Efficacy and safety of methylphenidate on attention deficit hyperactivity disorder in children with Down syndrome.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common co-morbidity that affects up to 44% of children with Down syndrome (DS). There is a need for reliable, good quality research on the use of methylphenidate within this population. The objective of this study is to report our experience regarding the management of ADHD in these children using methylphenidate. METHODS: This study is a retrospective observation of 21 children with DS, followed at Jérôme Lejeune Institute between 2000 and 2018. The diagnosis of ADHD was made using the Diagnostic and Statistical Manual of Mental Disorders criteria. Efficacy was measured as response or non-response on two main symptoms: attention/concentration and hyperactivity/impulsivity. Safety was evaluated by the presence or absence of side effects. RESULTS: Sixteen out of the 21 children (76%) showed improvement with methylphenidate. The average age of treatment onset in responding children was 8 years and 10 months versus 6 years and 3 months in non-responders (P = 0.05). Average dose/weight was significantly different in responders and non-responders (0.82 vs. 0.54 mg/kg/day, respectively; P = 0.03). Twelve children out of 21 (57%) experienced side effects; only three experienced side effects severe enough to require treatment interruption. Most common side effects were loss of appetite and difficulties in falling asleep. CONCLUSION: Methylphenidate was effective and safe in treating ADHD in 76% of cases in children with DS, with few serious side effects to report. Early diagnosis of ADHD is important to improve the quality of life, learning, inclusion and socialisation of children with DS.

Handgrip fatiguing exercise can provide objective assessment of cancer-related fatigue: a pilot study.

PURPOSE: As a subjective symptom, cancer-related fatigue is assessed via patient-reported outcomes. Due to the inherent bias of such evaluation, screening and treatment for cancer-related fatigue remains suboptimal. The purpose is to evaluate whether objective cancer patients' hand muscle mechanical parameters (maximal force, critical force, force variability) extracted from a fatiguing handgrip exercise may be correlated to the different dimensions (physical, emotional, and cognitive) of cancer-related fatigue. METHODS: Fourteen women with advanced breast cancer, still under or having previously received chemotherapy within the preceding 3 months, and 11 healthy women participated to the present study. Cancer-related fatigue was first assessed through the EORTC QLQ-30 and its fatigue module. Fatigability was then measured during 60 maximal repeated handgrip contractions. The maximum force, critical force (asymptote of the force-time evolution), and force variability (root mean square of the successive differences) were extracted. Multiple regression models were performed to investigate the influence of the force parameters on cancer-related fatigue's dimensions. RESULTS: The multiple linear regression analysis evidenced that physical fatigue was best explained by maximum force and critical force (r = 0.81; p = 0.029). The emotional fatigue was best explained by maximum force, critical force, and force variability (r = 0.83; p = 0.008). The cognitive fatigue was best explained by critical force and force variability (r = 0.62; p = 0.035). CONCLUSION: The handgrip maximal force, critical force, and force variability may offer objective measures of the different dimensions of cancer-related fatigue and could provide a complementary approach to the patient reported outcomes.

Predicting value of prehospital body temperature for ICU admission of septic shock patients.

To specify whether an association exists between pre-hospital body temperature collected by the emergency medical services (EMS) call centre, and intensive care unit (ICU) admission of patients with septic shock. An observational study based on data collected by the EMS of Paris. All septic shocks were included. Among, the 140 calls concerning septic shock, 22 patients (16%) were admitted to ICU. The mean core temperature was 37.4±1.6°C for ICU and 38.6±1.1°C (p<4.10^-5) for non-ICU patients. Using propensity score analysis, the relative risk for ICU admission of patients with pre-hospital fever or hypothermia was 0.31 and 2 respectively. The study highlights the potential usefulness of early temperature measurement in septic shock patients to allow early proper orientation.

Multiple paternity in a wild population of Armadillidium vulgare: influence of infection with Wolbachia?

