No abstract

The results suggest that this therapeutic approach has an impact on quality of life and communication for people with aphasia and their relatives.

Soil-transmitted helminth (STH) infections affect persons living in areas with poor water, sanitation, and hygiene (WASH). Preschool-aged children (PSAC) and school-aged children (SAC) are disproportionately affected by STH infections. We aimed to identify WASH factors associated with STH infection among PSAC and SAC in Kibera, Kenya. In 2012, households containing a PSAC or SAC were randomly selected from those enrolled in the International Emerging Infections Program, a population-based surveillance system. We administered a household questionnaire, conducted environmental assessments for WASH, and tested three stools from each child for STH eggs using the Kato-Katz method. WASH factors were evaluated for associations with STH infection using univariable and multivariable Poisson regression. Any-STH prevalence was 40.8% among 201 PSAC and 40.0% among 475 SAC enrolled. Using the Joint Monitoring Programme water and sanitation classifications, 1.5% of households reported piped water on premises versus 98.5% another improved water source; 1.3% reported improved sanitation facilities, while 81.7% used shared sanitation facilities, 13.9% had unimproved facilities, and 3.1% reported no facilities (open defecation). On univariable analysis, STH infection was significantly associated with a household toilet located off-premises (prevalence ratio (PR) = 1.33; p = 0.047), while always treating water (PR = 0.81; p = 0.04), covering drinking water containers (PR = 0.75; p = 0.02), using clean towels during hand drying (PR = 0.58; p<0.01), having finished household floor material (PR = 0.76; p<0.01), having electricity (PR = 0.70; p<0.01), and increasing household elevation in 10-meter increments (PR = 0.89; p<0.01) were protective against STH infection. On multivariable analysis, usually versus always treating water was associated with increased STH prevalence (adjusted prevalence ratio (aPR) = 1.52; p<0.01), while having finished household floor material (aPR = 0.76; p = 0.03), reported child deworming in the last year (aPR = 0.76; p<0.01), and 10-meter household elevation increases (aPR = 0.89; p<0.01) were protective against infection. The intersection between WASH and STH infection is complex; site-specific WASH interventions should be considered to sustain the gains made by deworming activities.

Aberrant elevation in the levels of the pro-inflammatory cytokine interleukin-1b (IL-1b) contributes to neuroinflammatory diseases. Blood-brain barrier (BBB) dysfunction is a hallmark phenotype of neuroinflammation. It is known that IL-1b directly induces BBB hyperpermeability but the mechanisms remain unclear. Claudin-5 (Cldn5) is a tight junction protein found at endothelial cell-cell contacts that are crucial for maintaining brain microvascular endothelial cell (BMVEC) integrity. Transcriptional regulation of Cldn5 has been attributed to the transcription factors b-catenin and forkhead box protein O1 (FoxO1), and the signaling molecules regulating their nuclear translocation. Non-muscle myosin light chain kinase (nmMlck, encoded by the Mylk gene) is a key regulator involved in endothelial hyperpermeability, and IL-1b has been shown to mediate nmMlck-dependent barrier dysfunction in epithelia. Considering these factors, we tested the hypothesis that nmMlck modulates IL-1b-mediated downregulation of Cldn5 in BMVECs in a manner that depends on transcriptional repression mediated by b-catenin and FoxO1. We found that treating BMVECs with IL-1b induced barrier dysfunction concomitantly with the nuclear translocation of b-catenin and FoxO1 and the repression of Cldn5. Most importantly, using primary BMVECs isolated from mice null for nmMlck, we identified that Cldn5 repression caused by b-catenin and FoxO1 in IL-1b-mediated barrier dysfunction was dependent on nmMlck.