Differential regulation of cardiac sodium channels by intracellular fibroblast growth factors

Voltage-gated sodium (NaV) channels are responsible for the initiation and propagation of action potentials. In the heart, the predominant NaV1.5 α subunit is composed of four homologous repeats (I-IV) and forms a macromolecular complex with multiple accessory proteins, including intracellular fibroblast growth factors (iFGF). In spite of high homology, each of the iFGFs, iFGF11-iFGF14, as well as the individual iFGF splice variants, differentially regulates NaV channel gating, and the mechanisms underlying these differential effects remain elusive. Much of the work exploring iFGF regulation of NaV1.5 has been performed in mouse and rat ventricular myocytes in which iFGF13VY is the predominant iFGF expressed, whereas investigation into NaV1.5 regulation by the human heart-dominant iFGF12B is lacking. In this study, we used a mouse model with cardiac-specific Fgf13 deletion to study the consequences of iFGF13VY and iFGF12B expression. We observed distinct effects on the voltage-dependences of activation and inactivation of the sodium currents (INa), as well as on the kinetics of peak INa decay. Results in native myocytes were recapitulated with human NaV1.5 heterologously expressed in Xenopus oocytes, and additional experiments using voltage-clamp fluorometry (VCF) revealed iFGF-specific effects on the activation of the NaV1.5 voltage sensor domain in repeat IV (VSD-IV). iFGF chimeras further unveiled roles for all three iFGF domains (i.e., the N-terminus, core, and C-terminus) on the regulation of VSD-IV, and a slower time domain of inactivation. We present here a novel mechanism of iFGF regulation that is specific to individual iFGF isoforms and that leads to distinct functional effects on NaV channel/current kinetics

An allosteric modulator activates BK channels by perturbing coupling between Ca2+ binding and pore opening

BK type C

Remdesivir in Very Old Patients (≥80 Years) Hospitalized with COVID-19: Real World Data from the SEMI-COVID-19 Registry

Background: Large cohort studies of patients with COVID-19 treated with remdesivir have reported improved clinical outcomes, but data on older patients are scarce. Objective: This work aims to assess the potential benefit of remdesivir in unvaccinated very old patients hospitalized with COVID-19; (2) Methods: This is a retrospective analysis of patients >= 80 years hospitalized in Spain between 15 July and 31 December 2020 (SEMI-COVID-19 Registry). Differences in 30-day all-cause mortality were adjusted using a multivariable regression analysis. (3) Results: Of the 4331 patients admitted, 1312 (30.3%) were >= 80 years. Very old patients treated with remdesivir (n: 140, 10.7%) had a lower mortality rate than those not treated with remdesivir (OR (95% CI): 0.45 (0.29-0.69)). After multivariable adjustment by age, sex, and variables associated with lower mortality (place of COVID-19 acquisition; degree of dependence; comorbidities; dementia; duration of symptoms; admission qSOFA; chest X-ray; D-dimer; and treatment with corticosteroids, tocilizumab, beta-lactams, macrolides, and high-flow nasal canula oxygen), the use of remdesivir remained associated with a lower 30-day all-cause mortality rate (adjusted OR (95% CI): 0.40 (0.22-0.61) (p < 0.001)). (4) Conclusions: Remdesivir may reduce mortality in very old patients hospitalized with COVID-19

S de solidaridad

El documento muestra la experiencia y la reflexión que se hace a través de la fiesta solidaria que celebra INTERMÓN cada año: 'Un día para la esperanza'.CataluñaES

The mental health of employees with job loss and income loss during the COVID-19 pandemic: The mediating role of perceived financial stress

The COVID-19 outbreak, which was followed by home confinement, is expected to have had profound negative impact on the mental health of people. Associated factors, such as losing jobs and income, can be expected to lead to an increased risk of suffering from psychopathological problems. Therefore, this study was aimed at researching the associations of job and income loss with mental health, as well as the possible mediating role of perceived financial stress during the COVID-19 outbreak. The sample included 2381 Spanish workers who were interviewed right after the first COVID-19 lockdown. Measures were taken for generalized anxiety disorder, panic attacks, depression, post-traumatic stress disorder, substance abuse, suicidal thoughts and behaviors, working conditions, sociodemographic variables, and perceived financial stress. Logistic regression models were calculated with psychological variables as outcomes, and with job loss and income loss as predictors. Mediation analyses were performed by adding the financial threat as a mediator. Nineteen point six percent and 33.9% of participants reported having lost their jobs and incomes due to the pandemic, respectively. Only income loss was related to a higher risk of suffering from depression and panic attacks. When adding financial stress as a mediator, the indirect effects of job and income loss on the mental health measures were found to be significant, therefore indicating mediation. These findings pinpoint the vulnerability of this population, and highlight the need for interventional and preventive programs targeting mental health in economic crisis scenarios, such as the current one. They also highlight the importance of implementing social and income policies during the COVID-19 pandemic to prevent mental health problems

MEDLEM database, a data collection on large Elasmobranchs in the Mediterranean and Black seas

The Mediterranean Large Elasmobranchs Monitoring (MEDLEM) database contains over 3000 records (more than 4000 individuals) of large elasmobranch species from 20 different countries around the Mediterranean and Black seas, observed from 1666 to 2017. The main species included in the archive are the devil fish (1 813 individuals), the basking shark (939 individuals), the blue shark (585 individuals) and the great white shark (337 individuals).In the last decades other species such as the shortfin mako (166 individuals), the spiny butterfly ray (138) and the thresher shark (174 individuals) were reported with an increasing frequency. This was possibly due to an increased public awareness on the conservation status of sharks, and a consequent development of new monitoring programmes. MEDLEM does not have a homogeneous reporting coverage throughout the Mediterranean and Black seas and it should be considered as a database of observed species presence. Scientific monitoring efforts in the south-eastern Mediterranean and Black seas are generally lower than in the northern sectors and the absence in our database of some species does not imply their actual absence in these regions. Some considerations are made on the frequency and spatial distribution of records, size structure of the observed individuals for selected species, general area coverage and species involved as by-catch by fishing gear