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The use of Xenopus oocytes in electrophysiological and biophysical research constitutes a long and successful story, providing major advances to the knowledge of the function and modulation of membrane proteins, mostly receptors, ion channels, and transporters. Earlier reports showed that these cells are capable of correctly expressing heterologous proteins after injecting the corresponding mRNA or cDNA. More recently, the Xenopus oocyte has become an outstanding host–cell model to carry out detailed studies on the function of fully-processed foreign membrane proteins after their microtransplantation to the oocyte. This review focused on the latter overall process of transplanting foreign membrane proteins to the oocyte after injecting plasma membranes or purified and reconstituted proteins. This experimental approach allows for the study of both the function of mature proteins, with their native stoichiometry and post-translational modifications, and their putative modulation by surrounding lipids, mostly when the protein is purified and reconstituted in lipid matrices of defined composition. Remarkably, this methodology enables functional microtransplantation to the oocyte of membrane receptors, ion channels, and transporters from different sources including human post-mortem tissue banks. Despite the large progress achieved over the last decades on the structure, function, and modulation of neuroreceptors and ion channels in healthy and pathological tissues, many unanswered questions remain and, most likely, Xenopus oocytes will continue to help provide valuable responses.

The voltage-gated potassium channel Kv1.3 plays an apparent dual physiological role by participating in activation and proliferation of leukocytes as well as promoting apoptosis in several types of tumor cells. Therefore, Kv1.3 is considered a potential pharmacological target for immunodeficiency and cancer. Different cellular locations of Kv1.3, at the plasma membrane or the mitochondria, could be responsible for such duality. While plasma membrane Kv1.3 facilitates proliferation, the mitochondrial channel modulates apoptotic signaling. Several molecular determinants of Kv1.3 drive the channel to the cell surface, but no information is available about its mitochondrial targeting. Caveolins, which are able to modulate cell survival, participate in the plasma membrane targeting of Kv1.3. The channel, via a caveolin-binding domain (CBD), associates with caveolin 1 (Cav1), which localizes Kv1.3 to lipid raft membrane microdomains. The aim of our study was to understand the role of such interactions not only for channel targeting but also for cell survival in mammalian cells. By using a caveolin association-deficient channel (Kv1.3 CBDless), we demonstrate here that while the Kv1.3–Cav1 interaction is responsible for the channel localization in the plasma membrane, a lack of such interaction accumulates Kv1.3 in the mitochondria. Kv1.3 CBDless severely affects mitochondrial physiology and cell survival, indicating that a functional link of Kv1.3 with Cav1 within the mitochondria modulates the pro-apoptotic effects of the channel. Therefore, the balance exerted by these two complementary mechanisms fine-tune the physiological role of Kv1.3 during cell survival or apoptosis. Our data highlight an unexpected role for the mitochondrial caveolin–Kv1.3 axis during cell survival and apoptosis.

Douglas Sirk, now fully recognized as an influential filmmaker, was considered a successful but uninteresting director in the 1950s. His melodramas were considered bland and subsequently ignored because they focused on female-centric concerns. In the following decades, he started to be considered as an auteur that not only had an impeccable and vibrant mise-en-scène, but also a unique ability to deliver movies that might seem superficial on a surface level but were able to sneak in some subtle and revolutionary criticism about American society. The aim of this paper is to analyse the most rebellious and subversive aspects of Sirk’s classic All that Heaven Allows (1955) from a gender perspective and how Todd Haynes’s tribute Far from Heaven (2002) added new challenges by touching upon thorny subjects that already existed in Sirk’s time but were deemed taboo for mass audiences.

Adolescent idiopathic scoliosis (AIS) is characterized by the radiographic presence of a frontal plane curve, with a magnitude greater than 10° (Cobb technique). Diffusion MRI can be employed to assess the cerebral white matter. The aim of this study was to analyze, by means of MRI, the presence of any alteration in the connectivity of cerebral white matter in AIS patients. In this study, 22 patients with AIS participated. The imaging protocol consisted in T1 and diffusion-weighted acquisitions. Based on the information from one of the diffusion acquisitions, a whole brain tractography was performed with the MRtrix tool. Tractography is a method to deduce the trajectory of fiber bundles through the white matter based on the diffusion MRI data. By combining cortical segmentation with tractography, a connectivity matrix of size 84 × 84 was constructed using FA (fractional anisotropy), and the number of streamlines as connectomics metrics. The results obtained support the hypothesis that alterations in cerebral white matter connectivity in patients with adolescent idiopathic scoliosis (AIS) exist. We consider that the application of diffusion MRI, together with transcranial magnetic stimulation neurophysiologically, is useful to search the etiology of AIS.

