Dynamic Energy Storage Management for Dependable Renewable Electricity Generation

© 2013 Blonbou et al., licensee InTech. This is an open access chapter distributed under the terms of th

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

The yggH gene of Escherichia coli encodes a tRNA (m7G46) methyltransferase

We cloned, expressed, and purified the Escherichia coli YggH protein and show that it catalyzes the S-adenosyl-L-methionine-dependent formation of N(7)-methylguanosine at position 46 (m(7)G46) in tRNA. Additionally, we generated an E. coli strain with a disrupted yggH gene and show that the mutant strain lacks tRNA (m(7)G46) methyltransferase activity.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Guillain-Barré Syndrome and Chikungunya: Description of All Cases Diagnosed during the 2014 Outbreak in the French West Indies

International audienceThe Guillain–Barré syndrome (GBS) has been reported as a possible complication of acute chikungunya infection. The chikungunya epidemics, which occurred in Martinique and Guadeloupe in 2014, affected 308,000 people in these two islands. GBS occurred during or immediately after acute chikungunya infection in 13 patients (10 men, three women; mean age: 61 years). Median time from acute chikungunya to GBS onset was 9 days. Twelve patients were treated with intravenous polyvalent immunoglobulins, nine of whom improved within 7 days. Five of 13 patients required mechanical ventilation. Two patients with severe GBS died. At 6 months of follow-up, 7/13 achieved a good functional recovery with no or minor residual symptoms. A 2-fold increase in incidence was observed during the year of chikungunya outbreak. This study supports prior reports suggesting that GBS may be a complication of chikungunya

Antimullerian Hormone as a Serum Biomarker for Risk of Chemotherapy-Induced Amenorrhea.

Antimullerian hormone (AMH) is a promising biomarker for ovarian reserve. In this study, we assessed AMH before and 1 year after initiation of adjuvant chemotherapy on National Surgical Adjuvant Breast and Bowel Project (NSABP)/NRG Oncology B-47 in female participants aged 42 years and younger (median age = 39 years). At baseline, median AMH was 1.2 ng/mL; 13 (4.7%) values were less than 0.1 ng/mL (the threshold for detectable levels, in the perimenopause and menopause range), and 57 values (20.6%) were less than 0.5 ng/mL. At 1 year, 215 (77.6%) were less than 0.1 ng/mL, and 264 (95.3%) were less than 0.5 ng/mL. Postchemotherapy menses were reported by 46.2% of participants. Multivariable logistic regression found that the odds of having postchemotherapy menses increased with younger age, higher body mass index, and higher prechemotherapy AMH, but not by trastuzumab administration or by the choice of chemotherapy (doxorubicin-cyclophosphamide followed by paclitaxel vs docetaxel-cyclophosphamide). We conclude that higher prechemotherapy AMH predicts a lower risk of chemotherapy-induced amenorrhea and that AMH 1 year after chemotherapy initiation is not informative in this setting because it is likely to be very low

Guillain-Barré Syndrome Associated With Zika Virus Infection in Martinique in 2016: A Prospective Study

International audienceBackground: Guillain-Barré syndrome (GBS) has been reported to be associated with Zika virus (ZIKV) infection in case reports and retrospective studies, mostly on the basis of serological tests, with the problematic cross-reacting antibodies of the Flavivirus genus. Some GBS cases do not exhibit a high level of diagnostic certainty. This prospective study aimed to describe the clinical profiles and the frequency of GBS associated with ZIKV during the ZIKV outbreak in Martinique in 2016.Methods: We recorded prospective data from GBS meeting levels 1 or 2 of diagnostic certainty for the Brighton Collaboration, with proof of recent ZIKV infection and negative screening for etiologies of GBS.Results: Of the sample of 34 patients with suspected GBS during the outbreak, 30 had a proven presence of GBS, and 23 had a recent ZIKV infection. The estimated GBS incidence rate ratio (2016 vs 2006-2015) was 4.52 (95% confidence interval, 2.80-7.64; P = .0001). Recent ZIKV infection was confirmed by urine reverse-transcription polymerase chain reaction (RT-PCR) analysis in 17 cases and by serology in 6 cases. Patients, 65% of whom were male, had a median age of 61 years (interquartile range, 56-71 years) and experienced severe GBS. Electrophysiological tests were consistent with the primary demyelinating form of the disease.Conclusions: ZIKV infection is usually benign, when symptomatic, but in countries at risk of ZIKV epidemics, adequate intensive care bed capacity is required for management of severe GBS cases. Arbovirus RNA detection by RT-PCR should be part of the management of GBS cases

