[Health-related quality of life in Mexican women with obesity]. / Calidad de vida relacionada con la salud en mujeres mexicanas con obesidad.

Background: Obesity creates a burden of disease that affects the health-related quality of life (HRQoL) of women and in those between 20 to 59 years of age it implies greater morbidity and mortality compared to men or other age groups. Objective: To evaluate the HRQoL of Mexican women aged 20 to 59 years with obesity. Material and methods: Observational, cross-sectional, prospective, and retrospective study. It was obtained a sample of 104 women from 20 to 59 years of age diagnosed with obesity according to the NOM-008-SSA3-2017 Standard. The participants' main clinical and sociodemographic characteristics were collected, and their HRQoL was evaluated with the SF-36 questionnaire. For the analysis of the collected variables, descriptive statistics were used. To identify the association of these variables with HRQoL, the Kruskal-Wallis test was used. Results: 104 women with a median age of 40.0 years participated. Of these, 66.3% had grade I obesity, 21.2% grade II, and 12.5% grade III. In the overall sample, general health and vitality were the lowest dimensions. In the comparison by groups, the physical role and the emotional role had statistically significant differences (p = 0.007 and p = 0.009, respectively), with the most affected group being obesity grade II. Conclusions: Obesity mainly affected the perception of general health and vitality; likewise, those with grade II had a greater impact on the physical role and the emotional role.

Introducción: la obesidad crea una carga de enfermedad que afecta la calidad de vida relacionada con la salud (CVRS) de las mujeres y en aquellas de 20 a 59 años implica una mayor morbilidad y mortalidad respecto a los hombres u otros grupos etarios. Objetivo: evaluar la CVRS de mujeres mexicanas de 20 a 59 años con obesidad. Material y métodos: estudio observacional, transversal, prospectivo y retrolectivo. Se obtuvo una muestra de 104 mujeres de 20 a 59 años, diagnosticadas con obesidad según la NOM-008-SSA3-2017. Se recabaron las principales características clínicas y sociodemográficas de las participantes y se evaluó su CVRS con el cuestionario SF-36. Para analizar las variables recogidas, se usó estadística descriptiva. Para identificar la asociación de estas variables con la CVRS, se usó la prueba Kruskal-Wallis. Resultados: participaron 104 mujeres con una mediana de edad de 40.0 años. De estas, 66.3% tuvieron obesidad grado I, 21.2% grado II y 12.5% grado III. En la muestra general, la salud general y la vitalidad fueron las dimensiones más bajas. En la comparación por grupos, el rol físico y el rol emocional tuvieron diferencias estadísticamente significativas (p = 0.007 y p = 0.009, respectivamente), y el grupo más afectado fue el de obesidad grado II. Conclusiones: la obesidad afectó principalmente la percepción de la salud general y de la vitalidad; asimismo, aquellas con grado II tuvieron una mayor repercusión en los roles físico y emocional.

The Second Life Metaverse and Its Usefulness in Medical Education After a Quarter of a Century.

The immersive virtual world platform Second Life (SL) was conceived 25 years ago, when Philip Rosedale founded Linden Lab in 1999 with the intention of developing computing hardware that would allow people to immerse themselves in a virtual world. This initial effort was transformed 4 years later into SL, a universally accessible virtual world centered on the user, with commercial transactions and even its own virtual currency, which fully connects with the concept of the metaverse, recently repopularized after the statements of the chief executive officer of Meta (formerly Facebook) in October 2021. SL is considered the best known virtual environment among higher education professionals. This paper aimed to review medical education in the SL metaverse; its evolution; and its possibilities, limitations, and future perspectives, focusing especially on medical education experiences during undergraduate, residency, and continuing medical education. The concept of the metaverse and virtual worlds was described, making special reference to SL and its conceptual philosophy, historical evolution, and technical aspects and capabilities for higher education. A narrative review of the existing literature was performed, including at the same time a point of view from our teaching team after an uninterrupted practical experience of undergraduate and postgraduate medical education in the last 13 years with >4000 users and >10 publications on the subject. From an educational point of view, SL has the advantages of being available 24/7 and creating in the student the important feeling of "being there" and of copresence. This, together with the reproduction of the 3D world, real-time interaction, and the quality of voice communication, makes the immersive experiences unique, generating engagement and a fluid interrelation of students with each other and with their teachers. Various groups of researchers in medical education have developed experiences during these years, which have shown that courses, seminars, workshops and conferences, problem-based learning experiences, evaluations, teamwork, gamification, medical simulation, and virtual objective structured clinical examinations can be successfully carried out. Acceptance from students and faculty is generally positive, recognizing its usefulness for undergraduate medical education and continuing medical education. In the 25 years since its conception, SL has proven to be a virtual platform that connects with the concept of the metaverse, an interconnected, open, and globally accessible system that all humans can access to socialize or share products for free or using a virtual currency. SL remains active and technologically improved since its creation. It is necessary to continue carrying out educational experiences, outlining the organization, objectives, and content and measuring the actual educational impact to make SL a tool of more universal use.

