Differential effects of abaloparatide and teriparatide on hip cortical volumetric BMD by DXA-based 3D modeling.

In postmenopausal osteoporotic women in ACTIVE, abaloparatide reduced fracture risk and increased areal bone mineral density (BMD) more than teriparatide at the hip and wrist. DXA-based 3D modeling showed significantly greater increases in hip cortical volumetric BMD with abaloparatide versus teriparatide. This may explain differences reported in aBMD by DXA. INTRODUCTION: In ACTIVE, abaloparatide (ABL) increased bone mineral density (BMD) shown by dual-energy X-ray absorptiometry (DXA) while reducing fracture incidence in postmenopausal osteoporotic women. Changes in DXA BMD with ABL, 80 µg, were significantly greater than with open-label teriparatide (TPTD), 20 µg, at cortical sites including total hip, femoral neck, and 1/3 distal radius. The purpose of this study was to better understand the relative effects of ABL and TPTD on cortical and cancellous compartments in the proximal femur. METHODS: Hip DXA images from a subset of randomly selected patients in the ACTIVE trial (n = 250/arm) were retrospectively analyzed using three-dimensional modeling methods (3D-SHAPER software) to evaluate changes from baseline at months 6 and 18. RESULTS: Similar significant increases in trabecular volumetric BMD (vBMD, + 9%) and cortical thickness (+ 1.5%) were observed with ABL and TPTD by 3D-DXA at 18 months. In contrast, only ABL significantly increased cortical vBMD versus baseline (+ 1.3%), and changes in both cortical vBMD and cortical surface BMD were significantly greater with ABL versus TPTD. In the TPTD group, changes in cortical vBMD were inversely correlated with changes in serum CTX (carboxy-terminal telopeptide of type I collagen) and PINP (procollagen type I N-terminal propeptide), suggesting that higher bone turnover may have attenuated cortical gains. CONCLUSION: These results suggest previously reported differences in areal BMD increases between ABL and TPTD may be due to differential effects on cortical vBMD. Further studies are warranted to investigate how these differences affect therapeutic impact on hip strength in postmenopausal women with osteoporosis.

Feasibility, safety and effectiveness of a pilot 16-week home-based, impact exercise intervention in postmenopausal women with low bone mineral density.

The feasibility and efficacy of home-based, impact exercise are unclear. This pilot impact exercise intervention was feasible and safe, and improved bone health and physical function in postmenopausal women with low bone density. Appropriately designed randomised controlled trials are now required to determine whether such interventions can reduce fracture risk. INTRODUCTION: The feasibility and efficacy of impact exercise in postmenopausal women with low bone mineral density (BMD) are unclear. We aimed to determine adherence, safety and changes in BMD, bone microarchitecture and physical function following a pilot home-based, impact exercise intervention in postmenopausal women with low BMD. METHODS: Fifty community-dwelling postmenopausal women with BMD T-scores < - 1.0 participated in 16 weeks of home-based impact exercise progressively increasing to 50 multi-directional unilateral hops on each leg daily. Bone density and structure were assessed by lumbar spine and hip dual-energy X-ray absorptiometry (DXA), 3D modelling (3D-SHAPER) of hip DXA scans and distal tibial high-resolution peripheral quantitative computed tomography scans. Physical performance was assessed by repeated chair stand time and stair climb time. RESULTS: Forty-four women (mean ± SD age 64.5 ± 7.5 years) completed the intervention, with adherence of 85.3 ± 17.3%. Reasons for withdrawal were related soreness (n = 2), unrelated injury (n = 1) and loss of interest (n = 3). Femoral neck areal BMD increased by 1.13 ± 3.76% (p = 0.048). Trabecular volumetric BMD (vBMD) increased at the total hip (2.27 ± 7.03%; p = 0.038) and femoral neck increased (3.20 ± 5.39%; p < 0.001). Distal tibia total vBMD increased by 0.32 ± 0.88% (p = 0.032) and cortical cross-sectional area increased by 0.55 ± 1.54% (p = 0.034). Chair stand and stair climb time improved by 2.34 ± 1.88 s (p < 0.001) and 0.27 ± 0.49 s (p < 0.001), respectively. CONCLUSION: A 16-week home-based, impact exercise was feasible and may be effective in improving femoral neck areal BMD, total hip and distal tibial vBMD and physical function in postmenopausal women. Appropriately designed randomised controlled trials are now required to determine whether such interventions can reduce fracture risk in older populations.

