Glioma-derived M-CSF and IL-34 license M-MDSCs to suppress CD8+ T cells in a NOS-dependent manner.

Glioblastoma (GBM) is the most common malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a subset of myeloid cells, expressing monocytic (M)-MDSC markers and dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate the TME. This study evaluated the mechanism of CCR2+/CX3CR1+ M-MDSC differentiation and T cell suppressive function in murine glioma models. We determined that bone marrow-derived CCR2+/CX3CR1+ cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Glioma secreted CSF1R ligands M-CSF and IL-34 were identified as key drivers of M-MDSC differentiation while adenosine and iNOS pathways were implicated in M-MDSC suppression of T cells. Mining a human GBM spatial RNAseq database revealed a variety of different pathways that M-MDSCs utilize to exert their suppressive function that are driven by complex niches within the microenvironment. These data provide a more comprehensive understanding of the mechanism of M-MDSCs in glioblastoma.

Prognostic value of neutrophil-to-lymphocyte ratio at diagnosis in colorectal cancer: propensity score analysis.

INTRODUCTION: Baseline neutrophil-to-lymphocyte ratio (NLR) at the time of colorectal cancer (CRC) diagnosis has been proposed as a predictor of long-term survival. The aim of the study was to analyse its usefulness in a homogeneous population with control of the main confounding factors. METHODOLOGY: Observational study of 836 patients operated on for CRC who were divided into two groups: NLR ≤ 3.3 vs NLR > 3.3. To control for confounders, they were matched one-to-one by propensity analysis. A final sample of 526 patients remained for study. RESULTS: The two groups were mismatched in terms of age, comorbidity, tumour stage, rectal location, and neoadjuvant therapy. Once matching was performed, baseline NLR was statistically significantly associated with long-term survival (p < 0.001) and behaved as an independent prognostic factor for survival (p = 0.001; HR: 1,996; 95% CI: 1.32-3.00) when adjusted in a Cox regression model using age (p < 0,001; HR: 1,04; IC95%: 1,02-1,06) and the Charlson Comorbidity Index (p < 0,001; HR: 1,40; IC95%: 1,27-1,55). Neoadjuvant therapy lost its statistical significance (p = 0,137; HR: 1,59; IC95%: 0,86-2,93). CONCLUSIONS: A high baseline NLR (> 3.3) in patients with colorectal cancer at diagnosis represents a poor prognostic factor in terms of survival. Its use in routine practice could intensify therapeutic strategies and follow-up in these patients.

Relevance of comorbidities for main outcomes during different periods of the COVID-19 pandemic.

Background: Throughout the evolution of the COVID-19 pandemic, the severity of the disease has varied. The aim of this study was to determine how patients' comorbidities affected and were related to, different outcomes during this time. Methods: Retrospective cohort study of all patients testing positive for SARS-CoV-2 infection between March 1, 2020, and January 9, 2022. We extracted sociodemographic, basal comorbidities, prescribed treatments, COVID-19 vaccination data, and outcomes such as death and admission to hospital and intensive care unit (ICU) during the different periods of the pandemic. We used logistic regression to quantify the effect of each covariate in each outcome variable and a random forest algorithm to select the most relevant comorbidities. Results: Predictors of death included having dementia, heart failure, kidney disease, or cancer, while arterial hypertension, diabetes, ischemic heart, cerebrovascular, peripheral vascular diseases, and leukemia were also relevant. Heart failure, dementia, kidney disease, diabetes, and cancer were predictors of adverse evolution (death or ICU admission) with arterial hypertension, ischemic heart, cerebrovascular, peripheral vascular diseases, and leukemia also relevant. Arterial hypertension, heart failure, diabetes, kidney, ischemic heart diseases, and cancer were predictors of hospitalization, while dyslipidemia and respiratory, cerebrovascular, and peripheral vascular diseases were also relevant. Conclusions: Preexisting comorbidities such as dementia, cardiovascular and renal diseases, and cancers were those most related to adverse outcomes. Of particular note were the discrepancies between predictors of adverse outcomes and predictors of hospitalization and the fact that patients with dementia had a lower probability of being admitted in the first wave.

