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Find video protocols related to scientific articles indexed in Pubmed.
Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B.
N. Engl. J. Med.
PUBLISHED: 11-20-2014
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Background In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose-response relationship, and the level of persistent or late toxicity. Methods We evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2×10(12) vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring. Results A single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (±SD) of 5.1±1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment. Conclusions In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00979238 .).
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An outbreak of norovirus genogroup II associated with New South Wales oysters.
Commun Dis Intell Q Rep
PUBLISHED: 11-20-2014
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Introduction: Currently available antigen tests for norovirus (NoV) have excellent specificity but negative results do not always rule out infection. Real-time reverse transcription polymerase chain reaction (RT-PCR) is a useful method for detecting and genotyping NoV in humans and oysters. An outbreak of NoV associated with oyster consumption in northern New South Wales confirmed the value of real-time RT-PCR where immunochromatography (ICT) tests were negative. Methods: Eight cases of gastrointestinal illness in northern NSW, clinically suggestive of NoV infection, were associated with consumption of oysters. A joint environmental investigation was conducted by the New South Wales Food Authority and local council. One human sample was collected and tested for NoV using ICT and real-time RT-PCR. Oyster samples were tested for NoV utilising real-time RT-PCR. Results: The patient with a stool sample had NoV genogroup II (GII) confirmed by real-time RT-PCR after testing negative by ICT. Illness in all cases was consistent with NoV with median incubation and duration of 36 and 50.5 hours respectively. All cases consumed oysters that were harvested from the same area. Three oyster samples from the harvest area were also positive for NoV GII. A nearby leaking sewer line was identified as the likely source of the contamination with hydrological studies confirming its potential to contaminate implicated oyster leases. Conclusion: This investigation confirmed the value of real-time RT-PCR testing of human specimens where ICT tests are negative and clinical illness is suggestive of NoV infection. NoV real-time RT-PCR and epidemiological evidence effectively linked human infection with oyster contamination to motivate a thorough environmental investigation and appropriate action to mitigate further public health risk. Commun Dis Intell 2014;38(1):E9-E15.
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Putting compassion first.
Nurs Stand
PUBLISHED: 11-20-2014
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Our trust is the north west London pilot site for the Care Certificate being developed by Health Education England, Skills for Care and Skills for Health in response to the recommendations of the Cavendish review (see column, far right).
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Toxoplasmosis in a bar-shouldered dove (Geopelia humeralis) from the Zoo of Clères, France.
Parasite
PUBLISHED: 11-20-2014
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Toxoplasmosis causes mortality in several avian species, especially passerine birds. Toxoplasmosis was diagnosed in a bar-shouldered dove (Geopelia humeralis) found dead at the zoo of Clères (France). The bird had necrotizing pneumonia and nephritis with intralesional tachyzoites of Toxoplasma gondii. The diagnosis was confirmed by immunostaining with polyclonal rabbit T. gondii antibodies and by transmission electron microscopy. To our knowledge, the bar-shouldered dove is a new host record for T. gondii.
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Multi-disciplinary Care for the Elderly in Disasters: An Integrative Review.
Prehosp Disaster Med
PUBLISHED: 11-20-2014
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Introduction Older adults are disproportionately affected by disaster. Frail elders, individuals with chronic diseases, conditions, or disabilities, and those who live in long-term care facilities are especially vulnerable. Purpose The purpose of this integrative review of the literature was to describe the system-wide knowledge and skills that multi-disciplinary health care providers need to provide appropriate care for the elderly during domestic-humanitarian and disaster-relief efforts. Data sources A systematic search protocol was developed in conjunction with a research librarian. Searches of PubMed, CINAHL, and PsycINFO were conducted using terms such as Disaster, Geological Processes, Aged, Disaster Planning, and Vulnerable Populations. Forty-six articles met criteria for inclusion in the review.
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Development of recombinant stable house dust mite allergen Der p 3 molecules for component-resolved diagnosis and specific immunotherapy.
Clin. Exp. Allergy
PUBLISHED: 11-20-2014
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The allergen Der p 3 is underrepresented in house dust mite (HDM) extracts probably due to autolysis. Recombinant stable molecule of the allergen is thus needed to improve the diagnosis of allergy and the safety and efficacy of immunotherapy.
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[Genomics from bench to bedside: a change in perspective.]
Med Sci (Paris)
PUBLISHED: 11-17-2014
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While genomics is sometimes presented as an area of ??research where results can be rapidly translated into clinical practice, the facts are more ambiguous. To illustrate some of the pitfalls of translation, this article focuses on the applications of genome-wide association studies (GWAS) results. Following a brief scientific contextualization of GWAS, two emblematic examples are presented as illustrations. The case of Crohn's disease emphasizes the limits of GWAS results for individual risk prediction. The case of warfarin highlights the difficulties of demonstrating the clinical utility of genetic data in treatment decisions. The article outlines the simplification of disease causation that underlies the GWAS methodology. Whereas this reductionist approach is fruitful for exploratory research purposes, it shows its limits when applied to clinical conditions.
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Developing and implementing global gender policy to reduce HIV and AIDS in low- and middle -income countries: Policy makers' perspectives.
Afr J AIDS Res
PUBLISHED: 11-13-2014
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Gender inequalities have been recognised as central to the HIV epidemic for many years. In response, a range of gender policies have been developed in attempts to mitigate the impact and transform gender relations. However, the effects of these policies have been less than successful. In March 2010 the Joint United Nations Programme on HIV/AIDS (UNAIDS) launched the Agenda for accelerated country level action on women, girls, gender equality and HIV (the Agenda), an operational plan on how to integrate women, girls and gender equality into the HIV response. This paper explores the perspectives of those involved in developing and implementing the Agenda to understand its strengths and limitations. In-depth one-on-one interviews were conducted with 16 individuals involved in the development and implementation of the Agenda. The data were analysed using thematic network analysis. Facilitators of the Agenda centred on the Agenda's ability to create political space for women and girls within the global HIV/AIDS response and the collaborative process of developing the Agenda. Barriers to the implementation and development of the Agenda include the limited financial and non-financial resources, the top-down nature of the Agenda's development and implementation and a lack of political will from within UNAIDS to implement it. We suggest that the Agenda achieved many goals, but its effect was constrained by a wide range of factors.
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A national survey of marine biotoxins in wild-caught abalone in australia.
J. Food Prot.
PUBLISHED: 11-04-2014
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The first national survey of Australian wild-caught abalone was conducted between September 2012 and December 2013. The aim of the survey was to determine the presence of paralytic shellfish toxins (PSTs), amnesic shellfish toxins (ASTs), and diarrhetic shellfish toxins (DSTs) in wild-caught abalone at levels above the current Codex marine biotoxin limits during the 2013 fishing season. Abalone (n = 190) were collected from 68 abalone-fishing blocks for which the combined annual harvest accounts for 80 % of Australian production. Concurrent seawater samples were collected and enumerated for potentially toxic phytoplankton. The foot and viscera tissues of each abalone sample were analyzed separately for PSTs, ASTs, and DSTs. No samples (abalone foot or viscera) contained toxins at levels exceeding the marine biotoxin limits stipulated by Codex. The resulting prevalence estimate suggests that less than 1.6 % of the commercially caught wild abalone population in Australia were contaminated with marine biotoxins at levels above the regulatory limit during the survey period. ASTs were detected at very low (trace) levels in the foot and viscera tissue of four and three abalone samples, respectively. To our knowledge, this represents the first reported detection of domoic acid in Australian abalone. PSTs also were detected at very low levels in 17 samples of abalone foot tissue and 6 samples of abalone viscera. The association between the low levels of ASTs and PSTs detected in abalone and the presence of potential toxin-producing phytoplankton in seawater samples was weak. DSTs were not detected in any abalone despite the detection of very low levels of DST-producing phytoplankton in a small number (9 of 77) of seawater samples. The results of this survey should be useful for public health risk assessments and provide additional evidence that the prevalence of marine biotoxins in Australian wild-caught abalone is very low.
