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1.
Mol Biol Cell ; 35(8): ar112, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38985524

RESUMO

Centrosomes and spindle pole bodies (SPBs) are important for mitotic spindle formation and serve as cellular signaling platforms. Although centrosomes and SPBs differ in morphology, many mechanistic insights into centrosome function have been gleaned from SPB studies. In the fission yeast Schizosaccharomyces pombe, the α-helical protein Ppc89, identified based on its interaction with the septation initiation network scaffold Sid4, comprises the SPB core. High-resolution imaging has suggested that SPB proteins assemble on the Ppc89 core during SPB duplication, but such interactions are undefined. Here, we define a connection between Ppc89 and the essential pericentrin Pcp1. Specifically, we found that a predicted third helix within Ppc89 binds the Pcp1 pericentrin-AKAP450 centrosomal targeting (PACT) domain complexed with calmodulin. Ppc89 helix 3 contains similarity to present in the N-terminus of Cep57 (PINC) motifs found in the centrosomal proteins fly SAS-6 and human Cep57 and also to the S. cerevisiae SPB protein Spc42. These motifs bind pericentrin-calmodulin complexes and AlphaFold2 models suggest a homologous complex assembles in all four organisms. Mutational analysis of the S. pombe complex supports the importance of Ppc89-Pcp1 binding interface in vivo. Our studies provide insight into the core architecture of the S. pombe SPB and suggest an evolutionarily conserved mechanism of scaffolding pericentrin-calmodulin complexes for mitotic spindle formation.


Assuntos
Centrossomo , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Fuso Acromático , Corpos Polares do Fuso , Schizosaccharomyces/metabolismo , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Corpos Polares do Fuso/metabolismo , Centrossomo/metabolismo , Fuso Acromático/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Antígenos/metabolismo , Calmodulina/metabolismo , Ligação Proteica
2.
Opt Lett ; 49(12): 3508-3511, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875657

RESUMO

We develop and validate a model-based iterative reconstruction framework for digitally correcting coherent images corrupted by deep turbulence. In general, this framework is applicable to coherent-imaging approaches that gain access to the complex-optical field; however, we demonstrate our approach with multi-shot digital holography data. To test our image correction framework, we generate calibrated deep-turbulence conditions from our laboratory testbed. Using the resulting data, we demonstrate groundbreaking performance in terms of speckle-free image correction in deep-turbulence conditions.

3.
Acta Ortop Mex ; 38(3): 193-196, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38862150

RESUMO

Trans-scaphoid perilunate fractures-dislocations are rare injuries caused by high-energy trauma of the wrist. Diagnosis is based on medical history, physical examination, and tools such as radiographs, computed tomography scan, and magnetic resonance imaging. Early treatment consists of closed reduction and casting to stabilize the limb. Definitive treatment is surgical and includes bone and soft tissue repair. A case of trans-scaphoid perilunate fracture-dislocation is presented, along with diagnosis, management and outcome.


Las fracturas-luxaciones transescafo-perilunares son lesiones infrecuentes causadas por impactos de alta energía hacia la muñeca. El diagnóstico se basa en la historia clínica, exploración física y herramientas como la radiografía, la tomografía computarizada y la resonancia magnética. El manejo inmediato consiste en una reducción cerrada e inmovilización para estabilizar la extremidad. El tratamiento definitivo es de carácter quirúrgico e incluye la reparación ósea y de tejidos blandos. Se presenta un caso de fractura-luxación transescafo-perilunar, su diagnóstico, manejo y evolución.


Assuntos
Osso Escafoide , Humanos , Masculino , Osso Escafoide/lesões , Osso Escafoide/diagnóstico por imagem , Osso Semilunar/lesões , Osso Semilunar/diagnóstico por imagem , Osso Semilunar/cirurgia , Fraturas Ósseas/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fratura-Luxação/cirurgia , Fratura-Luxação/diagnóstico por imagem , Luxações Articulares/cirurgia , Luxações Articulares/diagnóstico por imagem , Adulto , Traumatismos do Punho/cirurgia , Traumatismos do Punho/diagnóstico por imagem
4.
Acta Ortop Mex ; 38(2): 109-112, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38782477

RESUMO

Epiphyseal fractures of the metatarsal head are a rare entity specially as an isolated injury and is rarely seen in patients with skeletal immaturity. Due lack of documentation for this type of fracture, the treatment of choice is uncertain. The purpose of the present study is to present two cases and treatment of epiphyseal fracture of the second metatarsal head, to our knowledge there are no publications for this injury.


