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PURPOSE: This study aimed to assess the extent to which structured approaches to implementation of clinical genomics, proposed or adapted, are informed by evidence. METHODS: A systematic approach was used to identify peer-reviewed articles and gray literature to report on 4 research questions: 1. What structured approaches have been proposed to support implementation? 2. To what extent are the structured approaches informed by evidence? 3. How have structured approaches been deployed in the genomic setting? 4. What are the intended outcomes of the structured approaches? RESULTS: A total of 30 unique structured approaches to implementation were reported across 23 peer-reviewed publications and 11 gray literature articles. Most approaches were process models, applied in the preadoption implementation phase, focusing on a "service" outcome. Key findings included a lack of implementation science theory informing the development/implementation of newly designed structured approaches in the genomic setting and a lack of measures to assess implementation effectiveness. CONCLUSION: This scoping review identified a significant number of structured approaches developed to inform the implementation of genomic medicine into clinical practice, with limited use of implementation science to support the process. We recommend the use of existing implementation science theory and the expertise of implementation scientists to inform the design of genomic programs being implemented into clinical care.
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Genómica , Ciencia de la Implementación , HumanosRESUMEN
Cutibacterium acnes (formally Propionibacterium acnes) is frequently identified within surgical device related infections. It is often co-isolated from infection sites with other opportunistic pathogens. Recent studies have demonstrated that C. acnes is able to form biofilms and when co-cultured with Staphylococcus spp. both inhibitory and stimulatory effects have been reported across several studies. Here, we investigated the biofilm-forming ability of 100 clinical C. acnes isolates from various infection sites in human patients, both deep tissue and superficial, followed by an investigation of how the supernatants of C. acnes cultures influenced the attachment and maturation of Staphylococcusaureus NCTC 6571 biofilms. All of the C. acnes isolates were able to form biofilms in vitro, although biofilm biomass varied between isolates. Nineteen isolates were weakly adherent, 33 were moderately adherent and the majority (48) showed strong adherence. The presence of C. acnes sterile supernatants reduced the biomass of S. aureus cultures, with a > 90% reduction observed in the presence of several of the C. acnes isolates. We observed that this decrease was not due to C. acnes affecting S. aureus viability, nor due to the presence of propionic acid. Biofilm maturation was however delayed over a 24-h period as was biofilm surface structure, although initial (up to 8 h) surface attachment was not affected. We hypothesis that this defective biofilm maturation is the cause of the observed biomass decrease. In turn, these altered biofilms showed a greater susceptibility to antibiotic treatments. In contrast the presence of C. acnes supernatant in planktonic (defined as a free moving, non-surface attached population within the liquid column) S. aureus cultures increased antibiotic tolerance, via a currently undefined mechanism. This study suggests that complex interactions between C. acnes and other opportunistic pathogens are likely to exist during colonisation and infection events. Further investigation of these interactions may lead to increased treatment options and a better prognosis for patients.
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Acné Vulgar , Propionibacterium acnes , Antibacterianos/farmacología , Biopelículas , Humanos , Staphylococcus , Staphylococcus aureusRESUMEN
Chronic wounds are a significant global problem with an increasing economic and patient welfare impact. How wounds move from an acute to chronic, non-healing, state is not well understood although it is likely that it is driven by a poorly regulated local inflammatory state. Opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa are well known to stimulate a pro-inflammatory response and so their presence may further drive chronicity. Studies have demonstrated that host cell extracellular vesicles (hEVs), in particular exosomes, have multiple roles in both increasing and decreasing chronicity within wounds; however, the role of bacterial extracellular vesicles (bEVs) is still poorly understood. The aim of this review is to evaluate bEV biogenesis and function within chronic wound relevant bacterial species to determine what, if any, role bEVs may have in driving wound chronicity. We determine that bEVs drive chronicity by both increasing persistence of key pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa and stimulating a pro-inflammatory response by the host. Data also suggest that both bEVs and hEVs show therapeutic promise, providing vaccine candidates, decoy targets for bacterial toxins or modulating the bacterial species within chronic wound biofilms. Caution should, however, be used when interpreting findings to date as the bEV field is still in its infancy and as such lacks consistency in bEV isolation and characterization. It is of primary importance that this is addressed, allowing meaningful conclusions to be drawn and increasing reproducibility within the field.
