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1.
Cancer Causes Control ; 35(2): 359-366, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37775609

RESUMO

Since its inception in 1991, the mission of the National Breast and Cervical Cancer Early Detection Program's (NBCCEDP) mission is to improve access to mammography. This program has demonstrated evidence showing that it has improved breast cancer screening rates for women who are uninsured and underinsured. However, the literature has shown that NBCCEDP screenings are decreasing, and only reach a portion of eligible women. Reliable estimates at the sub-county level are needed to identify and reach eligible women. Our work builds upon previous estimates by integrating uninsured and insurance status into spatially adaptive filters. We use spatially adaptive filters to create small area estimates of standardized incidence ratios describing the utilization rate of NBCCEDP services in Minnesota. We integrate the American Community Survey (2010-2014) insurance status data to account for the percentage that an individual is uninsured. We test five models that integrate insurance status by age, sex, and race/ethnicity. Our composite model, which adjusts for age, sex, and race/ethnicity insurance statuses, reduces 95% of the estimation error. We estimate that there approximately 49,913.7 women eligible to receive services for Minnesota. We also create small geography (i.e., county and sub-county) estimates for Minnesota. The integration of the insurance data improved our utilization estimate. The development of these methods will allow state programs to more efficiently use their resources and understand their reach.


Assuntos
Neoplasias da Mama , Neoplasias do Colo do Útero , Feminino , Humanos , Estados Unidos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Pessoas sem Cobertura de Seguro de Saúde , Detecção Precoce de Câncer , Minnesota/epidemiologia , Pobreza , Mamografia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Programas de Rastreamento
2.
Mar Drugs ; 21(7)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37504910

RESUMO

We examined the effect of a dietary seaweed extract-sulfated xylorhamnoglucuronan (SXRG84)-on individuals with inflammatory skin conditions. A subgroup analysis of a larger trial was undertaken, where 44 participants with skin conditions were enrolled in a double-blind placebo-controlled crossover design. Subjects ingested either SXRG84 extract (2 g/day) for six weeks and placebo for six weeks, or vice versa. At baseline, six- and twelve-weeks inflammatory markers and the gut microbiota were assessed, as well as skin assessments using the dermatology quality of life index (DQLI), psoriasis area severity index (PASI) and visual analogue scales (VAS). There were significant differences at weeks six and twelve for pro-inflammatory cytokines IFN-γ (p = 0.041), IL-1ß (p = 0.030), TNF-α (p = 0.008) and the anti-inflammatory cytokine IL-10 (p = 0.026), determined by ANCOVA. These cytokines were all significantly higher at six weeks post placebo compared to twelve weeks post placebo followed by SXRG84 treatment. A total of 23% of participants reported skin improvements, as measured by VAS (mean difference 3.1, p = 0.0005) and the DQLI score (mean difference -2.0, p = 0.049), compared to the 'non-responders'. Thus, the ingestion of SXRG84 for 6 weeks reduced inflammatory cytokines, and a subset of participants saw improvements.


Assuntos
Psoríase , Qualidade de Vida , Humanos , Psoríase/tratamento farmacológico , Citocinas , Fator de Necrose Tumoral alfa , Suplementos Nutricionais , Método Duplo-Cego , Resultado do Tratamento
3.
Res Sq ; 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37293106

RESUMO

The mission of the National Breast and Cervical Cancer Early Detection Program's (NBCCEDP) mission is to improve access to mammography and other health services for underserved women. Since its inception in 1991, this national program has improved breast cancer screening rates for women who are uninsured and underinsured. However, the literature has shown that NBCCEDP screenings are decreasing, and only reach a portion of eligible women. Reliable estimates at the sub-county level are needed to identify and reach eligible women. Our work builds upon previous estimates by integrating uninsured and insurance status into spatially adaptive filters. We use spatially adaptive filters to create small area estimates of standardized incidence ratios describing the utilization rate of NBCCEDP services in Minnesota. We integrate the American Community Survey (2010-2014) insurance status data to account for the percentage that an individual is uninsured. We test five models that integrate insurance status by age, sex, and race/ethnicity. Our composite model, which adjusts for age, sex, and race/ethnicity insurance statuses, reduces 95% of the estimation error. We estimate that there approximately 49,913.7 women eligible to receive services for Minnesota. We also create small geography (i.e., county and sub-county) estimates for Minnesota. The integration of the insurance data improved our utilization estimate. The development of these methods will allow state programs to more efficiently use their resources and understand their reach.

