RESUMEN
There are limited longitudinal data regarding relationships between changes in body composition and bone mineral density (BMD). In 3671 participants aged 46-70 years at baseline, ∆lean mass was a stronger determinant than ∆fat mass of ∆BMD over 6 years. Maintained or increased lean mass may slow down age-related bone loss. PURPOSE: There are limited longitudinal data regarding relationships between changes in body composition and bone mineral density (BMD) with ageing. We examined these in the Busselton Healthy Ageing Study. METHODS: We studied 3671 participants (2019 females) aged 46-70 years at baseline with body composition and BMD assessments by dual-energy x-ray absorptiometry at baseline and after ~6 years. Relationships between changes in total body mass (∆TM), lean mass (∆LM) and fat mass (∆FM) with ∆BMD at total hip, femoral neck and lumbar spine were evaluated using restricted cubic spline modelling (accounting for baseline covariates) and mid-quartile least square means were compared. RESULTS: ∆TM was positively associated with ∆BMD of total hip and femoral neck in both sexes, and spine in females; in females but not males, associations plateaued at ∆TM above ~5kg for all sites. In females, ∆LM was positively associated with ∆BMD of all three sites with plateauing of the relationship at ∆LM above ~1kg. Women in the highest quartile of ∆LM (Q4, mid-quartile value +1.6 kg) had 0.019-0.028 g/cm2 less reduction in BMD than those in the lowest quartile (Q1, -2.1 kg). In males, ∆LM was positively associated with ∆BMD of total hip and femoral neck; men in Q4 (+1.6 kg) had 0.015 and 0.011 g/cm2 less bone loss, respectively, compared with Q1 (-2.7 kg). ∆FM was positively associated with ∆BMD of total hip only in both sexes. CONCLUSION: ∆LM is a stronger determinant than ∆FM of ∆BMD. Maintained or increased LM is associated with less age-related bone loss.
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Densidad Ósea , Osteoporosis , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Australia/epidemiología , Composición Corporal , Osteoporosis/epidemiología , Absorciometría de Fotón , Vértebras LumbaresRESUMEN
Adiposity has a complex relationship with bone health. In 4865 Australian baby boomers (2642 females) aged 45-70 years, we found that higher visceral adipose tissue mass is associated with reduced bone density adjusting for body mass and lifestyle factors, suggesting that excess visceral fat may be deleterious to bone. INTRODUCTION: Increased body mass is associated with higher bone mineral density (BMD), but higher visceral adipose tissue (VAT) may have a negative impact on bone health. In the Busselton Healthy Ageing Study, we examined associations between VAT mass and BMD in 4865 participants (2642 females) aged 45-70 years. METHODS: VAT mass and BMD of whole body, total hip, femoral neck and lumbar spine were measured using DXA. VAT mass was examined as a continuous variable and in quartiles using sex-specific cut-offs. RESULTS: The mean age was 58.0 ± 5.8 years. Males had significantly higher BMI (28.3 ± 3.7 vs 27.5 ± 4.9 kg/m2) and VAT mass (1675 ± 878 vs 882 ± 600 g) than females (both P < 0.001). In males, after adjustment for age, body mass, height and lifestyle factors, VAT mass negatively associated with total body, total hip and femoral neck BMD (ß = - 0.153 to - 0.293, all P < 0.001). Males in the highest quartile of VAT mass (> 2200 g) had significantly lower BMD at all three sites than those in lower quartiles, with estimated BMD differences of 2.3-5.7% (all P < 0.05). In females, VAT mass negatively associated with total body, femoral neck and lumbar spine BMD (ß = - 0.067 to - 0.178, all P < 0.05) and those in the highest quartile (> 1250 g) had significantly lower total body BMD than other quartiles (by 1.7-3.7%, all P < 0.05). CONCLUSION: In middle-aged Australians, after covariate adjustment, higher DXA-derived VAT mass is associated with reduced bone density, suggesting that excess visceral fat may be deleterious to bone, especially in males.
