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1.
J Biol Chem ; 298(12): 102590, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36244453

RESUMEN

Type A γ-aminobutyric acid receptors (GABAARs) represent a family of pentameric GABA-gated Cl-/HCO3- ion channels which mediate inhibitory transmission in the central nervous system. Cell surface expression of GABAARs, a prerequisite for their function, is dependent on the appropriate assembly of the receptor subunits and their transient interactions with molecular chaperones within the endoplasmic reticulum (ER) and Golgi apparatus. Here, we describe a highly conserved amino acid sequence within the extracellular N-terminal domain of the receptor subunits adjoining the first transmembrane domain as a region important for GABAAR processing within the ER. Modifications of this region in the α1, ß3, and γ2 subunits using insertion or site-directed mutagenesis impaired GABAAR trafficking to the cell surface in heterologous cell systems although they had no effect on the subunit assembly. We found that mutated receptors accumulated in the ER where they were shown to associate with chaperones calnexin, BiP, and Grp94. However, their surface expression was increased when ER-associated degradation or proteosome function was inhibited, while modulation of ER calcium stores had little effect. When compared to the wt, mutated receptors showed decreased interaction with calnexin, similar binding to BiP, and increased association with Grp94. Structural modeling of calnexin interaction with the wt or mutated GABAAR revealed that disruption in structure caused by mutations in the conserved region adjoining the first transmembrane domain may impair calnexin binding. Thus, this previously uncharacterized region plays an important role in intracellular processing of GABAARs at least in part by stabilizing their interaction with calnexin.


Asunto(s)
Proteínas Portadoras , Receptores de GABA-A , Animales , Ratones , Calnexina/genética , Calnexina/metabolismo , Espacio Extracelular/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Chaperonas Moleculares/metabolismo , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Subunidades de Proteína/metabolismo
2.
BMC Gastroenterol ; 23(1): 61, 2023 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-36894909

RESUMEN

BACKGROUND: Increased familiarity with capsule endoscopy (CE) has been associated with a growing demand for urgent inpatient procedures. Limited data exists comparing the effect of admission status on colon capsule (CCE) and pan-intestinal capsule (PIC) performance. We aimed to compare the quality of inpatient versus outpatient CCE and PIC studies. METHODS: A retrospective nested case-control study. Patients were identified from a CE database. PillCam Colon 2 Capsules with standard bowel preparation and booster regimen were used in all studies. Basic demographics and key outcome measures were documented from procedure reports and hospital patient records, and compared between groups. RESULTS: 105 subjects were included, 35 cases and 70 controls. Cases were older, were more frequently referred with active bleeding and had more PICs. The diagnostic yield was high at 77% and was similar in both groups. Completion rates were significantly better for outpatients, 43% (n = 15) v's 71% (n = 50), OR 3, NN3. Neither gender nor age affected completion rates. Completion rates and preparation quality were similar for CCE and PIC inpatient procedures. CONCLUSION: Inpatient CCE and PIC have a clinical role. There is an increased risk of incomplete transit in inpatients, and strategies to mitigate against this are needed.


Asunto(s)
Endoscopía Capsular , Humanos , Endoscopía Capsular/métodos , Pacientes Ambulatorios , Pacientes Internos , Estudios de Casos y Controles , Estudios Retrospectivos , Colon
3.
Int J Behav Nutr Phys Act ; 19(1): 131, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36195954

