Search Results (14)

Background and Objectives: Alzheimer’s dementia is a progressive neurodegenerative disease that affects memory abilities due to genetic and environmental factors. A well-known gene that influences the risk of Alzheimer’s disease is the apolipoprotein E (APOE) gene. The APOE gene is involved in the production of a protein that helps transport cholesterol and other types of fat in the bloodstream. Problems in this process are thought to contribute to the development of Alzheimer’s disease. APOE comes in several forms, which are called alleles (ε2, ε3, ε4). Materials and Methods: Therefore, our study aims to identify those subjects with a higher genetic risk through the polymorphism of the APOE gene, using a population screening in patients with a clinical diagnosis of AD in a region of Spain, Castilla y León, as potential biomarkers and to identify individuals at increased genetic risk by polymorphism of the APOE gene. An observational case-control study was conducted in Castilla y León (Spain). Saliva samples were collected and the ApoE gene was analyzed by PCR and agarose gel electrophoresis, respecting ethical criteria. Results: In the Alzheimer’s population in Castilla y León, a high prevalence of ApoE3 (74%) was found, followed by ApoE4 (22%); in addition, a higher presence of the ε4 allele was found in the Alzheimer’s disease (AD) group than in the control group. It was also observed that the ε2/ε2 genotype was not found in any individual with AD but was found in healthy subjects and that the opposite was observed for the ε4/ε4 genotype. The odds ratio (OR) indicated a risk four times greater of having AD if having the ε4 allele. Conclusions: The demonstrated relation between the different isoforms and the likelihood of developing AD has led to its consideration as a biomarker and a potential pre-symptomatic therapy. The molecular mechanisms that confer a disruptive and protective role to ApoE4 and ApoE2, respectively, are still being studied. Full article

Introduction: Suspected preterm labor (SPL), defined as the presence of regular and painful uterine contractions and cervical shortening, represents a prenatal insult with potential long-term consequences. However, despite recent evidence demonstrating suboptimal neurodevelopment at 2 years in this population, it remains underestimated as a significant risk factor for neurodevelopmental disorders or other chronic diseases. The aim of this study is to assess the impact of suspected preterm labor during pregnancy on cardiometabolic profile and neurodevelopment during childhood (6–8 years). Methods and analysis: Prospective cohort study including children whose mothers suffered suspected preterm labour during pregnancy and paired controls. Neurodevelopmental, cardiovascular, and metabolic assessments will be performed at 6–8 years of age. A trained psychologist will carry out the neurodevelopment assessment including intelligence, visual perception, and behavioral assessment. Body composition and physical fitness assessment will be performed by one trained pediatrician and nurse. Finally, cardiovascular evaluation, including echocardiography and blood pressure, will be performed by two pediatric cardiologists. Data regarding perinatal and postnatal characteristics, diet, lifestyle, and weekly screen time of the child will be obtained from medical history and direct interviews with families. Primary outcome measures will include body mass index and adiposity, percentage of fat mass and total and regional lean mass, bone mineral content and density, cardiorespiratory resistance, isometric muscle strength, dynamic lower body strength, systolic and diastolic blood pressure, left ventricle (LV) systolic and diastolic function, general intelligence index, visuospatial working memory span, oculomotor control test, index of emotional, and behavioral problems. Full article

One of the main applications of small satellites is Earth observation. CubeSats and different kinds of nanosatellites usually form constellations that obtain images mainly using an optical payload. There is a massive amount of data generated by these satellites and a limited capacity of download due to volume and mass constraints that make it difficult to use high-speed communication systems and high-power systems. For this reason, it is important to develop satellites with the autonomy to process data on board. In this way, the limited communication channel can be used efficiently to download relevant images containing the required information. In this paper, a system for the satellite on-board processing of RGB images is proposed, which automatically detects the cloud coverage level to prioritize the images and effectively uses the download time and the mission operation center. The system implements a Convolutional Neural Network (CNN) on a Commercial off-the-Shelf (COTS) microcontroller that receives the image and returns the cloud level (priority). After training, the system was tested on a dataset of 100 images with an accuracy of 0.9 and it was also evaluated with CubeSat images to evaluate the performance of a different image sensor. This implementation contributes to the development of autonomous satellites with processing on board. Full article