Unforeseen plant phenotypic diversity in a dry and grazed world.

Earth harbours an extraordinary plant phenotypic diversity1 that is at risk from ongoing global changes2,3. However, it remains unknown how increasing aridity and livestock grazing pressure-two major drivers of global change4-6-shape the trait covariation that underlies plant phenotypic diversity1,7. Here we assessed how covariation among 20 chemical and morphological traits responds to aridity and grazing pressure within global drylands. Our analysis involved 133,769 trait measurements spanning 1,347 observations of 301 perennial plant species surveyed across 326 plots from 6 continents. Crossing an aridity threshold of approximately 0.7 (close to the transition between semi-arid and arid zones) led to an unexpected 88% increase in trait diversity. This threshold appeared in the presence of grazers, and moved toward lower aridity levels with increasing grazing pressure. Moreover, 57% of observed trait diversity occurred only in the most arid and grazed drylands, highlighting the phenotypic uniqueness of these extreme environments. Our work indicates that drylands act as a global reservoir of plant phenotypic diversity and challenge the pervasive view that harsh environmental conditions reduce plant trait diversity8-10. They also highlight that many alternative strategies may enable plants to cope with increases in environmental stress induced by climate change and land-use intensification.

(Preoperative instillation of epinephrine and lidocaine may reduce the surgical time of endoscopic treatment of GTPS.). / La instilación preoperatoria de epinefrina y lidocaína puede reducir el tiempo quirúrgico del tratamiento endoscópico de SDTM.

INTRODUCTION: Greater Trochanteric Pain Syndrome (GTPS) is a multifactorial clinical condition affecting the lateral area of the hip. Although conservative treatment shows good results, some patients may still require surgical bursectomy, which can be performed either openly or endoscopically. One of the main technical difficulties of the endoscopic procedure is intraoperative bleeding, which can hinder the medical team's vision and increase the operation time for endoscopic treatment of GTPS. HYPOTHESIS: An instillation of vasoconstrictors and local anesthetics before endoscopy will cause less intraoperative bleeding, which will translate into shorter surgical time. MATERIALS AND METHODS: A prospective cohort was retrospectively divided based on the use or absence of a preoperative instillation of physiological saline solution with epinephrine and lidocaine. Surgical time was measured in each procedure and compared between the two groups. RESULTS: 139 hips from 139 patients were included in the analysis. 102 patients were included in the instillation group versus 37 in the control group. The surgical time was significantly shorter in the instillation group than in the control group, with an average (standard deviation) of 52.01 (14.71) and 72.30 (11.70) minutes, respectively (p < 0.001). CONCLUSION: The instillation of a physiological saline solution with epinephrine and lidocaine prior to the surgical treatment of GTPS is effective in reducing surgical times, likely due to a reduction in intraoperative bleeding. Future research should focus on more direct outcomes such as intraoperative blood loss and between different instillation protocols.

Multi-omic characterization of antibody-producing CHO cell lines elucidates metabolic reprogramming and nutrient uptake bottlenecks.

Characterizing the phenotypic diversity and metabolic capabilities of industrially relevant manufacturing cell lines is critical to bioprocess optimization and cell line development. Metabolic capabilities of production hosts limit nutrient and resource channeling into desired cellular processes and can have a profound impact on productivity. These limitations cannot be directly inferred from measured data such as spent media concentrations or transcriptomics. Here, we present an integrated multi-omic analysis pipeline combining exo-metabolomics, transcriptomics, and genome-scale metabolic network analysis and apply it to three antibody-producing Chinese Hamster Ovary cell lines to identify reprogramming features associated with high-producing clones and metabolic bottlenecks limiting product formation in an industrial bioprocess. Analysis of individual datatypes revealed a decreased nitrogenous byproduct secretion in high-producing clones and the topological changes in peripheral metabolic pathway expression associated with phase shifts. An integrated omics analysis in the context of the genome-scale metabolic model elucidated the differences in central metabolism and identified amino acid utilization bottlenecks limiting cell growth and antibody production that were not evident from exo-metabolomics or transcriptomics alone. Thus, we demonstrate the utility of a multi-omics characterization in providing an in-depth understanding of cellular metabolism, which is critical to efforts in cell engineering and bioprocess optimization.

