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1.
Infancy ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38768285

RESUMO

Cognitive control is a predictor of later-life outcomes and may underpin higher order executive processes. The present study examines the development of early cognitive control during the first 24-month. We evaluated a tablet-based assessment of cognitive control among infants aged 18- and 24-month. We also examined concurrent and longitudinal associations between attentional disengagement, general cognitive skills and cognitive control. Participants (N = 60, 30 female) completed the tablet-task at 18- and 24-month of age. Attentional disengagement and general cognitive development were assessed at 5-, 8-, 12-, 18- and 24-month using an eye-tracking measure and the Mullen Scales of Early Learning (MSEL), respectively. The cognitive control task demonstrated good internal consistency, sensitivity to age-related change in performance and stable individual differences. No associations were found between infant cognitive control and MSEL scores longitudinally or concurrently. The eye-tracking task revealed that slower attentional disengagement at 8-month, but faster disengagement at 18-month, predicted higher cognitive control scores at 24-month. This task may represent a useful tool for measuring emergent cognitive control. The multifaceted relationship between attention and infant cognitive control suggests that the rapid development of the attentional system in infancy results in distinct attentional skills, at different ages, being relevant for cognitive control development.

2.
bioRxiv ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38260280

RESUMO

Functional brain network organization, measured by functional connectivity (FC), reflects key neurodevelopmental processes for healthy development. Early exposure to adversity, e.g. undernutrition, affects neurodevelopment, observable via disrupted FC, and leads to poorer outcomes from preschool age onward. We assessed longitudinally the impact of early growth trajectories on developmental FC in a rural Gambian population from age 5 to 24 months. To investigate how these early trajectories relate to later childhood outcomes, we assessed cognitive flexibility at 3-5 years. We observed that early physical growth before the fifth month of life drove optimal developmental trajectories of FC that in turn predicted cognitive flexibility at pre-school age. In contrast to previously studied developmental populations, this Gambian sample exhibited long-range interhemispheric FC that decreased with age. Our results highlight the measurable effects that poor growth in early infancy has on brain development and the subsequent impact on pre-school age cognitive development, underscoring the need for early life interventions throughout global settings of adversity.

3.
Hosp Pediatr ; 14(1): 45-51, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38093648

RESUMO

OBJECTIVES: To identify risk factors of high flow nasal cannula (HFNC) failure at a US pediatric hospital without a co-located ICU. METHODS: Retrospective cohort study of patients aged 0 to 18 years who were started on HFNC in the emergency department or inpatient unit at a community hospital over a 16-month period. Children with chronic medical conditions were excluded. Outcome was HFNC failure, defined as HFNC need greater than floor limit, noninvasive positive pressure, or mechanical ventilation. In bivariate analysis, we compared demographic and clinical factors between those with and without failure. We included variables in a multivariable model on the basis of statistical significance. We used Poisson regression with robust error variance to calculate the adjusted relative risk (aRR) of failure for each variable. RESULTS: Of 195 children, 51% had HFNC failure. In adjusted analysis, failure was higher in all age groups <12 months as compared with older children. For example, children aged 3 to 5 months had a higher risk of failure compared with patients 12 months or older (aRR 1.85, confidence interval [CI] 1.34-2.54). Patients with an asthma exacerbation had a higher risk of failure (aRR 1.39, CI 1.03-1.88). Patients whose respiratory rate or heart rate did not improve also had a higher risk of failure (aRR 1.73, CI 1.24-2.41; aRR 1.47, CI 1.14-1.90). CONCLUSIONS: Patients who were younger, had asthma, and did not have improved respiratory rate or heart rate after HFNC were more likely to experience HFNC failure.


