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1.
Article de Anglais | MEDLINE | ID: mdl-39318176

RÉSUMÉ

AIMS: To identify the prevalence, trends, and outcomes of same-day discharge following elective percutaneous coronary intervention among six public hospitals in one Australian State. METHODS AND RESULTS: A retrospective observational research design was used. A total of 4387 cases were obtained from the State Cardiac Outcomes Registry and National Hospital Cost Data Collection. The two datasets were linked using identifiable data items. Patients were those who had elective percutaneous coronary intervention between December 2012 and December 2019 either discharged the same day of the procedure or the next day. Data were analysed using descriptive and inferential statistics. The overall same-day discharge prevalence was 6.5%, with a trend increasing from 0.2% in 2013 to 9.0% in 2019. The prevalence varied at the individual hospital level. Two hospitals did not perform same-day discharge during the study period. The remaining hospitals demonstrated variability in same-day discharge prevalence, with the highest from one hospital being 28.2% in 2019. Almost all same-day discharge patients experienced no complications during or following percutaneous coronary intervention within 24 hours. Compared to next-day discharge, same-day discharge reduced the length of stay by 18 hours and conferred an average of $3695 cost-savings per patient. CONCLUSIONS: There was limited implementation of same-day discharge in the six public hospitals contributing data to this study. Improvement in the same-day discharge rate could result in better hospital resource utilisation and reduce low-value care. Hence, strategies to implement and promote same-day discharge are warranted.

2.
J Exp Biol ; 2024 Sep 25.
Article de Anglais | MEDLINE | ID: mdl-39319442

RÉSUMÉ

Cross-sectional area (CSA) is a fundamental variable in characterizing muscle mechanical properties. Typically, the CSA of a single muscle fibre is assessed by measuring either one or two diameters, and assuming the cross-section is either circular or elliptical in shape. However, fibre cross-sections have irregular shapes. The accuracy and precision of CSAs determined using circular and elliptical shape assumptions are unclear for mammalian skinned muscle fibres. Second harmonic generation imaging of skinned rabbit soleus fibres revealed that the circular assumption overstated real CSA by 5.3±25.9% whereas the elliptical assumption overstated real CSA by 2.8±6.9%. A preferred rotational alignment can bias the circular assumption, as real CSA was overstated by 22.1±24.8% when using the large diameter and understated by 11.4±13% when using the small diameter. With 73% lower variable error and reduced bias, the elliptical assumption is superior to the circular assumption when assessing the CSA of skinned mammalian fibres.

3.
PLoS One ; 19(7): e0307144, 2024.
Article de Anglais | MEDLINE | ID: mdl-39058702

RÉSUMÉ

Idiopathic inflammatory myopathies (IIMs) are rare disorders characterized by inflammation of skeletal muscle, which can result in fatty replacement of muscle, muscle atrophy, and subsequent weakness. Therapeutic advancements have improved clinical outcomes but impose an economic impact on healthcare systems. We aimed to summarize the direct and indirect costs associated with IIMs in a systematic review (PROSPERO Registration #CRD42023443143). Electronic databases (MEDLINE, Embase, CINAHL, and Scopus) were systematically searched for full-length articles (excluding case reports) reporting costs specific to patients diagnosed with an IIM, published between database inception and April 19, 2023. Direct cost categories included inpatient, outpatient, medication, home/long-term care, and durable medical equipment such as mobility and respiratory aids. Indirect costs included lost productivity. Eligibility criteria were met by 21 of the 3,193 unique titles identified. Costs are expressed in 2023 United States of America dollars, with adjustments for differences in purchasing power applied to currency conversions. As no study reported on all cost categories, annualized cost of IIM per patient was estimated by calculating the mean cost per category, and then adding the means of the different cost categories. By this method, IIM was estimated to cost $52,210 per patient per year. Proportional contributions by category were lost productivity (0.278), outpatient care (0.214), medications (0.171), inpatient care (0.161), home/long-term care (0.122), and durable medical equipment (0.053). Newer findings with intravenous immunoglobulin considered first line therapy for IIM demonstrated markedly higher annual medication costs per patient, upwards of $33,900 compared to an average of $3,908 ± $1,042 in older studies. Future cost-effectiveness studies require updated cost-of-illness studies reflecting the evolving sub-classification and treatment options for IIM, and should consider the impact of IIM on patients and their families.