Female multiple mating has been extensively studied to understand how nonobvious benefits, generally thought to be of genetic nature, could overcome heavy costs such as an increased risk of infection during mating. However, the impact of infection itself on multiple mating has rarely been addressed. The interaction between the bacterium Wolbachia and its terrestrial crustacean host, Armadillidium vulgare, is a relevant model to investigate this question. In this association, Wolbachia is able to turn genetic males into functional females (i.e. feminization), thereby distorting the sex ratio and decreasing the number of available males at the population scale. Moreover, in A. vulgare, females have been shown to mate multiply under laboratory conditions and males prefer uninfected females over infected ones. Additionally, different Wolbachia strains are known to infect A. vulgare and these strains differ in their transmission rate and virulence. All these elements suggest a potential impact of different Wolbachia strains on multiple mating. To investigate this assumption, we collected gravid females in a wild A. vulgare population harbouring both uninfected females and females infected with one of two different Wolbachia strains (wVulM and wVulC) and performed paternity analyses on the obtained broods using microsatellite markers. We demonstrate that (i) multiple paternity is common in this wild population of A. vulgare, with a mean number of fathers of 4.48 ± 1.24 per brood and (ii) females infected with wVulC produced broods with a lower multiple paternity level compared with females infected with wVulM and uninfected ones. This work improves our knowledge of the impact of infections on reproductive strategies.

Prevention of hepatitis C virus infection by adoptive allogeneic immunotherapy using suicide gene-modified lymphocytes: an in vitro proof-of-concept.

Hepatitis C virus (HCV)-induced, end-stage liver disease is a major indication for liver transplantation, but systematic graft reinfection accelerates liver disease recurrence. Transplantation recipients may be ineligible for direct-acting antivirals, owing to toxicity, resistance or advanced liver disease. Adoptive immunotherapy with liver graft-derived, ex vivo-activated lymphocytes was previously shown to prevent HCV-induced graft reinfections. Alternatively, the applicability and therapeutic efficacy of adoptive immunotherapy may be enhanced by 'ready for use' suicide gene-modified lymphocytes from healthy blood donors; moreover, conditional, prodrug-induced cell suicide may prevent potential side effects. Here, we demonstrate that allogeneic suicide gene-modified lymphocytes (SGMLs) could potently, dose- and time-dependently, inhibit viral replication. The effect occurs at effector:target cell ratios that exhibits no concomitant cytotoxicity toward virus-infected target cells. The effect, mediated mostly by CD56+ lymphocytes, is interleukin-2-dependent, IFN-γ-mediated and, importantly, resistant to calcineurin inhibitors. Thus, post-transplant immunosuppression may not interfere with this adoptive cell immunotherapy approach. Furthermore, these cells are indeed amenable to conditional cell suicide; in particular, the inducible caspase 9 suicide gene is superior to the herpes simplex virus thymidine kinase suicide gene. Our data provide in vitro proof-of-concept that allogeneic, third-party, SGMLs may prevent HCV-induced liver graft reinfection.

Evidence for a vasomotor cyclo-oxygenase dependent mechanism of sensitization at the cutaneous level.

AIMS: Current-induced vasodilation (CIV) is an axon-reflex response observed during monopolar current application such as iontophoresis. Cyclo-oxygenase derivates (COD) participate in CIV and act as sensitizing agents at the anodal level. Mechanisms involved during cathodal current application (CCA) are partially unknown. In a randomized double-blind crossover trial, we tested in 16 healthy subjects (i) the influence of the inter-stimulation interval (I-I) by comparing CIV following all-at-once 10 s CCA against 2 × 5 s CCA with intervals ranging from15 s-16 min and (ii) the participation of COD in CIV using 1 g aspirin or placebo intake. METHODS: Measurements were repeated 2 h and 14 days after treatment. Laser Doppler flowmetry assessed cutaneous blood flow, reported in multiples of baseline. RESULTS: Before treatment, peak vasodilation 10 min after the last current application (CVCstim2 ) increased compared with baseline whatever the I-I. Increase in CVCstim2 from baseline was greater for the 4 min (9.4 (5.3, 10.9) times; median (1(st) percentile, 3(rd) percentile)) and higher I-Is compared with all-at-once delivery (3.0 (2.1, 4.3) times, P < 0.05). The response was similar after placebo but aspirin abolished this vasodilation (increase by 1.2 (1.1, 1.3) times for all-at-once delivery and by 1.5 (1.3, 1.7) ± 0.3 times for 4 min interval, 2 h after aspirin intake) that recovered after 14 days. CONCLUSIONS: This confirms the participation of COD in CIV with CCA and their sensitizing action. This model can represent an attractive way to study the axon-reflex and sensitizing function of COD in humans.

