Molecular Evolution of Peste des Petits Ruminants Virus

Despite safe and efficacious vaccines against peste des petits ruminants virus (PPRV), this virus has emerged as the cause of a highly contagious disease with serious economic consequences for small ruminant agriculture across Asia, the Middle East, and Africa. We used complete and partial genome sequences of all 4 lineages of the virus to investigate evolutionary and epidemiologic dynamics of PPRV. A Bayesian phylogenetic analysis of all PPRV lineages mapped the time to most recent common ancestor and initial divergence of PPRV to a lineage III isolate at the beginning of 20th century. A phylogeographic approach estimated the probability for root location of an ancestral PPRV and individual lineages as being Nigeria for PPRV, Senegal for lineage I, Nigeria/Ghana for lineage II, Sudan for lineage III, and India for lineage IV. Substitution rates are critical parameters for understanding virus evolution because restrictions in genetic variation can lead to lower adaptability and pathogenicity.     

Dominant negative DISC1 mutant mice display specific social behaviour deficits and aberration in BDNF and cannabinoid receptor expression

Objectives. Disrupted in schizophrenia 1 (DISC1) is considered the most prominent candidate gene for schizophrenia. In this study, we aimed to characterize behavioural and brain biochemical traits in a mouse expressing a dominant negative DISC1mutant (DN-DISC1). Methods. DN-DISC1 mice underwent behavioural tests to evaluate object recognition, social preference and social novelty seeking. ELISA was conducted on brain tissue to evaluate BDNF levels. Western blot was employed to measure BDNF receptor (TrkB) and cannabinoid receptor CB1. Results. The mutant DISC1 mice displayed deficits in preference to social novelty while both social preference and object recognition were intact. Biochemical analysis of prefrontal cortex and hippocampus revealed a modest reduction in cortical TrkB protein levels of male mice while no differences in BDNF levels were observed. We found sex dependent differences in the expression of cannabinoid-1 receptors. Conclusions. We describe novel behavioural and biochemical abnormalities in the DN-DISC1 mouse model of schizophrenia. The data shows for the first time a possible link between DISC1 mutation and the cannabinoid system.     

Expansion of the spectrum of TUBB4A-related disorders: a new phenotype associated with a novel mutation in the TUBB4A gene

Mutations in the TUBB4A gene have been identified so far in two neurodegenerative disorders with extremely different clinical features and course: whispering dysphonia, also known as dystonia type 4 (DYT4), and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). We describe a patient with slowly progressive spastic paraparesis, segmental dystonia, intellectual disability, behavioral problems, and evidence of permanent, incomplete myelination associated with progressive cerebellar atrophy. Whole exome sequencing revealed a novel E410K de novo heterozygous mutation in the TUBB4A gene. The clinical and radiological picture of our patient is different from the classic phenotype; thus, it expands the phenotypic variation of TUBB4A-gene-related disorders.     

A motor learning-based intervention to ameliorate freezing of gait in subjects with Parkinson’s disease

Freezing of gait (FOG) is an episodic gait disturbance that is commonly seen in Parkinson’s disease (PD). To date, treatment efficacy is limited. We tested the hypothesis that an intervention that utilizes motor learning provided through intensive cueing can alleviate this symptom. Fifteen subjects with PD suffering from FOG participated in a 6 week progressive motor learning program (three training sessions per week—open trial). A training session included FOG-provoking situations (e.g., turns). Prior to each presumed FOG provocation (e.g., just before a turn), rhythmic auditory stimulation (RAS) was elicited and the subject was trained to walk rhythmically, coordinate left–right stepping and to increase step size, utilizing the RAS cueing. Net training duration increased from week to week and secondary cognitive tasks while walking were added to increase FOG propensity. FOG symptom burden was assessed before, immediately, and 4 weeks after the training period. The mean number of FOG episodes (±SEM) per 10 m of walking in a standardized gait assessment decreased from 0.52 ± 0.29 in the pre-testing to 0.15 ± 0.04 in the post-testing (p < 0.05). The duration of FOG episodes decreased from 4.3 ± 2.1 to 2.6 ± 0.6 s (p < 0.05). Additional measures (e.g., FOG questionnaire, gait speed) varied in their responsiveness to the treatment. These effects were retained 4 weeks after the training. The results of this open label study support the possibility that a motor learning-based intervention is apparently effective in reducing FOG burden, suggesting that RAS can deliver ‘anti-FOG’ training.     

