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1.
Osteoporos Int ; 34(3): 551-561, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36580097

RESUMEN

Osteoporosis care in men is suboptimal due to low rates of testing and treatment. Applying biomechanical computed tomography (BCT) analysis to existing CT scans, we found a high proportion of men with osteoporosis have never been diagnosed or treated. BCT may improve identification of patients at high risk of fracture. PURPOSE: Osteoporosis care in men is suboptimal due to low rates of DXA testing and treatment. Biomechanical computed tomography analysis (BCT) can be applied "opportunistically" to prior hip-containing CT scans to measure femoral bone strength and hip BMD. METHODS: In this retrospective, cross-sectional study, we used BCT in male veterans with existing CT scans to investigate the prevalence of osteoporosis, defined by hip BMD (T-score ≤ - 2.5) or fragile bone strength (≤ 3500 N). 577 men, age ≥ 65 with abdominal/pelvic CTs performed in 2017-2019, were randomly selected for BCT analysis. Clinical data were collected via electronic health records and used with the femoral neck BMD T-score from BCT to estimate 10-year hip fracture risks by FRAX. RESULTS: Prevalence of osteoporosis by BCT increased with age (13.5% age 65-74; 18.2% age 75-84; 34.3% age ≥ 85), with an estimated overall prevalence of 18.3% for men age ≥ 65. In those with osteoporosis (n = 108/577), only 38.0% (41/108) had a prior DXA and 18.6% (7/108) had received osteoporosis pharmacotherapy. Elevated hip fracture risk by FRAX (≥ 3%) did not fully capture those with fragile bone strength. In a multivariate logistic regression model adjusted for age, BMI, race, and CT location, end stage renal disease (odds ratio 7.4; 95% confidence interval 2.3-23.9), COPD (2.2; 1.2-4.0), and high-dose inhaled corticosteroid use (3.7; 1.2-11.8) were associated with increased odds of having osteoporosis by BCT. CONCLUSION: Opportunistic BCT in male veterans provides an additional avenue to identify patients who are at high risk of fractures.


Asunto(s)
Fracturas de Cadera , Osteoporosis , Veteranos , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Densidad Ósea , Estudios Retrospectivos , Prevalencia , Estudios Transversales , Absorciometría de Fotón/métodos , Osteoporosis/diagnóstico por imagen , Osteoporosis/epidemiología , Osteoporosis/complicaciones , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/epidemiología , Fracturas de Cadera/etiología , Tomografía Computarizada por Rayos X/métodos
2.
Rev Endocr Metab Disord ; 24(6): 1011-1029, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37665480

RESUMEN

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.


Asunto(s)
Cirugía Bariátrica , Deficiencia de Vitamina D , Humanos , Vitamina D , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/etiología , Suplementos Dietéticos , Vitaminas/uso terapéutico
3.
Medicina (Kaunas) ; 59(4)2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37109706