Cutaneous microvascular functional assessment during exercise: a novel approach using laser speckle contrast imaging.

Cardiovascular diseases are often revealed during exercise and are associated with cutaneous blood flow (CBF) dysfunction. Studies of CBF during exercise are consequently of interest. Laser speckle contrast imaging (LSCI) allows for non-contact and real-time recording of CBF at rest. We tested whether LSCI could allow the study of CBF during a cycling exercise using a specific signal treatment procedure that removes movement-induced artefacts from the LSCI raw signal. We recorded the baseline CBF and peak post-occlusive reactive hyperaemia (PORH) from the cutaneous forearm using LSCI and the mean blood pressure before and during cycling (80 W at 70 rpm) in nine healthy subjects. We determined the cross-correlation coefficient r between LSCI traces obtained before and during cycling and before and after a specifically designed signal processing technique. The results are presented as the median (25th-75th centile) and expressed as the cutaneous vascular conductance (laser speckle perfusion units (LSPU) per millimetre of mercury). Cross-correlation r increased from 0.226 ± 0.140 before to 0.683 ± 0.170 after post-processing. After signal processing, the peak PORH during exercise was reduced [0.38 (0.30-0.52) LSPU/mmHg] compared with the peak PORH during the non-exercise phase [0.69 (0.63-0.74) LSPU/mmHg, p < 0.01], whereas no difference was found between the baseline values. With adequate signal processing, LSCI appears valuable for investigating CBF during exercise. During constant-load lower limb cycling exercise, the upper limb peak PORH is reduced compared with the peak PORH during non-exercise. The underlying mechanisms warrant further investigations in both healthy (trained) subjects and diseased (e.g., coronary heart disease) patients.

3D-planned corrective osteotomy of metacarpal arch disruption after Motec® wrist prosthesis.

We report two cases of metacarpal arch disruption after Motec® total wrist arthroplasty, with hyperextension of the third metacarpal and dorsal protrusion of the head. Correction osteotomies of the adjacent metacarpals using preoperative 3D surgical planning were successful. This report seeks to shed light on the origin of this deformation and to recommend some operative precautions. It is important that surgeons should be aware of the existence of this complication, as disruption of the transverse metacarpal arch affects both grasp and hand esthetics. LEVEL OF EVIDENCE: IV.

Anakinra treatment of acute calcium deposits in hand and wrist.

Acute calcium deposit (ACD) in the hand and wrist is a cause of acute pain due to crystal-induced soft-tissue inflammation. There are no standard management guidelines for this condition, which is frequently treated with non-steroidal anti-inflammatory drugs (NSAIDs), with variable efficacy, some patients presenting symptoms for several months. We retrospectively analyzed the results of all patients treated with anakinra for hand or wrist ACD in our department in 2020. We extracted data on treatment duration, pain, range of motion, skin erythema, hypervascularization, edema, and X-ray findings. Ten patients were treated for hand or wrist ACD with anakinra 100 mg per day for a mean 2.7 days. We observed rapid and significant improvement in pain, range of motion, local erythema and edema from day 2 and a decrease in skin temperature from day 3. Calcifications significantly decreased in size or disappeared in the majority of the patients. There were no adverse events or recurrences at 1 year's follow-up. Anakinra was associated with significant clinical improvement after only two days' treatment and may be considered to treat patients with hand or wrist ACD, especially in case of contraindications to NSAIDs or glucocorticoids. Further controlled studies are needed to confirm the present observations.

High lead level in the Alps in XIXth century, learning from the analysis of 138 historical hair stands.

