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Abstract Background The increasing incidence of coeliac disease is leading to a growing interest in active search for associated factors, even the intrauterine and early life. The exposome approach to disease encompasses a life course perspective from conception onwards has recently been highlighted. Knowledge of early exposure to gluten immunogenic peptides (GIP) in utero could challenge the chronology of early prenatal tolerance or inflammation, rather than after the infant’s solid diet after birth. Methods We developed an accurate and specific immunoassay to detect GIP in amniotic fluid (AF) and studied their accumulates, excretion dynamics and foetal exposure resulting from AF swallowing. One hundred twenty-five pregnant women with different gluten diets and gestational ages were recruited. Results GIP were detectable in AF from at least the 16th gestational week in gluten-consuming women. Although no significant differences in GIP levels were observed during gestation, amniotic GIP late pregnancy was not altered by maternal fasting, suggesting closed-loop entailing foetal swallowing of GIP-containing AF and subsequent excretion via the foetal kidneys. Conclusions The study shows evidence, for the first time, of the foetal exposure to gluten immunogenic peptides and establishes a positive correlation with maternal gluten intake. The results obtained point to a novel physiological concept as they describe a plausible closed-loop circuit entailing foetal swallowing of GIP contained in AF and its subsequent excretion through the foetal kidneys. The study adds important new information to understanding the coeliac exposome.

ABSTRACT Aim To implement shared decision‐making (SDM) through a patient decision aid (PtDA) for the initiation of palliative care (PC) in end‐of‐life (EOL) cancer patients. Methodology A comprehensive Scoping Review was conducted on SDM in PubMed, CINAHL and PsycInfo. An evidence‐based implementation of PtDAs was created using the Joanna Briggs Institute framework, which followed rigorous pillars: (1) context, (2) facilitation and (3) evaluation. Results Fifteen studies were identified and categorised into (1) Implementation characteristics and (2) Strategies for implementing SDM in terminally ill cancer patients. SDM should consider the decision‐making location, optimal timing, participants and decision type. Strategies include professional training, PtDAs and implementation programmes. A PtDA implementation protocol in video format for deciding to initiate PC is proposed, following International Patient Decision Aid Standards (IPDAS) and Clinical Practice Guidelines (CPG). Conclusions SDM implementation should be guided by evidence‐based methodological models justifying and structuring its execution, especially in complex and interdisciplinary contexts. National or international frameworks facilitate the adoption of health innovations, such as PtDAs, benefiting patients and improving their usage. Practice Implications SDM is not just a concept but an important approach to the Care of cancer patients at EOL, enhancing patient satisfaction and improving care quality. The success and sustainability of SDM hinge on the fundamental aspects of staff training, interdisciplinary collaboration and ongoing evaluation. The lack of specific aid in Spanish underscores the immediate need for local development. Further research is needed in this area, as most reviewed studies did not measure SDM effectiveness in diverse hospital settings. Patient or Public Contribution This proposal was developed based on the experience and input of the nursing staff from the healthcare service where it is intended to be implemented.

Abstract Background Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy. Methods Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage. Results Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25). Conclusions The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype.

Mientras que Miguel de Unamuno vivió, su libro Del sentimiento trágico de la vida fue traducido a siete idiomas. Esta circunstancia provocó que los traductores se dirigieran a su autor para comentar la obra así como para hacerle partícipe de algunos problemas que les iban surgiendo. El epistolario conservado entre Miguel de Unamuno y sus traductores nos ofrece así una fuente inestimable de conocimiento para comprender mejor la génesis y el alcance de la que, según Unamuno, fue su obra capital. Gracias al hallazgo de unas cartas inéditas, podemos reconstruir cómo fue el proceso de traducir Del sentimiento trágico de la vida, teniendo en cuenta todos los acontecimientos que se sucedieron al inicio del siglo XX.

Measuring the sociocultural productivity of heritage sites remains an ongoing issue for international organizations concerned with the conservation and promotion of traditional sites. The productivity of these locations is not only affected by tangible elements but also by intangible factors, such as the emotions generated by the experiences. For this purpose, 597 employees of hotels in these historical locations who had visited one of the 14 heritage sites in Spain assessed what role emotions play in this contribution. The methodology used was the application of structural equations. Several conclusions have been drawn utilizing the SmartPLS 4 software. The first is that the generation of positive emotions comes exclusively from cultural and historical dynamization and not from technological advances or an eagerness to learn. The second is that both the application of technological advances and cultural dynamization have a direct impact on productivity.

El artículo presenta parte de los resultados de la investigación titulada “Desigualdades de las deportistas de alta competición en España y medidas para la igualdad efectiva” (Exp. 23CM0003), impulsado por el Servicio de Educación y Deportes del Instituto de las Mujeres del Ministerio de Igualdad y realizado por la Universidad de Córdoba. Se pretendía detectar situaciones de desigualdad de género en el ámbito del deporte de competición y profesional, tanto a nivel deportivo como social, y realizar propuestas para la implementación de medidas de igualdad efectiva de género en el sistema deportivo español. Se entrevistó a mujeres deportistas de primera línea del deporte español, responsables de organizaciones deportivas, periodistas de reconocido prestigio y profesionales con gran experticia. En total, se realizaron 26 entrevistas individuales, registrando 1.260 minutos de grabación de voz. Los resultados resultan de gran utilidad para mejorar el conocimiento de las situaciones de desigualdad de género del deporte femenino profesional y de competición, identificando los hándicaps que aún viven aquéllas y las fórmulas con las que cambiar esa situación en el presente y el futuro del deporte nacional.

Introduction: Kaposi’s varicelliform eruption (KVE), also known as eczema herpeticum or eczema vaccinatum, is an acute dermatosis that affects patients with chronic dermatopathies. The diagnosis is primarily clinical and is characterised by the presence of a vesicular exanthema on physical examination. The exanthema subsequently evolves into crusted lesions with typical circular ulcerations in ‘punched-out’ areas on the skin affected by the underlying dermatopathy. Case description: We present the case of a 6-year-old patient who presented to the Paediatric Emergency department with skin lesions consistent with eczema herpeticum. The patient’s management was initially outpatient; however, due to the slow progression of the condition, hospitalisation and intravenous antiviral treatment were initiated. Discussion: KVE affects patients with chronic dermatoses, especially atopic dermatitis. It is important to know the clinical presentation for an early suspicion. KVE is a medical emergency that requires prompt diagnosis and treatment. It can progress to secondary viraemia, which can be fatal in up to 10% of immunocompetent individuals and up to 50% of immunocompromised individuals. It is important to be aware of this condition and to start early treatment with antivirals, especially given the high prevalence of atopic dermatitis in our population. This condition is one of the most serious complications that can occur in these patients.

