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1.
J Community Psychol ; 2024 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-39462303

RESUMO

Wealth inequality is rising, and millennials will be the future recipients of the largest intergenerational wealth transfer. Meanwhile, there is a need to move more money to support transformative social justice movements. This study examines the impact of spirituality as a motivator for the social justice movement giving among progressive young adult activists with wealth and class privilege, organizing toward the equitable redistribution of wealth, land, and power. Using survey data (n = 560), regressions and mediation models suggest that spiritual motivation was a significant positive predictor of how much participants monetarily gave to social justice movements. While religion did not significantly predict movement giving, indirect effects models showed that spirituality positively mediated the effect of being raised with any religion on movement giving compared to those indicating no religion. Implications are explored for how transformative organizing models draw upon secular spiritual practices in their pursuit of individual and collective change.

2.
Arch Orthop Trauma Surg ; 143(8): 5333-5343, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36695907

RESUMO

BACKGROUND: The primary aim was to assess the Oxford knee scores (OKS) on patients who underwent a total knee arthroplasty (TKA) with patellar resurfacing compared to those who did not. Secondary aims were to identify: (1) factors associated with resurfacing, (2) the effect of resurfacing on specific components of the OKS related to patellofemoral function, (3) the influence on patient satisfaction, and (4) whether a subgroup of patients had an improved outcome when resurfacing was undertaken. METHODS: A retrospective cohort study was undertaken using outcome data from the arthroplasty database held at the study centre. Patient demographics and OKS were collected preoperatively and at 1 and 2 years postoperatively. Patient satisfaction was assessed at 1 and 2 years postoperatively. RESULTS: Three thousand one hundred and twenty-two patients met the inclusion criteria of which 46.5% (n = 1453) underwent resurfacing. There were no differences in the OKS change at 1 or 2 years between those undergoing and not undergoing resurfacing (difference 0.2, p ≥ 0.469). Patients undergoing resurfacing were more likely to be female (odds ratio (OR) 1.53, 95% CI 1.30-1.79, p < 0.001), undergo a posterior stabilised knee (OR 6.87, 95% CI 5.71-8.27, p < 0.001) or had a worse response to question 5-standing from a chair, (p = 0.011) or 12-stair descent, (p = 0.017) of the OKS preoperatively. There was no difference in postoperative patient satisfaction (p ≥ 0.180). There was a significantly greater improvement in question 12 of the OKS at 1 year (p = 0.019) in the resurfaced group. There were no patient-related factors or symptoms that were associated with a clinically significant (≥ 5 points) greater postoperative OKS. CONCLUSION: Patella resurfacing was not associated with a clinically important improvement in OKS. No specific indications for patella resurfacing were identified that offered an improved outcome, but when it was undertaken there was a greater improvement in the ability to descend stairs. Level of evidence Retrospective diagnostic study, Level III.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Feminino , Masculino , Artroplastia do Joelho/efeitos adversos , Patela/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Osteoartrite do Joelho/cirurgia , Articulação do Joelho/cirurgia
3.
Eur J Orthop Surg Traumatol ; 33(8): 3729-3733, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37129734

RESUMO

An instructional review of the anatomy, investigation, and management of scapholunate ligament injuries. Aimed at the knowledge level required for the trauma and orthopaedic FRCS examination.


Assuntos
Osso Semilunar , Fraturas do Rádio , Osso Escafoide , Traumatismos do Punho , Humanos , Traumatismos do Punho/diagnóstico , Traumatismos do Punho/cirurgia , Articulação do Punho , Ligamentos Articulares/lesões , Exame Físico , Osso Semilunar/diagnóstico por imagem , Osso Escafoide/diagnóstico por imagem
4.
Int J Gynecol Pathol ; 38(2): 157-170, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29485423

