Effect of Probiotics on Host-Microbiota in Bacterial Infections

Diseases caused by bacteria cause millions of deaths every year. In addition, the problem of resistance to antibiotics is so serious that it threatens the achievements of modern medicine. This is a very important global problem as some bacteria can also develop persistence. Indeed, the persistence of pathogenic bacteria has evolved as a potent survival strategy to overcome host organisms’ defense mechanisms. Additionally, chronic or persistent infections may be caused by persisters which could facilitate antibiotic resistance. Probiotics are considered good bacteria. It has been described that the modulation of gut microbiota by probiotics could have a great potential to counteract the deleterious impact and/or regulate gut microbiota after bacterial infection. Probiotics might provide health benefits through the inhibition of pathogen growth or the replacement of pathogenic bacteria. Bearing in mind that current strategies to avoid bacterial persistence and prevent antibiotic resistance are not effective, other strategies need to be assessed. We have carried out a comprehensive review, which included the reported literature between 2016 and 2021, highlighting the clinical trials that reported the probiotics’ potential to regulate gut microbiota after bacterial infection and focusing in particular on the context of antibiotic resistance and persister cells.Regional Ministry of Health and Families (Andalucia, Spain) RPS 2466

PAX4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus

[Aims/hypothesis]: A strategy to enhance pancreatic islet functional beta cell mass (BCM) while restraining inflammation, through the manipulation of molecular and cellular targets, would provide a means to counteract the deteriorating glycaemic control associated with diabetes mellitus. The aims of the current study were to investigate the therapeutic potential of such a target, the islet-enriched and diabetes-linked transcription factor paired box 4 (PAX4), to restrain experimental autoimmune diabetes (EAD) in the RIP-B7.1 mouse model background and to characterise putative cellular mechanisms associated with preserved BCM. [Methods]: Two groups of RIP-B7.1 mice were genetically engineered to: (1) conditionally express either PAX4 (BPTL) or its diabetes-linked mutant variant R129W (mutBPTL) using doxycycline (DOX); and (2) constitutively express luciferase in beta cells through the use of RIP. Mice were treated or not with DOX, and EAD was induced by immunisation with a murine preproinsulin II cDNA expression plasmid. The development of hyperglycaemia was monitored for up to 4 weeks following immunisation and alterations in the BCM were assessed weekly by non-invasive in vivo bioluminescence intensity (BLI). In parallel, BCM, islet cell proliferation and apoptosis were evaluated by immunocytochemistry. Alterations in PAX4- and PAX4R129W-mediated islet gene expression were investigated by microarray profiling. PAX4 preservation of endoplasmic reticulum (ER) homeostasis was assessed using thapsigargin, electron microscopy and intracellular calcium measurements. [Results]: PAX4 overexpression blunted EAD, whereas the diabetes-linked mutant variant PAX4R129W did not convey protection. PAX4-expressing islets exhibited reduced insulitis and decreased beta cell apoptosis, correlating with diminished DNA damage and increased islet cell proliferation. Microarray profiling revealed that PAX4 but not PAX4R129W targeted expression of genes implicated in cell cycle and ER homeostasis. Consistent with the latter, islets overexpressing PAX4 were protected against thapsigargin-mediated ER-stress-related apoptosis. Luminal swelling associated with ER stress induced by thapsigargin was rescued in PAX4-overexpressing beta cells, correlating with preserved cytosolic calcium oscillations in response to glucose. In contrast, RNA interference mediated repression of PAX4-sensitised MIN6 cells to thapsigargin cell death. [Conclusions/interpretation]: The coordinated regulation of distinct cellular pathways particularly related to ER homeostasis by PAX4 not achieved by the mutant variant PAX4R129W alleviates beta cell degeneration and protects against diabetes mellitus. The raw data for the RNA microarray described herein are accessible in the Gene Expression Omnibus database under accession number GSE62846

Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design

The diagnosis of myeloid neoplasms (MN) has significantly evolved through the last few decades. Next Generation Sequencing (NGS) is gradually becoming an essential tool to help clinicians with disease management. To this end, most specialized genetic laboratories have implemented NGS panels targeting a number of different genes relevant to MN. The aim of the present study is to evaluate the performance of four different targeted NGS gene panels based on their technical features and clinical utility. A total of 32 patient bone marrow samples were accrued and sequenced with 3 commercially available panels and 1 custom panel. Variants were classified by two geneticists based on their clinical relevance in MN. There was a difference in panel¿s depth of coverage. We found 11 discordant clinically relevant variants between panels, with a trend to miss long insertions. Our data show that there is a high risk of finding different mutations depending on the panel of choice, due both to the panel design and the data analysis method. Of note, CEBPA, CALR and FLT3 genes, remains challenging the use of NGS for diagnosis of MN in compliance with current guidelines. Therefore, conventional molecular testing might need to be kept in place for the correct diagnosis of MN for now

