Gut microbiota and its relationship with early vascular ageing in a Spanish population (MIVAS study).

BACKGROUND: Gut microbiota and its by-products are increasingly recognized as having a decisive role in cardiovascular diseases. The aim is to study the relationship between gut microbiota and early vascular ageing (EVA). METHODS: A cross-sectional study was developed in Salamanca (Spain) in which 180 subjects aged 45-74 years were recruited. EVA was defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), cardio-ankle vascular index (CAVI) or brachial-ankle pulse wave velocity (ba-PWV) above the 90th percentile of the reference population. All other cases were considered normal vascular ageing (NVA). MEASUREMENTS: cf-PWV was measured by SphygmoCor® System; CAVI and ba-PWV were determined by Vasera 2000® device. Gut microbiome composition in faecal samples was determined by 16S rRNA Illumina sequencing. RESULTS: Mean age was 64.4 ± 6.9 in EVA group and 60.4 ± 7.6 years in NVA (p < .01). Women in EVA group were 41% and 53% in NVA. There were no differences in the overall composition of gut microbiota between the two groups when evaluating Firmicutes/Bacteriodetes ratio, alfa diversity (Shannon Index) and beta diversity (Bray-Curtis). Bilophila, Faecalibacterium sp.UBA1819 and Phocea, are increased in EVA group. While Cedecea, Lactococcus, Pseudomonas, Succiniclasticum and Dielma exist in lower abundance. In logistic regression analysis, Bilophila (OR: 1.71, 95% CI: 1.12-2.6, p = .013) remained significant. CONCLUSIONS: In the studied Spanish population, early vascular ageing is positively associated with gut microbiota abundance of the genus Bilophila. No relationship was found between phyla abundance and measures of diversity.

Risk factors of death or chronic renal replacement therapy requirements in patients with thrombotic microangiopathies without ADAMTS-13 deficiency.

Thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and multisystem organ dysfunction, is a life-threatening disease. Patients with TMA who do not exhibit a severe ADAMTS-13 deficiency (defined as a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 activity ≥10%: TMA-13n) continue to experience elevated mortality rates. This study explores the prognostic indicators for augmented mortality risk or necessitating chronic renal replacement therapy (composite outcome: CO) in TMA-13n patients. We included 42 TMA-13n patients from January 2008 to May 2018. Median age of 41 years and 60% were female. At presentation, 62% required dialysis, and 57% warranted intensive care unit admission. CO was observed in 45% of patients, including a 9-patient mortality subset. Multivariate logistic regression revealed three independent prognostic factors for CO: early administration of eculizumab (median time from hospitalization to eculizumab initiation: 5 days, range 0-19 days; odds ratio [OR], 0.14; 95% confidence interval [CI], 0.02-0.94), presence of neuroradiological lesions (OR, 6.67; 95% CI, 1.12-39.80), and a PLASMIC score ≤4 (OR, 7.39; 95% CI, 1.18-46.11). In conclusion, TMA-13n patients exhibit a heightened risk of CO in the presence of low PLASMIC scores and neuroradiological lesions, while early eculizumab therapy was the only protective factor.

Is immediate weight bearing safe for subtrochanteric femur fractures in elderly patients treated by cephalomedullary nailing? A multicentric study in one hundred eighty-two patients.

PURPOSE: Biomechanical superiority of intramedullary nails over extramedullary implants has been proved for subtrochanteric fractures. Nevertheless, postoperative management of these patients has not changed, with high rates of protected weight-bearing after intramedullary nailing. The purpose of this study is to determine the mechanical complications of immediate postoperative full weigh-bearing for subtrochanteric femur fractures in elderly patients treated with a cephalomedullary nail. METHODS: We performed a retrospective case series study from patients treated with a cephalomedullary nail for subtrochanteric fractures (AO/OTA 31A.3 and 32A-32C) over a nine-year period. Patients in the immediate full weight-bearing (IFWB) group received orders for immediate full weight bear as tolerated on postoperative 48 h. Patients in the non- or limited- weight-bearing (NLWB) group received orders not to full weight bear in the immediate postoperative. RESULTS: There were five (2.7%) cases of implant failure including four cutouts and one nail breakage that needed a reoperation. Of them, one (2.2%) followed the NLWB protocol and four (2.9%) followed the IFWB protocol. Mean length of stay was 7.9 days (median 8, range 3-21) in the NLWB group and 10.7 days (median 8, range 2-60) in the IWBAT group. The NLWB group observed a 2.8-day shorter postoperative length of stay when compared to the IFWB, but the median remained equal. CONCLUSION: This study suggests that geriatric patients with subtrochanteric fractures treated by intramedullary nailing and in which a good fracture reduction was achieved, may be able to tolerate immediate postoperative full weight-bearing, not increasing reoperation rates due to implant failure.

