factor in terms of disease dissemination. Many biosecurity studies have highlighted professional visitors such as veterinary practitioners as representing a high-risk factor in terms of disease introduction in animal facilities but, to date, very few studies have focused on the implementation level of biosecurity measures by veterinarians. An online survey was implemented in three European countries (Belgium, France and Spain) to assess the behaviour of rural veterinarians towards biosecurity, as well as their implementation level of the biosecurity measures. A descriptive analysis of data and a scoring system were applied to assess the implementation level of measures. The influence of different factors on the implementation level of biosecurity measures was investigated through a negative binomial regression model. The study identified different strengths, weaknesses, possible constraints and solutions in terms of veterinary perspectives. Veterinarians are considered as key informants by the farmers and could therefore play a more active role in terms of guidance and improvement of biosecurity at farm level. Based on the survey outcomes, two factors seemed to influence significantly the implementation level of measures: the country where he/she practices and the veterinarian's perception level of biosecurity. The biosecurity stages with the lowest application level, therefore representing the biggest threats, were bio-exclusion (increasing the risk of disease introduction) and biocontainment (increasing the risk of inter-herd transmission).

Methods for delivering the UK's multi-centre prison-based naloxone-on-release pilot randomised trial (N-ALIVE): Europe's largest prison-based randomised controlled trial.

Naloxone is an opioid antagonist used for emergency resuscitation following opioid overdose. Prisoners with a history of heroin use by injection have a high risk of drug-related death in the first weeks after prison-release. The N-ALIVE trial was planned as a large prison-based randomised controlled trial (RCT) to test the effectiveness of naloxone-on-release in the prevention of fatal opiate overdoses soon after release. The N-ALIVE pilot trial was conducted to test the main trial's assumptions on recruitment of prisons and prisoners, and the logistics for ensuring that participants received their N-ALIVE pack on release.

Cornerstones of patient blood management in surgery.

Pre-operative anaemia and perioperative red blood cell transfusion carry significant consequence when it comes to surgical outcomes. The establishment of patient-centred clinical pathways has been designed to harness and endorse good transfusion practice, termed the three pillars of patient blood management (PBM). These focus on the timely and appropriate management of anaemia, prevention of blood loss and restrictive transfusion where appropriate. This article reviews the current evidence and ongoing research in the field of PBM in surgery. Strategies to implement PBM have shown significant benefits in appropriate transfusion practice, reduced costs and improved length of hospital stay. Recently published national quality standards have recognised the features of the PBM blueprint such as the consideration of alternatives to red blood cell transfusion, the active measures to reduce perioperative blood loss and the appropriate management of post-operative anaemia. Adopting PBM in surgical patients should be paramount to reduce the risks posed by perioperative anaemia and blood transfusions. The principles of PBM help structure the interventions and decisions relating to anaemia and blood transfusion, but, more importantly, represent a paradigm shift towards a more considered approach to blood transfusion, acknowledging its risks, preventatives and alternatives.

The built environment and older adults: A literature review and an applied approach to engaging older adults in built environment improvements for health.

This paper presents a review of the literature about the built environment as it impacts the health of older people. It then introduces the gerontological nurse and researcher to the Our Voice framework for engaging older people as citizen scientists in order to empower them as agents of change in improving their local built environment and ultimately advancing community health.

Financial and Health Barriers and Caregiving-Related Difficulties Among Rural and Urban Caregivers.

To assess whether financial or health-related barriers were more common among rural caregivers and whether rural caregivers experienced more caregiving-related difficulties than their urban peers.

Epidemiology of Helicobacter pylori infection in asymptomatic schoolchildren in Bhutan.

Bhutan is a small mountainous country between Tibet and India with relatively homogenous population. According to the World Health Organization, gastric cancer is the most frequent cause of cancer death in Bhutan. This study examined the prevalence of Helicobacter pylori among children in Bhutan with emphasis on water source and living conditions.

Extensive orf infection in a toddler with associated id reaction.

Orf is a zoonotic parapoxvirus typically transmitted to humans by a bite from goats or sheep. We present an unusual case of multiple orf lesions on the fingers of a 13-month-old child who was bitten by a goat and subsequently developed progressive swelling, blistering, and necrotic papulonodules of the hand followed by an additional diffuse, pruritic, papular rash. A primary diagnosis of orf infection was confirmed using real-time polymerase chain reaction, and the diffuse eruption was clinically consistent with an id reaction. Extensive necrosis and papular id reaction associated with orf rarely have been described.