PD-1/PD-L1 axis: implications in immune regulation, cancer progression, and translational applications.

The PD-1/PD-L1 axis is a complex signaling pathway that has an important role in the immune system cells. Programmed cell death protein 1 (PD-1) acts as an immune checkpoint on the T lymphocytes, B lymphocytes, natural killer (NK), macrophages, dendritic cells (DCs), monocytes, and myeloid cells. Its ligand, the programmed cell death 1 ligand (PD-L1), is expressed in the surface of the antigen-presenting cells (APCs). The binding of both promotes the downregulation of the T cell response to ensure the activation to prevent the onset of chronic immune inflammation. This axis in the tumor microenvironment (TME) performs a crucial role in the tumor progression and the escape of the tumor by neutralizing the immune system, the engagement of PD-L1 with PD-1 in the T cell causes dysfunctions, neutralization, and exhaustion, providing the tumor mass production. This review will provide a comprehensive overview of the functions of the PD-1/PD-L1 system in immune function, cancer, and the potential therapeutic implications of the PD-1/PD-L1 pathway for cancer management.

Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study.

BACKGROUND: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. METHODS: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. RESULTS: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. CONCLUSIONS: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.

Hearing Function and Nutritional Status in Aviation Pilots from Spain Exposed to High Acoustic Damage.

Noise-induced hearing loss is the most frequent and preventable occupational disease. Aviation pilots are a vulnerable population, as they spend many hours exposed to noise pollution in their working environment. Different studies suggest that certain dietary compounds may play a key role in the etiology and prevention of this pathology. We aimed to study the relationship linking auditory function, dietary intake, and some serum biomarkers in pilots, exposed to noise in the work environment. A total of 235 pilots, who undergo a periodic medical examination at the Centro de Instrucción de Medicina Aeroespacial (Madrid, SPAIN), were evaluated. Auditory function was assessed by tonal audiometry. Energy and nutrient intakes were estimated by 24 h recall (DIALTM program). Serum homocysteine (Hcy) was determined in a Cobas 6000TM multi-analyzer while folate, vitamin B12, and D were analyzed in a Cobas e411TM. The prevalence of hearing loss (HL) was 64.3%. HL was significantly related to age (r = 0.588, p ≤ 0.001) and flight hours (r = 0.283, p ≤ 0.001). A multiple linear regression model was used to assess the relationship among HL, flight hours, serum folate, and Hcy serum levels. HL was significantly (p < 0.050) associated with flight hours (ß = 0.246), serum folate (ß = −0.143), and serum Hcy (ß = 0.227). Nutritional interventions would be of great interest to monitor and slow down the HL progression in populations exposed to noise pollution in their workplace.

Effectiveness of Community-Based Interventions Programs in Childhood Obesity Prevention in a Spanish Population According to Different Socioeconomic School Settings.

Overweight and obesity amongst childhood are currently global health issues. However, this is the best stage of life to prevent diseases and to promote healthy habits. In our study, we evaluate the effectiveness of the THAO Salud Infantil, a community-based intervention program, by means of a cross-sectional study carried out from 2009 to 2019 surveying children aged 3 to 12 years old (n = 27,686). During the study timeframe, overweight and obesity prevalence, according to both the International Obesity Task Force and Orbegozo Foundation criteria, showed a downward trend. Differences in the anthropometric variables were observed from the beginning to the end of the study, mainly in girls. Analysis of the influence of the socioeconomic status revealed that children from families with lower incomes are in greater risk of suffering from overweight and obesity and showed lower effectiveness of the actions proposed by the program. The overall results of the study confirmed the effectiveness of community-based interventions in terms of childhood overweight/obesity prevention.

Pangenome-wide and molecular evolution analyses of the Pseudomonas aeruginosa species.

