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Abstract Improved phenotyping in pneumonia is necessary to strengthen risk assessment. Via a feasible and multidimensional approach with basic parameters, we aimed to evaluate the effect of host response at admission on severity stratification in COVID-19 and community-acquired pneumonia (CAP). Three COVID-19 and one CAP multicenter cohorts including hospitalized patients were recruited. Three easily available variables reflecting different pathophysiologic mechanisms—immune, inflammation, and respiratory—were selected (absolute lymphocyte count [ALC], C-reactive protein [CRP] and, SpO2/FiO2). In-hospital mortality and intensive care unit (ICU) admission were analyzed as outcomes. A multivariable, penalized maximum likelihood logistic regression was performed with ALC ( 60 mg/L), and, SpO2/FiO2 (

Objective: This review aimed to synthesize and analyze the relationship between regulatory processes (self-regulation, emotion regulation, self-control and impulsivity) and problematic social media use (PSMU) in the general population. Method: A systematic search was conducted in five databases, and all articles published from May 2013 to April 2024 were identified. Results: After screening 2655 articles, 45 studies were included in the review. The total sample comprised 34,332 participants. The results confirm the effect of regulatory processes on the PSMU. This relationship is present in all age groups and in different cultures. Furthermore, the mediating effect of regulation on the relationship between PSMU and variables like anxiety, depression, self-esteem or attachment has been observed. Despite the confirmatory nature of these studies, their results should be interpreted with caution because they may be influenced by certain methodological limitations in the research on which they are based. Conclusion: Regulatory processes play a fundamental role in the PSMU. These findings contribute to a deeper understanding of this behavior and offer insights for the development of effective prevention and intervention strategies.

ContextThe study of internal and external regulation in the use of Information and Communications Technology (ICT) and the analysis of academic emotions have become increasingly important due to their impact on academic life at university.ObjectivesThis research aims to investigate the links between internal vs. external regulation factors, achievement emotions, and gender in the problematic use of ICT among university students.MethodologyThe study recruited 317 university students, predominantly female (72.51%), using an ex-post facto design. The SRT-ERT scale was used to assess technology-related behaviors, and the AEQ Scales measured academic emotions before, during, and after class. Correlation analysis, multiple regression analysis, and ANOVA were employed to identify significant relationships.ResultsSignificant relationships were identified between regulatory behaviors, with male students exhibiting more dysregulated behavior and greater exposure to dysregulatory technology environments. Individual and contextual behavioral nonregulation and dysregulation in the use of ICT were significantly predictive of negative academic emotions.ConclusionThe findings suggest that both personal and contextual factors of regulation significantly influence the emotional experiences of students in academic settings. The study highlights the need for psycho-educational interventions to promote better regulatory behaviors among university students, particularly males.

Abstract Introduction and objectives High‐flow nasal cannula oxygen therapy (HFNC) has been successfully used for the treatment of acute hypoxaemic respiratory failure (AHRF) secondary to SARS‐CoV‐2 pneumonia and being effective in reducing progression to invasive mechanical ventilation. The objective of this study was to assess the usefulness of HFNC on a hospital ward for the treatment of AHRF secondary to SARS‐CoV‐2 pneumonia and its impact on the need for intensive care unit (ICU) admission and endotracheal intubation. Other objectives include identifying potential physiological parameters and/or biomarkers for predicting treatment failure and assessing the clinical course and survival. Methods Observational study based on data collected prospectively between March 2020 and February 2021 in a single hospital on patients diagnosed with AHRF secondary to SARS‐CoV‐2 pneumonia who received HFNC outside an ICU. Results One hundred and seventy‐one patients out of 1090 patients hospitalised for SARS‐CoV‐2 infection. HFNC was set as the ceiling of treatment in 44 cases; 12 survived (27.3%). Among the other 127 patients, intubation was performed in 25.9% of cases with a mortality of 11.8%. Higher creatinine levels (OR 1.942, 95% CI 1.04; 3.732; p = 0.036) and Comorbidity‐Age‐Lymphocyte‐LDH (CALL) score (OR 1.273, 95% CI 1.033; 1.617; p = 0.033) were associated with a higher risk of intubation. High platelet count at HFNC initiation was predictive of good treatment response (OR 0.935, 95% CI 0.884; 0.983; p = 0.012). Conclusions HFNC outside an ICU is a treatment with high success rate in patients with AHRF secondary to SARS‐CoV‐2 pneumonia, including in patients in whom this therapy was deemed to be the ceiling of treatment.