Analysis of hair is known to provide useful information about environmental and toxic exposures. Very little historical use has been made of this type of investigation. Here we study 138 human hair samples from 19th century in France. In order to examine the potential association between contamination and historical health impacts, we characterized contamination by 33 elements in a set of hair strands sampled during the last quarter of the 19th century in the Savoy region of France. After a selected washing step on 138 hair strands conserved at the Museum National d'Histoire Naturelle in Paris (France), we assessed the presence of inorganics by ICP/MS, and lead level was higher than values reported in literature. We then compared concentrations and distributions between women and men, sampling locations and crossing gender and geographical origin. Hair lead level was high throughout Savoy at the end of the 19th century: significantly higher for people living in towns or industrial valleys, and lower for those of countryside and mountains areas. Environmental and economic changes (industrialization and urbanization with water adduction and leaded paints), living habits (kitchenware, cosmetics, wine, and tobacco), and local features (mines exploitation, railroad development, and industrialized narrow valleys) could be envisaged for explaining the level of lead contamination. In the same period, the two main industrial valleys of Savoy (Maurienne and Tarentaise) had high rates of endemic goiter and cretinism and among the highest hair lead levels. Other lines of evidence will need to be explore to investigate a possible link between historical Pb exposure and goiter in the study area.

Reconstruction using vascularized extensor indicis proprius tendon.

The choice of the donor tendon in tendon reconstruction of the hand theoretically influences the results of the surgery because of the interactions of its structure with the healing process. The objective of our study was to specify the surgical bases of vascularized extensor indicis proprius (EIP) in tendon reconstruction of the hand and to present its application from a series of observations. According to our observations, the EIP's vascularization arises from a branch of the 2nd dorsal metacarpal artery, 3-4 cm proximally to the metacarpophalangeal joint (MCP). We demonstrate the feasibility and effectiveness of a vascularized EIP graft for finger flexor tendon reconstruction, for defects of the extensor mechanism at the MCP joint level and for reconstruction of the extensor pollicis longus. Our biomimetic approach in tendon reconstruction has led us to factor in the complexity of the tendon and peritendinous structure. The use of vascularized EIP offers theoretical advantages for the tendon healing process, demonstrates encouraging first results with interesting versatility and very low iatrogenicity.

Biomimicry of the flexor digitorum superficialis: Systematic literature review.

Biomimicry consists in imitating nature to solve complex human problems. The hand surgeon usually tries to copy and recreate the structure-to-function and function-to-control relationships of the native tissues after damage. With its exceptional structure and biomechanics, the flexor digitorum superficialis (FDS) has been an important source of inspiration for artificial hand system reconstruction. The present systematic literature review highlights the twenty-two artificial hand system reconstructions derived from the FDS, and presents biomimicry as an alternative approach in clinical research in hand surgery.

Leg ability factors in tennis players.

We investigated the effects of leg stiffness on running speed, jump height and leg power in 13 male 2(nd)- and 3(rd)-series ranked tennis players (23 ± 3 years old, 73.2 ± 8.4 kg, 1.81 ± 0.06 m). Leg stiffness and jump height were assessed using jumping and hopping tests. Mean running speeds over 20 m and 40 m (speed20 and speed40, respectively) were determined from a sprint test. Theoretical maximal leg power (P(maxth)) was extrapolated from a force-velocity test performed on a cycle ergometer. Leg stiffness averaged 478.7 ± 181.7 N.m⁻¹.kg⁻¹ (34,808 ± 12,573 N.m⁻¹. It was significantly correlated to speed20 and counter movement jump height (r=0.60, P=0.028 and r=0.58, P=0.0407, respectively). There were also significant correlations between P (maxth) and counter-movement jump height (r=0.59, P=0.0335) and between P(maxth) and speed40 (r=0.58, P=0.0393). This study characterizes leg stiffness in tennis players and brings new information concerning the way it is related to several other muscular biomechanical parameters.

Imaging Study by Mass Spectrometry of the Spatial Variation of Cellulose and Hemicellulose Structures in Corn Stalks.

