Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes.

The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality of the central nervous system (CNS). Astrocytes are vital in orchestrating neuronal development by releasing synaptogenic molecules and eliminating excessive synapses. They also modulate neuronal excitability and contribute to CNS homeostasis, promoting neuronal survival by clearance of neurotransmitters, transporting metabolites, and secreting trophic factors. Astrocytes are highly heterogeneous and respond to CNS injuries and diseases through a process known as reactive astrogliosis, which can contribute to both inflammation and its resolution. Recent evidence has revealed remarkable alterations in astrocyte transcriptomes in response to several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic and A2 or neuroprotective astrocytes. However, due to the vast heterogeneity of these cells, it is limited to classify them into only two phenotypes. This review explores the various physiological and pathophysiological roles, potential markers, and pathways that might be activated in different astrocytic phenotypes. Furthermore, we discuss the astrocyte heterogeneity in the main neurodegenerative diseases and identify potential therapeutic strategies. Understanding the underlying mechanisms in the differentiation and imbalance of the astrocytic population will allow the identification of specific biomarkers and timely therapeutic approaches in various neurodegenerative diseases.

Manejo de la osteoporosis en el paciente con enfermedad renal crónica (Estudio ERCOS): un desafío en la asistencia nefrológica / Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care

La valoración del riesgo de fractura del paciente con enfermedad renal crónica (ERC) ha sido incluida en el complejo Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD) en guías nefrológicas internacionales y nacionales, sugiriéndose por primera vez la evaluación de la densidad mineral ósea (DMO) si los resultados pueden condicionar la toma de decisiones terapéuticas. Sin embargo, existe muy poca información en práctica clínica real en esta población. El objetivo principal del estudio ERC-Osteoporosis (ERCOS) es describir el perfil de los pacientes con ERC G3-5D con osteoporosis (OP) y/o fracturas por fragilidad atendidos en consultas especializadas de nefrología, reumatología y medicina interna en España. Participaron 15 centros y se incluyeron 162 pacientes (siendo en su mayoría mujeres [71,2%] posmenopáusicas [98,3%]) con una mediana de edad de 77 años. La mediana del filtrado glomerular estimado (FGe) fue de 36ml/min/1,73m2 y el 38% de pacientes incluidos estaban en diálisis. Destacamos la elevada frecuencia de fracturas por fragilidad prevalentes ([37,7%), principalmente vertebrales [52,5%] y de cadera 24,6%]), el antecedente desproporcionado de pacientes con enfermedad glomerular en comparación con series puramente nefrológicas (corticoides) y el infratratamiento para la prevención de fracturas, fundamentalmente en consultas nefrológicas. Este estudio supone una inmediata llamada a la acción con la difusión de las nuevas guías clínicas, más proactivas, y subraya la necesidad de homogeneizar el enfoque asistencial/terapéutico multidisciplinar coordinado de estos pacientes de un modo eficiente para evitar las actuales discrepancias y el nihilismo terapéutico. (AU)

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD) complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results will impact treatment decisions. However, there is very little information on actual clinical practice in this population. The main objective of the ERC-Osteoporosis (ERCOS) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36ml/min/1.73m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures ([37.7%], mainly vertebral [52.5%] and hip [24.6%]), the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and efficient multidisciplinary care/therapeutic approach to these patients to avoid current discrepancies and therapeutic nihilism. (AU)

Examining the relationship between COVID-19 and suicide in media coverage through Natural Language Processing analysis

Background and objectives Suicide is a major public health concern, media can influence its awareness, contagion, and prevention. In this study, we evaluated the relationship between the COVID-19 pandemic and suicide in media coverage through Natural Language Processing analysis (NPL). Methods To study how suicide is depicted in news media, Artificial Intelligence and Big Data techniques were used to analyze news and tweets, to extract or classify the topic to which they belonged. Results A granger causality analysis showed with significant p-value that an increase in covid news at the beginning of the pandemic explains a later rise in suicide-related news. An analysis based on correlation and structural causal models show a strong relationship between the appearance of subjects “health” and “covid”, and also between “covid” and “suicide”. Conclusions Our analysis also uncovers that the inclusion of suicide-related news in the category health has grown since the outbreak of the pandemic. The COVID-19 pandemic has posed an inflection point in the way suicide-related news are reported. Our study found that the increased media attention on suicide during the COVID-19 pandemic may indicate rising social awareness of suicide and mental health, which could lead to the development of new prevention tools. (AU)

Digital Twin Platform for Water Treatment Plants Using Microservices Architecture.

