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Background: Stress and anxiety are common problems among nursing students, affecting their mental health and academic performance. Compassion training has been shown to be effective in reducing these states. Objectives: This study evaluated the effects of a compassion-based course on perceived stress and anxiety (state and trait) among nursing students at a state university in Chile. Methods: A pre-experimental design was implemented with 45 second-year students, who completed evaluations before and after the intervention. The course included 10 sessions involving compassion meditation, mindfulness, self-compassion exercises, and autonomous practice. Results: The results showed significant reductions in and a high effect size regarding perceived stress (Cohen’s d = 0.83) and state anxiety (Cohen’s d = 0.74), while trait anxiety showed a moderate reduction (Cohen’s d = 0.34). Mediation analysis revealed that increases in self-compassion mediated the relationship between autonomous practice time and reductions in stress and trait anxiety. Conclusions: These findings suggest that compassion training is an effective strategy for reducing stress and anxiety in nursing students, improving their emotional regulation and preparation for professional practice. Therefore, it is necessary to include this approach in students’ curricular programs.

Introduction: Ophthalmological conditions in international travelers may be associated with low mortality but high morbidity. Eye involvement in travelers is less frequently reported than febrile, gastrointestinal and respiratory infections, but data probably represent a degree of under-notification. Methods: an extensive narrative review of the main viral, bacterial, fungal and parasitic infections affecting the eye in travelers was performed. Main findings: Common respiratory tract viral infections may cause ocular complications in travelers, human influenza viruses have been associated with conjunctivitis and emerging avian influenza subtypes may also affect the eye. Vector-borne viral infections may affect travelers, usually with systemic symptoms, but eye disease may be the first presenting feature. A spectrum of manifestations have been described with dengue, chikungunya and Zika infections, including conjunctivitis, anterior uveitis, posterior uveitis with chorioretinitis and macular involvement. Staphylococcus spp, Streptococcus spp, and Pseudomonas spp (especially associated with use of contact lenses) are common causes of keratitis, however, resistance patterns to antimicrobials might vary depending on area of travel. Less frequent infections, such as Burkholderia pseudomallei, associated with environmental exposure, and Bartonella spp. may rarely present with ophthalmological involvement in travelers. Fungal ocular infections, especially after ocular trauma caused by plants and contact lens use, should be considered in patients with stromal keratitis not improving with antibiotic eye drops. Parasitic eye infections tend to occur in tropical areas, but some, such as acanthamoebic keratitis or Toxoplasma spp retinitis, are found worldwide. Increasing exposure to animals, undercooked food consumption or poor hygiene during international travels might be leading to the emergence of certain parasitic eye diseases. Conclusions: Clinical features, with identification of risk factors and geographical region of exposure, can assist in the definitive diagnosis of imported ophthalmological infections. Management of imported eye infections requires a multi-disciplinary approach involving ophthalmologists, travel medicine/infectious diseases physicians and other specialists.

Pain assessment is essential in laboratory and farm animals. Grimace scales have been used for this purpose since 2010. The aim of the present study was to investigate how pain (due to disease presence) affects the main facial expressions of goat kids. For this purpose, 60 goat kids aged 1 to 20 days were included in the study. An experienced veterinarian graded the animals’ pain based on his experience (pain 0, 1, and 2), and two photographs (frontal and lateral) were taken. The following measurements were recorded: Height and width of the palpebral fissure, mouth angle, angles of the nose in profile and front. Pain level affected the height (0.83 and 1.29 cm, pain level 0 and 2 respectively, p

Chromosomal instability (CIN) is a hallmark of cancer aggressiveness, providing genetic plasticity and tumor heterogeneity that allows the tumor to evolve and adapt to stress conditions. CIN is considered a cancer therapeutic biomarker because healthy cells do not exhibit CIN. Despite recent efforts to identify therapeutic strategies related to CIN, the results obtained have been very limited. CIN is characterized by a genetic signature where a collection of genes, mostly mitotic regulators, are overexpressed in CIN‐positive tumors, providing aggressiveness and poor prognosis. We attempted to identify new therapeutic strategies related to CIN genes by performing a drug screen, using cells that individually express CIN‐associated genes in an inducible manner. We find that the overexpression of targeting protein for Xklp2 (TPX2) enhances sensitivity to the proto‐oncogene c‐Src (SRC) inhibitor dasatinib due to activation of the Yes‐associated protein 1 (YAP) pathway. Furthermore, using breast cancer data from The Cancer Genome Atlas (TCGA) and a cohort of cancer‐derived patient samples, we find that both TPX2 overexpression and YAP activation are present in a significant percentage of cancer tumor samples and are associated with poor prognosis; therefore, they are putative biomarkers for selection for dasatinib therapy.