Background Large‐scale studies describing modern populations using an implantable cardioverter‐defibrillator (ICD) are lacking. We aimed to analyze the incidence of arrhythmia, device interventions, and mortality in a broad spectrum of real‐world ICD patients with different heart disorders. Methods and Results The UMBRELLA study is a prospective, multicenter, nationwide study of contemporary patients using an ICD followed up by remote monitoring, with a blinded review of arrhythmic episodes. From November 2005 to November 2017, 4296 patients were followed up. After 46.6±27.3 months, 16 067 episodes of sustained ventricular arrhythmia occurred in 1344 patients (31.3%). Appropriate ICD therapy occurred in 27.3% of study population. Patients with ischemic cardiomyopathy (hazard ratio [HR], 1.51; 95% CI, 1.29–1.78), dilated cardiomyopathy (HR, 1.28; 95% CI, 1.07–1.53), and valvular heart disease (HR, 1.94; 95% CI, 1.43–2.62) exhibited a higher risk of appropriate ICD therapies, whereas patients with hypertrophic cardiomyopathy (HR, 0.72; 95% CI, 0.54–0.96) and Brugada syndrome (HR, 0.25; 95% CI, 0.14–0.45) showed a lower risk. All‐cause death was 13.4% at follow‐up. Ischemic cardiomyopathy (HR, 3.09; 95% CI, 2.58–5.90), dilated cardiomyopathy (HR, 3.33; 95% CI, 2.18–5.10), and valvular heart disease (HR, 3.97; 95% CI, 2.25–6.99) had the worst prognoses. Delayed high‐rate detection was enabled in 39.7% of patients, and single‐zone programming occurred in 52.6% of primary prevention patients. Both parameters correlated with lower risk of first appropriate ICD therapy, with no excess risk of mortality. The rate of inappropriate shocks at follow‐up was low (6%) and did not differ among type of ICD but was lower in SmartShock‐capable devices. Conclusions Irrespective of the cause, contemporary ICD patients with heart failure–related disorders had a similar risk of ICD life‐saving interventions and death. Current ICD programming recommendations still need to be implemented. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NTC01561144.

Objective To estimate the 6-year radiographic progression of sacroiliitis in patients with early spondyloarthritis (SpA).Patients and methods Sacroiliac joint (SIJ) radiographs (baseline and 6 years) of 94 patients with recent-onset SpA from the Esperanza cohort were scored, blindly and in a random order, by nine readers. The modified New York criteria were used to define the presence of sacroiliitis. As the gold standard for radiographic (r) sacroiliitis, the categorical opinion of at least five readers was used. Progression was defined as the shift from non-radiographic (nr) to r-sacroiliitis.Results In the 94 SIJ radiographs (baseline and 6 years), 78/94 (83%) pairs of radiographs had not changed from baseline to 6 years. Sacroiliitis was present in 20 patients at baseline (21.3%) and in 18 (19.2%) patients at 6 years; 11 patients had sacroiliitis at both the baseline and final visits; 9 patients changed from baseline r-sacroiliitis to nr-sacroiliitis at 6 years, and 7 changed from baseline nr-sacroiliitis to r-sacroiliitis at 6 years. The mean continuous change score (range: −8 to +8) was 2.80 at baseline and 2.55 at 6 years (mean net progression of −0.25). The reliability of the readers was fair (mean inter-reader kappa of 0.375 (0.146–0.652) and mean agreement of 73.7% (58.7–90%)).Conclusion In the early SpA Esperanza cohort, progression from nr-axSpA to r-axSpA over 6 years was not observed, although the SIJ radiographs scoring has limitations to detect low levels of radiographic progression.

