The Efficacy of Intratissue Percutaneous Electrolysis (EPI®) and Nutritional Factors for the Treatment of Induced Tendinopathy in Wistar Rats: Hepatic Intermediary Metabolism Effects.

Achilles tendinopathy (TP) is characterized as the third most common disease of the musculoskeletal system, and occurs in three phases. There is currently no evidence of effective treatment for this medical condition. In this study, the modulatory effects of the minimally invasive technique intratissue percutaneous electrolysis (EPI) and combinations of EPI with four nutritional factors included in the diet, hydroxytyrosol (HT), maslinic acid (MA), glycine, and aspartate (AA), on hepatic intermediary metabolism was examined in Wistar rats with induced tendinopathy at various stages of TP. Results obtained showed that induced tendinopathy produced alterations in the liver intermediary metabolisms of the rats. Regarding carbohydrate metabolism, a reduction in the activity of pro-inflammatory enzymes in the later stages of TP was observed following treatment with EPI alone. Among the combined treatments using nutritional factors with EPI, HT+EPI and AA+EPI had the greatest effect on reducing inflammation in the late stages of TP. In terms of lipid metabolism, the HT+EPI and AA+EPI groups showed a decrease in lipogenesis. In protein metabolism, the HT+EPI group more effectively reduced the inflammatory effects of induced TP. Treatment with EPI combined with nutritional factors might help regulate intermediary metabolism in TP disease and reduce the inflammation process.

Content, educational value and quality analysis of videos about neurorehabilitation in people with multiple sclerosis on YouTube®. / Análisis de contenido, valor educativo y calidad de los vídeos sobre neurorrehabilitación de la esclerosis múltiple en YouTube®.

INTRODUCTION: The use of YouTube® has spread among patients with chronic diseases such as multiple sclerosis (MS). These patients consult the available videos to learn more about their disease in terms of diagnosis and making decisions about treatments, including rehabilitation. The aim of this study was to evaluate the content, educational value, and quality analysis of MS videos about neurorehabilitation on YouTube® using quantitative instruments. MATERIALS AND METHODS: A search was conducted on YouTube®. The first 30 videos that met the inclusion criteria were reviewed. The videos were classified according to the upload source and the content. All videos included in the review were assessed by the DISCERN questionnaire, the JAMA benchmark, the global quality scale (GQS) and the video information and quality index (VIQI). RESULTS: The mean scores were: 28.3 (±9.33) in DISCERN, 2 (±0.81) in JAMA, 2.57 (±1.22) in GQS, and 11.73 (±4.06) in VIQI. JAMA score statistically significantly differed according to upload source (p = 0.002), video content (p = 0.023) and the speaker (p = 0.002). The DISCERN, JAMA, GQS, and VIQI scores showed significant correlations with each other. CONCLUSIONS: The analyzed videos about neurorehabilitation in people with MS on YouTube® were quite old since the upload, with a moderate duration and number of views, but with a poor quality of the content, educational value, and quality analysis of the videos. Our research showed that there were statistically significant differences in terms of quality, transparency, and reliability of the information, depending on the upload source, video content and the speaker.

TITLE: Análisis de contenido, valor educativo y calidad de los vídeos sobre neurorrehabilitación de la esclerosis múltiple en YouTube®.Introducción. El uso de YouTube® se ha extendido entre los pacientes con enfermedades crónicas como la esclerosis múltiple (EM). Estos pacientes tienden a consultar los vídeos disponibles para aprender más sobre su enfermedad, en términos de diagnóstico y toma de decisiones sobre tratamientos, incluida la rehabilitación. El objetivo de este estudio fue evaluar el contenido, el valor educativo y el análisis de la calidad de los vídeos sobre neurorrehabilitación de la EM en la plataforma YouTube®, empleando instrumentos cuantitativos validados. Materiales y métodos. Se realizó una búsqueda en la plataforma YouTube®. Se revisaron los 30 primeros vídeos que cumplían los criterios de inclusión establecidos. Los vídeos se clasificaron según la fuente de subida y el contenido. Todos los vídeos incluidos en la revisión se evaluaron mediante el cuestionario DISCERN, el índice de referencia JAMA, la escala de calidad global (GQS) y el índice de información y calidad de vídeo (VIQI). Resultados. Las puntuaciones medias fueron: 28,3 (±9,33) en DISCERN, 2 (±0,81) en JAMA, 2,57 (±1,22) en GQS y 11,73 (±4,06) en VIQI. La puntuación en la escala JAMA difirió de forma estadísticamente significativa según la fuente de carga (p = 0,002), el contenido del vídeo (p = 0,023) y el perfil de la persona que lo ejecutaba (p = 0,002). Las puntuaciones en DISCERN, JAMA, GQS y VIQI mostraron correlaciones significativas entre sí. Conclusiones. Los vídeos analizados sobre neurorrehabilitación en personas con EM y que aparecen en la plataforma YouTube® eran bastante antiguos desde su fecha de subida, con una duración y un número de visualizaciones moderados, y con una calidad deficiente en su contenido, en su valor educativo y en el propio análisis de los mismos. Nuestra investigación mostró que había diferencias estadísticamente significativas en términos de calidad, transparencia y fiabilidad de la información, dependiendo de la fuente de subida, el contenido del vídeo y el perfil de la persona que lo ejecutaba.