RESUMEN

The adrenomedullin level increases in pulmonary arterial hypertension (PAH, and correlates with a high mortality rate. Its active form, bioactive adrenomedullin (bio-ADM), has been recently developed and has significant prognostic applications in acute clinical settings. Aside from idiopathic/hereditary PAH (I/H-PAH), atrial septal defects-associated pulmonary artery hypertension (ASD-PAH) is still prevalent in developing countries and associated with increased mortality. This study aimed to investigate the mortality-wise prognostic value of the plasma bio-ADM level by comparing subjects with ASD-PAH and I/H-PAH with ASD patients without pulmonary hypertension (PH) as a control group. This was a retrospective, observational cohort study. The subjects were Indonesian adult patients who were recruited from the Congenital Heart Disease and Pulmonary Hypertension (COHARD-PH) registry and divided into three groups: (1) ASD without PH (control group), (2) ASD-PAH and (3) I/H-PAH. During right-heart catheterization at the time of diagnosis, a plasma sample was taken and assayed for bio-ADM using a chemiluminescence immunoassay. Follow-up was performed as a part of the COHARD-PH registry protocol in order to evaluate the mortality rate. Among the 120 subjects enrolled: 20 turned out to have ASD without PH, 85 had ASD-PAH and 15 had I/H-PAH. Compared to the control group (5.15 (3.0-7.95 pg/mL)) and ASD-PAH group (7.30 (4.10-13.50 pg/mL)), bio-ADM levels were significantly higher in the I/H-PAH group (median (interquartile range (IQR)): 15.50 (7.50-24.10 pg/mL)). Moreover, plasma bio-ADM levels were significantly higher in subjects who died (n = 21, 17.5%) compared to those who survived (median (IQR): 11.70 (7.20-16.40 pg/mL) vs. 6.90 (4.10-10.20 pg/mL), p = 0.031). There was a tendency toward higher bio-ADM levels in those who died among the PAH subjects, in both ASD-PAH and I/H-PAH groups. In conclusion, the plasma bio-ADM level is elevated in subjects with PAH from both ASD-PAH and I/H-PAH origins, reaching the highest levels in subjects with the I/H-PAH form. A high bio-ADM level tended to be associated with a high mortality rate in all subjects with PAH, indicating a relevant prognostic value for this biomarker. In patients with I/H-PAH, monitoring bio-ADM could represent a valid tool for predicting outcomes, allowing more appropriate therapeutical choices.


Asunto(s)
Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Adulto , Humanos , Pronóstico , Estudios de Cohortes , Adrenomedulina , Biomarcadores , Sistema de Registros
4.
Glob Chang Biol ; 27(20): 5070-5083, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34297435

RESUMEN

Arctic plants are adapted to climatic variability, but their long-term responses to warming remain unclear. Responses may occur by range shifts, phenological adjustments in growth and reproduction, or both. Here, we compare distribution and phenology of 83 arctic and boreal mountain species, sampled identically in the early 20th (1917-1919) and 21st centuries (2017-2018) from a region of northern Sweden that has warmed significantly. We test two compensatory hypotheses to high-latitude warming-upward shifts in distribution, and earlier or extended growth and reproduction. For distribution, we show dramatic upward migration by 69% of species, averaging 6.1 m per decade, especially boreal woodland taxa whose upward expansion has reduced arctic montane habitat by 30%. Twenty percent of summit species showed distributional shifts but downward, especially moisture-associated snowbed flora. For phenology, we detected wide inter-annual variability in the onset of leafing and flowering in both eras. However, there was no detectable change in growing-season length, relating to two mechanisms. First, plot-level snow melt data starting in 1917 demonstrated that melt date, rather than vernal temperatures, better predicts plant emergence, with snow melt influenced by warmer years having greater snowfall-warmer springs did not always result in earlier emergence because snowbeds can persist longer. Second, the onset of reproductive senescence between eras was similar, even when plant emergence was earlier by a month, possibly due to intensified summer heat stress or hard-wired 'canalization' where senescence occurs regardless of summer temperature. Migrations in this system have possibly buffered arctic species against displacement by boreal expansion and warming, but ongoing temperature increases, woody plant invasion, and a potential lack of flexibility in timing of senescence may foreshadow challenges.


Asunto(s)
Ecosistema , Nieve , Regiones Árticas , Cambio Climático , Estaciones del Año , Temperatura
5.
Br J Nutr ; 126(6): 942-949, 2021 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-33272337

RESUMEN

In the past, food-based dietary guidelines (FBDGs) were derived nearly exclusively by using systematic reviews on diet-health relationships and translating dietary reference values for nutrient intake into foods. This approach neglects many other implications that dietary recommendations have on society, the economy and environment. In view of pressing challenges, such as climate change and the rising burden of diet-related diseases, the simultaneous integration of evidence-based findings from different dimensions into FBDGs is required. Consequently, mathematical methods and data processing are evolving as powerful tools in nutritional sciences. The possibilities and reasons for the derivation of FBDGs via mathematical approaches were the subject of a joint workshop hosted by the German Nutrition Society (DGE) and the Federation of European Nutrition Societies (FENS) in September 2019 in Bonn, Germany. European scientists were invited to discuss and exchange on the topics of mathematical optimisation for the development of FBDGs and different approaches to integrate various dimensions into FBDGs. We concluded that mathematical optimisation is a suitable tool to formulate FBDGs finding trade-offs between conflicting goals and taking several dimensions into account. We identified a lack of evidence for the extent to which constraints and weights for different dimensions are set and the challenge to compile diverse data that suit the demands of optimisation models. We also found that individualisation via mathematical optimisation is one perspective of FBDGs to increase consumer acceptance, but the application of mathematical optimisation for population-based and individual FBDGs requires more experience and evaluation for further improvements.


