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Abstract Trauma teams handle severely injured patients under high temporal demands and need to coordinate and achieve collaborative decision-making and task execution through communication. Specific coordination and communication behaviours are taught in simulation training to enhance team performance. An examination of the role and nature of communication could increase the understanding of educational possibilities and assess the validity of in situ simulation on behalf of communication. Our study aim was to describe the relative use of communication within information and task management, the use of coordinating behaviours, and the use of talking to the room and closed-loop communication in in-real-life trauma assessment and in the simulated domain. We video-recorded all verbal communicative events in four real-world trauma teams and four teams during simulation training. The analysis showed that although the teamwork was task-oriented, information management dominated task management at 64% of all the utterances in-real-life and 68% during simulation. In-real-life, information management was dominated by the codes “request information” (24%) and “confirmation” (21%), whereas “task distribution” (43%) was most frequently used for task management. The only difference between domains was that “give information after request” represented a smaller proportion of the utterances in-real-life compared to simulation (p ≤ 0.001). Talking to the room was primarily used by the teams in both domains to provide information without request and to delegate tasks. Closed-loop communication was used at a low frequency, 3.6% in-real-life, but was significantly higher, 7.7%, in simulation training. We suspect that this outcome reflects the Hawthorne effect. In the simulations, greater information delivery was provided in response to questions, probably accounting for instructor information. Our results may be valuable for research on trauma team behaviour in a simulated environment to draw conclusions about similar activities in-real-life.

Introduction: The objective of the study was to establish the normal range for the levels of antithrombin (AT), protein C (PC), and protein S (PS) in the first week post birth in mother–infant pairings, adjusting for obstetric and perinatal factors, based on 2 different laboratory methods. Methods: Determinations were carried out in 83 healthy term neonates and their mothers, establishing 3 postpartum age groups: 1−2 days, 3 days, and 4−7 days. Results: There were no differences in the levels of any of the proteins between the different age groups in neonates or mothers in the first week post birth. The adjusted analysis found no association with obstetric or perinatal factors. The AT and PC levels were higher in mothers compared to infants (P

Abstract Allergic sensitization is initiated by protein and epithelia interaction, although the molecular mechanisms leading this encounter toward an allergic phenotype remain unknown. Here, we apply the two-hit hypothesis of inflammatory diseases to the study of food allergy sensitization. First, we studied the effects of long-term depilation in mice by analyzing samples at different time points. Several weeks of depilation were needed until clear immunological changes were evidenced, starting with upregulation of NLRP3 protein levels, which was followed by overexpression of Il1b and Il18 transcripts. Secondly, we assessed the effects of allergen addition (in this case, Pru p 3 in complex with its natural lipid ligand) over depilated skin. Systemic sensitization was evaluated by intraperitoneal provocation with Pru p 3 and measure of body temperature. Anaphylaxis was achieved, but only in mice sensitized with Prup3_complex and not treated with the NLRP3 inhibitor MCC950, thus demonstrating the importance of both hits (depilation + allergen addition) in the consecution of the allergic phenotype. In addition, allergen encounter (but not depilation) promoted skin remodeling, as well as CD45+ infiltration not only in the sensitized area (the skin), but across several mucosal tissues (skin, lungs, and gut), furtherly validating the systemization of the response. Finally, a low-scale study with human ILC2s is reported, where we demonstrate that Prup3_complex can induce their phenotype switch (↑CD86, ↑S1P1) when cultured in vitro, although more data is needed to understand the implications of these changes in food allergy development.

Virus-like particles (VLPs) have been gaining attention as potential platforms for delivery of cargos in nanomedicine. Although animal viruses are largely selected due to their immunostimulatory capacities, VLPs from plant viruses constitute a promising alternative to be considered. VLPs derived from Turnip mosaic virus (TuMV) have proven to present a tridimensional structure suited to display molecules of interest on their surface, making them interesting tools to be studied in theragnostic strategies. Here, we study their potential in the treatment of food allergy by genetically coupling TuMV-derived VLPs to Pru p 3, one of the most dominant allergens in Mediterranean climates. VLPs-Pru p 3 were generated by cloning a synthetic gene encoding the TuMV coat protein and Pru p 3, separated by a linker, into a transient high-expression vector, followed by agroinfiltration in Nicotiana benthamiana plants. The generated fusion protein self-assembled in planta to form the VLPs, which were purified by exclusion chromatography. Their elongated morphology was confirmed by electron microscopy and their size (~400 nm), and monodispersity was confirmed by dynamic light scattering. Initial in vitro characterization confirmed that they were able to induce proliferation of human immune cells. This proliferative capability was enhanced when coupled with the natural lipid ligand of Pru p 3. The resultant formulation, called VLP-Complex, was also able to be transported by intestinal epithelial cells, without affecting the monolayer integrity. In light of all these results, VLP-Complex was furtherly tested in a mouse model of food allergy. Sublingual administration of VLP-Complex could effectively reduce some serological markers associated with allergic responses in mice, such as anti-Pru p 3 sIgE and sIgG2a. Noteworthy, no associated macroscopic, nephritic, or hepatic toxicity was detected, as assessed by weight, blood urea nitrogen (BUN) and galectin-3 analyses, respectively. Our results highlight the standardized production of allergen-coated TuMV-VLPs in N. benthamiana plants. The resulting formula exerts notable immunomodulatory properties without the need for potentially hazardous adjuvants. Accordingly, no detectable toxicity associated to their administration was detected. As a result, we propose them as good candidates to be furtherly studied in the treatment of immune-based pathologies.

The mold Alternaria alternata is one of the main sources of asthma exacerbation, being its major allergen, Alt a 1, indispensable for its development. The main objective of this work was to answer two main questions: 1) can Alt a 1 by itself (without any other context) induce an asthmatic profile in vivo?; and 2) Which molecular mechanisms take place during this phenomenon? To answer both questions, we have developed a mouse model of allergic asthma using only Alt a 1 for mice sensitization. We also made use of in-vitro cellular models and computational studies to support some aspects of our hypothesis. Our results showed that Alt a 1 can induce an asthmatic phenotype, promoting tissue remodeling and infiltration of CD45+ cells, especially eosinophils and macrophages (Siglec F+ and F4/80+). Also, we have found that Alt a 1 sensitization is mediated by the TLR4-macrophage axis.