The effects of climate change and the rapid growth of societies often lead to water scarcity and inadequate water quality, resulting in a significant number of diseases. The digitalization of infrastructure and the use of Digital Twins are presented as alternatives for optimizing resources and the necessary infrastructure in the water cycle. This paper presents a framework for the development of a Digital Twin platform for a wastewater treatment plant, based on a microservices architecture which optimized its design for edge computing implementation. The platform aims to optimize the operation and maintenance processes of the plant's systems, by employing machine learning techniques, process modeling and simulation, as well as leveraging the information contained in BIM models to support decision-making.

Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism.

Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows.

Shortly after the discovery of Klotho, interest grew in its potential role in chronic kidney disease (CKD). There are three isoforms of the Klotho protein: αKlotho, ßKlotho and γKlotho. This review will focus on αKlotho due to its relevance as a biomarker in CKD. αKlotho is synthesized mainly in the kidneys, but it can be released into the bloodstream and urine as soluble Klotho (sKlotho), which undertakes systemic actions, independently or in combination with FGF23. It is usually accepted that sKlotho levels are reduced early in CKD and that lower levels of sKlotho might be associated with the main chronic kidney disease-mineral bone disorders (CKD-MBDs): cardiovascular and bone disease. However, as results are inconsistent, the applicability of sKlotho as a CKD-MBD biomarker is still a matter of controversy. Much of the inconsistency can be explained due to low sample numbers, the low quality of clinical studies, the lack of standardized assays to assess sKlotho and a lack of consensus on sample processing, especially in urine. In recent decades, because of our longer life expectancies, the prevalence of accelerated-ageing diseases, such as CKD, has increased. Exercise, social interaction and caloric restriction are considered key factors for healthy ageing. While exercise and social interaction seem to be related to higher serum sKlotho levels, it is not clear whether serum sKlotho might be influenced by caloric restriction. This review focuses on the possible role of sKlotho as a biomarker in CKD-MBD, highlighting the difference between solid knowledge and areas requiring further research, including the role of sKlotho in healthy ageing.

Miastenia gravis y enfermedad de Alzheimer: una asociación a estudio / Association between myasthenia gravis and Alzheimer’s disease

Introducción La miastenia gravis (MG) y la enfermedad de Alzheimer (EA) son dos de las enfermedades neurológicas en cuya fisiopatología interviene la acetilcolina en distintos niveles. En la primera, la alteración de este neurotransmisor se produce en la unión neuromuscular, y en la segunda, en el sistema nervioso central. Objetivo Analizar la posible relación entre dichas patologías estudiando la prevalencia y la odds ratio de la EA dentro de los pacientes diagnosticados de MG con respecto a la prevalencia de EA en la población general. Pacientes y métodos Se han examinado datos de las historias clínicas electrónicas del sistema de salud de Castilla-La Mancha utilizando el procesamiento de lenguaje natural a través de la plataforma clínica de inteligencia artificial Savana Manager?. Resultados Se ha identificado a 970.503 pacientes mayores de 60 años, de los que 1.028 tenían diagnóstico de MG. La proporción de pacientes con diagnóstico de EA dentro de este grupo (4,28%) es mayor que en el resto de la población (2,82%; p = 0,0047), con una odds ratio de 1,54 (intervalo de confianza al 95%: 1,13-2,08; p = 0,0051), sin que se encuentren diferencias significativas en el análisis bivariante del resto de los factores de riesgo para EA más importantes conocidos hasta ahora. Conclusiones Nuestros resultados sugieren que podría existir un aumento de la prevalencia de EA en pacientes con MG. (AU)