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Vesículas Extracelulares , Infecciones por Pseudomonas , Infección de Heridas , Biopelículas , Humanos , Pseudomonas aeruginosa , Reproducibilidad de los Resultados , Cicatrización de HeridasRESUMEN
Staphylococcus pseudintermedius causes opportunistic infections in dogs. It also has significant zoonotic potential, with the emergence of multidrug resistance leading to difficulty treating both animal and human infections. Manuka honey has previously been reported to inhibit many bacterial pathogens, including methicillin-resistant Staphylococcus aureus, and is successfully utilized in both clinical and veterinary practice. Here, we evaluated the ability of manuka honey to inhibit strains of S. pseudintermedius grown alone and in combination with antibiotics, as well as its capacity to modulate virulence within multiple S. pseudintermedius isolates. All 18 of the genetically diverse S. pseudintermedius strains sequenced and tested were inhibited by ≤12% (wt/vol) medical-grade manuka honey, although tolerance to five clinically relevant antibiotics was observed. The susceptibility of the isolates to four of these antibiotics was significantly increased (P ≤ 0.05) when combined with sublethal concentrations of honey, although sensitivity to oxacillin was decreased. Virulence factor (DNase, protease, and hemolysin) activity was also significantly reduced (P ≤ 0.05) in over half of isolates when cultured with sublethal concentrations of honey (13, 9, and 10 isolates, respectively). These findings highlight the potential for manuka honey to be utilized against S. pseudintermedius infections.IMPORTANCEStaphylococcus pseudintermedius is an important member of the skin microbial community in animals and can cause opportunistic infections in both pets and their owners. The high incidence of antimicrobial resistance in S. pseudintermedius highlights that this opportunistic zoonotic pathogen can cause infections which require prolonged and intensive treatment to resolve. Manuka honey has proven efficacy against many bacterial pathogens and is an accepted topical treatment for infections in both veterinary and clinical practice, and so it is a particularly appropriate antimicrobial for use with zoonotic pathogens such as S. pseudintermedius Here, we demonstrate that not only is manuka honey highly potent against novel multidrug-resistant S. pseudintermedius isolates, it also acts synergistically with clinically relevant antibiotics. In addition, manuka honey modulates S. pseudintermedius virulence activity, even at subinhibitory concentrations. In a clinical setting, these attributes may assist in controlling infection, allowing a more rapid resolution and reducing antibiotic use.
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Antibacterianos/farmacología , Miel/análisis , Staphylococcus/efectos de los fármacos , Antibacterianos/análisis , Staphylococcus/genética , Staphylococcus/patogenicidad , Staphylococcus/fisiología , Virulencia/efectos de los fármacosRESUMEN
BACKGROUND: Clusters of adolescents differentiated by patterns of physical activity and sedentary behavior (activity-related typologies) are common. Understanding both the characteristics of adolescents and modifiable correlates of these typologies, can help to develop interventions for those most at risk. This systematic review aimed to synthesize the socio-demographic characteristics and modifiable correlates of activity-related behavioral typologies among adolescents. METHODS: A systematic search of seven electronic databases was conducted to identify quantitative studies using person-oriented statistical approaches to identify activity-related behavioral typologies among 12-18 year-olds. This systematic review was registered in Prospero (registration number: CRD42016046879). RESULTS: Thirty-six studies met the inclusion criteria and were classified according to three sub-themes based on behaviors included in the typologies (1. physical activity and sedentary behavior only; 2. physical activity, sedentary behavior and risk-related behaviors; 3. physical activity, sedentary behavior and diet). Studies were mostly cross-sectional and relied on self-report measures. Methods were considerably heterogeneous, however results revealed some consistency in typologies within specific groups. For example, typologies characterized by unhealthy behavior patterns (e.g., characterized by physical inactivity, high sedentary behavior and poor diet or high risk-related behaviors) comprised more older adolescents. With the exception of socio-demographics (age, sex, body mass index and socio-economic status), very few correlates have been studied to date (mostly school-related behavioral factors and intrapersonal influences), with evidence largely from typologies comprised of physical activity, sedentary behavior and diet. CONCLUSIONS: More research is needed to assess a range of modifiable correlates associated with activity-related behavior typologies among adolescents. This will allow for more targeted interventions, to achieve long-lasting, positive behavior change in adolescent populations.