RESUMO

African American women with high-grade serous ovarian carcinoma have worse outcomes compared with women of European descent. Although the discrepancy is partially attributed to differences in access to care, the tumor immune microenvironment may also contribute. Expression of targetable immune regulatory molecules such as programmed cell death ligand-1 (PD-L1) and indoleamine 2,3 dioxygenase (IDO) is of particular interest as it may help guide therapy in this population. Using cases from the largest study of African American women with ovarian cancer, the African American Cancer Epidemiology Study, we characterized PD-L1 and IDO expression in 112 high-grade serous ovarian carcinomas. Immunohistochemistry for PD-L1, IDO, CD8, FOX3p, and CD68 was performed. PD-L1 and IDO were scored as the percentage of positive tumor cells and tumor-associated immune cells. CD8 and FOX3p counts were averaged across 10 high-power fields. Cox proportional hazards regression was used to evaluate the association between PD-L1 and IDO expression and survival. Tumor cells were positive for PD-L1 and IDO in 29% and 58% of cases, respectively. The majority showed <10% staining, and no cases exceeded 25% positivity. The majority of PD-L1-positive cases coexpressed IDO. PD-L1 and IDO expression was associated with higher CD8 and FOX3p counts (P<0.05). No association was observed between PD-L1 and IDO and survival. In summary, expression of PD-L1 and IDO is seen in a subset of high-grade serous ovarian carcinoma from African American women and is correlated with elevated lymphocyte infiltration. While PD-L1 and IDO co-expression suggests a role for dual immunotherapy, diffuse expression of PD-L1 and IDO is rare, invoking caution regarding the potential for immunotherapeutic response.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/diagnóstico , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Neoplasias Ovarianas/diagnóstico , Negro ou Afro-Americano , Idoso , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Feminino , Humanos , Imuno-Histoquímica , Imunoterapia , Linfócitos do Interstício Tumoral , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Prognóstico , Microambiente Tumoral
5.
Cancer Causes Control ; 29(1): 77-86, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29188593

RESUMO

PURPOSE: While recreational physical activity (RPA) has been associated with reduced mortality in breast, colorectal, and prostate cancers, evidence for epithelial ovarian cancer (EOC) is limited. Most EOC studies have been in predominantly white populations, although inactivity is more prevalent and survival is poorer among African-American (AA) women. We examined RPA before and after EOC diagnosis and associations with survival among AA women. METHODS: We analyzed data from 264 EOC survivors enrolled in a population-based, case-control study who completed surveys that included questions about pre- and post-diagnosis RPA. Data were collected on RPA frequency, intensity, and duration before diagnosis and approximately 1 year after the baseline interview. We calculated metabolic equivalent of task (MET)-hours/week for pre- and post-diagnosis RPA, and evaluated associations with risk of mortality using Cox proportional hazards models. RESULTS: RPA before diagnosis was not associated with mortality. Hazard ratios (HRs) for post-diagnosis RPA were < 1.0 but not statistically significant after adjustment for covariates; HRs were 0.94 (95% CI 0.58, 1.54) for > 0-9 MET-hours/week and 0.53 (95% CI 0.21, 1.35) for > 9 MET-hours/week. CONCLUSIONS: Our results suggest that RPA may be inversely associated with mortality among AA women with ovarian cancer, although it is possible that the present study was underpowered to detect an association. There is a clear need for more studies of RPA after diagnosis in EOC survivors with attention to potential differences by race.


Assuntos
Negro ou Afro-Americano , Carcinoma Epitelial do Ovário/epidemiologia , Exercício Físico , Neoplasias Ovarianas/epidemiologia , Recreação , Idoso , Carcinoma Epitelial do Ovário/etnologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/etnologia , Modelos de Riscos Proporcionais , Fatores de Risco
6.
Int J Cancer ; 140(3): 535-543, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27727481

RESUMO

Chronic inflammation has been implicated in the development of epithelial ovarian cancer (EOC); yet the contribution of inflammatory foods and nutrients to EOC risk has been understudied. We investigated the association between the dietary inflammatory index (DII), a novel literature-derived tool to assess the inflammatory potential of one's diet, and EOC risk in African American (AA) women in the African American Cancer Epidemiology Study, the largest population-based case-control study of EOC in AA women to date. The energy-adjusted DII (E-DII) was computed per 1,000 kilocalories from dietary intake data collected through a food frequency questionnaire, which measured usual dietary intake in the year prior to diagnosis for cases or interview for controls. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression for the association between the E-DII and EOC risk. 493 cases and 662 controls were included in the analyses. We observed a 10% increase in EOC risk per a one-unit change in the E-DII (OR = 1.10, 95% CI = 1.03-1.17). Similarly, women consuming the most pro-inflammatory diet had a statistically significant increased EOC risk in comparison to the most anti-inflammatory diet (ORQuartile4/Quartile1 = 1.72; 95% CI = 1.18-2.51). We also observed effect modification by age (p < 0.05), where a strong, significant association between the E-DII and EOC risk was observed among women older than 60 years, but no association was observed in women aged 60 years or younger. Our findings suggest that a more pro-inflammatory diet was associated with an increased EOC risk, especially among women older than 60 years.


