Cross-sector co-creation of a community-based physical activity program for breast cancer survivors in Colombia.

Benefits of physical activity (PA) in breast cancer survivors (BCS) are well established. However, programs to promote PA among BCS tailored to real-world contexts within low- to middle-income countries are limited. Cross-sector co-creation can be key to effective and scalable programs for BCS in these countries. This study aimed to evaluate the networking process to engage multisector stakeholders in the co-creation of a PA program for Colombian BCS called My Body. We employed a mixed-methods design including semistructured interviews, workshops and a social network analysis of centrality measures to assess stakeholders' engagement, resources and skills enabling the collaborative work, challenges, outcomes and lessons learned. The descriptive analysis and the centrality measures of the network revealed that 19 cross-sector stakeholders engaged in the My Body collaborative network. Through ongoing communication and cooperation, My Body built relationships between the academic lead institutions (local and international), and local and national public, private and academic institutions working in public health, sports and recreation, social sciences and engineering fields. The outcomes included the co-creation of the community-based PA program for BCS, its implementation through cross-sector synergies, increased relationships and communications among stakeholders, and successful dissemination of evidence and project results to the collaboration partners and other relevant stakeholders and community members. The mixed-methods assessment enabled understanding of ways to advance cross-sector co-creation of health promotion programs. The findings can help to enable continued development of sustainable cross-sector co-creation processes aimed at advancing PA promotion.

Collaborative work among stakeholders and researchers from different governmental sectors and disciplinary fields can be key to design and implement effective and scalable programs to promote physical activity (PA) among breast cancer survivors (BCS). This might be particularly critical in low- to middle-income countries where the implementation of evidence-based health-promoting programs tailored to real-world contexts are limited. This study aimed to evaluate the networking process to engage multisector stakeholders in the co-creation of a PA program for Colombian BCS. We employed qualitative methods and social network analyses to assess stakeholders' engagement, resources and skills enabling the collaborative work, challenges, outcomes and lessons learned. The co-creation of the program improved synergies between research, policy and practice. Communication through several channels including e-mail and workshops was the key resource to advance the collaborative work. Stakeholders underscored that cross-sector networking allowed allocating resources and achieving shared goals. Sustainable cross-sector collaborative processes are key for health promotion.

College integration and social class.

What is the impact of social class on college integration? Higher education institutions are becoming more diverse, yet the integration of underprivileged students remains a challenge. Using a social network approach, we analyze the general integration of low socioeconomic status (SES) students, as well as how segregated by class these friends are. The object of analysis is the extreme case of an elite university that, based on a government loan program (Ser Pilo Paga), opened its doors to many low-SES students in a very unequal country, Colombia. Using a mixed methods perspective, including a survey, 61 in depth interviews, and ethnographic observation, we analyze friendship networks and their meanings, barriers, and facilitators. Contrary to the literature, we find that low-SES students had, on average, the same number of connections and were no more isolated than students from upper social classes. Also, low-SES students' networks were not more segregated, even if relations with the upper classes were less likely and required more relational work than with middle or lower class friends. This high level of social integration stemmed from the intense relational work that low-SES students engage in, so as to fit in. Middle class friends act as a catalyst that can enable cross-class friendships.

MyD88 controls airway epithelial Muc5ac expression during TLR activation conditions from agricultural organic dust exposure.