Objectives: To analyze the differences in short- and long-term prognosis and the predictors of survival between patients with community-acquired Legionella and Streptococcus pneumoniae pneumonia, diagnosed early by urinary antigen testing (UAT). Methods: Prospective multicenter study conducted in immunocompetent patients hospitalized with community-acquired Legionella or pneumococcal pneumonia (L-CAP or P-CAP) between 2002-2020. All cases were diagnosed based on positive UAT. Results: We included 1452 patients, 260 with community-acquired Legionella pneumonia (L-CAP) and 1192 with community-acquired pneumococcal pneumonia (P-CAP). The 30-day mortality was higher for L-CAP (6.2%) than for P-CAP (5%). After discharge and during the median follow-up durations of 11.4 and 8.43 years, 32.4% and 47.9% of patients with L-CAP and P-CAP died, and 82.3% and 97.4% died earlier than expected, respectively. The independent risk factors for shorter long-term survival were age >65 years, chronic obstructive pulmonary disease, cardiac arrhythmia, and congestive heart failure in L-CAP and the same first three factors plus nursing home residence, cancer, diabetes mellitus, cerebrovascular disease, altered mental status, blood urea nitrogen ≥30 mg/dl, and congestive heart failure as a cardiac complication during hospitalization in P-CAP. Conclusion: In patients diagnosed early by UAT, the long-term survival after L-CAP or P-CAP was shorter (particularly after P-CAP) than expected, and this shorter survival was mainly associated with age and comorbidities.

IntroductionThere are no data on the association of type of pneumonia and long-term mortality by the type of pneumonia (COVID-19 or community-acquired pneumonia [CAP]) on long-term mortality after an adjustment for potential confounding variables. We aimed to assess the type of pneumonia and risk factors for long-term mortality in patients who were hospitalized in conventional ward and later discharged.MethodsRetrospective analysis of two prospective and multicentre cohorts of hospitalized patients with COVID-19 and CAP. The main outcome under study was 1-year mortality in hospitalized patients in conventional ward and later discharged. We adjusted a Bayesian logistic regression model to assess associations between the type of pneumonia and 1-year mortality controlling for confounders.ResultsThe study included a total of 1,693 and 2,374 discharged patients in the COVID-19 and CAP cohorts, respectively. Of these, 1,525 (90.1%) and 2,249 (95%) patients underwent analysis. Until 1-year follow-up, 69 (4.5%) and 148 (6.6%) patients from the COVID-19 and CAP cohorts, respectively, died (p = 0.008). However, the Bayesian model showed a low probability of effect (PE) of finding relevant differences in long-term mortality between CAP and COVID-19 (odds ratio 1.127, 95% credibility interval 0.862–1.591; PE = 0.774).ConclusionCOVID-19 and CAP have similar long-term mortality after adjusting for potential confounders.

Posidonia oceanica balls (POB), a kind of seagrass, are a significant environmental issue since they are annually discharged onto beaches. Their current usefulness limits interest in their management and enhances the environmental problem. Therefore, in this research, the potential of this lignocellulosic biomass was studied from a holistic biorefinery point of view. To this end, an in-depth study was carried out to select the best pathway for the integral valorization of POBs. First, an autohydrolysis process was studied for the recovery of oligosaccharides. Then, a delignification stage was applied, where, in addition to studying different delignification methods, the influence of the autohydrolysis pre-treatment was also investigated. Finally, cellulose nanofibers (CNFs) were obtained through a chemo-mechanical treatment. The results showed that autohydrolysis not only improved the delignification process and its products, but also allowed the hemicelluloses to be valorized. Acetoformosolv delignification proved to be the most successful in terms of lignin and cellulose properties. However, alkaline delignification was able to extract the highest amount of lignin with low purity. CNFs were also successfully produced from bleached solids. Therefore, the potential of POB as a feedstock for a biorefinery was confirmed, and the pathway should be chosen according to the requirements of the desired end products.

In this study, the plausible role of trimethylamine N-oxide (TMAO), a microbiota metabolite, was investigated as a link between peripheral inflammation and the inflammation of the central nervous system using different cell lines. TMAO treatment favored the differentiation of adipocytes from preadipocytes (3T3-L1 cell line). In macrophages (RAW 264.7 cell line), which infiltrate adipose tissue in obesity, TMAO increased the expression of pro-inflammatory cytokines. The treatment with 200 μM of TMAO seemed to disrupt the blood–brain barrier as it induced a significant decrease in the expression of occludin in hCMECs. TMAO also increased the expression of pro-inflammatory cytokines in primary neuronal cultures, induced a pro-inflammatory state in primary microglial cultures, and promoted phagocytosis. Data obtained from this project suggest that microbial dysbiosis and increased TMAO secretion could be a key link between peripheral and central inflammation. Thus, TMAO-decreasing compounds may be a promising therapeutic strategy for neurodegenerative diseases.

