Integrated Building Modelling Using Geomatics and GPR Techniques for Cultural Heritage Preservation: A Case Study of the Charles V Pavilion in Seville (Spain).

This paper highlights the fundamental role of integrating different geomatics and geophysical imaging technologies in understanding and preserving cultural heritage, with a focus on the Pavilion of Charles V in Seville (Spain). Using a terrestrial laser scanner, global navigation satellite system, and ground-penetrating radar, we constructed a building information modelling (BIM) system to derive comprehensive decision-making models to preserve this historical asset. These models enable the generation of virtual reconstructions, encompassing not only the building but also its subsurface, distributable as augmented reality or virtual reality online. By leveraging these technologies, the research investigates complex details of the pavilion, capturing its current structure and revealing insights into past soil compositions and potential subsurface structures. This detailed analysis empowers stakeholders to make informed decisions about conservation and management. Furthermore, transparent data sharing fosters collaboration, advancing collective understanding and practices in heritage preservation.

Mitochondrial Role on Cellular Apoptosis, Autophagy, and Senescence during Osteoarthritis Pathogenesis.

Authors have demonstrated that apoptosis activation is a pathway related to cartilage degradation characteristics of the OA process. Autophagy is an adaptive response to protect cells from various environmental changes, and defects in autophagy are linked to cell death. In this sense, decreased autophagy of chondrocytes has been observed in OA articular cartilage. The aim of this work was to study the role of OA mitochondria in apoptosis, autophagy, and senescence, using OA and Normal (N) transmitochondrial cybrids. Results: OA cybrids incubated with menadione showed a higher percentage of late apoptosis and necrosis than N cybrids. Stimulation of cybrids with staurosporine and IL-1ß showed that OA cybrids were more susceptible to undergoing apoptosis than N cybrids. An analysis of the antioxidant response using menadione on gene expression revealed a lower expression of nuclear factor erythroid 2-like 2 and superoxide dismutase 2 in OA than N cybrids. Activation of microtubule-associated protein 1A/1B-light chain 3 was reduced in OA compared to N cybrids. However, the percentage of senescent cells was higher in OA than N cybrids. Conclusion: This work suggests that mitochondria from OA patients could be involved in the apoptosis, autophagy, and senescence of chondrocytes described in OA cartilage.

Prevalence of Gastrointestinal Parasites in Small Ruminant Farms in Southern Spain.

The primary population of small ruminants in Spain is concentrated in the southern region, a critical area for the country's livestock production. Indirect economic losses can occur when this livestock is affected by gastrointestinal parasites. This study aimed to determine the prevalence of these parasites in small ruminant herds (159 sheep and 39 goats) through coprological analyses and conducted a survey on farmers' management practices related to gastrointestinal parasite control. The survey results revealed some important aspects: monitoring through coprological analyses is not a common practice; veterinarians are not typically involved in deworming plans; anthelmintic treatment in adults is often applied twice a year in sheep and once a year in goats; and finally, drug rotation was higher in sheep farms. Coprological analyses showed Eimeria spp. as the most common parasitic infection, followed by Strongyles infection. Other parasites like Moniezia spp., Trichuris spp., and D. dendriticum were less important, although their prevalence was higher in sheep than goats. This constitutes the first report on the epidemiological status of gastrointestinal parasites in small ruminants in southern Spain. Based on the survey findings, the introduction of certain management measures on farms could potentially mitigate parasite infections.

Diagnostic and prognostic value of calf circumference for sarcopenia in community-dwelling older adults.