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Can local communities 'sustain' HIV/AIDS programmes? A South African example.
Health Promot Int
PUBLISHED: 10-30-2014
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Globally, there is a renewed interest in building the local sustainability of HIV/AIDS programmes to ensure that once funders withdraw, local communities can sustain programmes. While the 'local sustainability assumption' is widespread, little research has assessed this. In this article, we assess the sustainability of the Entabeni Project, a community-based intervention that sought to build women's local leadership and capacity to respond to HIV/AIDS through a group of volunteer carers, 3 years after external support was withdrawn. Overall, the sustainability of the Entabeni Project was limited. The wider social and political context undermined volunteer carers' sense that they could affect change, with little external support for them from government and NGOs, who struggled to engage with local community organizations. At the community level, some church leaders and community members recognized the important role of health volunteers, many continued to devalue the work of the carers, especially once there was no external organization to support and validate their work. Within the health volunteer group, despite extensive efforts to change dynamics, it remained dominated by a local male leader who denied others active participation while lacking the skills to meaningfully lead the project. Our case study suggests that the local-sustainability assumption is wishful thinking. Small-scale local projects are unlikely to be able to challenge the broader social and political dynamics hindering their sustainability without meaningful external support.
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Genomic classification of serous ovarian cancer with adjacent borderline differentiates RAS-pathway and TP53-mutant tumors and identifies NRAS as an oncogenic driver.
Clin. Cancer Res.
PUBLISHED: 10-16-2014
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Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras-pathway mutated, TP53 wild-type, and frequently associated with borderline tumors. LGSC patients respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with Grade-2 or -3 carcinoma was an indicator of Ras mutation, and explored the molecular relationship between co-existing invasive and borderline histologies. Experimental Design: We reviewed >1200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses including candidate mutation screening, copy number and gene expression profiling. Results: We found a similar frequency of low, moderate and high-grade carcinomas with co-existing borderline histology. BRAF/KRAS alterations were common in LGSC, however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Co-existing borderline and invasive components showed near identical genomic profiles. Grade-2 cases with co-existing borderline included tumors with molecular features of LGSC, while others were typical of HGSC. However, all Grade-3 carcinomas with co-existing borderline histology were molecularly indistinguishable from typical HGSC. Conclusion: Our findings suggest NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras-pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents.
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Inhibition of cell expansion by rapid ABP1-mediated auxin effect on microtubules.
Nature
PUBLISHED: 09-23-2014
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The prominent and evolutionarily ancient role of the plant hormone auxin is the regulation of cell expansion. Cell expansion requires ordered arrangement of the cytoskeleton but molecular mechanisms underlying its regulation by signalling molecules including auxin are unknown. Here we show in the model plant Arabidopsis thaliana that in elongating cells exogenous application of auxin or redistribution of endogenous auxin induces very rapid microtubule re-orientation from transverse to longitudinal, coherent with the inhibition of cell expansion. This fast auxin effect requires auxin binding protein 1 (ABP1) and involves a contribution of downstream signalling components such as ROP6 GTPase, ROP-interactive protein RIC1 and the microtubule-severing protein katanin. These components are required for rapid auxin- and ABP1-mediated re-orientation of microtubules to regulate cell elongation in roots and dark-grown hypocotyls as well as asymmetric growth during gravitropic responses.
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Widespread Effects of Alcohol on White Matter Microstructure.
Alcohol. Clin. Exp. Res.
PUBLISHED: 09-05-2014
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Evidence suggests that chronic misuse of alcohol may preferentially affect the integrity of frontal white matter (WM) tracts, which can impact executive functions important to achieve and maintain abstinence.
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Using a Dedicated Education Unit Clinical Education Model With Second-Degree Accelerated Nursing Program Students.
J Nurs Educ
PUBLISHED: 09-03-2014
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Rising health care costs have underscored the need for new graduates to effectively transition to professional practice. Effective academic-practice partnerships, such as dedicated education units (DEUs), can be useful in facilitating the transfer of knowledge from the classroom to the clinical setting. This randomized experimental study found the DEU clinical model to be valuable in facilitating the transfer of knowledge in second-degree accelerated program students as evaluated by course, simulation, and standardized assessment scores and self-evaluations. Successful transition to clinical practice is reported by practice partners; time allotted for orientation program requirements was reduced and retention on the unit of hire was improved. Additional research is needed to understand the effectiveness of second-degree accelerated nursing programs and how to revise the clinical education element of the program to meet the unique needs of these students. [J Nurs Educ. 2014;53(x):xxx-xxx.].
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Approaches to Determination of a Full Profile of Blood Group Genotypes: Single Nucleotide Variant Mapping and Massively Parallel Sequencing.
Comput Struct Biotechnol J
PUBLISHED: 09-01-2014
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The number of blood group systems, currently 35, has increased in the recent years as genetic variations defining red cell antigens continue to be discovered. At present, 44 genes and 1568 alleles have been defined as encoding antigens within the 35 blood group systems. This paper provides a brief overview of two genetic technologies: single nucleotide variant (SNV) mapping by DNA microarray and massively parallel sequencing, with respect to blood group genotyping. The most frequent genetic change associated with blood group antigens are SNVs. To predict blood group antigen phenotypes, SNV mapping which involves highly multiplexed genotyping, can be performed on commercial microarray platforms. Microarrays detect only known SNVs, therefore, to type rare or novel alleles not represented in the array, further Sanger sequencing of the region is often required to resolve genotype. An example discussed in this article is the identification of rare and novel RHD alleles in the Australian population. Massively parallel sequencing, also known as next generation sequencing, has a high-throughput capacity and maps all points of variation from a reference sequence, allowing for identification of novel SNVs. Examples of the application of this technology to resolve the genetic basis of orphan blood group antigens are presented here. Overall, the determination of a full profile of blood group SNVs, in addition to serological phenotyping, provides a basis for provision of compatible blood thus offering improved transfusion safety.
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Paralytic shellfish toxins, including deoxydecarbamoyl-STX, in wild-caught Tasmanian abalone (Haliotis rubra).
Toxicon
PUBLISHED: 08-23-2014
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For the first time wild-caught Tasmanian abalone, Haliotis rubra, have been reported to contain paralytic shellfish toxins (PSTs). This observation followed blooms of the toxic dinoflagellate Gymnodinium catenatum. No illnesses were reported, but harvesting restrictions were enforced in commercial areas. Abalone were assayed using HPLC-FLD methodology based on AOAC official method 2005.06. An uncommon congener, deoxydecarbamoyl-STX (doSTX), was observed in addition to regulated PSTs as unassigned chromatographic peaks. A quantitative reference material was prepared from contaminated Tasmanian abalone viscera and ampouled at 54.2 ?mol/L. The LD50 of doSTX via intraperitoneal injection was 1069 nmol/kg (95% confidence limits 983-1100 nmol/kg), indicating it is nearly 40 times less toxic than STX. A toxicity equivalence factor of 0.042 was generated using the mouse bioassay. Levels of PSTs varied among individuals from the same site, although the toxin profile remained relatively consistent. In the foot tissue, STX, decarbamoyl-STX and doSTX were identified. On a molar basis doSTX was the dominant congener in both foot and viscera samples. The viscera toxin profile was more complex, with other less toxic PST congeners observed and was similar to mussels from the same site. This finding implicates localised dinoflagellate blooms as the PST source in Tasmanian abalone.
