Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 146
Filter
1.
Article in English | MEDLINE | ID: mdl-38875163

ABSTRACT

AIM: To synthesise the qualitative evidence on dyadic relationships between informal caregivers (ICs) and older adults with chronic heart failure (HF). METHODS AND RESULTS: A systematic review and meta-synthesis were conducted. Eight databases were searched for English peer-reviewed studies and grey literature published from inception to 27 February 2024. Qualitative and mixed-method studies involving older adults ≥ 55 years old with chronic HF and discussing patient-caregiver relationships in community settings were included. Data were synthesised using Sandelowski and Barroso's 2-step framework. A meta-summary was developed using thematic analysis, and findings were synthesised using the Theory of Dyadic Illness Management. Twenty-four studies from 2008 to 2024 were included (n = 580 participants). The meta-summary consisted of four themes and nine subthemes: (1) Characteristics of dyad relationships, (2) How both parts of the dyad care for each other, (3) Chronic HF and dyad relationships, (4) Knowledge of managing chronic HF. These were reorganised into the meta-synthesis: dyadic appraisal, dyadic management behaviours, dyadic health, contextual factors affecting dyadic relationships and management behaviours, and illness management as a dyadic phenomenon. CONCLUSION: Investigating relationship dynamics and their impact on dyads and chronic HF self-care is vital. Where possible, healthcare providers should prioritise dyadic care when caregivers are involved and deliver individualised care to improve patient and caregiver outcomes. Assessing and optimising dyadic relations, addressing individual perceptions and needs as part of clinical care, and before implementing self-care interventions in research may help ensure that self-care is appropriately tailored and would not be hindered by relationship conflicts.

2.
Front Public Health ; 12: 1374484, 2024.
Article in English | MEDLINE | ID: mdl-38746007

ABSTRACT

Background: The COVID-19 pandemic brought on a range of stressors in homes and workplaces. With no sign of ending after one year, burnout was a concern. Resilience has been known to shield against the effects of stress. While often thought of as an individual trait, previous studies have shown social support to improve resilience. The study aimed to examine the extent of burnout in the Singapore population and whether social support and resilience cushioned the impact of COVID-19 related stressors a year into the pandemic. Methods: Participants were 858 Singapore residents who participated in a larger study between October 2021 and September 2022. The Copenhagen Burnout Inventory provided Work-and Personal-related burnout scores. Multivariable linear regression was used to identify demographic variables associated with burnout. Path analysis revealed the associations between COVID-19 stressors, social support, resilience and burnout. Results: 22 and 19% of the sample reported work and personal burnout respectively, with younger adults being more burnt out than older adults. Higher stress was associated with higher burnout and higher social support was associated with lower burnout. Path analysis revealed that the relationship between social support and burnout was partially accounted for by increased resilience. Conclusion: Managing altered work arrangements, career expectations, and increased responsibilities at home may contribute to greater levels of burnout in the younger adults. Increased employer support and targeted interventions could mitigate the impact of these stressors. The study also highlighted the importance of maintaining social connections even while physically distancing.


Subject(s)
COVID-19 , Resilience, Psychological , Social Support , Humans , COVID-19/psychology , COVID-19/epidemiology , Singapore/epidemiology , Female , Male , Adult , Middle Aged , Aged , Pandemics , Surveys and Questionnaires , SARS-CoV-2 , Burnout, Psychological/psychology , Burnout, Professional/psychology , Young Adult , Stress, Psychological/psychology
3.
J Affect Disord ; 361: 209-216, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38821368

ABSTRACT

BACKGROUND: Social support is a robust predictor of post-traumatic stress disorder (PTSD). Although the inverse relationship between perceived social support and PTSD (social causation model) is supported, less is understood about the antecedents of the social causation model. Further, there is limited research in non-Western psychiatric populations that experience elevated rates of trauma and PTSD (e.g., mood disorders). The present study evaluated whether cumulative traumatic life events influenced current PTSD symptoms through maladaptive personality traits and perceptions of social support among Asian patients with mood disorders. METHODS: A total of 200 Asian patients (77.5 % Chinese) with mood disorders were assessed for maladaptive personality traits, perceptions of social support, cumulative traumatic life events, PTSD, and depressive symptoms. Structural equation modelling was conducted to evaluate the extended social causation model. RESULTS: The extended social causation model demonstrated acceptable fit to the data (Comparative Fit Index [CFI] = 0.90; absolute Root Mean Square Error of Approximation [RMSEA] = 0.08). There were significant indirect effects of cumulative traumatic life events on current PTSD symptoms (ß = 0.29, p < .001; 85 % variance explained) and depressive symptoms (ß = 0.28, p < .001; 69 % variance explained). LIMITATIONS: Results may not be generalizable beyond the Singapore population due to the socio-cultural and environmental context. CONCLUSIONS: The present findings provide conceptual support for a maladaptive personality-informed model of social support and PTSD, which could better inform trauma-focused interventions in preventing and treating the debilitating effects of PTSD in psychiatric populations.