Assuntos
Asma , Insuficiência Respiratória , Criança , Humanos , Adolescente , Cânula , Estudos Retrospectivos , Hospitais Comunitários , Respiração Artificial , Oxigenoterapia , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/terapia
4.
Infant Behav Dev ; 74: 101913, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38056188

RESUMO

INTRODUCTION: There is substantial diversity within and between contexts globally in caregiving practices and family composition, which may have implications for the early interaction's infants engage in. We draw on data from the Brain Imaging for Global Health (BRIGHT, www.globalfnirs.org/the-bright-project) project, which longitudinally examined infants in the UK and in rural Gambia, West Africa. In The Gambia, households are commonly characterized by multigenerational, frequently polygamous family structures, which, in part, is reflected in the diversity of caregivers a child spends time with. In this paper, we aim to 1) evaluate and validate the Language Environment Analysis (LENA) for use in the Mandinka speaking families in The Gambia, 2) examine the nature (i.e., prevalence of turn taking) and amount (i.e., adult and child vocalizations) of conversation that infants are exposed to from 12 to 24 months of age and 3) investigate the link between caregiver diversity and child language outcomes, examining the mediating role of contingent turn taking. METHOD: We obtained naturalistic seven-hour-long LENA recordings at 12, 18 and 24 months of age from a cohort of N = 204 infants from Mandinka speaking households in The Gambia and N = 61 infants in the UK. We examined developmental changes and site differences in LENA counts of adult word counts (AWC), contingent turn taking (CTT) and child vocalizations (CVC). In the larger and more heterogenous Gambian sample, we also investigated caregiver predictors of turn taking frequency. We hereby examined the number of caregivers present over the recording day and the consistency of caregivers across two subsequent days per age point. We controlled for children's cognitive development via the Mullen Scales of Early Learning (MSEL). RESULTS: Our LENA validation showed high internal consistency between the human coders and automated LENA outputs (Cronbach's alpha's all >.8). All LENA counts were higher in the UK compared to the Gambian cohort. In The Gambia, controlling for overall neurodevelopment via the MSEL, CTT at 12 and 18 months predicted CVC at 18 and 24 months. Caregiver consistency was associated with CTT counts at 18 and 24 months. The number of caregivers and CTT counts showed an inverted u-shape relationship at 18 and 24 months, with an intermediate number of caregivers being associated with the highest CTT frequencies. Mediation analyses showed a partial mediation by number of caregivers and CTT and 24-month CVC. DISCUSSION: The LENA provided reliable estimates for the Mandinka language in the home recording context. We showed that turn taking is associated with subsequent child vocalizations and explored contextual caregiving factors contributing to turn taking in the Gambian cohort.


Assuntos
Cuidadores , Idioma , Criança , Lactente , Adulto , Humanos , Pré-Escolar , Gâmbia , Aprendizagem , Reino Unido , Desenvolvimento da Linguagem
5.
PLOS Glob Public Health ; 3(11): e0002531, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37910494

RESUMO

INTRODUCTION: Iron deficiency is among the leading risk factors for poor cognitive development. However, interventions targeting iron deficiency have had mixed results on cognitive outcomes. This may be due to previous interventions focusing on the correction of iron deficiency anaemia in late infancy and early childhood, at which point long lasting neural impacts may already be established. We hypothesise that the relationship between iron status and cognitive development will be observable in the first months of life and will not be recovered by 5 years of age. METHODS: Using data from the Brain Imaging for Global Health (BRIGHT) Study in Gambia (n = 179), we conducted mixed effects modelling to assess the relationship between iron status at 5 months of age and trajectories of cognitive development from 5 months- 5 years using (i) a standardised measure of cognitive development (Mullen Scales of Early Learning) and (ii) an eye-tracking assessment of attention processing (visual disengagement time). RESULTS: All infants were iron sufficient at 1 month of age. At 5 and 12 months of age 30% and 55% of infants were iron deficient respectively. In fully adjusted analyses, infants in the lowest tercile of soluble transferrin receptor (sTfR) (best iron status) achieved MSEL Cognitive Scores on average 1.9 points higher than infants in the highest sTfR tercile (p = 0.009, effect size = 0.48). There was no evidence that this group difference was recovered by 5 years of age. Infants in the lowest sTfR tercile had visual disengagement time 57ms faster than the highest tercile (p = 0.001, effect size = 0.59). However, this difference diminished by early childhood (p = 0.024). CONCLUSION: Infants are at risk of iron deficiency in early infancy. A relationship between iron status and cognitive development is apparent from 5 months of age and remains observable at 5 years of age. One mechanism by which iron availability in early infancy impacts brain development may be through effects on early attentional processing, which is rapidly developing and has substantial nutritional requirements during this period. To support neurocognitive development, prevention of iron deficiency in pre- and early postnatal life may be more effective than correcting iron deficiency once already established.

