Sonic hedgehog (Shh) signaling plays a critical role during development and carcinogenesis. While Gli family members govern the transcriptional output of Shh signaling, little is known how Gli-mediated transcriptional activity is regulated. Here we identify the actin-binding protein Missing in Metastasis (MIM) as a new Shhresponsive gene. Together, Gli1 and MIM recapitulate Shh-mediated epidermal proliferation and invasion in regenerated human skin. MIM is part of a Gli/Suppressor of Fused complex and potentiates Gli-dependent transcription using domains distinct from those used for monomeric actin binding. These data define MIM as both a Shh-responsive gene and a new member of the pathway that modulates Gli responses during growth and tumorigenesis.Supplemental material is available at http://www.genesdev.org.

In Bangladesh, full vaccination rates among children living in rural hard-to-reach areas and urban streets are low. We conducted a quasi-experimental pre-post study of a 12-month mobile phone intervention to improve vaccination among 0–11 months old children in rural hard-to-reach and urban street dweller areas. Software named “mTika” was employed within the existing public health system to electronically register each child’s birth and remind mothers about upcoming vaccination dates with text messages. Android smart phones with mTika were provided to all health assistants/vaccinators and supervisors in intervention areas, while mothers used plain cell phones already owned by themselves or their families. Pre and post-intervention vaccination coverage was surveyed in intervention and control areas. Among children over 298 days old, full vaccination coverage actually decreased in control areas – rural baseline 65.9% to endline 55.2% and urban baseline 44.5% to endline 33.9% – while increasing in intervention areas from rural baseline 58.9% to endline 76*8%, difference +18.8% (95% CI 5.7–31.9) and urban baseline 40.7% to endline 57.1%, difference +16.5% (95% CI 3.9–29.0). Difference-in-difference (DID) estimates were +29.5% for rural intervention versus control areas and +27.1% for urban areas for full vaccination in children over 298 days old, and logistic regression adjusting for maternal education, mobile phone ownership, and sex of child showed intervention effect odds ratio (OR) of 3.8 (95% CI 1.5–9.2) in rural areas and 3.0 (95% CI 1.4–6.4) in urban areas. Among all age groups, intervention effects on age-appropriate vaccination coverage were positive: DIDs +13.1–30.5% and ORs 2.5–4.6 (p < 0.001 in all comparisons). Qualitative data showed the intervention was well-accepted. Our study demonstrated that a mobile phone intervention can improve vaccination coverage in rural hard-to-reach and urban street dweller communities in Bangladesh. This small-scale successful demonstration should serve as an example to other low-income countries with high mobile phone usage.

SUMMARYBackgroundHealthcare facility hand hygiene impacts patient care, healthcare worker safety, and infection control, but low-income countries have few data to guide interventions.AimTo conduct a nationally representative survey of hand hygiene infrastructure and behaviour in Bangladeshi healthcare facilities to establish baseline data to aid policy.MethodsThe 2013 Bangladesh National Hygiene Baseline Survey examined water, sanitation, and hand hygiene across households, schools, restaurants and food vendors, traditional birth attendants, and healthcare facilities. We used probability proportional to size sampling to select 100 rural and urban population clusters, and then surveyed hand hygiene infrastructure in 875 inpatient healthcare facilities, observing behaviour in 100 facilities.FindingsMore than 96% of facilities had ‘improved’ water sources, but environmental contamination occurred frequently around water sources. Soap was available at 78–92% of handwashing locations for doctors and nurses, but just 4–30% for patients and family. Only 2% of 4676 hand hygiene opportunities resulted in recommended actions: using alcohol sanitizer or washing both hands with soap, then drying by air or clean cloth. Healthcare workers performed recommended hand hygiene in 9% of 919 opportunities: more after patient contact (26%) than before (11%). Family caregivers frequently washed hands with only water (48% of 2751 opportunities), but with little soap (3%).ConclusionHealthcare workers had more access to hand hygiene materials and performed better hand hygiene than family, but still had low adherence. Increasing hand hygiene materials and behaviour could improve infection control in Bangladeshi health-care facilities.