INTRODUCTION Myasthenia gravis (MG) and Alzheimer’s disease (AD) are two of the most important diseases where the dysregulation of acetylcholine activity plays a crucial role. In the first, this dysregulation happens at the level of the neu­romuscular junction and in the second, in the central nervous system (CNS). AIM To analyze the possible relationship between these two pathologies, analyzing the prevalence and the odds ratio of AD within patients previously diagnosed with MG. We will compare these data with respect to the prevalence of AD in the general population. PATIENTS AND METHODS We examined the data obtained by the electronic medical records of patients in the health care system of Castilla La Mancha using the Natural Language Process provided by a clinical platform of artificial intelligence known as the Savana Manager?. RESULTS We identified 970,503 patients over the age of 60 years, of which 1,028 were diagnosed with MG. The proportion of the patients diagnosed with AD within this group (4.28%) was greater than the rest of the population (2.82%) (p = 0,0047) with an odds ratio of 1.54 (confidence interval at 95% 1.13-2.08; p = 0.0051) without finding significant differences in the bivariate analysis for the rest of the most important actual known risk factors for AD. CONCLUSION. Our results suggest that there might be an increase in the prevalence of AD in patients previously diagnosed with MG. (AU)

Customized Subperiosteal Implants for the Rehabilitation of Atrophic Jaws: A Consensus Report and Literature Review.

(1) Background: The aim was to perform a literature review on customized subperiosteal implants (CSIs) and provide clinical guidelines based on the results of an expert consensus meeting held in 2023. (2) Methods: A literature search was performed in Pubmed (MEDLINE) in July 2023, including case series and cohort studies with a minimum follow-up of 6 months that analyzed totally or partially edentulous patients treated with CSIs. Previously, an expert consensus meeting had been held in May 2023 to establish the most relevant clinical guidelines. (3) Results: Six papers (four case series and two retrospective cohort studies) were finally included in the review. Biological and mechanical complication rates ranged from 5.7% to 43.8% and from 6.3% to 20%, respectively. Thorough digital planning to ensure the passive fit of the CSI is mandatory to avoid implant failure. (4) Conclusions: CSIs are a promising treatment option for rehabilitating edentulous patients with atrophic jaws; they seem to have an excellent short-term survival rate, a low incidence of major complications, and less morbidity in comparison with complex bone grafting procedures. As the available data on the use of CSIs are very scarce, it is not possible to establish clinical recommendations based on scientific evidence.

New Short RNA Motifs Potentially Relevant in the SARS-CoV-2 Genome.

Background: The coronavirus disease has led to an exhaustive exploration of the SARS-CoV-2 genome. Despite the amount of information accumulated, the prediction of short RNA motifs encoding peptides mediating protein-protein or protein-drug interactions has received limited attention. Objective: The study aims to predict short RNA motifs that are interspersed in the SARS-CoV-2 genome. Methods: A method in which 14 trinucleotide families, each characterized by being composed of triplets with identical nucleotides in all possible configurations, was used to find short peptides with biological relevance. The novelty of the approach lies in using these families to search how they are distributed across genomes of different CoV genera and then to compare the distributions of these families with each other. Results: We identified distributions of trinucleotide families in different CoV genera and also how they are related, using a selection criterion that identified short RNA motifs. The motifs were reported to be conserved in SARS-CoVs; in the remaining CoV genomes analysed, motifs contained, exclusively, different configurations of the trinucleotides A, T, G and A, C, G. Eighty-eight short RNA motifs, ranging in length from 12 to 49 nucleotides, were found: 50 motifs in the 1a polyprotein-encoding orf, 27 in the 1b polyprotein-encoding orf, 5 in the spike-encoding orf, and 6 in the nucleocapsid-encoding orf. Although some motifs (~27%) were found to be intercalated or attached to functional peptides, most of them have not yet been associated with any known functions. Conclusion: Some of the trinucleotide family distributions in different CoV genera are not random; they are present in short peptides that, in many cases, are intercalated or attached to functional sites of the proteome.

