Conectar
by Andrea Peloso, Stéphanie Lacotte, Quentin Gex, Florence Slits, Beat Moeckli, Graziano Oldani, Matthieu Tihy, Aurélie Hautefort, Brenda Kwak, Laura Rubbia-Brandt, Christian Toso
Background and aimsNon-alcoholic fatty liver disease (NAFLD) is one of the leading cause of hepatocellular carcinoma (HCC). This association is supported by the translocation of bacteria products into the portal system, which acts on the liver through the gut-liver axis. We hypothesize that portosystemic shunting can disrupt this relationship, and prevent NAFLD-associated HCC.
MethodsHCC carcinogenesis was tested in C57BL/6 mice fed a high-fat high-sucrose diet (HFD) and injected with diethylnitrosamine (DEN) at two weeks of age, and in double transgenic LAP-tTA and TRE-MYC (LAP-Myc) mice fed a methionine-choline-deficient diet. Portosystemic shunts were established by transposing the spleen to the sub-cutaneous tissue at eight weeks of age.
ResultsSpleen transposition led to a consistent deviation of part of the portal flow and a significant decrease in portal pressure. It was associated with a decrease in the number of HCC in both models. This effect was supported by the presence of less severe liver steatosis after 40 weeks, and lower expression levels of liver fatty acid synthase. Also, shunted mice exhibited lower liver oxygen levels, a key factor in preventing HCC as confirmed by the development of less HCCs in mice with hepatic artery ligation.
ConclusionsThe present data show that portosystemic shunting prevents NAFLD-associated HCC, utilizing two independent mouse models. This effect is supported by the development of less steatosis, and a restored liver oxygen level. Portal pressure modulation and shunting deserve further exploration as potential prevention/treatment options for NAFLD and HCC.
by Naimisha Movva, Heidi Reichert, Naushin Hooda, Lauren C. Bylsma, Meghan Mitchell, Sarah S. Cohen
BackgroundNutrition affects both physical and mental health but evidence is mixed regarding potential associations between anxiety and diet, particularly dairy consumption. We conducted a systematic literature review (SLR) of dairy consumption and/or various dietary patterns and risk of anxiety.
MethodsLiterature searches were conducted in PubMed and Embase. All study designs except case reports, small case series, and SLRs were considered for inclusion. Reference lists of previously published SLRs were reviewed for any relevant additional studies. Studies of populations without dairy sensitivities exploring the association between dietary patterns and/or dairy consumption and anxiety published through May 2022 were identified using predefined eligibility criteria. Study quality was determined using the Academy of Nutrition and Dietetics Quality Criteria Checklist.
ResultsFor this SLR, 132 studies were included; 80 were cross-sectional. Studies examined different dietary patterns (e.g., Mediterranean, gluten-free) and anxiety using various anxiety scales, with 19 studies specifically reporting on whole dairy consumption and anxiety. Dairy consumption was significantly associated with a lower risk of anxiety in 7 studies, while the remaining 12 studies showed no significant associations. Evidence was mixed for the association between various dietary patterns and anxiety, but more studies observed a lower risk of anxiety with greater adherence to “healthy” diets (e.g., Mediterranean, diet quality score, vegetarian/vegan) than a higher risk. Notable heterogeneity in study populations, time periods, geographical locations, dietary assessment methods, and anxiety scales was observed.
ConclusionsThe results of this SLR suggest a potential link between diet including diary consumption and anxiety, but future studies, especially with longitudinal designs that measure diet and anxiety at several timepoints and comprehensively adjust for confounders, are needed to fully understand the relationship between diet and anxiety.
A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri-wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA-Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine-like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing.
by Reinie Cordier, Lauren Parsons, Sarah Wilkes-Gillan, Matthew Cook, Matthew McCloskey-Martinez, Pamela Graham, David Littlefair, Cally Kent, Renée Speyer
RationaleChildren with neurodevelopmental disorders such as attention-deficit hyperactivity disorder (ADHD), autism, developmental language disorder (DLD), intellectual disability (ID), and social (pragmatic) communication disorder (SPCD) experience difficulties with social functioning due to differences in their social, emotional and cognitive skills. Previous systematic reviews have focussed on specific aspects of social functioning rather than broader peer functioning and friendships.