Potential Role for Observation in Small Solid Pseudopapillary Neoplasm (SPN).

BACKGROUND: Solid pseudopapillary neoplasms (SPN) are rare tumors of the pancreas, typically affecting young women. Resection is the mainstay of treatment but is associated with significant morbidity and potential mortality. We explore the idea that small, localized SPN could be safely observed. METHODS: This retrospective review of the Pancreas National Cancer Database from 2004 to 2018 identified SPN via histology code 8452. RESULTS: A total of 994 SPNs were identified. Mean age was 36.8 ± 0.5 years, 84.9% (n = 844) were female, and most had a Charlson-Deyo Comorbidity Coefficient (CDCC) of 0-1 (96.6%, n = 960). Patients were most often staged clinically as cT2 (69.5%, n = 457) followed by cT3 (17.6%, n = 116), cT1 (11.2%, n = 74), and cT4 (1.7%, n = 11). Clinical lymph node and distant metastasis rates were 3.0 and 4.0%, respectively. Surgical resection was performed in 96.6% of patients (n = 960), most commonly partial pancreatectomy (44.3%) followed by pancreatoduodenectomy (31.3%) and total pancreatectomy (8.1%). In patients clinically staged as node (N0) and distant metastasis (M0) negative, occult pathologic lymph node involvement was found in 0% (n = 28) of patients with stage cT1 and 0.5% (n = 185) of patients with cT2 disease. The risk of occult nodal metastasis significantly increased to 8.9% (n = 61) for patients with cT3 disease. The risk further increased to 50% (n = 2) in patients with cT4 disease. CONCLUSIONS: Herein, the specificity of excluding nodal involvement clinically is 99.5% in tumors ≤ 4 cm and 100% in tumors ≤ 2 cm. Therefore, there may be a role for close observation in patients with cT1N0 lesions to mitigate morbidity from major pancreatic resection.

Effect of Flu Vaccination on Severity and Outcome of Heart Failure Decompensations.

OBJECTIVE: To investigate the relationship of seasonal flu vaccination with the severity of decompensation and long-term outcomes of patients with heart failure (HF). METHODS: We analyzed 6147 consecutively enrolled patients with decompensated HF who presented to 33 Spanish emergency departments (EDs) during January and February of 2018 and 2019, grouped according to seasonal flu vaccination status. The severity of HF decompensation was assessed by the Multiple Estimation of Risk Based on the Emergency Department Spanish Score in Patients With Acute Heart Failure (MEESSI-AHF) + MEESSI scale, need of hospitalization and in-hospital all-cause mortality. The long-term outcomes analyzed were 90-day postdischarge adverse events and 90-day all-cause death. Associations between vaccination, HF decompensation severity and long-term outcomes were explored by unadjusted and adjusted logistic and Cox regressions by using 14 covariables that could act as potential confounders. RESULTS: Overall median (IQR) age was 84 (IQR = 77-89) years, and 56% were women. Vaccinated patients (n = 1139; 19%) were older, had more comorbidities and had worse baseline status, as assessed by New York Heart Association class and Barthel index, than did unvaccinated patients (n = 5008; 81%). Infection triggering decompensation was more common in vaccinated patients (50% vs 41%; P < 0.001). In vaccinated and unvaccinated patients, high or very-high risk decompensation was seen in 21.9% and 21.1%; hospitalization occurred in 72.5% and 73.7%; in-hospital mortality was 7.4% and 7.0%; 90-day postdischarge adverse events were 57.4% and 53.2%; and the 90-day mortality rate was 15.8% and 16.6%, respectively, with no significant differences between cohorts. After adjusting, vaccinated decompensated patients with HF had decreased odds for hospitalization (OR = 0.823, 95%CI = 0.709-0.955). CONCLUSION: In patients with HF, seasonal flu vaccination is associated with less severe decompensations.