Inflammasomes are cytosolic signaling hubs that promote the inflammatory response (i.e. an immune reaction to counteract threats in physiological conditions). Their potential role in lymphomagenesis remains to be elucidated. Depending on the context, innate immune cells, such as macrophages, may induce inflammation that contributes to the anti-tumor function; however, if uncontrolled, inflammation can promote cancer development. Here, we exploited bioinformatic tools, TCGA data, and tumor tissue samples from patients with diffuse large B-cell lymphoma (DLBCL), one of the most frequent non-Hodgkin lymphomas of B-cell origin, to investigate the distribution of the different immune cell subpopulations in DLBCL samples in order to characterize the immune landscape of their microenvironment. We found a clear prominence of macrophages in the DLBCL microenvironment. Particularly, the proportions of resting M0 and pro-inflammatory M1 macrophages were higher in DLBCL than spleen samples (controls). As each inflammasome has unique sensor activation and platform assembly mechanisms, we examined the expression of a large panel of inflammasome actors. We found that inflammasome components, cytokines and Toll-like receptors were upregulated in DLBCL samples, particularly in M0 and M1 macrophages, compared with controls. Moreover, their expression level was positively correlated with that of CD68 (a pan-macrophage marker). We confirmed the positive correlation between CD68 and IRF8 expression at the protein level in DLBCL tissue samples, where we observed increased infiltration of CD68- and IRF8-positive cells compared with normal lymph nodes. Altogether, our results highlight the inflammatory status of the DLBCL microenvironment orchestrated by macrophages. More work is needed to understand the complexity and potential therapeutic implications of inflammasomes in DLBCL.

ABSTRACT: Objective: To analyse differences in clinical presentation and outcome between bacteraemic pneumococcal community-acquired pneumonia (B-PCAP) and sSvere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pneumonia. Methods: This observational multi-centre study was conducted on patients hospitalized with B-PCAP between 2000 and 2020 and SARS-CoV-2 pneumonia in 2020. Thirty-day survival, predictors of mortality, and intensive care unit (ICU) admission were compared. Results: In total, 663 patients with B-PCAP and 1561 patients with SARS-CoV-2 pneumonia were included in this study. Patients with B-PCAP had more severe disease, a higher ICU admission rate and more complications. Patients with SARS-CoV-2 pneumonia had higher in-hospital mortality (10.8% vs 6.8%; P=0.004). Among patients admitted to the ICU, the need for invasive mechanical ventilation (69.7% vs 36.2%; P

Current vaccines against SARS-CoV-2, based on the original Wuhan sequence, induce antibodies with different degrees of cross-recognition of new viral variants of concern. Despite potent responses generated in vaccinated and infected individuals, the Omicron (B.1.1.529) variant causes breakthrough infections, facilitating viral transmission. We previously reported a vaccine based on a cyclic peptide containing the 446-488 S1 sequence (446-488cc) of the SARS-CoV-2 spike (S) protein from Wuhan isolate. To provide the best immunity against Omicron, here we compared Omicron-specific immunity induced by a Wuhan-based 446-488cc peptide, by a Wuhan-based recombinant receptor-binding domain (RBD) vaccine and by a new 446-488cc peptide vaccine based on the Omicron sequence. Antibodies induced by Wuhan peptide 446-488cc in three murine strains not only recognized the Wuhan and Omicron 446-488 peptides similarly, but also Wuhan and Omicron RBD protein variants. By contrast, antibodies induced by the Wuhan recombinant RBD vaccine showed a much poorer cross-reactivity for the Omicron RBD despite similar recognition of Wuhan and Omicron peptide variants. Finally, although the Omicron-based 446-488cc peptide vaccine was poorly immunogenic in mice due to the loss of T cell epitopes, co-immunization with Omicron peptide 446-488cc and exogenous T cell epitopes induced strong cross-reactive antibodies that neutralized Omicron SARS-CoV-2 virus. Since mutations occurring within this sequence do not alter T cell epitopes in humans, these results indicate the robust immunogenicity of 446-488cc-based peptide vaccines that induce antibodies with a high cross-recognition capacity against Omicron, and suggest that this sequence could be included in future vaccines targeting the Omicron variant.

Immune checkpoint inhibitor (ICI)-based immunotherapy in triple negative breast cancer (TNBC) is achieving limited therapeutic results, requiring the development of more potent strategies. Combination of ICI with vaccination strategies would enhance antitumor immunity and response rates to ICI in patients having poorly infiltrated tumors. In heavily mutated tumors, neoantigens (neoAgs) resulting from tumor mutations have induced potent responses when used as vaccines. Thus, our aim was the identification of immunogenic neoAgs suitable as vaccines in TNBC patients. By using whole exome sequencing, RNAseq and HLA binding algorithms of tumor samples from a cohort of eight TNBC patients, we identified a median of 60 mutations/patient, which originated a putative median number of 98 HLA class I-restricted neoAgs. Considering a group of 27 predicted neoAgs presented by HLA-A*02:01 allele in two patients, peptide binding to HLA was experimentally confirmed in 63% of them, whereas 55% were immunogenic in vivo in HLA-A*02:01+ transgenic mice, inducing T-cells against the mutated but not the wild-type peptide sequence. Vaccination with peptide pools or DNA plasmids expressing these neoAgs induced polyepitopic T-cell responses, which recognized neoAg-expressing tumor cells. These results suggest that TNBC tumors harbor neoAgs potentially useful in therapeutic vaccines, opening the way for new combined immunotherapies.

