Early deficits in olfaction are associated with structural and molecular alterations in the olfactory system of a Huntington disease mouse model.

Olfactory dysfunction and altered neurogenesis are observed in several neurodegenerative disorders including Huntington disease (HD). These deficits occur early and correlate with a decline in global cognitive performance, depression and structural abnormalities of the olfactory system including the olfactory epithelium, bulb and cortices. However, the role of olfactory system dysfunction in the pathogenesis of HD remains poorly understood and the mechanisms underlying this dysfunction are unknown. We show that deficits in odour identification, discrimination and memory occur in HD individuals. Assessment of the olfactory system in an HD murine model demonstrates structural abnormalities in the olfactory bulb (OB) and piriform cortex, the primary cortical recipient of OB projections. Furthermore, a decrease in piriform neuronal counts and altered expression levels of neuronal nuclei and tyrosine hydroxylase in the OB are observed in the YAC128 HD model. Similar to the human HD condition, olfactory dysfunction is an early phenotype in the YAC128 mice and concurrent with caspase activation in the murine HD OB. These data provide a link between the structural olfactory brain region atrophy and olfactory dysfunction in HD and suggest that cell proliferation and cell death pathways are compromised and may contribute to the olfactory deficits in HD.

Loss of bone mineral density in hemiplegic patients after stroke: Prospective single-center study.

The aim of our prospective single-center study was to assess the loss of bone mineral density (BMD) in the year following stroke with hemiplegia. We evaluated functional disability and bone mineral density (BMD) in 18 patients immediately following and at 1 year of stroke with hemiplegia. The most significant variation in BMD concerns the femoral neck on the hemiplegic side: -0.0551±0.0548g/cm2: -6.85%. This loss is correlated with the functional motor score (Fugl-Meyer Assessment) (r=0.7573; P=0.0004). During follow-up, 11/18 patients fell and 2/18 had a fracture.

Olfactory bulb atrophy and caspase activation observed in the BACHD rat models of Huntington disease.

Olfactory dysfunction is observed in several neurological disorders, including Huntington disease (HD), and correlates with global cognitive performance, depression and degeneration of olfactory regions in the brain. Despite clear evidence demonstrating olfactory dysfunction in HD patients, only limited details are available in murine models and the underlying mechanisms are unknown. In order to determine if alterations in the olfactory bulb (OB) are observed in HD we assessed OB weight or area from 3 to 12 months of age in the BACHD transgenic lines (TG5 and TG9). A significant decrease in the OB was observed at 6 and 12 months of age compared to WT. We also detected increased mRNA and protein expression of mutant huntingtin (mHTT) in the OB of TG5 compared to TG9 at specific ages. Despite the higher expression of mHTT in the TG5 OBs, there was increased nuclear accumulation of mHTT in the OB of TG9 compared to WT and TG5 rats. As we observed atrophy of the OB in the BACHD rats we assessed for caspase activation, a known mechanism underlying the cell death observed in HD. We characterized caspase-3, -6, -8 and - 9 mRNA and protein expression levels in the OB of the BACHD transgenic lines at 3, 6 and 12 months of age. Alterations in caspase mRNA and protein expression were detected in the TG5 and TG9 lines. However, the changes observed in the mRNA and protein levels are in some cases discordant, suggesting that the caspase protein modifications detected may be more attributable to post-translational modifications. The caspase activation studies support that cell death may be increased in the rodent HD OB and further our understanding of the olfactory dysfunction and the role of caspases in the pathogenesis of HD.

Higher prevalence of vertebral fractures in systemic mastocytosis, but not in cutaneous mastocytosis and idiopathic mast cell activation syndrome.

