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1.
BMJ Open Sport Exerc Med ; 10(2): e001909, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601122

RESUMO

Objectives: The study aims to (1) report the process of recruiting young adults into a secondary knee osteoarthritis prevention randomised controlled trial (RCT) after anterior cruciate ligament reconstruction (ACLR); (2) determine the number of individuals needed to be screened to include one participant (NNS) and (3) report baseline characteristics of randomised participants. Methods: The SUpervised exercise-therapy and Patient Education Rehabilitation (SUPER)-Knee RCT compares SUPER and minimal intervention for young adults (aged 18-40 years) with ongoing symptoms (ie, mean score of <80/100 from four Knee injury and Osteoarthritis Outcome Score subscales (KOOS4)) 9-36 months post-ACLR. The NNS was calculated as the number of prospective participants screened to enrol one person. At baseline, participants provided medical history, completed questionnaires (demographic, injury/surgery, rehabilitation characteristics) and underwent physical examination. Results: 1044 individuals were screened to identify 567 eligible people, from which 184 participants (63% male) enrolled. The sample of enrolled participants was multicultural (29% born outside Australia; 2% Indigenous Australians). The NNS was 5.7. For randomised participants, mean±SD age was 30±6 years. The mean body mass index was 27.3±5.2 kg/m2, with overweight (43%) and obesity (21%) common. Participants were, on average, 2.3 years post-ACLR. Over half completed <8 months of postoperative rehabilitation, with 56% having concurrent injury/surgery to meniscus and/or cartilage. The most affected KOOS (0=worst, 100=best) subscale was quality of life (mean 43.7±19.1). Conclusion: Young adults post-ACLR were willing to participate in a secondary osteoarthritis prevention trial. Sample size calculations should be multiplied by at least 5.7 to provide an estimate of the NNS. The SUPER-Knee cohort is ideally positioned to monitor and intervene in the early development and trajectory of osteoarthritis. Trial registration number: ACTRN12620001164987.

2.
J Orthop Sports Phys Ther ; 54(4): 234-247, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38284344

RESUMO

OBJECTIVES: To (1) compare activity-related psychological factors between individuals with and without knee conditions, and (2) assess associations between these factors and objective measures of function in individuals with knee conditions. DESIGN: A priori registered systematic review with meta-analysis. LITERATURE SEARCH: MEDLINE-Ovid, Embase-Ovid, Scopus-Elsevier, CINAHL-EBSCO, SPORTDiscus-EBSCO, and Cochrane Library were searched to May 27, 2022. STUDY SELECTION CRITERIA: We included peer-reviewed primary data studies (observational and experimental) of human participants with and without knee conditions reporting knee confidence, fear of movement/avoidance beliefs, and/or psychological readiness to return to sport (RTS) or reporting correlations between these factors and objective measures of function in knee conditions. DATA SYNTHESIS: Where possible, data were pooled by knee conditions, otherwise performed narrative syntheses. The Downs and Black checklist assessed the methodological quality of the included studies. RESULTS: Forty studies (3546 participants with knee conditions; 616 participants without knee conditions) were included. There was very low-certainty evidence of higher fear of movement in individuals with knee osteoarthritis (standardized mean difference [SMD], 0.46; 95% confidence interval [CI]: 0.41, 0.52), but not in individuals with patellofemoral pain (SMD, 0.66; 95% CI: -7.98, 9.29) when compared with those without knee conditions. There was very low-certainty evidence of no differences in psychological readiness to RTS after anterior cruciate ligament reconstruction (SMD, -1.14; 95% CI: -2.97, 0.70) compared to no knee condition, and negligible to weak positive correlations between psychological readiness to RTS and objective measures of function. CONCLUSION: There was very low-certainty evidence of higher fear of movement in individuals with knee osteoarthritis compared to those without, and very low-certainty evidence of no correlations between these factors and objective measures of function following anterior cruciate ligament reconstruction. J Orthop Sports Phys Ther 2024;54(4):1-14. Epub 29 January 2024. doi:10.2519/jospt.2024.12070.


