Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 371
Filtrar
1.
Parkinsons Dis ; 2024: 8515400, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828214

RESUMO

Introduction: Pain in Parkinson's disease (PD) is common but poorly understood, with most research to date taking a mechanistic approach. This mixed methods study takes a broader biopsychosocial approach to assess and describe contributors of pain and explore pain management and the relationship between pain and physical activity in people with PD (PwPD) and chronic pain. Methods: A structured survey evaluated respondents' contributors of pain using standardized, self-report assessments of the following: pain, peripheral neuropathy, central nociplastic change, emotional dysregulation or pathology, and maladaptive cognitions. Semistructured individual interviews were conducted with purposively sampled survey participants and analyzed using inductive thematic analysis. Results: Eighty-nine PwPD (mean age 67 years, 55% female) completed the survey. The most common pain contributors were maladaptive cognitions (62%), central nociplastic change (49%), and emotional dysregulation (44%). Approaches to pain management and the response to physical activity were variable within and across individuals with different pain contributors. Four themes emerged from interviews with 24 participants: (1) causative perceptions of pain are diverse; (2) sense of control influences disease acceptance and exercise self-efficacy; (3) belief in the value of therapy; and (4) pain as the unspoken PD symptom. Physical activity was used by PwPD for pain management; however, the relationship between pain and physical activity varied based on sense of control. Conclusions: Clinicians should screen for pain and assess its contributors to provide individualized, multidimensional pain management that considers the biological, psychological, and social factors of pain in PwPD. It is plausible that such an approach would promote a better sense of control for PwPD.

2.
Brain Cogn ; 178: 106178, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38823196

RESUMO

Creativity has previously been linked with various attentional phenomena, including unfocused or broad attention. Although this has typically been interpreted through an executive functioning framework, such phenomena may also arise from atypical incentive salience processing. Across two studies, we examine this hypothesis both neurally and psychologically. First we examine the relationship between figural creativity and event-related potentials during an audio-visual oddball task, finding that rater creativity of drawings is associated with a diminished P300 response at midline electrodes, while abstractness and elaborateness of the drawings is associated with an altered distribution of the P300 over posterior electrodes. These findings support the notion that creativity may involve an atypical attribution of salience to prominent information. We further explore the incentive salience hypothesis by examining relationships between creativity and a psychological indicator of incentive salience captured by participants' ratings of enjoyment (liking) and their motivation to pursue (wanting) diverse real world rewards, as well as their positive spontaneous thoughts about those rewards. Here we find enhanced motivation to pursue activities as well as a reduced relationship between the overall tendency to enjoy rewards and the tendency to pursue them. Collectively, these findings indicate that creativity may be associated with atypical allocation of attentional and motivational resources to novel and rewarding information, potentially allowing more types of information access to attentional resources and motivating more diverse behaviors. We discuss the possibility that salience attribution in creatives may be less dependent on task-relevance or hedonic pleasure, and suggest that atypical salience attribution may represent a trait-like feature of creativity.


Assuntos
Atenção , Criatividade , Eletroencefalografia , Motivação , Humanos , Masculino , Feminino , Motivação/fisiologia , Atenção/fisiologia , Adulto Jovem , Eletroencefalografia/métodos , Adulto , Potenciais Evocados P300/fisiologia , Potenciais Evocados/fisiologia , Encéfalo/fisiologia , Recompensa , Adolescente
3.
Int J Pharm ; : 124369, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914354

RESUMO

The magnitude of the frictional forces during the ejection of porous pharmaceutical tablets plays an important role in determining the occurrence of tabletting defects. Here, we perform a systematic comparison between the maximum ejection force, static friction coefficient, and kinetic friction coefficient. All of these metrics have different physical meanings, corresponding to different stages of ejection. However, experimental limitations have previously complicated comparisons, as static and kinetic friction could not be measured simultaneously. This study presents a method for simultaneously measuring the maximum ejection force, static friction coefficient, and kinetic friction coefficient in situ during tablet ejection in routine compaction simulator experiments. Using this method, we performed a systematic comparison, including variations of (1) ejection speed, (2) compaction pressure, (3) material, and (4) lubrication method. The relative importance of each variable is discussed in detail, including how ejection speed alone can be a decisive factor in tablet chipping. The reliability of the newly developed method is supported by excellent agreement with previous studies and finite element method (FEM) simulations. Finally, we discuss the suitability of friction coefficients derived from Janssen-Walker theory and explanations for the phenomenon of die-wall static friction coefficients with apparent values far above one.