Inflammation from airborne microbes can overwhelm compensatory mucociliary clearance mechanisms, leading to mucous cell metaplasia. Toll-like receptor (TLR) activation via myeloid differentiation factor 88 (MyD88) signaling is central to pathogen responses. We have previously shown that agricultural organic dust extract (ODE), with abundant microbial component diversity, activates TLR-induced airway inflammation. With the use of an established model, C57BL/6J wild-type (WT) and global MyD88 knockout (KO) mice were treated with intranasal inhalation of ODE or saline, daily for 1 wk. ODE primarily increased mucin (Muc)5ac levels relative to Muc5b. Compared with ODE-challenged WT mice, ODE-challenged, MyD88-deficient mice demonstrated significantly increased Muc5ac immunostaining, protein levels by immunoblot, and expression by quantitative PCR. The enhanced Muc5ac levels in MyD88-deficient mice were not explained by differences in the differentiation program of airway secretory cells in naïve mice. Increased Muc5ac levels in MyD88-deficient mice were also not explained by augmented inflammation, IL-17A, or neutrophil elastase levels. Furthermore, the enhanced airway mucins in the MyD88-deficient mice were not due to defective secretion, as the mucin secretory capacity of MyD88-KO mice remained intact. Finally, ODE-induced Muc5ac levels were enhanced in MyD88-deficient airway epithelial cells in vitro. In conclusion, MyD88 deficiency enhances airway mucous cell metaplasia under environments with high TLR activation.

Vector competence analysis of two Aedes aegypti lineages from Bello, Colombia, reveals that they are affected similarly by dengue-2 virus infection.

Dengue is the second most prevalent vector-borne disease after malaria in Colombia. It is caused by dengue virus, an arbovirus that exhibits high epidemic power, which is evidenced by its occurrence in more than 80% of the country, largely because of the extensive dispersion of the mosquito vector Aedes aegypti. The existence of two lineages of Ae. aegypti has been proposed based on genetic differences at the mitochondrial level, and they have been reported to circulate in similar proportions in the municipality of Bello (Colombia). It has been suggested that the differentiation of these lineages could influence features such as vector competence (VC) and life table. With the aim of testing this hypothesis, female mosquitoes from both lineages collected from Bello were orally challenged with dengue virus serotype 2 (strain D2-HAN) to measure infection, dissemination, survival and fecundity. Analysis of VC showed an increase in viral titer over time; however, no significant differences were observed between the lineages. The survival rate was not different between the infected lineages, but comparing lineages, it was lower in infected mosquitoes, which may affect the intensity of transmission. Finally, we conclude that the genetic differentiation of Ae. aegypti into lineages did not confer differences in epidemiological status when the mosquitoes were infected with this D2 serotype strain.

Transcriptome and Functional Genomics Reveal the Participation of Adenine Phosphoribosyltransferase in Trypanosoma cruzi Resistance to Benznidazole.

Currently, the only available treatments for Trypanosoma cruzi are benznidazole (Bz) and nifurtimox (Nfx). The mechanisms of action and resistance to these drugs in this parasite are not complete known. In order to identify differentially expressed transcripts between sensitive and resistant parasites, a massive pyrosequencing of the T. cruzi transcriptome was carried out. Additionally, the 2D gel electrophoresis profile of sensitive and resistant parasites was analyzed and the data were supported with functional genomics. The results showed 133 differentially expressed genes in resistant parasites. The transcriptome analysis revealed the regulation of different genes with several functions and metabolic pathways, which could suggest that resistance in T. cruzi is a multigenic process. Additionally, using transcriptomics, one gene, adenine phosphoribosyltransferase (APRT), was found to be down-regulated in the resistant parasites and its expression profile was confirmed by 2D electrophoresis analysis. The role of this gene in the resistance to Bz was confirmed overexpressing it in sensitive and resistant parasites. Interestingly, both parasites became more sensitive to Bz and H2 O2 . This is the first RNA-seq study to identify regulated genes in T. cruzi associated with Bz resistance and to show the role of APRT in T. cruzi resistance. Although T. cruzi regulation is mainly post-transcriptional, the transcriptome analysis, supported by 2D gel analysis and functional genomic, provides an overall idea of the expression profiles of genes under resistance conditions. These results contribute essential information to further the understanding of the mechanisms of action and resistance to Bz in T. cruzi. J. Cell. Biochem. 118: 1936-1945, 2017. © 2017 Wiley Periodicals, Inc.

Phage therapy: resurrecting a historical solution for the contemporary challenge of rising antibiotic resistance in Latin America.

