RESUMEN
Introduction: Diabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT). Methods: Thirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups. Results: At baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020). Conclusion: Our data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength-depending on the amount of early cortical pre-damage.
Asunto(s)
Huesos/química , Diabetes Mellitus Tipo 2/fisiopatología , Fracturas Óseas/fisiopatología , Anciano , Densidad Ósea , Huesos/diagnóstico por imagen , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/etiología , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Porosidad , Posmenopausia , Tomografía Computarizada por Rayos XRESUMEN
CONTEXT: Most labs set the lower limit of normal for testosterone at the 2.5th percentile of values in young or age-matched men, an approach that does not consider the physiologic changes associated with various testosterone concentrations. OBJECTIVE: To characterize the dose-response relationships between gonadal steroid concentrations and measures regulated by gonadal steroids in older men. DESIGN, PARTICIPANTS, AND INTERVENTION: 177 men aged 60 to 80 were randomly assigned to receive goserelin acetate plus either 0 (placebo), 1.25, 2.5, 5, or 10 grams of a 1% testosterone gel daily for 16 weeks or placebos for both medications (controls). PRIMARY OUTCOMES: Changes in serum C-telopeptide (CTX), total body fat by dual energy X-ray absorptiometry, and self-reported sexual desire. RESULTS: Clear relationships between the testosterone dosage (or the resulting testosterone levels) and a variety of outcome measures were observed. Changes in serum CTX exceeded changes in the controls in men whose testosterone levels were 0 to 99, 100 to 199, 200 to 299, or 300 to 499 ng/dL, whereas increases in total body fat, subcutaneous fat, and thigh fat exceeded controls when testosterone levels were 0 to 99 or 100 to 199 ng/dL. Sexual desire and erectile function were indistinguishable from controls until testosterone levels were <100 ng/dL. CONCLUSION: Changes in measures of bone resorption, body fat, and sexual function begin at a variety of testosterone concentrations with many outcome measures remaining stable until testosterone levels are well below the stated normal ranges. In light of this variation, novel approaches for establishing the normal range for testosterone are needed.
Asunto(s)
Adiposidad/efectos de los fármacos , Envejecimiento/fisiología , Densidad Ósea/efectos de los fármacos , Goserelina/administración & dosificación , Libido/efectos de los fármacos , Testosterona/administración & dosificación , Adiposidad/fisiología , Administración Cutánea , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , Distribución de la Grasa Corporal , Densidad Ósea/fisiología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada/métodos , Geles , Humanos , Inyecciones Subcutáneas , Libido/fisiología , Masculino , Persona de Mediana Edad , Erección Peniana/efectos de los fármacos , Erección Peniana/fisiología , Testosterona/sangre , Resultado del TratamientoRESUMEN
BACKGROUND: A test that helps predict the time to the final menstrual period (FMP) has been sought for many years. OBJECTIVE: To assess the ability of antimullerian hormone (AMH) measurements to predictions the time to FMP. DESIGN: Prospective longitudinal cohort study. SETTING: The Study of Women's Health Across the Nation. PARTICIPANTS AND MEASUREMENTS: AMH and FSH were measured in 1537 pre- or early perimenopausal women, mean age 47.5â ±â 2.6 years at baseline, then serially until 12 months of amenorrhea occurred. AMH was measured using a 2-site ELISA with a detection limit of 1.85 pg/mL. MAIN OUTCOME MEASURE: Areas under the receiver operating curves (AUC) for AMH-based and FSH-based predictions of time to FMP, stratified by age. Probabilities that women would undergo their FMP in the next 12, 24, or 36 months across a range of AMH values were assessed. RESULTS: AUCs for predicting that the FMP will occur within the next 24 months were significantly greater for AMH-based than FSH-based models. The probability that a woman with an AMH <10 pg/mL would undergo her FMP within the next 12 months ranged from 51% at h<48 years of age to 79% at ≥51 years. The probability that a woman with an AMH >100 pg/mL would not undergo her FMP within the next 12 months ranged from 97% in women <48 years old to 90% in women ≥51 years old. CONCLUSIONS: AMH measurement helps estimate when a woman will undergo her FMP, and, in general, does so better than FSH.