BACKGROUND: An age-dependent normative values of calf circumference (CC) has been recently proposed as an accessible proxy for muscle mass. However, its usefulness to estimate sarcopenia has not been assessed. The objectives of the present study were to determine if the substitution of the classical way to assess muscle mass by these values have enough diagnostic accuracy and prognostic value among older adults living in the community. METHODS: Data from the Toledo Study of Healthy Ageing (TSHA) were used. CC was measured using an anthropometric tape. We used two age-groups CC cut-off points: the TSHA CC median and the one proposed in the Longevity Check-up 7+ (Lookup 7+) project. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People (EWGSOP2), the Foundation for the National Institutes of Health (FNIH), and FNIH criteria standardized for our population (sFNIH). Frailty (according to the Frailty Phenotype and the Frailty Trait Scale-5) and disability (Katz index) were assessed at baseline and follow-up. Mortality and first hospitalization were also recorded. Logistic (incident frailty and worsening disability) and Cox (mortality and hospitalization) regressions were performed. Diagnostic accuracy was assessed through Kappa index, AUCs, positive and negative predictive values. Predictive ability was assessed through AUCs and integrated AUCs (IAUCs). RESULTS: 1531 participants (74.8 ± 5.8 years; 45.6% men) were included in the analysis. Prevalence rates of sarcopenia were 22.7% (sFNIH), 15.0% (FNIH), and 13.9% (EWGSOP2). Using TSHA-based cut-points of CC, the prevalence of sarcopenia was 16.8% (sFNIH), 11.0% (FNIH), and 11.5% (EWGSOP2). According to LC7+-based CC cut-off points, sarcopenia prevalence was 17.6% (sFNIH), 11.9% (FNIH), and 12.4% (EWGSOP2). CC cut-off points showed low-to-moderate agreement (Kappa Index values between 0.49 and 0.69) with appendicular lean mass for the evaluation of sarcopenia. Sarcopenia identified by Lookup 7+ and TSHA CC cut-off points was associated with the adverse events examined, with similar AUCs and IAUCs than original sarcopenia definitions, and were lost after adjustment by baseline frailty, except when the original EWGSOP2 definition was used. CONCLUSIONS: Using normalized values of CC as a criteria of muscle mass shows moderate agreement with classical criteria for diagnosing sarcopenia and offer similar predictive value in community-dwelling older adults.

Decrease in platelet count in patients with AKI and its association with major adverse kidney events.

INTRODUCTION: A reduction in platelet count in critically ill patients is a marker of severity of the clinical condition. However, whether this association holds true in acute kidney injury (AKI) is unknown. We analyzed the association between platelet reduction in patients with AKI and major adverse kidney events (MAKE). METHODS: In this retrospective cohort, we included AKI patients at the Hospital Civil of Guadalajara, in Jalisco, Mexico. Patients were divided according to whether their platelet count fell >21% during the first 10 days. Our objectives were to analyze the associations between a platelet reduction >21% and MAKE at 10 days (MAKE10) or at 30-90 days (MAKE30-90) and death. RESULTS: From 2017 to 2023, 400 AKI patients were included, 134 of whom had a > 21% reduction in platelet count. The mean age was 54 years, 60% were male, and 44% had sepsis. The mean baseline platelet count was 194 x 103 cells/µL, and 65% of the KDIGO3 patients met these criteria. Those who underwent hemodialysis (HD) had lower platelet counts. After multiple adjustments, a platelet reduction >21% was associated with MAKE10 (OR 4.2, CI 2.1-8.5) but not with MAKE30-90. The mortality risk increased 3-fold (OR 2.9, CI 1.1-7.7, p = 0.02) with a greater decrease in the platelets (<90 x 103 cells/µL). As the platelets decreased, the incidence of MAKE was more likely to increase. These associations lost significance when accounting for starting HD. CONCLUSION: In our retrospective cohort of patients with AKI, a > 21% reduction in platelet count was associated with MAKE. Our results are useful for generating hypotheses and motivating us to continue studying this association with a more robust design.

A reduction in platelet count in critically ill patients has been associated with a worse prognosis, but it is not yet known whether this relationship also exists in patients with acute kidney injury, who are more susceptible to platelet decrease due to the syndrome or due to the onset of hemodialysis. In our study of acute kidney injury patients, we found that those whose platelet count decreased >21% during the first days were more likely to experience a major kidney event. In addition, the greater the decrease in platelet count was, the more likely these events were to occur. The significance of this association was lost in patients who start hemodialysis. Our conclusions could serve to generate hypotheses about this interesting relationship.