Lipid Transfer Proteins (LTPs) have been described as one of the most prevalent and cross-reactive allergen families in the general population. They are widely distributed among the plant kingdom, as well as in different plant organs ranging from pollen to fruits. Thus, they can initiate allergic reactions with very different outcomes, such as asthma and food allergy. Several mouse models have been developed to unravel the mechanisms that lead LTPs to promote such strong sensitization patterns. Interestingly, the union of certain ligands can strengthen the allergenic capacity of LTPs, suggesting that not only is the protein relevant in the sensitization process, but also the ligands that LTPs carry in their cavity. In fact, different LTPs with pro-allergenic capacity have been shown to transport similar ligands, thus positioning lipids in a central role during the first stages of the allergic response. Here, we offer the latest advances in the use of experimental animals to study the topic, remarking differences among them and providing future researchers a tool to choose the most suitable model to achieve their goals. Also, recent results derived from metabolomic studies in humans are included, highlighting how allergic diseases alter the lipidic metabolism toward a pathogenic state in the individual. Altogether, this review offers a comprehensive body of work that sums up the background evidence supporting the role of lipids as modulators of allergic diseases. Studying the role of lipids during allergic sensitization might broaden our understanding of the molecular events leading to tolerance breakdown in the epithelium, thus helping us to understand how allergy is initiated and established in the individuals.

Non-specific lipid transfer proteins (nsLTPs) are small, cysteine-rich proteins, a part of the pathogenesis-related protein family, and numerous of them act as positive regulators during plant disease resistance, growth, and reproduction. These proteins are involved also in the intracellular transfer of lipids, as well as in plant immune responses. Besides their differences in sequences, they show similar features in their structure. However, they show distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. This study reports the identification, in silico characterization and purification of a novel member of the nsLTP2 protein family from durum wheat, TdLTP2. It was generated and purified using the combination of gel filtration chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). Its identity was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry (MALDI-TOF). TdLTP2 had been expressed in different stress to detect its localization; therefore, fluor-immunolocalization studies accomplished this data. In this approach, to assess the allergenicity of TdLTP2, thirty patients with baker’s asthma were enrolled and ELISA to detect the presence of specific IgE antibodies tested their sera. Moreover, the lipid-binding properties of TdLTP2 were examined in vitro and validated using a molecular docking study. In summary, our results demonstrate a new addition of member in plant nsLTPs family, TdLTP2, which can develop a better understanding about its biological functions and shed light on future applications.

Cutaneous melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors programmed death cell protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) constituted a main breakthrough in the treatment of metastatic CM, particularly for the achievement of long-term benefits. Even though it is a very promising therapy, resistance to primary immune checkpoint blockade (ICB) arises in about 70% of CM patients treated with a CTLA-4 inhibitor, and 40–65% of CM patients administered with a PD-1-targeting treatment. Some long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are implicated in triggering pro- and anti-tumorigenic responses to various cancer treatments. The relationship between lncRNAs, circRNAs and ICB immunotherapy has not been explored in cutaneous metastatic melanoma (CMM). The aim of this pilot study is to evaluate the potential role of circRNA and lncRNA expression variability as pre-treatment predictor of the clinical response to immunotherapy in CMM patients. RNA-seq from 12 formalin-fixed paraffin-embedded (FFPE) samples from the metastatic biopsies of CMM patients treated with nivolumab was used to identify response-associated transcripts. Our findings indicate that specific lncRNAs and circRNAs, probably acting as competitive endogenous RNAs (ceRNAs), are involved in the regulatory networks of the immune response against metastatic melanoma that these patients have under treatment with nivolumab. Moreover, we established a risk score that yields predictions of the overall survival (OS) and progression-free survival (PFS) of CMM patients with high accuracy. This proof-of-principle work provides a possible insight into the function of ceRNAs, contributing to efforts to decipher the complex molecular mechanisms of ICB cancer treatment response.

Alternaria alternata is a saprophytic mold whose spores are disseminated in warm dry air, the typical weather of the Mediterranean climate region (from 30° to 45°), with a peak during the late summer and early autumn. Alternaria spores are known to be biological contaminants and a potent source of aeroallergens. One consequence of human exposure to Alternaria is an increased risk of developing asthma, with Alt a 1 as its main elicitor and a marker of primary sensitization. Although the action mechanism needs further investigation, a key role of the epithelium in cytokine production, TLR-activated alveolar macrophages and innate lymphoid cells in the adaptive response was demonstrated. Furthermore, sensitization to A. alternata seems to be a trigger for the development of co-sensitization to other allergen sources and may act as an exacerbator of symptoms and an elicitor of food allergies. The prevalence of A. alternata allergy is increasing and has led to expanding research on the role of this fungal species in the induction of IgE-mediated respiratory diseases. Indeed, recent research has allowed new perspectives to be considered in the assessment of exposure and diagnosis of fungi-induced allergies, although more studies are needed for the standardization of immunotherapy formulations.

Little is known about the pathogenesis of cerebral sinovenous thrombosis (CSVT) in the neonate. Although thrombophilia has been described as increasing the risk of CSVT in adults, it remains controversial in pediatric patients, and prospective case–control studies regarding neonatal CSVT are lacking. From 2008 to 2017, all 26 consecutive newborn infants ≥35 weeks of gestation diagnosed with neonatal CSVT, and their mothers, were tested for factor V Leiden (FV) G1691A, FII G20210A, and methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations. Eighty-five mother–infant pairs were recruited as controls. All infants except 1 with CSVT were suspected due to clinical symptoms, mainly seizures (22/25). Magnetic resonance imaging was performed in 24/26 infants. Heterozygous FV G1691A, FII G20210A, and homozygous MTHFR C677T mutations were present in 1/26, 3/26, and 3/20 infants with CSVT, respectively. FII (odds ratio: 10.96; 95% confidence interval [CI]: 1.09-110.35) and male sex (3.93; 95% CI: 1.43-10.76) were associated with CSVT. When FII G20210A analysis was adjusted for sex, the OR for FII G20210A was 6.70 (95% CI: 0.65-69.22). No differences were found for FV G1691A or homozygous MTHFR mutations between neonates with CSVT and their mothers, compared to controls.

