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1.
Curr Oncol Rep ; 26(7): 804-817, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38780676

RESUMO

PURPOSE OF REVIEW: This review summarizes the latest advancements in survivorship care for patients with advanced melanoma who received systemic therapy and emphasizes the areas where more research is needed. RECENT FINDINGS: Over the last decade there have been remarkable advances in the treatment of advanced and metastatic melanoma. Due to these novel treatments, including several immune checkpoint inhibitors and tyrosine kinase inhibitors, there are and will continue to be increasing numbers of long-term melanoma survivors who have been treated with systemic therapy. These patients will navigate new challenges are they are essentially among the first long term survivors after these novel therapies. Survivorship care focuses on improving the health-related quality of life of patients including the physical, emotional, social and functional effects of cancer that begin at diagnosis and continue through the end of life. Survivorship also includes screening for cancer recurrence and second cancers. As the number of melanoma survivors who received systemic therapy continues to grow, the survivorship care plan will become increasingly important for optimal care of patients even after their cancer treatments. Understanding the many domains of survivorship care for this group of patients is imperative for their care now and to identify unmet needs for future research.


Assuntos
Sobreviventes de Câncer , Melanoma , Qualidade de Vida , Humanos , Melanoma/tratamento farmacológico , Melanoma/terapia , Inibidores de Checkpoint Imunológico/uso terapêutico , Sobrevivência
2.
Support Care Cancer ; 31(12): 655, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37882860

RESUMO

PURPOSE: National mandates require cancer centers provide comprehensive survivorship care. We created an 8-session, group intervention, the Survivorship Wellness Group Program (SWGP), that covered 8 topics: nutrition, physical activity, stress, sleep/fatigue, sexuality/body image, emotional wellbeing/fear of cancer recurrence, spirituality/meaning, and health promotion/goal setting. This study examined the acceptability and preliminary outcomes of SWGP. METHODS: We evaluated SWGP using questionnaire data collected at program entry and 15-week follow-up. Questionnaires assessed acceptability and impact on anxiety, depression, quality of life, and perceived knowledge of topics. Enrollees who consented to participate in research and completed the baseline and 15-week follow-up were included in the analysis (N = 53). We assessed acceptability and preliminary outcomes using paired-samples t-tests. Due to the COVID-19 pandemic, SWGP transitioned to telehealth partway through data collection. Post-hoc analyses compared outcomes by intervention delivery. RESULTS: Participants completed an average of 7.44/8 classes. Participants reported a mean response of 3.42/4 regarding overall program satisfaction and 90.6% reported being "very likely" to recommend SWGP. SWGP was associated with decreases in anxiety and depression; increases in physical, emotional, functional, and overall quality of life; and increases in knowledge of all health behavior domains. No outcomes differed significantly between delivery in person versus telehealth. CONCLUSIONS: SWGP offers an acceptable and replicable model for cancer centers to meet national survivorship care guidelines. IMPLICATION FOR CANCER SURVIVORS: SWGP provides a comprehensive service for cancer survivors post-treatment, and was associated with better quality of life, fewer mental health symptoms, and increased knowledge in multiple domains of wellness.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Sobreviventes de Câncer/psicologia , Sobrevivência , Qualidade de Vida/psicologia , Pandemias , Exercício Físico , Neoplasias/terapia , Neoplasias/psicologia
3.
Endocr Pract ; 28(4): 405-413, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35032648