The main aim of this study was to compare refraction measurements with and without cycloplegia from two refractors devices, (TRK-2P autorefractometer (TRK-2P) and wavefront-based refraction Visionix 130 (VX130)) in children and adolescents. This descriptive observational study included 20 myopic eyes and 40 hyperopic eyes measured in two different Spanish hospitals. Cycloplegia was carried out by three drops of cyclopentolate hydrochloride 1% (Colircusí cycloplegic, Alcon Healthcare S.A., Barcelona). The mean age of the myopia group was 12.40 ± 3.48 years; for the hyperopia group, the mean age was 7.37 ± 2.47 years. In the myopia group, autorefraction and wavefront-based refraction did not show clinically significant differences in any components between with and without cycloplegia. The hyperopia group showed statistical and clinically significant differences in sphere and SE components between relaxed and non-relaxed states of accommodation, although the cylindrical components were not clinically different. In this study, we considered a value of ≥0.50D as a clinically significant difference in refraction. Therefore, both devices were capable of obtaining accurate refractions without cyclopegia in myopia children, although they did not avoid instrument myopia and accommodation involved in hyperopia children. Moreover, both refractometers could be useful for astigmatism monitoring in children without the need for cycloplegic drops. Full article

In the phase II MAJA trial, maintenance therapy with vinflunine resulted in longer progression-free survival compared to best supportive care in advanced urothelial cell carcinoma (aUCC) patients who did not progress after first-line platinum-based chemotherapy. However, despite an initial benefit observed in some patients, unequivocal resistance appears which underlying mechanisms are presently unknown. We have performed gene expression and functional enrichment analyses to shed light on the discovery of these underlying resistance mechanisms. Differential gene expression profile of eight patients with poor outcome and nine with good outcome to vinflunine administered in the MAJA trial were analyzed. RNA was isolated from tumor tissue and gene expression was assessed by microarray. Differential expression was determined with linear models for microarray data. Gene Set Enrichment Analysis (GSEA) was used for the functional classification of the genes. In vitro functional studies were performed using UCC cell lines. Hierarchical clustering showed a differential gene expression pattern between patients with good and poor outcome to vinflunine treatment. GSEA identified epithelial-to-mesenchymal transition (EMT) as the top negatively enriched hallmark in patients with good outcome. In vitro analyses showed that the polyphenol curcumin downregulated EMT markers and sensitized UCC cells to vinflunine. We conclude that EMT mediates resistance to vinflunine and suggest that the reversion of this process could enhance the effect of vinflunine in aUCC patients. Full article

Background: B lymphocytes (BL) seem to play an important role in transplantation, although the and role of different subpopulations in monitoring and outcome is not clear. Our aim was to monitoring immunological profiles based on BL subpopulations in kidney recipients (KR) with the risk of acute rejection (AR). Methods: Monitoring of BL subpopulations was performed by flow cytometry in PBLs before transplantation and three and six months after transplantation (PTX). We used two methodological approaches, a traditional analysis, and a novel cluster analysis, to determine the association between BL subpopulations, AR incidence, and graft function. Results: After three months of PTX, KRs with a B phenotype enriched in transitional BL and plasmablasts had better kidney function and lower AR incidence. KRs with decreased transitional BL and plasmablasts were associated with lower kidney function and higher AR PTX. KRs that had an increase in transitional BL PTX had a better clinical outcome. The increase in transitory BL during PTX was also associated with an increase in Tregs. Indeed, KRs receiving thymoglobulin as induction therapy showed a slight decrease in the relative frequency of naive BLs after three months of PTX. Conclusion: The monitoring of BL subpopulations may serve as a non-invasive tool to improve immunological follow-up of patients after kidney transplantation. However, further studies are needed to confirm the obtained results, define cut-off values, and standardize more optimal and even custom/customized protocols. Full article

Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol. Full article

Longitudinal changes of physical activity (PA) from childhood into adolescence have not been accurately described yet for the Spanish population. The aim of this study is to evaluate the changes of PA, assessed by accelerometry and anthropometric measures in a cohort of 213 children from the prepubertal to pubertal period, focusing on those with valid data from both time points (n = 75). Sedentary time (ST) increased about 50%, while all PA intensities declined from the pre-pubertal to pubertal period. Light PA (LPA) was the major contributor, decreasing by about 30%. Boys were more active than girls in both periods, but they showed a higher decline in PA, especially moderate-to-vigorous PA (MVPA). The proportion who reached the recommendation of 60 min of MVPA decreased by 33.3% in boys and 4.6% in girls. Children with obesity or overweight had lower MVPA than those with normal-weight in the pre-pubertal period, but no differences were found in the pubertal period. This study shows a decrease of PA and an increase of sedentarism in the transition from childhood to adolescence, particularly in boys. Regardless of body weight, adolescents tend to be less active. Therefore, prevention programs should be implemented to achieve optimal PA and reduce sedentarism during infancy considering the differences found by sex. Full article

Despite the existence of global recommendations for physical activity and lifestyle to avoid childhood obesity, there are no specific recommendations for school-age children. The aim of this meta-analysis was to measure the effects of current interventions with a physical activity component on body mass index (BMI) Z-score and on the moderate and vigorous physical activity (MVPA) time, measured by accelerometry, and focused on children with obesity. Randomized controlled trial studies (RCTs) based on physical activity interventions focused on children with obesity (6 to 12 years old) from January 1991 to August 2018 were included. The post-intervention mean and standard deviation of the BMI Z-score and MVPA engaged time were extracted to calculate the results using random effects models. Of a total of 229 studies considered potentially eligible, only 10 RCTs met the inclusion criteria. There were improvements in the BMI Z-score for physical activity intervention groups, compared with non-intervention children in addition to a significant increase in time engaged in MVPA. In conclusion, interventions with a physical activity component in school-children with obesity seem to be effective at reducing BMI and producing an increase in time spent engaged in physical activity. Therefore, interventions based on physical activity should be considered one of the main strategies in treating childhood obesity. Full article

Polygenetic risk scores (pGRSs) consisting of adult body mass index (BMI) genetic variants have been widely associated with obesity in children populations. The implication of such obesity pGRSs in the development of cardio-metabolic alterations during childhood as well as their utility for the clinical prediction of pubertal obesity outcomes has been barely investigated otherwise. In the present study, we evaluated the utility of an adult BMI predisposing pGRS for the prediction and pharmacological management of obesity in Spanish children, further investigating its implication in the appearance of cardio-metabolic alterations. For that purpose, we counted on genetics data from three well-characterized children populations (composed of 574, 96 and 124 individuals), following both cross-sectional and longitudinal designs, expanding childhood and puberty. As a result, we demonstrated that the pGRS is strongly associated with childhood BMI Z-Score (B = 1.56, SE = 0.27 and p-value = 1.90 × 10⁻⁸), and that could be used as a good predictor of obesity longitudinal trajectories during puberty. On the other hand, we showed that the pGRS is not associated with cardio-metabolic comorbidities in children and that certain environmental factors interact with the genetic predisposition to the disease. Finally, according to the results derived from a weight-reduction metformin intervention in children with obesity, we discarded the utility of the pGRS as a pharmacogenetics marker of metformin response. Full article