SGLT2i treatment during AKI and its association with major adverse kidney events.

Background: The association between the administration of sodium-glucose cotransporter 2 inhibitors (SGLT2is) during acute kidney injury (AKI) and the incidence of major adverse kidney events (MAKEs) is not known. Methods: This retrospective cohort study included patients with AKI and compared the outcomes for those who were treated with SGLT2is during hospitalization and those without SGLT2i treatment. The associations of SGLT2i use with MAKEs at 10 and 30-90 days, each individual MAKE component, and the pre-specified patient subgroups were analyzed. Results: From 2021 to 2023, 374 patients were included in the study-316 without SGLT2i use and 58 with SGLT2i use. Patients who were treated with SGLT2is were older; had a greater prevalence of diabetes, hypertension, chronic heart failure, and chronic kidney disease; required hemodialysis less often; and presented stage 3 AKI less frequently than those who were not treated with SGLT2is. Logistic regression analysis with nearest-neighbor matching revealed that SGLT2i use was not associated with the risk of MAKE10 (OR 1.08 [0.45-2.56]) or with MAKE30-90 (OR 0.76 [0.42-1.36]). For death, the stepwise approach demonstrated that SGLT2i use was associated with a reduced risk (OR 0.08; 0.01-0.64), and no effect was found for kidney replacement therapy (KRT). The subgroups of patients who experienced a reduction in the risk of MAKEs in patients with AKI treated with SGLT2is were those older than 61 years, those with an eGFR >81, and those without a history of hypertension or DM (p ≤ 0.05 for all). Conclusion: The use of SGLT2is during AKI had no effect on short- or medium-term MAKEs, but some subgroups of patients may have experienced benefits from SGLT2i treatment.

Blastocystis hominis -Associated Acute Appendicular Peritonitis in a 9-Year-Old Boy: A Case Report and a Comprehensive Review of the Literature.

Although Blastocystis sp. has been classically considered a commensal parasite with limited pathogenicity, recent studies suggest that its pathogenic potential is high. We report the case of a 9-year-old Spanish male who presented with peritonitis secondary to acute appendicitis with abundant intra-abdominal turbid-free fluid. A standard appendectomy was performed, and a sample of the fluid was taken for microbiological culture. Multimicrobial flora was isolated in peritoneal fluid culture. The antibiotic resistance study showed that all the microorganisms were sensitive to meropenem. On the 5th postoperative day, a control blood test showed relative eosinophilia and a persistently elevated C-reactive protein. A stool parasitological study showed abundant cysts morphologically compatible with Blastocystis hominis . The hematoxylin & eosin and Giemsa study identified abundant parasitic cysts in the appendix. The patient evolved favorably and is currently asymptomatic and under follow-up. Regarding acute appendicitis, there is only one report in the literature of peritonitis of appendiceal origin associated with Blastocystis sp. In conclusion, although infrequent, parasitosis should be considered as a potential etiological agent of acute appendicitis, even in nonendemic areas. Relative eosinophilia or persistently elevated acute phase reactants despite adequate antibiotic coverage should help to establish diagnostic suspicion.

Reliability of a Trunk Flexion and Extensor Muscle Strength Test with Hand-Held and Isokinetic Dynamometers in Female Athletes.