RESUMO

OBJECTIVE: Cancer patients and survivors may be disproportionately affected by COVID-19. We sought to determine the effects of the pandemic on thyroid cancer survivors' health care interactions and quality of life. METHODS: An anonymous survey including questions about COVID-19 and the Patient-Reported Outcomes Measurement Information System profile (PROMIS-29, version 2.0) was hosted on the Thyroid Cancer Survivors' Association, Inc website. PROMIS scores were compared to previously published data. Factors associated with greater anxiety were evaluated with univariable and multivariable logistic regression. RESULTS: From May 6, 2020, to October 8, 2020, 413 participants consented to take the survey; 378 (92%) met the inclusion criteria: diagnosed with thyroid cancer or noninvasive follicular neoplasm with papillary-like nuclear features, located within the United States, and completed all sections of the survey. The mean age was 53 years, 89% were women, and 74% had papillary thyroid cancer. Most respondents agreed/strongly agreed (83%) that their lives were very different during the COVID-19 pandemic, as were their interactions with doctors (79%). A minority (43%) were satisfied with the information from their doctor regarding COVID-19 changes. Compared to pre-COVID-19, PROMIS scores were higher for anxiety (57.8 vs 56.5; P < .05) and lower for the ability to participate in social activities (46.2 vs 48.1; P < .01), fatigue (55.8 vs 57.9; P < .01), and sleep disturbance (54.7 vs 56.1; P < .01). After adjusting for confounders, higher anxiety was associated with younger age (P < .01) and change in treatment plan (P = .04). CONCLUSION: During the COVID-19 pandemic, thyroid cancer survivors reported increased anxiety compared to a pre-COVID cohort. To deliver comprehensive care, providers must better understand patient concerns and improve communication about potential changes to treatment plans.


Assuntos
COVID-19 , Sobreviventes de Câncer , Neoplasias da Glândula Tireoide , Ansiedade/epidemiologia , COVID-19/epidemiologia , Feminino , Humanos , Internet , Pessoa de Meia-Idade , Pandemias , Qualidade de Vida , Inquéritos e Questionários , Neoplasias da Glândula Tireoide/epidemiologia , Estados Unidos/epidemiologia
4.
Cancer ; 126(10): 2296-2304, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32105350

RESUMO

BACKGROUND: The goal of this study was to compare health-related quality of life (HRQL) from diagnosis to 10 years postdiagnosis among breast cancer survivors (BCS) and women without cancer over the same period and to identify BCS subgroups exhibiting different HRQL trajectories. METHODS: Our analysis included 141 BCS and 2086 controls from the Study of Women's Health Across the Nation (SWAN), a multiracial/ethnic cohort study of mid-life women assessed approximately annually from 1995 to 2015. Pink SWAN participants reported no cancer at SWAN enrollment and developed (cases) or did not develop (controls) incident breast cancer after enrollment. We assessed HRQL with SF-36 Mental Component Summary and Physical Component Summary scores. We modeled each as a function of case/control status, years since diagnosis, years since diagnosis squared, and the interaction terms between case/control status and the 2 time variables in linear models. We characterized heterogeneity in postdiagnosis HRQL of cases using group-based trajectories. RESULTS: BCS had significantly lower HRQL compared with controls at diagnosis and 1 year postdiagnosis. By 2 years, BCS and controls no longer differed significantly. Among BCS, 2 trajectory groups were identified for both scores. For the Mental Component Summary, 88.4% of BCS had consistently good and 11.6% had very low scores. For the Physical Component Summary, 73.9% had good scores, and 26.1% had consistently low scores. Prediagnosis perceived stress and current smoking were related to being in the low mental trajectory group, and a higher number of comorbidities was related to being in the low physical trajectory group. CONCLUSION: Although the majority of BCS have HRQL similar to non-cancer controls after 2 years, subgroups of BCS continue to have low HRQL. Prediagnosis stress, comorbidities, and smoking are vulnerability factors for long-term, low HRQL in BCS.


Assuntos
Neoplasias da Mama/terapia , Sobreviventes de Câncer/psicologia , Qualidade de Vida/psicologia , Adulto , Neoplasias da Mama/etnologia , Neoplasias da Mama/psicologia , Estudos de Casos e Controles , Feminino , Humanos , Avaliação de Estado de Karnofsky , Pessoa de Meia-Idade
5.
J Cardiovasc Magn Reson ; 21(1): 46, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31391036