Molecularly imprinted nanoparticle-based assay (MINA) for microcystin-LR detection in water.

Microcystins (MCs) are highly toxic peptides produced by cyanobacteria during algal blooms. Microcystin-leucine-arginine (MC-LR) is the most toxic and common MC variant with major effects on human and animal health upon exposure. MC-LR detection has become critical to ensure water safety, therefore robust and reliable analytical methods are needed. This work reports the development of a simple and optimized Molecularly Imprinted Nanoparticle-Based Assay (MINA) for MC-LR detection in water. Molecularly Imprinted Nanoparticles (MINs) were prepared by solid-phase polymerization on glass beads conjugated to MC-LR through (3-aminopropyl) triethoxysilane (APTES) via amide bonding. APTES-modified glass beads were obtained under optimized conditions to maximize the density of surface amino groups available for MC-LR conjugation. Two quinary mixtures of acrylic monomers differing in charge, polarity, and functionality were selected from molecular docking calculations and used to obtain MINs for MC-LR recognition using N,N'-methylene-bis-acrylamide (BIS) as the crosslinking agent. MINs were immobilized by physical adsorption onto 96-well polystyrene microplate and evaluated as per their rebinding capacity toward the analyte by using a covalent conjugate between MC-LR and the enzyme horseradish peroxidase (HRP). Experimental conditions for the MINs immobilization protocol, HRP-MC-LR concentration, and composition of the blocking solution were set to maximize the colorimetric response of the MINs compared to non-treated wells. Optimized conditions were then applied to conduct competitive MINAs with the HRP-MC-LR conjugate and the free analyte, which confirmed the preferential binding of MC-LR to the immobilized MINs for analyte concentrations ranging from 1 × 10-5 nmol L-1 to 100 nmol L-1. The best competitive MINA showed a limit of detection of 2.49 × 10-4 nmol L-1 and coefficients of variation less than 10% (n = 6), which are auspicious for the use of MINs as analytical tools for MC-LR detection below the permissible limits issued by WHO for safe water consumption (1.00 nmol L-1). This assay also proved to be selective to the analyte in cross-reactivity studies with two analogous microcystins (MC-RR and MC-YR). Analyses of lagoon and drinking water samples enriched with MC-LR revealed strong matrix effects that reduce the MINA response to the analyte, thus suggesting the need for sample pretreatment methods in future development in this subject.

LAURDAN since Weber: The Quest for Visualizing Membrane Heterogeneity.

Any chemist studying the interaction of molecules with lipid assemblies will eventually be confronted by the topic of membrane bilayer heterogeneity and may ultimately encounter the heterogeneity of natural membranes. In artificial bilayers, heterogeneity is defined by phase segregation that can be in the nano- and micrometer range. In biological bilayers, heterogeneity is considered in the context of small (10-200 nm) sterol and sphingolipid-enriched heterogeneous and highly dynamic domains. Several techniques can be used to assess membrane heterogeneity in living systems. Our approach is to use a fluorescent reporter molecule immersed in the bilayer, which, by changes in its spectroscopic properties, senses physical-chemistry aspects of the membrane. This dye in combination with microscopy and fluctuation techniques can give information about membrane heterogeneity at different temporal and spatial levels: going from average fluidity to number and diffusion coefficient of nanodomains. LAURDAN (6-dodecanoyl-2-(dimethylamino) naphthalene), is a fluorescent probe designed and synthesized in 1979 by Gregorio Weber with the purpose to study the phenomenon of dipolar relaxation. The spectral displacement observed when LAURDAN is either in fluid or gel phase permitted the use of the technique in the field of membrane dynamics. The quantitation of the spectral displacement was first addressed by the generalized polarization (GP) function in the cuvette, a ratio of the difference in intensity at two wavelengths divided by their sum. In 1997, GP measurements were done for the first time in the microscope, adding to the technique the spatial resolution and allowing the visualization of lipid segregation both in liposomes and cells. A new prospective to the membrane heterogeneity was obtained when LAURDAN fluorescent lifetime measurements were done in the microscope. Two channel lifetime imaging provides information on membrane polarity and dipole relaxation (the two parameters responsible for the spectral shift of LAURDAN), and the application of phasor analysis allows pixel by pixel understanding of these two parameters in the membrane. To increase temporal resolution, LAURDAN GP was combined with fluctuation correlation spectroscopy (FCS) and the motility of nanometric highly packed structures in biological membranes was registered. Lately the application of phasor analysis to spectral images from membranes labeled with LAURDAN allows us to study the full spectra pixel by pixel in an image. All these methodologies, using LAURDAN, offer the possibility to address different properties of membranes depending on the question being asked. In this Account, we will focus on the principles, advantages, and limitations of different approaches to orient the reader to select the most appropriate technique for their research.