Assuntos
Dieta/efeitos adversos , Inflamação/complicações , Neoplasias Epiteliais e Glandulares/etiologia , Neoplasias Ovarianas/etiologia , Adulto , Negro ou Afro-Americano , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Adulto Jovem
7.
Am J Epidemiol ; 186(1): 46-53, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28444120

RESUMO

Although the inverse association between hysterectomy and epithelial ovarian cancer (EOC) was considered well established, investigators in recent studies including women diagnosed after 2000 have observed modest increases in risk. Most studies have been conducted in white women with little representation of African-American women. We examined the relationship between premenopausal hysterectomy and EOC in African-American women and explored whether hormone therapy (HT) modified this association in 614 cases and 743 controls enrolled in the African American Cancer Epidemiology Study (2010-2015). Premenopausal hysterectomy was inversely associated with the odds of EOC (odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.56, 1.01). Qualitative interaction by estrogen-only HT was present; among never users of estrogen-only HT, premenopausal hysterectomy was associated with a significantly decreased odds of EOC (OR = 0.65, 95% CI: 0.46, 0.92), whereas among users of estrogen-only HT, a positive association was observed (OR = 1.71, 95% CI: 0.76, 3.84). In a population of African-American women diagnosed after 2000, our overall results are consistent with the inverse association observed in the era before 2000, yet the effect modification by HT suggests that HT use among women who have had hysterectomies may negate the protective effects of hysterectomy on EOC, creating the appearance of a null or slightly increased risk.


Assuntos
Negro ou Afro-Americano , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Histerectomia/estatística & dados numéricos , Neoplasias Epiteliais e Glandulares/etnologia , Neoplasias Ovarianas/etnologia , Pré-Menopausa , Idoso , Índice de Massa Corporal , Carcinoma Epitelial do Ovário , Terapia de Reposição de Estrogênios/métodos , Feminino , Terapia de Reposição Hormonal , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Fatores de Risco , Estados Unidos/epidemiologia , Saúde da Mulher
8.
Cancer Causes Control ; 28(5): 405-414, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28251458

RESUMO

PURPOSE: Incessant ovulation has been consistently linked to epithelial ovarian cancer (EOC). Although reproductive characteristics differ substantially by race, the association between incessant ovulation and EOC has been evaluated only in populations of predominantly white women. In the present study, we examined the association between lifetime number of ovulatory cycles (LOCs) and EOC risk among African American (AA) women. METHODS: We used data from 534 cases and 722 controls enrolled in the African American Cancer Epidemiology Study. LOCs were determined using the standard method, with modifications to include episodes of irregular or missed periods. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between LOCs and EOC risk overall and by age, while adjusting for appropriate confounders. RESULTS: The mean number of LOCs was 378.2 ± 105.8 for cases and 346.4 ± 117.3 for controls. Women in the highest tertile of LOCs had 59% higher odds of EOC compared to women in the lowest tertile (OR = 1.59; 95% CI = 1.15-2.20). When examining this relationship by age, the positive association with EOC was stronger among women <50 years of age (OR for highest vs. lowest tertile = 2.61; 95% CI = 1.15-5.94), followed by women aged 50-60 years (OR = 2.27; 95% CI = 1.30-3.94). Yet, no association was present among women aged >60 years (OR = 0.79; 95% CI = 0.45-1.40). CONCLUSIONS: In a population of AA women, we observed a positive association between LOCs and EOC risk, providing further support for the hypothesis that incessant ovulation contributes to the etiology of EOC.