4.
Cells ; 13(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38727297

ABSTRACT

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.


Subject(s)
Exosomes , Mesenchymal Stem Cells , Rats, Sprague-Dawley , Spinal Fusion , Animals , Exosomes/metabolism , Exosomes/transplantation , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Spinal Fusion/methods , Rats , Osteogenesis/drug effects , Calcium Phosphates/pharmacology , Male , Humans , Tissue Scaffolds/chemistry , Bone Morphogenetic Protein 2/metabolism , Mesenchymal Stem Cell Transplantation/methods
5.
Front Oncol ; 14: 1307839, 2024.
Article in English | MEDLINE | ID: mdl-38347838

ABSTRACT

Deregulation of the DNA damage response (DDR) plays a critical role in the pathogenesis and progression of many cancers. The dependency of certain cancers on DDR pathways has enabled exploitation of such through synthetically lethal relationships e.g., Poly ADP-Ribose Polymerase (PARP) inhibitors for BRCA deficient ovarian cancers. Though lagging behind that of solid cancers, DDR inhibitors (DDRi) are being clinically developed for haematological cancers. Furthermore, a high proliferative index characterize many such cancers, suggesting a rationale for combinatorial strategies targeting DDR and replicative stress. In this review, we summarize pre-clinical and clinical data on DDR inhibition in haematological malignancies and highlight distinct haematological cancer subtypes with activity of DDR agents as single agents or in combination with chemotherapeutics and targeted agents. We aim to provide a framework to guide the design of future clinical trials involving haematological cancers for this important class of drugs.

6.
BMC Psychol ; 12(1): 14, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38178150

ABSTRACT

BACKGROUND: For young people who engage in non-suicidal self-injury (NSSI), receiving negative responses to their NSSI can pose a barrier to future help-seeking. This qualitative study aimed to explore helpful and unhelpful ways in which professionals and non-professionals respond to NSSI, from the perspectives of individuals with lived experiences of NSSI. METHODS: Semi-structured interviews were conducted with 20 outpatients (6 males, 14 females) aged 17 to 29 years from a tertiary psychiatric hospital in Singapore, who had reported engaging in NSSI behavior in an earlier study. The interviews were audio recorded and transcribed verbatim. Thematic analysis was used to identify themes and subthemes in the data. RESULTS: Professionals' responses were organized into three main themes: 'prescribing solutions without understanding needs', 'disapproval or judgment', and 'helpful responses'. Non-professionals' responses were organized into four main themes: 'emotionally charged responses', 'avoidance and inaction', 'poor understanding of reasons for NSSI', and 'providing tangible support and acknowledging NSSI'. Participants also described how unhelpful responses negatively impacted their willingness to seek help. CONCLUSIONS: Our findings provide a better understanding of responses to NSSI that are considered helpful and unhelpful, and can be used to improve existing guidelines on responding to NSSI.


Subject(s)
Outpatients , Self-Injurious Behavior , Male , Female , Humans , Adolescent , Singapore , Self-Injurious Behavior/psychology , Qualitative Research
7.
Psychol Trauma ; 16(Suppl 1): S233-S241, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37695361