4.
Work ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38578910

RESUMO

BACKGROUND: This scoping review aimed to identify the barriers, facilitators and benefits of returning to work following burn injury, outcome measures used, management strategies, and models of care. OBJECTIVE: To provide a comprehensive overview about working-aged adults returning to their preinjury employment after burn injury. METHODS: We followed a pre-determined scoping review protocol to search MEDLINE, CINAHL, Embase, PsycINFO, PubMed, Scopus, CCRCT and CDSR databases between 2000 to December 2023. Papers reporting primary data from previously employed adults with cutaneous burn injuries were included. RESULTS: In all, 90 articles met the review criteria. Return-to-work was both an outcome goal and process of recovery from burn injury. Physical and psychological impairments were identified barriers. Job accommodations and modifications were important for supporting the transition from hospital to workplace. Employment status and quality of life sub-scales were used to measure return-to-work. CONCLUSIONS: Consistent definitions of work and measurements of return-to-employment after burn injury are priorities for future research. Longitudinal studies are more likely to capture the complexity of the return-to-employment process, its impact on work participation and changes in employment over time. The social context of work may assist or hinder return-to-work more than physical environmental constraints. Equitable vocational support systems would help address disparities in vocational rehabilitation services available after burn injury.

5.
J Biomech ; 168: 112096, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38640828

RESUMO

Clinical management of whiplash-associated disorders is challenging and often unsuccessful, with over a third of whiplash injuries progressing to chronic neck pain. Previous imaging studies have identified muscle fat infiltration, indicative of muscle weakness, in the deep cervical extensor muscles (multifidus and semispinalis cervicis). Yet, kinematic and muscle redundancy prevent the direct assessment of individual neck muscle strength, making it difficult to determine the role of these muscles in motor dysfunction. The purpose of this study was to determine the effects of deep cervical extensor muscle weakness on multi-directional neck strength and muscle activation patterns. Maximum isometric forces and associated muscle activation patterns were computed in 25 test directions using a 3-joint, 24-muscle musculoskeletal model of the head and neck. The computational approach accounts for differential torques about the upper and lower cervical spine. To facilitate clinical translation, the test directions were selected based on locations where resistance could realistically be applied to the head during clinical strength assessments. Simulation results reveal that the deep cervical extensor muscles are active and contribute to neck strength in directions with an extension component. Weakness of this muscle group leads to complex compensatory muscle activation patterns characterized primarily by increased activation of the superficial extensors and deep upper cervical flexors, and decreased activation of the deep upper cervical extensors. These results provide a biomechanistic explanation for movement dysfunction that can be used to develop targeted diagnostics and treatments for chronic neck pain in whiplash-associated disorders.


Assuntos
Contração Isométrica , Força Muscular , Músculos do Pescoço , Humanos , Músculos do Pescoço/fisiologia , Músculos do Pescoço/fisiopatologia , Força Muscular/fisiologia , Contração Isométrica/fisiologia , Traumatismos em Chicotada/fisiopatologia , Modelos Biológicos , Fenômenos Biomecânicos , Cervicalgia/fisiopatologia , Pescoço/fisiopatologia , Pescoço/fisiologia , Vértebras Cervicais/fisiopatologia , Vértebras Cervicais/fisiologia , Feminino , Simulação por Computador , Debilidade Muscular/fisiopatologia
6.
Diabetologia ; 67(6): 1079-1094, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38512414

