Search

Background: Switching between therapies is a recommended strategy for psoriatic arthritis (PsA) patients who experience treatment failure; however, studies including real-life data are scarce. Objectives: To assess the incidence rate (IR) of switching between biologics and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) due to inefficacy in PsA, and to compare the risk of switching due to inefficacy across different b/tsDMARDs groups. Design: A longitudinal retrospective study, spanning from 2007 to 2022, was conducted on patients with PsA treated with b/tsDMARDs at an outpatient rheumatology clinic. Methods: The primary outcome was switching between b/tsDMARDs due to inefficacy. The independent variable was the exposure to b/tsDMARDs during follow-up. As covariates, clinical, treatment-related, and sociodemographic variables were considered. Survival techniques were run to estimate the IR of switching due to inefficacy per 100 patients*year and confidence interval at 95% (95% CI). Cox multivariate regression analyses were run to assess the risk of b/tsDMARDs switching due to inefficacy, expressed as hazard ratio (HR) and 95% CI. Results: In all, 141 patients were included, with 893.09 patients*year follow-ups. 52.48% of them were females in their fifties. In total, 262 courses of treatment were recorded. During the study period, 56 patients presented 121 switches and 103 related to inefficacy (IR: 11.53 (9.51–13.98)). Tumor necrosis factor-alpha inhibitors (TNFi) showed the lowest IR. In the bivariate analysis, all b/tsDMARDs had more risk of switching compared to TNFi (HR: anti-lL-17 vs TNFi: 2.26 (1.17–4.36); others vs TNFi: 3.21 (1.59–6.45)); however, this statistical significance was no longer present in the multivariate analysis once adjustments were made for the covariates. Still, the final model achieved statistical significance in the following variables: gender, clinical symptoms, prescription year, therapy courses, glucocorticoids, and sulfasalazine. Conclusion: In this study, we did not find differences in the rate of switching due to inefficacy among different groups of b/tsDMARDs. Other concomitant treatments, sociodemographic, and clinical variables were identified as risk factors for switching due to inefficacy.

Abstract In real-world scenarios, Janus Kinase (JAK) inhibitors are often offered to "difficult-to-treat" rheumatoid arthritis patients, quite different from those included in randomized controlled trials. Our study aimed to evaluate the influence of patient-related factors on the effectiveness and safety of JAK inhibitors in real-world clinical practice. This observational retrospective study involved rheumatoid arthritis patients who received treatment with either tofacitinib, baricitinib, upadacitinib, or filgotinib. At 12 months of treatment, reasons for and rates of JAK inhibitor treatment discontinuation were examined. Treatment retentions were analyzed through Cox proportional hazard regression models and Kaplan–Meier estimates. Patient-related factors that could influence treatment retention were evaluated for the discontinuation reasons of lack of effectiveness and adverse events. At 12 months of treatment, discontinuation rates for 189 JAK inhibitor treatments were: lack of effectiveness (24.3%), adverse events (20.6%), and other reasons (3.7%). The remaining 51.4% represents the treatment continuation rate. No patient-related factors evaluated had an influence on treatment discontinuation due to lack of effectiveness. Ae significantly increased the risk of treatment discontinuation due to adverse events (p = 0.030). In terms of age, at 12 month of treatment, discontinuation rates due to adverse events were:

Abstract Background: Currently, there is no uniform and official terminology in Portuguese for reflectance confocal microscopy analysis, despite the increasing number of Brazilian dermatologists using this new tool. Objective: To present the terminology in Brazilian Portuguese for the description of reflectance confocal microscopy and establish the first Brazilian consensus on terms related to normal skin and cutaneous tumors. Methods: 10 Brazilian specialists from different institutions and states of Brazil were selected to evaluate the best corresponding terms in Portuguese for normal skin, melanocytic and non-melanocytic tumors. The terms used were translated from international consensuses in the English language. The modified Delphi method was used to create the consensus in 3 steps. Results: The terms considered the most appropriate in the Portuguese language to describe the findings of normal skin, melanocytic and non-melanocytic lesions in the reflectance confocal microscopy analysis were presented. Study limitations: The limitations of the present study include the number of participants and limited regional representation (only two of the five Brazilian regions were represented). Conclusion: This Brazilian consensus represents an opportunity for dermatologists and physicians specializing in cutaneous oncology to become familiar with reflectance confocal microscopy, propagating the technique in clinical and research environments to stimulate national and international publications on this subject.

In order to address current challenges on security certification of European ICT products, processes and services, the European Comission, through ENISA (European Union Agency for Cybersecurity), has developed the European Cybersecurity Certification Scheme for Cloud Services (EUCS). This paper presents the overview of the H2020 MEDINA project approach and tools to support the adoption of EUCS and offers a detailed description of one of the core components of the framework, the MEDINA Catalogue of Controls and Metrics. The main objective of the MEDINA Catalogue is to provide automated functionalities for CSPs’ compliance managers and auditors to ease the certification process towards EUCS, through the provision of all information and guidance related to the scheme, namely categories, controls, security requirements, assurance levels, etc. The tool has been enhanced with all the research and implementation works performed in MEDINA, such as definition of compliance metrics, suggestion of related implementation guidelines, alignment of similar controls in other schemes, and a set of self-assessment questionnaires, which are presented and discussed in this paper.

Abstract Objective: To test a culturally tailored obesity prevention intervention in low-income, minority preschool age children. Design: A three-group clustered randomised controlled trial. Setting: Twelve Head Start centres were randomly assigned to a centre-based intervention, a combined centre- and home-based intervention, or control using a 1:1:1 ratio. The centre-based intervention modified centre physical activity and nutrition policies, staff practices, and child behaviours, while the home-based intervention supported parents for obesity prevention at home. Study outcomes: The primary end point was change in children’s BMI (kg/m2) at post-test immediately following completion of the 8-month intervention. Secondary end points included standardised scores for BMI (BMIz) and body weight (WAZ), and BMI percentiles (BMI pctl). Participants: Three-year-old children enrolled in Head Start in San Antonio, Texas, with written parent consent (n 325), 87 % Latino, 57 % female with mean age (sd) of 3·58 years (0·29). Results: Change in BMI at post-test was 1·28 (0·97), 1·28 (0·87) and 1·41 (0·71) in the centre + home-based intervention, centre-based intervention and control, respectively. There was no significant difference in BMI change between centre + home-based intervention and control or centre-based intervention and control at post-test. BMIz (adjusted difference –0·12 (95 % CI, –0·24, 0·01), P = 0·06) and WAZ (adjusted difference, –0·09 (–0·17, –0·002), P = 0·04) were reduced for children in centre + home-based intervention compared with control group. Conclusions: There was no reduction in BMI at post-test in children who received the intervention. Findings shed light on methodological challenges in childhood obesity research and offer future directions to explore health equity-oriented obesity prevention.