Las fracturas epifisarias de la cabeza metatarsiana son una entidad poco frecuente, principalmente cuando se presentan de forma aislada y en raras ocasiones se ven en pacientes con inmadurez esquelética. Debido a la escasez de documentación para este tipo de fractura, el tratamiento de elección es incierto. El motivo del presente estudio es presentar dos casos de fractura epifisaria de la cabeza del segundo metatarsiano y su tratamiento, ya que para nuestro conocimiento no hay publicaciones al respecto.


Assuntos
Epífises , Fraturas Ósseas , Ossos do Metatarso , Humanos , Ossos do Metatarso/lesões , Ossos do Metatarso/diagnóstico por imagem , Adolescente , Fraturas Ósseas/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Masculino , Epífises/lesões , Feminino
5.
Gait Posture ; 111: 14-21, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38608470

RESUMO

BACKGROUND: Balance deficits are a major concern for people with multiple sclerosis (pwMS). Measuring complexity of motor behaviour can offer an insight into MS-related changes in adaptability of the balance control system when dealing with increasingly complex tasks. QUESTION: Does postural behaviour complexity differ between pwMS at early stages of the disease and healthy controls (HC)? Does postural behaviour complexity change across increasingly complex tasks? METHODS: Forty-eight pwMS and 24 HC performed four increasingly complex postural tasks with eyes open (EO), eyes closed (EC), on firm (FS) and compliant surface (CS). Lumbar and sternum sensors recorded 3D acceleration, from which complexity index (CI) was calculated using multiscale sample entropy (MSE) in the frontal and sagittal planes. RESULTS: We found that only the complexity index in both planes during the eyes closed on compliant surface (EC-CS) task was significantly lower in pwMS compared to HC. We also found that complexity in pwMS was significantly lower during EC-CS compared to the other three tasks when using both lumbar and sternum sensors. SIGNIFICANCE: Increasing the complexity of postural tasks reduces the complexity of postural behaviour in pwMS. This paradox may reflect reduced adaptability of the sensorimotor integration processes at early stages of MS. CI can provide a different perspective on balance deficits and could potentially be a more sensitive biomarker of MS progression and an early indicator of balance deficit.


Assuntos
Esclerose Múltipla , Equilíbrio Postural , Humanos , Equilíbrio Postural/fisiologia , Feminino , Masculino , Adulto , Esclerose Múltipla/fisiopatologia , Pessoa de Meia-Idade , Estudos de Casos e Controles
6.
bioRxiv ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38659967

RESUMO

It has been well established that cardiovascular diseases exhibit significant differences between sexes in both preclinical models and humans. In addition, there is growing recognition that disrupted circadian rhythms can contribute to the onset and progression of cardiovascular diseases. However little is known about sex differences between the cardiac circadian clock and circadian transcriptomes in mice. Here, we show that the the core clock genes are expressed in common in both sexes but the circadian transcriptome of the mouse heart is very sex-specific. Hearts from female mice expressed significantly more rhythmically expressed genes (REGs) than male hearts and the temporal pattern of REGs was distinctly different between sexes. We next used a cardiomyocyte-specific knock out of the core clock gene, Bmal1, to investigate its role in sex-specific gene expression in the heart. All sex differences in the circadian transcriptomes were significantly diminished with cardiomyocyte-specific loss of Bmal1. Surprisingly, loss of cardiomyocyte Bmal1 also resulted in a roughly 8-fold reduction in the number of all the differentially expressed genes between male and female hearts. We conclude that cardiomyocyte-specific Bmal1, and potentially the core clock mechanism, is vital in conferring sex-specific gene expression in the adult mouse heart.

