RESUMEN
PURPOSE: The severity of the stress response to experiencing disaster depends on individual exposure and background stress prior to the event. To date, there is limited research on the interaction between neighborhood environmental stress and experiencing an oil spill, and their effects on depression. The objective of the current study was to assess if the association between exposure to the Deepwater Horizon Oil Spill (DHOS) and depressive symptoms varied by neighborhood characteristics. METHODS: US Census data (2010) and longitudinal data collected in two waves (2012-2014 and 2014-2016) from female residents [N = 889 (Wave I), 737 (Wave II)] of an area highly affected by the DHOS were analyzed. Multilevel and individual-level negative binomial regressions were performed to estimate associations with depressive symptoms in both waves. An interaction term was included to estimate effect modification of the association between DHOS exposure and depressive symptoms by neighborhood characteristics. Generalized estimating equations were applied to the negative binomial regression testing longitudinal associations. RESULTS: Census tract-level neighborhood characteristics were not associated with depressive symptoms. Exposure to the DHOS and neighborhood physical disorder were associated with depressive symptoms cross-sectionally. There was no evidence of effect modification; however, physical/environmental exposure to the DHOS was associated with increased depressive symptoms only among women living in areas with physical disorder. Exposure to the DHOS remained associated with depressive symptoms over time. CONCLUSIONS: Findings support the enduring consequences of disaster exposure on depressive symptoms in women and identify potential targets for post-disaster intervention based on residential characteristics.
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Depresión/epidemiología , Desastres/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Louisiana/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: The study analyzed the impact of first-trimester screening on the spectrum of congenital heart defects (CHDs) later in pregnancy and on the outcome of fetuses and children born alive with a CHD. METHODS: The spectrum of CHDs, associated comorbidities, and outcome of fetuses, either diagnosed with a CHD in the first trimester (Group I, 127 fetuses) or only in the second-trimester screening (Group II, 344 fetuses), were analyzed retrospectively between 2007 and 2013. Second-trimester fetuses diagnosed with a CHD between 2007 and 2013 were also compared with Group III (532 fetuses diagnosed with a CHD in the second trimester from 1996 to 2001, the period before first-trimester screening was introduced). RESULTS: The spectrum of CHDs diagnosed in the first and second trimesters in the same time period differed significantly, with a greater number of comorbidities (P<0.0001), CHDs with univentricular outcome (P<0.0001), intrauterine deaths (P=0.01), and terminations of pregnancy (P<0.0001) in Group I compared with Group II. In Group III, significantly more cases of CHDs with univentricular outcome (P<0.0001), intrauterine demise (P=0.036), and early termination (P<0.0001) were identified compared with fetuses diagnosed with CHDs in the second trimester between 2007 and 2013. The spectrum of CHDs seen in the second-trimester groups differed after first-trimester screening was implemented. CONCLUSIONS: First-trimester screening had a significant impact on the spectrum of CHDs and the outcomes of pregnancies with CHDs diagnosed in the second trimester. Early detection of severe forms of CHDs and significant comorbidities resulted in an increased pregnancy termination rate in the first trimester.
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Cardiopatías Congénitas/diagnóstico , Aberraciones Cromosómicas , Comorbilidad , República Checa , Ecocardiografía , Femenino , Feto/diagnóstico por imagen , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/genética , Humanos , Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Estudios Retrospectivos , Ultrasonografía PrenatalRESUMEN
BACKGROUND: Total knee arthroplasty (TKA) is a common procedure resulting in significant post-operative pain. Percutaneous cryoneurolysis targeting the infrapatellar branch of the saphenous nerve and anterior femoral cutaneous nerve could relieve post-operative knee pain by temporarily blocking sensory nerve conduction. METHODS: A retrospective chart review of 100 patients who underwent TKA was conducted to assess the value of adding perioperative cryoneurolysis to a multimodal pain management program. The treatment group consisted of the first 50 patients consecutively treated after the practice introduced perioperative (five days prior to surgery) cryoneurolysis as part of its standard pain management protocol. The control group consisted of the 50 patients treated before cryoneurolysis was introduced. Outcomes included hospital length of stay (LOS), post-operative opioid requirements, and patient-reported outcomes of pain and function. RESULTS: A significantly lower proportion of patients in the treatment group had a LOS of ≥2days compared with the control group (6% vs. 67%, p<0.0001) and required 45% less opioids during the first 12weeks after surgery. The treatment group reported a statistically significant reduction in symptoms at the six- and 12-week follow-up compared with the control group and within-group significant reductions in pain intensity and pain interference at two- and six-week follow-up, respectively. CONCLUSIONS: Perioperative cryoneurolysis in combination with multimodal pain management may significantly improve outcomes in patients undergoing TKA. Promising results from this preliminary retrospective study warrant further investigation of this novel treatment in prospective, randomized trials. LEVEL OF EVIDENCE: III.