Exudate and Propolis from Escallonia pulverulenta: Phytochemical Characterization and Antibacterial Activity.

Propolis is a complex mixture formed from exudates that bees collect from plants and then mix with beeswax and their own salivary enzymes. Chilean propolis is characterized by the presence of phenolic compounds, which are considered responsible for the biological activities. The endemic species Escallonia pulverulenta (Ruiz and Pav.) Pers. [Escalloniaceae] is a recognized source of exudate to produce propolis. This study reports for the first time the chemical profile and antibacterial activity of E. pulverulenta exudate and leaves, as well as two samples of Chilean propolis. Palynological and morphological analysis showed the presence of E. pulverulenta as one of the main species in the propolis samples. UPLC-MS/MS analyses enabled the identification of phenolic acids in the leaves and in the propolis. Conversely, flavonoids are mainly present in exudates and propolis. Quercetin is the most abundant flavonol in the exudate, with similar concentrations in the propolis samples. Nevertheless, the main compound present in both samples of propolis was the flavanone pinocembrin. The antibacterial results obtained for exudate and propolis have shown a similar behavior, especially in the inhibition of Streptococcus pyogenes. These results show the importance of the exudates collected by the bees in the chemical composition and antibacterial capacity of propolis.

Frequency and intensity of maximal and submaximal demanding scenarios in U19 professional soccer players.

This study examined the frequency of the most demanding scenarios (MDS) during official soccer matches using rolling averages over 1, 5, and 10 min. Forty-two Under-19 players from different positions (central defenders, full-backs, central midfielders, wide midfielders, offensive midfielders, and forwards) were monitored across 27 matches using GPS to track distance covered, high-speed running, sprint distance, accelerations, and decelerations. Intensity thresholds were established based on percentiles (0-25, 25-50, 50-75, 75-100, and ≥100). The main findings suggest that: (i) Peak Demands occur in less than 1% of all time windows and variables for all positions; (ii) Most efforts occur below peak demands, with around 95% for high-speed running and sprint distance, and 85% for accelerations, decelerations, and total distance; (iii) Significant differences in intensity distributions were found between positions, particularly at medium-low and high intensities. Regarding training prescription, relying solely on MDS may be limited, highlighting the need to supplement MDS with other metrics for a comprehensive understanding of match demands. This approach ensures better-informed training programs for soccer players.

The occurrence of peak demand events during soccer matches is infrequent. Therefore, understanding the frequency of efforts below the intensity threshold of the most demanding passages for each playing position and across various analysed variables and periods is of utmost importance.MDS might not be enough for effective soccer training planning. Complementing with additional metrics like GPS, tactical analysis, physiological data and psychological factors is essential for a comprehensive understanding of the game's demands and tailored training programmes.

Home-Court Advantage is Greater for Teams Competing at Higher Playing Levels: An Exploratory Analysis of Spanish Male Basketball Leagues.

This study aimed to (i) compare the extent of home-court advantage (HA) and home win percentage (HW) between Spanish basketball leagues across different playing levels (i.e., leagues) and (ii) analyze the influence of team ability on HA and HW within each playing level. We gathered data for game locations and results from open online sources for all games in the First Division (ACB), Second Division (LEB Gold), and Third Division (LEB Silver) Spanish male basketball leagues between 2010-2023. The dataset included 12 seasons, 635 teams (215 First Division, 203, Second Division, and 217 Third Division), and 19,539 games (7075 First Division, 6344 Second Division, and 5520 Third Division). We calculated HA [(total home wins/total wins) * 100] and HW [(total home wins/total home games) * 100] for each team across each season. We performed Kruskal Wallis tests, calculated partial eta squared (ηp2), and performed Mann-Whitney U tests with rank biserial correlation (rb) effect sizes and Dwass-Steel-Critchlow-Fligner pairwise comparisons to compare HA and HW between leagues and between team abilities (low, medium, and/or high) within each league. There was a significant effect for HA between leagues (p = .01) with post hoc comparisons revealing a higher HA for the First Division than for the Third Division (p = .01), but HW was not significantly different between leagues. In turn, variations in HA and HW between team abilities were consistent across playing levels, with HW significantly increasing in a progressive manner with higher team abilities (p < .001) and with HA significantly lower among high-level teams compared to lower-ability team clusters (p < .01). These findings emphasize the importance of considering playing level and team ability and interpreting HA and HW together to contextualize an apparent home advantage in Spanish basketball.

