The excitability of some neural circuits involved in walking and affected in individuals with chronic stroke can be modulated during and/or immediately after anodal transcranial direct current ...stimulation (a-tDCS). This study was designed to investigate the effects of a-tDCS during and immediately after application on leg muscle activity during gait, and on spatiotemporal and kinematic gait parameters in patients with chronic stroke.
This study was randomized, sham-controlled and double-blinded with a cross-over design and included 24 individuals with chronic stroke. Each participant underwent one 30-minute session each of effective a-tDCS at 2mA and sham tDCS. In both sessions, the anode was placed over the leg motor cortex of the affected hemisphere and the cathode over the contralateral orbit. Six gait trials were performed before, during and immediately after each effective/sham tDCS session. Electromyographic activity of leg muscles, as well as spatiotemporal (e.g. gait speed) and kinematic (e.g. peak knee flexion and ankle dorsiflexion in the swing phase of gait) gait parameters were recorded. Genotyping for the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism was undertaken since this gene may influence motor skill learning and the effects of tDCS.
No significant effects of a-tDCS on gait parameters were found either for the total group or for the Val66Met (N=10) and Val66Val (N=14) subgroups.
A single session of a-tDCS delivered to the leg motor cortex did not immediately improve gait parameters in individuals with chronic stroke, regardless of their BDNF genotype.
Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform ...papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned the disease locus to an ∼9-cM region at chromosome 2q35-q36.2, located between markers
rs16853834 and
D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c.697G→T (p.Glu233X) homozygous nonsense mutation in exon 3 of the
WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in
WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases.
Variant identification underlying inherited dysfibrinogenemia quite exceptionally fails. We report on two dysfibrinogenemia cases whose underlying DNA variant could not be identified by Sanger ...analysis. These failures result from two distinct mechanisms. The first case involved raw signal overcorrection by a built-in software, and the second constituted the first description of mosaicism for one of the fibrinogen genes. This mosaicism was subsequently identified by next-generation sequencing reanalysis of the sample.
To measure mitochondrial content and the expression of estrogen-related receptor-γ (ERRγ, a major inducer of mitochondrial biogenesis) in placentas from women with intrauterine growth restriction ...(IUGR) associated or not with pre-eclampsia (PE), relative to control placentas.
Case-control study.
Teaching hospital and university research laboratory.
Thirty-nine placentas from women with IUGR, 8 IUGR+PE, and 30 controls.
None.
Mitochondrial DNA and protein content, gene and protein expression.
We observed significantly lower placental mitochondrial DNA and protein contents (associated with down-regulation of ERRγ expression) in IUGR and IUGR+PE placentas, relative to control placentas. Our results also revealed that the placental mitochondrial DNA content was directly correlated with fetal weight. Moreover, we observed significantly lower peroxisome proliferator-activated receptor-γ coactivator-1α and sirtuin 1 messenger RNA expression levels in IUGR+PE placentas, relative to control placentas.
The low mitochondrial DNA and protein contents observed in IUGR placentas are probably due to down-regulation of ERRγ expression. This finding suggests that ERRγ has a major role in the control of placental development.
Introduction
Dominant‐negative effects have been described for 10 F11 variants in the literature.
Aim
The current study aimed at identifying putative dominant‐negative F11 variants.
Material and ...methods
This research consisted in a retrospective analysis of routine laboratory data.
Results
In a series of 170 patients with moderate/mild factor XI (FXI) deficiencies, we identified heterozygous carriers of previously reported dominant‐negative variants (p.Ser243Phe, p.Cys416Tyr, and p.Gly418Val) with FXI activities inconsistent with a dominant‐negative effect. Our findings also do not support a dominant‐negative effect of p.Gly418Ala. We also identified a set of patients carrying heterozygous variants, among which five out of 11 are novel, with FXI activities suggesting a dominant‐negative effect (p.His53Tyr, p.Cys110Gly, p.Cys140Tyr, p.Glu245Lys, p.Trp246Cys, p.Glu315Lys, p.Ile421Thr, p.Trp425Cys, p.Glu565Lys, p.Thr593Met, and p.Trp617Ter). However, for all but two of these variants, individuals with close to half normal FXI coagulant activity (FXI:C) were identified, indicating an inconstant dominant effect.