RESUMO

OBJECTIVES: We sought to: (1) determine the agreement in cardiovascular magnetic resonance (CMR) and speckle tracking echocardiography (STE) derived strain measurements, (2) compare their reproducibility, (3) determine which approach is best related to CMR late gadolinium enhancement (LGE). BACKGROUND: While STE-derived strain is routinely used to assess left ventricular (LV) function, CMR strain measurements are not yet standardized. Strain can be measured using dedicated pulse sequences (strain-encoding, SENC), or post-processing of cine images (feature tracking, FT). It is unclear whether these measurements are interchangeable, and whether strain can be used as an alternative to LGE. METHODS: Fifty patients underwent 2D echocardiography and 1.5 T CMR. Global longitudinal strain (GLS) was measured by STE (Epsilon), FT (NeoSoft) and SENC (Myocardial Solutions) and circumferential strain (GCS) by FT and SENC. RESULTS: GLS showed good inter-modality agreement (r-values: 0.71-0.75), small biases (< 1%) but considerable limits of agreement (- 7 to 8%). The agreement between the CMR techniques was better for GLS than GCS (r = 0.81 vs 0.67; smaller bias). Repeated measurements showed low intra- and inter-observer variability for both GLS and GCS (intraclass correlations 0.86-0.99; coefficients of variation 3-13%). LGE was present in 22 (44%) of patients. Both SENC- and FT-derived GLS and GCS were associated with LGE, while STE-GLS was not. Irrespective of CMR technique, this association was stronger for GCS (AUC 0.77-0.78) than GLS (AUC 0.67-0.72) and STE-GLS (AUC = 0.58). CONCLUSION: There is good inter-technique agreement in strain measurements, which were highly reproducible, irrespective of modality or analysis technique. GCS may better reflect the presence of underlying LGE than GLS.


Assuntos
Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Contração Miocárdica , Isquemia Miocárdica/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Adulto , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Isquemia Miocárdica/fisiopatologia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Volume Sistólico , Disfunção Ventricular Esquerda/fisiopatologia
6.
Support Care Cancer ; 27(6): 2229-2235, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30317432

RESUMO

PURPOSE: This longitudinal study sought to examine the reciprocal relationship between spirituality and physical health status among breast cancer survivors. METHODS: Breast cancer survivors (N = 634) completed baseline assessments (T1) within 8 months of breast cancer diagnosis and 12 (T2) and 18 months (T3) after their baseline assessment. Spirituality was assessed by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) scale which consists of three subscales: meaning, peace, and faith. Physical health status was measured with the SF-36 Physical Component Summary (PCS). A cross-lagged structural equation model (SEM) was used to analyze the three-wave data to examine the reciprocal relationships between the observed variable, PCS, and the three subscales of the FACIT-Sp, treated as latent variables. RESULTS: The cross-lagged SEM yielded an adequate fit to the data: RMSEA = .036, CFI = 0.97, TLI = 0.96. After controlling for relevant sociodemographic and cancer-related variables, only higher PCS at T2 predicted greater meaning at T3. PCS at T1 did not predict meaning at T2 and the reciprocal relationship of meaning predicting PCS was not significant. Neither peace nor faith was reciprocally related to PCS. CONCLUSIONS: Results provide evidence of a unidirectional relationship between self-reported physical health status and subsequent meaning among breast cancer survivors during the period of early to later survivorship. Additional studies are needed that examine the longitudinal and directional relationships between spirituality and physical health among diverse samples of cancer survivors.


Assuntos
Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Nível de Saúde , Qualidade de Vida/psicologia , Espiritualidade , Neoplasias da Mama/mortalidade , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade
7.
Cell Mol Life Sci ; 75(10): 1827-1837, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29387902

RESUMO

Type 2 diabetes is a complex metabolic disorder characterized by insulin resistance and pancreatic ß-cell dysfunction. Deregulated glucose and lipid metabolism are the primary underlying manifestations associated with this disease and its complications. Long non-coding RNAs (lncRNAs) are a novel class of functional RNAs that regulate a variety of biological processes by a diverse interplay of mechanisms including recruitment of epigenetic modifiers, transcriptional and post-transcriptional regulation, control of mRNA decay, and sequestration of transcription factors. Although the underlying causes that define the diabetic phenotype are extremely intricate, most of the studies in the last decades were mostly centered on protein-coding genes. However, current opinion in the recent past has authenticated the contributions of diverse lncRNAs as critical regulatory players during the manifestation of diabetes. The current review will highlight the importance of lncRNAs in regulating cellular processes that govern metabolic homeostasis in key metabolic tissues. A more in-depth understanding of lncRNAs may enable their exploitation as biomarkers or for therapeutic applications during diabetes and its associated complications.


Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético/genética , RNA Longo não Codificante/fisiologia , Animais , Epigênese Genética/fisiologia , Regulação da Expressão Gênica , Humanos
8.
Nephrology (Carlton) ; 24(7): 689-695, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29737591

RESUMO

AIM: Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA) are part of first-line anti-tuberculosis therapy used against infection caused by Mycobacterium tuberculosis. However, these drugs are known to be potentially harmful as these are associated with numerous side effects and when taken together their harmful outcomes are elevated in a synergistic manner. Identification of possible mechanism underlying RIF + INH + PZA induced nephrotoxicity may be advantageous in developing strategies to prevent their toxic implications. METHODS: In this study rats were distributed in two groups of six each: Control (tap water) and Toxicant (INH + RIF + PZA) in dosage derived through extrapolation from human dosage for 28 days once in a day. Antioxidant activity and histology of kidney were examined. In addition, apoptosis was also studied using pro and anti-apoptotic markers and TUNEL staining to check nephrotoxicity. RESULTS: Findings indicated that combined (INH, RIF and PZA) 28 day exposure in Wistar rats caused increase in number of free radicals/ reactive oxygen species which further cause changes in levels of enzymatic antioxidants such as glutathione, Superoxide dismutase, Catalase, and Glutathione-s-transferase. Altered content of pro (BAD&BAX) and anti-apoptotic genes (BCL-2&BCL2L1) genes, TUNEL positive cells and DNA fragmentation emphasized involvement of apoptosis. CONCLUSION: This study concluded that nephrotoxicity is accompanied during combinational anti-tuberculosis drug therapy.


Assuntos
Antituberculosos/efeitos adversos , Apoptose/efeitos dos fármacos , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
9.
Echocardiography ; 36(2): 285-291, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30592782

RESUMO

BACKGROUND: Despite routine use of echocardiographic parameters to evaluate the severity of cardiac amyloidosis (CA), this methodology has not been well validated. We developed a histopathologic schema for quantifying CA burden and evaluated its relationship with clinical outcomes. Additionally, echocardiographic parameters were tested as potential noninvasive indices of CA burden. METHODS: We retrospectively studied 59 patients with CA (17 light chain, 42 transthyretin) who underwent endomyocardial biopsies. Light microscopy with staining was used to categorize CA burden as mild-to-moderate (<50%) or high (≥50%). Kaplan-Meier survival analysis was performed for the two groups. In 34 patients with good-quality echocardiograms, we measured left ventricular volumes, ejection fraction (EF), interventricular septal thickness (IVSt), posterior wall thickness (PWt), LV mass, lateral e'-velocity, and global longitudinal strain (GLS). These parameters were compared between the two groups. RESULTS: Thirty-five patients had mild-to-moderate and 24 severe amyloid burden. Kaplan-Meier curves demonstrated a trend toward worse mortality with high CA burden, which was more common and associated with higher mortality specifically in transthyretin-type patients. Echocardiography-derived IVSt, PWt, and LV mass were directly related to CA burden, while LV EF, e'-velocity, and GLS magnitude were inversely related to CA burden. CONCLUSIONS: Our findings provided a signal that CA burden is a clinically important entity with potentially valuable prognostic information. Echocardiographic parameters of LV anatomy and function correlate with histopathologic burden of CA, which is inversely related to survival. Further studies are needed to determine whether these parameters could be used as imaging biomarkers of treatment-related changes in CA burden.