Do High Doses of Multiple Antibiotics Loaded into Bone Cement Spacers Improve the Success Rate in Staphylococcal Periprosthetic Joint Infection When Rifampicin Cannot Be Employed?

Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10-147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment.

Loss of Kmt2c or Kmt2d drives brain metastasis via KDM6A-dependent upregulation of MMP3.

KMT2C and KMT2D, encoding histone H3 lysine 4 methyltransferases, are among the most commonly mutated genes in triple-negative breast cancer (TNBC). However, how these mutations may shape epigenomic and transcriptomic landscapes to promote tumorigenesis is largely unknown. Here we describe that deletion of Kmt2c or Kmt2d in non-metastatic murine models of TNBC drives metastasis, especially to the brain. Global chromatin profiling and chromatin immunoprecipitation followed by sequencing revealed altered H3K4me1, H3K27ac and H3K27me3 chromatin marks in knockout cells and demonstrated enhanced binding of the H3K27me3 lysine demethylase KDM6A, which significantly correlated with gene expression. We identified Mmp3 as being commonly upregulated via epigenetic mechanisms in both knockout models. Consistent with these findings, samples from patients with KMT2C-mutant TNBC have higher MMP3 levels. Downregulation or pharmacological inhibition of KDM6A diminished Mmp3 upregulation induced by the loss of histone-lysine N-methyltransferase 2 (KMT2) and prevented brain metastasis similar to direct downregulation of Mmp3. Taken together, we identified the KDM6A-matrix metalloproteinase 3 axis as a key mediator of KMT2C/D loss-driven metastasis in TNBC.

Sensory, emotional, and appropriateness of plant- and meat-based burgers.

The plant-based meat alternative market is experiencing rapid growth. However, whether this growth extends to mainstream consumers will depend on the sensory profile, emotional profile, and situational appropriateness of these products. This study provides a sensory comparison between two plant-based burgers, one hybrid burger, and a conventional 100% ground beef burger. The sensory evaluation was carried out under blind and informed conditions using a between-subject design. Participants (n = 177) were asked to rate the appearance, flavor, odor, and texture of each product and indicate their overall liking. In addition, 26 sensory terms were evaluated using the rate-all-that-apply technique. The study also measured the emotional profile and the situational appropriateness elicited by each product using the check-all-that-apply technique. The results showed that (a) in the blind condition, there were no significant differences observed in overall liking across the four burgers; (b) the plant-based burger made with pea protein received the lowest overall liking score, and its evaluation was not positively influenced by product information disclosure; (c) providing product information influenced the perceived intensity of the attributes associated with meat; (d) discriminatory ability for emotions was higher in the informed condition; and (e) for the situational appropriateness, when prioritizing healthy eating, participants considered plant-based burgers more suitable than the groundbeef burger. PRACTICAL APPLICATION: Our results demonstrate that product descriptions could have an impact on consumer acceptance of different meat burger alternatives. In order to launch successfull meat alternatives, product developers and communication marketing specialists should consider the extent to which these alternatives resemble regular meat products in terms of their sensory and emotional profiles and context of use.

HoopTransformer: Advancing NBA Offensive Play Recognition with Self-Supervised Learning from Player Trajectories.

BACKGROUND AND OBJECTIVE: Understanding and recognizing basketball offensive set plays, which involve intricate interactions between players, have always been regarded as challenging tasks for untrained humans, not to mention machines. In this study, our objective is to propose an artificial intelligence model that can automatically recognize offensive plays using a novel self-supervised learning approach. METHODS: The dataset was collected by SportVU from 632 games during the 2015-2016 season of the National Basketball Association (NBA), with a total of 90,524 possessions. A multi-agent motion prediction pretraining model was built on the basis of axial-attention transformer and trained with different masking strategies: motion prediction (MP), motion reconstruction (MR), and MP + MR joint strategy. A downstream play-level classification task and similarity search were used to evaluate the models' performance. RESULTS: The results showed that the MP + MR joint masking strategy maximized the ability of the model compared with individual masking strategies. For the classification task, the joint strategy achieved a top-1 accuracy of 81.5% and top-3 accuracy of 97.5%. In the similarity search evaluation, the joint strategy attained a top-5 accuracy of 76% and top-10 accuracy of 59%. Additionally, with the same MP + MR joint masking strategy, our HoopTransformer model outperformed the two baseline models in the classification task and similarity search. CONCLUSION: This study presents a self-supervised learning model and demonstrates the effectiveness and potential of the model in accurately comprehending and capturing player movements and complex interactions during offensive plays.