Little is known about osteoporosis in mast cell disorders (MCDs) not related to systemic mastocytosis. We described osteoporosis and fractures in MCDs and showed that systemic mastocytosis was the only studied MCDs associated with osteoporotic vertebral fractures. INTRODUCTION: To describe osteoporosis (OP) and fragility fractures in mast cell disorders (MCDs). METHODS: We retrospectively analyzed data concerning all successive patients with systemic mastocytosis (SM), cutaneous mastocytosis (CM), and mast cell activation syndromes (MCAS) diagnosed in our mastocytosis expert center between 2004 and 2015. We collected data concerning demographic profiles, clinical signs of MCD, osteoporosis, fractures, densitometry, and biological assessment of MCD. We compared CM and MCAS patients with SM patients with regard to the characteristics of OP and fragility fractures. RESULTS: We assessed 89 SM patients, 20 CM patients, and 20 MCAS patients. Osteoporosis was less frequent in CM (15.0%) and MCAS (10.0%) than in SM (44.9%). Similarly, fractures were less frequent in non-SM MCDs, respectively 5.0%, 5.0%, and 28.1%. SM patients displayed high prevalence of vertebral fractures (22.5%), mostly multiple. Conversely, in non-SM patients, vertebral fractures appeared to be uncommon (5%) and more frequently associated with risk factors for osteoporosis. CONCLUSIONS: SM is associated with multiple vertebral osteoporotic fractures, whereas CM and MCAS do not appear to be associated with this phenotype.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry as a useful tool for the rapid identification of wild flea vectors preserved in alcohol.

Flea identification is a significant issue because some species are considered as important vectors of several human pathogens that have emerged or re-emerged recently, such as Bartonella henselae (Rhizobiales: Bartonellaceae) and Rickettsia felis (Rickettsiales: Rickettsiaceae). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been evaluated in recent years for the identification of multicellular organisms, including arthropods. A preliminary study corroborated the usefulness of this technique for the rapid identification of fleas, creating a preliminary database containing the spectra of five species of flea. However, longterm flea preservation in ethanol did not appear to be an adequate method of storage in the context of specimen identification by MALDI-TOF MS profiling. The goal of the present work was to assess the performance of MALDI-TOF MS in the identification of seven flea species [Ctenocephalides felis (Siphonaptera: Pulicidae), Ctenocephalides canis, Pulex irritans (Siphonaptera: Pulicidae), Archaeopsylla erinacei (Siphonaptera: Pulicidae), Leptopsylla taschenbergi (Siphonaptera: Ceratophyllidae), Stenoponia tripectinata (Siphonaptera: Stenoponiidae) and Nosopsyllus fasciatus (Siphonaptera: Ceratophyllidae)] collected in the field and stored in ethanol for different periods of time. The results confirmed that MALDI-TOF MS can be used for the identification of wild fleas stored in ethanol. Furthermore, this technique was able to discriminate not only different flea genera, but also the two congeneric species C. felis and C. canis.

Frequency of isolated cutaneous involvement in adult mastocytosis: a cohort study.

BACKGROUND: Mastocytosis is characterized by the accumulation/proliferation of abnormal mast cells. The frequency of isolated cutaneous involvement in adults with mastocytosis has not been fully determined. The main objective of our study was to assess the frequency of isolated cutaneous mastocytosis (CM) in adults with mastocytosis skin lesions. The second objective was to compare the clinical, histological, biological and imaging features in patients with isolated CM and patients with systemic mastocytosis (SM). METHODS: We included all patients with histology-proven mastocytosis skin lesions between January 2009 and December 2017. The mastocytosis diagnosis was made according to the international diagnostic criteria. All data were collected from a dedicated specific case report. RESULTS: Among 160 patients with mastocytosis skin lesions, 25 patients had isolated CM (15.6%), 105 had SM and 30 (18.7%) patients had undetermined mastocytosis. Skin KIT mutation (OR: 51.9, 95% CI: 3.9-678, P = 0.001) and high bone marrow tryptase (OR: 97.4, 95% CI: 10.3-915, P = 0.001) were strong predictors of SM. The prevalence of osteoporosis was higher in the SM population than in the isolated CM population. Moreover, a decrease in bone mineral density over a short period of follow-up (1-2 years) was associated with SM. There were no differences between the two groups regarding the frequency of mast cell activation symptoms, the presentation of skin lesions, the number of mast cells in the dermis and the level of serum tryptase. We propose considering the KIT mutation status and bone marrow tryptase levels to aid the diagnosis of isolated CM in adult mastocytosis patients. CONCLUSION: Only a small minority of adults with mastocytosis skin lesions has isolated cutaneous involvement. In 18.7% of mastocytosis cases, even complete workup does not allow for a precise classification of patients.