RESUMEN

BACKGROUND: The time that children spend in physical activity, sedentary behaviour, and sleep each day (i.e., 24-h time-use behaviours), is related to physical and mental health outcomes. Currently, there is no comprehensive evidence on New Zealand school-aged children's 24-h time-use behaviours, adherence to the New Zealand 24-h Movement Guidelines, and how these vary among different sociodemographic groups. METHODS: This study utilises data from the 8-year wave of the Growing Up in New Zealand longitudinal study. Using two Axivity AX3 accelerometers, children's 24-h time-use behaviours were described from two perspectives: activity intensity and activity type. Compositional data analysis techniques were used to explore the differences in 24-h time-use compositions across various sociodemographic groups. RESULTS: Children spent on average, 31.1%, 22.3%, 6.8%, and 39.8% of their time in sedentary, light physical activity, moderate-to-vigorous physical activity, and sleep, respectively. However, the daily distribution of time in different activity types was 33.2% sitting, 10.8% standing, 7.3% walking, 0.4% running, and 48.2% lying. Both the activity intensity and activity type compositions varied across groups of child ethnicity, gender, and household income or deprivation. The proportion of children meeting each of the guidelines was 90% for physical activity, 62.5% for sleep, 16% for screen time, and 10.6% for the combined guidelines. Both gender and residence location (i.e., urban vs. rural) were associated with meeting the physical activity guideline, whereas child ethnicity, mother's education and residence location were associated with meeting the screen time guideline. Child ethnicity and mother's education were also significantly associated with the adherence to the combined 24-h Movement Guidelines. CONCLUSIONS: This study provided comprehensive evidence on how New Zealand children engage in 24-h time-use behaviours, adherence to the New Zealand 24-h Movement Guidelines, and how these behaviours differ across key sociodemographic groups. These findings should be considered in designing future interventions for promoting healthy time-use patterns in New Zealand children.


Asunto(s)
Ejercicio Físico , Conducta Sedentaria , Niño , Humanos , Estudios Longitudinales , Nueva Zelanda , Tiempo de Pantalla , Sueño
4.
Arch Womens Ment Health ; 25(2): 451-461, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35137331

RESUMEN

The primary objective of this study was to delineate classes of individuals based on depression trajectories from the antenatal period through 54-month postpartum and internal and external resources that are associated with low depression risk. Participants came from the Growing Up in New Zealand (GUiNZ) study (n = 5664), which is a pregnancy cohort study and is nationally representative of the ethnic and socioeconomic diversity of contemporary New Zealand births. Growth curve mixture modeling was used to identify distinct subgroups based on depression scores from the antenatal period through 54-month postpartum. Logistic regression models were run to investigate socioeconomic factors and internal and external resources that were associated with depression class membership. A two-class model, "low risk" and "high risk," resulted in the best model fit. Most of the sample (n = 5110, 90%) fell into the "low-risk" class defined by no-to-mild depression symptoms during pregnancy and decreasing depressive symptoms over time (bintercept = - .05, bslope = - .05). Approximately 10% of the sample fell into the "high-risk" class (n = 554, 10%) defined by mild-to-moderate depressive symptoms during pregnancy and increasing depressive symptomology over time (bintercept = .39, bslope = .57). More positive parenting-related attitudes, better pre-pregnancy self-reported health, informal social supports, and community belonging were significantly associated with greater odds of being in the "low-risk" class, after controlling for socioeconomic factors. These findings suggest that targeting internal and external resources for individuals across the perinatal and early childhood periods is important to mitigating maternal depression.


Asunto(s)
Depresión Posparto , Madres , Preescolar , Estudios de Cohortes , Depresión/diagnóstico , Depresión Posparto/diagnóstico , Depresión Posparto/prevención & control , Femenino , Humanos , Embarazo , Escalas de Valoración Psiquiátrica , Factores de Riesgo
5.
Adv Exp Med Biol ; 1356: 1-29, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35146615