Analysis of Madrid Primary Health-Care staff for the implementation of exercise prescription.

OBJECTIVE: To assess the self-perception of nurses and general practitioners (GPs) toward Physical Activity on Prescription (PAP) in Madrid Primary Health-Care (PHC). DESIGN: A survey-cohort study. SITE: Nurses and GPs of Madrid PHC System. PARTICIPANTS: A total of 319 GPs and 285 nurses' responders. MEASUREMENTS: Data were analyzed under a classification tree analysis by four predictor variables: (i) Health professional (Nurses/GPs); (ii) Exercise prescription collaboration with all health professionals: physicians, nurses, psychologists, physical therapists, sports medicine physicians, sports scientists, nutritionists, and teachers (Yes/No); (iii) PA promotion collaboration with Sports Scientists (Yes/No); and (iv) The stage of change of PHC staff to PA promotion (0-4 Likert scale). RESULTS: Regarding the predictor variable (i), responders without PA guidelines knowledge and positive attitude to collaborate with nurses in PA promotion are more GPs of female sex (nurses n=33 and GPs n=175) than male sex (nurses n=3 and GPs n=59) (p<.001). For the predictor variable (ii) only 9.30% of PHC staff with a positive attitude to collaborate with all health professionals in PA promotion and exercise prescription. For the predictor variable (iii) was shown low collaboration with sports physicians and sports scientists under a multidisciplinary PAP approach (26.50% responders). Finally, in the predictor variable (iv) Staff maintaining PAP for at least 6 months, self-considered active, and with PAP knowledge want to collaborate with Sports scientists (Yes=233; No=133). CONCLUSIONS: Nurses and GPs are conscious of health-related PA benefits despite the lack of PAP knowledge and lack of willingness to collaborate with other health personnel, exercise professionals, and community resources available.

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation.

Enteroendocrine cells (EECs) secrete serotonin (enterochromaffin [EC] cells) or specific peptide hormones (non-EC cells) that serve vital metabolic functions. The basis for terminal EEC diversity remains obscure. By forcing activity of the transcription factor (TF) NEUROG3 in 2D cultures of human intestinal stem cells, we replicated physiologic EEC differentiation and examined transcriptional and cis-regulatory dynamics that culminate in discrete cell types. Abundant EEC precursors expressed stage-specific genes and TFs. Before expressing pre-terminal NEUROD1, post-mitotic precursors oscillated between transcriptionally distinct ASCL1+ and HES6hi cell states. Loss of either factor accelerated EEC differentiation substantially and disrupted EEC individuality; ASCL1 or NEUROD1 deficiency had opposing consequences on EC and non-EC cell features. These TFs mainly bind cis-elements that are accessible in undifferentiated stem cells, and they tailor subsequent expression of TF combinations that underlie discrete EEC identities. Thus, early TF oscillations retard EEC maturation to enable accurate diversity within a medically important cell lineage.

Adherence to the Mediterranean Diet and its association with sustainable dietary behaviors, sociodemographic factors, and lifestyle: a cross-sectional study in US University students.

BACKGROUND: Promoting healthy and sustainable diets is increasingly important and the Mediterranean Diet (MD) has been recognized as an appropriate example that can be adapted to different countries. Considering that the college years are the time when US young adults are most likely to adopt unhealthy eating habits, the present study assessed adherence to the MD and the sustainability of dietary behaviors in a nationally representative sample of US university students, aiming to identify crucial levers for improving their eating behaviors. METHODS: MD adherence and the adoption of healthy and sustainable dietary patterns were assessed through the KIDMED and the Sustainable-HEalthy-Diet (SHED Index questionnaires, respectively, administered through an online survey that also included sociodemographic and behavioral questions. Non-parametric and logistic regression analyses were performed. RESULTS: A sample of 1485 participants (median (IQR) age 21.0 (19.0-22.0); 59% women) correctly completed the survey. A medium adherence to the MD was the most prevalent (47%). According to multivariate logistic regression analysis, the likelihood of being more compliant with the MD increased when meeting physical activity recommendations, having a high SHED Index score, having the willingness to purchase and eat healthy and sustainable dishes, eating ultra-processed plant-based meat alternatives foods daily, and regularly attending the university canteen. CONCLUSIONS: Encouraging dietary patterns rich in plant-based foods and with a moderate intake of animal products is crucial to increasing the adoption of healthy and sustainable diets, and university dining services represent a suitable setting to build a supportive environment that educates students on human and planetary health.