INTRODUCTION: Antimicrobial resistance in Latin America is a growing concern in both human and non-human animal populations. The economic burden that is likely to be imposed through increased resistance will cause further strains on public health systems and the population at large. AREAS COVERED: We propose the rapid adoption and implementation of phage therapy as a necessary addition to the medical arsenal to help mitigate antimicrobial resistance, with an emphasis on considering the potential benefits that highly biodiverse countries such as Ecuador may have on phage discovery. However, programs may count on limited government support and/or facilitation, which could slow progress. EXPERT OPINION: We highlight the need for educational campaigns to be implemented in parallel with the development of phage therapy programs, particularly to implement these novel treatments in rural and indigenous communities.

CRISPR-Cas9 high-throughput screening to study drug resistance in Leishmania infantum.

Parasites of the genus Leishmania pose a global health threat with limited treatment options. New drugs are urgently needed, and genomic screens have the potential to accelerate target discovery, mode of action, and resistance mechanisms against these new drugs. We describe here our effort in developing a genome-wide CRISPR-Cas9 screen in Leishmania, an organism lacking a functional nonhomologous end joining system that must rely on microhomology-mediated end joining, single-strand annealing, or homologous recombination for repairing Cas9-induced double-stranded DNA breaks. A new vector for cloning and expressing single guide RNAs (sgRNAs) was designed and proven to be effective in a small pilot project while enriching specific sgRNAs during drug selection. We then developed a whole-genome library of 49,754 sgRNAs, targeting all the genes of Leishmania infantum. This library was transfected in L. infantum expressing Cas9, and these cells were selected for resistance to two antileishmanials, miltefosine and amphotericin B. The sgRNAs the most enriched in the miltefosine screen targeted the miltefosine transporter gene, but sgRNAs targeting genes coding for a RING-variant protein and a transmembrane protein were also enriched. The sgRNAs the most enriched by amphotericin B targeted the sterol 24 C methyltransferase genes and a hypothetical gene. Through gene disruption experiments, we proved that loss of function of these genes was associated with resistance. This study describes the feasibility of carrying out whole-genome CRISPR-Cas9 screens in Leishmania provided that a strong selective pressure is applied. Such a screen can be used for accelerating the development of urgently needed antileishmanial drugs.IMPORTANCELeishmaniasis, a global health threat, lacks adequate treatment options and drug resistance exacerbates the challenge. This study introduces a CRISPR-Cas9 screening approach in Leishmania infantum, unraveling mechanisms of drug resistance at a genome-wide scale. Our screen was applied against two main antileishmanial drugs, and guides were enriched upon drug selection. These guides targeted known and new targets, hence validating the use of this screen against Leishmania. This strategy provides a powerful tool to expedite drug discovery as well as potential therapeutic targets against this neglected tropical disease.

PUF3 RNA binding protein of Trypanosoma cruzi regulates mitochondrial morphology and function.

The RNA-binding PUF proteins are post-transcriptional regulators found throughout the eukaryotic domain. In Trypanosoma cruzi, ten Puf genes termed Puf1 to Puf10 have been identified. Considering that the control of gene expression in this parasite is mainly at the post-transcriptional level, we characterized the PUF3 protein by knocking out and overexpressing the gene in T. cruzi epimastigotes and studied different genetic and biological features. The RNA-seq analyses in both genotypes showed significant changes in the number of regulated transcripts compared with wild-type parasites. Thus, the number of differentially expressed genes in the knockout (ΔTcPuf3) and the overexpressor (pTEXTcPuf3) were 238 and 187, respectively. In the knockout, a more significant proportion of genes was negatively regulated (166 out of 238). In contrast, in the overexpressor, positively regulated genes were predominant (149 out of 170). Additionally, when we predicted the subcellular location of the differentially expressed genes, the results revealed an important representation of nuclear genes encoding mitochondrial proteins. Therefore, we determined whether overexpression or knockout of TcPuf3 could lead to changes in both mitochondrial structure and cellular respiration. When mitochondria from ΔTcPuf3 and pTEXTcPuf3 parasites were analyzed by transmission electron microscopy (TEM), it was observed that the overexpressor had an abnormal mitochondrial morphology, evidenced by swelling. The results associated with cellular respiration showed that both the ΔTcPuf3 and pTEXTcPuf3 had a lower efficiency in routine respiration and the electron transport system capacity. Likewise, the mitochondria from overexpressing parasites showed a slight hyperpolarization. Additionally, several biological features, depending on the function of the mitochondria, were altered, such as growth, cell division, metacyclogenesis, ROS production, and response to benznidazole. In conclusion, our results suggest that although PUF3 is not an essential protein in T. cruzi, it influences mitochondrial transcripts, affecting mitochondrial morphology and function.