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Artroplastia de Reemplazo de Rodilla , Criocirugía/métodos , Desnervación/métodos , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Dolor Postoperatorio/cirugía , Anciano , Femenino , Congelación , Humanos , Rodilla/inervación , Articulación de la Rodilla/inervación , Masculino , Persona de Mediana Edad , Nervios Periféricos/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Alcohol use disorders (AUDs) are a frequent comorbidity in a large percentage of people living with HIV/AIDS (PLWHA). PLWHA with comorbid AUDs are consistently found to perform poorly at most levels of the HIV treatment cascade, resulting in a higher likelihood of virologic nonsuppression. This has been partly attributed to lower rates of persistence with and adherence to antiretroviral therapies (ART). Focus groups of in-care PLWHA identify the need to suspend ART on drinking days because of the potential for toxicity and/or lack of therapeutic effectiveness. The aim of this study was to examine whether chronic binge alcohol (CBA) consumption decreases the effectiveness of uninterrupted ART, specifically that of nucleoside reverse-transcriptase inhibitors (NRTI) tenofovir and emtricitabine in suppressing viral replication, or results in drug toxicity in simian immunodeficiency virus (SIV)-infected rhesus macaques. METHODS: Daily CBA or isocaloric sucrose (SUC) administration was initiated 3 months prior to intrarectal SIVmac251 inoculation and continued throughout the study period. ART was initiated 2.5 months after SIV infection and continued through the study period. RESULTS: CBA administration did not prevent or delay the ART-mediated reduction in viral load. Following ART, circulating levels of total protein and creatinine were significantly higher than baseline values in both SUC- and CBA-treated animals, but still within a normal range. No evidence of ART toxicity was observed in either CBA- or SUC-administered macaques. CONCLUSIONS: These findings indicate that CBA does not attenuate effectiveness of NRTI suppression of viral load, nor does it appear to interact with NRTI to produce toxicity during the initial 2 months of treatment. We conclude that while efforts to reduce AUD in PLWHA should be a priority, counseling on the importance of adherence to ART even on drinking days should also be promoted.
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Antirretrovirales/uso terapéutico , Consumo Excesivo de Bebidas Alcohólicas/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/inmunología , Carga Viral/inmunología , Animales , Antirretrovirales/farmacología , Consumo Excesivo de Bebidas Alcohólicas/complicaciones , Enfermedad Crónica , Macaca mulatta , Masculino , Síndrome de Inmunodeficiencia Adquirida del Simio/complicaciones , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Carga Viral/efectos de los fármacosRESUMEN
Alcohol abuse is a widespread problem among those at risk for and living with HIV and can impact transmission and disease progression. In this study we sought to use the simian immunodeficiency virus (SIV)-macaque model to evaluate the immunological and virological changes in the genital microenvironment of females exposed to chronic alcohol. Female rhesus macaques were treated with alcohol (n=6) or isocaloric sucrose (n=6) for 3 months and then inoculated with SIVmac251. To assess the effects of chronic alcohol on SIV disease and the genital microenvironment, we quantified plasma and genital SIV levels, measured inflammatory cells in genital fluids, and characterized microbial flora by gram stains over 10 weeks post-SIV infection. Following 3 months of alcohol/sucrose treatment, significant differences were observed in the vaginal microenvironment of alcohol-treated animals as compared to controls. Microbial flora of alcohol-treated animals had decreased levels of lactobacillus morphotypes and increased levels of gram-positive cocci relative to sucrose controls. Alcohol-treated animals were also more likely to have white blood cells in vaginal fluids prior to SIV inoculation, which persisted through viral set point. Similar levels of cell-free SIV were observed in plasma and vaginal fluids of both groups, but alcohol-treated animals had a higher incidence and levels of cell-associated SIV shed in vaginal secretions. Chronic alcohol treatment negatively impacts the genital microenvironment prior to and over the course of SIV infection and may increase the risk of genital virus shedding and transmission.