BACKGROUND: Drug treatments and vaccine designs against the opportunistic human pathogen Pseudomonas aeruginosa have multiple issues, all associated with the diverse genetic traits present in this pathogen, ranging from multi-drug resistant genes to the molecular machinery for the biosynthesis of biofilms. Several candidate vaccines against P. aeruginosa have been developed, which target the outer membrane proteins; however, major issues arise when attempting to establish complete protection against this pathogen due to its presumably genotypic variation at the strain level. To shed light on this concern, we proposed this study to assess the P. aeruginosa pangenome and its molecular evolution across multiple strains. RESULTS: The P. aeruginosa pangenome was estimated to contain more than 16,000 non-redundant genes, and approximately 15 % of these constituted the core genome. Functional analyses of the accessory genome indicated a wide presence of genetic elements directly associated with pathogenicity. An in-depth molecular evolution analysis revealed the full landscape of selection forces acting on the P. aeruginosa pangenome, in which purifying selection drives evolution in the genome of this human pathogen. We also detected distinctive positive selection in a wide variety of outer membrane proteins, with the data supporting the concept of substantial genetic variation in proteins probably recognized as antigens. Approaching the evolutionary information of genes under extremely positive selection, we designed a new Multi-Locus Sequencing Typing assay for an informative, rapid, and cost-effective genotyping of P. aeruginosa clinical isolates. CONCLUSIONS: We report the unprecedented pangenome characterization of P. aeruginosa on a large scale, which included almost 200 bacterial genomes from one single species and a molecular evolutionary analysis at the pangenome scale. Evolutionary information presented here provides a clear explanation of the issues associated with the use of protein conjugates from pili, flagella, or secretion systems as antigens for vaccine design, which exhibit high genetic variation in terms of non-synonymous substitutions in P. aeruginosa strains.

Dietary alkylresorcinols and lignans in the Spanish diet: development of the alignia database.

The intake of alkylresorcinols and lignans in Spain is unknown due to the lack of information on the content of these compounds in particular foods. This paper describes the development of the first alkylresorcinol and lignan database adapted to the Spanish diet, including foods items especially relevant for this population. The values of alkylresorcinols and lignans in common foods and beverages were collected from scientific publications in refereed journals, and other foods particularly consumed in Spain, for which values were not available, were analyzed by standardized protocols and included into the database. The Alignia database presents the content of alkylresorcinols in 88 food items and the lignan content of 593 foods and beverages. Using the database, the intake of lignans in Spain, calculated using data from the Food Composition Panel based on household consumption, was estimated to be 0.76 mg/day.

Effectiveness of an implementation strategy for a breastfeeding guideline in Primary Care: cluster randomised trial.

BACKGROUND: The protection and promotion of breastfeeding is considered a priority in Europe where only 22% of infants less than 6 months old are exclusively breastfed. In Spain this percentage reaches 24.8% but in our city it falls to 18.26%. Various studies emphasise that the improvement of these results should be based upon the training of health professionals. Following the recommendations of a breastfeeding guide can modify the practice of health professionals and improve results with respect to exclusively or predominatly breastfed children at 6 months of age. METHOD/DESIGN: This study involves a community based cluster randomized trial in primary healthcare centres in Leganés (Madrid, Spain). The project aims to determine whether the use of an implementation strategy (including training session, information distribution, opinion leader) of a breastfeeding guideline in primary care is more effective than usual diffusion. The number of patients required will be 240 (120 in each arm). It will be included all the mothers of infants born during the study period (6 months) who come to the health centre on the first visit of the child care programme and who give their consent to participate. The main outcome variable is the exclusive o predominant breastfeeding at 6 moths of age..Main effectiveness will be analyzed by comparing the percentage of infants with exclusive or predominant breastfeeding at 6 months between the intervention group and the control group. All statistical tests will be performed with intention to treat. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. DISCUSSION: Strategies need to be found which facilitate the giving of effective advice on breastfeeding by professionals and which provide support to women during the breastfeeding period. By applying the guide's recommendations, clinical variability can be reduced and the care received by patients can be improved. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT01474096.