The study used mass spectrometry imaging (MSI) to map the distribution of enzymatically degraded cell wall polysaccharides in maize stems for two genotypes and at several stages of development. The context was the production of biofuels, and the overall objective was to better describe the structural determinants of recalcitrance of grasses in bioconversion. The selected genotypes showed contrasting characteristics in bioconversion assays as well as in their lignin deposition pattern. We compared the pattern of cell wall polysaccharide degradation observed by MSI following the enzymatic degradation of tissues with that of lignin deposition. Several enzymes targeting the main families of wall polysaccharides were used. In the early stages of development, cellulose and mixed-linked ß-glucans appeared as the main polysaccharides degraded from the walls, while heteroxylan products were barely detected, suggesting subsequent deposition of heteroxylans in the walls. At all stages and for both genotypes, enzymatic degradation occurred preferentially in nonlignified walls for all structural families of polysaccharides studied here. However, our results showed heterogeneity in the distribution of heteroxylan products according to their chemical structure: arabinosylated products were mostly represented in the pith center, while glucuronylated products were found at the pith periphery. The conclusions of our work are in agreement with those of previous studies. The MSI approach presented here is unique and attractive for addressing the histological and biochemical aspects of biomass recalcitrance to conversion, as it allows for a simultaneous interpretation of cell wall degradation and lignification patterns at the scale of an entire stem section.

Activation and modulation of antiviral and apoptotic genes in pigs infected with classical swine fever viruses of high, moderate or low virulence.

The immune response to CSFV and the strategies of this virus to evade and suppress the pigs' immune system are still poorly understood. Therefore, we investigated the transcriptional response in the tonsils, median retropharyngeal lymph node (MRLN), and spleen of pigs infected with CSFV strains of similar origin with high, moderate, and low virulence. Using a porcine spleen/intestinal cDNA microarray, expression levels in RNA pools prepared from infected tissue at 3 dpi (three pigs per virus strain) were compared to levels in pools prepared from uninfected homologue tissues (nine pigs). A total of 44 genes were found to be differentially expressed. The genes were functionally clustered in six groups: innate and adaptive immune response, interferon-regulated genes, apoptosis, ubiquitin-mediated proteolysis, oxidative phosphorylation and cytoskeleton. Significant up-regulation of three IFN-gamma-induced genes in the MRLNs of pigs infected with the low virulence strain was the only clear qualitative difference in gene expression observed between the strains with high, moderate and low virulence. Real-time PCR analysis of four response genes in all individual samples largely confirmed the microarray data at 3 dpi. Additional PCR analysis of infected tonsil, MRLN, and spleen samples collected at 7 and 10 dpi indicated that the strong induction of expression of the antiviral response genes chemokine CXCL10 and 2'-5' oligoadenylate synthetase 2, and of the TNF-related apoptosis-inducing ligand (TRAIL) gene at 3 dpi, decreased to lower levels at 7 and 10 dpi. For the highly and moderately virulent strains, this decrease in antiviral and apoptotic gene expression coincided with higher levels of virus in these immune tissues.

Nerve transfers in brachial plexus palsies.

It has been many years now since the introduction of nerve transfers for repair of traumatic brachial plexus lesions and more recently, we have seen its application in the field of obstetric brachial plexus palsy. These nerve transfers do not represent an alternative to anatomical repair by means of nerve grafting, but represent an additional possibility to increase the reconstructive options and improve the final results. This pushes the surgeon to decide: which function is to be restored by nerve grafting, which one by nerve transfer? What is the more reliable procedure? Does the age of the patient, the delay after the accident, or the type of accident influence this choice? If we add in the possibilities of palliative treatment, one can state that many therapeutic options are available today for brachial plexus reconstruction, and that no real consensus does exist. But some tendencies, some trends are apparent.

Applying FAIR Principles to Plant Phenotypic Data Management in GnpIS.

GnpIS is a data repository for plant phenomics that stores whole field and greenhouse experimental data including environment measures. It allows long-term access to datasets following the FAIR principles: Findable, Accessible, Interoperable, and Reusable, by using a flexible and original approach. It is based on a generic and ontology driven data model and an innovative software architecture that uncouples data integration, storage, and querying. It takes advantage of international standards including the Crop Ontology, MIAPPE, and the Breeding API. GnpIS allows handling data for a wide range of species and experiment types, including multiannual perennial plants experimental network or annual plant trials with either raw data, i.e., direct measures, or computed traits. It also ensures the integration and the interoperability among phenotyping datasets and with genotyping data. This is achieved through a careful curation and annotation of the key resources conducted in close collaboration with the communities providing data. Our repository follows the Open Science data publication principles by ensuring citability of each dataset. Finally, GnpIS compliance with international standards enables its interoperability with other data repositories hence allowing data links between phenotype and other data types. GnpIS can therefore contribute to emerging international federations of information systems.