Asunto(s)
Dieta , Alimentos , Política Nutricional , Alemania , Estado Nutricional
6.
Hum Mol Genet ; 26(9): 1716-1731, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-28334964

RESUMEN

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease in children. As CAKUT is a genetically heterogeneous disorder and most cases are genetically unexplained, we aimed to identify new CAKUT causing genes. Using whole-exome sequencing and trio-based de novo analysis, we identified a novel heterozygous de novo frameshift variant in the leukemia inhibitory factor receptor (LIFR) gene causing instability of the mRNA in a patient presenting with bilateral CAKUT and requiring kidney transplantation at one year of age. LIFR encodes a transmembrane receptor utilized by IL-6 family cytokines, mainly by the leukemia inhibitory factor (LIF). Mutational analysis of 121 further patients with severe CAKUT yielded two rare heterozygous LIFR missense variants predicted to be pathogenic in three unrelated patients. LIFR mutants showed decreased half-life and cell membrane localization resulting in reduced LIF-stimulated STAT3 phosphorylation. LIFR showed high expression in human fetal kidney and the human ureter, and was also expressed in the developing murine urogenital system. Lifr knockout mice displayed urinary tract malformations including hydronephrosis, hydroureter, ureter ectopia, and, consistently, reduced ureteral lumen and muscular hypertrophy, similar to the phenotypes observed in patients carrying LIFR variants. Additionally, a form of cryptorchidism was detected in all Lifr-/- mice and the patient carrying the LIFR frameshift mutation. Altogether, we demonstrate heterozygous novel or rare LIFR mutations in 3.3% of CAKUT patients, and provide evidence that Lifr deficiency and deactivating LIFR mutations cause highly similar anomalies of the urogenital tract in mice and humans.


Asunto(s)
Receptores OSM-LIF/genética , Receptores OSM-LIF/metabolismo , Anomalías Urogenitales/genética , Adolescente , Adulto , Animales , Niño , Preescolar , Análisis Mutacional de ADN , Exoma , Femenino , Heterocigoto , Humanos , Lactante , Riñón/anomalías , Riñón/patología , Factor Inhibidor de Leucemia/genética , Factor Inhibidor de Leucemia/metabolismo , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/genética , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/metabolismo , Masculino , Ratones , Ratones Noqueados , Mutación , Análisis de Secuencia de ADN , Uréter/anomalías , Uréter/patología , Sistema Urinario/patología
7.
J Vasc Surg ; 69(2): 497-506, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30292618

