Depression, antidepressants and driving safety.

BackgroundThe purpose of this study was to review to review the reported associations of depression and antidepressants with motor vehicle crashes.PurposeA literature search for material published in the English language between January, 1995, and October, 2015, in bibliographic databases was combined with a search for other relevant material referenced in the retrieved articles.MethodsRetrieved articles were systematically reviewed for inclusion criteria: 19 epidemiological studies (17 case-control and 2 cohort studies) fulfilled the inclusion criteria by estimating the crash risk associated with depression and/or psychotropic medications in naturalistic settings.ResultsThe estimates of the odds ratio (OR) of crash involvement associated with depression ranged from 1.78 to 3.99. All classes of antidepressants were reported to have side effects with the potential to affect driving safety. The majority of studies of antidepressant effects on driving reported an elevated crash risk, and ORs ranged from 1.19 to 2.03 for all crashes, and 3.19 for fatal crashes. In meta-analysis, depression was associated with approximately 2-fold increased crash risk (summary OR = 1.90; 95% CI, 1.06 to 3.39), and antidepressants were associated with approximately 40% increased crash risk (summary OR = 1.40; 95%CI, 1.18 to 1.66).ConclusionBased on the findings of the studies reviewed, depression, antidepressants or the combination of depression and antidepressants may pose a potential hazard to driving safety. More research is needed to understand the individual contributions of depression and the medications used to treat depression

Activation of epiplexus macrophages in hydrocephalus caused by subarachnoid hemorrhage and thrombin

AimsWe have found that hydrocephalus development in spontaneously hypertensive rats was associated with activation of epiplexus cells. The current study examined whether epiplexus cell activation occurs in a rat subarachnoid hemorrhage (SAH), whether activation would be greater in a subset of rats that developed hydrocephalus and the potential role of thrombin in epiplexus cell activation.MethodsThere were two parts in this study. First, an endovascular perforation was performed in rats to induce SAH. Second, rats received an intraventricular infusion of either thrombin or saline. Magnetic resonance imaging was used to measure the ventricular volumes. Immunofluorescence and immunohistochemistry were used to study epiplexus cell activation.ResultsIba‐1, OX‐6, and CD68 were expressed in the epiplexus cells of the choroid plexus in sham‐operated rats. SAH increased Iba‐1 and CD68 immunoreactivity in epiplexus cells in addition to an increase in Iba‐1‐positive cell soma size. Those effects were greater in rats that developed hydrocephalus. Intraventricular thrombin mimicked the effects of SAH on epiplexus cell activation and hydrocephalus.ConclusionThis study supports the concept that epiplexus cell activation is associated with hydrocephalus development. Epiplexus cell activation may be in response to thrombin production after hemorrhage, and it may be a therapeutic target.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151813/1/cns13203_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151813/2/cns13203.pd

Root architecture and rhizosphere–microbe interactions

Plant roots fulfil crucial tasks during a plant’s life. As roots encounter very diverse conditions while exploring the soil for resources, their growth and development must be responsive to changes in the rhizosphere, resulting in root architectures that are tailor-made for all prevailing circumstances. Using multi-disciplinary approaches, we are gaining more intricate insights into the regulatory mechanisms directing root system architecture. This Special Issue provides insights into our advancement of knowledge on different aspects of root development and identifies opportunities for future research

Comparing the potential of Bacillus amyloliquefaciens CGMCC18230 with antimicrobial growth promoters for growth performance, bone development, expression of phosphorus transporters, and excreta microbiome in broiler chickens.

peer reviewedBone health of broiler chickens is essential for welfare and production. In this study, the probiotic Bacillus amyloliquefaciens (BA) CGMCC18230 was compared with antimicrobial growth promoters (AGPs) for its ability to promote growth and bone health. To address this, a total of 180 Arbor Acres (AA) 1-day-old, male, broiler chicks were randomly allocated into 3 treatment groups, with 6 replicates, containing 10 chicks in each replicate. The treatment groups were: control group (CON) fed a corn-soybean based diet; BA treatment group fed the basal diet supplemented with 2.5 × 1010 CFU/kg BA CGMCC18230; AGPs treatment group was fed the basal diet containing the antibiotics aureomycin (75 mg/kg), flavomycin (5 mg/kg) and kitasamycin (20 mg/kg). Over the 42 d experiment, broilers fed BA and AGPs diets both had higher BW, and the ADG was significantly (P < 0.05) higher than that of the CON group both in the grower phase (22-42 d) and overall. Moreover, with BA birds had higher (P < 0.05) serum concentrations of phosphorus (P, day 42) and alkaline phosphatase (ALP, days 21 and 42). Conversely, the content of P in excreta decreased significantly (P < 0.05) on days 21 and 42. Tibia bone mineralization was improved in BA, and the mRNA of P transport related genes PiT-1,2 in the duodenum and jejunum were significantly up-regulated in the BA group than in the CON group (P < 0.05). 16S rRNA gene sequencing revealed that dietary BA supplementation increased the relative abundance of butyrate-producing bacteria (Ruminococcaceae) and polyamine-producing bacteria (Akkermansia and Alistipes), which had a positive effect on bone development. These data show that dietary supplementation of BA CGMCC18320 improves broiler growth performance and bone health similar to supplementation with AGPs through up-regulation of intestinal P transporters, microbial modulation and increase P retention. However, no significant influence of BA CGMCC18320 supplementation on the retention of Ca was found