Evaluación de la densidad mineral ósea y de los parámetros de 3D-Shaper en la hipofosfatasia congénita del adulto / Agitated/inattentive children: explanatory models

Objetivo: Evaluar la densidad mineral ósea (DMO) y parámetros de 3D-Shaper a nivel de fémur proximal (FP) en adultos con hipofosfatasia (HPP) confirmada genéticamente y compararlos en aquellos sujetos con y sin fracturas. Material y métodos: Análisis transversal de datos densitométricos y de arquitectura ósea de la visita basal de un estudio longitudinal en el que se incluyeron pacientes con HPP. Se realizó un estudio densitométrico (Lunar Prodigy, GE iDXA) en FP y se empleó el software 3D-Shaper (version 2,7. Galgo Medical). Resultados: Se incluyeron 33 adultos con HPP con mutaciones en heterocigosis. Un 63,6% (21/33) fueron mujeres (42,9% postmenopáusicas), y 8 de los varones (66,6%) fueron mayores de 50 años. La media de edad fue 50,56±15,08 años, el 30,3% (10/33) tuvieron fracturas previas traumáticas, y un 15,2% (5/33), de estrés. La prevalencia de osteoporosis en CF fue del 11,8% (2/17) y de osteopenia, 82,4% (14/17). En premenopáusicas y varones jóvenes se detectó baja masa ósea para la edad en un 12,5% (2/16). Al comparar sujetos con fracturas de estrés y sin ellas, así como con traumáticas, no hubo diferencias en DMO. El 3D-Shaper mostró disminución del grosor cortical (mm) en pacientes con fracturas de estrés [1,8 (1,77-1,89)] frente a sujetos sin ellas [1,94 (1,87-2,03, p=0,03)] y en comparación con los que tuvieron fracturas traumáticas [1,97 (1,88-2,04), p=0,03]. Conclusión: Estos datos reflejan una discreta repercusión densitométrica en formas más leves del adulto. Estudios de arquitectura ósea pudieran resultar de interés para determinar pacientes susceptibles de presentar fracturas de estrés. (AU)

Objetivo: To evaluate bone mineral density (BMD) and 3D-Shaper parameters at the proximal femur (FP) level in adults with genetically confirmed hypophosphatasia (HPP) and to compare them in those subjects with and without fractures. Material and methods: Crosssectional analysis of densitometric data and bone architecture from the baseline visit of a longitudinal study in which patients with HPP were included. A densitometric study (Lunar Prodigy, GE iDXA) was carried out in FP using 3D-Shaper software (version 2.7. Galgo Medical). Results: 33 adults with HPP with heterozygous mutations were included. 63.6% (21/33) were women (42.9% postmenopausal), and 8 of the men (66.6%) were older than 50 years. The mean age was 50.56±15.08 years, 30.3% (10/33) had previous traumatic fractures and 15.2% (5/33) presented stress fractures. The prevalence of osteoporosis in CF was 11.8% (2/17) and of osteopenia, 82.4% (14/17). In premenopausal women and young men, low bone mass was detected for age in 12.5% (2/16). When comparing subjects with and without stress fractures, as well as traumatic ones, there were no differences in BMD. The 3D-Shaper showed a decrease in cortical thickness (mm) in patients with stress fractures [1.8 (1.77-1.89)] compared to subjects without them [1.94 (1.87-2.03, p=0.03)] and compared to those with traumatic fractures [1.97 (1.88-2.04), p=0.03]. Conclusions: These data reflect a discrete densitometric impact in milder forms of the adult. Bone architecture studies could be of interest in determining patients susceptible to stress fractures. (AU)

¿Pueden las mediciones 3D derivadas de la DXA lumbar predecir fracturas en las vértebras dorsales? / Can 3D measurements obtained by lumbar DXA predict fractures in the dorsal vertebrae?