Variability of Denosumab densitometric response in postmenopausal osteoporosis.

The objective of our prospective study is to specify the variability of densitometric response to Denosumab, given in the second line, and to try to understand the reasons. All menopausal patients with primary osteoporosis, treated by Denosumab in our centre from 2014 to 2015, were included in this open prospective work. At T0, the patient's age, type of fracture, and previous treatments were collated. At T0 and T1, after 1 year of treatment by Dmab, a DXA of the spine and the hip and a determination of CTX were performed. Sixty-three patients aged 68.8 ± 8.3 years were included. The median number of treatments prescribed for osteoporosis before switch to Denosumab was 2.4. The median duration of these treatments was 7.2 years. At T1, CTX was less than 33 pg/ml (minimum threshold for our assay kit) in all patients. The median BMD in the spine increased by + 5.44% compared to T0. 14 patients in the upper quartile had a median BMD gain in the spine of + 11.07%. Fourteen patients in the lower quartile had a median BMD gain in the spine of + 0.6%. Only the duration of previous treatments, which was greater in the non-responder group, differed between these two groups. In the total cohort, the spinal densitometric gain was negatively correlated with the age of the patient at baseline (p = 0.04), the duration of previous treatment (p = 0.02), and positively with the CTX level (p = 0.05). The Dmab densitometric response is highly variable, partly explained by the duration of previous treatments and the level of bone resorption at initiation of treatment.

Pregnancy-related fractures: a retrospective study of a French cohort of 52 patients and review of the literature.

A retrospective, multicentre study involving 52 patients was carried out to define the causes and characteristics of pregnancy-related osteoporosis. The mean number of vertebral fractures occurring during the last trimester of pregnancy or at the time of delivery was 3.8. This is often promoted by risk factors before or during pregnancy. INTRODUCTION: In order to define the causes or predisposing factors of pregnancy-related osteoporosis and its clinical, radiological and bone density characteristics, laboratory findings, course and outcome, we carried out a retrospective multicentre study. METHODS: The records of 52 women hospitalised over the last 10 years in the rheumatology departments of six French university hospitals and with a diagnosis of pregnancy-related osteoporosis were examined. RESULTS: The patients' mean age at time of fracture was 32.1 years. In 10 patients, the fractures had occurred during the last trimester of pregnancy, and in 36 at the time of delivery or during the first 2 months post-partum. The mean number of vertebral fractures was 3.8 ± 2.0. Thirty three of the 52 patients had a risk factor of low bone mass before pregnancy. Twelve had disorders or treatments (heparin) that might promote osteoporosis during pregnancy, while 14 had no trigger factors before or during pregnancy. Overall, phosphate and calcium levels were normal, except for hyperphosphoraemia in lactating women (90%). On DXA scan, osteoporosis predominated in the trabecular bone (spinal T-score - 3.4, hip T-score - 2). Only 10 patients had a repeat fracture, and the increase in bone mineral density during follow-up was considerable, and improved by bisphosphonates (annual gain + 10% in the spine) or teriparatide (+ 15%). CONCLUSIONS: Pregnancy-related osteoporosis gives rise to multiple vertebral fractures. It is often promoted by risk factors before or during pregnancy. Its mechanism is still unknown. Treatment with bisphosphonates or teriparatide appears to improve the recovery of bone mineral density.