RESUMEN

OBJECTIVE: Resistin is a hormone that has been associated with metabolic syndrome and cardiovascular disease. The role of resistin in patients with peripheral artery disease (PAD) has not been fully explored. This study seeks to understand the relationship between serum resistin, vascular function, and cardiovascular outcomes in patients with PAD. METHODS: There were 106 patients with PAD who were recruited between 2011 and 2016. Patients attended a baseline visit during which a comprehensive vascular physiology assessment including medical and surgical history, radial artery tonometry, and flow mediated-vasodilation (FMD) was completed. A blood sample was drawn, and serum resistin was assayed using enzyme-linked immunosorbent assay kits. Using the time of study enrollment as the time of origin, incident major adverse cardiac events (MACEs) were identified by subsequent chart review and defined as a composite end point of myocardial infarction, coronary revascularization, transient ischemic attack, stroke, or death from a cardiac cause. RESULTS: Patients had a mean age of 68 ± 8 years, were largely white (75%), and had comorbidities commonly associated with PAD including hypertension (92%), hyperlipidemia (87%), coronary artery disease (37%), and diabetes mellitus (38%). After stratification by resistin quartile, higher resistin quartiles were significantly associated with an older age, a greater number of pack-years smoked, and a lower estimated glomerular filtration rate. Despite similar comorbidities and medication use, endothelial function, as measured by FMD, was significantly lower with increasing resistin quartile (I, 9.1% ± 3.3%; II, 7.1% ± 3.5%; III, 5.8% ± 4.0%; IV, 5.6% ± 3.5%; P = .002). In multivariable linear regression, higher resistin quartiles (III and IV) were associated with lower FMD relative to quartile I after adjusting for several patient characteristics, medications, and comorbidities (III, -2.26 [95% confidence interval (CI), -4.51 to -0.01; P = .05]; IV, -2.53 [95% CI, -4.87 to -0.20; P = .03]). During a median follow-up period of 36 months (interquartile range, 29-45 months), 21 patients experienced the primary end point. In a Cox proportional hazards model adjusted for smoking status, coronary artery disease, and age, each 1 ng/mL increase in resistin was associated with a 10% increased risk of MACEs (hazard ratio, 1.10; 95% CI, 1.00-1.20; P = .04). CONCLUSIONS: In patients with PAD, higher levels of resistin were associated with impaired endothelial function and an increased rate of MACEs. These results suggest that resistin may be a marker or effector of impaired vascular physiology and adverse cardiac outcomes in patients with PAD. Further research is needed to determine the potential mechanisms by which resistin may impair endothelial function and increase MACEs in this population.


Asunto(s)
Endotelio Vascular/fisiopatología , Cardiopatías/etiología , Enfermedad Arterial Periférica/sangre , Resistina/sangre , Rigidez Vascular , Vasodilatación , Anciano , Biomarcadores/sangre , Femenino , Cardiopatías/sangre , Cardiopatías/diagnóstico , Cardiopatías/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Regulación hacia Arriba
9.
J Surg Res ; 238: 48-56, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30738358

RESUMEN

BACKGROUND: Leptin, adiponectin, and resistin are in a class of hormones called adipokines that are produced by adipocytes and have been implicated in the causal pathway of atherosclerosis. We examined the association between adipokine levels and peripheral artery disease (PAD), hypothesizing that after adjusting for fat mass, leptin and resistin would be higher, whereas adiponectin would be lower, in patients with PAD. METHODS: A cross-sectional sample of 179 predominately male (97%) vascular surgery outpatients was recruited from the San Francisco Veterans Affairs Medical Center (SFVAMC). PAD was defined as either an ankle-brachial index < 0.9 plus symptoms of claudication or prior revascularization for symptomatic PAD (n = 141). Controls had an ankle-brachial index ≥0.9 and no history of atherosclerotic disease (n = 38). Adipokines were assayed using commercially available ELISA kits and values were log-transformed. Fat mass was measured using bioelectrical impedance. RESULTS: In an analysis adjusting for body mass index (BMI) and atherosclerotic risk factors, higher serum leptin was associated with PAD (OR 2.54, 95% CI 1.07-6.01, P = 0.03), whereas high molecular weight adiponectin was inversely associated, though not significantly (OR 0.60, 95% CI 0.33-1.08, P = 0.09). Resistin was not associated with PAD. Sensitivity analyses using fat mass/height2 rather than BMI yielded similar results. CONCLUSIONS: These results indicate that after adjusting for BMI or fat mass, serum leptin levels are positively and independently associated with PAD, whereas high molecular weight adiponectin might be inversely associated. Using a more representative, nonveteran sample, further investigations should focus on the potential role of adipokines in the pathophysiology of PAD as well as determine whether leptin levels have clinical utility in predicting PAD outcomes.