Abstract Background In non-endemic countries, malaria can be transmitted through blood donations from imported cases. To ensure standards of quality and safety of human blood, the European Union and Spanish national law, requires a deferral period, or a screening by immunological or genomic test among those donors with potential risk of malaria. Scientific societies, European Committee on Blood Transfusion, and Spanish Society of Haematology and Haemotherapy, refer only to the result of the immunological test. Methods An observational retrospective study was performed in potential donors with a positive immunological test for malaria done in the Regional Transfusion Center in Madrid and referred to the National Reference Unit for Tropical Diseases in Madrid between 2015–2020. At consultation a Polymerase Chain Reaction (PCR) for malaria was performed. Results During the study period, 121 possible donors attended for consultation at NRU-Trop. Median age: 38.5 (IQR:33–48); median time to consultation was 32 months (IQR:12.5–110). Eighty-two (67.8%) donors were migrants and thirty-nine were travellers (32.2%). ELISA values were available for 109 subjects (90.1%), 56 individual left malaria endemic area > 3 years before. All donors tested negative for Plasmodium spp PCR test (n = 121, 100%). Conclusions None of the subjects with a positive immunologic test deferred as blood donors had a positive genomic test. The presence of Plasmodium spp in collected blood was not detected by molecular techniques. To avoid the loss of potential blood donors, especially those with low incidence red blood cell antigens, as more precise microbiology techniques become available, updating the existing legislation becomes necessary to increase the availability of donated blood.

Este ensayo expone el trabajo realizado en la asignatura “Diseño de la investigación”, del Grado en Ingeniería de Diseño Industrial de Elisava. Observamos como se unen los métodos de trabajo de la ingeniería, el método de proyectar, el proceso de diseño industrial, y la narrativa utilizada para la conexión entre la academia y lo profesional. Desarrollamos un trabajo de indización que aporta un índice de contenidos como nexo para sincronizar: la definición de la propuesta de investigación, el desarrollo de la investigación, y la configuración de la estructura dåe contenidos que se mostrará en la memoria de investigación del TFG.

This review explores the state‐of‐the‐art of thermoelectric materials, covering different crystalline structures and material families (e.g., chalcogenides, Zintl phases, skutterudites, clathrates, oxides, half‐Heusler, organic–inorganic composites, metal–organic frameworks, and silicides). It examines their corresponding thermoelectric properties while considering the synthesis methods employed, paying significant attention to those that particularly follow sustainable routes. Additionally, the work addresses current challenges in the field, such as enhancing stability at high temperatures and reducing manufacturing costs. The understanding gained in this field opens avenues for designing more efficient and sustainable devices to convert waste heat into electrical energy, thereby advancing cleaner technologies.

IntroductionNowadays, many dairy sheep farms opt for milk replacers after birth. Weaning lambs from milk replacers is expected to be a stressful situation.MethodsWith the aim of researching this practice on the animal behavior, body weight yields, and sanitary status of Lacaune lambs, 60 healthy animals from the same lambing house were employed. Lambs were housed in a pen and had ad libitum access to forage, compound feed, and milk replacers. During a 4 days preexperimental period in which all the animals were fed with milk replacers, behavior, hematologic parameters, body weight and seric and fecal stress indicators were recorded. Later, an experimental period took place in which 20 lambs remained in the same conditions. Another 20 lambs were kept in a separate pen in the same barn under the same conditions, but the artificial milk feeding was interrupted (weaning). The third 20 lambs were weaned and also rehoused in fattening pens. After 4 days, the variables previously recorded in the three groups during the pre-experimental period were recorded again.ResultsResults showed that change of location and change of feed can have different and synergic effects on the behavior of the lambs. Change of feed had not specifically different effect on body weight than change of location. In the other hand, weaning had no significative effects on hematologic parameters and seric and fecal stress indicators.DiscussionWeaning from artificial milk had significative effects on lambs weight and behavior. More research is needed to improve this ethical aspect in ovine production.

Abstract Background Control of the zoonotic food-borne parasite Fasciola hepatica remains a major challenge in humans and livestock. It is estimated that annual economic losses due to fasciolosis can reach US$3.2 billion in agriculture and livestock. Moreover, the wide distribution of drug-resistant parasite populations and the absence of a vaccine threaten sustainable control, reinforcing the need for novel flukicides. Methods The present work analyses the flukicidal activity of a total of 70 benzimidazole derivatives on different stages of F. hepatica. With the aim to select the most potent ones, and screenings were first performed on eggs at decreasing concentrations ranging from 50 to 5 µM and then on adult worms at 10 µM. Only the most effective compounds were also evaluated using a resistant isolate of the parasite. Results After the first screenings at 50 and 10 µM, four hit compounds (BZD31, BZD46, BZD56, and BZD59) were selected and progressed to the next assays. At 5 µM, all hit compounds showed ovicidal activities higher than 71% on the susceptible isolate, but only BZD31 remained considerably active (53%) when they were tested on an albendazol-resistant isolate, even with values superior to the reference drug, albendazole sulfoxide. On the other hand, BZD59 displayed a high motility inhibition when tested on adult worms from an albendazole-resistant isolate after 72 h of incubation. Conclusions BZD31 and BZD59 compounds could be promising candidates for the development of fasciolicidal compounds or as starting point for the new synthesis of structure-related compounds. Graphical Abstract