Molecular dynamics simulations in pre-polymerization mixtures for peptide recognition.

CONTEXT: Molecularly imprinted polymers (MIPs) have promising applications as synthetic antibodies for protein and peptide recognition. A critical aspect of MIP design is the selection of functional monomers and their adequate proportions to achieve materials with high recognition capacity toward their targets. To contribute to this goal, we calibrated a molecular dynamics protocol to reproduce the experimental trends in peptide recognition of 13 pre-polymerization mixtures reported in the literature for the peptide toxin melittin. METHODS: Three simulation conditions were tested for each mixture by changing the box size and the number of monomers and cross-linkers surrounding the template in a solvent-explicit environment. Fully atomistic MD simulations of 350 ns were conducted with the AMBER20 software, with ff19SB parameters for the peptide, gaff2 parameters for the monomers and cross-linkers, and the OPC water model. Template-monomer interaction energies under the LIE approach showed significant differences between high-affinity and low-affinity mixtures. Simulation systems containing 100 monomers plus cross-linkers in a cubic box of 90 Å3 successfully ranked the mixtures according to their experimental performance. Systems with higher monomer densities resulted in non-specific intermolecular contacts that could not account for the experimental trends in melittin recognition. The mixture with the best recognition capacity showed preferential binding to the 13-26-α-helix, suggesting a relevant role for this segment in melittin imprinting and recognition. Our findings provide insightful information to assist the computational design of molecularly imprinted materials with a validated protocol that can be easily extended to other templates.

To what extent are ephippia of Mexican Anomopoda (Crustacea, Cladocera) identifiable?

Diapausing embryos encased within cladoceran ephippia result from sexual reproduction and increase genetic diversity. They are also important means by which species bypass harsh environmental conditions and disperse in space and time. Once released, ephippia usually sink to the benthos and remain there until hatching. Using the Sars' method (incubating sediments to identify cladoceran hatchlings), ephippial egg bank biodiversity can be evaluated. Yet, even when samples are incubated under a variety of conditions, it is not possible to warrant that all have hatched. Few keys are available that facilitate the identification of cladocerans by using only ephippial morphology. Our goal was to analyze some cladoceran ephippia from Mexico, to develop a means to identify them using easily recognizable characteristics. Ephippia of 23 cladoceran species from waters in Aguascalientes (México) in 11 genera (Alona, Biapertura, Ceriodaphnia, Chydorus, Daphnia, Dunhevedia, Ilyocryptus, Macrothrix, Moina, Pleuroxus, and Simocephalus) were analyzed. In our analysis six morphological features were selected that permitted the identification of ephippia to species(-group) level. The results demonstrate that with a proper catalog of features, some ephippia can be identified.

Radial extracorporeal shock wave therapy for the management of spasticity in cerebral palsy: study protocol for a randomized controlled trial.