Cyber–physical systems involve the creation, continuous updating, and monitoring of virtual replicas that closely mirror their physical counterparts. These virtual representations are fed by real-time data from sensors, Internet of Things (IoT) devices, and other sources, enabling a dynamic and accurate reflection of the state of the physical system. This emphasizes the importance of data synchronization, visualization, and interaction within virtual environments as a means to improve decision-making, training, maintenance, and overall operational efficiency. This paper presents a novel approach to a cyber–physical system that integrates virtual reality (VR)-based digital twins and 3D SCADA in the context of Industry 4.0 for the monitoring and optimization of an olive mill. The methodology leverages virtual reality to create a digital twin that enables immersive data-driven simulations for olive mill monitoring. The proposed CPS takes data from the physical environment through the existing sensors and measurement elements in the olive mill, concentrates them, and exposes them to the virtual environment through the Open Platform Communication United Architecture (OPC-UA) protocol, thus establishing bidirectional and real-time communication. Furthermore, in the proposed virtual environment, the digital twin is interfaced with the 3D SCADA system, allowing it to create virtual models of the process. This innovative approach has the potential to revolutionize the olive oil industry by improving operational efficiency, product quality, and sustainability while optimizing maintenance practices.

Background and Objectives: Recently, a randomized controlled trial suggested a potential benefit of baricitinib in patients with diabetes mellitus, preserving β-cell function. However, the clinical evidence currently available is limited. We aimed to assess the potential impact of tofacitinib and baricitinib on type 2 diabetes mellitus (T2DM) patients with rheumatoid arthritis. Materials and Methods: The candidates for this observational, retrospective, single-center study were selected from a cohort of 120 rheumatoid arthritis patients treated with tofacitinib or baricitinib between September 2017 and September 2023. The eligibility criteria included patients with T2DM who were receiving oral antidiabetic drugs (OADs). The primary outcome was the glycosylated hemoglobin (HbA1c) value after 6 months of a JAK inhibitor treatment. Secondary outcomes included body mass index (BMI) and rheumatoid arthritis disease activity. Differences were evaluated using Fisher’s exact test, as well as the Mann–Whitney test or the Wilcoxon test. Results: Thirteen patients were included; 46.2% (6/13) underwent treatment with tofacitinib, while 53.8% (7/13) were treated with baricitinib. At 6 months, baricitinib treatment resulted in a reduction in HbA1c (p = 0.035), with 57.1% (4/7) of patients achieving values p = 0.022) was observed at 6 months following baricitinib administration. All the patients treated with either tofacitinib or baricitinib achieved remission or low disease activity, without requiring statistically significant changes in concomitant rheumatoid arthritis treatment. Conclusions: In T2DM patients with rheumatoid arthritis, baricitinib can improve insulin sensitivity and glucose uptake, enabling the optimization of T2DM management.

Abstract Background Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www.clinicaltrials.gov (ID: NCT04180319)

Abstract Aims To describe the phenotype, genetics, and events associated with the development of hypertrophic cardiomyopathy (HCM) with reduced ventricular function (HCMr). Heart failure in HCM is usually associated with preserved ejection fraction, yet some HCM patients develop impaired systolic function that is associated with worse outcomes. Methods and results Our registry included 1328 HCM patients from two centres in Spain and Israel. Patients with normal baseline ventricular function were matched, and a competing‐risk analysis was performed to find factors associated with HCMr development. Patient records were reviewed to recognize clinically significant events that occurred closely before the development of HCMr. Genetic data were collected in patients with HCMr. A composite of all‐cause mortality or ventricular assist device (VAD)/heart transplantation was assessed according to ventricular function. Median age was 56, and 34% were female patients. HCMr at evaluation was seen in 37 (2.8%) patients, and 46 (3.5%) developed HCMr during median follow up of 9 years. HCMr was associated with younger age of diagnosis, poor functional class, and ventricular arrhythmia. Atrial fibrillation, pacemaker implantation, and baseline left ventricular ejection fraction (LVEF) of ≤55% were significant predictors of future HCMr development, while LV obstruction predicted a lower risk. Genetic testing performed in 53 HCMr patients, identifying one or more pathogenic variant in 38 (72%): most commonly in myosin binding protein C (n = 20). Six of these patients had an additional pathogenic variant in one of the sarcomere genes. Patients with baseline HCMr had a higher risk (hazard ratio 6.4, 4.1–10.1) for the composite outcome and for the individual components. Patients who developed HCMr in the course of the study had similar mortality but a higher rate of VAD/heart transplantation compared with HCM with normal LVEF. Conclusions Hypertrophic cardiomyopathy with reduced ejection fraction is associated with heart failure and poor outcome. Arrhythmia, cardiac surgery, and device implantation were commonly documented prior to HCMr development, suggesting they may be either a trigger or the result of adverse remodelling. Future studies should focus on prediction and prevention of HCMr.

IntroductionDevelopment of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public–private partnership (PPP) that aimed to provide annual, brand-specific estimates of influenza vaccine effectiveness (IVE) for regulatory and public health purposes. DRIVE was launched in 2017 under the umbrella of the Innovative Medicines Initiative (IMI) and conducted IVE studies from its pilot season in 2017–2018 to its final season in 2021–2022.MethodsIn 2021–2022, DRIVE conducted four primary care-based test-negative design (TND) studies (Austria, Italy, Iceland, and England; involving >1,000 general practitioners), nine hospital-based TND studies (France, Iceland, Italy, Romania, and Spain, for a total of 21 hospitals), and one population-based cohort study in Finland. In the TND studies, patients with influenza-like illness (primary care) or severe acute respiratory infection (hospital) were enrolled, and laboratory tested for influenza using RT-PCR. Study contributor-specific IVE was calculated using logistic regression, adjusting for age, sex, and calendar time, and pooled by meta-analysis.ResultsIn 2021–2022, pooled confounder-adjusted influenza vaccine effectiveness (IVE) estimates against laboratory-confirmed influenza (LCI) overall and per type and subtype/lineage was produced, albeit with wide confidence intervals (CI). The limited circulation of influenza in Europe did not allow the network to reach the optimal sample size to produce precise IVE estimates for all the brands included. The most significant IVE estimates were 76% (95% CI 23%−93%) for any vaccine and 81% (22%−95%) for Vaxigrip Tetra in adults ≥65 years old and 64% (25%−83%) for Fluenz Tetra in children (TND primary care setting), 85% (12%−97%) for any vaccine in adults 18–64 years (TND hospital setting), and 38% (1%−62%) in children 6 months−6 years (population-based cohort, mixed setting).DiscussionOver five seasons, DRIVE collected data on >35,000 patients, more than 60 variables, and 13 influenza vaccines. DRIVE demonstrated that estimating brand-specific IVE across Europe is possible, but achieving sufficient sample size to obtain precise estimates for all relevant stratifications remains a challenge. Finally, DRIVE's network of study contributors and lessons learned have greatly contributed to the development of the COVID-19 vaccine effectiveness platform COVIDRIVE.

