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Background: Community Health Workers (CHWs) play an instrumental role in promoting socio-behavioural change at the community level, which results in changed indicators of community health. While outcomes are mostly reviewed for achieving program objectives, it is pertinent to understand the process of program implementation mainly from the perception of participating CHWs., Methods: A qualitative study to understand the perception of Sakhi's (CHWs) regarding the outcomes of their participation in Home-Based Neonatal Care (HBNC) Program implemented by a non-governmental organization (NGO). Data consisted of 3 FGDs and 20 in-depth unstructured interviews with participating Sakhis., Results: Sakhis perceived their ability to take decisions at critical phases of the program as an important factor influencing their performance. The opportunity to participate as a Sakhi in the health programme initiated a process of change at the personal level. The changes perceived by Sakhis were enhancement in knowledge, skills and capabilities of Sakhis. The combination of improved skills, knowledge and attitude had culminated in the process of experiencing self-empowerment for the participating Sakhis. Their ability to positively influence the individuals and community with their initiatives to improve women and child health and save lives in critical situations facilitated development of a new identity and improved societal status in their communities. Changed power-relations at the family and community level promoted the involvement of Sakhis in the broader development agenda. Sakhis' ability to strategize goals, evaluate their own abilities, their willingness to upgrade knowledge and take others along in bringing social change, was an evident movement towards self-development., Conclusion: An opportunity for local women to participate in development programs creates potential for self-development as a cascading effect in addition to the accomplishment of planned program objective.

Background: In India, community health workers' (CHW) effectiveness in providing home-based neonatal care (HBNC) has been well documented. The nature of challenges faced and strategies adopted while providing HBNC services need to be studied in-depth., Methods: A qualitative study to understand the challenges faced and strategies used by Sakhis (women CHW) while providing services as part of a HBNC program implemented by a non-profit organization. Data consisted of 20 in-depth interviews and three focus group discussions (FGD) with Sakhis., Results: Sakhis negotiated with the community to start working as a CHW. They faced challenges while changing behaviors at individual level and also while bringing about a change in harmful normative practices that increased chances of maternal and neonatal mortality. Managing crises at the time of deliveries and facilitating a safe delivery was the most critical challenge faced by many Sakhis. The key strategies used by Sakhis included: proactively and persistently providing services even when they faced resistance from the woman or her family; evolving contextually suitable counseling techniques and tactics to bring about behavioral change; balancing compliance to traditional practices and promoting HBNC; defying traditional practices and assisting the woman in times of an emergency to save lives. Having on-call support from supervisors and cultivating a good working relationship with health providers facilitated effective service provision by Sakhis., Conclusion: CHWs having a strong sense of commitment can develop strategies to address challenges and provide HBNC services effectively if they also have strong supervisory support.

Background: Aberrant Hedgehog (Hh) signaling is associated with the development of many cancers including prostate cancer, gastrointestinal cancer, lung cancer, pancreatic cancer, ovarian cancer, and basal cell carcinoma. The Hh signaling pathway has been one of the most intensely investigated targets for cancer therapy, and a number of compounds inhibiting Hh signaling are being tested clinically for treating many cancers. Lung cancer causes more deaths than the next three most common cancers (colon, breast, and prostate) combined. Cyclopamine was the first compound found to inhibit Hh signaling and has been invaluable for understanding the function of Hh signaling in development and cancer. To find novel strategies for combating lung cancer, we decided to characterize the effect of cyclopamine tartrate (CycT), an improved analogue of cyclopamine, on lung cancer cells and its mechanism of action., Methods: The effect of CycT on oxygen consumption and proliferation of non-small-cell lung cancer (NSCLC) cell lines was quantified by using an Oxygraph system and live cell counting, respectively. Apoptosis was detected by using Annexin V and Propidium Iodide staining. CycT's impact on ROS generation, mitochondrial membrane potential, and mitochondrial morphology in NSCLC cells was monitored by using fluorometry and fluorescent microscopy. Western blotting and fluorescent microscopy were used to detect the levels and localization of Hh signaling targets, mitochondrial fission protein Drp1, and heme-related proteins in various NSCLC cells., Results: Our findings identified a novel function of CycT, as well as another Hh inhibitor SANT1, to disrupt mitochondrial function and aerobic respiration. Our results showed that CycT, like glutamine depletion, caused a substantial decrease in oxygen consumption in a number of NSCLC cell lines, suppressed NSCLC cell proliferation, and induced apoptosis. Further, we found that CycT increased ROS generation, mitochondrial membrane hyperpolarization, and mitochondrial fragmentation, thereby disrupting mitochondrial function in NSCLC cells., Conclusions: Together, our work demonstrates that CycT, and likely other Hh signaling inhibitors, can interrupt NSCLC cell function by promoting mitochondrial fission and fragmentation, mitochondrial membrane hyperpolarization, and ROS generation, thereby diminishing mitochondrial respiration, suppressing cell proliferation, and causing apoptosis. Our work provides novel mechanistic insights into the action of Hh inhibitors in cancer cells.