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1.
Nat Commun ; 15(1): 3145, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605005

RESUMO

Naked mole-rats (NMRs) are best known for their extreme longevity and cancer resistance, suggesting that their immune system might have evolved to facilitate these phenotypes. Natural killer (NK) and T cells have evolved to detect and destroy cells infected with pathogens and to provide an early response to malignancies. While it is known that NMRs lack NK cells, likely lost during evolution, little is known about their T-cell subsets in terms of the evolution of the genes that regulate their function, their clonotypic diversity, and the thymus where they mature. Here we find, using single-cell transcriptomics, that NMRs have a large circulating population of γδT cells, which in mice and humans mostly reside in peripheral tissues and induce anti-cancer cytotoxicity. Using single-cell-T-cell-receptor sequencing, we find that a cytotoxic γδT-cell subset of NMRs harbors a dominant clonotype, and that their conventional CD8 αßT cells exhibit modest clonotypic diversity. Consistently, perinatal NMR thymuses are considerably smaller than those of mice yet follow similar involution progression. Our findings suggest that NMRs have evolved under a relaxed intracellular pathogenic selective pressure that may have allowed cancer resistance and longevity to become stronger targets of selection to which the immune system has responded by utilizing γδT cells.


Assuntos
Longevidade , Neoplasias , Humanos , Animais , Camundongos , Longevidade/fisiologia , Neoplasias/genética , Subpopulações de Linfócitos T , Células Matadoras Naturais , Ratos-Toupeira/fisiologia
2.
Integr Cancer Ther ; 22: 15347354231210874, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37961905

RESUMO

BACKGROUND: Chemotherapy for breast cancer can increase the risk of cancer therapy related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD, however, research to date has indicated high degrees of individual variability following exercise interventions in this population. AIM: This study aimed to explore the impact of regular, individualized aerobic exercise on CTRCD incidence (defined by global longitudinal strain [GLS]) during and immediately upon the completion of dose-dense anthracycline (DDAC) chemotherapy in 5 women with breast cancer. METHODS: Five women receiving DDAC with stage I-III breast cancer enrolled. Participants underwent resting echocardiography and exercise testing before, during, upon the completion of, and 3 months after the completion of DDAC treatment to measure GLS and aerobic fitness (VO2peak). Participants opted-in to an individualized 8-week aerobic exercise intervention (3 sessions per week, 24 sessions total) or standard care for the duration of their DDAC treatment. Data for each participant were presented descriptively. RESULTS: Four of the 5 participants completed the exercise intervention during DDAC treatment (adherence 79.2%-91.7%). Mild asymptomatic CTRCD occurred in 2 of the 4 exercising participants, of whom both were at an increased risk (one was >65 years of age and diagnosed with hypertension, with the other receiving trastuzumab prior to DDAC treatment). Varied responses in VO2peak were observed and did not align with changes in GLS. The only participant not to complete the exercise intervention reported poorer health related quality of life and increased cancer related fatigue at all measurement timepoints. CONCLUSION: This study details the individual variability in cardiovascular responses to exercise that can occur during DDAC treatment in women with breast cancer, which can inform exercise professionals and researchers when designing individualized exercise programs for this population.


Assuntos
Neoplasias da Mama , Cardiopatias , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Antraciclinas/efeitos adversos , Qualidade de Vida , Antibióticos Antineoplásicos/efeitos adversos , Exercício Físico , Cardiopatias/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente
3.
J Sci Med Sport ; 26(12): 650-658, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37806824