Abstract Background Galcanezumab has shown efficacy and effectiveness in the treatment of episodic and chronic migraine (CM), however, the population represented in randomized clinical trials (RCTs) differs from the population observed in real-world setting. To describe the long-term effectiveness and tolerability of galcanezumab in clinical practice in patients excluded from RCTs. Methods Multicenter prospective cohort study of consecutive patients with chronic and high-frequency episodic migraine (HFEM) with prior failure to three or more migraine preventive drugs, treated with galcanezumab and followed up for 12 months. Results We enrolled 1055 patients, aged 50 (IQR: 42–58), 82.9% female, 76.4% chronic migraine, 69% with at least one exclusion criteria for RCTs, including age > 65 (n = 121), concomitant use of onabotulinumtoxinA (n = 185), daily headache at baseline (n = 347), chronic painful syndromes (n = 206), fibromyalgia (n = 101) or treatment resistance (n = 957). The median number of prior preventive treatments was 4 (IQR: 3–5). The retention rate was 90.8%, 76.8% and 71.4% at 3, 6 and 12 months. The main reasons for treatment discontinuation were lack of effectiveness (21.1%) and inadequate tolerability (6.6%). The 30%, 50% and 75% responder rates were 62.6%, 49.8% and 24.2% between weeks 8–12; 60.9%, 48.8% and 24.6% between weeks 20–24; and 59.7%, 48.3% and 24.6% between weeks 44–48. Daily headache at baseline (OR: 0.619; 95%CI: 0.469–0.817) and patient’s age (OR: 1.016; 95%CI: 1.005–1.026) were associated with 50% response at weeks 20–24. The variables that were associated with a higher reduction of headache days between weeks 20–24 were patient’s age (0.068; 95% CI: 0.018–0.119) and headache days per month at baseline (0.451; 95% CI: 0.319–0.583), while psychiatric comorbidity (-1.587; 95% CI: -2.626—0.538) and daily headache at baseline (-2.718; 95% CI: -4.58—0.869) were associated with fewer reduction in the number of headache days between weeks 20–24. Conclusion This study provides class III evidence of effectiveness and tolerability of galcanezumab in patients with HFEM and CM with comorbidities that would result in exclusion of the pivotal RCTs. Nonetheless, the clinical results over a 12-month period were similar to the efficacy observed in randomized controlled trials. Few patients discontinued the drug due to inadequate tolerability.

Isavuconazole is used to treat fungal infections. This study aims to describe isavuconazole pharmacokinetics in critically ill patients and evaluate their relationship with clinical efficacy and patient safety. We conducted a prospective, observational study in patients treated with intravenous isavuconazole. Samples were collected at predose (Cmin), 1 h (Cmax) and 12 h (C50) after the last dose. The plasma concentration was determined by high-performance liquid chromatography. The relationship between plasma concentration and clinical and microbiological outcomes and safety was evaluated. The influence of covariates (age, sex, weight, SAPS3, creatinine, liver enzymes and extracorporeal devices: continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO)) was analysed. Population pharmacokinetic modelling was performed using NONMEN®. A total of 71 isavuconazole samples from 24 patients were analysed. The mean Cmin was 1.76 (1.02) mg/L; 87.5% reached the optimal therapeutic target and 12.5% were below 1 mg/L. Population pharmacokinetics were best described by a one-compartment model with first-order elimination. No factor had a significant impact on the plasma concentration or pharmacokinetic parameters. Thus, isavuconazole could be safely used in a critically ill population, even in those treated with CRRT and ECMO, from a pharmacokinetic standpoint. Therefore, routine therapeutic drug monitoring may not be strictly necessary in daily clinical practice.

The objective of this study was to evaluate the possible use of spectrophotometric assays for the measurement of trace elements, including Zinc (Zn), Copper (Cu), Magnesium (Mg), and iron (Fe) in the saliva of horses and study their possible changes in equine gastric ulcer syndrome (EGUS). EGUS is a highly prevalent disease, with a current high incidence due to the increase in intensive management conditions. There are two EGUS diseases: equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD), which can appear individually or together. For this purpose, automated spectrophotometric assays for measuring these analytes in horse saliva were analytically validated. Then, these analytes were measured in the saliva of horses with only ESGD, only EGGD, both ESGD and EGGD and a group of healthy horses. The methods used to measure the analytes were precise and accurate. Horses diagnosed with EGGD presented significantly lower levels of Zn and Mg. Fe concentrations were significantly lower in the saliva of horses with ESGD and EGGD. Overall, these results indicate that there are changes in trace elements in saliva in EGUS that could reflect the physiopathological mechanisms involved in this process and open the possibility of using trace elements as biomarkers of this syndrome.

Sodium-glucose cotransporter-2 (iSGLT2) inhibitors, which include dapagliflozin, canagliflozin and empagliflozin, are a class of drugs initially used in the oral treatment of diabetes, heart failure and renal failure. They target the reabsorption of glucose in the kidney. Although they bring benefit to patients with these conditions and in general produce few adverse effects, in some cases, iSGLT2 can cause serious adverse effects such as metabolic acidosis, and fungal or bacterial urinary infections. Oncology patients, who in general have a weak immune system and are usually treated with chemotherapy and/or immunotherapy, are more susceptible to this type of adverse events than other patients. For this reason, it is necessary to adequately select the patients eligible to receive this type of drug and evaluate the potential benefits for them. In this series of five cases, we present two cases of metabolic acidosis, two cases of bacterial urinary sepsis, and one case of fungal urinary sepsis that occurred in patients admitted to the Medical Oncology Department of the University Hospital of Salamanca in 2023.

The prompt management of patients with massive burns is essential to maximize survival by preventing infection, hemorrhage, fluid and heat loss, and to optimally prepare the wound bed for the application of autografts or cultured tissue-engineered artificial autologous skin. Acute treatments are typically based on temporary bio-dressings, commonly cadaveric skin allografts, but supply challenges, high costs and increasingly stringent regulatory requirements preclude their widespread use. Nanostructured fibrin-agarose hydrogels (NFAH) have been proven to be safe and effective biomaterials in preclinical and clinical studies, and show good hemostatic and biomechanical properties. Here we generated and tested NFAH with embedded allogeneic dermal fibroblasts (NFAH-F) under Good Manufacturing Practice (GMP) conditions. Fibroblasts were first expanded and characterized to create a GMP bank and the NFAH-F was manufactured on demand. Three patients with major burns were treated with this product as a temporary bio-dressing under compassionate use. Our results suggest that NFAH-F product was a safe product and no adverse reactions were observed. In all cases, the patients survived until definitive treatment. Therefore, the application of NFAH-F might be a temporary bio-dressing for patients with massive burns when cadaveric skin allografts are not available.

Abstract Background There remains much interest in improving cryopreservation techniques for advanced therapy medicinal products (ATMPs). Recently, human platelet lysate (hPL) has emerged as a promising candidate to replace fetal bovine serum (FBS) as a xeno-free culture supplement for the expansion of human cell therapy products. Whether hPL can also substitute for FBS in cryopreservation procedures remains poorly studied. Here, we evaluated several cryoprotective formulations based on a proprietary hPL for the cryopreservation of bioengineered tissues and cell therapy products. Methods We tested different xenogeneic-free, pathogen-inactivated hPL (ihPL)- and non-inactivated-based formulations for cryopreserving bioengineered tissue (cellularized nanostructured fibrin agarose hydrogels (NFAHs)) and common cell therapy products including bone marrow-derived mesenchymal stromal cells (BM-MSCs), human dermal fibroblasts (FBs) and neural stem cells (NSCs). To assess the tissue and cellular properties post-thaw of NFAHs, we analyzed their cell viability, identity and structural and biomechanical properties. Also, we evaluated cell viability, recovery and identity post-thaw in cryopreserved cells. Further properties like immunomodulation, apoptosis and cell proliferation were assessed in certain cell types. Additionally, we examined the stability of the formulated solutions. The formulations are under a bidding process with MD Bioproducts (Zurich, Switzerland) and are proprietary. Results Amongst the tissue-specific solutions, Ti5 (low-DMSO and ihPL-based) preserved the viability and the phenotype of embedded cells in NFAHs and preserved the matrix integrity and biomechanical properties similar to those of the standard cryopreservation solution (70% DMEM + 20% FBS + 10% DMSO). All solutions were stable at − 20 °C for at least 3 months. Regarding cell-specific solutions, CeA maintained the viability of all cell types > 80%, preserved the immunomodulatory properties of BM-MSCs and promoted good recovery post-thaw. Besides, both tested solutions were stable at − 20 °C for 18 months. Finally, we established that there is a 3-h window in which thawed NFAHs and FBs maintain optimum viability immersed in the formulated solutions and at least 2 h for BM-MSCs. Conclusions Our results show that pathogen-inactivated solutions Ti5 allocated for bioengineered tissues and CeA allocated for cells are efficient and safe candidates to cryopreserve ATMPs and offer a xenogeneic-free and low-DMSO alternative to commercially available cryoprotective solutions.

