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Purpose: Our objective was to synthesize and determine whether there are sex differences in physical function following exercise interventions in older adults. Materials and Methods: A systematic search was conducted in four databases from inception to July 8th, 2023 searching for prospective trials that conducted exercise interventions in older adults and results for physical function were reported by sex. Pooled standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were estimated using a randomeffects method. The Sidik-Jonkman estimator was used to calculate the variance of heterogeneity (I2). Results: A total of 19 studies involving 20,133 older adults (mean age ≥60 years, 33.7% female) were included. After exercise interventions, males reported significantly greater pre-post changes compared to females for upper body strength (SMD=- 0.40, 95% CI: -0.71 to -0.09; I2=75.6%; n=8), lower body strength (SMD=-0.32, 95% CI: -0.55 to -0.10; I2=52.0%; n=11), and cardiorespiratory fitness (SMD=-0.29, 95% CI: -0.48 to -0.10; I2=89.1%; n=12). Conversely, the pooled SMDs showed a significant effect favoring females for motor fitness (SMD=0.21, 95% CI: 0.03 to 0.39; I2=0%; n=7). Limited and inconsistent results were observed for flexibility. Conclusions: Our study suggests the existence of sex-related differences on physical function after an exercise intervention in the older population.

Abstract Vaccines are the most effective and sustainable intervention to control ticks and tick-borne diseases (TBD). Using a personalized vaccine design based on regional tick genotypes, a Rhipicephalus appendiculatus Subolesin protective antigen was used in a field trial evaluating tick vaccine efficacy, effectiveness, and safety in cattle infested with multiple tick species in different Ugandan agro-ecological zones. Vaccination with SUB was safe with a protective capacity against anemia and infection, and reduced the number of infested cattle, tick fitness (feeding and reproduction) with vaccine effectiveness against multiple tick species between 93.2% at 167-196 days post-vaccination (dpv) and 61.4% at 251–327 dpv. Total integrated vaccine efficacy/effectiveness was estimated as 98.8%. The Subolesin-based vaccine is protective against multiple cattle tick infestations under field conditions in Uganda. These results support registration and commercialization of the vaccine to reduce tick populations and associated risks for human and animal TBD and chemical acaracides in Uganda.

Abstract Impulse control disorders and their consequences display variability among individuals, indicating potential involvement of environmental and genetic factors. In this retrospective study, we analyzed a cohort of Parkinson's disease patients treated with dopamine agonists and investigated the influence of the dopamine D4 receptor gene polymorphism, DRD4 7R+, which is linked to psychiatric disorders, impulsive traits, and addictive behaviors. We found that DRD4 7R+ is a significant genetic risk factor associated with the severity of ICD.

Abstract Systemic light chain (LC) amyloidosis (AL) is a disease where organs are damaged by an overload of a misfolded patient-specific antibody-derived LC, secreted by an abnormal B cell clone. The high LC concentration in the blood leads to amyloid deposition at organ sites. Indeed, cryogenic electron microscopy (cryo-EM) has revealed unique amyloid folds for heart-derived fibrils taken from different patients. Here, we present the cryo-EM structure of heart-derived AL amyloid (AL59) from another patient with severe cardiac involvement. The double-layered structure displays a u-shaped core that is closed by a β-arc lid and extended by a straight tail. Noteworthy, the fibril harbours an extended constant domain fragment, thus ruling out the variable domain as sole amyloid building block. Surprisingly, the fibrils were abundantly concatenated with a proteinaceous polymer, here identified as collagen VI (COLVI) by immuno-electron microscopy (IEM) and mass-spectrometry. Cryogenic electron tomography (cryo-ET) showed how COLVI wraps around the amyloid forming a helical superstructure, likely stabilizing and protecting the fibrils from clearance. Thus, here we report structural evidence of interactions between amyloid and collagen, potentially signifying a distinct pathophysiological mechanism of amyloid deposits.

Abstract Background Examination and understanding of neural hyperactivity are some of the greatest scientific challenges faced in the present day. For this reason, the present study aimed to examine this phenomenon in the context of higher education. Method Likewise, this work will enable an instrument to be created to appropriately and reliably estimate neural hyperactivity associated with chronic stress in university students undertaking a Physiotherapy degree. Results Analysis of content validity was carried out according to agreement and consensus between nineteen experts with Education Science or Psychology degrees, via the Delphi method. On the other hand, face validity was established by administering the questionnaire to a sample of 194 university students aged between 18 and 45 years (M = 30.48%; SD = 13.152). Conclusion The final self-report measure, denominated mental hyperactivity, was composed of 10 items which showed adequate fit with regards to face and content validity (α = 0.775). Confirmatory factor analysis confirmed that the questionnaire was unidimensional.

Abstract Background Obesity is a complex chronic disease associated with several adverse health outcomes that increase mortality risk. Physical activity (PA) is recommended for the prevention and treatment of obesity and is related to a decreased risk of cardiovascular disease, cancer and all-cause mortality. This systematic review and meta-analysis estimates the effect of PA levels on mortality (cardiovascular, cancer and all-cause mortality) in adults with obesity. Methods A systematic search was conducted in MEDLINE, Embase, Web of Science and SPORTDiscus from inception to June 2024. Prospective cohort studies that explored the association between PA and mortality in adults with obesity (according to their body mass index, ≥ 30 kg/m2) aged ≥ 18 years were included. Our main outcomes were all-cause mortality, and cardiovascular, and cancer mortality reported in primary studies by hazard ratios or relative risk, which were pooled for the meta-analysis when at least two studies reported the effect estimate for the same outcome. The PRISMA recommendations and the MOOSE guidelines were followed. The reported mortality risk estimates comparing insufficiently active versus active (moderate to very active) adults with obesity were pooled using the DerSimonian and Laird random-effects model. Results A total of 9 prospective cohort studies involving 199,425 adults with obesity (age range: 35–85 years) were included, of which 59,873 were insufficiently active and 84,328 were active. Active individuals had a 21% lower risk of all-cause mortality (HR: 0.79, 95%CI: 0.74 to 0.84; I2 = 38.2%), and a 24% lower risk of cardiovascular mortality (HR: 0.76, 95%CI: 0.66 to 0.87; I2 = 0.0%) than insufficiently active individuals. The HR for cancer mortality was 0.91 (95%CI: 0.80 to 1.02; I2 = 0.0%), and although this was mostly consistent with a benefit, it was based on only two studies. Conclusion Our data support that moderate to high levels of PA are associated with a 21% lower risk of all-cause and 24% cardiovascular disease mortality in adults with obesity. Although data from the only two published studies seem to indicate a protective effect of PA on cancer risk, the estimates are not statistically significant. Systematic review registration PROSPERO CRD42022309346.

