Do robotic and non-robotic arm movement training drive motor recovery after stroke by a common neural mechanism? Experimental evidence and a computational model.

Different dose-matched, upper extremity rehabilitation training techniques, including robotic and non-robotic techniques, can result in similar improvement in movement ability after stroke, suggesting they may elicit a common drive for recovery. Here we report experimental results that support the hypothesis of a common drive, and develop a computational model of a putative neural mechanism for the common drive. We compared weekly motor control recovery during robotic and unassisted movement training techniques after chronic stroke (n = 27), as assessed with quantitative measures of strength, speed, and coordination. The results showed that recovery in both groups followed an exponential time course with a time constant of about 4-5 weeks. Despite the greater range and speed of movement practiced by the robot group, motor recovery was very similar between the groups. The premise of the computational model is that improvements in motor control are caused by improvements in the ability to activate spared portions of the damaged corticospinal system, as learned by a biologically plausible search algorithm. Robot-assisted and unassisted training would in theory equally drive this search process

The high burden of hospitalizations for primary EBV infection: a 6-year prospective survey in a French hospital

AbstractPrimary Epstein-Barr virus infection (PEI) is acquired increasingly later in life in developed countries, involving a growing number of adults. No studies have examined the effect of age on PEI. We conducted a prospective, single-centre, noninterventional survey to assess the clinical and economic effects of PEI care according to age. We included all serology-confirmed cases observed in all departments of a large regional hospital. Clinical and biologic data, therapeutics and costs of care were examined. Over a 6-year period, we included 292 subjects (148 children and 144 adults) with a median age of 15.4 years (range 9 months to 79 years). Adults were hospitalized more often (83% vs. 60%) and for longer periods of time (median 4 days vs. 2 days) than children (p ≤ 0.0001 for both). Two adults required a secondary transfer into the intensive care unit, although no children did. Typically, adults showed higher levels of activated lymphocytes and liver abnormalities. They also required the use of systemic corticosteroids more often (45% vs. 23%, p < 0.0001) and for longer periods of time (median 7 days vs. 3 days, p 0.02) than children. Overall, the costs were significantly higher for adults than for children (median, €1940 vs. €1130, p < 0.0001), mainly because of the frequency and duration of hospitalizations. Age increases the immune response and clinical severity of PEI, resulting in substantial additional costs for the community. Better recognition of the disease in adults could shorten the average length of hospital stay

MHD in von Kármán swirling flows, development and first run of the sodium experiment

URL: http://www-spht.cea.fr/articles/s01/004 MHD dans les écoulements de von Kármán | Collaboration VKSNATO Science Series II 26, 35-50 (2001). NATO Advanced Research Workshop, Dynamo and Dynamics, A Mathematical ChallengeWe describe the motivations, development and first run of the Von Kármán Sodium (VKS) experiment built to study high Reynolds number magnetohydrodynamics and applications to the dynamo effect. The flow is optimized using water experiments at scale 1/2 and kinematic dynamo simulations. In VKS run1, induction measurements are made in the presence of an externally applied field. Results are reported concerning the geometry of the induced field and its fluctuations in time

Recovery in Stroke Rehabilitation through the Rotation of Preferred Directions Induced by Bimanual Movements: A Computational Study

Stroke patients recover more effectively when they are rehabilitated with bimanual movement rather than with unimanual movement; however, it remains unclear why bimanual movement is more effective for stroke recovery. Using a computational model of stroke recovery, this study suggests that bimanual movement facilitates the reorganization of a damaged motor cortex because this movement induces rotations in the preferred directions (PDs) of motor cortex neurons. Although the tuning curves of these neurons differ during unimanual and bimanual movement, changes in PD, but not changes in modulation depth, facilitate such reorganization. In addition, this reorganization was facilitated only when encoding PDs are rotated, but decoding PDs are not rotated. Bimanual movement facilitates reorganization because this movement changes neural activities through inter-hemispheric inhibition without changing cortical-spinal-muscle connections. Furthermore, stronger inter-hemispheric inhibition between motor cortices results in more effective reorganization. Thus, this study suggests that bimanual movement is effective for stroke rehabilitation because this movement rotates the encoding PDs of motor cortex neurons

Optimization of Topical Therapy for Leishmania major Localized Cutaneous Leishmaniasis Using a Reliable C57BL/6 Model

When initiating the cutaneous disease named cutaneous leishmaniasis (CL), Leishmania parasites develop within the parasitophorous vacuoles of phagocytes residing in and/or recruited to the dermis, a process leading to more or less chronic dermis and epidermis-damaging inflammatory processes. Topical treatment of CL could be a mainstay in its management. Any improvements of topicals, such as new vehicles and shorter optimal contact regimes, could facilitate their use as an ambulatory treatment. Recently, WR279396, a third-generation aminoglycoside ointment, was designed with the aim to provide stability and optimal bioavailability for the molecules expected to target intracellular Leishmania. Two endpoints were expected to be reached: i) accelerated clearance of the maximal number of parasites, and ii) accelerated and stable repair processes without scars. A mouse model of CL was designed: it relies on the intradermal inoculation of luciferase-expressing Leishmania, allowing for in vivo bioluminescence imaging of the parasite load fluctuation, which can then be quantified simultaneously with the onset and resolution of clinical signs. These quantitative readout assays, deployed in real time, provide robust methods to rapidly assess efficacy of drugs/compounds i) to screen treatment modalities and ii) allow standardized comparison of different therapeutic agents

A homozygous FANCM mutation underlies a familial case of non-syndromic primary ovarian insufficiency