RESUMO

OBJECTIVES: This study aimed to understand the key factors experienced accredited exercise physiologists (AEPs) and medical professionals consider when prescribing/recommending aerobic exercise to patients with breast cancer undergoing chemotherapy. DESIGN: Modified Delphi Survey. METHODS: A four-round, two-phase survey was conducted. Following a Delphi approach, four cancer-specific AEPs, four oncologists, and one breast cancer surgeon (median 13-yr breast-cancer-specific experience) completed phase one. Eighty-four AEPs (median 5-yr experience) completed phase two. Phase one participants answered open- and close-ended questions regarding key considerations for aerobic exercise in patients with breast cancer undergoing chemotherapy, and what information should be collected to guide exercise prescription. All questions and considerations agreed upon in phase one (>70 % rating 7-9 on a 0-9 Likert Scale) were rated by AEPs in phase two. RESULTS: Key considerations for exercise assessment and prescription aligned closely with exercise guidelines for cancer survivors. Common strategies for exercise individualisation were identified by AEPs, including separating aerobic exercise into 5-to--9-minute bouts when required and avoiding exercising to complete exhaustion. Exercise intensity and duration should be adjusted throughout chemotherapy to improve tolerance and adherence. Novel considerations for subjective questioning and objective assessments to tailor exercise prescription were outlined. CONCLUSIONS: This study identifies how professionals approach exercise assessment and prescription in patients with breast cancer undergoing chemotherapy. Findings can guide AEPs in practice when prescribing tailored exercise to breast cancer patients undergoing chemotherapy and inform future guidelines.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Exercício Físico , Terapia por Exercício , Inquéritos e Questionários
4.
Patient Educ Couns ; 105(7): 2443-2449, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35272904

RESUMO

OBJECTIVES: Low exercise adherence is common amongst breast cancer (BC) patients. This study aimed to understand BC patients exercise identity and fears of exercise to identify barriers to exercise participation. METHODS: Women (18 years plus) currently undergoing, or completed (in remission), chemotherapy for BC, and women (18 years plus) with no cancer history completed three validated questionnaires: Exercise Identity Scale (EI), Exercise Fear Avoidance Scale (EFAS) and Fear of Physical Activity/Exercise Scale - Breast Cancer. RESULTS: 86 women were included (BC: n = 51 - non-cancer: n = 35). There were no significant differences between groups when comparing overall EI (p = 0.240; d=0.127) and EFAS (p = 0.060; d=0.203) scores. BC reported significantly higher scores on specific questions related to fear during exercise (EFAS 2,3, and 5; p = <0.005). Associations were observed between EI and EFAS questionnaire scores in BC (r = -0.342; p = 0.014), and EI scores and exercise levels in both groups (BC, r = 0.527; p = <0.001; non-cancer, r = 0.639; p = <0.001). CONCLUSION: Results suggest women with BC may have specific concerns and fears of exercise compared to age-matched controls. Education may mitigate fears, increase exercise identity, and promote exercise uptake. PRACTICAL IMPLICATIONS: Education provided by clinicians at BC diagnosis regarding the benefits and safety of exercise may help mitigate fear and promote exercise identity.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Exercício Físico , Medo , Feminino , Humanos , Inquéritos e Questionários
5.
Cureus ; 14(1): e21320, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35186579

RESUMO

We present a case of intussusception of a gastric remnant in a patient years after undergoing a Billroth II procedure that was treated with esophagogastroduodenoscopy. Although rare in adults, intussusception has been documented with increasing frequency in adult patients who have undergone Billroth II, mini-gastric bypass, and Roux-en-Y gastric bypass surgery. Timely management can decrease damage due to ischemia.

6.
Eur J Prev Cardiol ; 29(3): 463-472, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33693524

RESUMO

AIMS: Breast cancer (BC) patients undergoing chemotherapy are at risk of developing cancer therapy-related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD; however, its effectiveness remains unclear. The aim of this systematic review was to establish the effect of exercise on global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) in BC patients undergoing chemotherapy, to determine if exercise can prevent the development of CTRCD. METHODS AND RESULTS: Four databases (Medline, Scopus, eMbase, SPORTDiscus) were searched. Studies were eligible for inclusion if they measured GLS or LVEF prior to and following an exercise intervention of any length in BC patients undergoing chemotherapy and were published in English from 2000 onwards. Risk of bias was evaluated using the QUADAS-2 tool. Of the 398 studies screened, eight were eligible. Changes were similar in exercising (EX) and non-exercising (CON) groups for GLS (EX: pre: -19.6 ± 0.4, post: -20.1 ± 1.0, CON: pre: -20.0 ± 0.4, post: -20.1 ± 1) and LVEF (EX: pre: 58.5 ± 4.1%, post: 58.6 ± 2%, CON: pre: 56.6 ± 4.2%, post: 55.6 ± 4.6%). Exercise maintained or improved peak oxygen uptake (VO2peak) during chemotherapy, while declines were observed in non-exercising groups. The included studies were limited by methodological deficiencies. CONCLUSION: The ability of exercise to prevent CTRCD is unclear. However, exercise positively impacts cardiorespiratory fitness in BC patients undergoing chemotherapy. Future research must address the methodological limitations of current research to understand the true effect of exercise in the prevention of CTRCD.


