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.

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.

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.

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.

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.

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.

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.

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.

Posttranscriptional effect of insulin-like growth factor-I on interleukin-1beta-induced type II-secreted phospholipase A2 gene expression in rabbit articular chondrocytes.

Large amounts of type II-secreted phospholipase A2 (type II sPLA2) are secreted into inflammatory synovial fluid and they are believed to induce the synthesis of lipid mediators by articular chondrocytes. Preliminary experiments showed that insulin-like growth factor-I, which counteracts cartilage degradation in arthritis, inhibits interleukin-1beta-induced type II sPLA2 gene expression in rabbit articular chondrocytes (Berenbaum, F., G. Thomas, S. Poiraudeau, G. Bereziat, M.T. Corvol, and J. Masliah. 1994. FEBS Lett. 340: 51-55). The present study showed that IL-1beta induced the sustained synthesis of prostaglandin E2 and a parallel increase in type II sPLA2 gene expression (assessed by enzymatic activity and Northern blot analysis), but no increase in cytosolic PLA2 gene expression (assessed by Northern and Western blot analysis) or cytosolic PLA2 activity in rabbit articular chondrocytes. IGF-I inhibited both IL-1beta-stimulated PGE2 synthesis and type II sPLA2 gene expression, but had no effect on cytosolic PLA2 gene expression. Nuclear run-on experiments revealed that IL-1beta stimulated the transcription rate of type II sPLA2 gene, giving rise to long-lived mRNA in cells treated with actinomycin D. IGF-I did not affect transcription rate, suggesting that it acts as a post-transcriptional step. Sucrose density gradient analysis of the translation step showed no effect of IGF-I on the entry of type II sPLA2 mRNA into the polysomal pool or on its distribution into the various polysomal complexes, suggesting that IGF-I does not act on the translation of the mRNA. Lastly, IGF-I strongly decreased the half-life of IL-1beta-induced type II sPLA2 mRNA (from 92 to 12 h), suggesting that IGF-I destabilizes mRNA. These data demonstrate that IL-1beta stimulates the transcription rate of the type II sPLA2 gene and gives rise to a very stable mRNA. In contrast, IGF-I decreases the half-life of the type II sPLA2 message.

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.

Hair analysis by LC-MS as evidence of nalbuphine abuse by a nurse.

Individuals in any profession can succumb to chemical abuse. Among the healthcare profession, nurses represent a specific group because of their ease of access to drugs, particularly narcotics. Opioids, potentially highly addictive agents, are usually their drug of choice. Nalbuphine, a synthetic opioid analgesic, is prescribed for moderate-to-severe acute pain, for chronic pain syndromes, and in obstetrics to decrease the adverse respiratory effect of opioid epidural administration. The case of a nurse who was suspected of drug misuse after the disappearance of two nalbuphine ampules in an obstetrics service is described. Because of discrepancies in the results of her blood and urine samples, a sample of head hair was subsequently collected from the nurse. A hair analysis of nalbuphine by liquid chromatography-mass spectrometry has not been previously described. Following decontamination and grinding, hair was mixed with a Söerensen buffer, then subjected to ultrasonic treatment (1 h), and extracted with ethyl acetate. A quantitative analysis was performed with two channels (30 and 45 V), and it is based on a m/z 358 for nalbuphine and a m/z 330 for methylclonazepam as an internal standard. The method was linear from 0.020 to 12 ng/mg of hair (R(2) = 0.972), and the limit of detection and limit of quantitation are 0.020 ng/mg. Accuracy (CV), assessed at 0.4 and 1.6 ng/mg of hair, was 6.18% and 5.77%, respectively, for intraday assays and 4.5% and 10.9% for interday assays. Recovery efficiency at 1.6 ng/mg and 8 ng/mg of hair was 100% and 97.4%, respectively. The hair specimen from the nurse (6 cm) was cut into three equal lengths. Nalbuphine, venlafaxine, and nordiazepam were detected. The concentration of nalbuphine was similar in the three hair locks: 5.07, 7.06, and 5.70 ng/mg of hair. A hair analysis revealed the repeated intake of nalbuphine by the nurse. This person was treated for depression for several months with Effexor (venlafaxine) and Nordaz (nordiazepam) prior to the investigation. Hair appears to be a unique matrix to provide evidence for chronic drug exposure by establishing a historic record that is not possible by blood or urine analysis.