Background: Spasticity is the most common motor disorder in cerebral palsy (CP), and its management is complex, posing a significant challenge for the rehabilitation team. Radial extracorporeal shock wave therapy (rESWT) has emerged in recent years as an effective, non-invasive, and low-risk alternative for the management of spasticity in CP patients, with only minor side effects such as small bruises or discomfort during application. There is great variability in rESWT administration protocols, ranging from a single session up to the 12 sessions. The most extensively studied protocol involves 3 rESWT sessions with a one-week interval between session. According to current literature, the effect of rESWT has not been investigated by extending the time interval between sessions beyond 1 week to determine if therapeutic effects on spasticity can be prolonged over time. Methods: Following a power calculation using the minimal clinical important difference of our primary outcome (R2 of Modified Tardieu Scale), 72 patients will be included in the study. Enrolment is based upon inclusion/exclusion criteria outlined in the Methods section. Participants will be randomized in 3 groups. Each patient will receive 2000 impulses in the Triceps Sural muscle (distributed by all the plantar flexor muscles: soleus and gastrocnemius), at a 2.2 Bars pressure and a frequency of 8 Hz. The Control Group will receive 3 rESWT sessions with a time interval of 1 week between each session. The Experimental Group A will receive 3 rESTW sessions with a time interval of 2 weeks between each session and the Experimental Group B will receive 3 rESTW sessions with a time interval of 4 weeks between each session. Discussion: This study will provide further information regarding the effect of rESWT on spasticity in patients with CP. If an increase in the time interval between rESWT sessions allows for the prolongation of therapeutic benefits on spasticity, it will be clinically relevant fact. With the same treatment dosage, patients will be able to benefit from its effects for a longer period of time. Clinical trial registration: ClinicalTrials.gov, identifier NCT05702606.

Slab melting boosts the mantle wedge contribution to Li-rich magmas.

The lithium cycling in the supra-subduction mantle wedge is crucial for understanding the generation of Li-rich magmas that may potentially source ore deposition in continental arcs. Here, we look from the mantle source perspective at the geological processes controlling the Li mobility in convergent margins, by characterizing a set of sub-arc mantle xenoliths from the southern Andes (Coyhaique, western Patagonia). The mineral trace element signatures and oxygen fugacity estimates (FMQ > + 3) in some of these peridotite xenoliths record the interaction with arc magmas enriched in fluid-mobile elements originally scavenged by slab dehydration. This subduction-related metasomatism was poorly effective on enhancing the Li inventory of the sub-arc lithospheric mantle, underpinning the inefficiency of slab-derived fluids on mobilizing Li through the mantle wedge. However, major and trace element compositions of mantle minerals in other xenoliths also record transient thermal and chemical anomalies associated with the percolation of slab window-related magmas, which exhibit an "adakite"-type geochemical fingerprint inherited by slab-derived melts produced during ridge subduction and slab window opening event. As these melts percolated through the shallow (7.2-16.8 kbar) and hot (952-1054 °C) lithospheric mantle wedge, they promoted the crystallization of metasomatic clinopyroxene having exceptionally high Li abundances (6-15 ppm). Numerical modeling shows that low degrees (< 10%) of partial melting of this Li-rich and fertile sub-arc lithospheric mantle generates primitive melts having two-fold Li enrichment (~13 ppm) compared with average subduction-zone basalts. Prolonged fractional crystallization of these melts produces extremely Li-enriched silicic rocks, which may stoke the Li inventory of mineralizing fluids in the shallow crust.

Experiences of patients, parents, and healthcare professionals in the process of transitioning from hospital to community after inpatient pediatric rehabilitation among children with special health care needs.

PURPOSE: Children with Special Health Care Needs (CSHCN) may experience disruptions in education due to extended hospitalizations. The purpose of this study was to describe how CSHCN experience educational supports during inpatient rehabilitation and identify the ongoing challenges when planning to return to school. MATERIALS AND METHODS: Semi-structured focus groups were conducted with parents (n = 12), former patients (n = 20), and rehabilitation professionals (n = 8). RESULTS: Through qualitative thematic analysis based on descriptive phenomenology, we developed three themes: 1) Inpatient educational support such as instruction and schoolwork helped reduce the learning loss during hospitalization. However, these supports were sometimes complicated by lags in school approvals and challenges in coordination between systems. 2) Transition planning involved establishing necessary services to support CSHCN's educational and healthcare needs at school re-entry. However, families reported limited information and guidance as key barriers. 3) Dynamic courses of school re-entry required continued support after discharge. The participants recommended that reassessment and adjustment of transition plans were often necessary to account for evolving developmental and educational needs but were not always received. CONCLUSIONS: There is an ongoing need to improve communication between clinicians and educators, information for families, and long-term follow-up on the changing educational needs for CSHCN after rehabilitation.

