The mineralocorticoid receptor plays a transient role in mouse skin development

3 páginas, 2 figuras. Contiene material suplemenarioGlucocorticoid (GC) hormones can bind two structurally and functionally related steroid receptors: the GC Receptor (GR or Nr3c1) and the mineralocorticoid receptor (MR or Nr3c2), which recognize the same DNA response elements and act as ligand-dependent transcription factors. While the crucial role of GR for skin homeostasis has been widely characterized, the exact role of MR in this tissue deserves further study. We assessed NR3C2 expression in developing and adult WT mouse skin and found a transient peak at embryonic day (E)16.5, which along with low levels of HSD11B2, the enzyme inactivating GCs, supports a role for GC-MR complexes in epidermal maturation. Consistent with this observation, MR-/- embryonic skin showed alterations in early epidermal differentiation that resolved postnatally. The lack of a more severe skin phenotype of MR-/- mice suggests functional compensation by GR in this tissue in the perinatal period.This work was supported by JSPS KAKENHI grant numbers 25870545 and 15K09772. Spanish Ministerio de Ciencia e Innovación. Grant Numbers: SAF2011-28115, SAF2014-59474-RPeer Reviewe

MRI Investigation of the Differential Impact of Left Ventricular Ejection Fraction After Myocardial Infarction in Elderly vs. Nonelderly Patients to Predict Readmission for Heart Failure

Acute heart failure; Acute myocardial infarction; ElderlyInsuficiència cardíaca aguda; Infart agut de miocardi; Gent granInsuficiencia cardíaca aguda; Infarto agudo de miocardio; AncianoBackground Patients with ST-segment elevation myocardial infarction (STEMI), especially elderly individuals, have an increased risk of readmission for acute heart failure (AHF). Purpose To study the impact of left ventricular ejection fraction (LVEF) by MRI to predict AHF in elderly (>70 years) and nonelderly patients after STEMI. Study Type Prospective. Population Multicenter registry of 759 reperfused STEMI patients (23.3% elderly). Field Strength/Sequence 1.5-T. Balanced steady-state free precession (cine imaging) and segmented inversion recovery steady-state free precession (late gadolinium enhancement) sequences. Assessment One-week MRI-derived LVEF (%) was quantified. Sequential MRI data were recorded in 579 patients. Patients were categorized according to their MRI-derived LVEF as preserved (p-LVEF, ≥50%), mildly reduced (mr-LVEF, 41%–49%), or reduced (r-LVEF, ≤40%). Median follow-up was 5 [2.33–7.54] years. Statistical Tests Univariable (Student's t, Mann–Whitney U, chi-square, and Fisher's exact tests) and multivariable (Cox proportional hazard regression) comparisons and continuous-time multistate Markov model to analyze transitions between LVEF categories and to AHF. Hazard ratios (HR) with 95% confidence intervals (CIs) were computed. P < 0.05 was considered statistically significant. Results Over the follow-up period, 79 (10.4%) patients presented AHF. MRI-LVEF was the most robust predictor in nonelderly (HR 0.94 [0.91–0.98]) and elderly patients (HR 0.94 [0.91–0.97]). Elderly patients had an increased AHF risk across the LVEF spectrum. An excess of risk (compared to p-LVEF) was noted in patients with r-LVEF both in nonelderly (HR 11.25 [5.67–22.32]) and elderly patients (HR 7.55 [3.29–17.34]). However, the mr-LVEF category was associated with increased AHF risk only in elderly patients (HR 3.66 [1.54–8.68]). Less transitions to higher LVEF states (n = 19, 30.2% vs. n = 98, 53%) and more transitions to AHF state (n = 34, 53.9% vs. n = 45, 24.3%) were observed in elderly than nonelderly patients. Data Conclusion MRI-derived p-LVEF confers a favorable prognosis and r-LVEF identifies individuals at the highest risk of AHF in both elderly and nonelderly patients. Nevertheless, an excess of risk was also found in the mr-LVEF category in the elderly group. Evidence Level 2. Technical Efficacy Stage 2.Grant sponsor: This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (grant numbers PI20/00637, PI15/00531, and CIBERCV16/11/00486, CIBERCV16/11/00420, CIBERCV16/11/00479, and CM21/00175 to V.M.-G.), Fundació La Marató TV3 (grant 20153030-31-32), La Caixa Banking Foundation (HR17-00527) and by Conselleria de Educación – Generalitat Valenciana (PROMETEO/2021/008). J.G. acknowledges financial support from the “Agencia Estatal de Investigación” (grant FJC2020-043981-I/AEI/10.13039/501100011033)

Prognostic value of cardiac magnetic resonance early after ST-segment elevation myocardial infarction in older patients

