Combinatorial immune checkpoint blockade increases myocardial expression of NLRP-3 and secretion of H-FABP, NT-Pro-BNP, interleukin-1ß and interleukin-6: biochemical implications in cardio-immuno-oncology.

Background: Immune checkpoint blockade in monotherapy or combinatorial regimens with chemotherapy or radiotherapy have become an integral part of oncology in recent years. Monoclonal antibodies against CTLA-4 or PD-1 or PDL-1 are the most studied ICIs in randomized clinical trials, however, more recently, an anti-LAG3 (Lymphocyte activation gene-3) antibody, Relatlimab, has been approved by FDA in combination with Nivolumab for metastatic melanoma therapy. Moreover, Atezolizumab is actually under study in association with Ipilimumab for therapy of metastatic lung cancer. Myocarditis, vasculitis and endothelitis are rarely observed in these patients on monotherapy, however new combination therapies could expose patients to more adverse cardiovascular events. Methods: Human cardiomyocytes co-cultured with human peripheral blood lymphocytes (hPBMCs) were exposed to monotherapy and combinatorial ICIs (PD-L1 and CTLA-4 or PD-1 and LAG-3 blocking agents, at 100 nM) for 48 h. After treatments, cardiac cell lysis and secretion of biomarkers of cardiotoxicity (H-FABP, troponin-T, BNP, NT-Pro-BNP), NLRP3-inflammasome and Interleukin 1 and 6 were determined through colorimetric and enzymatic assays. Mitochondrial functions were studied in cardiomyocyte cell lysates through quantification of intracellular Ca++, ATP content and NADH:ubiquinone oxidoreductase core subunit S1 (Ndufs1) levels. Histone deacetylases type 4 (HDAC-4) protein levels were also determined in cardiomyocyte cell lysates to study potential epigenetic changes induced by immunotherapy regimens. Results: Both combinations of immune checkpoint inhibitors exert more potent cardiotoxic side effects compared to monotherapies against human cardiac cells co-cultured with human lymphocytes. LDH release from cardiac cells was 43% higher in PD-L1/CTLA-4 blocking agents, and 35.7% higher in PD-1/LAG-3 blocking agents compared to monotherapies. HDAC4 and intracellular Ca++ levels were increased, instead ATP content and Ndufs1 were reduced in myocardial cell lysates (p < 0.001 vs. untreated cells). Troponin-T, BNP, NT-Pro-BNP and H-FABP, were also strongly increased in combination therapy compared to monotherapy regimen. NLRP3 expression, IL-6 and IL-1ß levels were also increased by PDL-1/CTLA-4 and PD-1/LAG-3 combined blocking agents compared to untreated cells and monotherapies. Conclusions: Data of the present study, although in vitro, indicate that combinatorial immune checkpoint blockade, induce a pro- inflammatory phenotype, thus indicating that these therapies should be closely monitored by the multidisciplinary team consisting of oncologists, cardiologists and immunologists.

Five-year (2015-2019) follow-up study of 6,526 cases of medical repatriation of Filipino seafarers.

BACKGROUND: There is a limited number of studies on the medical repatriation of seafarers. The aim of the study was to follow up on the previous 2010-2014 study using data from 2015-2019 to evaluate the epidemiology of medical repatriation among Filipino seafarers. MATERIALS AND METHODS: Data from medical repatriation records of Filipino seafarers from January 2015 to December 2019 were collected from various claims departments of different manning agencies in Manila, Philippines. RESULTS: Data from a total of 6,526 medical repatriation cases and 464,418 deployments in a 5-year period resulted in a medical repatriation rate calculated at 1.4%. We used the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) to determine the most common causes of repatriation. We found that these were musculoskeletal disorders, gastrointestinal problems, and traumatic injuries. The distribution of the specific illnesses per organ system is presented. CONCLUSIONS: Filipinos continue to represent the most numerous group of seafarers in the world. The continued profiling of health issues should lead to better health protocols and controlling medical costs. It should also lead to better prioritisation of health protection and care on board ships. Within the present 10-year database of medical repatriations coinciding with the implementation of Maritime Convention Labour Convention 2006, there is a compelling need to compare the two data sets to have an objective evaluation of the convention's projected goals.

Hypersensitivity to Non-Steroidal Anti-Inflammatory Drugs on a pediatric Portuguese cohort.