4.
Nutrients ; 15(3)2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36771195

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) affects approximately one in six pregnancies, causing a significant burden on maternal and infant health. Lifestyle interventions are first-line therapies to manage blood glucose levels (BGLs) and prevent future cardiometabolic complications. However, women with GDM experience considerable barriers to lifestyle interventions; thus, the aim of this study was to determine how women with GDM manage their condition and to identify the primary supports and barriers to lifestyle intervention participation. METHODS: An online cross-sectional survey of women in Australia with a history of GDM was conducted. Questions included participant demographics, strategies used to manage BGLs, physical activity and dietary habits, and barriers and supports to lifestyle interventions. RESULTS: A total of 665 individuals consented and responded to the advertisement, of which 564 were eligible and provided partial or complete responses to the survey questions. Most respondents were between 35 and 39 years of age (35.5%), not pregnant (75.4%), working part-time (26.7%), university-educated (58.0%), and had only one child (40.1%). Most respondents managed their BGLs through diet (88.3%), with "low-carbohydrate" diets being the most popular (72.3%), and 46.2% of respondents were undertaking insulin therapy. Only 42.2% and 19.8% of respondents reported meeting the aerobic and strengthening exercise recommendations, respectively. Women with one child or currently pregnant expecting their first child were 1.51 times more likely (95% CI, 1.02, 2.25) to meet the aerobic exercise recommendations than those with two or more children. The most common reported barriers to lifestyle intervention participation were "lack of time" (71.4%) and "childcare" commitments (57.7%). Lifestyle interventions delivered between 6 and 12 months postpartum (59.0%), involving an exercise program (82.6%), and delivered one-on-one were the most popular (64.9%). CONCLUSION: Most women report managing their GDM with lifestyle strategies. The most common strategies reported involve approaches not currently included in the clinical practice guidelines such as reducing carbohydrate consumption. Furthermore, despite being willing to participate in lifestyle interventions, respondents report significant barriers, including lack of time and childcare commitments, whereas mentioned supports included having an online format. Lifestyle interventions for women with a history of GDM should be designed in a manner that is both tailored to the individual and considerate of existing barriers and supports to participation.


Assuntos
Diabetes Gestacional , Criança , Gravidez , Humanos , Feminino , Diabetes Gestacional/prevenção & controle , Estudos Transversais , Dieta , Estilo de Vida , Carboidratos
6.
Am J Clin Nutr ; 116(5): 1251-1264, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36083989

RESUMO

BACKGROUND: Consuming a bedtime snack is often recommended for people with type 2 diabetes. OBJECTIVE: This systematic review aims to evaluate the evidence from intervention studies to determine whether consuming a bedtime snack improves fasting hyperglycemia and/or overall glycemic control in individuals with type 2 diabetes. METHODS: PubMed, Medline (EBSCO), Cochrane Library, and CINAHL Plus (EBSCO) databases were searched until 20 July, 2022. We included prospective studies in people with type 2 diabetes or prediabetes that included the intervention of a bedtime snack, consumed >30 min after dinner and <2 h before bed and reported glycemic outcomes. RESULTS: The systematic review included 16 studies. There was no consistent relationship between consumption of a bedtime snack and improved glycemic control, especially when a no-snack control was included. Of the 4 studies that included the use of corn starch, a low dose seemed to have benefits over high-dose corn starch in terms of improved nocturnal and fasting glucose concentrations. CONCLUSIONS: Current advice to consume a bedtime snack is based on a limited number of intervention studies that often do not include a no-snack control, nor have used a feasible bedtime snack option that could be translated into everyday clinical practice. Further research is needed in type 2 diabetes patients treated with or without insulin. This review was registered at the Prospective Register of Systematic Reviews (PROSPERO) as CRD42020182523.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hiperglicemia , Hipoglicemia , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicemia , Estudos Prospectivos , Revisões Sistemáticas como Assunto , Hiperglicemia/tratamento farmacológico , Hiperglicemia/prevenção & controle , Insulina , Amido
7.
Mar Drugs ; 20(8)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-36005503