School re-entry after extended hospitalization is challenging for children with special health care needs (CSHCN) due to school disruption, social disconnection, and change in functional abilities.The hospital-to-school transition processes include inpatient educational programs during hospitalization, pre-discharge transition planning, and the subsequent implementation and adjustment of transition plans to facilitate individualized school re-entry.Key areas in need of improving school re-entry include coordination between the hospital and school about rehabilitation and educational goals and information provided to families about transition processes, particularly for newly acquired health conditions.A common need expressed by parents and CSHCN is to simplify and accelerate the process to establish services that support children's educational and healthcare needs.

STOP-Bang questionnaire in patients hospitalized with acute symptomatic pulmonary embolism.

STUDY OBJECTIVES: The STOP-Bang questionnaire is a validated screening tool for obstructive sleep apnea (OSA). We conducted this study to validate it among patients hospitalized with acute symptomatic pulmonary embolism (PE). METHODS: This prospective cohort study enrolled consecutive stable patients with acute PE who underwent an overnight sleep study within 7 days after diagnosis. Our outcomes were: i) the STOP-Bang questionnaire's utility for risk stratification, ii) the discrimination of the STOP-Bang questionnaire categories, iii) the false negative rate of STOP-Bang questionnaire prediction, and iv) the clinical utility of the STOP-Bang questionnaire to exclude OSA. We also calculated the test performance characteristics to predict OSA. RESULTS: During the study period, 268 patients completed a sleep study. OSA was found in 47% of patients. OSA incidence in low-, moderate-, and high-risk STOP-Bang groups was 22.4%, 48.2%, and 61.5%, respectively (P <0.001). The area under the receiver operating characteristics curve of the STOP-Bang questionnaire for risk of OSA was 0.65. The false negative rate of a low-risk STOP-Bang questionnaire result to rule out OSA was 22.4% and the clinical utility was 21.6%. The sensitivity was 89.8% (97.2% for men and 80.4% for women). CONCLUSIONS: The STOP-Bang questionnaire showed poor discrimination for the risk of OSA in hospitalized patients with acute symptomatic PE. It had a high false negative rate and a low clinical utility. The STOP-Bang questionnaire had a good sensitivity in men, and might be used to rule out OSA in this population.

Quantifying Siglec-sialylated ligand interactions: a versatile 19F-T2 CPMG filtered competitive NMR displacement assay.

Sialic-acid-binding immunoglobulin-like lectins (Siglecs) are integral cell surface proteins crucial for the regulation of immune responses and the maintenance of immune tolerance through interactions with sialic acids. Siglecs recognize sialic acid moieties, usually found at the end of N-glycan and O-glycan chains. However, the different Siglecs prefer diverse presentations of the recognized sialic acid, depending on the type of glycosidic linkage used to link to the contiguous Gal/GalNAc or sialic acid moieties. This fact, together with possible O- or N-substitutions at the recognized glycan epitope significantly influences their roles in various immune-related processes. Understanding the molecular details of Siglec-sialoglycan interactions is essential for unraveling their specificities and for the development of new molecules targeting these receptors. While traditional biophysical methods like isothermal titration calorimetry (ITC) have been utilized to measure binding between lectins and glycans, contemporary techniques such as surface plasmon resonance (SPR), microscale thermophoresis (MST), and biolayer interferometry (BLI) offer improved throughput. However, these methodologies require chemical modification and immobilization of at least one binding partner, which can interfere the recognition between the lectin and the ligand. Since Siglecs display a large range of dissociation constants, depending on the (bio)chemical nature of the interacting partner, a general and robust method that could monitor and quantify binding would be highly welcomed. Herein, we propose the application of an NMR-based a competitive displacement assay, grounded on 19F T2-relaxation NMR and on the design, synthesis, and use of a strategic spy molecule, to assess and quantify sialoside ligand binding to Siglecs. We show that the use of this specific approach allows the quantification of Siglec binding for natural and modified sialosides, multivalent sialosides, and sialylated glycoproteins in solution, which differ in binding affinities in more than two orders of magnitude, thus providing invaluable insights into sialoglycan-mediated interactions.

Cognitive functioning in patients with neuro-PASC: the role of fatigue, mood, and hospitalization status.