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First versus second generation electronic cigarettes: predictors of choice and effects on urge to smoke and withdrawal symptoms.
Addiction
PUBLISHED: 08-08-2014
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To 1) estimate predictors of first vs. second generation electronic cigarette (e-cigarette) choice; 2) determine whether a second generation device was i) superior for reducing urge to smoke and withdrawal symptoms (WS) and ii) associated with enhanced positive subjective effects.
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Long term follow up of high risk children: who, why and how?
BMC Pediatr
PUBLISHED: 07-23-2014
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Most babies are born healthy and grow and develop normally through childhood. There are, however, clearly identifiable high-risk groups of survivors, such as those born preterm or with ill-health, who are destined to have higher than expected rates of health or developmental problems, and for whom more structured and specialised follow-up programs are warranted.
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From rhetoric to reality? Putting HIV and AIDS rights talk into practice in a South African rural community.
Cult Health Sex
PUBLISHED: 07-08-2014
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Whilst international rhetoric on HIV and AIDS frequently invokes discourses of human rights to inspire and guide action, translating universal rights talk into practice in specific settings remains a challenge. Community mobilisation is often strategy of choice. We present a case study of the Entabeni Project in South Africa - in which a foreign-funded NGO sought to work with female health volunteers in a deep rural community to increase their access to two HIV-relevant rights: women's rights (especially gender equality) and rights to health (especially access to HIV- and AIDS-related services). Whilst the project had short-term health-related successes, it was less successful in implementing a gender empowerment agenda. The concept of women's rights had no purchase with women who had little interest in directly challenging male power, foregrounding the fight against poverty as their main preoccupation. The area's traditional chief and gatekeeper insisted the project should remain 'apolitical'. Project funders prioritised 'numbers reached' over a gender empowerment orientation. In the absence of (1) a marginalised group who are willing to assert their rights; and (2) a context where powerful people are willing to support these claims, 'rights' may be a blunt tool for HIV-related work with women in deeply oppressive and remote rural communities beyond the reach of international treaties and urban-based activist movements.
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The contribution of schools to supporting the well being of children affected by HIV in eastern Zimbabwe.
AIDS
PUBLISHED: 07-04-2014
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Schools are often cited as a source of support for orphans and children affected by HIV/AIDS in populations experiencing generalized HIV epidemics and severe poverty. Here we investigate the success of schools at including and supporting the well being of vulnerable children in rural Zimbabwe.
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Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure.
Am. J. Physiol. Regul. Integr. Comp. Physiol.
PUBLISHED: 07-02-2014
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Central oxytocin reduces food intake and increases energy expenditure. The ventromedial hypothalamic nucleus (VMN) is associated with energy balance and contains a high density of oxytocin receptors. We hypothesized that oxytocin in the VMN is a negative regulator of energy balance acting to reduce feeding and increase energy expenditure. To test this idea, oxytocin or vehicle was injected directly into the VMN of Sprague-Dawley rats during fasted and nonfasted conditions. Energy expenditure (via indirect calorimetry) and spontaneous physical activity (SPA) were recorded simultaneously. Animals were also exposed to a conditioned taste aversion test, to determine whether oxytocin's effects on food intake were associated with malaise. When food was available during testing, oxytocin-induced elevations in energy expenditure lasted for 1 h, after which overall energy expenditure was reduced. In the absence of food during the testing period, oxytocin similarly increased energy expenditure during the first hour, but differences in 12-h energy expenditure were eliminated, implying that the differences may have been due to the thermic effects of feeding (digestion, absorption, and metabolic processing). Oxytocin acutely elevated SPA and reduced feeding at doses that did not cause a conditioned taste aversion during both the fed and fasted states. Together, these data suggest that oxytocin in the VMN promotes satiety and acutely elevates energy expenditure and SPA and implicates the VMN as a relevant site for the antiobesity effects of oxytocin.
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Molecular typing for the Indian blood group associated 252G>C single nucleotide polymorphism in a selected cohort of Australian blood donors.
Blood Transfus
PUBLISHED: 06-25-2014
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The Indian blood group antigens, In(a) and In(b), are clinically significant in transfusion medicine. However, antisera to type these antigens are difficult to obtain. The In(b) antigen is a high frequency antigen present in all populations, while the frequency of the antithetical In(a) ranges from 0.1% in Caucasians up to 11% in Middle Eastern groups. This antigen polymorphism is encoded by the single nucleotide polymorphism (SNP) 252G>C in CD44. The aim of this study was to establish and compare two genotyping methods to measure the frequency of the IN*A and IN*B alleles in a blood donor cohort.
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[Improving the management of rare brain cancers with the POLA network].
Rev Infirm
PUBLISHED: 06-03-2014
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The national POLA network is dedicated to the management of certain rare brain tumours, mainly anaplastic oligodendrogliomas, anaplastic oligoastrocytomas and glioblastomas with oligodendroglioma component. The nursing team and the patient are at the heart of the organisation.
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White Matter and Cognitive Changes in Veterans Diagnosed with Alcoholism and PTSD.
J Alcohol Drug Depend
PUBLISHED: 05-24-2014
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Alcoholism frequently occurs in returning U.S. Veterans, and is often comorbid with Post Traumatic Stress Disorder (PTSD). The goal of this study was to investigate the relationship between white matter changes and neuropsychological alterations in Operation Enduring Freedom, and/or Operation Iraqi Freedom (OEF/OIF) alcoholic Veterans with two primary aims: (1) to examine the relationship of alcoholism to brain structure and function while controlling for the potential effects of comorbid PTSD, and (2) to examine whether the effects of alcoholism are moderated by the quantity of lifetime alcohol consumption. Our sample consisted of 71 deployed OEF/OIF Veterans stratified into four groups: alcoholics without PTSD, alcoholics with PTSD, participants with PTSD without comorbid alcoholism, and control participants without alcoholism or PTSD. Participants were given an extensive neuropsychological and psychiatric assessment battery, as well as Magnetic Resonance Diffusion Tensor Imaging (DT-MRI) scans. Results showed that disruption of executive functioning, and abnormal fractional anisotropy (FA; a measure of axonal integrity) within the frontal subcortical and dorsolateral frontal-parietal regions, occurred independently of the effects of PTSD. Furthermore, these cognitive and neuronal alterations were unique to the most severe subgroup of alcoholics who consumed the greatest amount of alcohol over the course of their lifetime, as compared to the rest of the sample. Axonal integrity within this subgroup, in regions underlying the frontal subcortical area, was shown to be decreased independently of cognitive changes. Integrity of axons underlying the dorsolateral frontal-parietal region, however, was increased. We hypothesized that this is a compensatory mechanism for executive dysfunction.
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Do Serrated Neoplasms of the Small Intestine Represent a Distinctive Entity? Pathological Findings and Molecular Alterations in a Series of 13 cases.
Histopathology
PUBLISHED: 05-20-2014
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To characterise pathological, immunohistochemical and molecular features of small intestinal serrated neoplasms.
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The laboratory mouse in routine food safety testing for marine algal biotoxins and harmful algal bloom toxin research: past, present and future.
