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Background: Evidence suggests that a combination of biological and social factors influence risk of dementia differently for women and men. In healthy older women, several factors may contribute to changes in cognition. Objective: Describe the characteristics associated with variation in cognition in a sample of cognitively healthy older Panamanian women. Methods: The study includes cross-sectional analyses of cognitive domains at baseline (n = 357) and 17-month (SD = 2.0) follow-up (n = 200) for women aged 60 years and older enrolled in the Panama Aging Research Initiative-Health Disparities (PARI-HD) study. Instruments included clinical questionnaires, physiological measures, and a neuropsychological test battery assessing global cognition and seven cognitive domains. Multiple regression analyses examined the associations between demographic and clinical characteristics and cognition at baseline. Repeated measures analyses were used to investigate changes in cognition from baseline to follow-up. Results: On average, participants were 68.6 years of age (SD = 5.9) with 16.1 years of education (SD = 4.7). Age, income, and education showed robust associations with baseline cognition. Subjective cognitive impairment was associated with lower performance in global cognition, verbal learning, and memory domains. Only performance in the attention domain decreased at follow-up, and subjective health state and depressive symptoms significantly predicted the change in attention. Discussion: Our study findings contribute to the investigation of cognitive health in older Hispanic women and to the understanding of sociodemographic and health-related factors associated with cognitive decline and the progression to cognitive impairment and dementia.
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Background: A growing body of evidence points to potential risks associated with polypharmacy (using ≥5 medications) in older adults, but most evidence is derived from studies where racial and ethnic minorities remain underrepresented among research participants. Objective: Investigate the association between polypharmacy and cognitive function, subjective health state, frailty, and falls in Hispanic older adults. Methods: Panama Aging Research Initiative-Health Disparities (PARI-HD) is a community-based cohort study of older adults free of dementia at baseline. Cognitive function was measured with a neuropsychological test battery. Frailty assessment was based on the Fried criteria. Subjective health state and falls were self-reported. Linear and multinomial logistic regression analyses were used to examine association. Results: Baseline evaluations of 468 individuals with a mean age of 69.9 years (SDâ=â6.8) were included. The median number of medications was 2 (IQR: 1-4); the rate of polypharmacy was 19.7% (95% confidence interval [CI]â=â16.1-23.3). Polypharmacy was inversely associated with self-rated overall health (bâ=-5.89, pâ<â0.01). Polypharmacy users had 2.3 times higher odds of reporting two or more falls in the previous 12 months (odds ratio [OR]â=â2.31, 95% CIâ=â1.06-5.04). Polypharmacy was independently associated with Fried's criteria for pre-frailty (ORâ=â2.90, 95% CIâ=â1.36-5.96) and frailty (ORâ=â5.14, 95% CIâ=â1.83-14.42). Polypharmacy was not associated with cognitive impairment. Conclusions: These findings illustrate the potential risks associated with polypharmacy among older adults in Panama and may inform interventions to improve health outcomes in this population.
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Fragilidade , Humanos , Idoso , Fragilidade/epidemiologia , Estudos de Coortes , Polimedicação , Gerociência , Avaliação de Resultados em Cuidados de Saúde , Idoso FragilizadoRESUMO
In the original publication [...].
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The diverse clinical outcomes of prostate cancer have led to the development of gene signature assays predicting disease progression. Improved prostate cancer progression biomarkers are needed as current RNA biomarker tests have varying success for intermediate prostate cancer. Interest grows in universal gene signatures for invasive carcinoma progression. Early breast and prostate cancers share characteristics, including hormone dependence and BRCA1/2 mutations. Given the similarities in the pathobiology of breast and prostate cancer, we utilized the NanoString BC360 panel, comprising the validated PAM50 classifier and pathway-specific signatures associated with general tumor progression as well as breast cancer-specific classifiers. This retrospective cohort of primary prostate cancers (n=53) was stratified according to biochemical recurrence (BCR) status and the CAPRA-S to identify genes related to high-risk disease. Two public cohort (TCGA-PRAD and GSE54460) were used to validate the results. Expression profiling of our cohort uncovered associations between PIP and INHBA with BCR and high CAPRA-S score, as well as associations between VCAN, SFRP2, and THBS4 and BCR. Despite low levels of the ESR1 gene compared to AR, we found strong expression of the ER signaling signature, suggesting that BCR may be driven by ER-mediated pathways. Kaplan-Meier and univariate Cox proportional hazards regression analysis indicated the expression of ESR1, PGR, VCAN, and SFRP2 could predict the occurrence of relapse events. This is in keeping with the pathways represented by these genes which contribute to angiogenesis and the epithelial-mesenchymal transition. It is likely that VCAN works by activating the stroma and remodeling the tumor microenvironment. Additionally, SFRP2 overexpression has been associated with increased tumor size and reduced survival rates in breast cancer and among prostate cancer patients who experienced BCR. ESR1 influences disease progression by activating stroma, stimulating stem/progenitor prostate cancer, and inducing TGF-ß. Estrogen signaling may therefore serve as a surrogate to AR signaling during progression and in hormone-refractory disease, particularly in prostate cancer patients with stromal-rich tumors. Collectively, the use of agnostic biomarkers developed for breast cancer stratification has facilitated a precise clinical classification of patients undergoing radical prostatectomy and highlighted the therapeutic potential of targeting estrogen signaling in prostate cancer.