Vaccination using optimized strategies may increase response rates to immune checkpoint inhibitors (ICI) in some tumors. To enhance vaccine potency and improve thus responses to ICI, we analyzed the gene expression profile of an immunosuppressive dendritic cell (DC) population induced during vaccination, with the goal of identifying druggable inhibitory mechanisms. RNAseq studies revealed targetable genes, but their inhibition did not result in improved vaccines. However, we proved that immunosuppressive DC had a monocytic origin. Thus, monocyte depletion by gemcitabine administration reduced the generation of these DC and increased vaccine-induced immunity, which rejected about 20% of LLC-OVA and B16-OVA tumors, which are non-responders to anti-PD-1. This improved efficacy was associated with higher tumor T-cell infiltration and overexpression of PD-1/PD-L1. Therefore, the combination of vaccine + gemcitabine with anti-PD-1 was superior to anti-PD-1 monotherapy in both models. B16-OVA tumors benefited from a synergistic effect, reaching 75% of tumor rejection, but higher levels of exhausted T-cells in LLC-OVA tumors co-expressing PD-1, LAG3 and TIM3 precluded similar levels of efficacy. Our results indicate that gemcitabine is a suitable combination therapy with vaccines aimed at enhancing PD-1 therapies by targeting vaccine-induced immunosuppressive DC.

IntroductionObstructive sleep apnea (OSA) severity is based on the apnea-hypopnea index (AHI). The AHI is a simplistic measure that is inadequate for capturing disease severity and its consequences in cardiovascular diseases (CVDs). Deleterious effects of OSA have been suggested to influence the prognosis of specific endotypes of patients with acute coronary syndrome (ACS). We aim to identify respiratory polygraphy (RP) patterns that contribute to identifying the risk of recurrent cardiovascular events in patients with ACS.MethodsPost hoc analysis of the ISAACC study, including 723 patients admitted for a first ACS (NCT01335087) in which RP was performed. To identify specific RP patterns, a principal component analysis (PCA) was performed using six RP parameters: AHI, oxygen desaturation index, mean and minimum oxygen saturation (SaO2), average duration of events and percentage of time with SaO2 < 90%. An independent HypnoLaus population-based cohort was used to validate the RP components.ResultsFrom the ISAACC study, PCA showed that two RP components accounted for 70% of the variance in the RP data. These components were validated in the HypnoLaus cohort, with two similar RP components that explained 71.3% of the variance in the RP data. The first component (component 1) was mainly characterized by low mean SaO2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO2 and long-duration obstructive respiratory events without severe desaturation. In the ISAACC cohort, component 2 was associated with an increased risk of recurrent cardiovascular events in the third tertile with an adjusted hazard ratio (95% CI) of 2.44 (1.07 to 5.56; p-value = 0.03) compared to first tertile. For component 1, no significant association was found for the risk of recurrent cardiovascular events.ConclusionA RP component, mainly characterized by intermittent hypoxemia, is associated with a high risk of recurrent cardiovascular events in patients without previous CVD who have suffered a first ACS.

BackgroundCurrent treatments for Alzheimer’s disease (AD) modulate global neurotransmission but are neither specific nor anatomically directed. Tailored stimulation of target nuclei will increase treatment efficacy while reducing side effects. We report the results of the first directional deep brain stimulation (dDBS) surgery and treatment of a patient with AD in an attempt to slow the progression of the disease in a woman with multi-domain, amnestic cognitive status.MethodsWe aimed to assess the safety of dDBS in patients with AD using the fornix as stimulation target (primary objective) and the clinical impact of the stimulation (secondary objective). In a registered clinical trial, a female patient aged 81 years with a 2-year history of cognitive decline and diagnoses of AD underwent a bilateral dDBS surgery targeting the fornix. Stimulation parameters were set between 3.9 and 7.5 mA, 90 μs, 130 Hz for 24 months, controlling stimulation effects by 18F-fluoro-2-deoxy-D-glucose (18F-FDG) scans (baseline, 12 and 24 months), magnetoencephalography (MEG) and clinical/neuropsychological assessment (baseline, 6, 12, 18, and 24 months).ResultsThere were no important complications related to the procedure. In general terms, the patient showed cognitive fluctuations over the period, related to attention and executive function patterns, with no meaningful changes in any other cognitive functions, as is shown in the clinical dementia rating scale (CDR = 1) scores over the 24 months. Such stability in neuropsychological scores corresponds to the stability of the brain metabolic function, seen in PET scans. The MEG studies described low functional connectivity at baseline and a subsequent increase in the number of significant connections, mainly in the theta band, at 12 months.ConclusionThe dDBS stimulation in the fornix seems to be a safe treatment for patients in the first stage of AD. Effects on cognition seem to be mild to moderate during the first months of stimulation and return to baseline levels after 24 months, except for verbal fluency.Clinical Trial Registration[https://clinicaltrials.gov/ct2/show/NCT03290274], identifier [NCT03290274].

Uniportal VATS has become an accepted approach in minimally invasive thoracic surgery since its first report for lobectomy in 2011. Since the initial restrictions in indications, it has been used in almost all procedures, from conventional lobectomies to sublobar resections, bronchial and vascular sleeve procedures and even tracheal and carinal resections. In addition to its use for treatment, it provides an excellent approach for suspicious solitary undiagnosed nodules after bronchoscopic or transthoracic image-guided biopsy. Uniportal VATS is also used as a surgical staging method in NSCLC due to its low invasiveness in terms of chest tube duration, hospital stay and postoperative pain. In this article, we review the evidence of uniportal VATS accuracy for NSCLC diagnosis and staging and provide technical details and recommendations for its safe performance for that purpose.

