Spatiotemporal dynamics of fetal liver hematopoietic niches.

Embryonic hematopoietic cells develop in the fetal liver (FL), surrounded by diverse non-hematopoietic stromal cells. However, the spatial organization and cytokine production patterns of the stroma during FL development remain poorly understood. Here, we characterized and mapped the hematopoietic and stromal cell populations at early (E12.

Impact of formalin fixation on mismatch repair protein evaluation by immunohistochemistry.

Mismatch repair/microsatellite instability (MMR/MSI) status in colorectal cancer (CRC) has become fundamental as a diagnostic, prognostic, and predictive factor. MMR immunohistochemistry (IHC) is considered a simple and reliable approach; however, its effectiveness depends on pre-analytic factors. Aim of this study was to investigate the impact of different fixation times/protocols on MMR protein IHC quality.

Spatiotemporal dynamics of cytokines expression dictate fetal liver hematopoiesis.

During embryogenesis, yolk-sac and intra-embryonic-derived hematopoietic progenitors, comprising the precursors of adult hematopoietic stem cells, converge into the fetal liver. With a new staining strategy, we defined all non-hematopoietic components of the fetal liver and found that hepatoblasts are the major producers of hematopoietic growth factors. We identified mesothelial cells, a novel component of the stromal compartment, producing Kit ligand, a major hematopoietic cytokine.

Barriers and facilitators for safe sex behaviors in students from universidad de Santiago de Chile (USACH) through the COM-B model.

Background: Unsafe sex is one of the main morbidity and mortality risk factors associated with sexually transmitted infections (STIs) in young people. Behavioral change interventions for promoting safe sex have lacked specificity and theoretical elements about behavior in their designs, which may have affected the outcomes for HIV/AIDS and STI prevention, as well as for safe sex promotion. This study offers an analysis of the barriers and facilitators that, according to the university students who participated in the focus groups, impede or promote the success of interventions promoting healthy sexuality from the perspective of the actions stakeholders should undertake.

Prognostic Role of Soluble and Extracellular Vesicle-Associated PD-L1, B7-H3 and B7-H4 in Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors.

The treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the advent of immune checkpoint inhibitors (ICIs). Despite encouraging results, their efficacy remains limited to a subgroup of patients. Circulating immune checkpoints in soluble (s) form and associated with extracellular vesicles (EVs) represent promising markers, especially in ICI-based therapeutic settings.

In Vitro Generation of Human Dendritic Cell Subsets from CD34+ Cord Blood Progenitors.

Dendritic cells (DCs) are professional antigen-presenting cells controlling the activation of T cells and thus regulating adaptive immune response against pathogens or tumors. Modeling human DC differentiation and function is crucial for our understanding of immune response and the development of new therapies. Considering DC rarity in human blood, in vitro systems allowing their faithful generation are needed.

Dynamic Runx1 chromatin boundaries affect gene expression in hematopoietic development.

The transcription factor RUNX1 is a critical regulator of developmental hematopoiesis and is frequently disrupted in leukemia. Runx1 is a large, complex gene that is expressed from two alternative promoters under the spatiotemporal control of multiple hematopoietic enhancers. To dissect the dynamic regulation of Runx1 in hematopoietic development, we analyzed its three-dimensional chromatin conformation in mouse embryonic stem cell (ESC) differentiation cultures.

Respiratory syncytial virus in pediatric influenza-like illness cases in Lombardy, Northern Italy, during seven consecutive winter seasons (from 2014-2015 to 2020-2021).

Introduction: Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract illness in young children and can also cause influenza-like illness (ILI). Here we investigated the epidemiological features of RSV infection in pediatric ILI cases in Lombardy (a region in Northern Italy accounting nearly 10 million inhabitants) from 2014-2015 to 2020-2021 winter seasons.

Material And Methods: Data for this study were retrieved and statistically analyzed from the database of virological influenza surveillance of the regional reference laboratory for Lombardy within the Italian influenza surveillance network (InfluNet).

The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition.

Hematopoietic stem cells (HSCs) emerge during development from the vascular wall of the main embryonic arteries. The onset of circulation triggers several processes that provide critical external factors for HSC generation. Nevertheless, it is not fully understood how and when the onset of circulation affects HSC emergence.

Early identification of keratoconus using pachymetric indexes obtained with spectral domain optical coherence tomography.

Purpose: To evaluate the diagnostic ability of pachymetric indexes obtained with Spectral Domain Optical Coherence Tomography (SD-OCT) for early detection of keratoconus (Kc).

Methods: 64 patients with Kc in at least one eye (95 eyes, 46 men and 18 women, average age 27.84 ±13.

When the COVID-19 Pandemic Surges during Influenza Season: Lessons Learnt from the Sentinel Laboratory-Based Surveillance of Influenza-Like Illness in Lombardy during the 2019-2020 Season.

This paper outlines the role of Lombardy's regional influenza reference laboratory (Northern Italy) in the surveillance of influenza-like illnesses (ILIs) in monitoring SARS-CoV-2 circulation by analyzing 631 consecutive nasopharyngeal swabs (NPSs) collected from ILI outpatients by sentinel physicians during the 2019-2020 season. The samples were tested by specific real-time RT-PCRs targeting SARS-CoV-2, influenza viruses, and RSVs. Results: Of these NPSs, 31% tested positive for influenza viruses, 10% for SARS-CoV-2, and 7% for RSV.