Assuntos
Cinesiofobia , Osteoartrite do Joelho , Volta ao Esporte , Humanos , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/psicologia , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Cinesiofobia/psicologia , Osteoartrite do Joelho/psicologia , Osteoartrite do Joelho/cirurgia , Síndrome da Dor Patelofemoral/psicologia , Volta ao Esporte/psicologia
3.
AJR Am J Roentgenol ; 222(1): e2330189, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37937836

RESUMO

BACKGROUND. CT scanners' net scan state (i.e., image acquisition period) represents a potential target for energy savings through protocol adjustments. However, gauging CT energy savings is difficult without installing costly energy monitors. OBJECTIVE. The purpose of this article was to assess correlations between CT dose report metrics and energy consumption during the system net scan state and to compare theoretic energy savings from matching percentage reductions in energy consumption during net scan and idle system states. METHODS. Current sensors were installed on a single CT scanner. A phantom was scanned at varying kilovoltage settings and effective tube current-rotation time settings. A retrospective assessment was performed in 32 patients (mean age, 61.2 ± 17.9 [SD] years; 17 men, 15 women) who underwent 32 single-energy noncontrast abdominopelvic CT examinations from September 22, 2021, to September 27, 2021, on the same scanner. Correlations between dose report metrics and net scan energy consumption were assessed in the phantom and clinical scans, and equations were generated to derive net scan energy consumption from DLP. An additional retrospective assessment was performed in 1355 patients (mean age, 59.3 ± 16.9 years; 663 men, 692 women) who underwent 1728 single-energy noncontrast abdominopelvic CT examinations from January 1, 2021, through December 31, 2021, on the same scanner to estimate net scan energy consumption per examination. This information was integrated with literature-derived values to compare estimated annual national energy savings resulting from 20% reductions in net scan and idle state energy consumption. RESULTS. Net scan energy consumption in the phantom scans showed high linear correlation with DLP (R2 = 0.87), and, in the clinical scans, high linear correlation with CTDIvol (R2 = 0.89) and very high linear correlation with DLP (R2 = 0.92). When combining mean DLP in examinations performed in the 1-year interval, an equation relating DLP and net scan energy consumption and literature values estimated that annual national energy savings was 14.9 times greater (40,437,870 kWh/2,704,000 kWh) by targeting the idle state rather than net scan state. CONCLUSION. CT net scan energy savings can be inferred from reductions in dose report metrics. However, targeting net scan energy consumption has modest impact relative to targeting idle state energy consumption. CLINICAL IMPACT. Environmental sustainability efforts should target the idle state energy consumption of CT.


Assuntos
Tomografia Computadorizada por Raios X , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Doses de Radiação , Estudos Retrospectivos , Tomógrafos Computadorizados , Imagens de Fantasmas
5.
Nature ; 622(7983): 507-513, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37730997

RESUMO

Marine-derived cyclic imine toxins, portimine A and portimine B, have attracted attention because of their chemical structure and notable anti-cancer therapeutic potential1-4. However, access to large quantities of these toxins is currently not feasible, and the molecular mechanism underlying their potent activity remains unknown until now. To address this, a scalable and concise synthesis of portimines is presented, which benefits from the logic used in the two-phase terpenoid synthesis5,6 along with other tactics such as exploiting ring-chain tautomerization and skeletal reorganization to minimize protecting group chemistry through self-protection. Notably, this total synthesis enabled a structural reassignment of portimine B and an in-depth functional evaluation of portimine A, revealing that it induces apoptosis selectively in human cancer cell lines with high potency and is efficacious in vivo in tumour-clearance models. Finally, practical access to the portimines and their analogues simplified the development of photoaffinity analogues, which were used in chemical proteomic experiments to identify a primary target of portimine A as the 60S ribosomal export protein NMD3.


Assuntos
Antineoplásicos , Técnicas de Química Sintética , Iminas , Compostos de Espiro , Humanos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Iminas/síntese química , Iminas/química , Iminas/farmacologia , Neoplasias/tratamento farmacológico , Proteômica , Ribossomos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Compostos de Espiro/síntese química , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Relação Estrutura-Atividade , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia
6.
Phys Ther Sport ; 63: 104-111, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37544286