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Alcoholismo , Alcoholes/toxicidad , Síndrome de Inmunodeficiencia Adquirida del Simio/complicaciones , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Vagina/inmunología , Vagina/virología , Animales , Femenino , Lactobacillus/aislamiento & purificación , Leucocitos/virología , Macaca mulatta , Microbiota , Plasma/virología , Vagina/efectos de los fármacos , Carga ViralRESUMEN
The objective of this study was to determine the effect of increased physical activity on subsequent sleeping energy expenditure (SEE) measured in a whole room calorimeter under differing levels of dietary fat. We hypothesized that increased physical activity would increase SEE. Six healthy young men participated in a randomized, single-blind, crossover study. Subjects repeated an 8-day protocol under four conditions separated by at least 7 days. During each condition, subjects consumed an isoenergetic diet consisting of 37% fat, 15% protein, and 48% carbohydrate for the first 4 days, and for the following 4 days SEE and energy balance were measured in a respiration chamber. The first chamber day served as a baseline measurement, and for the remaining 3 days diet and activity were randomly assigned as high-fat/exercise, high-fat/sedentary, low-fat/exercise, or low-fat/sedentary. Energy balance was not different between conditions. When the dietary fat was increased to 50%, SEE increased by 7.4% during exercise (P < 0.05) relative to being sedentary (baseline day), but SEE did not increase with exercise when fat was lowered to 20%. SEE did not change when dietary fat was manipulated under sedentary conditions. Physical activity causes an increase in SEE when dietary fat is high (50%) but not when dietary fat is low (20%). Dietary fat content influences the impact of postexercise-induced increases in SEE. This finding may help explain the conflicting data regarding the effect of exercise on energy expenditure.
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Grasas de la Dieta/administración & dosificación , Ejercicio Físico/fisiología , Consumo de Oxígeno , Adulto , Estudios Cruzados , Dieta Alta en Grasa , Ingestión de Energía/fisiología , Metabolismo Energético/efectos de los fármacos , Humanos , Masculino , Respiración , Descanso/fisiología , Método Simple Ciego , Adulto JovenRESUMEN
Social support has been shown to influence health outcomes in later life. In this study, we focus on social engagement as an umbrella construct that covers select social behaviors in a life span sample that included oldest-old adults, a segment of the adult population for whom very little data currently exist. We examined relationships among social engagement, positive health behaviors, and physical health to provide new evidence that addresses gaps in the extant literature concerning social engagement and healthy aging in very old adults. Participants were younger (21-59 years), older (60-89 years), and oldest-old (90-97 years) adults (N = 364) in the Louisiana Healthy Aging Study (LHAS). Linear regression analyses indicated that age, gender, and hours spent outside of the house were significantly associated with self-reported health. The number of clubs and hours outside of home were more important factors in the analyses of objective health status than positive health behaviors, after considering age group and education level. These data strongly suggest that social engagement remains an important determinant of physical health into very late adulthood. The discussion focuses on practical applications of these results including social support interventions to maintain or improve late-life health.
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Envejecimiento/psicología , Evaluación Geriátrica/métodos , Estado de Salud , Conducta Social , Apoyo Social , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Louisiana , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: We evaluated the effects of the site of ventricular pacing on left ventricular (LV) synchrony and function in children requiring permanent pacing. METHODS AND RESULTS: One hundred seventy-eight children (aged <18 years) from 21 centers with atrioventricular block and a structurally normal heart undergoing permanent pacing were studied cross-sectionally. Median age at evaluation was 11.2 (interquartile range, 6.3-15.0) years. Median pacing duration was 5.4 (interquartile range, 3.1-8.8) years. Pacing sites were the free wall of the right ventricular (RV) outflow tract (n=8), lateral RV (n=44), RV apex (n=61), RV septum (n=29), LV apex (n=12), LV midlateral wall (n=17), and LV base (n=7). LV synchrony, pump function, and contraction efficiency were significantly affected by pacing site and were superior in children paced at the LV apex/LV midlateral wall. LV dyssynchrony correlated inversely with LV ejection fraction (R=0.80, P=0.031). Pacing from the RV outflow tract/lateral RV predicted significantly decreased LV function (LV ejection fraction <45%; odds ratio, 10.72; confidence interval, 2.07-55.60; P=0.005), whereas LV apex/LV midlateral wall pacing was associated with preserved LV function (LV ejection fraction ≥55%; odds ratio, 8.26; confidence interval, 1.46-47.62; P=0.018). Presence of maternal autoantibodies, gender, age at implantation, duration of pacing, DDD mode, and QRS duration had no significant impact on LV ejection fraction. CONCLUSIONS: The site of ventricular pacing has a major impact on LV mechanical synchrony, efficiency, and pump function in children who require lifelong pacing. Of the sites studied, LV apex/LV midlateral wall pacing has the greatest potential to prevent pacing-induced reduction of cardiac pump function.
