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Inter-regional patient mobility represents both a resource and a challenge for the organization and financing of health systems, particularly in decentralised countries. We use cross-sectional time series regression analysis to test the determinants of imbalances in regional funds to finance inter-regional patient mobility for the 17 Spanish regions for the period 2014-2020. The findings indicate that highly specialised health centres and bilateral agreements partly explain the budget imbalance from inter-regional patient referrals, while local tourism partly explains the budget imbalance from non-referred patient mobility. Developing effective national schemes to compensate net patient recipient regions would be fundamental to addressing territorial imbalances., (© 2024 The Authors. The International Journal of Health Planning and Management published by John Wiley & Sons Ltd.)

Cross-border patient mobility has become a topic of increasing interest for policy-makers and academic scholars. However, the focus on international dynamics hinders the fact that healthcare mobility takes place within national boundaries as well, particularly in countries characterized by decentralized health systems. This paper shifts the focus from the drivers of international patient mobility to the ones of policy-making on patient mobility within national borders, analyzing more than fifty policy arrangements adopted between Spanish Regions in the period 2000-2020. As the findings indicate, geographical/historical, economic and political factors are key to understanding the development of cross-border healthcare agreements, as well as the conflicts that may arise therefrom. Accordingly, these arrangements may become a controversial issue and a key arena for partisan competition, affecting the articulation of effective responses to patient mobility in Spain and, ultimately, patients' rights., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Detection and quantification of diverse analytes such as molecules, cells receptor and even particles and nanoparticles, play an important role in biomedical research, particularly in electrochemical sensing platform technologies. In this study, gold nanoparticles (AuNPs) prepared by green synthesis from Sargassum sp. were characterized using ultraviolet-visible (UV-Vis) and Fourier transform-infrared (FT-IR) spectroscopies, X-ray diffraction (XRD), scanning electron microscopy (SEM), dynamic light scattering (DLS) and zeta potential (ζ) obtaining organic capped face-centered cubic 80-100 nm AuNPs with an excellent stability in a wide range of pH. The AuNPs were used to modify a carbon nanotubes-screen printed electrode (CNT-SPE), through the drop-casting method, to assemble a novel portable electrochemical sensing platform for glucose, using a novel combination of components, which together have not been employed. The ability to sense and measure glucose was demonstrated, and its electrochemical fundamentals was studied using cyclic voltammetry (CV). The limits of detection (LOD) and quantification (LOQ) to glucose were 50 μM and 98 μM, respectively, and these were compared to those of other sensing platforms.