Brain glucose hypometabolism and insulin alterations are common features of many neurological diseases. Herein we sought to corroborate the brain glucose hypometabolism that develops with ageing in 12-months old Tau-VLW transgenic mice, a model of tauopathy, as well as to determine whether this model showed signs of altered peripheral glucose metabolism. Our results demonstrated that 12-old months Tau mice exhibited brain glucose hypometabolism as well as basal hyperglycemia, impaired glucose tolerance, hyperinsulinemia, and signs of insulin resistance. Then, we further studied the effect of chronic metformin treatment (9 months) in Tau-VLW mice from 9 to 18 months of age. Longitudinal PET neuroimaging studies revealed that chronic metformin altered the temporal profile in the progression of brain glucose hypometabolism associated with ageing. Besides, metformin altered the content and/or phosphorylation of key components of the insulin signal transduction pathway in the frontal cortex leading to significant changes in the content of the active forms. Thus, metformin increased the expression of pAKT-Y474 while reducing pmTOR-S2448 and pGSK3β. These changes might be related, at least partially, to a slow progression of ageing, neurological damage, and cognitive decline. Metformin also improved the peripheral glucose tolerance and the ability of the Tau-VLW mice to maintain their body weight through ageing. Altogether our study shows that the tau-VLW mice could be a useful model to study the potential interrelationship between tauopathy and central and peripheral glucose metabolism alterations. More importantly our results suggest that chronic metformin treatment may have direct beneficial central effects by post-transcriptional modulation of key components of the insulin signal transduction pathway.

Introduction Rotator cuff-related shoulder pain (RCRSP) is the most common cause of shoulder pain. Currently, exercise is proposed as the first-line treatment for patients suffering from RCRSP. However, adherence to therapeutic exercise programmes can be poor in the long term in a home setting. The aim of this study is to evaluate the effects of adding video animations to a traditional paper-based exercise programme.Methods and analysis A single-centre, randomised, open-labelled clinical trial will be conducted in a hospital in Spain. Adults aged between 18 and 80 years diagnosed with RCRSP who meet the eligibility criteria will be included. Patients (n=132) will be randomised into two groups, with both receiving paper-based exercises, and the experimental group will also be provided with video animations. The participants will receive seven face-to-face physical therapy sessions and will be asked to perform the exercises at home for 6 months. The primary outcome measure will be the Shoulder Pain and Disability Index, measured at baseline, 3 weeks, 3 months (primary analysis) and 6 months. Secondary outcomes will be the patient’s pain intensity during the last week (rest, during movement and at night); expectations of improvement; satisfaction with treatment; impression of improvement; perceived usability, usefulness and satisfaction of multimedia animations; and adherence to exercises. Generalised least squares regression models with an autoregressive-moving average lag one correlation structure will be implemented, with an intention-to-treat analysis.Ethics and dissemination This study has been approved by the ethics committee of Hospital Universitario Fundación Alcorcón (Madrid, Spain), reference number CI18/16. All participants will sign an informed consent. The results will be published in a peer-reviewed scientific journal.Trial registration ClinicalTrials.gov, NCT05770908.

AimTo determine the efficacy and safety of pharmacogenomics (PGx)-guided antidepressant prescribing in patients with depression through an umbrella review and updated meta-analysis.MethodsA comprehensive systematic search was conducted on PsycINFO, PubMed, Embase and the Cochrane databases. The pooled effect sizes of randomized controlled trials (RCTs) were expressed as mean differences for continuous data and risk ratios for noncontinuous data.ResultsPatients who received PGx-guided medications were 41% to 78% more likely to achieve remission and 20% to 49% more likely to respond to antidepressants than patients receiving treatment-as-usual (TAU).ConclusionPGx-guided antidepressant prescribing improves the treatment of depression. However, the significance and magnitude of the benefit varies widely between studies and different PGx testing panels.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022321324.

Abstract Mammary gland development occurs primarily in adulthood, undergoing extensive expansion during puberty followed by cycles of functional specialization and regression with every round of pregnancy/lactation/involution. This process is ultimately driven by the coordinated proliferation and differentiation of mammary epithelial cells. However, the endogenous molecular factors regulating these developmental dynamics are still poorly defined. Endocannabinoid signaling is known to determine cell fate-related events during the development of different organs in the central nervous system and the periphery. Here, we report that the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) plays a pivotal role in adult mammary gland development. Specifically, it is required for luminal lineage specification in the mammary gland, and it promotes hormone-driven secretory differentiation of mammary epithelial cells by controlling the endogenous levels of anandamide and the subsequent activation of cannabinoid CB1 receptors. Together, our findings shed light on the role of the endocannabinoid system in breast development and point to FAAH as a therapeutic target in milk-production deficits.

La violencia hacia las mujeres con discapacidad constituye un grave problema social que afecta a los diferentes ámbitos de sus vidas. Por ello, los objetivos de este estudio son: (a) identificar los tipos de violencia que sufren y las posibles diferencias en función del tipo de discapacidad y (b) determinar las consecuencias de la violencia. Se realizó una revisión de la literatura siguiendo los criterios PRISMA en las bases de datos Web of Science, PsycINFO y Scopus. Un total de 28 artículos cumplieron los criterios de inclusión. Los resultados muestran que las mujeres con discapacidad sufren diversos tipos de violencia, destacando la violencia sexual, especialmente en mujeres con discapacidad intelectual. Los maltratos son perpetrados sobre todo por sus parejas y cuidadores. Estas situaciones generan consecuencias negativas en todas las áreas de sus vidas y obstaculizan su inclusión social. Es necesario consensuar criterios más precisos para categorizar las diversas formas de violencia, aumentar la investigación sobre los factores de riesgo asociados a cada tipo de violencia y discapacidad, así como implementar programas de intervención adaptados a las necesidades específicas de las mujeres víctimas de violencia.