Primary Ovarian Insufficiency (P01) affects 1% of women under forty. Exome sequencing of two Finnish sisters with non-syndromic P01 revealed a homozygous mutation in FANCM, leading to a truncated protein (p.GIn1701*). FANCM is a DNA-damage response gene whose heterozygous mutations predispose to breast cancer. Compared to the mother's cells, the patients' lymphocytes displayed higher levels of basal and mitomycin C (MMC)-induced chromosomal abnormalities. Their lymphoblasts were hypersensitive to MMC and MMC-induced monoubiquitination of FANCD2 was impaired. Genetic complementation of patient's cells with wild-type FANCM improved their resistance to MMC re-establishing FANCD2 monoubiquitination. FANCM was more strongly expressed in human fetal germ cells than in somatic cells. FANCM protein was preferentially expressed along the chromosomes in pachytene cells, which undergo meiotic recombination. This mutation may provoke meiotic defects leading to a depleted follicular stock, as in Fancrril- mice. Our findings document the first Mendelian phenotype due to a biallelic FANCM mutation

Correlation between phenotypic antibiotic susceptibility and the resistome in Pseudomonas aeruginosa

Genetic determinants of antibiotic resistance (AR) have been extensively investigated. High-throughput sequencing allows for the assessment of the relationship between genotype and phenotype. A panel of 672 Pseudomonas aeruginosa strains was analysed, including representatives of globally disseminated multidrug-resistant and extensively drug-resistant clones; genomes and multiple antibiograms were available. This panel was annotated for AR gene presence and polymorphism, defining a resistome in which integrons were included. Integrons were present in >70 distinct cassettes, with In5 being the most prevalent. Some cassettes closely associated with clonal complexes, whereas others spread across the phylogenetic diversity, highlighting the importance of horizontal transfer. A resistome-wide association study (RWAS) was performed for clinically relevant antibiotics by correlating the variability in minimum inhibitory concentration (MIC) values with resistome data. Resistome annotation identified 147 loci associated with AR. These loci consisted mainly of acquired genomic elements and intrinsic genes. The RWAS allowed for correct identification of resistance mechanisms for meropenem, amikacin, levofloxacin and cefepime, and added 46 novel mutations. Among these, 29 were variants of the oprD gene associated with variation in meropenem MIC. Using genomic and MIC data, phenotypic AR was successfully correlated with molecular determinants at the whole-genome sequence level

Genomic Content of Bordetella pertussis Clinical Isolates Circulating in Areas of Intensive Children Vaccination

BACKGROUND: The objective of the study was to analyse the evolution of Bordetella pertussis population and the influence of herd immunity in different areas of the world where newborns and infants are highly vaccinated. METHODOLOGY: The analysis was performed using DNA microarray on 15 isolates, PCR on 111 isolates as well as GS-FLX sequencing technology on 3 isolates and the B. pertussis reference strain, Tohama I. PRINCIPAL FINDINGS: Our analyses demonstrate that the current circulating isolates are continuing to lose genetic material as compared to isolates circulating during the pre-vaccine era whatever the area of the world considered. The lost genetic material does not seem to be important for virulence. Our study confirms that the use of whole cell vaccines has led to the control of isolates that were similar to vaccine strains. GS-FLX sequencing technology shows that current isolates did not acquire any additional material when compared with vaccine strains or with isolates of the pre-vaccine era and that the sequenced strain Tohama I is not representative of the isolates. Furthermore, this technology allowed us to observe that the number of Insertion Sequence elements contained in the genome of the isolates is temporally increasing or varying between isolates. CONCLUSIONS: B. pertussis adaptation to humans is still in progress by losing genetic material via Insertion Sequence elements. Furthermore, recent isolates did not acquire any additional material when compared with vaccine strains or with isolates of the pre-vaccine era. Herd immunity, following intensive vaccination of infants and children with whole cell vaccines, has controlled isolates similar to the vaccine strains without modifying significantly the virulence of the isolates. With the replacement of whole cell vaccines by subunit vaccines, containing only few bacterial antigens targeting the virulence of the bacterium, one could hypothesize the circulation of isolates expressing less or modified vaccine antigens

CRISPR Typing and Subtyping for Improved Laboratory Surveillance of Salmonella Infections

Laboratory surveillance systems for salmonellosis should ideally be based on the rapid serotyping and subtyping of isolates. However, current typing methods are limited in both speed and precision. Using 783 strains and isolates belonging to 130 serotypes, we show here that a new family of DNA repeats named CRISPR (clustered regularly interspaced short palindromic repeats) is highly polymorphic in Salmonella. We found that CRISPR polymorphism was strongly correlated with both serotype and multilocus sequence type. Furthermore, spacer microevolution discriminated between subtypes within prevalent serotypes, making it possible to carry out typing and subtyping in a single step. We developed a high-throughput subtyping assay for the most prevalent serotype, Typhimurium. An open web-accessible database was set up, providing a serotype/spacer dictionary and an international tool for strain tracking based on this innovative, powerful typing and subtyping tool

MHD measurements in the von Kármán sodium experiment

We study the magnetic induction in a confined swirling flow of liquid sodium, at integral magnetic Reynolds numbers up to 50. More precisely, we measure in situ the magnetic field induced by the flow motion in the presence of a weak external field. Because of the very small value of the magnetic Prandtl number of all liquid metals, flows with even modest Rm are strongly turbulent. Large mean induction effects are observed over a fluctuating background. As expected from the von Kármán flow geometry, the induction is strongly anisotropic. The main contributions are the generation of an azimuthal induced field when the applied field is in the axial direction ~an V effect! and the generation of axial induced field when the applied field is the transverse direction ~as in a large scale a effect!. Strong fluctuations of the induced field, due to the flow nonstationarity, occur over time scales slower than the flow forcing frequency. In the spectral domain, they display a f21 spectral slope. At smaller scales ~and larger frequencies! the turbulent fluctuations are in agreement with a Kolmogorov modeling of passive vector dynamics