Sujet(s)
Coûts des soins de santé , Myosite , Humains , Myosite/économie , Myosite/thérapie , Adulte , Coûts indirects de la maladie
4.
Cell Calcium ; 123: 102923, 2024 Nov.
Article de Anglais | MEDLINE | ID: mdl-38970922

RÉSUMÉ

The central nervous system (CNS) is constantly surveilled by microglia, highly motile and dynamic cells deputed to act as the first line of immune defense in the brain and spinal cord. Alterations in the homeostasis of the CNS are detected by microglia that respond by extending their processes or - following major injuries - by migrating toward the affected area. Understanding the mechanisms controlling directed cell migration of microglia is crucial to dissect their responses to neuroinflammation and injury. We used a combination of pharmacological and genetic approaches to explore the involvement of calcium (Ca2+) signaling in the directed migration of human induced pluripotent stem cell (iPSC)-derived microglia challenged with a purinergic stimulus. This approach mimics cues originating from injury of the CNS. Unexpectedly, simultaneous imaging of microglia migration and intracellular Ca2+ changes revealed that this phenomenon does not require Ca2+ signals generated from the endoplasmic reticulum (ER) and store-operated Ca2+ entry (SOCE) pathways. Instead, we find evidence that human microglial chemotaxis to purinergic signals is mediated by cyclic AMP in a Ca2+-independent manner. These results challenge prevailing notions, with important implications in neurological conditions characterized by perturbation in Ca2+ homeostasis.


Sujet(s)
Signalisation calcique , Calcium , Mouvement cellulaire , Réticulum endoplasmique , Cellules souches pluripotentes induites , Microglie , Humains , Microglie/métabolisme , Cellules souches pluripotentes induites/métabolisme , Cellules souches pluripotentes induites/cytologie , Réticulum endoplasmique/métabolisme , Calcium/métabolisme , AMP cyclique/métabolisme , Chimiotaxie
5.
bioRxiv ; 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38948841

RÉSUMÉ

Cellular mechanical properties influence cellular functions across pathological and physiological systems. The observation of these mechanical properties is limited in part by methods with a low throughput of acquisition or with low accessibility. To overcome these limitations, we have designed, developed, validated, and optimized a microfluidic cellular deformation system (MCDS) capable of mechanotyping suspended cells on a population level at a high throughput rate of ∼300 cells pers second. The MCDS provides researchers with a viable method for efficiently quantifying cellular mechanical properties towards defining prognostic implications of mechanical changes in pathology or screening drugs to modulate cytoskeletal integrity.

6.
Brain Plast ; 9(1-2): 75-95, 2024.
Article de Anglais | MEDLINE | ID: mdl-38993580

RÉSUMÉ

Brain plasticity, also termed neuroplasticity, refers to the brain's life-long ability to reorganize itself in response to various changes in the environment, experiences, and learning. The brain is a dynamic organ capable of responding to stimulating or depriving environments, activities, and circumstances from changes in gene expression, release of neurotransmitters and neurotrophic factors, to cellular reorganization and reprogrammed functional connectivity. The rate of neuroplastic alteration varies across the lifespan, creating further challenges for understanding and manipulating these processes to benefit motor control, learning, memory, and neural remodeling after injury. Neuroplasticity-related research spans several decades, and hundreds of reviews have been written and published since its inception. Here we present an overview of the empirical papers published between 2017 and 2023 that address the unique effects of exercise, plasticity-stimulating activities, and the depriving effect of social isolation on brain plasticity and behavior.

7.
bioRxiv ; 2024 Mar 27.
Article de Anglais | MEDLINE | ID: mdl-38585873

RÉSUMÉ

Lysosomal storage diseases (LSDs) comprised ~50 monogenic diseases characterized by the accumulation of cellular material in lysosomes and associated defects in lysosomal function, but systematic molecular phenotyping is lacking. Here, we develop a nanoflow-based multi-omic single-shot technology (nMOST) workflow allowing simultaneously quantify HeLa cell proteomes and lipidomes from more than two dozen LSD mutants, revealing diverse molecular phenotypes. Defects in delivery of ferritin and its autophagic receptor NCOA4 to lysosomes (ferritinophagy) were pronounced in NPC2-/- cells, which correlated with increased lyso-phosphatidylcholine species and multi-lamellar membrane structures visualized by cryo-electron-tomography. Ferritinophagy defects correlated with loss of mitochondrial cristae, MICOS-complex components, and electron transport chain complexes rich in iron-sulfur cluster proteins. Strikingly, mitochondrial defects were alleviated when iron was provided through the transferrin system. This resource reveals how defects in lysosomal function can impact mitochondrial homeostasis in trans and highlights nMOST as a discovery tool for illuminating molecular phenotypes across LSDs.