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Densidad Ósea , Grasa Intraabdominal , Absorciometría de Fotón , Tejido Adiposo , Adiposidad , Anciano , Australia/epidemiología , Femenino , Cuello Femoral , Humanos , Grasa Intraabdominal/diagnóstico por imagen , Masculino , Persona de Mediana EdadRESUMEN
Although acute ischemic stroke remains one of the most common causes of death and disability worldwide, it is a potentially treatable condition if appropriately managed in a timely manner. The goals of acute stroke imaging include establishing a diagnosis as fast as possible with (1) accurate infarct quantification, (2) intracranial and cervical vasculature assessment, and (3) brain perfusion analysis for detection of infarct core and potentially salvageable penumbra allowing optimal patient selection for appropriate therapy. Given the extensive number of images generated from acute stroke imaging studies and as "time is brain," this article aims to highlight a logical approach for the radiologist in acute stroke computed tomography imaging in order to accurately interpret and communicate results in a timely manner.
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Isquemia Encefálica/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Angiografía Cerebral/métodos , Angiografía por Tomografía Computarizada/métodos , Humanos , Interpretación de Imagen Radiográfica Asistida por ComputadorRESUMEN
Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47â¯045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.
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Enfermedades Autoinmunes/diagnóstico , Yoduro Peroxidasa/inmunología , Complicaciones del Embarazo/diagnóstico , Nacimiento Prematuro/etiología , Enfermedades de la Tiroides/diagnóstico , Pruebas de Función de la Tiroides , Adulto , Autoanticuerpos/sangre , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/complicaciones , Femenino , Edad Gestacional , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/diagnóstico , Recién Nacido , Embarazo , Complicaciones del Embarazo/sangre , Enfermedades de la Tiroides/sangre , Enfermedades de la Tiroides/complicaciones , Tirotropina/sangre , Tiroxina/sangreRESUMEN
BACKGROUND: An association between depression and obesity is well recognised, but longitudinal studies of depressive symptoms in adolescents as a predictor of body composition are lacking. OBJECTIVE: We examined depressive symptoms at age 14, 17 and 20 years as predictors of lean, fat and bone mass at age 20 years in a birth cohort. SUBJECTS/METHODS: In 1161 participants (569 females) in the Western Australia Pregnancy Cohort (Raine) Study, depressive symptoms were assessed using the Beck Depression Inventory for Youth at age 14 and 17 years, and the Depression, Anxiety and Stress Scale 21 at age 20 years. Participants were further classified into two trajectories using latent class analysis: no/transient and persistent/recurrent depression. At age 20 years, lean body mass (LBM), fat body mass (FBM) and total body bone mass were measured by dual-energy X-ray absorptiometry. RESULTS: In females, accounting for age and lifestyle factors, depression scores at age 14 and 20 years were positively associated with body weight, body mass index (BMI), FBM and % FBM (r=0.110-0.184, P<0.05) but negatively correlated with % LBM (r=-0.120, P<0.05) at age 20 years. Females in the persistent/recurrent depression trajectory (n=99) had significantly higher body weight (+5.1 kg), BMI (+1.8 kg m-2), FBM (+3.9 kg) and % FBM (+2.2%) and significantly lower % LBM (-2.2%) at age 20 years than those with no/transient depression (n=470; all P<0.05). In males, depression scores at age 17 and 20 years were negatively associated with LBM but not weight or BMI, and depression trajectory was not a predictor of body composition at age 20 years. Depression scores and trajectories did not predict bone mass in either males or females. CONCLUSIONS: Depressive symptoms and persistent/recurrent depression in adolescence are predictors of greater adiposity at age 20 years in females, but not males, but do not predict bone mass in either gender.