RESUMO

OBJECTIVE: To explore if one-leg rise test performance is associated with quadriceps strength following anterior cruciate ligament reconstruction (ACLR). DESIGN: Cross-sectional. PARTICIPANTS: 100 individuals (50 females, 50 males) aged 18-40 years, 9-36 months post-ACLR with ongoing knee symptoms (KOOS4 <80/100). MAIN OUTCOME MEASURES: Number of one-leg rise repetitions (using an adjustable-height plinth) and isometric quadriceps strength using isokinetic dynamometry (60° flexion, normalised to body mass). Multivariable fractional polynomial regression models adjusted for sex explored relationships between one-leg rise performance (repetitions) and quadriceps strength (Nm/kg) for each limb. RESULTS: A non-linear, increasing association between one-leg rise performance and quadriceps strength was observed, with the rate of increase attenuating at higher values of one-leg rise performance. Similar relationships were observed in the ACLR (ß = 0.15, 95%CI 0.10 to 0.20; adjusted r2 = 0.51) and contralateral limb (ß = 0.14, 95%CI 0.08 to 0.19; r2 = 0.42). CONCLUSION: The one-leg rise test can be an indicator of quadriceps strength in individuals after ACLR, enabling clinicians to easily monitor quadriceps strength recovery without specialised equipment. With the relationship between one-leg rise performance and quadriceps strength attenuating with a larger number of one-leg rises achieved, other factors (e.g., motivation, endurance) likely contribute to one-leg rise performance at higher values.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Masculino , Feminino , Humanos , Estudos Transversais , Perna (Membro) , Lesões do Ligamento Cruzado Anterior/cirurgia , Músculo Quadríceps , Força Muscular
7.
J Am Chem Soc ; 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37017374

RESUMO

Glioblastoma (GBM) is the most prevalent and aggressive primary central nervous system (CNS) malignancy. YM155 is a highly potent broad-spectrum anti-cancer drug that was derived from a phenotypic screen for functional inhibitors of survivin expression, but for which the relevant biomolecular target remains unknown. Presumably as a result of its lack of cell-type selectivity, YM155 has suffered from tolerability issues in the clinic. Based on its structural similarity to the GBM-selective prodrug RIPGBM, here, we report the design, synthesis, and characterization of a prodrug form of YM155, termed aYM155. aYM155 displays potent cell killing activity against a broad panel of patient-derived GBM cancer stem-like cells (IC50 = 0.7-10 nM), as well as EGFR-amplified and EGFR variant III-expressing (EGFRvIII) cell lines (IC50 = 3.8-36 nM), and becomes activated in a cell-type-dependent manner. Mass spectrometry-based analysis indicates that enhanced cell-type selectivity results from relative rates of prodrug activation in transformed versus non-transformed cell types. The prodrug strategy also facilitates transport into the brain (brain-to-plasma ratio, aYM155 = 0.56; YM155 = BLQ). In addition, we determine that the survivin-suppressing and apoptosis-inducing activities of YM155 involve its interaction with receptor-interacting protein kinase 2 (RIPK2). In an orthotopic intracranial GBM xenograft model, aYM155 prodrug significantly inhibits brain tumor growth in vivo, which correlates with cell-type selective survivin-based pharmacodynamic effects.

9.
Br J Sports Med ; 57(10): 602-610, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36889918

RESUMO

OBJECTIVE: Investigate sex/gender differences in self-reported activity and knee-related outcomes after anterior cruciate ligament (ACL) injury. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Seven databases were searched in December 2021. ELIGIBILITY CRITERIA: Observational or interventional studies with self-reported activity (including return to sport) or knee-related outcomes after ACL injury. RESULTS: We included 242 studies (n=123 687, 43% females/women/girls, mean age 26 years at surgery). One hundred and six studies contributed to 1 of 35 meta-analyses (n=59 552). After ACL injury/reconstruction, very low-certainty evidence suggests females/women/girls had inferior self-reported activity (ie, return to sport, Tegner Activity Score, Marx Activity Scale) compared with males/men/boys on most (88%, 7/8) meta-analyses. Females/women/girls had 23%-25% reduced odds of returning to sport within 1-year post-ACL injury/reconstruction (12 studies, OR 0.76 95% CI 0.63 to 0.92), 1-5 years (45 studies, OR 0.75 95% CI 0.69 to 0.82) and 5-10 years (9 studies, OR 0.77 95% CI 0.57 to 1.04). Age-stratified analysis (<19 years) suggests female athletes/girls had 32% reduced odds of returning to sport compared with male athletes/boys (OR 0.68, 95% CI 0.41 to 1.13, I2 0.0%). Very low-certainty evidence suggests females/women/girls experienced inferior knee-related outcomes (eg, function, quality of life) on many (70%, 19/27) meta-analyses: standardised mean difference ranging from -0.02 (Knee injury and Osteoarthritis Outcome Score, KOOS-activities of daily living, 9 studies, 95% CI -0.05 to 0.02) to -0.31 (KOOS-sport and recreation, 7 studies, 95% CI -0.36 to -0.26). CONCLUSIONS: Very low-certainty evidence suggests inferior self-reported activity and knee-related outcomes for females/women/girls compared with males/men/boys after an ACL injury. Future studies should explore factors and design targeted interventions to improve outcomes for females/women/girls. PROSPERO REGISTRATION NUMBER: CRD42021205998.