Assuntos
Neoplasias da Mama , Cardiopatias , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade , Feminino , Humanos , Volume Sistólico , Função Ventricular Esquerda
7.
Heart ; 108(2): 137-144, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33833069

RESUMO

OBJECTIVE: To investigate the prognostic value of left atrial volume index (LAVI) in patients with moderate to severe aortic regurgitation (AR) and bicuspid aortic valve (BAV). METHODS: 554 individuals (45 (IQR 33-57) years, 80% male) with BAV and moderate or severe AR were selected from an international, multicentre registry. The association between LAVI and the combined endpoint of all-cause mortality or aortic valve surgery was investigated with Cox proportional hazard regression analyses. RESULTS: Dilated LAVI was observed in 181 (32.7%) patients. The mean indexed aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta diameters were 13.0±2.0 mm/m2, 19.4±3.7 mm/m2, 16.5±3.8 mm/m2 and 20.4±4.5 mm/m2, respectively. After a median follow-up of 23 (4-82) months, 272 patients underwent aortic valve surgery (89%) or died (11%). When compared with patients with normal LAVI (<35 mL/m2), those with a dilated LAVI (≥35 mL/m2) had significantly higher rates of aortic valve surgery or mortality (43% and 60% vs 23% and 36%, at 1 and 5 years of follow-up, respectively, p<0.001). Dilated LAVI was independently associated with reduced event-free survival (HR=1.450, 95% CI 1.085 to 1.938, p=0.012) after adjustment for LV ejection fraction, aortic root diameter, LV end-diastolic diameter and LV end-systolic diameter. CONCLUSIONS: In this large, multicentre registry of patients with BAV and moderate to severe AR, left atrial dilation was independently associated with reduced event-free survival. The role of this parameter for the risk stratification of individuals with significant AR merits further investigation.


Assuntos
Insuficiência da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/cirurgia , Dilatação , Dilatação Patológica , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
8.
JACC Cardiovasc Imaging ; 13(2 Pt 2): 604-612, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31607658

RESUMO

OBJECTIVES: This study sought to determine the long-term prognostic value of myocardial deformation imaging by echocardiography in risk stratification of sudden cardiac death (SCD) and malignant ventricular arrhythmias (VAs) in a large consecutive cohort of patients with left ventricular (LV) systolic impairment, irrespective of its etiology. BACKGROUND: Left ventricular ejection fraction (LVEF) is limited for prediction of SCD. Echocardiographic strain-derived mechanical dispersion (MD) and global longitudinal strain (GLS) has been linked to VA and SCD. However, due to low event rates, the role of these parameters has not been fully elucidated. METHODS: Consecutive clinically stable patients who underwent echocardiographic study performed in an outpatient setting from 2008 to 2014 with a Simpson left ventricular ejection fraction (LVEF) ≤45% were included in the study. Strain analysis was performed in which the LV was separated into 16 segments for regional analysis. Mechanical dispersion (MD) was calculated as the SD of the time to peak of each of the 16 regions. Outcome data were obtained from medical records. RESULTS: A total of 939 patients were included in the study, with median LVEF of 37% (interquartile range 30% to 42%). At follow-up (91.4 ± 23.4 months), 96 VA events had occurred. Multivariate analysis demonstrated that only MD ≥75 ms (hazard ratio: 9.45; 95% confidence interval: 4.75 to 18.81; p < 0.0001) was predictive of VA events. Low MD predicted a low event rate, irrespective of LVEF. CONCLUSIONS: Using LVEF alone is inferior for prediction of VA and SCD, particularly in patients with moderately reduced LVEF. MD is easily obtained from standard echocardiographic images and can be used to improve risk prognosis, particularly in patients who are currently excluded from cardiac defibrillator insertion based on LVEF.