An accurate trunk muscle strength assessment seems very important to design and individualize training and rehabilitation programs in clinical and sport settings. Hand-held dynamometers (HHDs) are interesting alternatives to isokinetic dynamometers for assessing trunk isometric muscle strength because they are inexpensive instruments and easy to use. This cross-sectional observational study aimed to examine the reliability of two novel sitting tests for assessing trunk flexion and extension isometric strength using an HHD and their relationship with two other novel isometric tests that use an isokinetic dynamometer. Twenty-four female amateur athletes (age: 24.5 ± 2.64 years; body height: 164.45 ± 6.33 cm; body mass: 63.17 ± 10.35 kg) participated in this study. A test-retest design was carried out one-week apart to examine the reliability. The relationship and the degree of agreement between the HHD and the isokinetic dynamometer measurements were analysed using Pearson correlation and Bland-Altman analysis, respectively. In general, the reliability of all isometric strength tests was good, with ICCs ranging from 0.65 to 0.87 and typical error < 15%. Pearson correlations were moderate, with values of r = 0.47 (R2 = 0.22) and r = 0.42 (R2 = 0.18) for flexion and extension strength, respectively. Bland-Altman plots showed no agreement between HHDs and isokinetic measurements. All trunk isometric tests using both, an isokinetic dynamometer and HHDs, provide reliable measurements for assessing trunk flexion and extension strength. According to the comparative analysis, both measurement types are different and cannot be used interchangeably. Health and sport professionals should choose the test that best suits the biomechanical characteristics required for functional goals or success in a given sport.

Correlation between the results of cultures and the molecular BIOFIRE® joint infection panel in a cohort of pediatric patients with bone and joint infections in Bogotá, Colombia.

Introduction: Bone and Joint Infections (BJI) have high morbidity. Methicillin resistant Staphylococcus aureus (MRSA) has increased. Culture-based diagnosis has difficult to recovering fastidious bacteria and detecting polymicrobial infections, molecular methods offer a promising improvement for the diagnosis of BJI with reduced time to result. The aim of the study was to determine the correlation between culture results and the Biofire joint infection panel (BJIP) in a cohort of pediatric patients with BJI. Materials and methods: Descriptive study. Patients admitted with probable o confirmed BJI between July 1, 2019 and February 28, 2021 at HOMI. Blood cultures, synovial and bone fluid samples were taken. Samples were kept at -70 °C. On September 2022, the panel was performed. Results: 32 patients were included. The average age was 83m (RIQ: 32-145). 23 (71.8%) patients had a positive culture. The most frequent microorganism were S. aureus 19 (83%), 11/19 (57.9%) Staphylococci isolates were MRSA. 24/32 (75%) were positive by panel, 20 positive detections were concordant with culture, there were 6 additional isolates by panel (2 S. aureus, 2 S. pyogenes, 1 K. kingae and 1 C. albicans), three microorganisms were isolated in culture but not in the panel. (2 S. aureus and 1 S. agalactiae). Two patients with coinfection were detected. All MRSA were detected by culture and panel. In 26 (81.3%) patients the etiology was documented by any method. Conclusion: These results showed a moderate level of agreement between BJIP and culture (κ = 0.47). The panel allowed the detection of fastidious bacteria including K. kingae and polymicrobial samples. There was a very good level of agreement between the panel and culture for the MRSA detection (κ = 1).

Implementation of a virtual community of practice to promote the empowerment of middle-aged people with multimorbidity: study protocol of a randomised controlled trial.