RESUMO

AIMS/HYPOTHESIS: Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly connected 'hub' cells, important for the propagation of intercellular Ca2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood. Changes at the level of the epigenome provide one such possibility, which we explore here by focusing on the imprinted gene Nnat (encoding neuronatin [NNAT]), which is required for normal insulin synthesis and secretion. METHODS: Single-cell RNA-seq datasets were examined using Seurat 4.0 and ClusterProfiler running under R. Transgenic mice expressing enhanced GFP under the control of the Nnat enhancer/promoter regions were generated for FACS of beta cells and downstream analysis of CpG methylation by bisulphite sequencing and RNA-seq, respectively. Animals deleted for the de novo methyltransferase DNA methyltransferase 3 alpha (DNMT3A) from the pancreatic progenitor stage were used to explore control of promoter methylation. Proteomics was performed using affinity purification mass spectrometry and Ca2+ dynamics explored by rapid confocal imaging of Cal-520 AM and Cal-590 AM. Insulin secretion was measured using homogeneous time-resolved fluorescence imaging. RESULTS: Nnat mRNA was differentially expressed in a discrete beta cell population in a developmental stage- and DNA methylation (DNMT3A)-dependent manner. Thus, pseudo-time analysis of embryonic datasets demonstrated the early establishment of Nnat-positive and -negative subpopulations during embryogenesis. NNAT expression is also restricted to a subset of beta cells across the human islet that is maintained throughout adult life. NNAT+ beta cells also displayed a discrete transcriptome at adult stages, representing a subpopulation specialised for insulin production, and were diminished in db/db mice. 'Hub' cells were less abundant in the NNAT+ population, consistent with epigenetic control of this functional specialisation. CONCLUSIONS/INTERPRETATION: These findings demonstrate that differential DNA methylation at Nnat represents a novel means through which beta cell heterogeneity is established during development. We therefore hypothesise that changes in methylation at this locus may contribute to a loss of beta cell hierarchy and connectivity, potentially contributing to defective insulin secretion in some forms of diabetes. DATA AVAILABILITY: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD048465.


Assuntos
Ilhas de CpG , Metilação de DNA , Células Secretoras de Insulina , Células Secretoras de Insulina/metabolismo , Animais , Camundongos , Ilhas de CpG/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Transgênicos , DNA Metiltransferase 3A/metabolismo , Humanos , Insulina/metabolismo , Secreção de Insulina/fisiologia
7.
BMC Geriatr ; 24(1): 149, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38350882

RESUMO

BACKGROUND: Hip fracture has a devastating impact on individuals and is an increasing burden for health systems and society. Compared to usual care, increased physiotherapy provision has demonstrated efficacy in improving patient and health service outcomes in this population. However, physiotherapy workforce challenges prevent sustained implementation. METHODS: Our aim was to evaluate the safety, feasibility, acceptability, effectiveness and implementation cost of thrice daily physiotherapy for patients in the acute care setting after hip fracture at two public hospitals. We added twice-daily exercise implemented by an alternative workforce, to usual care consisting of daily mobility practice by a physiotherapist. Sites identified their preferred alternative workforce, with pre-registration physiotherapy students and allied health assistants chosen. We used a mixed methods approach, using the Consolidated Framework for Implementation Research (CFIR) as a determinant framework to guide implementation planning and data collection. We compared hospital length of stay data to a reference cohort. RESULTS: We recruited 25 patients during the study period. Acute care hospital length of stay decreased from 11 days in the reference cohort to 8 days in the BOOST cohort (mean difference - 3.3 days, 95%CI -5.4 to -1.2 days, p = 0.003). Intervention fidelity was 72% indicating feasibility, no safety concerns were attributed to the intervention, and uptake was 96% of all eligible patients. The intervention was acceptable to patients, carers and healthcare providers. This intervention was cost-effective from the acute orthopaedic service perspective. CONCLUSION: Higher daily frequency of physiotherapy can be safely, feasibly and effectively implemented by an alternative workforce for patients in the acute care setting following hip fracture surgery.