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.

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.

Use of acetaminophen in young subelite athletes.

AIM: The purpose of the present investigation was to look for other drugs besides doping substances in the urine of subelite athletes submitted to heavy training. METHODS: One hundred and forty-one young subelite athletes (in sprint, cycling, middle distance running and handball) were included in the study, with a control group of 89 high school pupils. Drugs were researched by high performance liquid chromatography using a diode array detector. RESULTS: Among the 212 subjects who agreed to give a urine sample, acetaminophen was detected: 9.5% for the subelite athletes versus 1.3% for the control group with a greater difference for sprint and cycling training (26.7% and 20%, respectively). Acetaminophen is used to treat both acute and chronic pains. It relieves pain by elevating the pain threshold. CONCLUSIONS: The use of acetaminophen has to be taken into account by medical staff, trainers and educators.

Influence of acetaminophen consumption on perceived exertion at the lactate concentration threshold.

The purpose of this investigation was to study effects of acetaminophen consumption on ratings of perceived exertion and estimated time limit responses at the lactate threshold. 98 young regional to national level athletes performed a graded exhausting exercise on an outdoor running track to estimate their maximal aerobic velocity and the velocity associated with their lactate concentration threshold. Urine (30 mL) was collected during this test and analysed for numerous substances. During urinary screening for doping substances, 9 acetaminophen consumers (9.2%) among the 98 included athletes were detected. These acetaminophen consumers have significantly lower perceived exertion at velocity corresponding to the lactate concentration threshold than nonconsumers (11.9 +/- 2.1 vs 13.6 +/- 2.1, respectively) although they were at the same relative exercise intensity. This result shows that acetaminophen consumption may have mediated the perceived exertion response at the lactate concentration threshold. This may then suggest that the pain induced by training load could be a factor in use of self-prescribed pain relievers. Such consumption must be taken into account by medical staff, trainers, or educators who have to give information on the use and adverse effects of this substance and to propose palliative methods to their athletes.

Tetrachloroethylene and trichloroethylene fatality: case report and simple headspace SPME-capillary gas chromatographic determination in tissues.

We describe a simple, precise, and sensitive assay of tetrachloroethylene and trichloroethylene in tissues, suitable both for emergency cases and forensic medicine. The method employs headspace solid phase microextraction-capillary gas chromatography and electron capture detection. The case is relative to a 45-year-old woman discovered unconscious in a laundry area. The concentrations of the solvents in tissues were determined and compared to other previously published fatalities.

Smoking behaviour and dietary restraint in young adolescent women: the role of physical self-perceptions.

OBJECTIVE: To investigate the relationship among BMI, smoking consumption, dietary restraint, smoking to control weight, physical self-perception and self-esteem in young female adolescents. METHODS: 702 grade 9 students (14-15 yrs old) completed self-reported validated measures in classroom settings. RESULTS: 26.7% of students had smoked in the last 30 days. Cigarette consumption was low with only 13% smoking one or more cigarettes a day. MANOVA revealed smokers had higher dietary restraint and lower perceptions of physical appearance, conditioning, and self-esteem. A similar pattern emerged for those girls classified as using smoking to control weight. Multiple regression found dietary restraint was predicted by higher BMI, and lower body appearance and self-esteem. CONCLUSIONS: The data provided converging evidence that girls with low self-perceptions are more likely to engage in health-compromising behaviours. Smoking behaviours and dietary restraint were also linked. However, the small effect sizes for smoking behaviours warrants caution.