8.
J Pain Symptom Manage ; 68(1): 43-52.e2, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38574876

RÉSUMÉ

BACKGROUND: Palliative care (PC) benefits patients with amyotrophic lateral sclerosis (ALS), however the needs of patients and caregivers and the optimal timing of PC discussions remains unclear. This study reports the analysis of PC consult notes from a larger feasibility trial. The specific aims of this analysis were to i) identify the PC needs of patients with ALS via qualitative analysis and ii) identify characteristics of patients and caregivers that could predict specific PC needs. METHODS: This study was nested within a nonrandomized, prospective study of patients with ALS (and their caregivers) being treated at a multidisciplinary ALS clinic. Exclusion criteria of the main study were age <18 years, inability to complete questionnaires, and prior receipt of PC. All patients were offered a PC consultation (PCC); those who accepted were included in this nested study. Consultation notes were reviewed and thematic and content analyses were conducted. The occurrence of themes across patient and caregiver contextual variables were examined. RESULTS: Thirty-two PCCs were completed between October 2020 and April 2022. Six major themes were identified: PC roles (with subthemes encompassing the spectrum of specialist PC practice including symptom management and advance care planning), engagement with PC, patients' concerns for their caregivers, caregiver-specific concerns, finances, and COVID-19. An average of 12 topics were discussed per PCC (range = 3-22). Discussion of advance care planning, care coordination, and symptom management was common, and these topics were not discussed more frequently in PCCs with patients with lower functional status, more bulbar symptoms, or lower quality of life. Time from diagnosis did not impact topics of discussion. Patients reporting more symptoms of depression more frequently required psychological support, particularly regarding loss of independence, employment, and leisure activities. DISCUSSION: Patients with ALS and their caregivers have a wide range of PC needs. These needs vary irrespective of time from diagnosis, functional status, or quality of life, therefore PCC is recommended for all patients with ALS. PCC should be individualized based on patient and caregiver preferences. TRIAL REGISTRATION INFORMATION: The study was registered with ClinicalTrials.gov (NCT04257760; https://clinicaltrials.gov/ct2/show/NCT04257760) on February 6, 2020. The first enrollment occurred on October 20, 2020.


Sujet(s)
Sclérose latérale amyotrophique , Aidants , Soins palliatifs , Recherche qualitative , Orientation vers un spécialiste , Humains , Sclérose latérale amyotrophique/thérapie , Mâle , Femelle , Adulte d'âge moyen , Aidants/psychologie , Sujet âgé , Études prospectives , COVID-19 , Adulte , Planification anticipée des soins , Études de faisabilité
9.
Front Health Serv ; 4: 1210166, 2024.
Article de Anglais | MEDLINE | ID: mdl-38590731

RÉSUMÉ

Introduction: To support rigorous evaluation across a national portfolio of grants, the United States Department of Veterans Affairs (VA) Office of Rural Health (ORH) adopted an analytic framework to guide their grantees' evaluation of initiatives that reach rural veterans and to standardize the reporting of outcomes and impacts. Advance Care Planning via Group Visits (ACP-GV), one of ORH's Enterprise-Wide Initiatives, also followed the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. ACP-GV is a national patient-centered intervention delivered in a large, veterans integrated healthcare system. This manuscript describes how RE-AIM was used to evaluate this national program and lessons learned from ORH's annual reporting feedback to ACP-GV on their use of the framework to describe evaluation impacts. Methods: We used patient, provider, and site-level administrative health care data from the VA Corporate Data Warehouse and national program management databases for federal fiscal years (FY) spanning October 1, 2018-September 30, 2023. Measures included cumulative and past FY metrics developed to assess program impacts. Results: RE-AIM constructs included the following cumulative and annual program evaluation results. ACP-GV reached 54,167 unique veterans, including 19,032 unique rural veterans between FY 2018 to FY 2023. During FY 2023, implementation adherence to the ACP-GV model was noted in 91.7% of program completers, with 55% of these completers reporting a knowledge increase and 14% reporting a substantial knowledge increase (effectiveness). As of FY 2023, 66 ACP-GV sites were active, and 1,556 VA staff were trained in the intervention (adoption). Of the 66 active sites in FY 2023, 27 were sites previously funded by ORH and continued to offer ACP-GV after the conclusion of three years of seed funding (maintenance). Discussion: Lessons learned developing RE-AIM metrics collaboratively with program developers, implementers, and evaluators allowed for a balance of clinical and scientific input in decision-making, while the ORH annual reporting feedback provided specificity and emphasis for including both cumulative, annual, and rural specific metrics. ACP-GV's use of RE-AIM metrics is a key step towards improving rural veteran health outcomes and describing real world program impacts.