Our study evaluated the morphological and functional outcomes, and the side effects, of voretigene neparvovec (VN) gene therapy for RPE65-mediated inherited retinal dystrophies (IRDs) in 12 eyes (six patients) at the Oxford Eye Hospital with a mean follow-up duration of 8.2 (range 1–12) months. All patients reported a subjective vision improvement 1 month after gene therapy. Best-corrected visual acuity (BCVA) remained stable (baseline: 1.28 (±0.71) vs. last follow-up: 1.46 (±0.60); p = 0.25). Average white Full-Field Stimulus Testing (FST) showed a trend towards improvement (baseline: −4.41 (±10.62) dB vs. last follow-up: −11.98 (±13.83) dB; p = 0.18). No changes in central retinal thickness or macular volume were observed. The side effects included mild intraocular inflammation (two eyes) and cataracts (four eyes). Retinal atrophy occurred in 10 eyes (eight mild, two severe) but did not impact FST measurements during the follow-up period. Increased intraocular pressure (IOP) was noted in three patients (six eyes); four eyes (two patients) required glaucoma surgery. The overall safety and effectiveness of VN treatment in our cohort align with previous VN clinical trials, except for the higher occurrence of retinal atrophy and increased IOP in our cohort. This suggests that raised IOP and retinal atrophy may be more common than previously reported.

Background: Early melanoma detection allows for timely intervention and treatment, significantly improving the chances of favorable outcomes for patients. Small-diameter melanoma (SDM) typically represents an initial growth phase of cutaneous melanoma. One of the challenges in detecting melanoma in their early stage lies in the fact that dermoscopy criteria have been primarily designed for fully developed lesions. Early-stage melanomas may be difficult to detect and possibly even be overlooked or misinterpreted during examinations. Methods: The primary aim of this study was to identify valuable clinical and dermoscopic clues to enhance the detection of SDMs. To achieve this objective, we conducted a comprehensive retrospective analysis, including forty SDMs with a diameter of 5 mm or less. These cases were diagnosed over an 8-year period and were collected from five referral centers across Brazil. Seven experienced dermatologists independently assessed the dermoscopic features of each lesion. Additionally, this study includes demographic and histological information. Results: The study encompassed a total of 28 patients, of which 16 were females, accounting for 58% of the participants, with an average age of 43.6 years. Among the small-diameter melanomas (SDMs) under investigation, the majority, constituting 27 cases (69.2%), were identified as “de novo” lesions, i.e., not associated with a nevus. Additionally, eight SDMs (20%) exhibited invasive characteristics, with Breslow index measurements ranging between 0.2 to 0.4 mm, suggesting an early stage of malignancy. During dermoscopic examinations, the most prevalent features observed were irregular dots and globules, present in 95% and 87.5% of cases, respectively. Moreover, brown structureless areas were identified in 70% of lesions, followed by atypical network (67.5%), pseudopods (55%), dotted vessels (47.5%), flat structureless blue-gray areas (42.5%), and irregular blotches (40%). Notably, all SDM were diagnosed in patients under surveillance through total body skin photography (TBSP) and Digital Dermoscopy (DD). Conclusions: Dermoscopy significantly enhances the diagnostic accuracy of melanoma, even in its early stages. Particularly for high-risk patients with numerous nevi, the identification of a new lesion or subtle changes on dermoscopy during follow-up may serve as the sole clue for an early diagnosis. This emphasizes the critical role of dermoscopy in SDM detection and reinforces the importance of surveillance in high-risk patients for timely and effective management.

Although adeno-associated viral (AAV) vector-mediated retinal gene therapies have demonstrated efficacy, the mechanisms underlying dose-dependent retinal inflammation remain poorly understood. Here, we present a quantitative analysis of cellular immune response to subretinal AAV gene therapy in mice using multicolor flow cytometry with a panel of key immune cell markers. A significant increase in CD45+ retinal leukocytes was detected from day 14 post-subretinal injection of an AAV8 vector (1 × 109 genome copies) encoding green fluorescent protein (GFP) driven by a ubiquitous promoter. These predominantly consisted of infiltrating peripheral leukocytes including macrophages, natural killer cells, CD4 and CD8 T cells, and natural killer T cells; no significant change in resident microglia population was detected. This cellular response was persistent at 28 days and suggestive of type 1 cell-mediated effector immunity. High levels (80%) of GFP fluorescence were found in the microglia, implicating their role in viral antigen presentation and peripheral leukocyte recruitment. When compared against AAV.GFP in paired eyes, an equivalent dose of an otherwise identical vector encoding the human therapeutic transgene Rab-escort protein 1 (REP1) elicited a significantly diminished cellular immune response (4.2-fold; p = 0.0221). However, the distribution of immune cell populations remained similar, indicating a common mechanism of AAV-induced immune activation.

Rhodopsin-related dominant retinitis pigmentosa is a degenerative disease of the retina of the eye for which there is no current treatment. In this study, the authors use a novel form of RNA-interference- artificial mirtrons- to slow retinal degeneration in a mouse model of the disease.

Background Neoadjuvant chemoimmunotherapy for non-small cell lung cancer (NSCLC) has improved pathological responses and survival rates compared with chemotherapy alone, leading to Food and Drug Administration (FDA) approval of nivolumab plus chemotherapy for resectable stage IB-IIIA NSCLC (AJCC 7th edition) without ALK or EGFR alterations. Unfortunately, a considerable percentage of tumors do not completely respond to therapy, which has been associated with early disease progression. So far, it is impossible to predict these events due to lack of knowledge. In this study, we characterized the gene expression profile of tumor samples to identify new biomarkers and mechanisms behind tumor responses to neoadjuvant chemoimmunotherapy and disease recurrence after surgery.Methods Tumor bulk RNA sequencing was performed in 16 pretreatment and 36 post-treatment tissue samples from 41 patients with resectable stage IIIA NSCLC treated with neoadjuvant chemoimmunotherapy from NADIM trial. A panel targeting 395 genes related to immunological processes was used. Tumors were classified as complete pathological response (CPR) and non-CPR, based on the total absence of viable tumor cells in tumor bed and lymph nodes tested at surgery. Differential-expressed genes between groups and pathway enrichment analysis were assessed using DESeq2 and gene set enrichment analysis. CIBERSORTx was used to estimate the proportions of immune cell subtypes.Results CPR tumors had a stronger pre-established immune infiltrate at baseline than non-CPR, characterized by higher levels of IFNG, GZMB, NKG7, and M1 macrophages, all with a significant area under the receiver operating characteristic curve (ROC) >0.9 for CPR prediction. A greater effect of neoadjuvant therapy was also seen in CPR tumors with a reduction of tumor markers and IFNγ signaling after treatment. Additionally, the higher expression of several genes, including AKT1, BST2, OAS3, or CD8B; or higher dendritic cells and neutrophils proportions in post-treatment non-CPR samples, were associated with relapse after surgery. Also, high pretreatment PD-L1 and tumor mutational burden levels influenced the post-treatment immune landscape with the downregulation of proliferation markers and type I interferon signaling molecules in surgery samples.Conclusions Our results reinforce the differences between CPR and non-CPR responses, describing possible response and relapse immune mechanisms, opening the possibility of therapy personalization of immunotherapy-based regimens in the neoadjuvant setting of NSCLC.