J AOAC Int
PUBLISHED: 05-17-2014
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Mouse bioassays have been a mainstay for detecting harmful concentrations of marine algal toxins in shellfish for over 70 years. Routine monitoring involves intraperitoneal injection of shellfish extracts into mice; shellfish contaminated with algal toxins are thus identified by mortality in exposed mice. With the advent of alternative test methods to detect and quantify specific algal toxins has come increasing criticism of enduring use of mouse bioassays for shellfish safety testing. However, the complete replacement of shellfish safety mouse bioassays by chemical, antibody-based, and functional assays has been and will continue to be a gradual process for various reasons, including skills availability and instrument costs for chromatography-based toxin monitoring. Mouse bioassays for shellfish safety testing do not comply with modern standards for laboratory animal welfare, specifically the requirement in published official methods for death as a test outcome. Mouse bioassays for algal biotoxins in shellfish, as well as fundamental algal toxin research endeavors using in vivo models, are amenable to revision and refinement from a humane endpoints perspective. Regulated hypothermia may be a useful and easily acquired nonlethal toxicological endpoint; objective determination of neuromuscular blockade may allow algal neurotoxin testing and research to enter the domain of humane endpoints evaluation. Relinquishing reliance on subjective test endpoints, including death, will likely also deliver collateral improvements in assay variability and sensitivity.
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Supplementary prognostic variables for pleural mesothelioma: a report from the IASLC staging committee.
J Thorac Oncol
PUBLISHED: 05-09-2014
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The staging system for malignant pleural mesothelioma is controversial. To revise this system, the International Association for the Study of Lung Cancer Staging Committee developed an international database. This report analyzes prognostic variables in a surgical population, which are supplementary to previously published CORE variables (stage, histology, sex, age, and type of procedure).
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Use of a caspase multiplexing assay to determine apoptosis in a hypothalamic cell model.
J Vis Exp
PUBLISHED: 05-07-2014
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The ability to multiplex assays in studies of complex cellular mechanisms eliminates the need for repetitive experiments, provides internal controls, and decreases waste in costs and reagents. Here we describe optimization of a multiplex assay to assess apoptosis following a palmitic acid (PA) challenge in an in vitro hypothalamic model, using both fluorescent and luminescent based assays to measure viable cell counts and caspase-3/7 activity in a 96-well microtiter plate format. Following PA challenge, viable cells were determined by a resazurin-based fluorescent assay. Caspase-3/7 activity was then determined using a luminogenic substrate, DEVD, and normalized to cell number. This multiplexing assay is a useful technique for determining change in caspase activity following an apoptotic stimulus, such as saturated fatty acid challenge. The saturated fatty acid PA can increase hypothalamic oxidative stress and apoptosis, indicating the potential importance of assays such as that described here in studying the relationship between saturated fatty acids and neuronal function.
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A survey of Australian oysters for the presence of human noroviruses.
Food Microbiol.
PUBLISHED: 04-29-2014
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Impending international policies for norovirus in oysters and the lack of Australian data suggested there was a need to undertake a national survey of norovirus in oysters. Two geographically distinct oyster-growing areas from each of three Australian states were sampled on 4 occasions during 2010 and 2011. The sites selected were considered by state shellfish authorities to be the most compromised with respect to the potential for human faecal contamination as identified by shoreline surveys. The oysters were tested for norovirus GI, GII and Escherichia coli. Norovirus GII was detected in two of 120 (1.7%) samples and norovirus GI was not detected. One of the norovirus positive samples was cloned and sequenced as GII.3. Five of 120 (4.2%) samples were found to have more than the guidance concentration of 230 E. coli per 100 g of shellfish but these samples did not contain detectable concentrations of norovirus. The apparently low prevalence of norovirus in oysters from Australian growing areas supports epidemiological data that suggests norovirus contamination of Australian oysters is rare. The results from this study emphasise the need for future norovirus control measures for shellfish to be commensurate with the risk associated with the growing area.
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Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats.
Physiol. Behav.
PUBLISHED: 04-18-2014
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Anorexia nervosa (AN) is a chronic eating disorder affecting females and males, defined by body weight loss, higher physical activity levels and restricted food intake. Currently, the commonalities and differences between genders in etiology of AN are not well understood. Animal models of AN, such as activity-based anorexia (ABA), can be helpful in identifying factors determining individual susceptibility to AN. In ABA, rodents are given an access to a running wheel while food restricted, resulting in paradoxical increased physical activity levels and weight loss. Recent studies suggest that different behavioral traits, including voluntary exercise, can predict individual weight loss in ABA. A higher inherent drive for movement may promote development and severity of AN, but this hypothesis remains untested. In rodents and humans, drive for movement is defined as spontaneous physical activity (SPA), which is time spent in low-intensity, non-volitional movements. In this paper, we show that a profile of body weight history and behavioral traits, including SPA, can predict individual weight loss caused by ABA in male and female rats with high accuracy. Analysis of the influence of SPA on ABA susceptibility in males and females rats suggests that either high or low levels of SPA increase the probability of high weight loss in ABA, but with larger effects in males compared to females. These results suggest that the same behavioral profile can identify individuals at-risk of AN for both male and female populations and that SPA has predictive value for susceptibility to AN.
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Children's representations of school support for HIV-affected peers in rural Zimbabwe.
BMC Public Health
PUBLISHED: 04-08-2014
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HIV has left many African children caring for sick relatives, orphaned or themselves HIV-positive, often facing immense challenges in the absence of significant support from adults. With reductions in development funding, public sector budgetary constraints, and a growing emphasis on the importance of indigenous resources in the HIV response, international policy allocates schools a key role in 'substituting for families' (Ansell, 2008) in supporting child health and well-being. We explore children's own accounts of the challenges facing their HIV-affected peers and the role of schools in providing such support.
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Community resistance to a peer education programme in Zimbabwe.
BMC Health Serv Res
PUBLISHED: 04-04-2014
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BackgroundThis paper presents community perceptions of a state-of-the-art peer education programme in Manicaland, Zimbabwe. While the intervention succeeded in increasing HIV knowledge among men and condom acceptability among women, and reduced HIV incidence and rates of unprotected sex among men who attended education events, it did not succeed in reducing population-level HIV incidence. To understand the possible reasons for this disappointing result, we conducted a qualitative study of local perspectives of the intervention.MethodsEight focus group discussions and 11 interviews with 81 community members and local project staff were conducted. Transcripts were interrogated and analysed thematically.ResultsWe identified three factors that may have contributed to the programme¿s disappointing outcomes: (1) difficulties of implementing all elements of the programme, particularly the proposed income generation component in the wider context of economic strain; (2) a moralistic approach to commercial sex work by programme staff; and (3) limitations in the programme¿s ability to engage with social realities facing community members.ConclusionsWe conclude that externally-imposed programmes that present new information without adequately engaging with local realities and constraints on action can be met by resistance to change.
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Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons.
Neurobiol Learn Mem
PUBLISHED: 04-01-2014
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Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF.
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Duration of participation in continuous quality improvement: a key factor explaining improved delivery of Type 2 diabetes services.
BMC Health Serv Res
PUBLISHED: 03-29-2014
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BackgroundIt is generally recognised that continuous quality improvement (CQI) programs support development of high quality primary health care systems. However, there is limited evidence demonstrating their system-wide effectiveness. We examined variation in quality of Type 2 diabetes service delivery in over 100 Aboriginal and Torres Strait Islander primary health care centres participating in a wide-scale CQI project over the past decade, and determined the influence of health centre and patient level factors on quality of care, with specific attention to health centre duration of participation in a CQI program.MethodsWe analysed over 10,000 clinical audit records to assess quality of Type 2 diabetes care of patients in 132 Aboriginal and Torres Strait Islander community health centres in five states/territories participating in the ABCD project for varying periods between 2005 and 2012. Process indicators of quality of care for each patient were calculated by determining the proportion of recommended guideline scheduled services that were documented as delivered. Multilevel regression models were used to quantify the amount of variation in Type 2 diabetes service delivery attributable to health centre or patient level factors and to identify those factors associated with greater adherence to best practice guidelines.ResultsHealth centre factors that were independently associated with adherence to best practice guidelines included longer participation in the CQI program, remoteness of health centres, and regularity of client attendance. Significantly associated patient level variables included greater age, and number of co-morbidities and disease complications. Health centre factors explained 37% of the differences in level of service delivery between jurisdictions with patient factors explaining only a further 1%.ConclusionsAt the health centre level, Type 2 diabetes service delivery could be improved through long term commitment to CQI, encouraging regular attendance (for example, through patient reminder systems) and improved recording and coordination of patient care in the complex service provider environments that are characteristic of non-remote areas.