Asunto(s)
Hormona Antimülleriana/sangre , Biomarcadores/sangre , Menopausia , Ciclo Menstrual , Reproducción , Adulto , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estados Unidos , Salud de la MujerRESUMEN
OBJECTIVE: 25-hydroxyvitamin D (25(OH)D) is critical for bone mineralization and may prevent fractures. Understanding vitamin D deficiency trends in midlife women is particularly important given their concurrent menopausal changes that increase risk for fracture. We aimed to evaluate changes in mean 25(OH)D over time and their determinants in a racially, ethnically and socioeconomically diverse cohort of midlife women. DESIGN: A multi-centre prospective cohort study. PATIENTS: 1585 women ages 42-52 years at baseline. MEASUREMENTS: We measured serum 25(OH)D at 2 time points (1998-2000 and 2009-2011). Between-visit change was assessed in the whole cohort and in socioeconomic and demographic subgroups. Among those with vitamin D deficiency (25(OH)D <30 nmol/L) at baseline, we evaluated determinants of persistent deficiency at follow-up. RESULTS: Mean 25(OH)D increased from 53.8 to 70.0 nmol/L (P < 0.001), and the prevalence of deficiency decreased from 20.4% to 9.7% (P < 0.001). While baseline 25(OH)D differed among subgroups, the changes in 25(OH)D were similar among groups. The proportion of women reporting dietary supplement use increased from 40.8% to 67.1% (P < 0.001), and the increase in 25(OH)D was significantly higher in supplement users. Among women with vitamin D deficiency at baseline, White women and supplement users were less likely to remain deficient at follow-up. CONCLUSIONS: Among midlife women, temporal increases in 25(OH)D concentrations are driven largely by increases in supplement use. The proportion of women with 25(OH)D <30 nmol/L and thus at high risk for skeletal consequences remains substantial. Targeted screening for vitamin D deficiency in populations at risk for fragility fracture may be advisable.
Asunto(s)
Vitamina D/análogos & derivados , Adulto , Suplementos Dietéticos , Femenino , Humanos , Estudios Longitudinales , Menopausia , Persona de Mediana Edad , Estudios Prospectivos , Factores Socioeconómicos , Vitamina D/sangre , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/tratamiento farmacológico , Salud de la MujerRESUMEN
OBJECTIVE: To evaluate if baseline pathological knee conditions as assessed via single features of the MR-based Whole-Organ Magnetic Resonance Imaging Scoring (WORMS), standard T2, and T2 gray-level co-occurrence matrix (GLCM) texture parameters of knee cartilage can serve as potential long-term radiological predictors of incident total knee arthroplasty (TKA) 4-7 years later. MATERIALS AND METHODS: Baseline 3-T knee MRIs of 309 subjects from the Osteoarthritis Initiative (n = 81 TKA cases, with right-knee TKA 4-7 years after enrolment, and n = 228 TKA-free matched controls) were evaluated for the presence and severity of pathological knee conditions via modified WORMS. Knee cartilage was segmented and standard T2 cartilage and T2 GLCM texture measures (contrast, variance) were computed. Statistical analysis employed conditional logistic regression. RESULTS: We found that a one-point increase on the joint effusion scale, the bone marrow edema scale or on the cartilage lesion scale at baseline predicted incident TKA (ORs: 2.45, 1.65, and 1.37 respectively (p ≤ 0.003)). For T2 cartilage measurements, we observed that in the lateral femur, a 1-SD increase in T2 relaxation time yielded a 28% increase in the odds of TKA (1.28 [1.09-1.643], p = 0.046). When looking at cartilage texture, we similarly noted that a 1-SD increase in the cartilage texture parameter "contrast" was associated with a 33-40% increased risk of incident TKA in the lateral femur and tibia (0.003 ≤ p ≤ 0.021), as was a 1-SD increase in the texture parameter "variance" in the lateral femur (p = 0.002). CONCLUSION: Radiological evaluation of standard knee MR images via single WORMS features and T2 standard and texture analysis at baseline can help predict the patient's individual risk for an incident TKA 4-7 years later.