Changes in lifestyles, cognitive impairment, quality of life and activity day living after combined use of smartphone and smartband technology: a randomized clinical trial (EVIDENT-Age study).

BACKGROUND: The aim of this study was to assess the efficacy of the combined use of smartphone and smartband technology for 3-months alongside brief lifestyle counselling, versus counselling alone, in increasing physical activity. As secondary objectives, the effects of the intervention on dietary habits, body composition, quality of life, level of functionality and cognitive performance were assessed. METHODS: This study employed a randomized clinical trial of two-parallel groups design - control group (CG) and intervention group (IG). The study was conducted in 3 Spanish health-centres between October 2018-February 2020. Eligible participants were people of both sexes and aged between 65-80 years attending the health-centres with a score ≥ 24 points on the Mini-Mental State Examination. Key variables included physical activity, dietary pattern, body composition, cognitive performance, level of functionality and quality of life. All variables were measured at baseline and after 3-months. Both groups received a brief nutritional and physical activity advice. Intervention group participants were instructed to use a smartphone application for a period of 3-months. This application integrates information on physical activity received from a fitness bracelet and self-reported information on the patient's daily nutritional composition. RESULTS: The study population comprised 160 participants (IG = 81, CG = 79), with a mean age of 70.8 ± 4.0 years (61.3% women). No difference was found in the primary and secondary outcomes analyzed (physical activity (steps/min -0.4 (-1.0 to 0.2) p = 0.174), and dietary habits (Mediterranean diet score 0.0 (-0.6 to 0.6) p = 0.956) that could be attributed to either group after an ANCOVA test. A difference attributable to the intervention was observed in the total Clock test score (0.7 (0.1 to 1.2) p = 0.018. CONCLUSIONS: In a sample of people over 65 years of age, the combined use of the EVIDENT 3 smartphone app and an activity tracking bracelet for 3-months did not result in lifestyles changes related to the amount and level of physical activity or the eating habits, compared to brief lifestyle advice. Other clinical parameters were not changed either, although at the cognitive level, a slight improvement was observed in the score on the Clock test assessing a variety of cognitive functions such as memory. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov Identifier: NCT03574480. Date of trial Registration 02/07/2018.

The inflammatory role of silent urate crystal deposition in intercritical gout.

OBJECTIVE: To study subclinical inflammation in intercritical gout patients and its relation to the estimated size of monosodium urate crystal deposition and cardiovascular risk factors. METHODS: We performed a secretome analysis and the quantification of cytokine and adipokine plasma levels [IL-1ß, IL-18, IL-6, soluble IL-6 receptor (sIL-6R), TNF-α, C-X-C motif chemokine 5, RANTES (Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted), leptin, resistin and adiponectin] to analyse subclinical inflammation in intercritical gout patients. Since it is currently not feasible to determinate the whole body deposit of monosodium urate crystals, we created an indirect clinical classification to estimate it. Then we compared cytokine levels in controls and gout patients and in patients with different crystal deposition sizes. We also studied the association between cytokine-levels and the number of cardiovascular risk factors. RESULTS: Ninety consecutive patients attending a crystal arthritis unit were studied. IL-18, sIL-6R, RANTES, leptin and adiponectin were higher in intercritical gout patients than in controls. An association was observed between IL-18, sIL6-R and RANTES levels and the size of crystal deposition. IL-18, sIL6-R, RANTES and leptin were higher in patients with no cardiovascular risk factors compared with controls with no risk factors. CONCLUSION: Our results showed that the levels of some pro-inflammatory cytokines and metabolic proteins are elevated in intercritical gout patients. The levels of certain cytokines were related to the estimated size of the monosodium urate crystal deposition and to the number of cardiovascular risk factors. These cytokine changes may help to explain the increase in cardiovascular events in gout patients.