Advancing Alzheimer's Therapeutics: Exploring the Impact of Physical Exercise in Animal Models and Patients.

Alzheimer's disease (AD) is the main neurodegenerative disorder characterized by several pathophysiological features, including the misfolding of the tau protein and the amyloid beta (Aß) peptide, neuroinflammation, oxidative stress, synaptic dysfunction, metabolic alterations, and cognitive impairment. These mechanisms collectively contribute to neurodegeneration, necessitating the exploration of therapeutic approaches with multiple targets. Physical exercise has emerged as a promising non-pharmacological intervention for AD, with demonstrated effects on promoting neurogenesis, activating neurotrophic factors, reducing Aß aggregates, minimizing the formation of neurofibrillary tangles (NFTs), dampening inflammatory processes, mitigating oxidative stress, and improving the functionality of the neurovascular unit (NVU). Overall, the neuroprotective effects of exercise are not singular, but are multi-targets. Numerous studies have investigated physical exercise's potential in both AD patients and animal models, employing various exercise protocols to elucidate the underlying neurobiological mechanisms and effects. The objective of this review is to analyze the neurological therapeutic effects of these exercise protocols in animal models and compare them with studies conducted in AD patients. By translating findings from different approaches, this review aims to identify opportune, specific, and personalized therapeutic windows, thus advancing research on the use of physical exercise with AD patients.

Impact of the workforce allocation on the technical performance of mental health services: the collective case of Helsinki-Uusimaa (Finland).

BACKGROUND: Long-term mental health (MH) policies in Finland aimed at investing in community care and promoting reforms have led to a reduction in the number of psychiatric hospital beds. However, most resources are still allocated to hospital and community residential services due to various social, economic and political factors. Despite previous research focussing on the number and cost of these services, no study has evaluated the emerging patterns of use, their technical performance and the relationship with the workforce structure. OBJECTIVE: The purpose of this study was to observe the patterns of use and their technical performance (efficiency) of the main types of care of MH services in the Helsinki-Uusimaa region (Finland), and to analyse the potential relationship between technical performance and the corresponding workforce structure. METHODS: The sample included acute hospital residential care, non-hospital residential care and outpatient care services. The analysis was conducted using regression analysis, Monte Carlo simulation, fuzzy inference and data envelopment analysis. RESULTS: The analysis showed a statistically significant linear relationship between the number of service users and the length of stay, number of beds in non-hospital residential care and number of contacts in outpatient care services. The three service types displayed a similar pattern of technical performance, with high relative technical efficiency on average and a low probability of being efficient. The most efficient acute hospital and outpatient care services integrated multidisciplinary teams, while psychiatrists and nurses characterized non-hospital residential care. CONCLUSIONS: The results indicated that the number of resources and utilization variables were linearly related to the number of users and that the relative technical efficiency of the services was similar across all types. This suggests homogenous MH management with small variations based on workforce allocation. Therefore, the distribution of workforce capacity should be considered in the development of effective policies and interventions in the southern Finnish MH system.

Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients.

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

Asociación de la gamma glutamil transferasa con la presencia y progresión de calcificaciones aórticas abdominales y con cambios en densidad mineral ósea / Association of gamma glutamyl transferase in the presence and progression of abdominal aortic calcifications and changes to bone mineral density