Maternal occupational exposures to nanoscale particles and small for gestational age outcome in the French Longitudinal Study of Children.

OBJECTIVES: To investigate the association between maternal occupational exposures to nanoscale particles (NPs) during pregnancy and small for gestational age (SGA). METHODS: This study included 11,224 mothers and singleton birth pairs from the French Longitudinal Study of Children (ELFE cohort), which included infants born after 33 weeks of gestation or more in continental France in 2011. Mothers who did not work during pregnancy were excluded from the analyses. Maternal occupational exposures to NPs was estimated using a job-exposure matrix for the probability (>50%: occupationally exposed group, n = 569; 0%: occupationally non-exposed group, n = 9113; between these two thresholds: uncertain group, n = 1542) and frequency of exposure. Associations were estimated from multivariate logistic regression models for occupationally exposed vs occupationally unexposed groups in a first analysis, and with the frequency-weighted duration of work for the occupationally exposed group only in a second analysis. RESULTS: Among working mothers, 5.1% were occupationally exposed to NPs. Maternal occupational exposures to NPs was associated with SGA (ORa = 1.63, 95% CI: 1.22, 2.18). The frequency-weighted duration of work for the occupationally exposed group (n = 569) was not associated with SGA (ORa = 1.02, 95% CI: 0.97, 1.08) in adjusted analyses. CONCLUSIONS: These results, showing a significant association between occupational exposures to NPs and SGA, should encourage further studies to examine the adverse effect of NPs exposure on fetal development.

Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway.

By comparing mRNA profiles in cultured fibroblasts from patients affected with lysosomal storage diseases, we identified differentially expressed genes common to these conditions. These studies, confirmed by biochemical experiments, demonstrated that lysosomal storage is associated with downregulation of ubiquitin C-terminal hydrolase, UCH-L1 in the cells of eight different lysosomal disorders, as well as in the brain of a mouse model of Sandhoff disease. Induction of lysosomal storage by the cysteine protease inhibitor E-64 also reduced UCH-L1 mRNA, protein level and activity. All cells exhibiting lysosomal storage contained ubiquitinated protein aggregates and showed reduced levels of free ubiquitin and decreased proteasome activity. The caspase-mediated apoptosis in E-64-treated fibroblasts was reversed by transfection with a UCH-L1 plasmid, and increased after downregulation of UCH-L1 by siRNA, suggesting that UCH-L1 deficiency and impairment of the ubiquitin-dependent protein degradation pathway can contribute to the increased cell death observed in many lysosomal storage disorders.

Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The Netherlands.

Mucopolysaccharidosis IIIC (MPS IIIC, Sanfilippo C syndrome) is a lysosomal storage disorder caused by deficiency of the lysosomal enzyme acetyl-CoA:alpha-glucosaminide N-acetyltransferase (HGSNAT). We performed a clinical study on 29 Dutch MPS IIIC patients and determined causative mutations in the recently identified HGSNAT gene. Psychomotor development was reported to be normal in all patients during the first year of life. First clinical signs were usually noted between 1 and 6 years (mean 3.5 years), and consisted of delayed psychomotor development and behavioral problems. Other symptoms included sleeping and hearing problems, recurrent infections, diarrhoea and epilepsy. Two sisters had attenuated disease and did not have symptoms until the third decade. Mean age of death was 34 years (range 25-48). Molecular analysis revealed mutations in both alleles for all patients except one. Altogether 14 different mutations were found: two splice site mutations, one frame shift mutation due to an insertion, three nonsense mutations and eight missense mutations. Two mutations, p.R344C and p.S518F, were frequent among probands of Dutch origin representing 22.0% and 29.3%, respectively, of the mutant alleles. This study demonstrates that MPS IIIC has a milder course than previously reported and that both severity and clinical course are highly variable even between sibs, complicating prediction of the clinical phenotype for individual patients. A clear phenotype-genotype correlation could not be established, except that the mutations p.G262R and p.S539C were only found in two sisters with late-onset disease and presumably convey a mild phenotype.