Harnessing Mesenchymal Stromal Cells for the Engineering of Human Hematopoietic Niches.

Tissue engineering opens multiple opportunities in regenerative medicine, drug testing, and modeling of the hematopoiesis in health and disease. Recapitulating the organization of physiological microenvironments supporting leukocyte development is essential to model faithfully the development of immune cells. Hematopoietic organs are shaped by spatially organized niches defined by multiple cellular contributions.

Implementing NGS-based tumour tissue testing in FFPE ovarian carcinoma specimens: hints from a real-life experience within the framework of expert recommendations.

Aims: Next Generation Sequencing (NGS)-based tumour tissue testing poses several challenges. As a first step of its implementation within a regional health service network, an in-house validation study was compared with published recommendations.

Methods: Epithelial ovarian cancer (EOC) formalin-fixed paraffin-embedded specimens stored in the archives of the eight regional pathology units were selected from a consecutive series of patients with known germline status.

Development and function of human dendritic cells in humanized mice models.

Dendritic cells (DCs) are sentinel cells of the immune system arising from hematopoietic stem cells. DCs play a key role in the regulation of both adaptive and innate lymphocyte responses. As such, experimental models enabling a thorough analysis of human DCs development and function are needed.

Gut Microbiota and Cardiovascular Diseases: A Critical Review.

The human intestine contains the largest and most diverse ecosystem of microbes. The main function of the intestinal bacterial flora is to limit the growth of potentially pathogenic microorganisms. However, the intestinal microbiota is increasingly emerging as a risk factor for the development of cardiovascular disease (CVD).

Transcriptional and Functional Analysis of CD1c Human Dendritic Cells Identifies a CD163 Subset Priming CD8CD103 T Cells.

Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88CD1cCD163 DCs (called DC3s) as immediate precursors of inflammatory CD88CD14CD1cCD163FcεRI DCs.

Engineered niches support the development of human dendritic cells in humanized mice.

Classical dendritic cells (cDCs) are rare sentinel cells specialized in the regulation of adaptive immunity. Modeling cDC development is crucial to study cDCs and harness their therapeutic potential. Here we address whether cDCs could differentiate in response to trophic cues delivered by mesenchymal components of the hematopoietic niche.

Respiratory syncytial virus in influenza-like illness cases: Epidemiology and molecular analyses of four consecutive winter seasons (2014-2015/2017-2018) in Lombardy (Northern Italy).

Background: Besides seasonal influenza viruses (IV), several other pathogens-including respiratory syncytial virus (RSV)-are involved in clinically undistinguished influenza-like illnesses (ILIs). This study aimed at investigating the contribution of RSV in ILI cases in Lombardy (Northern Italy) during four consecutive winter seasons.

Materials And Methods: In the framework of influenza surveillance, respiratory samples from ILI outpatients were collected from 2014-2015 to 2017-2018 season.

Influenza Vaccination in Italian Healthcare Workers (2018-2019 Season): Strengths and Weaknesses. Results of a Cohort Study in Two Large Italian Hospitals.

Background: Annual vaccination is the most effective way to combat influenza. As influenza viruses evolve, seasonal vaccines are updated annually. Within the European project Development of Robust and Innovative Vaccine Effectiveness (DRIVE), a cohort study involving Italian healthcare workers (HCWs) was carried out during the 2018-2019 season.

Characterization of pUL5, an HCMV protein interacting with the cellular protein IQGAP1.

Among the Herpesviridae, human cytomegalovirus (HCMV) owns the largest genome and displays a huge coding potential. Here, we characterized the UL5 gene product (pUL5) of the clinical isolate TR strain. The protein was predicted as a 166-amino-acid membrane protein with a theoretical mass of 19 kDa.

Molecular Characterization of Influenza Strains in Patients Admitted to Intensive Care Units during the 2017-2018 Season.

This study aimed at assessing the frequency and the distribution of influenza virus types/subtypes in 172 laboratory-confirmed influenza-positive patients admitted to intensive care units (ICUs) during the 2017-2018 season in the Lombardy region (Northern Italy), and to investigate the presence of molecular pathogenicity markers. A total of 102/172 (59.3%) patients had influenza A infections (83 A/H1N1pdm09, 2 H3N2 and 17 were untyped), while the remaining 70/172 (40.

Tag-based next generation sequencing: a feasible and reliable assay for EGFR T790M mutation detection in circulating tumor DNA of non small cell lung cancer patients.

Background: The demonstration of EGFR T790M gene mutation in plasma is crucial to assess the eligibility of Non Small Cell Lung Cancer (NSCLC) patients, who have acquired resistance to first or second generation Tyrosine Kinase Inhibitors (TKIs), to receive a subsequent treatment with osimertinib. Since circulating tumor DNA (ctDNA) is present in very low amounts in plasma, high sensitive and specific methods are required for molecular analysis. Improving sensitivity of T790M mutation detection in plasma ctDNA enables a larger number of NSCLC patients to receive the appropriate therapy without any further invasive procedure.

The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut⁻Retina Axis.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged ≥65 years in developed countries. Globally, it affects 30⁻50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form.