RESUMEN

Three-Dimensional (3D) medical animations incorporated into applications are highly beneficial for clinical outreach and medical communication purposes that work towards educating the clinician and patient. Aortic aneurysms are a clinically important area to communicate with multiple audiences about various treatment options; both abdominal and thoracic aortic aneurysms were selected to create 3D animations and applications to educate medical professionals and patients regarding treatment options. Fenestrated endovascular aortic repair (FEVAR) and thoracic endovascular aortic repair (TEVAR) are both tried and tested minimally invasive surgical methods for treating thoracic aortic aneurysms respectively. The Terumo Aortic Custom Relay Proximal Scalloped stent graft and Fenestrated Anaconda stent graft were both designed specifically for these procedures; however, it can be difficult to visually communicate to clinicians and patients in a straightforward way how these devices work. Therefore, we have developed two interactive applications that use 3D visualisation techniques to demonstrate how these aortic devices function and are implemented. The objective of these applications is to engage both clinicians and patients, therefore demonstrating that the addition of anatomically accurate 3D visualisations within an interactive interface would have a positive impact on public engagement while also ensuring that clinicians will have the best possible understanding of the potential uses of both devices, enabling them to exploit their key features to effectively broaden the treatable patient population.Detailed anatomical modelling and animation was used to generate realistic and accurate rendered videos showcasing both products. These videos were integrated into an interactive application within a modern, professional graphic interface that allowed the user to explore all aspects of the stent device. The resulting applications were broken down into three modules: deployment, clinical performance and features. Following application development, these applications were evaluated by professionals in the field. Overall, positive feedback was received regarding the user-friendly nature of the applications and highly effective animations to showcase the products. The clinical applications and feature modules were particularly successful, while the deployment modules had a neutral response. Biomedical applications such as these show great potential for communicating the key features of medical devices and promoting discussion between clinicians and patients; further testing would need to be conducted on a larger group of participants in order to validate the learning effectiveness of the applications.


Asunto(s)
Aneurisma de la Aorta Torácica , Procedimientos Endovasculares , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Prótesis Vascular , Humanos , Diseño de Prótesis , Stents , Resultado del Tratamiento
6.
Dig Dis Sci ; 66(1): 263-272, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32189102

RESUMEN

INTRODUCTION: The prevalence of coronary artery disease (CAD) is high among patients with cirrhosis; however, the impact of it on cardiovascular disease (CVD) is not known. The aim of the current study was to evaluate CVD events in patients with cirrhosis and impact of cirrhosis on biomarkers of atherogenesis. METHODS: The study included 682 patients with decompensated cirrhosis referred for liver transplantation (LT) evaluation between 2010 and 2017. All patients were followed until they experienced a CVD event, non-cardiac death, liver transplantation or last follow-up. To evaluate mechanistic link, patients with NASH cirrhosis were propensity matched 1:2 to non-cirrhosis NASH patients and biomarkers of atherogenic risk were compared. RESULTS: The composite CVD outcome occurred in 23(3.4%) patients after a median follow-up period of 585 days (IQR 139, 747). A strong association between presence of any CAD and CVD event was noted (HR = 6.8, 95% CI 2.9, 15.9) that was independent of age, gender, BMI, and MELD score. In competing risk model, the combined rate of LT and non-cardiac was significantly higher when compared to the rate of CVD events. Marker of insulin resistance and inflammation-related markers were similar in patients with and without cirrhosis. Patients with cirrhosis were more likely to have reduced VLDL, sdLDL-C, LDL-C, and triglycerides. Interestingly, patients with cirrhosis had an increase in serum HDL-2, the anti-atherogenic lipoprotein, and adiponectin, a protective serum adipokine. CONCLUSION: The risk of CVD events in patients with cirrhosis is low and may potentially be due to improvement in markers of atherogenic risk.


Asunto(s)
Enfermedades Cardiovasculares/sangre , Progresión de la Enfermedad , Mediadores de Inflamación/sangre , Trasplante de Hígado/tendencias , Enfermedad del Hígado Graso no Alcohólico/sangre , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Enfermedades Cardiovasculares/diagnóstico , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/cirugía , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/cirugía , Estudios Retrospectivos
7.
BMC Pregnancy Childbirth ; 21(1): 827, 2021 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-34903186