Assuntos
Morte Súbita Cardíaca/etiologia , Ecocardiografia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Austrália do Sul , Volume Sistólico , Sístole , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia
10.
JACC Cardiovasc Imaging ; 12(7 Pt 1): 1230-1242, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31272606

RESUMO

Anderson-Fabry disease (AFD) is a rare X-linked inherited metabolic disorder which results in a deficiency or absence of the enzyme α-galactosidase A, leading to the accumulation of glycosphingolipids in various cells and organs including the heart. Cardiac involvement is common and results in increased myocardial inflammation, left ventricular hypertrophy (LVH), and myocardial fibrosis. Echocardiography and cardiovascular magnetic resonance (CMR) offer distinctive and often complementary use to assist in the diagnosis and monitoring pharmacologic therapy in AFD, including detection of the AFD cardiac phenotype, differentiation from other forms of LVH, and patient selection for therapeutic intervention. Advanced cardiac imaging holds promise in subclinical detection of AFD-related abnormalities as well as disease staging and prognostication.


Assuntos
Ecocardiografia , Doença de Fabry/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Imageamento por Ressonância Magnética , Diagnóstico Diferencial , Doença de Fabry/tratamento farmacológico , Doença de Fabry/fisiopatologia , Feminino , Fibrose , Humanos , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Miocárdio/patologia , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Função Ventricular Esquerda , Remodelação Ventricular
11.
J Am Soc Echocardiogr ; 32(8): 978-986, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31202591

RESUMO

BACKGROUND: Extreme levels of both strength and aerobic training result in increased left ventricular (LV) and right ventricular (RV) volumes and LV mass, a key component of athletes' heart. The aim of this study was to document temporal changes in the hearts of elite professional athletes (Australian Football League players) over a 2- to 6-year period. METHODS: Thirty-six Australian Football League players with 3.5 ± 2.7 years of professional training at enrollment prospectively underwent echocardiography in the preseasons of 2009, 2013, and 2015. At each time point, LV dimension and contractility and RV dimension, area, and contractility were measured using two-dimensional echocardiography. LV volumes, ejection fraction, and mass were measured using three-dimensional echocardiography. RESULTS: The mean age at baseline was 21.8 ± 2.6 years (range, 18-29 years). Most players (n = 20) had increases in fitness between studies (mean maximal oxygen uptake, 62.3 ± 3.6 vs 64.3 ± 2.1 mL/kg/min). In these players, there were increases in both LV and RV size and in LV mass. Players who were >25 years of age at their baseline scans demonstrated a trend toward increases in RV size and a decline in RV global longitudinal strain. Fitness level and playing position also affected the degree of physiological athletic cardiac remodeling. CONCLUSIONS: Australian football is a sport that involves both strength and aerobic training. This study, unique in its length and detail, demonstrates that remodeling in the athlete's heart is a continuous spectrum of change. This remodeling occurs over time in response to high levels of exercise, with proportional increase in LV mass and LV dimensions.


Assuntos
Adaptação Fisiológica , Atletas , Fenômenos Fisiológicos Cardiovasculares , Ecocardiografia , Remodelação Ventricular , Adolescente , Adulto , Fatores Etários , Composição Corporal , Humanos , Masculino , Estudos Prospectivos
12.
Heart Lung Circ ; 28(9): 1365-1375, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31109889

RESUMO

Left ventricular (LV) wall thickening can occur due to both physiological and pathological processes. Some LV wall thickening is caused by infiltrative cardiac deposition diseases - rare disorders from both inherited and acquired conditions, with varying systemic manifestations. They portend a poor prognosis and are generally not reversible except in rare circumstances when early diagnosis and treatment may alter the outcome (e.g., Fabry disease). Cardiac involvement is variable and depends on the degree of infiltration and type of infiltrate. These changes often lead to the development of abnormalities in both the relaxation and contractile function of the heart ultimately resulting in heart failure. Echocardiography is generally the first investigation of choice as it is easily available and gives valuable information about the thickness of the ventricular walls as well as systolic and diastolic function. It is also able to identify unique, characteristic features of the disease as well as detecting any haemodynamic sequelae. This review looks at the role of echocardiography in the diagnosis and prognosis of infiltrative cardiac deposition diseases.


