Bioethical conflicts in current dermatology: a narrative review. / Conflictos bioéticos en la dermatología actual: una revisión narrativa.

Both the functions and equipment of dermatologists have increased over the past few years, some examples being cosmetic dermatology, artificial intelligence, tele-dermatology, and social media, which added to the pharmaceutical industry and cosmetic selling has become a source of bioethical conflicts. The objective of this narrative review is to identify the bioethical conflicts of everyday dermatology practice and highlight the proposed solutions. Therefore, we conducted searches across PubMed, Web of Science and Scopus databases. Also, the main Spanish and American deontological codes of physicians and dermatologists have been revised. The authors recommend declaring all conflicts of interest while respecting the patients' autonomy, confidentiality, and privacy. Cosmetic dermatology, cosmetic selling, artificial intelligence, tele-dermatology, and social media are feasible as long as the same standards of conventional dermatology are applied. Nonetheless, the deontological codes associated with these innovations need to be refurbished.

Exploring the potential of Physics-Informed Neural Networks to extract vascularization data from DCE-MRI in the presence of diffusion.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is widely used to assess tissue vascularization, particularly in oncological applications. However, the most widely used pharmacokinetic (PK) models do not account for contrast agent (CA) diffusion between neighboring voxels, which can limit the accuracy of the results, especially in cases of heterogeneous tumors. To address this issue, previous works have proposed algorithms that incorporate diffusion phenomena into the formulation. However, these algorithms often face convergence problems due to the ill-posed nature of the problem. In this work, we present a new approach to fitting DCE-MRI data that incorporates CA diffusion by using Physics-Informed Neural Networks (PINNs). PINNs can be trained to fit measured data obtained from DCE-MRI while ensuring the mass conservation equation from the PK model. We compare the performance of PINNs to previous algorithms on different 1D cases inspired by previous works from literature. Results show that PINNs retrieve vascularization parameters more accurately from diffusion-corrected tracer-kinetic models. Furthermore, we demonstrate the robustness of PINNs compared to other traditional algorithms when faced with noisy or incomplete data. Overall, our results suggest that PINNs can be a valuable tool for improving the accuracy of DCE-MRI data analysis, particularly in cases where CA diffusion plays a significant role.

Allelic variants of the estrogen receptor genes and frailty phenotype in postmenopausal women.

OBJECTIVE: The prevalence of frailty has been related to menopause. Our main objective was to investigate whether single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER) ERα and ERß genes were related to the frailty phenotype in a population of community-dwelling postmenopausal women. METHODS: A cross-sectional study was performed in which we selected five SNPs, three in the ERα gene and two in the ERß. Linear regression was used to estimate the percentage of phenotypic variance after adjusting for confounding variables. RESULTS: A total of 470 women (mean ± standard deviation age 63.83 ± 8.16 years) were included, of whom 137 women were frail. The SNP rs3798577 of the ERα gene was the only variant associated with frailty, but this significance faded in the multivariant analysis. Body mass index (p = 0.012), number of comorbidities (0 vs. ≥2, p = 0.002) and two reproductive variables, number of miscarriages (none vs. ≥2, p = 0.036) and of childbirths (one vs. ≥3, p = 0.008), were independently related to frailty. CONCLUSION: The five SNPs of the ERα and ERß genes tested were not correlated with frailty. Other SNPs of the ER warrant analysis to clarify whether variance in the gene response affects frailty status.

Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population.

OBJECTIVES: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. METHODS: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. RESULTS: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. CONCLUSIONS: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.

Effect of air pollutants on ambulatory blood pressure.

BACKGROUND AND METHODOLOGY: Air pollutants have a significant impact on public health. The aim of the study was to find out the relationship between ambulatory blood pressure measured by 24-h ambulatory blood pressure monitoring (ABPM) and the atmospheric pollutants that are measured regularly (PM10, PM2.5, NO2 and SO2). An observational study of temporal and geographic measurements of individual patients (case-time series design) was carried out in Primary Care Centres and Hypertension Units in the Barcelona metropolitan area. We included 2888 hypertensive patients≥18 years old, untreated, with a first valid ABPM performed between 2005 and 2014 and with at least one air pollution station within a radius of <3km. RESULTS AND CONCLUSIONS: The mean age was 54.3 (SD 14.6) years. 50.1% were women and 16.9% of the sample were smokers. Mean 24-h blood pressure (BP) was 128.0 (12.7)/77.4 (9.7) mmHg. After adjusting for mean ambient temperature and different risk factors, a significant association was found between ambulatory diastolic BP (DBP) and PM10 concentrations the day before ABPM. For each increase of 10µg/m3 of PM10, an increase of 1.37mmHg 24-h DBP and 1.48mmHg daytime DBP was observed. No relationship was found between PM2.5, NO2 and SO2 and ambulatory BP, nor between any pollutant and clinical BP. The concentration of PM10 the day before the ABPM is significantly associated with an increase in 24-h DBP and daytime DBP.

