Ruptured aortic aneurysm in an adolescent with systemic lupus erythematosus. / Ruptura de aneurisma de aorta en una adolescente con lupus eritematoso sistémico.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease. Cardiovascular involvement is frequent; however, aneurysm and/or aortic dissection are rare entities with fatal evolution. The objective is to describe a rare and fatal complication of SLE in pediatrics and review the literature. We present the case of a 16-year-old girl with SLE with multisystem involvement without cardiovascular disease at diagnosis. She consulted for severe chest pain. Chest X-ray showed a dilated aortic arch with no cardiomegaly. The presence of a dissection was suspected, and an angiotomography was performed. A descending aortic aneurysm without a dissection flap was confirmed. Antihypertensive treatment was started. After a Valsalva maneuver, she presented an aneurysmal rupture. She died 12 hours after admission. Aneurysm and dissection are infrequent complications in pediatric SLE. As they have high mortality, it is essential to consider them in a patient with SLE and chest pain.

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, multisistémica y crónica. La afectación cardiovascular es frecuente, sin embargo, el aneurisma y/o la disección de aorta son entidades raras de evolución fatal. El objetivo es describir una complicación poco frecuente y fatal del LES en pediatría, y realizar una revisión de la literatura. Se presenta el caso de una mujer de 16 años con LES con afectación multisistémica, sin compromiso cardiovascular al diagnóstico. Consultó por dolor torácico grave. Radiografía de tórax sin cardiomegalia, con arco aórtico dilatado. Ante la sospecha de disección, se efectuó angiotomografía. Se confirmó aneurisma de aorta descendente sin flap de disección. Inició tratamiento antihipertensivo. Ante una maniobra de Valsalva, presentó ruptura aneurismática. Falleció a las 12 horas de su ingreso. El aneurisma y/o disección son complicaciones muy poco frecuentes en LES pediátrico. Al tener elevada mortalidad, es importante considerarlos ante un paciente con LES y dolor torácico.

Influence of maternal health status during pregnancy and the child´s medical history on molar-incisor hypomineralization in a group of Spanish children (aged 6-14 years): a retrospective case-control study.

BACKGROUND: Molar-incisor hypomineralization (MIH) is a qualitative enamel defect that is highly prevalent in children. It has been reported that patients with MIH have higher caries occurrence with an increased need and frequency of dental treatment compared to patients without MIH. The objective of this study was to analyze the association between MIH and a series of factors related to maternal health status during pregnancy and children´s medical history in early childhood. METHODS: A retrospective study of cases (patients with MIH) and controls (patients without MIH) was designed between 2023 and 2024. A total of 280 children (cases = 140; controls = 140) aged 6 to 14 years (138 boys and 142 girls) were examined according to the European Academy of Pediatric Dentistry (EAPD) criteria for MIH. A survey was carried out with mothers regarding the potential exposure of their children to etiological factors of MIH. Possible prenatal and postnatal etiological factors were obtained through a personal interview with the patients' mothers. The statistical analysis was carried out with the contrast test and the chi-square test. RESULTS: During pregnancy, folic acid consumption, alcohol intake, systemic viral and/or bacterial infections, and gestational diabetes were statistically significantly related to MIH, as were breastfeeding, asthma, and corticosteroid consumption during childhood. CONCLUSIONS: Although there are different factors that may have statistically significant relationships with MIH, they cannot be predicted. Therefore, longitudinal studies, with a large sample size, are needed to determine the influence of prenatal and postnatal factors on the prevalence and severity of MIH in children.

Paleoenvironmental characterization and historical trends of polycyclic aromatic hydrocarbons (PAHs) of Nutrias Lagoon, Uruguay.