This study sought to characterize cognitive functioning in patients with neurological post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) and investigate the association of subjective and objective functioning along with other relevant factors with prior hospitalization for COVID-19. Participants were 106 adult outpatients with Neuro-PASC referred for abbreviated neuropsychological assessment after scoring worse than one standard deviation below the mean on cognitive screening. Of these patients, 23 had been hospitalized and 83 had not been hospitalized for COVID-19. Subjective cognitive impairment was evaluated with the self-report cognition subscale from the Patient-Reported Outcome Measurement Information System. Objective cognitive performance was assessed using a composite score derived from multiple standardized cognitive measures. Other relevant factors, including fatigue and depression/mood symptoms, were assessed via the Patient-Reported Outcome Measurement Information System. Subjective cognitive impairment measures exceeded the minimal difficulties noted on objective tests and were associated with depression/mood symptoms as well as fatigue. However, fatigue independently explained the most variance (17.51%) in patients' subjective cognitive ratings. When adjusting for fatigue and time since onset of COVID-19 symptoms, neither objective nor subjective impairment were associated with prior hospitalization for COVID-19. Findings suggest that abbreviated neuropsychological assessment may not reveal objective difficulties beyond initial cognitive screening in patients with Neuro-PASC. However, subjective cognitive concerns may persist irrespective of hospitalization status, and are likely influenced by fatigue and depression/mood symptoms. The impact of concomitant management of fatigue and mood in patients with Neuro-PASC who report cognitive concerns deserve further study.

Value of nutritional indices in predicting survival free from pump replacement and driveline infections in centrifugal left ventricular assist devices.

Objective: There is a paucity of data assessing the impact of nutritional status on outcomes in patients supported with the HeartMate 3 (HM3) left ventricular assist device (LVAD). Methods: Patients ≥18 years of age who underwent HM3 LVAD implantation between 2015 and 2020 were identified from a single tertiary care center. The primary outcome assessed was death or device replacement. A secondary outcome of driveline infection was also evaluated. Kaplan-Meier survival analysis and a multivariate Cox-proportional hazards model were used to identify predictors of outcome. Results: Of the 289 patients identified, 94 (33%) experienced a primary outcome and 96 (33%) a secondary outcome during a median follow-up time of 2.3 years. Independent predictors of the primary outcome included peripheral vascular disease (hazard ratio [HR], 3.40; 95% confidence interval [CI], 1.66-6.97, P < .01), diabetes mellitus (HR, 0.46; 95% CI, 0.27-0.80, P < .01), body mass index ≥40 kg/m2 (HR, 2.63 per 1 kg/m2 increase; 95% CI, 1.22-5.70, P < .05), preoperative creatinine level (HR, 1.86 per 1 mg/dL increase; 95% CI, 1.31-2.65, P < .01), and preoperative prognostic nutritional index (PNI) score (HR, 0.88 per 1-point increase; 95% CI, 0.81-0.96, P < .01). Independent predictors of driveline infection included age at the time of implantation (HR, 0.97; 95% CI, 0.96-0.99, P < .01) and diabetes mellitus (HR, 1.79; 95% CI, 1.17-2.73, P < .01). Conclusions: Preoperative PNI scores may independently predict mortality and the need for device replacement in patients with HM3 LVAD. Routine use of the PNI score during preoperative evaluation and, when possible, supplementation to PNI >33, may be of value in this population.

Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy.

Introduction: Scarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era. Purpose: To assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting. Methods: A retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed. Results: Nearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality. Conclusions: The results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.

Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors.

PURPOSE: Access to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis. METHODS: Three-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021. RESULTS: Included were 10,025 HCT recipients (7,272 recipients of MUD with CNI, 1,681 MUD with PTCy, 613 MMUD with CNI, and 459 MMUD with PTCy) who underwent HCT for acute leukemia (70.9%) or myelodysplastic syndromes (29.2%). Median patient age was 60.7 years (range, 18.0-82.7) and median follow-up was 36.6 (range, 3.0-77.8) months. When compared with MUD HCT with PTCy, MMUD HCT with PTCy had similar OS (hazard ratio [HR], 0.96 [95% CI, 0.823 to 1.11]; P = .60) and GRFS (HR, 0.90 [0.79 to 1.02]; P = .1). When compared with MUD HCT with CNI, OS was improved after MUD HCT with PTCy (HR, 0.88 [0.80 to 0.96]; P = .004) and GRFS was improved with PTCy after either MUD (HR, 0.61 [0.57 to 0.66]; P < .0001) or MMUD (HR, 0.68 [0.60 to 0.76]; P < .0001) HCT. Benefit from PTCy was independent of patient ancestry. Global registry level analysis demonstrated that inclusion of MMUD increased donor availability regardless of recipient ancestry. CONCLUSION: Use of PTCy results in comparable OS and GRFS using either MUD or MMUD HCT, expanding access to HCT for patients from all racial and ethnic ancestry groups.