ObjectiveTo systematically review and methodologically appraise the quality and effectiveness of existing intervention studies that measured friendship outcomes for children with ADHD, autism, DLD, ID, and SPCD.
MethodFollowing PRISMA guidelines, we searched five electronic databases: CINAHL, Embase, Eric, PsycINFO, and PubMed. Two independent researchers screened all abstracts and disagreements were discussed with a third researcher to reach consensus. The methodological quality of studies was assessed using the Cochrane Risk of Bias Tool for Randomised Trials.
ResultsTwelve studies involving 15 interventions were included. Studies included 683 children with a neurodevelopmental disorder and 190 typically-developing children and diagnosed with either autism or ADHD. Within-group meta-analysis showed that the pooled intervention effects for friendship across all interventions were small to moderate (z = 2.761, p = 0.006, g = 0.485). The pooled intervention effect between intervention and comparison groups was not significant (z = 1.206, p = 0.400, g = 0.215).
ConclusionFindings provide evidence that some individual interventions are effective in improving social functioning and fostering more meaningful friendships between children with neurodevelopmental disorders and their peers. Effective interventions involved educators, targeted child characteristics known to moderate peer functioning, actively involved peers, and incorporated techniques to facilitate positive peer perceptions and strategies to support peers. Future research should evaluate the effectiveness of friendship interventions for children with DLD, ID and SPCD, more comprehensively assess peer functioning, include child self-report measures of friendship, and longitudinally evaluate downstream effects on friendship.
(1) To identify, evaluate and summarize evidence about the objectives and characteristics of mentoring programmes for specialized nurses (SNs) or nurse navigators (NNs) and advanced practice nurses (APNs) and (2) to identify the effectiveness of these programmes.
A systematic review based on PRISMA guidelines.
From November 2022 until 7 December 2022, four databases were searched: PubMed, EMBASE, CINAHL and The Cochrane Library.
Study selection was performed independently by two researchers. Disagreements were discussed until consensus was reached. Data extraction was undertaken for included studies. Data synthesis was conducted using narrative analysis. Quality appraisal was performed using the Critical Appraisal Skill Programme (CASP) and Mixed Methods Appraisal Tool (MMAT).
Twelve articles were included, all of which focused on mentoring programmes for APNs. Different forms of mentorship (e.g. (in)formal mentorship, work shadowing, workshops) were reported. Studies reported positive outcomes on job retention (n = 5), job satisfaction (n = 6), skills improvement (n = 7), satisfaction with the programme (n = 7) and confidence improvement (n = 4) among participants of mentoring programmes.
There is a lack of uniformity and consistency in various elements of mentoring programmes. Further research is needed to develop mentoring programmes for both APNs and SNs/NNs in a systematic and theoretically underpinned manner. It is necessary to establish a thorough evaluation methodology, preferably using a mixed methods design that includes both a qualitative process evaluation and a comprehensive outcome evaluation using validated questionnaires, taking into account the NN/APN, the interprofessional team and organizational level.
The synthesis of evidence may be useful to organizations developing and implementing mentoring programmes for both SN/NN and APN. The development of a mentoring programme for nursing experts should be considered a complex intervention that requires theoretical frameworks and contextual considerations.
Not applicable, as no patients or public were involved.
Objetivo: Comprender la relación que establecen profesores, estudiantes y enfermeras asistenciales, entre teoría y práctica del cuidado cultural.
Métodos: Cualitativo, hermenéutico, con enfoque crítico. Se utilizó cuestionario socio demográfico, grupos de discusión y entrevistas episódicas.
Muestra: 34 participantes entre estudiantes, profesores y enfermeros asistenciales.