Proteostasis is essential during cochlear development for neuron survival and hair cell polarity.

Protein homeostasis is essential to cell function, and a compromised ability to reduce the load of misfolded and aggregated proteins is linked to numerous age-related diseases, including hearing loss. Here, we show that altered proteostasis consequent to Elongator complex deficiency also impacts the proper development of the cochlea and results in deafness. In the absence of the catalytic subunit Elp3, differentiating spiral ganglion neurons display large aggresome-like structures and undergo apoptosis before birth. The cochlear mechanosensory cells are able to survive proteostasis disruption but suffer defects in polarity and stereociliary bundle morphogenesis. We demonstrate that protein aggregates accumulate at the apical surface of hair cells, where they cause a local slowdown of microtubular trafficking, altering the distribution of intrinsic polarity proteins and affecting kinocilium position and length. Alleviation of protein misfolding using the chemical chaperone 4-phenylbutyric acid during embryonic development ameliorates hair cell polarity in Elp3-deficient animals. Our study highlights the importance of developmental proteostasis in the cochlea and unveils an unexpected link between proteome integrity and polarized organization of cellular components.

Risk factors for symptomatic anastomotic postoperative recurrence following ileo-colic resection in Crohn's disease.

AIM: Crohn's disease is a chronic inflammatory bowel disease characterized by alternating periods of exacerbation and remission. Surgical resection is not curative and postoperative recurrence (POR) remains a challenge in these patients. The aim of this study was to identify clinical variables that influence the risk of symptomatic anastomotic POR in patients with ileo-colonic Crohn's disease. METHOD: A retrospective study of Crohn's disease patients who had undergone ileo-colic resection between January 2014 and December 2018 was performed. For each patient, data including demographic information, Crohn's disease clinical setting, preoperative radiological data, operative and histological data, pre- and postoperative medication history and postoperative clinical course, including recurrence of disease, were extracted. Symptomatic anastomotic POR was defined as symptoms of Crohn's disease in the presence of confirmed anastomotic POR (endoscopic and/or radiological POR). RESULTS: For the study period, 104 patients were eligible and included for analysis. The cumulative probability of symptomatic anastomotic POR was 14%, 30%, 42%, 50% and 50% at 1, 2, 3, 4 and 5 years, respectively. Two clinical variables on multivariate analysis were associated with increased risk of symptomatic anastomotic POR, namely age <17 years at diagnosis [hazard ratio (HR) 2.17, p = 0.019] and gastrointestinal involvement (extent) >30 cm (HR 1.85, p = 0.048). CONCLUSION: This study describes the natural history of POR after ileo-colic resection for Crohn's disease, as defined by endoscopic, radiological and clinical outcomes. Age <17 years at diagnosis and gastrointestinal involvement (extent) >30 cm were independent risk factors for symptomatic anastomotic POR.

Factors associated with poor prognosis in patients with atrial fibrillation: An emergency department perspective the EMERG-AF study.

OBJECTIVE: We sought to identify the factors associated with a worse prognosis in Emergency Department (ED) patients with atrial fibrillation (AF), crucial information to guide management decisions. METHODS: This is a secondary analysis of a prospective, multicenter, observational cohort of consecutive AF patients attended in 62 EDs in Spain. Clinical variables were collected on enrollment. Follow-up was performed at 30 days and one year. The primary composite outcome was all-cause mortality, major bleeding and/or stroke at one year. Secondary outcomes were each of these components considered separately, plus one-year cardiovascular mortality and the composite outcome at 30 days. RESULTS: We analyzed 1107 patients. The primary outcome occurred in 209 patients (18.9%), one-year all-cause mortality in 151 (13.6%), major bleeding in 47 (4.2%), and stroke in 31 (2.8%). Disability (HR 2.064, 95% CI 1.478-2.882), previous known AF (HR 1.829, 95% CI 1.096-3.051), long duration of the AF episode (HR 1.849, 95% CI 1.052-3.252) and renal failure (HR 2.073, 95% CI 1.433-2.999) were independently associated with the primary outcome, whereas anticoagulation at discharge was inversely associated (HR 0.576, 95% CI 0.415-0.801). Disability was associated with mortality, cardiovascular mortality, and the composite at 30 days, and renal failure with mortality and major bleeding. CONCLUSIONS: Comorbidities like renal failure, long AF duration and disability were related to adverse outcomes and should be decisive to guide management decisions in ED patients with AF. Anticoagulation had a positive impact on prognosis and should be the mainstay of therapy in AF patients attended in ED.