Asunto(s)
Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Médula Ósea/diagnóstico por imagen , Cartílago Articular/diagnóstico por imagen , Edema/diagnóstico por imagen , Fémur/diagnóstico por imagen , Hidrartrosis/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Anciano , Médula Ósea/patología , Cartílago Articular/patología , Estudios de Casos y Controles , Edema/patología , Femenino , Fémur/patología , Humanos , Hidrartrosis/patología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/patología , Dimensión del Dolor , Valor Predictivo de las PruebasRESUMEN
Medicinal leeches (Hirudo verbana) thermoregulate with respect to their sanguivorous feeding behavior. Immediate postprandial preferences are for warmer than their initial acclimation temperature (Ta, 21°C, Petersen et al. 2011), while unfed leeches have a lower preferred temperature (Tpref, 12.5°C). This may reduce energy expenditure and defer starvation if feeding opportunities are limited. Energetic benefits may have an associated cost if low temperatures reduce mobility and the ability to locate further hosts. These costs could be limited if mobility is unimpaired at low temperatures, or if acclimation can restore locomotor performance to the levels at Ta. The transition from Ta to the unfed Tpref significantly reduced speed and propulsive cycle frequency during swimming, and extension and retraction rates during crawling. Aerobic metabolic rate was also reduced from 0.20±0.03Wkg-1 at Ta to 0.10±0.03Wkg-1 at Tpref. The Q10 values of 1.7-2.9 for energetic and swimming parameters indicate a substantial temperature effect, although part of the decline in swimming performance can be attributed to temperature-related changes in water viscosity. 6 weeks at Ta resulted in no detectable acclimation in locomotor performance or aerobic metabolism. The energetic savings associated with a lower Tpref in unfed leeches effectively doubled the estimated time until depletion of energy reserves. Given that some mobility is still retained at Tpref, and that acclimation is in itself costly, the energetic benefits of selecting cooler temperatures between feedings may outweigh the costs associated with reduced locomotor performance.
Asunto(s)
Regulación de la Temperatura Corporal , Hirudo medicinalis/fisiología , Aclimatación , Animales , Frío , Metabolismo Energético , Conducta Alimentaria , Locomoción , NataciónRESUMEN
Black women have lower fracture risk compared with white women, which may be partly explained by improved volumetric bone mineral density (vBMD) and bone microarchitecture primarily within the cortical bone compartment. To determine if there are differences in trabecular microstructure, connectivity, and alignment according to race/ethnicity, we performed individual trabecular segmentation (ITS) analyses on high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia in 273 peri- and postmenopausal black (n = 100) and white (n = 173) women participating in the Study of Women's Health Across the Nation in Boston. Unadjusted analyses showed that black women had greater trabecular plate volume fraction, plate thickness, plate number density, and plate surface area along with greater axial alignment of trabeculae, whereas white women had greater trabecular rod tissue fraction (p < 0.05 for all). Adjustment for clinical covariates augmented these race/ethnicity-related differences in plates and rods, such that white women had greater trabecular rod number density and rod-rod connectivity, whereas black women continued to have superior plate structural characteristics and axial alignment (p < 0.05 for all). These differences remained significant after adjustment for hip BMD and trabecular vBMD. In conclusion, black women had more plate-like trabecular morphology and higher axial alignment of trabeculae, whereas white women had more rod-like trabeculae. These differences may contribute to the improved bone strength and lower fracture risk observed in black women. © 2016 American Society for Bone and Mineral Research.