Resultados: Se identificaron tres temas: 1. Teoría y práctica del cuidado cultural en enfermería: lo aprendido. El cuidado cultural no está formalizado en el currículo, algunos aspectos del cuidado cultural son incluidos en la teoría de los cursos. 2. Práctica y teoría del cuidado cultural en enfermería: lo vivido. Los protocolos rígidos y homogeneizantes de las instituciones de salud fueron los mayores obstáculos para concretar en la práctica el cuidado cultural. 3. Relación entre la teoría y la práctica en Enfermería: lo reconocido. Los profesores reconocen su escasa preparación para formar a los estudiantes en el cuidado cultural.
Conclusiones: Existe una fisura entre la teoría y la práctica en torno al cuidado cultural. Se requiere incluir el cuidado cultural en el currículo y hacerlo congruente con la teoría y la práctica, permitiendo el diálogo de saberes y superando no solo barreras comunicativas, sino actitudinales e institucionales, las cuales se encontraron presentes en el estudio.
Introducción: La anticoncepción ha sido protagonista de gran parte de la historia del ser humano y ha sido influenciada por la cultura durante el proceso. Desde que se separó la reproducción de la sexualidad y el exceso de población empezó a generar falta de recursos en las poblaciones, se han buscado métodos que controlasen la concepción.
Método: Se realizó una revisión narrativa en las bases de datos biomédicas: Scielo, Pubmed, Dialnet, CUIDEN y Google Scholar. La búsqueda bibliográfica se realizó entre los meses de Agosto y Diciembre de 2021.
Resultados: Las estrategias de búsqueda iniciales identificaron un total de 48247 artículos. Una vez aplicados los criterios de exclusión, se seleccionaron 19 artículos de revista (6 en Scielo, 3 en Pubmed, 2 en Dialnet, 2 en CUIDEN y 6 en Google Scholar) y 2 libros.
Conclusiones: Los recursos y la cultura de la sociedad han sido condicionantes de la sexualidad y la reproducción en cada momento histórico. En el s.XX se inició la lucha por el derecho y libertad de la mujer sobre el control de la natalidad, implementándose así la planificación familiar, que, desde entonces, proporciona información sobre los métodos anticonceptivos y facilita su acceso de forma libre y confidencial.
Background
Controlling high blood pressure (BP) continues to be a major concern because the associated complications can lead to an increased risk of heart, brain, and kidney disease. Those with hypertension, despite lifestyle and diet modifications and pharmacotherapy, defined as resistant hypertension, are at increased risk for further risk for morbidity and mortality. Understanding inflammation in this population may provide novel avenues for treatment.
Objectives
This study aimed to examine a broad range of cytokines in adults with cardiovascular disease and identify specific cytokines associated with resistant hypertension.
Methods
A secondary data analysis was conducted. The parent study included 156 adults with a history of myocardial infarction within the past 3–7 years and with a multiplex plasma analysis yielding a cytokine panel. A network analysis with lasso penalization for sparsity was performed to explore associations between cytokines and BP. Associated network centrality measures by cytokine were produced, and a community graph was extracted. A sensitivity analysis BP was also performed.
Results
Cytokines with larger node strength measures were sTNFR2 and CX3. The graphical network highlighted six cytokines strongly associated with resistant hypertension. Cytokines IL-29 and CCL3 were found to be negatively associated with resistant hypertension, whereas CXCL12, MMP3, sCD163, and sIL6Rb were positively associated with resistant hypertension.
Discussion
Understanding the network of associations through exploring oxidative stress and vascular inflammation may provide insight into treatment approaches for resistant hypertension.
Background
The prevalence of short sleep duration is rising and is linked to chronic comorbidities, such as metabolic syndrome (MetS). Sleep extension interventions in adults with MetS comorbidities and short sleep duration are limited and vary widely in terms of approach and duration.
Objectives
This pilot study aimed to test the feasibility and acceptability of a personalized 12-week systematic sleep time extension intervention on post-intervention sleep outcomes in middle-aged adults at risk for MetS with actigraphy-estimated short sleep duration.