Molecular insight into endosulfan degradation by Ese protein from Arthrobacter: Evidence-based structural bioinformatics and quantum mechanical calculations.

Endosulfan is an organochlorine insecticide widely used for agricultural pest control. Many nations worldwide have restricted or completely banned it due to its extreme toxicity to fish and aquatic invertebrates. Arthrobacter sp. strain KW has the ability to degrade α, ß endosulfan and its intermediate metabolite endosulfate; this degradation is associated with Ese protein, a two-component flavin-dependent monooxygenase (TC-FDM). Employing in silico tools, we obtained the 3D model of Ese protein, and our results suggest that it belongs to the Luciferase Like Monooxygenase family (LLM). Docking studies showed that the residues V59, V315, D316, and T335 interact with α-endosulfan. The residues: V59, T60, V315, D316, and T335 are implicated in the interacting site with ß-endosulfan, and the residues: H17, V315, D316, T335, N364, and Q363 participate in the interaction with endosulfate. Topological analysis of the electron density by means of the Quantum Theory of Atoms in Molecules (QTAIM) and the Non-Covalent Interaction (NCI) index reveals that the Ese-ligands complexes are formed mainly by dispersive forces, where Cl atoms have a predominant role. As Ese is a monooxygenase member, we predict the homodimer formation. However, enzymatic studies must be developed to investigate the Ese protein's enzymatic and catalytic activity.

Teoría de Rango Medio: Factores personales, ambientales y consumo de alcohol / Middle Range Theory: Personal, environmental factors and alcohol consumption / Teoria do Médio Alcance: Fatores pessoais, ambientais e consumo de álcool

El consumo de alcohol se considera un fenómeno complejo y multifactorial que puede estudiarse a través de diversas posturas teóricas, sin embargo, algunas teorías existentes carecen de sufi-cientes elementos para explorar y comprender dicho fenómeno. Por lo anterior, se propone una Teoría de Rango Medio que aborde los factores personales, ambientales y representaciones so-ciales del consumo de alcohol en jóvenes universitarios a partir de la Teoría Cognitiva Social de Bandura y de la conceptualización de la representación social de Moscovici. Para ello, se utilizó el método de Estructura Conceptual-Teórico-Empírico propuesto por Fawcett, compuesto por cinco pasos. La teoría derivada de este método contribuye en la identificación de un fenómeno específico para la disciplina mediante la determinación de conceptos y su relación con el con-sumo de alcohol en jóvenes universitarios. Además, de la incorporación de las representaciones sociales como elemento innovador para la profundización del fenómeno. Esta propuesta puede ser considerada en futuras investigaciones para ser probada y contribuir significativamente en el desarrollo de conocimiento sobre el consumo de alcohol

Alcohol consumption is considered a complex and multifactorial phenomenon that can be studied through various theoretical positions; however, some existing theories lack sufficient elements to explore and understand this phenomenon. Therefore, a Middle Range Theory is proposed that addresses personal, environmental, and social representations of alcohol consumption in young university students based on Bandura's Social Cognitive Theory and Moscovici's conceptualiza-tion of social representation. For this, the method of Conceptual-Theoretical-Empirical Structure proposed by Fawcett was used, consisting of five steps. The theory derived from this method con-tributes to the identification of a specific phenomenon for the discipline by determining concepts and their relationship with alcohol consumption in young university students. In addition, the incorporation of social representations as an innovative element for the deepening of the phenom-enon. This proposal can be considered in future research to be tested and contribute significantly to the development of knowledge about alcohol consumption