6.
Cortex ; 169: 18-34, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37847979

RESUMO

Autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) are highly prevalent neurodevelopmental conditions that often co-occur and present both common and distinct neurodevelopmental profiles. Studying the developmental pathways leading to the emergence of ASD and/or ADHD symptomatology is crucial in understanding neurodiversity and discovering the mechanisms that underpin it. This study used functional near-infrared spectroscopy (fNIRS) to investigate differences in cortical specialization to social stimuli between 4- to 6-month-old infants at typical and elevated likelihood of ASD and/or ADHD. Results showed that infants at both elevated likelihood of ASD and ADHD had reduced selectivity to vocal sounds in left middle and superior temporal gyrus. Furthermore, infants at elevated likelihood of ASD showed attenuated responses to visual social stimuli in several cortical regions compared to infants at typical likelihood. Individual brain responses to visual social stimuli were associated with later autism traits, but not ADHD traits. These outcomes support our previous observations showing atypical social brain responses in infants at elevated likelihood of ASD and align with later atypical brain responses to social stimuli observed in children and adults with ASD. These findings highlight the importance of characterizing antecedent biomarkers of atypicalities in processing socially relevant information that might contribute to both phenotypic overlap and divergence across ASD and ADHD conditions and their association with the later emergence of behavioural symptoms.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Criança , Lactente , Adulto , Humanos , Estudos Prospectivos , Encéfalo , Lobo Temporal
7.
Lab Anim Res ; 39(1): 25, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891640

RESUMO

BACKGROUND: Chronic skin wounds are a common complication of many diseases such as diabetes. Various traditional methods for assessing skin wound closure are used in animal studies, including wound tracing, calliper measurements and histological analysis. However, these methods have poorly defined wound closure or practical limitations. Digital image analysis of wounds is an increasingly popular, accessible alternative, but it is unclear whether digital assessment is consistent with traditional methods. This study aimed to optimise and compare digital wound closure assessment with traditional methods, using a diabetic mouse model. Diabetes was induced in male C57BL/6J mice by high-fat diet feeding combined with low dose (65 mg/kg of body weight) streptozotocin injections. Mice fed normal chow were included as controls. After 18 weeks, four circular full-thickness dorsal skin wounds of 4 mm diameter were created per mouse. The wounds were photographed and measured by callipers. Wound closure rate (WCR) was digitally assessed by two reporters using two methods: wound outline (WCR-O) and re-epithelialisation (WCR-E). Wounded skin tissues were collected at 10-days post-wounding and wound width was measured from haematoxylin and eosin-stained skin tissue. RESULTS: Between reporters, WCR-O was more consistent than WCR-E, and WCR-O correlated with calliper measurements. Histological analysis supported digital assessments, especially WCR-E, when wounds were histologically closed. CONCLUSIONS: WCR-O could replace calliper measurements to measure skin wound closure, but WCR-E assessment requires further refinement. Small animal studies of skin wound healing can greatly benefit from standardised definitions of wound closure and more consistent digital assessment protocols.

8.
Elife ; 122023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37818944

RESUMO

The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of functional specialisation in the infant brain is based on evidence from unitary imaging modalities and has thus focused on isolated estimates of spatial or temporal selectivity of neural or haemodynamic activation, giving an incomplete picture. We speculate that functional specialisation will be underpinned by better coordinated haemodynamic and metabolic changes in a broadly orchestrated physiological response. To enable researchers to track this process through development, we develop new tools that allow the simultaneous measurement of coordinated neural activity (EEG), metabolic rate, and oxygenated blood supply (broadband near-infrared spectroscopy) in the awake infant. In 4- to 7-month-old infants, we use these new tools to show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing, coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high-frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high-frequency brain activity. The development of simultaneous multimodal neural measures will enable future researchers to open new vistas in understanding functional specialisation of the brain.