Nosocomial SARS-CoV-2 infection in urology departments: Results of a prospective multicentric study.

OBJECTIVE: To evaluate the coronavirus disease 2019 perioperative infection rate and mortality rate of patients undergoing urological surgeries during the early pandemic period in Spain. METHODS: This was a non-interventional multicenter prospective study carried out from 9 March to 3 May 2020 in two urology departments in Madrid, Spain. Clinical, microbiological and radiological data of patients who underwent surgery were collected from computerized medical records. RESULTS: A total of 148 patients were included in the study, and 141 were analyzed for nosocomial infection risk, after excluding previous and concomitant severe acute respiratory syndrome coronavirus type 2 infections. Elective surgeries represented 76.6% of the procedures, whereas emergent surgeries represented 23.4%. Preoperative screening was carried out with polymerase chain reaction test in 34 patients, all were negative. A total of 14 patients also had chest X-ray (not suspicious in all cases). Three patients (2.1%) developed severe acute respiratory syndrome coronavirus type 2 nosocomial infection (symptoms developed between the third day after surgery to the 14th day after hospital discharge). Time from admission to a compatible clinical case was 5.5 days (4-12 days). Two patients underwent surgery with concomitant diagnosis of coronavirus disease. The mortality rate due to severe acute respiratory syndrome coronavirus type 2 infection is 0.7%, and the specific mortality rate in patients undergoing surgery with community-acquired coronavirus disease 2019 infection was 50% (1/2). CONCLUSIONS: The nosocomial severe acute respiratory syndrome coronavirus type 2 infection rate was low in patients undergoing urological surgical procedures during the peak of the pandemic in Madrid. With appropriate perioperative screening, urological surgical activity can be carried out in safety conditions.

Effect of an intensive intervention on the increase of physical activity and the decrease of sedentary lifestyle in inactive postmenopausal.

BACKGROUND: During the transition to menopause, women experience different psychological, hormonal, and physical alterations that can affect their health. Physical activity is considered an important strategy in the prevention and control of such changes. AIM: To evaluate the short-term effect of an intensive intervention, based on a combined exercise programme using a Smartband, on the increase of physical activity and the decrease of sedentary lifestyle in postmenopausal and inactive women. DESIGN: Randomized clinical trial with two parallel groups. METHODS: In total, 100 postmenopausal and inactive women aged 45-70 years will be randomized to a control group or an intervention group. Both groups will be given a standardized advice about physical activity. The intervention group will carry out a supervised 12-week programme of aerobic and muscle strengthening exercise; moreover, the women in this group will receive a Smartband to assist them in the intervention. The main result will be the increase of physical activity and the decrease of sedentary lifestyle, measured with an accelerometer for 1 week. This programme will be conducted by a nurse and a physiotherapist of the health centre. The study was approved by the Drug Research Ethics Committee of the Salamanca Health Service on 15 February 2019. The project was funded by the Autonomous Government of Castile and Leon and by the Carlos III Health Institute. DISCUSSION: Physical activity is an important strategy to consider when addressing the changes caused by menopause, although the current evidence shows that further studies should be carried out with longer intervention periods and new technologies. IMPACT: This study will allow determining the effectiveness of the intensive intervention based on a combined programme of physical activity using a Smartband in postmenopausal and inactive women. TRIALS REGISTRATION: ClinicalTrials.gov with identifying code NCT03872258.

Behavioural intervention to reduce disruptive behaviours in adult day care centres users: A randomizsed clinical trial (PROCENDIAS study).