O consumo de álcool é considerado um fenômeno complexo e multifatorial que pode ser estu-dado por meio de vários posicionamentos teóricos, porém, algumas teorias existentes carecem de elementos suficientes para explorar e compreender esse fenômeno. Assim, propõe-se uma Teoria de Médio Alcance que aborda as representações pessoais, ambientais e sociais do consu-mo de álcool em universitários com base na Teoria Social Cognitiva de Bandura e na conceitu-ação de representação social de Moscovici. Para isso, foi utilizado o método da Estrutura Con-ceitual-Teórico-Empírica proposto por Fawcett, composto por cinco etapas. A teoria derivada desse método contribui para a identificação de um fenômeno específico da disciplina ao deter-minar conceitos e sua relação com o consumo de álcool em jovens universitários. Além disso, a incorporação das representações sociais como elemento inovador para o aprofundamento do fenômeno. Essa proposta pode ser considerada em pesquisas futuras a serem testadas e contribuir significativamente para o desenvolvimento do conhecimento sobre o consumo de álcool

Fibre4life: Investigating older adults dietary fibre preferences and the role of targeted educational materials on modulating future dietary fibre intake.

The UK has an ever-increasing ageing population; hence, promoting balanced nutrition can have fundamental health and cost benefits. In addition, the majority of older adults' dietary fibre intake is below recommendations and this is despite its well-cited benefits; therefore, more emphasis should be placed on identifying viable age-suitable strategies to overcome the associated dietary fibre-related knowledge gap. Accordingly, one hundred and seventy older adults (65-87 years) were recruited to partake in two survey related studies: (1) initial insights (e.g., dietary fibre-related knowledge, awareness, attitudes and behaviour as well as information preferences) were captured to inform the design of educational materials; and (2) the impact of two targeted educational materials on modulating older adults' future dietary fibre intake was tested. Older adults were willing to learn more about dietary fibre and requested additional information relating to its benefits, recommendations and food-based examples in a clear and accessible format. Therefore, two educational materials (factsheet and practical tips) were developed encompassing key themes. Overall, older adults engaged with the educational materials (regardless of topic and format); thus, demonstrating the potential benefits of this approach going forwards. There was strong agreement with all variables: learning something new, change future dietary fibre intake, format liking, content engaging and share with others as well as the overall experience being cited as useful/helpful. Going forwards, importance should be placed on measuring dietary fibre consumption post engaging with educational materials. In addition, utilising a holistic approach incorporating support from different sources (e.g., health professionals, government, food companies, supermarkets and community) could be fundamental in helping older adults to consume more dietary fibre and subsequently contributing to positive health outcomes.

Inoculation with Azospirillum argentinense Az19 improves the yield of maize subjected to water déficit at key stages of plant development / La inoculación con Azospirillum argentinense Az19 mejora el rendimiento del maíz expuesto a déficit hídrico durante estadios clave del desarrollo vegetal

Resumen El déficit hídrico constituye una severa limitación a la productividad agrícola. En el marco de la producción sostenible de cultivos, la biotecnología microbiana está cobrando relevancia para aumentar la tolerancia a la sequía y mejorar el rendimiento de los cultivos en condiciones adversas. El propósito de este trabajo fue comparar la acción de la cepa de Azospirillum argentinense Az19, con tolerancia in vitro a estresores abióticos, con la cepa Az39, utilizada ampliamente para la formulación de inoculantes comerciales, al inocularlas en plantas sometidas a déficit hídrico. Se realizaron ensayos de invernadero y de campo. En invernadero, la cepa Az19 evitó el impacto adverso del déficit hídrico en el estadio V2 sobre el crecimiento del maíz. Además, el porcentaje de plantas con espigas y el peso de la espiga disminuyó significativamente con la restricción hídrica aplicada en V2 y en floración en plantas inoculadas con la cepa Az39, pero no en las inoculadas con Az19. En el primer ensayo de campo con el maíz híbrido comercial DOW DS 515 PW las plantas inoculadas con Az19 fueron las que mejor toleraron la deficiencia hídrica. En el segundo ensayo de campo se utilizaron dos genotipos de maíz con sensibilidad diferencial a la sequía. La inoculación con Az19 condujo a una mayor tolerancia al déficit hídrico, con un efecto detectable en algunos componentes del rendimiento en el genotipo sensible. Sobre la base de estos resultados, proponemos el empleo de A. argentinense Az19 para la formulación de inoculantes basados en Azospirillum especialmente indicados para áreas agroecológicas que experimenten períodos de déficit hídrico.