Psychosocial stress may alter cortisol and/or affect the normal functioning of the immune system. Curcuminoids can promote beneficial effects in neuropsychiatric diseases. We evaluated whether curcumin supplementation for 15 consecutive days (1800 mg/day) would decrease systemic MCP-1, sCD14, and TNF alpha levels in patients with moderate anxiety (n = 81). A total number of 81 subjects were enrolled in this study, divided into the following groups according to their Hamilton scores: a control group including patients without anxiety who were not taking curcumin (Cont, n = 22) and an anxiety group including patients with moderate anxiety (Anx, n = 22). The curcumin-treated patients experienced moderate anxiety, and they take curcumin for 15 consecutive days (Anx-Cur (after), n = 15, 1800 mg/day). An evaluation of 128 patients was conducted, which allowed for their assignment to the study groups according to their scores on Hamilton scale II. The cortisol levels were quantified in salivary samples through ELISA (ng/mL), and malonaldehyde (MDA) levels were measured in plasma via the TBARS assay as an index of lipoperoxidation. Several systemic proinflammatory cytokines (pg/mL: MCP-1, TNF alpha, IL-1 beta) and mediators were quantified through ELISA (pg/mL), including systemic sCD14 levels as a marker of monocyte activation. A two-way bifactorial ANOVA was conducted to evaluate the contributions of the anxiety factor (Anx) and/or curcumin factor (Cur) in all the tested markers, including interactions between both factors. High systemic MCP-1 and elevated sCD14 levels were observed in patients with moderate anxiety, which were reduced with curcumin supplementation. In addition, curcumin prevented cortisol overexpression and decreased MDA levels as an antioxidant response in these patients. Collectively, curcumin presented anti-chemotactic effects by reducing systemic MCP-1 levels in anxiety. Curcumin decreased systemic MCP-1 as well as sCD14 levels in patients with moderate anxiety.

Background: Longitudinal data on reverse cardiac remodeling and outcomes after transcatheter edge-to-edge repair (TEER) are limited. Methods: A total of 78 patients with severe mitral regurgitation (MR) were included retrospectively. All patients had echocardiography at baseline and again six months after TEER. They were monitored for a primary composite endpoint, consisting of heart failure hospitalization and cardiovascular death, over 13 months. Results: Significant decreases in the left ventricular ejection fraction (LVEF), all myocardial work indices (except global wasted work), and the left atrial reservoir were observed after TEER. Additionally, there was a decrease in the pulmonary artery systolic pressure and an increase in the tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. A post-TEER TAPSE/PASP ratio of p-value = 0.039), and a post-TEER left atrial reservoir of p-value = 0.047) were associated with the primary endpoint. Conclusions: Echocardiography post-TEER reflects impairment in ventricular performance due to preload reduction and right ventricle and pulmonary artery coupling improvement. Short-term echocardiography after TEER identifies high-risk patients who could benefit from a close clinical follow-up. The prognostic significance of LA strain and the TAPSE/PASP ratio should be validated in subsequent large-scale prospective studies.

In vitro cell activation through specific IgE bound to high-affinity receptors on the basophil surface is a widely used strategy for the evaluation of IgE-mediated immediate hypersensitivity reactions to betalactams. Cellular activation requires drug conjugation to a protein to form a large enough structure displaying a certain distance between haptens to allow the cross-linking of two IgE antibodies bound to the basophil’s surface, triggering their degranulation. However, no information about the size and composition of these conjugates is available. Routine in vitro diagnosis using the basophil activation test uses free amoxicillin, which is assumed to conjugate to a carrier present in blood. To standardize the methodology, we propose the use of well-controlled and defined nanomaterials functionalized with amoxicilloyl. Silica nanoparticles decorated with PAMAM–dendrimer–amoxicilloyl conjugates (NpDeAXO) of different sizes and amoxicilloyl densities (50–300 µmol amoxicilloyl/gram nanoparticle) have been prepared and chemically characterized. Two methods of synthesis were performed to ensure reproducibility and stability. Their functional effect on basophils was measured using an in-house basophil activation test (BAT) that determines CD63+ or CD203chigh activation markers. It was observed that NpDeAXO nanocomposites are not only able to specifically activate basophils but also do so in a more effective way than free amoxicillin, pointing to a translational potential diagnosis.

Se comparte el análisis descriptivo de las percepciones sobre destrezas transferibles del alumnado y docentes de una institución de educación universitaria que imparte grados en Artes Escénicas, Cinematografía, Música, Bellas Artes y Fotografía. Se considera que la inclusión de destrezas transferibles en la enseñanza artística superior puede favorecer el desarrollo personal y profesional del estudiantado y promover su empleabilidad. Con esta hipótesis se indaga en la percepción del alumnado y profesorado con relación a estas destrezas a través de un estudio comparativo-descriptivo con una metodología cuantitativa. En los resultados se identifica en primer lugar, que las destrezas menos valoradas por ambos colectivos son precisamente las que reclama el sector empleador. En segundo lugar, existen claras diferencias en las valoraciones realizadas por el profesorado y por el alumnado y entre las cinco ramas artísticas. Finalmente, se evidencia la necesidad de incluir estas destrezas para mejorar la empleabilidad de las personas graduadas.

BackgroundDiffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients.Methods78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients.ResultsOur results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients.ConclusionCD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL.Clinical trial registrationhttps://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

Background: The measurement of aortic dimensions and their evolution are key in the management of patients with aortic diseases. Manual assessment, the current guideline-recommended method and clinical standard, is subjective, poorly reproducible, and time-consuming, limiting the capacity to track aortic growth in everyday practice. Aortic geometry mapping (AGM) via image registration of serial computed tomography angiograms outperforms manual assessment, providing accurate and reproducible 3D maps of aortic diameter and growth rate. This observational study aimed to evaluate the accuracy and reproducibility of AGM on non-gated contrast-enhanced (CE-) and cardiac- and respiratory-gated (GN-) magnetic resonance angiographies (MRA). Methods: Patients with thoracic aortic disease followed with serial CE-MRA (n = 30) or GN-MRA (n = 15) acquired at least 1 year apart were retrospectively and consecutively identified. Two independent observers measured aortic diameters and growth rates (GR) manually at several thoracic aorta reference levels and with AGM. Agreement between manual and AGM measurements and their inter-observer reproducibility were compared. Reproducibility for aortic diameter and GR maps assessed with AGM was obtained. Results: Mean follow-up was 3.8 ± 2.3 years for CE- and 2.7 ± 1.6 years for GN-MRA. AGM was feasible in the 93% of CE-MRA pairs and in the 100% of GN-MRA pairs. Manual and AGM diameters showed excellent agreement and inter-observer reproducibility (ICC>0.9) at all anatomical levels. Agreement between manual and AGM GR was more limited, both in the aortic root by GN-MRA (ICC=0.47) and in the thoracic aorta, where higher accuracy was obtained with GN- than with CE-MRA (ICC=0.55 vs 0.43). The inter-observer reproducibility of GR by AGM was superior compared to manual assessment, both with CE- (thoracic: ICC= 0.91 vs 0.51) and GN-MRA (root: ICC=0.84 vs 0.52; thoracic: ICC=0.93 vs 0.60). AGM-based 3D aortic size and growth maps were highly reproducible (median ICC >0.9 for diameters and >0.80 for GR). Conclusion: Mapping aortic diameter and growth on MRA via 3D image registration is feasible, accurate and outperforms the current manual clinical standard. This technique could broaden the possibilities of clinical and research evaluation of patients with aortic thoracic diseases.