Methods
A single-arm, 12-week, 12-session systematic sleep time extension intervention was delivered weekly via videoconferencing. Feasibility and acceptability were assessed using retention rates and mean sleep diary completions. Sleep was estimated for 14 consecutive days prior to and immediately following the 12-week intervention using wrist actigraphy. Daytime sleepiness was assessed using the Epworth Sleepiness Scale. Paired sample t-tests modeled changes in study outcomes.
Results
Study participants (N = 41) had a mean age of 52 years and were mostly female and White; 86% attended >80% of sessions, and mean sleep diary completion was 6.7 diaries/week. Significant improvements in sleep from pre- to post-intervention included increased total sleep time, earlier sleep onsets, more regular sleep onsets, a higher sleep regularity index, and reduced daytime sleepiness. Extending sleep, as well as improving sleep timing and regularity in middle-aged adults with actigraphy-estimated short sleep duration and at risk for MetS, is feasible and acceptable.
Discussion
Behavioral sleep characteristics may be modifiable and present a novel behavioral paradigm for mitigating MetS risk. This pilot study provides a proof of concept for the feasibility, acceptability, and preliminary effectiveness of a systematic sleep time extension for middle-aged adults at risk for MetS with actigraphy-estimated short sleep duration.
The Improving the Wellbeing of people with Opioid Treated CHronic pain (I-WOTCH) randomised controlled trial found that a group-based educational intervention to support people using strong opioids for chronic non-malignant pain helped a significant proportion of people to stop or decrease opioid use with no increase in pain-related disability. We report a linked process evaluation of the group-based intervention evaluated in comparison to a usual-care control group that received a self-help booklet and relaxation CD.
We interviewed 18 intervention facilitators, and 20 intervention and 20 control participants who had chronic non-malignant pain and were recruited from general (family) practices in the UK. Quantitative data included change mechanism questions on the trial questionnaires which explored motivation, expectations and self-efficacy. Fidelity was assessed by listening to a sample of audio-recorded group sessions and nurse consultations. Quantitative and qualitative data were integrated using ‘follow a thread’ and a mixed-methods matrix.
Four overarching themes emerged: (1) the right time to taper, (2) the backdrop of a life with chronic pain, (3) needing support and (4) the benefits of being in a group. Delivery fidelity was good, adherence (83%) and competence (79%) across a range of intervention groups. Staff delivering the intervention found three typical responses to the intervention: resistance, open to trying and feeling it was not the right time. The group experience was important to those in the intervention arm. It provided people with a forum in which to learn about the current thinking about opioid usage and its effects. It also gave them examples of how feasible or personally relevant coming off opioids might be.
The process evaluation data showed that the I-WOTCH intervention was well delivered, well received and useful for most interviewees. Being ‘the right time’ to taper and having support throughout tapering, emerged as important factors within the context of living with chronic pain.
The Wound-QoL assesses the impact of chronic wounds on patients' health-related quality of life (HRQoL). A 17-item and a shortened 14-item version are available. The Wound-QoL-17 has been validated for multiple languages. For the Wound-QoL-14, psychometric properties beyond internal consistency were lacking. We aimed to validate both Wound-QoL versions for international samples representing a broad range of European countries, including countries for which validation data had yet been pending. Patients with chronic wounds of any aetiology or location were recruited in Austria, Lithuania, the Netherlands, Poland, Slovakia, Spain, Switzerland and Ukraine. Psychometric properties were determined for both Wound-QoL versions for the overall sample and, if feasible, country-wise. We included 305 patients (age 68.5 years; 52.8% males). Internal consistency was high in both Wound-QoL-17 (Cronbach's α: 0.820–0.933) and Wound-QoL-14 (0.779–0.925). Test–retest reliability was moderate to good (intraclass correlation coefficient: 0.618–0.808). For Wound-QoL-17 and Wound-QoL-14, convergent validity analyses showed highest correlations with global HRQoL rating (r = 0.765; r = 0.751) and DLQI total score (r = 0.684; r = 0.681). Regarding clinical data, correlations were largest with odour (r = −0.371; r = −0.388) and wound size (r = 0.381; r = 0.383). Country-wise results were similar. Both Wound-QoL versions are valid to assess HRQoL of patients with chronic wounds. Due to its psychometric properties and brevity, the Wound-QoL-14 might be preferrable in clinical practice where time is rare. The availability of various language versions allows for the use of this questionnaire in international studies and in clinical practice when foreign language patients are being treated.