In recent years geoparks, helped by governmental policies, have become tourist destinations especially among senior visitors. The paper aimed to analyse whether geoparks contribute to improving the health of tourists older than 65 years and what were their main motives to visit geoparks. The data were collected from 398 senior tourists who visited the Villuerca- Ibores-Jara Geopark (Spain) in 2023, presenting our results using SmartPLS version 4. The results showed that senior tourists are very interested in visiting this geopark for psychotherapeutic reasons, given its high environmental and geological interest. In addition, they consider geoparks as spaces where they can socialise, which is beneficial considering the isolation that many often experience during the year. These findings are highly relevant for public authorities to protect, maintain and promote geoparks among senior tourists.

IntroductionTo decrease psychological risk for content moderators, the study initiated the first steps of developing a robust employment screening tool, namely, the Cognitive Adaptability and Resiliency Employment Screener.MethodThe study consisted of three phases with 4,839 total participants.ResultsIn Phase 1, a set of 75 items were developed and tested via exploratory factor analysis, yielding three factors (i.e., Psychological Perseverance & Agility, Rumination & Emotional Lingering, and Expressiveness & Sociability) and also reducing the scale to 67 items. In Phase 2 through confirmatory factor analysis, the three-factor structure showed good fit (CFI = .93, RMSEA = .05) and demonstrated sufficient overall reliability. In Phase 3, the convergent validity and divergent validity of the tool were established relative to constructs such as resilience, cognitive control and flexibility, emotion regulation, and optimism.DiscussionAltogether, the findings revealed that the scale demonstrated good psychometric properties that, pending future studies, may serve as a promising employment screener for content moderators.

Abstract Background Severe community-acquired pneumococcal meningitis is a medical emergency. The aim of the present investigation was to evaluate the epidemiology, management and outcomes of this condition. Methods This was a retrospective, observational and multicenter cohort study. Sixteen Spanish intensive care units (ICUs) were included. Demographic, clinical and microbiological variables from patients with Streptococcus pneumoniae meningitis admitted to ICU were evaluated. Clinical response was evaluated at 72 h after antibiotic treatment initiation, and meningitis complications, length of stay and 30-day mortality were also recorded. Results In total, 255 patients were included. Cerebrospinal fluid (CSF) culture was positive in 89.7%; 25.7% were non-susceptible to penicillin, and 5.2% were non-susceptible to ceftriaxone or cefotaxime. The most frequent empiric antibiotic regimen was third-generation cephalosporin (47.5%) plus vancomycin (27.8%) or linezolid (12.9%). A steroid treatment regimen was administered to 88.6% of the patients. Clinical response was achieved in 65.8% of patients after 72 h of antibiotic treatment. Multivariate analysis identified two factors associated with early treatment failure: invasive mechanical ventilation (OR 10.74; 95% CI 3.04–37.95, p

Dada la necesidad de abordar desde la prevención el problema de las familias en situación de separación o divorcio inmersas en alta conflictividad y que tienden a judicializar sus relaciones, y ante la inexistencia de un instrumento que sirva para identificar esta tendencia, se pretende elaborar un cuestionario que mida las características predictoras de judicialización. El trabajo se centra en la validación de contenido e interna del C-JUDIFA, pudiendo concluir que los ítems utilizados explican bien las características que pretenden medir, así como que se obtiene una buena representatividad de las escalas propuestas. El análisis factorial confirma la estructura de tres factores propuesta teóricamente para el instrumento, encontrando también una buena correlación entre los 9 constructos aportados. Asimismo, se requiere investigar sobre la relación que todos estos factores tienen realmente en la tendencia a judicializar los conflictos derivados de situaciones de separación, analizando su validez externa.

Este artículo analiza las lecturas que realizó Martin Heidegger de la Ética a Nicómaco de Aristóteles a partir de las anotaciones y subrayados que se conservan en un ejemplar que perteneció al filósofo alemán y que actualmente se custodia en la Biblioteca Histórica de la Universidad de Salamanca. Las diversas notas y glosas manuscritas que Heidegger anota al margen de las páginas en la obra de Aristóteles permiten conocer mejor la influencia que este libro ejerció en la filosofía heideggeriana y descubren que «el taller histórico y filológico» que Martin Heidegger instauró a partir del texto aristotélico fue crucial para el desarrollo de algunos conceptos fundamentales de su pensamiento.

Resumen: se presenta en esta sección una revisión de los artículos científicos de mayor impacto publicados entre febrero y mayo del 2023 en las revistas internacionales sobre Sexología con mayor reconocimiento a nivel nacional e internacional (Journal of Sexual Medicine; International Journal of Sexual Health; Archives of Sexual Behavior; Sex roles; Sexual Health & Compulsivity, Psychology and Sexuality; Culture, Health and Sexuality; DeSexología, Psicología de la orientación sexual y la diversidad, American Journal of Sexual Education, Journal of Sex & Marital Therapy y Violence Against Woman).

Ammonia (NH3) and bicarbonate (HCO3) have been related to gastric ulcers in humans. Ammonia is considered a possible cause of gastric ulcers, whereas bicarbonate has a protective function. The presence of ulcers in the stomach of horses is defined as Equine Gastric Ulcer Syndrome (EGUS), which is a frequent disease in this species, and it has been associated with changes in saliva composition, such as in analytes related to inflammation, immune system and oxidative stress. The objectives of this study were (1) to perform an analytical validation of two automated spectrophotometric assays, one for ammonia and one for bicarbonate, in the horses’ saliva and (2) to evaluate their possible variations with EGUS. Analytical validation of the automated assays for ammonia and bicarbonate in the saliva of horses showed that both assays were precise and accurate. In addition, significantly higher values of ammonia and lower values of bicarbonate were found in the saliva of horses with EGUS compared to healthy horses. It can be concluded that ammonia and bicarbonate can be measured in the saliva of horses and that ammonia increases and bicarbonate decreases in this sample type could be related to the presence of EGUS in this species.

Stress leukogram includes eosinopenia as one of its main markers (neutrophilia, eosinopenia, lymphopenia, and mild monocytosis). Cortisol is the main stress biomarker, which is also strongly correlated with the severity of gastrointestinal diseases. This study aimed to determine the relationship between salivary cortisol and the eosinophil cell count (EC) in equids with abdominal pain. To do this, 39 horses with abdominal pain referred to an emergency service were included. All samples were taken on admission, and several parameters and clinical data were included. Equids were classified according to the outcome as survivors and non-survivors. Non-surviving equids presented higher salivary cortisol concentrations (Non-Survivors: 1.580 ± 0.816 µg/dL; Survivors 0.988 ± 0.653 µg/dL; p < 0.05) and lower EC (Non-Survivors: 0.0000 × 103/µL (0.000/0.0075); Survivors: 0.0450 × 103/µL (0.010/0.1825); p < 0.01). In addition, the relationship between salivary cortisol concentration, EC, and the WBC was determined. Only a strong correlation (negative) was observed between cortisol and EC (r = −0.523, p < 0.01). Since cortisol is not an analyte that can be measured routinely in clinical settings such as emergencies, the EC could be a good alternative. While the results are promising, further studies are needed before EC can be used confidently in routine practice to predict survival in cases of abdominal pain.