Introduction Rotator cuff calcific tendinopathy (RCCT) involves calcific deposits in the rotator cuff. Non-surgical interventions such as extracorporeal shockwave therapy (ESWT) and ultrasound-guided percutaneous irrigation of calcific tendinopathy (US-PICT) are recommended for its early management. Exercise therapy (ET) has shown to be an effective intervention for people with rotator cuff tendinopathy, but it has not been formally tested in RCCT. The main objective of this study is to compare the effectiveness of an ET programme with ESWT and US-PICT in people with RCCT. As a secondary aim, this study aims to describe the natural history of RCCT.Methods and analysis A randomised, single-blinded four-group clinical trial will be conducted. Adults from 30 to 75 years diagnosed with RCCT who accomplish eligibility criteria will be recruited. Participants (n=116) will be randomised into four groups: ET group will receive a 12-week rehabilitation programme; ESWT group will receive four sessions with 1 week rest between sessions during 1 month; US-PICT group will receive two sessions with 3 months of rest between sessions; and (actual) wait-and-see group will not receive any intervention during the 12-month follow-up. The primary outcome will be shoulder pain assessed with the Shoulder Pain and Disability Index at baseline, 2 weeks, 4 months, 6 months and 12 months from baseline. The primary analysis will be performed at 12 months from baseline. Secondary outcomes will include pain, range of motion, patient satisfaction and imaging-related variables. Moreover, the following psychosocial questionnaires with their corresponding outcome measure will be assessed: Central Sensitization Inventory (symptoms related to central sensitization); Pain Catastrophizing Scale (pain catastrophizing); Tampa Scale for Kinesiophobia 11 items (fear of movement); Fear Avoidance Belief Questionnaire (fear avoidance behaviour); Hospital Anxiety and Depression Scale (anxiety and depression); Pittsburgh Sleep Quality Index (sleep quality); and the EuroQol-5D (quality of life). An intention-to-treat analysis will be performed to reduce the risk of bias using a worst-case and best-case scenario analysis.Ethics and dissemination Ethics committee approval for this study has been obtained (reference number: 1718862). The results of the main trial will be submitted for publication in a peer-reviewed journal.Trial registration number NCT05478902.

Abstract: This study aims to determine the association of adherence to the Mediterranean diet and its food groups with depressive symptoms in Chilean university students. The study design was cross-sectional. A total of 934 first-year students at a Chilean public university completed a self-report questionnaire. To assess adherence to Mediterranean diet, an index validated in Chile (Chilean-MDI) was used, and depression, anxiety, and stress symptoms were assessed using the Depression Anxiety and Stress Scale (DASS-21). Logistic regression models were used to analyze the association of adherence to Mediterranean diet and its food groups with depression, anxiety, and stress symptoms adjusted for the main confounders. Students with moderate and high adherence to Mediterranean diet showed lower odds of depression [DASS-21 > 5, odds ratio (OR) = 0.64; 95% confidence interval (95%CI): 0.47-0.88] than those with low adherence to Mediterranean diet. The consumption of 1-2 servings/day of vegetables (OR = 0.63; 95%CI: 0.43-0.92), > 2 servings/week of nuts (OR = 0.41; 95%CI: 0.21-0.80), 1-2 servings/day of fruits (OR = 0.60; 95%CI: 0.42-0.85), 1-2 servings/week of fish and seafood (OR = 0.67; 95%CI: 0.48-0.94), and 1/2-3 units/week of avocado (OR = 0.67; 95%CI: 0.48-0.93) showed low odds of depressive symptoms. The consumption of whole grains and cereals (> 2 servings/day) (OR = 1.63; 95%CI: 1.02-2.61) showed the opposite association. Adherence to Mediterranean diet and consumption of fruits, vegetables, nuts, avocado, fish, and seafood are associated with a lower likelihood of depression in Chilean university students. New policies and educational strategies are recommended to improve diet quality and the mental health of the entire university community.

Este artículo pretende actualizar el estado de la cuestión del escultor tardogótico Alonso de Portillo, atribuyendo una serie de obras fáciles de reconocer gracias a su particular estilo. Además de añadir a su catálogo varias piezas en la catedral de Palencia, también se adscriben unas cuántas imágenes distribuidas por distintos puntos de la provincia de Palencia.

In this paper we study the seizure of a galiot or small galley of Barbary corsairs carried out at the beginning of the 17th century by a small fleet commanded by the 11th Count of Niebla. Historic documents and derived literary works are contrasted to clarify the event.

Fuente de la Loma, es un yacimiento que alberga una ocupación prolongada, situado en una posición estratégica en una vía de comunicación secundaria en la intersección que une el noroeste murciano con el sur de Albacete y el norte de Granada. Tiene sus comienzos en un pequeño asentamiento durante la Edad del Bronce, posteriormente se convierte en un poblado de cierta envergadura durante el Ibérico Pleno perdurando hasta la romanización, convirtiéndose primero en una villa o asentamiento en época republicana continuando hasta época tardorromana y preandalusí cuando desaparece. Sufre un periodo de regresión a finales del s. IV o durante el s. V d.C., aunque con una cierta perduración en el periodo tardorromano-emiral (ss.VII-VIII). El yacimiento se sitúa en el extremo occidental del Término Municipal de Moratalla. Con este trabajo se da conocimiento sobre este enclave así como sobre el poblamiento del entorno siendo prácticamente inédito.

Abstract The LRRK2 G2019S pathogenic mutation causes LRRK2-associated Parkinson’s disease (L2PD) with incomplete penetrance. LRRK2 non-manifesting carriers (L2NMC) are at PD high risk but predicting pheno-conversion is challenging given the lack of progression biomarkers. To investigate novel biomarkers for PD premotor stages, we performed a longitudinal microRNA (miRNA) assessment of serum samples from G2019S L2NMC followed-up over 8 years. Our cohort consisted of G2019S L2NMC stratified by dopamine transporter single-photon emission computed tomography (DaT-SPECT) into DaT-negative (n = 20) and DaT-positive L2NMC (n = 20), pheno-converted G2019S L2PD patients (n = 20), idiopathic PD (iPD) (n = 19), and controls (n = 40). We also screened a second cohort of L2PD patients (n = 19) and controls (n = 20) (Total n = 158). Compared to healthy controls, we identified eight deregulated miRNAs in DaT-negative L2NMC, six in DaT-positive L2NMC, and one in L2PD. Between groups, the highest miRNA differences, 24 candidate miRNAs, occurred between DaT-positive L2NMC and L2PD. Longitudinally, we found 11 common miRNAs with sustained variation in DaT-negative and DaT-positive L2NMCs compared to their baselines. Our study identifies novel miRNA alterations in premotor stages of PD co-occurring with progressive DaT-SPECT decline before motor manifestation, whose deregulation seems to attenuate after the diagnosis of L2PD. Moreover, we identified four miRNAs with relatively high discriminative ability (AUC = 0.82) between non-pheno-converted DaT-positive G2019S carriers and pheno-converted L2PD patients (miR-4505, miR-8069, miR-6125, and miR-451a), which hold potential as early progression biomarkers for PD.