[EN] Background older patients with ST-segment elevation myocardial infarction (STEMI) represent a very high-risk population. Data on the prognostic value of cardiac magnetic resonance (CMR) in this scenario are scarce. Methods the registry comprised 247 STEMI patients over 70 years of age treated with percutaneous intervention and included in a multicenter registry. Baseline characteristics, echocardiographic parameters and CMR-derived left ventricular ejection fraction (LVEF, %), infarct size (% of left ventricular mass) and microvascular obstruction (MVO, number of segments) were prospectively collected. The additional prognostic power of CMR was assessed using adjusted C-statistic, net reclassification index (NRI) and integrated discrimination improvement index (IDI). Results during a 4.8-year mean follow-up, the number of first major adverse cardiac events (MACE) was 66 (26.7%): 27 all-cause deaths and 39 re-admissions for acute heart failure. Predictors of MACE were GRACE score (HR 1.03 [1.02-1.04], P 155, LVEF = 2 segments. A simple score (0, 1, 2, 3) based on the number of altered factors accurately predicted the MACE per 100 person-years: 0.78, 5.53, 11.51 and 78.79, respectively (P < 0.001). Conclusions CMR data contribute valuable prognostic information in older patients submitted to undergo CMR soon after STEMI. The Older-STEMI-CMR score should be externally validated.This work was supported by Instituto de Salud Carlos III and Fondos Europeos de Desarrollo Regional FEDER (grant numbers PI20/00637, PI15/00531, and CIBERCV16/11/00486,CIBERCV16/11/00420, CIBERCV16/11/00479), apostgraduate contract FI18/00320 to C.R.-N., CM21/00175 to V.M.-G. and JR21/00041 to C.B., Fundacio La MaratoTV3 (grant 20153030-31-32), La Caixa Banking Foundation (HR17-00527), by Conselleria de Educacion-Generalitat Valenciana (PROMETEO/2021/008) and by Sociedad Espanola de Cardiologia (grant SEC/FEC-INV-CLI 21/024). J.G. acknowledges financial support from the Agencia Estatal de Investigacion (grant FJC2020-043981-I/AEI/10.13039/501100011033). D.M. acknowledges financial support from the Conselleria d'Educacio,Investigacio, Cultura i Esport, Generalitat Valenciana (grants AEST/2019/037, AEST/2020/029).Gabaldón-Pérez A; Marcos-Garcés, V.; Gavara-Doñate, J.; López-Lereu, MP.; Monmeneu, JV.; Pérez, N.; Ríos-Navarro, C.... (2022). Prognostic value of cardiac magnetic resonance early after ST-segment elevation myocardial infarction in older patients. Age and Ageing. 51(11):1-11. https://doi.org/10.1093/ageing/afac248111511

Cardiac magnetic resonance outperforms echocardiography to predict subsequent implantable cardioverter defibrillator therapies in ST-segment elevation myocardial infarction patients

Altres ajuts: Conselleria de Educación-Generalitat Valenciana (PROMETEO/2021/008); Sociedad Española de Cardiología (Grant SEC/FEC-INVCLI 21/024)Implantable cardioverter defibrillators (ICD) are effective as a primary prevention measure of ventricular tachyarrhythmias in patients with ST-segment elevation myocardial infarction (STEMI) and depressed left ventricular ejection fraction (LVEF). The implications of using cardiac magnetic resonance (CMR) instead of echocardiography (Echo) to assess LVEF prior to the indication of ICD in this setting are unknown. We evaluated 52 STEMI patients (56.6 ± 11 years, 88.5% male) treated with ICD in primary prevention who underwent echocardiography and CMR prior to ICD implantation. ICD implantation was indicated based on the presence of heart failure and depressed LVEF (≤ 35%) by echocardiography, CMR, or both. Prediction of ICD therapies (ICD-T) during follow-up by echocardiography and CMR before ICD implantation was assessed. Compared to echocardiography, LVEF was lower by cardiac CMR (30.2 ± 9% vs. 37.4 ± 7.6%, p < 0.001). LVEF ≤ 35% was detected in 24 patients (46.2%) by Echo and in 42 (80.7%) by CMR. During a mean follow-up of 6.1 ± 4.2 years, 10 patients received appropriate ICD-T (3.16 ICD-T per 100 person-years): 5 direct shocks to treat very fast ventricular tachycardia or ventricular fibrillation, 3 effective antitachycardia pacing (ATP) for treatment of ventricular tachycardia, and 2 ineffective ATP followed by shock to treat ventricular tachycardia. Echo-LVEF ≤ 35% correctly predicted ICD-T in 4/10 (40%) patients and CMR-LVEF ≤ 35% in 10/10 (100%) patients. CMR-LVEF improved on Echo-LVEF for predicting ICD-T (area under the curve: 0.76 vs. 0.48, p = 0.04). In STEMI patients treated with ICD, assessment of LVEF by CMR outperforms Echo-LVEF to predict the subsequent use of appropriate ICD therapies