RESUMO

Seaweed polysaccharides in the diet may influence both inflammation and the gut microbiome. Here we describe two clinical studies with an Ulva sp. 84-derived sulfated polysaccharide­"xylorhamnoglucuronan" (SXRG84)­on metabolic markers, inflammation, and gut flora composition. The first study was a double-blind, randomized placebo-controlled trial with placebo, and either 2 g/day or 4 g/day of SXRG84 daily for six weeks in 64 overweight or obese participants (median age 55 years, median body mass index (BMI) 29 kg/m2). The second study was a randomized double-blind placebo-controlled crossover trial with 64 participants (median BMI 29 kg/m2, average age 52) on placebo for six weeks and then 2 g/day of SXRG84 treatment for six weeks, or vice versa. In Study 1, the 2 g/day dose exhibited a significant reduction in non-HDL (high-density lipoprotein) cholesterol (−10% or −0.37 mmol/L, p = 0.02) and in the atherogenic index (−50%, p = 0.05), and two-hour insulin (−12% or −4.83 mU/L) showed trends for reduction in overweight participants. CRP (C-reactive protein) was significantly reduced (−27% or −0.78 mg/L, p = 0.03) with the 4 g/day dose in overweight participants. Significant gut flora shifts included increases in Bifidobacteria, Akkermansia, Pseudobutyrivibrio, and Clostridium and a decrease in Bilophila. In Study 2, no significant differences in lipid measures were observed, but inflammatory cytokines were improved. At twelve weeks after the SXRG84 treatment, plasma cytokine concentrations were significantly lower than at six weeks post placebo for IFN-γ (3.4 vs. 7.3 pg/mL), IL-1ß (16.2 vs. 23.2 pg/mL), TNF-α (9.3 vs. 12.6 pg/mL), and IL-10 (1.6 vs. 2.1 pg/mL) (p < 0.05). Gut microbiota abundance and composition did not significantly differ between groups (p > 0.05). Together, the studies illustrate improvements in plasma lipids and an anti-inflammatory effect of dietary SXRG84 that is participant specific.


Assuntos
Microbiota , Sobrepeso , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Proteína C-Reativa , Pré-Escolar , HDL-Colesterol , Carboidratos da Dieta , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Lactente , Inflamação/tratamento farmacológico , Pessoa de Meia-Idade , Sobrepeso/tratamento farmacológico , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Sulfatos
8.
BMC Pregnancy Childbirth ; 22(1): 591, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879694

RESUMO

BACKGROUND: Establishing a healthy lifestyle post-delivery is pivotal to reduce the incidence of chronic diseases. Due to COVID-19 restrictions, access to postpartum health programs has been increasingly difficult. The aim of this study was to inform, develop and evaluate Beyond the Bump (BtB); an online program to improve access to health and wellbeing education and support for physical activity in the postpartum. METHODS: A three-phase mixed-methods design of a 10-week Australia-wide online pilot program during COVID-19 with women less than 1 year postpartum and their primary care health professionals was utilised. Phase-one: needs assessment focus groups and interviews. Phase-two: BtB program implementation pre-post health measures survey, attendance and engagement with the program. Phase-three: program evaluation with feedback surveys and interviews. RESULTS: Women (n = 12) and health professionals (n = 16) expressed strong need for a postpartum program with access to education from experts on exercise, pelvic floor, sleep and baby nutrition. Despite BtB being developed from women's suggestions (including time-of-day 'morning'), attendance to all ten sessions was poor (of 162 registrations; 23% participated in the first session and 5% in the last session). Barriers to attendance included 'too busy',' forgot' and 'topic not relevant for age of child'. 88% of women reported the education as the most enjoyable component of the program. 100% (n = 26) of women interviewed would recommend the program to a friend. CONCLUSIONS: There is a continuing need for postpartum support. Online programs with access to expert education and exercise were reported to be of significant interest and value. However, more research is needed to improve the uptake and value placed on mothers' wellbeing and physical activity.