Introducción y objetivo: la calcificación aórtica abdominal (CAA) es predictora de eventos cardiovasculares. El objetivo de este trabajo fue valorar la asociación de la gamma glutamil transferasa (GGT) con presencia y progresión de CAA y los cambios en densidad mineral ósea (DMO) en columna lumbar y cuello femoral. Material y métodos: se seleccionaron 326 hombres y mujeres mayores de 50 años que realizaron un cuestionario, dos radiografías laterales dorso-lumbares y DMO, repitiendo a los 4 años las mismas pruebas y un estudio analítico. Resultados: la presencia y progresión de CAA (nuevas o mayor severidad) fue inferior en el cuartil 1 (Q1) de GGT respecto a los otros cuartiles (40 % vs. 58 %, p = 0,021; 24 % vs. 44 %, p = 0,022). Comparado con Q1, el análisis de regresión logística ajustado por confusores mostró que los Q2 y Q4 se asociaron con aumentos en la presencia de CAA [odds ratio (OR) = 2,53, intervalo de confianza del 95 % (IC 96 %) = (1,22-5,25) y OR = 3,04, IC 95 % = (1,36-6,77)] y Q2, Q3 y Q4 se asociaron con aumentos en progresión de CAA [OR = 2,24, IC 95 % = (1,07-4,67); OR = 2,35, IC 95 % = (1,09-5,07) y OR = 3,47, IC 95 % = (1,56-7,70)]. El análisis multivariante por sexos mostró que tanto en hombres como mujeres el Q4 de GGT se asoció con progresión de CAA [OR = 3,27, IC 95 % = (1,14-9,36) y OR = 3,26, IC 95 % = (1,03-10,29) respectivamente] y en mujeres con mayores pérdidas de DMO a nivel lumbar. No hubo efecto con respecto a la prevalencia de CAA. Conclusiones: valores elevados de GGT podrían ser un indicador de presencia y progresión de CAA en población mayor de 50 años. De forma separada por sexo, los mayores niveles de GGT se asociaron con progresión de CAA, siendo un marcador pronóstico de daño cardiovascular.(AU)

Introduction and objective: abdominal aortic calcification (AAC) is a predictor of cardiovascular events. This study aimedto assess the association of gamma glutamyl transferase (GGT) in the presence and progression of AAC, as well as changesto bone mineral density (BMD) in the lumbar spine and femoral neck.Materials and methods: a total of 326 men and women over 50 years of age were selected for this study. They completeda questionnaire, underwent two lateral dorso-lumbar spine X-rays, and BMD measurements. The same tests and 1 analyticalassessment were repeated after 4 years.Results: the presence and progression of AAC (new occurrences or increased severity) were lower in GGT quartile 1 (Q1)compared with the other quartiles (40 % vs 58 %; p = 0.021; 24 % vs 44 %; p = 0.022). Compared with Q1, the confound -ers-adjusted logistic regression analysis showed that Q2 and Q4 were associated with more presence of AAC [odds ratio(OR), 2.53; 95 % confidence interval (95 % CI), 1.22-5.25 and OR, 3.04; 95 % CI, 1.36-6.77]. Additionally, Q2, Q3, and Q4were associated with more AAC progression [OR, 2.24; 95 % CI, 1.07-4.67; OR, 2.35; 95 % CI, 1.09-5.07; and OR, 3.47;95 % CI, 1.56-7.70]. The gender-stratified multivariate analysis revealed that in both men and women, the Q4 of GGT wasassociated with AAC progression [OR, 3.27; 95 % CI, 1.14-9.36, and OR, 3.26; 95 % CI, 1.03-10.29, respectively], and inwomen alone, with greater lumbar BMD losses. There were no effects regarding the prevalence of AAC.Conclusions: elevated GGT levels could serve as an indicator of the presence and progression of AAC in individuals olderthan 50 years. When analyzed separately by gender, higher GGT levels were associated with AAC progression, which actedas a prognostic marker for cardiovascular disease.(AU)

¿Debería la herramienta FRAX tener en cuenta otras variables para evaluar la fractura osteoporótica por fragilidad? / Should the FRAX tool include other variables to assess fragility-related osteoporotic fractures?