Summary: Background. Non-steroidal anti-inflammatory drugs (NSAID)/analgesics (paracetamol) are among the most common causes of drug hypersensitivity reactions in children, with a reported prevalence of around 0.3% in the pediatric population. Paracetamol and ibuprofen are the most commonly reported culprits in the pediatric population. Our objective was to describe the allergy workup to NSAID/paracetamol of a pediatric population monitored in an allergy outpatient clinic. Methods. Retrospective observational study by consulting the medical records of patients evaluated in a pediatric outpatient clinic with history of NSAID/paracetamol, between January 2016 to August 2022. Results. A total of 43 patients have been evaluated for NSAID/paracetamol suspected allergy: 53.5% females, mean age of 9.8 ± 5.1 years, 47.7% atopic. The drugs reported as culprits were: ibuprofen (75.6%), paracetamol (17.8%), metamizole (4.4%) and naproxen (2.2%) and clinical manifestations were mainly urticaria/angioedema and maculopapular exanthema. Skin tests were performed in 7 patients: paracetamol (n = 5) and metamizole (n = 2), which were all negative. Fourty-six drug provocation tests were performed: 28 with the culprit drug and 18 with an alternative one; only 2 were positive (ibuprofen - culprit NSAID group): one immediate periorbital angioedema and one delayed lip edema with oropharyngeal tightness. Conclusions. The investigation of allergy to NSAID/paracetamol in children remains a challenge. In our population, ibuprofen was the most common NSAID reported. There were only 2 (4.3%) mild reactions on DPT. We could allow the use of the culprit NSAID/analgesic in 11 patients and an alternative one in 9 patients. This study highlights the importance of DPT in children for a correct diagnosis of NSAID hypersensitivity and selection of an alternative drug.

Synergy between Genome Mining, Metabolomics, and Bioinformatics Uncovers Antibacterial Chlorinated Carbazole Alkaloids and Their Biosynthetic Gene Cluster from Streptomyces tubbatahanensis sp. nov., a Novel Actinomycete Isolated from Sulu Sea, Philippines.

In this study, a novel actinomycete strain, DSD3025T, isolated from the underexplored marine sediments in Tubbataha Reefs Natural Park, Sulu Sea, Philippines, with the proposed name Streptomyces tubbatahanensis sp. nov., was described using polyphasic approaches and characterized using whole-genome sequencing. Its specialized metabolites were profiled using mass spectrometry and nuclear magnetic resonance analyses, followed by antibacterial, anticancer, and toxicity screening. The S. tubbatahanensis DSD3025T genome was comprised of 7.76 Mbp with a 72.3% G+C content. The average nucleotide identity and digital DNA-DNA hybridization values were 96.5% and 64.1%, respectively, compared with its closest related species, thus delineating the novelty of Streptomyces species. The genome encoded 29 putative biosynthetic gene clusters (BGCs), including a BGC region containing tryptophan halogenase and its associated flavin reductase, which were not found in its close Streptomyces relatives. The metabolite profiling unfolded six rare halogenated carbazole alkaloids, with chlocarbazomycin A as the major compound. A biosynthetic pathway for chlocarbazomycin A was proposed using genome mining, metabolomics, and bioinformatics platforms. Chlocarbazomycin A produced by S. tubbatahanensis DSD3025T has antibacterial activities against Staphylococcus aureus ATCC BAA-44 and Streptococcus pyogenes and showed antiproliferative activity against colon (HCT-116) and ovarian (A2780) human cancer cell lines. Chlocarbazomycin A exhibited no toxicity to liver cells but moderate and high toxicity to kidney and cardiac cell lines, respectively. IMPORTANCE Streptomyces tubbatahanensis DSD3025T is a novel actinomycete with antibiotic and anticancer activities from Tubbataha Reefs Natural Park, a United Nations Educational, Scientific and Cultural Organization World Heritage Site in Sulu Sea and considered one of the Philippines' oldest and most-well-protected marine ecosystems. In silico genome mining tools were used to identify putative BGCs that led to the discovery of genes involved in the production of halogenated carbazole alkaloids and new natural products. By integrating bioinformatics-driven genome mining and metabolomics, we unearthed the hidden biosynthetic richness and mined the associated chemical entities from the novel Streptomyces species. The bioprospecting of novel Streptomyces species from marine sediments of underexplored ecological niches serves as an important source of antibiotic and anticancer drug leads with unique chemical scaffolds.