Watt-level single-frequency tunable neodymium MOPA fiber laser operating at 915-937 nm.

We have developed a Watt-level single-frequency tunable fiber laser in the 915-937 nm spectral window. The laser is based on a neodymium-doped fiber master oscillator power amplifier architecture, with two amplification stages using a 20 mW extended cavity diode laser as seed. The system output power is higher than 2 W from 921 to 933 nm, with a stability better than 1.4% and a low relative intensity noise.

Bone marrow tryptase as a possible diagnostic criterion for adult systemic mastocytosis.

BACKGROUND: Mastocytosis is difficult to diagnose, especially when systemic mast cell activation symptoms are not present or involve only one extracutaneous organ. OBJECTIVE: The main objective was to evaluate the accuracy of the bone marrow tryptase level in the diagnosis of systemic mastocytosis in patients with a clinical suspicion of mastocytosis. METHODS: We included all adult patients evaluated in our centre between December 2009 and 2013 for suspected mastocytosis as part of a standardized procedure and who had a bone marrow and serum tryptase assay on the same day. The diagnosis of systemic mastocytosis was established on the basis of the World Health Organization criteria as the gold standard. The accuracy of the bone marrow tryptase level in the diagnosis of systemic mastocytosis was assessed by a receiver operating characteristics curve analysis. The different sensitivity and specificity values, corresponding to the set of possible bone marrow tryptase level cut-off values, were estimated with 95% confidence intervals. RESULTS: Seventy-three patients were included. The diagnosis of systemic mastocytosis was established in 43 patients (58.9%). The median bone marrow tryptase level was 423 µg/L [95% CI: 217-868] in the systemic mastocytosis group and 7.5 µg/L [95% CI: 4.6-17.1] in the non-systemic mastocytosis group (P < 0.001). A cut-off value of 50 µg/L for bone marrow tryptase identified systemic mastocytosis with a sensitivity of 93.0% [95% CI: 80.9-98.5%] and a specificity of 90.0% [95% CI: 73.5-97.9%]. CONCLUSION AND CLINICAL RELEVANCE: The bone marrow tryptase level appears to be a valuable diagnostic criterion for confirming systemic mastocytosis. If this diagnosis can reliably be excluded by evaluation of the bone marrow tryptase level, there would be no need to perform a bone marrow biopsy.

Extended tunability of Nd-doped fiber lasers operating at 872-936 nm.

Efficient operation of an Nd-doped fiber laser operating in a wavelength-tunable configuration using a volume Bragg grating (VBG) is reported in this Letter. A high-power operation on the 4F3/2-4I9/2 transition of Nd3+ at short wavelengths below 900 nm is demonstrated for the first time in silica fibers. A high-efficiency (47% laser conversion) output power up to 22 W and a narrow linewidth of 0.035 nm are achieved. This configuration is compared with a more conventional fiber laser setup using a bandpass filter and a highly reflective dichroic mirror.

Effect of oral monthly ibandronate on bone microarchitecture in women with osteopenia-a randomized placebo-controlled trial.