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Composición Corporal , Depresión/epidemiología , Obesidad/epidemiología , Tamaño de los Órganos , Absorciometría de Fotón , Adiposidad , Adolescente , Imagen Corporal/psicología , Índice de Masa Corporal , Densidad Ósea , Depresión/etiología , Depresión/psicología , Femenino , Humanos , Estilo de Vida , Estudios Longitudinales , Masculino , Encuestas Nutricionales , Obesidad/complicaciones , Obesidad/psicología , Embarazo , Estudios Prospectivos , Factores Sexuales , Medio Social , Factores Socioeconómicos , Australia Occidental/epidemiología , Adulto JovenRESUMEN
The obesity-BMD relationship is complex. In 3045 middle-aged adults, we found that in women (but not men) with discordant fat mass index (FMI)/BMI categories, higher body fat for BMI was associated with lower BMD, suggesting that increased fat mass without an accompanying increase in lean mass may be deleterious to bone. INTRODUCTION: The relationship between obesity and BMD is complex. FMI (fat mass (kg) / height (m)2) is a more accurate measure of fatness than BMI, and depending on body composition, some individuals have discordant BMI/FMI categories. We examined associations between FMI, BMI and BMD in participants in the Busselton Healthy Ageing Study. METHODS: Body composition and BMD of the hip, spine and total body were measured using DXA in 3045 participants (1644 females) aged 45-67 years. Using standard BMI/FMI categories, the participants were classified as underweight/fat deficit, normal, overweight/excess fat, obese I and obese II-III. RESULTS: BMI and FMI categories were concordant in 77.3 % of females and 71.2 % of males. There were 12.9 % females and 13.2 % males in a higher FMI than BMI category (high body fat for BMI), whereas 9.8 % females and 15.6 % males were in a lower category (low body fat for BMI). Females with high body fat for BMI had significantly lower covariate-adjusted BMD at the femoral neck, total hip and total body (differences of 3.8, 5.1 and 2.6 %, respectively, all P < 0.05) than females with low body fat for BMI and lower total body BMD than women with concordant FMI/BMI (by 1.4 %, P = 0.04). In males, BMD did not differ significantly between those who were concordant or discordant for FMI/BMI categories. CONCLUSION: In women (but not men) with discordant FMI/BMI categories, higher body fat for BMI was associated with lower BMD, suggesting that increased fat mass without an accompanying increase in lean mass may be deleterious to bone.
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Tejido Adiposo/anatomía & histología , Índice de Masa Corporal , Densidad Ósea/fisiología , Caracteres Sexuales , Absorciometría de Fotón/métodos , Tejido Adiposo/fisiología , Anciano , Antropometría/métodos , Composición Corporal/fisiología , Femenino , Envejecimiento Saludable/fisiología , Articulación de la Cadera/fisiología , Humanos , Vértebras Lumbares/fisiología , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Sobrepeso/fisiopatologíaRESUMEN
UNLABELLED: The relationships between fat mass and bone mass in young adults are unclear. In 1,183 young Australians, lean body mass had a strong positive relationship with total body bone mass in both genders. Fat mass was a positive predictor of total body bone mass in females, with weaker association in males. INTRODUCTION: Body weight and lean body mass are established as major determinants of bone mass, but the relationships between fat mass (including visceral fat) and peak bone mass in young adults are unclear. The aim of this study was to evaluate the associations between bone mass in young adults and three body composition measurements: lean body mass, fat mass and trunk-to-limb fat mass ratio (a surrogate measure of visceral fat). METHODS: Study participants were 574 women and 609 men aged 19-22 years from the Raine study. Body composition, total body bone mineral content (TBBMC), bone area and areal bone mineral density (TBBMD) were measured using DXA. RESULTS: In multivariate linear regression models with height, lean body mass, fat mass and trunk-to-limb fat mass ratio as predictor variables, lean mass was uniquely associated with the largest proportion of variance of TBBMC and TBBMD in males (semi-partial R(2) 0.275 and 0.345, respectively) and TBBMC in females (semi-partial R(2) 0.183). Fat mass was a more important predictor of TBBMC and TBBMD in females (semi-partial R(2) 0.126 and 0.039, respectively) than males (semi-partial R(2) 0.006 and 0.018, respectively). Trunk-to-limb fat mass ratio had a weak, negative association with TBBMC and bone area in both genders (semi-partial R(2) 0.004 to 0.034). CONCLUSIONS: Lean body mass has strong positive relationship with total body bone mass in both genders. Fat mass may play a positive role in peak bone mass attainment in women but the association was weaker in men; different fat compartments may have different effects.