Assuntos
Negro ou Afro-Americano , Neoplasias Epiteliais e Glandulares/etiologia , Neoplasias Ovarianas/etiologia , Ovulação , Adulto , Fatores Etários , Idoso , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Fumar/efeitos adversos , Saúde da Mulher
9.
Cancer Causes Control ; 28(10): 1033-1041, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28871344

RESUMO

PURPOSE: Tubal ligation has been associated with reduced risk of epithelial ovarian cancer (EOC) in studies of primarily white women, but less is known about the association in African American (AA) women. We sought to evaluate the associations among 597 invasive ovarian cancer cases and 742 controls of AA descent recruited from the African American Cancer Epidemiology Study, a population-based case-control study in 11 geographical areas in the US. METHODS: Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potentially confounding factors. RESULTS: An inverse association between tubal ligation and EOC was observed that was not statistically significant (OR 0.88, 95% CI 0.68-1.14). However, an inverse association with EOC risk was observed among women who had a tubal ligation at age 35 years or older (OR 0.64; 95% CI 0.41-0.98), but not among those who had a tubal ligation before age 35 (OR 0.98; 95% CI 0.74-1.29) (p for interaction = 0.08). The association also varied considerably by tumor subtype. A strong inverse association was observed for endometrioid tumors (OR 0.31, 95% CI 0.14-0.70), whereas associations with mucinous (OR 0.87, 95% CI 0.36-2.12) and serous (OR 0.94, 95% CI 0.71-1.24) tumors were weaker and not statistically significant. A statistically non-significant positive association for clear cell tumors (OR 1.84, 95% CI 0.58-5.82) was based on a low number of cases. CONCLUSIONS: Our findings show that tubal ligation may confer a reduced risk for EOC among AA women that is comparable to the associations that have been previously observed in primarily white populations.


Assuntos
Neoplasias Ovarianas/epidemiologia , Esterilização Tubária , Adulto , Negro ou Afro-Americano , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Estados Unidos , Adulto Jovem
10.
Cancer Causes Control ; 28(7): 699-708, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28466107

RESUMO

BACKGROUND: Smoking is a risk factor for mucinous ovarian cancer (OvCa) in Caucasians. Whether a similar association exists in African Americans (AA) is unknown. METHODS: We conducted a population-based case-control study of incident OvCa in AA women across 11 geographic locations in the US. A structured telephone interview asked about smoking, demographic, health, and lifestyle factors. Odds ratios and 95% confidence intervals (OR, 95% CI) were estimated from 613 cases and 752 controls using unconditional logistic regression in multivariable adjusted models. RESULTS: Associations were greater in magnitude for serous OvCa than for all OvCa combined. Compared to never smokers, increased risk for serous OvCa was observed for lifetime ever smokers (1.46, 1.11-1.92), former smokers who quit within 0-2 years of diagnosis (5.48, 3.04-9.86), and for total pack-years smoked among lifetime ever smokers (0-5 pack-years: 1.79, 1.23-2.59; >5-20 pack-years: 1.52, 1.05-2.18; >20 pack-years: 0.98, 0.61-1.56); however, we observed no dose-response relationship with increasing duration or consumption and no significant associations among current smokers. Smoking was not significantly associated with mucinous OvCa. Associations for all OvCa combined were consistently elevated among former smokers. The proportion of ever smokers who quit within 0-2 years was greater among cases (23%) than controls (7%). CONCLUSIONS: Cigarette smoking may be associated with serous OvCa among AA, which differs from associations reported among Caucasians. Exposure misclassification or reverse causality may partially explain the absence of increased risk among current smokers and lack of dose-response associations. Better characterization of smoking patterns is needed in this understudied population.


Assuntos
Neoplasias Ovarianas/epidemiologia , Fumar/epidemiologia , Negro ou Afro-Americano , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
11.
Anal Biochem ; 524: 45-55, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27651163

RESUMO

As the field of lipidomics grows and its application becomes wide and varied it is important that we don't forget its foundation, i.e. the identification and measurement of molecular lipids. Advances in liquid chromatography and the emergence of ion mobility as a useful tool in lipid analysis are allowing greater separation of lipid isomers than ever before. At the same time, novel ion activation techniques, such as ozone-induced dissociation, are pushing lipid structural characterization by mass spectrometry to new levels. Nevertheless, the quantitative capacity of these techniques is yet to be proven and further refinements are required to unravel the high level of lipid complexity found in biological samples. At present there is no one technique capable of providing full structural characterization of lipids from a biological sample. There are however, numerous techniques now available (as discussed in this review) that could be deployed in a targeted approach. Moving forward, the combination of advanced separation and ion activation techniques is likely to provide mass spectrometry-based lipidomics with its best opportunity to achieve complete molecular-level lipid characterization and measurement from complex mixtures.