RESUMEN

BACKGROUND: Perinatal (antenatal and postpartum) depression impacts approximately 12% of mothers. Perinatal depression can impact everyday functioning for mothers, and the relationship with, and development of, their children. The purpose of this study was to investigate depression trajectories from the antenatal period through 54-months postpartum and associations with child body mass index at 54-months postpartum. METHODS: This study applied latent growth modeling to the Growing Up in New Zealand study, which is a longitudinal pregnancy cohort study that provides nationally representative-level data, to investigate associations between depression at three time points (antenatal, 9-months postpartum, 54-months postpartum) and child body mass index at 54-months (n=4897). RESULTS: The average slope of depression for this sample is low and decreases over time. When child BMI was added to the model as an outcome variable, both antenatal depression (B=.25, p<.01), and the rate of change of depression across the perinatal and postpartum periods (B=.09, p<.01) were associated with child BMI at 54-months postpartum. After controlling for sociodemographic characteristics, antenatal depression, but not the slope of depression, remained significantly associated with child BMI (B=.05, p<.05). When controlling for maternal pre-pregnancy BMI the effect of antenatal depression on child BMI at 54-months was entirely attenuated (χ2 (9) = 39.60, p < .05, SRMR = 0.01, CFI = .99, RMSEA = 0.03, BIC=53213). CONCLUSIONS: Our findings align with the Developmental Origins of Health and Disease theory and imply that both the physical and mental health of mothers during pregnancy may be important indicators of child growth and development outcomes. Early intervention directed towards women who have even mild depression scores during pregnancy may promote healthy child development outcomes. Additionally, given the heterogeneity of depressive symptoms over time seen in this study, multiple assessment periods across the postpartum period may be valuable to adequately address and support maternal mental health.


Asunto(s)
Índice de Masa Corporal , Desarrollo Infantil , Depresión Posparto/epidemiología , Depresión/epidemiología , Madres/psicología , Preescolar , Estudios de Cohortes , Depresión/clasificación , Depresión Posparto/clasificación , Etnicidad , Femenino , Humanos , Lactante , Análisis de Clases Latentes , Estudios Longitudinales , Nueva Zelanda/epidemiología , Cuestionario de Salud del Paciente , Embarazo , Escalas de Valoración Psiquiátrica
8.
Hum Resour Health ; 18(1): 66, 2020 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-32958066

RESUMEN

BACKGROUND: Community health workers (CHWs) are increasingly engaged to address human resource shortages and fill primary healthcare gaps. In Eswatini, a cadre of CHWs called Rural Health Motivators (RHM) was introduced in 1976 to respond to key public health challenges. However, the emergence of health needs, particularly HIV/TB, has been met with inadequate programme amendments, and the role of RHMs has become marginalised following the addition of other CHWs supported by non-governmental organisations. This study was implemented to understand the role of RHMs in decentralised HIV/TB activities. In this paper, we explore the findings in relation to the recognition of RHMs and the programme. METHODS: This exploratory qualitative study utilised individual in-depth interviews, group and focus group discussions, participatory methods (utilising a game format) and observations. Participants were purposively selected and comprised RHM programme implementers, community stakeholders and local and non-governmental personnel. Data collection took place between August and September 2019. Interviews were conducted in English or siSwati and transcribed. SiSwati interviews were translated directly into English. All interviews were audio-recorded, manually coded and thematically analysed. Data was validated through methodical triangulation. RESULTS: Suboptimal organisational structure and support, primarily insufficient training and supervision for activities were factors identified through interviews and observation activities. Significant confusion of the RHM role was observed, with community expectations beyond formally endorsed tasks. Community participants expressed dissatisfaction with receiving health information only, preferring physical assistance in the form of goods. Additionally, gender emerged as a significant influencing factor on the acceptability of health messages and the engagement of RHMs with community members. Expectations and structurally limiting factors shape the extent to which RHMs are recognised as integral to the health system, at all social and organisational levels. CONCLUSIONS: Findings highlight the lack of recognition of RHMs and the programme at both community and national levels. This, along with historical neglect, has hindered the capacity of RHMs to successfully contribute to positive health outcomes for rural communities. Renewed attention and support mechanisms for this cadre are needed. Clarification of the RHM role in line with current health challenges and clearer role parameters is essential.