The NCIWEB Server: A Novel Implementation of the Noncovalent Interactions Index for Biomolecular Systems.

It is well-known that the activity and function of proteins is strictly correlated with their secondary, tertiary, and quaternary structures. Their biological role is regulated by their conformational flexibility and global fold, which, in turn, is largely governed by complex noncovalent interaction networks. Because of the large size of proteins, the analysis of their noncovalent interaction networks is challenging, but can provide insights into the energetics of conformational changes or protein-protein and protein-ligand interactions. The noncovalent interaction (NCI) index, based on the reduced density gradient, is a well-established tool for the detection of weak contacts in biological systems. In this work, we present a web-based application to expand the use of this index to proteins, which only requires a molecular structure as input and provides a mapping of the number, type, and strength of noncovalent interactions. Structure preparation is automated and allows direct importing from the PDB database, making this server (https://nciweb.dsi.upmc.fr) accessible to scientists with limited experience in bioinformatics. A quick overview of this tool and concise instructions are presented, together with an illustrative application.

Physician Perceptions of and Barriers to Pediatric Palliative Care for Children With Cancer in Brazil.

PURPOSE: Early integration of pediatric palliative care (PPC) for children with cancer is critical to improving the quality of life of both the patient and family. Understanding physician perceptions of palliative care and perceived barriers to early integration is necessary to develop PPC in Brazil. METHODS: The Assessing Doctors' Attitudes on Palliative Treatment survey was modified for use in Brazil. The survey was open from January 2022 to June 2022 and distributed to physicians of all specialties from participating institutions who treat children with cancer. Statistical analysis was complemented by qualitative analysis of open-ended responses. RESULTS: A total of 272 respondents participated. Most respondents reported access to PPC experts for consultation (77.2%) and 34.5% indicated previous palliative care training. Physician knowledge of PPC was generally aligned with WHO guidance (median alignment, 93.0%; range, 80.5%-98.2%). However, about half (53.3%) felt comfortable addressing physical needs of patients receiving PPC, 35.3% addressing emotional needs, 25.8% addressing spiritual needs, and 33.5% addressing grief and bereavement needs. Most respondents (65.4%) felt palliative care should be involved from diagnosis, but only 10.3% stated that this occurred in their setting. The most important barriers identified were physician discomfort (89.0%), limited physician knowledge (88.6%), and lack of home-based services (83.8%). CONCLUSION: Despite a strong understanding of the role of palliative care, physicians in Brazil reported low confidence delivering PPC to children with cancer. Additionally, physicians generally believed that PPC should be integrated earlier in the disease trajectory of children with cancer. This work will direct educational and capacity building initiatives to ensure greater access to high-quality PPC for children with cancer in Brazil to address patient and family suffering.

Clinical prediction rules for adverse evolution in patients with COVID-19 by the Omicron variant.