To describe the application of selected creative and participatory research methods in nursing science.
Research methodology paper.
Researcher-initiated role play, stimulated recall interviews, the Storycrafting method, painting and drawing. Altogether, 11 children (5–7 years old) and 12 parents participated in the research.
Each small group (n = 3) acted differently during the data collection. Not every child wanted to play, draw or tell stories, but they all expressed their views through some method. Although the same themes emerged from children's narratives, they could not have been verified by just one method.
Using creative and participatory methods and the principles of studies of child perspectives are applicable ways of conducting research in nursing science. Children must be treated as individuals during the research process, and they must have opportunities to use several communication methods to express their views.
Understanding different ways to interact with children and hear children's views will help nurses to encounter children.
In this article, we present a valid way of conducting research with children. By following our protocol, nursing research from a child perspective can be implemented.
Consolidated criteria for reporting qualitative research (COREQ).
The child participants were involved in choosing physical places for data collection and the usage and order of the selected methods. Both the children and the adult participants took part in interpreting the research data.
Chronic wounds can severely limit patient's social life. This cross-sectional study investigated quantitatively social support of patients with chronic wounds, its association with health-related quality of life as well as qualitatively changes in social participation of these patients. Overall, 263 patients from seven countries participated. The most frequent wound class was leg ulcer (49.2%). Results revealed generally high levels of social support (mean global score: 5.5) as measured with the Multidimensional Scale of Perceived Social Support. However, individuals differed considerably (range 1.0–7.0). All dimensions of social support differed by patients' family and living situations (p < 0.001 to p = 0.040) and were positively correlated with generic health-related quality of life (r = 0.136–0.172). Having children, living with others and being in a relationship were significant predictors of having higher global social support. Patients reported great support from family members. Many participants reported no changes in relationships with friends. Wound care managers took an important role and provided additional emotional support. Patients reported a range of discontinued activities. Despite the high overall level of social support, inter-individual differences should be acknowledged. The importance of family carers should be acknowledged to be able to reduce caregiver burden and to ensure high-qualitative wound care.
by Laurie Simard, Julie Bouchard, Martin Lavallière, Tommy Chevrette
This article discussed the issue of low PA levels among school-aged children and highlights the promising approach of school-based interventions, including physically active learning (PAL), to increase PA levels. The study aimed to co-design and to assess the implementation of a PAL program for 8 weeks in 4 elementary classrooms (82 students and 7 teachers), emphasizing the potential of integrating PA with academic learning and the importance of co-designing programs with teachers to maximize their effectiveness. Technology was found to support PAL practices in promoting PA and academic achievement. The study underscores the need for further research to explore the societal implications of PAL programs, including their potential to improve the health and well-being of children while promoting positive academic outcomes.
by Frederick P. Rivara, Ashley B. Hink, Deborah Kuhls, Samantha Banks, Lauren L. Agoubi, Shelbie Kirkendoll, Alex Winchester, Christopher Hoeft, Bhavin Patel, Avery Nathens
Firearm deaths continue to be a major public health problem, but the number of non-fatal firearm injuries and the characteristics of patients and injuries is not well known. The American College of Surgeons Committee on Trauma, with support from the National Collaborative on Gun Violence Research, leveraged an existing data system to capture lethal and non-lethal injuries, including patients treated and discharged from the emergency department and collect additional data on firearm injuries that present to trauma centers. In 2020, Missouri had the 4th highest firearm mortality rate in the country at 23.75/100,000 population compared to 13.58/100,000 for the US overall. We examined the characteristics of patients from Missouri with firearm injuries in this cross-sectional study. Of the overall 17,395 patients, 1,336 (7.7%) were treated at one of the 11 participating trauma centers in Missouri during the 12-month study period. Patients were mostly male and much more likely to be Black and uninsured than residents in the state as a whole. Nearly three-fourths of the injuries were due to assaults, and overall 7.7% died. Few patients received post-discharge services.