7.
MicroPubl Biol ; 20242024.
Artigo em Inglês | MEDLINE | ID: mdl-38511077

RESUMO

The Schizosaccharomyces pombe Gas family of ß-1,3-glucanosyltransferases modify the cell wall by elongating ß-1,3-glucan chains. While gas1Δ cells are inviable under standard laboratory growth conditions, they are viable in the presence of an osmotic stabilizer. Even under these conditions however, gas1Δ cells are slow-growing and display cell separation and morphology defects. Here, we isolated and characterized two gas1 temperature-sensitive alleles. Our data support that Gas1 is the primary S. pombe ß-1,3-glucanosyltransferase important for cell separation and cell viability and provide useful tools for further analysis of S. pombe cell wall formation.

8.
Sensors (Basel) ; 24(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38339590

RESUMO

Postural impairment in people with multiple sclerosis (pwMS) is an early indicator of disease progression. Common measures of disease assessment are not sensitive to early-stage MS. Sample entropy (SE) may better identify early impairments. We compared the sensitivity and specificity of SE with linear measurements, differentiating pwMS (EDSS 0-4) from healthy controls (HC). 58 pwMS (EDSS ≤ 4) and 23 HC performed quiet standing tasks, combining a hard or foam surface with eyes open or eyes closed as a condition. Sway was recorded at the sternum and lumbar spine. Linear measures, mediolateral acceleration range with eyes open, mediolateral jerk with eyes closed, and SE in the anteroposterior and mediolateral directions were calculated. A multivariate ANOVA and AUC-ROC were used to determine between-groups differences and discriminative ability, respectively. Mild MS (EDSS ≤ 2.0) discriminability was secondarily assessed. Significantly lower SE was observed under most conditions in pwMS compared to HC, except for lumbar and sternum SE when on a hard surface with eyes closed and in the anteroposterior direction, which also offered the strongest discriminability (AUC = 0.747), even for mild MS. Overall, between-groups differences were task-dependent, and SE (anteroposterior, hard surface, eyes closed) was the best pwMS classifier. SE may prove a useful tool to detect subtle MS progression and intervention effectiveness.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico , Entropia , Equilíbrio Postural , Posição Ortostática , Aceleração
9.
Microbiol Resour Announc ; 13(2): e0099023, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38231182

RESUMO

We report the discovery of two mycobacteriophages isolated from soil in Rock Hill, South Carolina. Ashballer has a genome sequence length of 52,231 bp, while Bombitas is relatively larger at 110,129 bp. Both have siphovirus morphologies and have temperate lifecycles.

10.
PLoS Genet ; 19(10): e1010987, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37792890

RESUMO

Coupling cell wall expansion with cell growth is a universal challenge faced by walled organisms. Mutations in Schizosaccharomyces pombe css1, which encodes a PM inositol phosphosphingolipid phospholipase C, prevent cell wall expansion but not synthesis of cell wall material. To probe how Css1 modulates cell wall formation we used classical and chemical genetics coupled with quantitative mass spectrometry. We found that elevated levels of the sphingolipid biosynthetic pathway's final product, mannosylinositol phosphorylceramide (MIPC), specifically correlated with the css1-3 phenotype. We also found that an apparent indicator of sphingolipids and a sterol biosensor accumulated at the cytosolic face of the PM at cell tips and the division site of css1-3 cells and, in accord, the PM in css1-3 was less dynamic than in wildtype cells. Interestingly, disrupting the protein glycosylation machinery recapitulated the css1-3 phenotype and led us to investigate Ghs2, a glycosylated PM protein predicted to modify cell wall material. Disrupting Ghs2 function led to aberrant cell wall material accumulation suggesting Ghs2 is dysfunctional in css1-3. We conclude that preventing an excess of MIPC in the S. pombe PM is critical to the function of key PM-localized proteins necessary for coupling growth with cell wall formation.