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Conducta del Adolescente/fisiología , Ejercicio Físico/fisiología , Conductas Relacionadas con la Salud/fisiología , Adolescente , Niño , Humanos , Conducta SedentariaRESUMEN
INTRODUCTION: Synthetic midurethral slings are the most common procedures currently performed for stress urinary incontinence in women. Infection is a frequent complication of urogynecologic surgery. We performed a systematic review and meta-analysis to identify interventions that successfully prevent infections, including urinary tract infection (UTI) and/or bacteriuria, compared with no intervention, in women undergoing midurethral sling surgery with or without concomitant pelvic reconstructive procedures for prolapse. MATERIAL AND METHODS: The primary outcome was the development of any infection post-midurethral sling placement in women. MEDLINE, Embase, CINAHL and the Cochrane Library were searched for comparative studies from inception to July 2017, with no language restrictions. We used search terms related to midurethral sling, infections and infection-reduction interventions. Two independent reviewers abstracted data and assessed study quality. Pooled effect size estimates were calculated. We conducted meta-analysis of eligible studies. A protocol for this review has been registered and can be accessed online (http://hdl.handle.net/2429/64731). RESULTS: We identified seven eligible studies of infection risk-reducing interventions; all focused on UTIs. Only one study assessed preoperative antibiotics with midurethral sling alone and was halted early because of low UTI rates. All other studies (three randomized control trials and three observational studies) examined whether postoperative antibiotics decrease UTI/bacteriuria rates after midurethral sling with or without reconstructive procedures for pelvic organ prolapse and using bladder catheterization postoperatively. Due to considerable clinical heterogeneity, we only combined four studies for meta-analysis. Postoperative oral prophylactic nitrofurantoin showed no significant benefit in reducing UTI/bacteriuria in women post-midurethral sling with or without concomitant reconstructive pelvic surgery and the need for bladder catheterization, when compared with the reference group (pooled relative risk 0.73, 95% confidence interval [CI] 0.42-1.25). CONCLUSIONS: Based on the best available evidence, postoperative oral nitrofurantoin is not effective at reducing UTI/bacteriuria rates in catheterized women after midurethral sling with or without concomitant pelvic reconstructive surgery for prolapse. For midurethral sling alone, preoperative antibiotic prophylaxis may not be needed for UTI prevention.
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Antibacterianos/uso terapéutico , Cabestrillo Suburetral/efectos adversos , Infecciones Urinarias/prevención & control , Bacteriuria/etiología , Bacteriuria/prevención & control , Femenino , Humanos , Nitrofurantoína/uso terapéutico , Prolapso de Órgano Pélvico/cirugía , Cuidados Posoperatorios , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Procedimientos de Cirugía Plástica/efectos adversos , Incontinencia Urinaria de Esfuerzo/cirugía , Infecciones Urinarias/etiologíaRESUMEN
BACKGROUND: Adolescents engage in various combinations (typologies) of physical activity and sedentary behaviors, which impact their health and wellbeing in different ways. As such, there is a need to understand the factors that may inhibit or facilitate engagement in combinations of activity-related behaviors to help inform effective intervention strategies targeting those most in need. The aim of this study was to identify ecological correlates of adolescent physical activity and sedentary behavior typologies. METHODS: Cross-sectional study of 473 adolescents (15.0 ± 1.6 years, 41.4% boys) from 18 secondary schools in Melbourne, Australia. Intrapersonal, interpersonal and neighborhood-physical environmental factors were assessed via self-report surveys and Geographic Information Systems. Multinomial logistic regression models determined the relative risk ratio of membership of three homogenous activity-related behavior typologies based on the potential correlates. RESULTS: Higher levels of self-efficacy for physical activity, parental screen-time restriction rules, parental support for physical activity, sibling screen-time co-participation and perceptions of neighborhood pedestrian/traffic safety were associated with greater likelihood of adolescents being in the typology defined as highly active and low sedentary compared to the physically inactive, highly sedentary typology. Higher frequency of co-participation in screen-time with friends was associated with greater likelihood of adolescents being in the typology defined as moderately active, high screen-time compared to physically inactive, highly sedentary. CONCLUSIONS: A range of intrapersonal, interpersonal and environmental correlates appear to play a role in adolescent activity-related typology membership. The findings may inform public health interventions targeting unique adolescent subgroups most at risk of poor health outcomes based on their engagement in combinations of activity-related behaviors.