OBJECTIVE: We identify factors related to SARS-CoV-2 infection linked to hospitalization, ICU admission, and mortality and develop clinical prediction rules. METHODS: Retrospective cohort study of 380,081 patients with SARS-CoV-2 infection from March 1, 2020 to January 9, 2022, including a subsample of 46,402 patients who attended Emergency Departments (EDs) having data on vital signs. For derivation and external validation of the prediction rule, two different periods were considered: before and after emergence of the Omicron variant, respectively. Data collected included sociodemographic data, COVID-19 vaccination status, baseline comorbidities and treatments, other background data and vital signs at triage at EDs. The predictive models for the EDs and the whole samples were developed using multivariate logistic regression models using Lasso penalization. RESULTS: In the multivariable models, common predictive factors of death among EDs patients were greater age; being male; having no vaccination, dementia; heart failure; liver and kidney disease; hemiplegia or paraplegia; coagulopathy; interstitial pulmonary disease; malignant tumors; use chronic systemic use of steroids, higher temperature, low O2 saturation and altered blood pressure-heart rate. The predictors of an adverse evolution were the same, with the exception of liver disease and the inclusion of cystic fibrosis. Similar predictors were found to be related to hospital admission, including liver disease, arterial hypertension, and basal prescription of immunosuppressants. Similarly, models for the whole sample, without vital signs, are presented. CONCLUSIONS: We propose risk scales, based on basic information, easily-calculable, high-predictive that also function with the current Omicron variant and may help manage such patients in primary, emergency, and hospital care.

Extracting Quantitative Information at Quantum Mechanical Level from Noncovalent Interaction Index Analyses.

The noncovalent interaction (NCI) index is nowadays a well-known strategy to detect NCIs in molecular systems. Even though it initially provided only qualitative descriptions, the technique has been recently extended to also extract quantitative information. To accomplish this task, integrals of powers of the electron distribution were considered, with the requirement that the overall electron density can be clearly decomposed as sum of distinct fragment contributions to enable the definition of the (noncovalent) integration region. So far, this was done by only exploiting approximate promolecular electron densities, which are given by the sum of spherically averaged atomic electron distributions and thus represent too crude approximations. Therefore, to obtain more quantum mechanically (QM) rigorous results from NCI index analyses, in this work, we propose to use electron densities obtained through the transfer of extremely localized molecular orbitals (ELMOs) or through the recently developed QM/ELMO embedding technique. Although still approximate, the electron distributions resulting from the abovementioned methods are fully QM and, above all, are again partitionable into subunit contributions, which makes them completely suitable for the NCI integral approach. Therefore, we benchmarked the integrals resulting from NCI index analyses (both those based on the promolecular densities and those based on ELMO electron distributions) against interaction energies computed at a high quantum chemical level (in particular, at the coupled cluster level). The performed test calculations have indicated that the NCI integrals based on ELMO electron densities outperform the promolecular ones. Furthermore, it was observed that the novel quantitative NCI-(QM/)ELMO approach can be also profitably exploited both to characterize and evaluate the strength of specific interactions between ligand subunits and protein residues in protein-ligand complexes and to follow the evolution of NCIs along trajectories of molecular dynamics simulations. Although further methodological improvements are still possible, the new quantitative ELMO-based technique could be already exploited in situations in which fast and reliable assessments of NCIs are crucial, such as in computational high-throughput screenings for drug discovery.

Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer.

The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE-177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1-57.8) months with pembrolizumab and 43.9 (range 36.6-55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval [CI] 1.9 months-NR) with pembrolizumab versus 10.4 (95% CI 6.3-22.0) months with chemotherapy (hazard ratio [HR] 0.56, 95% CI 0.26-1.20). Median OS was NR (range 13.8 months-NR) versus 30.0 (14.7-NR) months (HR 0.65, 95% CI 0.27-1.55) and ORR was 50% (95% CI 28-72) versus 46% (95% CI 27-67). Grade 3/4 treatment-related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune-mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first-line pembrolizumab as a standard of care for patients from Asia with MSI-H/dMMR mCRC. ClinicalTrials.gov identifier: NCT02563002.

High Patient Satisfaction for up to 6 Months With OnabotulinumtoxinA Treatment for Upper Facial Lines.