Assuntos
Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Esfingolipídeos/genética , Esfingolipídeos/metabolismo , Schizosaccharomyces/metabolismo , Saccharomyces cerevisiae/genética , Membrana Celular/genética , Membrana Celular/metabolismo , Parede Celular/genética , Parede Celular/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo
11.
Nat Cell Biol ; 25(11): 1691-1703, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37845327

RESUMO

Ribosome biogenesis is among the most resource-intensive cellular processes, with ribosomal proteins accounting for up to half of all newly synthesized proteins in eukaryotic cells. During stress, cells shut down ribosome biogenesis in part by halting rRNA synthesis, potentially leading to massive accumulation of aggregation-prone 'orphan' ribosomal proteins (oRPs). Here we show that, during heat shock in yeast and human cells, oRPs accumulate as reversible peri-nucleolar condensates recognized by the Hsp70 co-chaperone Sis1/DnaJB6. oRP condensates are liquid-like in cell-free lysate but solidify upon depletion of Sis1 or inhibition of Hsp70. When cells recover from heat shock, oRP condensates disperse in a Sis1- and Hsp70-dependent manner, and the oRP constituents are incorporated into functional ribosomes in the cytosol, enabling cells to efficiently resume growth. Preserving biomolecules in reversible condensates-like mRNAs in cytosolic stress granules and oRPs at the nucleolar periphery-may be a primary function of the Hsp70 chaperone system.


Assuntos
Proteínas Ribossômicas , Proteínas de Saccharomyces cerevisiae , Humanos , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ribossomos/genética , Ribossomos/metabolismo
12.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37746062

RESUMO

The Schizosaccharomyces pombe F-BAR protein, Cdc15, facilitates the linkage between the cytokinetic ring and the plasma membrane. Cdc15 is phosphorylated on many sites by four polarity kinases and this antagonizes membrane interaction. Dephosphorylation of Cdc15 during mitosis induces its phase separation, allowing oligomerization, membrane association, and protein partner binding. Here, using live cell imaging we examined whether spatial separation of Cdc15 from its four identified kinases potentially explains their diverse effects on tip septation and the mitotic Cdc15 phosphorylation state. We identified a correlation between kinase localization and their ability to antagonize Cdc15 cytokinetic ring and membrane localization.

13.
Lancet Psychiatry ; 10(10): 780-789, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37739584

RESUMO

BACKGROUND: Although structured tools have been widely used to predict violence risk in specialist mental health settings, there is uncertainty about the extent and quality of evidence of their predictive performance. We aimed to systematically review the predictive performance of tools used to assess violence risk in forensic mental health, where they are routinely administered. METHODS: In our systematic review and meta-analysis, we followed PRISMA guidelines and searched four databases (PsycINFO, Embase, Medline, and Global Health) from database inception to Nov 1, 2022, to identify studies examining the predictive performance of risk assessment tools in people discharged from forensic (secure) mental health hospitals. Systematic and narrative reviews were excluded from the review. Performance measures and descriptive statistics were extracted from published reports. A quality assessment was performed for each study using the Prediction Model Risk of Bias Assessment Tool. Meta-analysis was conducted on the performance of instruments that were independently externally validated with a sample size greater than 100. The study was registered with PROSPERO, CRD42022304716. FINDINGS: We conducted a systematic review of 50 eligible publications, assessing the predictive performance of 36 tools, providing data for 10 460 participants (88% men, 12% women; median age [from 47 studies] was 35 years, IQR 33-38) from 12 different countries. Post-discharge interpersonal violence and crime was most often measured by new criminal offences or recidivism (47 [94%] of 50 studies); only three studies used informant or self-report data on physical aggression or violent behaviour. Overall, the predictive performance of risk assessment tools was mixed. Most studies reported one discrimination metric, the area under the receiver operating characteristic curve (AUC); other key performance measures such as calibration, sensitivity, and specificity were not presented. Most studies had a high risk of bias (49 [98%] of 50), partly due to poor analytical approaches. A meta-analysis was conducted for violent recidivism on 29 independent external validations from 19 studies with at least 100 patients. Pooled AUCs for predicting violent outcomes ranged from 0·72 (0·65-0·79; I2=0%) for H10, to 0·69 for the Historical Clinical Risk Management-20 version 2 (95% CI 0·65-0·72; I2=0%) and Violence Risk Appraisal Guide (0·63-0·75; I2=0%), to 0·64 for the Static-99 (0·53-0·73; I2=45%). INTERPRETATION: Current violence risk assessment tools in forensic mental health have mixed evidence of predictive performance. Forensic mental health services should review their use of current risk assessment tools and consider implementing those with higher-quality evidence in support. FUNDING: Wellcome Trust.