10.
Nat Cell Biol ; 26(3): 378-392, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38429475

RÉSUMÉ

The endoplasmic reticulum (ER) employs a diverse proteome landscape to orchestrate many cellular functions, ranging from protein and lipid synthesis to calcium ion flux and inter-organelle communication. A case in point concerns the process of neurogenesis, where a refined tubular ER network is assembled via ER shaping proteins into the newly formed neuronal projections to create highly polarized dendrites and axons. Previous studies have suggested a role for autophagy in ER remodelling, as autophagy-deficient neurons in vivo display axonal ER accumulation within synaptic boutons, and the membrane-embedded ER-phagy receptor FAM134B has been genetically linked with human sensory and autonomic neuropathy. However, our understanding of the mechanisms underlying selective removal of the ER and the role of individual ER-phagy receptors is limited. Here we combine a genetically tractable induced neuron (iNeuron) system for monitoring ER remodelling during in vitro differentiation with proteomic and computational tools to create a quantitative landscape of ER proteome remodelling via selective autophagy. Through analysis of single and combinatorial ER-phagy receptor mutants, we delineate the extent to which each receptor contributes to both the magnitude and selectivity of ER protein clearance. We define specific subsets of ER membrane or lumenal proteins as preferred clients for distinct receptors. Using spatial sensors and flux reporters, we demonstrate receptor-specific autophagic capture of ER in axons, and directly visualize tubular ER membranes within autophagosomes in neuronal projections by cryo-electron tomography. This molecular inventory of ER proteome remodelling and versatile genetic toolkit provide a quantitative framework for understanding the contributions of individual ER-phagy receptors for reshaping ER during cell state transitions.


Sujet(s)
Protéome , Protéomique , Humains , Réticulum endoplasmique/métabolisme , Autophagie/physiologie , Stress du réticulum endoplasmique , Protéines de transport/métabolisme , Neurogenèse
11.
Alzheimers Dement ; 20(4): 2922-2942, 2024 04.
Article de Anglais | MEDLINE | ID: mdl-38460121

RÉSUMÉ

INTRODUCTION: The BIN1 coding variant rs138047593 (K358R) is linked to Late-Onset Alzheimer's Disease (LOAD) via targeted exome sequencing. METHODS: To elucidate the functional consequences of this rare coding variant on brain amyloidosis and neuroinflammation, we generated BIN1K358R knock-in mice using CRISPR/Cas9 technology. These mice were subsequently bred with 5xFAD transgenic mice, which serve as a model for Alzheimer's pathology. RESULTS: The presence of the BIN1K358R variant leads to increased cerebral amyloid deposition, with a dampened response of astrocytes and oligodendrocytes, but not microglia, at both the cellular and transcriptional levels. This correlates with decreased neurofilament light chain in both plasma and brain tissue. Synaptic densities are significantly increased in both wild-type and 5xFAD backgrounds homozygous for the BIN1K358R variant. DISCUSSION: The BIN1 K358R variant modulates amyloid pathology in 5xFAD mice, attenuates the astrocytic and oligodendrocytic responses to amyloid plaques, decreases damage markers, and elevates synaptic densities. HIGHLIGHTS: BIN1 rs138047593 (K358R) coding variant is associated with increased risk of LOAD. BIN1 K358R variant increases amyloid plaque load in 12-month-old 5xFAD mice. BIN1 K358R variant dampens astrocytic and oligodendrocytic response to plaques. BIN1 K358R variant decreases neuronal damage in 5xFAD mice. BIN1 K358R upregulates synaptic densities and modulates synaptic transmission.