Assuntos
Amiloidose/diagnóstico por imagem , Amiloidose/patologia , Ecocardiografia/métodos , Cardiopatias/diagnóstico por imagem , Cardiopatias/patologia , Idoso , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Estudos Retrospectivos , Análise de Sobrevida
11.
Cancer ; 124(15): 3240-3248, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29757455

RESUMO

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia, with profound disease-related cellular, humoral, and innate immune suppression. The objective of this study was to study the correlations between stress and disease-specific, negative prognostic cellular, cytokine, and chemokine markers in patients with CLL. METHODS: A single-group, observational design was used. Patients with relapsed/refractory CLL (N = 96) who were entering a phase 2 trial of an experimental therapy (ibrutinib) were studied. Before the first dose, a validated self-report measure of stress (the Impact of Event Scale) was completed, and blood was drawn for absolute lymphocyte counts (ALCs) and for cytokine and chemokine enzyme-linked immunosorbent assays. Multiple linear regression models tested stress as a concurrent predictor of ALCs; of cytokines (tumor necrosis factor α [TNFα], a proliferation-inducing ligand [APRIL], B-cell activating factor [BAFF], interleukin 6 [IL-6], IL-10, IL-16, and vascular endothelial growth factor [VEGF]); and of the chemokine (C-C motif) ligand 3 (CCL3). RESULTS: Controlling for relevant demographic variables, comorbidities, CLL genetic risk (deletion of the short arm of chromosome 17 [del17p]), and correlates of inflammation, stress predicted higher ALCs (P < .05), and higher levels of TNFα (P < .05), IL-16 (P < .01), and CCL3 (P < .05). Stress was not associated with APRIL, BAFF, IL-6, IL-10, or VEGF. CONCLUSIONS: Novel biobehavioral data from patients with relapsed/refractory CLL demonstrate that stress is related to heightened levels of cellular, cytokine, and chemokine markers associated previously with progressive disease in CLL. The current results indicate that stress is related to immune and inflammatory processes that contribute to cancer cell proliferation and survival. These data provide a first look into these processes. Cancer 2018. © 2018 American Cancer Society.


Assuntos
Biomarcadores Tumorais/sangue , Inflamação/psicologia , Leucemia Linfocítica Crônica de Células B/psicologia , Estresse Psicológico/psicologia , Adenina/análogos & derivados , Idoso , Fator Ativador de Células B/sangue , Biomarcadores Tumorais/imunologia , Proliferação de Células/genética , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Inflamação/sangue , Inflamação/complicações , Inflamação/imunologia , Interleucina-6/sangue , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Piperidinas , Prognóstico , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/imunologia , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue
12.
Breast Cancer Res Treat ; 169(1): 163-173, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29368310

RESUMO

PURPOSE: Although quality of life (QoL) improves over time for most breast cancer survivors (BCS), BCS may show different patterns of QoL. This study sought to identify distinct QoL trajectories among BCS and to examine characteristics associated with trajectory group membership. METHODS: BCS (N = 653) completed baseline assessments within 8 months of diagnosis. QoL was assessed by the Functional Assessment of Cancer Therapy-Breast (FACT-B) at baseline and 6, 12, and 18 months later. Finite mixture modeling was used to determine QoL trajectories of the trial outcome index (TOI; a composite of physical well-being, functional well-being, and breast cancer-specific subscales) and emotional and social/family well-being subscales. Chi-square tests and F tests were used to examine group differences in demographic, cancer-related, and psychosocial variables. RESULTS: Unique trajectories were identified for all three subscales. Within each subscale, the majority of BCS had consistently medium or high QoL. The TOI analysis revealed only stable or improving groups, but the emotional and social/family subscales had groups that were stable, improved, or declined. Across all subscales, women in "consistently high" groups had the most favorable psychosocial characteristics. For the TOI and emotional subscales, psychosocial variables also differed significantly between women who started similarly but had differing trajectories. CONCLUSIONS: The majority of BCS report good QoL as they transition from treatment to survivorship. However, some women have persistently low QoL in each domain and some experience declines in emotional and/or social/family well-being. Psychosocial variables are consistently associated with improving and/or declining trajectories of physical/functional and emotional well-being.