The effect of retained embryos on pregnancy outcome in an in vitro fertilization and embryo transfer program

OBJECTIVE: The purpose of this study was to determine the incidence of retained embryos and its impact on pregnancy outcome in the absence of known risk factors like blood and mucus in the transfer catheter. The factors that could be associated with embryo retention were also investigated. STUDY DESIGN: The results of all embryo transfer procedures performed at Ankara IVF Center between January 2003 and December 2005 were analyzed retrospectively. Three hundred and five embryo transfers, in which the transfer catheter was contaminated with blood or mucus, were excluded and the remaining 1,454 embryo transfers, with clean catheter, were enrolled into the study. Both fresh (n=1,422) and frozen (n=32) embryo transfers were included. RESULTS: The overall incidence of retained embryos during study period was 2.8% (41/1,454) following a clean initial embryo transfer. The mean age of the female partner, mean number of retrieved oocytes, MII oocytes, fertilized oocytes and the embryos transferred were similar in patients with and without retained embryos. The 1,454 embryo transfers performed during the study period resulted in 712 pregnancies (49%), of which 639 proved to be clinical pregnancies with a rate of 44%. The implantation rate was 22.8%. Pregnancy outcomes including positive beta-hCG (58.5% versus 48.7%), biochemical (4.7% versus 5.1%) and clinical pregnancy rates (53.6% versus 43.6%), implantation rate (24% versus 22.7%) and multiple pregnancy rate (36.3% versus 44.7%) were not significantly different between patients with and without retained embryos. An influence of individual physicians and embryologists on the frequency of retained embryos was not detected. The type of embryo transfer catheter used did not show any difference in terms of embryo retention. The cleavage stages of embryos were not different between groups. Although it was not statistically significant, the number of embryos transferred appeared to be a potentially confounding factor for retained embryos (p=0.053) and it might be significant in a slightly larger sample. When transfer of one or two embryos was compared to three or more embryos, the likelihood of retained embryos increased from 1.2% (4/321) to 3.2% (37/1,133). CONCLUSION: Retained embryos in the transfer catheter and immediate retransfer of them have no adverse impact on clinical pregnancy and implantation rates unless other previously reported signs of difficult transfer are also observed.     

Feasibility Study of Automated Overnight Closed-Loop Glucose Control Under MD-Logic Artificial Pancreas in Patients with Type 1 Diabetes: The DREAM Project

Abstract Background: Artificial pancreas systems may offer a potential major impact on the normalization of metabolic control and preventing hypoglycemic events. This study aims to establish near-normal overnight glucose control and reduce the risk of nocturnal hypoglycemia using the MD-Logic Artificial Pancreas (MDLAP), an algorithm that was developed by our research group. This inpatient feasibility study is the first step towards implementing an overnight closed-loop MDLAP system at the patient's home. Subjects and Methods: Seven patients with type 1 diabetes (three adolescents and four adults; mean±SD age, 20.6±4.7 years; duration of diabetes, 9.6±2.6 years; body mass index, 24.3±3.9 kg/m(2); and glycated hemoglobin, 7.8±0.8%) participated in a total of 14 closed-loop overnight sessions. Each participant underwent two closed-loop inpatient sessions starting at dinner alone and at dinner following exercise. The closed-loop inpatient sessions were compared with data derived from nights spent at home with an open-loop system in a similar scenario to the study protocol. Results: The mean percentage of time spent in the near normal glucose range of 63-140?mg/dL was 83±16%, and the median (interquartile range) was 85% (78-92%) for the overnight closed-loop sessions compared with 34±31% and 27% (6-57%) in the homecare open-loop setting, respectively. During the overnight closed-loop sessions at dinner alone 92±9% of the sensor values ranged within target range, compared with 73±19% for the sessions following exercise (P=0.03). No hypoglycemic (<63?mg/dL) events occurred during the closed-loop sessions. Conclusion: Closed-loop insulin delivery under MDLAP is a feasible and safe solution to control overnight glycemia.