Assuntos
COVID-19 , COVID-19/prevenção & controle , Criança , Feminino , Humanos , Estilo de Vida , Mães , Projetos Piloto , Período Pós-Parto
9.
Nutrients ; 13(10)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34684562

RESUMO

Supplementation of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) may enhance self-regulation (SR) and executive functioning (EF) in children of preschool age. The aim of the Omega Kid Study was to investigate the effect of n-3 LCPUFA supplementation on SR and EF in typically developing preschool-aged children. A double-blind placebo-controlled pilot trial was undertaken, the intervention was 12 weeks and consisted of 1.6 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day compared to placebo. The HS-Omega-3 Index® was assessed by capillary blood samples at baseline and post-intervention. Seventy-eight children were enrolled and randomised to either the n-3 LCPUFA treatment (n = 39) or placebo (n = 39) group. Post intervention, there was a significant three-fold increase in the HS-Omega-3 Index® in the n-3 LCPUFA group (p < 0.001). There were no improvements in SR or EF outcome variables for the n-3 LCPUFA group post intervention compared to the placebo group determined by linear mixed models. At baseline, there were significant modest positive Spearman correlations found between the HS-Omega-3 index® and both behavioural self-regulation and cognitive self-regulation (r = 0.287, p = 0.015 and r = 0.242, p = 0.015 respectively). Although no treatment effects were found in typically developing children, further research is required to target children with sub-optimal self-regulation who may benefit most from n-3 LCPUFA supplementation.


Assuntos
Desenvolvimento Infantil , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Autocontrole , Pré-Escolar , Método Duplo-Cego , Ingestão de Alimentos , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Placebos
10.
Exp Physiol ; 106(12): 2385-2390, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34676616

RESUMO

NEW FINDINGS: What is the central question of this study? Is the estrous cycle affected during disuse atrophies and if so, how do estrous cycle changes relate to musculoskeletal outcomes? What is the main finding and its importance? Rodent estrous cycles are altered during disuse atrophy, which corresponds to musculoskeletal outcomes. However, the estrous cycle does not appear changed in Lewis Lung Carcinoma, which corresponded to no differences in muscle size compared to healthy controls. These findings suggest a relationship between estrous cycle and muscle size during atrophic pathologies. ABSTRACT: Hyperglycemia can cause disruptions in vascular function, whereas exercise has been shown to restore vascular function. The primary aim of this study is to investigate the effect of performing whole-body resistance exercise, 30-min before, immediately following, or 30- or 60-min after a high carbohydrate meal, on endothelial function, measured by flow-mediated dilation (FMD). Healthy adults will be recruited to this randomized crossover trial to compare the postprandial glycaemic and vascular responses to four different exercise timing conditions and a control: i) C- control, high carbohydrate meal/no exercise, ii) 30Pre- 30 min of resistance exercises (~30% of 1RM [Repetition Maximum]), 30 min before a high carbohydrate meal, iii) IP- 30 min of resistance exercises (~30% of 1RM), immediately following a high carbohydrate meal, iv) 30Post- 30 min of resistance exercises, 30 min after a high carbohydrate meal and v) 60Post- 30 min of resistance exercises, 60 min after a high carbohydrate meal. Measures of metabolic and vascular function will be assessed at baseline and for two hours following the carbohydrate-based breakfast meal.


Assuntos
Hiperglicemia , Treinamento Resistido , Glicemia/metabolismo , Estudos Cross-Over , Exercício Físico , Humanos , Insulina/metabolismo , Período Pós-Prandial/fisiologia
11.
Am J Clin Nutr ; 114(4): 1455-1466, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34159352