Assuntos
Neoplasias da Mama/psicologia , Mama/patologia , Qualidade de Vida/psicologia , Estresse Psicológico/psicologia , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Saúde Mental , Pessoa de Meia-Idade , Estresse Psicológico/epidemiologia , Sobreviventes
13.
Ann Behav Med ; 52(4): 287-298, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30084895

RESUMO

Background: Chronic lymphocytic leukemia is the most prevalent adult leukemia. The disease is incurable with a cycling of treatment and relapse common. Little is known about the psychological and physical functioning of patients with relapsed/refractory chronic lymphocytic leukemia. Cancer-specific stress is an important individual difference variable that predicts psychological and physical outcomes. Purpose: To examine cancer-specific stress at treatment initiation as a predictor of psychological and physical functioning trajectories in patients with relapsed/refractory chronic lymphocytic leukemia during the first 5 months of treatment. Methods: Patients with relapsed/refractory chronic lymphocytic leukemia (N = 152) enrolled in a phase II clinical trial completed self-report measures at treatment initiation (baseline), 1, 2, and 5 months of treatment. Cancer-specific stress at baseline was examined as a predictor of psychological (cognitive-affective depressive symptoms, negative mood, mental health quality of life) and physical functioning (fatigue interference, sleep problems, physical health quality of life), controlling for demographic and treatment variables. Results: Using multilevel modeling, higher baseline cancer-specific stress was related to worse psychological (cognitive-affective depressive symptoms, negative mood, mental health quality of life) and physical functioning (fatigue interference, sleep problems) at baseline and more rapid improvements during the next 5 months. Despite these improvements, higher baseline cancer-specific stress remained associated with poorer 5-month psychological, though not physical, functioning. Conclusions: Findings suggest cancer-specific stress at treatment initiation may be a risk factor for poorer psychological functioning during treatment for patients with relapsed/refractory chronic lymphocytic leukemia.


Assuntos
Depressão , Fadiga , Leucemia Linfocítica Crônica de Células B , Qualidade de Vida/psicologia , Transtornos do Sono-Vigília , Estresse Psicológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/etiologia , Depressão/fisiopatologia , Depressão/psicologia , Fadiga/etiologia , Fadiga/fisiopatologia , Fadiga/psicologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/psicologia , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/psicologia , Estresse Psicológico/etiologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia
14.
Echocardiography ; 35(5): 743-746, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29510457

RESUMO

Good-quality chest compressions improve outcomes in cardiac arrest. While manual chest compressions are suboptimal in this regard, the LUCAS device has been shown to improve the effectiveness of chest compressions during cardiopulmonary resuscitation (CPR). The complication rate associated with mechanical CPR, however, has not been adequately studied. Limited evidence suggests no difference in internal injury between manual and mechanical CPR. We report the case of a patient on anticoagulation who developed a mediastinal hematoma post mechanical CPR and on whom subtle findings on initial echocardiography could have alerted the clinician to this complication early during the clinical course. This case further suggests that there may be special populations of patients in whom we may need to be more vigilant in the use of mechanical CPR.


Assuntos
Anticoagulantes/efeitos adversos , Diagnóstico Precoce , Ecocardiografia/métodos , Parada Cardíaca/terapia , Massagem Cardíaca/efeitos adversos , Hemotórax/diagnóstico , Fibrilação Ventricular/diagnóstico , Anticoagulantes/uso terapêutico , Diagnóstico Diferencial , Serviços Médicos de Emergência , Parada Cardíaca/diagnóstico , Parada Cardíaca/etiologia , Massagem Cardíaca/instrumentação , Hemotórax/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Fibrilação Ventricular/complicações , Fibrilação Ventricular/tratamento farmacológico
15.
Environ Monit Assess ; 190(7): 410, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29923094