Assuntos
Cardiomiopatias , Ecocardiografia , Doença de Fabry , Insuficiência Cardíaca , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Doença de Fabry/diagnóstico por imagem , Doença de Fabry/fisiopatologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos
13.
Health Educ Behav ; 46(4): 689-699, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30770033

RESUMO

Despite the promise of incentive-based chronic disease prevention programs, comprehensive evidence on their accessibility among low-income populations remains limited. We adapted Aday and Andersen's framework to examine accessibility and consumer satisfaction within the Medicaid Incentives for the Prevention of Chronic Disease (MIPCD) cross-site demonstration. MIPCD provided 10 states with 5-year grants to implement incentivized chronic disease prevention and management programs for low-income and/or disabled-Medicaid enrolled-Americans. We conducted 36 focus group discussions between July 2014 and December 2015 with Medicaid enrollees participating in the MIPCD programs. We assessed participants' satisfaction by program type (i.e., diabetes prevention, diabetes management, hypertension reduction, smoking cessation, and weight management) related to three components: program enrollment and participation, staff courtesy, and program convenience. Based on Aday and Andersen's framework, we conducted thematic analysis to determine similarities and differences across MIPCD programs by type. Participant feedback confirmed the importance of several features of the Aday and Andersen framework, particularly programs with easy enrollment and participation procedures, courteous and helpful staff, and those that are convenient and flexible for participants. Participants valued programming around the clock via telephone and flexible, in-person hours of operation as well as proximity of the program to reliable transportation. We observed that most participants, despite enrollment and participation barriers, perceived programs as accessible and were willing to engage and continue to participate. This finding may reflect behavior change theory's perspective on personal readiness to change. Individuals in the preparation stage of change can effectively change health habits despite barriers they may encounter. In some cases, personal readiness to change was more impactful than consumer satisfaction at encouraging ongoing participation and perceived access to the programs. Thus, program developers may want to consider individual participant readiness to change and its impact on consumer satisfaction when designing, implementing, and evaluating behavior change initiatives.


Assuntos
Doença Crônica/prevenção & controle , Acessibilidade aos Serviços de Saúde , Satisfação do Paciente , Prevenção Primária , Diabetes Mellitus/prevenção & controle , Diabetes Mellitus/terapia , Feminino , Grupos Focais , Humanos , Hipertensão/prevenção & controle , Hipertensão/terapia , Masculino , Medicaid , Prevenção Primária/métodos , Prevenção Primária/normas , Abandono do Hábito de Fumar , Estados Unidos , Programas de Redução de Peso
15.
Eur Heart J Cardiovasc Imaging ; 20(8): 932-938, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668650

RESUMO

AIMS: Myocardial oxygenation is impaired in hypertrophic cardiomyopathy (HCM) patients with left ventricular hypertrophy (LVH), and possibly also in HCM gene carriers without LVH. Whether these oxygenation changes are also associated with abnormalities in diastolic function or left ventricular (LV) strain are unknown. METHODS AND RESULTS: We evaluated 60 subjects: 20 MYBPC3 gene positive patients with LVH (G+LVH+), 18 MYBPC3 gene positive without LVH (G+LVH-), 11 gene negative siblings (G-), and 11 normal controls (NC). All subjects underwent 2D transthoracic echocardiography and cardiovascular magnetic resonance imaging for assessment of ventricular volumes, mass, and myocardial oxygenation at rest and adenosine stress using the blood oxygen level dependent (BOLD) technique. Maximal septal thickness was 20 mm in the G+LVH+ group, vs. 9 mm for the G+LVH- group. As expected, the G+LVH+ group had a more blunted myocardial oxygenation response to stress when compared with the G+LVH- group (-5% ± 3% vs. 2% ± 4%, P < 0.05), G- siblings (-5% ± 3% vs. 11% ± 4%, P < 0.0001) and NC (-5% ± 3% vs. 15% ± 4%, P < 0.0001). A blunted BOLD response to stress was also seen in G+LVH- subjects when compared with gene negative siblings (2% ± 4% vs. 11% ± 4%, P < 0.05) and NC (15% ± 4%, P < 0.050). G+LVH+ patients exhibited abnormal diastolic function including lower E', higher E to E' ratio and greater left atrial area compared with the G+LVH- subjects who all had normal values for these indices. CONCLUSION: Myocardial deoxygenation during stress is observed in MYBPC3 HCM patients, even in the presence of normal LV diastolic function, LV global longitudinal strain, and LV wall thickness.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/genética , Ecocardiografia/métodos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/genética , Imagem Cinética por Ressonância Magnética/métodos , Consumo de Oxigênio , Técnicas de Imagem de Sincronização Cardíaca , Proteínas de Transporte , Estudos de Casos e Controles , Meios de Contraste , Diástole , Teste de Esforço , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Miocárdio , Compostos Organometálicos
16.
J Am Soc Nephrol ; 29(9): 2418-2431, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29967284