Analysis of inpatient data on dengue fever, malaria and leishmaniasis in Ecuador: A cross-sectional national study, 2015-2022.

Background: Despite concerted efforts in South America, these diseases continue to pose a significant burden of morbidity and mortality in endemic regions. This study aimed to analyse hospital data and investigate the hospitalisation rates of dengue fever, leishmaniasis, and malaria in Ecuador between 2015 and 2022. Methods: Open-access databases from the National Institute of Statistics and Censuses of Ecuador between 2015 and 2022 were analysed. Data were filtered using specific terms for each disease (ICD-10), and descriptive statistics of geographical distributions were calculated using Microsoft Excel, Stata 14.2, and Rstudio. Results: Dengue had the highest burden, with 31,616 reported cases, followed by malaria (1,316) and leishmaniasis (283). From 2015 to 2022, the highest hospitalisation rate per 105 inhabitants for dengue was observed in Sucumbios province (697.2), for malaria in Pastaza province (108.4), and for leishmaniasis in Morona Santiago province (18.8). The data's trend analysis revealed a slight increase in dengue and mild downward trends in hospitalisation for malaria and leishmaniasis. Conclusions: The results suggest that vector-borne disease control has failed in Ecuador. Unfortunately, there was no significant trend towards a decrease in dengue, malaria, and leishmaniasis in Ecuador during the years studied. This study highlights the need to optimise sustainable vector control programs and emphasises continuous monitoring of disease incidence and control measures.

Mental, neurological and substance use disorders among the Latino migrant population in the United States who visited the Health Windows and Mobile Health Units in 2021.

Background: Mental health is defined by the World Health Organization as a state of wellbeing in which people are aware of their own abilities to cope with the normal stresses of life, work productively and fruitfully, and contribute to their community. Among the minority groups that may be vulnerable to experiencing greater risks for their physical and mental health and full development is the migrant population. The mobile population's migration experience, from their place of origin to destination translates into psychosocial problems and clearly stressful conditions which could be resolved using certain coping strategies. Accordingly, numerous epidemiological studies have found differences in the prevalence of mental health problems between migrants and native-born residents of destination countries, as well as between migrants and their non-migrant co-nationals. Purpose: To describe sociodemographic characteristics of the Latino migrant population in the United States who visited the Health Windows (HW) and Mobile Health Units (MHU) in 2021, who may have been at risk for mental, neurological or substance use disorders and agreed to a screening for signs and symptoms of mental health conditions. Method: Users of the HW and MHU were offered preventive health services and completed a mental health screening. These variables were registered in SICRESAL. If their results showed signs and symptoms of mental health conditions, they were screened by credentialed professionals from the Psychology Faculty of the National Autonomous University of Mexico. Screened individuals received a diagnosis and specialized care remotely and/or online with the MHU and HW network partners. To analyze sociodemographic variables corresponding to neurological or substance induced mental illness among the Latino migrant population in the United States who visited the Ventanillas de Salud (VDS)/Health Windows (HW), and Unidades Móviles de Salud (UMS)/Mobile Health Units (MHU), during 2021; contingency tables were created showing percentages and chi square with a significant p < 0.05. Findings: During 2021 HW and MHU completed a total of 794 mental health screenings of which 84% were completed at HW. Further, 59% were women with an average age of 43, ranging from 7 to 86 years of age. Twenty percent 20% of the population who voluntarily agreed to screening yielded a positive result for some type of mental health symptom or problem. This percentage (37%) was greater among those who consulted MHU. With respect to age, results showed that youth were at greatest risk for mental health problems. Among the screened population, the independent variables, type of Health Window attended, gender, age group, and place of origin are related to the existence of some type of mental health symptom or problem yielding a significance level of <0.05 for depression and anxiety symptoms. Discussion and prospects: In this study, as in others, the migrant population that visited the HW and UMS in 2021 reported a greater risk of mental health problems, with symptoms related to depression and anxiety among the socio-demographic variables of gender, age group, and place of origin. Thus, these symptoms relate to being a female aged between 18 and 38 and originating from Mexico. Finally, the possibility of screening the migrant population for signs and symptoms of mental health conditions that attended the Health Windows or Mobile Health Units during 2021, made it possible to refer them to psychology or psychiatry services and improve the quality of life of those who accessed the services and, consequently, that of their families and communities. Limitations: The main limitation is associated with the information source since we worked with secondary data and relied on the information provided by those who attended both the HW and the MHU.