Introducción y objetivo: el objetivo fue valorar la relevancia de variables no contenidas en el FRAX sobre la incidencia de fractura osteoporótica. Material y métodos: participaron 316 mujeres > 50 años seguidas 8 años. Se evaluaron variables que recoge FRAX (edad, IMC, fractura previa, antecedentes parentales de fractura de cadera, hábito tabáquico, glucocorticoides, DMO cuello femoral) y que no recoge (edad de menarquia, menopausia, años fértiles y nuliparidad). Resultados: edad y antecedentes parentales de fractura de cadera se asociaron con fractura de cadera, pero también edad de menopausia y años fértiles. La edad [odds ratio (OR) = 1,09, Intervalo de confianza del 95 % (IC 95 %) = (1,01-1,17)] y edad de menopausia [OR = 0,90, IC 95 % = (0,82-0,99)] se asociaron con fractura de cadera tras análisis multivariante ajustado por edad e IMC. IMC, DMO en cuello femoral y nuliparidad se asociaron con fractura de Colles. En el análisis multivariante, solo nuliparidad se asoció con fractura de Colles [OR = 4,59, IC 95 % = (1,59-13,26)]. La fractura mayor osteoporótica se asoció significativamente con antecedentes parentales de fractura de cadera, nuliparidad y años fértiles. En el análisis multivariante, antecedentes parentales de fractura de cadera [OR = 3,26, IC 95 % = (1,23-8,61)], nuliparidad [OR = 3,07; IC 95 % = (1,48-6,37)] y años fértiles [OR = 0,92, IC 95 % = (0,87-0,98)] se asociaron con fractura mayor osteoporótica. Conclusiones: de las variables del FRAX, edad y antecedentes parentales de fractura de cadera se asociaron con incidencia de fractura mayor osteoporótica y de cadera, pero otras variables ginecológicas tuvieron un peso similar, lo que sugiere que deben ser tenidas muy en cuenta a la hora de realizar la anamnesis de las pacientes.(AU)

Introduction and objective: the objective of this study was to assess the significance of variables not included in the FRAXtool regarding the incidence of osteoporotic fractures.Materials and methods: a total of 316 women older than 50 years were followed for 8 years. The variables collected (age,BMI, previous fracture, parental history of hip fracture, smoking habit, use of glucocorticoids, femoral neck BMD) and thosenot collected by the FRAX tool (age at menarche, menopause, fertile years, nulliparity) were studied.Results: age and parental history of hip fracture were associated with hip fractures, but so were age at menopause andfertile years. Age [odds ratio (OR), 1.09; 95 % confidence interval (CI), 1.01-1.17] and age at menopause [OR, 0.90; 95 %CI,0.82-0.99] were associated with hip fractures after the multivariate analysis adjusted for age and BMI. BMI, femoral neckBMD and nulliparity were associated with the occurrence of Colles fractures. According to the multivariate analysis, onlynulliparity was associated with Colles fractures [OR, 4.59; 95 %CI, 1.59-13.26)]. Major osteoporotic fractures were signifi-cantly associated with parental history of hip fracture, nulliparity, and fertile years. According to the multivariate analysis,the parental history of hip fracture [OR, 3.26; 95 %CI, 1.23-8.61], nulliparity [OR, 3.07; 95 %CI, 1.48-6.37], and fertile years[OR, 0.92; 95 %CI, 0.87-0.98] were associated with the occurrence of major osteoporotic fractures.Conclusions: among the FRAX variables, age and parental history of hip fracture were associated with the incidence ofmajor osteoporotic and hip fractures. However, the significance of other gynecological variables was similar, which is indic-ative that they should certainlay be taken into consideration during patient history assessment.(AU)

Las células senescentes como factores patogénicos y posibles dianas terapéuticas en osteoporosis / Cellular senescence as a pathogenic factor and potential therapeutic target in osteoporosis