Precision oncology and systemic targeted therapy in Pseudomyxoma Peritonei.

PURPOSE: Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains the mainstay of treatment but disease recurrence and death after relapse frequently occur in PMP patients. New therapeutic strategies are therefore urgently needed for these patients. EXPERIMENTAL DESIGN: A total of 120 PMP samples from 50 patients were processed to generate a collection of 50 patient-derived organoids (PDO) and xenograft (PDX) models. Whole exome sequencing (WES), immunohistochemistry analyses and in vitro and in vivo drug efficacy studies were performed. RESULTS: In this study, we have generated a collection of PMP preclinical models and identified druggable targets, including BRAFV600E, KRASG12C and KRASG12D,that could also be detected in intra-abdominal mucin biopsies of PMP patients using droplet digital PCR. Preclinical models preserved the histopathological markers from the original patient sample. The BRAFV600E inhibitor encorafenib reduced cell viability of BRAFV600E PMP-PDO models. Proof-of-concept in vivo experiments showed that a systemic treatment with encorafenib significantly reduced tumor growth and prolonged survival in subcutaneous and orthotopic BRAFV600E-PMP-PDX mouse models. CONCLUSIONS: Our study demonstrates for the first time that systemic targeted therapies can effectively control PMP tumors. BRAF signaling pathway inhibition represents a new therapeutic opportunity for BRAFV600E PMP patients who have a poor prognosis. Importantly, our present data and collection of preclinical models pave the way for evaluating the efficacy of other systemic targeted therapies toward extending the promise of precision oncology to PMP patients.

[Self-care education during Cardiac Rehabilitation programs for patients with Heart Failure with preserved Ejection Fraction: a Delphi Study]. / Educación en autocuidado durante programas de rehabilitación cardiaca para pacientes con insuficiencia cardiaca con fracción de eyección preservada: estudio Delphi.

OBJECTIVES: To develop a decalogue of self-care competencies to manage educational intervention during Cardiac Rehabilitation (CR) programs in Heart Failure with preserved Ejection Fraction (HFpEF) patients through multidisciplinary consensus. DESIGN: 3-round e-Delphi study using an initial questionnaire of 23 competencies based on the main recommendations of the CR and self-care guidelines. SITE: It was framed under the ethics of a randomised clinical trial developed at the Regional Hospital of Malaga. The survey was designed and disseminated as an online questionnaire. PARTICIPANTS: The expert panel comprised two patients with HFpEF and 13 healthcare professionals from Internal Medicine (n=3), Cardiology (n=2), Physiotherapy (n=3), Nursing (n=3) and Occupational Therapy (n=2). METHOD: The analysis of results included the content validity index, the percentage of agreement, and the concordance using Fleiss Kappa and Krippendorff's alpha. RESULTS: After the third round, 20 self-care competencies were identified, grouped into 12 domains, with sufficient consensus for their inclusion in the decalogue. CONCLUSIONS: The decalogue of self-care competencies generated from the multidisciplinary consensus guides education in patients with HFpEF, systematically addressing educational content tailored to patients for clinical practice in CR programs.

"I have not been doing it because of my fear of something happening." Exploring perspectives on healthy dietary behaviors and physical activity in Mexican pregnant women and health care professionals: A qualitative study.