Asunto(s)
Agentes Comunitarios de Salud , Salud Rural , Esuatini , Femenino , Grupos Focales , Humanos , Masculino , Motivación , Embarazo , Investigación Cualitativa
9.
Curr Opin Gastroenterol ; 35(4): 288-295, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-33216483

RESUMEN

PURPOSE OF REVIEW: Women's health includes comprehensive physical, mental and preventive care. This section will provide an overview of some of the most common disorders that can impact the health and quality of life (QOL) of women with inflammatory bowel diseases (IBDs). RECENT FINDINGS: Women with IBD are at higher risk for cervical dysplasia compared to healthy controls with most cases preventable with vaccination. Current rates of cervical cancer screening and human papilloma virus vaccination remain low. Irritable bowel syndrome is highly prevalent among women with IBD and may present with similar symptoms. In addition, gastrointestinal symptoms may worsen during the menstrual cycle. Evaluation for active inflammation and infection should be undertaken prior to changing IBD medications. Fecal incontinence is prevalent but highly underreported in women with IBD. Further, sexual dysfunction is ubiquitous in women with IBD. Many aspects of IBD impact sexual function, including side-effects of medications, changes in body image and surgical interventions. SUMMARY: Understanding other disorders that may cause symptoms in women with IBD is important for providers to obtain a clear history, provide the appropriate treatment and improve QOL. Caring for women with IBD involves more comprehensive care beyond the treatment of active luminal inflammation.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Neoplasias del Cuello Uterino , Detección Precoz del Cáncer , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Embarazo , Calidad de Vida , Salud de la Mujer
10.
J Dairy Res ; 85(2): 185-192, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29785904

RESUMEN

Inflammation of the mammary gland following bacterial infection, commonly known as mastitis, affects all mammalian species. Although the aetiology and epidemiology of mastitis in the dairy cow are well described, the genetic factors mediating resistance to mammary gland infection are not well known, due in part to the difficulty in obtaining robust phenotypic information from sufficiently large numbers of individuals. To address this problem, an experimental mammary gland infection experiment was undertaken, using a Friesian-Jersey cross breed F2 herd. A total of 604 animals received an intramammary infusion of Streptococcus uberis in one gland, and the clinical response over 13 milkings was used for linkage mapping and genome-wide association analysis. A quantitative trait locus (QTL) was detected on bovine chromosome 11 for clinical mastitis status using micro-satellite and Affymetrix 10 K SNP markers, and then exome and genome sequence data used from the six F1 sires of the experimental animals to examine this region in more detail. A total of 485 sequence variants were typed in the QTL interval, and association mapping using these and an additional 37 986 genome-wide markers from the Illumina SNP50 bovine SNP panel revealed association with markers encompassing the interleukin-1 gene cluster locus. This study highlights a region on bovine chromosome 11, consistent with earlier studies, as conferring resistance to experimentally induced mammary gland infection, and newly prioritises the IL1 gene cluster for further analysis in genetic resistance to mastitis.


Asunto(s)
Mastitis Bovina/genética , Mastitis Bovina/inmunología , Infecciones Estreptocócicas/veterinaria , Animales , Bovinos , Mapeo Cromosómico/veterinaria , Modelos Animales de Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Estudio de Asociación del Genoma Completo/veterinaria , Genotipo , Hibridación Genética , Mastitis Bovina/microbiología , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo/genética
11.
Genet Med ; 19(5): 546-552, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-27657686

RESUMEN

PURPOSE: It has been argued that rare diseases should be recognized as a public health priority. However, there is a shortage of epidemiological data describing the true burden of rare diseases. This study investigated hospital service use to provide a better understanding of the collective health and economic impacts of rare diseases. METHODS: Novel methodology was developed using a carefully constructed set of diagnostic codes, a selection of rare disease cohorts from hospital administrative data, and advanced data-linkage technologies. Outcomes included health-service use and hospital admission costs. RESULTS: In 2010, cohort members who were alive represented approximately 2.0% of the Western Australian population. The cohort accounted for 4.6% of people discharged from hospital and 9.9% of hospital discharges, and it had a greater average length of stay than the general population. The total cost of hospital discharges for the cohort represented 10.5% of 2010 state inpatient hospital costs. CONCLUSIONS: This population-based cohort study provides strong new evidence of a marked disparity between the proportion of the population with rare diseases and their combined health-system costs. The methodology will inform future rare-disease studies, and the evidence will guide government strategies for managing the service needs of people living with rare diseases.Genet Med advance online publication 22 September 2016.