Abstract Background Calcium (Ca) is a well-known element in bone metabolism and blood coagulation. Here, we investigate the link between the protein adsorption pattern and the in vivo responses of surfaces modified with calcium ions (Ca-ion) as compared to standard titanium implant surfaces (control). We used LC–MS/MS to identify the proteins adhered to the surfaces after incubation with human serum and performed bilateral surgeries in the medial section of the femoral condyles of 18 New Zealand white rabbits to test osseointegration at 2 and 8 weeks post-implantation (n=9). Results Ca-ion surfaces adsorbed 181.42 times more FA10 and 3.85 times less FA12 (p

Noncommunicable diseases (NCDs), including cancer, are responsible for almost 70% of all deaths worldwide. Tobacco use is a risk factor common to most NCDs. This article discusses tobacco control policies and highlights major achievements and open challenges to reduce smoking prevalence and attributable morbidity and mortality in the 21st century. The introduction of the WHO Framework Convention on Tobacco Control in 2005 has been a key achievement in the field and has already facilitated a drop in both smoking prevalence and exposure to secondhand smoke. Indicatively, the size of the worldwide population benefiting from at least one cost‐effective tobacco control policy has quadrupled since 2007. In addition, plain cigarette packaging has been successfully introduced as a tobacco control policy, surmounting efforts of the tobacco industry to challenge this based on trade and investment law. Nevertheless, tobacco control still faces major challenges. Smoking prevalence needs to be further reduced in a rather expedited manner. Smoke‐free environments should be extended, and the use of plain tobacco packaging with large pictorial health warnings for all tobacco products should be further promoted in some parts of the world. Some of these measures will require prompt determination and diligence. For example, bold political decisions are needed to significantly increase real prices of tobacco products through excise taxes, ban added ingredients that are currently used to increase the attractiveness of tobacco products and ban the tobacco industry's corporate social responsibility initiatives. Finally, the debate on harm reduction strategies for tobacco control still needs to be resolved.

Deep brain stimulation and epidural electrical stimulation of the spinal cord enable locomotion in humans with spinal cord injury (SCI) but the potential synergy between both approaches is unclear. The authors show that a complex technological approach is required to enable volitional walking in rats with SCI.

El conocimiento del Modelo Hidrogeológico Conceptual permite adoptar y adaptar un procedimiento adecuado para cada caso de estudio, considerando acuíferos libres y acuíferos confinados, teniendo en cuenta las diferencias estructurales entre rocas duras, rocas blandas y depósitos no consolidados; y evaluando el rol de la textura y la capacidad de infiltración del suelo, en la dimensión de la función de la recarga directa. Para el sistema hidrogeológico del Eje Bananero del Urabá Antioqueño- Colombia la tarea de entender la recarga puso de manifiesto la necesidad de establecer una escala de calificación para evaluar el factor estructural en rocas blandas y depósitos no consolidados y definir categorías de importancia, basados en propiedades texturales y tasas de infiltración para las zonas de recarga directa difusa en acuíferos libres; también se determinó un procedimiento para delimitar zonas asociadas a las unidades hidrogeológicas que subrayasen a los acuíferos confinados.

Objectives: The aim of this study was to assess the cause-specific mortality rate related to COVID-19 (CMR) in patients with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 and to analyze the role of the different RMDs in their mortality risk. Methods: An observational longitudinal study was conducted during the first pandemic wave in our center. Patients with the diagnosis of RMDs and COVID-19 were included. Main outcome is the death related to COVID-19. Independent variable – type of RMDs: autoimmune rheumatic diseases (ARD), such as chronic inflammatory arthritis (CIA) and connective tissue diseases (CTD) and non-autoimmune Rheumatic Diseases (non-ARD). Survival techniques were used to estimate the CMR per 1000 patients-month with a 95% confidence interval (CI), and Cox multivariate regression analysis was run to examine the effect of ARD compared to non-ARD on mortality risk adjusted by confounders. Results were expressed by Hazard Ratio (HR) and CI. Results: Overall, 405 patients were included (642.5 patients-month). During the study period, 44 (10.86%) deaths were recorded. CMR was 68.48 (50.96–92.01). After adjusting for confounders, HR of mortality in ARD compared to non-ARD did not achieve statistical significance [HR: 1.15 (0.64–2.07)], neither CTD versus CIA nor CTD versus non-ARD. Age and certain comorbidities which are being diagnosed in March compared to April or May [HR: 2.43 (1.1–5.55)] increased the mortality risk. Glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) dropped from the final model. Conclusion: In patients with RMDs and COVID-19, CMR was 6.8% patients-month. This study shows that mortality risk is higher in males, older patients, and similar between CTD, CIA, and non-ARD. COVID-19 management improved after the first month of pandemic. Plain Language Summaries Mortality related to the outbreak of COVID-19 in patients with rheumatic and musculoskeletal diseases Why was this study done? - To report the COVID-19-specific mortality rate in patients with a variety of RMDs during the first pandemic peak in a tertiary hospital in Madrid and to analyze the role of specific types of ARD and other possible factors in the risk of death related to COVID-19. What did the researchers do? - We performed a retrospective observational study during the first wave of the COVID-19 pandemic in Madrid, Spain. What did the researchers find? - In this study, neither the different diagnoses of RMDs, including CIA, CTD, or non-ARD disease or its treatment were not implicated as a potential risk of death related to COVID-19 - In consonance with other studies, RMDs patients and COVID-19, older age, male sex, and certain comorbidities implied more mortality risk - Our data reflect COVID-19 severity in a particular context, time, and population. In times of the absence of COVID-19 vaccine, healthcare, social, and political measures taken to contain the coronavirus outbreak have worked properly. What do the findings mean? - The presence of comorbidities in RMDs patients represents a greater risk than the different types of RMDs themselves, in the development of COVID-19 fatal outcome. It is important to integrate the control of comorbidities in the daily management.

El análisis que se ofrece a continuación, intenta situar conceptos, ideas y referencias de una propuesta teórica del aprendizaje con uso de nuevas tecnologías (NT), en la observación de una instancia de aprendizaje no formal mediada por videojuegos, con el objetivo de indagar en sus implicancias cognitivas. La situación que se expone en este relato, describe un momento de vinculación entre Valentina, una niña chilena de 6 años, y un videojuego que lleva por nombre Sound Shapes, disponible en la plataforma PlayStation 3. El diseño de investigación es de carácter cualitativo, coherente con el objetivo de describir y analizar una situación de aprendizaje en contexto, recuperando sus especificidades como insumo para interpretar la relación entre el sujeto y su entorno. Se busca interpretar la realidad del sujeto en cuestión, desde los marcos teóricos de James Paul Gee, que han sido seleccionados para esta investigación

Abstract Background The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. Methods BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. Results The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. Conclusions Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening.