The Poincaré plot is a geometrical technique used to visualize and quantify the correlation between two consecutive data points in a time-series. Since the dynamics of fluctuations in physiological rhythms exhibit long-term correlation and memory, this study aimed to extend the Poincaré plot by calculating the correlation between sequential data points in a time-series, rather than between two consecutive points. By incorporating this so-called lag, we hope to integrate a temporal aspect into quantifying the correlation, to depict whether a physiological system holds prolonged association between events separated by time. In doing so, it attempts to instantaneously characterize the intrinsic behavior of a complex system. We tested this hypothesis on three different physiological time-series: heart rate variability in patients with liver cirrhosis, respiratory rhythm in asthma and body temperature fluctuation in patients with cirrhosis, to evaluate the potential application of the extended Poincaré method in clinical practice. When studying the cardiac inter-beat intervals, the extended Poincaré plot revealed a stronger autocorrelation for patients with decompensated liver cirrhosis compared to less severe cases using Pearson’s correlation coefficient. In addition, long-term variability (known as SD2 in the extended Poincaré plot) appeared as an independent prognostic variable. This holds significance by acting as a non-invasive tool to evaluate patients with chronic liver disease and potentially facilitate transplant selection as an adjuvant to traditional criteria. For asthmatics, employing the extended Poincaré plot allowed for a non-invasive tool to differentially diagnose various classifications of respiratory disease. In the respiratory inter-breath interval analysis, the receiver operating characteristic (ROC) curve provided evidence that the extension of the Poincaré plot holds a greater advantage in the classification of asthmatic patients, over the traditional Poincaré plot. Lastly, the analysis of body temperature from patients using the extended Poincaré plot helped identify inpatients from outpatients with cirrhosis. Through these analyses, the extended Poincaré plot provided unique and additional information which could potentially make a difference in clinical practice. Conclusively, the potential use of our work lies in its possible application of predicting mortality for the organ allocation procedure in patients with cirrhosis and non-invasively distinguish between atopic and non-atopic asthma.

A popular method to estimate proximal/distal temperature (TPROX and TDIST) consists in calculating a weighted average of nine wireless sensors placed on pre-defined skin locations. Specifically, TPROX is derived from five sensors placed on the infra-clavicular and mid-thigh area (left and right) and abdomen, and TDIST from four sensors located on the hands and feet. In clinical practice, the loss/removal of one or more sensors is a common occurrence, but limited information is available on how this affects the accuracy of temperature estimates. The aim of this study was to determine the accuracy of temperature estimates in relation to number/position of sensors removed. Thirteen healthy subjects wore all nine sensors for 24 hours and reference TPROX and TDIST time-courses were calculated using all sensors. Then, all possible combinations of reduced subsets of sensors were simulated and suitable weights for each sensor calculated. The accuracy of TPROX and TDIST estimates resulting from the reduced subsets of sensors, compared to reference values, was assessed by the mean squared error, the mean absolute error (MAE), the cross-validation error and the 25th and 75th percentiles of the reconstruction error. Tables of the accuracy and sensor weights for all possible combinations of sensors are provided. For instance, in relation to TPROX, a subset of three sensors placed in any combination of three non-homologous areas (abdominal, right or left infra-clavicular, right or left mid-thigh) produced an error of 0.13°C MAE, while the loss/removal of the abdominal sensor resulted in an error of 0.25°C MAE, with the greater impact on the quality of the reconstruction. This information may help researchers/clinicians: i) evaluate the expected goodness of their TPROX and TDIST estimates based on the number of available sensors; ii) select the most appropriate subset of sensors, depending on goals and operational constraints.

BackgroundApple allergy manifests as two main groups of clinical entities reflecting different patterns of allergen sensitization: oral allergy syndrome (OAS) and generalized symptoms (GS).ObjectiveWe analysed the sensitization profile to a wide panel of different components of food allergens (rMal d 1, Mal d 2, rMal d 3, rMal d 4, rPru p 3, rBet v 1 and Pho d 2) for a population of Mediterranean patients with OAS and GS to apple.MethodsPatients (N = 81) with a history of apple allergy that could be confirmed by positive prick-prick test and/or double-blind-placebo-controlled food challenge (DBPCFC), were included. Skin prick test (SPT) and ELISA were performed using a panel of inhalant, fruit and nut allergens. ELISA and ELISA inhibition studies were performed in order to analyse the sensitization patterns.ResultsThirty-five cases (43.2%) had OAS and 46 (56.8%) GS. SPT showed a significantly higher number of positive results with peach, cherry and hazelnut in those with GS. ELISA showed a significantly high percentage of positive cases to rMal d 3, rMal d 4, rPru p 3 and Pho d 2 in patients with OAS and GS compared to controls, and to rBet v 1 in patients with OAS vs controls and between OAS and GS patients. Three different patterns of recognition were detected: positive to LTP (rMal d 3 or rPru p 3), positive to profilin (rMal d 4 and Pho d 2), or positive to both. There were also patients with rMal d 1 recognition who showed cross-reactivity to rBet v 1.ConclusionIn an apple allergy population with a high incidence of pollinosis different patterns of sensitization may occur. LTP is most often involved in those with GS. Profilin, though more prevalent in patients with OAS, has been shown to sensitise patients with both types of symptoms.

En la presente investigación, se analizó la influencia in vitro de los plaguicidas peletizados simultáneamente con el fungicida (principios activos: carboxin: 5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3 carboxamide y tiram: tetrame- thylthioperoxydicarbonic diamide) y un insecticida (principio activo: malatión: S-1,2-Bis(ethoxycarbonyl)ethyl-0,0 imethyithiophosphate) en las semillas de algodón sobre la viabilidad del biofertilizante Monibac®-Corpoica con base en Azotobacter chroococcum AC1, cuando fueron aplicados conjuntamente en bandejas experimentales. Se analizó la práctica de recubrir las semillas con los agroquimicos como posible causa de descenso poblacional de la bacteria bajo este modelo de aplicación. Los resultados obtenidos por el Test de Duncan (p

IntroductionWhile there is agreement on the positive link between psychological resilience and athletic performance, conclusive findings regarding the association between psychological resilience and other variables of interest (for example, age, gender, type of sport, or competitive level) remain elusive.ObjectiveThe study aimed to assess psychological resilience levels among judokas and explore potential associations with demographic factors, judo experience and competitive level.MethodsA total of 702 judokas (469 men and 233 women) participated in the study, of whom 194 (27.6%) were classified as TOP by their competitive level. Psychological resilience was evaluated using the Spanish version of the 10 item Connor-Davidson Resilience Scale (CD-RISC 10), with a score range from 0 to 40. Independent T-test and Pearson’s coefficient were used for bivariate analysis. A two-way non-parametric ANCOVA was carried out to analyse the impact of gender and competitive level on psychological resilience.ResultsThe judokas showed total mean scores in the CD-RISC 10 of 33.08 points (SD = 4.79), considered high. Levels of psychological resilience were significantly higher among men (33.36 ± 4.76) than women (32.53 ± 4.80) and were positively correlated with age and number of years practicing and competing in Judo (p = 0.019). Judokas with a higher competitive level (TOP judokas) showed significantly higher levels of resilience than the others (non-TOP judokas) (p