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Contextualising women's mental distress and coping strategies in the time of AIDS: A rural South African case study.
Transcult Psychiatry
PUBLISHED: 03-26-2014
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Increasing attention is paid to impacts of HIV/AIDS on women's mental health, often framed by decontextualized psychiatric understandings of emotional distress and treatment. We contribute to the small qualitative literature extending these findings through exploring HIV/AIDS-affected women's own accounts of their distress-focusing on the impacts of social context, and women's efforts to cope outside of medical support services. Nineteen in-depth interviews were conducted with women experiencing depression or anxiety-like symptoms in a wider study of services in KwaZulu-Natal, South Africa. Thematic analysis was framed by Summerfield's emphasis on contexts and resilience. Women highlighted family conflicts (particularly abandonment by men), community-level violence, poverty and HIV/AIDS as drivers of distress. Whilst HIV/AIDS placed significant burdens on women, poverty and relationship difficulties were more central in their accounts. Four coping mechanisms were identified. Women drew on indigenous local resources in their psychological re-framing of negative situations, and their mobilisation of emotional and financial support from inter-personal networks, churches and HIV support groups. Less commonly, they sought expert advice from traditional healers, medical services or social workers, but access to these was limited. Though all tried to supplement government grants with income generation efforts, only a minority regarded these as successful. Findings support ongoing efforts to bolster strained mental health services with support groups, which often offer valuable emotional and practical support. Without parallel poverty alleviation strategies, however, support groups may sometimes offer little more than encouraging passive acceptance of the inevitability of suffering-potentially exacerbating the hopelessness underpinning women's distress.
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The impact of Community Mobilisation on HIV Prevention in Middle and Low Income Countries: A Systematic Review and Critique.
AIDS Behav
PUBLISHED: 03-25-2014
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While community mobilisation (CM) is increasingly advocated for HIV prevention, its impact on measurable outcomes has not been established. We performed a systematic review of the impact of CM within HIV prevention interventions (N = 20), on biomedical, behavioural and social outcomes. Among most at risk groups (particularly sex workers), the evidence is somewhat consistent, indicating a tendency for positive impact, with stronger results for behavioural and social outcomes than for biomedical ones. Among youth and general communities, the evidence remains inconclusive. Success appears to be enhanced by engaging groups with a strong collective identity and by simultaneously addressing the socio-political context. We suggest that the inconclusiveness of the findings reflects problems with the evidence, rather than indicating that CM is ineffective. We discuss weaknesses in the operationalization of CM, neglect of social context, and incompatibility between context-specific CM processes and the aspiration of review methodologies to provide simple, context-transcending answers.
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The impact of HIV on children's education in eastern Zimbabwe.
AIDS Care
PUBLISHED: 03-14-2014
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Little is known about how HIV impacts directly and indirectly on receiving, or particularly succeeding in, education in sub-Saharan Africa. To address this gap, we used multivariable logistic regression to determine the correlation between education outcomes in youth (aged 15-24) (being in the correct grade-for-age, primary school completion and having at least five "O" level passes) and being HIV-positive; having an HIV-positive parent; being a young carer; or being a maternal, paternal or double orphan, in five rounds (1998-2011) of a general population survey from eastern Zimbabwe. The fifth survey round (2009-2011) included data on children aged 6-17, which were analysed for the impacts of the above risk factors on regular attendance in primary and secondary schools and being in the correct grade-for-age. For data pooled over all rounds, being HIV-positive had no association with primary school completion, "O" level passes, or being in the correct grade-for-age in adolescents aged 16-17 years. Additionally, HIV status had no significant association with any education outcomes in children aged 6-17 surveyed in 2009-2011. In 2009-2011, being a young carer was associated with lower attendance in secondary school (69% vs. 85%, AOR: 0.44; p=0.02), whilst being a maternal (75% vs. 83%, AOR: 0.67; p<0.01), paternal (76% vs. 83%, AOR: 0.67; p=0.02) or double (75% vs. 83%, AOR: 0.68; p=0.02) orphan was associated with decreased odds of being in the correct grade-for-age. All forms of orphanhood also significantly decreased the odds of primary school completion in youths surveyed from 1998 to 2011 (all p<0.01). We found no evidence that HIV status affects education but further evidence that orphans do experience worse education outcomes than other children. Combination approaches that provide incentives for children to attend school and equip schools with tools to support vulnerable children may be most effective in improving education outcomes and should be developed and evaluated.
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Methodological considerations for measuring spontaneous physical activity in rodents.
Am. J. Physiol. Regul. Integr. Comp. Physiol.
PUBLISHED: 03-05-2014
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When exploring biological determinants of spontaneous physical activity (SPA), it is critical to consider whether methodological factors differentially affect rodents and the measured SPA. We determined whether acclimation time, sensory stimulation, vendor, or chamber size affected measures in rodents with varying propensity for SPA. We used principal component analysis to determine which SPA components (ambulatory and vertical counts, time in SPA, and distance traveled) best described the variability in SPA measurements. We compared radiotelemetry and infrared photobeams used to measure SPA and exploratory activity. Acclimation time, sensory stimulation, vendor, and chamber size independently influenced SPA, and the effect was moderated by the propensity for SPA. A 24-h acclimation period prior to SPA measurement was sufficient for habituation. Principal component analysis showed that ambulatory and vertical measurements of SPA describe different dimensions of the rodent's SPA behavior. Smaller testing chambers and a sensory attenuation cubicle around the chamber reduced SPA. SPA varies between rodents purchased from different vendors. Radiotelemetry and infrared photobeams differ in their sensitivity to detect phenotypic differences in SPA and exploratory activity. These data highlight methodological considerations in rodent SPA measurement and a need to standardize SPA methodology.
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The RHD(1227G>A)?DEL-associated allele is the most prevalent DEL allele in Australian D- blood donors with C+ and/or E+ phenotypes.
Transfusion
PUBLISHED: 02-20-2014
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Red blood cells (RBCs) with D antigen levels only detected by anti-D adsorption-elution and an antiglobulin test express a DEL phenotype. For two DEL types, including RHD(1227G>A), immunization of D- recipients has been reported. This study's aim was to measure the prevalence of DEL-associated RHD alleles in a cohort of Australian D- donors to develop a model to estimate alloimmunization risk.
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Increased expression of GCNT1 is associated with altered O-glycosylation of PSA, PAP, and MUC1 in human prostate cancers.
Prostate
PUBLISHED: 02-19-2014
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Protein glycosylation is a common posttranslational modification and glycan structural changes have been observed in several malignancies including prostate cancer. We hypothesized that altered glycosylation could be related to differences in gene expression levels of glycoprotein synthetic enzymes between normal and malignant prostate tissues.
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Effects of OEF/OIF-related physical and emotional co-morbidities on associative learning: concurrent delay and trace eyeblink classical conditioning.