INTRODUCTION: Empowering people living with multimorbidity (multiple chronic conditions) to gain greater confidence in managing their health can enhance their quality of life. Education focused on self-management is a key tool for fostering patient empowerment and is mostly provided on an individual basis. Virtual communities of practice (VCoP) present a unique opportunity for online education in chronic condition self-management within a social context. This research aims to evaluate the effectiveness/cost-effectiveness of individualised, online self-management education compared with VCoP among middle-aged individuals living with multiple chronic conditions. METHODS AND ANALYSIS: People aged 30-60, living with ≥2 chronic conditions and receiving care in primary care (PC) centres and outpatient hospital-based clinics in Madrid and Canary Islands will enrol in an 18-month parallel-design, blinded (intervention assessment and data analysts), pragmatic (adhering to the intention-to-treat principle), individually randomised trial. The trial will compare two 12-month web-based educational offers of identical content; one delivered individually (control) and the other with online social interaction (VCoP, intervention). Using repeated measures mixed linear models, with the patient as random effect and allocation groups and time per group as fixed effects, we will estimate between-arm differences in the change in Patient Activation Measure from baseline to 12 months (primary endpoint), including measurements at 6-month and 18-month follow-up. Other outcomes will include measures of depression and anxiety, treatment burden, quality of life. In addition to a process evaluation of the VCoP, we will conduct an economic evaluation estimating the relative cost-effectiveness of the VCoP from the perspectives of both the National Health System and the Community. ETHICS AND DISSEMINATION: The trial was approved by Clinical Research Ethics Committees of Gregorio Marañón University Hospital in Madrid/Nuestra Señora Candelaria University Hospital in Santa Cruz de Tenerife. The results will be disseminated through workshops, policy briefs, peer-reviewed publications and local/international conferences. TRIAL REGISTRATION NUMBER: NCT06046326.

Data-Monitoring Solution for Desalination Processes: Cooling Tower and Mechanical Vapor Compression Hybrid System.

The advancement of novel water treatment technologies requires the implementation of both accurate data measurement and recording processes. These procedures are essential for acquiring results and conducting thorough analyses to enhance operational efficiency. In addition, accurate sensor data facilitate precise control over chemical treatment dosages, ensuring optimal water quality and corrosion inhibition while minimizing chemical usage and associated costs. Under this framework, this paper describes the sensoring and monitoring solution for a hybrid system based on a cooling tower (CT) connected to mechanical vapor compression (MVC) equipment for desalination and brine concentration purposes. Sensors connected to the data commercial logger solution, Almemo 2890-9, are also discussed in detail such as temperature, relative humidity, pressure, flow rate, etc. The monitoring system allows remote control of the MVC based on a server, GateManager, and TightVNC. In this way, the proposed solution provides remote access to the hybrid system, being able to visualize gathered data in real time. A case study located in Cartagena (Spain) is used to assess the proposed solution. Collected data from temperature transmitters, pneumatic valves, level sensors, and power demand are included and discussed in the paper. These variables allow a subsequent forecasting process to estimate brine concentration values. Different sample times are included in this paper to minimize the collected data from the hybrid system within suitable operation conditions. This solution is suitable to be applied to other desalination processes and locations.

Carotid-femoral pulse wave velocity score, an estimator of cognitive performance in the elderly: results from the Toledo Study for Healthy Aging.

Ageing-related changes in the vascular wall influence the function of different organs; for this reason, we assessed how arterial stiffness measured by carotid-femoral pulse wave velocity (cf-PWV) modulates: the basal cognitive performance and the change in cognitive performance over the follow-up time. We developed a prospective, population-based cohort study with 1581 participants aged > 65 years were obtained from the Toledo Study for Healthy Aging. Participants from the second wave (2011-2013) were selected for the cross-sectional analysis. Those who also performed the cognitive assessment in the third wave (2015-2017) were selected for the prospective analysis. Arterial stiffness was evaluated by cf-PWV. Multivariate segmented regression models were used to evaluate the association between cf-PWV scores and basal neuropsychological evaluation scores and change of neuropsychological evaluation scores along follow-up. Cross-sectional analysis showed that as cf-PWV grew within the cf-PWV (5- < 10) category an improvement was observed in 7-min test, free short-term memory, and hole peg test. Furthermore, in the cf-PWV (> 13-18) category a decrease was observed in total short-term memory, free long-term memory, and total long-term memory. Prospective analysis showed a progressive worsening of cognitive function as cf-PWV increases within the cf-PWV (> 13-18) category in 7-min test, object denomination, immediate and short-term memory, and hole peg test, while in the cf-PWV (5- < 10) category, there was observed a decrease in Cumulative Executive Dysfunction Index score and short-term memory. In conclusion, a higher cf-PWV score is associated with worse cognitive performance, and with a worse evolution, reinforcing the need to plan interventions to delay arterial stiffness and its consequences.