Unidades de convivencia en psicogeriatría / Coexistence units in psychogeriatrics

Las unidades de Psicogeriatría están realizando una evolución en su asistencia con la implantación de nuevos modelos asistenciales que pivotan sobre las personas atendidas, apoyados en la reforma de sus instalaciones, en la formación de los profesionales y en la aplicación de innovación terapéutica que repercute en una mejora de la calidad de vida de sus residentes. Se expone la experiencia en el área de mayores del Centro Sociosanitario Hermanas Hospitalarias en Palencia, en donde se ha realizado la transformación de plazas residenciales tradicionales en “unidades de convivencia” bajo el modelo de Atención Centrada en la Persona. Esto ha supuesto un cambio cultural en la asistencia y una evolución de los roles profesionales, tanto del personal técnico como del personal de atención directa, orientados hacia una mayor autonomía de la persona atendida. De forma paralela, como complemento necesario, se llevó a cabo el proceso de retirada de sujeciones en personas mayores (AU)

The Psychogeriatric units are making an evolution in their care with the implementation of new care models that pivot on the people served, supported by the reform of their facilities, the training of professionals and the application of therapeutic innovation that has repercussions on a improvement of the quality of life of its residents. The experience in the elderly area of the Sisters Hospitallers center in Palencia is exposed, where the transformation of traditional residential places into "coexistence units" has been carried out under the Person-Centered Care model. This has meant a cultural change in care and an evolution of professional roles, both for technical staff and direct care staff, oriented towards greater autonomy for the person being cared for. In parallel, as a necessary complement, the process of removing restraints in older people was carried out (AU)

High migratory propensity constitutes a single stock of an exploited cutlassfish species in the Northwest Pacific: A microsatellite approach.

Cutlassfishes, also known as hairtails, include multiple predatory fishes of the family Trichiuridae. They constitute a top marine fish commodity globally, yet the knowledge about their composition and intraspecific genetic structures is still limited. Trichiurus japonicus accounts for a major amount in the northwest Pacific fishery. Previous studies based on mitochondrial DNA markers reported incongruences in its population structure, hence prompting the need for high-resolution markers and avoiding possible shortcomings in its management. Here we genotyped ten novel de novo-assembled transcriptome-derived microsatellite markers on a total of 150 samples across five major fishing grounds (encompassing latitudes 22-39°N). These markers presented a high number of alleles and heterozygosity compared to other marine fishes, corresponding to the large effective population size of ~20,000 per location and cohort differentiation. Population structuring analyses suggested T. japonicus to be a homogenous well-mixed population. This configuration is likely attributed to the majority of its effective population migrates across locations, and the absence of oceanographic barriers at the continental shelves. Qingdao with reportedly high ocean productivity could be a genetic pseudosink based on the high heterozygosity and migratory preference. Moreover, the results of sign tests suggest that T. japonicus experienced a recent bottleneck likely concurrent with historical glaciation events. Further, we demonstrated satisfactory cross-amplifications of our markers on several congeners, indicating a great promise to use these markers to study the population genetics of trichiurids. Together, our findings will serve as an essential groundwork for enhancing resource conservation and management of cutlassfishes.

Use of Facebook, Instagram, and Twitter for recruiting healthy participants in nutrition-, physical activity-, or obesity-related studies: a systematic review.

BACKGROUND: There are limited systematic reviews exploring the use of social media for recruiting participants specifically for nutrition-, physical activity-, and obesity-related studies. OBJECTIVES: The aim was to conduct a systematic review on the effectiveness of using social media (Facebook, Instagram, and Twitter) for recruiting healthy participants in nutrition-, physical activity-, or obesity-related studies. METHODS: Studies were identified from 5 databases and included if they reported the number of participants recruited by social media (Facebook, Instagram, or Twitter) vs. traditional (print, e-mail, etc.). The effectiveness of recruitment was compared between methods by study procedures (in-person vs. online procedures). The cost-effectiveness of methods was also explored. The protocol was published in the Prospero database (ID# CRD42020204414). RESULTS: Twenty-six studies were included. Among studies with both types of recruitment methods, 49% of the sample was reached through traditional methods, 40% through social media, and the rest by other methods. For in-person study procedures, the median number of participants recruited using social media was 19 (range: 3-278) and for online study procedures, it was 298 (range: 3-17,069). Median recruitment cost using social media (n = 14 studies) was $11.90 (range: $0-517) per participant, while this varied considerably for traditional methods depending on how it was calculated ($214, $18.9-$777). The ratio of participants reached vs. recruited was 0.12%; the overall ratio of participants interactions vs. recruited was 21.2%. CONCLUSIONS: For in-person study procedures, traditional recruitment methods were more effective than social media, but for online study procedures, about half reported that social media was more effective. While more potential participants were reached through social media, only 21.2% of those who interacted with ads were enrolled. With the increased use of social media, their use for recruitment may be more frequent; therefore, future reviews may show different results.