Asunto(s)
Claudicación Intermitente/diagnóstico , Leptina/sangre , Enfermedad Arterial Periférica/diagnóstico , Adiponectina/sangre , Anciano , Estudios Transversales , Femenino , Humanos , Claudicación Intermitente/sangre , Claudicación Intermitente/cirugía , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/cirugía , Estados Unidos , United States Department of Veterans Affairs , Veteranos
10.
Arch Phys Med Rehabil ; 100(9): 1663-1671, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30578772

RESUMEN

OBJECTIVE: To determine if hip fracture patients would have smaller cross-sectional area (CSA) and lower radiological attenuation (suggesting greater fat infiltration) in all trunk muscles as compared to older adults without hip fractures. DESIGN: Cross-sectional analysis of computed tomography (CT) scans. SETTING: Clinical imaging facility. PARTICIPANTS: Forty-one white participants (19 men, 22 women) from the Baltimore Hip Studies seventh cohort at 2 months postfracture were compared to 693 white participants (424 men, 269 women) from the Health, Aging and Body Composition (Health ABC) study at the year 6 visit (N=734). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Trunk muscle CSA and attenuation values were obtained from a single 10-mm, axial CT scan completed at the L4-L5 disc space in each participant. RESULTS: The hip fracture cohort had significantly smaller CSA for all trunk muscles (range: 12.1%-38% smaller) compared to the Health ABC cohort (P<.01), with the exception of the rectus abdominus muscle in men (P=.12). But, hip fracture patients, particularly female patients, had higher attenuation levels (lower intramuscular fat) in all trunk muscles (P<.0001). CONCLUSIONS: Findings are consistent with atrophy of the trunk muscles in the hip fracture population without a high level of intramuscular fat. Future work should evaluate the role of trunk muscle composition in the functional recovery of older adults after hip fracture.


Asunto(s)
Fracturas de Cadera/complicaciones , Fracturas de Cadera/fisiopatología , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Músculos Oblicuos del Abdomen/diagnóstico por imagen , Músculos Oblicuos del Abdomen/patología , Adiposidad , Anciano , Anciano de 80 o más Años , Atrofia/diagnóstico por imagen , Atrofia/etiología , Estudios de Casos y Controles , Femenino , Humanos , Vértebras Lumbares , Masculino , Músculos Paraespinales/diagnóstico por imagen , Músculos Paraespinales/patología , Músculos Psoas/diagnóstico por imagen , Músculos Psoas/patología , Recto del Abdomen/diagnóstico por imagen , Recto del Abdomen/patología , Tomografía Computarizada por Rayos X , Torso
12.
J Ren Nutr ; 28(4): 278-282, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29606304

RESUMEN

OBJECTIVE: Fibroblast growth factor 23 (FGF-23) may be involved in signaling between bone and adipose tissue in dialysis patients, but its role is uncertain. We sought to examine the association between FGF-23 and adiposity and whether this association is mediated in part by leptin. DESIGN/SETTING: We performed univariate and multivariate linear regression analyses using data from 611 participants in a cohort of prevalent hemodialysis patients recruited from dialysis centers in Atlanta, GA and San Francisco, CA from 2009 to 2011. We also investigated the role of leptin in these relationships. SUBJECTS: Participants were aged ≥18 years, English or Spanish speaking, and receiving hemodialysis for at least 3 months. MAIN OUTCOME MEASURES: Outcome measures of adiposity included body mass index, waist circumference, and body fat measured by bioelectrical impedance spectroscopy. RESULTS: Mean age was 56 ± 14 years, 39.8% were female, and median serum FGF-23 was 807 pg/mL. In fully adjusted models, FGF-23 was inversely associated with body mass index (-0.24 kg/m2 per 50% higher FGF-23, 95% confidence interval [CI]: -0.38 to -0.10), waist circumference (-0.44 cm per 50% higher FGF-23, 95% CI: -0.79 to -0.08), and percent body fat (-0.58% per 50% higher FGF-23, 95% CI: -0.79 to -0.37). Leptin was inversely associated with FGF-23. Addition of leptin to body composition models attenuated the associations between FGF-23 and measures of adiposity, but FGF-23 remained significantly associated with percent body fat (-0.17% per 50% higher FGF-23, 95% CI: -0.32 to -0.02). CONCLUSION: We found a negative association between FGF-23 and adiposity that appears to be mediated in part by leptin. As adipose tissue provides a "protective energy depot" for patients with chronic illness, a decrease in adipose tissue may be one mechanism in which higher FGF-23 levels may contribute to increased mortality in dialysis patients.