Abstract Despite the historically documented regularity in human mobility patterns, the relaxation of spatial and temporal constraints, brought by the widespread adoption of telecommuting and e-commerce during the COVID-19 pandemic, as well as a growing desire for flexible work arrangements in a post-pandemic work, indicates a potential reshaping of these patterns. In this paper, we investigate the multifaceted impacts of relaxed spatio-temporal constraints on human mobility, using well-established metrics from the travel behavior literature. Further, we introduce a novel metric for schedule regularity, accounting for specific day-of-week characteristics that previous approaches overlooked. Building on the large body of literature on the impacts of COVID-19 on human mobility, we make use of passively tracked Point of Interest (POI) data for approximately 21,700 smartphone users in the US, and analyze data between January 2020 and September 2022 to answer two key questions: (1) has the COVID-19 pandemic and its associated relaxation of spatio-temporal activity patterns reshaped the different aspects of human mobility, and (2) have we achieved a state of stable post-pandemic “new normal”? We hypothesize that the relaxation of the spatiotemporal constraints around key activities will result in people exhibiting less regular schedules. Findings reveal a complex landscape: while some mobility indicators have reverted to pre-pandemic norms, such as trip frequency and travel distance, others, notably at-home dwell-time, persist at altered levels, suggesting a recalibration rather than a return to past behaviors. Most notably, our analysis reveals a paradox: despite the documented large-scale shift towards flexible work arrangements, schedule habits have strengthened rather than relaxed, defying our initial hypotheses and highlighting a desire for regularity. The study’s results contribute to a deeper understanding of the post-pandemic “new normal”, offering key insights on how multiple facets of travel behavior were reshaped, if at all, by the COVID-19 pandemic, and will help inform transportation planning in a post-pandemic world.

Background: Chronic schistosomiasis can lead to significant morbidity. Serology is highly sensitive; however, its role in assessing treatment response is controversial. This study aimed to analyze serological values following treatment of chronic imported schistosomiasis. Methods: A retrospective observational study was performed including patients treated for chronic imported schistosomiasis from 2018 to 2022 who had at least one serological result at baseline and during follow-up. Demographic, clinical, and laboratory data were evaluated. Generalized estimating equation (GEE) models and Kaplan–Meier curves were used to analyze the evolution of serological values. Results: Of the 83 patients included, 72 (86.7%) were male, and the median age was 26 years (IQR 22–83). Most patients, 76 (91.6%), were migrants from sub-Saharan Africa. While 24 cases (28.9%) presented with urinary symptoms, the majority (59; 71.1%) were asymptomatic. Schistosoma haematobium eggs were observed in five cases (6.2%). Eosinophilia was present in 34 participants (40.9%). All patients had an initial positive Schistosoma ELISA serology, median ODI 2.3 (IQR 1.5–4.4); the indirect hemagglutination (IHA) test was positive/indeterminate in 34 cases (43.1%). Following treatment with praziquantel, serology values significantly decreased: −0.04 (IC95% −0.073, −0.0021) and −5.73 (IC95% −9.92, −1.53) units per month for ELISA and IHA, respectively. A quarter of patients (25%) had negative ELISA results 63 weeks after treatment. All symptomatic cases were clinically cured. Conclusions: Serial serological determinations could be helpful for monitoring chronic schistosomiasis in non-endemic regions. The ideal timing for these follow-up tests is yet to be determined. Further research is needed to determine the factors that influence a negative result during follow-up.

No hospitalizations or deaths occurred in residents with the COVID-19 infection, treated with antihistamines and azithromycin, of two external nursing homes during the first wave. We assessed whether patients receiving chronic antihistamines in our institution showed better clinical evolution. COVID-19 admissions and related deaths in the public Hospital of Terrassa (n = 1461) during the pandemic period (11 March 2020–5 May 2023) and cases (n = 32,888) during the period of full suspicion diagnosis (1 June 2020–23 March 2022) were referred to as the number of chronic treatments (nT) including or not including antihistamines (AntiHm or NOAntiHm), and their vaccination status before the first infection (VAC or NoVAC) in our assigned population (n = 140,681 at March 2020) was recorded. No deaths occurred in patients treated with up to ≤6 nT in the AntiHm group in all ages. A significant reduction in hospital admission was observed in the 2–7 nT groups either below or over 60 years old [Odds Ratio (OR) NoAntiHm/AntiHm = 1.76–1.32, respectively, in NoVAC or VAC (OR = 2.10 overall] and in the older ≥8 nT group (OR = 2.08 in NoVac]. In conclusion, patients with chronic antihistamine prescriptions, alone or with polypharmacy, showed reduced hospital admission and mortality rates, suggesting the safety of antihistamine treatment and the need to confirm its effectiveness in a prospective trial.