Assuntos
Fraturas do Quadril , Pacientes Internados , Modalidades de Fisioterapia , Humanos , Exercício Físico , Fraturas do Quadril/reabilitação , Fraturas do Quadril/cirurgia , Recursos Humanos , Ciência da Implementação
8.
Spine J ; 24(7): 1253-1266, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38417587

RESUMO

BACKGROUND CONTEXT: The role of lumbar paraspinal muscle health in back pain (BP) is not straightforward. Challenges in this field have included the lack of tools and large, heterogenous datasets to interrogate the association between muscle health and BP. Computer-vision models have been transformative in this space, enabling the automated quantification of muscle health and the processing of large datasets. PURPOSE: To investigate the associations between lumbar paraspinal muscle health and age, sex, BMI, physical activity, and BP in a large, heterogenous dataset using an automated computer-vision model. DESIGN: Cross-sectional study. PATIENT SAMPLE: Participants from the UK Biobank with abdominal Dixon fat-water MRI (N=9,564) were included (41.8% women, mean [SD] age: 63.5 [7.6] years, BMI: 26.4 [4.1] kg/m2) of whom 6,953 reported no pain, 930 acute BP, and 1,681 chronic BP. OUTCOME MEASURES: Intramuscular fat (IMF) and average cross-sectional area (aCSA) were automatically derived using a computer-vision model for the left and right lumbar multifidus (LM), erector spinae (ES), and psoas major (PM) from the L1 to L5 vertebral levels. METHODS: Two-tailed partial Pearson correlations were generated for each muscle to assess the relationships between the muscle measures (IMF and aCSA) and age (controlling for BMI, sex, and physical activity), BMI (controlling for age, sex, and physical activity), and physical activity (controlling for age, sex, and BMI). One-way ANCOVA was used to identify sex differences in IMF and aCSA for each muscle while controlling for age, BMI, and physical activity. Similarly, one-way ANCOVA was used to identify between-group differences (no pain, acute BP, and chronic BP) for each muscle and along the superior-inferior expanse of the lumbar spine while controlling for age, BMI, sex, and physical activity (α=0.05). RESULTS: Females had higher IMF (LM mean difference [MD]=11.1%, ES MD=10.2%, PM MD=0.3%, p<.001) and lower aCSA (LM MD=47.6 mm2, ES MD=350.0 mm2, PM MD=321.5 mm2, p<.001) for all muscles. Higher age was associated with higher IMF and lower aCSA for all muscles (r≥0.232, p<.001) except for LM and aCSA (r≤0.013, p≥.267). Higher BMI was associated with higher IMF and aCSA for all muscles (r≥0.174, p<.001). Higher physical activity was associated with lower IMF and higher aCSA for all muscles (r≥0.036, p≤.002) except for LM and aCSA (r≤0.010, p≥.405). People with chronic BP had higher IMF and lower aCSA than people with no pain (IMF MD≤1.6%, aCSA MD≤27.4 mm2, p<.001) and higher IMF compared to acute BP (IMF MD≤1.1%, p≤.044). The differences between people with BP and people with no pain were not spatially localized to the inferior lumbar levels but broadly distributed across the lumbar spine. CONCLUSIONS: Paraspinal muscle health is associated with age, BMI, sex, and physical activity with the exception of the association between LM aCSA and age and physical activity. People with BP (chronic>acute) have higher IMF and lower aCSA than people reporting no pain. The differences were not localized but broadly distributed across the lumbar spine. When interpreting measures of paraspinal muscle health in the research or clinical setting, the associations with age, BMI, sex, and physical activity should be considered.


Assuntos
Índice de Massa Corporal , Exercício Físico , Músculos Paraespinais , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Músculos Paraespinais/diagnóstico por imagem , Idoso , Reino Unido , Exercício Físico/fisiologia , Estudos Transversais , Fatores Etários , Imageamento por Ressonância Magnética , Fatores Sexuais , Região Lombossacral , Dor nas Costas/fisiopatologia , Dor nas Costas/epidemiologia , Vértebras Lombares/diagnóstico por imagem , Dor Lombar/fisiopatologia , Biobanco do Reino Unido
9.
Adv Skin Wound Care ; 37(2): 76-84, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38241450