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Bloqueo Atrioventricular/patología , Bloqueo Atrioventricular/terapia , Estimulación Cardíaca Artificial/métodos , Ventrículos Cardíacos/patología , Marcapaso Artificial , Adolescente , Bloqueo Atrioventricular/fisiopatología , Niño , Estudios Transversales , Electrocardiografía , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Modelos Cardiovasculares , Radiografía Torácica , Estudios Retrospectivos , Volumen Sistólico/fisiología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: How signals from fatty acid metabolism are translated into changes in food intake remains unclear. Previously we reported that mice with a genetic inactivation of Acads (acyl-coenzyme A dehydrogenase, short-chain), the enzyme responsible for mitochondrial beta-oxidation of C4-C6 short-chain fatty acids (SCFAs), shift consumption away from fat and toward carbohydrate when offered a choice between diets. In the current study, we sought to indentify candidate genes and pathways underlying the effects of SCFA oxidation deficiency on food intake in Acads-/- mice. METHODOLOGY/PRINCIPAL FINDINGS: We performed a transcriptional analysis of gene expression in brain tissue of Acads-/- and Acads+/+ mice fed either a high-fat (HF) or low-fat (LF) diet for 2 d. Ingenuity Pathway Analysis revealed three top-scoring pathways significantly modified by genotype or diet: oxidative phosphorylation, mitochondrial dysfunction, and CREB signaling in neurons. A comparison of statistically significant responses in HF Acads-/- vs. HF Acads+/+ (3917) and Acads+/+ HF vs. LF Acads+/+ (3879) revealed 2551 genes or approximately 65% in common between the two experimental comparisons. All but one of these genes were expressed in opposite direction with similar magnitude, demonstrating that HF-fed Acads-deficient mice display transcriptional responses that strongly resemble those of Acads+/+ mice fed LF diet. Intriguingly, genes involved in both AMP-kinase regulation and the neural control of food intake followed this pattern. Quantitative RT-PCR in hypothalamus confirmed the dysregulation of genes in these pathways. Western blotting showed an increase in hypothalamic AMP-kinase in Acads-/- mice and HF diet increased, a key protein in an energy-sensing cascade that responds to depletion of ATP. CONCLUSIONS: Our results suggest that the decreased beta-oxidation of short-chain fatty acids in Acads-deficient mice fed HF diet produces a state of energy deficiency in the brain and that AMP-kinase may be the cellular energy-sensing mechanism linking fatty acid oxidation to feeding behavior in this model.
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Acil-CoA Deshidrogenasa/deficiencia , Dieta Alta en Grasa/efectos adversos , Transducción de Señal/efectos de los fármacos , Acil-CoA Deshidrogenasa/genética , Adenosina Trifosfato/metabolismo , Animales , Encéfalo , Ácidos Grasos/metabolismo , Hipotálamo/metabolismo , Masculino , Ratones , Ratones Mutantes , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/genéticaRESUMEN
Insulin sensitivity is impaired and ectopic fat (accretion of lipids outside of typical adipose tissue depots) increased in obese adults and adolescents. It is unknown how early in life this occurs; thus, it is important to evaluate young children to identify potential factors leading to the development of metabolic syndrome. We examined an ethnically diverse cohort of healthy, exclusively prepubertal children (N = 123; F = 57, M = 66; age 8.04 ± 0.77 years) to examine differences in insulin sensitivity and ectopic and visceral fat deposition between obese and nonobese youth. Obesity was categorized by age- and sex-adjusted BMI z-scores (nonobese = z-score <2 (N = 94) and obese = z-score ≥2 (N = 29)). Insulin sensitivity was assessed by both a frequently sampled intravenous glucose tolerance test (S(i)) and the homeostatic model assessment of insulin resistance (HOMA(IR)). Intramyocellular lipids (IMCLs) from soleus and intrahepatic lipids (IHLs) were assessed by magnetic resonance spectroscopy, visceral adipose tissue (VAT) by magnetic resonance imaging, and total body fat by dual-energy X-ray absorptiometry. We also examined serum lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol) and blood pressure (diastolic and systolic). Obese children exhibited significantly lower S(i) (5.9 ± 5.98 vs. 13.43 ± 8.18 (mµ/l)(-1)·min(-1), P = 0.01) and HDL-C and higher HOMA(IR) (1.68 ± 1.49 vs. 0.63 ± 0.47, P < 0.0001), IMCL (0.74 ± 0.39 vs. 0.44 ± 0.21% water peak, P < 0.0001), IHL (1.49 ± 1.13 vs. 0.54 ± 0.42% water peak, P < 0.0001), VAT (20.16 ± 8.01 vs. 10.62 ± 5.44 cm(2), P < 0.0001), total cholesterol, triglycerides, low-density lipoprotein cholesterol, and systolic blood pressure relative to nonobese children. These results confirm significantly increased ectopic fat and insulin resistance in healthy obese vs. nonobese children prior to puberty. Excessive adiposity during early development appears concomitant with precursors of type 2 diabetes and the metabolic syndrome.