The depletion of fossil resources and the growing environmental concerns of the actual society have leaded to an urgent need of shifting from petroleum-based products to natural substitutes. In this context, lignocellulosic biomass has emerged as a potential alternative to obtain bio-precursors for the synthesis of new chemicals and materials. Wood residues from unexploited Atlantic mixed forests have become an interesting type of biomass, not only for their content on structural compounds, but also for their non-structural fractions such as extractives. These compounds usually present antioxidant and antifungal capacities and, thus, they can be interesting for multiple applications. However, their extraction can be complex and costly and, hence, intensification techniques such as ultrasound assisted experiments have been studied. The aim of this work was the evaluation of the potential of five hardwood species coming from Atlantic mixed forests for the obtaining of biologically active compounds. For this aim, after studying the chemical composition of the woods, extractive compounds were obtained through ethanol-water based conventional and ultrasound assisted extraction methods. The obtained extracts were characterised and their antioxidant and antifungal capacities were determined. The yields of the extracts for ultrasound assisted experiments were, in general, higher than those for conventional ones and they also resulted to be richer in phenolic compounds. The obtained extractives seemed to have both antioxidant and antifungal activities, although the latest should be studied in depth in future

Clinical trials of cell therapies that target stroke started at the beginning of this century and they have experienced a significant boost in recent years as a result of promising data from basic research studies. The increase in the information available has paved the way to carry out more innovative and varied human studies. Efforts have focused on the search for a safe and effective treatment to stimulate neuro-regeneration in the brain and to reduce the sequelae of stroke in patients. Therefore, this review aims to evaluate the clinical trials using cell therapy to treat stroke published to date and assess their limitations. From 2000 to date, most of the published clinical trials have focused on phases I or II, and the vast majority of them demonstrate that stem cells are essentially safe to use when administered by different routes, with transient and mild adverse events that do not generally have severe consequences for health. In general, there is considerable variation in the trials in terms of statistical design, sample size, the cells used, the routes of administration, and the functional assessments (both at baseline and follow-up), making it difficult to compare the studies. From this general description, possibly the experimental protocol is the main element to improve in future studies. Establishing an adequate experimental and statistical design will be essential to obtain favorable and reliable results when conducting phase III clinical trials. Thus, it is necessary to standardize the criteria used in these clinical trials in order to aid comparison. Shortly, cell therapy will be a key approach in the treatment of stroke if adequate and comprehensive levels of recovery are to be achieved.

Desde el ámbito penal, se establecen una serie de garantías a favor del justiciable, pero -igualmente- hay una finalidad de tutela penal a una sociedad que clama protección y lucha contra la criminalidad. Abordamos, en este estudio, la relación de la enfermedad mental con los delitos contra la vida, poniendo de relieve que -con frecuencia- confundimos la enfermedad mental con peligrosidad, explicando el crimen en base a la dolencia que presenta el autor. Se hace necesario, en este sentido, ahondar en las posibles condiciones asociadas al hecho delictivo (etiología), así como a sus manifestaciones (fenomenología), procurando la prevención y tratamiento.

There is an increase in the demand of natural and environmentally more sustainable products, for that the biorefinery is a very promising tool due to its capacity to develop more sustainable products. Biorefinery processes are being optimized to reduce the global energy consumption and environmental impact by increasing extraction yields. In this work, two intensification techniques, microwave-assisted extraction and ultrasound-assisted extraction, have been tested and their results have been compared with those obtained by the conventional method. The best results were obtained with microwave-assisted extraction. Another studied aspect was the selectivity of the solvent, for which three ionic liquids ([C4C1im][Br], [C4C1im][OAc] and [C4C1im][BF4]) and two deep eutectic solvents (Choline Chloride:Urea (1:2) and Choline Chloride: 1,4-butanediol (1:2)) were tested. The best extraction yield was obtained with Choline Chloride:Urea (1:2). The objective of this work was the evaluation of the impact of the processes in terms of energy consumption and solvents’ toxicity, in addition to the determination of the extraction process performance. For this, an analysis of energy consumption was performed, with microwave assisted extraction having the lowest consumption. For the toxicity study different parameters were taken into account, concluding that deep eutectic solvents are a good option. In conclusion, the combination of microwave assisted extraction with deep eutectic solvents can be considered the most efficient extraction method.

Ischemic stroke (IS) is the leading cause of disability in the western world, assuming a high socio-economic cost. One of the most used strategies in the last decade has been biomaterials, which have been initially used with a structural support function. They have been perfected, different compounds have been combined, and they have been used together with cell therapy or controlled release chemical compounds. This double function has driven them as potential candidates for the chronic treatment of IS. In fact, the most developed are in different phases of clinical trial. In this review, we will show the ischemic scenario and address the most important criteria to achieve a successful neuroreparation from the point of view of biomaterials. The spontaneous processes that are activated and how to enhance them is one of the keys that contribute to the success of the therapeutic approach. In addition, the different routes of administration and how they affect the design of biomaterials are analyzed. Future perspectives show where this broad scientific field is heading, which advances every day with the help of technology and advanced therapies.

