Hear my voice: understanding how community health workers in the Peruvian Amazon expanded their roles to mitigate the impact of the COVID-19 pandemic through community-based participatory research.

INTRODUCTION: The COVID-19 pandemic led to the collapse of the Peruvian health system, disrupting healthcare access for indigenous communities in the Amazon. Our study analysed how community health workers (CHWs) from indigenous communities in the Peruvian Amazon expanded their roles to mitigate the effects of the COVID-19 pandemic. METHODS: Fourteen CHWs from Loreto, Peru, participated in a community-based participatory research project using Photovoice, a technique encouraging vulnerable groups to take photos and develop stories illustrating their lived experiences. Participants were recruited from Mamás del Río, a local university-based programme, through purposive sampling. CHWs were asked to photograph how the pandemic affected their lives and work. Participants met four times over 5 months to share photos and develop action items. Data were organised into key themes using thematic analysis. CHWs shared photo galleries with policy-makers in Loreto and Lima. RESULTS: CHWs produced 36 photos with 33 texts highlighting their roles during COVID-19. Three core themes emerged: the (1) collapse of health infrastructure, (2) use of medicinal plants versus pharmaceuticals and (3) community adaptations and struggles. The leadership of CHWs emerged as a cross-cutting theme as CHWs supported COVID-19 efforts without government training or resources. CHWs asked policy-makers for formal integration into the health system, standardisation of training and management of community pharmacies. CONCLUSION: CHWs demonstrated their leadership and expanded their roles during the pandemic with little to no training from the government. Global investment in robust CHW programmes can fortify healthcare delivery.

Pharmacological screening and transcriptomic functional analyses identify a synergistic interaction between dasatinib and olaparib in triple-negative breast cancer.

Identification of druggable vulnerabilities is a main objective in triple-negative breast cancer (TNBC), where no curative therapies exist. Gene set enrichment analyses (GSEA) and a pharmacological evaluation using a library of compounds were used to select potential druggable combinations. MTT and studies with semi-solid media were performed to explore the activity of the combinations. TNBC cell lines (MDAMB-231, BT549, HS-578T and HCC3153) and an additional panel of 16 cell lines were used to assess the activity of the two compounds. Flow cytometry experiments and biochemical studies were also performed to explore the mechanism of action. GSEA were performed using several data sets (GSE21422, GSE26910, GSE3744, GSE65194 and GSE42568), and more than 35 compounds against the identified functions were evaluated to discover druggable opportunities. Analyses done with the Chou and Talalay algorithm confirmed the synergy of dasatinib and olaparib. The combination of both agents significantly induced apoptosis in a caspase-dependent manner and revealed a pleotropic effect on cell cycle: Dasatinib arrested cells in G0/G1 and olaparib in G2/M. Dasatinib inhibited pChk1 and induced DNA damage measured by pH2AX, and olaparib increased pH3. Finally, the effect of the combination was also evaluated in a panel of 18 cell lines representative of the most frequent solid tumours, observing a particularly synergism in ovarian cancer. Breast cancer, triple negative, dasatinib, olaparib, screening.

ERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy.

Resistance to Imatinib Mesylate (IM) is a major problem in Chronic Myelogenous Leukaemia management. Most of the studies about resistance have focused on point mutations on BCR/ABL. However, other types of resistance that do not imply mutations in BCR/ABL have been also described. In the present report we aim to study the role of several MAPK in IM resistance not associate to BCR/ABL mutations. Therefore we used an experimental system of resistant cell lines generated by co-culturing with IM (K562, Lama 84) as well as primary material from resistant and responder patient without BCR/ABL mutations. Here we demonstrate that Erk5 and p38MAPK signaling pathways are not implicated in the acquired resistance phenotype. However, Erk2, but not Erk1, is critical for the acquired resistance to IM. In fact, Bcr/Abl activates preferentially Erk2 in transient transfection in a dose dependent fashion through the c-Abl part of the chimeric protein. Finally, we present evidences demonstrating how constitutive activation of Erk2 is a de novo mechanism of resistance to IM. In summary our data support the use of therapeutic approaches based on Erk2 inhibition, which could be added to the therapeutic armamentarium to fight CML, especially when IM resistance develops secondary to Erk2 activation.