Discapacidad intelectual y medidas adoptadas durante la pandemia de COVID-19: efectos comportamentales / Intellectual disability and adopted measures during the COVID-19 pandemic: behavioral effects

Actualmente, y en el contexto del estadode emergencia sanitaria, se han implantadouna serie de medidas de prevención y contenciónaplicables a toda la población. Enparticular, los centros sociosanitarios hantenido que adaptarse, diseñando medidasespeciales y aplicando planes de contingencia,que han provocado modificaciones en elentorno habitual de los residentes. Con elfin de observar los efectos de la pandemiasobre la conducta de personas con discapacidadintelectual residentes en un centrosociosanitario, se aplicó el Inventario parala Planificación de Servicios y ProgramaciónIndividual (ICAP). Los resultados, comparadoscon evaluaciones previas a la pandemiapor COVID-19, mostraron que el funcionamientoadaptativo era similar al anterior aeste periodo, pero existía un déficit en destrezasmotoras y en las destrezas de la vidaen comunidad. Así mismo, las alteracionesdel comportamiento habían aumentado, tantoen la puntuación general como en cadauno de sus índices específicos. Además, seencontró una relación inversa entre la edady la conducta adaptativa y una correlación positiva entre la edad y las alteraciones de la conducta. (AU)

Currently, and due to the existing healthemergency context, prevention and containmentmeasures applicable to the entirepopulation have been implemented. In particular,social and health centers have hadto adapt, designing a package of specialmeasures and applying guidelines and contingencyplans that have caused changes inthe habitual environment of the residents.In order to observe the effects of the pandemicon people with intellectual disabilitiesin social health centers, the Inventoryfor Client and Agency Planning (ICAP) wasapplied. The results, compared to previousevaluation, showed that adaptive functioningwas similar to that before this period,but there was a decrease in motor and socialskills. Furthermore, behavioral problems hadincreased, in the general index and in each of its specific index. In addition, an inverse relationship was found between age and adaptive behavior and a positive correlation between age and behavior disorders. (AU)

Hiperprolactinemia inducida por antipsicóticos en residentes de un centro sociosanitario / Antipsychotic-induced hyperprolactinemia in residents of a social health center

Hiperprolactinemia inducida por antipsicóticosen una población de un centro sociosanitario.Objetivos: La hiperprolactinemia es unefecto secundario de los antipsicóticos. Elobjetivo principal de este trabajo es conocerel nivel de prolactina en una muestrade pacientes ingresados en nuestro centroque toman antipsicóticos (APS) y si existeuna asociación significativa entre tener hiperprolactinemiay tomar cada uno de losantipsicóticos (solos o combinados).Método: Se mide el nivel de prolactina enuna muestra de pacientes (N=295; 71.1%son mujeres y 47.3% hombres), ingresadosen nuestro centro que toman antipsicóticos.Consideramos un nivel normal de prolactinahasta 25 ng/ml en mujeres y 20 ng/ml enhombres, por encima de estas cifras hablamosde hiperprolactinemia. Utilizamos paraanalizar los datos la herramienta SPSS 24.0para Windows: estudio descriptivo con tablasde frecuencias, la prueba de hipótesisChi-cuadrado y las medidas de asociación Vde Cramer y Lambda.Resultados: El 57.95% de los pacientestienen hiperprolactinemia. Cuando tomanAPS de 1ª generación (N=59) el 71.18 %,si toman APS de 2ª generación(N=168) el52.97% y cuando toman ambos (N= 68) el58.82%. Además, existe una asociación estadísticamentesignificativa entre tener hiperprolactinemiay tomar antipsicóticos deprimera generación, de segunda generación o ambos, así como que se tome un antipsicótico o dos, o más de dos. En nuestro trabajo los fármacos que máselevan la prolactina son: amisulpiride, ziprasidona,clorpromacina, risperidona y haloperidol.Y los que menos la elevan son:clozapina, risperidona depot, aripiprazol yolanzapina.(AU)