by Laura Capitán-Moyano, Nerea Cañellas-Iniesta, María Arias-Fernández, Miquel Bennasar-Veny, Aina M. Yáñez, Enrique Castro-Sánchez
Food insecurity in recent years has increased worldwide due to many planetary events such as the COVID-19 pandemic, geopolitical conflicts, the climate crisis, and globalization of markets. Adolescents are a particularly vulnerable group to food insecurity, as they enter adulthood with less parental supervision and greater personal autonomy, but less legislative or institutional protection. The experience of food insecurity in adolescents is influenced by several environmental factors at different levels (interpersonal, organizational, community, and societal), although they are not usually addressed in the design of interventions, prioritizing the individual behavioural factors. We present a scoping review protocol for assessing and identifying the environmental factors that could influence adolescents’ food insecurity. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the PRISMA guidelines for Scoping Reviews (PRISMA-ScR) to prepare the protocol. The search strategy will be performed in the following databases: Pubmed/Medline, EMBASE, Biblioteca Virtual de Salud, EBSCOHost, Scopus, Web of Science, and Cochrane Library Plus. The reference list of the included studies will also be hand-searched. Grey literature will be search through the electronic database Grey Literature Report, and local, provincial, national, and international organisations’ websites. Assessment of eligibility after screening of titles, abstract and full text, and the resolution of discrepancies will be performed by three independent reviewers. This scoping review will contribute to refine the “logic model of the problem” which constitutes the first step in the intervention mapping protocol. The “logic model of the problem” from the intervention mapping protocol will serve to classify and analyse the environmental factors. The findings from this review will be presented to relevant stakeholders that have a role in shaping the environmental factors.
by Camilla Michalski, Apira Ragunathan, Adrian Foster, Lief Pagalan, Casey Chu, Lori M. Diemert, John F. Helliwell, Diana Urajnik, Ruth Speidel, Tina Malti, Dianne Fierheller, Laura Fusca, Ian Zenlea, Scott McKean, Laura C. Rosella
BackgroundUnderstanding what promotes or hinders a community’s capacity to serve the priorities of its residents is essential for the alignment of citizen needs and governance. Participatory approaches that engage community residents on the topic of community wellbeing are useful methods for defining outcomes that reflect a community’s goals and priorities. Using qualitative focus group methods, the aim of this study was to outline bottom-up definitions of community wellbeing from a diverse pool of community residents in Ontario, Canada.
MethodsSemi-structured, two-hour group interviews were conducted with adult (≥18 years) participants (N = 15) residing in four communities across Canada’s largest province of Ontario. Participants were purposively selected from a pool of screening questionnaires to ensure diverse group compositions based on race, gender, age, and educational attainment. Interviews were thematically analysed using descriptive and interpretive methods to characterize resident conceptions of community wellbeing.
ResultsFocus group participants were between 18 and 75 years of age and most had lived in their local community for 5 or more years. Four major themes emerged: (1) a sense of community belonging is cultivated through shared spaces, routines, support, and identities; (2) a community constitutes the amenities and social contexts that enable residents to thrive; (3) effective regional decision-making must be community-informed; and (4) the wellbeing of a community relies on equal opportunities for engagement and participation.