Assuntos
Lipídeos/análise , Lipídeos/química , Espectrometria de Massas/métodos , Animais , Humanos , Estrutura Molecular
12.
Br J Cancer ; 114(7): 819-25, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-26908324

RESUMO

BACKGROUND: Existing literature examining analgesic medication use and epithelial ovarian cancer (EOC) risk has been inconsistent, with the majority of studies reporting an inverse association. Race-specific effects of this relationship have not been adequately addressed. METHODS: Utilising data from the largest population-based case-control study of EOC in African Americans, the African American Cancer Epidemiology Study, the relationship between analgesic use (aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen) and risk of EOC was estimated by multivariate logistic regression. The association of frequency, duration, and indication of analgesic use on EOC risk was also assessed. RESULTS: Aspirin use, overall, was associated with a 44% lower EOC risk (OR=0.56; 95% CI=0.35-0.92) and a 26% lower EOC risk was observed for non-aspirin NSAID use (OR=0.74; 95% CI=0.52-1.05). The inverse association was strongest for women taking aspirin to prevent cardiovascular disease and women taking non-aspirin NSAIDs for arthritis. Significantly decreased EOC risks were observed for low-dose aspirin use, daily aspirin use, aspirin use for <5 years, and occasional non-aspirin NSAID use for a duration of ⩾5 years. No association was observed for acetaminophen use. CONCLUSIONS: Collectively, these findings support previous evidence that any NSAID use is inversely associated with EOC risk.


Assuntos
Adenocarcinoma de Células Claras/prevenção & controle , Adenocarcinoma Mucinoso/prevenção & controle , Analgésicos/uso terapêutico , Cistadenocarcinoma Seroso/prevenção & controle , Neoplasias do Endométrio/prevenção & controle , Neoplasias Ovarianas/prevenção & controle , Substâncias Protetoras/uso terapêutico , Adenocarcinoma de Células Claras/epidemiologia , Adenocarcinoma Mucinoso/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticarcinógenos/uso terapêutico , Estudos de Casos e Controles , Cistadenocarcinoma Seroso/epidemiologia , Neoplasias do Endométrio/epidemiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Prognóstico , Fatores de Risco , Estados Unidos/epidemiologia
13.
Mov Disord ; 30(12): 1639-47, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25594542

RESUMO

Lysosomes are the primary catabolic compartment for the degradation of intracellular proteins through autophagy. The presence of abnormal intracellular α-synuclein-positive aggregates in Parkinson's disease (PD) indicates that the degradative capacity of lysosomes is impaired in PD. Specific dysfunction of chaperone-mediated autophagy (CMA) in PD is suggested by reductions in the CMA membrane receptor, lysosomal-associated membrane protein (LAMP) 2A, although whether LAMP2A is the only LAMP2 isoform affected by PD is unknown. Messenger RNA (mRNA) and protein expression of all three LAMP2 isoforms was assessed in brain extracts from regions with and without PD-related increases in α-synuclein in autopsy samples from subjects in the early pathological stage of PD (n = 9), compared to age- and postmortem delay-matched controls (n = 10). In the early stages of PD, mRNA expression of all LAMP2 isoforms was not different from controls, with LAMP2B and LAMP2C protein levels also unchanged in PD. The selective loss of LAMP2A protein directly correlated with the increased levels of α-synuclein and decreased levels of the CMA chaperone heat shock cognate protein 70 in the same PD samples, as well as with the accumulation of cytosolic CMA substrate proteins. Our data show that LAMP2 protein isoforms are differentially affected in the early stages of PD, with LAMP2A selectively reduced in association with increased α-synuclein, and suggests that dysregulation of CMA-mediated protein degradation occurs before substantial α-synuclein aggregation in PD.


Assuntos
Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Isoformas de Proteínas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Colesterol/metabolismo , Feminino , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Metabolismo dos Lipídeos , Proteína 2 de Membrana Associada ao Lisossomo/genética , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , RNA Mensageiro/metabolismo , Estatísticas não Paramétricas , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
14.
Brain ; 137(Pt 3): 834-48, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24477431