Metabolic equivalents intensity thresholds for physical activity classification in older adults.

BACKGROUND: Although the metabolic equivalents (METs) system is a common procedure to quantify the intensity of physical activity in older adults, it remains unclear whether the conventional METs intensity thresholds (CTs) used for this purpose are appropriate in this population. Therefore, this study aimed (i) to derive overall and fitness-specific METs intensity thresholds in older adults ≥ 60 years old (OATs) expressed both in standard METs (VO2/3.5 mL O2·kg-1·min-1) and older adults METs60+ (VO2/2.7 mL O2·kg-1·min-1), and (ii) to compare them with the CTs. METHODS: A total of 93 subjects were assessed for cardiorespiratory fitness. Graded exercise test protocols using indirect calorimetry were performed to calculate individual VO2max and categorize subjects as "very poor/fair" or "good/superior" fitness. Overall and fitness-specific OATs expressed in standard METs (OATsstandard) and METs60+ (OATs60+) were derived based on the %VO2max and the ventilatory thresholds (VTs) physical intensity categories. RESULTS: Significantly higher VO2max, VO2 at VT1 and VO2 at VT2 (p < 0.001) were obtained in the "good/superior" subgroup compared to the "very poor/fair" fitness subgroup. Accordingly, OATs were approximately 69% higher in individuals with a "good/superior" fitness compared to those with a "very poor/fair" fitness. Furthermore, this study showed that OATsstandard were approximately 21-24% lower than OATs60+, and 10-22% higher OATs were observed when following the VTs intensity categories (heavy-intensity physical activity [HPA] and severe-intensity physical activity [SPA]) compared to the %VO2max categories (moderate-intensity physical activity [MPA] and vigorous-intensity physical activity [VPA]). When compared with the CTs, similar or higher OATsstandard and OATs60+ for MPA, and HPA were obtained compared to the conventional MPA threshold (3.0 METs). Conversely, for VPA and SPA, lower, similar, or higher OATs were obtained depending on the METs derivation approach (OATsstandard or OATs60+) or the intensity categories (VO2max or VTs), compared to the conventional VPA threshold (6.0 METs). CONCLUSIONS: None of the derived OATs were concurrently similar to the CTs, suggesting that fitness-specific METs intensity thresholds adapted to the METs derivation approach should be used in older adults. TRIAL REGISTRATION: FenotipAGING (Non-health-care intervention study), PRO-Training (NCT05619250).

Frailty Influences the Relationship between the Soluble Receptor for Advanced Glycation-End Products and Mortality in Older Adults with Diabetes Mellitus.

INTRODUCTION: Frailty is prevalent among older adults with diabetes mellitus. Elevated serum levels of the soluble receptor for advanced glycation-end products (sRAGE) predict mortality in frail older adults. The evidence that sRAGE is also related to higher mortality in older adults with diabetes mellitus is inconsistent. Therefore, this study explored if frailty status influences the relationship between sRAGE and mortality in older adults with this condition. METHODS: We analysed data of 391 participants with diabetes mellitus (median age, 76 years) from four European cohorts enrolled in the FRAILOMIC project. Frailty was evaluated at baseline using Fried's criteria. Serum sRAGE was determined by ELISA. Participants were stratified by frailty status (n = 280 non-frail and 111 frail). Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between sRAGE and mortality. RESULTS: During 6 years of follow-up, 98 participants died (46 non-frail and 52 frail). Non-survivors had significantly higher baseline levels of sRAGE than survivors (median [IQR]: 1,392 [962-2,043] pg/mL vs. 1,212 [963-1,514], p = 0.008). High serum sRAGE (>1,617 pg/mL) was associated with increased mortality in the whole diabetes sample after adjustment for relevant confounders (HR 2.06, 95% CI: 1.36-3.11, p < 0.001), and there was an interaction between sRAGE and frailty (p = 0.006). Accordingly, the association between sRAGE and mortality was stronger in the frail group compared to the non-frail group (HR 2.52, 95% CI: 1.30-4.90, p = 0.006 vs. HR 1.71, 95% CI: 0.91-3.23, p = 0.099, respectively). Likewise, Kaplan-Meier curves showed a significant difference in survival rates between frail participants with high sRAGE and those with low sRAGE (p = 0.001), whereas no survival difference was seen in the non-frail group (p = 0.09). CONCLUSIONS: Frailty status influences the relationship between sRAGE and mortality in older adults with diabetes mellitus. Determination of sRAGE in this population could be a useful tool for risk stratification.