OBJETIVO: Valorar la asociación de las mediciones tridimensionales (3D) derivadas de la absorciometría de rayos X de energía dual (DXA) lumbar con las fracturas osteoporóticas en las vértebras dorsales. MATERIAL Y MÉTODOS: Analizamos retrospectivamente 32 mujeres postmenopáusicas: 16 con fracturas incidentes en las vértebras dorsales y 16 controles sin ningún tipo de fractura. Las DXA lumbares se adquirieron en la visita inicial (es decir, antes del evento de fractura) y se midió la densidad mineral ósea de área (DMOa) en las vértebras L1 a L4. Las mediciones 3D derivadas de la DXA se evaluaron utilizando un software de modelado 3D (3D-SHAPER). La densidad mineral ósea volumétrica (DMOv) se calculó en el hueso trabecular, cortical e integral. También se midió el grosor cortical y la DMO superficial (DMOs) cortical. Las diferencias en las mediciones derivadas de la DXA entre los grupos de fracturados y controles se evaluaron utilizando una prueba t de Student no pareada. También se calculó la razón de probabilidades (OR) y el área bajo la curva característica operativa del receptor (AUC). RESULTADOS: En el presente estudio caso-control ajustado por edad no se encontraron diferencias significativas entre los grupos de fracturados y controles en términos de peso (ρ = 0,44), altura (ρ = 0,25) y DMOa (ρ = 0,11). Sin embargo, sí se encontraron diferencias significativas (ρ < 0,05) en la DMOv integral y trabecular y en la DMOs cortical. La DMOv trabecular en el cuerpo vertebral fue la medida que mejor discriminó entre ambos grupos, con un AUC de 0,733, respecto a 0,682 para la DMOa. CONCLUSIÓN: Este estudio muestra la capacidad de los modelos 3D derivados de la DXA lumbar para discriminar entre sujetos con fracturas incidentes en las vértebras dorsales y controles. Es necesario analizar cohortes mayores para determinar si estas mediciones podrían mejorar la predicción del riesgo de fractura en la práctica clínica

OBJECTIVE: To assess the relation between three-dimensional (3D) measurements obtained by lumbar dual energy X-ray absorptiometry (DXA) and osteoporotic fractures in dorsal vertebrae. MATERIAL AND METHODS: We analysed retrospectively 32 postmenopausal women, allocated to two groups: 16 women in the experimental group, who presented incident fractures of the dorsal vertebrae, and 16 women in the control group, who did not show any type of fracture. Measurements of the (aBMD) of vertebrae L1 through L4 were taken at the initial visit (i.e., prior to the fracture event) by lumbar dual-energy x-ray absorptiometries (DXA). 3D measurements obtained by DXA were evaluated using 3D modelling software (3D-SHAPER). Volumetric bone mineral density (vBMD) was calculated in the trabecular, cortical and integral bone. Cortical thickness and cortical surface BMD (sBMD) were also measured. Differences in measurements derived from the DXA between the experimental and control groups were assessed using an unpaired Student t-test. The odds ratio (OR) and the area under the receiver operating characteristic curve (AUC) were also determined. RESULTS: In the present age-adjusted case-control study, no significant differences were found between the experimental and control groups in terms of weight (ρ = 0.44), height (ρ = 0.25) and aBMD (ρ = 0.11). However, significant differences (ρ < 0.05) were found in the integral and trabecular vBMD and in the cortical sBMD. Trabecular vBMD in the vertebral body was the measure that best discriminated between both groups, with an AUC of 0.733, compared to 0.682 of the aBMD. CONCLUSION: This study shows the ability of 3D models resultant from lumbar DXAs to discern between subjects with incident fractures in the dorsal vertebrae and control subjects. It is necessary to analyse larger cohorts to establish if these measurements could improve the prediction of fracture risk in clinical practice

Fragilidad relativa de fémures osteoporóticos evaluados con DXA y simulación de caídas con elementos finitos guiados por radiografías de urgencias / Relative fragility of osteoporotic femurs assessed withDXA and simulation of finite element falls guided byemergency X-rays

OBJETIVO: El diagnóstico de osteoporosis se ha fundamentado en la medición de la densidad mineral ósea, si bien esta variable tiene una capacidad limitada en la discriminación de pacientes con o sin fracturas. La aplicación del análisis de elementos finitos (FE) sobre imágenes volumétricas de tomografía computarizada ha mejorado la clasificación de sujetos hasta 90%, aunque la dosis de radiación, complejidad y coste no aconsejan su práctica regular. Nuestro objetivo es aplicar el análisis FE a modelos tridimensionales con absorciometría radiológica dual (3D-DXA), para clasificar pacientes con fractura osteoporótica de fémur proximal y sin fractura. MATERIAL Y MÉTODOS: Se seleccionó una cohorte de 111 pacientes con osteoporosis densitométrica: 62 con fractura y 49 sin ella. Se utilizaron modelos FE sujeto-específicos para el impacto, como la simulación estática de la caída lateral. Las simulaciones de impacto permiten identificar la región crítica en el 95% de los casos, y la respuesta mecánica a una fuerza lateral máxima. Se realizó un análisis mediante un clasificador discriminativo (Support Vector Machine) por tipo de fractura, tejido y género, utilizando las mediciones DXA y parámetros biomecánicos. RESULTADOS: Los resultados mostraron una sensibilidad de clasificación del 100%, y una tasa de falsos negativos de 0% para los casos de fractura de cuello para el hueso trabecular en las mujeres. Se identifica la variable tensión principal mayor (MPS) como el mejor parámetro para la clasificación. CONCLUSIÓN: Los resultados sugieren que el uso de modelos 3D-DXA podría ayudar a discriminar mejor a los pacientes con elevado riesgo de fracturarse