RESUMO

Heterozygous mutations in GBA1, the gene encoding lysosomal glucocerebrosidase, are the most frequent known genetic risk factor for Parkinson's disease. Reduced glucocerebrosidase and α-synuclein accumulation are directly related in cell models of Parkinson's disease. We investigated relationships between Parkinson's disease-specific glucocerebrosidase deficits, glucocerebrosidase-related pathways, and α-synuclein levels in brain tissue from subjects with sporadic Parkinson's disease without GBA1 mutations. Brain regions with and without a Parkinson's disease-related increase in α-synuclein levels were assessed in autopsy samples from subjects with sporadic Parkinson's disease (n = 19) and age- and post-mortem delay-matched controls (n = 10). Levels of glucocerebrosidase, α-synuclein and related lysosomal and autophagic proteins were assessed by western blotting. Glucocerebrosidase enzyme activity was measured using a fluorimetric assay, and glucocerebrosidase and α-synuclein messenger RNA expression determined by quantitative polymerase chain reaction. Related sphingolipids were analysed by mass spectrometry. Multivariate statistical analyses were performed to identify differences between disease groups and regions, with non-parametric correlations used to identify relationships between variables. Glucocerebrosidase protein levels and enzyme activity were selectively reduced in the early stages of Parkinson's disease in regions with increased α-synuclein levels although limited inclusion formation, whereas GBA1 messenger RNA expression was non-selectively reduced in Parkinson's disease. The selective loss of lysosomal glucocerebrosidase was directly related to reduced lysosomal chaperone-mediated autophagy, increased α-synuclein and decreased ceramide. Glucocerebrosidase deficits in sporadic Parkinson's disease are related to the abnormal accumulation of α-synuclein and are associated with substantial alterations in lysosomal chaperone-mediated autophagy pathways and lipid metabolism. Our data suggest that the early selective Parkinson's disease changes are likely a result of the redistribution of cellular membrane proteins leading to a chronic reduction in lysosome function in brain regions vulnerable to Parkinson's disease pathology.


Assuntos
Glucosilceramidase/antagonistas & inibidores , Doença de Parkinson/metabolismo , Regulação para Cima/fisiologia , alfa-Sinucleína/biossíntese , Idoso , Idoso de 80 Anos ou mais , Autofagia/fisiologia , Encéfalo/enzimologia , Encéfalo/metabolismo , Encéfalo/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Glucosilceramidase/genética , Glucosilceramidase/metabolismo , Humanos , Lisossomos/enzimologia , Masculino , Chaperonas Moleculares/fisiologia , Mutação/genética , Doença de Parkinson/enzimologia , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo
15.
Mov Disord ; 29(4): 518-26, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24822250

RESUMO

Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson's disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case-control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase genes that regulate ceramide acyl chain composition in the same tissue using quantitative PCR. In PD anterior cingulate cortex but not occipital cortex, total ceramide and sphingomyelin levels were reduced from control levels by 53% (P < 0.001) and 42% (P < 0.001), respectively. Of the 13 ceramide and 15 sphingomyelin molecular lipid species identified and quantified, there was a significant shift in the ceramide acyl chain composition toward shorter acyl chain length in the PD anterior cingulate cortex. This PD-associated change in ceramide acyl chain composition was accompanied by an upregulation of ceramide synthase-1 gene expression, which we consider may represent a response to reduced ceramide levels. These data suggest a significant shift in ceramide function in lipid membranes and signaling pathways occurs in regions with PD pathology. Identifying the regulatory mechanisms precipitating this change may provide novel targets for future therapeutics.


Assuntos
Encéfalo/metabolismo , Ceramidas/metabolismo , Expressão Gênica , Oxirredutases/genética , Doença de Parkinson/genética , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia
16.
Biochim Biophys Acta ; 1818(5): 1309-17, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22285120

RESUMO

In one of the most extensive analyses to date we show that the balance of diet n-3 and n-6 polyunsaturated fatty acids (PUFA) is the most important determinant of membrane composition in the rat under 'normal' conditions. Young adult male Sprague-Dawley rats were fed one of twelve moderate-fat diets (25% of total energy) for 8weeks. Diets differed only in fatty acid (FA) profiles, with saturate (SFA) content ranging 8-88% of total FAs, monounsaturate (MUFA) 6-65%, total PUFA 4-81%, n-6 PUFA 3-70% and n-3 PUFA 1-70%. Diet PUFA included only essential FAs 18:2n-6 and 18:3n-3. Balance between n-3 and n-6 PUFA is defined as the PUFA balance (n-3 PUFA as % of total PUFA) and ranged 1-86% in the diets. FA composition was measured for brain, heart, liver, skeletal muscle, erythrocytes and plasma phospholipids, as well as adipose tissue and plasma triglycerides. The conformer-regulator model was used (slope=1 indicates membrane composition completely conforming to diet). Extensive changes in diet SFA, MUFA and PUFA had minimal effect on membranes (average slopes 0.01, 0.07, 0.07 respectively), but considerable influence on adipose tissue and plasma triglycerides (average slopes 0.27, 0.53, 0.47 respectively). Diet balance between n-3 and n-6 PUFA had a biphasic influence on membrane composition. When n-3 PUFA<10% of total PUFA, membrane composition completely conformed to diet (average slope 0.95), while diet PUFA balance>10% had little influence (average slope 0.19). The modern human diet has an average PUFA balance ~10% and this will likely have significant health implications.