UNLABELLED: We have examined the effect of oral monthly ibandronate on distal radius and tibia microarchitecture with high-resolution peripheral quantitative tomography compared with placebo, in women with osteopenia, and found that ibandronate did not significantly affect trabecular bone but improved cortical density and thickness at the tibia. METHODS: We have examined the effect of ibandronate on bone microarchitecture with peripheral high-resolution quantitative computed tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women with osteopenia. Patients received either oral 150 mg monthly ibandronate or placebo over 24 months. Bone microarchitecture was assessed at baseline, 6, 12, and 24 months, using HR-pQCT at the distal radius and tibia; areal bone mineral density (aBMD) was measured with DXA at the spine, hip, and radius. RESULTS: At 12 months, there was no significant difference in trabecular bone volume at the radius (the primary end point) between women on ibandronate (10.8 ± 2.5%) and placebo (10.5 ± 2.9%), p = 0.25. There was no significant difference in other radius trabecular and cortical microarchitecture parameters at 12 and 24 months. In contrast, at the tibia, cortical vBMD in the ibandronate group was significantly greater than in the placebo group at 6, 12, and 24 months, with better cortical thickness at 6, 12, and 24 months. With ibandronate, aBMD was significantly increased at the hip and spine at 12 and 24 months but at the radius was significantly superior to placebo only at 24 months. Most of the adverse events related to ibandronate were expected with bisphosphonate use, and none of them were serious. CONCLUSION: We conclude that 12 months of treatment with ibandronate in women with osteopenia did not affect trabecular bone microarchitecture, but improved cortical vBMD at the tibia at 12 and 24 months, and preserved cortical thickness at the tibia.

20 W continuous-wave cladding-pumped Nd-doped fiber laser at 910 nm.

We demonstrate a double-clad fiber laser operating at 910 nm with a record power of 20 W. Laser emission on the three-level scheme is enabled by the combination of a small inner cladding-to-core diameter ratio and a high brightness pump source at 808 nm. A laser conversion efficiency as high as 44% was achieved in CW operating regime by using resonant fiber Bragg reflectors at 910 nm that prevent the lasing at the 1060 nm competing wavelength. Furthermore, in a master oscillator power-amplifier scheme, an amplified power of 14.8 W was achieved at 914 nm in the same fiber.

Gastrointestinal campylobacteriosis in industrialised countries: comparison of the disease situation with salmonellosis, and microbiological contamination assessment.

The science-based assessment of foodborne zoonotic risk is used to evaluate the public health impact of a hazard and to guide public decision-making on control measures. Key information for the hazard characterisation and microbiological contamination assessment phases of risk assessment may be obtained from the collection and structured statistical analysis of international data. This approach was used for the hazard characterisation phase of a risk assessment of gastrointestinal campylobacteriosis and salmonellosis in 30 industrialised countries over the period 2005-2009. The results showed an overall increase in the annual ratio campylobacteriosis/salmonellosis (R(moy) > 2), despite significant differences among countries (P < 0.0001). For countries with complete data over 20 years, the results showed significantly higher exposure to campylobacteriosis among certain population segments (men, children under 5 years of age and adults aged between 20 and 30), as well as in summer. A number of paired factors (Campylobacter species/animal species-meat type) are observed in this consumer exposure. However, the overall rate of bacterial transfer in meat supply chains varies widely, with far lower values for cattle (0.16) and pigs (0.24) than for poultry (0.60) and chickens (1.17). A lack of harmonised epidemiological data on the contamination status of foodstuffs (frequency, level, site, and species) further hampers the accurate identification of critical points of contamination and of the spread of the hazard throughout the food chain.

High-peak-power nanosecond pulse generation by stimulated Brillouin scattering pulse compression in a seeded Yb-doped fiber amplifier.

We demonstrate the generation of nanosecond and multikilowatt peak-power pulses in a double-clad Yb-doped fiber amplifier seeded by a spectrally narrowed gain-switched laser diode. Injected pulses with 100 ns duration were simultaneously compressed and amplified by the combination of high amplifier gain and stimulated Brillouin scattering. A maximum peak power of 20 kW has been obtained, corresponding to a single-pass gain of +57 dB in terms of peak power. Part of this output signal was also converted into IR continuum light by splicing a length of single-mode fiber at the end of the fiber amplifier.

Generation of 520 mW pulsed blue light by frequency doubling of an all-fiberized 978 nm Yb-doped fiber laser source.