BackgroundPrograms that aim to improve the detection hypoxic-ischemic encephalopathy (HIE) should establish which neonates suffering from perinatal asphyxia need to be monitored within the first 6 h of life.MethodAn observational prospective cohort study of infants with gestational age ≥35 weeks, and above 1,800g, were included according to their arterial cord pH value (ApH): ≤7.00 vs. 7.01–7.10. Data was collected including obstetrical history, as well as neonatal comorbidities, including the presence of HIE, that happened within 6 h of life. A standardized neurological exam was performed at discharge.ResultsThere were 9,537 births; 176 infants with ApH 7.01–7.10 and 117 infants with ApH ≤7.00. All 9 cases with moderate-to-severe HIE occurred among infants with ApH ≤7.00. The incidence of global and moderate-severe HIE was 3/1,000 and 1/1,000 births, respectively. Outcome at discharge (abnormal exam or death) showed an OR 12.03 (95% CI 1.53, 94.96) in infants with ApH ≤7.00 compared to ApH 7.01–7.10 cohort. Ventilation support was 5.1 times (95% CI 2.87, 9.03) more likely to be needed by those with cord ApH ≤7.00 compared to those with ApH 7.01–7.10, as well as hypoglycemia (37% vs. 25%; p = 0.026). In 55%, hypoglycemia occurred despite oral and/or intravenous glucose administration had been already initiated.ConclusionsCord pH 7.00 might be a safe pH cut-off point when developing protocols to monitor infants born with acidemia in order to identify infants with moderate or severe HIE early on. There is non-negligible comorbidity in the ApH ≤7.00 cohort, but also in the 7.01–7.10 cohort.

[This corrects the article DOI: 10.1371/journal.pone.0230010.].

Purpose. Basal cell carcinoma (BCC) is the most frequent malignant periocular tumor. It is associated with exposure to ultraviolet radiation, and its incidence is gradually increasing. It may occasionally display more aggressive behavior and result in orbital or intracranial invasion. Mortality from periocular BBC with orbital invasion is very low, but the associated morbidity can be significant, from disfigurement to blindness. Traditionally, these cases have been treated with orbital exenteration or with radiotherapy (RT), but in recent years, hedgehog pathway inhibitors (HPIs) have emerged, are effective in more serious cases, and are used primarily or combined with surgery, changing our perspective on the management of these patients. Methods. We studied 24 cases of periocular BCC with orbital invasion, some primary and others recurrent, which were treated between 2011 and 2021 in the same hospital. All patients had clinical or radiological evidence of orbital invasion. Orbital exenteration was performed on 9/24 of the patients (1 received vismodegib after surgery), and 12/24 were treated, surgically preserving the eyeball, with 3 of them receiving adjuvant vismodegib. Three of the twenty-four patients were treated exclusively with vismodegib (Erivedge®, Genentech). Results. One patient died due to poor tumor evolution, but the rest evolved favorably and they have had no recurrences. Vismodegib was generally well tolerated, except for in one patient who discontinued treatment due to the side effects. Conclusions. In advanced BBC with orbital invasion, mutilating surgical treatments such as exenteration or potentially vision-threatening treatments such as RT remain as options. In recent years, however, very promising new medical therapies have emerged, such as HPI, which can be used effectively instead of surgery or in combination with it, preserving the eye and vision, which implies a new approach to treatment.

Cherry is a fruit which contains elevated amounts of antioxidant compounds, such as anthocyanins, pigments, and vitamins. Furthermore, it possesses high water, sugar, mineral, and indolamine contents. The general objective of this study was to characterise a cherry-based fermented beverage (the ‘sweetheart’ variety) and analyse the effects of its ingestion on (i) circulating serum levels of melatonin and serotonin, (ii) inflammatory response, and iii) serum total antioxidant capacity in rats (Rattus norvegicus). For cherry-based fermented beverage manufacturing, the cherries were washed, the stems and woody endocarps were removed, and ascorbic acid was added (to avoid enzymatic browning). After the homogenisation of the cherry fruit, lactic acid bacteria were inoculated, and the fermentation process was conducted for 36 h. The main bioactive compounds in the cherry beverage were characterised, as well as their total antioxidant capacity. Moreover, an in vivo assay was developed, in which rats ingested the fermented beverage ad libitum for seven days. The inflammatory mediators, the total antioxidant capacity, and the serum levels of melatonin and serotonin were measured. Based on these results, the intake of the cherry-based fermented beverage assayed in this study increased the total antioxidant status of rats, elevated the melatonin and serotonin levels in the serum, and improved the regulation of the inflammatory systemic processes.

The interaction between the plant lipid transfer protein Pru p 3 and phytosphingosine was assessed using an atomic force microscope. Phytosphingosine was covalently immobilized on DeepTipTM probes and Pru p 3 on MicroDeckTM functionalized substrates. Single-molecular interaction events between both molecules were retrieved and classified and the distribution for each one of the identified types was calculated. A success rate of over 70% was found by comparing the number of specific Pru p 3-phytosphingosine interaction events with the total number of recorded curves. The analysis of the distribution established among the various types of curves was further pursued to distinguish between those curves that can mainly be used for assessing the recognition between phytosphingosine (sensor molecule) and Pru p 3 (target molecule) in the context of affinity atomic force microscopy, and those that entail details of the interaction and might be employed in the context of force spectroscopy. The successful application of these functionalized probes and substrates to the characterization of the low-intensity hydrophobic interaction characteristic of this system is a clear indication of the potential of exploiting this approach with an extremely wide range of different biological molecules of interest. The possibility of characterizing molecular assembly events with single-molecule resolution offers an advantageous procedure to plough into the field of molecular biomimetics.

Emotional intelligence is a determinant factor in sports performance. The present study analysed differences in total emotional intelligence and its four dimensions in 2166 Spanish athletes (25.20 ± 10.17 years) from eight sports (volleyball, track and field, shooting, football, basketball, handball, gymnastics, and judo). A total of 1200 men and 966 women answered anonymously using a Google Forms questionnaire sent via WhatsApp about demographics and psychological variables. A Pearson correlation was conducted to assess the age–emotional intelligence relationship. An independent T-test and One-Way ANOVA were carried out to check for age differences between biological sex and sport and a One-Way ANCOVA to determine differences between sports controlled by age. Age differences were observed by sex and sport (p < 0.001). An association was found between age and emotional intelligence dimensions (p < 0.001), except for other’s emotional appraisal (p > 0.05). Judo was the sport with the highest levels of regulation of emotions, other’s emotional appraisal, use of emotion, and total emotional intelligence (p < 0.05). Generally, emotional intelligence was found to be more developed in individual sports than in team sports, except football. Consequently, psychological skills like emotional intelligence could be critical to achieving high performance, depending on the sport.

Fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome that is accompanied by fatigue, sleep disturbances, anxiety, depression, lack of concentration, and neurocognitive impairment. As the currently available drugs are not completely successful against these symptoms and frequently have several side effects, many scientists have taken on the task of looking for nonpharmacological remedies. Many of the FMS-related symptoms have been suggested to be associated with an altered pattern of endogenous melatonin. Melatonin is involved in the regulation of several physiological processes, including circadian rhythms, pain, mood, and oxidative as well as immunomodulatory balance. Preliminary clinical studies have propounded that the administration of different doses of melatonin to patients with FMS can reduce pain levels and ameliorate mood and sleep disturbances. Moreover, the total antioxidant capacity, 6-sulfatoxymelatonin and urinary cortisol levels, and other biological parameters improve after the ingestion of melatonin. Recent investigations have proposed a pathophysiological relationship between mitochondrial dysfunction, oxidative stress, and FMS by looking at certain proteins involved in mitochondrial homeostasis according to the etiopathogenesis of this syndrome. These improvements exert positive effects on the quality of life of FMS patients, suggesting that the use of melatonin as a coadjuvant may be a successful strategy for the management of this syndrome.

Plant-based extracts possess biological potential due to their high content of phytochemicals. Nevertheless, photosynthetic pigments (e.g., chlorophylls) that are also present in plant extracts could produce undesirable pro-oxidant activity that might cause a negative impact on their eventual application. Herein, the phenolic content of olive leaf (OLE) and green tea (GTE) extracts was assayed, and their antioxidant and anticancer activities were evaluated before and after the removal of chlorophylls. Regarding phenolic content, OLE was rich in hydroxytyrosol, tyrosol as well as oleuropein, whereas the main compounds present in GTE were gallocatechin, epigallocatechin (EGC), epigallocatechin gallate (EGCG), gallocatechin gallate, and caffeine. Interestingly, fresh extracts’ antioxidant ability was dependent on phenolic compounds; however, the elimination of chlorophyll compounds did not modify the antioxidant activity of extracts. In addition, both OLE and GTE had high cytotoxicity against HL-60 leukemic cell line. Of note, the removal of chlorophyll pigments remarkably reduced the cytotoxic effect in both cases. Therefore, our findings emphasize the remarkable antioxidant and anticancer potential of OLE and GTE and suggest that chlorophylls are of paramount importance for the tumor-killing ability of such plant-derived extracts.

Infertility is an increasing global public health concern with socio-psychological implications for affected couples. Remarkable advances in reproductive medicine have led to successful treatments such as assisted reproductive techniques (ART). However, the search for new therapeutic tools to improve ART success rates has become a research hotspot. In the last few years, pineal indolamine melatonin has been investigated for its powerful antioxidant properties and its role in reproductive physiology. It is considered a promising therapeutical agent to counteract the detrimental effects associated with oxidative stress in fertility treatments. The aim of the present narrative review was to summarize the current state of the art on the importance of melatonin in reproductive physiology and to provide a critical evaluation of the data available encompassing basic, translational and clinical studies on its potential use in ART to improve fertility success rates.

The in vitro antimicrobial potency of the bacteriocin AS-48 is well documented, but its clinical application requires investigation, as its toxicity could be different in in vitro (haemolytic and antibacterial activity in blood and cytotoxicity towards normal human cell lines) and in vivo (e.g. mice and zebrafish embryos) models. Overall, the results obtained are promising. They reveal the negligible propensity of AS-48 to cause cell death or impede cell growth at therapeutic concentrations (up to 27 μM) and support the suitability of this peptide as a potential therapeutic agent against several microbial infections, due to its selectivity and potency at low concentrations (in the range of 0.3–8.9 μM). In addition, AS-48 exhibits low haemolytic activity in whole blood and does not induce nitrite accumulation in non-stimulated RAW macrophages, indicating a lack of pro-inflammatory effects. The unexpected heightened sensitivity of zebrafish embryos to AS-48 could be due to the low differentiation state of these cells. The low cytotoxicity of AS-48, the absence of lymphocyte proliferation in vivo after skin sensitization in mice, and the lack of toxicity in a murine model support the consideration of the broad spectrum antimicrobial peptide AS-48 as a promising therapeutic agent for the control of a vast array of microbial infections, in particular, those involved in skin and soft tissue diseases. Keywords: Cytotoxicity, Antimicrobial peptides, Haemolysis, Topical delivery, Zebrafish model, Mouse model

In the present work, highly multiplexed diagnostic KITs based on an Interferometric Optical Detection Method (IODM) were developed to evaluate six Coronavirus Disease 2019 (COVID-19)-related biomarkers. These biomarkers of COVID-19 were evaluated in 74 serum samples from severe, moderate, and mild patients with positive polymerase chain reaction (PCR), collected at the end of March 2020 in the Hospital Clínico San Carlos, in Madrid (Spain). The developed multiplexed diagnostic KITs were biofunctionalized to simultaneously measure different types of specific biomarkers involved in COVID-19. Thus, the serum samples were investigated by measuring the total specific Immunoglobulins (sIgT), specific Immunoglobulins G (sIgG), specific Immunoglobulins M (sIgM), specific Immunoglobulins A (sIgA), all of them against SARS-CoV-2, together with two biomarkers involved in inflammatory disorders, Ferritin (FER) and C Reactive Protein (CRP). To assess the results, a Multiple Linear Regression Model (MLRM) was carried out to study the influence of IgGs, IgMs, IgAs, FER, and CRP against the total sIgTs in these serum samples with a goodness of fit of 73.01% (Adjusted R-Squared).

Allergy is defined as a complex chronic inflammatory condition in which genetic and environmental factors are implicated. Sphingolipids are involved in multiple biological functions, from cell membrane components to critical signaling molecules. To date, sphingolipids have been studied in different human pathologies such as neurological disorders, cancer, autoimmunity, and infections. Sphingolipid metabolites, in particular, ceramide and sphingosine-1-phosphate (S1P), regulate a diverse range of cellular processes that are important in immunity and inflammation. Moreover, variations in the sphingolipid concentrations have been strongly associated with allergic diseases. This review will focus on the role of sphingolipids in the development of allergic sensitization and allergic inflammation through the activation of immune cells resident in tissues, as well as their role in barrier remodeling and anaphylaxis. The knowledge gained in this emerging field will help to develop new therapeutic options for allergic disorders.