Background: Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH., Objectives: Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH., Methods: Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol., Results: We collected data for 52 patients (28 females, 24 males; 31.1 ± 17.1 years of age; baseline LDL-C: 571.9 ± 171.7 mg/dl). During a mean follow-up of 14.1 ± 7.3 years, there was a significant increase in the use of high-intensity statin and ezetimibe in combination with lipoprotein apheresis; in 6 patients, lomitapide was also added. Mean LDL-C achieved at nadir was 164.0 ± 85.1 mg/dl (-69.6% from baseline), with a better response in patients taking lomitapide (-88.3%). Overall, 23.1% of ARH patients reached LDL-C of <100 mg/dl. During follow-up, 26.9% of patients had incident ASCVD, and 11.5% had a new diagnosis of aortic valve stenosis (absolute risk per year of 1.9% and 0.8%, respectively). No incident stroke was observed. Age (≥30 years) and the presence of coronary artery disease at diagnosis were the major predictors of incident ASCVD., Conclusions: Despite intensive treatment, LDL-C in ARH patients remains far from targets, and this translates into a poor long-term cardiovascular prognosis. Our data highlight the importance of an early diagnosis and treatment and confirm the fact that an effective treatment protocol for ARH is still lacking., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Cornelia de Lange syndrome (CdLS) is produced by mutations in genes that encode regulatory or structural proteins of the cohesin complex. Congenital heart disease (CHD) is not a major criterion of the disease, but it affects many individuals. The objective of this study was to study the incidence and type of CHD in patients with CdLS., Material and Method: Cardiological findings were evaluated in 149 patients with CdLS and their possible relationship with clinical and genetic variables., Results: A percentage of 34.9 had CHD (septal defects 50%, pulmonary stenosis 27%, aortic coarctation 9.6%). The presence of CHD was related with neonatal hospitalisation (P=.04), hearing loss (P=.002), mortality (P=.09) and lower hyperactivity (P=.02), it being more frequent in HDAC8+ patients (60%), followed by NIPBL+ (33%) and SMC1A+ (28.5%). While septal defects predominate in NIPBL+, pulmonary stenosis is more common in HDAC8+., Conclusions: Patients with CdLS have a high incidence of CHD, which varies according to the affected gene, the most frequent findings being septal defects and pulmonary stenosis. Perform a cardiologic study in all these patients is suggested., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL protein receptor adaptor 1 (LDLRAP1). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain., Methods and Results: Data were collected from the Spanish Dyslipidemia Registry of the Spanish Atherosclerosis Society and from all molecular diagnoses performed for familial hypercholesterolemia in Spain between 1996 and 2015 (n=16 751). Clinical data included baseline lipid levels and atherosclerotic cardiovascular disease events. A total of 97 subjects were identified as having HoFH-of whom, 47 were true homozygous (1 for APOB, 5 for LDLRAP1, and 41 for LDLR), 45 compound heterozygous for LDLR, 3 double heterozygous for LDLR and PSCK9, and 2 double heterozygous for LDLR and APOB. No PSCK9 homozygous cases were identified. Two variants in LDLR were identified in 4.8% of the molecular studies. Over 50% of patients did not meet the classical HoFH diagnosis criteria. The estimated HoFH prevalence was 1:450 000. Compared with compound heterozygous cases, true homozygous cases showed more aggressive phenotypes with higher LDL-C and more atherosclerotic cardiovascular disease events., Conclusions: HoFH frequency in Spain was higher than expected. Clinical criteria would underestimate the actual prevalence of individuals with genetic HoFH, highlighting the importance of genetic analysis to improve familial hypercholesterolemia diagnosis accuracy., (© 2016 American Heart Association, Inc.)

Humans lacking sclerostin display progressive bone overgrowth due to increased bone formation. Although it is well established that sclerostin is an osteocyte-secreted bone formation inhibitor, the underlying molecular mechanisms are not fully elucidated. We identified in tandem affinity purification proteomics screens LRP4 (low density lipoprotein-related protein 4) as a sclerostin interaction partner. Biochemical assays with recombinant proteins confirmed that sclerostin LRP4 interaction is direct. Interestingly, in vitro overexpression and RNAi-mediated knockdown experiments revealed that LRP4 specifically facilitates the previously described inhibitory action of sclerostin on Wnt1/β-catenin signaling. We found the extracellular β-propeller structured domain of LRP4 to be required for this sclerostin facilitator activity. Immunohistochemistry demonstrated that LRP4 protein is present in human and rodent osteoblasts and osteocytes, both presumed target cells of sclerostin action. Silencing of LRP4 by lentivirus-mediated shRNA delivery blocked sclerostin inhibitory action on in vitro bone mineralization. Notably, we identified two mutations in LRP4 (R1170W and W1186S) in patients suffering from bone overgrowth. We found that these mutations impair LRP4 interaction with sclerostin and its concomitant sclerostin facilitator effect. Together these data indicate that the interaction of sclerostin with LRP4 is required to mediate the inhibitory function of sclerostin on bone formation, thus identifying a novel role for LRP4 in bone.

In France, Germany, Spain, and the United Kingdom, the decades from the late 1980s to the present have witnessed significant change in health policy. Although this has included the spread of internal competition and growing autonomy for certain nonstate and parastate actors, it does not follow that the mechanism at work is a "neoliberal convergence." Rather, the translation into diverse national settings of quasi-market mechanisms is accompanied by a reassertion of regulatory authority and strengthening of statist, as opposed to corporatist, management of national insurance systems. Thus the use of quasi-market tools brings state-strengthening reform. The proximate and necessary cause of this dual transformation is found in the work of small, closely integrated groups of policy professionals, whom we label "programmatic actors." While their identity differs across cases, these actors are strikingly similar in functional role and motivation. Motivated by a desire to wield authority through the promotion of programmatic ideas, rather than by material or careerist interests, these elite groups act both as importers and translators of ideas and as architects of policy. The resulting elite-driven model of policy change integrates ideational and institutionalist elements to explain programmatically coherent change despite institutional resistance and partisan instability.