Assuntos
Encéfalo , Neuroimagem , Adulto , Humanos , Lactente , Encéfalo/diagnóstico por imagem , Neuroimagem/métodos , Eletroencefalografia/métodos
9.
Australas J Ageing ; 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563782

RESUMO

OBJECTIVE(S): To understand Australian health professionals' perceptions of their knowledge and previous training about frailty, as well as barriers to frailty assessment and management in their practice. METHODS: A cross-sectional online survey was developed and distributed to health professionals (medical, nursing and allied health) engaged in clinical practice in Australia through convenience and snowball sampling techniques from March to May 2022. The survey consisted of five sections: frailty training and knowledge; confidence in recognising and managing adults with frailty; the importance and relevance of frailty; barriers to assessing and managing frailty in practice; and interest in further frailty training. Responses were analysed using descriptive statistics. RESULTS: The survey was taken by 736 health professionals. Less than half of respondents (44%, 321/733) reported receiving any training on frailty, with 14% (105/733) receiving training specifically focussed on frailty. Most respondents (78%, 556/712) reported 'good' or 'fair' understanding of frailty. The majority (64%, 448/694) reported being 'fairly' or 'somewhat' confident with identifying frailty. Almost all respondents (>90%) recognised frailty as having an important impact on outcomes and believed that there are beneficial interventions for frailty. Commonly reported barriers to frailty assessment in practice included 'lack of defined protocol for managing frailty' and 'lack of consensus about which frailty assessment tool to use'. Most respondents (88%, 521/595) were interested in receiving further education on frailty, with a high preference for online training. CONCLUSIONS: The findings suggest frailty is important to health professionals in Australia, and there is a need for and interest in further frailty education.

10.
Evid Based Nurs ; 26(4): 137, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37438086
11.
Am Surg ; 89(9): 3977-3978, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37344963

RESUMO

An inferior epigastric artery pseudoaneurysm is an exceptionally rare occurrence. Formation of an inferior epigastric artery pseudoaneurysm can be seen following surgical intervention and is more common after laparoscopy. A sixty-eight-year-old male presented with a right upper quadrant bulge at his incision site two months following laparoscopic appendectomy. The patient reported sudden onset of a non-reducible bulge at a 5 mm trocar incision site with minimal pain and without obstructive symptoms. Computed tomography of his abdomen and pelvis with intravenous contrast revealed a 4.2 cm pseudoaneurysm with peripheral thrombosis within the right inferior epigastric artery. The patient subsequently underwent open exploration with the evacuation of pseudoaneurysm thrombus and ligation of arteriovenous fistula. The patient recovered well without complication from pseudoaneurysm. Inferior epigastric artery pseudoaneurysm following any laparoscopic procedure is rare. This case highlights the importance of understanding the abdominal wall anatomy and its vascular supply to avoid such injury. We present this case to bring light to this rare occurrence and to highlight the importance of proper trocar placement during any laparoscopic procedure.


Assuntos
Parede Abdominal , Falso Aneurisma , Laparoscopia , Masculino , Humanos , Idoso , Artérias Epigástricas/anatomia & histologia , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Apendicectomia/efeitos adversos , Laparoscopia/efeitos adversos
12.
Neuroimage ; 274: 120153, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37146782