RESUMO

OBJECTIVE: To describe a virtual, competency-based skin and wound care (SWC) skills training model. The ECHO (Extension for Community Healthcare Outcomes) Ontario SWC pivoted from an in-person boot camp to a virtual format because of the COVID-19 pandemic. METHODS: An outcome-based program evaluation was conducted. Participants first watched guided commentary and videos of experts performing in nine SWC multiskills videos, then practiced and video-recorded themselves performing those skills; these recordings were assessed by facilitators. Data were collected using pre-post surveys and rubric-based assessments. Descriptive statistics and thematic analysis were applied to data analysis. RESULTS: Fifty-five healthcare professionals participated in the virtual boot camp, measured by the submission of at least one video. A total of 216 videos were submitted and 215 assessment rubrics were completed. Twenty-nine participants completed the pre-boot camp survey (53% response rate) and 26 responded to the post-boot camp survey (47% response rate). The strengths of the boot camp included the applicability of virtual learning to clinical settings, boot camp supplies, tool kits, and teaching strategies. The analysis of survey responses indicated that average proficiency scores were greater than 80% for three videos, 50% to 70% for three of the videos, and less than 50% for three of the videos. Participants received lower scores in local wound care and hand washing points of contact. The barriers of the boot camp included technical issues, time, level of knowledge required at times, and lack of equipment and access to interprofessional teams. CONCLUSIONS: This virtual ECHO SWC model expanded access to practical skills acquisition. The professional development model presented here is generalizable to other healthcare domains.


Assuntos
COVID-19 , Internato e Residência , Humanos , Ontário , Currículo , Pandemias , COVID-19/epidemiologia , Competência Clínica
10.
Psychol Med ; 54(2): 338-349, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37309917

RESUMO

BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.


Assuntos
Cannabis , Transtornos de Estresse Pós-Traumáticos , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Depressão/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/complicações , Psicopatologia
11.
Heart Rhythm ; 21(3): 303-312, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38048935

RESUMO

BACKGROUND: Remote monitoring (RM) of implantable cardiac devices provides substantial and complex information, presenting new challenges such as detection of a patient's death. OBJECTIVE: This study aims to describe RM transmissions indicating death and propose a management strategy for services. METHODS: The study included consecutive ambulatory outpatients whose deaths were detected via RM. Clinical and device data were collected from electronic records, and ethical approval was obtained from the service's institutional review board. RESULTS: Over a 9-year period (2014-2023), 28 patients were detected. The deceased patients had implantable cardioverter-defibrillators, pacemakers, and implantable loop recorders. In 54% of the cases, the patient's death had already been recognized. Alert transmissions indicating death were commonly related to ventricular arrhythmia events, but also due to lead measurements, and implantable loop recorder battery status. Several diagnostic features may indicate a patient's death. The most reliable was the presenting electrogram, demonstrating base rate pacing with no capture. Device diagnostics, lead parameters, and arrhythmia recordings may indicate death; however, not all cases present with recordings and diagnosis may not be conclusive. A majority (82%) had ventricular arrhythmia at the time of death. In cases where defibrillator shocks were delivered, the arrhythmia reinitiated shortly after successful cardioversion. Delayed therapy was observed, and some patients did not receive defibrillator shocks because of discriminators or because the arrhythmia rate fell below the shock zone. CONCLUSION: Detecting a patient death via RM presents unique challenges and considerations for services. Standard operational policies and legal consultation should be established to address the implications.


Assuntos
Desfibriladores Implantáveis , Humanos , Desfibriladores Implantáveis/efeitos adversos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Cardioversão Elétrica/efeitos adversos , Monitorização Fisiológica , Coração
12.
Phys Ther Sport ; 65: 95-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38101293

RESUMO

OBJECTIVES: To investigate associations between lateral hip muscle size/intramuscular fat infiltration (MFI) and hip strength in active young adults with longstanding hip/groin pain. DESIGN: Cross-sectional study. SETTING: University/Clinical. PARTICIPANTS: Sub-elite soccer and Australian Football players (n = 180; 37 female) with long standing hip/groin pain. MAIN OUTCOME MEASURES: Muscle size (volume) and MFI of gluteus maximus, medius, and minimis, and tensor fascia latae (TFL) were assessed using magnetic resonance imaging. Isometric hip strength was measured with handheld dynamometry. Associations between muscle size/MFI were assessed using linear regression models, adjusted for body mass index and age, with sex-specific interactions. RESULTS: Positive associations were identified between lateral hip muscle volume and hip muscle strength, particularly for gluteus maximus and gluteus minimus volume. For all muscles, hip abduction was associated with an increase in strength by up to 0.69 N (R2 ranging from 0.29 to 0.39). These relationships were consistent across sexes with no sex interactions observed. No associations were found between MFI and strength measures. CONCLUSION: Greater lateral hip muscle volumes are associated with greater hip strength in active young adults with long standing hip/groin pain, irrespective of sex. Gluteus maximus and minimus volume showed the most consistent relationships with hip strength across multiple directions.