Antipsychotic-induced hyperprolactinemiain residents of a social health center.Objective: Hyperprolactinemia is a sideeffect of treatment with antipsychotics. Themain aim of this report was to study theprolactin level and assess the associationbetween hyperprolactinemia and receive antipsychoticsmedication (alone or in combination)in a sample of patiens admitted toour centre.Method: Prolactin level was measured in asample of inpatients in our centre (N=295:71.1% women and 47.3 % men). Hyperprolactinemiais usually defined by a sustainedprolactin level above the laboratory upper levelof normal. In our study, this normal levelwas considered at 25 ng/ml for woman andat 20ng/ml for men. Tha data were analyzedwith the SPSS 24.0 tool for Windows: adescriptive study by frequencies, hypothesistesting the Chi-square and the measure ofassociation Cramer's V and Lambda.Results: The 57.95% of the patients hadhyperprolactinemia. Among the ones whowere receiving first-generation antipsychotics(N = 59) the 71.18% have hyperprolactinemia.If they were receiving secondgenerationantipsychotics (N = 168) 52.97%and when they were receiving both (N = 68)58.82%.In addition, there is a statistically significantassociation between having hyperprolactinemiaand receiving first-generation orsecond-generation antipsychotics, or both;as well as receiving one antipsychotic or twoor more than two.In our study, the drugs that increase prolactinlevel the most were: amisulpiride, ziprasidone,chlorpromazine, risperidone andhaloperidol. And those that raise it the leastwere: clozapine, depot risperidone, aripiprazoleand olanzapine. (AU)

Instrucciones previas: breve guía para un ejercicio de autonomía / Advance instructions: short guide to an exercise of autonomy

Las instrucciones previas, también denominadas decisiones o voluntades anticipadas,o testamento vital, constituyen una manifestación de la voluntad de los pacientes y, por tanto, son expresión de la autonomía de la persona. Se definen como el proceso en el que una persona planifica los cuidados sanitarios y la asistencia que desea recibir en el futuro, en el momento en que no sea capaz de tomar decisiones por sí misma.La planificación anticipada de cuidados y decisiones (PACD), que incluye elaborar esos documentos de voluntades anticipadas, es un modo de relación asistencial sobre la que todavía hay poca experiencia en nuestro país.La PACD se define como un "proceso voluntario de comunicación y deliberación entre una persona capaz y profesionales implicados en su atención, acerca de los valores, deseosy preferencias que quiere que se tengan encuenta en la atención sanitaria que recibirácomo paciente, fundamentalmente en losmomentos finales de la vida" (1).El objetivo es que la persona, junto conlos profesionales, delibere y establezca cómoquiere ser tratada durante el proceso terapéutico.Incluye los valores relevantes delpaciente, las preferencias sanitarias de caráctergeneral, las indicaciones sanitariasconcretas (rechazo o solicitud de intervenciones,donación de órganos...), expresiónde sentimientos hacia otros ("lo siento","gracias", "te perdono", etc), y/o designarun representante.A través del documento de instruccionesprevias que confirma que se ha dado el procesode reflexión, comunicación y descripciónde esas voluntades anticipadas, las personaspueden decidir acerca de los tratamientos ycuidados de salud que desean o no recibircuando se encuentren en una circunstanciaen la que no puedan manifestar su voluntadpersonalmente.Su fundamento ético es:Respetar y promover la autonomía del paciente.Asegurar que se valoren las situaciones decompetencias limitadas o inexistentes. (AU)