RESUMO

INTRODUCTION: Habituation and novelty detection are two fundamental and widely studied neurocognitive processes. Whilst neural responses to repetitive and novel sensory input have been well-documented across a range of neuroimaging modalities, it is not yet fully understood how well these different modalities are able to describe consistent neural response patterns. This is particularly true for infants and young children, as different assessment modalities might show differential sensitivity to underlying neural processes across age. Thus far, many neurodevelopmental studies are limited in either sample size, longitudinal scope or breadth of measures employed, impeding investigations of how well common developmental trends can be captured via different methods. METHOD: This study assessed habituation and novelty detection in N = 204 infants using EEG and fNIRS measured in two separate paradigms, but within the same study visit, at 1, 5 and 18 months of age in an infant cohort in rural Gambia. EEG was acquired during an auditory oddball paradigm during which infants were presented with Frequent, Infrequent and Trial Unique sounds. In the fNIRS paradigm, infants were familiarised to a sentence of infant-directed speech, novelty detection was assessed via a change in speaker. Indices for habituation and novelty detection were extracted for both EEG and NIRS RESULTS: We found evidence for weak to medium positive correlations between responses on the fNIRS and the EEG paradigms for indices of both habituation and novelty detection at most age points. Habituation indices correlated across modalities at 1 month and 5 months but not 18 months of age, and novelty responses were significantly correlated at 5 months and 18 months, but not at 1 month. Infants who showed robust habituation responses also showed robust novelty responses across both assessment modalities. DISCUSSION: This study is the first to examine concurrent correlations across two neuroimaging modalities across several longitudinal age points. Examining habituation and novelty detection, we show that despite the use of two different testing modalities, stimuli and timescale, it is possible to extract common neural metrics across a wide age range in infants. We suggest that these positive correlations might be strongest at times of greatest developmental change.


Assuntos
Habituação Psicofisiológica , Fala , Criança , Humanos , Lactente , Pré-Escolar , Habituação Psicofisiológica/fisiologia , Análise Espectral , Som , Eletroencefalografia/métodos
13.
Dev Sci ; : e13407, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37128134

RESUMO

Executive functions (EFs) in early childhood are predictors of later developmental outcomes and school readiness. Much of the research on EFs and their psychosocial correlates has been conducted in high-income, minority world countries, which represent a small and biased portion of children globally. The aim of this study is to examine EFs among children aged 3-5 years in two African countries, South Africa (SA) and The Gambia (GM), and to explore shared and distinct predictors of EFs in these settings. The SA sample (N = 243, 51.9% female) was recruited from low-income communities within the Cape Town Metropolitan area. In GM, participants (N = 171, 49.7% female) were recruited from the rural West Kiang region. EFs, working memory (WM), inhibitory control (IC) and cognitive flexibility (CF), were measured using tablet-based tasks. Associations between EF task performance and indicators of socioeconomic status (household assets, caregiver education) and family enrichment factors (enrichment activities, diversity of caregivers) were assessed. Participants in SA scored higher on all EF tasks, but children in both sites predominantly scored within the expected range for their age. There were no associations between EFs and household or familial variables in SA, except for a trend-level association between caregiver education and CF. Patterns were similar in GM, where there was a trend-level association between WM and enrichment activities but no other relationships. We challenge the postulation that children in low-income settings have poorer EFs, simply due to lower socioeconomic status, but highlight the need to identify predictors of EFs in diverse, global settings. RESEARCH HIGHLIGHTS: Assessed Executive Functioning (EF) skills and their psychosocial predictors among pre-school aged children (aged 3-5 years) in two African settings (The Gambia and South Africa). On average, children within each setting performed within the expected range for their age, although children in South Africa had higher scores across tasks. There was little evidence of any association between socioeconomic variables and EFs in either site. Enrichment activities were marginally associated with better working memory in The Gambia, and caregiver education with cognitive flexibility in South Africa, both associations were trend-level significance.

14.
J Clin Invest ; 133(11)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37071481

RESUMO

Neuropathic pain remains poorly managed by current therapies, highlighting the need to improve our knowledge of chronic pain mechanisms. In neuropathic pain models, dorsal root ganglia (DRG) nociceptive neurons transfer miR-21 packaged in extracellular vesicles to macrophages that promote a proinflammatory phenotype and contribute to allodynia. Here we show that miR-21 conditional deletion in DRG neurons was coupled with lack of upregulation of chemokine CCL2 after nerve injury and reduced accumulation of CCR2-expressing macrophages, which showed TGF-ß-related pathway activation and acquired an M2-like antinociceptive phenotype. Indeed, neuropathic allodynia was attenuated after conditional knockout of miR-21 and restored by TGF-ßR inhibitor (SB431542) administration. Since TGF-ßR2 and TGF-ß1 are known miR-21 targets, we suggest that miR-21 transfer from injured neurons to macrophages maintains a proinflammatory phenotype via suppression of such an antiinflammatory pathway. These data support miR-21 inhibition as a possible approach to maintain polarization of DRG macrophages at an M2-like state and attenuate neuropathic pain.