Asunto(s)
Servicios de Salud/economía , Tiempo de Internación/economía , Enfermedades Raras/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Servicios de Salud/estadística & datos numéricos , Humanos , Almacenamiento y Recuperación de la Información/economía , Persona de Mediana Edad , Enfermedades Raras/economía , Estudios Retrospectivos , Australia Occidental/epidemiología , Adulto Joven
12.
Adv Exp Med Biol ; 1031: 55-94, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29214566

RESUMEN

Public health relies on technologies to produce and analyse data, as well as effectively develop and implement policies and practices. An example is the public health practice of epidemiology, which relies on computational technology to monitor the health status of populations, identify disadvantaged or at risk population groups and thereby inform health policy and priority setting. Critical to achieving health improvements for the underserved population of people living with rare diseases is early diagnosis and best care. In the rare diseases field, the vast majority of diseases are caused by destructive but previously difficult to identify protein-coding gene mutations. The reduction in cost of genetic testing and advances in the clinical use of genome sequencing, data science and imaging are converging to provide more precise understandings of the 'person-time-place' triad. That is: who is affected (people); when the disease is occurring (time); and where the disease is occurring (place). Consequently we are witnessing a paradigm shift in public health policy and practice towards 'precision public health'.Patient and stakeholder engagement has informed the need for a national public health policy framework for rare diseases. The engagement approach in different countries has produced highly comparable outcomes and objectives. Knowledge and experience sharing across the international rare diseases networks and partnerships has informed the development of the Western Australian Rare Diseases Strategic Framework 2015-2018 (RD Framework) and Australian government health briefings on the need for a National plan.The RD Framework is guiding the translation of genomic and other technologies into the Western Australian health system, leading to greater precision in diagnostic pathways and care, and is an example of how a precision public health framework can improve health outcomes for the rare diseases population.Five vignettes are used to illustrate how policy decisions provide the scaffolding for translation of new genomics knowledge, and catalyze transformative change in delivery of clinical services. The vignettes presented here are from an Australian perspective and are not intended to be comprehensive, but rather to provide insights into how a new and emerging 'precision public health' paradigm can improve the experiences of patients living with rare diseases, their caregivers and families.The conclusion is that genomic public health is informed by the individual and family needs, and the population health imperatives of an early and accurate diagnosis; which is the portal to best practice care. Knowledge sharing is critical for public health policy development and improving the lives of people living with rare diseases.


Asunto(s)
Genómica/métodos , Política de Salud , Medicina de Precisión , Salud Pública , Enfermedades Raras/terapia , Predisposición Genética a la Enfermedad , Genómica/organización & administración , Política de Salud/legislación & jurisprudencia , Humanos , Fenotipo , Formulación de Políticas , Valor Predictivo de las Pruebas , Pronóstico , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Salud Pública/legislación & jurisprudencia , Enfermedades Raras/diagnóstico , Enfermedades Raras/epidemiología , Enfermedades Raras/genética
13.
Heart Lung Circ ; 26(6): 635-639, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28065523

RESUMEN

Familial hypercholesterolaemia (FH) is the most common and serious monogenic disorder of lipoprotein metabolism that leads to premature coronary heart disease. Patients with FH are often under-treated, and many remain undiagnosed. The deployment of the FH Australasia Network Registry is a crucial component of the comprehensive model of care for FH, which aims to provide a standardised, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes. The FH Australasia Network Registry was customised using a registry framework that is an open source, interoperable system that enables the efficient customisation and deployment of national and international web-based disease registries that can be modified dynamically as registry requirements evolve. The FH Australasia Network Registry can be employed to improve health services for FH patients across the Australasia-Pacific region, through the collation of data to facilitate clinical service planning, clinical trials, clinical audits, and to inform clinical best practice.