The phenomenological characteristics of the psychotic process are illustrated by a case discussion of a 15-year-old adolescent boy who suffered from a first psychotic episode and was admitted to a children’s psychiatric hospital. The differential diagnostic questions raised important issues about the nature of psychopathology in a first episode of psychosis. It is extremely important to integrate biological, environmental, and psychological aspects in clinical evaluations in order to develop comprehensive psychiatric formulations. [ABSTRACT FROM PUBLISHER]

[This corrects the article DOI: 10.1371/journal.pone.0230010.].

Peach tree (PT) pollen sensitization is highly prevalent in subjects living in areas where this tree is widely cultivated. None of the allergens responsible for these sensitizations have been identified so far. Our aim was to identify the most relevant PT pollen allergens and analyze their capacity for inducing respiratory symptoms. We studied sixty-two individuals sensitized to PT pollen who developed symptoms after its exposure. The IgE binding profile on peach pollen extract by means of immunoblotting using sera from these subjects was analyzed. Protein extract was fractionated by anion-exchange chromatography and HPLC, fractions run in SDS-PAGE and proteins were identified from IgE-binding bands by mass spectrometry. Several allergenic proteins in the PT pollen extract were recognized by patients' IgE: a glucan endo-1,3-beta-glucosidase-like, a polygalacturonase, an UTP-glucose-1-phosphate uridylyltransferase and a PR-1a protein. This PR-1a protein is a novel allergen frequently recognized with a molecular mass of 18 kDa, named as Pru p 9 following the WHO-IUIS nomenclature. Skin Prick Test (SPT) performed with this allergen was positive in 41% of the PT pollen-sensitized clinical cases. Most of them had rhinitis or rhinoconjunctivitis, but a significant percentage experienced asthma with seasonal symptoms during the period of PT flowering. Nasal Provocation test (NPT) with Pru p 9 was positive in all cases with positive SPT to this new allergen eliciting nasal symptoms similar to those challenged with PT pollen. We demonstrate that PT pollen can induce sensitization and allergy in an exposed population, being Pru p 9 a relevant allergen responsible of respiratory symptoms. Considering the extensive peach worldwide production with a large number of people involved, our results add a great value for the diagnosis and management of subjects allergic to this pollen.

Phenolic compounds are secondary metabolites widely spread throughout the plant kingdom that can be categorized as flavonoids and non-flavonoids. Interest in phenolic compounds has dramatically increased during the last decade due to their biological effects and promising therapeutic applications. In this review, we discuss the importance of phenolic compounds’ bioavailability to accomplish their physiological functions, and highlight main factors affecting such parameter throughout metabolism of phenolics, from absorption to excretion. Besides, we give an updated overview of the health benefits of phenolic compounds, which are mainly linked to both their direct (e.g., free-radical scavenging ability) and indirect (e.g., by stimulating activity of antioxidant enzymes) antioxidant properties. Such antioxidant actions reportedly help them to prevent chronic and oxidative stress-related disorders such as cancer, cardiovascular and neurodegenerative diseases, among others. Last, we comment on development of cutting-edge delivery systems intended to improve bioavailability and enhance stability of phenolic compounds in the human body.

CD1 molecules present lipid antigens to T-cells in early stages of immune responses. Whereas CD1‒lipid‒T-cell receptors interactions are reasonably understood, molecular details on initial trafficking and loading of lipids onto CD1 proteins are less complete. We present a molecular dynamics (MD) study of human CD1d, the isotype that activates iNKT cells. MD simulations and calculations of properties and Poisson-Boltzmann electrostatic potentials were used to explore the dynamics of the antigen-binding domain of the apo-form, CD1d complexes with three lipid–antigens that activate iNKT cells and CD1d complex with GM2AP, a protein that assists lipid loading onto CD1 molecules in endosomes/lysosomes. The study was done at pH 7 and 4.5, values representative of strongly acidic environments in endosomal compartments. Our findings revealed dynamic features of the entrance to the hydrophobic channels of CD1d modulated by two α helices with sensitivity to the type of lipid. We also found lipid- and pH-dependent dynamic changes in three exposed tryptophans unique to CD1d among the five human CD1 isotypes. On the basis of modelled structures, our data also revealed external effects produced by the helper protein GM2AP only when it interacts in its open form, thus suggesting that the own assistant protein also adapts conformation to association with CD1d.

Este artículo estudia la apropiación como repetición y copia. Propone un análisis del Apropiacionismo desde dos enfoques: la desviación de significados debida a cambios de temporalidad de la obra y su contexto, y la desviación generada con la aparición de la conectividad global gracias a la web 2.0, y a la materialización del Arte Digital. El artículo propone, en primer lugar, un análisis temporal de la obra After Walker Evans de Sherrie Levine, como forma de apropiación clásica derivada de la desviación contextual. En segundo, un acercamiento al mundo del Arte Digital para analizar la apropiación de la apropiación, copias de copias, como forma de remediación basada en el concepto de “Arte como bien común” y su enfoque hacia la materialización del Arte Digital. Para ello serán estudiadas las obras aftersherrielevine.com y Printwikipedia de Michael Mandiberg y Street Ghost y Overexposed Series de Paolo Cirio.

Anaphylaxis, the most serious and life-threatening allergic reaction, produces the release of inflammatory mediators by mast cells and basophils. Regulator of calcineurin 1 (Rcan1) is a negative regulator of mast-cell degranulation. The action of mediators leads to vasodilation and an increase in vascular permeability, causing great loss of intravascular volume in a short time. Nevertheless, the molecular basis remains unexplored on the vascular level. We investigated Rcan1 expression induced by histamine, platelet-activating factor (PAF), and epinephrine in primary human vein (HV)-/artery (HA)-derived endothelial cells (ECs) and human dermal microvascular ECs (HMVEC-D). Vascular permeability was analyzed in vitro in human ECs with forced Rcan1 expression using Transwell migration assays and in vivo using Rcan1 knockout mice. Histamine, but neither PAF nor epinephrine, induced Rcan1-4 mRNA and protein expression in primary HV-ECs, HA-ECs, and HMVEC-D through histamine receptor 1 (H1R). These effects were prevented by pharmacological inhibition of calcineurin with cyclosporine A. Moreover, intravenous histamine administration increased Rcan1 expression in lung tissues of mice undergoing experimental anaphylaxis. Functional in vitro assays showed that overexpression of Rcan1 promotes barrier integrity, suggesting a role played by this molecule in vascular permeability. Consistent with these findings, in vivo models of subcutaneous and intravenous histamine-mediated fluid extravasation showed increased response in skin, aorta, and lungs of Rcan1-deficient mice compared with wild-type animals. These findings reveal that endothelial Rcan1 is synthesized in response to histamine through a calcineurin-sensitive pathway and may reduce barrier breakdown, thus contributing to the strengthening of the endothelium and resistance to anaphylaxis. These new insights underscore its potential role as a regulator of sensitivity to anaphylaxis in humans.