Circulating immunoglobulin G (IgG) concentrations in newborn goat kids are not sufficient to protect the animal against external agents. Therefore, consumption of colostrum, rich in immune components, shortly after birth is crucial. Traditional laboratory methods used to measure IgG concentrations, such as ELISA or RID, are reliable but costly and impractical for many farmers. This study proposes a more accessible alternative for farmers to predict IgG concentration in goat colostrum by integrating color-based techniques with machine learning models, specifically decision trees and neural networks, through the development of two regression models based on colostrum color data from Majorera dairy goats. A total of 813 colostrum samples were collected in a previous study (June 1997–April 2003) that utilized multiple regression analysis as a reference to verify that applying data science techniques improves accuracy and reliability. The decision tree model outperformed the neural network, achieving higher accuracy and lower error rates. Both models provided predictions that closely matched IgG concentrations obtained by ELISA. Therefore, this methodology offers a practical and affordable solution for the on-farm assessment of colostrum quality (i.e., IgG concentration). This approach could significantly improve farm management practices, ensuring better health outcomes in newborn animals by facilitating timely and accurate colostrum quality evaluation.

Background: Cytomegalovirus (CMV) infection is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in patients receiving novel hematological therapies. Its impact on morbidity and mortality necessitates effective management strategies. Despite recent advances in diagnostics and treatment, unresolved questions persist regarding monitoring and treatment, prompting the need for updated recommendations. Methods: A consensus was reached among a panel of experts selected for their expertise in CMV research and clinical practice. Key clinical areas and questions were identified based on previous surveys and literature reviews. Recommendations were formulated through consensus and graded using established guidelines. Results: Recommendations were provided for virological monitoring, including the timing and frequency of CMV DNAemia surveillance, especially during letermovir (LMV) prophylaxis. We evaluated the role of CMV DNA load quantification in diagnosing CMV disease, particularly pneumonia and gastrointestinal involvement, along with the utility of specific CMV immune monitoring in identifying at-risk patients. Strategies for tailoring LMV prophylaxis, managing breakthrough DNAemia, and implementing secondary prophylaxis in refractory cases were outlined. Additionally, criteria for initiating early antiviral treatment based on viral load dynamics were discussed. Conclusion: The consensus provides updated recommendations for managing CMV infection in hematological patients, focusing on unresolved issues in monitoring, prophylaxis, treatment, and resistance. These recommendations aim to guide clinical practice and improve outcomes in this high-risk population. Further research is warranted to validate these recommendations and address ongoing challenges in CMV management with emerging antiviral combinations, particularly in pediatric populations.

Abstract A single and rapid method to obtain an antigenic fraction of excretory-secretory antigens (ESAs) from Fasciola hepatica suitable for serodiagnosis of fascioliasis is reported. The procedure consists in the negative selection of F. hepatica ESAs by hydroxyapatite (HA) chromatography (HAC; fraction HAC-NR) followed by antigen precipitation with 50% ammonium sulphate (AS) and subsequent recovery by means of a Millex-GV or equivalent filter (Fi-SOLE fraction). Tested in indirect ELISA, the Fi-SOLE antigens detected natural infections by F. hepatica with 100% sensitivity and 98.9% specificity in sheep, and 97.7% sensitivity and 97.7% specificity in cattle, as determined by ROC analysis. The SDS-PAGE and proteomic nano-UHPLC-Tims-QTOF MS/MS analysis of fractions showed that the relative abundance of L-cathepsins and fragments thereof was 57% in fraction HAC-NR and 93.8% in fraction Fi-SOLE. The second most abundant proteins in fraction HAC-NR were fatty-acid binding proteins (11.9%). In contrast, free heme, and heme:MF6p/FhHDM-1 complexes remained strongly bond to the HA particles during HAC. Interestingly, phosphorylcholine (PC)-bearing antigens, which are a frequent source of cross-reactivity, were detected with an anti-PC mAb (BH8) in ESAs and fraction HAC-NR but were almost absent in fraction Fi-SOLE.