Advance instructions, also called decisionsor advance directives, or living wills,constitute a manifestation of the will of the patients and, therefore, are an expression of the autonomy of the person. They are defined as the process in which a person plans the health care and assistance they want to receive in the future, at the time when they are not able to make decisions for themselves. Advance Care Planning and Decisions(ACPD) which includes developing these advance directives documents. It is something that the law does not collect but does not prevent, and there is very little experience and research on it. They define it as a "voluntary process of communication and deliberation between a capable person and professionals involved in their care, about the values, desires and preferences that they want to betaken into account in the health care thatthey will receive as a patient, fundamentallyin the moments end of life" (1).The objective is for the person, togetherwith the professionals, to establish how theywant to be treated during the therapeuticprocess. It includes the relevant values ofthe patient, general health preferences, specifichealth indications (refusal or requestfor interventions, organ donation ...), expressionof feelings towards others ("I'm sorry","thank you", "I forgive you", etc), and/or appoint a representative.Through the advance directive documentthat confirms that the process of reflection,communication and description of these advancedirectives has been given, people candecide about the treatments and health carethey want or not to receive when they are ina circumstance in the one that cannot expresstheir will personally.Its ethical foundation is:Respect and promote the autonomy of thepatient.Preserve that value in situations of limited or nonexistent skills. (AU)

Combined treatment of myo-inositol and d-chiro-inositol (80:1) as a therapeutic approach to restore inositol eumetabolism in patients with bipolar disorder taking lithium and valproic acid.

OBJECTIVE: Patients with bipolar disorder (BD) experience a poor quality of life (QoL) and a weak adherence to the therapy due to the various side effects occurring during the pharmacological therapy. To date clinicians have no tools to intervene on such effects, considering them as an unavoidable part of the therapy. This review paves the way for a step forward in the management of patients with BD bridging the therapeutic gap in clinical practice. MATERIALS AND METHODS: We reviewed the literature, searching through different databases (MEDLINE, Scopus, Google Scholar). We used different keywords, including bipolar disorder, lithium and valproic acid, inositol role in bipolar disorder, side effects, inositol depletion, supplementation of inositols under lithium treatment, inositol role in metabolism, hypothyroidism, renal and cardiac functionality. In particular, we narrowed the search down to English literature, excluding works before 1980s. Regarding clinical studies, we included case reports and both preclinical and clinical studies, especially only those exhibiting a control group. The outcome of the database search was to highlight the threat of side effects and the relationship with inositol lower levels, paving the way for a step forward in the management of patients with BD. RESULTS: Based on the collected evidence, the combined administration of myo-inositol (myo-ins) and d-chiro-inositol (d-chiro-ins) is strongly recommended in order to restore levels and metabolism of inositols. Previous studies pointed out the beneficial effects of inositols in recovering pathological conditions, like polycystic ovary syndrome (PCOS), hypothyroidism, weight gain, cardiac functionality, being all these conditions related to the depletion of inositols. Furthermore, a controlled dosage of inositols, up to 6 grams/daily, may reduce the side effects caused by lithium therapy, without hindering its central therapeutic role on patients' mood. CONCLUSIONS: Considering the iatrogenic depletion of inositols, the tailored ratio 80:1 in favour of myo-ins, may become a safe and effective strategy to counteract side effects, by providing a large amount of myo-ins and an adequate one of d-chiro-ins. The clinical dosage of inositols used as dietary supplementation is 4 grams/daily, and it may allow the recovery of the side effects and improve patients' QoL, without reducing the central therapeutic effect of the pharmacological therapy.

Hybrid Methacrylated Gelatin and Hyaluronic Acid Hydrogel Scaffolds. Preparation and Systematic Characterization for Prospective Tissue Engineering Applications.

Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels' mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.

Estigma y esquizofrenia / Stigma and schizophrenia

Revisión sobre el estigma en la esquizofrenia. Se abordan el concepto, los diferentes tipos de estigma y las consecuencias en las personas que lo padecen. Se aportan estrategias de tratamiento según la Organización Mundial de la Salud y otros autores. (AU)

Review of stigma in schizophrenia. The concept, the different types of stigma and the consequences for people who suffer from it are addressed. Treatment strategies according to the World Health Organisation and other authors are provided. (AU)

Simultaneous assessment of colon motility in children with functional constipation by cine-MRI and colonic manometry: a feasibility study.