Sujet(s)
Maladie d'Alzheimer , Animaux , Souris , Maladie d'Alzheimer/génétique , Maladie d'Alzheimer/anatomopathologie , Peptides bêta-amyloïdes , Modèles animaux de maladie humaine , Souris transgéniques , Névroglie/anatomopathologie , Plaque amyloïde/anatomopathologie , Humains
12.
Eur J Surg Oncol ; 50(6): 108277, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38522333

RÉSUMÉ

Modern neoadjuvant systemic therapy (NST) can result in high pathologic complete response rates (pCR) in triple negative (TN) and human epidermal growth factor receptor 2 positive (HER2+) breast cancer. The role of surgery is, therefore, being reconsidered in this rapidly evolving field. This report presents oncological outcomes of seven patients with TN or HER2+ breast cancer, with exceptional response to NST, and a post-NST image-guided vacuum assisted biopsy showing no residual disease (ypT0), who opted not to have breast surgery. The median age was 49 (IQR 36-61) years and the median tumour size at diagnosis was 50 (IQR 16-65) mm. All patients received breast radiotherapy and continued adjuvant systemic therapies as appropriate. At a median follow-up of 67 (IQR 61-77) months, all patients were alive and free of disease. This small case series supports the need for further research in 'exceptional responders' to provide safe, individualized patient-centred care.


Sujet(s)
Tumeurs du sein , Traitement néoadjuvant , Humains , Femelle , Adulte d'âge moyen , Adulte , Tumeurs du sein/anatomopathologie , Tumeurs du sein/chirurgie , Tumeurs du sein/thérapie , Tumeurs du sein triple-négatives/thérapie , Tumeurs du sein triple-négatives/anatomopathologie , Tumeurs du sein triple-négatives/chirurgie , Tumeurs du sein triple-négatives/traitement médicamenteux , Récepteur ErbB-2/métabolisme , Traitement médicamenteux adjuvant , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Mastectomie , Résultat thérapeutique , Radiothérapie adjuvante
13.
Heart Lung Circ ; 33(4): 518-523, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38365499

RÉSUMÉ

BACKGROUND: Blood transfusion in the perioperative cardiothoracic setting has accepted risks including deep sternal wound infection, increased intensive care unit length of stay, lung injury, and cost. It has an immunomodulatory effect which may cause allo-immunisation. This may influence long-term survival through immune-mediated factors. Targeting coagulation defects to reduce unnecessary or inappropriate transfusions may reduce these complications. METHODS: In 2012, an institution-wide patient blood management evidence-based algorithmic bleeding management protocol was implemented at The Prince Charles Hospital, Brisbane, Australia. The benefit of this has been previously reported in our lung transplant and cardiac surgery (excluding transplants) cohorts. This study aimed to investigate the effect of this on our orthotopic heart transplant recipients. RESULTS: After the implementation of the protocol, despite no difference in preoperative haemoglobin levels and higher risk patients (EuroSCORE 20 vs 26; p=0.013), the use of packed red blood cells (13.0 U vs 4.4 U; p=0.046) was significantly lower postoperatively and fresh frozen plasma was significantly lower both intra- and postoperatively (7.4 U vs 0.6 U; p<0.001, and 3.3 U vs 0.6 U; p=0.011 respectively). Concurrently, the use of prothrombin complex concentrate (33% vs 78%; p<0.001) and desmopressin (5% vs 22%; p=0.0028) was significantly higher in the post-protocol group, while there was less use of recombinant factor VIIa (15% vs 4%; p=0.058). Intraoperative units of cryoprecipitate also rose from 0.9 to 2.0 (p=0.006). CONCLUSIONS: We have demonstrated that a targeted patient blood management protocol with point-of-care testing for heart transplant recipients is correlated with fewer blood products used postoperatively, with some increase in haemostatic products and no evidence of increased adverse events.