Assuntos
MicroRNAs , Neuralgia , Humanos , Hiperalgesia/genética , Hiperalgesia/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Macrófagos/metabolismo , Neuralgia/genética , Neuralgia/terapia , Neuralgia/metabolismo , Células Receptoras Sensoriais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Gânglios Espinais/metabolismo
15.
Neurophotonics ; 10(2): 023519, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37020727

RESUMO

Significance: Functional near-infrared spectroscopy (fNIRS) is a frequently used neuroimaging tool to explore the developing brain, particularly in infancy, with studies spanning from birth to toddlerhood (0 to 2 years). We provide an overview of the challenges and opportunities that the developmental fNIRS field faces, after almost 25 years of research. Aim: We discuss the most recent advances in fNIRS brain imaging with infants and outlines the trends and perspectives that will likely influence progress in the field in the near future. Approach: We discuss recent progress and future challenges in various areas and applications of developmental fNIRS from methodological and technological innovations to data processing and statistical approaches. Results and Conclusions: The major trends identified include uses of fNIRS "in the wild," such as global health contexts, home and community testing, and hyperscanning; advances in hardware, such as wearable technology; assessment of individual variation and developmental trajectories particularly while embedded in studies examining other environmental, health, and context specific factors and longitudinal designs; statistical advances including resting-state network and connectivity, machine learning and reproducibility, and collaborative studies. Standardization and larger studies have been, and will likely continue to be, a major goal in the field, and new data analysis techniques, statistical methods, and collaborative cross-site projects are emerging.

16.
Maturitas ; 170: 39-41, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36773498

RESUMO

Whether menopausal hormone therapy (MHT) lessens the severity of COVID-19 among women is unclear. Leveraging a U.S. national COVID-19 cohort and a cross-sectional analysis, we found MHT use was marginally associated with a lower risk of mortality (odds ratio [OR] 0.73, 95 % CI 0.53-1.01) and significantly associated with a lower risk of prolonged hospital stay (0.7, 0.49-0.99) among inpatient women. When stratifying by MHT type, estrogen-only and estrogen-plus-progestin therapies had a more prominent protective effect than progestin-only therapy, although this difference did not achieve statistical significance. Women with COVID-19 can continue to use MHT. Clinical trials are needed to evaluate MHT's therapeutic effect on COVID-19, especially in terms of severity.


Assuntos
COVID-19 , Menopausa , Feminino , Humanos , Terapia de Reposição de Estrogênios , Progestinas , Estudos Transversais , Terapia de Reposição Hormonal , Estrogênios
17.
Brain Pathol ; 33(3): e13128, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36321260

RESUMO

Selective loss of discrete neuronal populations is a prominent feature of many neurodegenerative conditions, but the molecular basis of this is poorly understood. A central role of α-synuclein in the selective neurodegeneration of Parkinson's disease has been speculated, as its level of expression critically determines the propensity of this protein to misfold. To investigate whether the propensity of neuronal cell loss is associated with the level of endogenous α-synuclein expression, non-transgenic rats were given a single intravenous administration of α-synuclein pre-formed fibrils (PFFs) reversibly complexed with the rabies virus glycoprotein peptide (RVG9R). The number of surviving cells in different neuronal populations was systematically quantified using unbiased stereology. Our data demonstrated that a non-selective, transvascular delivery of α-synuclein PFFs led to a time-dependent loss of specific populations of midbrain (but not olfactory) dopaminergic neurons, medullary (but not pontine) cholinergic neurons, and brainstem serotonergic neurons. Contrary to the central role of endogenous α-synuclein expression in determining the seeding and aggregation propensity of pathological α-synuclein, we did not observe an association between the levels of α-synuclein expression in different regions of the rodent brain (although did not ascertain this at the individual cell level) and neurodegenerative propensity. The results from our study highlight the complexity of the neurodegenerative process generated by α-synuclein seeding. Further investigations are therefore required to elucidate the molecular basis of neurodegeneration driven by exogenous pathogenic α-synuclein spread.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Ratos , Animais , alfa-Sinucleína/metabolismo , Doença de Parkinson/metabolismo , Encéfalo/patologia , Neurônios Dopaminérgicos/metabolismo , Administração Intravenosa
18.
Australas J Ageing ; 42(1): 127-139, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36324247