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Background: The COVID-19 pandemic was characterized by global increases in depression, anxiety, and stress symptoms. Previous studies have shown that resilience mitigates these symptoms, however there is limited research exploring the link between resilience and mental illness during the COVID-19 pandemic in Central America. Objective: To examine the role of resilience as it relates to the perceived effect of the pandemic on mental health symptoms. Methods: A sample of 480 adults in Panama were recruited from March to May 2021 to complete an online survey. The online survey consisted of sociodemographic questions and scale measures assessing depression, anxiety and stress symptoms, resilience, and social support. Results: Results indicated that resilience mediated the relationship between the perceived effect of the COVID-19 pandemic and mental health symptoms; participants who felt more personally affected by the pandemic reported more depression, anxiety, and stress symptoms via decreased resilience. Further analyses revealed that resilience was moderated by sex and social support, showing that the indirect effect of resilience was greater for women and individuals who perceived low social support. Discussion: These findings contribute to a growing body of research documenting the adverse effects of the COVID-19 pandemic on mental health and reveal potential mechanisms through which pandemic-related distress decreases resilience, thereby increasing symptoms of mental illness.
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Snake venom neutralization potency tests are required for quality control assessment by manufacturers and regulatory authorities. These assays require the use of large numbers of mice that manifest severe signs associated with pain and distress and long periods of suffering. Despite this, many animals make a full recovery; therefore, the observation of clinical signs as a predictor of animal death is highly subjective and could affect the accuracy of the results. The use of a more objective parameter such as body temperature measurement could help establish a humane endpoint that would contribute to significantly reducing the suffering of large numbers of animals. We determined the temperature drop in BALB/c mice exposed to the mixtures of Bothrops asper or Lachesis stenophrys venom and a polyvalent antivenom by using an infrared thermometer. Our data show that, based on the temperature change from baseline, it is possible to predict which animals will survive during the first 3 h after inoculation. The data provided in this study may contribute to future reductions in animal suffering, in concordance with general trends in the use of laboratory animals for the quality control of biologicals.
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Temperatura Corporal , Venenos de Serpentes , Animais , Camundongos , Testes de Neutralização , Venenos de Serpentes/toxicidade , Antivenenos , Bioensaio , Camundongos Endogâmicos BALB CRESUMO
Background: The impact of the COVID-19 pandemic and the associated restrictions on mental health is being studied. Objective: To analyze the psychosocial response to the COVID-19 pandemic in adults residing in Panama. Methods: A community sample of 480 adult residents of Panama completed a survey that included sociodemographic questions, COVID-19 related questions (e.g., health concerns regarding the virus, knowledge and behaviors in biosafety) and scales of stress, anxiety, depression, prosocial behavior, resilience, perceived social support, and insomnia. Results: Most of the participants (>60%) reported being negatively affected by the pandemic. Women experienced greater depression, anxiety, and stress symptoms than men, and age was negatively associated with depression, anxiety, and stress symptoms. Self-perceived health status and self-perceived social support were negatively associated with depression, anxiety, and stress symptoms. Self-perceived social isolation was positively associated with depression, anxiety, and stress symptoms. Psychiatric illness and insomnia were positively associated with depression, anxiety, and stress symptoms, whereas psychological resilience was negatively associated with depression, anxiety, and stress symptoms. Discussion: These results corroborate other studies regarding COVID-19 and mental health. This study highlights the need for specific prevention and intervention mechanisms related to the COVID-19 pandemic in different population groups. This is the first report of the psychological impact of COVID-19 in the general Panamanian population and one of the only studies in the Latin American region and, therefore, contributes to research in the Latino population and lower-middle income countries.