La situación de América Latina y el Caribe nos muestra un escenario económico, político, social y ambiental incierto que coloca a la región ante la oportunidad para transformar la trayectoria de su desarrollo, superando las desigualdades y la brecha existente entre los avances que han significado las legislaciones y la realidad cotidiana de las mujeres. El desarrollo humano sostenible constituye hoy un imperativo de supervivencia, para lograrlo es necesario involucrar a las instituciones y a la ciudadanía, hombres y mujeres empeñados en un mismo fin. La participación de la mujer en el ámbito económico social y ambiental como dimensiones del desarrollo sostenible es un objetivo irrenunciable para garantizar la perpetuidad del planeta, por el protagonismo que representa su actuación en la vida política, económica y familiar. La Agenda Regional de Género para América Latina en especial sinergia con la Agenda 2030, proporciona objetivos y estrategias para lograr estos propósitos. Valorar el marco jurídico e institucional para el desarrollo de estas estrategias encaminadas a reparar la posición desigual de las mujeres en las áreas críticas de preocupación, que incluye no solo la educación, y la salud, sino también la contribución en la economía, los procesos de decisión política y el respeto a los derechos humanos, es el objetivo de nuestro trabajo.

La densidad, o concentración de materia, es un concepto muy relevante pero que genera muchas dificultades de comprensión. Para medir la competencia en la estimación de la densidad del alumnado de la ESO, se pasó un cuestionario acompañado de un juego de materiales a 196 alumnos de los cuatro cursos de la ESO en dos colegios. La estimación de la densidad depende del peso percibido, el tamaño o la viscosidad, lo que a veces lleva a estimaciones erróneas. En todos los cursos, más del 40 % de los alumnos consideran la densidad como una propiedad extensiva; en torno a un 50 % usan modelos –no siempre coherentes– más cercanos a una propiedad intensiva y específica. Existen además dificultades para predecir los cambios en densidad con el estado de agregación o la temperatura, lo que sugiere que deben introducirse cambios en su enseñanza.

Understanding mechanisms associated to dendritic cell (DC) functions has allowed developing new antitumor therapeutic vaccination strategies. However, these vaccines have demonstrated limited clinical results. Although the low immunogenicity of tumor antigens used and the presence of tumor-associated suppressive factors may in part account for these results, intrinsic vaccine-related factors may also be involved. Vaccines modulate DC functions by inducing activating and inhibitory signals that determine ensuing T cell responses. In this mini review, we focus on IL-10, inhibitory cytokine induced in DC upon vaccination, which defines a suppressive cell subset, discussing its implications as a potential target in combined vaccination immunotherapies.

Bark is considered as waste generated by wood processing industries. Bark is being used for horticulture applications and energy production, but due to its complex structure, bark can become biorenewable source. It is rich in high add-value compounds, as bioactive compounds, which are used in medicine, nutrition or personal care products. The most used extraction method for this bio-compounds is the conventional (liquid extraction), but in recent years others are being investigated. In this work conventional extraction (CE), ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE) were optimized to obtain the highest extraction yield (%). In the optimal point of the design, total phenolic content (TPC) and total flavonoids content (TFC) of the extract of each method were determined. Their antioxidant capacity was also measured using 2,2-diphenyl-1-picrylhydrazyl assay (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) assay (ABTS) and ferric reducing antioxidant power (FRAP) assay. The best extraction yield (%) as well as the highest antioxidant capacities were obtained with microwaves. The results showed the potential of the bark of Larix Decidua as source of bioactive compounds. Using microwaves for extraction could save energy and reduce the processing time.

Tumor infiltrating lymphocytes have been associated with a better prognostic and with higher response rates in patients treated with checkpoint inhibiting antibodies, suggesting that strategies promoting tumor inflammation may enhance the efficacy of these currently available therapies. Our aim was thus to develop a new vaccination platform based on cold-inducible RNA binding protein (CIRP), an endogenous TLR4 ligand generated during inflammatory processes, and characterize whether it was amenable to combination with checkpoint inhibitors. In vitro, CIRP induced dendritic cell activation, migration and enhanced presentation of CIRP-bound antigens to T-cells. Accordingly, antigen conjugation to CIRP conferred immunogenicity, dependent on immunostimulatory and antigen-targeting capacities of CIRP. When applied in a therapeutic setting, vaccination led to CD8-dependent tumor rejection in several tumor models. Moreover, immunogenicity of this vaccination platform was enhanced not only by combination with additional adjuvants, but also with antibodies blocking PD-1/PD-L1, CTLA-4 and IL-10, immunosuppressive molecules usually present in the tumor environment and also induced by the vaccine. Therefore, priming with a CIRP-based vaccine combined with immune checkpoint-inhibiting antibodies rejected established B16-OVA tumors. Finally, equivalent activation and T-cell stimulatory effects were observed when using CIRP in vitro with human cells, suggesting that CIRP-based vaccination strategies could be a valuable clinical tool to include in combinatorial immunotherapeutic strategies in cancer patients.