Tau aggregates are associated with several neurodegenerative disorders. In this work, I. Saha and colleagues show that valosin-containing protein (VCP) recruited to Tau fibrils disaggregates them. However, this process comes at a cost: it generates seeding-active Tau species as byproduct.

Background Type 2 diabetes mellitus (T2DM) is related to increased inflammatory processes. The effects of resistance exercise on inflammatory biomarkers in T2DM are controversial. Our purpose was to determine the effectiveness of resistance exercise on inflammatory biomarkers in patients diagnosed with T2DM. Methods We searched four databases until September 2021. We included randomized clinical trials (RCTs) of the effects of resistance exercise on inflammatory biomarkers (C-reactive protein [CRP], tumor necrosis factor alpha, interleukin-6, and interleukin-10) in patients with T2DM. A random effects meta-analysis was conducted to determine the standardized mean difference (SMD) and the raw mean difference (MD) for CRP. Results Thirteen RCTs were included in the review, and 11 in the meta-analysis for CRP. Lower CRP levels were observed when resistance exercise was compared with the control groups (SMD=–0.20; 95% confidence interval [CI], –0.37 to –0.02). When conducting the MD meta-analysis, resistance exercise showed a significant decrease in CRP of –0.59 mg/dL (95% CI, –0.88 to –0.30); otherwise, in the control groups, the CRP values increased 0.19 mg/dL (95% CI, 0.17 to 0.21). Conclusion Evidence supports resistance exercise as an effective strategy to manage systemic inflammation by decreasing CRP levels in patients with T2DM. The evidence is still inconclusive for other inflammatory biomarkers.

Abstract The objective of this study was to evaluate the association of egg consumption with blood pressure (BP) and glycated hemoglobin (HbA1c). In addition, it was assessed whether this association changes according to body weight status. This cross-sectional study is based on multicenter data from Spanish adult participants in the EVIDENT II trial. Egg consumption was assessed with a Food Frequency Questionnaire, and data on BP and HbA1c were collected using standardized procedures. Linear regression and ANCOVA models adjusted for the main confounders were performed. The analyses were stratified by body weight status. A total of 668 participants were analyzed (mean age 52.4 ± 11.8 years, 62.3% women). Compared with lower consumption, higher egg consumption was associated with lower systolic (ß = − 6.15 ± 1.74; p-for-trend = 0.017), diastolic (ß = − 4.41 ± 1.03; p-for-trend = 0.002), and mean arterial pressure (ß = − 4.99 ± 1.17; p-for-trend = 0.003) and with lower HbA1c (ß = − 0.19 ± 0.06; p-for-trend = 0.019) levels. These associations lost statistical significance in the adjusted analyses. The results did not vary by body weight status. In conclusion, consumption of up to 1 egg per day is not associated with BP or HbA1c, even in overweight or obese individuals. Our findings suggested that this frequency of egg consumption is safe as part of a healthy diet and lifestyle for cardiometabolic risk.

Las abundantes investigaciones sobre los sistemas educativos han permitido identificar los factores fundamentales que determinan el éxito educativo del alumnado. Sin embargo, estas investigaciones no han sido muy eficientes a la hora de transferir los resultados a los contextos aplicados en los que se mueven los profesionales y directivos que toman las decisiones sobre los sistemas educativos. La razón principal de este fracaso proviene de la poca familiarización de los profesionales de la educación con la sofisticada metodología estadística y psicométrica utilizada por la mayoría de los investigadores. El objetivo del presente trabajo es analizar los sistemas educativos mediante la metodología de análisis de redes, la cual es muy asequible, clara e intuitiva para profesionales y directivos educativos sin una gran sofisticación metodológica. Se utilizó una muestra de 7,882 estudiantes de segundo curso de la Enseñanza Secundaria Obligatoria. Se evaluó su competencia matemática y se obtuvieron datos relativos al contexto educativo. Se utilizó para los análisis el análisis de redes, calculando indicadores de centralidad, así como de precisión y estabilidad de la red. Los resultados indican que el autoconcepto y las expectativas académicas tienen un importante efecto sobre los resultados en matemáticas. Los hallazgos convergen con los obtenidos previamente con otros enfoques. El acercamiento de análisis de redes ofrece una combinación idónea entre rigor analítico y sencillez interpretativa, lo que le confiere gran potencial para ser empleado en contextos educativos aplicados para la toma de decisiones basadas en datos.

Background: Although brain-derived neurotrophic factor (BDNF) has been identified as a molecular biomarker of the neurophysiological effects induced by exercise, the acute effects of high-intensity exercise (HIE) on BDNF levels are inconclusive. This study aims to estimate the immediate effects of HIE on BDNF levels in healthy young adults. Methods: A systematic search was conducted in the MEDLINE, Scopus, Cochrane CENTRAL, and SPORTDiscuss databases up to December 2020. Randomized controlled trials (RCTs) and non-RCTs reporting pre–post changes in serum or plasma BDNF after an acute intervention of HIE compared to a control condition were included. Pooled effect sizes (p-ESs) and 95% confidence intervals (95%CIs) were calculated for RCTs using a random effects model with Stata/SE (Version 15.0; StataCorp., College Station, TX, USA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. PROPERO registration number: CRD42020221047. Results: A total of 22 studies with 552 individuals (age range: 20–31 years; 59.1% male) were included. The meta-analysis included 10 RCTs that reported valid outcome data. Higher BDNF levels were observed when HIE interventions were compared with non-exercise (p-ES = 0.55, 95%CI: 0.12–0.98; I2 = 25.7%; n = 4 studies) and light-intensity exercise (p-ES = 0.78, 95%CI: 0.15–1.40; I2 = 52.4%; n = 3 studies) but not moderate-intensity exercise (p-ES = 0.93, 95%CI: –0.16 to 2.02; I2 = 88.5%; n = 4 studies) conditions. Conclusion: In comparison to non-exercise or light-intensity exercises, an immediate increase in BDNF levels may occur when young adults perform HIE. Given the benefits obtained maximizing circulating BDNF when performing HIE and its potential effects on brain health, our findings suggest that HIE could be recommended by clinicians as a useful exercise strategy to healthy adults.