Abstract With the development of new cancer therapies, systemic toxicity profile and effects on survival achieved an important improvement. However, a constellation of toxicities has emerged, even more remarkably, cutaneous adverse events. This report, developed by a board of Brazilian experts in oncodermatology, aims to establish a guideline for the dermatological care of oncologic patients. When possible, evidence-based recommendations were made, but in many cases, when strong evidence was not available, a consensus was reached, based on some data supporting therapies combined with personal experiences.

Recent advances in recombinant adeno-associated virus (rAAV) gene therapy for choroideremia show gene replacement to be a promising approach. It is, however, well known that contact of vector solution with plastic materials in the surgical device may result in non-specific adsorption with resulting loss of physical titer and/or level of protein expression and activity. Here we assessed the biocompatibility and stability of rAAV2-REP1 (Rab Escort Protein-1) before and following passage through the injection device over a period of time to mimic the clinical scenario. Three identical devices were screened using two concentrations of vector: high (1E+12 DNase-resistant particles [DRP]/mL) and low (1E+11 DRP/mL), to mimic high- and low-dose administrations of vector product. The low dose was prepared using either formulation buffer that contained 0.001% of a non-ionic surfactant (PF68) or balanced salt solution (BSS). We observed significant losses in the genomic titer of samples diluted with BSS for all time points. The addition of 0.001% PF68 did not, however, affect rAAV physical titer, or REP1 protein expression and biological activity. Hence we observed that neither the genomic titer nor the biological activity of a rAAV2-REP1-containing solution was affected following passage through the surgical device when PF68 was present as a surfactant and this was maintained over a period up to 10 h.

Oat consumption has increased during the last decade because of the health benefits associated with its soluble dietary fiber (β-glucan), functional proteins, lipids, and the presence of specific phytochemicals, such as avenanthramides. Oat is consumed mainly as whole grain, and the hull (seed coat), comprising 25–35% of the entire grain, is removed, generating a large amount of waste/by-product from the milling industry. The objective of this study was to evaluate the use of biotechnological strategies, such as sprouting for oat grain (OG) and hydrolysis for oat hull (OH), to enhance antioxidant and anti-inflammatory properties and lower the glycemic index (GI). Sprouting produced significant (p ≤ 0.05) increases in free (32.10 to 76.62 mg GAE (100 g)−1) and bound phenols (60.45 to 124.36 mg GAE (100 g)−1), increasing significantly (p ≤ 0.05) the avenanthramide (2c, 2p and 2f) soluble phenolic alkaloid content and anti-inflammatory properties of OG. On the other hand, the hydrolysis of OH using Viscoferm (EH2-OH) and Ultraflo XL (EH21-OH) increased by 4.5 and 5-fold the release of bound phenols, respectively; meanwhile, the use of Viscoferm increased the 4.55-fold soluble β-glucan content in OH, reaching values close to those of OG (4.04 vs. 4.46 g (100 g)−1). The study shows the potential of both strategies to enhance the nutritional and bioactive properties of OG and OH and describes these processes as feasible for the industry to obtain an ingredient with high antioxidant and anti-inflammatory activities. Single or combined biotechnological tools can be used on oat grains and hulls to provide nutraceutical ingredients.

The aim of this study was to determine the impact of three different technological processes and in vitro digestion on the profile and content of betalains and inhibition of angiotensin I converting enzyme (ACE) in red beet. Betalains were analysed by the micro-HPLC-TOF-MS/MS method, while ACE inhibition was determined by an in vitro assay. In the tested samples, thirteen betalains were identified, constituting nine betacyanins, two betaxanthins and two betalain precursors. The applied technological processes (boiling, fermentation and microwave-vacuuming treatment) reduced the content of betalain by 42–70% in the obtained products. The contribution of betalains released from red beet products after in vitro digestion was detected within the range of 0.001–0.10%. The applied treatments reduced the inhibition of ACE by the non-digested red beet products, while in vitro digestion caused an increase in ACE inhibition in the case of the digested solid red beet products.

Introduction: Acute aortic dissection after endovascular repair of an aortic aneurysm is a rare but serious condition, with potential complications that can result in the death of the patient. Report: This is the case of a patient diagnosed with a type IV thoraco-abdominal aneurysm with involvement of both iliac arteries who underwent endovascular repair with a four fenestration device and a left iliac branch. One month after the procedure, the patient presented with a type B acute aortic dissection that extended from the left subclavian artery to the proximal stent of the fenestrated graft. This dissection was treated by thoracic endovascular aortic repair, and after a problematic post-operative period, the patient was discharged after 30 days. Discussion: Occurrence of an acute aortic dissection after endovascular repair of an aortic aneurysm has rarely been reported in the literature. Development of these dissections has been related to factors such as excessive oversizing, use of devices with active fixation systems, or injuries during the procedure, although it is believed that the late onset would indicate that it was a de novo dissection. The presence of an aortic dissection can lead to the collapse and occlusion of the previous endograft and even to aortic rupture, and mortality in reported cases reaches 30%. The authors suggest that endovascular treatment should be considered in these patients. Keywords: Aortic aneurysm, Fenestrated endovascular aneurysm repair, Thoracic endovascular aortic repair, Type B aortic dissection

Eosinophils are innate immune granulocytes actively involved in defensive responses and in local and systemic inflammatory processes. Beyond these effector roles, eosinophils are fundamental to maintaining homeostasis in the tissues they reside. Gastrointestinal eosinophils modulate barrier function and mucosal immunity and promote tissue development through their direct communication with almost every cellular component. This is possible thanks to the variety of receptors they express and the bioactive molecules they store and release, including cytotoxic proteins, cytokines, growth factors, and neuropeptides and neurotrophines. A growing body of evidence points to the eosinophil as a key neuro-immune player in the regulation of gastrointestinal function, with potential implications in pathophysiological processes. Eosinophil–neuron interactions are facilitated by chemotaxis and adhesion molecules, and the mediators released may have excitatory or inhibitory effects on each cell type, with physiological consequences dependent on the type of innervation involved. Of special interest are the disorders of the brain–gut interaction (DBGIs), mainly functional dyspepsia (FD) and irritable bowel syndrome (IBS), in which mucosal eosinophilia and eosinophil activation have been identified. In this review, we summarize the main roles of gastrointestinal eosinophils in supporting gut homeostasis and the evidence available on eosinophil–neuron interactions to bring new insights that support the fundamental role of this neuro-immune crosstalk in maintaining gut health and contributing to the pathophysiology of DBGIs.