Los ministros de Asuntos Exteriores de la Unión Europea recordaban en la reunión de principios de octubre de 2023 en Kiev, que Rusia es una amenaza existencial y que la victoria de la guerra depende de la cooperación con Europa. Mientras que los antiguos integrantes del bloque soviético perciben la amenaza rusa como inmediata y existencial, los países mediterráneos, sienten que su foco inmediato de atención está en la Frontera Sur y en el llamado Sur Global. La necesidad de cambiar el enfoque de la Unión Europea hacia los países en desarrollo es fundamental para la supervivencia, como actor geopolítico, de una Europa que no logra superar la visión eurocéntrica y occidental del mundo, y que sigue considerando el reordenamiento global en curso como complicado, pero no imposible de manejar.

The dorsomedial hypothalamus nucleus (DMH) plays a pivotal role in the orchestration of sympathetic nervous system activities. Through its projections to the brainstem and pontomedullary nuclei, it controls heart rate, contractility, blood pressure, and respiratory activity, such as timing and volumes. The DMH integrates inputs from higher brain centers and processes these signals in order to modulate autonomic outflow accordingly. It has been demonstrated to be of particular significance in the context of stress responses, where it orchestrates the physiological adaptations that are necessary for all adaptative responses. The perifornical region (PeF), which is closely associated with the DMH, also makes a contribution to autonomic regulation. The involvement of the PeF region in autonomic control is evidenced by its function in coordinating the autonomic and endocrine responses to stress, frequently in conjunction with the DMH. The DMH and the PeF do not function in an isolated manner; rather, they are components of a comprehensive hypothalamic network that integrates several autonomic responses. This neural network could serve as a target for developing therapeutic strategies in cardiovascular diseases.

Endemic in over 45 countries globally, recent reports of locally acquired melioidosis in novel geographical areas, such as the Southern US, have highlighted the expanding geographical range of Burkholderia pseudomallei. Climate change and severe weather events have been linked to an increase in cases of melioidosis, which follows environmental exposure to the bacterium. Healthcare professionals should be aware of the possibility of the disease, with its diverse and often delayed presentations, even in areas not previously known to have risk. Over 200 cases of travel-associated melioidosis have been reported in the literature, highlighting the need to consider this disease in non-endemic areas, as diagnostic delays of up to 18 months have been identified. The review updates the global epidemiology of melioidosis, focusing on new geographical areas where cases have been diagnosed and imported cases, unusual clinical presentations and co-infections, and less frequent modes of transmission (laboratory exposures and the risk of acquisition due to imported infected animals and contaminated products).

The effect of liver fibrosis on mild cognitive impairment (MCI) and dementia risk in type 2 diabetes mellitus (T2DM) patients is unclear. Therefore, we performed a prospective cross-sectional study on 219 patients with T2DM and older than 60 years to evaluate the association between liver fibrosis, liver steatosis, and cognitive impairment. The Montreal Cognitive Assessment (MoCA) was used to screen for MCI or dementia. Liver fibrosis was estimated using the non-invasive Fibrosis-4 (FIB-4) score, and liver steatosis was assessed with the hepatic steatosis index. The mean age was 71 ± 6 years, 47% were women and according to MoCA cut-off values, 53.88% had MCI and 16.43% had dementia. A moderate or high risk of advanced fibrosis was significantly higher in patients with MCI or dementia compared to those with normal cognition (p < 0.001). After adjusting for confounders, a FIB-4 score greater than 1.54 was associated with MCI or dementia (p = 0.039). Multivariate analysis identified age over 70.5 years, antiplatelet medication use, and a FIB-4 score above 1.54 as the most relevant risk factors. Liver fibrosis, but not liver steatosis, is associated with MCI or dementia in older T2DM patients, suggesting that FIB-4 score might be a simple biomarker for the detection of cognitive impairment.

Background: Observational studies reported worse COVID-19 evolution in relation to polypharmacy and reductions in COVID-19 hospital admissions and death in patients receiving chronic antihistamine treatment. The current profile of hospitalized patients with regard to different variants was analyzed to identify specific targets for future prospective trials. Methods: COVID-19 admissions to the Hospital of Terrassa (11 March 2020–28 August 2024 (n = 1457), from the integral Consorci Sanitari de Terrassa population (n = 167,386 people) were studied. Age, gender, the number of chronic treatments (nT), and immunization status were analyzed. Results: After 5 May 2023, 291 patients (54% females) required COVID hospitalization. Of these, 39% received >8 nT (23% receiving 5–7 nT), 70.2% were >70 years, and 93.4% survived. In total, 12% of patients admitted after 5 May 2024 were not vaccinated, while 59% received ≥4 vaccines (43% within the last 12 months). In total, 49% of admitted patients presented no previous infection (while 3% presented infection during the last year). Delta or Omicron variants would have accounted for ≥80% of admissions > 60 years compared to the first pandemic wave if no vaccines existed. Conclusions: Patients > 70 years who receive ≥5 nT, without prior COVID-19 infections, should be the priority for prevention, with updated vaccination and early treatments to reduce hospitalizations.

