Both doublecortin and doublecortin-like kinase play a role in cortical interneuron migration

Type I lissencephaly, a genetic disease characterized by disorganized cortical layers and gyral abnormalities, is associated with severe cognitive impairment and epilepsy. Two genes, LIS1 and doublecortin (DCX), have been shown to be responsible for a large proportion of cases of type I lissencephaly. Both genes encode microtubule-associated proteins that have been shown to be important for radial migration of cortical pyramidal neurons. To investigate whether DCX also plays a role in cortical interneuron migration, we inactivated DCX in the ganglionic eminence of rat embryonic day 17 brain slices using short hairpin RNA. We found that, when DCX expression was blocked, the migration of interneurons from the ganglionic eminence to the cerebral cortex was slowed but not absent, similar to what had previously been reported for radial neuronal migration. In addition, the processes of DCX-deficient migrating interneurons were more branched than their counterparts in control experiments. These effects were rescued by DCX overexpression, confirming the specificity to DCX inactivation. A similar delay in interneuron migration was observed when Doublecortin-like kinase (DCLK), a microtubule-associated protein related to DCX, was inactivated, although the morphology of the cells was not affected. The importance of these genes in interneuron migration was confirmed by our finding that the cortices of Dcx, Dclk, and Dcx/Dclk mutant mice contained a reduced number of such cells in the cortex and their distribution was different compared with wild-type controls. However, the defect was different for each group of mutant animals, suggesting that DCX and DCLK have distinct roles in cortical interneuron migration

Can a blended learning approach enhance students transition into higher education? A study to explore perception , engagement and progression.

This paper is concerned with one programme‟s approach when using blended learning activities to support student transition into an English university. Its intention was to capture students‟ attention and curiosity whilst setting patterns for learning and study. The approach combined face-to-face sessions with on-line learning tasks. Research findings support the progress of students in regard to the level of attainment throughout the weekly tasks, although the students were initially challenged by the intensity of the use of ICT applications to support their learning. In conclusion this learning approach was found to be an effective method to support students during the initial weeks at university

Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. METHODS: Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. RESULTS: We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI,.1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. CONCLUSIONS: This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided

Identification of circulating tumour cells in early stage breast cancer patients using multi marker immunobead RT-PCR

Introduction The ability to screen blood of early stage operable breast cancer patients for circulating tumour cells is of potential importance for identifying patients at risk of developing distant relapse. We present the results of a study of the efficacy of the immunobead RT-PCR method in identifying patients with circulating tumour cells. Results Immunomagnetic enrichment of circulating tumour cells followed by RT-PCR (immunobead RT-PCR) with a panel of five epithelial specific markers (ELF3, EPHB4, EGFR, MGB1 and TACSTD1) was used to screen for circulating tumour cells in the peripheral blood of 56 breast cancer patients. Twenty patients were positive for two or more RT-PCR markers, including seven patients who were node negative by conventional techniques. Significant increases in the frequency of marker positivity was seen in lymph node positive patients, in patients with high grade tumours and in patients with lymphovascular invasion. A strong trend towards improved disease free survival was seen for marker negative patients although it did not reach significance (p = 0.08). Conclusion Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients

How do people with knee osteoarthritis use osteoarthritis pain medications and does this change over time? Data from the Osteoarthritis Initiative.

Introduction: The aim of this analysis was to describe comprehensively the cross-sectional and longitudinal patterns of analgesic and nutraceutical medication use for knee osteoarthritis (OA) in a contemporary US cohort and to investigate associated demographic and clinical factors. Methods: Baseline, 12, 24 and 36 month data were obtained retrospectively from the National Institutes of Health Osteoarthritis Initiative. Participants had symptomatic radiographic knee OA. Multiple binary logistic regression models identified characteristics independently associated with the use of analgesics or nutraceuticals. Results: We included 987 subjects (55.9% female, mean age 61.5 years, 71.0% white). At baseline, 68.2% reported frequent use of a conventional analgesic or nutraceutical for joint pain (for more than half of the previous month). Non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) were the most frequently reported medications (26.8%), even in those more than 75-years old. Multiple conventional analgesics were used by 11.9%. Frequent analgesic use was more likely in women (odds ratio (OR) 1.8 (95% confidence interval (CI) 1.3 to 2.3)) and people with more pain (moderate 1.7 (1.2 to 2.4); severe 3.1 (2.1 to 4.7)); nutraceutical use was less likely in non-whites (0.4 (0.3 to 0.6)), those more than 74-years old (0.6 (0.3 to 0.9)) and those with comorbidities (0.6 (0.5 to 0.9)) and more likely in people with Kellgren-Lawrence (KL) grade 4 (2.2 (1.5 to 3.3)). Overall there was no change in the proportion of participants frequently using prescription or over the counter (OTC) analgesics at 36 months, although most people had changed medication type; of those using a traditional analgesic at baseline approximately one third were still using the same type at 36 months (ranging from 26.2% of baseline prescription NSAID users to 40.6% of baseline acetaminophen users). All participants reporting baseline analgesic use also reported 36 month analgesic use. Female participants (OR 95% CI 1.2 to 3.2, P = 0.009), those with high body mass index (1.2 to 4.8, P = 0.010) and those with moderate (1.6 to 2.6, P = 0.090) or severe (1.8 to 12.0, P = 0.002) baseline pain were more likely to use pain medication during the 36 month follow-up period; participants more than 75-years old were less likely (0.2 to 1.0, P = 0.053). CONCLUSIONS: Most people with knee OA used pharmacological therapies frequently, and use appeared to be according to American College of Rheumatology recommendations. Change in medication type used was common. Persistent non-prescription NSAID use in older people is an area of concern

Measuring optimism bias among military personnel

High numbers of young military personnel die due to road traffic collisions (RTCs). Yet, there is a paucity of research related to the contributing factors (i.e., optimism bias and willingness to take risks) associated with RTCs and the examination of road safety education program tailored at reducing young military fatalities. In order to address this gap in the literature, we examined one specific road safety educational intervention tailored for the UK military personnel and investigated their attitudes towards the program, optimism bias and willingness to take risks. Measures evaluating their optimism bias, willingness to take risks and attitudes towards the program were asked after the participants attended the road safety interventions. The results revealed that young military personnel, aged 18–25, had higher optimism bias and willingness to take risks compared to older military personnel, and that this effect diminishes with age. The results provide importance evidence related to military personnel's attitudes to risk-taking

The miswired brain: making connections from neurodevelopment to psychopathology

Developmental neurobiologists have made great progress in elucidating the molecular mechanisms underlying nervous system development. There has been less focus, however, on the consequences when these processes go wrong. As the evidence increases that mutations in neurodevelopmental genes are associated with major psychiatric disorders, defining these consequences assumes paramount importance in elucidating pathogenic mechanisms