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Tejido Adiposo/anatomía & histología , Composición Corporal/fisiología , Densidad Ósea/fisiología , Caracteres Sexuales , Absorciometría de Fotón/métodos , Antropometría/métodos , Estatura/fisiología , Índice de Masa Corporal , Femenino , Humanos , Masculino , Delgadez/patología , Adulto JovenRESUMEN
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid-type glutamate receptor (AMPAR) plays a critical role in modulating experience-dependent neuroplasticity, and alterations in AMPAR expression may underlie synaptic dysfunction and disease pathophysiology. Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of dopamine (DA) depletion, our previous work showed exercise increases total GluA2 subunit expression and the contribution of GluA2-containing channels in MPTP mice. The purpose of this study was to determine whether exercise-dependent changes in AMPAR expression after MPTP are specific to the striatopallidal (D2 R) or striatonigral (D1 R) medium spiny neuron (MSN) striatal projection pathways. Drd2 -eGFP-BAC transgenic mice were used to delineate differences in AMPAR expression between striatal D2 R-MSNs and D1 R-MSNs. Striatal AMPAR expression was assessed by immunohistochemical (IHC) staining, Western immunoblotting (WB) of preparations enriched for postsynaptic density (PSD), and alterations in the current-voltage relationship of MSNs. We found DA depletion results in the emergence of GluA2-lacking AMPARs selectively in striatopallidal D2 R-MSNs and that exercise reverses this effect in MPTP mice. Exercise-induced changes in AMPAR channels observed after DA depletion were associated with alterations in GluA1 and GluA2 subunit expression in postsynaptic protein, D2 R-MSN cell surface expression, and restoration of corticostriatal plasticity. Mechanisms regulating experience-dependent changes in AMPAR expression may provide innovative therapeutic targets to increase the efficacy of treatments for basal ganglia disorders, including Parkinson's disease.
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Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Trastornos Parkinsonianos/metabolismo , Condicionamiento Físico Animal/fisiología , Receptores AMPA/biosíntesis , Animales , Western Blotting , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Inmunohistoquímica , Masculino , Ratones , Ratones Transgénicos , Técnicas de Placa-ClampRESUMEN
Plastics are an important new component of the global sedimentary system, and much concern exists about their transport, fate and impact. This study presents the first system-scale assessment of sedimentary storage of microplastic for an estuary, Narragansett Bay, RI (USA), and the measurements of shoreline and seabed sediments add to the growing body of literature demonstrating high coastal concentrations. Microplastic concentrations in sediments ranged from 396 to over 13,000 MP particles kg-1 dry sediment (DW), comparable to other shoreline and seafloor sites located near urban centers. As previously reported for fine sediment and other pollutants, estuarine plastic storage is extensive in Narragansett Bay, especially within the upper urbanized reaches. Over 16 trillion pieces of plastic weighing near 1000 tonnes is calculated to be stored in surface sediments of the Bay based on a power-law fit. This work highlights that estuaries may serve as a significant filter for plastic pollution, and this trapping may have negative consequences for these valuable, productive ecosystems but offer potential for efficient removal.
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Plásticos , Contaminantes Químicos del Agua , Microplásticos , Contaminantes Químicos del Agua/análisis , Bahías , Rhode Island , Ecosistema , Monitoreo del Ambiente , Estuarios , Sedimentos GeológicosRESUMEN
BACKGROUND: Postpartum thyroid dysfunction (PPTD) is characterized by an early hyperthyroid phase followed, with peak prevalence at 6 months, by a hypothyroid phase which carries a risk of long-term hypothyroidism. Iodine has a major effect on thyroid function. Western Australia has previously been shown to be iodine replete. OBJECTIVE: To examine the iodine status of women with and without PPTD and the relationship of iodine status postpartum with long-term hypothyroidism. DESIGN: Case-control with follow-up. PATIENTS: A total of 149 women at 6 months postpartum (74 PPTD, 75 controls) with 98 (46 PPTD, 52 controls) followed up at 12 years. MEASUREMENTS: Urinary iodine concentration (UIC) and thyroid function at 6 months postpartum; thyroid function at 12-year follow-up. RESULTS: At 6 months postpartum, median UIC (quartiles) for observed TSH ranges were: for TSH < 0·4 mU/l 130·0 µg/l (82·0, 170·0); for TSH 0·4-4·0 mU/l 123·0 µg/l (80·5, 168·0); for TSH > 4·0 mU/l 85·0 µg/l (40·0, 141·5), P = 0·018. The odds ratio (OR) of hypothyroid PPTD with each unit of decreasing log iodine was 2·54, (95%CI: 1·47, 4·35), and with UIC < 50 µg/l, OR 4·22, (95%CI: 1·54, 11·55). In the long term, decreased log UIC significantly predicted hypothyroidism at 12-year follow-up (P = 0·002); as did UIC < 100 µg/l (P = 0·03) and UIC < 50 µg/l (P = 0·02). The association was independent of antibody status. CONCLUSION: Low UIC measured at 6 months postpartum is associated with hypothyroid PPTD and independently predicts long-term hypothyroidism. We believe that it results from more severe preceding destructive thyroiditis, with discharge of thyroidal iodine, and thereby predicts a greater risk of long-term hypothyroidism.