Cinq mentions inhabituelles de tribus pour les femmes sur des inscriptions de la colonie Iulia Sicca Veneria et sa pertica sont étudiées. La recherche des nomina nous éclaire sur ce que l'on voulait transmettre en incluant la tribu dans le contexte démographique et onomastique des lieux où elles ont été trouvées.

Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myeloma control and immunological scape as mechanism of disease progression. We retrospectively analyzed the clinical impact of the CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. Patients with a CD200 rs1131199 GG genotype showed a median overall survival (OS) significantly lower than those with CC+CG genotype (67.8 months versus 94.4 months respectively; p: 0.022) maintaining significance in the multivariate analysis. This effect was specially detected in patients not receiving an autologous stem cell transplant (auto-SCT) (p < 0.001). In these patients the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM (p: 0.02) mainly due to infections events.

Abstract INTRODUCTION Biomarker‐informed criteria were proposed for the diagnosis of Alzheimer's disease (AD) by the National Institute on Aging and the Alzheimer's Association (NIA‐AA) in 2011; however, the adequacy of this criteria has not been sufficiently evaluated. METHODS ReDeMa (Red de Demencias de Madrid) is a regional cohort of patients attending memory and neurology clinics. Core cerebrospinal fluid biomarkers were obtained, NIA‐AA diagnostic criteria were considered, and changes in diagnosis and management were evaluated. RESULTS A total of 233 patients were analyzed (mean age 70 years, 50% women, 73% AD). The diagnostic language was modified significantly, with a majority assumption of NIA‐AA definitions (69%). Confidence in diagnosis increased from 70% to 92% (p < 0.0005) and management was changed in 71% of patient/caregivers. The influence of neurologist's age or expertise on study results was minimal. DISCUSSION The NIA‐AA criteria are adequate and utile for usual practice in memory and neurology clinics, improving diagnostic confidence and significantly modifying patient management. HIGHLIGHTS Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers increase diagnostic certainty regardless of the neurologist. AD CSF biomarkers lead to changes in disease management . Biomarker‐enriched, 2011 NIA‐AA diagnostic criteria are adequate for usual practice.

Objective. To review the scientific literature related to human microbiota and cutaneous T-cell lymphoma. Methodology. An exploratory and systematic review of the articles retrieved from the bibliographic databases MEDLINE (PubMed), Embase, The Cochrane Library, and Scopus, published in the last 10 years with the following descriptors: “lymphoma, T-cell, cutaneous,” “microbiota,” “Mycosis Fungoides,” “Sézary Syndrome,” “lymphoma, primary cutaneous anaplastic large cell,” “Lymphomatoid Papulosis” and “Microbiota,” “microbiota,” “Microbial Community,” and “Microbial Communities.” Results. Of the 87 references retrieved, after applying the inclusion and exclusion criteria, 21 articles were selected. Most studies linking cutaneous T-cell lymphoma and the microbiota focus on the cutaneous microbiome, with Staphylococcus aureus being the main related agent. Skin colonization by this bacterium could be involved in the hyperactivation of the STAT3 inflammatory pathway and in the overproduction of IL-17, both of which are widely related to the development of more aggressive and advanced forms of cutaneous T-cell lymphoma. We also found evidence of a possible relationship between intestinal dysbiosis and the development of cutaneous T-cell lymphoma, observing a decrease in taxonomic variability and an increase in certain genera such as Prevotella in the intestinal microbiome of patients with cutaneous T-cell lymphoma. The possible etiopathogenic mechanism underlying this relationship could be explained by an increase in systemic cytokine release, promoting the hyperactivation of STAT3 at the skin level. Conclusion. There appears to be a relationship between cutaneous T-cell lymphoma and the cutaneous and intestinal microbiome, as well as a possible pathophysiological pathway involved. The possible modulation of the cutaneous and intestinal microbiome or the action on the signaling inflammatory pathway, using pharmacological tools such as JAK inhibitors or IL-17 inhibitors in the latter case, could open the possibility for future therapeutic studies for cutaneous T-cell lymphoma.