Pulsed blue light at 489 nm has been generated by second-harmonic-generation of a nanosecond pulsed master-oscillator power amplifier system based on a short Yb(3+) doped single-mode fiber amplifier at 978 nm and an external-cavity diode laser as seed source. The Yb(3+)-doped fiber was core-pumped by a W type Nd(3+) doped double-clad fiber laser operating on the transition near 930 nm ((4)F(3/2)→(4)I(9/2)). 520 mW of average power was generated at 489 nm using a periodically poled MgO:LiNbO(3), corresponding to a conversion efficiency of 34%.

Potentially inappropriate drug prescription in the elderly in France: a population-based study from the French National Insurance Healthcare system.

BACKGROUND: Inappropriate prescribing is a known risk factor for adverse drug event occurrence in the elderly. In various countries, several studies have used insurance healthcare databases to estimate the national prevalence of potentially inappropriate medications (PIM) in the elderly, as defined by explicit PIM lists. Recently, a representative sample of the French National Insurance Healthcare database, known as the "Echantillon Généraliste des Bénéficiaires" (EGB), was created, making it possible to assess the quality of drug prescription in France. Our objective was to evaluate the prevalence and the regional distribution of PIM prescription in the elderly aged 75 years and over in France, using the French PIM list and the EGB database. METHODS: The list of drugs reimbursed to patients aged 75 years and over from 1 March 2007 to 29 February 2008 was extracted from the EGB. Drugs were classified as inappropriate using the French PIM list. A PIM user was defined as a person receiving at least one PIM reimbursement during the study period. Interregion variability was estimated from logistic regression. RESULTS: In 53.6% (95% CI: 53.0-54.1) of the elderly aged 75 years and over, at least one PIM was given during the study period. The three main drug groups identified were cerebral vasodilators (19.4%), drugs with antimuscarinic properties (19.3%), and long half-life benzodiazepines (17.8%). There was an important disparity in PIM prescription among the French regions. In 14 out of 22 regions, the risk of PIM prescription was significantly elevated. This geographical variation differed for the different drug groups. CONCLUSION: PIM prescription in the elderly is a major and worrying problem in France. As in other countries, recent accessibility of the National Insurance Healthcare database makes it possible to create local indicators that the regional health agencies could use to manage public health policy in closer alignment to the needs of the patients within each French region.

[Tuberculosis and healthcare workers: Risk reduction and disease prevention in health care settings]. / Tuberculose et personnel soignant : prévention du risque en milieu de soins.

Tuberculosis is a human disease caused by Mycobacteriumtuberculosis, and transmitted by airborne pathway. Documented cases of tuberculosis infection in healthcare workers have been reported in both developed and developing countries. Early recognition of potentially infectious cases, immediate implementation of airborne precautions and prompt medical treatment of cases, are required to lower the risk of disease transmission. Molecular biology techniques allow earlier diagnosis. In the event of non-compliance with airborne precautions, the investigation will further have to establish exhaustive lists of potentially exposed healthcare workers and patients, looking for cases of latent tuberculosis infections whose treatment should help avoid active tuberculosis disease.

[An abscessed granulomatous prostatitis]. / Une prostatite granulomateuse abcédée.

INTRODUCTION: Prostatic abscesses are usually diagnosed in the setting of bacterial prostatitis. Rarely, they reveal or complicate granulomatous prostatitis. CASE REPORT: A 55-year-old man was admitted for acute urinary retention. Urine culture was sterile, with leukocyturia > 106/ml. After failure of antibiotic therapy with cefotaxime, CT scan revealed a necrotic prostatic collection and a nodular non-necrotic tissular lesion in the left upper lung lobe. Trans-rectal drainage of the prostatic lesion and lung biopsies revealed granuloma with multinucleated giant cells (without mycobacteria). The diagnosis of granulomatosis with polyangiitis was confirmed by high level of anti-proteinase 3 antibodies. Treatment with steroids and rituximab resulted in apyrexia, regression of the inflammatory syndrome and clinical manifestations. CONCLUSION: The diagnosis of granulomatosis with polyangiitis should be considered in the presence of a non-infectious granulomatous prostatitis with systemic involvement.