Shipwrecked on the Rock, or Not Quite: Gypsophytes and Edaphic Islands.

Species-area relationships (SAR) constitute a key aspect of ecological theory and are integral to other scientific disciplines, such as biogeography, which have played a crucial role in advancing biology. The theory of insular biogeography provides a clear example. This theory initially expanded from true islands to other types of systems characterized by their insularity. One such approach was linked to geoedaphic islands, as seen in gypsum outcrops. While these continental areas have been considered insular systems, only limited and mostly indirect evidence thereof has been provided. This study utilized SAR to advance the understanding of gypsum outcrops as insular continental territories. It is hereby hypothesized that gypsum outcrops are edaphic islands, although their insular nature depends on the different functional or ecological plant types, and this nature will be reflected in the potential Arrhenius model z values. The results obtained support both hypotheses and provide insight into the ecological factors that help interpret the insularity of these areas. This interpretation goes beyond their mere extent and the distance among outcrops, emphasizing the importance of environmental filters. Said filters vary in permeability depending on the degree of gypsophily, or preference for gypsum, exhibited by different species.

RhoA/rho kinase pathway activation in age-associated endothelial cell dysfunction and thrombosis.

The small GTPase RhoA and the downstream Rho kinase (ROCK) regulate several cell functions and pathological processes in the vascular system that contribute to the age-dependent risk of cardiovascular disease, including endothelial dysfunction, excessive permeability, inflammation, impaired angiogenesis, abnormal vasoconstriction, decreased nitric oxide production and apoptosis. Frailty is a loss of physiological reserve and adaptive capacity with advanced age and is accompanied by a pro-inflammatory and pro-oxidative state that promotes vascular dysfunction and thrombosis. This review summarises the role of the RhoA/Rho kinase signalling pathway in endothelial dysfunction, the acquisition of the pro-thrombotic state and vascular ageing. We also discuss the possible role of RhoA/Rho kinase signalling as a promising therapeutic target for the prevention and treatment of age-related cardiovascular disease.

SER recommendations on treatment of refractory Behçet's syndrome.

OBJECTIVE: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (BS) (difficult to treat, severe resistant, severe relapse) to conventional treatment. METHODS: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format (patient, intervention, comparison and outcome). Systematic reviews of the evidence were conducted, the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations Assessment, Development, and Evaluation (GRADE). After that, the multidisciplinary panel formulated the specific recommendations. RESULTS: 4 PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with BS with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. CONCLUSIONS: The treatment of most severe clinical manifestations of BS lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official Recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.

Relationship of endogenous plasma concentrations of ß-hydroxy ß-methyl butyrate (HMB) with frailty in community dwelling older adults with type-2 diabetes mellitus.