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Glucemia/metabolismo , Composición Corporal/fisiología , Hígado Graso/diagnóstico , Lípidos/sangre , Síndrome Metabólico/diagnóstico , Obesidad/diagnóstico , Absorciometría de Fotón , Niño , Estudios de Cohortes , Estudios Transversales , Hígado Graso/epidemiología , Hígado Graso/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Espectroscopía de Resonancia Magnética , Masculino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/metabolismo , Obesidad/epidemiología , Obesidad/metabolismoRESUMEN
ABSTRACT We examined the effect of a semantic orienting task during encoding on free recall and recognition of simple line drawings and matching words in middle-aged (44-59 years), older (60-89 years), and oldest-old (90+ years) adults. Participants studied line drawings and matching words presented in blocked order. Half of the participants were given a semantic orienting task and the other half received standard intentional learning instructions. Results confirmed that the pictorial superiority effect was greater in magnitude following semantic encoding compared to the control condition. Analyses of clustering in free recall revealed that oldest-old adults' encoding and retrieval strategies were generally similar to the two younger groups. Self-reported strategy use was less frequent among the oldest-old adults. These data strongly suggest that semantic elaboration is an effective compensatory mechanism underlying preserved episodic memory performance that persists well into the ninth decade of life.
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Envejecimiento/psicología , Memoria Episódica , Memoria , Recuerdo Mental , Reconocimiento en Psicología , Semántica , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Aprendizaje VerbalRESUMEN
In the present study, we examined adult age differences in short-term and working memory performance in middle-aged (45-64 years), young-old (65-74 years), old-old (75-89 years), and oldest-old adults (90 years and over) in the Louisiana Healthy Aging Study. Previous research suggests that measures of working memory are more sensitive to age effects than are simple tests of short-term memory Bopp and Verhaeghen (Journal of Gerontology: Psychological Sciences 60:223-233, 2005), Myerson, Emery, White, and Hale, (Aging, Neuropsychology, and Cognition 10:20-27, 2003). To test this hypothesis, we examined output serial position curves of recall data from three span tasks: forward and backward digit span and size judgment span. Participants' recall patterns in the size judgment span task revealed that the two oldest groups of adults showed the largest decreases in recall performance across output serial positions, but did not differ significantly from each other. Correlation analyses indicated the strongest negative correlation with age occurred with the size judgment span task. Implications of these findings for understanding strategic processing abilities in late life are discussed.
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Memoria a Corto Plazo/fisiología , Recuerdo Mental/fisiología , Anciano , Anciano de 80 o más Años , Encuestas Epidemiológicas , Humanos , Louisiana , Persona de Mediana Edad , Pruebas Neuropsicológicas , Percepción del Tamaño/fisiología , Escalas de WechslerRESUMEN
The authors examined the effects of Hurricanes Katrina and Rita (HKR) on cognitive and psychosocial functioning in a lifespan sample of adults 6 to 14 months after the storms. Participants were recruited from the Louisiana Healthy Aging Study (LHAS). Most were assessed during the immediate impact period and retested for this study. Analyses of pre-and post-disaster cognitive data confirmed that storm-related decrements in working memory for middle-aged and older adults observed in the immediate impact period had returned to pre-hurricane levels in the post-disaster recovery period. Middle-aged adults reported more storm-related stressors and greater levels of stress than the two older groups at both waves of testing. These results are consistent with a burden perspective on post-disaster psychological reactions.