Asunto(s)
Atención a la Salud , Hiperlipoproteinemia Tipo II/epidemiología , Internet , Sistema de Registros , Australia/epidemiología , Femenino , Humanos , Hiperlipoproteinemia Tipo II/terapia , Masculino
14.
J Dairy Sci ; 99(3): 2329-2338, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26778312

RESUMEN

Precalving feeding level affects dry matter intake, postcalving energy balance, the risk of hepatic lipidosis and metabolic disease, and gene expression in liver and adipose tissue. These coincide with a higher risk of disease postpartum and, very likely, a failure to reach optimum production as well as reproductive targets. Current interpretation of the available evidence suggest that metabolic stressors affect the immune system of transition dairy cows and lead to reduced immunocompetence. The objective of the current study was to investigate the effect of precalving body condition score (BCS) and level of feeding on immunocompetence during the peripartum period. Twenty-three weeks before calving, 78 cows were allocated randomly to 1 of 6 treatment groups (n=13) in a 2 × 3 factorial arrangement: 2 precalving BCS categories (4.0 and 5.0, based on a 10-point scale) and 3 levels of energy intake during the 3 wk preceding calving (75, 100, and 125% of estimated requirements). Blood was sampled precalving and at 1, 2 and 4 wk after calving. Cells were analyzed by flow cytometry and quantitative real-time PCR. The numbers of T helper lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), natural killer cells (CD335+), and γδ T lymphocytes (WC1+) as well as their activation status [IL-2 receptor (CD25)+ cells] were highly variable between animals, but there was no evident effect of BCS, feeding level, or time. All groups presented with an increase in expression of cytokines in unstimulated blood cells in the week after calving, although this was significant only for IFNG in the BCS 4.0 group. Analysis of in vitro-stimulated cells allowed 2 general observations: (1) cows with high energy intake precalving (125%) had increased cytokine expression precalving, and (2) all cows had increased cytokine expression in the week after calving. The present study provides evidence that prepartum feed management can affect immunocompetence during the transition period. Considering the current results, optimally conditioned animals might benefit from a restricted precalving diet, whereas underconditioned cows can be fed to requirements.


Asunto(s)
Composición Corporal , Bovinos/fisiología , Conducta Alimentaria , Inmunocompetencia , Animales , Bovinos/inmunología , Industria Lechera , Femenino , Periodo Periparto
15.
Physiol Genomics ; 47(4): 89-101, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25604124

RESUMEN

Postpartum uterine inflammation (endometritis) in the dairy cow is associated with lower fertility at both the time of infection and after the inflammation has resolved. We hypothesized that aberrant DNA methylation may be involved in the subfertility associated with uterine inflammation. The objective of this study was to characterize genome-wide DNA methylation and gene expression in the endometrium of dairy cows with subclinical endometritis (SCE). Endometrial tissues were obtained at 29 days postpartum (n = 12), and microarrays were used to characterize transcription and DNA methylation. Analyses revealed 1,856 probes differentially expressed in animals with SCE (n = 6) compared with controls (CON, n = 6, P < 0.05, Storey Multiple testing correction) and 2,976 probes with significant correlation between gene expression and bacteriology score. No significant associations among DNA methylation and gene expression were detected. Analysis of transcription data using the Database for Annotation, Visualization, and Integrated Discovery and Gene Set Enrichment Analysis identified several pathways and processes enriched in SCE cows, with the majority related to the immune response. Furthermore, the top ontology terms enriched in genes that had expression data correlated to bacteriology score were: Defense response, inflammatory response, and innate immune response. Gene expression profiles in cows with subclinical endometritis in this study indicate that the immune response is activated, potentially resulting in a local proinflammatory environment in the uterus. If this period of inflammation is prolonged it could result in tissue damage or failure to complete involution of the uterus, which may create a suboptimal environment for future pregnancy.