Abstract Neuroinflammation, in which activated microglia are involved, appears to contribute to the development of Parkinson’s disease (PD). However, the role of microglial activation and the mechanisms governing this process remain uncertain. We focused on one inhibitory mechanism involved in the control of microglial activation, the microglia inhibitory receptor CD200R1, and its ligand CD200, mainly expressed by neurons. The human CD200R1 gene encodes two membrane-associated and two soluble protein isoforms and the human CD200 gene encodes full-length proteins (CD200full) but also truncated (CD200tr) proteins which act as CD200R1 antagonists. Little is known about their expression in the human brain under pathological conditions. We used human peripheral blood monocytes and monocyte-derived microglia-like cells from control subjects to characterize the expression of the CD200R1 mRNA variants, which showed stimulus-specific responses. We provide evidence of increased CD200R1 (mRNA variants and protein isoforms) and CD200 expression (CD200tr mRNA) in brain tissue of PD patients, mainly in the hippocampus, as well as increased CD200 expression (CD200full and CD200tr mRNAs) in iPSCs-derived dopaminergic neurons generated from skin fibroblasts of PD patients. Our results suggest that CD200-CD200R1 signalling is altered in PD, which may affect the microglial function and constitute a potential target in therapeutic strategies for PD.

Being a proficient reader in a digital world requires a strong reading foundation, but also the ability to think critically, which is a challenge for many students in Spain. Computerized adaptive tests and process data (information about students’ actions when responding to the test) are especially important when assessing skills such as reading. This work aims to analyze how the use of technology is changing the concept of reading and the ways to evaluate it. This has implications for Spanish students and any professional in charge of interpreting and designing educational assessments. The researcher must ensure that the use of data and technology is adequate for the purposes of the assessment and that it works in a reliable, valid, and fair way for the people involved, but also the user must know when, how, and for what purposes to use the data

Objectives: The aim of this study was twofold: a) to establish the prevalence of adolescents with disordered eating and b) to determine the factors associated with this prevalence in a sample of Spanish adolescents from the Valle de Ricote (Region of Murcia, Spain).Methods: This cross-sectional study analyzed data from 730 adolescents (56.2% girls) from the EHDLA study. To determine the prevalence of disordered eating, the Sick, Control, One stone, Fat, Food (SCOFF) questionnaire was used. A socioecological approach was used to identify individual-, interpersonal-, or organizational-level factors associated with disordered eating.Results: The prevalence of disordered eating was 30.1%. This condition was associated with female sex (odds ratio [OR] = 2.60; 95% confidence interval [CI], 1.81–3.73), immigrant status (OR = 2.22; 95% CI, 1.51–3.25), or excess weight (OR = 2.74; 95% CI, 1.93–3.89). Furthermore, for each additional hour slept, lower odds of having disordered eating were found (OR = 0.81; 95% CI, 0.67–0.98).Discussion: Almost one-third of the sample of Spanish adolescents analyzed reported disordered eating. Female sex, immigrant status and excess weight are individual aspects that seem to be related to disordered eating among Spanish adolescents.

Abstract Type-2 diabetes (T2D) and glucose metabolic imbalances have been linked to neurodegenerative diseases, including Parkinson’s disease (PD). To detect potential effects of different glucose levels on gene expression, by RNA-seq we analyzed the transcriptome of dermal fibroblasts from idiopathic PD (iPD) patients, LRRK2-associated PD (L2PD) patients, and healthy controls (total n = 21 cell lines), which were cultured at two different glucose concentrations (25 and 5 mM glucose). In PD patients we identified differentially expressed genes (DEGs) that were related to biological processes mainly involving the plasmatic cell membrane, the extracellular matrix, and also neuronal functions. Such pathway deregulation was largely similar in iPD or L2PD fibroblasts. Overall, the gene expression changes detected in this study were associated with PD independently of glucose concentration.

Colgadas de los muros del coro de la catedral de Palencia se conservan seis tablas de pequeño formato que, por el estilo que presentan, pueden atribuirse al pintor Juan de Villoldo, discípulo de Alonso Berruguete. Se hace una breve biografía de Villoldo, se analiza su estilo y se dan a conocer las pinturas con los cuatro Evangelistas, San Andrés y Santa Ana, la Virgen y el Niño, comparando sus formas con las de otras obras documentadas y atribuidas al maestro. Además, se propone el posible origen de las mismas.

BackgroundBoth dietary and sleep patterns can influence both blood pressure levels and heart rate, but these associations have been understudied in adolescents. Furthermore, it is not known whether diet and sleep could exert a synergistic effect with respect to the maintenance of optimal BP levels in this population.ObjectiveTo investigate the relationship of blood pressure levels with the combination of higher adherence to the Mediterranean diet and the habit of siesta (daytime napping) in Spanish adolescents.MethodsA cross-sectional study was conducted with data obtained through personal interviews and physical examination from a representative sample of 1,378 adolescents (12–17 years of age) from the Valle de Ricote (Region of Murcia, Spain) selected using a simple random sampling technique. Adherence to the Mediterranean diet was assessed with the Mediterranean Diet Quality Index in Children and Adolescents, and the frequency and duration of siesta were self-reported. Objective measurements of systolic and diastolic blood pressure were obtained under standardized conditions. Statistical procedures were performed with SPSS software (v.25) and included logistic and generalized regression models adjusted for sex, age, socioeconomic status, body mass index, total energy intake, nighttime sleep duration, and moderate-to-vigorous physical activity.ResultsOf the 698 adolescents finally studied (mean age 13.9 ± 1.5 years; 56.2% female), 37.1% (n = 259) had high adherence to the Mediterranean diet and 19.6% (n = 137) reported frequent siesta. In the completely adjusted models, compared to adolescents with low Mediterranean diet adherence and no or infrequent siesta, those with high Mediterranean diet adherence and frequent siesta were less likely to have high-normal blood pressure or hypertension (odds ratio = 0.47; 95% confidence interval: 0.26, 0.88) and showed slightly lower systolic blood pressure (ß-coef. = −2.60; 95% CI: −5.18, −0.02).ConclusionGreater adherence to the Mediterranean diet and frequent siesta have a synergistic effect on maintaining lower blood pressure levels in adolescence. These findings reinforce that adherence to both Mediterranean lifestyle behaviors early in life may be an important strategy to prevent hypertension throughout adulthood.

Controlling rockfall-related risks is a requirement for safe pit operations and primarily mitigated through adequate bench geometry design and implementation. This paper presents a method for rockfall hazard analysis for in-pit operations potentially impacting external sensible areas, adapted from natural rockfall hazard analyses. The method considers the natural susceptibility to rockfalls pre-mining, rockfalls originated from bench failures, and those initiated as flyrock. Rockfall trajectory models are used to estimate the potential for blocks reaching exposed elements. Natural susceptibility to rockfalls and trajectories are used as a baseline on which to evaluate the potential effects of open pit operations on the environment and perceptions of communities in the area. The method is illustrated for an open pit in steep terrain in the Peruvian Andes at a feasibility level of study. The paper illustrates the flexibility for including considerations of pre-mining rockfall impacts on the external elements of interest, and for developing rockfall mitigation strategies that consider rock block velocities, heights, energies and the spatial distribution of trajectories. The results highlight the importance of considering the three-dimensional effects of the terrain on block trajectories, and how such insights allow for increasing the efficiency of resources available for rockfall protection structures.