Asunto(s)
Negro o Afroamericano , Hueso Esponjoso , Fracturas de la Tibia , Población Blanca , Adulto , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Factores de Riesgo , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/epidemiología , Fracturas de la Tibia/metabolismoRESUMEN
Escape maneuvers are essential to the survival and fitness of many animals. Escapes are frequently initiated when an animal is already in motion. This may introduce constraints that alter the escape performance. In fish, escape maneuvers and steady, body caudal fin (BCF) swimming are driven by distinct patterns of curvature of the body axis. Pre-existing muscle activity may therefore delay or diminish a response. To quantify the performance consequences of escaping in flow, escape behavior was examined in bluegill sunfish (Lepomis macrochirus) in both still-water and during steady swimming. Escapes executed during swimming were kinematically less variable than those made in still-water. Swimming escapes also had increased response latencies and lower peak velocities and accelerations than those made in still-water. Performance was also lower for escapes made up rather than down-stream, and a preference for down-stream escapes may be associated with maximizing performance. The constraints imposed by pre-existing motion and flow, therefore, have the potential to shape predator-prey interactions under field conditions by shifting the optimal strategies for both predators and prey.
Asunto(s)
Reacción de Fuga , Perciformes , Natación , Análisis de Varianza , Animales , Fenómenos Biomecánicos , Reacción de Fuga/fisiología , Perciformes/fisiología , Conducta Predatoria , Natación/fisiologíaRESUMEN
The evolution of imaginal cells, or stem cell-like cells, contributed to the spectacular diversification of holometabolous insects, which undergo complete metamorphosis. The proliferation and differentiation of these imaginal cells is under the control of juvenile hormone (JH), but which patterning genes respond to JH is currently unknown. Here, the role of Hedgehog (Hh) signaling in the development of imaginal cells was investigated. RNA interference-mediated knockdown of the components of the Hh signaling pathway showed that Hh is required for the proliferation of polymorphic and imaginal cells in Tribolium castaneum. Hh was also necessary for the regeneration of larval appendages. In contrast, knockdown of Hh signaling antagonists, patched and costal 2 led to the overgrowth and precocious maturation of structures derived from imaginal cells and the occasional appearance of ectopic appendages from the head epidermis. In addition, JH suppressed the expression of hh both in vivo and in vitro. Our findings suggest that imaginal cells are created and maintained by modulating Hh signaling. Thus, Hh signaling may have played a critical role during the evolution of complete metamorphosis.
Asunto(s)
Proteínas Hedgehog/metabolismo , Discos Imaginales/citología , Hormonas Juveniles/genética , Metamorfosis Biológica/genética , Tribolium/embriología , Animales , Diferenciación Celular , Proliferación Celular , Regulación del Desarrollo de la Expresión Génica , Proteínas Hedgehog/genética , Proteínas de Insectos/genética , Cinesinas/genética , Larva/crecimiento & desarrollo , Metamorfosis Biológica/fisiología , Receptores Patched , Pupa/crecimiento & desarrollo , Interferencia de ARN , ARN Interferente Pequeño , Receptores de Superficie Celular/genética , Regeneración/genética , Transducción de SeñalRESUMEN
Successful predator evasion is essential to the fitness of many animals. Variation in escape behaviour may be adaptive as it reduces predictability, enhancing escape success. High escape velocities and accelerations also increase escape success, but biomechanical factors likely constrain the behavioural range over which performance can be maximized. There may therefore be a trade-off between variation and performance during escape responses. We have used bluegill sunfish (Lepomis macrochirus) escape responses to examine this potential trade-off, determining the full repertoire of escape behaviour for individual bluegill sunfish and linking this to performance as indicated by escape velocity and acceleration. Fish escapes involve an initial C-bend of the body axis, followed by variable steering movements. These generate thrust and establish the escape direction. Directional changes during the initial C-bend were less variable than the final escape angle, and the most frequent directions were associated with high escape velocity. Significant inter-individual differences in escape angles magnified the overall variation, maintaining unpredictability from a predator perspective. Steering in the latter stages of the escape to establish the final escape trajectory also affected performance, with turns away from the stimulus associated with reduced velocity. This suggests that modulation of escape behaviour by steering may also have an associated performance cost. This has important implications for understanding the scope and control of intra- and inter-individual variation in escape behaviour and the associated costs and benefits.