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.

Emerging cell and molecular targets for treating mucus hypersecretion in asthma.

Mucus provides a protective barrier that is crucial for host defense in the lungs. However, excessive or abnormal mucus can have pathophysiological consequences in many pulmonary diseases, including asthma. Patients with asthma are treated with agents that relax airway smooth muscle and reduce airway inflammation, but responses are often inadequate. In part, this is due to the inability of existing therapeutic agents to directly target mucus. Accordingly, there is a critical need to better understand how mucus hypersecretion and airway plugging are affected by the epithelial cells that synthesize, secrete, and transport mucus components. This review highlights recent advances in the biology of mucin glycoproteins with a specific focus on MUC5AC and MUC5B, the chief macromolecular components of airway mucus. An improved mechanistic understanding of key steps in mucin production and secretion will help reveal novel potential therapeutic strategies.

Effect of a Lactococcus lactis culture supernatant on diarrhea and performance parameters of piglets in the post-weaning period and on expression of the faeG gene in vitro.

Objectives: To evaluate the effects of a cell-free supernatant from Lactococcus lactis (CFSM) on performance and diarrhearelated parameters and the presence of F4+ enterotoxigenic E. coli (ETEC) in piglets during post-weaning, and to evaluate the in vitro effect of the CFSM on faeG gene expression in an E. coli F4+. Animals and procedure: In 3 trials with 90 piglets per trial, pigs were assigned to receive a placebo or 1 of 2 CFSM treatments and observed for diarrhea and performance. Fecal swabs were taken to determine the presence of ETEC. Quantitative RT-PCR was used to assess faeG gene expression in E. coli 21259 after treatment with CFSM at 50 mg/mL. Results: The CFSM administered for 14 d at a dose of 24 mg/kg BW (2X) reduced diarrhea-related parameters compared to the placebo. Quantitative RT-PCR showed that, in E. coli 21259 treated with CFSM at 50 mg/mL, expression of the faeG gene was significantly repressed (P < 0.0001) relative to that in the untreated control. Conclusion: The evaluated CFSM reduced the frequency and prevalence of diarrhea in a field situation. The in vitro treatment had an inhibitory effect on the expression of the faeG gene in F4+ E. coli 21259.

Effet d'un surnageant de culture de Lactococcus lactis sur la diarrhée et les paramètres de performance des porcelets en période post-sevrage et sur l'expression du gène faeG in vitro. Objectifs: Évaluer les effets d'un surnageant acellulaire de Lactococcus lactis (CFSM) sur les paramètres de performance et de diarrhée et la présence d'E. coli entérotoxinogène F4+ (ETEC) chez les porcelets en post-sevrage, et évaluer l'effet in vitro du CFSM sur l'expression du gène faeG dans un E. coli F4+. Animaux et procédure: Dans 3 essais portant sur 90 porcelets par essai, les porcs ont reçu un placebo ou 1 des 2 traitements CFSM et ont été observés pour détecter la diarrhée et leurs performances. Des prélèvements fécaux ont été effectués pour déterminer la présence d'ETEC. La RT-PCR quantitative a été utilisée pour évaluer l'expression du gène faeG dans E. coli 21259 après traitement avec CFSM à 50 mg/mL. Résultats: Le CFSM administré pendant 14 jours à une dose de 24 mg/kg de poids corporel (2X) a réduit les paramètres liés à la diarrhée par rapport au placebo. La RT-PCR quantitative a montré que, chez E. coli 21259 traité avec CFSM à 50 mg/mL, l'expression du gène faeG était significativement réprimée (P < 0,0001) par rapport à celle du témoin non traité. Conclusion: Le CFSM évalué a réduit la fréquence et la prévalence de la diarrhée sur le terrain. Le traitement in vitro a eu un effet inhibiteur sur l'expression du gène faeG chez F4+ E. coli 21259.(Traduit par Dr Serge Messier).

Rasch analysis of the dermatology life quality index (DLQI) in patients with mild to moderate-severe psoriasis.