Concentrations of polycyclic aromatic hydrocarbons were assessed in a sediment core retrieved from Nutrias Lagoon, located within the Rocha Lagoon Protected Area along the SE Uruguayan coast. Using a 210Pb chronology, we reconstructed the historical accumulation of polycyclic aromatic hydrocarbons over the past 123 years (1895-2018). This study, the first of its kind in Uruguay, fills a research gap in understanding historical PAH accumulation and source changes. Our examination of dating, geochemical, and sedimentological data unveiled four main events, with minor instances in 1956±5 and 1964±4, and more significant occurrences in 1914±9 and 1997±2. Additionally, two prominent trend shifts were identified, one predating 1900 and the other in 1986±2. Before 1900, a dry spell was apparent, supported by all proxies, alongside a notable surge in heavy polycyclic aromatic hydrocarbons, likely attributed to fires during this arid period. Post-1986±2, a rise in sedimentation rates in the lagoon was observed, possibly due to increased rainfall. Also, the eutrophication of the lagoon over the years can be observed. Furthermore, a recent increase in polycyclic aromatic hydrocarbons influx at the core's surface was linked to the construction of a nearby lagoon bridge and associated roadwork. Our findings suggest that atmospheric deposition constitutes the primary source of polycyclic aromatic hydrocarbons in the lagoon, offering insights into its recent environmental history and basin dynamics. This study establishes a critical baseline for future research in the region and facilitates the development of effective and sustainable environmental management strategies.

International review of blood donation screening for anti-HBc and occult hepatitis B virus infection.

BACKGROUND: Hepatitis B core antibody (anti-HBc) screening has been implemented in many blood establishments to help prevent transmission of hepatitis B virus (HBV), including from donors with occult HBV infection (OBI). We review HBV screening algorithms across blood establishments globally and their potential effectiveness in reducing transmission risk. MATERIALS AND METHODS: A questionnaire on HBV screening and follow-up strategies was distributed to members of the International Society of Blood Transfusion working party on transfusion-transmitted infectious diseases. Screening data from 2022 were assimilated and analyzed. RESULTS: A total of 30 unique responses were received from 25 countries. Sixteen respondents screened all donations for anti-HBc, with 14 also screening all donations for HBV DNA. Anti-HBc prevalence was 0.42% in all blood donors and 1.19% in new donors in low-endemic countries; however, only 44% of respondents performed additional anti-HBc testing to exclude false reactivity. 0.68% of anti-HBc positive, HBsAg-negative donors had detectable HBV DNA. Ten respondents did universal HBV DNA screening without anti-HBc, whereas four respondents did not screen for either. Deferral strategies for anti-HBc positive donors were highly variable. One transfusion-transmission from an anti-HBc negative donor was reported. DISCUSSION: Anti-HBc screening identifies donors with OBI but also results in the unnecessary deferral of a significant number of donors with resolved HBV infection and donors with false-reactive anti-HBc results. Whilst confirmation of anti-HBc results could be improved to reduce donor deferral, transmission risks associated with anti-HBc negative OBI donors must be considered. In high-endemic areas, highly sensitive HBV DNA testing is required to identify infectious donors.

Association Between Accelerometer-Assessed Physical Activity and Cognitive Function in Older Adults: A Cross-Sectional Study.

OBJECTIVE: Research suggests that physical activity (PA) improves cognitive function across various domains. However, the specific role of different PA measures, including step count, remains to be explored. Our aim was to assess the correlation between objectively measured PA and cognitive function. METHODS: We included 663 adults, aged ≥66 years, from the Swedish SNAC-K study (2016-2019). Global cognition and three cognitive domains (processing speed, executive function, and episodic memory) were assessed with validated tests. PA was measured through ActivPAL3 accelerometers. We applied age-stratified (<70 vs. ≥80 years), multi-adjusted, quantile regression to examine the cross-sectional associations between cognitive function and PA, considering steps/day and time spent in moderate-to-vigorous PA (MVPA). RESULTS: Each 1000-step increment (ß = 0.04; 95% CI: 0.01, 0.07) and each additional hour of MVPA per day (ß = 0.28; 95% CI: 0.02, 0.54) were correlated with better processing speed in the youngest-old, but not in the oldest-old. When further stratifying by MVPA (<60 min vs. ≥60 min/week), each 1000-step increment was associated with better processing speed in the youngest-old, regardless of their MVPA levels. CONCLUSION: Our study links accelerometer-assessed PA (steps and MVPA) with better processing speed in the youngest-old adults. Step count correlated with processing speed regardless of intensity. Further research is needed to determine the directionality of these associations.

Stability and Spin Waves of Skyrmion Tubes in Curved FeGe Nanowires.