The Varroa destructor mite infests Apis mellifera colonies and causes significant harm. Traditional treatments have become less effective because of mite resistance development and can also generate residues inside beehives. This study aimed to gauge the efficacy of a beehive-derived postbiotic in reducing V. destructor viability and to explore its synergies with organic compounds. Four lactic acid bacteria (LAB) species, Leuconostoc mesenteroides, Lactobacillus helsingborgensis, Bacillus velezensis, and Apilactobacillus kunkeei, were isolated and tested in a postbiotic form (preparations of inanimate microorganisms and/or their components) via bioassays. L. mesenteroides, L. helsingborgensis, and B. velezensis notably reduced the mite viability compared to the control, and they were further tested together as a single postbiotic product (POS). Further bioassays were performed to assess the impact of the POS and its combinations with oxalic acid and oregano essential oil. The simple products and combinations (POS/Oregano, POS/Oxalic, Oregano/Oxalic, and POS/Oregano/Oxalic) decreased the mite viability. The most effective were the oxalic acid combinations (POS/Oregano/Oxalic, Oxalic/Oregano, POS/Oxalic), showing significant improvements compared to the individual products. These findings highlight the potential of combining organic products as a vital strategy for controlling V. destructor infection. This study suggests that these combinations could serve as essential tools for combating the impact of mites on bee colonies.

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat builds up in the liver. To date, there is a lack of knowledge about the subtype of lipid structures affected in the early stages of NAFLD. The aim of this study was to analyze serum and liver lipid moieties, specifically unsaturations and carbonyls, by nuclear magnetic resonance (NMR) in a subclinical Wistar rat model of NAFLD for detecting early alterations and potential sex dimorphisms. Twelve weeks of a high-fat diet (HFD) induced fat accumulation in the liver to a similar extent in male and female Wistar rats. In addition to total liver fat accumulation, Wistar rats showed a shift in lipid subtype composition. HFD rats displayed increased lipid carbonyls in both liver and serum, and decreased in unsaturated fatty acids (UFAs) and polyunsaturated fatty acids (PUFAs), with a much stronger effect in male than female animals. Our results revealed that the change in fat was not only quantitative but also qualitative, with dramatic shifts in relevant lipid structures. Finally, we compared the results found in Wistar rats with an analysis in a human patient cohort of extreme obesity. For the first time to our knowledge, lipid carbonyl levels and lipoproteins profiles were analyzed in the context of subclinical NAFLD. The association found between lipid carbonyls and alanine aminotransferase (ALT) in a human cohort of extremely obese individuals further supports the potential role of lipid moieties as biomarkers of early NAFLD.

Abstract The human respiratory syncytial virus (HRSV) causes severe lower respiratory tract infections in infants and the elderly. An exuberant inadequate immune response is behind most of the pathology caused by the HRSV. The main targets of HRSV infection are the epithelial cells of the respiratory tract, where the immune response against the virus begins. This early innate immune response consists of the expression of hundreds of pro-inflammatory and anti-viral genes that stimulates subsequent innate and adaptive immunity. The early innate response in infected cells is mediated by intracellular signaling pathways composed of pattern recognition receptors (PRRs), adapters, kinases, and transcriptions factors. These pathways are tightly regulated by complex networks of post-translational modifications, including ubiquitination. Numerous ubiquitinases and deubiquitinases make these modifications reversible and highly dynamic. The intricate nature of the signaling pathways and their regulation offers the opportunity for fine-tuning the innate immune response against HRSV to control virus replication and immunopathology.

Abstract Background The full catalog of satellite DNA (satDNA) within a same genome constitutes the satellitome. The Library Hypothesis predicts that satDNA in relative species reflects that in their common ancestor, but the evolutionary mechanisms and pathways of satDNA evolution have never been analyzed for full satellitomes. We compare here the satellitomes of two Oedipodine grasshoppers (Locusta migratoria and Oedaleus decorus) which shared their most recent common ancestor about 22.8 Ma ago. Results We found that about one third of their satDNA families (near 60 in every species) showed sequence homology and were grouped into 12 orthologous superfamilies. The turnover rate of consensus sequences was extremely variable among the 20 orthologous family pairs analyzed in both species. The satDNAs shared by both species showed poor association with sequence signatures and motives frequently argued as functional, except for short inverted repeats allowing short dyad symmetries and non-B DNA conformations. Orthologous satDNAs frequently showed different FISH patterns at both intra- and interspecific levels. We defined indices of homogenization and degeneration and quantified the level of incomplete library sorting between species. Conclusions Our analyses revealed that satDNA degenerates through point mutation and homogenizes through partial turnovers caused by massive tandem duplications (the so-called satDNA amplification). Remarkably, satDNA amplification increases homogenization, at intragenomic level, and diversification between species, thus constituting the basis for concerted evolution. We suggest a model of satDNA evolution by means of recursive cycles of amplification and degeneration, leading to mostly contingent evolutionary pathways where concerted evolution emerges promptly after lineages split.

Abstract Background To investigate the role of cell senescence in systemic sclerosis (SSc), we analyzed telomere shortening (TS) in SSc patients and the effect of targeting DNA damage in the bleomycin model of skin fibrosis. Results Telomere length (TL) in blood leukocytes of 174 SSc patients and 68 healthy controls was measured by Southern blot, and we found shorter age-standardized TL in SSc patients compared to healthy controls. TL was shorter in SSc patients with ILD compared to those without ILD and in anti-topoisomerase I positive compared to anti-centromere positive patients. To analyze the potential role of DNA damage in skin fibrosis, we evaluated the effects of the DNA protective GSE4 peptide in the bleomycin mouse model of scleroderma and the fibrotic response of cultured human dermal fibroblasts. Administration of GSE4-nanoparticles attenuated bleomycin-induced skin fibrosis as measured by Masson’s staining of collagen and reduced Acta2 and Ctgf mRNA expression, whereas transduction of dermal fibroblasts with a lentiviral GSE4 expression vector reduced COL1A1, ACTA2 and CTGF gene expression after stimulation with bleomycin or TGF-β, in parallel to a reduction of the phospho-histone H2A.X marker of DNA damage. Conclusions SSc is associated with TS, particularly in patients with lung disease or anti-topoisomerase I antibodies. Administration of GSE4 peptide attenuated experimental skin fibrosis and reduced fibroblast expression of profibrotic factors, supporting a role for oxidative DNA damage in scleroderma.

Zooarchaeological analyses of the skeletal remains of 52 animals unearthed in the courtyard of an Iron Age Tartessian building known as Casas del Turuñuelo (Badajoz, Spain) shed light on a massive sacrifice forming part of a series of rituals linked to the site's last period of activity and final abandonment. The rites took place towards the end of the 5th century BCE when both the building (intentionally destroyed) and the sacrificed animals were intentionally buried under a tumulus 90 m in diameter and 6 m high. The main objective of the zooarchaeological and microstratigraphic analyses was to determine the phasing of the sacrificial depositions. Evidence gathered from taphonomic assessments and a series of radiocarbon datings indicate that the sacrifices fall into three consecutive phases spanning several years. The findings of the zooarchaeological analyses clearly point to a selection of equid and cattle males. Adult equids predominate (MNI = 41) followed by adult and sub-adult cattle (MNI = 6). Pigs, in turn, are only represented by a few adults and sub-adult females (MNI = 4). Among the animals is a single dog of undetermined sex between 3 and 4 years of age. The fact that the animals are mostly adults discards the likelihood that they died from natural causes or an epidemic. In addition, the scenographic deposition of certain equids in pairs, as well as evidence of the burning of plant offerings, suggest an intentional ritualistic sacrifice. Nine of the initial depositions of Phase 1 in the SE quadrant were scattered and certain of their bones bear marks characteristic of both prolonged open air exposure and scavengers. Another 31 animals from Phases 1 and 2 are represented by almost complete, articulated skeletons, indicating they were promptly covered. Phase 3, by contrast, reveals both almost complete and partial animals bearing clear signs of processing for human consumption. This study thus sheds light on both the sequence of the animal sacrifices and the protocols linked to rites accompanied by the celebration of banquets. Certain features associated with the sealing of this building under a tumulus offer evidence of the decline of the Tartessian Culture. This study thus advances notions serving to contextualize ritual animal sacrifices in the framework of practice observed at other Iron Age sites in the Iberian Peninsula and elsewhere throughout Europe.