OBJETIVE: The diagnosis of osteoporosis has been based on the measurement of bone mineral density, although this variable has a limited capacity in discriminating patients with or without fractures. The application of finite element analysis (FE) on computed tomography volumetric images has improved the classification of subjects by up to 90%, although the radiation dose, complexity, and cost do not favor their regular practice. Our objective is to apply FE analysis to three-dimensional models with dual-energy x-ray absorptiometry (3D-DXA), to classify patients who present osteoporotic fracture of the proximal femur and those without fracture. MATERIAL AND METHODS: A cohort of 111 patients with densitometric osteoporosis was selected: 62 with fracture and 49 without it. Subject-specific FE models for impact were used, such as static simulation of lateral fall. Impact simulations allow identifying the critical region in 95% of cases, and the mechanical response to maximum lateral force. An analysis was performed using a discriminative classifier (Support Vector Machine) by fracture type, tissue and gender, using DXA measurements and biomechanical parameters. RESULTS: The results showed a classification sensitivity of 100%, and a false negative rate of 0% for cases of neck fracture for trabecular bone in women. The variable major main stress (MPS) is identified as the best parameter for the classification. CONCLUSION: The results suggest that using 3D-DXA models help in order to better discriminate patients with raised fracture risk

Associations between physical activity and bone structure in older adults: does the use of self-reported versus objective assessments of physical activity influence the relationship?

Associations of current and previous physical activity (PA) with bone health are unclear. In postmenopausal women with low bone mineral density (BMD), current PA was positively associated with femoral neck BMD and microarchitecture. Past PA was positively associated with tibial microarchitecture. PA appears beneficial for bone health throughout the lifespan. INTRODUCTION: To compare associations of current and past self-reported bone-specific physical activity, and current accelerometer-determined physical activity (PA), with bone structure (bone mineral density [BMD] and microarchitecture) in postmenopausal women with osteopenia or osteoporosis. METHODS: Fifty community-dwelling postmenopausal women (mean age 64.4 ± 7.7) with hip or spine BMD T-score < - 1.0 SD were recruited for an exercise intervention. At baseline, current, past and total Bone-specific Physical Questionnaire (BPAQ) scores were self-reported, and percentages of sedentary, light and moderate to vigorous PA (MVPA) were objectively determined by accelerometer measurements. Bone structure was assessed by lumbar spine and hip dual-energy X-ray absorptiometry (DXA), 3D modelling algorithms (3D-SHAPER) of hip DXA scans and distal tibial high-resolution peripheral quantitative computed tomography (HR-pQCT) scans. RESULTS: Current BPAQ scores and MVPA were significantly positively associated with femoral neck areal BMD (ß = 0.315, p = 0.031 and ß = 0.311, p = 0.042, respectively) following multivariable adjustments. MVPA was also positively associated with femoral cortical surface BMD (ß = 0.333, p = 0.028) and mean cortical thickness (ß = 0.374, p = 0.013). Past and total BPAQ scores demonstrated positive associations with tibial trabecular number (ß = 0.391, p = 0.008 and ß = 0.381, p = 0.010, respectively), and negative associations with trabecular separation (ß = - 0.396, p = 0.006 and ß = - 0.380, p = 0.009, respectively) and distribution (ß = - 0.411, p = 0.004 and ß = - 0.396, p = 0.006, respectively). Current BPAQ score was positively associated with tibial cortical periosteal perimeter (ß = 0.278, p = 0.014). CONCLUSION: BPAQ scores were most consistently associated with tibial bone parameters in older women, with past PA having lasting benefits for trabecular microarchitecture, and current PA positively associated with cortical bone.

Discrimination of osteoporosis-related vertebral fractures by DXA-derived 3D measurements: a retrospective case-control study.