Association of breast and gut microbiota dysbiosis and the risk of breast cancer: a case-control clinical study

We would like to thank M Luisa Puertas-Martin and Isabel Manzano-Jimenez, nurses at the Unit of Mammary Pathology, General Surgery Service, San Cecilio University Hospital (Granada), without whose enthusiasm the enrolment of participants in Granada would still be stalled. We are indebted to all the women taking part in the study.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Trial registration ClinicalTrials.gov NCT03885648, 03/25/2019. Retrospectively registered.Background Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota. Methods We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed. Discussion: This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease.This work is funded by grants PI-0538-2017 (Junta de Andalucía, Spain, to LF) and Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP) of the Institute of Health Carlos III -supported by European Regional Development Fund/FEDER (FIS-PI16/01812) (to MFF)

Role of small-sized phytoplankton in triggering an ecosystem disruptive algal bloom in a Mediterranean hypersaline coastal lagoon

Preprint2,35

Spanish guidelines for the use of targeted deep sequencing in myelodysplastic syndromes and chronic myelomonocytic leukaemia

The landscape of medical sequencing has rapidly changed with the evolution of next generation sequencing (NGS). These technologies have contributed to the molecular characterization of the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), through the identification of recurrent gene mutations, which are present in >80% of patients. These mutations contribute to a better classification and risk stratification of the patients. Currently, clinical laboratories include NGS genomic analyses in their routine clinical practice, in an effort to personalize the diagnosis, prognosis and treatment of MDS and CMML. NGS technologies have reduced the cost of large-scale sequencing, but there are additional challenges involving the clinical validation of these technologies, as continuous advances are constantly being made. In this context, it is of major importance to standardize the generation, analysis, clinical interpretation and reporting of NGS data. To that end, the Spanish MDS Group (GESMD) has expanded the present set of guidelines, aiming to establish common quality standards for the adequate implementation of NGS and clinical interpretation of the results, hoping that this effort will ultimately contribute to the benefit of patients with myeloid malignancies

Coastal Marine Planning: Vision of the Maritime Authority. Case of the Department of Bolivar, Colombia

La Planificación Espacial Marina es una herramienta que ha tomado gran importancia a nivel mundial. Alrededor de 70 países han implementado esta iniciativa debido a la creciente actividad en el sector marítimo y a la presión sobre los recursos marinos. Las metodologías aplicadas se ajustan a las características propias de cada país y se pueden articular con otros procesos de ordenamiento. En Colombia aunque se han adelantado procesos en este tema a través de diferentes entidades, no se ha generado un ordenamiento espacial de los usos relacionados con las actividades marítimas. Es por esta razón que la Dirección General Marítima (DIMAR) con su compromiso de convertir a Colombia en una potencia bioceánica, bajo un enfoque holístico y de seguridad integral marítima, realiza su aporte a la gestión de los espacios marino - costeros a través de una metodología de Ordenamiento Marino Costero con una Visión de Autoridad Marítima (OMC: VAM), en la cual se busca analizar las condiciones actuales y futuras empleando Sistemas de Información Geográfica (SIG), análisis multicriterio y un Modelo de Asignación y Co-localización (MAYC). La metodología se aplicó en la zona marino – costera del departamento de Bolívar identificando 55 usos/actividades, obteniendo la zonificación por índice y número de conflictos y el mapa de zonas libres. Con esta información se pretende mejorar el seguimiento, evaluación y actualización de las actividades marítimas en estas áreas, y al ser aplicable en todo el territorio colombiano, facilita la toma de decisiones de las diferentes entidades gubernamentales del país.Marine Spatial Planning is a tool that has acquired significant importance worldwide. Around 70 countries have implemented this initiative given the increased activity within the maritime sector and pressure on marine resources. The methods used are adapted to each country’s characteristics and articulated with other management processes. Although Colombia has progressed through on the processes regarding this issue, through different agencies, marine spatial planning related to maritime activities is absent. Therefore, the General Maritime Directorate (DIMAR in Spanish) through its commitment to turning Colombia into a bi-oceanic power, under a holistic and comprehensive maritime safety approach, contributes to marine and coastal areas management with a methodology for Marine and Coastal Management with a Maritime Authority Vision (MCM: MAV), focused on analyzed current and future conditions using Geographic Information Systems (GIS), multi-criteria analysis, and an Allocation and Co-location Model (ACM). The method was applied to Bolivar Department marine and coastal area, resulting in the identification of 55 uses/activities, and obtaining zoning by index and by the number of conflicts, as well as a map of free areas. This information is intended to improve monitoring, evaluation, and updating of maritime activities in these areas, and because it is applicable throughout the Colombian territory, it facilitates decision-making by several national governmental agencies

Interactive Effect of UVR and Phosphorus on the Coastal Phytoplankton Community of the Western Mediterranean Sea: Unravelling Eco- Physiological Mechanisms

Versión del editor4,411