Assuntos
Assistência ao Convalescente , Alta do Paciente , Masculino , Humanos , Feminino , Adulto , Violência , Medição de Risco , Hospitais Psiquiátricos
14.
BMC Geriatr ; 23(1): 426, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438710

RESUMO

The Seniors Exercise Park program is an evidence-based outdoor physical and social activity program designed originally for older people with no cognitive impairment. This study aimed to pilot this program for people living with dementia in residential aged care. We examined the feasibility of delivering the program, evaluating its structure, safety, and supervision needs. In addition, physical, social, health and cognitive benefits of participation were examined. Method This was a feasibility pilot randomised controlled design. Adults aged ≥ 60 years with symptoms of dementia and/or diagnoses of dementia were recruited from an aged care facility in Australia. Participants allocated to the intervention underwent a 12-week structured supervised physical activity program using the outdoor Seniors Exercise Park equipment followed by a 12-week maintenance phase, while the controls received usual care programs. Assessments occurred at baseline, 12 and 24-weeks. Feasibility evaluation included recruitment rate, retention, attendance, overall adherence, dropout rate, adverse events, program delivery modifications and supervision requirements. A suite of cognitive and health-related questionnaires and physical function measures were also collected. Results Sixteen participants were recruited (recruitment rate: 58.6%), eight for the intervention (83.3 ± 7.5 years, 87.5% women) and eight for the control (age 87.5 ± 3.0 years, 87.5% women). Eighty-eight percent completed the 12-week structured program, with 75% retention at 24-weeks. Across the 24-week period, 84.3% participation adherence was reported. No falls or adverse events occurred. Modifications of the program mainly related to method of communication, cueing and adjustments to suit individual personality and characteristics. A ratio of one trainer to two participants was practical and safe. There were no significant changes over time between groups in any of the secondary outcomes. High level of engagement, enjoyment and mood was reported throughout the exercise program. Conclusion The Seniors Exercise Park physical activity program was safe and feasible for people living with dementia in residential care, with high levels of enjoyment, positive attitude, and engagement reported in the intervention group. Individualised communication during program delivery was needed to facilitate motivation and participation. Further research is needed to assess the program effectiveness on physical and cognitive function on a larger scale. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry-Registry Number ACTRN12620000733976 . Registered on the 13/07/2020.


Assuntos
Demência , Terapia por Exercício , Feminino , Humanos , Idoso , Masculino , Projetos Piloto , Estudos de Viabilidade , Austrália/epidemiologia , Demência/terapia
15.
Front Cell Neurosci ; 17: 1193485, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37260580

RESUMO

Introduction: Dynamic physiological changes in brain extracellular calcium ([Ca2+]o) occur when high levels of neuronal activity lead to substantial Ca2+ entry via ion channels reducing local [Ca2+]o. Perturbations of the extracellular microenvironment that increase [Ca2+]o are commonly used to study how [Ca2+] regulates neuronal activity. At excitatory synapses, the Ca2+-sensing receptor (CaSR) and other G-protein coupled receptors link [Ca2+]o and spontaneous glutamate release. Phospholipase C (PLC) is activated by G-proteins and is hypothesized to mediate this process. Methods: Patch-clamping cultured neocortical neurons, we tested how spontaneous glutamate release was affected by [Ca2+]o and inhibition of PLC activity. We used hypertonic sucrose (HS) to evaluate the readily releasable pool (RRP) and test if it was affected by inhibition of PLC activity. Results: Spontaneous glutamate release substantially increased with [Ca2+]o, and inhibition of PLC activity, with U73122, abolished this effect. PLC-ß1 is an abundant isoform in the neocortex, however, [Ca2+]o-dependent spontaneous release was unchanged in PLC-ß1 null mutants (PLC-ß1-/-). U73122 completely suppressed this response in PLC-ß1-/- neurons, indicating that this residual [Ca2+]o-sensitivity may be mediated by other PLC isoforms. The RRP size was substantially reduced after incubation in U73122, but not U73343. Phorbol esters increased RRP size after PLC inhibition. Discussion: Together these data point to a strong role for PLC in mediating changes in spontaneous release elicited by [Ca2+]o and other extracellular cues, possibly by modifying the size of the RRP.