In this work, we investigate the influence of curvature on the dynamic susceptibility in FeGe nanowires, both curved and straight, hosting a skyrmionic tube texture under the action of an external bias field, using micromagnetic simulations. Our results demonstrate that both the resonance frequencies and the number of resonant peaks are highly dependent on the curvature of the system. To further understand the nature of the spin wave modes, we analyze the spatial distributions of the resonant mode amplitudes and phases, describing the differences among resonance modes observed. The ability to control the dynamic properties and frequencies of these nanostructures underscores their potential application in frequency-selective magnetic devices.

Onasemnogene-abeparvovec administration to premature infants with spinal muscular atrophy.

Twin girls born at 30 weeks' gestation with spinal muscular atrophy (SMA) received onsasemnogene-abeparvovec (OA) at 3.5 weeks of life. They had no treatment-related adverse events, normal acquisition of motor milestones, and normal neurological examination at 19 months. Genotyping revealed 0 copies of SMN1 and a single, hybrid SMN2 gene containing the positive genetic modifier c.835-44A>G. This was associated with full-length SMN2 blood mRNA expression levels similar to a 2 copy SMA infant. The observed favorable outcomes are likely due to the genetic modifier combined with early drug administration enabled by prematurity.

Geriatric conditions and invasive management in frail patients with NSTEMI. A subgroup analysis of a randomized clinical trial.

INTRODUCTION AND OBJECTIVES: Invasive management in frail patients with non-ST-segment elevation myocardial infarction (NSTEMI) remains controversial. We investigated the impact of various geriatric conditions. METHODS: The MOSCA-FRAIL trial included 167 adults aged ≥ 70 years with frailty (Clinical Frailty Scale [CFS] ≥ 4 points) and NSTEMI, who were randomized to either an invasive (n=84) or conservative (n=83) strategy. In addition to frailty, we measured activities of daily living (Barthel index), cognitive impairment (Pfeiffer test), and comorbidities (Charlson index). The primary endpoint was the difference (invasive minus conservative) in restricted mean survival time (RMST) for all-cause mortality at a median follow-up of 3.9 years. RESULTS: A total of 93 patients died. The RMST difference favored invasive management at the CFS 25th percentile (CFS=4; 157 days, 95%CI, 18-295; P=.027), which changed to a nonsignificant effect at the 50th and 75th percentiles. The RMST difference remained nonsignificant, irrespective of the severity of other geriatric assessments. In time-to-event analysis, invasive management was associated with an initially lower life expectancy, peaking at around 1 year, among all subgroups. However, patients with CFS=4 experienced a benefit at the end of follow-up (181 days, 95%CI, 19-343), whereas those with CFS >4 did not (-16 days, 95%CI, -217 to 186; interaction P=.16). Subgroups defined by other geriatric markers showed a similar time-dependent trend, albeit with weaker statistical interaction. CONCLUSIONS: Among adults with frailty and NSTEMI, the CFS might be useful for evaluating the relative risks and benefits of invasive management. A CFS >4 could serve as a valuable threshold for decision-making.

Can the Location of the Iris Claw Lens Influence the Development and Timing of Pseudophakic Macular Edema?

Purpose: This study aims to analyze the incidence of pseudophakic macular edema (PME) and the role of contributing risk factors following prepupillary or retropupillary implantation of iris-claw lenses. Methods: This retrospective cohort study included patients who underwent iris-claw intraocular lens implantation over a 16-year period at the University Hospital of Santiago de Compostela, Spain. The presence of risk factors for PME was recorded, and surgical outcomes included visual acuity, macular OCT scans, and description of complications. Results: A total of 148 eyes from 147 patients were included. Seventy-nine eyes (54.4%) underwent prepupillary iris-claw lens implantation and 69 eyes (46.6%) underwent retropupillary implantation. The mean age of the patients was 68.9 ± 17.2 years. The incidence of PME post-surgery was 23.0% (26.6% prepupillary and 18.8% retropupillary), and the mean time between surgery and diagnosis was similar for both locations (4.8 and 4.7 months, respectively). PME recurred in 33% of the patients, reaching a high rate of 72.7% when the lens location was prepupillary. The mean best-corrected visual acuity was 0.66±0.55 logMAR preoperatively and 0.38±0.50 logMAR postoperatively. Postoperative complications occurred in 29 patients (19.6%). Conclusion: PME following iris-claw lens implantation tends to be more frequent and recurrent when the location is prepupillary. Planning for iris-claw lens surgery should consider the risk factors for the development of PME.