Sarcopenia in patients after an episode of acute decompensated heart failure: An underdiagnosed problem with serious impact

International audienceBackground & aims: Sarcopenia is a multifactorial syndrome resulting in a decrease in both muscle mass and function. Little is known about the prevalence and prognostic impact of sarcopenia in patients with acutely decompensated chronic heart failure (ADHF). We aimed to evaluate the prevalence (main endpoint) and impact of sarcopenia on ADHF patients.Methods: 140 ADHF patients were enrolled between November 2014 and September 2018 in a multi-center prospective longitudinal study. A similar, independent multi-departmental cross-sectional study in 165 ADHF patients was used for external validation of prevalence data. All subjects were assessed on the European Working Group on Sarcopenia criteria.Results: Ninety-one patients (65%) had sarcopenia (vs. 53.6% in the external replication regional cohort). Patients with sarcopenia were older and more likely to have eGFR <60 ml/min/1.73 m(2) (p < 0.001 and p = 0.002). Sarcopenia was associated with impaired functional status [lower 6 min walking test (220 +/- 108 vs. 279 +/- 170, p = 0.03) and 4 m gait speed (0.56 +/- 0.24 vs. 0.80 +/- 0.37, p < 0.001)] and autonomy [Instrumental activities of daily living: 6.7 +/- 1.4 vs. 7.3 +/- 1.2, p = 0.005]. Over up to 4 years' follow-up, 30 cardiovascular (CV) deaths and 42 non-CV deaths occurred. In a multivariable analysis, sarcopenia was associated with time to first non-CV hospitalization (hazard ratio 1.93; 95% confidence interval 1.14-3.24; p = 0.014) but not with any other hospitalization, any mortality endpoint, or a composite endpoint of CV death and HF hospitalization.Conclusions: The prevalence of sarcopenia in ADHF patients is high and associated with greater risk of non-CV hospitalizations, highlighting the importance of identifying and managing the condition in a multidisciplinary approach

Long-term Outcome in Neurozika: When Biological Diagnosis Matters

International audienceObjective: To characterize the full spectrum, relative frequency and prognosis of the neurological manifestations in Zika virus (ZIKV) postnatal infection. Background: Zika virus (ZIKV) postnatal infection has been associated with both central and peripheral neurological manifestations. The full spectrum, relative frequency and prognosis of these neurological manifestations have yet to be described. Design/Methods: We conducted an observational study in consecutive ZIKV-infected patients presenting with neurological manifestations during the French West Indies 2016 outbreak. Results: Eighty-eight patients, including six children, were enrolled. Ninety-five percent of all cases required hospitalization. Guillain-Barré syndrome was the most frequent manifestation (46.6%) followed by encephalitis or encephalomyelitis (20.5%), isolated single or multiple cranial nerve palsies (9.1%), other peripheral manifestations (6.8%), and stroke (1.1%). Fourteen patients (15.9%) including one child, developed a mixed disorder involving both the central and peripheral nervous system. Mechanical ventilation was required in 21 cases all of whom had ZIKV RNA in at least one biological fluid. Two adult patients died due to neuroZika. Clinical follow-up (median 14 months; interquartile range, 12-17) was available for 77 patients. Residual disability (modified Rankin scale ≥2) was identified in 19 (24.7%) patients, in 6 cases (7.8%), disability was severe (modified Rankin scale ≥4). Amongst patients with ZIKV RNA detected in one biological fluid, the risk of residual disability or death was higher (odd ratio, 9.97; CI, 1.22 to 81.21; P=0.032). Conclusions: NeuroZika spectrum represents a heterogenous group of clinical neurological manifestations. During an outbreak, clinicians should consider neuroZika in patients presenting with cranial nerve palsies and a mixed neurological disorder. Long-term sequelae are frequent in NeuroZika. ZIKV reverse-transcription PCR status at admission can inform prognosis and should therefore be taken into consideration in the management of hospitalised patients