Emotional dysregulation, age, gender, and obesity are transdiagnostic risk factors for the development and maintenance of eating disorders (EDs). Previous studies found that patients with ED had less meaning in life than the non-clinical population, and that meaning in life acted as a buffer in the course of ED; however, to the data, there are no studies about the mediator role of meaning in life in association between the emotional dysregulation and the ED psychopathology.Objective: To analyze the mediating role of meaning in life in the relationship between emotional dysregulation and the ED psychopathology in three samples with diverse risk factors for ED.Method: Sample 1, n = 153 undergraduate young women; sample 2, n = 122 participants with obesity; and sample 3, n = 292 participants with ED. Multiple mediation analysis was performed.Results: Sample 1: meaning in life showed a mediation effect between emotional dysregulation and the ED psychopathology (direct effect β = 0.390, p < 0.05) (indirect effect β = 0.227, p < 0.05), body satisfaction (direct effect β = −0.017, p < 0.05) (indirect effect β = −0.013, p < 0.01), and depression symptoms (direct effect β = 1.112, p < 0.001) (indirect effect β = 0.414, p < 0.001); sample 2: meaning in life showed a mediation effect between emotional dysregulation and binge eating and purging behaviors (direct effect β = 0.194, p < 0.01) (indirect effect β = 0.054, p < 0.05) and depression symptoms (direct effect β = 0.357, p < 0.001) (indirect effect β = 0.063, p < 0.05); sample 3: meaning in life showed a mediation effect between emotional dysregulation and the ED psychopathology (direct effect β = 0.884, p < 0.001) (indirect effect β = 0.252, p < 0.007), body satisfaction (direct effect β = −0.033, p < 0.05) (indirect effect β = −0.021, p < 0.001), borderline symptoms (direct effect β = 0.040, p < 0.001) (indirect effect β = 0.025, p < 0.001), and hopelessness (direct effect β = 0.211, p < 0.001) (indirect effect β = 0.087, p < 0.001).Conclusions: These studies suggest the importance of considering meaning in life as a variable in the onset and maintenance of ED.

Several studies have implied a role of brain-derived neurotrophic factor (BDNF) in abdominal pain modulation in irritable bowel syndrome (IBS). The aim of this study was to establish BDNF protein expression in human colonic biopsies and to show variation in IBS compared to controls. BDNF protein and mRNA levels were correlated with IBS symptom severity based on the IBS-symptom severity score (IBS-SSS). Biopsies from the descending colon and IBS-SSS were obtained from 10 controls and 20 IBS patients. Total protein of biopsies was extracted and assessed by ELISA and Western Blot. Total mRNA was extracted and gene expression measured by nCounter analysis. In IBS patients, symptom severity scores ranged from 124 to 486 (mean ± sem: 314.2 ± 21.2, >300 represents severe IBS) while controls ranged from 0 to 72 (mean ± sem: 27.7 ± 9.0,

There is debate over the functional basis of student evaluations of academics, and fresh potential for looking at the data in new ways. Student evaluation data was collated over a three year period (Semester 2 2015 to Semester 1 2018). We used a General Linear Model to estimate the variation in course scores explained by a number of coordinator and course attributes. Three significant factors collectively explain 49% of the School’s variation in course scores—individual coordinator, student evaluation response rate, and mode of delivery. Next, we used hierarchical clustering to explore the inter-relationships among the eight course and teaching evaluation questions. Learning appears to be related to stimulation, whereas overall satisfaction appears to be related to quality of learning materials and course structure (i.e. aspects of course organisation). Student evaluation response rate is positively correlated to all eight course questions, but most positively to a question relating to receiving adequate feedback. This perhaps implies some reciprocity in the flow of information between student and coordinator. The overall teaching rating awarded to academics clusters most with approachability and encouragement of student input—aspects of temperament and style—and not with explanatory skill or organisational ability.

Summary: Spatial learning requires estimates of location that may be obtained by path integration or from positional cues. Grid and other spatial firing patterns of neurons in the superficial medial entorhinal cortex (MEC) suggest roles in behavioral estimation of location. However, distinguishing the contributions of path integration and cue-based signals to spatial behaviors is challenging, and the roles of identified MEC neurons are unclear. We use virtual reality to dissociate linear path integration from other strategies for behavioral estimation of location. We find that mice learn to path integrate using motor-related self-motion signals, with accuracy that decreases steeply as a function of distance. We show that inactivation of stellate cells in superficial MEC impairs spatial learning in virtual reality and in a real world object location recognition task. Our results quantify contributions of path integration to behavior and corroborate key predictions of models in which stellate cells contribute to location estimation. : Tennant et al. develop virtual reality tasks that dissociate beaconing and path integration strategies for location estimation. In combination with genetically targeted inactivation of synaptic output, the authors provide evidence for a critical role for entorhinal stellate cells in spatial learning. Keywords: spatial cognition, learning, memory, neural computation, location estimation, cue-based navigation, path integration, entorhinal cortex, virtual reality, behavior

The current work aimed to investigate the effect of seed priming with different agents (CaCl2, KCl, and KNO3) on germination and seedling establishment in seeds of the barley species of both Hordeum vulgare (L. Manel) and Hordeum maritimum germinated with three salt concentrations (0, 100, and 200 mM NaCl). The results showed that under unprimed conditions, salt stress significantly reduced the final germination rate, the mean daily germination, and the seedling length and dry weight. It led to a decrease in the essential nutrient content (iron, calcium, magnesium, and potassium) against an increase in sodium level in both of the barley species. Moreover, this environmental constraint provoked a membrane injury caused by a considerable increase in electrolyte leakage and the malondialdehyde content (MDA). Data analysis proved that seed priming with CaCl2, KCl, and KNO3 was an effective method for alleviating barley seed germination caused by salt stress to varying degrees. Different priming treatments clearly stimulated germination parameters and the essential nutrient concentration, in addition to increasing the seedling growth rate. The application of seed priming reduced the accumulation of sodium ions and mitigated the oxidative stress of seeds caused by salt. This mitigation was traduced by the maintenance of low levels of MDA and electrolyte leakage. We conclude that the priming agents can be classed into three ranges based on their efficacy on the different parameters analyzed; CaCl2 was placed in the first range, followed closely by KNO3, while the least effective was KCl, which placed in the third range.