Examining the Role of Fan Support on Home Advantage and Home Win Percentage in Professional Women's Basketball.

Our main aim in this study was to analyze any differences in Win Percentages at Home (HW) that might represent a Home-Court Advantage (HA) in women's professional basketball. A secondary objective was to analyze how team ability might modify the HA effect by comparing any interaction effect between HW and team ability in games played with and without fans. We collected data from first Spanish female basketball divisions, using a linear mixed model (LMM) for repeated measures to identify differences between time periods (games with fans vs. games without fans) for HA and HW. When comparing games with and without fans, we found no significant HA and HW differences (p = .283 and p = .872, respectively). In fact, interestingly, we observed higher win values when fans were absent. Additionally, during the COVID-19 shut down stage, HA increased; but it returned to pre-pandemic levels afterward, with no significant differences between these periods (p = .482). Similarly, while HW seemed to increase during the COVID-19 shut down period and continued improving in the post-pandemic phase, there were actually no statistically significant differences (p = .772). Higher HA and HW were evident without fans during the pandemic compared to the pre-pandemic period when fans were present in women's professional basketball. During the post-pandemic period, HA decreased upon fans' return, while HW continued increasing. We discuss possible bases for these unexpected findings.

Early response to Tezepelumab in type-2 severe asthma patients non-responders to other biological treatments: a real-life study.

BACKGROUND: Biologic therapies play a crucial role in the treatment of severe asthma. Tezepelumab, a human monoclonal antibody (mAb), inhibits thymic stromal lymphopoietin, a pivotal factor in the pathophysiology of asthma. Although randomized clinical trials have demonstrated the efficacy of Tezepelumab, evidence gaps remain in real-world scenarios. OBJECTIVE: We sought investigate Tezepelumab's response in a clinical setting, focusing on patients who previously failed to other asthma mAbs. METHODS: Real-life study with severe uncontrolled asthma patients despite mAb treatment, requiring a switch to Tezepelumab. Follow-up was done four to six months after initiation of Tezepelumab. The primary endpoint was to evaluate the response in patients with poor response or intolerance to other mAbs. RESULTS: Nine patients were followed up during 7 months. Patients were predominantly middle-aged females with eosinophilic or eosinophilic-allergic phenotypes. Patients had a median failure rate of 2 mAbs (IQR 2-3), with an uncontrolled asthma (median of 2 severe exacerbations the previous year, airflow obstruction and 78% corticosteroid dependence). Tezepelumab demonstrated after 4 to 6 months of treatment reduce corticosteroid dependence (complete withdrawal in 2/7 patients), no exacerbations in 6/9, symptoms control improvement (Asthma Control Test score improved in 5/9) and modulate lung function (improving in 3/9 patients). These findings align with clinical trial results, suggesting Tezepelumab's potential in real-world settings. CONCLUSION: In real-world scenarios, despite the study's limitations, our results underscore Tezepelumab's promise as a therapeutic option for uncontrolled severe asthma, and may be useful for non-responders to other mAbs. Further studies are needed to corroborate these findings.

Hotspots of biogeochemical activity linked to aridity and plant traits across global drylands.

Perennial plants create productive and biodiverse hotspots, known as fertile islands, beneath their canopies. These hotspots largely determine the structure and functioning of drylands worldwide. Despite their ubiquity, the factors controlling fertile islands under conditions of contrasting grazing by livestock, the most prevalent land use in drylands, remain virtually unknown. Here we evaluated the relative importance of grazing pressure and herbivore type, climate and plant functional traits on 24 soil physical and chemical attributes that represent proxies of key ecosystem services related to decomposition, soil fertility, and soil and water conservation. To do this, we conducted a standardized global survey of 288 plots at 88 sites in 25 countries worldwide. We show that aridity and plant traits are the major factors associated with the magnitude of plant effects on fertile islands in grazed drylands worldwide. Grazing pressure had little influence on the capacity of plants to support fertile islands. Taller and wider shrubs and grasses supported stronger island effects. Stable and functional soils tended to be linked to species-rich sites with taller plants. Together, our findings dispel the notion that grazing pressure or herbivore type are linked to the formation or intensification of fertile islands in drylands. Rather, our study suggests that changes in aridity, and processes that alter island identity and therefore plant traits, will have marked effects on how perennial plants support and maintain the functioning of drylands in a more arid and grazed world.