Coffee pulp is an underutilized by-product of coffee industrial production rich in bioactive compounds such as phenolic compounds, caffeine, and dietary fiber. The widely known antioxidant, anti-inflammatory, anti-aging, antimicrobial and hepatoprotective health-promoting properties attributed to mentioned compounds enhance the use of coffee pulp as a bioactive food ingredient. Furthermore, the application of green sustainable extraction techniques pursuing highly efficient and selective extraction processes promotes this by-product exploitation in food science. Hence, this review gathers the available information relative to the impact of the extraction processes on the bioactive compound's recovery from coffee pulp, providing an overview of the most recent advances. An in-depth comparison workout between conventional and alternative extraction methods was performed to identify the most suitable techniques for coffee pulp valorization as functional ingredient until date. A critical discussion focused on advantages and drawbacks of the extraction methods applied to coffee pulp was included together a prospective of emerging extraction techniques.

Se presentan los resultados de las excavaciones (2006, 2017 y 2021) en un sector de la aldea del Hierro I del Cerro de San Vicente (Salamanca). Se ha exhumado un agregado informal de edificios y estructuras adjetivas de adobe cuyo patrón espacial es afín al esquema transcultural patrilocal. El artículo se centra en la casa 1 y sus cenizales. Tal vivienda fue excepcional por su larga e ininterrumpida biografía, su mobiliario de barro –con dos poyos que pudieron acoger hasta 20 personas y un hogar con forma de piel de toro extendida– y su abandono ritualizado –quemada c. 650-575 a.C. y recrecida con adobes de sus paredes–. La excavación reveló una alta concentración de molinos y vajilla fina local pintada, así como instrumental de labores especializadas y altamente cualificadas –alfarería e hilado–. Sobresale un lote de hallazgos inéditos en el interior de la península ibérica: exóticos abalorios y vajilla de fayenza del Mediterráneo oriental, cerámica de engobe rojo fenicia y objetos litúrgicos y coroplástica con paralelos tartésicos y mediterráneos. Todos estos hallazgos indican que la casa 1 acogió una asidua actividad social –banquetes y transacciones con huéspedes– como cabaña de reuniones de un grupo corporativo extenso, donde acabaron tan destacados objetos.

Aortic valve stenosis is the most frequent valve disease in developed countries and its prevalence will increase with population aging. There is still no pharmaceutical treatment nor biomarker to determine the susceptibility to develop aortic stenosis. Therefore, we analyzed the association of polymorphisms in risk loci with calcific aortic stenosis. Patients with aortic valve disease were genotyped for PALMD rs6702619, LPA rs10455872, and IL6 rs1800795 polymorphisms and circulating levels of interleukin-6 (IL-6) were measured. Calcium content of leaflets obtained in valve replacement surgeries was determined by micro-computed tomography. In the genotyping of 578 individuals, we found significant association between PALMD and IL6 polymorphisms and aortic stenosis in patients with tricuspid aortic valve, independently of other potentially confounding variables such as age and dyslipidemia. There was no association of these polymorphisms with valve calcium content, but this value correlated with the mean aortic pressure gradient (r = 0.44; P < 0.001). The CC genotype of IL6 polymorphism was associated with higher levels of serum IL-6 compared to other genotypes (23.5 vs. 10.5 pg/ml, respectively; P = 0.029). Therefore, patients carrying the CC genotype of IL6 rs1800795 polymorphism present higher levels of circulating IL-6 and this could contribute to the severity of the aortic valve stenosis. Our results agree with the identification of IL6 as a locus risk for stenosis and also with the intervention of this cytokine in aortic valve calcification. A more exhaustive follow-up of those patients carrying risk genotypes is therefore recommended.

Resumen: Se presenta en esta sección una revisión de los artículos científicos de mayor impacto publicados entre mayo de 2022 y agosto del 2022 en las revistas internacionales sobre Sexología con mayor reconocimiento a nivel nacional e internacional (Journal of Sexual Medicine; International Journal of Sexual Health; Archives of Sexual Behavior; Sex roles; Sexual Addiction & Compulsivity, Psychology and Sexuality; Culture, Health and Sexuality; DeSexología, Psicología de la orientación sexual y la diversidad, American Journal of Sexual Education, Journal of Sex & Marital Therapy y Violence Against Woman).

Cocoa shell is a by-product of cocoa manufacturing. We obtained an aqueous extract (CSE) rich in polyphenols and methylxanthines with antioxidant and vasodilatory properties. We aimed to evaluate the effects of CSE supplementation in aged hypertensive rats on blood pressure and the mechanism implicated. Eighteen-month-old male and female rats exposed to undernutrition during the fetal period who developed hypertension, with a milder form in females, were used (MUN rats). Systolic blood pressure (SBP; tail-cuff plethysmography) and a blood sample were obtained before (basal) and after CSE supplementation (250 mg/kg; 2 weeks, 5 days/week). Plasma SOD, catalase activity, GSH, carbonyls, and lipid peroxidation were assessed (spectrophotometry). In hearts and aortas from supplemented and non-supplemented age-matched rats, we evaluated the protein expression of SOD-2, catalase, HO-1, UCP-2, total and phosphorylated Nrf2 and e-NOS (Western blot), and aorta media thickness (confocal microscopy). MUN males had higher SBP compared with females, which was reduced via CSE supplementation with a significant difference for group, sex, and interaction effect. After supplementation with plasma, GSH, but not catalase or SOD, was elevated in males and females. Compared with non-supplemented rats, CSE-supplemented males and females exhibited increased aorta e-NOS and Nrf2 protein expression and cardiac phosphorylated-Nrf2, without changes in SOD-2, catalase, HO-1, or UCP-2 in cardiovascular tissues or aorta remodeling. In conclusion, CSE supplementation induces antihypertensive actions related to the upregulation of e-NOS and Nrf2 expression and GSH elevation and a possible direct antioxidant effect of CSE bioactive components. Two weeks of supplementation may be insufficient to increase antioxidant enzyme expression.

Fibrin is widely used for tissue engineering applications. The use of blood derivatives, however, carries a high risk of transmission of infectious agents, necessitating the application of pathogen reduction technology (PRT). The impact of this process on the structural and biomechanical properties of the final products is unknown. We used normal plasma (PLc) and plasma inactivated by riboflavin and ultraviolet light exposure (PLi) to manufacture nanostructured cellularized fibrin-agarose hydrogels (NFAHs), and then compared their structural and biomechanical properties. We also measured functional protein C, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and coagulation factors [fibrinogen, Factor (F) V, FVIII, FX, FXI, FXIII] in plasma samples before and after inactivation. The use of PLi to manufacture cellularized NFAHs increased the interfibrillar spacing and modified their biomechanical properties as compared with cellularized NFAH manufactured with PLc. PLi was also associated with a significant reduction in functional protein C, FV, FX, and FXI, and an increase in the international normalized ratio (derived from the PT), APTT, and TT. Our findings demonstrate that the use of PRT for fibrin-agarose bioartificial tissue manufacturing does not adequately preserve the structural and biomechanical properties of the product. Further investigations into PRT-induced changes are warranted to determine the applications of NFAH manufactured with inactivated plasma as a medicinal product.