BACKGROUND: Colonic manometry is the current reference standard for assessing colonic neuromuscular function in children with intractable functional constipation (FC). Recently, cine magnetic resonance imaging (cine-MRI) has been proposed as a non-invasive alternative. We compared colonic motility patterns on cine-MRI with those obtained by manometry in children, by stimulating high-amplitude propagating contractions (HAPCs) with bisacodyl under manometric control while simultaneously acquiring cine-MRI. METHODS: After Institutional Review Board approval, adolescents with FC scheduled to undergo colonic manometry were included. A water-perfused 8-lumen catheter was used for colonic manometry recordings. After an intraluminal bisacodyl infusion, cine-MRI sequences of the descending colon were acquired for about 30 min simultaneously with colonic manometry. Manometry recordings were analysed for HAPCs. MRI images were processed with spatiotemporal motility MRI techniques. The anonymised motility results of both techniques were visually compared for the identification of HAPCs in the descending colon. RESULTS: Data regarding six patients (three males) were analysed (median age 14 years, range 12-17). After bisacodyl infusion, three patients showed a total of eleven HAPCs with colonic manometry. Corresponding cine-MRI recorded high colonic activity during two of these HAPCs, minimal activity during seven HAPCs, while two HAPCs were not recorded. In two of three patients with absent HAPCs on manometry, colonic activity was recorded with cine-MRI. CONCLUSIONS: Simultaneous acquisition of colonic cine-MRI and manometry in children with FC is feasible. Their motility results did not completely overlap in the identification of HAPCs. Research is needed to unravel the role of cine-MRI in this setting.

Embryo size regulates the timing and mechanism of pluripotent tissue morphogenesis.

Mammalian embryogenesis is a paradigm of regulative development as mouse embryos show plasticity in the regulation of cell fate, cell number, and tissue morphogenesis. However, the mechanisms behind embryo plasticity remain largely unknown. Here, we determine how mouse embryos respond to an increase in cell numbers to regulate the timing and mechanism of embryonic morphogenesis, leading to the formation of the pro-amniotic cavity. Using embryos and embryonic stem cell aggregates of different size, we show that while pro-amniotic cavity formation in normal-sized embryos is achieved through basement membrane-induced polarization and exocytosis, cavity formation of increased-size embryos is delayed and achieved through apoptosis of cells that lack contact with the basement membrane. Importantly, blocking apoptosis, both genetically and pharmacologically, alters pro-amniotic cavity formation but does not affect size regulation in enlarged embryos. We conclude that the regulation of embryonic size and morphogenesis, albeit concomitant, have distinct molecular underpinnings.

The Use of Re-entry Devices in Aortoiliac Occlusive Disease.

Endovascular approach is the first-choice treatment in patients suffering from aortoiliac occlusions. Nevertheless, standard endoluminal revascularization fails in treating occlusions in about 20% (1) of cases. Thus, subintimal revascularization can be a solution, but it fails in 25% (2) of cases as well. In the last decades, different devices have been created, in order to ease the cross back into the true lumen, when standard subintimal revascularization does not work or risks to occlude important collateral vessels. Herein, we revise the currently available re-entry devices and their application in the aortoiliac occlusive pathology.

Virome of crab-eating (Cerdocyon thous) and pampas foxes (Lycalopex gymnocercus) from southern Brazil and Uruguay.

Crab-eating (Cerdocyon thous) and Pampas foxes (Lycalopex gymnocercus) are wild canids distributed in South America. Domestic dogs (Canis lupus familiaris) and wild canids may share viral pathogens, including rabies virus (RABV), canine distemper virus (CDV), and canine parvovirus 2 (CPV-2). To characterize the virome of these wild canid species, the present work evaluated the spleen and mesenteric lymph node virome of 17 crab-eating and five Pampas foxes using high-throughput sequencing (HTS). Organ samples were pooled and sequenced using an Illumina MiSeq platform. Additional PCR analyses were performed to identify the frequencies and host origin for each virus detected by HTS. Sequences more closely related to the Paramyxoviridae, Parvoviridae and Anelloviridae families were detected, as well as circular Rep-encoding single-stranded (CRESS) DNA viruses. CDV was found only in crab-eating foxes, whereas CPV-2 was found in both canid species; both viruses were closely related to sequences reported in domestic dogs from southern Brazil. Moreover, the present work reported the detection of canine bocavirus (CBoV) strains that were genetically divergent from CBoV-1 and 2 lineages. Finally, we also characterized CRESS DNA viruses and anelloviruses with marked diversity. The results of this study contribute to the body of knowledge regarding wild canid viruses that can potentially be shared with domestic canids or other species.