RESUMO

OBJECTIVE: Despite Comprehensive Geriatric Assessment (CGA) being central to the work of geriatricians, little is known about geriatricians' views on CGA. This study was designed to understand how geriatricians conceptualise and practise CGA, and whether differences exist between groups (more experienced geriatricians vs. less experienced geriatricians and registrars; those practising in rural vs. metropolitan environments; in private vs. public sectors). METHODS: An anonymous 90-item electronic questionnaire was emailed to members of the Australian and New Zealand Society for Geriatric Medicine. RESULTS: There were 243 respondents (response rate 19%). Respondents stated that core features of CGA were multidimensional assessment (89%), implementation of a management plan (84%), and involvement of a geriatrician (70%). Important features in predicting CGA success were ability to implement health management recommendations (55%), and ease of communication with general practitioners (46%), and with the multidisciplinary team (45%). Functional decline (88%) and frailty (88%) were thought to predict patients likely to benefit from CGA, compared to age (48%) or multimorbidity (19%). Junior consultants and registrars were less likely to prioritise the importance of clinical leadership (10% vs. 30%), and more likely to report the importance of a structured format (17% vs. 7%) to CGA effectiveness. CONCLUSIONS: There was some agreement about the core features of CGA and who is likely to benefit, but little agreement on features that predict CGA success. Further research that explores these points of difference would be helpful.


Assuntos
Avaliação Geriátrica , Geriatras , Humanos , Idoso , Avaliação Geriátrica/métodos , Nova Zelândia , Austrália , Inquéritos e Questionários
19.
Aging Clin Exp Res ; 35(2): 417-423, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36451033

RESUMO

Comprehensive geriatric assessment (CGA) is the gold standard model of care for older adults with frailty. However, despite a large number of published clinical trials, there remain many unanswered questions about how CGA works in different circumstances. This uncertainty stems from CGA being a deeply complex intervention that is heavily modified by context. This review describes recent and novel methodological approaches that explore the active ingredients of CGA and their interaction with context. Future research should continue to embrace broad methodologies that can help us better understand this intervention, in such a way that it can be implemented with fidelity and associated with positive outcomes for older adults.


Assuntos
Fragilidade , Avaliação Geriátrica , Humanos , Idoso , Avaliação Geriátrica/métodos , Fragilidade/diagnóstico
20.
Arch Physiol Biochem ; 129(1): 41-45, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32715774

RESUMO

CONTEXT: Research has described that adiponectin plays a key role in cardiomyocytes metabolism, however, the effects of exercise during obesity on cardiac adiponectin levels is unclear. OBJECTIVE: To investigate the effects of constant-moderate endurance (END) and high-intensity interval training (HIIT), on heart adiponectin levels in mice. MATERIAL AND METHODS: Two experiments were conducted: (1) preventive (EX1): 10 week-old male mice were fed standard (CHOW) or high-fat diet (HFD;45% fat) and simultaneously trained with END and HIIT for 10 weeks; (2) Treatment (EX2): after 10 weeks of dietary intervention, another cohort of 10 week-old mice were trained by both programmes for 10 weeks. RESULTS: In EX1, END and HIIT decreased low-molecular weight adiponectin (∼0.5-fold; p < 0.05) and increased GLUT4 levels (∼2-fold; p < .05). In EX2, HFD significantly decreased high-molecular weight adiponectin (∼0.7-fold; p < .05), and END reversed this change.Discussion and conclusion: HFD and exercise influence heart adiponectin isoforms and therefore might impact cardiomyocyte metabolism.


Assuntos
Adiponectina , Treinamento Intervalado de Alta Intensidade , Masculino , Camundongos , Animais , Adiponectina/metabolismo , Obesidade/etiologia , Obesidade/prevenção & controle , Coração , Dieta Hiperlipídica/efeitos adversos
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