Sujet(s)
Transplantation cardiaque , Humains , Transplantation cardiaque/effets indésirables , Études rétrospectives , Femelle , Mâle , Adulte d'âge moyen , Transfusion sanguine/statistiques et données numériques , Transfusion sanguine/méthodes , Facteurs de la coagulation sanguine/usage thérapeutique , Sujet âgé , Adulte
14.
PLoS One ; 19(2): e0296860, 2024.
Article de Anglais | MEDLINE | ID: mdl-38315694

RÉSUMÉ

A substantial body of research has demonstrated that science knowledge is correlated with attitudes towards science, with most studies finding a positive relationship between the two constructs; people who are more knowledgeable about science tend to be more positive about it. However, this evidence base has been almost exclusively confined to high and middle-income democracies, with poorer and less developed nations excluded from consideration. In this study, we conduct the first global investigation of the science knowledge-attitude relationship, using the 2018 Wellcome Global Monitor survey. Our results show a positive knowledge-attitude correlation in all but one of the 144 countries investigated. This robust cross-national relationship is consistent across both science literacy and self-assessed measures of science knowledge.


Sujet(s)
Attitude , Revenu , Humains , Enquêtes et questionnaires , Pays en voie de développement , Savoir , Connaissances, attitudes et pratiques en santé
15.
Radiol Case Rep ; 19(5): 1764-1767, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38384694

RÉSUMÉ

This report presents a unique case of a 42-year-old female with a history of acute myeloid leukemia (AML) who exhibited an extramedullary relapse in the breast. Given the rarity of such presentations, this case underscores the importance of considering AML in the differential diagnosis of breast lesions, especially in patients with a pertinent medical history. Additionally, this case highlights the radiological and pathological challenges in distinguishing AML from other breast malignancies. The importance of timely diagnosis and the clinical implications of such a presentation are also discussed.

16.
bioRxiv ; 2024 Jan 19.
Article de Anglais | MEDLINE | ID: mdl-38293075

RÉSUMÉ

The central nervous system (CNS) is constantly surveilled by microglia, highly motile and dynamic cells deputed to act as the first line of immune defense in the brain and spinal cord. Alterations in the homeostasis of the CNS are detected by microglia that respond by migrating toward the affected area. Understanding the mechanisms controlling directed cell migration of microglia is crucial to dissect their responses to neuroinflammation and injury. We used a combination of pharmacological and genetic approaches to explore the involvement of calcium (Ca2+) signaling in the directed migration of induced pluripotent stem cell (iPSC)-derived microglia challenged with a purinergic stimulus. This approach mimics cues originating from injury of the CNS. Unexpectedly, simultaneous imaging of microglia migration and intracellular Ca2+ changes revealed that this phenomenon does not require Ca2+ signals generated from the endoplasmic reticulum (ER) and store-operated Ca2+ entry (SOCE) pathways. Instead, we find evidence that human microglial chemotaxis to purinergic signals is mediated by cyclic AMP in a Ca2+-independent manner. These results challenge prevailing notions, with important implications in neurological conditions characterized by perturbation in Ca2+ homeostasis.

17.
Alcohol Clin Exp Res (Hoboken) ; 48(3): 466-477, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38225180

RÉSUMÉ

BACKGROUND: Fetal alcohol spectrum disorders (FASD), a group of prevalent conditions resulting from prenatal alcohol exposure, affect the maturation of cerebral white matter as first identified with neuroimaging. However, traditional methods are unable to track subtle microstructural alterations to white matter. This preliminary study uses a highly sensitive and clinically translatable magnetic resonance elastography (MRE) protocol to assess brain tissue microstructure through its mechanical properties following an exercise intervention in a rat model of FASD. METHODS: Female rat pups were either alcohol-exposed (AE) via intragastric intubation of alcohol in milk substitute (5.25 g/kg/day) or sham-intubated (SI) on postnatal days (PD) four through nine to model alcohol exposure during the brain growth spurt. On PD 30, half of AE and SI rats were randomly assigned to either a wheel-running or standard cage for 12 days. Magnetic resonance elastography was used to measure whole brain and callosal mechanical properties at the end of the intervention (around PD 42) and at 1 month post-intervention, and findings were validated with histological quantification of oligoglia. RESULTS: Alcohol exposure reduced forebrain stiffness (p = 0.02) in standard-housed rats. The adolescent exercise intervention mitigated this effect, confirming that increased aerobic activity supports proper neurodevelopmental trajectories. Forebrain damping ratio was lowest in standard-housed AE rats (p < 0.01), but this effect was not mitigated by intervention exposure. At 1 month post-intervention, all rats exhibited comparable forebrain stiffness and damping ratio (p > 0.05). Callosal stiffness and damping ratio increased with age. With cessation of exercise, there was a negative rebound effect on the quantity of callosal oligodendrocytes, irrespective of treatment group, which diverged from our MRE results. CONCLUSIONS: This is the first application of MRE to measure the brain's mechanical properties in a rodent model of FASD. MRE successfully captured alcohol-related changes in forebrain stiffness and damping ratio. Additionally, MRE identified an exercise-related increase to forebrain stiffness in AE rats.