ABSTRACT

OBJECTIVE: Global emotion dysregulation mediates the relationship between child maltreatment and severe depressive symptoms; however, there is a lack of research on maladaptive personality traits and their contribution to individual differences in global emotion dysregulation within this conceptual model. The present study tested a preliminary serial mediation model where maladaptive personality traits and global emotion dysregulation mediate the relationship between child maltreatment and severe depressive symptoms. METHOD: A total of 200 patients with mood disorders (Mage = 36.5 years; 54% females) were assessed for maladaptive personality traits (Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders [5th ed.] Brief Form), global emotion dysregulation (Difficulties in Emotion Regulation Scale-Short), childhood trauma (Childhood Trauma Questionnaire), and depressive symptoms (Patient Health Questionnaire-9). RESULTS: Ordinary least squares regression and partial least squares-structural equation modeling revealed a consistent and significant indirect effect of child maltreatment on severe depressive symptoms through negative affectivity, detachment, psychoticism, and global emotion dysregulation. Among child maltreatment types, only emotional abuse had a significant indirect effect on severe depressive symptoms through maladaptive personality traits and global emotion dysregulation, b = 0.50, SE = 0.09, 95% confidence intervals [0.326, 0.694] after controlling for age, gender, and remaining types of child maltreatment. CONCLUSIONS: Findings support the view that maladaptive personality traits shed important insights on individual differences in global emotion dysregulation, and this information could aid clinical formulation and treatment of childhood adversity-related psychopathology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Adult Survivors of Child Abuse , Depression , Personality Disorders , Adult , Female , Humans , Male , Depression/psychology , Emotions , Individuality , Psychological Tests , Self Report , Adult Survivors of Child Abuse/psychology
8.
Soc Psychiatry Psychiatr Epidemiol ; 59(2): 375-383, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36786835

ABSTRACT

PURPOSE: Although the trajectory of mental disorders can be improved with timely treatment, many people defer treatment-seeking. This study aimed to examine the prevalence and correlates of treatment delays for mental disorders in Singapore, as well as perceived effectiveness of treatment received. METHODS: A total of 6126 respondents, aged 18 and above, participated in the Singapore Mental Health Study 2016-a cross-sectional, nationwide study conducted in Singapore from 2016 to 2018. Lifetime treatment contact for mood, anxiety, and alcohol use disorders (AUD) was assessed using the World Mental Health-Composite International Diagnostic Interview (Version 3.0). Multivariable logistic regression was conducted to examine correlates of delayed treatment. RESULTS: A total of 137 participants had made lifetime treatment contact for a mental disorder. The proportion of respondents who received delayed treatment (i.e., at least one year after onset of disorder) was 60.8% for any disorder, 59.5% for mood disorders, 56.3% for anxiety disorders, and 92.7% for AUD. The median delay was 5 years for mood disorders, one year for anxiety disorders, and 4 years for AUD. Treatment delay was significantly associated with older age, higher educational qualification, lifetime AUD, and earlier age of onset of disorder. 58.4% of respondents with lifetime treatment contact had received treatment that they considered effective. CONCLUSION: The high prevalence and long durations of treatment delay underscore the need to encourage help-seeking for mental disorders, especially since treatment is generally perceived to be helpful. Our findings also highlight several population groups more susceptible to receiving delayed treatment.


Subject(s)
Alcoholism , Mental Disorders , Humans , Mental Health , Singapore/epidemiology , Cross-Sectional Studies , Treatment Delay , Mental Disorders/diagnosis , Mental Disorders/epidemiology , Mental Disorders/therapy , Prevalence
9.
Support Care Cancer ; 32(1): 14, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38060009

ABSTRACT

BACKGROUND: Although both EQ-5D-3L(3L) and EQ-5D-5L(5L) have demonstrated good measurement properties in several patient populations, there is currently limited evidence comparing the measurement properties of 3L and 5L in family caregivers (FCs) of cancer patients. PURPOSE: This study aimed to compare the measurement properties of 3L and 5L in a sample of family caregivers of cancer patients. METHODS: A consecutive sample of FCs of cancer patients recruited from three tertiary hospitals were invited to complete the two versions of the EQ-5D in two rounds of interviews. We compared i) the ceiling effect using the McNemar's test, ii) test-retest reliability using intraclass correlation coefficient (ICC) and Cohen's Kappa, iii) convergent validity using Spearman's rank correlation coefficient, iv) known-group validity using F-statistic, v) and discriminant capacity using ordinal logistic regression. RESULTS: A total of 416 FCs completed the baseline questionnaire and 120 caregivers completed the follow-up questionnaire. Ceiling effects were smaller in 5L (12.5%) than in 3L (20.7%). The convergent validity (r = 0.344-0.771), known-groups validity (Fratio5L/3L = 2.06-4.09), discriminant capacity (ES = 0.341-0.396), and test-retest reliability (ICC = 0.725) of the 5L were slightly better than those of the 3L in China. CONCLUSION: The current study found both 3L and 5L to be suitable for use by FCs of cancer patients. However, 5L showed superior measurement properties compared to 3L and therefore could be the preferred instrument when EQ-5D data of cancer patients FCs is required.