Methane, the main component of natural gas, is an interesting source of chemicals and clean liquid fuels, and a promising alternative raw material to oil. Among the possible direct routes for methane conversion, its aromatization under non-oxidative conditions has received increasing attention, despite the low conversions obtained due to thermodynamic limitations, because of its high selectivity to benzene. Mo/H-ZSM-5, the first bifunctional zeolite-catalyst proposed for this reaction, is still considered as one of the most adequate and has been widely studied. Although the mono- or bifunctional nature of the MDA mechanism is still under debate, it is generally accepted that the Mo species activate the C-H bond in methane, producing the intermediates. These will aromatize on the Brønsted acid sites of the zeolite, whose pore dimensions will provide the shape selectivity needed for converting methane into benzene. An additional role of the zeolite’s Brønsted acid sites is to promote the dispersion of the Mo oxide precursor. Here, we show the influence of the different preparation steps—metal incorporation, calcination and activation of the Mo/ZSM-5- on the metal dispersion and, therefore, on the activity and selectivity of the final catalyst. Metal dispersion is enhanced when the samples are calcined under dynamic conditions (DC) and activated in N2, and the benefits are larger when the metal has been incorporated by solid state reaction (SSR), as observed by FESEM-BSE and H2-TPR. This leads to catalysts with higher activity, increased aromatic selectivity and improved stability towards deactivation.

Objective: Persistent right umbilical vein (PRUV) is a vascular anomaly where the right umbilical vein remains as the only conduit that returns oxygenated blood to the fetus. It has classically been described as associated with numerous defects. We distinguish the intrahepatic variant (better prognosis) and the extrahepatic variant (associated with worse prognosis). The objective of this study was to compare rates of congenital malformations in fetuses with intrahepatic PRUV (I-PRUV) versus singleton pregnancies without risk factors. Materials and Methods: A multicenter, crossover design, comparative study was performed between 2003 and 2013 on fetuses diagnosed with I-PRUV (n=56), and singleton pregnancies without congenital malformation risk factors (n=4050). Results: Fifty-six cases of I-PRUV were diagnosed (incidence 1:770). A statistically significant association between I-PRUV and the presence of congenital malformations (odds ratio 4.321; 95% confidence interval 2.15–8.69) was found. This positive association was only observed with genitourinary malformations (odds ratio 3.038; 95% confidence interval 1.08–8.56). Conclusion: Our rate of malformations associated with I-PRUV (17.9%) is similar to previously published rates. I-PRUV has shown a significant increase in the rate of associated malformations, although this association has only been found to be statistically significant in the genitourinary system. Noteworthy is the fact that this comparative study has not pointed to a significant increase in the congenital heart malformation rate. Diagnosis of isolated I-PRUV does not carry a worse prognosis.

Filamentous proteins are responsible for the superior mechanical strength of our cells and tissues. The remarkable mechanical properties of protein filaments are tied to their complex molecular packing structure. However, since these filaments have widths of several to tens of nanometers, it has remained challenging to quantitatively probe their molecular mass density and three-dimensional packing order. Scanning transmission electron microscopy (STEM) is a powerful tool to perform simultaneous mass and morphology measurements on filamentous proteins at high resolution, but its applicability has been greatly limited by the lack of automated image processing methods. Here, we demonstrate a semi-automated tracking algorithm that is capable of analyzing the molecular packing density of intra- and extracellular protein filaments over a broad mass range from STEM images. We prove the wide applicability of the technique by analyzing the mass densities of two cytoskeletal proteins (actin and microtubules) and of the main protein in the extracellular matrix, collagen. The high-throughput and spatial resolution of our approach allow us to quantify the internal packing of these filaments and their polymorphism by correlating mass and morphology information. Moreover, we are able to identify periodic mass variations in collagen fibrils that reveal details of their axially ordered longitudinal self-assembly. STEM-based mass mapping coupled with our tracking algorithm is therefore a powerful technique in the characterization of a wide range of biological and synthetic filaments.

Cernunnos/XLF deficiency is a rare primary immunodeficiency classified within the DNA repair defects. Patients present with severe growth retardation, microcephaly, lymphopenia and increased cellular sensitivity to ionizing radiation. Here, we describe two unrelated cases with the same non-sense mutation in the NHEJ1 gene showing significant differences in clinical presentation and immunological profile but a similar DNA repair defect.

Subjects with diabetes mellitus (DM) have an increased risk of arterial thrombosis, to which changes in clot structure and mechanics may contribute. Another contributing factor might be an increased formation of neutrophil extracellular traps (NETs) in DM. NETs are mainly formed during the acute phase of disease and form a network within the fibrin matrix, thereby influencing clot properties. Previous research has shown separate effects of NETs and DM on clot properties, therefore our aim was to study how DM affects clot properties in a model resembling an acute phase of disease with NETs formation. Clots were prepared from citrated plasma from subjects with and without DM with the addition of NETs, induced in neutrophils by S. aureus bacteria or phorbol myristate acetate (PMA). Structural parameters were measured using scanning electron microscopy, mechanical properties using rheology, and sensitivity to lysis using a fluorescence-based fibrinolysis assay. Plasma clots from subjects with DM had significantly thicker fibers and fewer pores and branch points than clots from subjects without DM. In addition, fibrinolysis was significantly slower, while mechanical properties were similar between both groups. In conclusion, in a model of acute NETs formation, DM plasma shows prothrombotic effects on fibrin clots.

The study evaluated the effect of autoclaving as a hydrothermal treatment on the quality and bioactivity of wheat bran (WB) with the objective of producing a natural ingredient with enhanced healthy properties. Nutritional, antioxidant, techno-functional and sensorial parameters were studied, and temperatures of 100, 115 and 130 °C were explored. Of these, 130 °C was found to be the best treatment, resulting in an ingredient with high storage stability, antioxidant properties, a four-fold increase in the concentration of free ferulic acid (compared with non-treated WB), and increased content of apigenin-6-C-arabinoside-8-C-hexoside, a flavonoid with reported antioxidant and antifungal properties. On the other hand, the autoclave treatment enhanced water absorption capacity and reduced WB pasting viscosity, mainly at higher temperature (130 °C), which would allow incorporation of the treated WB in liquid matrices such as juices, soups or milkshakes, among others. Although the glycemic index (GI) of the autoclaved samples increased, the use of intermediate particle size of 106 to 300 µm could contribute to the reduction of the glycemic load.

Knowledge on the specific variation in the phenolic composition of wheat defined by germination conditions and its relationship with antioxidant and anti-inflammatory properties of sprouts would be useful to improve the functional value of wheat-derived products. Variation in soluble phenolic composition, antioxidant and anti-inflammatory potential of wheat was examined in a range of germination temperature (12–21 °C) and time (1–7 d). Response surface methodology was applied for building lineal and quadratic models to find optimal germination conditions to improve nutraceutical value of wheat sprouts using the desirability (D) function. Phenolics were determined by HPLC-DAD-ESI-MS. In vitro biochemical methods and lipopolysaccharide stimulated RAW264.7 macrophages were used to determine antiradical and anti-inflammatory activities of wheat sprouts. Accumulation of soluble phenolic acids, flavone C-glycosides and lignans in sprouts was positively influenced by germination temperature and time. Increased concentration of individual polyphenols was directly associated with improved ability of sprouts for radical scavenging and reduction of tumor necrosis factor α and interleukin 6 in macrophages. Optimal desirability (D = 0.89) for improved nutraceutical value of wheat sprouts was achieved at 21 °C for 7 d. This information would be useful for food industry aiming at producing wheat-based products with better nutritional and healthy properties.