We present a case of acute myocarditis with left ventricular dysfunction and intracavitary thrombosis in a 55-year-old man with severe acute respiratory syndrome coronavirus 2 infection (coronavirus disease 2019) who was admitted with bilateral atypical pneumonia. The patient was treated with anticoagulation and optimal heart failure therapy and had an improvement of left ventricular function and thrombus resolution. (Level of Difficulty: Intermediate.)

The molecular architecture of α-Synuclein (α-Syn) inclusions, pathognomonic of various neurodegenerative disorders, remains unclear. Here, authors use cryo-electron tomography to image neuronal α-Syn inclusions in situ and find that inclusions consist of α-Syn fibrils intermixed with cellular organelles without interacting directly.

Background: Epilepsy is one of the most common neurologic diseases, and around 30% of all epilepsies, particularly the temporal lobe epilepsy (TLE), are highly refractory to current pharmacological treatments. Abnormal synchronic neuronal activity, brain glucose metabolism alterations, neurodegeneration and neuroinflammation are features of epilepsy. Further, neuroinflammation has been shown to contribute to dysregulation of neuronal excitability and the progression of epileptogenesis. Flufenamic acid (FLU), a non-steroidal anti-inflammatory drug, is also characterized by its wide properties as a dose-dependent ion channel modulator. In this context, in vitro studies have shown that it abolishes seizure-like events in neocortical slices stimulated with a gamma-aminobutyric acid A (GABAA) receptor blocker. However, little is known about its effects in animal models. Thus, our goal was to assess the efficacy and safety of a relatively high dose of FLU in the lithium-pilocarpine rat model of status epilepticus (SE). This animal model reproduces many behavioral and neurobiological features of TLE such as short-term brain hypometabolism, severe hippocampal neurodegeneration and inflammation reflected by a marked reactive astrogliosis. Methods: FLU (100 mg/kg, i.p.) was administered to adult male rats, 150 min before SE induced by pilocarpine. Three days after the SE, brain glucose metabolism was assessed by 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) positron emission tomography (PET). Markers of hippocampal integrity, neurodegeneration and reactive astrogliosis were also evaluated. Results: FLU neither prevented the occurrence of the SE nor affected brain glucose hypometabolism as assessed by [18F]FDG PET. Regarding the neurohistochemical studies, FLU neither prevented neuronal damage nor hippocampal reactive astrogliosis. On the contrary, FLU increased the mortality rate and negatively affected body weight in the rats that survived the SE. Conclusions: Our results do not support an acute anticonvulsant effect of a single dose of FLU. Besides, FLU did not show short-term neuroprotective or anti-inflammatory effects in the rat lithium-pilocarpine model of SE. Moreover, at the dose administered, FLU resulted in deleterious effects.

Over the past few years, spatial memory has been studied using virtual-reality-based tasks. Reversal learning has been widely used in spatial orientation tasks for testing, among other things, new learning and flexibility. By means of a reversal-learning protocol, we assessed spatial memory in men and women. A total of sixty participants (half of them women) performed a task that included two phases: during the acquisition phase, participants were asked to find one or three rewarded positions in the virtual room across ten trials. During the reversal phase, the rewarded boxes were moved to a new position and maintained for four trials. The results showed that men and women differed in the reversal phase, with men outperforming women in high demanding conditions. Dissimilarities in several cognitive abilities between both genders are the base of these differences and are discussed.

Abstract We propose and demonstrate a compact and simple vector bending sensor capable of distinguishing any direction and amplitude with high accuracy. The sensor consists of a short segment of asymmetric multicore fiber (MCF) fusion spliced to a standard single mode fiber. The reflection spectrum of such a structure shifts and shrinks in specific manners depending on the direction in which the MCF is bent. By monitoring simultaneously wavelength shift and light power variations, the amplitude and bend direction of the MCF can be unmistakably measured in any orientation, from 0° to 360°. The bending sensor proposed here is highly sensitive even for small bending angles (below 1°).

Abstract The use of non‐pegylated liposomal doxorubicin (Myocet®) in diffuse large B‐cell lymphoma (DLBCL) has been investigated in retrospective and single‐arm prospective studies. This was a prospective phase 2 trial of DLBCL patients ≥60 years old with left ventricular ejection fraction (LVEF) ≥55% randomized to standard R‐CHOP or investigational R‐COMP (with Myocet® instead of conventional doxorubicin). The primary end point was to evaluate the differences in subclinical cardiotoxicity, defined as decrease in LVEF to

Consumption of organic foods has increased recently, but evidence about their potential health benefits is still limited. This systematic review aims to synthesize the available scientific evidence on the association between organic egg consumption and human health. We searched for peer-reviewed articles on this subject indexed in the MEDLINE, EMBASE, Web of Science and Cochrane Library databases from the inception date to April 13, 2022. This review was based on PRISMA guideline recommendations. Three studies on organic egg consumption in humans were included. After 8 weeks of consuming organic eggs, one randomized crossover trial found that participants had higher serum concentrations of the beta-carotene lutein compared to the period without consuming organic eggs. Moreover, in a cross-sectional study with nationally representative data from Americans over the age of 50, it was found that consumption of organic eggs was associated with lower levels of the inflammatory markers C-reactive protein and cystine C compared with conventional eggs. Finally, in a cohort of children aged 0 to 2 years, no significant association was observed between consuming organic eggs and the risk of eczema. In conclusion, the evidence about the potential benefits of organic egg consumption and human health is promising but still requires further research. A human research agenda is proposed based on laboratory studies pointing out that organic eggs have a more desirable nutritional profile than conventional eggs.

The current great concern about plastic pollution opens up opportunities for the production of more sustainable polymers. Inverse vulcanization has emerged as a novel procedure to obtain inorganic-organic hybrid polymeric materials. Sulfur is attained as a by-product of oil refining production and makes inverse vulcanization a sustainable process due to a large amount of sulfur without a useful life. In previous studies, vegetable oils were used as a comonomer with sulfur to form copolymers based on sustainable raw material. Nevertheless, compounds from agro-wastes, could be a third comonomer that improves new copolymers bio-applications. In this study, a new series of copolymers with castor oil as vegetable oil and sulfur was formulated by adding a third compound bearing double bonds or heteroatoms. A study was conducted to assess the antimicrobial capacity and antioxidant activity of the copolymers obtained to demonstrate the benefits of adding a new comonomer to improve their bioactivity.