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Hipotiroidismo/orina , Yodo/orina , Periodo Posparto , Valor Predictivo de las Pruebas , Trastornos Puerperales , Estudios de Casos y Controles , Femenino , Humanos , Hipotiroidismo/epidemiología , Yodo/metabolismo , Estudios Longitudinales , Trastornos Puerperales/epidemiología , Enfermedades de la Tiroides , Australia OccidentalRESUMEN
BACKGROUND: The long-term risk of hypothyroidism following postpartum thyroid dysfunction (PPTD) is uncertain. Most previous studies have been small, short-term or have lacked a control group. OBJECTIVE: To ascertain the long-term risk of hypothyroidism in women following PPTD. Design and participants A 12-year longitudinal study of 409 women (including 71 with PPTD) who previously participated in a PPTD prevalence study. MEASUREMENTS: The primary outcome measure was hypothyroidism (defined as TSH greater than 4 mU/l or on thyroxine replacement) at follow-up. Outcomes in women with and without PPTD were compared by logistic regression. Receiver operating characteristic analysis was used to determine the optimal cut-off for baseline TSH as a predictor of hypothyroidism in the cohort. RESULTS: At follow-up, hypothyroidism was present in 27 of 71 women who had PPTD at baseline (38%) and 14 of 338 women without PPTD (4%). From multivariate analysis, odds ratios (with 95% confidence intervals) for hypothyroidism were - 4.8 (1.6, 14.1) for PPTD; 8.2 (2.8, 24.6) for positive thyroid peroxidase antibodies (TPOAb); 9.7 (2.6, 37.0) for the hypothyroid phase of PPTD and 51.4 (19.2, 137.5) for hypothyroid PPTD with positive TPOAb. A baseline TSH above 2.6 mU/l was the optimal cut-off for predicting hypothyroidism (sensitivity 76%, specificity 86%). CONCLUSIONS: PPTD is a strong predictor of hypothyroidism in the long-term. Women who present with postpartum hypothyroidism or have positive TPOAb are at particularly high risk, suggesting that close long-term follow-up is advisable if thyroxine replacement is not instituted at an early stage.
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Hipotiroidismo/sangre , Enfermedades de la Tiroides/sangre , Tirotropina/sangre , Adulto , Autoanticuerpos/sangre , Femenino , Estudios de Seguimiento , Humanos , Hipotiroidismo/etiología , Yoduro Peroxidasa/inmunología , Modelos Logísticos , Estudios Longitudinales , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Periodo Posparto , Medición de Riesgo , Factores de Riesgo , Enfermedades de la Tiroides/complicaciones , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: Brain parenchymal hyperdensity on postthrombectomy CT in patients with acute stroke can be due to hemorrhage and/or contrast staining. We aimed to determine whether iodine concentration within contrast-stained parenchyma compared with an internal reference in the superior sagittal sinus on dual-energy CT could predict subsequent intracerebral hemorrhage. MATERIALS AND METHODS: Seventy-one patients with small infarct cores (ASPECTS ≥ 7) and good endovascular recanalization (modified TICI 2b or 3) for anterior circulation large-vessel occlusion were included. Brain parenchymal iodine concentration as per dual-energy CT and the percentage of contrast staining relative to the superior sagittal sinus were recorded and correlated with the development of intracerebral hemorrhage using Mann-Whitney U and Fisher exact tests. RESULTS: Forty-three of 71 patients had parenchymal hyperdensity on initial dual-energy CT. The median relative iodine concentration compared with the superior sagittal sinus was significantly higher in those with subsequent intracerebral hemorrhage (137.9% versus 109.2%, P = .007). By means of receiver operating characteristic analysis, a cutoff value of 100% (iodine concentration relative to the superior sagittal sinus) enabled identification of patients going on to develop intracerebral hemorrhage with 94.75% sensitivity, 43.4% specificity, and a likelihood ratio of 1.71. CONCLUSIONS: Within our cohort of patients, the relative percentage of iodine concentration at dual-energy CT compared with the superior sagittal sinus was a reliable predictor of intracerebral hemorrhage development and may be a useful imaging biomarker for risk stratification after endovascular treatment.