A retrospective case-control study assessing the association of DXA-derived 3D measurements with osteoporosis-related vertebral fractures was performed. Trabecular volumetric bone mineral density was the measurement that best discriminates between fracture and control groups. INTRODUCTION: The aim of the present study was to evaluate the association of DXA-derived 3D measurements at the lumbar spine with osteoporosis-related vertebral fractures. METHODS: We retrospectively analyzed a database of 74 postmenopausal women: 37 subjects with incident vertebral fractures and 37 age-matched controls without any type of fracture. DXA scans at the lumbar spine were acquired at baseline (i.e., before the fracture event for subjects in the fracture group), and areal bone mineral density (aBMD) was measured. DXA-derived 3D measurements, such as volumetric BMD (vBMD), were assessed using a DXA-based 3D modeling software (3D-SHAPER). vBMD was computed at the trabecular, cortical, and integral bone. Cortical thickness and cortical surface BMD were also measured. Differences in DXA-derived measurements between fracture and control groups were evaluated using unpaired t test. Odds ratio (OR) and area under the receiver operating curve (AUC) were also computed. Subgroup analyses according to fractured vertebra were performed. RESULTS: aBMD of fracture group was 9.3% lower compared with control group (p < 0.01); a higher difference was found for trabecular vBMD in the vertebral body (- 16.1%, p < 0.001). Trabecular vBMD was the measurement that best discriminates between fracture and control groups, with an AUC of 0.733, against 0.682 for aBMD. Overall, similar findings were observed within the subgroup analyses. The L1 vertebral fractures subgroup had the highest AUC at trabecular vBMD (0.827), against aBMD (0.758). CONCLUSION: This study showed the ability of cortical and trabecular measurements from DXA-derived 3D models to discriminate between fracture and control groups. Large cohorts need to be analyzed to determine if these measurements could improve fracture risk prediction in clinical practice.

Cardiometabolic assessment of lamin A/C gene mutation carriers: a phenotype-genotype correlation.

AIMS: Mutations of the LMNA gene encoding lamin A/C induce heterogeneous phenotypes ranging from cardiopathies and myopathies to lipodystrophies. The aim of this study was to compare cardiometabolic complications in patients with heterozygous LMNA mutations at the 482nd codon, the 'hotspot' for partial lipodystrophy, with carriers of other, non-R482 LMNA mutations. METHODS AND RESULTS: This study included 29 patients with R482 LMNA mutations, 29 carriers of non-R482 LMNA mutation and 19 control subjects. Cardiac and metabolic phenotypes were compared between groups. A family history of either cardiac implantable electronic devices (CIEDs; P < 0.001) or sudden death (P < 0.01) was more frequent in non-R482 than R482 carriers. The non-R482 carriers also had more abnormalities on electrocardiography and received CIEDs more often than R482 carriers (P < 0.001). On cardiac ultrasound, non-R482 patients had greater frequencies of left atrial enlargement (P < 0.05) and lower left ventricular ejection fractions (P < 0.01) than R482 carriers. In contrast, R482 carriers had lower BMI (P < 0.05), leptin (P < 0.01) and fat mass (P < 0.001), but higher intra-/total abdominal fat-mass ratios (P < 0.001) and prevalences of diabetes (P < 0.01) and hypertriglyceridaemia (P < 0.05) than non-R482 carriers, with a trend towards more coronary artery disease. However, non-R482 carriers had higher intra-/total abdominal fat-mass ratios (P < 0.02) and prevalences of diabetes (P < 0.001) and hypertriglyceridaemia (P < 0.05) than the controls. CONCLUSION: Non-R482 carriers present more frequently with arrhythmias than R482 carriers, who twice as often have diabetes, suggesting that follow-up for laminopathies could be adjusted for genotype. Non-R482 mutations require ultra-specialized cardiac follow-up, and coronary artery disease should not be overlooked. Although overlapping phenotypes are found, LMNA mutations essentially lead to tissue-specific diseases, favouring genotype-specific pathophysiological mechanisms.

Effects of osteoporosis drug treatments on cortical and trabecular bone in the femur using DXA-based 3D modeling.

Effects of osteoporosis drugs on proximal femur cortical and trabecular bone were studied using dual-energy x-ray absorptiometry (DXA)-based 3D modeling method. Changes observed in this head-to-head study were consistent with those obtained using computed tomography in the literature. INTRODUCTION: The aim of the present study was to assess the effects of osteoporosis drugs on cortical and trabecular bone at the proximal femur using DXA-based 3D modeling. METHODS: We retrospectively analyzed 155 patients stratified by treatments: naive of treatment (NAIVE), alendronate (AL), denosumab (DMAB), and teriparatide (TPTD). DXA scans were performed at baseline and after treatment, and areal bone mineral density at spine and femur were measured. A software algorithm (3D-SHAPER) was used to derive 3D models from hip DXA scans and compute: trabecular and cortical volumetric BMD (vBMD), cortical thickness (Cth), and cortical surface BMD (cortical sBMD). Changes from baseline were normalized at 24 months and evaluated in terms or percentage. RESULTS: After 24 months, a non-significant decrease was observed for trabecular vBMD, Cortical sBMD, Cth, and cortical vBMD (- 2.3, - 0.8, - 0.3, and - 0.5%) in the NAIVE group. Under AL and DMAB, significant increases were observed in trabecular vBMD (3.8 and 7.3%), cortical vBMD (1.4 and 2.0%), and cortical sBMD (1.5 and 3.6%). An increase in Cth was observed in patients under DMAB (1.8%). Under TPTD, a significant increase in Trabecular vBMD was observed (5.9%) associated with a non-significant increase of Cth (+ 1%) concomitant with a decrease in cortical vBMD (- 1.1%). CONCLUSION: Results obtained in this head-to-head study are consistent with those obtained using computed tomography in the literature. DXA-based modeling techniques could complement standard DXA examination to monitor treatment effects on trabecular and cortical compartments.