AIM: This study assesses the effect of an intervention to reduce the disruptive behaviours (DB) presented by care recipient users of adult day care centres (ADCC), thereby reducing caregiver overload. While ADCC offer beneficial respite for family caregivers, the DB that many care recipients show promote resistance to attending these centres, which can be a great burden on their family caregivers. DESIGN: Randomized controlled clinical trial. METHODS: The study was carried out with 130 family caregivers of people attending seven ADCC in the municipality of Salamanca (Spain), randomly distributed into intervention and control groups. The intervention was applied across eight sessions, one per week, in groups of 8-10 people where caregivers were trained in the Antecedent-Behavior-Consequence (ABC) model of functional behaviour analysis. The primary outcome was the reduction of DB measured with the Revised Memory and Behavior Problems Checklist (RMBPC). RESULTS: An average reduction in the RMBPC of 4.34 points was obtained in the intervention group after applying the intervention (p < 0.01 (U de Mann-Whitney); Cohen d = 1.00); furthermore, differences were found in the Center for Epidemiologic Studies Depression Scale (CES-D) (U = -2.67; p = 0.008; Cohen d = 0.50) and in the Short Zarit Burden Interview (Short ZBI) (t = -4.10; p < 0.01; Cohen d = 0.98). CONCLUSION: The results obtained suggest that the implementation of this intervention could reduce both the frequency of DB occurrence and the reaction of the caregiver to their appearance. Improvement was also noted in the results regarding overload and emotional state of the family caregiver. IMPACT: To our knowledge, this is the first randomized clinical trial to show that an intervention based on the ABC model could reduce the frequency and reaction of DB of care recipients in ADCC increasing their quality of life, and improving the mental health and overload of their family caregivers.

Development and Characterization of a Compact Device for Measuring the Braking Torque of a Vehicle.

In this article, a new force transducer is designed, developed and built for the measurement of braking forces in the wheel rim of a motor vehicle. The parameters of the transducer design are justified using numerical simulation. In order to install it in the vehicle in a simple and interference-free way, the metal base of the caliper rod is used. It is manufactured and installed in a vehicle in order to obtain the signals of the wheel braking torque, in real time, and at different speeds of circulation, carrying out several tests on the track. Subsequently, data are obtained from calculations of the disc brake system itself. The latter provides instantaneous adherence values between the brake pad and the disc.

Simultaneous Estimation of Vehicle Roll and Sideslip Angles through a Deep Learning Approach.

Presently, autonomous vehicles are on the rise and are expected to be on the roads in the coming years. In this sense, it becomes necessary to have adequate knowledge about its states to design controllers capable of providing adequate performance in all driving scenarios. Sideslip and roll angles are critical parameters in vehicular lateral stability. The later has a high impact on vehicles with an elevated center of gravity, such as trucks, buses, and industrial vehicles, among others, as they are prone to rollover. Due to the high cost of the current sensors used to measure these angles directly, much of the research is focused on estimating them. One of the drawbacks is that vehicles are strong non-linear systems that require specific methods able to tackle this feature. The evolution in Artificial Intelligence models, such as the complex Artificial Neural Network architectures that compose the Deep Learning paradigm, has shown to provide excellent performance for complex and non-linear control problems. In this paper, the authors propose an inexpensive but powerful model based on Deep Learning to estimate the roll and sideslip angles simultaneously in mass production vehicles. The model uses input signals which can be obtained directly from onboard vehicle sensors such as the longitudinal and lateral accelerations, steering angle and roll and yaw rates. The model was trained using hundreds of thousands of data provided by Trucksim® and validated using data captured from real driving maneuvers using a calibrated ground truth device such as VBOX3i dual-antenna GPS from Racelogic®. The use of both Trucksim® software and the VBOX measuring equipment is recognized and widely used in the automotive sector, providing robust data for the research shown in this article.

Scanning fluorescence correlation spectroscopy comes full circle.