BACKGROUND: Supplementation with ß-hydroxy ß-methyl butyrate (HMB) appears to be effective in preserving muscle in older adults. However, the association between endogenously produced HMB with frailty has not been studied in people with chronic disease. OBJECTIVES: The purpose of this study is to explore whether an association exists between endogenous HMB levels and frailty status in older adults with type-2 diabetes mellitus (T2DM). METHODS: Data were taken from the Toledo Study of Healthy Ageing, a community-dwelling aged (65 years+) cohort. Frailty was assessed at baseline and at 2.99 median years according to the Frailty Phenotype (FP) standardized to our population and the Frailty Trait Scale 12 (FTS12). The associations between HMB levels and frailty were assessed using three nested multivariate logistic regressions and segmented by sex. Glucose, HMB and glucose interaction, age and body composition were used as covariables. RESULTS: 255 participants (mean age 75.3 years, 52.94% men) were included. HMB levels showed an inverse cross-sectional association with frailty, which was modified when the interaction term HMB*glucose was included, remaining significant only for FTS12 [OR (95% CI): 0.436 (0.253, 0.751), p-value 0.003]. The association between HMB endogenous levels and FTS12 appears to be independent of sex, in which the association was maintained after adjusting for the covariates. However, there appears to be threshold points for glucose levels, above which the protective effect of HMB is lost: 145.4 mg/dl adjusted by gender for the whole sample and 149.6 mg/dl and 138.9 mg/dl for men and women, respectively. Endogenous HMB levels were not found to be associated with incident frailty. CONCLUSIONS: Cross-sectional analysis revealed that endogenous HMB levels were inversely associated with frailty as assessed by the FTS12 in older people with T2DM. This association was found to be dependent on circulating fasted glucose levels.

The Role of Heparin in Postural Orthostatic Tachycardia Syndrome and Other Post-Acute Sequelae of COVID-19.

The therapeutic management and short-term consequences of the coronavirus disease 2019 (COVID-19) are well known. However, COVID-19 post-acute sequelae are less known and represent a public health problem worldwide. Patients with COVID-19 who present post-acute sequelae may display immune dysregulation, a procoagulant state, and persistent microvascular endotheliopathy that could trigger microvascular thrombosis. These elements have also been implicated in the physiopathology of postural orthostatic tachycardia syndrome, a frequent sequela in post-COVID-19 patients. These mechanisms, directly associated with post-acute sequelae, might determine the thrombotic consequences of COVID-19 and the need for early anticoagulation therapy. In this context, heparin has several potential benefits, including immunomodulatory, anticoagulant, antiviral, pro-endothelial, and vascular effects, that could be helpful in the treatment of COVID-19 post-acute sequelae. In this article, we review the evidence surrounding the post-acute sequelae of COVID-19 and the potential benefits of the use of heparin, with a special focus on the treatment of postural orthostatic tachycardia syndrome.

Vaccination in pregnancy. Consensus document of the CAV-AEP and the SEGO.

During pregnancy, physiological changes in the immune response make pregnant women more susceptible to serious infection, increasing the risk for the mother as well as the foetus, newborn and infant. All women should be correctly and fully vaccinated as they enter their reproductive years, especially against diseases such as tetanus, hepatitis B, measles, rubella and varicella. In addition to the recommended vaccines, in risk situations, inactivated vaccines could be administered to women who were not correctly vaccinated before, while attenuated vaccines are contraindicated. Despite the fact that vaccination during pregnancy is a very important preventive measure and the existing recommendations from public health authorities, scientific societies and health professionals, the vaccination coverage could clearly be improved, especially against influenza and SARS-CoV-2, so any health professional involved in the care of pregnant women should proactively recommend these vaccines. The Spanish Association of Pediatrics (AEP), through its Advisory Committee on Vaccines, and the Spanish Society of Gynaecology and Obstetrics (SEGO) recommend vaccination against the following diseases during pregnancy: against influenza and COVID-19, in any trimester of pregnancy and during the postpartum period (up to 6 months post birth) in women not vaccinated during pregnancy; against pertussis, with the Tdap vaccine, between weeks 27 and 36 of gestation (in the CAV-AEP recommendations, preferably between weeks 27 and 28); and against RSV, with RSVPreF, between weeks 24 and 36 of gestation, preferably between weeks 32 and 36.