The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease.

BACKGROUND: Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. AIM: The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. METHODS: Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. RESULTS: The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. CONCLUSIONS: Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.

Prevalence of new psychoactive substances and prescription drugs in the Belgian driving under the influence of drugs population.

Driving under the influence of drugs (DUID) is a worldwide problem. Several countries have adopted DUID legislations which prove their deterrent effect and impact on road safety. However, the use of new psychoactive substances (NPS) and prescription drugs is not known, as the applied roadside screening tests have not yet been adapted for these compounds. In this study, 558 blood samples obtained during roadside controls in Belgium (January to August 2015) after a positive Drugwipe 5S® test and 199 oral fluid (OF) samples obtained from negatively screened test pads were analyzed. The NPS positivity rate was 7% in blood, while it reached 11% in OF. NPS detected were: diphenidine, ketamine, 4-fluoroamphetamine, 2-amino-indane, methoxetamine, α-PVP, methiopropamine, a mix of 5-MAPB/5-EAPB, TH-PVP, mephedrone, methedrone, 4-methylethylcathinone, 5-MeO-DALT, 4-Acetoxy-DiPT, AB Fubinaca, FUB-JWH018, JWH020, trifluoromethylphenylpiperazine, and ethylphenidate. Moreover, 17% of blood samples (and 5% of OF) contained an analgesic drug, 10% (0.5%) a benzodiazepine/hypnotic, 5% (2%) an antidepressant, 2% (3%) an antipsychotic, 2% an antiepileptic drug, and 1% methylphenidate. The presence of NPS in the young (and predominately male) DUID population is proven. Furthermore, a high level of poly-drug use including combinations of NPS, licit, and drugs of abuse was observed. Further research concerning the development of on-site NPS detection techniques should be established. Meanwhile, the effects of combined drug use on driving ability and the physical/psychological signs after NPS use should be performed to improve the on-site DUID detection of NPS by police officers, so they can engage in blood sampling for a general unknown screening.

Analysis of the evolution of cortical and trabecular bone compartments in the proximal femur after spinal cord injury by 3D-DXA.

Marked trabecular and cortical bone loss was observed at the proximal femur short-term after spinal cord injury (SCI). 3D-DXA provided measurement of vBMD evolution at both femoral compartments and cortical thinning, thereby suggesting that this technique could be useful for bone analysis in these patients. INTRODUCTION: SCI is associated with a marked increase in bone loss and risk of osteoporosis development short-term after injury. 3D-DXA is a new imaging analysis technique providing 3D analysis of the cortical and trabecular bone from DXA scans. The aim of this study was to assess the evolution of trabecular macrostructure and cortical bone using 3D-DXA in patients with recent SCI followed over 12 months. METHODS: Sixteen males with recent SCI (< 3 months since injury) and without antiosteoporotic treatment were included. Clinical assessment, bone mineral density (BMD) measurements by DXA, and 3D-DXA evaluation at proximal femur (analyzing the integral, trabecular and cortical volumetric BMD [vBMD] and cortical thickness) were performed at baseline and at 6 and 12 months of follow-up. RESULTS: vBMD significantly decreased at integral, trabecular, and cortical compartments at 6 months (- 8.8, - 11.6, and - 2.4%), with a further decrease at 12 months, resulting in an overall decrease of - 16.6, - 21.9, and - 5.0%, respectively. Cortical thickness also decreased at 6 and 12 months (- 8.0 and - 11.4%), with the maximal decrease being observed during the first 6 months. The mean BMD losses by DXA at femoral neck and total femur were - 17.7 and - 21.1%, at 12 months, respectively. CONCLUSIONS: Marked trabecular and cortical bone loss was observed at the proximal femur short-term after SCI. 3D-DXA measured vBMD evolution at both femoral compartments and cortical thinning, providing better knowledge of their differential contributory role to bone strength and probably of the effect of therapy in these patients.