Assuntos
Lesões do Ligamento Cruzado Anterior , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Lesões do Ligamento Cruzado Anterior/cirurgia , Autorrelato , Qualidade de Vida , Atividades Cotidianas , Articulação do Joelho/cirurgia , Volta ao Esporte
10.
BMJ Open ; 13(2): e068040, 2023 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-36759025

RESUMO

INTRODUCTION: Running is one of the most popular recreational activities worldwide, due to its low cost and accessibility. However, little is known about the impact of running on knee joint health in runners with and without a history of knee surgery. The primary aim of this longitudinal cohort study is to compare knee joint structural features on MRI and knee symptoms at baseline and 4-year follow-up in runners with and without a history of knee surgery. Secondary aims are to explore the relationships between training load exposures (volume and/or intensity) and changes in knee joint structure and symptoms over 4 years; explore the relationship between baseline running biomechanics, and changes in knee joint structure and symptoms over 4 years. In addition, we will explore whether additional variables confound, modify or mediate these associations, including sex, baseline lower-limb functional performance, knee muscle strength, psychological and sociodemographic factors. METHODS AND ANALYSIS: A convenience sample of at least 200 runners (sex/gender balanced) with (n=100) and without (n=100) a history of knee surgery will be recruited. Primary outcomes will be knee joint health (MRI) and knee symptoms (baseline; 4 years). Exposure variables for secondary outcomes include training load exposure, obtained daily throughout the study from wearable devices and three-dimensional running biomechanics (baseline). Additional variables include lower limb functional performance, knee extensor and flexor muscle strength, biomarkers, psychological and sociodemographic factors (baseline). Knowledge and beliefs about osteoarthritis will be obtained through predefined questions and semi-structured interviews with a subset of participants. Multivariable logistic and linear regression models, adjusting for potential confounding factors, will explore changes in knee joint structural features and symptoms, and the influence of potential modifiers and mediators. ETHICS AND DISSEMINATION: Approved by the La Trobe University Ethics Committee (HEC-19524). Findings will be disseminated to stakeholders, peer-review journals and conferences.


Assuntos
Osteoartrite do Joelho , Osteoartrite , Humanos , Estudos Longitudinais , Estudos Prospectivos , Articulação do Joelho/diagnóstico por imagem , Extremidade Inferior , Osteoartrite do Joelho/diagnóstico por imagem
11.
BMJ Open ; 13(1): e068279, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36657757

RESUMO

INTRODUCTION: Anterior cruciate ligament injury and reconstruction (ACLR) is often associated with pain, functional loss, poor quality of life and accelerated knee osteoarthritis development. The effectiveness of interventions to enhance outcomes for those at high risk of early-onset osteoarthritis is unknown. This study will investigate if SUpervised exercise-therapy and Patient Education Rehabilitation (SUPER) is superior to a minimal intervention control for improving pain, function and quality of life in young adults with ongoing symptoms following ACLR. METHODS AND ANALYSIS: The SUPER-Knee Study is a parallel-group, assessor-blinded, randomised controlled trial. Following baseline assessment, 184 participants aged 18-40 years and 9-36 months post-ACLR with ongoing symptoms will be randomly allocated to one of two treatment groups (1:1 ratio). Ongoing symptoms will be defined as a mean score of <80/100 from four Knee injury and Osteoarthritis Outcome Score (KOOS4) subscales covering pain, symptoms, function in sports and recreational activities and knee-related quality of life. Participants randomised to SUPER will receive a 4-month individualised, physiotherapist-supervised strengthening and neuromuscular programme with education. Participants randomised to minimal intervention (ie, control group) will receive a printed best-practice guide for completing neuromuscular and strengthening exercises following ACLR. The primary outcome will be change in the KOOS4 from baseline to 4 months with a secondary endpoint at 12 months. Secondary outcomes include change in individual KOOS subscale scores, patient-perceived improvement, health-related quality of life, kinesiophobia, physical activity, thigh muscle strength, knee function and knee cartilage morphology (ie, lesions, thickness) and composition (T2 mapping) on MRI. Blinded intention-to-treat analyses will be performed. Findings will also inform cost-effectiveness analyses. ETHICS AND DISSEMINATION: This study is approved by the La Trobe University and Alfred Hospital Ethics Committees. Results will be presented in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12620001164987.