Prevalence of food-induced anaphylaxis increases progressively and occurs in an unpredictable manner, seriously affecting the quality of life of patients. Intrinsic factors including age, physiological, and genetic features of the patient as well as extrinsic factors such as the intake of drugs and exposure to environmental agents modulate this disorder. It has been proven that diseases, such as mastocytosis, defects in HLA, or filaggrin genes, increase the risk of severe allergic episodes. Certain allergen families such as storage proteins, lipid transfer proteins, or parvalbumins have also been linked to anaphylaxis. Environmental factors such as inhaled allergens or sensitization through the skin can exacerbate or trigger acute anaphylaxis. Moreover, the effect of dietary habits such as the early introduction of certain foods in the diet, and the advantage of the breastfeeding remain as yet unresolved. Interaction of allergens with the intestinal cell barrier together with a set of effector cells represents the primary pathways of food-induced anaphylaxis. After an antigen cross-links the IgEs on the membrane of effector cells, a complex intracellular signaling cascade is initiated, which leads cells to release preformed mediators stored in their granules that are responsible for the acute symptoms of anaphylaxis. Afterward, they can also rapidly synthesize lipid compounds such as prostaglandins or leukotrienes. Cytokines or chemokines are also released, leading to the recruitment and activation of immune cells in the inflammatory microenvironment. Multiple factors that affect food-induced anaphylaxis are discussed in this review, paying special attention to dietary habits and environmental and genetic conditions.

Simultaneous modulation of several targets or pathological events with a key pathogenic role isa promising strategy to tackle thus far difficult-to-cure or incurable multifactorial diseases [...]

Introdução: O interesse por estudos na área de Avaliação de Tecnologia em Saúde (ATS) vem crescendo devido à sua importância no adequado direcionamento das políticas no que se refere à incorporação de novas tecnologias na atenção à saúde. A incorporação de tecnologias responde por cerca de um terço do aumento dos gastos com saúde no mundo, comprometendo a sustentabilidade dos sistemas de saúde. Na Secretaria da Saúde do Estado da Bahia (SESAB), a Diretoria de Ciência, Tecnologia e Inovação em Saúde (DITEC) atua na área de desenvolvimento de base científica, tecnológica e de inovação em saúde. A Coordenação de Avaliação de Tecnologia em Saúde (COATS) foi criada em abril de 2016, vinculada à DITEC, com o objetivo de institucionalizar o uso dos métodos de ATS na tomada de decisão no âmbito estadual do SUS e como missão subsidiar a tomada de decisão sobre incorporação, alteração ou exclusão de tecnologias em saúde e difundir o uso da ATS no âmbito do SUS/Ba. Objetivo: Relatar a experiência da estruturação de uma coordenação de avaliação de tecnologia em uma secretaria estadual de saúde. Métodos: Trata-se de um relato de experiência acerca da estruturação da COATS, com foco nos resultados obtidos no período de um ano de implantação do serviço. Os dados primários referem-se ao período compreendido entre abril de 2016 e abril 2017 e foram coletados a partir da análise documental dos relatórios de gestão e de atividade da equipe técnica, do banco de dados do Sistema Integrado de Material, Patrimônio e Serviços (SIMPAS) e outros documentos produzidos no setor. Resultados: Nesse período, a COATS acumulou resultados relevantes: construção de documentos norteadores como fluxo de incorporação de tecnologias em saúde no SUS estadual, formulário de solicitação de descritivos de novas tecnologias pelas unidades da rede da SESAB e procedimentos operacionais padrão para elaboração de descritivos; elaboração da minuta da portaria da Comissão Estadual de ATS; condução de Grupo de Trabalho de Padronização de Descritivos de Medicamentos para o SIMPAS; elaboração/ revisão de cerca de 209 descritivos; atendimento de aproximadamente 31 fornecedores de tecnologias em saúde, elaboração de 03 notas técnicas e 05 informes técnicos. Conclusão: Considerando que até abril de 2016 inexistia na SESAB uma coordenação de ATS, a criação da COATS representou um avanço na disseminação da cultura, consolidação e institucionalização da metodologia de ATS no Estado da Bahia. A partir dos resultados apresentados, conclui-se que a centralização das ações de ATS na COATS favorece o acompanhamento, avaliação e monitoramento de seus impactos e resultados.

Introdução: O Diabetes mellitus (DM) é uma doença crônica, cujo controle glicêmico inadequado resulta no aparecimento de graves complicações que reduzem a expectativa de vida e comprometem a qualidade de vida do portador desta doença. Entre os insumos disponibilizados pelo SUS, em cumprimento da contrapartida do Componente Básico da Assistência Farmacêutica (Portaria MS/GM 1.555, de 30/07/2013), estão as tiras reagentes utilizadas para o controle glicêmico de usuários do SUS portadores de DM. As tiras funcionam em conjunto com glicosímetros que são aparelhos portáteis que medem a glicemia capilar com precisão satisfatória em pouco tempo em comparação com os métodos laboratoriais. A Secretaria de Saúde do Estado da Bahia (SESAB) enfrentava problemas em suas licitações para compra de tiras de glicemia pois as especificações técnicas estavam sempre direcionadas para os métodos fotométrico ou amperométrico dos glicosímetros. Objetivos: Correlacionar os métodos amperométrico e fotométrico dos glicosímetros quanto às semelhanças nos resultados apresentados de glicemia capilar; revisar o descritivo técnico das tiras de glicemia para evitar impugnações em licitações futuras e garantir o princípio da ampla concorrência nos processos licitatórios. Métodos: Trata-se de um trabalho de revisão técnica de descritivo de tiras reagentes realizado pela Coordenação de Avaliação de Tecnologias em Saúde (COATS) motivado pelos direcionamentos provocados por conta dos métodos amperométrico ou fotométrico. Buscou-se verificar quais as diferenças entre eles em termos de acurácia. Foi realizada busca quanto a alertas de tecnovigilância nas agências regulatórias e evidências na literatura para análise de resultados apresentados pelos dois métodos. Resultados: Foi identificado que os dois métodos de leitura dos glicosímetros não interferem nos resultados de acurácia do teste. Dessa forma, foi elaborado um novo descritivo técnico para as tiras, possibilitando que diferentes fabricantes pudessem participar das licitações. Essa mudança permitiu a redução do preço unitário da tira de R$ 0,4430 para R$0,3090, gerando uma economia de 30,2% provocada pela maior concorrência. Conclusão: Na análise técnica dos descritivos anteriores, identificou-se que apenas poucas empresas poderiam concorrer ao edital, ocasionando processos licitatórios com número limitado de participantes, além de impugnações subsequentes. Este trabalho garantiu ampla concorrência nos pregões e economia para o estado. Considerando uma estimativa mínima de 35 milhões de tiras reagentes compradas, o Estado chegou a um montante economizado de R$4,5 milhões em recursos.

Fundamento: Conocer el nivel de adherencia de las personas a las recomendaciones de actividad física (AF) es de interés socio-sanitario. El objetivo del presente estudio fue describir el nivel de adherencia a las recomendaciones de AF por los adultos de la Comunidad de Madrid, así como analizar su asociación con posibles determinantes socio-demográficos. Métodos: En el presente estudio transversal se realizó una encuesta telefónica a una muestra de 1.500 personas de 15 a 74 años de la Comunidad de Madrid. La AF se evaluó con la versión 2 del Global Physical Activity Questionnaire (GPAQv2) y se clasificó en tres niveles de intensidad (bajo, moderado y alto), según procedimiento de análisis del GPAQv2. Las variables socio-demográficas estudiadas fueron: sexo, edad, nivel de estudios, ocupación, estado civil, consumo de tabaco y salud percibida. Para analizar la asociación entre las características socio-demográficas y la AF, se realizaron análisis de regresión logística multinomial. Resultados: El 82% de los varones y 78% de las mujeres (80% en total) tenían un nivel global de AF moderado o alto, y el 40,1% y el 22,6% (31% en total) de los varones y mujeres, respectivamente, alcanzó las recomendaciones de AF en el tiempo libre. Tenían más probabilidades de no alcanzar las recomendaciones de AF los participantes con estudios superiores (OR: 2,05; 95%IC: 1,48-2,86), los fumadores habituales (OR: 1,41; 95%IC: 1,04-1,90) y los que percibían su salud como mala (OR: 3,58; 95%IC: 2,39-5,38). En cuanto a la edad fueron las personas del grupo entre 35-44 años las que tenían menos probabilidades de no cumplirlas (OR: 0,61; 95%IC: 0,39-0,95) y 45-54 (OR: 0,52; 95%IC: 0,32-0,83). Conclusiones: El 20% de las personas de la Comunidad de Madrid que tienen entre 15 y 74 años no cumplen con las recomendaciones mínimas de AF, y cuando se considera la AF realizada exclusivamente durante el tiempo libre se llega al 69% de los participantes que no alcanzan las recomendaciones de AF. El nivel de estudios, el hábito de fumar y la percepción de tener mala salud influyen en los niveles de AF.

ResumenEl principal objetivo del presente estudio fue aportar más evidencias sobre la relación entre el consumo de tabaco y la práctica de actividad física, así como sobre el efecto modulador que podrían ejercer las variables sexo y edad en la misma. Se efectuó un estudio transversal con una muestra de 625 personas. El muestreo fue polietápico, utilizándose un cuestionario ad hoc. Los resultados obtenidos mostraron que la práctica de actividad física y el consumo de tabaco eran conductas relacionadas [2(1)=7,373; p=,007; φ=,11]. Esa relación se explicaba por una incidencia del sedentarismo superior a la esperada (p menor que ,01) entre fumadores (51,9%). Además, dicha asociación difería según sexo [2(1)=12,172; p=,000; φ=,20] y se daba sólo en determinados grupos de edad: 15-19 [2(1)=5,012; p=,025; φ=,27] y 20-29 años [2(1)=7,580; p=,006; φ=,20]. Por tanto, de los resultados de este estudio se desprende que el tabaquismo y la práctica de actividad física son conductas que parecen estar inversamente relacionadas. No obstante, esta asociación se da en los varones, pero no en las mujeres y, en función de la edad, solamente entre jóvenes y adolescentes.AbstractThe aim of this study was to provide more evidence about the relationship between smoking and leisure time physical activity. We also clarified the effect of sex and age on this relationship. A descriptive study with cross sectional design was used and 625 people were selected. Sampling was multistage and an ad hoc questionnaire was used. A significant relationship between leisure time physical activity and smoking [2(1)=7.373; p=.007; φ=.11] was found. A sedentary life was prevalent among smokers (51.9%) but not among non smokers (40.5%). This association was different by sex [2(1)=12.172; p=.000; φ=.20] and exist only in some age groups: 15-19 [2(1)=5.012; p=.025; φ=.27] and 20-29 [2(1)=7.580; p=.006; φ=.20]. Tobacco consumption and leisure time physical activity seem to be inversely related among men and amongst the young and adolescent of both sexes.

Saposins are small proteins implicated in trafficking and loading of lipids onto Cluster of Differentiation 1 (CD1) receptor proteins that in turn present lipid antigens to T cells and a variety of T-cell receptors, thus playing a crucial role in innate and adaptive immune responses in humans. Despite their low sequence identity, the four types of human saposins share a similar folding pattern consisting of four helices linked by three conserved disulfide bridges. However, their lipid-binding abilities as well as their activities in extracting, transporting and loading onto CD1 molecules a variety of sphingo- and phospholipids in biological membranes display two striking characteristics: a strong pH-dependence and a structural change between a compact, closed conformation and an open conformation. In this work, we present a comparative computational study of structural, electrostatic, and dynamic features of human saposins based upon their available experimental structures. By means of structural alignments, surface analyses, calculation of pH-dependent protonation states, Poisson-Boltzmann electrostatic potentials, and molecular dynamics simulations at three pH values representative of biological media where saposins fulfill their function, our results shed light into their intrinsic features. The similarities and differences in this class of proteins depend on tiny variations of local structural details that allow saposins to be key players in triggering responses in the human immune system.