Subject(s)
Neoplasms , Quality of Life , Humans , Caregivers , Reproducibility of Results , East Asian People , Psychometrics , Surveys and Questionnaires , Health Status
11.
Acta Neuropathol Commun ; 11(1): 180, 2023 11 13.
Article in English | MEDLINE | ID: mdl-37957721

ABSTRACT

BACKGROUND: Despite the presence of significant cortical pTDP-43 inclusions of heterogeneous morphologies in patients diagnosed with amyotrophic lateral sclerosis (ALS), pathological subclassification is routinely performed in the minority of patients with concomitant frontotemporal dementia (FTD). OBJECTIVE: In order to improve current understanding of the presence and relevance of pathological pTDP-43 subtypes in ALS, the present study examined the pattern of cortical pTDP-43 aggregates in 61 ALS cases without FTD. RESULTS: Based on the presence, morphology and composition of pTDP-43 pathology, three distinct ALS-TDP subtypes were delineated: (1) A predominant pattern of pTDP-43 granulofilamentous neuronal inclusions (GFNIs) and grains that were immuno-negative for p62 was identified in 18% of cases designated ALS-TDP type E; (2) neuronal cytoplasmic inclusions (NCIs) that were immuno-positive for both pTDP-43 and p62 were observed in 67% of cases assigned ALS-TDP type B; and (3) scarce cortical pTDP-43 and p62 aggregates were identified in 15% of cases coined ALS-TDP type SC (scarce cortical). Quantitative analyses revealed a significantly greater burden of pTDP-43 GFNI and grains in ALS-TDP type E. Principal component analysis demonstrated significant relationships between GFNIs, grains and ALS-TDP subtypes to support the distinction of subtypes E and B. No significant difference in age at death or disease duration was found between ALS-TDP subgroups to suggest that these subtypes represent earlier or later stages of the same disease process. Instead, a significantly higher ALS-TDP stage, indicating greater topographical spread of pTDP-43, was identified in ALS-TDP type E. Alzheimer's disease neuropathological change (ABC score ≥ intermediate) and Lewy body disease (Braak stage ≥ IV) was more prevalent in the ALS-TDP type SC cohort, which also demonstrated a significantly lower overall cognitive score. CONCLUSION: In summary, the present study demonstrates that ALS-TDP does not represent a single homogenous neuropathology. We propose the subclassification of ALS-TDP into three distinct subtypes using standard immuno-stains for pTDP-43 and p62 in the motor cortex, which is routinely sampled and evaluated for diagnostic neuropathological characterisation of ALS. We propose that future studies specify both clinicopathological group and pTDP-43 subtype to advance current understanding of the pathogenesis of clinical phenotypes in pTDP-43 proteinopathies, which will have significant relevance to the development of targeted therapies for this heterogeneous disorder.


Subject(s)
Amyotrophic Lateral Sclerosis , Frontotemporal Dementia , Humans , Amyotrophic Lateral Sclerosis/pathology , Frontotemporal Dementia/pathology , DNA-Binding Proteins/genetics , Neurons/pathology , Phenotype
12.
Adv Healthc Mater ; 12(32): e2301472, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37758297

ABSTRACT

Gingiva plays a crucial barrier role at the interface of teeth, tooth-supporting structures, microbiome, and external agents. To mimic this complex microenvironment, an in vitro microphysiological platform and biofabricated full-thickness gingival equivalents (gingiva-on-chip) within a vertically stacked microfluidic device is developed. This design allowed long-term and air-liquid interface culture, and host-material interactions under flow conditions. Compared to static cultures, dynamic cultures on-chip enabled the biofabrication of gingival equivalents with stable mucosal matrix, improved epithelial morphogenesis, and barrier features. Additionally, a diseased state with disrupted barrier function representative of gingival/oral mucosal ulcers is modeled. The apical flow feature is utilized to emulate the mechanical action of mouth rinse and integrate the assessment of host-material interactions and transmucosal permeation of oral-care formulations in both healthy and diseased states. Although the gingiva-on-chip cultures have thicker and more mature epithelium, the flow of oral-care formulations induced increased tissue disruption and cytotoxic features compared to static conditions. The realistic emulation of mouth rinsing action facilitated a more physiological assessment of mucosal irritation potential. Overall, this microphysiological system enables biofabrication of human gingiva equivalents in intact and ulcerated states, providing a miniaturized and integrated platform for downstream host-material and host-microbiome applications in gingival and oral mucosa research.