[Systematic review on the efficacy and safety of cytisine against nicotine dependence]. / Revisión sistemática sobre la eficacia y seguridad de la citisina contra la dependencia de nicotina.

Introduction: Tobacco is one of the main causes of preventable mortality in our environment, in addition to having been correlated with numerous diseases. Smoking cessation improves health status and life expectancy. Pharmacological treatment of smoking cessation increases the likelihood that patient will successfully quit smoking. Method and design: A search was carried out in the PubMed and UpToDate databases, obtaining a total of 11 systematic reviews or meta-analyses published in the last five years. After applying inclusion criteria and reading summaries, 5 total articles were obtained for the final review. Results and discussion: Cytisine is a safe and effective treatment for smoking cessation. The most effective treatment in the clinical trials reviewed is varenicline associated with nicotine replacement therapy.There is less evidence collected on cytisine treatment, but it shows that it is also an effective therapy in smoking cessation, also demonstrating its usefulness in the long term. In addition, therapy with cytisine seems to entail fewer adverse effects than treatment with varenicline.

Expanding Xpert MTB/RIF Ultra® and LF-LAM testing for diagnosis of tuberculosis among HIV-positive adults admitted to hospitals in Tanzania and Mozambique: a randomized controlled trial (the EXULTANT trial).

INTRODUCTION: Tuberculosis (TB) is an important cause of morbidity and mortality among people living with HIV (PLHIV). Current WHO-recommended strategies for diagnosing TB among hospitalized PLHIV rely on symptom screening and disease severity to assess eligibility for urine lipoarabinomannan lateral flow (LF-LAM) and molecular testing. Despite these recommendations, autopsy studies show a large burden of undiagnosed TB among admitted PLHIV. The EXULTANT trial aims to assess the impact of an expanded screening strategy using three specimens (sputum, stool, and urine) for TB diagnosis among PLHIV admitted to hospitals in two high HIV and TB burden African countries. METHODS: This is a multicenter, pragmatic, individually randomized controlled trial conducted across eleven hospitals in Tanzania and Mozambique. Participants in the intervention arm will be tested with Xpert MTB/RIF Ultra® from expectorated sputum, stool, and urine samples, with additional urine LF-LAM testing in the first 24 h after hospital admission, irrespective of the presence of the symptoms. The control arm will implement the WHO standard of care recommendations. Hospitalized adults (≥ 18 years) with a confirmed HIV-diagnosis, irrespective of antiretroviral (ART) therapy status or presence of TB symptoms will be assessed for eligibility at admission. Patients with a pre-existing TB diagnosis, those receiving anti-tuberculosis therapy or tuberculosis preventive treatment in the 6 months prior to enrolment, and those transferred from other hospitals will not be eligible. Also, participants admitted for traumatic reasons such as acute abdomen, maternal conditions, scheduled surgery, having a positive SARS-CoV2 test will be ineligible. The primary endpoint is the proportion of participants with microbiologically confirmed TB starting treatment within 3 days of enrolment. DISCUSSION: The EXULTANT trial investigates rapid implementation after admission of a new diagnostic algorithm using Xpert MTB/RIF Ultra® in several non-invasive specimens, in addition to LF-LAM, in hospitalized PLHIV regardless of TB symptoms. This enhanced strategy is anticipated to detect frequently missed TB cases in this population and is being evaluated as an implementable and scalable intervention. TRIAL REGISTRATION: Trial reference number: NCT04568967 (ClinicalTrials.gov) registered on 2020-09-29.

Global Dynamics of Gastrointestinal Colonisations and Antimicrobial Resistance: Insights from International Travellers to Low- and Middle-Income Countries.

Gastrointestinal microorganism resistance and dissemination are increasing, partly due to international travel. This study investigated gastrointestinal colonisations and the acquisition of antimicrobial resistance (AMR) genes among international travellers moving between Spain and low- and middle-income countries (Peru and Ethiopia). We analysed 102 stool samples from 51 volunteers collected before and after travel, revealing significantly higher rates of colonisation by both bacteria and protists upon return. Diarrhoeagenic strains of E. coli were the most notable microorganism detected using RT-PCR with the Seegene Allplex™ Gastrointestinal Panel Assays. A striking prevalence of ß-lactamase resistance genes, particularly the TEM gene, was observed both before and after travel. No significant differences in AMR genes were found between the different locations. These findings highlight the need for rigorous surveillance and preventive strategies, as travel does not significantly impact AMR gene acquisition but does affect microbial colonisations. This study provides valuable insights into the intersection of gastrointestinal microorganism acquisition and AMR in international travellers, underscoring the need for targeted interventions and increased awareness.