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Conducta del Adolescente , Fenómenos Ecológicos y Ambientales , Ejercicio Físico/psicología , Adolescente , Australia , Estudios Transversales , Femenino , Amigos/psicología , Humanos , Masculino , Padres/psicología , Características de la Residencia/estadística & datos numéricos , Tiempo de Pantalla , Conducta Sedentaria , AutoinformeRESUMEN
The bacterial pathogen Campylobacter jejuni is primarily transmitted via the consumption of contaminated foodstuffs, especially poultry meat. In food processing environments, C. jejuni is required to survive a multitude of stresses and requires the use of specific survival mechanisms, such as biofilms. An initial step in biofilm formation is bacterial attachment to a surface. Here, we investigated the effects of a chicken meat exudate (chicken juice) on C. jejuni surface attachment and biofilm formation. Supplementation of brucella broth with ≥5% chicken juice resulted in increased biofilm formation on glass, polystyrene, and stainless steel surfaces with four C. jejuni isolates and one C. coli isolate in both microaerobic and aerobic conditions. When incubated with chicken juice, C. jejuni was both able to grow and form biofilms in static cultures in aerobic conditions. Electron microscopy showed that C. jejuni cells were associated with chicken juice particulates attached to the abiotic surface rather than the surface itself. This suggests that chicken juice contributes to C. jejuni biofilm formation by covering and conditioning the abiotic surface and is a source of nutrients. Chicken juice was able to complement the reduction in biofilm formation of an aflagellated mutant of C. jejuni, indicating that chicken juice may support food chain transmission of isolates with lowered motility. We provide here a useful model for studying the interaction of C. jejuni biofilms in food chain-relevant conditions and also show a possible mechanism for C. jejuni cell attachment and biofilm initiation on abiotic surfaces within the food chain.
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Adhesión Bacteriana , Biopelículas , Campylobacter jejuni/fisiología , Contaminación de Alimentos/análisis , Carne/microbiología , Animales , Pollos , Manipulación de AlimentosRESUMEN
Objective: This study aimed to identify intrapersonal, interpersonal, and environmental correlates of leisure-time participation in sports and examine whether they are also associated with screen-time among adolescents. Methods: Adolescents from eight schools in Victoria, Australia were recruited for this study. Participants (n = 400) comprised of an even distribution of boys (51%) and girls (49%) aged 12-16 years. Their engagement in leisure-time activities (including sports and screen-time) and 13 potential correlates were self-reported. Multinomial logistic regression analyses examined correlates of sports and screen-time participation categories, accounting for clustering by school and adjusting for significant sociodemographic characteristics. Results: The majority (76%) participated in leisure-time sports and exceeded screen-time recommendations (<2 h/day) on both weekdays (69%) and weekend days (85%). Greater internal motivation for sports was positively associated with sports participation and inversely associated with screen-time on weekend days, respectively. Fewer barriers, positive family and coach support and more neighborhood sporting opportunities were significantly associated with greater sports participation. Neighborhood social norms were inversely associated with sports participation. Preference for sports was associated with less weekday and weekend screen-time. Friend support for sports was inversely associated with weekday screen-time. Access to sports facilities in the local neighborhood was associated with more weekday and weekend screen-time. Conclusion: Internal motivation for sports was associated with both sports participation and less screen-time. Preference for leisure-time sports and friend support for sports were associated with less screen-time. Future research should continue to explore common correlates of multiple leisure-time behaviors to inform the development of effective intervention strategies.