RESUMO

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease caused by mucin-1 gene (MUC1) mutations (ADTKD-MUC1) is characterized by progressive kidney failure. Genetic evaluation for ADTKD-MUC1 specifically tests for a cytosine duplication that creates a unique frameshift protein (MUC1fs). Our goal was to develop immunohistochemical methods to detect the MUC1fs created by the cytosine duplication and, possibly, by other similar frameshift mutations and to identify novel MUC1 mutations in individuals with positive immunohistochemical staining for the MUC1fs protein. METHODS: We performed MUC1fs immunostaining on urinary cell smears and various tissues from ADTKD-MUC1-positive and -negative controls as well as in individuals from 37 ADTKD families that were negative for mutations in known ADTKD genes. We used novel analytic methods to identify MUC1 frameshift mutations. RESULTS: After technique refinement, the sensitivity and specificity for MUC1fs immunostaining of urinary cell smears were 94.2% and 88.6%, respectively. Further genetic testing on 17 families with positive MUC1fs immunostaining revealed six families with five novel MUC1 frameshift mutations that all predict production of the identical MUC1fs protein. CONCLUSIONS: We developed a noninvasive immunohistochemical method to detect MUC1fs that, after further validation, may be useful in the future for diagnostic testing. Production of the MUC1fs protein may be central to the pathogenesis of ADTKD-MUC1.


Assuntos
Predisposição Genética para Doença/epidemiologia , Mucina-1/genética , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/patologia , Biópsia por Agulha , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Incidência , Masculino , Mutação/genética , Linhagem , Rim Policístico Autossômico Dominante/mortalidade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco
17.
Int J Cardiol ; 261: 159-161, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29576422

RESUMO

BACKGROUND: Anthracycline (A) and trastuzumab (T) chemotherapy have well-recognized cardiac toxicity, potentially leading to significant morbidity and mortality. Our previous work in 46 prospectively enrolled breast cancer patients showed early left ventricular (LV) and right ventricular (RV) function decline at 1 and 3 months, but only persistent RV dysfunction at 12 months which correlated with myocardial oedema observed early (1 and 3 months) after administration of chemotherapy regimes. METHOD: To investigate late cardiac effects, the same cohort were re-imaged with advanced Cardiovascular Magnetic Resonance (CMR) imaging including T1 mapping 5 ±â€¯1 year post chemotherapy. RESULTS: Twenty-six out of 46 (50%) patients underwent follow-up imaging. A statistical but non-clinically significant decrease was observed in LV ejection fraction (EF) from baseline to 5 years (72.2 ±â€¯6.6 to 65.4 ±â€¯9.3, p < 0.005). Subjects with initial drop of LVEF by >10% at 3 months (n = 5) or at 12 months (n = 3) did not demonstrate any difference in LV or RVEF at 5 years. No correlation was observed between myocardial oedema and LV or RVEF at 5 years. At 5 years, T1 values were within normal limits overall (935 ±â€¯48 ms). One patients had significantly elevated (>1000 ms) T1 values with no correlation to LV or RVEF. No subjects demonstrated replacement myocardial fibrosis at 5 years. CONCLUSION: Using advanced CMR, contemporary chemotherapy regimes demonstrate minimal long-term cardiac toxicity. There is minimal diffuse and no replacement fibrosis as demonstrated by LGE, following chemotherapy. This study suggests limiting serial imaging in these patients at 12 months post chemotherapy.


Assuntos
Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/diagnóstico por imagem , Trastuzumab/administração & dosagem , Adulto , Antraciclinas/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/epidemiologia , Cardiotoxicidade/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Imagem Cinética por Ressonância Magnética/tendências , Pessoa de Meia-Idade , Trastuzumab/efeitos adversos , Resultado do Tratamento , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem
18.
J Nutr Educ Behav ; 50(5): 516-521, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29449153

RESUMO

Childhood obesity remains a significant public health issue. Because lifestyle behaviors and weight are established early and track through life stages, prevention strategies must commence in the first years of life. Traditionally, such strategies target parents or formal child care providers. Yet grandparents are increasingly providing care to grandchildren and therefore have an important role in their eating and activity behaviors, which creates a major research gap. This commentary piece, focusing on the Australian context, argues that it is imperative and timely for obesity prevention research to include investigations regarding the role of grandparents in the prevention of obesity-related behaviors in young children.