Molecular characterization of Ehrlichia canis and Babesia vogeli reveals multiple genogroups associated with clinical traits in dogs from urban areas of Colombia.

Ehrlichia canis and Babesia vogeli are vector-borne pathogens that infect blood cells and produce the diseases Canine Monocytic Ehrlichiosis (CME) and Babesiosis in dogs. Considering the lack of studies on these pathogens in Colombia, this study aims to determine the molecular prevalence and genetic characterization of E. canis and Babesia spp., in dogs from the Metropolitan Area of Bucaramanga (MAB), Santander, a region with one of the greatest pet densities in Colombia. One hundred eighty-five dogs were surveyed and analyzed through molecular, clinical, and hematological approaches. The molecular detection of E. canis and Babesia spp., was performed by conventional PCR targeting the dsb and 18S rRNA genes, respectively. To identify genogroups, E. canis positive samples underwent a hemi-nested PCR of the trp36 gene, and the PCR products were subsequently sequenced. Molecular analyses showed a prevalence of 13% (24/185; CI 95%, 8.1 - 18.0%) and 1.09% (2/185; CI 95,% -0.43 - 2.6%) for E. canis and B. vogeli respectively, as well as the presence of the genogroups US (USA), BR (Brazil), and CR (Costa Rica), in 62.5, 16.6, and 16.6% of E. canis positive samples, respectively. Values of hematocrit, hemoglobin, platelets, erythrocytes, white blood cell (WBC) count, lymphocytes, and eosinophils showed significant differences between animals infected with the different genogroups of E. canis (p< 0.05). In contrast, hematocrit values, hemoglobin, platelets, red blood cells, and creatine kinase MB isoenzyme (CK-MB) were lower in B. vogeli positive animals. Statistical analysis indicated that E. canis infection was associated with specific socioeconomic sectors as well as with some household features (p< 0.05). In conclusion, our results present evidence of the circulation of multiple genogroups of E. canis in the MAB, which is associated with different geographical origins and clinical traits. Epidemiological analyses suggest a need to increase molecular surveillance and prevention campaigns especially in lower socioeconomic sectors.

Tackling the cytotoxicity and genotoxicity of cellulose nanofibers from the banana rachis: A new food packaging alternative.