In the study presented here we identified transcriptomic markers for fertility in the cargo of pig ejaculated spermatozoa using porcine-specific micro-arrays (GeneChip® miRNA 4.0 and GeneChip® Porcine Gene 1.0 ST). We report (i) the relative abundance of the ssc-miR-1285, miR-16, miR-4332, miR-92a, miR-671-5p, miR-4334-5p, miR-425-5p, miR-191, miR-92b-5p and miR-15b miRNAs, and (ii) the presence of 347 up-regulated and 174 down-regulated RNA transcripts in high-fertility breeding boars, based on differences of farrowing rate (FS) and litter size (LS), relative to low-fertility boars in the (Artificial Insemination) AI program. An overrepresentation analysis of the protein class (PANTHER) identified significant fold-increases for C-C chemokine binding (GO:0019957): CCR7, which activates B- and T-lymphocytes, 8-fold increase), XCR1 and CXCR4 (with ubiquitin as a natural ligand, 1.24-fold increase), cytokine receptor activity (GO:0005126): IL23R receptor of the IL23 protein, associated to JAK2 and STAT3, 3.4-fold increase), the TGF-receptor (PC00035) genes ACVR1C and ACVR2B (12-fold increase). Moreover, two micro-RNAs (miR-221 and mir-621) were down- and up-regulated, respectively, in high-fertility males. In conclusion, boars with different fertility performance possess a wide variety of differentially expressed RNA present in spermatozoa that would be attractive targets as non-invasive molecular markers for predicting fertility.

Background Tobacco cessation training programs are scarce in Spanish speaking low-income countries. Based on a previous program developed in Spain, the Fruitful Study adapted, implemented and evaluated the effectiveness of an online brief intervention smoking cessation training program addressed to hospital workers from Bolivia, Guatemala and Paraguay. The aim of this study is to examine the degree of implementation of the 5A brief intervention model before and after the training and identify changes in cognitive, behavioral factors and in the perception of organizational support. Methods Pre-post evaluation through a questionnaire that evaluated 43 items previously identified in the literature. The questionnaires were completed immediately before and six months after the course. To examine pre-post changes in scores, the non-parametric test for paired data (Wilcoxon) was used. Results 202 professionals completed the questionnaires before and after the course. For this analysis, only those with clinical tasks (n = 154) were selected (57.1% were Doctors, 31.2% were Nurses, 11.7% were Other professionals). Overall, significant increases were achieved in all components of the brief intervention [Ask (5.5 to 7.6); Advise (5.9 to 8.0); Assess (5.0 to 7.1); Assist (2.7 to 5.8); and Arrange a follow up (1.8 to 5.1); p < 0.001 for all components]. Doctors and Other Health professionals obtained higher scores compared to Nurses. By country, the health workers from Paraguay obtained higher scores. Overall, the perception of the degree of preparation, preparedness in the management of medication, level of competence and, familiarity with resources such as quitlines, Internet, etc, increased (p < 0.001). Conclusions The online training had a positive impact on the implementation of the brief intervention in the three countries. Online education in tobacco cessation is feasible and effective to improve evidence-based treatment for tobacco dependence in these countries

Background Smoking is still highly prevalent in Europe. According to the WHO, tobacco control policies vary substantially across countries. The Tobacco Control Scale (TCS) was developed to quantify the implementation of tobacco control policies at country level in Europe. The objective was to assess the impact of tobacco control policies (quantified by TCS scores) on smoking prevalence and quit ratios and their relative changes from 2006-2014 in 27 European Union (EU27) countries. Methods We conducted an ecological study at the country level. We used TCS scores in EU27 in 2007, and the prevalence of tobacco and quit ratios (No. ex-smokers/ No. ever smokers) data from the Eurobarometer surveys (2006 and 2014 waves). We analysed the relationship between the TCS scores and smoking prevalence and quit ratios and their relative changes by means of scatter plots, Spearman rank-correlation coefficients (r sp ), and a multiple linear regression model adjusted for all TCS components. Results In EU27, the smoking prevalence decreased by 14% (95%CI:7.3%-20.6%) (2006-2014) and varied from a relative decrease of 48.9% in Sweden to 0.4% in Bulgaria. The increase in the quit ratio in EU27 was 19.2% (95%CI:5.4%-33.1%) (2006-2014) and ranged from 125.8% in Sweden to 4.3% in Bulgaria. The correlation between TCS scores and smoking prevalence was negative (r sp =-0.444;p=0.02). A positive correlation was observed between TCS scores and quit ratios in 2014 (r sp =0.373;p=0.06) and in the relative changes in smoking prevalence (r sp =0.415;p=0.03). The percentage of smoking prevalence in 2014 explained by all TCS components in the regression model was 28.9% Conclusions European countries with higher TCS scores, which indicates higher tobacco control efforts, have lower prevalence of smokers, higher quit ratios, and higher relative decreases in their smoking prevalence over the last decade. Funding: EC Horizon2020 HCO-6-2015 (EUREST-PLUS No. 681109); Government of Spain & European Regional Development Fund (RTICC RD12/0036/0053); Government of Catalonia (2014SGR999).

S'analitzen 373 activitats d'ensenyament i 103 qüestions d'avaluació dirigides a l'estudi de l'astronomia, aportades per 14 professors (7 de primària i 7 de secundària). Amb aquest anàlisi es pretén conèixer quins aspectes conceptuals i quines habilitats cognitiu-lingüístiques s'inclouen en elles. Els resultats mostren que el professorat tendeix a prioritzar l'estudi dels aspectes més complexos -la Terra a l'espai- i referent a les habilitats cognitiu-lingüístiques a sol·licitar la descripció de models teòrics. A més es detecten certes diferències entre els dos col·lectius de professors, el de secundària associa més equilibradament les habilitats als diferents aspectes astronòmics que el de primària. Finalment es presenten recomanacions didàctiques dels resultats.

En este trabajo se realiza una revisión histórica, de aquellos estudios/experiencias relacionados con los procesos de fotosíntesis y respiración que contribuyeron a la desestimación de la “teoría del humus” como modelo de nutrición vegetal. También se incluyen aquellos problemas que preocupaban a los investigadores en ese marco histórico. Se pondrá especial énfasis en la evolución de la formulación de “la fotosíntesis”, ya que en dicho conocimiento se localizó “la clave” que otorgó a los vegetales una importancia vital para la supervivencia de la vida en nuestro planeta. La evolución del conocimiento en ese campo, permitió pasar de un modelo de nutrición vegetal centrado únicamente en el nivel organismo, a la elaboración y aceptación del modelo actual que contempla la nutrición en tres niveles: organismo, celular y ecosistema. Finalmente se muestra la importancia que esta revisión histórica tiene para la enseñanza de este tema.