Cabrera (Madrid) low-Mg calcites exhibit: (i) an unusual twofold elevation in X-ray diffraction pattern intensity; (ii) a 60-fold elevation of luminescence emission, compared to six common natural calcites selected for comparison purposes; (iii) a natural relatively high radiation level of circa 200 nSvh(-1) not detected in 1300 other calcites from the Natural History Museum of Madrid. Calcites were analysed by the X-ray diffraction powder method (XRD), cathodo-luminescence spectroscopy in scanning electron microscopy (CL-SEM), thermoluminescence (TL), differential thermal analysis (DTA), X-ray fluorescence spectrometry (XRF) and particle size distribution (PSD). The Cabrera calcite study shows: (i) helicoidally distributed steps along the (0001) orientation; (ii) protuberance defects onto the (0001) surface, observed by SEM; (iii) XRF chemical contents of 0.03% MgO, 0.013% of Y(2)O(3), and 0.022% of U(3)O(8), with accessory amounts of rare earth elements (REE); (iv) DTA dissociation temperature of 879 degrees C; (v) TL maxima peaks at 233 and 297 degrees C whose areas are 60 times compared to other calcites; (vi) spectra CL-SEM bands at 2.0 and 3.4 eV in the classic structure of Mn(2+) activators; (vii) a twofold XRD pattern explained given that sample is a low-Mg calcite. The huge TL and CL emissions of the Cabrera calcite sample must be linked with the uranyl group presence. This intense XRD pattern in low-Mg calcites could bring into being analytical errors.

The Apolipoprotein A-V (apoA-V) gene promoter polymorphism -1131T>C modulates triacylglycerol (TG) concentrations. We evaluate whether this polymorphism could be involved in the interindividual variability observed during postprandial lipemia. Fifty-one healthy apo E3E3 male volunteers [12 with -1131CC/CT genotype, and 39 with -1131TT genotype] underwent a Vitamin A fat-load test consisting of 1g of fat/kg body weight and 60,000IU of Vitamin A. Blood samples were taken at time 0 and every hour until the 6th and every 2h and 30 min until the 11th. Cholesterol (Chol) and TG were determined in plasma and Chol, TG, ApoB-100, ApoB-48, and retinyl palmitate (RP) were determined in lipoprotein fractions. Data of postprandial lipemia revealed that subjects with the -1131CT/CC genotype had a higher postprandial response of total plasma TG (p=0.043), large triacylglycerol-rich lipoproteins-TG (TRL-TG) (p=0.002), large TRL-Chol (p=0.004), small TRL-Chol (p=0.004) and small TRL-RP (p=0.001) than subjects with the -1131TT genotype. The modifications observed in postprandial lipoprotein metabolism in subjects with the apoA-V -1131T>C polymorphism could be involved in the increased fasting plasma TG concentrations previously described in carriers of the C allele.

Beckwith-Wiedemann syndrome (BWS) is characterized by congenital overgrowth, macroglossia and omphalocele or umbilical hernia. Children with BWS may also have all or some of the following features: asymmetry (hemihypertrophy) of the limbs, torso or face, hypoglycemia, organomegaly, ear pits or creases, and embryonal tumors. The frequency of BWS is approximately 1:14,000 births. We present a guide for the management of children with BWS aimed at helping pediatricians and general practitioners or specialists in the clinical follow-up of these patients. This guide has been structured according to different age groups and is based on published evidence.

Introduction and Aims: Mental retardation (MR) affects approximately 2-3% of the general population and around 75% of the known causes of MR are thought to have a genetic origin. The aim of this work is to describe a standardised model of diagnostic approach to patients with mental retardation of a genetic origin (MRGO)., Development: The clinician has to draw up a detailed case history and carry out a thorough dysmorphological physical examination that enables a reasonable differential diagnosis to be reached. The next step will be to request the complementary studies needed to confirm or reject the initial suspected diagnosis. Accurate information about the personal, prenatal (pregnancy) and perinatal (childbirth) history must also be collected. The postnatal history will also provide relevant clinical information. The familial history is a fundamental element of any genetic disease and must be gathered by drawing up the family tree or lineage. The physical and dysmorphological examination must be ordered, completed and detailed, and measurements of the somatometric parameters required to demonstrate and quantify the existence of an anomaly in any anatomical structure will also have to be made. Photos of the patient are a great aid because they allow comparison with recognisable dysmorphic syndromes. The last phase involves requesting complementary studies, including consultations with other specialists. The confirmation or exclusion of MR usually results from biochemical-metabolic, cytogenetic or molecular studies., Conclusions: In cases of MRGO a good patient record accompanied by a thorough physical and dysmorphological study allow the clinical geneticist to orientate the diagnosis in the right direction and to request the specific genetic laboratory tests to confirm (or reject) its causation.