The chemical synthesis of new lipophilic polyphenols with improved properties presents technical difficulties. Here we describe the selection, isolation and identification of lipolytic bacteria from food-processing industrial wastes, and their use for tailoring a new set of compounds with great interest in the food industry. These bacteria were employed to produce lipolytic supernatants, which were applied without further purification as biocatalysts in the chemoselective and regioselective synthesis of lipophilic partially acetylated phenolic compounds derived from olive polyphenols. The chemoselectivity of polyphenols acylation/deacylation was analyzed, revealing the preference of the lipases for phenolic hydroxyl groups and phenolic esters. In addition, the alcoholysis of peracetylated 3,4-dihydroxyphenylglycol resulted in a series of lipophilic 2-alkoxy-2-(3,4-dihydroxyphenyl)ethyl acetate through an unexpected lipase-mediated etherification at the benzylic position. These new compounds are more lipophilic and retained their antioxidant properties. This approach can provide access to unprecedented derivatives of 3,4-dihydroxyphenylglycol with improved properties.

The lack of antiviral cellular immune responses in patients with chronic hepatitis C virus (HCV) infection suggests that T-cell vaccines may provide therapeutic benefit. Due to the central role that dendritic cells (DC) play in the activation of T-cell responses, our aim was to carry out a therapeutic vaccination clinical trial in HCV patients using DC. Five patients with chronic HCV infection were vaccinated with three doses of 5 Ã 106 or 107 autologous DC transduced with a recombinant adenovirus encoding NS3 using the adapter protein CFh40L, which facilitates DC transduction and maturation. No significant adverse effects were recorded after vaccination. Treatment caused no changes in serum liver enzymes nor in viral load. Vaccination induced weak but consistent expansion of T-cell responses against NS3 and adenoviral antigens. Patientsâ DC, as opposed to murine DC or DC from healthy subjects, secreted high IL-10 levels after transduction, inducing the activation of IL-10âproducing T cells. IL-10 blockade during vaccine preparation restored its ability to stimulate anti-NS3 Th1 responses. Thus, vaccination with adenovirus-transduced DC is safe and induces weak antiviral immune responses. IL-10 associated with vaccine preparation may be partly responsible for these effects, suggesting that future vaccines should consider concomitant inhibition of this cytokine.

The extension of a well-known inverse technique, inverse adding-doubling (IAD), is investigated for determining the volume scattering properties of diffusers for display and lighting applications. The luminance characteristics of volume scattering diffusers are vital for these applications. Through a simulation study, it is shown that fitting solely to the scattered (angular) intensity information with the extended IAD method, results in a volume scattering characterization that also reproduces the correct (spatial and angular) luminance characteristics for a wide range of samples. The gap between the simulation work and the experimental application of the investigated fitting procedure is bridged by considering the effect of experimental error in the scattered intensity distributions. This does not significantly alter the presented conclusions.

Luminescent materials are widely used in white LEDs to convert part of the blue LED light into light with a longer wavelength, resulting in white light when both colors are well mixed. One way to integrate the luminescent material in the LED package is to deposit a thin luminescent layer on a planar carrier or disperse luminescent particles in the carrier material and then position the resulting wavelength conversion plate above one or more LEDs. It is very important that these wavelength conversion plates have the right properties to ensure homogeneous white light with a high efficiency and desired correlated color temperature (CCT). Key properties are the absorption and emission spectrum and the scattering and absorption coefficients. These properties strongly influence the color of the resulting light, but also the efficiency and the angular uniformity. This work describes an extensive study of the effect of the scattering and absorption coefficients in terms of the desired CCT. A computationally efficient extended Adding-Doubling method is used for the simulation of the light distribution and conversion in the planar wavelength conversion element. Ultimately an optimal combination with a high efficiency and low angular color deviation is desired. Different systems are investigated and optimal coefficients are found. With these findings a more targeted approach can be used in the manufacturing of wavelength conversion plates for white LEDs. The addition of scatterers or non-scattering luminescent particles can be used to obtain optimal scattering properties of the wavelength conversion plate.

To perform adequate simulations of luminescent cascade systems, a hybrid method combining a commercial ray tracer and a programming tool is presented. True Monte Carlo algorithms for luminescent materials, treating each ray individually, are adapted to allow wavelength conversion of ray sets. Two solutions for the wavelength conversion of ray sets are discussed: a random approach, where absorption events are randomly selected to create emission events, and a combined approach, where information from multiple absorption events is combined to create emission events. Both methods are applied to simulate the performance of a virtual remote phosphor light-emitting diode module. When using the combined approach, the required computation time to achieve sufficient accuracy is a factor 2 lower, compared to the time required when applying the random approach.