Effect of air pollutants on ambulatory blood pressure / Efectos de los contaminantes aéreos en la presión arterial ambulatoria

Background and methodology: Air pollutants have a significant impact on public health. The aim of the study was to find out the relationship between ambulatory blood pressure measured by 24-h ambulatory blood pressure monitoring (ABPM) and the atmospheric pollutants that are measured regularly (PM10, PM2.5, NO2 and SO2). An observational study of temporal and geographic measurements of individual patients (case-time series design) was carried out in Primary Care Centres and Hypertension Units in the Barcelona metropolitan area. We included 2888 hypertensive patients≥18 years old, untreated, with a first valid ABPM performed between 2005 and 2014 and with at least one air pollution station within a radius of <3km. Results and conclusions: The mean age was 54.3 (SD 14.6) years. 50.1% were women and 16.9% of the sample were smokers. Mean 24-h blood pressure (BP) was 128.0 (12.7)/77.4 (9.7) mmHg. After adjusting for mean ambient temperature and different risk factors, a significant association was found between ambulatory diastolic BP (DBP) and PM10 concentrations the day before ABPM. For each increase of 10μg/m3 of PM10, an increase of 1.37mmHg 24-h DBP and 1.48mmHg daytime DBP was observed. No relationship was found between PM2.5, NO2 and SO2 and ambulatory BP, nor between any pollutant and clinical BP. The concentration of PM10 the day before the ABPM is significantly associated with an increase in 24-h DBP and daytime DBP. (AU)

Antecedentes y metodología: Los contaminantes aéreos tienen un impacto importante en la salud pública. El objetivo del estudio era conocer la relación entre la presión arterial ambulatoria medida mediante monitorización ambulatoria de la presión arterial (MAPA) de 24h y los contaminantes atmosféricos que se miden regularmente (PM10, PM2,5, NO2 y SO2). Se realizó un estudio observacional de medidas temporales y geográficas de pacientes individuales (case-time series design) en centros de atención primaria y unidades de hipertensión del área metropolitana de Barcelona. Se incluyeron 2.888 pacientes hipertensos≥18 años, no tratados, con una primera MAPA válida realizada entre 2005-2014 y al menos con una estación de contaminación atmosférica en un radio<3km. Resultados y conclusiones: La media de edad fue de 54,3 (DE 14,6) años. El 50,1% eran mujeres y el 16,9% de la muestra eran fumadores. La presión arterial (PA) de 24h fue de 128,0 (12,7)/77,4 (9,7)mmHg. Tras ajustarse por la temperatura ambiental media y por los diferentes factores de riesgo se halló una asociación significativa entre PA diastólica (PAD) ambulatoria y las concentraciones de PM10 del día anterior a la MAPA. Por cada incremento de 10μg/m3 de PM10 se observaba un aumento de 1,37mmHg PAD 24h y de 1,48mmHg PAD diurna. No se halló relación entre PM2,5, NO2 y SO2 y PA ambulatoria, ni entre ningún contaminante y PA clínica. La concentración de PM10 del día anterior a la realización de la MAPA se asocia significativamente con un aumento de PAD 24h y PAD diurna. (AU)

APOE3 Christchurch modulates tau phosphorylation and ß-catenin/Wnt/Cadherin signaling in induced pluripotent stem cell-derived cerebral organoids from Alzheimer's cases.

Alzheimer's disease (AD) is the most common cause of dementia among older adults. APOE3 Christchurch (R136S, APOE3Ch ) variant homozygosity was reported in an individual with extreme resistance to autosomal dominant AD due to the PSEN1 E280A mutation. This subject had a delayed clinical age at onset and resistance to tauopathy and neurodegeneration despite extremely high amyloid plaque burden. We established induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and from a non-protected kindred control (with PSEN1 E280A and APOE3/3 ). We used CRISPR/Cas9 gene editing to successfully remove the APOE3Ch to wild type in iPS cells from the protected case and to introduce the APOE3Ch as homozygote in iPS cells from the non-protected case to examine causality. We found significant reduction of tau phosphorylation (pTau 202/205 and pTau396) in cerebral organoids with the APOE3Ch variant, consistent with the strikingly reduced tau pathology found in the resistant case. We identified Cadherin and Wnt pathways as signaling mechanisms regulated by the APOE3Ch variant through single cell RNA sequencing in cerebral organoids. We also identified elevated ß-catenin protein, a regulator of tau phosphorylation, as a candidate mediator of APOE3Ch resistance to tauopathy. Our findings show that APOE3Ch is necessary and sufficient to confer resistance to tauopathy in an experimental ex-vivo model establishing a foundation for the development of novel, protected case-inspired therapeutics for tauopathies, including Alzheimer's.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.