Int J Environ Res Public Health
PUBLISHED: 02-19-2014
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This study examined the performance of veterans and active duty personnel who served in Operation Enduring Freedom and/or Operation Iraqi Freedom (OEF/OIF) on a basic associative learning task. Eighty-eight individuals participated in this study. All received a comprehensive clinical evaluation to determine the presence and severity of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). The eyeblink conditioning task was composed of randomly intermixed delay and trace conditioned stimulus (CS) and unconditioned stimulus (US) pairs (acquisition) followed by a series of CS only trials (extinction). Results revealed that those with a clinical diagnosis of PTSD or a diagnosis of PTSD with comorbid mTBI acquired delay and trace conditioned responses (CRs) to levels and at rates similar to a deployed control group, thus suggesting intact basic associative learning. Differential extinction impairment was observed in the two clinical groups. Acquisition of CRs for both delay and trace conditioning, as well as extinction of trace CRs, was associated with alcoholic behavior across all participants. These findings help characterize the learning and memory function of individuals with PTSD and mTBI from OEF/OIF and raise the alarming possibility that the use of alcohol in this group may lead to more significant cognitive dysfunction.
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Impact of living with kin/non-kin on the life history traits of Tetranychus urticae (Acari: Tetranychidae).
Exp. Appl. Acarol.
PUBLISHED: 02-18-2014
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In many vertebrates and invertebrates, living in a group may influence the life history traits, physiology and behaviour of its individual members, whereas genetic relatedness affects social interactions among individuals in a group. The two-spotted spider mite Tetranychus urticae is characterised by a communal organization, in which silk production plays a key role. A silken web protects the colony against biotic and abiotic agents such as predators, competitors, humidity, wind, rain and acaricides. To evaluate the potential costs and benefits of being associated with genetically distant vs genetically close individuals in T. urticae, we assessed various fitness indicators (faecal pellet production, fecundity, death rate) in pure and mixed groups of two distinct populations of T. urticae: a red-form population from Tunisia and a green-form population from Belgium. If genetic origin had no influence, the values of fitness indicators in mixed groups composed of green and red individuals, would be intermediate between those of the pure green-form and red-form groups. Our results show that in a mixed group, faecal pellet production and death rate were statistically similar to the values obtained in the pure group of green-form individuals. Therefore, our study suggests that strain recognition ability may occur in T. urticae and that the genetic background of an individual may have a great impact on several of its life history traits.
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Opioid prescribing patterns for non-malignant chronic pain for rural versus non-rural US adults: a population-based study using 2010 NAMCS data.
BMC Health Serv Res
PUBLISHED: 01-31-2014
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BackgroundNon-malignant chronic pain (NMCP) is one of the most common reasons for primary care visits. Pain management health care disparities have been documented in relation to patient gender, race, and socioeconomic status. Although not studied in relation to chronic pain management, studies have found that living in a rural community in the US is associated with health care disparities. Rurality as a social determinant of health may influence opioid prescribing. We examined rural and non-rural differences in opioid prescribing patterns for NMCP management, hypothesizing that distinct from education, income, racial or gender differences, rural residency is a significant and independent factor in opioid prescribing patterns.Methods2010 National Ambulatory Medical Care Survey (NAMCS) data were examined using bivariate and multivariate techniques. NAMCS data are collected using a multi-stage sampling strategy. For the multivariate analysis performed the SPSS complex samples algorithm for logistic regression was used.ResultsIn 2010 an estimated 9,325,603 US adults (weighted from a sample of 2745) seen in primary care clinics had a diagnosis of NMCP; 36.4% were prescribed an opioid. For US adults with a NMCP diagnosis bivariate analysis revealed rural residents had higher odds of having an opioid prescription than similar non-rural adults (OR¿=¿1.515, 95% CI 1.513-1.518). Complex samples logistic regression analysis confirmed the importance of rurality and yielded that US adults with NMCP who were prescribed an opioid had higher odds of: being non-Caucasian (AOR =2.459, 95% CI 1.194-5.066), and living in a rural area (AOR =2.935, 95% CI 1.416-6.083).ConclusionsOur results clearly indicated that rurality is an important factor in opioid prescribing patterns that cannot be ignored and bears further investigation. Further research on the growing concern about the over-prescribing of opioids in the US should now include rurality as a variable in data generation and analysis. Future research should also attempt to document the ecological, sociological and political factors impacting opioid prescribing and care in rural communities. Prescribers and health care policy makers need to critically evaluate the implications of our findings and their relationship to patient needs, best practices in a rural setting, and the overall consequences of increased opioid prescribing on rural communities.
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Liver toxicity prediction with stereotactic body radiation therapy: The impact of accounting for fraction size.
Pract Radiat Oncol
PUBLISHED: 01-28-2014
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Current liver SBRT protocols rely on the calculation of "effective volume" without accounting for the biologic effect of fraction size to estimate the risk of liver toxicity, which subsequently defines tumor prescription doses. This study compared effective volume and liver toxicity predictions with and without correction for fraction size.
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Proteomic strategies for the discovery of novel diagnostic and therapeutic targets for infectious diseases.
Pathog Dis
PUBLISHED: 01-18-2014
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Viruses have developed numerous and elegant strategies to manipulate the host cell machinery to establish a productive infectious cycle. The interaction of viral proteins with host proteins plays an important role in infection and pathogenesis, often bypassing traditional host defenses such as the interferon response and apoptosis. Host-viral protein interactions can be studied using a variety of proteomic approaches ranging from genetic and biochemical to large-scale high-throughput technologies. Protein interactions between host and viral proteins are greatly influenced by host signal transduction pathways. In this review, we will focus on comparing proteomic information obtained through differing technologies and how their integration can be used to determine the functional aspect of the host response to infection. We will briefly review and evaluate techniques employed to elucidate viral-host interactions with a primary focus on Protein Microarrays (PMA) and Mass Spectrometry (MS) as potential tools in the discovery of novel therapeutic targets. As many potential molecular markers and targets are proteins, proteomic profiling is expected to yield both clearer and more direct answers to functional and pharmacologic questions.
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AUXIN BINDING PROTEIN1 links cell wall remodeling, auxin signaling, and cell expansion in arabidopsis.
Plant Cell
PUBLISHED: 01-14-2014
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Cell expansion is an increase in cell size and thus plays an essential role in plant growth and development. Phytohormones and the primary plant cell wall play major roles in the complex process of cell expansion. In shoot tissues, cell expansion requires the auxin receptor AUXIN BINDING PROTEIN1 (ABP1), but the mechanism by which ABP1 affects expansion remains unknown. We analyzed the effect of functional inactivation of ABP1 on transcriptomic changes in dark-grown hypocotyls and investigated the consequences of gene expression on cell wall composition and cell expansion. Molecular and genetic evidence indicates that ABP1 affects the expression of a broad range of cell wall-related genes, especially cell wall remodeling genes, mainly via an SCF(TIR/AFB)-dependent pathway. ABP1 also functions in the modulation of hemicellulose xyloglucan structure. Furthermore, fucosidase-mediated defucosylation of xyloglucan, but not biosynthesis of nonfucosylated xyloglucan, rescued dark-grown hypocotyl lengthening of ABP1 knockdown seedlings. In muro remodeling of xyloglucan side chains via an ABP1-dependent pathway appears to be of critical importance for temporal and spatial control of cell expansion.
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Chest Computed Tomography Findings in HIV-Infected Individuals in the Era of Antiretroviral Therapy.
PLoS ONE
PUBLISHED: 01-01-2014
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Chest radiographic abnormalities were common in HIV-infected individuals in the pre-combination antiretroviral therapy era, but findings may differ now due to a changing spectrum of pulmonary complications.
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Is the radiographic subsidence of stand-alone cages associated with adverse clinical outcomes after cervical spine fusion? An observational cohort study with 2-year follow-up outcome scoring.