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Ejercicio Físico , Deportes , Masculino , Femenino , Humanos , Adolescente , Tiempo de Pantalla , Actividades Recreativas , VictoriaRESUMEN
OBJECTIVE: To assess whether editorial desk rejection at general medical journals (without peer review) of two clinical research manuscripts may relate to author gender or women's physiology topics. Given evidence for bias related to women in science and medicine, and editorial board attitudes, our hypothesis was that submissions by women authors, on women's reproductive, non-disease topics received differential editorial assessment. DESIGN: A prospective investigation of publications, author gender and topics in general medical journals in two issues following the editorial rejections of two clinical research manuscripts by five major English-language general medical journals. The rejected manuscripts (subsequently published in lower impact journals) described research funded by national granting bodies, in population-based samples, authored by well-published women scientists at accredited institutions and describing innovative women's reproductive physiology results. SETTING: Tertiary academic medical centre. MAIN OUTCOME MEASURES: All clinical research published in the two issues following rejection date by each of the five major general medical journals were examined for first/senior author gender. The publication topic was assessed for its gendered population relevance, whether disease or physiology focused, and its funding. Rejection letters assessed editor gender and status. RESULTS: Women were underrepresented as original research authors; men were 84% of senior and 69% of first authors. There were no, non-disease focused publications relating to women's health, although most topics were relevant to both genders. The majority (80%) of rejection letters appeared to be written by junior-ranked women editors. CONCLUSION: Sex/gender accountability is necessary for clinical research-based editorial decisions by major general medical journals. Suggestions to improve gender equity in general medical journal publication: (1) an editorial board sex/gender champion with power to advocate for manuscripts that are well-performed research of relevance to women's health/physiology; (2) an editorial rejection adjudication committee to review author challenges; and (3) gender parity in double-blind peer review.
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Políticas Editoriales , Medicina , Publicaciones Periódicas como Asunto , Femenino , Humanos , Masculino , Estudios ProspectivosRESUMEN
Managing an issue of the magnitude, scope and complexity of climate change is a daunting prospect, yet one which nations around the world must face. Climate change is an issue without boundaries--impacts will cut across administrative and geographical borders and be felt by every sector of society. Responses to climate change will need to employ system approaches that take into account the relationships that cross organisational and sectoral boundaries. Solutions designed in isolation from these interdependencies will be unlikely to succeed, squandering opportunities for long-term effective adaptation. Health Impact Assessment (HIA) provides a structural approach to identify, evaluate and manage health impacts of climate change that is inclusive of a wide range of stakeholders. Climate change will affect decision-making across every government level and sector and the health implications of these decisions can also be addressed with HIA. Given the nature of the issue, HIA of climate change will identify a large number of variables that influence the type and extent of health impacts and the management of these impacts. In order to implement the most effective adaptation measures, it is critica that an understanding of the interactions between these variables is developed. The outcome of HIA of climate change can therefore be strengthened by the introduction of system dynamics tools, such as causal loop diagrams, that are designed to examine interactions between variables and the resulting behaviour of complex systems.
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Aclimatación , Cambio Climático , Promoción de la Salud , Política de Salud , Humanos , Salud Pública , Medición de RiesgoRESUMEN
Knowledge synthesis constitutes a key part of evidence-based medicine and a scoping review is a type of knowledge synthesis that maps the breadth of literature on a topic. Conducting a scoping review is resource intensive and, as a result, it can be challenging to maintain best practices throughout the process. Much of the current guidance describes a scoping review framework or broad ways to conduct a scoping review. However, little detailed guidance exists on how to complete each stage to optimise the process. We present five recommendations based on our experience when conducting a particularly challenging scoping review: (1) engage the expertise of a librarian throughout the process, (2) conduct a truly systematic search, (3) facilitate communication and collaboration, (4) explore new tools or repurpose old ones, and (5) test every stage of the process. These recommendations add to the literature by providing specific and detailed advice on each stage of a scoping review. Our intent is for these recommendations to aid other teams that are undertaking knowledge synthesis projects.
