Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan : Evidence from two longitudinal cohort studies 15 years apart

Funding Information: Study 1 was funded through the Applied Diarrheal Disease Research Program at Harvard Institute for International Development with a grant from USAID (Project 936–5952, Cooperative Agreement # DPE-5952-A-00-5073-00), and the Aga Khan Health Service, Northern Areas and Chitral, Pakistan. Study 2 was funded by the Pakistan US S&T Cooperative Agreement between the Pakistan Higher Education Commission (HEC) (No.4–421/PAK-US/HEC/2010/955, grant to the Karakoram International University) and US National Academies of Science (Grant Number PGA-P211012 from NAS to the Fogarty International Center). The funding bodies had no role in the design of the study, data collection, analysis, interpretation, or writing of the manuscript. Publisher Copyright: © 2020 The Author(s).Peer reviewedPublisher PD

E-learning: An Effective Approach for Enhancing Social and Behavior Change Communication Capacity in Bangladesh

To strengthen social and behavior change communication (SBCC) capacity of Ministry of Health and Family Welfare (MoHFW) of the Government of Bangladesh, BCCP/BKMI developed two eLearning courses providing opportunities for professional development of SBCC Program Managers who have no access to training or refreshers training. The two eLearning courses – Message and Material Development (MMD) and Monitoring and Evaluation (MandE) of SBCC programs – went online in September 2015, where all users could register their participation so results could be monitored. Methodology: To assess the uses of these courses a randomly selected sample was collected to run a pre and post-test analyses and a phone survey were conducted. Systematic random sampling was used to select a sample of 75 MandE and 25 MMD course participants from a sampling frame of 179 and 51 respectively. Results: As of September 2016, more than 179 learners have completed the MandE course, and 49 learners have completed the MMD course. The users of these courses are program managers, university faculty members, and students. Encouraging results were revealed from the analysis of pre and post-test scores and a phone survey three months after course completion. Test scores suggested a substantial increase in knowledge. The pre-test scores findings suggested that about 19% learners scored high on the MandE. The post-test scores finding indicated a high score (92%) of the sample across 4 modules of MandE. For MMD course in pre-test scoring, 30% of the learners scored high, and 100% scored high at the post-test. It was found that all the learners in the phone survey have discussed the courses. Most of the sharing occurred with colleagues and friends, usually through face to face (70%) interaction. The learners reported that they did recommend the two courses to concerned people. About 67% MandE and 76% MMD learners stated that the concepts that they had to learn during the course were put into practice in their work settings. The respondents for both MandE and MMD courses have provided a valuable set of suggestions that would further strengthen the courses. Conclusions: The study showed that the initiative offered ample opportunities to build capacity in various ways in which the eLearning courses were used. It also highlighted the importance of scaling up these efforts to further strengthen the outcomes

MCC Gene Silencing Is a CpG Island Methylator Phenotype-Associated Factor That Predisposes Colon Cancer Cells to Irinotecan and Olaparib

Chemotherapy is a mainstay of colorectal cancer treatment, and often involves a combination drug regime. CpG island methylator phenotype (CIMP)-positive tumors are potentially more responsive to the topoisomerase-inhibitor irinotecan. The mechanistic basis of the increased sensitivity of CIMP cancers to irinotecan is poorly understood. Mutated in Colorectal Cancer (MCC) is emerging as a multifunctional tumor suppressor gene in colorectal and liver cancers, and has been implicated in drug responsiveness. Here, we found that CIMP tumors undergo MCC loss almost exclusively via promoter hypermethylation rather than copy number variation or mutations. A subset of cancers display hypomethylation which is also associated with low MCC expression, particularly in rectal cancer, where CIMP is rare. MCC knockdown or deletion was found to sensitize cells to SN38 (the active metabolite of irinotecan) or the PARP-inhibitor Olaparib. A synergistic effect on cell death was evident when these drugs were used concurrently. The improved SN38/irinotecan efficacy was accompanied by the down-regulation of DNA repair genes. Thus, differential methylation of MCC is potentially a valuable biomarker to identify colorectal cancers suitable for irinotecan therapy, possibly in combination with PARP inhibitors