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COVID-19 , Distúrbios do Início e da Manutenção do Sono , Adulto , Depressão , Feminino , Humanos , Masculino , Pandemias , SARS-CoV-2RESUMO
Recent advances in biomedical research in cancer immunotherapy have identified the use of an oxidative stress-based approach to treat cancers, which works by inducing immunogenic cell death (ICD) in cancer cells. Since the anti-cancer effects of non-thermal plasma (NTP) are largely attributed to the reactive oxygen and nitrogen species that are delivered to and generated inside the target cancer cells, it is reasonable to postulate that NTP would be an effective modality for ICD induction. NTP treatment of tumors has been shown to destroy cancer cells rapidly and, under specific treatment regimens, this leads to systemic tumor-specific immunity. The translational benefit of NTP for treatment of cancer relies on its ability to enhance the interactions between NTP-exposed tumor cells and local immune cells which initiates subsequent protective immune responses. This review discusses results from recent investigations of NTP application to induce immunogenic cell death in cancer cells. With further optimization of clinical devices and treatment protocols, NTP can become an essential part of the therapeutic armament against cancer.
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Growth and development rates may result from genetic programming of intrinsic processes that yield correlated rates between life stages. These intrinsic rates are thought to affect adult mortality probability and longevity. However, if proximate extrinsic factors (e.g., temperature, food) influence development rates differently between stages and yield low covariance between stages, then development rates may not explain adult mortality probability. We examined these issues based on study of 90 songbird species on four continents to capture the diverse life-history strategies observed across geographic space. The length of the embryonic period explained little variation (ca. 13%) in nestling periods and growth rates among species. This low covariance suggests that the relative importance of intrinsic and extrinsic influences on growth and development rates differs between stages. Consequently, nestling period durations and nestling growth rates were not related to annual adult mortality probability among diverse songbird species within or among sites. The absence of a clear effect of faster growth on adult mortality when examined in an evolutionary framework across species may indicate that species that evolve faster growth also evolve physiological mechanisms for ameliorating costs on adult mortality. Instead, adult mortality rates of species in the wild may be determined more strongly by extrinsic environmental causes.
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Mortalidade , Aves Canoras/embriologia , Aves Canoras/crescimento & desenvolvimento , Animais , Arizona , Evolução Biológica , Embrião não Mamífero/fisiologia , Desenvolvimento Embrionário , Malásia , Comportamento de Nidação/fisiologia , Comportamento Predatório/fisiologia , Análise de Regressão , África do Sul , VenezuelaRESUMO
The emergence of targeted cancer therapy has been limited by the paucity of determinants which are tumor-specific and generally associated with disease, and have cell dynamics which effectively deploy cytotoxic payloads. Guanylyl cyclase C (GUCY2C) may be ideal for targeting because it is normally expressed only in insulated barrier compartments, including intestine and brain, but over-expressed by systemic metastatic colorectal tumors. Here, we reveal that GUCY2C rapidly internalizes from the cell surface to lysosomes in intestinal and colorectal cancer cells. Endocytosis is independent of ligand binding and receptor activation, and is mediated by clathrin. This mechanism suggests a design for immunotoxins comprising a GUCY2C-directed monoclonal antibody conjugated through a reducible disulfide linkage to ricin A chain, which is activated to a potent cytotoxin in lysosomes. Indeed, this immunotoxin specifically killed GUCY2C-expressing colorectal cancer cells in a lysosomal- and clathrin-dependent fashion. Moreover, this immunotoxin reduced pulmonary tumors>80% (p<0.001), and improved survival 25% (p<0.001), in mice with established colorectal cancer metastases. Further, therapeutic efficacy was achieved without histologic evidence of toxicity in normal tissues. These observations support GUCY2C-targeted immunotoxins as novel therapeutics for metastatic tumors originating in the GI tract, including colorectum, stomach, esophagus, and pancreas.