Subject(s)
Gingiva , Microbiota , Humans , Mouth Mucosa
13.
JCPP Adv ; 3(3): e12156, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37720578

ABSTRACT

Background: Increasing research efforts have focused on understanding why some individuals develop severe psychopathology after exposure to adverse childhood experiences (ACEs). Sleep disturbances (insomnia, nightmares, and sleep disorders) are prevalent sequelae of ACEs and associated with psychopathology; however, there is no meta-analytic evidence on whether sleep disturbance functions as a transdiagnostic mediator in the relationship between ACEs and psychopathology (internalizing/externalizing disorders and psychosis) in children and adolescents. Methods: Systematic searches in three databases (PubMed; PsycINFO; Web of Science) identified 98 articles (N = 402,718; age range 1-17 years) and the present study used a novel two-stage meta-analytic structural equation model to investigate whether ACEs predict psychopathology through sleep disturbance. Subgroup analyses determined potential biases due to study design (cross-sectional vs. longitudinal) and geographical differences (Western vs. non-Western countries). Sensitivity analyses evaluated the influence of early childhood (<5 years old) and overlapping symptoms (i.e., nightmares and trauma symptoms) on model stability. Results: The pooled correlations among ACEs, sleep disturbance, and psychopathology were significant; the effect sizes ranged from moderate to high (r = 0.21 to r = 0.29). The indirect effect from ACEs via sleep disturbance to psychopathology was significant (ß = 0.05, 95% CI [0.04, 0.06]). The direct effect of ACEs on psychopathology was significant (ß = 0.18, 95% CI 0.13-0.24). Subgroup analyses revealed larger effects for cross-sectional studies than longitudinal studies (Δ χ2 (3) = 9.71, p = 0.021). Sensitivity analyses revealed stable and consistent results. Conclusions: The present meta-analytic results indicate that sleep disturbance is a transdiagnostic mediator in the relationship between ACEs and psychopathology among children and adolescents. Further research is required to determine the synergistic effects between sleep disturbance and other risk mechanisms, and elucidate the complex pathways that lead to disorder in the aftermath of childhood adversities.

14.
Front Nutr ; 10: 1217192, 2023.
Article in English | MEDLINE | ID: mdl-37485396

ABSTRACT

This study tested the hypothesis that co-ingesting nitrate (NO3-)-rich beetroot juice (BR) and pomegranate powder (POM) would enhance neuromuscular performance during vertical countermovement jumps, explosive kneeling countermovement push-ups, and back squats compared to BR ingestion alone. Fifteen recreationally-active males were assigned in a double-blind, randomized, crossover design, to supplement in 3 conditions: (1) NO3--depleted beetroot juice (PL; 0.10 mmol NO3-) with two empty gelatin capsules; (2) NO3--rich beetroot juice (BR; 11.8 mmol NO3-) with two empty gelatin capsules, and (3) BR with 1,000 mg of POM powder in two capsules (BR + POM). Participants completed 5 countermovement jumps and 5 kneeling countermovement push-ups interspersed by 1 min of recovery. Subsequently, participants performed 2 sets of 2 × 70% one-repetition maximum back squats, interspersed by 2 min of recovery. Plasma [NO3-] and nitrite ([NO2-]) were elevated following BR and BR + POM compared with PL and POM (p < 0.001) with no differences between BR and BR + POM (p > 0.05) or PL and POM (p > 0.05). Peak power during countermovement jumps increased by 3% following BR compared to BR + POM (88.50 ± 11.46 vs. 85.80 ± 10.14 W/Kg0.67, p = 0.009) but not PL (88.50 ± 11.46 vs. 85.58 ± 10.05 W/Kg0.67, p = 0.07). Neuromuscular performance was not different between conditions during explosive kneeling push-ups and back squats (p > 0.05). These data provide insight into the efficacy of NO3- to modulate explosive resistance exercise performance and indicate that supplementing with BR alone or combined with POM has limited ergogenic potential on resistance exercise. Furthermore, caution is required when combining BR with POM, as this could compromise aspects of resistance exercise performance, at least when compared to BR ingested independently.