Assuntos
Virilha , Músculo Esquelético , Masculino , Humanos , Feminino , Adulto Jovem , Estudos Transversais , Austrália , Músculo Esquelético/fisiologia , Articulação do Quadril/fisiologia , Artralgia , Força Muscular/fisiologia , Dor Pélvica
13.
bioRxiv ; 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38076935

RESUMO

Aims/hypothesis: Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly-connected 'hub' cells, important for the propagation of intercellular Ca2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood. Changes at the level of the epigenome provide one such possibility which we explore here by focussing on the imprinted gene neuronatin (Nnat), which is required for normal insulin synthesis and secretion. Methods: Single cell RNA-seq datasets were examined using Seurat 4.0 and ClusterProfiler running under R. Transgenic mice expressing eGFP under the control of the Nnat enhancer/promoter regions were generated for fluorescence-activated cell (FAC) sorting of beta cells and downstream analysis of CpG methylation by bisulphite and RNA sequencing, respectively. Animals deleted for the de novo methyltransferase, DNMT3A from the pancreatic progenitor stage were used to explore control of promoter methylation. Proteomics was performed using affinity purification mass spectrometry and Ca2+ dynamics explored by rapid confocal imaging of Cal-520 and Cal-590. Insulin secretion was measured using Homogeneous Time Resolved Fluorescence Imaging. Results: Nnat mRNA was differentially expressed in a discrete beta cell population in a developmental stage- and DNA methylation (DNMT3A)-dependent manner. Thus, pseudo-time analysis of embryonic data sets demonstrated the early establishment of Nnat-positive and negative subpopulations during embryogenesis. NNAT expression is also restricted to a subset of beta cells across the human islet that is maintained throughout adult life. NNAT+ beta cells also displayed a discrete transcriptome at adult stages, representing a sub-population specialised for insulin production, reminiscent of recently-described "ßHI" cells and were diminished in db/db mice. 'Hub' cells were less abundant in the NNAT+ population, consistent with epigenetic control of this functional specialization. Conclusions/interpretation: These findings demonstrate that differential DNA methylation at Nnat represents a novel means through which beta cell heterogeneity is established during development. We therefore hypothesise that changes in methylation at this locus may thus contribute to a loss of beta cell hierarchy and connectivity, potentially contributing to defective insulin secretion in some forms of diabetes.

14.
Biol Psychiatry Glob Open Sci ; 3(4): 705-715, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37881578

RESUMO

Background: Prior sexual trauma (ST) is associated with greater risk for posttraumatic stress disorder after a subsequent traumatic event; however, the underlying neurobiological mechanisms remain opaque. We investigated longitudinal posttraumatic dysfunction and amygdala functional dynamics following admission to an emergency department for new primarily nonsexual trauma in participants with and without previous ST. Methods: Participants (N = 2178) were recruited following acute trauma exposure (primarily motor vehicle collision). A subset (n = 242) completed magnetic resonance imaging that included a fearful faces task and a resting-state scan 2 weeks after the trauma. We investigated associations between prior ST and several dimensions of posttraumatic symptoms over 6 months. We further assessed amygdala activation and connectivity differences between groups with or without prior ST. Results: Prior ST was associated with greater posttraumatic depression (F1,1120 = 28.35, p = 1.22 × 10-7, ηp2 = 0.06), anxiety (F1,1113 = 17.43, p = 3.21 × 10-5, ηp2 = 0.05), and posttraumatic stress disorder (F1,1027 = 11.34, p = 7.85 × 10-4, ηp2 = 0.04) severity and more maladaptive beliefs about pain (F1,1113 = 8.51, p = .004, ηp2 = 0.02) but was not related to amygdala reactivity to fearful versus neutral faces (all ps > .05). A secondary analysis revealed an interaction between ST and lifetime trauma load on the left amygdala to visual cortex connectivity (peak Z value: -4.41, corrected p < .02). Conclusions: Findings suggest that prior ST is associated with heightened posttraumatic dysfunction following a new trauma exposure but not increased amygdala activity. In addition, ST may interact with lifetime trauma load to alter neural circuitry in visual processing regions following acute trauma exposure. Further research should probe the relationship between trauma type and visual circuitry in the acute aftermath of trauma.