Complex SMN Hybrids Detected in a Cohort of 31 Patients With Spinal Muscular Atrophy.

Background and Objectives: Spinal muscular atrophy (SMA) is a recessive neuromuscular disorder caused by the loss or presence of point pathogenic variants in the SMN1 gene. The main positive modifier of the SMA phenotype is the number of copies of the SMN2 gene, a paralog of SMN1, which only produces around 10%-15% of functional SMN protein. The SMN2 copy number is inversely correlated with phenotype severity; however, discrepancies between the SMA type and the SMN2 copy number have been reported. The presence of SMN2-SMN1 hybrids has been proposed as a possible modifier of SMA disease. Methods: We studied 31 patients with SMA, followed at a single center and molecularly diagnosed by Multiplex Ligand-Dependent Probe Amplification (MLPA), with a specific next-generation sequencing protocol to investigate their SMN2 genes in depth. Hybrid characterization also included bioinformatics haplotype phasing and specific PCRs to resolve each SMN2-SMN1 hybrid structure. Results: We detected SMN2-SMN1 hybrid genes in 45.2% of the patients (14/31), the highest rate reported to date. This represents a total of 25 hybrid alleles, with 9 different structures, of which only 4 are detectable by MLPA. Of particular interest were 2 patients who presented 4 SMN2-SMN1 hybrid copies each and no pure SMN2 copies, an event reported here for the first time. No clear trend between the presence of hybrids and a milder phenotype was observed, although 5 of the patients with hybrid copies showed a better-than-expected phenotype. The higher hybrid detection rate in our cohort may be due to both the methodology applied, which allows an in-depth characterization of the SMN genes and the ethnicity of the patients, mainly of African origin. Discussion: Although hybrid genes have been proposed to be beneficial for patients with SMA, our work revealed great complexity and variability between hybrid structures; therefore, each hybrid structure should be studied independently to determine its contribution to the SMA phenotype. Large-scale studies are needed to gain a better understanding of the function and implications of SMN2-SMN1 hybrid copies, improving genotype-phenotype correlations and prediction of the evolution of patients with SMA.

The Era of DAAs: Assessing the Patients' Characteristics, Clinical Impact, and Emergence of Comorbidities in HIV/HCV-Coinfected versus HIV-Infected Individuals.

Objective: To determine whether HIV-infected individuals versus individuals with HIV/HCV coinfection, in the era of interferon-free therapies, exhibit an increased incidence of comorbidities and non-AIDS-related events. Methods: A retrospective analysis was conducted by collecting data from clinical records of Spanish patients at a tertiary hospital involving HIV/HCV-coinfected and HIV-infected patients, all with effectively controlled HIV. Coinfected patients underwent HCV clearance using direct-acting antivirals (DAAs) and had no history of interferon treatment. The incidences of hypertension, diabetes mellitus, cardiovascular disease, kidney disease, liver disease, non-AIDS cancer, and death were compared between the groups. Multivariate adjustments for all factors potentially impacting outcomes were used to assess the risk of clinical event onset. Propensity score (PS) analyses were also conducted to support the multivariate model results. Results: Data were available from 229 HIV/HCV-coinfected patients and 229 HIV-infected patients. Both cohorts were comparable in terms of age, gender distribution, follow-up, and HIV-related characteristics. Multivariate models and PS showed that previous exposure to HCV was not associated with the onset of any clinical events studied. Significant differences between HIV/HCV-coinfected and HIV-infected were not found for survival according to the log-rank test (p = 0.402). Conclusions: Successful HCV elimination using DAAs improved the outlook regarding comorbidities and survival across HIV/HCV-coinfected cohorts. Early HCV detection and DAA therapy could enhance clinical results. These findings provide an optimistic perspective for those living with HIV/HCV coinfection and underscore the importance of continuing efforts toward early detection and DAA treatment initiation.