Assuntos
Gorduras Insaturadas na Dieta/metabolismo , Gorduras Insaturadas na Dieta/farmacologia , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Modelos Biológicos , Animais , Membrana Celular/metabolismo , Humanos , Metabolismo dos Lipídeos/fisiologia , Masculino , Especificidade de Órgãos/efeitos dos fármacos , Especificidade de Órgãos/fisiologia , Ratos , Ratos Sprague-Dawley
17.
ANZ J Surg ; 91(9): 1898-1902, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34268845

RESUMO

BACKGROUND: Meticulous prepping and draping of the surgical field is paramount to reduce the risk of infection. A consistent technique for draping for hip arthroplasty is not well established. One technique for preparing the operative field utilises a sterile stockinette over an unprepped foot. This study aims to assess surgical site contamination when draping for hip arthroplasty without disinfecting the foot. METHODS: Ultraviolet (UV) fluorescent powder was used as a surrogate for microbial presence on the foot. Powder was applied to a volunteer's foot to a level where antibacterial prep would stop. The leg was then draped according to three methods; directly with stockinette only, wrapping the foot without using an adhesive seal followed by stockinette, and wrapping the foot with the adhesive seal followed by stockinette. Proximal spread of powder after draping was assessed with UV light. RESULTS: Contamination of the sterile field was found with all draping methods. Spread was particularly noted in the groin, posterior to the thigh and distal to mid-thigh. Wrapping the foot in a small drape without the adhesive seal prior to stockinette application was associated with significantly greater contamination when compared with use of the seal (p = 0.004). CONCLUSION: Routine formal prepping of the foot during hip arthroplasty is recommended to reduce the risk of surgical site contamination. Surgeons who select not to prep the foot should make use of a small drape with occlusive, adhesive seal prior to stockinette application and consider applying a further U drape to the hip.


Assuntos
Artroplastia de Quadril , Campos Cirúrgicos , Bandagens , , Humanos , Infecção da Ferida Cirúrgica
18.
Ecol Evol ; 11(13): 9062-9078, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34257944

RESUMO

Juvenile mammals in their postweaning developmental stages face many challenges in transitioning to adulthood. Among large grazing species such as ruminant bovids and cervids, an overarching challenge is acquiring and processing sufficient nutrients to survive and grow, with a gut that may not yet be fully developed. Marsupial kangaroos of Australia face similar challenges; they also digest vegetation by fermentation in a large foregut. In red kangaroos, Osphranter rufus (=Macropus rufus), the dominant species of Australia's arid interior, females may breed continuously; however, juvenile recruitment to the adult population is irregular and coincident with sporadic rainfall.As compared with adult females, the nutritional requirements of juvenile O. rufus are high in relation to their body mass (BM), largely due to the cost of their rapid growth. We examined processes that juveniles have in their morphology, physiology, and behaviors to meet their elevated nutritional needs, by comparing recently weaned juveniles of both sexes and adult female O. rufus in their desert habitat. Features studied include relative body sizes, relative dimensions, and capacities of principal gut regions, the foregut, small intestine, caecum, and large intestine with rectum. Also examined were digesta attributes and rates of digesta excretion. Additionally, the rates of change in skull parameters and dental characteristics to maturity were assessed. Field determinations of diet choice were made for both age classes.In juveniles, the content masses of major gut structures were related to body mass (BM), as were those of adult females, that is, ~BM1.0. In both age classes, the digesta mass of the foreguts exceeded 75% of the total digesta mass. Diets of both juvenile and adult O. rufus largely focused on grasses. Juveniles had higher rates of digesta excretion while foraging than adults. In addition, the foregut contents in juveniles occupy proportionally less of the total gut than in adult females. Together, the higher excretion rate and smaller relative foregut of juveniles suggest that they necessarily focus on forage that can be rapidly digested, such as young, green grasses, or herbage.Comparison of the skulls of juveniles and adults revealed how this harvest can occur. Relative to BM, juveniles had skulls of larger volume than adults. Additionally, during growth the skull lengthens proportionally faster than increasing BM. By weaning, the dimensions of the incisor bite of juveniles neared those of adult females. The area of wear on premolars/molars increased only slowly relative to the development of incisors, further pointing to juveniles selecting more digestible forage than adults. The intermittent availability of such forage, principally young grasses, appears key to the significant recruitment into the O. rufus population in their arid habitat.