BACKGROUND: OnabotulinumtoxinA safety and efficacy are well established for upper facial lines (UFL), including forehead lines (FHL), glabellar lines (GL), and crow's feet lines (CFL). OBJECTIVE: To investigate the association of onabotulinumtoxinA efficacy with patient-reported psychological impacts and satisfaction in UFL. MATERIALS AND METHODS: A pooled analysis of data from 4 pivotal Phase 3 trials (onabotulinumtoxinA vs placebo in FHL ± GL, FHL + GL ± CFL, CFL, and CFL + GL for ≤180 days) evaluated investigator-assessed ≥1-grade severity improvement on the Allergan Facial Wrinkle Scale at Day 30 (responders). Facial Line Outcomes (FLO-11) Questionnaire, Facial Line Satisfaction Questionnaire (FLSQ), and Subject Assessment of Satisfaction of Appearance (SASA) were used to evaluate responder appearance-related psychological impacts and satisfaction. RESULTS: OnabotulinumtoxinA patients, by primary study focus (FHL, GL, or CFL), totaled 921, 921, and 833, respectively; 786 patients received placebo. Most patients were female, White, and aged 45 to 50 years (median). Through 150 days, >42% FHL, >43% GL, and ≥32% CFL patients were onabotulinumtoxinA responders. Responders reported improvements in appearance-related psychological impacts (FLO-11) and high satisfaction (FLSQ and SASA), sustained through ≥150 days. CONCLUSION: A ≥1-grade improvement with onabotulinumtoxinA is a clinically meaningful outcome in UFL, associated with long-lasting improved patient-reported psychological impacts and high satisfaction.

EHMT2 methyltransferase governs cell identity in the lung and is required for KRAS G12D tumor development and propagation.

Lung development, integrity and repair rely on precise Wnt signaling, which is corrupted in diverse diseases, including cancer. Here, we discover that EHMT2 methyltransferase regulates Wnt signaling in the lung by controlling the transcriptional activity of chromatin-bound ß-catenin, through a non-histone substrate in mouse lung. Inhibition of EHMT2 induces transcriptional, morphologic, and molecular changes consistent with alveolar type 2 (AT2) lineage commitment. Mechanistically, EHMT2 activity functions to support regenerative properties of KrasG12D tumors and normal AT2 cells-the predominant cell of origin of this cancer. Consequently, EHMT2 inhibition prevents KrasG12D lung adenocarcinoma (LUAD) tumor formation and propagation and disrupts normal AT2 cell differentiation. Consistent with these findings, low gene EHMT2 expression in human LUAD correlates with enhanced AT2 gene expression and improved prognosis. These data reveal EHMT2 as a critical regulator of Wnt signaling, implicating Ehmt2 as a potential target in lung cancer and other AT2-mediated lung pathologies.

Influence of depression on survival of colorectal cancer patients drawn from a large prospective cohort.

OBJECTIVE: The prevalence of depressive symptoms immediately after the diagnosis of colorectal cancer (CRC) is high and has important implications both psychologically and on the course of the disease. The aim of this study is to analyse the association between depressive symptoms and CRC survival at 5 years after diagnosis. METHODS: This multicentre, prospective, observational cohort study was conducted on a sample of 2602 patients with CRC who completed the Hospital Anxiety and Depression Scale (HADS-D) at 5 years of follow-up. Survival was analysed using the Kaplan-Meier method and Cox regression models. RESULTS: According to our analysis, the prevalence of depressive symptoms after a CRC diagnosis was 23.8%. The Cox regression analysis identified depression as an independent risk factor for survival (HR = 1.47; 95% CI: 1.21-1.8), a finding which persisted after adjusting for sex (female: HR = 0.63; 95% CI: 0.51-0.76), age (>70 years: HR = 3.78; 95% CI: 1.94-7.36), need for help (yes: HR = 1.43; 95% CI: 1.17-1.74), provision of social assistance (yes: HR = 1.46; 95% CI: 1.16-1.82), tumour size (T3-T4: HR = 1.56; 95% CI: 1.22-1.99), nodule staging (N1-N2: HR = 2.46; 95% CI: 2.04-2.96), and diagnosis during a screening test (yes: HR = 0.71; 95% CI: 0.55-0.91). CONCLUSIONS: There is a high prevalence of depressive symptoms in patients diagnosed with CRC. These symptoms were negatively associated with the survival rate independently of other clinical variables. Therefore, patients diagnosed with CRC should be screened for depressive symptoms to ensure appropriate treatment can be provided.