Light-emitting diodes (LEDs) are becoming increasingly important for general lighting applications. The remote phosphor technology, with the phosphor located at a distance from the LEDs, offers an increased extraction efficiency for phosphor converted LEDs compared to intimate phosphor LEDs where the phosphor is placed directly on the die. Additionally, the former offers new design possibilities that are not possible with the latter. In order to further improve the system efficiency of remote phosphor LEDs, realistic simulation models are required to optimize the actual performance. In this work, a complete characterization of a remote phosphor converter (RPC) consisting of a polycarbonate diffuser plate with a phosphor coating on one side via the bi-directional scattering distribution function (BSDF) is performed. Additionally, the bi-spectral BSDF which embraces the wavelength conversion resulting from the interaction of blue light with the RPC is determined. An iterative model to predict the remote phosphor module power and photon budget, including the recuperation of backward scattered light by a mixing chamber, is introduced. The input parameters for the model are the bi-spectral BSDF data for the RPC, the emission of the blue LEDs and the mixing chamber efficiency of the LED module. A good agreement between experimental and simulated results was found, demonstrating the potential of this model to analyze the system efficiency with errors smaller than 4%.

To enhance the efficiency of solar cells, a luminescent down shifting layer can be applied in order to adapt the solar spectrum to the spectral internal quantum efficiency of the semiconductor. Optimization of such luminescent down shifting layers benefits from quick and direct evaluation methods. In this paper, the potential of the adding-doubling method is investigated to simulate the optical behavior of an encapsulated solar cell including a planar luminescent down shifting layer. The results of the adding-doubling method are compared with traditional Monte Carlo ray tracing simulations. The average relative deviation is found to be less than 1.5% for the absorptance in the active layer and the reflectance from the encapsulated cell, while the computation time can be decreased with a factor 52. Furthermore, the adding-doubling method is adopted to investigate the suitability of the SrB4O7:5%Sm2 + ,5%Eu2 + phosphor as a luminescent down shifting material in combination with a Copper Indium Gallium Selenide solar cell. A maximum increase of 9.0% in the short-circuit current can be expected if precautions are taken to reduce the scattering by matching the refractive index of host material to the phosphor particles. To be useful as luminescent down shifting material, the minimal value of the quantum yield of the phosphor is determined to be 0.64.

The accuracy of optical simulations including bulk diffusors is heavily dependent on the accuracy of the bulk scattering properties. If no knowledge on the physical scattering effects is available, an iterative procedure is usually used to obtain the scattering properties, such as the inverse Monte Carlo method or the inverse adding-doubling (AD) method. In these methods, a predefined phase function with one free parameter is usually used to limit the number of free parameters. In this work, three predefined phase functions (Henyey-Greenstein, two-term Henyey-Greenstein, and Gegenbauer kernel (GK) phase function) are implemented in the inverse AD method to determine the optical properties of two strongly diffusing materials: low-density polyethylene and TiO₂ particles. Using the presented approach, an estimation of the effective phase function was made. It was found that the use of the GK phase function resulted in the best agreement between calculated and experimental transmittance, reflectance, and scattered radiant intensity distribution for the LDPE sample. For the TiO₂ sample, a good agreement was obtained with both the two-term Henyey-Greenstein and the GK phase function.

Diffusors are widely used optical components having numerous applications. They are commonly used to homogenize light beams and to create particular intensity distributions. The angular scattering profile of bulk scattering diffusing materials is determined by three bulk scattering parameters that are, however, not commonly available. This hampers an accurate implementation of bulk diffusors in ray tracing simulations. In this paper, the bulk scattering parameters of a concentration series of milk diluted with water were determined with the inverse adding-doubling method. Using these values as input, the macroscopic angular scattering profile was simulated using ray tracing software. The simulation results were compared to experimental data, and a good agreement between measured and simulated data was found. The method was also proven to be successful when applied to commercial diffusors.

Objectives: To describe the safety and efficacy of single-port access for laparoscopic surgery in gynecology with conventional laparoscopic instruments., Patients and Methods: In this prospective study, we report our experience with 90 patients who underwent Single Port Access (SPA) laparoscopic surgery for gynecologic pathology with the use of the SILS(®) Port Multiple Instrument Access Port (Covidien(®), Mansfield, MA)., Results: We realised 15 ovarian cystectomies, 30 salpingo-oophrectomies with 14 one side, 9 lysis of adhesions, 7 distal tubal repairs, 6 salpingectomy, 8 other procedures. The mean surgical time is 47 min (25-120). One conversion to conventional laparoscopy and one in laparotomy were performed. The mean duration stay is 2 days [1-3]., Discussion and Conclusion: SPA in gynecology is feasible with conventional laparoscopic instruments. SPA surgery represents the newest frontier in minimally invasive surgery., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

In this paper a fast, yet accurate method to estimate the spectral and angular distribution of the scattered radiation of a fluorescent material is described. The proposed method is an extension of the adding-doubling algorithm for non-fluorescent samples. The method is validated by comparing the spectral and angular transmittance and reflectance characteristics obtained with the extended algorithm with the results obtained using Monte Carlo simulations. The agreement using both methods is within 2%. However, the adding-doubling method achieves a reduction of the calculation time by a factor of 400. Due to the short calculation time, the extended adding-doubling method is very useful when fluorescent layers have to be optimized in an iterative process.