Cellulose nanofibrils from the banana rachis are a good alternative as packaging materials, food packaging, stabilizing agents, and functional food ingredients. To address the potential effects of ingested banana rachis cellulose nanofibrils (BR-CNFs), their toxicity in vitro and in vivo was evaluated using Caco-2 intestinal cells and mice, respectively. The results showed that BR-CNFs did not cause cytotoxic effects at the concentrations evaluated on Caco-2 cells. In addition to cytotoxicity tests, genotoxicity assays using comet assay indicated that Caco-2 cells showed no DNA damage at the concentrations of CNFs tested. Finally, acute in vivo cytotoxicity assays indicated that mice showed no sign of pathogenesis or lesions in the liver, kidney, or small intestine when treated with a single dose of BR-CNFs. Moreover, when the mice were treated daily for a month with BR-CNFs no hyperplasia or hypertrophy was observed in any of the organs evaluated. Additionally, biochemical parameters such as blood chemistry, creatinine, liver enzymes, and renal function showed that the BR-CNFs do not cause organ damage. Overall, this study shows that BR-CNFs are neither cytotoxic nor genotoxic. In conclusion, these studies are essential to guarantee the safety of this high value-added product in the food industry.

The epidemiological follow-up process for suspected and confirmed cases of COVID-19 in migrant shelters on the northern border of Mexico from July to December 2020: Between contagion underestimation and containment.

Background: Elements associated with an increased risk factor for the contagion of COVID-19 in shelters include the turnover and overcrowding of people, time spent in communal areas, daily supply needs, water availability, and sanitation levels. The "Report on the Effects of the COVID-19 Pandemic on Migrants and Refugees," shows that factors such as the shortage of food, supplies, water, sanitizing materials, spaces for healthy distancing, financial resources for rent and essential services, and the lack of medical or psychological care complicated providing care for migrants and applicants seeking international protection. Objective: We describe shelter operations regarding the detection and follow-up of suspected and confirmed COVID-19 cases showing mild symptoms among the migrant population housed in the border cities under study. Methods: We conducted semi-structured, in-depth interviews with study subjects (people in charge, managers, coordinators, shelter directors) from 22 migrant shelters, and 30 with key informants. We studied the cities of Tijuana (Baja California), Nogales (Sonora), Ciudad Juárez (Chihuahua), Piedras Negras (Coahuila), and Heroica Matamoros (Tamaulipas). The research was based on a qualitative methodological design with an ethnographic approach. The information collected was transcribed and systematized into two tables or analytical templates, one for interviews with study subjects, and another for interviews with key actors. Findings: Overall, seventy-eight registered shelters provided accommodation services for migrants in the five cities the study focused on: thirty-seven in Tijuana, five in Nogales, twenty-two in Ciudad Juárez, eight in Piedras Negras, and five plus a camp (six in total) in Matamoros. The major concentration of shelters was in Tijuana (47.4%) and Ciudad Juárez (28.2%). At the beginning of the pandemic, only a few shelter facilities met quarantine and isolation guidelines, such as having separate bathrooms and sufficient space to isolate the "asymptomatic" and "confirmed" from close "contacts". The lack of isolation space and the inability to support the monitoring of patients with COVID-19 posed a challenge for those housed in shelters, forcing many shelters to close or continue operating behind closed doors to avoid becoming a source of infection during the pandemic. Discussion and outlook: Contrary to speculation, during the onset of the pandemic northern border migrant shelters did not become sources of COVID-19 infection. According to the data analyzed from 78 shelters only seven had confirmed cases, and the classification of "outbreak" was applied only in two facilities. Contagion control or containment was successful as the result of following a preventive containment logic, including the isolation of all suspected but unconfirmed cases, without a clear understanding of the human and financial resources required to maintain isolation areas. However, shelters in the study implemented protocols for epidemiological surveillance, control, and prevention with elements that interfered with monitoring spaces, and processes that caused oversights that resulted in underestimating the number of cases. Limitations: Due to travel restrictions imposed to prevent and contain coronavirus infections it was impossible to stay on-site in the cities studied, except for Tijuana, or carry-out recordings of migrants' views in shelters.

Ventanillas de Salud (VDS) and Mobile Health Units (MHU): A binational collaborative models.