Mitochondrial Transfer Regulates Bioenergetics in Healthy and Chronic Obstructive Pulmonary Disease Airway Smooth Muscle.

Mitochondrial dysfunction has been reported in chronic obstructive pulmonary disease (COPD). Transfer of mitochondria from mesenchymal stem cells to airway smooth muscle cells (ASMCs) can attenuate oxidative stress-induced mitochondrial damage. It is not known whether mitochondrial transfer can occur between structural cells in the lungs or what role this may have in modulating bioenergetics and cellular function in healthy and COPD airways. Here, we show that ASMCs from both healthy ex-smokers and subjects with COPD can exchange mitochondria, a process that happens, at least partly, via extracellular vesicles. Exposure to cigarette smoke induces mitochondrial dysfunction and leads to an increase in the donation of mitochondria by ASMCs, suggesting that the latter may be a stress response mechanism. Healthy ex-smoker ASMCs that receive mitochondria show increases in mitochondrial biogenesis and respiration and a reduction in cell proliferation, irrespective of whether the mitochondria are transferred from healthy ex-smoker or COPD ASMCs. Our data indicate that mitochondrial transfer between structural cells is a homeostatic mechanism for the regulation of bioenergetics and cellular function within the airways and may represent an endogenous mechanism for reversing the functional consequences of mitochondrial dysfunction in diseases such as COPD.

The drop plate method as an alternative for Azospirillum spp viable cell enumeration within the consensus protocol of the REDCAI network

Abstract Quality evaluation of commercial inoculants is essential to warrant an adequate cropresponse to inoculation within a biosecurity framework. In this sense, this work is aimed at standardizing and validating the drop plate method for the enumeration of Azospirillum viable cellsas an alternative to the spread plate technique, which is currently proposed in the consensusprotocol of the REDCAI network. Between 14 and 25 private and public laboratories partici-pated in three independent trials. We obtained consistent and robust results that allowed toconfirm that both techniques are equivalent, concluding that the drop plate method is an alternative enumeration technique that is adequate to be included in the abovementioned consensusprotocol.

Resumen La evaluación de la calidad de los inoculantes comerciales es fundamental para garantizar una adecuada respuesta de los cultivos a la inoculación dentro de un marco de bioseguridad. En este sentido, el objetivo de este trabajo fue la estandarización y validación de la técnica de la microgota para la cuantificación de Azospirillum como metodología alternativa a la técnica de siembra en superficie, propuesta actualmente en el protocolo consenso de la Red de Calidad de Inoculantes, REDCAI. Entre 14 y 25 laboratorios, tanto privados como públicos, participaron de tres ensayos independientes. A partir de ellos se obtuvieron resultados reproducibles y robustos que permiten confirmar que ambas técnicas son equivalentes y concluir que la técnica de recuento por la microgota es una alternativa adecuada para ser incluida dentro del mencionado protocolo consenso.

Campylobacter fetus releases S-layered and immunoreactive outer membrane vesicles

Abstract The study of outer membrane vesicles (OMVs) became relevant because of theirprobable important role in the transfer of virulence factors to host cells. Campylobacter fetusis mainly a mammal pathogen whose virulence characterization is still limited. The aim of thisstudy was to evaluate and to characterize the secretion of OMVs in this bacterium. By trans-mission electron microscopy, we confirmed the production of OMVs in all the strains assayed.Purified OMVs showed a spherical shape and variable size, although comparable to those ofother gram-negative bacteria. We also confirmed the presence of the S-layer on the surface ofthe OMVs of all the strains assayed with the exception of those derived from the NTCC referencestrain. In addition, we demonstrated their immunoreactivity by the dot-blot assay. Hence, C.fetus OMVs could contribute to the modulation of the host response and constitute a candidateto be evaluated as an adjuvant of current vaccines used in the veterinary field. This work rep-resents a platform to drive future studies towards the role of these subcellular structures in C.fetus-host interaction.