Assuntos
Osteoartrite do Joelho , Humanos , Adulto Jovem , Terapia por Exercício/métodos , Articulação do Joelho , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/terapia , Dor , Educação de Pacientes como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adolescente , Adulto
12.
Br J Sports Med ; 57(13): 855-863, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36669871

RESUMO

OBJECTIVE: To investigate the prognostic capacity of individual hop tests, hop test batteries and other unilateral functional performance tests following anterior cruciate ligament (ACL) injury. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Six databases searched up to June 2021. ELIGIBILITY CRITERIA: Studies reporting associations between unilateral lower-limb function (eg, hop tests) following ACL injury and future (≥3 months) knee-related outcomes. RESULTS: Of 42 included studies (13 150 participants), all assessed the single-forward hop test and 32 assessed a repeated-forward hop test (crossover hop, triple hop, 6m-timed hop), mostly within a year after ACL injury/reconstruction. Results of meta-analyses indicated that higher single-forward and repeated-forward hop limb symmetry were associated with higher odds of return-to-sport 1-3 years post-ACL reconstruction (OR 2.15; 95% CI 1.30 to 3.54; OR 2.11; 95% CI 1.23 to 3.60, respectively). Higher single-forward and repeated-forward hop limb symmetry was associated with better self-reported symptoms and function 1-37 years after ACL injury (OR 2.51; 95% CI 1.62 to 3.88; OR 4.28; 95% CI 1.65 to 11.08, respectively). Higher limb symmetry on a repeated-forward hop does not appear to be associated with higher odds of successful rehabilitation without ACL reconstruction (OR 1.51; 95% CI 0.94 to 2.44). Achieving ≥90% limb symmetry on the single-forward hop was associated with reduced odds of knee osteoarthritis 5-37 years after ACL injury (OR 0.46; 95% CI 0.23 to 0.94). CONCLUSION: Very low certainty evidence suggests single-forward and repeated-forward hop tests are prognostic indicators for important knee-related outcomes in individuals after ACL injury and may help stratify individuals at risk of poor outcomes to target rehabilitation interventions. PROSPERO REGISTRATION NUMBER: CRD42018092197.


Assuntos
Lesões do Ligamento Cruzado Anterior , Adulto , Humanos , Adolescente , Lesões do Ligamento Cruzado Anterior/cirurgia , Prognóstico , Recuperação de Função Fisiológica , Joelho , Extremidade Inferior , Volta ao Esporte , Força Muscular
13.
Skeletal Radiol ; 52(11): 2085-2097, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36562820

RESUMO

OBJECTIVE: To evaluate the sex-specific association between low knee extensor and flexor muscle strength and the risk of knee structural worsening. MATERIALS AND METHODS: Systematic searches in five databases identified longitudinal studies (≥ 1 year follow-up) reporting an association between knee extensor or flexor strength and structural decline in individuals with, or at risk of, knee osteoarthritis. Results were pooled for tibiofemoral and patellofemoral osteoarthritis worsening (and stratified by sex/gender where possible) using a random-effects meta-analysis estimating the risk ratio and 95% confidence interval or a best-evidence synthesis. Risk of bias and overall certainty of evidence were assessed. RESULTS: Fourteen studies were included with participants (mean age 27-72 years) with osteoarthritis (n = 8), at risk of osteoarthritis (n = 3), or a combination with, or at risk of, osteoarthritis (n = 3). Low knee extensor strength was associated with an increased risk of worsening tibiofemoral (12 studies: RR 1.18, 95% CI 1.04 to 1.35) and patellofemoral osteoarthritis (4 studies: RR 1.62, 95% CI 1.01 to 2.61). Significant associations between low knee extensor strength and worsening tibiofemoral osteoarthritis were observed for women (4 studies: RR 1.25, 95% CI 1.04 to 1.51) but not men (4 studies: RR 1.10, 95% CI 0.87 to 1.39). Low knee flexor strength increased the risk of worsening tibiofemoral osteoarthritis (5 studies: RR 1.16, 95% CI 1.07 to 1.26). Ten studies were high risk of bias, and all estimates were graded as very low certainty of evidence. CONCLUSION: Low knee extensor and flexor strength increased the risk of worsening tibiofemoral osteoarthritis. Low knee extensor strength increased the risk of worsening patellofemoral osteoarthritis. The relationship between low knee extensor strength and worsening tibiofemoral osteoarthritis may be modified by sex/gender.