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Publicaciones , Proyectos de Investigación , Medicina Basada en la Evidencia , HumanosRESUMEN
BACKGROUND: Q3 conditions are progressive, metabolic, neurological or chromosomal childhood conditions without a cure. Children with these conditions face an unknown lifespan as well as unstable and uncomfortable symptoms. Clinicians and other healthcare professionals are challenged by a lack of evidence for symptom management for these conditions. AIMS: In this scoping review, we systematically identified and mapped the existing literature on symptom management for children with Q3 conditions. We focused on the most common and distressing symptoms, namely alertness, behavioural problems, bowel incontinence, breathing difficulties, constipation, feeding difficulties, sleep disturbance, temperature regulation, tone and motor problems and urinary incontinence. For children with complex health conditions, good symptom management is pertinent to ensure the highest possible quality of life. METHODS: Scoping review. Electronic database searches in Ovid MEDLINE, Embase and CINAHL and a comprehensive grey literature search. RESULTS: We included 292 studies in our final synthesis. The most commonly reported conditions in the studies were Rett syndrome (n=69), followed by Cornelia de Lange syndrome (n=25) and tuberous sclerosis (n=16). Tone and motor problems were the most commonly investigated symptom (n=141), followed by behavioural problems (n=82) and sleep disturbance (n=62). CONCLUSION: The evidence for symptom management in Q3 conditions is concentrated around a few conditions, and these studies may not be applicable to other conditions. The evidence is dispersed in the literature and difficult to access, which further challenges healthcare providers. More research needs to be done in these conditions to provide high-quality evidence for the care of these children.
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Enfermedad Crítica/psicología , Cuidados Paliativos/psicología , Calidad de Vida , Enfermedades Raras/psicología , Adolescente , Niño , Enfermedad Crítica/terapia , Femenino , Humanos , Masculino , Cuidados Paliativos/métodos , Enfermedades Raras/terapiaRESUMEN
OBJECTIVES: To identify typologies of activity-related behaviours and demographic characteristics of these typologies among Australian adolescents. DESIGN: Cross-sectional study of 473 Secondary School students (41.4% boys, mean age 14.95±1.61 years) conducted in 2014-15. METHODS: Active travel to school, sport participation, leisure-time sedentary and demographic variables were self-reported in a survey. Duration of sedentary time and moderate-to-vigorous physical activity (mins/day) were accelerometer-derived. Latent class analysis (LCA) was conducted to identify typologies of activity-related health behaviours. One-way ANOVAs and chi-square tests were used to explore differences by demographic characteristics. RESULTS: Three typologies were identified: (1) "Physically inactive, highly sedentary" (44%); (2) "Moderately active, high screen-time" (42%); and (3) "Highly active, low sedentary" (14%). Differences between typologies were evident for age, sex, body mass index (BMI), cultural identity, employment status and socioeconomic position (SEP). Those in typology 3 (optimal behaviour pattern) tended to be younger, of higher SEP and lower BMI. CONCLUSIONS: This study found that older adolescents have less active, more sedentary profiles than younger adolescents. The findings support the need for targeted interventions to improve adolescent activity-related behaviour engagement.
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Conducta del Adolescente , Conductas Relacionadas con la Salud , Adolescente , Factores de Edad , Australia , Índice de Masa Corporal , Estudios Transversales , Ejercicio Físico , Femenino , Humanos , Actividades Recreativas , Masculino , Conducta Sedentaria , Autoinforme , Clase SocialRESUMEN
HIV-specific CD4+ T helper lymphocytes are preferred targets for infection. Although complete interruption of combination antiretroviral therapy (ART) can form part of therapeutic manipulations, there is grave concern that the resumption of viral replication might destroy, perhaps irreversibly, these T helper populations. High viremia blocks the proliferation capacity of HIV-specific helper cells. However, cytokine production assays imply that some antigen-specific effector function is retained. Despite this careful work, it remains unclear whether the return of HIV-1 replication physically destroys HIV-1-specific T helper cells in the peripheral blood. Difficulties in producing stable peptide-MHC class II complexes and the very low frequencies of antigen-specific CD4+ T cells have delayed the application of this powerful technique. Here we employ HLA class II tetramers and validate a sensitive, quantitative cell-enrichment technique to detect HIV-1 T helper cells. We studied patients with early-stage HIV infection who were given a short, fixed course of ART as part of a clinical study. We did not find significant deletion of these cells from the peripheral circulation when ART was stopped and unfettered HIV replication returned. The turnover of these virus-specific cells increased and they adopted an effector phenotype when viremia returned.