La senescencia celular es un proceso inducido por varios tipos de estrés que causan una detención irreversible del ciclo celular y un cambio en las características y la funcionalidad de las células, además de la adquisición de un fenotipo secretor que genera un ambiente proinflamatorio. Si bien en determinados contextos es beneficiosa para los tejidos y promueve el desarrollo del organismo, la senescencia es un destino celular implicado en el proceso de envejecimiento y en las patologías degenerativas relacionadas con la edad. Los senolíticos son fármacos que eliminan específicamente a las células senescentes y los senomórficos son fármacos que suprimen su fenotipo secretor asociado a senescencia (SASP) sin inducir la muerte celular. Así, las estrategias terapéuticas enfocadas en las células senescentes (senolíticos y senomórficos) como mecanismo subyacente al envejecimiento, se erigen en una alternativa con gran potencial para luchar contra las enfermedades relacionadas con la edad en su conjunto, y no de forma individual. Una de estas patologías es la osteoporosis, donde además se han descrito, a nivel experimental, que fármacos como el ácido zoledrónico tiene efecto sobre los preosteoblastos y actúa sobre las células senescentes, prolongando la supervivencia y abriendo la puerta a la posibilidad de tratar las enfermedades relacionadas con la edad con fármacos que ya se empleen en la práctica, y que puedan tener un efecto más allá del propio hueso y aumentar la supervivencia. En este trabajo se va a realizar una revisión en este campo de vertiginoso crecimiento en los últimos años y con indudable interés traslacional.(AU)

Cellular senescence is a process induced by various types of stress that irreversibly cause cell cycle arrest and changes tothe characteristics and functionality of cells, as well as the acquisition of a secretory phenotype that generates a pro-in-flammatory environment. While, in certain contexts, it is beneficial for tissues and promotes organism development, senes-cence is a cellular fate implicated in the process of aging and age-related degenerative conditions. Senolytics are drugs thatspecifically eliminate senescent cells, and senomorphics are drugs that suppress their senescence-associated secretoryphenotype (SASP) without inducing cell death. Therefore, therapeutic strategies targeting senescent cells (senolytics andsenomorphics) as an underlying mechanism of aging emerge as an alternative with great potential to fight age-relateddiseases as a whole rather than individually. One of these conditions is osteoporosis where it has been experimentallydescribed that drugs such as zoledronic acid have effects on preosteoblasts and act on senescent cells extending survivaland opening up the possibility of treating age-related diseases with drugs already used in practice, which may have effectsbeyond the bone itself and increase overall survival. In this study, a review will be conducted in this rapidly growing fieldin recent years of undeniable translational interest.(AU)

Transition of patients with metabolic bone disease from paediatric to adult healthcare services: current situation and proposals for improvement.

BACKGROUND: There are currently no models for the transition of patients with metabolic bone diseases (MBDs) from paediatric to adult care. The aim of this project was to analyse information on the experience of physicians in the transition of these patients in Spain, and to draw up consensus recommendations with the specialists involved in their treatment and follow-up. METHODS: The project was carried out by a group of experts in MBDs and included a systematic review of the literature for the identification of critical points in the transition process. This was used to develop a questionnaire with a total of 48 questions that would determine the degree of consensus on: (a) the rationale for a transition programme and the optimal time for the patient to start the transition process; (b) transition models and plans; (c) the information that should be specified in the transition plan; and (d) the documentation to be created and the training required. Recommendations and a practical algorithm were developed using the findings. The project was endorsed by eight scientific societies. RESULTS: A total of 86 physicians from 53 Spanish hospitals participated. Consensus was reached on 45 of the 48 statements. There was no agreement that the age of 12 years was an appropriate and feasible point at which to initiate the transition in patients with MBD, nor that a gradual transition model could reasonably be implemented in their own hospital. According to the participants, the main barriers for successful transition in Spain today are lack of resources and lack of coordination between paediatric and adult units. CONCLUSIONS: The TEAM Project gives an overview of the transition of paediatric MBD patients to adult care in Spain and provides practical recommendations for its implementation.