Grit is a construct that is related to perseverance and passion for achieving set goals. Its relationship to school performance has been widely researched although the results are not conclusive. The aim of this study was to examine the temporal stability of grit and its relationship to adolescents’ school performance. A sample of 5,371 students were evaluated at two time points, four years apart. At first evaluation, mean age was 9.9 years old (SD = 0.41), at the second it was 13.87 (SD = 0.82). A longitudinal design was used, and the data were analysed using analysis of variance, factor analysis, and structural equations models. Adolescents’ academic grit and school achievement fall between ages of 10 and 14. Adolescents with higher levels of grit had higher academic achievement. The two constructs are correlated, which is why interventions aimed at improving academic grit could be important in improving school performance.

Abstract Background The huntingtin-associated protein 40 (HAP40) abundantly interacts with huntingtin (HTT), the protein that is altered in Huntington’s disease (HD). Therefore, we analysed the evolution of HAP40 and its interaction with HTT. Results We found that in amniotes HAP40 is encoded by a single-exon gene, whereas in all other organisms it is expressed from multi-exon genes. HAP40 co-occurs with HTT in unikonts, including filastereans such as Capsaspora owczarzaki and the amoebozoan Dictyostelium discoideum, but both proteins are absent from fungi. Outside unikonts, a few species, such as the free-living amoeboflagellate Naegleria gruberi, contain putative HTT and HAP40 orthologs. Biochemically we show that the interaction between HTT and HAP40 extends to fish, and bioinformatic analyses provide evidence for evolutionary conservation of this interaction. The closest homologue of HAP40 in current protein databases is the family of soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs). Conclusion Our results indicate that the transition from a multi-exon to a single-exon gene appears to have taken place by retroposition during the divergence of amphibians and amniotes, followed by the loss of the parental multi-exon gene. Furthermore, it appears that the two proteins probably originated at the root of eukaryotes. Conservation of the interaction between HAP40 and HTT and their likely coevolution strongly indicate functional importance of this interaction.

Abstract We report on a compact, highly sensitive all-fiber accelerometer suitable for low frequency and low amplitude vibration sensing. The sensing elements in the device are two short segments of strongly coupled asymmetric multicore fiber (MCF) fusion spliced at 180° with respect to each other. Such segments of MCF are sandwiched between standard single mode fibers. The reflection spectrum of the device exhibits a narrow spectrum whose height and position in wavelength changes when it is subjected to vibrations. The interrogation of the accelerometer was carried out by a spectrometer and a photodetector to measure simultaneously wavelength shift and light power variations. The device was subjected to a wide range of vibration frequencies, from 1 mHz to 30 Hz, and accelerations from 0.76 mg to 29.64 mg, and performed linearly, with a sensitivity of 2.213 nW/mg. Therefore, we believe the accelerometer reported here may represent an alternative to existing electronic and optical accelerometers, especially for low frequency and amplitude vibrations, thanks to its compactness, simplicity, cost-effectiveness, implementation easiness and high sensitivity.

Los conocimientos paisajísticos son fundamentales para poder comprender el espacio que nos rodea e interpretar la posible evolución a partir del análisis de los elementos que lo configuran. Por ello, es necesario dotar a los docentes en formación de las habilidades necesarias para incorporar adecuadamente y de forma eficiente los contenidos sobre el paisaje e incorporar al proceso de enseñanza-aprendizaje de las Ciencias Sociales el paisaje como instrumento. El desarrollo de este trabajo se centra en el análisis de los conocimientos y percepciones que tienen los maestros en formación sobre el paisaje. Para ello, a partir de una metodología de tipo mixto se ha diseñado y desarrollado un cuestionario que cuenta con la recogida de datos de tipo cuantitativo (ítems presentados en escala Likert) y con datos de tipo cualitativo (respuestas a unas cuestiones sobre tres imágenes de paisajes contrastados). Los resultados nos indican que según los datos cuantitativos existe un amplio número de sujetos de la muestra con conocimientos teóricos sobre el paisaje, número que se ve muy reducido tras el análisis de los datos cualitativos. Por ello, se podría indicar que disponen de conocimientos sobre el paisaje pero que les faltan las habilidades para incorporarlos a una descripción.

Anaplasma phagocytophilum Major surface protein 4 (MSP4) plays a role during infection and multiplication in host neutrophils and tick vector cells. Recently, vaccination trials with the A. phagocytophilum antigen MSP4 in sheep showed only partial protection against pathogen infection. However, in rabbits immunized with MSP4, this recombinant antigen was protective. Differences between rabbit and sheep antibody responses are probably associated with the recognition of non-protective epitopes by IgG of immunized lambs. To address this question, we applied quantum vaccinomics to identify and characterize MSP4 protective epitopes by a microarray epitope mapping using sera from vaccinated rabbits and sheep. The identified candidate protective epitopes or immunological quantum were used for the design and production of a chimeric protective antigen. Inhibition assays of A. phagocytophilum infection in human HL60 and Ixodes scapularis tick ISE6 cells evidenced protection by IgG from sheep and rabbits immunized with the chimeric antigen. These results supported that the design of new chimeric candidate protective antigens using quantum vaccinomics to improve the protective capacity of antigens in multiple hosts.

Background: Both idiopathic and familial Parkinson's disease are associated with mitochondrial dysfunction. Mitochondria have their own mitochondrial DNA (mtDNA) and previous studies have reported that the release of mtDNA is a biomarker of Parkinson's disease. Methods: We have now investigated the relationship between mtDNA replication, transcription and release in fibroblasts from patients with idiopathic (iPD) and Leucine-rich repeat kinase 2G2019S -associated Parkinson's disease (LRRK2-PD), using Selfie-digital PCR, a method that allows absolute quantification of mtDNA genomes and transcripts. Findings: In comparison with healthy controls, we found that fibroblasts from patients with iPD or LRRK2-PD had a high amount of mitochondrial 7S DNA along with a low mtDNA replication rate that was associated with a reduction of cf-mtDNA release. Accumulation of 7S DNA in iPD and LRRK2-PD fibroblasts was related with an increase in H-strand mtDNA transcription. Interpretation: These results show that 7S DNA accumulation, low mtDNA replication, high H-strand transcription, and low mtDNA release compose a pattern of mtDNA dysfunction shared by both iPD and LRRK2-PD fibroblasts. Moreover, these results suggest that the deregulation of the genetic switch formed by 7SDNA that alternates between mtDNA replication and transcription is a fundamental pathophysiological mechanism in both idiopathic and monogenic Parkinson's disease. Keywords: mtDNA, Digital PCR, 7S DNA, Parkinson's disease, LRRK2, G2019S LRRK2 missense mutation