15.
Nitric Oxide ; 138-139: 105-119, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37438201

ABSTRACT

Increasing evidence indicates that dietary nitrate supplementation has the potential to increase muscular power output during skeletal muscle contractions. However, there is still a paucity of data characterizing the impact of different nitrate dosing regimens on nitric oxide bioavailability and its potential ergogenic effects across various population groups. This review discusses the potential influence of different dietary nitrate supplementation strategies on nitric oxide bioavailability and muscular peak power output in healthy adults, athletes, older adults and some clinical populations. Effect sizes were calculated for peak power output and absolute and/or relative nitrate doses were considered where applicable. There was no relationship between the effect sizes of peak power output change following nitrate supplementation and when nitrate dosage when considered in absolute or relative terms. Areas for further research are also recommended including a focus on nitrate dosing regimens that optimize nitric oxide bioavailability for enhancing peak power at times of increased muscular work in a variety of healthy and disease populations.

16.
J Neuropathol Exp Neurol ; 82(9): 769-773, 2023 08 21.
Article in English | MEDLINE | ID: mdl-37414530

ABSTRACT

The autophagy marker p62 appears as a consistent component of pathological aggregates in amyotrophic lateral sclerosis (ALS) and its modulation to facilitate protein degradation has been proposed as a potential therapeutic target. Importantly, recent studies have implicated diffuse phosphorylated TDP-43 inclusions that are immuno-negative for p62 in more rapid disease, highlighting the need for better understanding of p62 involvement in ALS pathogenesis. The present study set out to assess p62 pathology in the motor neurons of 31 patients with sporadic ALS that had either a short (<2 years) or longer (4-7 years) disease duration to determine its association with pTDP-43 pathology, motor neuron loss, and survival in sporadic disease. Our results identified significantly more cytoplasmic p62 aggregates in the spinal cord of patients with a shorter survival. Disease duration demonstrated a negative association with p62 burden and density of remaining motor neurons in the spinal cord, suggesting that survival in sporadic ALS is associated with the successful clearance of lower motor neurons with p62 aggregates. These findings implicate the autophagy pathway in ALS survival and provide support for further study of p62 as a potential prognostic biomarker in ALS.


Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Amyotrophic Lateral Sclerosis/pathology , Motor Neurons/pathology , Spinal Cord/pathology , Inclusion Bodies/pathology
17.
Neuropathol Appl Neurobiol ; 49(4): e12919, 2023 08.
Article in English | MEDLINE | ID: mdl-37317638

ABSTRACT

AIMS: Although the orally available brain-penetrant copper compound CuATSM has demonstrated promising effects in SOD1-linked mouse models, the impact of CuATSM on disease pathology in patients with amyotrophic lateral sclerosis (ALS) remains unknown. METHODS: The present study set out to address this deficit by performing the first pilot comparative analysis of ALS pathology in patients that had been administered CuATSM and riluzole [N = 6 cases composed of ALS-TDP (n = 5) and ALS-SOD1 (n = 1)] versus riluzole only [N = 6 cases composed of ALS-TDP (n = 4) and ALS-SOD1 (n = 2)]. RESULTS: Our results revealed no significant difference in neuron density or TDP-43 burden in the motor cortex and spinal cord of patients that had received CuATSM compared with patients that had not. In patients that had received CuATSM, p62-immunoreactive astrocytes were observed in the motor cortex and reduced Iba1 density was found in the spinal cord. However, no significant difference in measures of astrocytic activity and SOD1 immunoreactivity was found with CuATSM treatment. DISCUSSION: These findings, in this first postmortem investigation of patients with ALS in CuATSM trials, demonstrate that in contrast to that seen in preclinical models of disease, CuATSM does not significantly alleviate neuronal pathology or astrogliosis in patients with ALS.