Lipoprotein lipase (LPL) is one of the key enzymes in the metabolism of triacylglycerol-rich lipoproteins (TRL). We evaluated whether the association of LPL HindIII (H1/H2) and Serine447-Stop (S447X) polymorphisms may explain the interindividual variability observed during postprandial lipemia. Fifty-one healthy male volunteers (26 with the H2S447 genotype, 15 with the H1X447 genotype, and 10 with the H1S447 genotype) were subjected to a vitamin A-fat load test consisting of 1 g fat/kg body weight and 60,000 IU vitamin A. Blood was drawn every hour until the 6th hour and every 2 h and 30 min until the 11th hour. Data revealed that subjects that are homozygous for the H2 allele (H2H2) showed a higher postprandial response for small TRL, retinyl palmitate (RP), large TRL-RP, large TRL-B48, and small TRL-B48 levels. Furthermore, in the case of the S447X polymorphism, 447Ter carriers had a lower postprandial response for small TRL-RP, large TRL-B48, and small TRL-RP. Subjects with the LPL H2S447 genotype had higher plasma triacylglycerol, large TRL-triacylglycerol, large TRL-RP, small TRL-RP, and large TRL-B48 (P < 0.037) than H1X447 subjects. The modifications observed in postprandial lipoprotein metabolism in young normolipemic males with LPL polymorphism could be involved in the lower risk of coronary artery disease associated with the H1X447 genotype.

Introduction: Fragile X syndrome (FXS) is the commonest cause of hereditary mental retardation. Although most affected patients, especially males, have a typical phenotype, molecular studies of the FMR1 gene are necessary to confirm the diagnosis, depending on the number of repeats of the CGG triplet of the gene., Development: In recent years an immunohistochemical technique has been developed which permits the study of the expression of the protein codified by the FMR1 gene, known as FMRP (Fragile X Mental Retardation Protein). This was done initially in peripheral blood lymphocytes and more recently in hair roots, thus permitting definite identification of males affected by FXS. The advantages of this technique compared with conventional molecular studies are speed (results available in a few hours), lower cost and ease of sample obtention, that in the case of hair roots is non-invasive. The affected males had significant lower levels of FMRP expression than normal or non fragile X males, without overlapping. This finding was observed in blood and hair roots. In females, interpretation is more difficult due to random inactivation of one of the X chromosomes. However, preliminary studies have shown that the level of FMRP expression in hair roots of females with the full mutation (usually with some degree of mental retardation) is significantly lower when compared to premutation carriers or normal females., Conclusion: The FMRP test, either in blood or hair, is an easy, cost-effective method for screening FXS in males with idiopathic mental retardation.

We report a patient with a mild form of the Baller-Gerold syndrome (craniosynostosis-radial aplasia syndrome). The patient, a 3-year 3 month-old boy, has trigonocephaly with bilateral absent radii and thumbs. His growth parameters and psychomotor development have been normal. No visceral anomalies were found. This patient represents a new case of the rare mild form of the syndrome.

Cortical auditory evoked potentials (CAEP) were recorded from scalp electrodes in 47 patients, who survived to bacterial meningitis in their childhood. CAEP were obtained from 1 month to 8 years after recovering from acute disease. Neisseria meningitidis was the microorganism more frequently isolated from CSF (43.5%). Exclusively abnormal values in amplitude of CAEP were registered in 15 cases (32%), mainly at the lower tones explored; 14 of them were subjected to conventional audiometric test, which demonstrated unilateral hearing loss only in 2. No alterations in the latency of P2 wave were seen. We recommend to include CAEP in search of hearing disorders in younger children after recovering from meningitis, since they can detect lesions in cortical-subcortical auditory tracts, which otherwise could go unnoticed.