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Infecciones por VIH/inmunología , VIH-1/fisiología , Antígenos de Histocompatibilidad Clase II/inmunología , Activación de Linfocitos/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Activación Viral/fisiología , Terapia Antirretroviral Altamente Activa , Proliferación Celular , Células Cultivadas , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Antígenos de Histocompatibilidad Clase II/farmacología , Humanos , Activación de Linfocitos/efectos de los fármacos , Linfocitos T Colaboradores-Inductores/patología , Linfocitos T Colaboradores-Inductores/virología , Viremia/inmunología , Viremia/patologíaRESUMEN
Despite huge advances in the field of islet transplantation over the last two decades, current islet isolation methods remain suboptimal, with transplantable yields obtained in less than half of all pancreases processed worldwide. Successful islet isolation is dependent on the ability of collagenase-based enzyme blends to digest extracellular matrix components at the islet-exocrine interface. The limited availability of donor pancreases hinders the use of full-scale islet isolations to characterize pancreas digestion by different enzyme components or blends, or allow the influence of inter-pancreatic variability between donors to be explored. We have developed a method that allows multiple enzyme components to be tested on any one pancreas. Biopsies of 0.5 cm3 were taken from seven standard (age ≥45) and eight young (age ≤35) pancreases. Serial cryosections were treated with Serva collagenase, neutral protease (NP), or the two enzymes together at clinically relevant concentrations. Following digestion, insulin and either collagen IV or laminin-α5 were detected by immunofluorescent labeling. Protein loss at the islet-exocrine interface was semi-quantified morphometrically, with reference to a control section. Differential digestion of the two proteins based on the enzyme components used was seen, with protein digestion significantly influenced by donor age. Treatment with collagenase and NP alone was significantly more effective at digesting collagen IV in the standard donor group, as was the NP mediated digestion of laminin-α5. Collagenase alone was not capable of significantly digesting laminin-α5 in either donor group. Combining the two enzymes ameliorated the age-related differences in the digestion of both proteins. No significant differences in protein loss were detected by the method when analyzed by two independent operators, demonstrating the reproducibility of the assay. The development of this simple yet reproducible assay has implications for both enzyme batch testing and identifying inter-donor digestion variability, while utilizing small amounts of both enzyme and human tissue.
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Colagenasas/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Matriz Extracelular/metabolismo , Islotes Pancreáticos/citología , Páncreas/metabolismo , Adulto , Separación Celular/métodos , Femenino , Humanos , Islotes Pancreáticos/metabolismo , Trasplante de Islotes Pancreáticos , Masculino , Persona de Mediana Edad , Páncreas/citología , ProteolisisRESUMEN
Internationally, childhood obesity is a major public health concern. Given the established difficulties in treating obesity, designing and evaluating effective obesity prevention interventions are research priorities. As parents play a crucial role in establishing positive health behaviours in children, they are a key target for child obesity prevention programs. However, recruiting and engaging parents in such interventions can be a considerable challenge for researchers and practitioners. Members of the 'Parenting, Child Behaviour and Well-being' stream of the Australasian Child and Adolescent Obesity Research Network (ACAORN) have considerable and varied expertise in conducting such interventions and can provide insights into addressing these challenges. This paper aims to highlight considerations regarding the design, implementation, and evaluation of obesity prevention interventions with families and provide practical insights and recommendations for researchers and practitioners conducting family-based research in this area. Case studies of three family-based interventions conducted by ACAORN members are highlighted to provide examples and contextualise the recommendations proposed.
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BACKGROUND: Gross motor competence confers health benefits, but levels in children and adolescents are low. While interventions can improve gross motor competence, it remains unclear which correlates should be targeted to ensure interventions are most effective, and for whom targeted and tailored interventions should be developed. OBJECTIVE: The aim of this systematic review was to identify the potential correlates of gross motor competence in typically developing children and adolescents (aged 3-18 years) using an ecological approach. METHODS: Motor competence was defined as gross motor skill competency, encompassing fundamental movement skills and motor coordination, but excluding motor fitness. Studies needed to assess a summary score of at least one aspect of motor competence (i.e., object control, locomotor, stability, or motor coordination). A structured electronic literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Six electronic databases (CINAHL Complete, ERIC, MEDLINE Complete, PsycINFO®, Scopus and SPORTDiscus with Full Text) were searched from 1994 to 5 August 2014. Meta-analyses were conducted to determine the relationship between potential correlates and motor competency if at least three individual studies investigated the same correlate and also reported standardized regression coefficients. RESULTS: A total of 59 studies were identified from 22 different countries, published between 1995 and 2014. Studies reflected the full range of age groups. The most examined correlates were biological and demographic factors. Age (increasing) was a correlate of children's motor competence. Weight status (healthy), sex (male) and socioeconomic background (higher) were consistent correlates for certain aspects of motor competence only. Physical activity and sport participation constituted the majority of investigations in the behavioral attributes and skills category. Whilst we found physical activity to be a positive correlate of skill composite and motor coordination, we also found indeterminate evidence for physical activity being a correlate of object control or locomotor skill competence. Few studies investigated cognitive, emotional and psychological factors, cultural and social factors or physical environment factors as correlates of motor competence. CONCLUSION: This systematic review is the first that has investigated correlates of gross motor competence in children and adolescents. A strength is that we categorized correlates according to the specific ways motor competence has been defined and operationalized (object control, motor coordination, etc.), which enables us to have an understanding of what correlates assist what types of motor competence. Indeed our findings do suggest that evidence for some correlates differs according to how motor competence is operationalized.