Acute Methiopropamine Intoxication After "Synthacaine" Consumption.

Use of methiopropamine (MPA), a synthetic metamfetamine analog, has been detected since 2011 in Europe, but there is limited information on its acute toxicity. A 30-year-old man was admitted to the emergency department in a confused state, with paranoid delusion, auditory and visual hallucinatory experiences, and incoherent speech following the use of "synthacaine" (a slang term derived from "synthetic" and "cocaine"). Toxicological screening for pharmaceuticals and drugs of abuse by liquid chromatography-diode-array detector, gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS-MS) detected MPA, which was subsequently quantified by a specific LC-MS-MS method. Of note, 13 h after presentation to the emergency department, the plasma concentration of MPA was 14 ng/mL. This case report confirms the toxicity of MPA and the need for toxicological analysis to confirm the substance actually ingested by users of new psychoactive substances.

Interplay between bile acid metabolism and microbiota in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) physiopathology is multifactorial and roles for both microbiota and bile acid (BA) modifications have been proposed. We investigated role of dysbiosis, transit pattern and BA metabolism in IBS. METHODS: Clinical data, serum, and stool samples were collected in 15 healthy subjects (HS), 16 diarrhea-predominant (IBS-D) and 15 constipation-predominant IBS (IBS-C). Fecal microbiota composition was analyzed by real-time PCR. Sera and fecal BA profiles, 7α-C4 levels, and in vitro BA transformation activity by fecal microbiota were measured by mass spectrometry. Serum Fibroblast Growth Factor 19 (FGF19) was assayed by ELISA. KEYS RESULTS: Dysbiosis was present in IBS patients with an increase in Escherichia coli in IBS-D patients (p = 0.03), and an increase in Bacteroides (p = 0.01) and Bifidobacterium (p = 0.04) in IBS-C patients. Sera primary and amino-conjugated BA were increased in IBS-D (63.5 ± 5.5%, p = 0.01 and 78.9 ± 6.3%, p = 0.03) and IBS-C patients (55.9 ± 5.5%, p = 0.04 and 65.3 ± 6.5%, p = 0.005) compared to HS (37.0 ± 5.8% and 56.7 ± 8.1%). Serum 7α-C4 and FGF19 levels were not different among all three groups. Fecal primary BA were increased in IBS-D patients compared to HS, including chenodeoxycholic acid which has laxative properties (25.6 ± 8.5% vs 3.5 ± 0.6%, p = 0.005). Bile acid deconjugation activity was decreased in IBS-D (p = 0.0001) and IBS-C (p = 0.003) feces. Abdominal pain was positively correlated with serum (R = 0.635, p < 0.001) and fecal (R = 0.391, p = 0.024) primary BA. CONCLUSIONS & INFERENCES: Different sera and fecal BA profiles in IBS patients could be secondary to dysbiosis and further differences between IBS-C and IBS-D could explain stool patterns. This study opens new fields in IBS physiopathology and suggests that modification of BA profiles could have therapeutic potential.

Prevention of isoniazid toxicity by NAT2 genotyping in Senegalese tuberculosis patients.

Isoniazid (INH), recommended by WHO (World Health Organization) in the treatment of tuberculosis (TB), is metabolized primarily by the genetically polymorphic N-acetyltransferase 2 (NAT2) enzyme. The human population is divided into three different phenotypic groups according to acetylation rate: slow, intermediate, and fast acetylators. The objective of this study was to explore the relationship between NAT2 genotypes and the serum concentrations of INH. Blood samples from 96 patients with TB were taken for the analysis. NAT2 polymorphisms on coding region were examined by polymerase chain reaction (PCR) direct sequencing; the acetylation status was obtained by measuring isoniazid (INH) and its metabolite, acetylisoniazid (AcINH) in plasma was obtained by using the liquid chromatography coupled to mass spectrometry. TB patients were distributed into two groups of fast and slow acetylators according to the acetylation index calculated based on the plasma concentration of INH in the 3rd hour (T3) after an oral dose. Our PCR analysis identified several alleles, where NAT2*4, NAT2*5A, NAT2*6A, and NAT2*13A were the most important. The concentrations of INH varied between 1.10 mg/L and 13.10 mg/L at the 3rd hour and between 0.1 and 9.5 mg/L at the 6th hour. The use of the acetylating index I3 allowed the classification of tested patients into two phenotypic groups: slow acetylators (44.3% of TB patients), and rapid acetylators (55.7%). Patient's acetylation profile provides valuable information on their therapeutic, pharmacological, and toxicological responses.

Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a multifactorial disease for which a dysbiosis of the gut microbiota has been described. Bile acids (BA) could play a role as they are endogenous laxatives and are metabolized by gut microbiota. We compared fecal BA profiles and microbiota in healthy subjects (HS) and patients with diarrhea-predominant IBS (IBS-D), and we searched for an association with symptoms. METHODS: Clinical features and stool samples were collected in IBS-D patients and HS. Fecal BA profiles were generated using HPLC coupled to tandem mass spectrometry. The fecal microbiota composition was assessed by q-PCR targeting dominant bacterial groups and species implicated in BA transformation. KEY RESULTS: Fourteen IBS-D patients and 18 HS were included. The two groups were comparable in terms of age and sex. The percentage of fecal primary BA was significantly higher in IBS-D patients than in HS, and it was significantly correlated with stool consistency and frequency. Fecal counts of all bacteria, lactobacillus, coccoides, leptum and Faecalibacterium prausnitzii were similar. There was a significant increase of Escherichia coli and a significant decrease of leptum and bifidobacterium in IBS-D patients. CONCLUSIONS & INFERENCES: We report an increase of primary BA in the feces of IBS-D patients compared to HS, correlated with stool consistency and frequency. A dysbiosis of different bacterial groups was detected, some of them involved in BA transformation. As the gut microbiota is the exclusive pathway to transform primary into secondary BA, this suggests a functional consequence of dysbiosis, leading to lower BA transformation.

In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells.

Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.

Coupling 2D/3D registration method and statistical model to perform 3D reconstruction from partial x-rays images data.

3D reconstructions of the spine from a frontal and sagittal radiographs is extremely challenging. The overlying features of soft tissues and air cavities interfere with image processing. It is also difficult to obtain information that is accurate enough to reconstruct complete 3D models. To overcome these problems, the proposed method efficiently combines the partial information contained in two images from a patient with a statistical 3D spine model generated from a database of scoliotic patients. The algorithm operates through two simultaneous iterating processes. The first one generates a personalized vertebra model using a 2D/3D registration process with bone boundaries extracted from radiographs, while the other one infers the position and the shape of other vertebrae from the current estimation of the registration process using a statistical 3D model. Experimental evaluations have shown good performances of the proposed approach in terms of accuracy and robustness when compared to CT-scan.

3D reconstruction of the spine from biplanar X-rays using parametric models based on transversal and longitudinal inferences.

Reconstruction methods from biplanar X-rays provide 3D analysis of spinal deformities for patients in standing position with a low radiation dose. However, such methods require an important reconstruction time and there is a clinical need for fast and accurate techniques. This study proposes and evaluates a novel reconstruction method of the spine from biplanar X-rays. The approach uses parametric models based on longitudinal and transversal inferences. A first reconstruction level, dedicated to routine clinical use, allows to get a fast estimate (reconstruction time: 2 min 30 s) of the 3D reconstruction and accurate clinical measurements. The clinical measurements precision (evaluated on asymptomatic subjects, moderate and severe scolioses) was between 1.2 degrees and 5.6 degrees. For a more accurate 3D reconstruction (complex pathologies or research purposes), a second reconstruction level can be obtained within a reduced reconstruction time (10 min) with a fine adjustment of the 3D models. The mean shape accuracy in comparison with CT-scan was 1.0 mm. The 3D reconstruction method precision was 1.8mm for the vertebrae position and between 2.3 degrees and 3.9 degrees for the orientation. With a reduced reconstruction time, an improved accuracy and precision and a method proposing two reconstruction levels, this approach is efficient for both clinical routine uses and research purposes.

Present forest biodiversity patterns in france related to former Roman agriculture.

Combined archaeological and ecological investigations in a large ancient oak forest in Central France have revealed a dense network of ancient human settlements dating from the Roman period. We demonstrate a strong correlation between present-day forest plant diversity patterns and the location of Roman farm buildings. Plant species richness strongly increases toward the center of the settlements, and the frequency of neutrophilous and nitrogen-demanding species is higher. This pattern is paralleled by an increase in soil pH, available P, and delta(15)N, indicating the long-term impact of former agricultural practices on forest biogeochemical cycles. These extensive observations in a forested region on acid soils complement and confirm previous results from a single Roman settlement on limestone. Ancient Roman agricultural systems are increasingly being identified in contemporary French forests; the broad extent and long-lasting effects of previous cultivation shown in this study require that land-use history be considered as a primary control over biodiversity variations in many forest landscapes, even after millennia of abandonment.