Asunto(s)
Tejido Adiposo/metabolismo , Adiposidad/fisiología , Factores de Crecimiento de Fibroblastos/sangre , Leptina/sangre , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/terapia , Circunferencia de la Cintura
14.
BMC Musculoskelet Disord ; 18(1): 509, 2017 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-29202732

RESUMEN

BACKGROUND: Hyperkyphosis, an excessive anterior curvature in the thoracic spine, is associated with reduced health status in older adults. Hyperkyphosis is highly prevalent, more common in older women than men. There is no standard intervention to reduce age-related hyperkyphosis. Sex differences in response to a kyphosis-specific exercise intervention are not known. METHODS: We conducted a randomized controlled trial of a targeted kyphosis-specific exercise and postural training program on the primary outcome Cobb angle of kyphosis, and investigated whether the magnitude of change differed between men and women. One hundred twelve participants aged ≥60 years with kyphosis ≥40° were enrolled and randomized to exercise or waitlist control, and 101 participants had analyzable baseline and follow-up radiographs for Cobb angle measurements. A group intervention including 10 participants per group was delivered by a physical therapist, 1-h, twice a week for 3-months. Controls were placed on a waitlist for 3 months before receiving a delayed intervention. Primary outcome was change from baseline to 3-months in Cobb angle measured from standing lateral spine radiographs. Secondary outcomes included change over 3-months in kyphometer-measured kyphosis, physical function and quality of life. Groups were combined for analysis after both received the intervention, and sex differences in response to the intervention were tested with ANOVA. RESULTS: Participants (60 women, 41 men) were 70.0 (SD = 5.7) years old with mean Cobb angle 55.9 (SD = 12.2) degrees at baseline. The active group had higher baseline modified Physical Performance Test scores than control, p = 0.03. Men had greater baseline kyphometer-measured kyphosis, p = 0.09, and higher bone mineral density (BMD), spine strength, more vertebral fractures and diffuse idiopathic skeletal hyperostosis (DISH) than women, p ≤ 0.01. There was no statistically significant difference between groups in change in Cobb at 3-months, p = 0.09, however change in kyphometer-measured kyphosis differed by 4.8 (95% CI:-6.8,-2.7) degrees, p < 0.001, favoring the active group. There were no differences between men and women in change in either kyphosis measurement after intervention, p > 0.1. CONCLUSIONS: A 3-month targeted spine strengthening exercise and posture training program reduced kyphometer-measured, but not radiographic-measured kyphosis. Despite sex differences in baseline kyphosis, BMD, spine strength, fractures and DISH, sex did not affect treatment response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01766674.


Asunto(s)
Terapia por Ejercicio/métodos , Vida Independiente , Cifosis/diagnóstico por imagen , Cifosis/rehabilitación , Postura/fisiología , Caracteres Sexuales , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad
15.
Int J Mol Sci ; 18(12)2017 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-29261130

RESUMEN

Tight regulation of inflammation is very important to guarantee a balanced immune response without developing chronic inflammation. One of the major mediators of the resolution of inflammation is the transcription factor: the nuclear factor erythroid 2-like 2 (Nrf2). Stabilized following oxidative stress, Nrf2 induces the expression of antioxidants as well as cytoprotective genes, which provoke an anti-inflammatory expression profile, and is crucial for the initiation of healing. In view of this fundamental modulatory role, it is clear that both hyper- or hypoactivation of Nrf2 contribute to the onset of chronic diseases. Understanding the tight regulation of Nrf2 expression/activation and its interaction with signaling pathways, known to affect inflammatory processes, will facilitate development of therapeutic approaches to prevent Nrf2 dysregulation and ameliorate chronic inflammatory diseases. We discuss in this review the principle mechanisms of Nrf2 regulation with a focus on inflammation and autophagy, extending the role of dysregulated Nrf2 to chronic diseases and tumor development.