During development, dynamic remodeling of the actin cytoskeleton allows the precise placement and morphology of tissues. Morphogens such as Sonic hedgehog (Shh) and local cues such as receptor protein tyrosine phosphatases (RPTPs) mediate this process, but how they regulate the cytoskeleton is poorly understood. We previously identified Basal cell carcinoma–enriched gene 4 (BEG4)/Missing in Metastasis (MIM), a Shh-inducible, Wiskott-Aldrich homology 2 domain–containing protein that potentiates Gli transcription (Callahan, C.A., T. Ofstad, L. Horng, J.K. Wang, H.H. Zhen, P.A. Coulombe, and A.E. Oro. 2004. Genes Dev. 18:2724–2729). Here, we show that endogenous MIM is induced in a patched1-dependent manner and regulates the actin cytoskeleton. MIM functions by bundling F-actin, a process that requires self-association but is independent of G-actin binding. Cytoskeletal remodeling requires an activation domain distinct from sequences required for bundling in vitro. This domain associates with RPTPδ and, in turn, enhances RPTPδ membrane localization. MIM-dependent cytoskeletal changes can be inhibited using a soluble RPTPδ-D2 domain. Our data suggest that the hedgehog-responsive gene MIM cooperates with RPTP to induce cytoskeletal changes.

Enteric fever remains a major cause of morbidity in developing countries with poor sanitation conditions that enable fecal contamination of water distribution systems. Historical evidence has shown that contamination of water systems used for household consumption or agriculture are key transmission routes for Salmonella Typhi and Salmonella Paratyphi A. The World Health Organization now recommends that typhoid conjugate vaccines (TCV) be used in settings with high typhoid incidence; consequently, governments face a challenge regarding how to prioritize typhoid against other emerging diseases. A key issue is the lack of typhoid burden data in many low- and middle-income countries where TCV could be deployed. Here we present an argument for utilizing environmental sampling for the surveillance of enteric fever organisms to provide data on community-level typhoid risk. Such an approach could complement traditional blood culture-based surveillance or even replace it in settings where population-based clinical surveillance is not feasible. We review historical studies characterizing the transmission of enteric fever organisms through sewage and water, discuss recent advances in the molecular detection of typhoidal Salmonella in the environment, and outline challenges and knowledge gaps that need to be addressed to establish environmental sampling as a tool for generating actionable data that can inform public health responses to enteric fever.

Background Typhoid fever prevention and control efforts are critical in an era of rising antimicrobial resistance among typhoid pathogens. India remains one of the highest typhoid disease burden countries, although a highly efficacious typhoid conjugate vaccine (TCV), prequalified by the World Health Organization in 2017, has been available since 2013. In 2018, the Navi Mumbai Municipal Corporation (NMMC) introduced TCV into its immunization program, targeting children aged 9 months to 14 years in 11 of 22 areas (Phase 1 campaign). We describe the decision making, implementation, and delivery costing to inform TCV use in other settings. Methods We collected information on the decision making and campaign implementation in addition to administrative coverage from NMMC and partners. We then used a microcosting approach from the local government (NMMC) perspective, using a new Microsoft Excel–based tool to estimate the financial and economic vaccination campaign costs. Results The planning and implementation of the campaign were led by NMMC with support from multiple partners. A fixed-post campaign was conducted during weekends and public holidays in July–August 2018 which achieved an administrative vaccination coverage of 71% (ranging from 46% in high-income to 92% in low-income areas). Not including vaccine and vaccination supplies, the average financial cost and economic cost per dose of TCV delivery were $0.45 and $1.42, respectively. Conclusion The first public sector TCV campaign was successfully implemented by NMMC, with high administrative coverage in slums and low-income areas. Delivery cost estimates provide important inputs to evaluate the cost-effectiveness and affordability of TCV vaccination through public sector preventive campaigns.

We conducted a nationally representative cross-sectional study of 875 health-care facilities (HCFs) to determine water, sanitation, and health-care waste disposal service levels in Bangladesh for doctors, staff, and patients/caregivers in 2013. We calculated proportions and prevalence ratios to compare urban versus rural and government versus other HCFs. We report World Health Organization (WHO)-defined basic HCF service levels. The most common HCF was nongovernmental private (80%, 698/875), with an average of 25 beds and 12 admissions per day. There was an improved water source inside the HCF for doctors (79%, 95% confidence intervals [CI]: 75, 82), staff (59%, 95% CI: 55, 64), and patients/caregivers (59%, 95% CI: 55, 63). Improved toilets for doctors (81%, 95% CI: 78, 85) and other staff (73%, 95% CI: 70, 77) were more common than for patients/caregivers (54%, 95% CI: 50, 58). Forty-three percentage (434/875) of HCFs had no disposal method for health-care waste. More urban than rural and more government than other HCFs had an improved water source on the premises and improved toilets for staff. WHO-defined basic service levels were detected in > 90% of HCFs for drinking water, among 46-77% for sanitation, and 68% for handwashing at point of care but 26% near toilets. Forty-seven percentage of HCFs attained basic health-care waste management service levels. Patient/caregiver access to water, sanitation, and hygiene facilities is inadequate in many HCFs across Bangladesh. Improving facilities for this group should be an integral part of accreditation.

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