RESUMO

BACKGROUND: LDL particle size and number (LDL-P) are emerging lipid risk factors. Nonsystematic reviews have suggested that diets lower in carbohydrates and higher in fats may result in increased LDL particle size when compared with higher-carbohydrate diets. OBJECTIVES: This study aimed to systematically review available evidence and conduct meta-analyses of studies addressing the association of carbohydrate restriction with LDL particle size and LDL-P. METHODS: We searched 6 electronic databases on 4 January, 2021 for randomized trials of any length that reported on dietary carbohydrate restriction (intervention) compared with higher carbohydrate intake (control). We calculated standardized mean differences (SMDs) in LDL particle size and LDL-P between the intervention and control groups of eligible studies, and pooled effect sizes using random-effects models. We performed prespecified subgroup analyses and examined the effect of potential explanatory factors. Internal validity and publication bias were assessed using Cochrane's risk-of-bias tool and funnel plots, respectively. Studies that could not be meta-analyzed were summarized qualitatively. RESULTS: This review summarizes findings from 38 randomized trials including a total of 1785 participants. Carbohydrate-restricted dietary interventions were associated with an increase in LDL peak particle size (SMD = 0.50; 95% CI: 0.15, 0.86; P < 0.01) and a reduction in LDL-P (SMD = -0.24; 95% CI: -0.43, -0.06; P = 0.02). The effect of carbohydrate-restricted dietary interventions on LDL peak particle size appeared to be partially explained by differences in weight loss between intervention groups and exploratory analysis revealed a shift from small dense to larger LDL subclasses. No statistically significant association was found between carbohydrate-restricted dietary interventions and mean LDL particle size (SMD = 0.20; 95% CI: -0.29, 0.69; P = 0.37). CONCLUSIONS: The available evidence indicates that dietary interventions restricted in carbohydrates increase LDL peak particle size and decrease the numbers of total and small LDL particles.This review was registered at www.crd.york.ac.uk/prospero/ as CRD42020188745.


Assuntos
LDL-Colesterol/sangue , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/farmacologia , Redução de Peso , Humanos
12.
Nutrients ; 13(1)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33451057

RESUMO

Self-regulation, the regulation of behaviour in early childhood, impacts children's success at school and is a predictor of health, wealth, and criminal outcomes in adulthood. Self-regulation may be optimised by dietary supplementation of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs). The aim of the "Omega Kid" study is to investigate the feasibility of a protocol to investigate whether n-3 LCPUFA supplementation enhances self-regulation in preschool-aged children. The protocol assessed involved a double-blind, randomised, placebo-controlled trial of 12 weeks duration, with an intervention of 1.6 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day (0.3 g EPA and 1.3 g DHA) in a microencapsulated powder compared to placebo. Children (n = 78; 40 boys and 38 girls) aged 3-5 years old were recruited and randomly allocated to the treatment (n = 39) or placebo group (n = 39). The HS-Omega-3 Index® served as a manipulation check on the delivery of either active (n-3 LCPUFAs) or placebo powders. Fifty-eight children (76%) completed the intervention (28-30 per group). Compliance to the study protocol was high, with 92% of children providing a finger-prick blood sample at baseline and high reported-adherence to the study intervention (88%). Results indicate that the protocol is feasible and may be employed in an adequately powered clinical trial to test the hypothesis that n-3 LCPUFA supplementation will improve the self-regulation of preschool-aged children.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Autocontrole , Biomarcadores/sangue , Pré-Escolar , Eletroencefalografia , Função Executiva , Estudos de Viabilidade , Feminino , Humanos , Masculino , Cooperação do Paciente
13.
Autism Res ; 13(5): 785-795, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31909874

RESUMO

Autistic children are at greater risk of developing anxiety than their nonautistic peers. Sensory reactivity differences have been implicated as one of the risk factors. Specifically, sensory hyperreactivity has previously been linked to anxiety, including separation anxiety and specific phobia; however, minimal research has explored the influence of sensory hyporeactivity and seeking. Therefore, the present study examined the correlational relationship between sensory reactivity differences and anxiety subtypes in 41 autistic children aged between 3 and 14 years, using parent- and self-reported measures. We found positive correlations between sensory hyperreactivity and total anxiety, separation anxiety and physical injury fears. However, when controlling for autism traits, we found sensory hyperreactivity to be related to physical injury fears and specific phobia, and sensory hyporeactivity to be related to lower total and social anxiety. We found no significant relationships between sensory seeking and anxiety. These results indicate that sensory hyperreactivity and hyporeactivity might be implicated in specific anxiety symptomology. Our results also indicate minimal agreement between parent- and self-reported anxieties, which highlights the limitations of informant reports for anxiety and the pressing need for objective anxiety assessments for autistic children to be developed. Our findings have important implications for limiting the development of anxiety in autistic children and suggest that sensory reactivity differences should be considered when developing targeted interventions for certain anxiety disorders. Autism Res 2020, 13: 785-795. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: The present study found that when considering autism traits, greater sensory hyperreactivity, such as being oversensitive to sounds, was related to elevated phobia-related symptoms and sensory hyporeactivity, such as being under-responsive to touch, was related to lower total and social anxieties. Sensory seeking, such as a fascination with lights, was not related to anxiety. Our results have important implications for targeted anxiety interventions for autistic children. However, due to minimal agreement between the parent- and child-reported scores, developing more objective measures of anxiety would be beneficial.