Assuntos
Doenças Ósseas , Osteoartrite do Joelho , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Osteoartrite do Joelho/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Joelho , Estudos Longitudinais , Força Muscular/fisiologia
14.
Mol Biol Cell ; 34(1): br1, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36350697

RESUMO

Dynein inactivates the spindle assembly checkpoint (SAC) by transporting checkpoint proteins away from kinetochores toward spindle poles in a process known as "stripping." We find that inhibition of Aurora A kinase, which is localized to spindle poles, enables the accumulation of the spindle checkpoint activator Mad1 at poles where it is normally absent. Aurora kinases phosphorylate the dynein activator NudE neurodevelopment protein 1 like 1 (Ndel1) on Ser285 and Mad1 accumulates at poles when Ndel1 is replaced by a nonphosphorylatable mutant in human cells. The pole focusing protein NuMA, transported to poles by dynein, also accumulates at poles in cells harboring a mutant Ndel1. Phosphorylation of Ndel1 on Ser285 is required for robust spindle checkpoint activity and regulates the poles of asters in Xenopus extracts. Our data suggest that dynein/SAC complexes that are generated at kinetochores and then transported directionally toward poles on microtubules are inhibited by Aurora A before they reach spindle poles. These data suggest that Aurora A generates a spatial signal at spindle poles that controls dynein transport and spindle function.


Assuntos
Dineínas , Fuso Acromático , Humanos , Dineínas/metabolismo , Fuso Acromático/metabolismo , Aurora Quinase A/metabolismo , Cinetocoros/metabolismo , Proteínas de Ciclo Celular/metabolismo , Polos do Fuso/metabolismo , Microtúbulos/metabolismo , Proteínas de Transporte/metabolismo
15.
Front Psychol ; 13: 1015573, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438336

RESUMO

The impact of psychosocial and behavioral factors on Cancer Related Cognitive Impairment manifestations is still under debate. Study's purpose is to determine the prevalence rate of cancer related cognitive impairment in a cohort of Italian breast cancer patients and to evaluate the implication of specific behavioral factors. For these purposes, a total of 233 women (106 breast cancer patients and 127 age-matched controls without oncological diagnosis) completed a questionnaire investigating cognitive functionality (FACT-Cog v3.0), sociodemographic characteristics, clinical information, psychosocial and behavioral factors (cognitive reserve, sleep quality, dietary habits, physical activity). The results indicated a higher prevalence rate of subjective cognitive complaints in breast cancer patients (37%) compared to a representative sample of women in the same age group without an oncological diagnosis (p < 0.001). Moreover, breast cancer patients showed significantly lower levels of cognitive reserve (p < 0.05) and worse sleep quality (p < 0.01) compared to age-matched controls. Further analysis revealed that breast cancer patients reporting subjective cognitive complaints differed significantly from breast cancer patients without subjective cognitive complaints on measures of perceived cognitive abilities (p < 0.001) and on the impact of cognitive difficulties on perceived quality of life (p < 0.01). Future studies are needed to examine behavioral directed interventions to prevent subjective cognitive deficits in breast cancer patients.