Patient Saf Surg
PUBLISHED: 01-01-2014
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The stand-alone treatment of degenerative cervical spine pathologies is a proven method in clinical practice. However, its impact on subsidence, the resulting changes to the profile of the cervical spine and the possible influence of clinical results compared to treatment with additive plate osteosynthesis remain under discussion until present.
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The orexin neuropeptide system: physical activity and hypothalamic function throughout the aging process.
Front Syst Neurosci
PUBLISHED: 01-01-2014
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There is a rising medical need for novel therapeutic targets of physical activity. Physical activity spans from spontaneous, low intensity movements to voluntary, high-intensity exercise. Regulation of spontaneous and voluntary movement is distributed over many brain areas and neural substrates, but the specific cellular and molecular mechanisms responsible for mediating overall activity levels are not well understood. The hypothalamus plays a central role in the control of physical activity, which is executed through coordination of multiple signaling systems, including the orexin neuropeptides. Orexin producing neurons integrate physiological and metabolic information to coordinate multiple behavioral states and modulate physical activity in response to the environment. This review is organized around three questions: (1) How do orexin peptides modulate physical activity? (2) What are the effects of aging and lifestyle choices on physical activity? (3) What are the effects of aging on hypothalamic function and the orexin peptides? Discussion of these questions will provide a summary of the current state of knowledge regarding hypothalamic orexin regulation of physical activity during aging and provide a platform on which to develop improved clinical outcomes in age-associated obesity and metabolic syndromes.
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Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression.
Neuro-oncology
PUBLISHED: 12-18-2013
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BackgroundThe aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs).MethodsThe MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays.ResultsMost of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2.ConclusionIn AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.
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Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas.
Neuro-oncology
PUBLISHED: 12-12-2013
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BackgroundDiffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs.MethodsWe characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis.ResultsOur study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs.ConclusionNovel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings.
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Role of the locus coeruleus in enhanced orexin A-induced spontaneous physical activity in obesity-resistant rats.
Am. J. Physiol. Regul. Integr. Comp. Physiol.
PUBLISHED: 10-02-2013
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Orexin/hypocretin terminals innervate noradrenergic locus coeruleus (LC) neurons that project to the prefrontral cortex, which may influence spontaneous physical activity (SPA) and energy balance. Obesity-resistant (OR) rats have higher orexin receptors (OXR) mRNA in the LC and other brain regions, as well as lower adiposity compared with obese rats. These findings led us to hypothesize that orexin activity in the LC is relevant for the OR phenotype. We compared OR rats to Sprague-Dawley rats. We predicted that: 1) brain OXR expression pattern is sufficient to differentiate OR from non-bred Sprague-Dawley rats; 2) nonresting energy expenditure (NREE) and orexin A (OXA)-stimulated SPA after injection in LC would be greater in OR rats; and 3) the effect of OXA on SPA would be greater than its effect on feeding. OXR mRNA from 11 brain sites and the SPA and feeding responses to OXA in the LC were determined. Body composition, basal SPA, and EE were determined. Principal component analysis of the OXR expression pattern differentiates OR and Sprague-Dawley rats and suggests the OXR mRNA in the LC is important in defining the OR phenotype. Compared with Sprague-Dawley rats, OR rats had greater SPA and NREE and lower resting EE and adiposity. SPA responsivity to OXA in the LC was greater in OR rats compared with Sprague-Dawley rats. OXA in the LC did not stimulate feeding in OR or Sprague-Dawley rats. These data suggest that the LC is a prominent site modulating OXA-stimulated SPA, which promotes lower adiposity and higher nonresting EE.
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Beyond ideal speech situations: Adapting to communication asymmetries in health care.
J Health Psychol
PUBLISHED: 09-20-2013
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Inclusive, unconstrained and honest communication is widely advocated as beneficial and ethical. We critically explore this assumption by reflecting upon our research in acute care, informal care and public health. Using Habermas ideals of dialogue to conceptualise ideal speech, we concur with observations that health care is often characterised by intractable exclusions and constraints. Rather than advocating implementing the ideals of dialogue, however, we examine how people adapt to these difficult and intransigent contexts. Non-ideal contexts, we find, sometimes call for non-ideal responses. Deception and furthering personal interests, and thus departing from the ideals of dialogue, can be adaptive responses.
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HIV/AIDS, beersellers and critical community health psychology in Cambodia: A case study.
J Health Psychol
PUBLISHED: 09-20-2013
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This case study illustrates a participatory framework for confronting critical community health issues using grass-roots research-guided community-defined interventions. Ongoing work in Cambodia has culturally adapted research, theory and practice for particular, local health-promotion responses to HIV/AIDS, alcohol abuse and other challenges in the community of Siem Reap. For resource-poor communities in Cambodia, we recycle such older concepts as empowerment and action research. We re-imagine community health psychology, when confronted with critical, life-and-death issues, as adjusting its research and practices to local, particular ontological and epistemological urgencies of trauma, morbidity and mortality.
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Grassroots community organizations contribution to the scale-up of HIV testing and counselling services in Zimbabwe.
AIDS
PUBLISHED: 09-20-2013
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To investigate whether community engagement (participation in grassroots organizations) contributed to increases in HIV testing in Zimbabwe.
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Orexin: pathways to obesity resistance?
Rev Endocr Metab Disord
PUBLISHED: 09-06-2013
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Obesity has increased in prevalence worldwide, attributed in part to the influences of an obesity-promoting environment and genetic factors. While obesity and overweight increasingly seem to be the norm, there remain individuals who resist obesity. We present here an overview of data supporting the idea that hypothalamic neuropeptide orexin A (OXA; hypocretin 1) may be a key component of brain mechanisms underlying obesity resistance. Prior work with models of obesity and obesity resistance in rodents has shown that increased orexin and/or orexin sensitivity is correlated with elevated spontaneous physical activity (SPA), and that orexin-induced SPA contributes to obesity resistance via increased non-exercise activity thermogenesis (NEAT). However, central hypothalamic orexin signaling mechanisms that regulate SPA remain undefined. Our ongoing studies and work of others support the hypothesis that one such mechanism may be upregulation of a hypoxia-inducible factor 1 alpha (HIF-1?)-dependent pathway, suggesting that orexin may promote obesity resistance both by increasing SPA and by influencing the metabolic state of orexin-responsive hypothalamic neurons. We discuss potential mechanisms based on both animal and in vitro pharmacological studies, in the context of elucidating potential molecular targets for obesity prevention and therapy.
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Community mobilisation in the 21st century: Updating our theory of social change?
J Health Psychol
PUBLISHED: 09-02-2013
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The article explores the Freirian theory of social change underpinning health-related community mobilisation in poor and marginalised communities. Highlighting potential shortcomings of its essentialist understandings of power and identity, and linear notions of change, it examines how lessons from the new left, and burgeoning global protest movements, can rejuvenate the field given the growing complexity of 21st-century social inequalities. It suggests the need for a pastiche of approaches to accommodate health struggles in different times and places. However, while needing some updating, Freires profound and actionable understandings of the symbolic and material dimensions of social inequalities remain a powerful starting point for activism.
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Reimagining community health psychology: Maps, journeys and new terrains.
J Health Psychol
PUBLISHED: 09-02-2013
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This special issue celebrates and maps out the coming of age of community health psychology, demonstrating its confident and productive expansion beyond its roots in the theory and practice of small-scale collective action in local settings. Articles demonstrate the fields engagement with the growing complexity of local and global inequalities, contemporary forms of collective social protest and developments in critical social science. These open up novel problem spaces for the application and extension of its theories and methods, deepening our understandings of power, identity, community, knowledge and social change - in the context of evolving understandings of the spatial, embodied, relational, collaborative and historical dimensions of health.