Presentamos un resumen de las actividades que algunos de los profesores de la Facultad de Medicina de Murcia han llevado a cabo durante las 3 semanas previas a las vacaciones de primavera. Durante este tiempo, debido a la pandemia provocada por la COVID-19, la docencia presencial tuvo que ser sustituída por actividades en línea o virtuales, a causa de la implantación del estado de alarma en España que motivó el cierre completo de las Universidades desde el 13 de marzo de 2020. Las experiencias son de Traumatología, Matemáticas, Medicina Legal, Medicina del Sistema Cardiovascular, Periodoncia y Odontología Preventiva y Comunitaria.

Background CD6 is a lymphocyte surface co-receptor physically associated with the T-cell receptor (TCR)/CD3 complex at the center of the immunological synapse. There, CD6 assists in cell-to-cell contact stabilization and modulation of activation/differentiation events through interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), its main reported ligand. While accumulating evidence is attracting new interest on targeting CD6 for therapeutic purposes in autoimmune disorders, little is known on its potential in cancer. In an attempt to elucidate the in vivo relevance of blocking CD6-mediated interactions in health and disease, we explored the consequences of expressing high circulating levels of a soluble form CD6 (sCD6) as a decoy receptor.Methods High sCD6 serum levels were achieved by using transgenic C57BL/6 mice expressing human sCD6 under the control of lymphoid-specific transcriptional elements (shCD6LckEμTg) or wild type either transduced with hepatotropic adeno-associated virus coding for mouse sCD6 or undergoing repeated infusions of recombinant human sCD6 protein. Characterization of sCD6-induced changes was performed by ex vivo flow cytometry and functional analyses of mouse lymphoid organ cells. The in vivo relevance of those changes was explored by challenging mice with subcutaneous or metastatic tumors induced by syngeneic cancer cells of different lineage origins.Results Through a combination of in vitro and in vivo studies, we show that circulating sCD6 expression induces defective regulatory T cell (Treg) generation and function, decreased CD166/ALCAM-mediated tumor cell proliferation/migration and impaired galectin-induced T-cell apoptosis, supporting the fact that sCD6 modulates antitumor lymphocyte effector function and tumorigenesis. Accordingly, sCD6 expression in vivo resulted in delayed subcutaneous tumor growth and/or reduced metastasis on challenge of mice with syngeneic cancer cells.Conclusions Evidence is provided for the disruption of CD6 receptor–ligand interactions as a feasible immunomodulatory approach in cancer.

Abstract Background Postoperative morbidity and mortality in patients undergoing surgery is high, especially in patients who are at risk of complications and undergoing major surgery. We hypothesize that perioperative, algorithm-driven, hemodynamic therapy based on individualized fluid status and cardiac output optimization is able to reduce mortality and postoperative moderate and severe complications as a major determinant of the patients’ postoperative quality of life, as well as health care costs. Methods/design This is a multi-center, international, prospective, randomized trial in 380 patients undergoing major abdominal surgery including visceral, urological, and gynecological operations. Eligible patients will be randomly allocated to two treatment arms within the participating centers. Patients of the intervention group will be treated perioperatively following a specific hemodynamic therapy algorithm based on pulse-pressure variation (PPV) and individualized optimization of cardiac output assessed by pulse-contour analysis (ProAQT© device; Pulsion Medical Systems, Feldkirchen, Germany). Patients in the control group will be treated according to standard local care based on established basic hemodynamic treatment. The primary endpoint is a composite comprising the occurrence of moderate or severe postoperative complications or death within 28 days post surgery. Secondary endpoints are: (1) the number of moderate and severe postoperative complications in total, per patient and for each individual complication; (2) the occurrence of at least one of these complications on days 1, 3, 5, 7, and 28 in total and for every complication; (3) the days alive and free of mechanical ventilation, vasopressor therapy and renal replacement therapy, length of intensive care unit, and hospital stay at day 7 and day 28; and (4) mortality and quality of life, assessed by the EQ-5D-5L™ questionnaire, after 6 months. Discussion This is a large, international randomized controlled study evaluating the effect of perioperative, individualized, algorithm-driven ,hemodynamic optimization on postoperative morbidity and mortality. Trial registration Trial registration: NCT03021525. Registered on 12 January 2017.