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Ejercicio Físico , Destreza Motora , Movimiento/fisiología , Adolescente , Peso Corporal , Niño , Preescolar , Humanos , Masculino , Aptitud Física/fisiologíaRESUMEN
Biofilms make an important contribution to survival and transmission of bacterial pathogens in the food chain. The human pathogen Campylobacter jejuni is known to form biofilms in vitro in food chain-relevant conditions, but the exact roles and composition of the extracellular matrix are still not clear. Extracellular DNA has been found in many bacterial biofilms and can be a major component of the extracellular matrix. Here we show that extracellular DNA is also an important component of the C. jejuni biofilm when attached to stainless steel surfaces, in aerobic conditions and on conditioned surfaces. Degradation of extracellular DNA by exogenous addition of DNase I led to rapid biofilm removal, without loss of C. jejuni viability. Following treatment of a surface with DNase I, C. jejuni was unable to re-establish a biofilm population within 48 h. Similar results were obtained by digesting extracellular DNA with restriction enzymes, suggesting the need for high molecular weight DNA. Addition of C. jejuni genomic DNA containing an antibiotic resistance marker resulted in transfer of the antibiotic resistance marker to susceptible cells in the biofilm, presumably by natural transformation. Taken together, this suggest that eDNA is not only an important component of C. jejuni biofilms and subsequent food chain survival of C. jejuni, but may also contribute to the spread of antimicrobial resistance in C. jejuni. The degradation of extracellular DNA with enzymes such as DNase I is a rapid method to remove C. jejuni biofilms, and is likely to potentiate the activity of antimicrobial treatments and thus synergistically aid disinfection treatments.
RESUMEN
The fastidious nature of the foodborne bacterial pathogen Campylobacter jejuni contrasts with its ability to survive in the food chain. The formation of biofilms, or the integration into existing biofilms by C. jejuni, is thought to contribute to food chain survival. As extracellular DNA (eDNA) has previously been proposed to play a role in C. jejuni biofilms, we have investigated the role of extracellular DNases (eDNases) produced by C. jejuni in biofilm formation. A search of 2791 C. jejuni genomes highlighted that almost half of C. jejuni genomes contains at least one eDNase gene, but only a minority of isolates contains two or three of these eDNase genes, such as C. jejuni strain RM1221 which contains the cje0256, cje0566 and cje1441 eDNase genes. Strain RM1221 did not form biofilms, whereas the eDNase-negative strains NCTC 11168 and 81116 did. Incubation of pre-formed biofilms of NCTC 11168 with live C. jejuni RM1221 or with spent medium from a RM1221 culture resulted in removal of the biofilm. Inactivation of the cje1441 eDNase gene in strain RM1221 restored biofilm formation, and made the mutant unable to degrade biofilms of strain NCTC 11168. Finally, C. jejuni strain RM1221 was able to degrade genomic DNA from C. jejuni NCTC 11168, 81116 and RM1221, whereas strain NCTC 11168 and the RM1221 cje1441 mutant were unable to do so. This was mirrored by an absence of eDNA in overnight cultures of C. jejuni RM1221. This suggests that the activity of eDNases in C. jejuni affects biofilm formation and is not conducive to a biofilm lifestyle. These eDNases do however have a potential role in controlling biofilm formation by C. jejuni strains in food chain relevant environments.