Assuntos
Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/psicologia , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/psicologia , Transtornos Fóbicos/complicações , Transtornos Fóbicos/psicologia , Adolescente , Transtornos de Ansiedade/fisiopatologia , Transtorno do Espectro Autista/fisiopatologia , Criança , Pré-Escolar , Medo/psicologia , Feminino , Humanos , Masculino , Transtornos Fóbicos/fisiopatologia
14.
Apoptosis ; 25(3-4): 247-260, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31993851

RESUMO

BIM is the master BH3-only BCL-2 family regulator of lymphocyte survival. To understand how long-term loss of BIM affects apoptotic resistance in T cells we studied animals with T cell-specific deletion of Bim. Unlike CD19CREBimfl/fl animals, LCKCREBimfl/fl mice have pronounced early lymphocytosis followed by normalization of lymphocyte counts over time. This normalization occurred in mature T cells, as thymocyte development and apoptotic sensitivity remained abnormal in LCKCREBimfl/fl mice. T cells from aged mice experienced normalization of their absolute cell numbers and responses against various apoptotic stimuli. mRNA expression levels of BCL-2 family proteins in CD4+ and CD8+ T cells from young and old mice revealed upregulation of several BH3-only proteins, including Puma, Noxa, and Bmf. Despite upregulation of various BH3 proteins, there were no differences in anti-apoptotic BCL-2 protein dependency in these cells. However, T cells had continued resistance to direct BIM BH3-induced mitochondrial depolarization. This study further highlights the importance of BIM in cell death maintenance in T cells and provides new insight into the dynamism underlying BH3-only regulation of T cell homeostasis versus induced cell death and suggests that CD4+ and CD8+ T cells compensate differently in response to loss of Bim.


Assuntos
Proteína 11 Semelhante a Bcl-2/metabolismo , Morte Celular , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Linfócitos T/patologia , Animais , Apoptose , Proteína 11 Semelhante a Bcl-2/deficiência , Proteína 11 Semelhante a Bcl-2/genética , Proteína 11 Semelhante a Bcl-2/farmacologia , Homeostase , Contagem de Linfócitos , Linfocitose , Camundongos , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Linfócitos T/metabolismo , Timócitos/metabolismo , Timócitos/patologia , Regulação para Cima
15.
Nutr Diet ; 77(1): 131-138, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30338904

RESUMO

AIM: To validate the polyunsaturated food frequency questionnaire (PUFA FFQ) and test for reproducibility in people with end stage renal disease on dialysis treatment. METHODS: Participants (n = 32) completed the PUFA FFQ and three 24-hour recalls. Erythrocyte samples (n = 29) were used for erythrocyte fatty acid analysis. The triangular relationship between the PUFA FFQ, 24-hour recalls and the biomarker was assessed using the method of triads. Agreement between the two dietary methods was also assessed using Bland-Altman plots and classification by quintiles. Reproducibility was tested on a subset of the group (n = 8). RESULTS: The PUFA FFQ was a valid measure of all PUFA except for docosapentaenoic acid (DPA) and arachidonic acid (AA). Strong validity coefficients were found for n-3 long-chain PUFA (LCPUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of 0.914 (95% CI: 0.665, 0.997) and 0.889 (95% CI: 0.706, 0.994), respectively. In the Bland-Altman plots 91-100% of observations fell between the limits of agreement for all PUFA. There were significant correlations between the initial FFQ and the repeat FFQ for all PUFA except DPA and AA. CONCLUSIONS: The PUFA FFQ is a valid tool for assessing PUFA intake in people with end stage renal disease.