Cross-sectional study of quality of life in relation with vascular access in hemodialysis patients. Study in a hospital and a satellite center

Introduction: Vascular access for hemodialysis (HD) is essential for the patient. Even though Arteriovenous fistula (AVF) is the preferred access, in certain age groups, the central venous catheter (CVC) may provide advantages. This study aims to investigate the quality of life related to vascular access. Methods: Cross-sectional study including patients from a hospital, a home HD unit and a satellite hemodialysis center. Clinical data was collected from the patients, who went through a quality-of-life questionnaire SF12 and a Vascular Access Questionnaire (VAQ). Results: 91 patients participated, mostly male (70 %), with a mean age of 68.9 ± 16.2 years. AVF was the current vascular access in 60.4 %, the rest used a CVC. Home HD was performed in 12.1 % of patients and 76 % started it via CVC. Regarding patients who have had both AVF and CVC, 58 % prefer AVF and only 26.5 % of current CVC carriers would have a new AVF, mostly due to fear of pain (52 %). Most people (72.5 %) reported having received sufficient information, with no differences between both accesses. The SF12 results showed no differences between patients with AVF or CVC. Regarding the VAQ, patients with AVF were more satisfied with the social aspect (p = 0.036) and complications (p = 0.006). Conclusion: Patients with AVF had better outcomes than those using CVC regarding complications and social aspects. These differences are not attributable to a worse overall quality of life status of CVC patients. Most patients with CVCs refuse to go through a new AVF for fear of puncture pain.

Introducción: el acceso vascular para la hemodiálisis (HD) es esencial para el paciente. Aunque la fístula arteriovenosa (FAV) es el acceso preferido, en ciertos grupos de edad el catéter venoso central (CVC) puede aportar ventajas. Este estudio pretende investigar la calidad de vida relacionada con el acceso vascular. Métodos: el estudio transversal incluye pacientes del hospital, de una unidad de HD domiciliaria y de un centro de hemodiálisis periférico. Se recogieron datos clínicos de los pacientes que contestaron el cuestionario de calidad de vida SF12 y Cuestionario de Acceso Vascular (VAQ). Resultados: 91 pacientes, en su mayoría varones (70 %), con una edad media de 68,9 ± 16,2 años. La FAV era el acceso vascular actual en el 60,4 %. La HD domiciliaria se realizó en el 12,1 % de los pacientes y el 76 % la inició mediante CVC. En cuanto a los pacientes que han tenido tanto FAV como CVC, el 58 % prefiere la FAV y sólo el 26,5 % de los actuales portadores de CVC se sometería a una nueva FAV, sobre todo por miedo al dolor (52 %). La mayoría de las personas (72,5 %) declararon haber recibido suficiente información, sin diferencias entre ambos accesos. Los resultados del SF12 no mostraron diferencias según el acceso. En cuanto al VAQ, los pacientes con AVF estaban más satisfechos con el aspecto social y las complicaciones. Conclusión: los pacientes con FAV tuvieron mejores resultados en comparación con los que utilizaron CVC en cuanto a complicaciones y aspectos sociales, sin deberse a un peor estado general de la calidad de vida. La mayoría de los pacientes con CVC se niegan a someterse a una nueva FAV por miedo al dolor de la punción.

Effects of Voluntary Physical Exercise on the Neurovascular Unit in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Histopathologically, AD presents two pathognomonic hallmarks: (1) neurofibrillary tangles, characterized by intracellular deposits of hyperphosphorylated tau protein, and (2) extracellular amyloid deposits (amyloid plaques) in the brain vasculature (cerebral amyloid angiopathy; CAA). It has been proposed that vascular amyloid deposits could trigger neurovascular unit (NVU) dysfunction in AD. The NVU is composed primarily of astrocytic feet, endothelial cells, pericytes, and basement membrane. Although physical exercise is hypothesized to have beneficial effects against AD, it is unknown whether its positive effects extend to ameliorating CAA and improving the physiology of the NVU. We used the triple transgenic animal model for AD (3xTg-AD) at 13 months old and analyzed through behavioral and histological assays, the effect of voluntary physical exercise on cognitive functions, amyloid angiopathy, and the NVU. Our results show that 3xTg-AD mice develop vascular amyloid deposits which correlate with cognitive deficits and NVU alteration. Interestingly, the physical exercise regimen decreases amyloid angiopathy and correlates with an improvement in cognitive function as well as in the underlying integrity of the NVU components. Physical exercise could represent a key therapeutic approach in cerebral amyloid angiopathy and NVU stability in AD patients.