Confounding Factors in Targeted Degradation of Short-Lived Proteins.

Targeted protein degradation has recently emerged as a novel option in drug discovery. Natural protein half-life is expected to affect the efficacy of degrading agents, but to what extent it influences target protein degradation has not been systematically explored. Using simple mathematical modeling of protein degradation, we find that the natural half-life of a target protein has a dramatic effect on the level of protein degradation induced by a degrader agent which can pose significant hurdles to screening efforts. Moreover, we show that upon screening for degraders of short-lived proteins, agents that stall protein synthesis, such as GSPT1 degraders and generally cytotoxic compounds, deceptively appear as protein-degrading agents. This is exemplified by the disappearance of short-lived proteins such as MCL1 and MDM2 upon GSPT1 degradation and upon treatment with cytotoxic agents such as doxorubicin. These findings have implications for target selection as well as for the type of control experiments required to conclude that a novel agent works as a bona fide targeted protein degrader.

Complications and adverse events in lymphadenectomy of the inguinal area: worldwide expert consensus.

BACKGROUND: Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes. The aim of this study was to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events in lymphadenectomy of the inguinal area (CALI) group. METHODS: A modified 3-round Delphi consensus approach surveyed a worldwide group of experts in inguinal lymph node dissection for melanoma, penile and vulval cancer. The group of experts included general surgeons, urologists and oncologists (gynaecological and surgical). The survey assessed expert agreement on inguinal lymph node dissection perioperative complications. Panel interrater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α. RESULTS: Forty-seven experienced consultants were enrolled: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons and 4 (8.5%) gynaecology oncologists. Based on their expertise, 31 (66%), 10 (21.3%) and 22 (46.8%) of the participants treat penile cancer, vulval cancer and melanoma using inguinal lymph node dissection respectively; 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into five macrocategories. Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer and penile cancer. CONCLUSION: The complications and adverse events in lymphadenectomy of the inguinal area classification system has been developed as a tool to standardize the assessment and reporting of complications during inguinal lymph node dissection for the treatment of melanoma, vulval and penile cancer.

Effectiveness of Therapeutic Exercise for Children Undergoing Treatment for Cancer: A Systematic Review.

PURPOSE: To evaluate the effectiveness of therapeutic physical exercise (TPE) interventions on the physical functioning, psychosocial well-being, and quality of life (QoL) of children undergoing treatment for cancer. METHOD: Systematic review: databases were searched in April 2023. Selection criteria: children (<18 years old) undergoing treatment for cancer or a malignant neoplasm, randomized controlled trial design, utilization of TPE, and including physical and psychosocial outcomes. Internal validity was measured with Physiotherapy Evidence Database scale. RESULTS: Seven randomized controlled trials were included. Most studies showed that strength, fatigue, and QoL improved after the intervention. Cardiorespiratory capacity through 6-minute walk test and physical activity levels were better in the experimental groups. No changes were noted in other variables. CONCLUSIONS: This review supports the importance of a TPE program during cancer treatment, with the aim of maintaining physical capacities and counteracting physical inactivity.

Structural basis of homodimerization of the JNK scaffold protein JIP2 and its heterodimerization with JIP1.

The scaffold proteins JIP1 and JIP2 intervene in the c-Jun N-terminal kinase (JNK) pathway to mediate signaling specificity by coordinating the simultaneous assembly of multiple kinases. Using NMR, we demonstrate that JIP1 and JIP2 heterodimerize via their SH3 domains with the affinity of heterodimerization being comparable to homodimerization. We present the high-resolution crystal structure of the JIP2-SH3 homodimer and the JIP1-JIP2-SH3 heterodimeric complex. The JIP2-SH3 structure reveals how charge differences in residues at its dimer interface lead to formation of compensatory hydrogen bonds and salt bridges, distinguishing it from JIP1-SH3. In the JIP1-JIP2-SH3 complex, structural features of each homodimer are employed to stabilize the heterodimer. Building on these insights, we identify key residues crucial for stabilizing the dimer of both JIP1 and JIP2. Through targeted mutations in cellulo, we demonstrate a functional role for the dimerization of the JIP1 and JIP2 scaffold proteins in activation of the JNK signaling pathway.

[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.