Assuntos
Ácidos Graxos Insaturados/sangue , Falência Renal Crônica/sangue , Diálise Renal , Inquéritos e Questionários , Idoso , Idoso de 80 Anos ou mais , Ácido Araquidônico/administração & dosagem , Ácido Araquidônico/sangue , Índice de Massa Corporal , Estudos de Coortes , Dieta , Registros de Dieta , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/sangue , Eritrócitos/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Insaturados/administração & dosagem , Feminino , Humanos , Falência Renal Crônica/tratamento farmacológico , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
16.
Oncotarget ; 10(58): 6219-6233, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31692812

RESUMO

BCL-2 family proteins are central regulators of apoptosis and represent prime therapeutic targets for overcoming cell death resistance in malignancies. However, plasticity of anti-apoptotic members, such as MCL-1, often allows for a switch in cell death dependency patterns that lie outside the binding profile of targeted BH3-mimetics. Therefore discovery of therapeutics that effectively inactivate all anti-apoptotic members is a high priority. To address this we tested the potency of a hydrocarbon stapled BIM BH3 peptide (BIM SAHB A ) to overcome both BCL-2 and MCL-1 apoptotic resistance given BIM's naturally wide ranging affinity for all BCL-2 family multidomain members. BIM SAHB A effectively killed diffuse large B-cell lymphoma (DLBCL) cell lines regardless of their anti-apoptotic dependence. Despite BIM BH3's ability to bind all BCL-2 anti-apoptotic proteins, BIM SAHB A 's dominant intracellular target was MCL-1 and this specificity was exploited in sequenced combination BH3-mimetic treatments targeting BCL-2, BCL-XL, and BCL-W. Extending this MCL-1 functional dependence, mouse embryonic fibroblasts (MEFs) deficient in MCL-1 were resistant to mitochondrial changes induced by BIM SAHB A . This study demonstrates the importance of understanding BH3 mimetic functional intracellular affinities for optimized use and highlights the diagnostic and therapeutic promise of a BIM BH3 peptide mimetic as a potential MCL-1 inhibitor.

17.
J Ren Care ; 43(4): 226-234, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28944596

RESUMO

BACKGROUND: People on haemodialysis (HD) are at risk of consuming a poor quality diet. This includes inadequate intake of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA). OBJECTIVE: This study aims to investigate diet quality, with a particular focus on n-3 LCPUFA intake, in a population of incentre HD patients. DESIGN: Dietary intake was measured using three 24 hour recalls; the Polyunsaturated food frequency questionnaire (PUFA FFQ) and the Total Diet Score (TDS). Dietary intake was also compared to evidence based practice guidelines (EBPG). Nutritional status was assessed using the Patient Generated Subjective Global Assessment (PG SGA). SUBJECTS: A total of 32 dialysis patients were recruited, from two regional HD centres in New South Wales, Australia. MAIN OUTCOME MEASURE: Diet quality was the main outcome measure. RESULTS: Diet quality of study participants was poor, with the majority not meeting the EBPG for energy, protein and potassium. All participants exceeded the recommended amount of saturated fat. The mean TDS of the dialysis cohort was 10.2, which was significantly higher than the TDS of 9.3 of a healthy disease free cohort (p < 0.05). Positive correlations were found between TDS and LC omega-3 intake (r = 0.392) and TDS and total omega-6 intake (r = 0.363). Only 22% of participants met the suggested dietary target for n-3 LCPUFA intake. CONCLUSION: Dialysis patients in this study had suboptimal diet quality. Improvements are required for better adherence to the EBPG. Increased consumption of n-3 LCPUFA fatty acids may also be of benefit.


Assuntos
Dieta/normas , Ácidos Graxos Ômega-3/análise , Falência Renal Crônica/dietoterapia , Idoso , Estudos de Coortes , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales , Avaliação Nutricional , Diálise Renal/métodos
18.
Child Psychiatry Hum Dev ; 47(2): 183-93, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26003419

RESUMO

This study examined the long-term outcomes of a nonclinical sample of anxious children (N = 61) who were randomized by school to 9 weeks of group cognitive-behavioral therapy (CBT) for children, group CBT for children plus parent training, or no-treatment control. Parents and children completed measures of anxiety symptoms at baseline, posttreatment, and at 3-, 6-, 12-month, 2-, and 3-year posttreatment follow-ups. Piecewise longitudinal growth curve analyses were applied to the data. When the two CBT groups were combined and compared with control, the combined treatment group showed significantly greater reduction in children's anxiety severity based on the parent ratings in the first longitudinal phase. However, on the parent Clinician Severity Rating, gains were maintained to 3 years. Child report revealed no significant differences between groups on anxiety reduction. This study maintained a small no-treatment control group during the entire follow-up period. From parental perspective only, school-based group CBT appeared to be beneficial in decreasing severity of anxiety symptoms and maintaining gains over time.