Asunto(s)
Enfermedades de los Bovinos/inmunología , Bovinos/fisiología , Endometritis/veterinaria , Fertilidad , Reacción de Fase Aguda/inmunología , Animales , Bovinos/inmunología , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/patología , Metilación de ADN , Endometritis/inmunología , Endometritis/microbiología , Endometritis/patología , Femenino , Sistema Inmunológico , Leche/química , Periodo Posparto/inmunología , Útero/patología
19.
J Dairy Sci ; 98(2): 937-46, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25483203

RESUMEN

Peripartum, and especially during the transition period, dairy cows undergo dramatic physiological changes. These coincide with an increased risk of disease during the first 2 wk after calving and have been linked to dairy cows failing to achieve production as well as reproductive targets. Previous evidence suggests that these physiological changes affect the immune system and that transition dairy cows experience some form of reduced immunocompetence. However, almost all of these studies were undertaken in high-production, housed dairy cows. Grazing cows have much lower levels of production and this study aimed to provide clarity whether or not the dysfunctional attributes of the peripartum immune system reported in high production housed cows are evident in these animals. Therefore, cell culture techniques, flow cytometry, and quantitative PCR were applied to analyze the cellular composition of peripheral blood mononuclear cells from transition dairy cows as well as the performance of these cells in an in vitro assay. First, a combination of in vitro stimulation and quantitative PCR for cytokines was validated as a quantifiable immunocompetence assay in 29 cattle and a correlation of quantitative PCR and ELISA demonstrated. Second, the relative number of T helper cells, cytotoxic T cells, B cells, γδ T cells, natural killer cells, and monocytes in peripheral blood was measured, of which B cells and natural killer cells increased in number postcalving (n=29) compared with precalving. Third, following in vitro stimulation cytokine profiles indicated decreased expression of IFNγ, tumor necrosis factor, and IL-17 and increased expression of IL-10 wk 1 after calving, which later all returned to precalving values (n=39). Additionally, treatment of transition cows with a nonsteroidal anti-inflammatory drug (i.e., carprofen) administered on d 1, 3, and 5 postcalving (n=19; untreated control n=20) did not affect the cytokine expression at any time point. In conclusion, an immunocompetence assay has been developed that highlights a characteristic expression pattern for IFNγ, tumor necrosis factor, IL-17, and IL-10 that reflects a state of reduced immunocompetence in moderate-yielding pasture-based transition cows after calving, which is similar to that described for higher-yielding housed cows.


Asunto(s)
Bovinos/fisiología , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Periodo Posparto/fisiología , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Femenino , Regulación de la Expresión Génica/fisiología , Interferón gamma/genética , Interleucina-10/genética , Interleucina-17/genética , Leucocitos Mononucleares , Monocitos/metabolismo , Factor de Necrosis Tumoral alfa/genética
20.
AJOB Neurosci ; 15(1): 32-45, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37450417

RESUMEN

BACKGROUND: Our objective was to evaluate whether the description of a machine learning (ML) app or brain imaging technology to predict the onset of schizophrenia or alcohol use disorder (AUD) influences healthcare professionals' judgments of stigma, empathy, and compassion. METHODS: We randomized healthcare professionals (N = 310) to one vignette about a person whose clinician seeks to predict schizophrenia or an AUD, using a ML app, brain imaging, or a psychosocial assessment. Participants used scales to measure their judgments of stigma, empathy, and compassion. RESULTS: Participants randomized to the ML vignette endorsed less anger and more fear relative to the psychosocial vignette, and the brain imaging vignette elicited higher pity ratings. The brain imaging and ML vignettes evoked lower personal responsibility judgments compared to the psychosocial vignette. Physicians and nurses reported less empathy than clinical psychologists. CONCLUSIONS: The use of predictive technologies may reinforce essentialist views about mental health and substance use that may increase specific aspects of stigma and reduce others.


Asunto(s)
Empatía , Juicio , Humanos , Estigma Social , Personal de Salud/psicología , Atención a la Salud
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