Performance of malolactic fermentation by inoculation of selected Lactobacillus plantarum and Oenococcus oeni strains isolated from Rioja red wines

Malolactic fermentations (MLF) of wines inoculated with selected lactic acid bacteria strains of the species Oenococcus oeni and Lactobacillus plantarum were studied and compared with spontaneous MLF. Bacterial populations were monitored along the whole process of MLF and bacteria identifications were carried out at species and strain level. Macrorestriction analysis with SfiI endonuclease and subsequent PFGE was carried out in order to identify O. oeni individual strains. L. plantarum active lyophila did not survive competing with the indigenous microbiota in a wine with 15.3 % (vol/vol) alcohol, whereas the selected O. oeni strains carried out wine MLF. The highest production of histamine took place during MLF in those wines that underwent spontaneous MLF with a mixed population of indigenous strains. The lowest levels of histamine were obtained with the selected commercial O. oeni strain that succeeded 100 % over the indigenous microbiota. Results indicate that development of MLF leaded by selected O. oeni active lyophila provides negligible histamine levels in red wines of quality that can be submitted to subsequent ageing in wood.

Autoantibodies against MHC class I polypeptide-related sequence A are associated with increased risk of concomitant autoimmune diseases in celiac patients

Background: Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence A (MICA) is highly expressed in the enterocytes of patients with celiac disease, which arises in response to gluten. The aim of this study was to investigate anti-MICA antibody formation in patients with celiac disease and its association with other autoimmune processes. Methods: We tested serum samples from 383 patients with celiac disease, obtained before they took up a gluten-free diet, 428 patients with diverse autoimmune diseases, and 200 controls for anti-MICA antibodies. All samples were also tested for anti-endomysium and anti-transglutaminase antibodies. Results: Antibodies against MICA were detected in samples from 41.7% of patients with celiac disease but in only 3.5% of those from controls (P <0.0001) and 8.2% from patients with autoimmune disease (P <0.0001). These antibodies disappeared after the instauration of a gluten-free diet. Anti-MICA antibodies were significantly prevalent in younger patients (P <0.01). Fifty-eight patients with celiac disease (15.1%) presented a concomitant autoimmune disease. Anti-MICA-positive patients had a higher risk of autoimmune disease than MICA antibody-negative patients (P <0.0001; odds ratio = 6.11). The risk was even higher when we also controlled for age (odds ratio = 11.69). Finally, we found that the associated risk of developing additional autoimmune diseases was 16 and 10 times as high in pediatric patients and adults with anti-MICA, respectively, as in those without. Conclusions: The development of anti-MICA antibodies could be related to a gluten-containing diet, and seems to be involved in the development of autoimmune diseases in patients with celiac disease, especially younger ones

Multiple myeloma and SARS-CoV-2 infection : clinical characteristics and prognostic factors of inpatient mortality

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19

CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome

Identification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study, we address the impact of CAR density on the functionality of BCMA CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with up-regulation of exhaustion markers and increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of gene regulatory networks using scRNA-seq identified regulons associated to activation and exhaustion up-regulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Last, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with notable impact on clinical response

Assessing the context of health care utilization in Ecuador: A spatial and multilevel analysis

<p>Abstract</p> <p>Background</p> <p>There are few studies that have analyzed the context of health care utilization, particularly in Latin America. This study examines the context of utilization of health services in Ecuador; focusing on the relationship between provision of services and use of both preventive and curative services.</p> <p>Methods</p> <p>This study is cross-sectional and analyzes data from the 2004 National Demographic and Maternal & Child Health dataset. Provider variables come from the Ecuadorian System of Social Indicators (SIISE). Global Moran's I statistic is used to assess spatial autocorrelation of the provider variables. Multilevel modeling is used for the simultaneous analysis of provision of services at the province-level with use of services at the individual level.</p> <p>Results</p> <p>Spatial analysis indicates no significant differences in the density of health care providers among Ecuadorian provinces. After adjusting for various predisposing, enabling, need factors and interaction terms, density of public practice health personnel was positively associated with use of preventive care, particularly among rural households. On the other hand, density of private practice physicians was positively associated with use of curative care, particularly among urban households.</p> <p>Conclusions</p> <p>There are significant public/private, urban/rural gaps in provision of services in Ecuador; which in turn affect people's use of services. It is necessary to strengthen the public health care delivery system (which includes addressing distribution of health workers) and national health information systems. These efforts could improve access to health care, and inform the civil society and policymakers on the advances of health care reform.</p

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

NKG2D expression in CD4+ T lymphocytes as a marker of senescence in the aged immune system

Human aging is characterized by changes in the immune system which have a profound impact on the T-cell compartment. These changes are more frequently found in CD8+ T cells, and there are not well-defined markers of differentiation in the CD4+ subset. Typical features of cell immunosenescence are characteristics of pathologies in which the aberrant expression of NKG2D in CD4+ T cells has been described. To evaluate a possible age-related expression of NKG2D in CD4+ T cells, we compared their percentage in peripheral blood from 100 elderly and 50 young adults. The median percentage of CD4+ NKG2D+ in elders was 5.3% (interquartile range (IR): 8.74%) versus 1.4% (IR: 1.7%) in young subjects (p < 0.3 × 10−10). CD28 expression distinguished two subsets of CD4+ NKG2D+ cells with distinct functional properties and differentiation status. CD28+ cells showed an immature phenotype associated with high frequencies of CD45RA and CD31. However, most of the NKG2D+ cells belonged to the CD28null compartment and shared their phenotypical properties. NKG2D+ cells represented a more advanced stage of maturation and exhibited greater response to CMV (5.3 ± 3.1% versus 3.4 ± 2%, p = 0.037), higher production of IFN-γ (40.56 ± 13.7% versus 24 ± 8.8%, p = 0.015), lower activation threshold and reduced TREC content. Moreover, the frequency of the CD4+ NKG2D+ subset was clearly related to the status of the T cells. Higher frequencies of the NKG2D+ subset were accompanied with a gradual decrease of NAIVE and central memory cells, but also with a higher level of more differentiated subsets of CD4+ T cells. In conclusion, CD4+ NKG2D+ represent a subset of highly differentiated T cells which characterizes the senescence of the immune system

Cómo poner puertas al campo : tres revisiones panorámicas sobre el uso de biomarcadores en prevención personalizada de enfermedades crónicas

Se incluye PDF de la presentación y vídeo del seminario.El seminario trata de dar respuesta a qué biomarcadores hay disponibles o en desarrollo para la prevención personalizada de enfermedades crónicas en la población general. Las revisiones realizadas resumen las principales características y conclusiones de la bibliografía sobre este tema. Abarca los tres principales grupos de enfermedades crónicas:11 tipos de cáncer, 9 enfermedades cardiovasculares y 7 enfermedades neurodegenerativas.N