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Anticorpos Monoclonais/imunologia , Neoplasias Gastrointestinais/tratamento farmacológico , Imunotoxinas/farmacologia , Receptores Acoplados a Guanilato Ciclase/metabolismo , Receptores de Peptídeos/metabolismo , Ricina/farmacologia , Animais , Anticorpos Monoclonais/administração & dosagem , Caveolinas/metabolismo , Linhagem Celular Tumoral , Clatrina/metabolismo , Portadores de Fármacos , Endocitose , Neoplasias Gastrointestinais/patologia , Imunoterapia , Imunotoxinas/administração & dosagem , Lisossomos , Camundongos , Terapia de Alvo Molecular , Transporte Proteico , Interferência de RNA , RNA Interferente Pequeno , Receptores de Enterotoxina , Ricina/administração & dosagem , Ricina/genéticaRESUMO
In this work, the design of a robust controller for an experimental laboratory-scale position control system based on a dc motor drive as well as the corresponding identification and robust stability analysis are presented. In order to carry out the robust design procedure, first, a classic closed-loop identification technique is applied and then, the parametrization by internal model control is used. The model uncertainty is evaluated under both parametric and global representation. For the latter case, an interesting discussion about the conservativeness of this description is presented by means of a comparison between the uncertainty disk and the critical perturbation radius approaches. Finally, conclusions about the performance of the experimental system with the robust controller are discussed using comparative graphics of the controlled variable and the Nyquist stability margin as a robustness measurement.
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Simulação por Computador , Retroalimentação , Modelos Lineares , Movimento (Física) , Processamento de Sinais Assistido por Computador , Análise Numérica Assistida por Computador , Controle de Qualidade , Processos EstocásticosRESUMO
BACKGROUND: Aortic prosthetic valves with superior hemodynamic performance are associated with more complete regression of left ventricular hypertrophy and better left ventricular function postoperatively. The near normal function of the pulmonary autografts at rest is well documented, however, exercise data has been seldom reported. The purpose of this study is to evaluate the hemodynamic performance of pulmonary autografts in the aortic position and the homografts used to reconstruct the right ventricular outflow tract during conditions of high cardiac output by means of dobutamine stress echocardiography. METHODS: Between May 1995 and February 1998, 67 patients were submitted to a Ross operation at our institution. Twenty of these patients had a mean age of 28.6+/-8.3 years and a mean follow-up time of 15.7+/-5.9 months. They were studied by dobutamine stress echocardiography to evaluate rest and exercise hemodynamics of the pulmonary autografts as well as of the aortic and pulmonary homografts used to reconstruct the right ventricular outflow tract. Dobutamine infusion was started at 5 microg/kg with incremental doses up to 40 microg/kg in every case. RESULTS: With dobutamine infusion, heart rate increased from 71+/-10 to 142+/-11 beats/min, left ventricular systolic volume from 86.8+/-33.9 mL to 115.9+/-52.6 mL, and cardiac output from 6.3+/-2.9 L/min to 16.8+/-7.4 L/min. Left ventricular function was considered satisfactory at rest and during exercise in all patients. The mean gradient across the autograft increased from 1.03+/-0.95 mmHg to 4.03+/-2.05 mmHg and maximal instantaneous gradient from 2.45+/-2.21 mmHg to 9.54+/-4.85 mmHg. The mean effective orifice area for the autografts were 3.5+/-1.3 cm2 at rest and 3.3+/-1.4 cm2 during exercise. The patients with mild aortic insufficiency at rest had no increase in the degree of regurgitation with exercise. In the right ventricular outflow tract, the mean gradient across the homograft increased from 9.06+/-5.29 mmHg to 17.55+/-9.76 mmHg and maximal instantaneous gradient from 21.4+/-12.5 mmHg to 41.5+/-23.1 mmHg. CONCLUSIONS: Pulmonary autografts exhibit normal hemodynamic performance at rest and during exercise after the Ross operation. However, mild-to-moderate gradients are common at the right ventricular outflow tract and should be carefully monitored.
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Valva Aórtica/cirurgia , Ecocardiografia , Exercício Físico/fisiologia , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Valva Pulmonar/transplante , Descanso/fisiologia , Adolescente , Adulto , Débito Cardíaco , Cardiotônicos/administração & dosagem , Dobutamina/administração & dosagem , Teste de Esforço/métodos , Feminino , Seguimentos , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Infusões Intravenosas , Masculino , Estudos Retrospectivos , Função Ventricular EsquerdaRESUMO
Ultrasonographic, blinded assessment was made of the extent of hepatic steatosis in 55 children with severe malnutrition: undernutrition (n = 6), marasmus (n = 18), marasmickwashiorkor (n = 17), and kwashiorkor (n = 14). The children were examined on admission, in early recovery (considered as baseline), and again at discharge. Eleven healthy control children and eight of the previously malnourished children were studied as comparison groups. Both oedematous and non-oedematous malnourished children had significantly more steatosis than the comparison groups at each time. Children with oedematous malnutrition had significantly greater steatosis than non-oedematous children at admission. Half of the non-oedematous malnourished children had appreciable hepatic steatosis at both admission and at baseline. Hepatic fat was only slowly mobilised. The rate constant was 1.4 +/- 0.3%/day. One quarter of the children did not change steatosis grades during the period they were in hospital. There was no overall correlation between the extent of steatosis and liver size. Hepatic steatosis in childhood malnutrition is not confined to oedematous children: it is frequently present in marasmic and undernourished children. Its extent is not necessarily related to the degree of hepatomegaly and accumulated lipid is only slowly mobilised.
