Temporal lobe epilepsy is a common, chronic neurologic disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate posttranscriptional expression of protein-coding mRNAs, which may have important roles in the pathogenesis of neurologic disorders. In models of prolonged, injurious seizures (status epilepticus) and in experimental and human epilepsy, we found up-regulation of miR-134, a brainspecific, activity-regulated miRNA implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21%, and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus reduced the later occurrence of spontaneous seizures by over 90% and mitigated attendant pathologic features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure suppressant and Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Summaryobjective To assess the extent and causes of microbiological contamination of household drinking water between source and point-of-use in developing countries.methods A systematic meta-analysis of 57 studies measuring bacteria counts for source water and stored water in the home to assess how contamination varied between settings.results The bacteriological quality of drinking water significantly declines after collection in many settings. The extent of contamination after water collection varies considerably between settings, but is proportionately greater where faecal and total coliform counts in source water are low.conclusions Policies that aim to improve water quality through source improvements may be compromised by post-collection contamination. Safer household water storage and treatment is recommended to prevent this, together with point-of-use water quality monitoring.

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Loneliness and social networks both independently affect mood and wellbeing in the elderly, underlying a very significant proportion of depressed mood.

A series of experiments is reported to identify and characterize the inactivation process in operation when drinking water, heavily contaminated with a Kenyan isolate of Escherichia coli, is stored in transparent plastic bottles that are then exposed to sunlight. The roles of optical and thermal inactivation mechanisms are studied in detail by simulating conditions of optical irradiance, water turbidity and temperature, which were recorded during a series of solar disinfection measurements carried out in the Kenyan Rift Valley. Optical inactivation effects are observed even in highly turbid water (200 ntu) and at low irradiances of only 10 mW cm−2. Thermal inactivation is found to be important only at water temperatures above 45 °C, at which point strong synergy between optical and thermal inactivation processes is observed. The results confirm that, where strong sunshine is available, solar disinfection of drinking water is an effective, low cost method for improving water quality and may be of particular use to refugee camps in disaster areas. Strategies for improving bacterial inactivation are discussed.

Background. Pressure ulcers are common, costly and impact negatively on individuals. Pressure is the prime cause, and immobility is the factor that exposes individuals to pressure. International guidelines advocate repositioning; however, there is confusion surrounding the best method and frequency required. Design. A pragmatic, multi-centre, open label, prospective, cluster-randomised controlled trial was conducted to compare the incidence of pressure ulcers among older persons nursed using two different repositioning regimens. Method. Ethical approval was received. Study sites (n = 12) were allocated to study arm using cluster randomisation. The experimental group (n = 99) were repositioned three hourly at night, using the 30°tilt; the control group (n = 114) received routine prevention (six-hourly repositioning, using 90°lateral rotation). Data analysis was by intention to treat; follow-up was for four weeks. Results. All participants (n = 213) were Irish and white, among them 77% were women and 65% aged 80 years or older. Three patients (3%) in the experimental group and 13 patients (11%) in the control group developed a pressure ulcer (p = 0AE035; 95% CI 0AE031-0AE038; ICC = 0AE001). All pressure ulcers were grade 1 (44%) or grade 2 (56%). Mobility and activity were the highest predictors of pressure ulcer development (b = À0AE246, 95% CI = À0AE319 to À0AE066; p = 0AE003); (b = 0AE227, 95% CI = 0AE041-0AE246; p = 0AE006). Conclusion. Repositioning older persons at risk of pressure ulcers every three hours at night, using the 30°tilt, reduces the incidence of pressure ulcers compared with usual care. The study supports the recommendations of the 2009 international pressure ulcer prevention guidelines. Relevance to clinical practice. An effective method of pressure ulcer prevention has been identified; in the light of the problem of pressures ulcers, current prevention strategies should be reviewed. It is important to implement appropriate prevention strategies, of which repositioning is one.

Summary Purpose ATP is an essential transmitter/cotransmitter in neuron function and pathophysiology and has recently emerged as a potential contributor to prolonged seizures (status epilepticus) through the activation of the purinergic ionotropic P2X7 receptor (P2X7R). Increased P2X7R expression has been reported in the hippocampus, and P2X7R antagonists reduced seizure‐induced damage to this brain region. However, status epilepticus also produces damage to the neocortex. The present study was designed to characterize P2X7R in the neocortex and assess effects of P2X7R antagonists on cortical injury after status epilepticus. Methods Status epilepticus was induced in mice by intraamygdala microinjection of kainic acid. Specific P2X7R inhibitors were administered into the ventricle before seizure induction, and cortical electroencephalography and behavior was recorded to assess seizure severity. P2X7R expression was examined in neocortex up to 24 h after status epilepticus, in epileptic mice, and in resected neocortex from patients with pharmacoresistent temporal lobe epilepsy (TLE). In addition, the induction of P2X7R after status epilepticus was investigated using transgenic P2X7R reporter mice, which express enhanced green fluorescent protein under the control of the p2x7r promoter. Key Findings Status epilepticus resulted in increased P2X7R protein levels in the neocortex of mice. Neocortical P2X7 receptor levels were also elevated in mice that developed epilepsy after status epilepticus and in resected neocortex from patients with pharmacoresistent TLE. Immunohistochemistry determined that neurons were the major cell population transcribing the P2X7R in the neocortex within the first 8 h after status epilepticus, whereas in epileptic mice, P2X7R up‐regulation occurred in microglia as well as in neurons. Pretreatment of mice with the specific P2X7R inhibitor A‐438079 reduced electrographic and clinical seizure severity during status epilepticus and reduced seizure‐induced neuronal death in the neocortex. Significance Our findings identify neurons in the neocortex as an important site of P2X7R up‐regulation after status epilepticus and in epilepsy, and provide support for the possible use of P2X7R antagonists for the treatment of status epilepticus and prevention of seizure‐induced brain damage.

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