The article aims to analyze, based on a multiple case study, the discourses of the individuals that promote social innovation (SI) initiatives for the reuse of abandoned riverside landscapes, connecting SI theory with land reutilization and management through discourse analysis. Following a qualitative methodology, the text analyses the characteristics of the promoting actors, the discourses storylines and the main actors’ discourses, describing some relevant aspects regarding SI, such as why, where and when it takes place; how it has been developed; who has promoted it; its main results, as well as the barriers faced for its development and future opportunities for the territory. Two main discursive tendencies are identified: a negationist trend and a possibilistic one, adopted by individuals who are not promoting initiatives of SI and by promoters of these kinds of experiences, respectively. Possibilistic discourse underlines the coherent articulation between the economic-managerial dimension and the emotional-territorial one, and there is, in this case, a tendency to change in the visions of the territory, reconfiguring the social practices of the actors involved in these initiatives of SI. We conclude that discourses behind successful processes of SI are associated with certain positions on the interrelationships between individual- collective-institutionality-nature and that there is a complex articulation between discourses on SI and social practices developed by individuals as part of these initiatives, in such a reflexive way that discourses advance the desired changes, drawing and modifying the future vision of the subjects, and making the impossible possible.

Abstract Background Eukaryote genomes frequently harbor supernumerary B chromosomes in addition to the “standard” A chromosome set. B chromosomes are thought to arise as byproducts of genome rearrangements and have mostly been considered intraspecific oddities. However, their evolutionary transcendence beyond species level has remained untested. Results Here we reveal that the large metacentric B chromosomes reported in several fish species of the genus Astyanax arose in a common ancestor at least 4 million years ago. We generated transcriptomes of A. scabripinnis and A. paranae 0B and 1B individuals and used these assemblies as a reference for mapping all gDNA and RNA libraries to quantify coverage differences between B-lacking and B-carrying genomes. We show that the B chromosomes of A. scabripinnis and A. paranae share 19 protein-coding genes, of which 14 and 11 were also present in the B chromosomes of A. bockmanni and A. fasciatus, respectively. Our search for B-specific single-nucleotide polymorphisms (SNPs) identified the presence of B-derived transcripts in B-carrying ovaries, 80% of which belonged to nobox, a gene involved in oogenesis regulation. Importantly, the B chromosome nobox paralog is expressed > 30× more than the A chromosome paralog. This indicates that the normal regulation of this gene is altered in B-carrying females, which could potentially facilitate B inheritance at higher rates than Mendelian law prediction. Conclusions Taken together, our results demonstrate the long-term survival of B chromosomes despite their lack of regular pairing and segregation during meiosis and that they can endure episodes of population divergence leading to species formation.

Breast milk (BM) cytokines support and modulate infant immunity, being particularly relevant in premature neonates with adverse outcomes (NAO). This study aimed to examine, in a cohort of Spanish breastfeeding women, changes in BM cytokines in the first month of lactation, their modulation by neonatal factors (sex, gestational age, and NAO), maternal factors (obstetric complications, C-section, and diet), and their relationship with oxidative status. Sixty-three mother-neonate dyads were studied at days 7 and 28 of lactation. Dietary habits were assessed by a 72-h dietary recall, and the maternal dietary inflammatory index (mDII) was calculated. BM cytokines (IL-10, IL-13, IL-8, MCP-1, and TNFα) were assessed by ultra-sensitive chemiluminescence. Total antioxidant capacity was assessed by the ABTS method and lipid peroxidation by the MDA+HNE kit. From days 7 to 28 of lactation, the levels of IL-10 and TNFα remained stable, while IL-13 increased (β = 0.85 ± 0.12, p < 0.001) and IL-8 and MCP-1 levels decreased (β = −0.64 ± 0.27, p = 0.019; β = −0.98 ± 0.22, p < 0.001; respectively). Antioxidant capacity and lipid peroxidation also decrease during lactation. Neonatal sex did not influence any of the cytokines, but BM from mothers with male infants had a higher antioxidant capacity. Gestational age was associated with male sex and NAO, being inversely correlated with the BM proinflammatory cytokines IL-8, MCP-1, and TNFα. From days 7 to 28 of lactation, BM from women with NAO infants increased MCP-1 levels and had a larger drop in antioxidant capacity, with the opposite trend in lipid peroxidation. MCP-1 was also significantly higher in women undergoing C-section; this cytokine declined in women who decreased mDII during lactation, while IL-10 increased. Linear mixed regression models evidenced that the most important factors modulating BM cytokines were lactation period and gestational age. In conclusion, during the first month of lactation, BM cytokines shift towards an anti-inflammatory profile, influenced mainly by prematurity. BM MCP-1 is associated with maternal and neonatal inflammatory processes.

Equine gastric ulcer syndrome (EGUS) is a highly prevalent disease that affects horses worldwide. Within EGUS, two different forms have been described: equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD). The associated clinical signs cause detrimental activity performance, reducing the quality of life of animals. Saliva can contain biomarkers for EGUS that could be potentially used as a complementary tool for diagnosis. The objective of this work was to evaluate the measurements of calprotectin (CALP) and aldolase in the saliva of horses as potential biomarkers of EGUS. For this purpose, automated assays for the quantification of these two proteins were analytically validated and applied for detecting EGUS in a total of 131 horses divided into 5 groups: healthy horses, ESGD, EGGD, combined ESGD and EGGD, and horses with other intestinal pathologies. The assays showed good precision and accuracy in analytical validation, and they were able to discriminate between horses with EGUS and healthy horses, especially in the case of CALP, although they did not show significant differences between horses with EGUS and horses with other diseases. In conclusion, salivary CALP and aldolase can be determined in the saliva of horses and further studies are warranted to elucidate the potential of these analytes as biomarkers in EGUS.

BackgroundCurrent benzodiazepine (BZD) prescription guidelines recommend short-term use to minimize the risk of dependence, cognitive impairment, and falls and fractures. However, many clinicians overprescribe BZDs and chronic use by patients is common. There is limited evidence on the effectiveness of interventions delivered by general practitioners (GPs) on reducing prescriptions and long-term use of BZDs. We aimed to evaluate the effectiveness of a multicomponent intervention for GPs that seeks to reduce BZD prescriptions and the prevalence of long-term users.Methods and findingsWe conducted a multicenter two-arm, cluster randomized controlled trial in 3 health districts in Spain (primary health centers [PHCs] in Balearic Islands, Catalonia, and Valencian Community) from September 2016 to May 2018. The 81 PHCs were randomly allocated to the intervention group (n = 41; 372 GPs) or the control group (n = 40; 377 GPs). GPs were not blinded to the allocation; however, pharmacists, researchers, and trial statisticians were blinded to the allocation arm. The intervention consisted of a workshop about the appropriate prescribing of BZDs and tapering-off long-term BZD use using a tailored stepped dose reduction with monthly BZD prescription feedback and access to a support web page. The primary outcome, based on 700 GPs (351 in the control group and 349 in the intervention group), compared changes in BZD prescriptions in defined daily doses (DDDs) per 1,000 inhabitants per day after 12 months. The 2 secondary outcomes were the proportion of long-term users (≥6 months) and the proportion of long-term users over age 65 years. Intention-to-treat (ITT) analysis was used to assess all clinical outcomes. Forty-nine GPs (21 intervention group and 28 control group) were lost to follow-up. However, all GPs were included in the ITT analysis. After 12 months, there were a statistically significant decline in total BZD prescription in the intervention group compared to the control group (mean difference: -3.24 DDDs per 1,000 inhabitants per day, 95% confidence interval (CI): -4.96, -1.53, p < 0.001). The intervention group also had a smaller number of long-term users. The adjusted absolute difference overall was -0.36 (95% CI: -0.55, -0.16, p > 0.001), and the adjusted absolute difference in long-term users over age 65 years was -0.87 (95% CI: -1.44, -0.30, p = 0.003). A key limitation of this clustered design clinical trial is the imbalance of some baseline characteristics. The control groups have a higher rate of baseline BZD prescription, and more GPs in the intervention group were women, GPs with a doctorate degree, and trainers of GP residents.ConclusionsA multicomponent intervention that targeted GPs and included educational meeting, feedback about BZD prescriptions, and a support web page led to a statistically significant reduction of BZD prescriptions and fewer long-term users. Although the effect size was small, the high prevalence of BZD use in the general population suggests that large-scale implementation of this intervention could have positive effects on the health of many patients.Trial registrationISRCTN ISRCTN28272199.