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Hemorragia Cerebral/diagnóstico por imagen , Yodo/análisis , Neuroimagen/métodos , Accidente Cerebrovascular/cirugía , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/cirugía , Hemorragia Cerebral/etiología , Estudios de Cohortes , Procedimientos Endovasculares , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Accidente Cerebrovascular/complicaciones , Seno Sagital Superior/diagnóstico por imagen , TrombectomíaRESUMEN
Paget's disease of bone (PDB) has a strong genetic component. Variants in SQSTM1 are found in up to 40% of patients with a family history of the disease, where a pattern of autosomal dominance with incomplete penetrance is apparent. By contrast, SQSTM1 variants are only found in up to 10% of patients with sporadic disease. It has been hypothesised that the remaining genetic susceptibility to PDB, particularly in familial cases, could be explained by rare genetic variants in loci previously identified by Genome Wide Association Studies. It is likely that polygenic factors are involved in many individuals. In this study we utilised whole exome sequencing to investigate predisposing genetic factors in an unsolved PDB kindred and identified a c.1189Câ¯>â¯T p.L397F variant in DC-STAMP, also known as TM7SF4, that co-segregated with disease. DCSTAMP was identified as a gene of interest in PDB following Genome Wide Association Studies and has been previously shown to play critical roles in osteoclast fusion. The variant we identified has also been reported in association with PDB in a French-Canadian cohort however the significance of this variant was inconclusive. Targeted screening of DCSTAMP in our familial cohort of PDB patients revealed an additional 8 variants; however we did not find a significant association between any of these, including p.L397F, with PDB. Osteoclastogenesis assays from the affected proband and his unaffected brother demonstrated an increase in osteoclast number and nucleation, consistent with the pagetic phenotype. In converse to other established Paget's associated genetic variations such as SQSTM1, TNFRSF11A and OPTN, expression of the mutant DC-STAMP protein attenuated the activation of transcription factors NFκB and AP-1 when exogenously expressed. We found that the p.L397F variant did not influence the subcellular localization of the protein. Based on these findings we conclude that genetic variation in DCSTAMP is not a significant predisposing factor in our specific cohort of PDB patients and the p.L397F variant is unlikely to be a contributing factor in PDB pathogenesis.
RESUMEN
Consensus guidelines for the treatment of Paget's disease of bone have been published, but it is not known how closely these reflect clinical practice. We conducted a multi-centre, stratified, retrospective review of case notes of 531 subjects treated for Paget's disease of bone between 2000 and 2005 in 29 Australian centres. The subjects received 1072 courses of bisphosphonate treatment (pamidronate 363, alendronate 324, risedronate 208, tiludronate 103, zoledronic acid 69, and etidronate 5). The most recent treatment received was oral therapy in 57% of patients (alendronate 29%, risedronate 24%, and tiludronate 4%) and intravenous in 43% (pamidronate 33%, and zoledronic acid 10%). For oral bisphosphonates, the percentages of courses which were at the recommended dosage and duration were: alendronate 33%, risedronate 60% and tiludronate 29%. Pamidronate was administered in a wide range of dosing schedules, most commonly 60 mg every 3 months (18%), 6 months (17%) or annually (12%), whereas zoledronic acid was mainly given as a 4 mg infusion (98%) as a single dose (52%) or annually (19%). Most clinicians reported taking into account symptoms, plasma alkaline phosphatase activity and anatomical location of disease in determining the need for treatment. Patient preference, intolerance of oral therapy and compliance were ranked highest in determining the choice between oral and intravenous therapy. We conclude that oral and intravenous bisphosphonate dosing regimens are both commonly used to treat Paget's disease of bone in Australia. Only a minority of courses of oral bisphosphonate treatment are at the recommended dosage and duration, and there is a lack of consensus on regimens for intravenous treatment.