Over the years, the Mexican population in the United States has faced high prevalence of health-related inequalities and disadvantages and represents one of the most vulnerable migrant groups in the country. To help reduce the gaps in health care for the Mexican population, the Mexican government, in collaboration with strategic allies from various sectors, launched the Ventanillas de Salud (VDS) strategy, which was subsequently reinforced through the Mobile Health Units (MHU) care model. Both the VDS strategy and the MHU care model are intended to contribute to the development of initiatives, projects, and actions in health that will benefit the Mexican community living in the United States, which lacks or has difficulty accessing health services. This article provides a descriptive, analytical analysis of the VDS strategy and the MHU care model, as unique collaborative models, which can be replicated, and have achieved a positive impact on the health of Mexican and other Hispanic communities in the United States, at both the individual and community level.

Enzootic Trypanosoma cruzi infection by Rhodnius prolixus shows transmission to humans and dogs in Vichada, Colombia.

Background: Rhodnius prolixus is considered the most relevant Trypanosoma cruzi vector in Colombia and Venezuela due it is responsible for domestic transmission in both countries. However, a wild population of this species is distributed in the eastern plains of the Orinoco region and Amazonia jungle, where its epidemiological importance has not been sufficiently elucidated. This study aimed to assess epidemiological parameters of T. cruzi transmission in the Department of Vichada, Colombia. Methods: We determined the characteristics of T. cruzi transmission using entomological studies in domestic and sylvatic ecotopes. We analyzed the T. cruzi infection in triatomine insects, identified blood meal sources, and conducted a serological determination of T. cruzi infection in scholar-aged children, domestic dogs, and wild hosts. Results: Fifty-four triatomine bugs, 40 T. maculata and 14 R. prolixus were collected in peridomestic and sylvatic ecotopes. Infected R. prolixus was observed in La Primavera, Santa Rosalia, and Cumaribo municipalities. All the T. maculata bugs were not infected. Serological analysis indicated that two of 3,425 children were T. cruzi positive. The seroprevalence in domestic dogs was 10,5% (49/465). Moreover, 22 synanthropic mammals were sampled, being Didelphis marsupialis the most common. TcI genotype was detected in seropositive dogs, R. prolixus, and D. marsupialis. Conclusion: The present work describes extra domestic R. prolixus and D. marsupialis in a sylvatic T. cruzi transmission cycle with transmission to humans and domestic dogs in Colombia's Vichada Department.

Pulmonary Inflammatory Response in Lethal COVID-19 Reveals Potential Therapeutic Targets and Drugs in Phases III/IV Clinical Trials.

Background: It is imperative to identify drugs that allow treating symptoms of severe COVID-19. Respiratory failure is the main cause of death in severe COVID-19 patients, and the host inflammatory response at the lungs remains poorly understood. Methods: Therefore, we retrieved data from post-mortem lungs from COVID-19 patients and performed in-depth in silico analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, and shortest pathways to physiological phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials. Results: Herein, we analyzed transcriptomics data of 719 inflammatory response genes across 19 cell types (116,313 nuclei) from lung autopsies. The functional enrichment analysis of the 233 significantly expressed genes showed that the most relevant biological annotations were inflammatory response, innate immune response, cytokine production, interferon production, macrophage activation, blood coagulation, NLRP3 inflammasome complex, and the TLR, JAK-STAT, NF-κB, TNF, oncostatin M signaling pathways. Subsequently, we identified 34 essential inflammatory proteins with both high-confidence protein interactions and shortest pathways to inflammation, cell death, glycolysis, and angiogenesis. Conclusion: We propose three small molecules (baricitinib, eritoran, and montelukast) that can be considered for treating severe COVID-19 symptoms after being thoroughly evaluated in COVID-19 clinical trials.

Social cohesion emerging from a community-based physical activity program: A temporal network analysis.