Background The Dermatology Life Quality Index (DLQI) is a valuable tool for assessing the quality of life in adult patients with psoriasis. Aims To analyse the reliability and validity of the DLQI to measure the quality of life in patients with mild to moderate-severe psoriasis. Methods This was a secondary validation study nested in a follow-up study. The Rasch-Andrich model was utilised to perform response function, item and person fit, differential item functioning, dimensionality, and reliability analyses. Results A total of 1439 patients were analysed, 52.1% male, mean age of 48.7 years (SD 16.1). Psoriasis vulgaris was the phenotype in 43.1% of patients, and 86% had a mild Psoriasis Area Severity Index (PASI). Adequate adjustment of the response function and the items was observed in the best-fit sample, except for item 7 (work and study). The measure explained 60.9% of the variance and presented a reliability of 0.86. Differential item functioning was identified by age, with a relevant bias in the estimation for older adults. Item-person maps are provided. Limitations This study was performed at a single centre, with most patients presenting a mild PASI score, limiting generalisation of the findings. Conclusion The validity evidence favours the use of the DLQI in moderate-severe psoriasis. However, the instrument biases the estimate of older adults. This population group should consider a specific version of the instrument.

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.

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.

Quantifying antimicrobial use on Canadian dairy farms using garbage can audits.

Antimicrobial resistance in pathogenic bacteria is one of the preeminent concerns for the future of global health. There is a dose-dependent relationship between antimicrobial use (AMU) and the prevalence of antimicrobial-resistant pathogens. As most AMU in Canada is related to animal agriculture, there is a need to reduce overall AMU, which could be accomplished through surveillance of AMU in animal agriculture, including the dairy industry. The objective of this study was to quantify AMU on dairy farms across Canada. This study had two parts: a description of data collected in 2019-2020, and a meta-analysis comparing this data to previous estimates of AMU in the Canadian dairy industry. The first included a garbage can audit (GCA) on 107 farms in four Canadian provinces (British Columbia, Alberta, Ontario, and Nova Scotia) in 2020; AMU data were converted to the dose-based metrics of defined course doses (DCD) and defined daily doses (DDD). Mixed-effect linear models were fit to determine the relationship between province and use of different classes of antimicrobials. On average, for every 100 animals on the farm, 117 DCD of antimicrobials were administered per year (IQR: 55, 158). These treatments amounted to 623 DDD / 100 animal-yr (IQR: 302, 677 DDD/100 animal-years). Penicillins were the most used class of antimicrobials, followed by first-and third-generation cephalosporins. Farms in Ontario used more third-generation cephalosporins than other provinces. The second part of this study compared AMU in 2020 to previously reported Canadian studies through a meta-analysis. A GCA was conducted in 2007-2008 in Alberta, Ontario, Québec, and the Maritime provinces (Prince Edward Island, New Brunswick and Nova Scotia); another GCA was conducted in Québec in 2018. Overall, AMU was lower in 2018-2020 than in 2007-2008, with the exception of third-generation cephalosporin use, which increased.

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.

The disulfide catalyst QSOX1 maintains the colon mucosal barrier by regulating Golgi glycosyltransferases.

Mucus is made of enormous mucin glycoproteins that polymerize by disulfide crosslinking in the Golgi apparatus. QSOX1 is a catalyst of disulfide bond formation localized to the Golgi. Both QSOX1 and mucins are highly expressed in goblet cells of mucosal tissues, leading to the hypothesis that QSOX1 catalyzes disulfide-mediated mucin polymerization. We found that knockout mice lacking QSOX1 had impaired mucus barrier function due to production of defective mucus. However, an investigation on the molecular level revealed normal disulfide-mediated polymerization of mucins and related glycoproteins. Instead, we detected a drastic decrease in sialic acid in the gut mucus glycome of the QSOX1 knockout mice, leading to the discovery that QSOX1 forms regulatory disulfides in Golgi glycosyltransferases. Sialylation defects in the colon are known to cause colitis in humans. Here we show that QSOX1 redox control of sialylation is essential for maintaining mucosal function.

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.

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.

Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice.

Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells can sense allergens via expression of myriad Toll-like receptors (TLRs) and other pattern-recognition receptors. We sought to determine whether the innate immune response stimulated by a combination of Pam2CSK4 ("Pam2", TLR2/6 ligand) and a class C oligodeoxynucleotide ODN362 ("ODN", TLR9 ligand), when delivered together by aerosol ("Pam2ODN"), can modulate the allergic immune response to allergens. Treatment with Pam2ODN 7 days before sensitization to House Dust Mite (HDM) extract resulted in a strong reduction in eosinophilic and lymphocytic inflammation. This Pam2ODN immunomodulatory effect was also seen using Ovalbumin (OVA) and A. oryzae (Ao) mouse models. The immunomodulatory effect was observed as much as 30 days before sensitization to HDM, but ineffective just 2 days after sensitization, suggesting that Pam2ODN immunomodulation lowers the allergic responsiveness of the lung, and reduces the likelihood of inappropriate sensitization to aeroallergens. Furthermore, Pam2 and ODN cooperated synergistically suggesting that this treatment is superior to any single agonist in the setting of allergen immunotherapy.

Mucins MUC5AC and MUC5B Are Variably Packaged in the Same and in Separate Secretory Granules.

Rationale: MUC5AC (mucin 5AC, oligomeric gel-forming) and MUC5B (mucin 5B, oligomeric gel-forming) are the predominant secreted polymeric mucins in mammalian airways. They contribute differently to the pathogenesis of various muco-obstructive and interstitial lung diseases, and their genes are separately regulated, but whether they are packaged together or in separate secretory granules is not known. Objectives: To determine the packaging of MUC5AC and MUC5B within individual secretory granules in mouse and human airways under varying conditions of inflammation and along the proximal-distal axis. Methods: Lung tissue was obtained from mice stimulated to upregulate mucin production by the cytokines IL-1ß and IL-13 or by porcine pancreatic elastase. Human lung tissue was obtained from donated normal lungs, biopsy samples of transplanted lungs, and explanted lungs from subjects with chronic obstructive pulmonary disease. MUC5AC and MUC5B were labeled with antibodies from different animal species or, in mice only, by transgenic chimeric mucin-fluorescent proteins and imaged using widefield deconvolution or Airyscan fluorescence microscopy. Measurements and Main Results: In both mouse and human airways, most secretory granules contained both mucins interdigitating within the granules. Smaller numbers of granules contained MUC5B alone, and even fewer contained MUC5AC alone. Conclusions: MUC5AC and MUC5B are variably stored both in the same and in separate secretory granules of both mice and humans. The high fraction of granules containing both mucins under a variety of conditions makes it unlikely that their secretion can be differentially controlled as a therapeutic strategy. This work also advances knowledge of the packaging of mucins within secretory granules to understand mechanisms of epithelial stress in the pathogenesis of chronic lung diseases.

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.

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.

Exploration of inhibitors of the bacterial LexA repressor-protease.

Resistant and tolerant bacterial infections lead to billions in healthcare costs and cause hundreds of thousands of deaths each year. The bulk of current antibiotic research efforts focus on molecules which, although novel, are not immune from acquired resistance and seldomly affect tolerant populations. The bacterial SOS response has been implicated in several resistance and tolerance mechanisms, making it an attractive antibiotic target. Using small molecule inhibitors targeting a key step in the deployment of the SOS response, our approach focused on preventing the deployment of mechanisms such as biofilm formation, horizontal gene transfer, and error-prone DNA repair. Herein we report the synthesis and testing of analogs of a triazole-containing tricyclic inhibitor of LexA proteolysis, the key event in the SOS response. Our results hint that our inhibitor's may function by adopting a ß-hairpin conformation, reminiscent of the native cleavage loop of LexA.

Is the anemia in men an effect of the risk of crude oil contamination?

Pollution from oil spills can seriously affect many ecosystem processes and human health. Many articles have evaluated the impact of oil spills on human health. However, most of these articles focus on occupational exposure. The effect on people living in the areas affected by oil pollution is rarely studied. Approximately 640 million people worldwide live in areas at risk of oil pollution. Thus, studying the impact of this pollution on human health should be a priority. Here, we evaluate the presence of anemia in relation to crude oil exposure in men living in areas at risk of oil contamination in the Ecuadorian Amazon (Orellana and Napo). We evaluated the hematological and biochemical parameters of 135 participants. We divided the participants into three groups according to exposure: low, medium, and high. Our results showed a significant association between exposure risk and hemoglobin and hematocrit concentration. Groups with medium- and high- contamination exposure had levels below normal values in hemoglobin and hematocrit in more than 30% and 26% of the population, respectively. In conclusion, we found that crude oil affected human health, and the prevalence of the anemia in men was dependent of the level of contamination.

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.