Assuntos
Avós , Comportamentos Relacionados com a Saúde , Relação entre Gerações , Estilo de Vida , Obesidade Infantil/prevenção & controle , Cuidado da Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido
19.
JCI Insight ; 2(23)2017 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-29212948

RESUMO

ER stress has emerged as a signaling platform underlying the pathogenesis of various kidney diseases. Thus, there is an urgent need to develop ER stress biomarkers in the incipient stages of ER stress-mediated kidney disease, when a kidney biopsy is not yet clinically indicated, for early therapeutic intervention. Cysteine-rich with EGF-like domains 2 (CRELD2) is a newly identified protein that is induced and secreted under ER stress. For the first time to our knowledge, we demonstrate that CRELD2 can serve as a sensitive urinary biomarker for detecting ER stress in podocytes or renal tubular cells in murine models of podocyte ER stress-induced nephrotic syndrome and tunicamycin- or ischemia-reperfusion-induced acute kidney injury (AKI), respectively. Most importantly, urinary CRELD2 elevation occurs in patients with autosomal dominant tubulointerstitial kidney disease caused by UMOD mutations, a prototypical tubular ER stress disease. In addition, in pediatric patients undergoing cardiac surgery, detectable urine levels of CRELD2 within postoperative 6 hours strongly associate with severe AKI after surgery. In conclusion, our study has identified CRELD2 as a potentially novel urinary ER stress biomarker with potential utility in early diagnosis, risk stratification, treatment response monitoring, and directing of ER-targeted therapies in selected patient subgroups in the emerging era of precision nephrology.


Assuntos
Injúria Renal Aguda/urina , Moléculas de Adesão Celular/urina , Estresse do Retículo Endoplasmático/fisiologia , Proteínas da Matriz Extracelular/urina , Síndrome Nefrótica/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Animais , Biomarcadores/urina , Procedimentos Cirúrgicos Cardíacos , Moléculas de Adesão Celular/fisiologia , Criança , Proteínas da Matriz Extracelular/fisiologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Mutação , Nefrite Intersticial/genética , Nefrite Intersticial/fisiopatologia , Nefrite Intersticial/urina , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/fisiopatologia , Podócitos/metabolismo , Complicações Pós-Operatórias/urina , Uromodulina/genética
20.
Echocardiography ; 33(5): 742-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26676176

RESUMO

Severe aortic stenosis causes chronic increased afterload on the left ventricle (LV) resulting in myocardial hypertrophy and ultimately dysfunction if left untreated. Transcatheter aortic valve implantation (TAVI) immediately decreases the afterload on the LV by reducing the pressure gradient through the aortic valve. In our study, we aim to evaluate immediate changes in LV mechanics using intra-procedural transesophageal echocardiography (TEE) to assess circumferential and radial strain via speckle tracking. Intra-operative TEE was performed during TAVI for 53 patients (mean age 84 ± 8 years). Two-dimensional images in the transgastric view were acquired at the level of the papillary muscle. Circumferential and radial strain was calculated using speckle tracking with Philips Qlab software. Global LV afterload was measured by calculating valvulo-arterial impedance (Zva). Immediately post-TAVI, there was a change in both radial strain rate (Pre: 0.73 ± 0.04 vs. Post: 0.88 ± 0.04 per second, P < 0.001) and circumferential strain rate (-0.53 ± 0.04 (pre) vs. -0.74 ± 0.04 (post) per second, P < 0.001). There was also an immediate improvement in circumferential global strain parameters (-14.5 ± 5% (pre) vs. -16.0 ± 4.7% (post), P < 0.05), whereas there was no significant change seen in global radial strain (15.6 ± 0.8% (pre) vs. 15.2 ± 0.9% (post), P = 0.69). No significant change was seen in LV ejection fraction (51.5 ± 14.2% (pre) vs. 52.1 ± 14.0% (post), P = 0.77). Speckle tracking using TEE images is feasible and identifies significant improvements in LV strain and strain rate immediately following TAVI that is not detected by conventional measure of LV function.


Assuntos
Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Ecocardiografia/métodos , Substituição da Valva Aórtica Transcateter , Disfunção Ventricular Esquerda/prevenção & controle , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/complicações , Módulo de Elasticidade , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estresse Mecânico , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Pressão Ventricular
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