Conclusion
Our data show that for some F11 variants recognized has having dominant‐negative effects, such effects actually do not occur in many individuals. The present data suggest that for these patients, the intracellular quality control mechanisms eliminate the variant monomeric polypeptide before homodimer assembly, thereby allowing only the wild‐type homodimer to assemble and resulting in half normal activities. In contrast, in patients with markedly decreased activities, some mutant polypeptides might escape this first quality control. In turn, assembly of heterodimeric molecules as well as mutant homodimers would result in activities closer to 1:4 of FXI:C normal range.
Introduction
The incidence of afibrinogenemia had not been previously reported in Algeria. Afibrinogenemia patients are prone to both haemorrhagic and thrombotic complications. Predictive markers of ...thrombosis in afibrinogenemia patients are not existent.
Aims and methods
Clinical and biological data from 46 afibrinogenemia patients are reported. Biological investigations included routine tests, genetics analysis and thrombin generation.
Results
FGA mutations (four novel and four previously described) and FGB mutations (seven mutations; five novels) were homozygous in all but one family as a result of 28 consanguineous marriages out of 30 discrete families. Incidence of afibrinogenemia in Algeria is at least 3 per million births. Umbilical bleeding was reported in 39/46 cases and was the main discovery circumstance. We also report post trauma or post‐surgery (3/46) bleeding and spontaneous deep vein thrombosis (DVT) in adulthood (1/46), as discovery circumstances. The median age (10.5‐year‐old) of the population reported here explains why there are few hemarthrosis and obstetrical or gynaecological complications in this series. Thrombotic events were reported in seven patients (four spontaneous). Endogenous Thrombin Potential was significantly increased in thrombosis‐prone patients compared to afibrinogenemic patients with and without personal or familial history (1118 vs. 744 and 817 nM IIa × min, respectively).
Conclusion
The incidence of afibrinogenemia in Algeria is the consequence of consanguineous marriage in families carrying private mutations. The thrombin generation test (TGT) could identify, among afibrinogenemic patients, those presenting a thrombotic risk.
OBJECTIVE: To measure the expression of adiponectin, leptin, and their respective receptors in the human endometria of fertile women compared with women with unexplained recurrent implantation ...failure (IF) during the window of implantation. DESIGN: Controlled, prospective, clinical study. SETTING: Teaching hospital and university research laboratory. PATIENT(S): Thirty-one endometrial biopsies from women with IF and 19 fertile controls. INTERVENTION(S): Human endometrial biopsies. MAIN OUTCOME MEASURE(S): Gene and protein expression of endometrial biopsies. RESULT(S): Endometrial leptin expression was significantly lower in the IF group compared with fertile women. In contrast, leptin receptor (Ob-R) expression was higher in endometria of women with IF. Concerning the adiponectin system, adiponectin was expressed to the same extent in both groups. Conversely, the expression of its two receptors, AdipoR1 and AdipoR2, was reduced in endometria of women with IF compared with fertile women. CONCLUSION(S): Although progesterone resistance seems to be a common state of the endometrium in some human reproductive disorders, such as endometriosis or polycystic ovary syndrome, modification in leptin endometrial expression seems to be specific to IF. These results strongly suggest that changes in Ob-R and AdipoR expression profiles 1 should be implicated in the development of uterine receptivity, and 2 may therefore be potential new targets for prediction of IF.
A system that automatically performs the PCR amplification and microchip electrophoretic (ME) separation for rapid forensic short tandem repeat (STR) forensic profiling in a single disposable plastic ...chip is demonstrated. The microchip subassays were optimized to deliver results comparable to conventional benchtop methods. The microchip process was accomplished in sub-90 min compared with >2.5 h for the conventional approach. An infrared laser with a noncontact temperature sensing system was optimized for a 45 min PCR compared with the conventional 90 min amplification time. The separation conditions were optimized using LPA-co-dihexylacrylamide block copolymers specifically designed for microchip separations to achieve accurate DNA size calling in an effective length of 7 cm in a plastic microchip. This effective separation length is less than half of other reports for integrated STR analysis and allows a compact, inexpensive microchip design. This separation quality was maintained when integrated with microchip PCR. Thirty samples were analyzed conventionally and then compared with data generated by the microfluidic chip system. The microfluidic system allele calling was 100% concordant with the conventional process. This study also investigated allelic ladder consistency over time. The PCR-ME genetic profiles were analyzed using binning palettes generated from two sets of allelic ladders run three and six months apart. Using these binning palettes, no allele calling errors were detected in the 30 samples demonstrating that a microfluidic platform can be highly consistent over long periods of time.
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