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Fígado Gorduroso/diagnóstico por imagem , Fígado/diagnóstico por imagem , Distúrbios Nutricionais/diagnóstico por imagem , Pré-Escolar , Edema , Fígado Gorduroso/patologia , Feminino , Humanos , Lactente , Fígado/patologia , Estudos Longitudinais , Masculino , Distúrbios Nutricionais/patologia , UltrassonografiaRESUMO
Ultrasonographic, blinded assessment was made of the extent of hepatic steatosis in 55 children with severe malnutrition: undernutrion (n=6), marasmus (n=18), marasmic-kwashiorkor (n=17), and kwashiorkor (n=14). The children were examined on admission, in early recovery (considered as baseline), and again discharge. Eleven healthy control children and eight of the previously malnourished children were studied as comparison groups. Both oedematous and non-oedematous malnourished children had significantly more steatosis than the comparison groups at each time. Children with oedematous malnutrition had significantly greater steatosis than non-oedematous children at admission, Half of the non-oedematous malnourished children had appreciable hepatic steatosis at both admission and at baseline. Hepatic fat was only slowly mobilised. The rate constant was 1.4 ñ 0.3 percent/day. One quarter of the children did not change steatosis grades during the period they were in hospital. There was no overall correlation between the extent of steatosis and liver size. Hepatic steatosis in childhood malnutrition is not confined to oedematous children: it is frequently present in marasmic and under-nourished children. Its extent is not necessarily related to the degree of hepatomegaly and accumulated lipid is only slowly mobilised (AU)
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Humanos , Lactente , Pré-Escolar , Masculino , Feminino , Fígado Gorduroso , Fígado , Distúrbios Nutricionais , Edema , Fígado/patologia , Fígado Gorduroso/patologia , Estudos Longitudinais , Distúrbios Nutricionais/patologiaRESUMO
Low levels of red cell glutathione (a scavenger of free radicals) have been previously shown to correlate well with the presence of oedema in malnourished children. We addressed the possibility that they may also correlate with the extent of hepatic steatosis. Thirty-three children were studied on three occasions - on admission, in early weight gain and at discharge. Ultrasonography was used to assess hepatic fat. The oedematous children had significantly more hepatic fat on admission than the non-oedmatous (p<0.01), but no child had a normal ultrasound. We found a significant inverse relationship (r = -0.53, p<0.001) between hepatic fat and the level of red cell glutathione that disappeared over time. We conclude that, firstly, hepatic steatosis occurs commmonly in even non-oedematous malnourished children. Secondly, this is associated with low levels of glutathione which may have aetiological implications (AU)
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Humanos , Criança , Necrose Gordurosa , Glutationa/metabolismo , Transtornos da Nutrição Infantil/metabolismo , UltrassonografiaRESUMO
A proper perspective of the association of Campylobacter pylori with various diseases can be achieved only when the incidence of C. pylori infection in the normal population is known. We used the 13C urea breath test (a simple, specific, noninvasive, safe, and reproducible method to assess the presence of active C. pylori infection) to compare the frequency of C. pylori infection in healthy young adults from three areas of the world. We studied 26 women and 32 men (ages 20 to 29): 29 from the United States, 10 from China, 6 from Mexico, and 13 from India. All foreign nationals had been in the United States 5 years or less. The frequency of C. pylori infection was 21%, 67%, 33% and 46%, for those from the U.S., China, Mexico and India, respectively. Although, we found no difference in the frequency of C. pylori infection among ethnic groups from North America (U.S. citizens compared with citizens of Mexico), all individuals studied were of middle to upper class socioeconomic status. Subsequent studies will investigate whether the prevalence of C. pylori infection is different in economically disadvantaged populations. Our results suggest that there may be major differences in the age-related frequency of C. pylori infection in individuals from different parts of the world.