RESUMEN
We examined health-related quality of life in adults in the Louisiana Health Aging Study (LHAS) after Hurricanes Katrina and Rita (HK/R) that made landfall on the U.S. Gulf Coast region in 2005. Analyses of pre- and post-disaster SF-36 scores yielded changes in physical function and bodily pain. Mental health scores were lower for women than men. Gender differences were observed in religious beliefs and religious coping, favoring women. Religious beliefs and religious coping were negatively correlated with physical function, implying that stronger reliance on religiosity as a coping mechanism may be more likely among those who are less physically capable.
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Actitud Frente a la Salud , Tormentas Ciclónicas , Desastres , Salud Mental/estadística & datos numéricos , Espiritualidad , Sobrevivientes/estadística & datos numéricos , Adaptación Psicológica , Factores de Edad , Femenino , Humanos , Louisiana/epidemiología , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Medio Social , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios , Sobrevivientes/psicologíaRESUMEN
The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity.
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Envejecimiento/genética , Apolipoproteínas E/genética , Longevidad/genética , Proteínas de la Membrana/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Variación Genética/genética , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Esfingosina N-AciltransferasaRESUMEN
C57BL/6 J (B6) and CAST/EiJ (CAST), the inbred strain derived from M. musculus castaneus, differ in nutrient intake behaviors, including dietary fat and carbohydrate consumption in a two-diet-choice paradigm. Significant quantitative trait loci (QTLs) for carbohydrate (Mnic1) and total energy intake (Kcal2) are present between these strains on chromosome (Chr) 17. Here we report the refinement of the Chr 17 QTL in a subcongenic strain of the B6.CAST-( D17Mit19-D17Mit91 ) congenic mice described previously. This new subcongenic strain possesses CAST Chr 17 donor alleles from 4.8 to 45.4 Mb on a B6 background. Similar to CAST, the subcongenic mice exhibit increased carbohydrate and total calorie intake per body weight, while fat intake remains equivalent. Unexpectedly, this CAST genomic segment also confers two new physical activity phenotypes: 22% higher spontaneous physical activity levels and significantly increased voluntary wheel-running activity compared with the parental B6 strain. Overall, these data suggest that gene(s) involved in carbohydrate preference and increased physical activity are contained within the proximal region of Chr 17. Interval-specific microarray analysis in hypothalamus and skeletal muscle revealed differentially expressed genes within the subcongenic region, including neuropeptide W (Npw); glyoxalase I (Glo1); cytochrome P450, family 4, subfamily f, polypeptide 1 (Cyp4f15); phospholipase A2, group VII (Pla2g7); and phosphodiesterase 9a (Pde9a). This subcongenic strain offers a unique model for dissecting the contributions and possible interactions among genes controlling food intake and physical activity, key components of energy balance.
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Cromosomas de los Mamíferos , Carbohidratos de la Dieta/administración & dosificación , Ingestión de Energía/genética , Actividad Motora/genética , Animales , Composición Corporal , Calorimetría Indirecta , Cruzamientos Genéticos , Ingestión de Alimentos/genética , Perfilación de la Expresión Génica , Ratones , Ratones Congénicos , Ratones Endogámicos C57BL , Actividad Motora/fisiología , Fenotipo , Análisis por Matrices de Proteínas , Sitios de Carácter Cuantitativo , Regulación hacia ArribaRESUMEN
OBJECTIVES: 1) Report the feasibility of completing the 180-minute Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) in healthy weight, overweight and obese pre-pubertal children and, 2) describe the finalized FSIVGTT protocol after addendums were implemented to decrease the frequency of mild adverse events and improve test completion rates. METHODS: Insulin sensitivity was determined by FSIVGTT. RESULTS: FSIVGTT was attempted in a total of 22 study participants. Insulin sensitivity was successfully assessed in 15 study participants (8 males, 7 females, 10 Caucasian, 4 African American, 1 Pacific Islander, age range 7-9 years). Mean insulin sensitivity was 15.1+/-9.8 (mmicro/l)(-1) min(-1) range 4.4-43.2 (mmicro/l)(-1) min(-1). However, seven study participants experienced mild adverse events of hypoglycemia. Several addendums were made to the FSIVGTT protocol to ensure study participants' comfort and safety, and to decrease the frequency of mild adverse events and increase test completion rates. CONCLUSIONS: Addendums made to FSIVGTT protocol allowed successful completion of FSIVGTT in 15 (68%) of the 22 children. These results demonstrate that FSIVGTT is challenging, yet feasible in healthy lean and obese pre-pubertal children.