15.
Clin Case Rep ; 11(11): e8010, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37900712

RESUMO

Reconceptualising acute Musculoskeletal (MSK) injuries with both stress- and tissue- based factors is required to consider prior influences of mental health disorders on acute persistent MSK pain presentations. This report describes repeated emergency presentations of an individual with acute persistent MSK pain in their twenties living with mental health. Their mental health diagnoses included depression, mood disorders, and anorexia nervosa. This person also had mental health related inpatient admissions that were not captured under the retrospective record review for a large district hospital emergency department using the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) classification system. This case report attempts to demonstrate that improving the understanding of preexisting vulnerabilities and mental health diagnoses may assist with informing healthcare design to develop specialised care pathways for acute injury presentations within triage settings.

16.
JOR Spine ; 6(3): e1278, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37780819

RESUMO

Background: Lumbar disc degeneration (DD) is widely regarded as a likely contributor to low back pain (LBP), but the association between DD and LBP is relatively weak. No known studies have normalized quantitative measures of DD severity relative to multiple variables such as age, height, and disc level. This study developed normalized quantitative measures (z-scores) of disc signal intensity (DSI) and disc height (DH) to rate relative severity of DD. Methods: Raw (unnormalized) quantitative measures of DSI and DH alongside potential normalization variables were acquired from MRI scans and clinical data of 76 patients. The associations between the raw quantitative measures and potential normalization variables were investigated to develop the normalized quantitative measures (z-scores) of DSI and DH. Construct validity was assessed by comparing the normalized measures to an experienced radiologist's subjective measures of relative severity of DSI and DH loss. Results: CSF signal intensity, age, and disc level were significantly associated with raw DSI (R 2 = 0.06, 0.25, and 0.09, respectively). Lumbar height and disc level were significantly associated with raw DH (R 2 = 0.13 and 0.31). Normalizing DSI and DH by these variables resulted in stronger relationships (R 2 = 0.39 and 0.37) than raw DSI and DH (R 2 = 0.24 and 0.31) with the radiologist's subjective measures. Normalized DSI and DH were both normally distributed (p = 0.32 and 0.12). Conclusions: Construct validity and the distributions suggested that normalized quantitative measures of DSI and DH are better than existing measures of DSI and DH at rating relative DD severity. Determining whether normalized quantitative measures are more predictive of clinical outcomes is important future research.

17.
J Clin Med ; 12(18)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37762861

RESUMO

Low back pain (LBP), a globally widespread and persistent musculoskeletal disorder, benefits from exercise therapy. However, it remains unclear which type leads to greater changes in paraspinal muscle health. This study aimed to (1) compare the effects of a combined motor control and isolated lumbar extension exercise (MC+ILEX) versus a general exercise (GE) intervention on paraspinal muscle morphology, composition, and function, and (2) examine whether alterations in paraspinal muscle health were correlated with improvements in pain, function, and quality of life. Fifty participants with chronic LBP were randomly assigned to each group and underwent a 12-week supervised intervention program. Magnetic resonance imaging and ultrasound assessments were acquired at baseline, 6 and 12 weeks to examine the impact of each intervention on erector spinae (ES) and multifidus (MF) muscle size (cross-sectional area, CSA), composition, and function at L4-L5 and L5-S1. Self-reported questionnaires were also acquired to assess participant-oriented outcomes. Our findings indicated that the MC+ILEX group demonstrated greater improvements in MF and ES CSA, along with MF thickness at both levels (all p < 0.01). Both groups significantly improved in pain, function, and quality of life. This study provided preliminary results suggesting that an MC+ILEX intervention may improve paraspinal morphology while decreasing pain and disability.

