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People vary both in their embrace of their society's traditions, and in their perception of hazards as salient and necessitating a response. Over evolutionary time, traditions have offered avenues for addressing hazards, plausibly resulting in linkages between orientations toward tradition and orientations toward danger. Emerging research documents connections between traditionalism and threat responsivity, including pathogen-avoidance motivations. Additionally, because hazard-mitigating behaviors can conflict with competing priorities, associations between traditionalism and pathogen avoidance may hinge on contextually contingent tradeoffs. The COVID-19 pandemic provides a real-world test of the posited relationship between traditionalism and hazard avoidance. Across 27 societies (N = 7844), we find that, in a majority of countries, individuals' endorsement of tradition positively correlates with their adherence to costly COVID-19-avoidance behaviors; accounting for some of the conflicts that arise between public health precautions and other objectives further strengthens this evidence that traditionalism is associated with greater attention to hazards.

The World Health Organization (2020) recommends that schoolchildren achieve at least 60 minutes of daily moderate-to-vigorous physical activity (PA). Unfortunately, only 19% of this population meets this recommendation (Guthold et al., 2020). Physical Education (PE) is an ideal setting to encourage students to practice regular PA (Association for PE, 2020). However, studentsʼ adherence to PA practice is mediated by psychological determinants like motivation (Rhodes et al., 2017) and intention to practice PA (Hagger & Chatzisarantis, 2016). Several strategies like the use of activity wristbands, education counselling (Casado-Robles et al., 2022) or gamification (Arufe-Giráldez et al., 2022) have been shown to be effective for promoting schoolchildrenʼs PA. Consequently, the purpose of this study was to analyse the effect of a gamified intermittent teaching unit based on the use of activity wristbands and behaviour modification strategies on primary school studentsʼ motivation towards PE, their intention to be physically active and their perceived PA. A sample of 182 primary school students (39% females; Mage = 10.1 ± 0.9 years old) was cluster-randomly assigned to the control group (CG, n = 80) and gamified group (GG, n = 102). The GG students performed a gamified intermittent teaching unit (Viciana & Mayorga-Vega, 2016) based on the use of activity wristbands, educational counselling and goal-setting strategies three times per week during five weeks. Specifically, the first 15 minutes of each lesson were used. The narrative of the intervention was a travel performed by its main character, “Andaluzo”, through the provinces of the Andalucia region. Before and after the intervention, students filled out the Spanish versions of the Motivation in PE (Miguel Leo et al., 2016), intention to be physically active (Arias-Estero et al., 2013), and Pictorial Childrenʼs PA (Morera-Castro et al., 2018) questionnaires. The Mann-Whitney U test showed statistically significant differences in identified regulation, autonomous motivation towards PE, and PA performed during school recess (p < 0.05). No statistically significant differences were found for the rest of the variables (p > 0.05). Results of this study suggest that a gamified intermittent teaching unit based on the use of activity wristbands and behaviour modification strategies seems to be effective for improving schoolchildrenʼs autonomous motivation towards PE, as well as PA performed during recess. Nevertheless, future research is needed to incorporate other social agents, such as parents or tutors, to try to obtain improvements in weekly PA, as well as in the different periods of it.

The benefits of regular PA practice have been clearly proved by research in previous literature (World Health Organization, 2020). Unfortunately, most children and adolescents do not accomplish the recommendations (60 minutes daily of moderate-to-vigorous PA) (Guthold et al., 2020). According to this situation, promoting adequate levels of PA in schoolchildren is a priority public health challenge. Consequently, this study aimed to analyse the effect of an intermittent teaching unit based on activity wristbands and behaviour modification strategies on habitual PA and SB levels in high school students in the Physical Education (PE) context. Following a cluster-randomized controlled trial, 176 participants (45.5% females) aged between 11-17 years old were divided into a control group (CG, n = 76) and an experimental group (EG, n = 100). The EG performed an intermittent teaching unit (Viciana & Mayorga-Vega, 2016) during eight weeks (with two PE sessions a week). Using scientific evidence regarding the use of behaviour modification techniques towards more active behaviour (Casado-Robles et al., 2022), PA wristbands, educational counselling, progressive objectives toward 10000 steps/day, and alerts and messages to encourage active behaviour were applied during the last 15 minutes of the 16 PE sessions. Objective measurements of PA and SB were registered by GT3X+ accelerometers during eight days with a one-second epochs before and after the intervention. Results of the Multilevel Lineal Model did not show statistically significant differences in PA variables (i.e., light PA, moderate-to-vigorous PA, steps per day) or SB between participants in the CG and the EG (p > 0.05). In previous research, the results of comparable interventions have been similar. For instance, Corepal et al. (2019) did not find any positive results in their 22-week intervention using the Fitbit Zip monitor in adolescents. Evans et al. (2017) with an intervention of six weeks, Kerner et al. (2019) with a five-week intervention program, and Remmert et al. (2019) with a 12-week program did not find any positive results either. Although it has been shown that wearing a PA wristband is considered a highly recommended tool to increase motivation towards PA practice in schoolchildren (Casado-Robles et al., 2022), as they have a great affinity to new technologies, it seems that similar to previous cases, short programs have not had positive results in changing active behaviour in PE setting.

SHOC2 acts as a strong synthetic lethal interactor with MEK inhibitors in multiple KRAS cancer cell lines. SHOC2 forms a heterotrimeric complex with MRAS and PP1C that is essential for regulating RAF and MAPK-pathway activation by dephosphorylating a specific phosphoserine on RAF kinases. Here we present the high-resolution crystal structure of the SHOC2-MRAS-PP1C (SMP) complex and apo-SHOC2. Our structures reveal that SHOC2, MRAS, and PP1C form a stable ternary complex in which all three proteins synergistically interact with each other. Our results show that dephosphorylation of RAF substrates by PP1C is enhanced upon interacting with SHOC2 and MRAS. The SMP complex forms only when MRAS is in an active state and is dependent on SHOC2 functioning as a scaffolding protein in the complex by bringing PP1C and MRAS together. Our results provide structural insights into the role of the SMP complex in RAF activation and how mutations found in Noonan syndrome enhance complex formation, and reveal new avenues for therapeutic interventions.

Today, it is difficult to have a high-field nuclear magnetic resonance (NMR) device due to the high cost of its acquisition and maintenance. These high-end machines require significant space and specialist personnel for operation and offer exceptional quality in the acquisition, processing, and other advanced functions associated with detected signals. However, alternative devices are low-field nuclear magnetic resonance devices. They benefit from the elimination of high-tech components that generate static magnetic fields and advanced instruments. Instead, they used magnetic fields induced by ordinary conductors. Another category of spectrometers uses the Earth’s magnetic field, which is simple and economical but limited in use. These devices are called Earth-Field Nuclear Magnetic Resonance (EFNMR) devices. This device is ideal for educational purposes, especially for engineers and those who study nuclear magnetic resonance, such as chemistry or other experimental sciences. Students can observe their internal workings and conduct experiments that complement their education without worrying about damaging equipment. This article provides a detailed explanation of the design and construction of electrical technology devices for the excitation of atomic spin resonance using Earth’s magnetic fields. It covers all necessary stages, from research to analysis, including simulation, assembly, construction of each component, and the development of comprehensive software for spectrometer control.

Language teaching and teaching through language have undergone a standardization process all over Europe. In the Spanish context, a myriad of programs has emerged in the last ten years whose main aim is to guarantee a plurilingual education. That means implementing and consolidating European directives on the matter from the Council of Europe. Universities have joined this trend in their need for internationalization. This contribution analyses pre-service teachers' perceptions on their English Foreign Language level and the professional requirements regarding language competence in the current context in which language is a key aspect in education at any level. In spite of the fact that most students (95.5%) consider that a language teacher should master the language (C1 CEFR level or at least B2), some of them (19.3%) acknowledge not having any language accreditation yet, and most are in between B1 and B2 (70%). Therefore, there is a lack of consistency between their real language level and their perception of what is needed in order to be a successful primary education language teacher. Unquestioningly, their desired level is above their real competence, that is the reason why they plan to continue their English studies once they finish their university degree.

Abstract To evaluate the diagnostic value of the combination of two broad‐range PCR assays targeting two different and conserved regions of the viral genome for the diagnosis of acute Hepatitis E virus (HEV) infection. Patients with acute hepatitis were prospectively recruited. In all, HEV‐IgM antibodies were tested together with evaluation of HEV viraemia by two PCR assays (ORF3 and ORF1). The number of individuals exhibiting negative IgM antibody results but carrying viral RNA was calculated by each PCR assay. Four‐hundred and seventy individuals were included, of whom 145 (30.8%) were diagnosed as having acute HEV. Of them, 122 (84.1%) exhibited HEV‐IgM antibodies, and 81 (55.8%) had detectable viral RNA for at least one PCR. Using the ORF3 molecular assay, 70 (48.3%) individuals were identified with HEV infection. When the ORF1 molecular assay was applied, 49 (33.8%) individuals were identified. The ORF3 assay detected viral RNA in 32 patients not detected by the ORF1 assay. In contrast, the ORF1 assay could amplify viral RNA in 11 patients who were not detected by the ORF3 assay. The parallel use of two broad‐range PCR assays significantly increased the performance of the molecular diagnosis of HEV.

Abstract People vary both in their embrace of their society’s traditions, and in their perception of hazards as salient and necessitating a response. Over evolutionary time, traditions have offered avenues for addressing hazards, plausibly resulting in linkages between orientations toward tradition and orientations toward danger. Emerging research documents connections between traditionalism and threat responsivity, including pathogen-avoidance motivations. Additionally, because hazard-mitigating behaviors can conflict with competing priorities, associations between traditionalism and pathogen avoidance may hinge on contextually contingent tradeoffs. The COVID-19 pandemic provides a real-world test of the posited relationship between traditionalism and hazard avoidance. Across 27 societies (N = 7844), we find that, in a majority of countries, individuals’ endorsement of tradition positively correlates with their adherence to costly COVID-19-avoidance behaviors; accounting for some of the conflicts that arise between public health precautions and other objectives further strengthens this evidence that traditionalism is associated with greater attention to hazards.

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition.

Purpose: To examine the effect of two physical education-based alternated teaching units on students' environmental knowledge for practicing out-of-school physical activity (PA), perceived autonomy support, self-determined and controlled motivation toward PA, intention to be physically active, self-reported and objective PA levels, and sedentary behavior. Method: A sample of 179 students (94 females) aged 13-15 years old was cluster randomly assigned to the innovative group (two alternated teaching units for practicing PA, with one lesson inside and one outside the school grounds) or the traditional group (a teaching unit for practicing PA, solely inside the school center). Results: The alternated teaching units improved students' knowledge of their environment for practicing PA, perceived autonomy, autonomous motivation, intention to be physically active, and self-reported PA during the whole week (p < 0.05). Discussion/Conclusion: The innovative program improved students' knowledge about their environment for practicing PA and self-reported PA but did not improve objectively measured PA levels.

The use of new assistive technologies in general, and Socially Assistive Robots (SARs) in particular, is becoming increasingly common for supporting people’s health and well-being. However, it still faces many issues regarding long-term adherence, acceptability and utility. Most of these issues are due to design processes that insufficiently take into account the needs, preferences and values of intended users. Other issues are related to the currently very limited amount of long-term evaluations, performed in real-world settings, for SARs. This study presents the results of two regional projects that consider as a starting hypothesis that the assessment in controlled environments and/or with short exposures may not be enough in the design of an SAR deployed in a retirement home and the necessity of designing for and with users. Thus, the proposed methodology has focused on use-cases definitions that follow a human-centred and participatory design approach. The main goals have been facilitating system acceptance and attachment by involving stakeholders in the robots design and evaluation, overcoming usage barriers and considering user’s needs integration. The implementation of the first use-case deployed and the two-phase pilot test performed in a retirement home are presented. In particular, a detailed description of the interface redesign process based on improving a basic prototype with users’ feedback and recommendations is presented, together with the main results of a formal evaluation that has highlighted the impact of changes and improvements addressed in the first redesign loop of the system.

ObjectiveThe main objective of the present study was to examine the effects of an intermittent teaching unit based on the use of activity wristbands and behavior modification strategies on high school studentsʼ perceptions of autonomy support, satisfaction of basic psychological needs, motivation toward Physical Education and physical activity, intention to be physically active, and habitual physical activity levels.Materials and methodsAn initial sample of 353 high school students (final sample = 175; 45.7% females; mean age = 13.3 ± 1.2 years) from two public high schools were cluster-randomly assigned into the intermittent (IG, n = 100) and control (CG, n = 75) groups. The IG performed an intermittent teaching unit twice a week for eight weeks. Specifically, the last 15 min of each lesson were used. As the main strategy to promote the practice of regular physical activity, students wore an activity wristband the whole day during the intervention period. Additionally, other behavior modification strategies were also applied (e.g., educational counseling, physical activity goals or reminders). Regarding the CG, during the intervention period (i.e,, the eight weeks that took place the intermittent teaching unit) they also performed two Physical Education sessions, but without using activity wristbands or other behavior modification strategies. Before and after the intervention, as well as at the end of the follow-up period (six weeks), students’ physical activity practice mediators and physical activity levels were measured by validated questionnaires.ResultsThe Multilevel Linear Model results showed that the IG students statistically significantly improved cognitive and procedural autonomy support from pre- to post-intervention (p

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

The RASopathies are a group of genetic disorders that result from germline pathogenic variants affecting RAS-mitogen activated protein kinase (MAPK) pathway genes. RASopathies share RAS/MAPK pathway dysregulation and share phenotypic manifestations affecting numerous organ systems, causing lifelong and at times life-limiting medical complications. RASopathies may benefit from precision medicine approaches. For this reason, the Sixth International RASopathies Symposium focused on exploring precision medicine. This meeting brought together basic science researchers, clinicians, clinician scientists, patient advocates, and representatives from pharmaceutical companies and the National Institutes of Health. Novel RASopathy genes, variants, and animal models were discussed in the context of medication trials and drug development. Attempts to define and measure meaningful endpoints for treatment trials were discussed, as was drug availability to patients after trial completion.

El síndrome de Contarini es una presentación infrecuente de derrame pleural bilateral en la cual el líquido pleural en cada hemitórax presenta diferentes características, y puede explicarse por diferentes causas. Hay escasa literatura al respecto, por lo que presentamos un caso de derrame pleural bilateral que sería compatible con dicho síndrome.

IntroductionThe use of activity wristbands to monitor and promote schoolchildren's physical activity (PA) is increasingly widespread. However, their validity has not been sufficiently studied, especially among primary schoolchildren. Consequently, the main purpose was to examine the validity of the daily steps and moderate-to-vigorous PA (MVPA) scores estimated by the activity wristbands Fitbit Ace 2, Garmin Vivofit Jr 2, and the Xiaomi Mi Band 5 in primary schoolchildren under free-living conditions.Materials and methodsAn initial sample of 67 schoolchildren (final sample = 62; 50% females), aged 9–12 years old (mean = 10.4 ± 1.0 years), participated in the present study. Each participant wore three activity wristbands (Fitbit Ace 2, Garmin Vivofit Jr 2, and Xiaomi Mi Band 5) on his/her non-dominant wrist and a research-grade accelerometer (ActiGraph wGT3X-BT) on his/her hip as the reference standard (number of steps and time in MVPA) during the waking time of one day.ResultsResults showed that the validity of the daily step scores estimated by the Garmin Vivofit Jr 2 and Xiaomi Mi Band 5 were good and acceptable (e.g., MAPE = 9.6/11.3%, and lower 95% IC of ICC = 0.87/0.73), respectively, as well as correctly classified schoolchildren as meeting or not meeting the daily 10,000/12,000-step-based recommendations, obtaining excellent/good and good/acceptable results (e.g., Garmin Vivofit Jr 2, k = 0.75/0.62; Xiaomi Mi Band 5, k = 0.73/0.53), respectively. However, the Fitbit Ace 2 did not show an acceptable validity (e.g., daily steps: MAPE = 21.1%, and lower 95% IC of ICC = 0.00; step-based recommendations: k = 0.48/0.36). None of the three activity wristbands showed an adequate validity for estimating daily MVPA (e.g., MAPE = 36.6–90.3%, and lower 95% IC of ICC = 0.00–0.41) and the validity for the MVPA-based recommendation tended to be considerably lower (e.g., k = −0.03–0.54).ConclusionsThe activity wristband Garmin Vivofit Jr 2 obtained the best validity for monitoring primary schoolchildren's daily steps, offering a feasible alternative to the research-grade accelerometers. Furthermore, this activity wristband could be used during PA promotion programs to provide accurate feedback to primary schoolchildren to ensure their accomplishment with the PA recommendations.

Introduction: Paslahepevirus balayani (HEV) is an endemic zoonotic disease ranked as a major cause of acute hepatitis in Europe. Most infections occurring in Europe are due to the endemic several subtypes of genotype 3, through the consumption of raw or undercooked pork, observing a genotype geographical distribution pattern among countries Because of global changes in the pig and pork trading markets, subtype distribution might vary. We aimed to evaluate the temporal distribution of HEV genotypes in patients from southern Spain with acute hepatitis to determine whether these changes were related to the pig import trade during the study period between 2018 and 2022. Methods: Prospective longitudinal study including patients with acute hepatitis from southern Spain between 2018 and 2022. HEV RNA and antibodies was tested in all patients. In patients with detectable HEV RNA, genotype was obtained. To determine the number of imported pigs and their origins, we checked the official data from the Spanish statistics on international trade of Spanish Minister of Industry during by country of origin during the same study period. Results: A total of 659 patients with acute hepatitis were included in the study. Among them, 162 (24.5%) had at least one marker (IgM or RNA) of acute HEV infection. Among the 71 patients with detectable viral RNA, genotypes could be obtained for 58 (81.6%). The most prevalent HEV genotype was 3f (n = 48; 78.6%), showing a decreasing prevalence of over time, from 100% in 2018 to 70.6% in 2022. Since 2021, the emergence of other genotypes has been determined. A significant increase in the number of animals imported was observed since the beginning of the study. Denmark experienced a significant rise, from 0.03% in 2018 of total imports to 10.4% in 2022. Conclusions: HEV molecular diversity is changing in Spain, could be linked to changes in fattening pig import origin.

Despite the crucial role of RAF kinases in cell signaling and disease, we still lack a complete understanding of their regulation. Heterodimerization of RAF kinases as well as dephosphorylation of a conserved "S259" inhibitory site are important steps for RAF activation but the precise mechanisms and dynamics remain unclear. A ternary complex comprised of SHOC2, MRAS, and PP1 (SHOC2 complex) functions as a RAF S259 holophosphatase and gain-of-function mutations in SHOC2, MRAS, and PP1 that promote complex formation are found in Noonan syndrome. Here we show that SHOC2 complex-mediated S259 RAF dephosphorylation is critically required for growth factor-induced RAF heterodimerization as well as for MEK dissociation from BRAF. We also uncover SHOC2-independent mechanisms of RAF and ERK pathway activation that rely on N-region phosphorylation of CRAF. In DLD-1 cells stimulated with EGF, SHOC2 function is essential for a rapid transient phase of ERK activation, but is not required for a slow, sustained phase that is instead driven by palmitoylated H/N-RAS proteins and CRAF. Whereas redundant SHOC2-dependent and -independent mechanisms of RAF and ERK activation make SHOC2 dispensable for proliferation in 2D, KRAS mutant cells preferentially rely on SHOC2 for ERK signaling under anchorage-independent conditions. Our study highlights a context-dependent contribution of SHOC2 to ERK pathway dynamics that is preferentially engaged by KRAS oncogenic signaling and provides a biochemical framework for selective ERK pathway inhibition by targeting the SHOC2 holophosphatase.

Targeted inhibition of the ERK-MAPK pathway, upregulated in a majority of human cancers, has been hindered in the clinic by drug resistance and toxicity. The MRAS-SHOC2-PP1 (SHOC2 phosphatase) complex plays a key role in RAF-ERK pathway activation by dephosphorylating a critical inhibitory site on RAF kinases. Here we show that genetic inhibition of SHOC2 suppresses tumorigenic growth in a subset of KRAS-mutant NSCLC cell lines and prominently inhibits tumour development in autochthonous murine KRAS-driven lung cancer models. On the other hand, systemic SHOC2 ablation in adult mice is relatively well tolerated. Furthermore, we show that SHOC2 deletion selectively sensitizes KRAS- and EGFR-mutant NSCLC cells to MEK inhibitors. Mechanistically, SHOC2 deletion prevents MEKi-induced RAF dimerization, leading to more potent and durable ERK pathway suppression that promotes BIM-dependent apoptosis. These results present a rationale for the generation of SHOC2 phosphatase targeted therapies, both as a monotherapy and to widen the therapeutic index of MEK inhibitors.

MRAS is the closest relative to the classical RAS oncoproteins and shares most regulatory and effector interactions. However, it also has unique functions, including its ability to function as a phosphatase regulatory subunit when in complex with SHOC2 and protein phosphatase 1 (PP1). This phosphatase complex regulates a crucial step in the activation cycle of RAF kinases and provides a key coordinate input required for efficient ERK pathway activation and transformation by RAS. MRAS mutations rarely occur in cancer but deregulated expression may play a role in tumorigenesis in some settings. Activating mutations in MRAS (as well as SHOC2 and PP1) do occur in the RASopathy Noonan syndrome, underscoring a key role for MRAS within the RAS-ERK pathway. MRAS also has unique roles in cell migration and differentiation and has properties consistent with a key role in the regulation of cell polarity. Further investigations should shed light on what remains a relatively understudied RAS family member.

The aim of the study was to compare the effect of a Sport Education-based irregular teaching unit on the high-school students' physical activity (PA) during school recess. A sample of 91 adolescents (45 girls) aged 13-16 years old met the exclusion criteria. The six classes were cluster-randomly assigned to the Irregular Sport Education group (Sport Education methodology with competitions in recess), Traditional Sport Education group (Sport Education methodology with competitions in Physical Education lessons), or to the control group (non-intervention). The students' PA during school recess periods were objectively assessed by GT3X accelerometers. The results of the repeated-measures nested analysis of variance showed that the Sport Education-based irregular teaching unit significantly improved the students' PA during recesses (p < 0.001). The competitions phase of the Sport Education model performed at school recesses seems to be a valuable strategy for increasing students' PA contributing to the achievement of the daily recommendations.

Dephosphorylation of the inhibitory "S259" site on RAF kinases (S259 on CRAF, S365 on BRAF) plays a key role in RAF activation. The MRAS GTPase, a close relative of RAS oncoproteins, interacts with SHOC2 and protein phosphatase 1 (PP1) to form a heterotrimeric holoenzyme that dephosphorylates this S259 RAF site. MRAS and SHOC2 function as PP1 regulatory subunits providing the complex with striking specificity against RAF. MRAS also functions as a targeting subunit as membrane localization is required for efficient RAF dephosphorylation and ERK pathway regulation in cells. SHOC2's predicted structure shows remarkable similarities to the A subunit of PP2A, suggesting a case of convergent structural evolution with the PP2A heterotrimer. We have identified multiple regions in SHOC2 involved in complex formation as well as residues in MRAS switch I and the interswitch region that help account for MRAS's unique effector specificity for SHOC2-PP1. MRAS, SHOC2, and PPP1CB are mutated in Noonan syndrome, and we show that syndromic mutations invariably promote complex formation with each other, but not necessarily with other interactors. Thus, Noonan syndrome in individuals with SHOC2, MRAS, or PPPC1B mutations is likely driven at the biochemical level by enhanced ternary complex formation and highlights the crucial role of this phosphatase holoenzyme in RAF S259 dephosphorylation, ERK pathway dynamics, and normal human development.

Laughter is a nonverbal vocalization occurring in every known culture, ubiquitous across all forms of human social interaction. Here, we examined whether listeners around the world, irrespective of their own native language and culture, can distinguish between spontaneous laughter and volitional laughter-laugh types likely generated by different vocal-production systems. Using a set of 36 recorded laughs produced by female English speakers in tests involving 884 participants from 21 societies across six regions of the world, we asked listeners to determine whether each laugh was real or fake, and listeners differentiated between the two laugh types with an accuracy of 56% to 69%. Acoustic analysis revealed that sound features associated with arousal in vocal production predicted listeners' judgments fairly uniformly across societies. These results demonstrate high consistency across cultures in laughter judgments, underscoring the potential importance of nonverbal vocal communicative phenomena in human affiliation and cooperation.

Summary:. Transposition flaps are useful for reconstruction of many skin defects. Limberg described a rhomboid rotation flap in 1946. Dufourmentel described an improved version of the Limberg flap in 1962. The Dufourmentel flap is also a quadrangular rhomboid flap which can be used in any area of the body except for the central face, the fingers, and the volar hand. The design of the Dufourmentel flap creates a wider base for this random flap, thus making it more reliable. Where tissue loss is significant, or where skin and soft tissue elasticity is limited, double opposing Dufourmentel flaps are useful. A variation of the Dufourmentel flap is described where a circular defect is converted to a square. The line of greatest extensibility is marked through the circular defect or lesion. A square is marked around the circle with one corner of the square tilted 10–20 degrees counterclockwise from the line of greatest extensibility. After marking corners A, B, C, and D, lines are marked extending BD and CD. The first incision, DE, will bisect the angle created by extending BD and CD. The second incision, EF, is roughly perpendicular to CD extended, but the angle at E is opened up a bit to create a wider base for the flap. Point D will rotate to point B, E rotates to C, and F translates to D. The invisible line DF should be approximately parallel to the line of greatest extensibility. When the defect is relatively large or where the surrounding tissues have limited elasticity, the above-described ideal variation of the Dufourmentel flap may not be possible because the flap may not rotate and advance all the way around without tension. In this case, double opposing Dufourmentel type flaps have been found to be useful by meeting each other at the halfway point.

Abstract Between 15% and 30% of HIV‐infected subjects fail to increase their CD4+ T‐cell counts despite continuous viral suppression (immunological nonresponders [INRs]). These subjects have a higher morbidity and mortality rate, but there are no effective treatments to reverse this situation so far. This study used data from an interrupted phase I/II clinical trial to evaluate safety and immune recovery after INRs were given four infusions, at baseline and at weeks 4, 8, and 20, with human allogeneic mesenchymal stromal cells from adipose tissue (Ad‐MSCs). Based on the study design, the first 5 out of 15 INRs recruited received unblinded Ad‐MSC infusions. They had a median CD4+ nadir count of 16/μL (range, 2‐180) and CD4+ count of 253 cells per microliter (171‐412) at baseline after 109 (54‐237) months on antiretroviral treatment and 69 (52‐91) months of continuous undetectable plasma HIV‐RNA. After a year of follow‐up, an independent committee recommended the suspension of the study because no increase of CD4+ T‐cell counts or CD4+/CD8+ ratios was observed. There were also no significant changes in the phenotype of different immunological lymphocyte subsets, percentages of natural killer cells, regulatory T cells, and dendritic cells, the inflammatory parameters analyzed, and cellular associated HIV‐DNA in peripheral blood mononuclear cells. Furthermore, three subjects suffered venous thrombosis events directly related to the Ad‐MSC infusions in the arms where the infusions were performed. Although the current study is based on a small sample of participants, the findings suggest that allogeneic Ad‐MSC infusions are not effective to improve immune recovery in INR patients or to reduce immune activation or inflammation. ClinicalTrials.gov identifier: NCT0229004. EudraCT number: 2014‐000307‐26.

All Latin-American countries are affected by the lack of physical activity and its consequences on youth. Chile's population has shown troublingly low levels of moderate-to-vigorous physical activity. This is the first study using objectively measured physical activity levels in Chilean adolescents. The objectives were to compare the compliance with daily recommendations of moderate-to-vigorous physical activity between physical education and non-physical education days, and to compare physical activity levels according to gender, age and weight status. A total of 123 Chilean secondary students (52 girls and 71 boys; 13.5 ± 0.7 years old) participated in this study. Physical activity was registered by GT3X accelerometers during an entire week. Results showed that there was a significant increase in the proportion of adolescents achieving the daily recommendation of moderate-to-vigorous physical activity on physical education days (23.6%) than on non-physical education days (14.6%) (p = 0.05). Boys and older adolescents presented statistically higher levels of moderate-to-vigorous physical activity on physical education days than on non-physical education days. No differences were found in weight status comparison. Physical education has been found to be a crucial element in achieving the daily recommendations of moderate-to-vigorous physical activity. Diverse strategies in order to increase the moderate-to-vigorous physical activity in physical education according to the factors analysed are reported and discussed.

Laughter is a nonverbal vocal expression that often communicates positive affect and cooperative intent in humans. Temporally coincident laughter occurring within groups is a potentially rich cue of affiliation to overhearers. We examined listeners' judgments of affiliation based on brief, decontextualized instances of colaughter between either established friends or recently acquainted strangers. In a sample of 966 participants from 24 societies, people reliably distinguished friends from strangers with an accuracy of 53-67%. Acoustic analyses of the individual laughter segments revealed that, across cultures, listeners' judgments were consistently predicted by voicing dynamics, suggesting perceptual sensitivity to emotionally triggered spontaneous production. Colaughter affords rapid and accurate appraisals of affiliation that transcend cultural and linguistic boundaries, and may constitute a universal means of signaling cooperative relationships.

Abstract Background The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014–2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL)

Resumen: Objetivo: Analizar la tendencia de las tasas de mortalidad por edad y sexo en España e identificar si se han producido cambios tras el comienzo de la crisis económica. Método: Estudio de tendencias de las tasas de mortalidad por grupos quinquenales de edad y sexo en el periodo 1981-2016, mediante regresión joint-point. Se detallan los resultados de los dos últimos periodos identificados en las regresiones, que permiten identificar cambios ocurridos después del inicio de la crisis. En caso de ralentización o estancamiento de la tendencia de mortalidad en varios grupos de edad sucesivos, se realizó un análisis de tendencias por causas. Resultados: La mortalidad se redujo de forma significativa entre 1981 y 2016. Tras el inicio de la crisis económica, la tendencia de la mortalidad total estandarizada no cambió en los hombres, y sufrió un estancamiento en las mujeres entre 2013 y 2016. En el análisis por grupos quinquenales de edad, la tendencia descendente de la mortalidad sufrió un estancamiento en los hombres en todos los grupos entre los 15 y 39 años, que se inició entre 2011 y 2014 y duró hasta 2016. En ambos sexos, en los cuatro grupos de edad entre 60 y 79 años, la reducción previa de la mortalidad sufrió una ralentización o estancamiento, que se inició entre 2009 y 2014, y continuó hasta 2016. Las causas que más contribuyeron al cambio de tendencia fueron las causas externas en hombres de 15-39 años, y las enfermedades del sistema circulatorio y respiratorio en las personas de 60-79 años. Conclusión: La tendencia descendente de la mortalidad ha sufrido una ralentización o un estancamiento después del inicio de la crisis económica, principalmente en hombres jóvenes, y en hombres y mujeres de 60-79 años. Abstract: Objective: To analyze trends in age-sex-specific mortality in Spain, and to identify if there have been changes following the onset of economic crisis. Method: A study of trends in mortality rates by sex and quinquennial groups of age was carried out, from 1981 to 2016. Time trends were established by joint-point regression models. The results of the last two periods identified in the regressions are presented in detail, identifying changes after the onset of the economic crisis. When slowdown or stagnation of the mortality trends were identified in several successive age groups, an analysis of trends by causes was carried out. Results: Mortality was significantly reduced between 1981 and 2016. After the beginning of the economic crisis, the trend in total age-standardized mortality did not change for men, but it stagnated for women from 2013 to 2016. In the analysis by quinquennial age groups, the downward trend in mortality suffered a stagnation in men in all the groups between 15 and 39 years, which started between 2011 and 2014, and lasted until 2016. In both women and men, in the four groups between 60 and 79 years, the previous decline in mortality suffered a slowdown or stagnation, which began between 2009 and 2014, and continued until 2016. Negative changes in mortality trends were mainly influenced by external causes (in 15-39 years men) and diseases of the circulatory and respiratory systems (in 60-79 years men and women). Conclusions: The downward trend of mortality suffered stagnation or deceleration after the onset of the economic crisis in young men and 60-79 years old men and women.

El objetivo principal del estudio fue comprobar el efecto de una unidad didáctica del Modelo de Educación Deportiva en Educación Física sobre la deportividad y los niveles de actividad física habitual en estudiantes de Educación Secundaria. Un total de 114 estudiantes (62 varones y 52 mujeres) de cuatro clases (dos de segundo y dos de cuarto) de Educación Secundaria Obligatoria se asignaron aleatoriamente por clases al grupo Tradicional (metodología basada en la instrucción directa) o al grupo Educación Deportiva (Modelo de Educación Deportiva). Ambos grupos participaron en 12 sesiones de Educación Física (2 sesiones por semana). Los resultados del Modelo Lineal Multinivel mostraron que el programa de Educación Deportiva mejoró la participación de la deportividad de los estudiantes. Sin embargo, no hubo diferencias significativas en el resto de las dimensiones de deportividad ni sobre los niveles de actividad física habitual de los escolares. En conclusión, el Modelo de Educación Deportiva mejora la voluntad de participación de los estudiantes en competiciones deportivas, pero no mejora el resto de dimensiones de la deportividad ni los niveles de práctica de actividad física.

This study sought to examine the perceived social well-being of students of educational sciences, based on sociodemographic factors. A non-experimental, ex-post-facto descriptive study was performed by way of a single measurement. The sample comprised 313 college students from different education degrees. The results show that women exhibit greater levels of social coherence and contribution, while students (men and women) that enter university through vocational training or other non-high school routes have greater perceived well-being. It was shown that social integration is greater in more urbanized areas and college students that live with other students display greater social acceptance. In addition, living in rural areas was associated with greater social actualization and coherence as social dynamics are more easily understood. Age correlated negatively with social coherence.

Abstract Aims of this study were to identify student clusters in physical appearance, sport competence, global physical self-concept and self-esteem, and to examine whether different physical self-concept groups differ in their moderate-to-vigorous physical activity (MVPA) and sedentary behaviour. Participants of the study were 211 boys and 183 girls aged 13-16 years. MVPA and sedentary behaviour were monitored by GT3X accelerometers during seven days. Participants’ physical self-concept was measured by the short Physical Self-Description Questionnaire. Latent profile analyses revealed a four-cluster solution: 1) “low sport competence, moderate global physical self-concept and self-esteem, and high physical appearance”; 2) “high sport competence, moderate global physical self-concept and self-esteem, and low physical appearance”; 3) “moderate sport competence, global physical self-concept, self-esteem, and physical appearance”, and 4) “moderate sport competence and global physical self-concept, high self-esteem, and low physical appearance”. Multivariate analysis of variance showed differences in MVPA between boys’ in clusters 2 and 3 (p < .05). Students’ MVPA levels differ by physical self-concept profiles. Resumen Los objetivos del estudio fueron identificar grupos de estudiantes en apariencia física, competencia deportiva, autoconcepto físico global y autoestima, y examinar si los diferentes grupos de autoconcepto físico difieren en su actividad física moderada-vigorosa (AFMV) y comportamiento sedentario. Los participantes del estudio fueron 211 varones y 183 mujeres de 13-16 años. La AFMV y el comportamiento sedentario fueron monitorizados por acelerómetros GT3X durante siete días. El autoconcepto físico de los estudiantes fue medido por la versión corta del Physical Self-Description Questionnaire. Los análisis de perfil latente revelaron una solución de cuatro grupos: 1) “baja competencia deportiva, moderado autoconcepto físico global y autoestima, y alta apariencia física”; 2) alta competencia deportiva, moderado autoconcepto físico global y autoestima, y baja apariencia física”; 3) “moderada competencia deportiva, autoconcepto físico global, autoestima, y apariencia física”; y 4) “moderada competencia deportiva y autoconcepto físico global, alta autoestima, y baja apariencia física”. Los análisis multivariados de la varianza mostraron diferencias en la AFMV entre los grupos de chicos 2 y 3 (p < ,05). Los niveles de AFMV de los estudiantes difieren según los perfiles de autoconcepto físico.

Summary: The COVID-19 pandemic is having a major impact on the mental health of populations in the Americas. Studies show high rates of depression and anxiety, among other psychological symptoms, particularly among women, young people, those with pre-existing mental health conditions, health workers, and persons living in vulnerable conditions. Mental health systems and services have also been severely disrupted. A lack of financial and human resource investments in mental health services, limited implementation of the decentralized community-based care approach and policies to address the mental health gap prior to the pandemic, have all contributed to the current crisis. Countries must urgently strengthen their mental health responses to COVID-19 by taking actions to scale up mental health and psychosocial support services for all, reach marginalized and at-risk populations, and build back better mental health systems and services for the future.Editorial Disclaimer: This translation in Spanish was submitted by the authors and we reproduce it as supplied. It has not been peer-reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as a reference for this manuscript. Disclaimer: The Authors hold sole responsibility for the views expressed in this article, which may not necessarily reflect the opinion or policy of the Pan American Health Organization/World Health Organization.

Water scarcity and the loss of fertilizer from agricultural soils through runoff, which also leads to contamination of other areas, are increasingly common problems in agriculture. To mitigate nitrate water pollution, the technology of controlled release formulations (CRFs) provides a promising alternative for improving the management of nutrient supply and decreasing environmental pollution while maintaining good quality and high crop yields. This study describes the influence of pH and crosslinking agent, ethylene glycol dimethacrylate (EGDMA) or N,N′-methylenebis (acrylamide) (NMBA), on the behavior of polymeric materials in swelling and nitrate release kinetics. The characterization of hydrogels and CRFs was performed by FTIR, SEM, and swelling properties. Kinetic results were adjusted to Fick, Schott, and a novel equation proposed by the authors. Fixed-bed experiments were carried out by using the NMBA systems, coconut fiber, and commercial KNO3. Results showed that on the one hand, no significant differences were observed in nitrate release kinetics for any system in the selected pH range, this fact allowing to apply these hydrogels to any type of soil. On the other hand, nitrate release from SLC-NMBA was found to be a slower and longer process versus commercial potassium nitrate. These features indicate that the NMBA polymeric system could potentially be applied as a controlled release fertilizer suitable for a wide variety of soil typologies.

Introduction: Traditionally, literature has contributed qualitative approaches for studying how to plan Physical Education (PE). To our knowledge there are not quantitative populationbased studies regarding the decision-making process among in-service Spanish PE teachers. The aim of this study was to analyze possible differences in the factors of influence on planning decision-making in PE with a large sample of Spanish in-service teachers depending on their characteristics (gender, teaching experience) and the educational context (educational stage, type of school). Method: The sample consisted of 618 teachers from 15 Spanish autonomous regions (422 males and 196 females; aged 23-63 years old). An electronic version of the validated Planning Decision-Making in PE Questionnaire was applied, using the google web platform. It is composed of eight factors (curriculum standards, pre-service training, physical environment, physical activity experiences, teaching experiences, socialization by other teachers, material and equipment, and level of preparation in the subject matters). Results: The results showed differences regarding the factors of influence in planning PE between teachers, caused by personal (teaching experience) and contextual (educational stage and type of school) factors. Habitual physical activity and pre-service training influenced novel teachers more in comparison to experienced teachers. Teachers from secondary schools were influenced more by their initial training, the curriculum standards, and the material and equipment. Public school teachers were more influenced by the curriculum standards and the physical environment, than those from private schools. Conclusion: According to previous qualitative research regarding the level of teaching experience, results suggest that initial training for PE teachers should consider including higher support from experienced teachers in order to avoid the dependence on the national curriculum standards. It is important to include the use of the physical environment of the school center regarding the effect that outdoor activities have on the students' physical activity habits in their leisure time.

Exosome-derived miR-21 was independently associated with CD4 T cell decline in HIV-1-infected elite controllers (OR 0.369, 95% CI 0.137–0.994, p = 0.049). Also, a negative correlation between miR-21 expression and MCP-1 level was found (r = −0.649, p = 0.020), while no correlation between soluble biomarkers or cellular immune activation was found. Keywords: Exosomes, miRNAs, HIV-1, Elite controllers, Immune activation, Soluble biomarkers

Targeted inhibition of the ERK-MAPK pathway is challenged by the development of resistance and toxicity. Here, the authors show that SHOC2 genetic inhibition impairs lung tumour development and improves MEK inhibitor efficacy in RAS- and EGFR-mutant cells.

Objective: To determine the required learning time for high-resolution anoscopy (HRA)-guided biopsy to detect histological high-risk squamous intraepithelial lesions (hHSIL) and to identify factors that impact on the training process. Methods: All HIV-infected, screening-naïve men-who-have-sex-with-men who underwent HRA conducted by one single observer from 2010 to 2017 in a Spanish HIV-outpatient clinic were analysed. Results: Eighty-five (14.7%) of the 581 patients included presented hHSIL. The factors associated with the capacity to detect hHSIL [adjusted odds ratio (aOR), 95% confidence interval (95%CI)] were the presence of cytological HSIL (3.04, 1.78–5.21; p