Assuntos
Transtornos de Ansiedade/terapia , Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Pais/educação , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Pais/psicologia , Instituições Acadêmicas , Resultado do Tratamento
19.
Mol Cell Biol ; 32(21): 4270-82, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22907756

RESUMO

In addition to cancer surveillance, p19(Arf) plays an essential role in blocking signals stemming from platelet-derived growth factor receptor ß (Pdgfrß) during eye development, but the underlying mechanisms have not been clear. We now show that without Arf, pericyte hyperplasia in the eye results from enhanced Pdgfrß-dependent proliferation from embryonic day 13.5 (E13.5) of mouse development. Loss of Arf in the eye increases Pdgfrß expression. In cultured fibroblasts and pericyte-like cells, ectopic p19(Arf) represses and Arf knockdown enhances the expression of Pdgfrß mRNA and protein. Ectopic Arf also represses primary Pdgfrß transcripts and a plasmid driven by a minimal promoter, including one missing the CCAAT element required for high-level expression. p19(Arf) uses both p53-dependent and -independent mechanisms to control Pdgfrß. In vivo, without p53, Pdgfrß mRNA is elevated and eye development abnormalities resemble the Arf (-/-) phenotype. However, effects of p53 on Pdgfrß mRNA do not appear to be due to direct p53 or RNA polymerase II recruitment to the promoter. Although p19(Arf) controls Pdgfrß mRNA in a p53-dependent manner, it also blunts Pdgfrß protein expression by blocking new protein synthesis in the absence of p53. Thus, our findings demonstrate a novel capacity for p19(Arf) to control Pdgfrß expression by p53-dependent and -independent mechanisms involving RNA transcription and protein synthesis, respectively, to promote the vascular remodeling needed for normal vision.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Olho/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Fatores de Ribosilação do ADP/genética , Animais , Linhagem Celular , Inibidor p16 de Quinase Dependente de Ciclina/deficiência , Inibidor p16 de Quinase Dependente de Ciclina/genética , Olho/irrigação sanguínea , Olho/embriologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pericitos/citologia , Pericitos/fisiologia , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-mdm2/genética , RNA Polimerase II/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Transdução de Sinais , Transcrição Gênica , Proteína Supressora de Tumor p53/deficiência , Proteína Supressora de Tumor p53/genética
20.
Am J Physiol Renal Physiol ; 302(6): F774-83, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22160775

RESUMO

Overnutrition during pre- and postnatal development both confer increased susceptibility to renal and metabolic risks later in life; however, whether they have an additive effect on the severity of renal and metabolic injury remains unknown. The present study tested the hypothesis that a combination of a pre- and postnatal diet high in fat/fructose would exacerbate renal and metabolic injury in male offspring later in life. Male offspring born to high fat/high-fructose-fed mothers and fed a high-fat/high-fructose diet postnatally (HF-HF) had increased urine albumin excretion (450%), glomerulosclerosis (190%), and tubulointerstitial fibrosis (101%) compared with offspring born to mothers fed a standard diet and fed a standard diet postnatally (NF-NF). No changes in blood pressure or glomerular filtration were observed between any of the treatment groups. The HF-HF offspring weighed ∼23% more than offspring born to mothers fed a high-fat/high-fructose diet and fed a normal diet postnatally (HF-NF), as well as offspring born to mothers fed a standard diet regardless of their postnatal diet. The HF-HF rats also had increased (and more variable) blood glucose levels over 12 wk of being fed a high-fat/high-fructose diet. A combination of exposure to a high-fat/high-fructose diet in utero and postnatally increased plasma insulin levels by 140% compared with NF-NF offspring. Our data suggest that the combined exposure to overnutrition during fetal development and early postnatal development potentiate the susceptibility to renal and metabolic disturbances later in life.


Assuntos
Gorduras na Dieta/efeitos adversos , Nefropatias/etiologia , Nefropatias/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Envelhecimento , Albuminúria , Animais , Glicemia , Composição Corporal , Peso Corporal , Dieta/efeitos adversos , Feminino , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Ratos , Ratos Sprague-Dawley
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