ConclusionsResidents described their communities and their associated wellbeing as a combination of accessible amenities and opportunities to engage without marginalization. This study underscores the value of participatory approaches in community wellbeing research, where the viewpoint and life experience of residents is used to inform local decision-making and service delivery. Future research will capture more diverse perspectives towards community belonging, particularly from community newcomers, for the development of regionally appropriate indicators of community wellbeing.
by Jimmy Zhang, Anh H. Nguyen, Daniel Jilani, Ramses Seferino Trigo Torres, Lauren Schmiess-Heine, Tai Le, Xing Xia, Hung Cao
Chronic methamphetamine use, a widespread drug epidemic, has been associated with cardiac morphological and electrical remodeling, leading to the development of numerous cardiovascular diseases. While methamphetamine has been documented to induce arrhythmia, most results originate from clinical trials from users who experienced different durations of methamphetamine abuse, providing no documentation on the use of methamphetamine in standardized settings. Additionally, the underlying molecular mechanism on how methamphetamine affects the cardiovascular system remains elusive. A relationship was sought between cardiotoxicity and arrhythmia with associated methamphetamine abuse in zebrafish to identify and to understand the adverse cardiac symptoms associated with methamphetamine. Zebrafish were first treated with methamphetamine 3 times a week over a 2-week duration. Immediately after treatment, zebrafish underwent electrocardiogram (ECG) measurement using an in-house developed acquisition system for electrophysiological analysis. Subsequent analyses of cAMP expression and Ca2+ regulation in zebrafish cardiomyocytes were conducted. cAMP is vital to development of myocardial fibrosis and arrhythmia, prominent symptoms in the development of cardiovascular diseases. Ca2+ dysregulation is also a factor in inducing arrhythmias. During the first week of treatment, zebrafish that were administered with methamphetamine displayed a decrease in heart rate, which persisted throughout the second week and remained significantly lower than the heart rate of untreated fish. Results also indicate an increased heart rate variability during the early stage of treatment followed by a decrease in the late stage for methamphetamine-treated fish over the duration of the experiment, suggesting a biphasic response to methamphetamine exposure. Methamphetamine-treated fish also exhibited reduced QTc intervals throughout the experiment. Results from the cAMP and Ca2+ assays demonstrate that cAMP was upregulated and Ca2+ was dysregulated in response to methamphetamine treatment. Collagenic assays indicated significant fibrotic response to methamphetamine treatment. These results provide potential insight into the role of methamphetamine in the development of fibrosis and arrhythmia due to downstream effectors of cAMP.
by Silvia A. Purro, Michael Farmer, Elizabeth Noble, Claire J. Sarell, Megan Powell, Daniel Yip, Lauren Giggins, Leila Zakka, David X. Thomas, Mark Farrow, Andrew J. Nicoll, Dominic Walsh, John Collinge
Oligomers formed from monomers of the amyloid β-protein (Aβ) are thought to be central to the pathogenesis of Alzheimer’s disease (AD). Unsurprisingly for a complex disease, current mouse models of AD fail to fully mimic the clinical disease in humans. Moreover, results obtained in a given mouse model are not always reproduced in a different model. Cellular prion protein (PrPC) is now an established receptor for Aβ oligomers. However, studies of the Aβ-PrPC interaction in different mouse models have yielded contradictory results. Here we performed a longitudinal study assessing a range of biochemical and histological features in the commonly used J20 and APP-PS1 mouse models. Our analysis demonstrated that PrPC ablation had no effect on amyloid accumulation or oligomer production. However, we found that APP-PS1 mice had higher levels of oligomers, that these could bind to recombinant PrPC, and were recognised by the OC antibody which distinguishes parallel, in register fibrils. On the other hand, J20 mice had a lower level of Aβ oligomers, which did not interact with PrPC when tested in vitro and were OC-negative. These results suggest the two mouse models produce diverse Aβ assemblies that could interact with different targets, highlighting the necessity to characterise the conformation of the Aβ oligomers concomitantly with the toxic cascade elicited by them. Our results provide an explanation for the apparent contradictory results found in APP-PS1 mice and the J20 mouse line in regards to Aβ toxicity mediated by PrPC.
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