Relevancia de la cuantificación en los estudios PET cerebrales con 18F-FDG / Relevance of quantification in brain PET studies with 18F-FDG

La inclusión de la PET 18F-FDG como biomarcador en los criterios de diagnóstico clínico de enfermedades neurodegenerativas y su indicación en el estudio precirugía en la epilepsia resistente a los fármacos permiten mejorar la especificidad del diagnóstico. La interpretación clásica de los estudios PET neurológicos se ha abordado de forma cualitativa, aunque en la última década hemos sido testigos del auge en los sistemas de evaluación cuantitativa. Este desarrollo técnico es de vital importancia en la práctica clínica, ya que mejora la especificidad y la reproducibilidad y reduce el efecto dependiente del observador derivado del análisis visual. Consideramos que es conveniente exponer la complejidad de las técnicas de procesamiento de imagen empleadas, lo que permitirá al especialista en Medicina Nuclear conocer sus ventajas e inconvenientes a la hora de incluirlas en la práctica clínica diaria

The inclusion of 18F-FDG PET as a biomarker in the diagnostic criteria of neurodegenerative diseases and its indication in the presurgical assessment for drug-resistant epilepsies allow to improve specificity of these diagnosis. The traditional interpretation of neurological PET studies has been performed qualitatively, although in the last decade, several quantitative evaluation methods have emerged. This technical development has become relevant in clinical practice, improving specificity, reproducibility and reducing the interrater reliability derived from visual analysis. In this article we update/review the main imaging processing techniques currently used. This may allow the Nuclear Medicine physician to know their advantages and disadvantages when including these procedures in daily clinical practice

Relevance of quantification in brain PET studies with 18F-FDG. / Relevancia de la cuantificación en los estudios PET cerebrales con 18F-FDG.

The inclusion of 18F-FDG PET as a biomarker in the diagnostic criteria of neurodegenerative diseases and its indication in the presurgical assessment for drug-resistant epilepsies allow to improve specificity of these diagnosis. The traditional interpretation of neurological PET studies has been performed qualitatively, although in the last decade, several quantitative evaluation methods have emerged. This technical development has become relevant in clinical practice, improving specificity, reproducibility and reducing the interrater reliability derived from visual analysis. In this article we update/review the main imaging processing techniques currently used. This may allow the Nuclear Medicine physician to know their advantages and disadvantages when including these procedures in daily clinical practice.

Effectiveness of a chat-bot for the adult population to quit smoking: protocol of a pragmatic clinical trial in primary care (Dejal@).

BACKGROUND: The wide scale and severity of consequences of tobacco use, benefits derived from cessation, low rates of intervention by healthcare professionals, and new opportunities stemming from novel communications technologies are the main factors motivating this project. Thus, the purpose of this study is to assess the effectiveness of an intervention that helps people cease smoking and increase their nicotine abstinence rates in the long term via a chat-bot, compared to usual practice, utilizing a chemical validation at 6 months. METHODS: Design: Randomized, controlled, multicentric, pragmatic clinical trial, with a 6-month follow-up. SETTING: Healthcare centers in the public healthcare system of the Community of Madrid (Madrid Regional Health Service). PARTICIPANTS: Smokers > 18 years of age who attend a healthcare center and accept help to quit smoking in the following month. N = 460 smokers (230 per arm) who will be recruited prior to randomization. Intervention group: use of a chat-bot with evidence-based contents to help quit smoking. CONTROL GROUP: Usual treatment (according to the protocol for tobacco cessation by the Madrid Regional Health Service Main variable: Continuous nicotine withdrawal with chemical validation (carbon monoxide in exhaled air). Intention-to-treat analysis. Difference between groups in continuous abstinence rates at 6 months with their corresponding 95% confidence interval. A logistic regression model will be built to adjust for confounding factors. RESULTS: First expected results in January 2020. DISCUSSION: Providing science-based evidence on the effectiveness of clinical interventions via information technologies, without the physical presence of a professional, is essential. In addition to being more efficient, the characteristics of these interventions can improve effectiveness, accessibility, and adherence to treatment. From an ethics perspective, this new type of intervention must be backed by scientific evidence to circumvent pressures from the market or particular interests, improve patient safety, and follow the standards of correct practices for clinical interventions. TRIAL REGISTRATION: ClinicalTrials.gov, reference number NCT03445507.