Objective: Embryonal tumor with multilayered rosettes (ETMR) is a rare and highly aggressive embryonal brain tumor in young children. Treatment of this tumor often includes maximal safe resection, radiotherapy, and high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT). Early radiation has been recommended according to recent outcome results. The combination of this multimodal treatment may provoke radiographic changes that can mimic tumor progression. This phenomenon is known as pseudoprogression. Methods: We report four consecutive patients under 5 years old with ETMR, treated according to CCG 99703 protocol (which includes conventional chemotherapy and HDCT with ASCT). Off protocol, radiation was given before (three patients) or after (one patient) high-dose chemotherapy. Results: All patients developed pseudoprogression. All patients but one presented symptoms such as irritability, hypotonia, headache and vomiting. Severe neurocognitive impairment was evident in all patients. At a median follow-up of 50.5 months (range, 37–64), three of the patients are alive. Patients who are alive, continue to require significant multidisciplinary support to address treatment sequelae. Conclusion: This case series demonstrates that, while survival rates appear encouraging, combining radiation therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) in the treatment of embryonal tumors with multilayered rosettes may carry a substantial risk of pseudoprogression and notable neurological damage.

(1) Introducción: La adopción generalizada de la simulación en salud como herramienta docente ha dado lugar a un crecimiento de los programas de formación para instructores de simulación. Sin embargo, son escasos los estudios documentando la eficacia de estos programas. El objetivo fue estudiar la transformación experimentada por los participantes en una edición in situ de un programa de formación específico y comparar las posibles diferencias observadas con una edición online del mismo programa, estudiada y publicada anteriormente. (2) Métodos. El programa consistió en un módulo interactivo online de 15 días, 4 días in situ de 8 horas y una sesión individual online con uno de los instructores. Cada día in situ resultó en reflexiones escritas individuales, que se categorizaron según los temas de aprendizaje descritos por Kolbe y Rudolph (2018). (3) Resultados: Se identificaron 25 subtemas que agrupan un total de 78 elementos identificados en las 38 respuestas de los participantes, categorizadas según cinco temas de aprendizaje: notas para uno mismo, evaluaciones, metacogniciones, anticipaciones de aplicaciones, y emociones. (4) Conclusión: Se identificó una progresión del desarrollo profesional comparable entre el formato presencial in situ (el estudio actual) y online (el estudio publicado anteriormente).

El presente artículo analiza la asociación entre la tipología de estructuras algorítmicas de programación y los modelos mentales construidos para su resolución. El estudio se inscribe en el paradigma cuantitativo con un diseño cuasi-experimental, y contó con la participación de 95 estudiantes de grado undécimo de media técnica en informática. La metodología implicó evaluar los procesos desarrollados por los estudiantes, a través de los modelos obtenidos en una prueba de resolución de problemas algorítmicos; los resultados fueron sometidos a un análisis descriptivo, con el fin de establecer diferencias estadísticamente significativas entre los niveles de consistencia de los modelos asociados al proceso de resolución y a los tipos de estructuras. Lo anterior, analizado en razón a la verosimilitud Chi-cuadrado, complementado con la magnitud del efecto V de Cramér; también, se aplicó la prueba de Dwass-Steel-Critchlow-Fligner (DSCF), para realizar comparaciones entre las estructuras. Los resultados indicaron modelos más consistentes en la estructura secuencial, en contraste con los modelos inconsistentes y ambiguos predominantes en las estructuras condicionales, cíclicas y anidadas. Las principales conclusiones exponen una relación significativa entre los modelos mentales y la tipología de las estructuras algorítmicas de programación, evidenciando la necesidad de enfocar las estrategias didácticas en la resolución de problemas.

Abstract Background To analyze evolution and factors related with greater gains in Health Related Quality of Life (HRQOL) and with a greater probability of exceed their corresponding minimal clinically important differences (MCID) in patients with Osteoarthritis of the knee, undergoing total knee arthroplasty (TKA) at long-term. Methods Data were obtained from two previously recruited multicenter cohorts of patients who underwent TKA in the Basque Country. Patients were follow-up at 6 months and 10 years after surgery. Patients completed specific and generic HRQOL questionnaires plus sociodemographic, and clinical data at 10 years. Associations were analysed using linear and logistic regression models. Results A total of 471 patients responded at 10-year follow-up. The multivariable analysis showed that low preoperative HRQOL scores, higher age, higher BMI, some comorbidities and readmissions at 6 months were associated with less gains in HRQOL. Apart from aforementioned, to have a peripheral vascular disease (odd ratio 0.49 (95% CI, 0.24–0.99)), complications (odd ratio 0.31 (95% CI, 0.11–0.91)), and readmissions within 6 months of discharge (odd ratio 2.12 (95% CI, 1.18–3.80)) were associated with a lower probability of exceeding the MCID. The effect sizes (ESs) of changes from baseline to 6 months (range, 1.20–1.96) and to 10 years (range, 1.54–1.99) were large in all dimensions, nevertheless the ESs from 6 months to 10 years were not appreciable for pain (ES = 0.03) or stiffness (ES = 0.09), and small for function (ES = 0.30). Conclusions Low preoperative HRQOL scores, to be elderly, severe obesity, the presence of some comorbidities -depression and rheumatology disease-, having readmissions or complications and not having rehabilitation of discharge, are good predictors of long-term lower gains in HRQOL. Some other non-registered parameters of the follow-up may also influence those outcomes. Key Indexing Terms (MeSH terms): Health-Related Quality of Life, Knee Arthroplasty, Total, Osteoarthritis