Asunto(s)
Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Animales , Antioxidantes/farmacología , Autofagia , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Factor 2 Relacionado con NF-E2/química , Factor 2 Relacionado con NF-E2/genética
16.
Hum Genet ; 135(1): 69-87, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26572137

RESUMEN

Congenital anomalies of the kidneys and urinary tract (CAKUT) are genetically highly heterogeneous leaving most cases unclear after mutational analysis of the around 30 causative genes known so far. Assuming that phenotypes frequently showing dominant inheritance, such as CAKUT, can be caused by de novo mutations, de novo analysis of whole-exome sequencing data was done on two patient-parent-trios to identify novel CAKUT genes. In one case, we detected a heterozygous de novo frameshift variant in TBC1D1 encoding a Rab-GTPase-activating protein regulating glucose transporter GLUT4 translocation. Sequence analysis of 100 further CAKUT cases yielded three novel or rare inherited heterozygous TBC1D1 missense variants predicted to be pathogenic. TBC1D1 mutations affected Ser237-phosphorylation or protein stability and thereby act as hypomorphs. Tbc1d1 showed widespread expression in the developing murine urogenital system. A mild CAKUT spectrum phenotype, including anomalies observed in patients carrying TBC1D1 mutations, was found in kidneys of some Tbc1d1 (-/-) mice. Significantly reduced Glut4 levels were detected in kidneys of Tbc1d1 (-/-) mice and the dysplastic kidney of a TBC1D1 mutation carrier versus controls. TBC1D1 and SLC2A4 encoding GLUT4 were highly expressed in human fetal kidney. The patient with the truncating TBC1D1 mutation showed evidence for insulin resistance. These data demonstrate heterozygous deactivating TBC1D1 mutations in CAKUT patients with a similar renal and ureteral phenotype, and provide evidence that TBC1D1 mutations may contribute to CAKUT pathogenesis, possibly via a role in glucose homeostasis.


Asunto(s)
Exoma , Proteínas Activadoras de GTPasa/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación , Anomalías Urogenitales/genética , Reflujo Vesicoureteral/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Animales , Niño , Preescolar , Femenino , Proteínas Activadoras de GTPasa/química , Humanos , Lactante , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Datos de Secuencia Molecular , Linaje , Homología de Secuencia de Aminoácido , Adulto Joven
17.
Development ; 140(10): 2139-48, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23633511

RESUMEN

Although the Hox genes are the main factors involved in the generation of diversity along the anterior/posterior body axis of segmented organisms, it is still largely unknown how these genes act in single cells to determine specific traits at precise developmental stages. The aim of this study was to understand the mechanisms by which Hox genes of the Bithorax complex (Bx-C) of Drosophila act to define segmental differences in the ventral nerve cord of the central nervous system. To achieve this, we have focused on the specification of the leucokinin-expressing neurons. We find that these neurons are specified from the same progenitor neuroblast at two different developmental stages: embryonic and larval neurogenesis. We show that genes of the Bx-C acted in postmitotic cells to specify the segment-specific appearance of leucokinergic cells in the larval and adult ventral nerve cord.


Asunto(s)
Drosophila melanogaster/embriología , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Sistema Nervioso/embriología , Animales , Tipificación del Cuerpo , Linaje de la Célula , Sistema Nervioso Central/embriología , Sistema Nervioso Central/metabolismo , Cruzamientos Genéticos , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Genotipo , Inmunohistoquímica , Neuropéptidos/metabolismo , Fenotipo , Células Madre/citología , Factores de Tiempo
18.
Curr Osteoporos Rep ; 14(6): 337-344, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27714580

RESUMEN

PURPOSE OF REVIEW: This study aims to describe bone marrow fat changes in diabetes and to discuss the potential role of marrow fat in skeletal fragility. RECENT FINDINGS: Advances in non-invasive imaging have facilitated marrow fat research in humans. In contrast to animal studies which clearly demonstrate higher levels of marrow fat in diabetes, human studies have shown smaller and less certain differences. Marrow fat has been reported to correlate with A1c, and there may be a distinct marrow lipid saturation profile in diabetes. Greater marrow fat is associated with impaired skeletal health. Marrow fat may be a mediator of skeletal fragility in diabetes. Circulating lipids, growth hormone alterations, visceral adiposity, and hypoleptinemia have been associated with greater marrow fat and may represent potential mechanisms for the putative effects of diabetes on marrow fat, although other factors likely contribute. Additional research is needed to further define the role of marrow fat in diabetic skeletal fragility and to determine whether marrow fat is a therapeutic target.