Image reconstruction from limited angle projections collected by multisource interior x-ray imaging systems

A multi-source x-ray interior imaging system with limited angle scanning is investigated to study the possibility of building an ultra-fast micro-CT for dynamic small animal imaging. And two methods are employed to perform interior reconstruction from a limited number of projections collected by the multi-source interior x-ray system. The first is total variation minimization with the steepest descent search (TVM-SD) and the second is total difference minimization with soft-threshold filtering (TDM-STF). Comprehensive numerical simulations and animal studies are performed to validate the associated reconstructed methods and demonstrate the feasibility and application of the proposed system configuration. The image reconstruction results show that both of the two reconstruction methods can significantly improve the image quality and the TDM-SFT is slightly superior to the TVM-SD. Finally, quantitative image analysis shows it is possible to make an ultra-fast micro-CT using a multi-source interior x-ray system scheme combined with the state-of-the-art interior tomography

Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain

Stem cell transplantation promises new hope for the treatment of stroke although significant questions remain about how the grafted cells elicit their effects. One hypothesis is that transplanted stem cells enhance endogenous repair mechanisms activated after cerebral ischaemia. Recognizing that bilateral reorganization of surviving circuits is associated with recovery after stroke, we investigated the ability of transplanted human neural progenitor cells to enhance this structural plasticity. Our results show the first evidence that human neural progenitor cell treatment can significantly increase dendritic plasticity in both the ipsi- and contralesional cortex and this coincides with stem cell-induced functional recovery. Moreover, stem cell-grafted rats demonstrated increased corticocortical, corticostriatal, corticothalamic and corticospinal axonal rewiring from the contralesional side; with the transcallosal and corticospinal axonal sprouting correlating with functional recovery. Furthermore, we demonstrate that axonal transport, which is critical for both proper axonal function and axonal sprouting, is inhibited by stroke and that this is rescued by the stem cell treatment, thus identifying another novel potential mechanism of action of transplanted cells. Finally, we established in vitro co-culture assays in which these stem cells mimicked the effects observed in vivo. Through immunodepletion studies, we identified vascular endothelial growth factor, thrombospondins 1 and 2, and slit as mediators partially responsible for stem cell-induced effects on dendritic sprouting, axonal plasticity and axonal transport in vitro. Thus, we postulate that human neural progenitor cells aid recovery after stroke through secretion of factors that enhance brain repair and plasticity

Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy:data from the ROCKET AF clinical trial

Background: Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results: TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR 3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions: Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing

Longitudinal Research on Aging Drivers (LongROAD): study design and methods

Background: As an important indicator of mobility, driving confers a host of social and health benefits to older adults. Despite the importance of safe mobility as the population ages, longitudinal data are lacking about the natural history and determinants of driving safety in older adults. Methods: The Longitudinal Research on Aging Drivers (LongROAD) project is a multisite prospective cohort study designed to generate empirical data for understanding the role of medical, behavioral, environmental and technological factors in driving safety during the process of aging. Results: A total of 2990 active drivers aged 65–79 years at baseline have been recruited through primary care clinics or health care systems in five study sites located in California, Colorado, Maryland, Michigan, and New York. Consented participants were assessed at baseline with standardized research protocols and instruments, including vehicle inspection, functional performance tests, and “brown-bag review” of medications. The primary vehicle of each participant was instrumented with a small data collection device that records detailed driving data whenever the vehicle is operating and detects when a participant is driving. Annual follow-up is being conducted for up to three years with a telephone questionnaire at 12 and 36 months and in-person assessment at 24 months. Medical records are reviewed annually to collect information on clinical diagnoses and healthcare utilization. Driving records, including crashes and violations, are collected annually from state motor vehicle departments. Pilot testing was conducted on 56 volunteers during March–May 2015. Recruitment and enrollment were completed between July 2015 and March 2017. Conclusions: Results of the LongROAD project will generate much-needed evidence for formulating public policy and developing intervention programs to maintain safe mobility while ensuring well-being for older adults

Prioritizing single-nucleotide variations that potentially regulate alternative splicing

Recent evidence suggests that many complex diseases are caused by genetic variations that play regulatory roles in controlling gene expression. Most genetic studies focus on nonsynonymous variations that can alter the amino acid composition of a protein and are therefore believed to have the highest impact on phenotype. Synonymous variations, however, can also play important roles in disease pathogenesis by regulating pre-mRNA processing and translational control. In this study, we systematically survey the effects of single-nucleotide variations (SNVs) on binding affinity of RNA-binding proteins (RBPs). Among the 10,113 synonymous SNVs identified in 697 individuals in the 1,000 Genomes Project and distributed by Genetic Analysis Workshop 17 (GAW17), we identified 182 variations located in alternatively spliced exons that can significantly change the binding affinity of nine RBPs whose binding preferences on 7-mer RNA sequences were previously reported. We found that the minor allele frequencies of these variations are similar to those of nonsynonymous SNVs, suggesting that they are in fact functional. We propose a workflow to identify phenotype-associated regulatory SNVs that might affect alternative splicing from exome-sequencing-derived genetic variations. Based on the affecting SNVs on the quantitative traits simulated in GAW17, we further identified two and four functional SNVs that are predicted to be involved in alternative splicing regulation in traits Q1 and Q2, respectively