(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.

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.

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.

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.

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.

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.

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.

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.

Development of a robotic cluster for automated and scalable cell therapy manufacturing.

BACKGROUND AIMS: The production of commercial autologous cell therapies such as chimeric antigen receptor T cells requires complex manual manufacturing processes. Skilled labor costs and challenges in manufacturing scale-out have contributed to high prices for these products. METHODS: We present a robotic system that uses industry-standard cell therapy manufacturing equipment to automate the steps involved in cell therapy manufacturing. The robotic cluster consists of a robotic arm and customized modules, allowing the robot to manipulate a variety of standard cell therapy instruments and materials such as incubators, bioreactors, and reagent bags. This system enables existing manual manufacturing processes to be rapidly adapted to robotic manufacturing, without having to adopt a completely new technology platform. Proof-of-concept for the robotic cluster's expansion module was demonstrated by expanding human CD8+ T cells. RESULTS: The robotic cultures showed comparable cell yields, viability, and identity to those manually performed. In addition, the robotic system was able to maintain culture sterility. CONCLUSIONS: Such modular robotic solutions may support scale-up and scale-out of cell therapies that are developed using classical manual methods in academic laboratories and biotechnology companies. This approach offers a pathway for overcoming manufacturing challenges associated with manual processes, ultimately contributing to the broader accessibility and affordability for personalized immunotherapies.

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.

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.

Predictive, preventive and personalised approach as a conceptual and technological innovation in primary and secondary care of inflammatory bowel disease benefiting affected individuals and populations.

Inflammatory bowel disease (IBD) is a global health burden which carries lifelong morbidity affecting all age groups in populations with the disease-specific peak of the age groups ranging between 15 and 35 years, which are of great economic importance for the society. An accelerating incidence of IBD is reported for newly industrialised countries, whereas stabilising incidence but increasing prevalence is typical for countries with a Westernised lifestyle, such as the European area and the USA. Although the aetiology of IBD is largely unknown, the interplay between the genetic, environmental, immunological, and microbial components is decisive for the disease manifestation, course, severity and individual outcomes. Contextually, the creation of an individualised patient profile is crucial for the cost-effective disease management in primary and secondary care of IBD. The proposed pathomechanisms include intestinal pathoflora and dysbiosis, chronic inflammation and mitochondrial impairments, amongst others, which collectively may reveal individual molecular signatures defining IBD subtypes and leading to clinical phenotypes, patient stratification and cost-effective protection against health-to-disease transition and treatments tailored to individualised patient profiles-all the pillars of an advanced 3PM approach. The paradigm change from reactive medical services to predictive diagnostics, cost-effective targeted prevention and treatments tailored to individualised patient profiles in overall IBD management holds a promise to meet patient needs in primary and secondary care, to increase the life-quality of affected individuals and to improve health economy in the area of IBD management. This article analyses current achievements and provides the roadmap for future developments in the area in the context of 3P medicine benefiting society at large.

Using the Mooney Space to Characterize the Non-Affine Behavior of Elastomers.

The formulation of the entropic statistical theory and the related neo-Hookean model has been a major advance in the modeling of rubber-like materials, but the failure to explain some experimental observations such as the slope in Mooney plots resulted in hundreds of micromechanical and phenomenological models. The origin of the difficulties, the reason for the apparent need for the second invariant, and the reason for the relative success of models based on the Valanis-Landel decomposition have been recently explained. From that insight, a new micro-macro chain stretch connection using the stretch tensor (instead of the right Cauchy-Green deformation tensor) has been proposed and supported both theoretically and from experimental data. A simple three-parameter model using this connection has been suggested. The purpose of this work is to provide further insight into the model, to provide an analytical expression for the Gaussian contribution, and to provide a simple procedure to obtain the parameters from a tensile test using the Mooney space or the Mooney-Rivlin constants. From different papers, a wide variety of experimental tests on different materials and loading conditions have been selected to demonstrate that the simple model calibrated only from a tensile test provides accurate predictions for a wide variety of elastomers under different deformation levels and multiaxial patterns.

RNA Expression of MMP12 Is Strongly Associated with Inflammatory Bowel Disease and Is Regulated by Metabolic Pathways in RAW 264.7 Macrophages.

Macrophage metalloelastase or matrix metalloproteinase-12 (MMP12) is a macrophage-specific proteolytic enzyme involved in the physiopathology of many inflammatory diseases, including inflammatory bowel disease. Although previously published data suggested that the modulation of MMP12 in macrophages could be a determinant for the development of intestinal inflammation, scarce information is available on the mechanisms underlying the regulation of MMP12 expression in those phagocytes. Therefore, in this study, we aimed to delineate the association of MMP12 with inflammatory bowel disease and the molecular events leading to the transcriptional control of this metalloproteinase. For that, we used publicly available transcriptional data. Also, we worked with the RAW 264.7 macrophage cell line for functional experiments. Our results showed a strong association of MMP12 expression with the severity of inflammatory bowel disease and the response to relevant biological therapies. In vitro assays revealed that the inhibition of mechanistic target of rapamycin complex 1 (mTORC1) and the stimulation of the AMP-activated protein kinase (AMPK) signaling pathway potentiated the expression of Mmp12. Additionally, AMPK and mTOR required a functional downstream glycolytic pathway to fully engage with Mmp12 expression. Finally, the pharmacological inhibition of MMP12 abolished the expression of the proinflammatory cytokine Interleukin-6 (Il6) in macrophages. Overall, our findings provide a better understanding of the mechanistic regulation of MMP12 in macrophages and its relationship with inflammation.

COSMIC-dFBA: A novel multi-scale hybrid framework for bioprocess modeling.

Metabolism governs cell performance in biomanufacturing, as it fuels growth and productivity. However, even in well-controlled culture systems, metabolism is dynamic, with shifting objectives and resources, thus limiting the predictive capability of mechanistic models for process design and optimization. Here, we present Cellular Objectives and State Modulation In bioreaCtors (COSMIC)-dFBA, a hybrid multi-scale modeling paradigm that accurately predicts cell density, antibody titer, and bioreactor metabolite concentration profiles. Using machine-learning, COSMIC-dFBA decomposes the instantaneous metabolite uptake and secretion rates in a bioreactor into weighted contributions from each cell state (growth or antibody-producing state) and integrates these with a genome-scale metabolic model. A major strength of COSMIC-dFBA is that it can be parameterized with only metabolite concentrations from spent media, although constraining the metabolic model with other omics data can further improve its capabilities. Using COSMIC-dFBA, we can predict the final cell density and antibody titer to within 10% of the measured data, and compared to a standard dFBA model, we found the framework showed a 90% and 72% improvement in cell density and antibody titer prediction, respectively. Thus, we demonstrate our hybrid modeling framework effectively captures cellular metabolism and expands the applicability of dFBA to model the dynamic conditions in a bioreactor.