Phosphatidylinositol–5 phosphate (PI5P) and other mono-phosphoinositides (mono-PIs) play second messenger roles in both physiological and pathological conditions. Despite this, their intracellular targets and mechanisms of action remain poorly characterized. Here, we show that Vav1, a protein that exhibits both Rac1 GDP/GTP exchange and adaptor activities, is positively modulated by PI5P and, possibly, other mono-PIs. Unlike other phospholipid–protein complexes, the affinity and specificity of the Vav1–lipid interaction entail a new structural solution that involves the synergistic action of the Vav1 C1 domain and an adjacent polybasic tail. This new regulatory layer, which is not conserved in the Vav family paralogs, favors the engagement of optimal Vav1 signaling outputs in lymphocytes. Full article

Ten-Koh is a 23.5 kg, low-cost satellite developed to conduct space environment effects research in low-Earth orbit (LEO). Ten-Koh was developed primarily by students of the Kyushu Institute of Technology (Kyutech) and launched on 29 October 2018 on-board HII-A rocket F40, as a piggyback payload of JAXA’s Greenhouse gas Observing Satellite (GOSAT-2). The satellite carries a double Langmuir probe, CMOS-based particle detectors and a Liulin spectrometer as main payloads. This paper reviews the design of the mission, specifies the exact hardware used, and outlines the implementation and operation phases of the project. This work is intended as a reference that other aspiring satellite developers may use to increase their chances of success. Such a reference is expected to be particularly useful to other university teams, which will likely face the same challenges as the Ten-Koh team at Kyutech. Various on-orbit failures of the satellite are also discussed here in order to help avoid them in future small spacecraft. Applicability of small satellites to conduct space-weather research is also illustrated on the Ten-Koh example, which carried out simultaneous measurements with JAXA’s ARASE satellite. Full article

As small satellites are becoming more widespread for new businesses and applications, the development time, failure rate and cost of the spacecraft must be reduced. One of the systems with the highest cost and the most frequent failure in the satellite is the Electrical Power System (EPS). One approach to achieve rapid development times while reducing the cost and failure rate is using scalable modules. We propose a solar module integrated converter (SMIC) and its verification process as a key component for power generation in EPS. SMIC integrates the solar array, its regulators and the telemetry acquisition unit. This paper details the design and verification process of the SMIC and presents the in-orbit results of 12 SMICs used in Ten-Koh satellite, which was developed in less than 1.5 years. The in-orbit data received since the launch reveal that solar module withstands not only the launching environment of H-IIA rocket but also more than 1500 orbits in LEO. The modular approach allowed the design, implementation and qualification of only one module, followed by manufacturing and integration of 12 subsequent flight units. The approach with the solar module can be followed in other components of the EPS such as battery and power regulators. Full article

(1) This study describes the good evolution of a 6-year-old girl genetically diagnosed (R106X) with Rett syndrome (RTT), after having been treated with IGF-I, melatonin (MT), blackcurrant extracts (BC) and rehabilitated for 6 months. (2) The patient stopped normal development in the first year of age. The patient showed short stature and weight and fulfilled the main criteria for typical RTT. Despite her young age, there was pubic hair (Tanner II), very high plasma testosterone, and low levels of plasma gonadotrophins. There were no adrenal enzymatic deficits, and abdominal ultrasound studies were normal. The treatment consisted of IGF-I (0.04 mg/kg/day, 5 days/week, subcutaneous (sc)) for 3 months and then 15 days of rest, MT (50 mg/day, orally, without interruption) and neurorehabilitation. A new blood test, after 3 months of treatment, was absolutely normal and the pubic hair disappeared (Tanner I). Then, a new treatment was started with IGF-I, MT, and BC for another 3 months. In this period, the degree of pubertal development increased to Tanner III (pubic level), without a known cause. (3) The treatment followed led to clear improvements in most of the initial abnormalities, perhaps due to the neurotrophic effect of IGF-I, the antioxidant effects of MT and BC, and the cerebral increase in the cyclic glycine-proline (cGP) achieved with administration of BC. (4) A continuous treatment with IGF-I, MT, and BC appears to be useful in RTT. Full article