RESUMO

Ricinus communis L. colonizes heterogeneous urban landscapes as monospecific thickets. The ecological understanding on colonization success of R. communis population due to variable light availability is lacking. Therefore, to understand the effect of intrinsic light heterogeneity on species' population dynamics, R. communis populations exposed to variable light availability (low, intermediate, and high) were examined for performance strategies through estimation of key vegetative, eco-physiological, biochemical, and reproductive traits. Considerable variability existed in studied plant traits in response to available light. Individuals inhabiting high-light conditions exhibited high eco-physiological efficiency and reproductive performance that potentially confers population boom. Individuals exposed to low light showed poor performance in terms of eco-physiology and reproduction, which attribute to bust. However, individuals in intermediate light were observed to be indeterminate to light availability, potentially undergoing trait modulations with uncertainty of available light. Heterogeneous light availability potentially drives the boom and bust cycles in R. communis monospecific thickets. Such boom and bust cycles subsequently affect species' dominance, persistence, collapse, and/or resurgence as an aggressive colonizer in contrasting urban environments. The study fosters extensive monitoring of R. communis thickets to probe underlying mechanism(s) affecting expansions and/or collapses of colonizing populations.


Assuntos
Monitoramento Ambiental , Ricinus/fisiologia , Ecologia , Dinâmica Populacional
16.
Arterioscler Thromb Vasc Biol ; 36(11): 2167-2175, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27659097

RESUMO

OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor that promotes and inhibits cell migration, plays a complex and important role in adverse vascular remodeling. Little is known about the effects of pharmacological PAI-1 inhibitors, an emerging drug class, on migration of vascular smooth muscle cells (SMCs) and endothelial cells (ECs), crucial mediators of vascular remodeling. We investigated the effects of PAI-039 (tiplaxtinin), a specific PAI-1 inhibitor, on SMC and EC migration in vitro and vascular remodeling in vivo. APPROACH AND RESULTS: PAI-039 inhibited SMC migration through collagen gels, including those supplemented with vitronectin and other extracellular matrix proteins, but did not inhibit migration of PAI-1-deficient SMCs, suggesting that its antimigratory effects were PAI-1-specific and physiologically relevant. However, PAI-039 did not inhibit EC migration. PAI-039 inhibited phosphorylation and nuclear translocation of signal transducers and activators of transcription-1 in SMCs, but had no discernable effect on signal transducer and activator of transcription-1 signaling in ECs. Expression of low-density lipoprotein receptor-related protein 1, a motogenic PAI-1 receptor that activates Janus kinase/signal transducers and activators of transcription-1 signaling, was markedly lower in ECs than in SMCs. Notably, PAI-039 significantly inhibited intimal hyperplasia and inflammation in murine models of adverse vascular remodeling, but did not adversely affect re-endothelialization after endothelium-denuding mechanical vascular injury. CONCLUSIONS: PAI-039 inhibits SMC migration and intimal hyperplasia, while having no inhibitory effect on ECs, which seems to be because of differences in PAI-1-dependent low-density lipoprotein receptor-related protein 1/Janus kinase/signal transducer and activator of transcription-1 signaling between SMCs and ECs. These findings suggest that PAI-1 may be an important therapeutic target in obstructive vascular diseases characterized by neointimal hyperplasia.


Assuntos
Lesões das Artérias Carótidas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácidos Indolacéticos/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Neointima , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Inibidores de Serina Proteinase/farmacologia , Animais , Lesões das Artérias Carótidas/genética , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Genótipo , Humanos , Hiperplasia , Janus Quinases/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Terapia de Alvo Molecular , Músculo Liso/metabolismo , Músculo Liso/patologia , Músculo Liso/transplante , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/transplante , Fenótipo , Fosforilação , Inibidor 1 de Ativador de Plasminogênio/deficiência , Inibidor 1 de Ativador de Plasminogênio/genética , Reepitelização/efeitos dos fármacos , Receptores de LDL/deficiência , Receptores de LDL/genética , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Supressoras de Tumor/deficiência , Proteínas Supressoras de Tumor/genética , Remodelação Vascular/efeitos dos fármacos , Veia Cava Inferior/efeitos dos fármacos , Veia Cava Inferior/metabolismo , Veia Cava Inferior/patologia , Veia Cava Inferior/transplante
18.
J Biol Chem ; 288(34): 24480-93, 2013 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-23824183