19.
Bone Jt Open ; 2(8): 655-660, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34404226

RESUMO

AIMS: Elective orthopaedic services have had to adapt to significant system-wide pressures since the emergence of COVID-19 in December 2019. Length of stay is often recognized as a key marker of quality of care in patients undergoing arthroplasty. Expeditious discharge is key in establishing early rehabilitation and in reducing infection risk, both procedure-related and from COVID-19. The primary aim was to determine the effects of the COVID-19 pandemic length of stay following hip and knee arthroplasty at a high-volume, elective orthopaedic centre. METHODS: A retrospective cohort study was performed. Patients undergoing primary or revision hip or knee arthroplasty over a six-month period, from 1 July to 31 December 2020, were compared to the same period in 2019 before the COVID-19 pandemic. Demographic data, American Society of Anesthesiologists (ASA) grade, wait to surgery, COVID-19 status, and length of hospital stay were recorded. RESULTS: A total of 1,311 patients underwent hip or knee arthroplasty in the six-month period following recommencement of elective services in 2020 compared to 1,527 patients the year before. Waiting time to surgery increased in post-COVID-19 group (137 days vs 78; p < 0.001). Length of stay also significantly increased (0.49 days; p < 0.001) despite no difference in age or ASA grade. There were no cases of postoperative COVID-19 infection. CONCLUSION: Time to surgery and length of hospital stay were significantly higher following recommencement of elective orthopaedic services in the latter part of 2020 in comparison to a similar patient cohort from the year before. Longer waiting times may have contributed to the clinical and radiological deterioration of arthritis and general musculoskeletal conditioning, which may in turn have affected immediate postoperative rehabilitation and mobilization, as well as increasing hospital stay. Cite this article: Bone Jt Open 2021;2(8):655-660.

20.
Br J Nutr ; 103(4): 522-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19825209

RESUMO

The present study quantifies the relationships between diet fatty acid profile and fatty acid composition of rat skeletal muscle phospholipids. Young adult male Sprague-Dawley rats were fed, for 8 weeks, on one of twelve moderate-fat diets (25 % of total energy) differing only in fatty acid profile. SFA content ranged from 8-88 % of total fatty acids, MUFA 6-65 %, total PUFA 4-81 %, n-6 PUFA 3-70 % and n-3 PUFA 1-70 %. Diet PUFA included only essential fatty acids 18 : 2n-6 and 18 : 3n-3. The balance between n-3 and n-6 PUFA (PUFA balance) in the diet ranged from 1 : 99 to 86 : 14 % n-3 PUFA:n-6 PUFA. The slope of muscle phospholipid composition plotted against diet composition quantifies the response of muscle membrane composition to dietary fat (0, no response; 1, complete conformity with diet). The resulting slopes were 0.02 (SFA), 0.10 (PUFA), 0.11 (MUFA), 0.14 (n-3 PUFA) and 0.23 (n-6 PUFA). The response to PUFA balance was biphasic with a slope of 0.98 below 10 % diet PUFA balance and 0.16 above 10 %. Thus, low diet PUFA balance has greater influence on muscle composition than 18-carbon n-3 or n-6 PUFA individually. Equations provided may allow prediction of muscle composition for other diet studies. Diet PUFA balance dramatically affects muscle 20 : 4n-6 and 22 : 6n-3. This may have significant implications for some disease states in human subjects.


Assuntos
Membrana Celular/metabolismo , Dieta , Gorduras na Dieta/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Músculo Esquelético/metabolismo , Fosfolipídeos/metabolismo , Animais , Ácidos Graxos/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley
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