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Strategy for managing maternal variant RHD alleles in Rhesus D negative obstetric populations during fetal RHD genotyping.
Prenat. Diagn.
PUBLISHED: 08-08-2013
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Fetal RHD screening programs that aim to reduce unnecessary antenatal anti-D prophylaxis are being introduced into clinical practice. Strategies to manage women serologically typed as Rhesus D negative who have maternal RHD variants are needed. This study describes maternal RHD allelic variants detected in nonselected and alloimmunised Rhesus D negative obstetric populations and explores a mathematical approach to identify these variants.
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Stranger Danger? Womens Self-Protection Intent and the Continuing Stigma of Online Dating.
Cyberpsychol Behav Soc Netw
PUBLISHED: 07-13-2013
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Abstract The present study examines the stigma associated with online relationship initiation and its relation to womens self-protective behavior. Self-protective behaviors are those an individual engages in to avoid becoming a victim of dating violence. Female participants from a Midwestern university (N=82) were asked to read scenarios describing a hypothetical date. In one scenario, the prospective date was only previously known through an online social networking site, while in the other scenario, the date was previously known through brief face-to-face interaction. After reading the scenario, participants rated the importance of engaging in self-protection behaviors if they were in the date situation being described. As we predicted, participants assigned greater importance to self-protective behavior after reading the online meeting scenario than the face-to-face scenario. This tendency was especially strong among participants who had never been on a date with someone they had met online.
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Auxin-binding protein 1 is a negative regulator of the SCF(TIR1/AFB) pathway.
Nat Commun
PUBLISHED: 07-03-2013
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Auxin is a major plant hormone that controls most aspects of plant growth and development. Auxin is perceived by two distinct classes of receptors: transport inhibitor response 1 (TIR1, or auxin-related F-box (AFB)) and auxin/indole-3-acetic acid (AUX/IAA) coreceptors, that control transcriptional responses to auxin, and the auxin-binding protein 1 (ABP1), that controls a wide variety of growth and developmental processes. To date, the mode of action of ABP1 is still poorly understood and its functional interaction with TIR1/AFB-AUX/IAA coreceptors remains elusive. Here we combine genetic and biochemical approaches to gain insight into the integration of these two pathways. We find that ABP1 is genetically upstream of TIR1/AFBs; ABP1 knockdown leads to an enhanced degradation of AUX/IAA repressors, independently of its effects on endocytosis, through the SCF(TIR1/AFB) E3 ubiquitin ligase pathway. Combining positive and negative regulation of SCF ubiquitin-dependent pathways might be a common mechanism conferring tight control of hormone-mediated responses.
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PTSD modifies performance on a task of affective executive control among deployed OEF/OIF veterans with mild traumatic brain injury.
J Int Neuropsychol Soc
PUBLISHED: 07-03-2013
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Individuals with post-traumatic stress disorder (PTSD) show a cognitive bias for threatening information, reflecting dysregulated executive control for affective stimuli. This study examined whether comorbid mild Traumatic Brain Injury (mTBI) with PTSD exacerbates this bias. A computer-administered Affective Go/No-Go task measured reaction times (RTs) and errors of omission and commission to words with a non-combat-related positive or negative valence in 72 deployed United States service members from the wars in Iraq and Afghanistan. Incidents of military-related mTBI were measured with the Boston Assessment of Traumatic Brain Injury-Lifetime. PTSD symptoms were measured with the Clinician-Administered PTSD Scale. Participants were divided into those with (mTBI+, n = 34) and without a history of military-related mTBI (mTBI-, n = 38). Valence of the target stimuli differentially impacted errors of commission and decision bias (criterion) in the mTBI+ and mTBI- groups. Specifically, within the mTBI+ group, increasing severity of PTSD symptoms was associated with an increasingly liberal response pattern (defined as more commission errors to negative distractors and greater hit rate for positive stimuli) in the positive compared to the negative blocks. This association was not observed in the mTBI- group. This study underscores the importance of considering the impact of a military-related mTBI and PTSD severity upon affective executive control.
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Assessing participation in a community-based health planning and services programme in Ghana.
BMC Health Serv Res
PUBLISHED: 06-18-2013
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Community participation is increasingly seen as a pre-requisite for successful health service uptake. It is notoriously difficult to assess participation and little has been done to advance tools for the assessment of community participation. In this paper we illustrate an approach that combines a social psychology of participation (theory) with spider-grams (method) to assess participation and apply it to a Community-based Health Planning and Services (CHPS) programme in rural Ghana.
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Der p 1 is the primary activator of Der p 3, Der p 6 and Der p 9 the proteolytic allergens produced by the house dust mite Dermatophagoides pteronyssinus.
Biochim. Biophys. Acta
PUBLISHED: 06-17-2013
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The enzymatic activity of the four proteases found in the house dust mite Dermatophagoides pteronyssinus is involved in the pathogenesis of allergy. Our aim was to elucidate the activation cascade of their corresponding precursor forms and particularly to highlight the interconnection between proteases during this cascade.
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Effectiveness of a physical activity intervention for Head Start preschoolers: a randomized intervention study.
Am J Occup Ther
PUBLISHED: 06-14-2013
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The level of childrens motor skill proficiency may be an important determinant of their physical activity behaviors. This study assessed the efficacy of an intervention on gross motor skill performance, physical activity, and weight status of preschoolers.
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Social capital and HIV competent communities: the role of community groups in managing HIV/AIDS in rural Zimbabwe.
AIDS Care
PUBLISHED: 06-11-2013
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Community involvement is increasingly identified as a "critical enabler" of an effective HIV/AIDS response. We explore pathways between community participation and HIV prevention, treatment and impact mitigation in Zimbabwe, reviewing six qualitative studies in Manicaland. These find that community group membership is often (not always) associated with decreased HIV incidence, reduced stigma and improved access to some services, particularly amongst women. Participation in formal community groups (e.g., church or womens groups) and informal local networks (e.g., neighbours, families) provides opportunities for critical dialogue about HIV/AIDS, often facilitating renegotiation of harmful social norms, sharing of previously hidden personal experiences of HIV/AIDS, formulation of positive action plans and solidarity to action them. However, implementation of new plans and insights is constrained by poverty, social uncertainty and poor service delivery. Furthermore, dialogue may have negative effects, spreading false information and entrenching negative norms. The extent that formal groups and informal networks facilitate externally imposed HIV/AIDS interventions varies. They potentially provide vital practical and emotional support, facilitating service access, treatment adherence and AIDS care. However, they may sometimes play a negative role in prevention activities, challenging stereotypes about sexuality or gender. There is an urgent need for greater recognition of the role of indigenous community groups and networks, and the inclusion of "strengthening local responses" as a key element of interventions and policy. Such efforts require great sensitivity. Heavy-handed external interference in complex indigenous relationships risks undermining the localism and bottom-up initiative and activism that might be central to their effectiveness. Cautious efforts might seek to enhance the potentially beneficial effects of groups, especially for women, and limit potentially damaging ones, especially for men. Efforts should be made to facilitate contexts that enable groups to have beneficial effects, through nesting them within wider comprehensive responses, and supporting them through strong partnerships with service providers.
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Community groups as critical enablers of the HIV response in Zimbabwe.
BMC Health Serv Res
PUBLISHED: 05-16-2013
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The Investment Framework for a more effective HIV response has become integral to discussions on how best to respond to the HIV epidemic. The Framework calls for greater synergy and attention to factors that serve as critical enablers and optimise HIV programmes. In this paper we argue for recognition of informal and indigenous community groups as critical enablers of the HIV response.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.