RESUMO

The fungal ATP-binding cassette (ABC) transporter Cdr1 protein (Cdr1p), responsible for clinically significant drug resistance, is composed of two transmembrane domains (TMDs) and two nucleotide binding domains (NBDs). We have probed the nature of the drug binding pocket by performing systematic mutagenesis of the primary sequences of the 12 transmembrane segments (TMSs) found in the TMDs. All mutated proteins were expressed equally well and localized properly at the plasma membrane in the heterologous host Saccharomyces cerevisiae, but some variants differed significantly in efflux activity, substrate specificity, and coupled ATPase activity. Replacement of the majority of the amino acid residues with alanine or glycine yielded neutral mutations, but about 42% of the variants lost resistance to drug efflux substrates completely or selectively. A predicted three-dimensional homology model shows that all the TMSs, apart from TMS4 and TMS10, interact directly with the drug-binding cavity in both the open and closed Cdr1p conformations. However, TMS4 and TMS10 mutations can also induce total or selective drug susceptibility. Functional data and homology modeling assisted identification of critical amino acids within a drug-binding cavity that, upon mutation, abolished resistance to all drugs tested singly or in combinations. The open and closed Cdr1p models enabled the identification of amino acid residues that bordered a drug-binding cavity dominated by hydrophobic residues. The disposition of TMD residues with differential effects on drug binding and transport are consistent with a large polyspecific drug binding pocket in this yeast multidrug transporter.


Assuntos
Candida albicans/metabolismo , Farmacorresistência Fúngica/fisiologia , Proteínas Fúngicas/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Substituição de Aminoácidos , Transporte Biológico Ativo/fisiologia , Candida albicans/química , Candida albicans/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/genética , Mutação de Sentido Incorreto , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
19.
Environ Monit Assess ; 186(11): 7941-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25103212

RESUMO

This paper addresses the phenotypic variation among Ricinus communis L. populations in four urban habitat types (road verges, garbage dumps, construction debris, and natural area) in Delhi, India, by evaluating important traits such as plant height, basal circumference, seeds per plant, seed size, seed weight, specific leaf area, and reproductive index. An important biochemical marker, proline, considered as a good plant performance indicator under stress was also quantified in leaves of R. communis to evaluate its response in different habitats. Interestingly, the species showed significant variation in plant height, specific leaf area, seed size, seed weight, and leaf proline content in different habitat types. Leaf proline content was positively related to plant height, specific leaf area, and seed size while negatively related to the total number of seeds/plant. Interestingly, reproductive index, calculated as a ratio of the total number of seeds to the plant height also showed a negative relation with leaf proline content. Results indicated that R. communis exhibits adaptive modulation of growth, reproductive traits, and leaf proline content in various urban habitats which contributes to invasiveness, range expansion, and establishment of the species. The study also gives evidence of how morphological and physiological traits could directly affect invasiveness of R. communis.


Assuntos
Ecossistema , Meio Ambiente , Espécies Introduzidas , Ricinus/crescimento & desenvolvimento , Monitoramento Ambiental , Índia , Fenótipo , Folhas de Planta/química , Prolina/análise , Sementes/química
20.
Saudi J Anaesth ; 18(2): 283-285, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654846

RESUMO

Frontoethmoidal encephalocele represents protrusion of meninges and brain in a sac through a defect in the anterior skull base, mostly as swelling over the nose. Rarely it is associated with facial dysmorphism and palatal cleft. There are various perioperative concerns like airway difficulties, leaking from the swelling causing fluid and electrolyte disturbances, risk of infection, compression of the swelling causing a rise in intracranial pressure, bleeding, hypothermia, etc., In neonates, these challenges rise exponentially because of the inherent difficulties in dealing with this group of patients. Frontoethmoidal encephaloceles are common in low socioeconomic strata and are often missed in the antenatal period. We are reporting a rare case of frontoethmoidal encephalocele, with a huge swelling protruding through the cleft palate and occupying more than 50% of the face and oral cavity, making mask ventilation impossible.

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