OBJECTIVES: Mexico exhibits one of the highest prevalence rates of overweight and obesity globally, accompanied by a surge in non-communicable diseases, which in turn leads to elevated mortality rates. Existing efforts to address rising obesity rates have shown limited effectiveness. Maternal weight, diet, and physical activity (PA) during pregnancy affect the mother's and offspring's health. Despite the importance of establishing and engaging in healthy behaviors during pregnancy, little is known about which factors impact these behaviors among pregnant women in Mexico. This study explored perspectives on factors impacting healthy dietary behaviors and PA in pregnancy from pregnant women and health care professionals in Mexico. METHODS: We conducted semistructured interviews with 11 pregnant women and 12 health care professionals working in prenatal care. Data were analyzed using qualitative content analysis in a stepwise inductive approach. RESULTS: Classifying factors at the 1) individual level, 2) relational level, and 3) health care system level, three overall themes emerged. At the individual level, challenges with lack of time and competing priorities as well as knowledge of healthy dietary behaviors and PA were identified. At the relational level, influencing factors encompassed financial, social, and emotional support along with descriptive norms. At the health care system level, guidelines for PA during pregnancy and the quality of care were noted. CONCLUSIONS: This study identified factors impacting healthy dietary behaviors and PA in pregnancy in Mexico. Important considerations for future interventions include addressing sociocultural norms around healthy dietary behaviors and PA in pregnancy and involving pregnant women's families, closest social networks, and health care professionals working at the prenatal care unit.

Thoracoscopic removal of cranial mediastinal masses in dogs is associated with a low conversion rate, excellent survival to discharge, and good long-term outcome.

OBJECTIVE: To report the complications and outcomes associated with thoracoscopic cranial mediastinal mass resection in dogs. ANIMALS: 49 client-owned dogs that underwent thoracoscopic cranial mediastinal mass removal. METHODS: This was a retrospective cohort study (January 1, 2014, to July 31, 2023), and the medical records of 49 client-owned dogs that underwent thoracoscopic cranial mediastinal mass removal were reviewed. The signalment, history, clinicopathologic features, perioperative complications, and long-term outcome were recorded. RESULTS: Preoperative myasthenia gravis (MG) and megaesophagus (ME) were identified in 17 of 49 (35%) dogs and 11 of 49 (22%) dogs, respectively. The median maximal tumor diameter on CT images was 4.7 cm (range, 2.7 to 8.5 cm). Nonemergent conversion to an open procedure was necessary in 4 of 49 (8%) dogs, and dogs with conversion to an open procedure had a significantly larger median maximal CT tumor diameter than dogs without conversion (P = .03). The most common tumor type was thymoma (37/49 [76%]). The overall median survival time for dogs with thymoma was 1,102 days (95% CI, 482 to upper bound not reached). The median survival time for dogs with thymoma and concurrent presurgical MG was 182 days (95% CI, 14 to upper bound not reached). Presurgical diagnosis of MG (P = .44) or ME (P = .69) was not associated with survival time. CLINICAL RELEVANCE: Thoracoscopic removal of cranial mediastinal masses was associated with low conversion and complication rates. Long-term survival is possible, and thoracoscopic removal should be considered for select cases.

Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens.

The dimeric architecture of tandem-repeat type galectins, such as galectin-4 (Gal-4), modulates their biological activities, although the underlying molecular mechanisms have remained elusive. Emerging evidence show that tandem-repeat galectins play an important role in innate immunity by recognizing carbohydrate antigens present on the surface of certain pathogens, which very often mimic the structures of the human self-glycan antigens. Herein, we have analyzed the binding preferences of the C-domain of Gal-4 (Gal-4C) towards the ABH-carbohydrate histo-blood antigens with different core presentations and their recognition features have been rationalized by employing a combined experimental approach including NMR, solid-phase and hemagglutination assays and molecular modeling. The data show that Gal-4C prefers A- over B-antigens (twofold in affinity), contrary to the N-domain (Gal-4N), although both domains share the same preference for the type-6 presentations. The behavior of the full-length tandem-repeat form (Gal-4FL) has been additionally scrutinized. ITC and NMR data demonstrate that both domains within Gal-4FL bind to the histo-blood antigens independently of each other, with no communication between them. In this context, the heterodimeric architecture does not play any major role, apart from the complementary A and B-antigen binding preferences. However, upon binding to a bacterial lipopolysaccharide (LPS) containing a multivalent version of an H-antigen mimetic as O-antigen, the significance of the galectin architecture was revealed. Indeed, our data point to the linker peptide domain and the F-face of the C-domain as key elements that provide Gal-4 with the ability to cross link multivalent ligands, beyond the glycan binding capacity of the dimer.