16.
BJPsych Open ; 9(3): e90, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37222105

RESUMO

BACKGROUND: There are limited longitudinal studies on the effects of the COVID-19 pandemic on mental health and well-being, including the effects of imposed restrictions and lockdowns. AIMS: This study investigates how living in a pandemic, and related lockdowns and restrictions, affected the mental health of people living in Australia during the first year of the COVID-19 pandemic. METHOD: A total of 875 people living in Australia participated in a longitudinal survey from 27 May to 14 December 2020. This time period includes dates that span pre-, during and post-wave 2 lockdowns in Australia, with strict and sustained public health measures. Linear mixed models were fitted to investigate the effect of lockdown on depression and anxiety symptoms. RESULTS: Symptoms of depression and anxiety improved over time, during and after lockdowns. More adverse mental health symptoms were observed for people with a history of medical or mental health problems, caring responsibilities, more neurotic personality traits or less conscientiousness, and for people who were younger. People who reported being more conscientious reported better mental health. CONCLUSIONS: Despite notoriously strict lockdowns, participants did not experience a deterioration of mental health over time. Results suggest a lack of significant adverse effects of lockdown restrictions on mental health and well-being. Findings highlight cohorts that could benefit from targeted mental health support and interventions, so that public policy can be better equipped to support them, particularly if future strict public health measures such as lockdowns are being considered or implemented for the COVID-19 pandemic and other disasters.

17.
J Phys Act Health ; 20(6): 555-565, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37024105

RESUMO

BACKGROUND: The Exercise interveNtion outdoor proJect in the cOmmunitY (ENJOY) Seniors Exercise Park program uses specialized outdoor equipment and a physical activity program to engage older people in physical activity, with multiple health benefits. We determined the cost-effectiveness of the ENJOY program. METHODS: The economic evaluation compared health care utilization costs 6 months prior to and 6 months post ENJOY program participation. Incremental cost-utility analysis for the primary aim (quality of life) and incremental cost-effectiveness analysis for the secondary aim (falls) were used. Analyses took a societal perspective inclusive of Australian government-funded health care and pharmaceuticals in addition to hospitalizations, community-based nursing and allied health, and community services. Productivity costs were also calculated. RESULTS: Fifty participants (average age 72.8 y [SD 7.4] and 78.0% [n = 39/50] women) were included. Participation in the ENJOY program reduced health care costs in the 6 months following the program: preintervention, $9764.49 (SD $26,033.35); postintervention, $5179.30 (SD $3826.64); observed postintervention reduction -$4.585.20 (95% confidence interval, -$12,113.99 to $2943.59; P = .227) without compromising quality of life (mean difference [MD] 0.011; 95% confidence interval, -0.034 to 0.056; P = .631) or increasing the likelihood of a fall (-0.5; 95% confidence interval, 0.00 to -0.50; P = .160). The ENJOY intervention is likely cost-effective. CONCLUSIONS: Planning for shared community spaces should consider the benefits of a Seniors Exercise Park as part of the built environment.