16.
Diagnostics (Basel) ; 12(11)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36428915

RESUMO

There is a paucity of radiologic literature regarding age-related cataract, and little is known about any differences in the imaging appearance of the natural crystalline lens on computed tomography (CT) exams among different demographic groups. In this retrospective review of 198 eyes in 103 adults who underwent dual-energy computed tomography (DECT) exams of the head, regions of interest spanning 3−5 mm were placed over the center of the lens, and the x-ray attenuation of each lens was recorded in Hounsfield Units (HU) at 3 energy levels: 40 keV, 70 keV, and 190 keV. Generalized estimating equations (GEEs) were used to assess the association of clinical or demographic data with lens attenuation. The mean HU values were significantly lower for the older vs. younger group at 40 keV (GEE p-value = 0.022), but there was no significant difference at higher energy levels (p > 0.05). Mean HU values were significantly higher for females vs. males and non-whites vs. non-Hispanic whites at all 3 energy levels in bivariate and multivariable analyses (all p-value < 0.05). There was no significant association between lens attenuation and either diabetes or smoking status. The crystalline lens of females and non-whites had higher attenuation on DECT which may suggest higher density or increased concentration of materials like calcium and increased potential for cataract formation. Given the large scope of cataracts as a cause of visual impairment and the racial disparities that exist in its detection and treatment, further investigation into the role of opportunistic imaging to detect cataract formation is warranted.

17.
Br J Sports Med ; 56(24): 1393-1405, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36379676

RESUMO

The goal of the OPTIKNEE consensus is to improve knee and overall health, to prevent osteoarthritis (OA) after a traumatic knee injury. The consensus followed a seven-step hybrid process. Expert groups conducted 7 systematic reviews to synthesise the current evidence and inform recommendations on the burden of knee injuries; risk factors for post-traumatic knee OA; rehabilitation to prevent post-traumatic knee OA; and patient-reported outcomes, muscle function and functional performance tests to monitor people at risk of post-traumatic knee OA. Draft consensus definitions, and clinical and research recommendations were generated, iteratively refined, and discussed at 6, tri-weekly, 2-hour videoconferencing meetings. After each meeting, items were finalised before the expert group (n=36) rated the level of appropriateness for each using a 9-point Likert scale, and recorded dissenting viewpoints through an anonymous online survey. Seven definitions, and 8 clinical recommendations (who to target, what to target and when, rehabilitation approach and interventions, what outcomes to monitor and how) and 6 research recommendations (research priorities, study design considerations, what outcomes to monitor and how) were voted on. All definitions and recommendations were rated appropriate (median appropriateness scores of 7-9) except for two subcomponents of one clinical recommendation, which were rated uncertain (median appropriateness score of 4.5-5.5). Varying levels of evidence supported each recommendation. Clinicians, patients, researchers and other stakeholders may use the definitions and recommendations to advocate for, guide, develop, test and implement person-centred evidence-based rehabilitation programmes following traumatic knee injury, and facilitate data synthesis to reduce the burden of knee post-traumatic knee OA.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/prevenção & controle , Consenso , Articulação do Joelho , Traumatismos do Joelho/prevenção & controle , Traumatismos do Joelho/complicações , Joelho , Lesões do Ligamento Cruzado Anterior/complicações
19.
Magn Reson Imaging Clin N Am ; 30(3): 409-424, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35995470

RESUMO

Use of magnetic resonance (MR) imaging in the emergency department continues to increase. Although computed tomography is the first-line imaging modality for most head and neck emergencies, MR is superior in some situations and imparts no ionizing radiation. This article provides a symptom-based approach to nontraumatic head and neck pathologic conditions most relevant to emergency head and neck MR imaging, emphasizing relevant anatomy, "do not miss" findings affecting clinical management, and features that may aid differentiation from potential mimics. Essential MR sequences and strategies for obtaining high-quality images when faced with patient motion and other technical challenges are also discussed.


Assuntos
Neoplasias de Cabeça e Pescoço , Imageamento por Ressonância Magnética , Emergências , Dor Ocular , Cabeça/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Pescoço/diagnóstico por imagem
20.
Magn Reson Imaging Clin N Am ; 30(3): 425-439, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35995471

RESUMO

The use of magnetic resonance (MR) imaging in the emergency department continues to increase. Although computed tomography is the first-line imaging modality for most head and neck emergencies, MR is superior in some situations and imparts no ionizing radiation. This article provides a symptom-based approach to nontraumatic head and neck pathologic conditions most relevant to emergency head and neck MR imaging, emphasizing relevant anatomy, "do not miss" findings affecting clinical management, and features that may aid differentiation from potential mimics. Essential MR sequences and strategies for obtaining high-quality images when faced with patient motion and other technical challenges are also discussed.


Assuntos
Neoplasias de Cabeça e Pescoço , Imageamento por Ressonância Magnética , Emergências , Dor Facial , Cabeça/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Pescoço/diagnóstico por imagem
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