In this article, we review the application of fluorescence correlation spectroscopy (FCS) methods to studies on live cells. We begin with a brief overview of the theory underlying FCS, highlighting the type of information obtainable. We then focus on circular scanning FCS. Specifically, we discuss instrumentation and data analysis and offer some considerations regarding sample preparation. Two examples from the literature are discussed in detail. First, we show how this method, coupled with the photon counting histogram analysis, can provide information on yeast ribosomal structures in live cells. The combination of scanning FCS with dual channel detection in the study of lipid domains in live cells is also illustrated.

Risk of cardiovascular involvement in pediatric patients with X-linked hypophosphatemia.

OBJECTIVE: To find out if cardiovascular alterations are present in pediatric patients with X-linked hypophosphatemia (XLH). STUDY DESIGN: Multicentre prospective clinical study on pediatric patients included in the RenalTube database ( www.renaltube.com ) with genetically confirmed diagnosis of XLH by mutations in the PHEX gene. The study's protocol consisted of biochemical work-up, 24-h ambulatory blood pressure monitoring (ABPM), carotid ultrasonography, and echocardiogram. All patients were on chronic treatment with phosphate supplements and 1-hydroxy vitamin D metabolites. RESULTS: Twenty-four patients (17 females, from 1 to 17 years of age) were studied. Serum concentrations (X ± SD) of phosphate and intact parathyroid hormone were 2.66 ± 0.60 mg/dl and 58.3 ± 26.8 pg/ml, respectively. Serum fibroblast growth factor 23 (FGF23) concentration was 278.18 ± 294.45 pg/ml (normal < 60 pg/ml). Abnormally high carotid intima media thickness was found in one patient, who was obese and hypertensive as revealed by ABPM, which disclosed arterial hypertension in two other patients. Z scores for echocardiographic interventricular septum end diastole and left ventricular posterior wall end diastole were + 0.77 ± 0.77 and + 0.94 ± 0.86, respectively. Left ventricular mass index (LVMI) was 44.93 ± 19.18 g/m2.7, and four patients, in addition to the obese one, had values greater than 51 g/m2.7, indicative of left ventricular hypertrophy. There was no correlation between these echocardiographic parameters and serum FGF23 concentrations. CONCLUSIONS: XLH pediatric patients receiving conventional treatment have echocardiographic measurements of ventricular mass within normal reference values, but above the mean, and 18% have LVMI suggestive of left ventricular hypertrophy without correlation with serum FGF23 concentrations. This might indicate an increased risk of cardiovascular involvement in XLH.

Combined use of smartphone and smartband technology in the improvement of lifestyles in the adult population over 65 years: study protocol for a randomized clinical trial (EVIDENT-Age study).

BACKGROUND: The increasing use of smartphones by older adults also increases their potential for improving different aspects of health in this population. Some studies have shown promising results in the improvement of cognitive performance through lifestyle modification. All this may have a broad impact on the quality of life and carrying out daily living activities. The objective of this study is to evaluate the effectiveness of combining the use of smartphone and smartband technology for 3 months with brief counseling on life habits, as opposed to providing counseling only, in increasing physical activity and improving adherence to the Mediterranean diet. Secondary objectives are to assess the effect of the intervention on body composition, quality of life, independence in daily living activities and cognitive performance. METHODS: This study is a two-arm cluster-randomized trial that will be carried out in urban health centers in Spain. We will recruit 160 people aged between 65 and 80 without cardiovascular disease or cognitive impairment (score in the Mini-mental State Examination ≥24). On a visit to their center, intervention group participants will be instructed to use a smartphone application for a period of 3 months. This application integrates information on physical activity received from a fitness bracelet and self-reported information on the patient's daily nutritional composition. The primary outcome will be the change in the number of steps measured by accelerometer. Secondary variables will be adherence to the Mediterranean diet, sitting time, body composition, quality of life, independence in daily living activities and cognitive performance. All variables will be measured at baseline and on the assessment visit after 3 months. A telephone follow-up will be carried out at 6 months to collect self-reported data regarding physical activity and adherence to the Mediterranean diet. DISCUSSION: Preventive healthy aging programs should include health education with training in nutrition and lifestyles, while stressing the importance of and enhancing physical activity; the inclusion of new technologies can facilitate these goals. The EVIDENT-AGE study will incorporate a simple, accessible intervention with potential implementation in the care of older adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03574480 . Date of trial Registration July 2, 2018.