Coronary slow flow (CSF) phenomenon, also known as cardiac syndrome Y, is defined as the delayed opacification of the coronary vasculature at the distal level. Different hypotheses and theories have been postulated about its substrate and mechanism, such as microvascular and endothelial dysfunction. Several studies have confirmed that CSF is a cause of ischaemia detected by non-invasive testing. Clinically, it can present as angina pectoris, acute coronary syndrome and sudden cardiac death. It has an incidence of 1–5% in patients undergoing coronary angiography and has been most frequently found in young men who are smokers with metabolic syndrome. There are no established treatments for CSF and further studies are still necessary.

Abstract Background Malformation of the right atrium is a rare cardiac abnormality and is usually reported as isolated malformation in the literature. Case presentation Prenatal giant atrial dilatation in an asymptomatic infant was treated surgically at 18 months of age, due to potential risk of thrombosis and arrhythmias. Post-surgical echocardiographic images illustrate residual atrial elevated pressure. Conclusions Sometimes, as seems in our case, right atrial dilatation hides an associated restrictive right ventricle.

Resumen: Introducción y objetivos: Las guías de práctica clínica recomiendan, en pacientes jóvenes y centros con experiencia, la cirugía conservadora valvular aórtica para el tratamiento de la insuficiencia aórtica como alternativa al reemplazo valvular aórtico. Es una cirugía compleja, pero demandada más frecuentemente. Debemos plantearla como opción terapéutica y explicar sus resultados. Métodos: Análisis prospectivo, no randomizado, de 138 pacientes intervenidos con cirugía conservadora valvular aórtica (2011-2019). Resultados: Presentaban: edad media 58,1 ± 14,2 años, 33 (23,9%) mujeres, 9 (6,5%) emergentes; EUROSCORE-II: 3,35 ± 2,9, EUROSCORE-LOGÍSTICO: 9,29±7. Morfología valvular: 83 (60,1%) - tricúspide, 44 (31,9%) - bicúspide, 11 (8%) -unicúspide. Procedimientos realizados: (reimplante valvular [DAVID] + plastia aórtica): 78 (56,5%); (remodelado aórtico [YACOUB] + plastia aórtica): 22 (15,9%); plastia aórtica + tubo supracoronario: 15 (10,9%); plastia aórtica: 23 (16,7%). El 69,36% de velos aórticos precisó múltiples técnicas: (63,5%) plicatura central, (10,3%) decalcificación y (20,9%) plastia pericardio.Hubo reoperación por sangrado 4 (2,9%). Fallecieron 8 (5,8%) pacientes en el postoperatorio inmediato (3,9% de electivos).La insuficiencia aórtica preoperatoria era: I-II(18,1%), III (17,4%) y IV (64,5%). En 16 (11,6%) pacientes persistía insuficiencia grado-II intraoperatoria, reconvirtiéndose a prótesis aórtica. El seguimiento medio fue 44,2±28,6 (mediana 42,5) meses.A 9 años están libres de insuficiencia aórtica ≥ III: 83,5% (serie entera); 84,6% (tratamiento raíz aórtica [DAVID+YACOUB]) vs. 81,9% (sin tratamiento raíz aórtica) (p=0,4); 88,8% (DAVID), 63,2% (YACOUB), 85,7% (plastia aórtica + tubo supracoronario) y 78,3% (plastia aórtica) (p=0,22); 63,5% (plastia pericardio) vs. 97,7% (sin plastia pericardio) (p

Resumen: Objetivo: Analizar la situación, evaluación y propuestas de mejora del Programa de Actividades Preventivas y de Promoción de la Salud (PAPPS). Material y métodos: Se realizó un estudio cualitativo de análisis de la situación para una evaluación del PAPPS en 2 fases: 1) generación de ideas y recogida de información a través de una matriz DAFO, a través de 2 tipos de criterios, internos (fortalezas y debilidades), y externos (amenazas y oportunidades); 2) priorización de las propuestas de mejora recogidas. Selección de participantes: se identificaron informadores-clave teniendo en cuenta su relación y conocimiento del programa PAPPS. Se incluyeron a todos los integrantes de los grupos de expertos del PAPPS y miembros con participación en el pasado, así como a los componentes del organismo de coordinación, incluidos los responsables autonómicos del PAPPS. Se enviaron dos invitaciones a participar en el estudio: la primera desde el 29 diciembre de 2017 al 11 febrero de 2018, y la segunda entre el 10 y el 23 de enero de 2019. La información se obtuvo a partir de un cuestionario concebido para ser autocumplimentado. Resultados y conclusiones: Respondieron el cuestionario un total de 73 sujetos. El 35% de los participantes eran miembros de los grupos de trabajo del PAPPS, siendo el grupo más numeroso, seguido de médicos de familia de otros ámbitos, con el 20,5%. El orden de priorización de las propuestas de mejora fue el siguiente: 1) unificar recomendaciones con otros grupos de trabajo de semFYC; 2) elaborar listados con «Recomendaciones No hacer» desde el punto de vista de la prevención; 3) incorporar el PAPPS en la agenda política; 4) mayor coordinación e interacción entre grupos con competencias comunes; 5) docencia en pregrado y en unidades docentes, darse a conocer también a los estudiantes de Medicina; 6) revisión, actualización y difusión a cualquier profesional de Atención Primaria. Abstract: Objective: To analyze the situation, evaluation and proposals for improvement of the Preventive Activities and Health Promotion Program (PAPPS). Material and methods: A qualitative study of situation analysis was carried out for the evaluation of the PAPPS in 2 phases: 1) Generation of ideas and collection of information through a DAFO matrix, using 2 types of criteria: internal (strengths and weaknesses), and external (threats and opportunities); 2) Prioritization of the improvement proposals collected. Selection of participants: Key informants were identified taking into account their relationship and knowledge of the PAPPS program. All members of the PAPPS, expert groups and members with past participation were included, as well as the coordinators, including the autonomous leaders of the PAPPS. Two invitations to participate in the study were sent: the first from December 29, 2017 to February 11, 2018, and the second from January 10 to 23, 2019. The information was obtained from a questionnaire designed to be self-completed. Results and conclusions: A total of 73 subjects answered the questionnaire. 35% of the participants were members of the PAPPS working groups, followed by family doctors from other areas, with 20.5%. The order of prioritization of the improvement proposals was as follows: 1) Unify recommendations with other semFYC working groups; 2) Prepare lists with “Recommendations not to do” from the point of view of prevention; 3) Incorporate PAPPS in the political agenda; 4) Greater coordination and interaction between groups with common competences; 5) Teaching in undergraduate and teaching units; 6) Review, update and dissemination of the program in Primary Care.

Abstract Background Measurement of adenosine deaminase (ADA) can provide information about cell-mediated immunity. This report’s objective was to study the enzymatic activity of total ADA (tADA) and its isoenzymes ADA1 and ADA2 in canine, equine, porcine, and bovine serum and saliva and their changes in different inflammatory situations in each species. Besides, an automated method for ADA2 measurement was developed and validated. Results tADA was present in serum and saliva of healthy animals of the four species. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) concentration of 0.47 mM was needed for ADA1 inhibition in canine and porcine samples (serum and saliva) and bovine saliva, whereas for equine saliva 0.94 mM was needed. ADA2 activity was not detected in bovine serum and was very low or absent in equine serum and bovine saliva. An automated procedure to measure ADA2 consisting of adding EHNA to a commercial reagent for tADA measurement provided repetitive (coefficients of variation 0.90) results, being equivalent to a manual incubation of the sample with EHNA at a similar concentration. Salivary tADA, as well as ADA1 and ADA2, were higher in dogs with leishmaniosis, horses with acute abdominal disease and pigs with lameness than in healthy animals. tADA and isoenzymes in saliva showed a positive significant correlation with serum ferritin in dogs (r = 0.602, P

Abstract Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology.