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

The mineralocorticoid receptor plays a transient role in mouse skin development

3 páginas, 2 figuras. Contiene material suplemenarioGlucocorticoid (GC) hormones can bind two structurally and functionally related steroid receptors: the GC Receptor (GR or Nr3c1) and the mineralocorticoid receptor (MR or Nr3c2), which recognize the same DNA response elements and act as ligand-dependent transcription factors. While the crucial role of GR for skin homeostasis has been widely characterized, the exact role of MR in this tissue deserves further study. We assessed NR3C2 expression in developing and adult WT mouse skin and found a transient peak at embryonic day (E)16.5, which along with low levels of HSD11B2, the enzyme inactivating GCs, supports a role for GC-MR complexes in epidermal maturation. Consistent with this observation, MR-/- embryonic skin showed alterations in early epidermal differentiation that resolved postnatally. The lack of a more severe skin phenotype of MR-/- mice suggests functional compensation by GR in this tissue in the perinatal period.This work was supported by JSPS KAKENHI grant numbers 25870545 and 15K09772. Spanish Ministerio de Ciencia e Innovación. Grant Numbers: SAF2011-28115, SAF2014-59474-RPeer Reviewe

Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress

Lafora disease is a rare, fatal form of progressive myoclonus epilepsy characterized by continuous neurodegeneration with epileptic seizures, characterized by the intracellular accumulation of aberrant polyglucosan granules called Lafora bodies. Several works have provided numerous evidence of molecular and cellular alterations in neural tissue from experimental mouse models deficient in either laforin or malin, two proteins related to the disease. Oxidative stress, alterations in proteostasis, and deregulation of inflammatory signals are some of the molecular alterations underlying this condition in both KO animal models. Lafora bodies appear early in the animal’s life, but many of the aforementioned molecular aberrant processes and the consequent neurological symptoms ensue only as animals age. Here, using small RNA-seq and quantitative PCR on brain extracts from laforin and malin KO male mice of different ages, we show that two different microRNA species, miR-155 and miR-146a, are overexpressed in an age-dependent manner. We also observed altered expression of putative target genes for each of the microRNAs studied in brain extracts. These results open the path for a detailed dissection of the molecular consequences of laforin and malin deficiency in brain tissue, as well as the potential role of miR-155 and miR-146a as specific biomarkers of disease progression in LD

Sex differences in mortality in stable patients undergoing vasodilator stress cardiovascular magnetic resonance

Objective We assessed the influence of the ischaemic burden (IB) as derived from vasodilator stress cardiovascular magnetic resonance (CMR) on the risk of death and the effect of revascularisation across sex.Methods We evaluated 6237 consecutive patients with known or suspected chronic coronary syndrome (CCS). Extensive ischaemia was defined as &gt;5 segments with perfusion deficit. Multivariate Cox proportional hazard regression models were used.Results A total of 2371 (38.0%) patients were women and 583 (9.3%) underwent CMR-related revascularisation. During a median follow-up of 5.13 years, 687 (11.0%) deaths were reported. We found an adjusted differential effect of CMR-derived IB across sex (p value for interaction=0.039). Women exhibited an adjusted lower risk of death and only equaled men’s risk when extensive ischaemia was present. Likewise, CMR-related revascularisation was shown to be differentially associated with the risk of mortality across sex (p value for interaction=0.025). In patients with non-extensive ischaemia, revascularisation was associated with a higher risk of death, with a greater extent in women. At higher IB, revascularisation was associated with a lower risk in men, with more uncertain results in women.Conclusions CMR-derived IB allows predicting the risk of death and gives insight into the potential effect of revascularisation in men and women with CCS. Compared with men, women with non-extensive ischaemia displayed a lower risk and a similar risk with a higher IB. The impact of CMR-related revascularisation on mortality risk was also significantly different according to IB and sex. Further research will be needed to confirm these hypothesis-generating findings

Pensamiento social español sobre América Latina

La antología Pensamiento social español sobre América Latina tiene el objetivo principal de acercar al público académico y general la rica y diversa tradición de ideas, autores y escuelas españolas que han pensado América Latina y que, también, han influido en el propio desarrollo de las ciencias sociales latinoamericanas como impactaron, igualmente, en los ámbitos académico, cultural y político de uno y otro lado del Atlántico. Pues el desarrollo de las ciencias sociales, tanto en España como en América Latina, ha seguido historias con bastantes entrecruzamientos, algunos elementos comunes y con importantes redes intelectuales de intercambio que han establecido un contrapunto dialéctico. Pues si las circunstancias y la gestación de la propia idea de ciencias sociales y de sociología latinoamericana fueron fundadas como tal a mediados del siglo XX como un campo de investigación regional y como un proceso endógeno de producción de ideas, de categorías y de teorías, no solo tiene un valor anecdótico el señalar, entonces, la particular participación de pensadores españoles en ese movimiento. Por tal motivo, ese interés sobresaliente por América Latina lo concebimos en este volumen como un puente tendido entre dos orillas y como un diálogo franco y plural. De la Introducción de Juan Jesús Morales Martín