Asunto(s)
Glucemia/metabolismo , Prueba de Tolerancia a la Glucosa , Glucosa , Insulina , Obesidad/sangre , Sobrepeso/sangre , Desarrollo Sexual , Negro o Afroamericano , Niño , Estudios Transversales , Estudios de Factibilidad , Femenino , Glucosa/administración & dosificación , Glucosa/efectos adversos , Humanos , Hipoglucemia/inducido químicamente , Infusiones Intravenosas , Insulina/administración & dosificación , Insulina/efectos adversos , Resistencia a la Insulina , Louisiana , Masculino , Nativos de Hawái y Otras Islas del Pacífico , Obesidad/etnología , Obesidad/fisiopatología , Sobrepeso/etnología , Sobrepeso/fisiopatología , Valor Predictivo de las Pruebas , Factores de Tiempo , Población BlancaRESUMEN
BACKGROUND: We tested the hypothesis that ad libitum food intake shows corrective responses over periods of 1-5 d. DESIGN: This was a prospective study of food intake in women. METHODS: Two methods, a weighed food intake and a measured food intake, were used to determine daily nutrient intake during 2 wk in 20 women. Energy expenditure with the use of doubly labeled water was done contemporaneously with the weighed food-intake record. The daily deviations in macronutrient and energy intake from the average 7-d values were compared with the deviations observed 1, 2, 3, 4, and 5 d later to estimate the corrective responses. RESULTS: Both methods of recording food intake gave similar patterns of macronutrient and total energy intakes and for deviations from average intakes. The intraindividual CVs for energy intake ranged from +/-12% to +/-47% with an average of +/-25%. Reported energy intake was 85.5-95.0% of total energy expenditure determined by doubly labeled water. Significant corrective responses were observed in food intakes with a 3- to 4-d lag that disappeared when data were randomized within each subject. CONCLUSIONS: Human beings show corrective responses to deviations from average energy and macronutrient intakes with a lag time of 3-4 d, but not 1-2 d. This suggests that short-term studies may fail to recognize important signals of food-intake regulation that operate over several days. These corrective responses probably play a crucial role in bringing about weight stability.
Asunto(s)
Registros de Dieta , Ingestión de Alimentos/fisiología , Ingestión de Alimentos/psicología , Ingestión de Energía/fisiología , Metabolismo Energético/fisiología , Respuesta de Saciedad/fisiología , Adulto , Consumo de Bebidas Alcohólicas , Agua Corporal/metabolismo , Deuterio , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Femenino , Humanos , Isótopos de Oxígeno , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de TiempoRESUMEN
We examined memory for pictures and words in middle-age (45-59 years), young-old (60-74 years), old-old (75-89 years), and the oldest-old adults (90-97 years) in the Louisiana Healthy Aging Study. Stimulus items were presented and retention was tested in a blocked order where half of the participants studied 16 simple line drawings and the other half studied matching words during acquisition. Free recall and recognition followed. In the next acquisition/test block a new set of items was used where the stimulus format was changed relative to the first block. Results yielded pictorial superiority effects in both retention measures for all age groups. Follow-up analyses of clustering in free recall revealed that a greater number of categories were accessed (which reflects participants' retrieval plan) and more items were recalled per category (which reflects participants' encoding strategy) when pictures served as stimuli compared to words. Cognitive status and working memory span were correlated with picture and word recall. Regression analyses confirmed that these individual difference variables accounted for significant age-related variance in recall. These data strongly suggest that the oldest-old can utilise nonverbal memory codes to support long-term retention as effectively as do younger adults.
Asunto(s)
Memoria/fisiología , Reconocimiento en Psicología/fisiología , Aprendizaje Verbal/fisiología , Percepción Visual/fisiología , Factores de Edad , Anciano/psicología , Anciano de 80 o más Años , Señales (Psicología) , Humanos , Louisiana , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. METHODS AND PROCEDURES: Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m(2)) were randomized to "control (CO)" = 100% energy requirements; "CR" = 25%; "caloric restriction and increased structured exercise (CR+EX)"= 12.5% CR + 12.5% increase in energy expenditure through exercise; or "low-calorie diet (LCD)" = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. RESULTS: At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. DISCUSSION: CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.