18.
J Neurol Sci ; 457: 122864, 2024 Feb 15.
Article de Anglais | MEDLINE | ID: mdl-38185014

RÉSUMÉ

Congenital myopathy with tremor (MYOTREM) is a recently described disorder characterized by mild myopathy and a postural and intention tremor present since early infancy. MYOTREM is associated with pathogenic variants in MYBPC1 which encodes slow myosin-binding protein C, a sarcomere protein with regulatory and structural roles. Here, we describe a family with three generations of variably affected members exhibiting a novel variant in MYBPC1 (c.656 T > C, p.Leu219Pro). Among the unique features of affected family members is the persistence of tremor in sleep. We also present the first muscle magnetic resonance images for this disorder, and report muscle atrophy and fatty infiltration.


Sujet(s)
Maladies musculaires , Tremblement , Humains , Famille , Mutation/génétique , Tremblement/imagerie diagnostique , Tremblement/génétique
19.
Public Health Res Pract ; 34(1)2024 Apr 04.
Article de Anglais | MEDLINE | ID: mdl-37559184

RÉSUMÉ

Objectives and importance of study: For public policy to respond effectively to social, economic, and health challenges, there is an urgent need for research-policy collaboration to advance evidence-informed policy. Many organisations seek to promote these engagement activities, but little is known about how this is experienced by researchers and policy actors. This study aimed to understand how policy actors and researchers in Australia experience collaboration and the impediments and enablers they encounter. Study type and methods: An online survey was developed, and using convenience sampling, self-identified Australian policy actors and researchers were invited to participate. Results: In total, 170 responses were analysed, comprising 58% policy actors and 42% researchers. Respondents reported the primary purpose for collaboration was evidence-informed policy making. Policy actors reported that the most common barrier to collaboration with academics was 'budget constraints' while academics reported 'budget, 'political risk' and 'structural barriers'. Reported enablers were 'leadership' and 'connections'. Conclusions: Our findings build upon existing evidence that highlights the importance of collaboration for facilitating evidence-informed policy. Structural deficits in both policy agencies and research funding systems and environments continue to present challenges to policy-research partnerships. Future initiatives could use these findings to implement preferred collaboration methods, alongside rigorous evaluation, to explore 'what works' in promoting engagement for evidence-informed policy.


Sujet(s)
Processus politique , Politique publique , Humains , Australie , Leadership , Plan de recherche , Politique de santé
20.
Patient ; 17(2): 179-190, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38103109

RÉSUMÉ

BACKGROUND AND OBJECTIVE: There has been an increase in the study and use of stated-preference methods to inform medicine development decisions. The objective of this study was to identify prioritized topics and questions relating to health preferences based on the perspective of members of the preference research community. METHODS: Preference research stakeholders from industry, academia, consultancy, health technology assessment/regulatory, and patient organizations were recruited using professional networks and preference-targeted e-mail listservs and surveyed about their perspectives on 19 topics and questions for future studies that would increase acceptance of preference methods and their results by decision makers. The online survey consisted of an initial importance prioritization task, a best-worst scaling case 1 instrument, and open-ended questions. Rating counts were used for analysis. The best-worst scaling used a balanced incomplete block design. RESULTS: One hundred and one participants responded to the survey invitation with 66 completing the best-worst scaling. The most important research topics related to the synthesis of preferences across studies, transferability across populations or related diseases, and method topics including comparison of methods and non-discrete choice experiment methods. Prioritization differences were found between respondents whose primary affiliation was academia versus other stakeholders. Academic researchers prioritized methodological/less studied topics; other stakeholders prioritized applied research topics relating to consistency of practice. CONCLUSIONS: As the field of health preference research grows, there is a need to revisit and communicate previous work on preference selection and study design to ensure that new stakeholders are aware of this work and to update these works where necessary. These findings might encourage discussion and alignment among different stakeholders who might hold different research priorities. Research on the application of previous preference research to new contexts will also help increase the acceptance of health preference information by decision makers.


Sujet(s)
Services de santé , Plan de recherche , Humains , Enquêtes et questionnaires , Personnel de recherche
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