Asunto(s)
Tejido Adiposo/metabolismo , Adiposidad , Médula Ósea/metabolismo , Diabetes Mellitus/metabolismo , Osteoporosis/metabolismo , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/patología , Animales , Densidad Ósea , Médula Ósea/diagnóstico por imagen , Médula Ósea/patología , Diabetes Mellitus/epidemiología , Humanos , Imagen por Resonancia Magnética , Osteoblastos , Osteoporosis/epidemiología , Espectroscopía de Protones por Resonancia Magnética
19.
BMC Genomics ; 15: 639, 2014 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-25081296

RESUMEN

BACKGROUND: DNA-based methods like PCR efficiently identify and quantify the taxon composition of complex biological materials, but are limited to detecting species targeted by the choice of the primer assay. We show here how untargeted deep sequencing of foodstuff total genomic DNA, followed by bioinformatic analysis of sequence reads, facilitates highly accurate identification of species from all kingdoms of life, at the same time enabling quantitative measurement of the main ingredients and detection of unanticipated food components. RESULTS: Sequence data simulation and real-case Illumina sequencing of DNA from reference sausages composed of mammalian (pig, cow, horse, sheep) and avian (chicken, turkey) species are able to quantify material correctly at the 1% discrimination level via a read counting approach. An additional metagenomic step facilitates identification of traces from animal, plant and microbial DNA including unexpected species, which is prospectively important for the detection of allergens and pathogens. CONCLUSIONS: Our data suggest that deep sequencing of total genomic DNA from samples of heterogeneous taxon composition promises to be a valuable screening tool for reference species identification and quantification in biosurveillance applications like food testing, potentially alleviating some of the problems in taxon representation and quantification associated with targeted PCR-based approaches.


Asunto(s)
Biovigilancia , Calidad de los Alimentos , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Análisis de Secuencia de ADN , Animales , Calibración , Mapeo Cromosómico , Bases de Datos Genéticas , Humanos , Carne , Especificidad de la Especie
20.
Prev Chronic Dis ; 11: E226, 2014 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-25539130

RESUMEN

INTRODUCTION: Nutrition counseling is important for veterans undergoing gastric bypass surgery. The aim of this study was to explore the relationship between the number of nutrition visits a patient attended and change in body mass index (BMI) after gastric bypass surgery for the veteran population. METHODS: A retrospective study examined veterans (N = 79) who underwent Roux-en-Y gastric bypass surgery from June 2004 through July 2010. Spearman's correlation and multivariate regression analysis were used to analyze data. RESULTS: A significant correlation was found between the number of postoperative nutrition visits and the change in postsurgery BMI at 2 years (Spearman's ρ = 0.21; P = .017). After adjusting for age, sex, and race, the association between postsurgery nutrition visits and BMI change persisted (ß = 0.255; 95% confidence interval, 0.015-0.581; P = .039). CONCLUSION: Veterans with more nutrition visits following Roux-en-Y gastric bypass surgery experienced greater declines in BMI. This finding underscores the importance of the dietitian on the bariatric surgery team.


Asunto(s)
Derivación Gástrica , Ciencias de la Nutrición/educación , Obesidad Mórbida/cirugía , Visita a Consultorio Médico/estadística & datos numéricos , Veteranos/estadística & datos numéricos , Adulto , Anciano , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Educación en Salud/métodos , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Obesidad Mórbida/epidemiología , Cuidados Posoperatorios , Estudios Retrospectivos , San Francisco , Resultado del Tratamiento , Estados Unidos
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