Assuntos
Exercício Físico , Qualidade de Vida , Humanos , Feminino , Idoso , Análise Custo-Benefício , Austrália , Terapia por Exercício
18.
Eur J Med Chem ; 254: 115386, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37094450

RESUMO

The modulatory interactions between neurotensin (NT) and the dopaminergic neurotransmitter system in the brain suggest that NT may be associated with the progression of Parkinson's disease (PD). NT exerts its neurophysiological effects by interactions with the human NT receptors type 1 (hNTS1) and 2 (hNTS2). Therefore, both receptor subtypes are promising targets for the development of novel NT-based analogs for the treatment of PD. In this study, we used a virtually guided molecular modeling approach to predict the activity of NT(8-13) analogs by investigating the docking models of ligands designed for binding to the human NTS1 and NTS2 receptors. The importance of the residues at positions 8 and/or 9 for hNTS1 and hNTS2 receptor binding affinity was experimentally confirmed by radioligand binding assays. Further in vitro ADME profiling and in vivo studies revealed that, compared to the parent peptide NT(8-13), compound 10 exhibited improved stability and BBB permeability combined with a significant enhancement of the motor function and memory in a mouse model of PD. The herein reported NTS1/NTS2 dual-specific NT(8-13) analogs represent an attractive tool for the development of therapeutic strategies against PD and potentially other CNS disorders.


Assuntos
Neurotensina , Doença de Parkinson , Animais , Humanos , Camundongos , Dopamina , Ligantes , Neurotensina/farmacologia , Neurotensina/metabolismo , Doença de Parkinson/tratamento farmacológico , Ligação Proteica , Receptores de Neurotensina/metabolismo
19.
Gait Posture ; 102: 39-42, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36889202

RESUMO

BACKGROUND: The local divergence exponent (LDE) has been used to assess gait stability in people with multiple sclerosis (pwMS). Although previous studies have consistently found that stability is lower in pwMS, inconsistent methodologies have been used to assess patients with a broad range of disability levels. QUESTIONS: What sensor location and movement direction(s) are better able to classify pwMS at early stages of the disease? METHODS: 49 pwMS with EDSS ≤ 2.5 and 24 healthy controls walked overground for 5 min while 3D acceleration data was obtained from sensors placed at the sternum (STR) and lumbar (LUM) areas. Unidirectional (vertical [VT], mediolateral [ML], and anteroposterior [AP]) and 3-dimensional (3D) LDEs were calculated using STR and LUM data over 150 strides. ROC analyses were performed to assess classification models using single and combined LDEs, with and without velocity per lap (VELLAP) as a covariate. RESULTS: Four models performed equally well by using combinations of VELLAP, LUM3D, LUMVT, LUMML, LUMAP, STRML, and STRAP (AUC = 0.879). The best model using single sensor LDEs included VELLAP, STR3D, STRML, and STRAP (AUC = 0.878), whereas using VELLAP + STRVT (AUC = 0.869) or VELLAP + STR3D (AUC=0.858) performed best using a single LDE. SIGNIFICANCE: The LDE offers an alternative to currently insensitive tests of gait impairment in pwMS at early stages, when deterioration is not clinically evident. For clinical purposes, the implementation of this measure can be simplified using a single sensor at the sternum and a single LDE measure, but speed should be considered. Longitudinal studies to determine the predictive power and responsiveness of the LDE to MS progression are still needed.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Marcha , Caminhada , Movimento , Equilíbrio Postural
20.
Artigo em Inglês | MEDLINE | ID: mdl-36960941

RESUMO

A series of 1,2,3-triazolyl nucleoside analogues bearing N-acetyl-D-glucosamine residue was synthesized by the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction of N1-ω-alkynyl derivatives of uracil, 6-methyluracil, thymine and 3,4,6-tri-O-acetyl-2-deoxy-2-acetamido-ß-D-glucopyranosyl azide. Antiviral assays revealed the lead compound 3f which showed both the same activity against the influenza virus A H1N1 (IC50=70.7 µM) as the antiviral drug Rimantadine in control (IC50=77 µM) and good activity against Coxsackievirus B3 (IC50=13.9 µM) which was one and a half times higher than the activity of the antiviral drug Pleconaril in control (IC50=21.6 µM). According to molecular docking simulations, the antiviral activity of the lead compound 3f against Coxsackie B3 virus can be explained by its binding to a key fragment of the capsid surface of this virus.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Nucleosídeos , Antivirais , Glucosamina/metabolismo , Acetilglucosamina , Simulação de Acoplamento Molecular , Azidas
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