Resumen El estudio de las vesículas de membrana externa (VME) tomó un rol protagónico, yaque se las ha relacionado con la transferencia de factores de virulencia a la célula hospedadora.Campylobacter fetus es, principalmente, un patógeno de mamíferos cuya virulencia solo hasido caracterizada de forma limitada. El objetivo de este trabajo fue evaluar y caracterizar la secreción de VME en esta bacteria. Mediante microscopía electrónica de transmisión confir-mamos la producción espontánea de VME en todas las cepas estudiadas. Las VME purificadasmostraron una morfología esférica y un tama˜no variable, pero compatible con el reporte deotras bacterias gram negativas. Asimismo, hemos demostrado que estas vesículas conservanla capa S en todas las cepas, menos en la cepa de referencia NCTC y hemos confirmado suinmunorreactividad por dot-blot inmunoblot. Estas VME de C. fetus podrían contribuir a la mod-ulación de la respuesta del hospedador y constituir un buen candidato como adyuvante de lasactuales vacunas empleadas en el campo veterinario. Este trabajo representa una plataformapara impulsar estudios futuros en torno al rol de estas estructuras subcelulares en la interfaseC. fetus-hospedador.

Características socioantropológicas y de salud de un asentamiento urbano desde la perspectiva de enfermería

RESUMEN Introducción: Se realizó una investigación de desarrollo tecnológico en el período 2019-2020 en Previsora, comunidad urbana, de Camagüey. Su ejecución fue liderada por investigadores y profesionales de enfermería comunitaria. El objetivo del presente trabajo está dirigido a caracterizar la comunidad desde la perspectiva histórico social y de salud para la identificación de las necesidades de aprendizaje de los profesionales de enfermería comunitaria. Métodos: Se realizó un estudio etnográfico como método de recopilación descriptivo de datos a partir de la combinación de técnicas y fuentes; de ellas se especifica: grupos focales, entrevista a profundidad, entrevista estructurada abierta y la observación participante y dentro del método cuantitativo: entrevista estructurada cerrada; así como los elementos más significativos del Análisis de la Situación de salud. Se realizó una triangulación teórica y metodológica de técnicas, instrumentos y fuentes en correspondencia con la metodología cualitativa y cuantitativa, según el momento de la investigación. Resultados: Se evidenció falta de sentido de pertenencia de los pobladores, indisciplinas sociales que perjudican la comunidad y su salud, deterioro de las relaciones interpersonales, sistema eco cultural deficiente y se identificó la necesidad de emprender otras acciones comunitarias que inciten el cambio y modifiquen el cuadro de salud comunitaria. Discusión: Los resultados que se exhiben coinciden con los de investigaciones desarrolladas por prestigiosos profesionales de las ciencias sociales y humanísticas.

ABSTRACT Introduction: A technological développent investigation was carried out in the period 2019-2020 in Previsora, an urban community, in Camagüey. Its execution was led by researchers and community nursing professionals. The objective of this work is aimed at characterizing the community from a historical, social and health perspective in order to identify the learning needs of community nursing professionals. Methods: An ethnographic study was carried out as a method of descriptive data collection from the combination of techniques and sources; of them are specified: focus groups, in-depth interview, open structured interview and participant observation and within the quantitative method: closed structured interview; as well as the most significant elements of the Health Situation Analysis. A theoretical and methodological triangulation of techniques, instruments and sources was carried out in correspondence with the qualitative and quantitative methodology, according to the moment of the investigation. Results: Lack of sense of belonging of the inhabitants was evidenced, social indiscipline that harms the community and its health, deterioration of interpersonal relationships, deficient eco-cultural system and it was identified the need to undertake other community actions that incite change the environment and modify the community health chart. Discussion: The results that are exhibited coincide with those of research carried out by prestigious professionals in the social and humanistic sciences.