Community-based physical activity programs, such as the Recreovía, are effective in promoting healthy behaviors in Latin America. To understand Recreovías' challenges and scalability, we characterized its social network longitudinally while studying its participants' social cohesion and interactions. First, we constructed the Main network of the program's Facebook profile in 2013 to determine the main stakeholders and communities of participants. Second, we studied the Temporal network growth of the Facebook profiles of three Recreovía locations from 2008 to 2016. We implemented a Time Windows in Networks algorithm to determine observation periods and a scaling model of cities' growth to measure social cohesion over time. Our results show physical activity instructors as the main stakeholders (20.84% nodes of the network). As emerging cohesion, we found: (1) incremental growth of Facebook users (43-272 nodes), friendships (55-2565 edges), clustering coefficient (0.19-0.21), and density (0.04-0.07); (2) no preferential attachment behavior; and (3) a social cohesion super-linear growth with 1.73 new friendships per joined user. Our results underscore the physical activity instructors' influence and the emergent cohesion in innovation periods as a co-benefit of the program. This analysis associates the social and healthy behavior dimensions of a program occurring in natural environments under a systemic approach.

Molecular surveillance of resistance to pyrethroids insecticides in Colombian Aedes aegypti populations.

INTRODUCTION: In Colombia, organochloride, organophosphate, carbamate, and pyrethroid insecticides are broadly used to control Aedes aegypti populations. However, Colombian mosquito populations have shown variability in their susceptibility profiles to these insecticides, with some expressing high resistance levels. MATERIALS AND METHODS: In this study, we analyzed the susceptibility status of ten Colombian field populations of Ae. aegypti to two pyrethroids; permethrin (type-I pyrethroid) and lambda-cyhalothrin (type-II pyrethroid). In addition, we evaluated if mosquitoes pressured with increasing lambda-cyhalothrin concentrations during some filial generations exhibited altered allelic frequency of these kdr mutations and the activity levels of some metabolic enzymes. RESULTS: Mosquitoes from all field populations showed resistance to lambda-cyhalothrin and permethrin. We found that resistance profiles could only be partially explained by kdr mutations and altered enzymatic activities such as esterases and mixed-function oxidases, indicating that other yet unknown mechanisms could be involved. The molecular and biochemical analyses of the most pyrethroid-resistant mosquito population (Acacías) indicated that kdr mutations and altered metabolic enzyme activity are involved in the resistance phenotype expression. CONCLUSIONS: In this context, we propose genetic surveillance of the mosquito populations to monitor the emergence of resistance as an excellent initiative to improve mosquito-borne disease control measures.

In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19.

Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively. Methods: We performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19. Results: We screened 1,584 high-confidence immune system proteins in ACE2 and TMPRSS2 co-expressing cells, finding 25 potential therapeutic targets significantly overexpressed in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies. Then, we performed fully connected deep neural networks to find the best multitask classification model to predict the activity of 10,672 drugs, obtaining several approved drugs, compounds under investigation, and experimental compounds with the highest area under the receiver operating characteristics. Conclusion: After being effectively analyzed in clinical trials, these drugs can be considered for treatment of severe COVID-19 patients. Scripts can be downloaded at https://github.com/muntisa/immuno-drug-repurposing-COVID-19.

Benchmarking seeding strategies for spreading processes in social networks: an interplay between influencers, topologies and sizes.

The explosion of network science has permitted an understanding of how the structure of social networks affects the dynamics of social contagion. In community-based interventions with spill-over effects, identifying influential spreaders may be harnessed to increase the spreading efficiency of social contagion, in terms of time needed to spread all the largest connected component of the network. Several strategies have been proved to be efficient using only data and simulation-based models in specific network topologies without a consensus of an overall result. Hence, the purpose of this paper is to benchmark the spreading efficiency of seeding strategies related to network structural properties and sizes. We simulate spreading processes on empirical and simulated social networks within a wide range of densities, clustering coefficients, and sizes. We also propose three new decentralized seeding strategies that are structurally different from well-known strategies: community hubs, ambassadors, and random hubs. We observe that the efficiency ranking of strategies varies with the network structure. In general, for sparse networks with community structure, decentralized influencers are suitable for increasing the spreading efficiency. By contrast, when the networks are denser, centralized influencers outperform. These results provide a framework for selecting efficient strategies according to different contexts in which social networks emerge.