Subject(s)
Amyotrophic Lateral Sclerosis , Mice , Animals , Amyotrophic Lateral Sclerosis/drug therapy , Amyotrophic Lateral Sclerosis/pathology , Copper , Superoxide Dismutase-1 , Riluzole , Superoxide Dismutase , Motor Neurons/pathology , Spinal Cord/pathology , DNA-Binding Proteins , Mice, Transgenic
18.
Nutrients ; 15(11)2023 May 27.
Article in English | MEDLINE | ID: mdl-37299456

ABSTRACT

This systematic review and meta-analysis investigated the influence of dietary nitrate supplementation on resistance exercise performance according to the PRISMA guidelines. Searches were conducted on MEDLINE, PubMed, ScienceDirect, Scopus and SPORTDiscus databases up to April 2023. Inclusion criteria were adult resistance-trained males who supplemented with a nitrate-rich supplement and nitrate-deficient placebo to assess repetitions-to-failure (RTF), peak power, mean power, peak velocity, and/or mean velocity during back squat and bench press exercise. A random effects model was performed on six studies and showed that nitrate supplementation improved RTF (standardized mean difference [SMD]: 0.43, 95% confidence intervals [95% CI]: 0.156 to 0.699, p = 0.002), mean power (SMD: 0.40, 95% CI: 0.127 to 0.678, p = 0.004), and mean velocity (SMD: 0.57, 95% CI: 0.07 to 1.061, p = 0.025) but had no effect on peak power (SMD: 0.204, 95% CI: -0.004 to 0.411, p = 0.054) or peak velocity (SMD: 0.00, 95% CI: -0.173 to 0.173, p = 1.000) when back squat and bench press were combined. Subgroup analyses revealed that back squats were more likely to be enhanced and that a dosing regimen may influence the efficacy of nitrate supplementation. Overall, nitrate supplementation had a small beneficial effect on some aspects of resistance exercise performance, but there were limited studies available and the variability was large. Additional studies that focus on upper and lower body resistance exercise and nitrate dosage are required to elucidate the efficacy of dietary nitrate supplementation on resistance exercise performance.


Subject(s)
Muscle Strength , Nitrates , Male , Adult , Humans , Nitrates/pharmacology , Muscle, Skeletal , Exercise Therapy , Dietary Supplements
19.
Cytotherapy ; 25(8): 837-846, 2023 08.
Article in English | MEDLINE | ID: mdl-37191613

ABSTRACT

Musculoskeletal disorders are one of the biggest contributors to morbidity and place an enormous burden on the health care system in an aging population. Owing to their immunomodulatory and regenerative properties, mesenchymal stromal/stem cells (MSCs) have demonstrated therapeutic efficacy for treatment of a wide variety of conditions, including musculoskeletal disorders. Although MSCs were originally thought to differentiate and replace injured/diseased tissues, it is now accepted that MSCs mediate tissue repair through secretion of trophic factors, particularly extracellular vesicles (EVs). Endowed with a diverse cargo of bioactive lipids, proteins, nucleic acids and metabolites, MSC-EVs have been shown to elicit diverse cellular responses and interact with many cell types needed in tissue repair. The present review aims to summarize the latest advances in the use of native MSC-EVs for musculoskeletal regeneration, examine the cargo molecules and mechanisms underlying their therapeutic effects, and discuss the progress and challenges in their translation to the clinic.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , Musculoskeletal Diseases , Humans , Aged , Extracellular Vesicles/metabolism , Musculoskeletal Diseases/therapy , Immunomodulation , Cell Communication , Mesenchymal Stem Cells/physiology
20.
Nitric Oxide ; 136-137: 33-47, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37244391

ABSTRACT

Increasing evidence indicates that dietary nitrate supplementation has the potential to increase muscular power output during skeletal muscle contractions. However, there is still a paucity of data characterizing the impact of different nitrate dosing regimens on nitric oxide bioavailability its potential ergogenic effects across various population groups. This narrative review discusses the potential influence of different dietary nitrate supplementation strategies on nitric oxide bioavailability and muscular power output in healthy adults, athletes, older adults and some clinical populations. Areas for further research are also recommended including a focus individualized nitrate dosing regimens to optimize nitric oxide bioavailability and to promote muscular power enhancements in different populations.


Subject(s)
Beta vulgaris , Nitrates , Humans , Aged , Nitric Oxide/metabolism , Dietary Supplements , Muscle Contraction , Biological Availability , Muscle, Skeletal/metabolism , Double-Blind Method
SELECTION OF CITATIONS
SEARCH DETAIL
...