Resumen: Introducción y objetivos: Las guías de práctica clínica no mencionan, específicamente, la reparación valvular en pacientes con insuficiencia aórtica y válvula aórtica bicúspide como alternativa al implante protésico. La reparación en bicúspides puede exigir técnicas complejas como la utilización de pericardio. Pretendemos analizar la evolución a largo plazo de la reparación en bicúspides y tricúspides. Métodos: Análisis prospectivo no-randomizado de 138 pacientes con reparación valvular aórtica (2011-2019). Dos grupos: bicúspides 55 (40%) y tricúspides 83 (60%). Resultados: Presentaban: grupo bicúspide: edad media 51,1 ± 13,8 años, 12 (21,8%) mujeres; EuroSCORE Logístico 6,7 ± 4; insuficiencia preoperatoria: I-II (25,4%), III-IV (74,6%). Grupo tricúspide: edad media 62,7 ± 12,6 años, 21 (25,3%) mujeres; 8 (9,6%) emergentes; EuroSCORE-Logístico 10,9 ± 8,1; insuficiencia preoperatoria: I-II (13,2%), III-IV (86,8%). Procedimientos realizados: bicúspides: reimplante valvular (DAVID) 24 (43,6%); remodelado aórtico (Yacoub) 18 (32,7%); tubo supracoronario + plastia aórtica 4 (7,3%); plastia aórtica 9 (16,4%); tricúspides: DAVID 54 (65,1%); Yacoub 4 (4,8%); tubo supracoronario + plastia aórtica 11 (13,3%); plastia aórtica 14 (16,9%). Procedimientos en velos: 56,6% (tricúspides) y 97,3% (bicúspides) p < 0,0001.Hubo conversión a prótesis intraoperatoria: 15 (18,1%) tricúspides y 1 (1,8%) bicúspides. Fallecieron 8 (5,8%) pacientes en el postoperatorio inmediato (3,9% de electivos).La mediana de seguimiento fue 42,5 meses. El gradiente pico (mmHg) en seguimiento: bicúspides 16,3 ± 5,4 vs. tricúspides 8,3 ± 1,4 (p < 0,0001).A nueve años están libres de insuficiencia aórtica ≥ III: 83,5%(serie-entera); 90,4% (tricúspides) vs. 73,9% (bicúspides), p = 0,07; 100% (tricúspides sin plastia pericardio) vs. 70,5% (tricúspides con plastia pericardio), p = 0,001; 92,9% (bicuspides sin plastia pericardio) vs. 57,7% (bicúspides con plastia pericardio), p = 0,009. Libres de reoperación: 88,4% (serie entera); 94,2% (tricúspides) vs. 80,1% (bicúspides), p = 0,086; 100% (tricúspides sin plastia pericardio) vs. 82,1% (tricúspides con plastia pericardio), p = 0,01; 100% (bicúspides sin plastia pericardio) vs. 62,7%(bicúspides con plastia pericardio), p = 0,007. Conclusiones: La válvula bicúspide precisa reparaciones complejas, pero menor conversión a prótesis intraoperatoria; la reparación en bicúspides ofrece resultados no inferiores a tricúspides, con buena durabilidad y hemodinámica; la utilización de pericardio, más frecuente en bicúspides, reduce la durabilidad. Abstract: Introduction and objectives: The clinical practice guidelines do not specifically mention valve repair in patients with aortic regurgitation and bicuspid aortic valve as an alternative to prosthesis implantation. Bicuspid repair may require complex techniques such as the use of pericardium. We intend to analyze the long-term evolution of bicuspid and tricuspid repair. Methods: prospective, non-randomized, analysis of 138 patients with aortic valve repair (2011-2019). Two groups: bicuspid valve 55 (40%) and tricuspid valve 83 (60%). Results: Bicuspid-group: mean age 51.1 ± 13.8 years, 12 (21.8%) women; EuroSCORE-Logistic 6.7 ± 4; preoperative-regurgitation: I-II (25.4%), III-IV (74.6%). Tricuspid-group: mean age 62.7 ± 12.6 years, 21 (25.3%) women; 8 (9.6%) emerging; EuroSCORE-Logistic 10.9 ± 8.1; preoperative-regurgitation: I-II (13.2%), III-IV (86.8%). Procedures performed: bicuspid-group: valve-reimplantation (DAVID) 24 (43.6%); aortic-remodeling (Yacoub) 18 (32.7%); supracoronary-tube + aortic-plasty-4 (7.3%); aortic-plasty 9 (16.4%). Tricuspid-group: DAVID 54 (65.1%); Yacoub 4 (4.8%); supracoronary-tube + aortic-plasty 11 (13.3%); aortic-plasty 14 (16.9%). Leaflet procedures: 56.6% (tricuspid-group) and 97.3% (bicuspid-group) p < 0.0001.There was conversion to intraoperative prosthesis: 15 (18.1%) tricuspid-group and 1(1.8%) bicuspid-group. Eight (5.8%) patients died in the immediate postoperative period (3.9% of electives).The median follow-up was 42.5 months. The peak gradient (mmHg) in follow-up: bicuspid-group 16.3 ± 5.4 vs. tricuspid-goup 8.3 ± 1.4 (p < 0.0001).At 9 years, they are free of aortic regurgitation ≥ III: 83.5% (whole-series); 90.4% (tricuspid-group) vs. 73.9% (bicuspid-group), p = 0.07; 100% (tricuspid-group-without-pericardium-plasty) vs. 70.5% (tricuspid-group-with-pericardium-plasty), p = 0.001; 92.9%(bicuspid-group-without-pericardium-plasty) vs. 57.7% (bicuspid-group-with-pericardium-plasty), p = 0.009. Free of re-operation: 88.4% (whole-series), 94.2% (tricuspid-group) vs. 80.1% (bicuspid-group), p = 0.086; 100%(tricuspid-group-without-pericardium-plasty) vs. 82.1% (tricuspid-group-with-pericardium-plasty), p = 0.01; 100% (bicuspid-group-without-pericardium-plasty) vs. 62.7% (bicuspid-group-with-pericardium-plasty), p = 0.007. Conclusions: The bicuspid valve requires complex repairs, but less conversion to an intraoperative prosthesis; bicuspid repair offers results not inferior to tricuspid repair, with good durability and hemodynamics; the use of pericardium, more frequent in bicuspid valves, reduces durability.

Summary Owing to its wide metabolic versatility and physiological robustness, together with amenability to genetic manipulations and high resistance to stressful conditions, Pseudomonas putida is increasingly becoming the organism of choice for a range of applications in both industrial and environmental applications. However, a range of applied synthetic biology and metabolic engineering approaches are still limited by the lack of specific genetic tools to effectively and efficiently regulate the expression of target genes. Here, we present a single‐plasmid CRISPR‐interference (CRISPRi) system expressing a nuclease‐deficient cas9 gene under the control of the inducible XylS/Pm expression system, along with the option of adopting constitutively expressed guide RNAs (either sgRNA or crRNA and tracrRNA). We showed that the system enables tunable, tightly controlled gene repression (up to 90%) of chromosomally expressed genes encoding fluorescent proteins, either individually or simultaneously. In addition, we demonstrate that this method allows for suppressing the expression of the essential genes pyrF and ftsZ, resulting in significantly low growth rates or morphological changes respectively. This versatile system expands the capabilities of the current CRISPRi toolbox for efficient, targeted and controllable manipulation of gene expression in P. putida.