18.
Front Neurol ; 14: 1209475, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745653

RESUMO

Objectives: This study aimed to examine whether preoperative cervical muscle size, composition, and asymmetry from magnetic resonance imaging (MRI) can predict post-operative outcomes in patients with degenerative cervical myelopathy (DCM). Methods: A total of 171 patients with DCM were included. Relative total cross-sectional area (RCSA), functional CSA (fat-free area, FCSA), ratio of FCSA/CSA (fatty infiltration) and asymmetry of the multifidus (MF) and semispinalis cervicis (SCer) together (MF + SCer), and cervical muscle as a group (MF, SCer, semispinalis capitis, and splenius capitis) were obtained from T2-weighted axial MR images at the mid-disk, at the level of maximum cord compression and the level below. Univariate and multivariate linear regression analyses were used to assess the relationship between baseline cervical muscle measurements of interest with the modified Japanese Orthopedic Association (mJOA), Nurick Classification, Neck Disability Index (NDI), and SF-36 health survey at 6-month and 12-month post-surgery. Results: Lower RCSA of MF + SCer, less CSA MF + SCer asymmetry and greater FCSA/CSA for the cervical muscle group (e.g., less fatty infiltration), and younger age were significant predictors of higher mJOA scores (e.g., less disability) at 6-month and 12-month post-surgery (all p < 0.05). Greater CSA asymmetry in MF + SCer and lower FCSA/CSA (e.g., more fatty infiltration) for the cervical muscle group were significant predictors of higher Nurick scores (e.g., more disability) at 6-month and 12-month post-surgery (all p < 0.05). Lower FCSA MF + Scer asymmetry, lower FCSA/CSA asymmetry of the muscle group, and greater RCSA MF + SCer were significant predictors of higher NDI scores at 6-month and 12-month post-surgery. Finally, greater FCSA/CSA asymmetry of the MF + SCer, greater FCSA asymmetry of the muscle group, greater RCSA of the muscle group, and greater CSA asymmetry of MF + SCer were significant predictors of lower post-operative SF-36 scores at 6- and 12-month post-surgery. Conclusion: Our result suggested that cervical paraspinal muscle morphology, specifically greater asymmetry, and fatty infiltration may be important predictors of functional recovery and post-surgical outcomes in patients with DCM.

19.
Vet Surg ; 52(8): 1191-1201, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37649180

RESUMO

OBJECTIVE: To describe a naso-facial reconstruction technique following bilateral rostral maxillectomy and its functional and cosmetic outcomes. ANIMALS: Two dogs. STUDY DESIGN: Clinical case series. METHODS: Two dogs were presented with a right rostral maxillary mass. Preoperative biopsy and staging revealed a biologically high-grade and histologically low-grade fibrosarcoma (Hi-Lo FSA). A combined nasal planectomy and radical bilateral rostral maxillectomy was performed sparing the labial/buccal mucocutaneous flaps bilaterally. Surgery resulted in asymmetry of the width of the flaps; the narrower flap was rotated medially to reconstruct the lip and create an oral vestibule. The wider flap was rotated medially to cover the remaining dorsolateral opening of the nasal conchae. The flaps overlapped in a parallel manner, discretely concealing the nasal passages, and separating them from the oral cavity. Hemorrhage occurred in both dogs, with one dog requiring a blood transfusion postoperatively. RESULTS: Oral Hi-Lo FSA with tumor-free margins was confirmed in both dogs. Both dogs recovered uneventfully within 4 weeks. Owners reported being very satisfied with the functional (return to normal exercise/activities and uncompromised respiration) and cosmetic outcomes. Based on the owners' telephone follow up, no tumor recurrence was noted at 15 (Dog 1) and 6 (Dog 2) months postoperatively. CONCLUSION: The full-thickness bilateral labial/buccal rotational flaps were used successfully to reconstruct the rostral maxilla, external nose and facial defects involving the nasal cavity. The technique resulted in acceptable functional and cosmetic outcomes and can be considered for naso-facial reconstruction in selected cases.


Assuntos
Doenças do Cão , Neoplasias Maxilares , Procedimentos de Cirurgia Plástica , Cães , Animais , Nariz/cirurgia , Neoplasias Maxilares/cirurgia , Neoplasias Maxilares/veterinária , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/veterinária , Retalhos Cirúrgicos/veterinária , Procedimentos de Cirurgia Plástica/veterinária , Doenças do Cão/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA