Relative decline in density of Northern Hemisphere tree species in warm and arid regions of their climate niches.

Although climate change is expected to drive tree species toward colder and wetter regions of their distribution, broadscale empirical evidence is lacking. One possibility is that past and present human activities in forests obscure or alter the effects of climate. Here, using data from more than two million monitored trees from 73 widely distributed species, we quantify changes in tree species density within their climatic niches across Northern Hemisphere forests. We observe a reduction in mean density across species, coupled with a tendency toward increasing tree size. However, the direction and magnitude of changes in density exhibit considerable variability between species, influenced by stand development that results from previous stand-level disturbances. Remarkably, when accounting for stand development, our findings show a significant change in density toward cold and wet climatic conditions for 43% of the species, compared to only 14% of species significantly changing their density toward warm and arid conditions in both early- and late-development stands. The observed changes in climate-driven density showed no clear association with species traits related to drought tolerance, recruitment and dispersal capacity, or resource use, nor with the temperature or aridity affiliation of the species, leaving the underlying mechanism uncertain. Forest conservation policies and associated management strategies might want to consider anticipated long-term species range shifts alongside the integration of contemporary within-distribution density changes.

Predicted impact of banning nonessential, energy-dense food and beverages in schools in Mexico: A microsimulation study.

BACKGROUND: Childhood obesity is a growing concern worldwide. School-based interventions have been proposed as effective means to improve nutritional knowledge and prevent obesity. In 2023, Mexico approved a reform to the General Education Law to strengthen the ban of sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools and surroundings. We aimed to predict the expected one-year change in total caloric intake and obesity prevalence by introducing the ban of NEDFBs sales in schools, among school-aged children and adolescents (6 to 17 years old) in Mexico. METHODS AND FINDINGS: We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and then estimated total energy intake (TEI) per day. The TEI after the intervention was estimated under 4 scenarios: (1) using national data to inform the intervention effect; (2) varying law compliance; (3) using meta-analytic data to inform the intervention effect size on calories; and (4) using national data to inform the intervention effect by sex and socioeconomic status (SES). We used Hall's microsimulation model to estimate the potential impact on body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools. We found that children could reduce their daily energy intake by 33 kcal/day/person (uncertainty interval, UI, [25, 42] kcal/day/person), reducing on average 0.8 kg/person (UI [0.6, 1.0] kg/person) and 1.5 percentage points (pp) in obesity (UI [1.1, 1.9] pp) 1 year after implementing the law. We showed that compliance will be key to the success of this intervention: considering a 50% compliance the intervention effect could reduce 0.4 kg/person (UI [0.3, 0.5] kg/person). Our sensitivity analysis showed that the ban could reduce body weight by 1.3 kg/person (UI [0.8, 1.8] kg/person) and up to 5.4 kg/person (UI [3.4, 7.5] kg/person) in the best-case scenario. Study limitations include assuming that obesity and the contribution of NEDFBs consumed at school remain constant over time, assuming full compliance, and not considering the potential effect of banning NEDFBs in stores near schools. CONCLUSIONS: Even in the most conservative scenario, banning sales of NEDFBs in schools is expected to significantly reduce obesity, but achieving high compliance will be key to its success. WHY WAS THIS STUDY DONE?: - School-based interventions have been recognized as effective means to improve nutritional knowledge and prevent obesity-related diseases.- In December 2023, the Chamber of Representatives of Mexico approved an amendment that strengthens and updates the General Education Law (Article 75) and nutritional guidelines to ban the sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools. WHAT DID THE RESEARCHERS DO AND FIND?: - We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and total energy intake (TEI) per day.- We used microsimulation modeling to predict body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools.- Our modeling study suggests that an important impact on obesity prevalence can be expected if the law is implemented and enforced as intended. WHAT DO THESE FINDINGS MEAN?: - If successful, this law could serve as an example beyond Mexico on how to achieve changes in body weight through school food regulation.- An important limitation of our main scenario is that we assumed full compliance of schools with the law, yet lower compliance will reduce its impact. We also did not consider historical trends on obesity or NEDFBs consumed in schools during our 1 year simulation, and we considered only the ban impact inside schools, excluding effects near and outside schools.

Previous pregnancies might mitigate cortical brain differences associated with surgical menopause.

Surgical menopause causes a sharp drop in estrogen levels in middle-aged women, thus preventing the gradual physiological adaptation that is characteristic of the perimenopause. Previous studies suggest that surgical menopause might increase the risk of dementia later in life. In addition, the transition to motherhood entails long-lasting endocrine and neuronal adaptations. We compared differences in whole-brain cortical volume between women who reached menopause by surgery and a group of women who reached spontaneous non-surgical menopause and determined whether these cortical differences were influenced by previous childbearing. Using surface-based neuroimaging techniques, we investigated cortical volume differences in 201 middle-aged women (134 women who experienced non-surgical menopause, 78 of whom were parous women; and 67 women who experienced surgical menopause, 39 of whom were parous women). We found significant atrophy in the frontal and temporal regions in women who experienced surgical menopause. Nulliparous women with surgical menopause showed significant lower cortical volume in the left temporal gyrus extending to the medial temporal lobe cortex, as well as in the precuneus bilaterally compared to parous women with surgical menopause; whereas our results revealed no significant differences between parous women with surgical menopause and both parous and nulliparous women who reached a non-surgical menopause. Furthermore, in the surgical menopause group, we found a negative correlation between cortical volume and age at first pregnancy in the temporal lobe. Our study suggests that the long-term brain remodeling of parity may mitigate the neural impact of the sudden drop in estrogen levels that characterizes surgical menopause.

Association between the FAAH C385A variant (rs324420) and obesity-related traits: a systematic review.

BACKGROUND: Overweight and obesity are the consequence of a sustained positive energy balance. Twin studies show high heritability rates pointing to genetics as one of the principal risk factors. By 2022, genomic studies led to the identification of almost 300 obesity-associated variants that could help to fill the gap of the high heritability rates. The endocannabinoid system is a critical regulator of metabolism for its effects on the central nervous system and peripheral tissues. Fatty acid amide hydrolase (FAAH) is a key enzyme in the inactivation of one of the two endocannabinoids, anandamide, and of its congeners. The rs324420 variant within the FAAH gene is a nucleotide missense change at position 385 from cytosine to adenine, resulting in a non-synonymous amino acid substitution from proline to threonine in the FAAH enzyme. This change increases sensitivity to proteolytic degradation, leading to reduced FAAH levels and increased levels of anandamide, associated with obesity-related traits. However, association studies of this variant with metabolic parameters have found conflicting results. This work aims to perform a systematic review of the existing literature on the association of the rs324420 variant in the FAAH gene with obesity and its related traits. METHODS: A literature search was conducted in PubMed, Web of Science, and Scopus. A total of 645 eligible studies were identified for the review. RESULTS/CONCLUSIONS: After the identification, duplicate elimination, title and abstract screening, and full-text evaluation, 28 studies were included, involving 28 183 individuals. We show some evidence of associations between the presence of the variant allele and higher body mass index, waist circumference, fat mass, and waist-to-hip ratio levels and alterations in glucose and lipid homeostasis. However, this evidence should be taken with caution, as many included studies did not report a significant difference between genotypes. These discordant results could be explained mainly by the pleiotropy of the endocannabinoid system, the increase of other anandamide-like mediators metabolized by FAAH, and the influence of gene-environment interactions. More research is necessary to study the endocannabinoidomic profiles and their association with metabolic diseases.

Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization.

BACKGROUND: Drug hypersensitivity reactions (DHRs) to platinum-based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground-breaking procedure for their re-introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD. METHODS: Seventy-nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed. RESULTS: Oxaliplatin-reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL-6 in CRR and Mx, indicating different mechanisms and endotypes. CONCLUSION: Carboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin-reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols.

SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells.

BACKGROUND: Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. METHODS: In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. RESULTS: S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1ß formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1ß. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. CONCLUSION: S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. Video Abstract.

Analysis of nonsynonymous SNPs in candidate genes that influence bovine temperament and evaluation of their effect in Brahman cattle.

BACKGROUND: Temperament is an important production trait in cattle and multiple strategies had been developed to generate molecular markers to assist animal selection. As nonsynonymous single nucleotide polymorphisms are markers with the potential to affect gene functions, they could be useful to predict phenotypic effects. Genetic selection of less stress-responsive, temperamental animals is desirable from an economic and welfare point of view. METHODS AND RESULTS: Two nonsynonymous single nucleotide polymorphisms identified in HTR1B and SLC18A2 candidate genes for temperament were analyzed in silico to determine their effects on protein structure. Those nsSNPs allowing changes in proteins were selected for a temperament association analysis in a Brahman population. Transversion effects on protein structure were evaluated in silico for each amino acid change model, revealing structural changes in the proteins of the HTR1B and SLC18A2 genes. The selected nsSNPs were genotyped in a Brahman population (n = 138), and their genotypic effects on three temperament traits were analyzed: exit velocity, pen score, and temperament score. Only the SNP rs209984404-HTR1B (C/A) showed a significant association (P = 0.0144) with pen score. The heterozygous genotype showed a pen score value 1.17 points lower than that of the homozygous CC genotype. CONCLUSION: The results showed that in silico analysis could direct the selection of nsSNPs with the potential to change the protein. Non-synonymous single nucleotide polymorphisms causing structural changes and reduced protein stability were identified. Only rs209984404-HTR1B shows that the allele affecting protein stability was associated with the genotype linked to docility in cattle.

Sexual Identity Development and Social Ecological Facilitators and Barriers of PrEP Uptake and Adherence Among Latinx Men Who Have Sex with Men.

Latinx gay, bisexual, and other men who have sex with men (LMSM) report lower pre-exposure prophylaxis (PrEP) use than their white, non-Latinx counterparts. We hypothesize that this disparity is partially attributable to social ecological factors that can be addressed via prevention interventions. In this retrospective study, we first examined data from 253 LMSM to determine whether theorized associations existed between acquisition of a PrEP prescription (uptake) in relation to several social ecological factors based on a conceptual framework of determinants of access to and uptake of PrEP for LMSM. We also explored relations between frequency of PrEP use (adherence) and social ecological factors with a subsample of 33 LMSM who had initiated PrEP 12 months prior to assessment. In this study, individual-level factors from this framework included age and socioeconomic status. Perceived access to medical care represented both individual- and community-level determinants of PrEP uptake and adherence. Interpersonal-level factors were social support and relationship status. Structural/cultural-level factors were sexual identity development status, the masculinity norm of heterosexual self-presentation, traditional Latinx masculine gender role beliefs of machismo and caballerismo, racial identity, and immigration status. Results indicated that older men and those who endorsed the synthesis/integration status of sexual identity development were more likely to acquire a PrEP prescription during their lifetime in comparison to peers. PrEP adherence was linked with being older, reporting higher socioeconomic status, reporting more appraisal social support, self-identifying as white-Latinx, being U.S.-born, and endorsing less sexual identity uncertainty and more heterosexual self-presentation. Results specify modifiable factors that may inform tailored, community-based prevention efforts to increase PrEP use and decrease existing HIV/AIDS disparities among LMSM.

Predictive factors for foot pain in the adult population.

BACKGROUND: Foot pain has been associated to factors like: fat, body mass index, age increased, female gender and the presence of pathologies. Although evidence is limited. The purpose is to determine the predictive factors for foot pain in the adult population. METHODS: From January to December 2021, 457 patients were > 18 years, gave signed informed consent to take part to this cross sectional study. All completed demographic data and various questionnaires related to pain: Foot Function Index, EuroQoL-5D and Visual Analogue Scale (foot pain). Anthropometric measurements were obtained using McPoil platform and foot posture was assessed by the Foot Posture Index (FPI). To determine whether a volume change is a predictive factor for foot pain, a parameter was established: the volumetric index for footwear (VIF). Factors linked to the presence of pain, including the considered VIF variables, were analyzed through multivariable logistic regression. RESULTS: Among the study population, 40.7% were male and 59.3% female. The mean age of 39.06 years and a body mass index of 25.58 Kg/cm2. The logistic regression model had a classification capability of 72.4%, a sensitivity of 72.3% and a specificity of 73%, in which, the predictors considered were the variables found to have a significant association with FFI-pain > 45 points,, showed that younger women, with a higher BMI, higher values of right FPI (pronation), poorer overall perceived health and with problems in walking were more likely to experience foot pain. CONCLUSION: Predictive factors for foot pain in the adult population include gender, age, Body Mass Index, FPI on the right foot, perceived health and mobility. Clinical implication, the presented measure aids physicians in assessing their patients´ foot pain likelihood.

Structural empowerment, personal initiative, and job satisfaction in service employees: Exploring the mediating role of psychological empowerment.

INTRODUCTION: This study explores how empowering human resource management (HRM) practices based on structural empowerment (access to opportunities, resources, support, and information) affect both personal initiative and job satisfaction of service employees through individual-level factors (psychological empowerment). METHODS: We conducted a cross-sectional survey study and collected 439 valid responses from service employees in Spain. The hypotheses were tested using structural equation modeling (SEM) with confidence intervals based on 10,000 resamples (i.e., bootstrapping technique). RESULTS: Our results showed that psychological empowerment partially mediated the relationship between structural empowerment and job satisfaction. It also fully mediated the relationship between structural empowerment and personal initiative at work. CONCLUSION: These findings emphasize the importance of HRM practices that can empower employees as key determinants of job satisfaction and personal initiative at service companies. Furthermore, a structural empowerment approach is a valid theoretical framework for studying and understanding employees' affective evaluations of work and, more specifically, their personal initiative.

Beyond digestive pathology: endoscopic study in systemic disease.

A 77-year-old male patient with heart disease, kidney disease under study, and quiescent multiple myeloma. He presented a 2 years history of weight loss and digestive symptoms. In the endoscopic study, multiple gastric ulcers were observed, whose histological study ruled out the initial suspicion. The patient died a month later from refractory shock.

Assessing the impact of long-term inhaled corticosteroid therapy on patients with COVID-19 and coexisting chronic lung disease: A multicenter retrospective cohort study.

Background: Patients with chronic lung disease (CLD), such as asthma or chronic obstructive pulmonary disease, were expected to have an increased risk of clinical manifestations and severity of COVID-19. However, these comorbidities have been reported less frequently than expected. Chronic treatment with inhaled corticosteroids (ICS) may impact the clinical course of COVID-19. The main objective of this study is to know the influence of chronic treatment with ICS on the prognosis of COVID-19 hospitalized patients with CLD. Methods: A multicenter retrospective cohort study was designed, including patients hospitalized with COVID-19. Epidemiological and clinical data were collected at admission and at seven days, and clinical outcomes were collected. Patients with CLD with and without chronic treatment with ICS were compared. Results: Two thousand five hundred ninety-eight patients were included, of which 1,171 patients had a diagnosis of asthma and 1,427 of COPD (53.37% and 41.41% with ICS, respectively). No differences were found in mortality, transfer to ICU, or development of moderate-severe ARDS. Patients with chronic ICS had a longer hospital stay in both asthma and COPD patients (9 vs. 8 days, p = 0.031 in asthma patients), (11 vs. 9 days, p = 0.018 in COPD patients); although they also had more comorbidity burden. Conclusions: Patients with chronic inhaled corticosteroids had longer hospital stays and more chronic comorbidities, measured by the Charlson comorbidity index, but they did not have more severe disease at admission, evaluated with qSOFA and PSI scores. Chronic treatment with inhaled corticosteroids had no influence on the prognosis of patients with chronic lung disease and COVID-19.

Reciprocity and interaction effectiveness in generalised mutualisms among free-living species.

Mutualistic interactions among free-living species generally involve low-frequency interactions and highly asymmetric dependence among partners, yet our understanding of factors behind their emergence is still limited. Using individual-based interactions of a super-generalist fleshy-fruited plant with its frugivore assemblage, we estimated the Resource Provisioning Effectiveness (RPE) and Seed Dispersal Effectiveness (SDE) to assess the balance in the exchange of resources. Plants were highly dependent on a few frugivore species, while frugivores interacted with most individual plants, resulting in strong asymmetries of mutual dependence. Interaction effectiveness was mainly driven by interaction frequency. Despite highly asymmetric dependences, the strong reliance on quantity of fruit consumed determined high reciprocity in rewards between partners (i.e. higher energy provided by the plant, more seedlings recruited), which was not obscured by minor variations in the quality of animal or plant service. We anticipate reciprocity will emerge in low-intimacy mutualisms where the mutualistic outcome largely relies upon interaction frequency.

Caloric reductions needed to achieve obesity goals in Mexico for 2030 and 2040: A modeling study.

BACKGROUND: In Mexico, obesity prevalence among adults increased from 23% in 2000 to 36% in 2018, approximately. Mexico has not defined short- or long-term obesity goals, obscuring the level of effort required to achieve a relevant impact. We aimed to explore potential obesity goals for 2030 and 2040 in Mexico and to estimate the required caloric reductions to achieve them. METHODS AND FINDINGS: We obtained anthropometric and demographic information on the Mexican adult population (age ≥20 years) from the Health and Nutrition Surveys conducted in 2000, 2006, 2012, 2016, and 2018 (n = 137,907). Each survey wave is cross-sectional, multistage, and representative of the Mexican population at the national, regional, and urban/rural levels. Obesity prevalence was projected for 2030 and 2040 by combining population projections of energy intake by socioeconomic status (SES) with a weight-change microsimulation model taking into account individual-level information on sex, age, physical activity, and initial body weight and height. If current trends continue, Mexico's obesity prevalence is expected to increase from 36% (95% CI 35% to 37%) in 2018 to 45% (uncertainty interval [UI] 41% to 48%) in 2030 and to 48% (UI 41% to 55%) in 2040. Based on expert opinion, we identified 3 obesity goals scenarios: (1) plausible (38% in 2030 and 36% in 2040); (2) intermediate (33% in 2030 and 29% in 2040); and (3) ideal based on the average prevalence of Organization for Economic Co-operation and Development countries (OECD; 19%). We estimated the caloric reductions needed to achieve the goal scenarios using the microsimulation model. Obesity was projected to increase more rapidly in the low SES (around 34% in 2018 to 48% (UI 41% to 55%) in 2040), than in the middle (around 38% to 52% (UI 45% to 56%)), or high SES group (around 36% to 45% (UI 36% to 54%)). Caloric reductions of 40 (UI 13 to 60), 75 (UI 49 to 95), and 190 (UI 163 to 215) kcal/person/day would be needed to reach the plausible, intermediate, and the ideal (OECD) average scenarios for 2030, respectively. To reach the 2040 goals, caloric reductions of 74 (UI 28 to 114), 124 (UI 78 to 169), and 209 (UI 163 to 254) kcal/person/day would be required, respectively. Study limitations include assuming a constant and sedentary physical activity level, not considering cohort-specific differences that could occur in the future, and assuming the same caloric trends under no intervention and the obesity goal scenarios. CONCLUSIONS: To reach the 3 obesity goals in 2040, caloric reductions between 74 and 209 kcal/day/person would be needed in Mexico. A package of new and stronger interventions should be added to existing efforts such as food taxes and warning labels on non-nutritious food.

Conventional versus extended-pulsed fidaxomicin dosing in patients at high risk of recurrence of Clostridioides difficile infection: a propensity score analysis.

INTRODUCTION: The main challenge in the treatment of Clostridioides difficile infection (CDI) is to reduce recurrence rates. Fidaxomicin improves the recurrence rate of CDI compared with vancomycin. Extended-pulsed dosing of fidaxomicin was associated with lower recurrence rates in one clinical trial but has never been directly compared with conventional fidaxomicin dosing. METHODS: To compare the recurrence rate of fidaxomicin conventional dosing (FCD) and fidaxomicin in extended-pulsed dosing (FEPD) in conditions of clinical practice at a single institution. We performed propensity score matching taking the variables age, severity and previous episode as confounders to evaluate patients with a similar recurrence risk. RESULTS: In total, 254 episodes of CDI treated with fidaxomicin were evaluated: 170 (66.9%) received FCD, and 84 (33.1%) received FEPD. More patients who received FCD were hospitalized for CDI, had severe CDI and had a diagnosis based on toxin detection. In contrast, the proportion of patients receiving proton pump inhibitors was higher in those receiving FEPD. The crude recurrence rates in FCD- and FEPD-treated patients were 20.0% and 10.7%, respectively (OR:0.48; 95% CI 0.22-1.05; P = 0.068). We did not find any differences in CDI recurrence rate in patients receiving FEPD versus FCD (OR = 0.74; 95% CI 0.27-2.04) by propensity score analysis. CONCLUSIONS: Although the recurrence rate with FEPD was numerically lower than that observed with FCD, we have not been able to show that the recurrence rate of CDI is different depending on the dosage regimen of fidaxomicin. Clinical trials or large observational studies comparing the two dosing regimens of fidaxomicin are needed.

Stilbenes: Characterization, bioactivity, encapsulation and structural modifications. A review of their current limitations and promising approaches.

Stilbenes are phenolic compounds naturally synthesized as secondary metabolites by the shikimate pathway in plants. Research on them has increased in recent years due to their therapeutic potential as antioxidant, antimicrobial, anti-inflammatory, anticancer, cardioprotective and anti-obesity agents. Amongst them, resveratrol has attracted the most attention, although there are other natural and synthesized stilbenes with enhanced properties. However, stilbenes have some physicochemical and pharmacokinetic problems that need to be overcome before considering their applications. Human clinical evidence of their bioactivity is still controversial due to this fact and hence, exhaustive basis science on stilbenes is needed before applied science. This review gathers the main physicochemical and biological properties of natural stilbenes, establishes structure-activity relationships among them, emphasizing the current problems that limit their applications and presenting some promising approaches to overcome these issues: the encapsulation in different agents and the structural modification to obtain novel stilbenes with better features. The bioactivity of stilbenes should move from promising to evident.

Effects of MIdazolam versus MOrphine in acute cardiogenic pulmonary edema and chronic obstructive pulmonary disease: An analysis of MIMO trial.

AIMS: Chronic obstructive pulmonary disease (COPD) is an important comorbidity in heart failure. The MIMO trial showed that patients with acute cardiogenic pulmonary edema (ACPE) treated with midazolam had fewer serious adverse events than those treated with morphine. In this post hoc analysis, we examined whether the presence/ absence of COPD modifies the reduced risk of midazolam over morphine. METHODS: Patients >18 years old clinically diagnosed with ACPE and with dyspnea and anxiety were randomized (1:1) at emergency department arrival to receive either intravenous midazolam or morphine. In this post hoc analysis, we calculated the relative risk (RR) of serious adverse events in patients with and without COPD. Calculating the CochranMantel-Haenszel interaction test, we evaluated if COPD modified the reduced risk of serious adverse events in the midazolam arm compared to morphine. RESULTS: Overall, 25 (22.5%) of the 111 patients randomized had a history of COPD. Patients with COPD were more commonly men with a history of previous episodes of heart failure, than participants without COPD. In the COPD group, the RR for the incidence of serious adverse events in the midazolam versus morphine arm was 0.36 (95%CI, 0.1-1.46). In the group without COPD, the RR was 0.44 (95%CI, 0.22-0.91). The presence of COPD did not modify the reduced risk of serious adverse events in the midazolam arm compared to morphine (p for interaction =0.79). CONCLUSIONS: The reduced risk of serious adverse events in the midazolam group compared with morphine is similar in patients with and without COPD.

Case Report: a novel CYP27A1 gene variant in a patient with cerebrotendinous xanthomatosis with unusual clinical findings.

PURPOSE/AIM OF THE STUDY: Cerebrotendinous xanthomatosis is a disease with important clinical and molecular heterogeneity. CYP27A1 gene was described as the cause of these defects, with more than 50 mutations involved in the disease. The objective of this study was to carry out a genetic study and a clinical description of a patient with unusual clinical manifestation of the disease. MATERIALS AND METHODS: DNA sequencing was used for the evaluation of CYP27A1 exon sequences and their intron/exon boundaries. Copy number variants were calculated using a method based on depth of sequencing coverage. In addition, the potential effects of the missense variants were analyzed, and an in-silico protein modeling tool was used. Finally, a patient case description was performed in order to evaluate patient phenotype according to genetic results. RESULTS: Patient clinical features indicate the possible presence of a disease milder phenotype. When analyzing the CYP27A1 gene, patient presents a pathogenic variant (p.Arg474Trp) and a variant of unknown significance (p.Met130Ile) that causes a slight modification of the protein functional structure. This variant in homozygosis or double or compound heterozygosis together with other biallelic pathological mutations may be the cause of the clinical phenotype observed in the reported patient. CONCLUSIONS: Clinical manifestations of cerebrotendinous xanthomatosis are heterogeneous, and sometimes wrongly suggest the presence of other diseases. Some patients seem to present an "incomplete" phenotype, which could be redefined as a variant of the disease with further studies. The evaluation of new mutations allows for earlier diagnosis and greater effectiveness in its treatment.

Impact of the MEESSI-AHF tool to guide disposition decision-making in patients with acute heart failure in the emergency department: a before-and-after study.

OBJECTIVES: To determine the impact of risk stratification using the MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with acute heart failure) scale to guide disposition decision-making on the outcomes of ED patients with acute heart failure (AHF), and assess the adherence of emergency physicians to risk stratification recommendations. METHODS: This was a prospective quasi-experimental study (before/after design) conducted in eight Spanish EDs which consecutively enrolled adult patients with AHF. In the pre-implementation stage, the admit/discharge decision was performed entirely based on emergency physician judgement. During the post-implementation phase, emergency physicians were advised to 'discharge' patients classified by the MEESSI-AHF scale as low risk and 'admit' patients classified as increased risk. Nonetheless, the final decision was left to treating emergency physicians. The primary outcome was 30-day all-cause mortality. Secondary outcomes were days alive and out of hospital, in-hospital mortality and 30-day post-discharge combined adverse event (ED revisit, hospitalisation or death). RESULTS: The pre-implementation and post-implementation cohorts included 1589 and 1575 patients, respectively (median age 85 years, 56% females) with similar characteristics, and 30-day all-cause mortality was 9.4% and 9.7%, respectively (post-implementation HR=1.03, 95% CI=0.82 to 1.29). There were no differences in secondary outcomes or in the percentage of patients entirely managed in the ED without hospitalisation (direct discharge from the ED, 23.5% vs 24.4%, OR=1.05, 95% CI=0.89 to 1.24). Adjusted models did not change these results. Emergency physicians followed the MEESSI-AHF-based recommendation on patient disposition in 70.9% of cases (recommendation over-ruling: 29.1%). Physicians were more likely to over-rule the recommendation when 'discharge' was recommended (56.4%; main reason: need for hospitalisation for a second diagnosis) than when 'admit' was recommended (12.8%; main reason: no appreciation of severity of AHF decompensation by emergency physician), with an OR for over-ruling the 'discharge' compared with the 'admit' recommendation of 8.78 (95% CI=6.84 to 11.3). CONCLUSIONS: Implementing the MEESSI-AHF risk stratification tool in the ED to guide disposition decision-making did not improve patient outcomes.

Sensing and Control Strategies for a Synergy-Based, Cable-Driven Exosuit via a Modular Test Bench.

Ageing results in the eventual loss of muscle mass and strength, joint problems, and overall slowing of movements, with a greater risk of suffering falls or other such accidents. The use of gait assistance exoskeletons can help in the active aging of this segment of the population. Given the user specificity of the mechanics and control these devices need, the facility used to test different design parameters is indispensable. This work deals with the modeling and construction of a modular test bench and prototype exosuit to test different mounting and control schemes for a cable-driven exoskeleton or exosuit. The test bench allows the experimental implementation of postural or kinematic synergies to assist multiple joints by using only one actuator and the optimization of the control scheme to better adapt to the characteristics of the specific patient. The design is open to the research community and it is expected to improve the design of cable-driven systems for exosuits.