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Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Osteítis Deformante/terapia , Guías de Práctica Clínica como Asunto , Anciano , Australia , Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Femenino , Guías como Asunto , Humanos , Cooperación del Paciente , Estudios RetrospectivosRESUMEN
OBJECTIVE: Thyroid hormone action influences many metabolic and synthetic processes, but the degree of regulation attributed to genes and environmental factors affecting normal variation remains controversial. DESIGN: We investigated the magnitude of the genetic and environmental determination of serum concentrations of free (f) T3, fT4, TSH and the fT4 x TSH product and their variation, in a large cohort of twin pairs. Female dizygous and monozygous twins (849 and 213 pairs, respectively) from the TwinsUK registry (mean age 45.5, range 18-80 years) were studied. RESULTS: Comparison of thyroid parameters within various groups showed no differences between smoking categories, and higher serum TSH and lower fT3 in subjects with positive thyroid antibodies. Using structural equation modelling, we estimated the heritable contribution to serum thyroid parameters (with 95% confidence intervals) to be 65% (58%-71%) for TSH, 65% (58%-71%) for the fT4 x TSH product, 39% (20%-55%) for fT4 and 23% (3%-41%) for fT3. CONCLUSIONS: We conclude that genetic regulation is a particularly important determinant of TSH and the fT4 x TSH product, and is a less important determinant of fT4 and fT3 concentrations in Caucasian women. These data from a large well-characterized cohort suggest that while there is a strong heritable contribution to serum TSH, variation in fT4 and fT3 concentrations may be less explained by genetic factors and more driven by environmental effects than previously thought.
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Hipófisis/fisiología , Glándula Tiroides/fisiología , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tirotropina/genética , Tiroxina/genética , Triyodotironina/genética , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genética , Reino UnidoRESUMEN
Increased sediment flux to the coastal ocean due to coastal development is considered a major threat to the viability of coral reefs. A change in the nature of sediment supply and storage has been identified in a variety of coastal settings, particularly in response to European colonization, but sedimentation around reefs has received less attention. This research examines the sedimentary record adjacent to a coastal village that has experienced considerable land-use change over the last few decades. Sediment cores were analyzed to characterize composition and sediment accumulation rates. Sedimentation rates decreased seaward across the shelf from 0.85 cm y(-1) in a nearshore bay to 0.19 cm y(-1) in a fore-reef setting. Data reflected a significant (up to 2x) increase over the last approximately 80 years in terrestrial sediment accumulating in the back-reef setting, suggesting greater terrestrial sediment flux to the area. Reef health has declined, and increased turbidity is believed to be an important impact, particularly when combined with additional stressors.
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Antozoos/fisiología , Conservación de los Recursos Naturales , Ecosistema , Monitoreo del Ambiente , Sedimentos Geológicos/análisis , Animales , Ácido Carbónico/química , Plomo/química , Puerto Rico , Agua de Mar/químicaRESUMEN
Emergency physicians will regularly be called upon to care for poisoned patients. The purpose of this article is to review the general approach to the poisoned patient. Specific signs and symptoms will be identified that may clue the clinician into a specific toxin class as a diagnosis. Necessary testing in poisonings will be highlighted. This article will also introduce the basics of gastrointestinal decontamination and antidotes against select poisons.
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Tratamiento de Urgencia/métodos , Intoxicación , Antídotos/uso terapéutico , Descontaminación/métodos , Diagnóstico Diferencial , Urgencias Médicas , Humanos , Intoxicación/diagnóstico , Intoxicación/etiología , Intoxicación/terapiaRESUMEN
BACKGROUND AND PURPOSE: Multiphase CTA, a technique to dynamically assess the vasculature in acute ischemic stroke, was primarily developed to evaluate collateral filling. We have observed that it is also useful in identifying distal anterior circulation occlusions due to delayed anterior circulation opacification on multiphase CTA, an observation we term the "delayed vessel sign." We aimed to determine the usefulness of this sign by comparing multiphase CTA with single-phase CTA. MATERIALS AND METHODS: All 23 distal anterior circulation occlusions during a 2-year period were included. Ten M1-segment occlusions and 10 cases without a vessel occlusion were also included. All patients had follow-up imaging confirming the diagnosis. Initially, the noncontrast CT and first phase of the multiphase CTA study for each patient were blindly evaluated (2 neuroradiologists, 2 radiology trainees) for an anterior circulation occlusion. Readers' confidence, speed, and sensitivity of detection were recorded. Readers were then educated on the "delayed vessel sign," and each multiphase CTA study was re-examined for a vessel occlusion after at least 14 days. RESULTS: There was significant improvement in the sensitivity of detection of distal anterior circulation vessel occlusions (P < .001), overall confidence (P < .001), and time taken to interpret (P < .001) with multiphase CTA compared with single-phase CTA. Readers preferred MIP images compared with source images in >90% of cases. CONCLUSIONS: The delayed vessel sign is a reliable indicator of anterior circulation vessel occlusion, particularly in cases involving distal branches. Assessment of the later phases of multiphase CTA for the delayed vessel sign leads to a significant improvement in the speed and confidence of interpretation, compared with single-phase CTA.