Muscle fibres have an important impact on meat quality. There are different types of skeletal muscle fibres, mainly oxidative and glycolytic. The present study showed that dairy breeds and goat kids raised with milk replacer had less oxidative fibres than meat breeds and goat kids raised with their dams. In addition, the muscle fibres measured in this study were smaller in dairy breeds and kids raised with milk replacer than in meat breeds and goat kids raised with the dams.

Background Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with thrombosis. Clinical scoring systems and the presence of anti-platelet factor 4 (anti-PF4)/heparin antibodies determine the diagnosis.Case presentation A 57-year-old man who was treated with acenocoumarol due to a chronic left ventricular thrombus was admitted to the hospital for severe SARS-CoV-2 pneumonia and pulmonary embolism. The patient was started on bemiparin and discharged. Left lower limb acute arterial ischemia and thrombocytopenia were diagnosed 18 days later. Computed tomography angiography revealed a large left ventricular thrombus and multiple arterial thrombi. Left femoral-popliteal thromboembolectomy was performed. Anti-PF4/heparin antibodies confirmed an HIT diagnosis. Fondaparinux (7.5 mg/24 h) was initiated, but cardiac surgery was necessary. Bivalirudin was used during surgery, with an initial load (1.25 mg/kg) and maintenance infusion (2.5 mg/kg/h). The cardiac thrombus was extracted, but the patient experienced a postsurgical myocardial infarction. Percutaneous cardiovascular intervention (PCI) required a bivalirudin load (0.75 mg/kg) and maintenance infusion (1.75 mg/kg/h). No coronary lesions were detected, and argatroban was started afterwards (0.5 µg/kg/min). When the platelet count exceeded 100 × 109/L, acenocoumarol was initiated. Thereupon, acetylsalicylic acid (100 mg/24 h) was added. No other complications have been reported to date.Conclusion The clinical presentation of intraventricular and multiple arterial thrombi is remarkable. SARS-CoV-2 infection likely contributed to a hypercoagulable state. The management of patients with HIT undergoing cardiac surgery is challenging. If surgery cannot be delayed, then treatment with bivalirudin is recommended. Additionally, this drug is recommended for PCI. Bivalirudin is safe and well-tolerated in both procedures.

Autochthonous breeds of livestock are considered a pivotal genetic resource for agriculture, rural development, and food and nutrition security. In the Italian Alps, local livestock breeds are maintained using the traditional alpine farming system based on vertical transhumance, with the use of alpine pastures from late spring to autumn and indoor housing with a hay-based diet for the remaining part of the year. Because of their tight link with the territory of origin, local breeds could be used to biomonitor environmental contaminations. Moreover, animal welfare should also be monitored during transhumance in animals, which are exposed to a sudden farming system change and different types of stressors. For these reasons, this investigation hypothesized that the content of trace elements, heavy metals, and cortisol in the hair of goats changes during vertical transhumance, possibly reflecting different dietary contents and activity of the hypothalamic–pituitary–adrenal (HPA) axis. This study aimed to assess the response of an Italian local goat breed to the change from indoor housing to alpine pasture in summer in terms of hair concentrations of (i) trace elements and heavy metals and (ii) cortisol. The regrown hair of Frisa goats was monthly collected for 2 consecutive years (n = 10 for heavy metals and trace elements and n = 6 for cortisol in 2021, n = 17 for both analyses in 2022), once before vertical transhumance and twice after that event. Hair was then analyzed for trace elements, heavy metals, and cortisol by inductively coupled plasma-optical emission spectrophotometer (ICP-OES) and enzyme immunoassay (EIA), respectively. Data were analyzed by multilevel models. The results showed an increase in As content during alpine pasture (p < 0.01), probably reflecting the soil and water As contents of the grazing area, while Mg, Zn, and Al (p < 0.01) followed the opposite trend, decreasing in the second month after vertical transhumance. Hair cortisol concentrations increased during 2 months of alpine pasture (p < 0.001), indicating an increase in the activation of the HPA axis, in agreement with previous studies. Future investigations can consider a longer study period and the development of ad hoc animal welfare indicators.

Research institutes and universities have strengthened the development of biomedicine outreach activities, constituing a non-formal education system of science literacy, although with little commitment from undergraduate students. However, as a Service-Learning methodology, these outreach activities could work as a tool for the acquisition of skills by students of Health Science Degrees. Described here is the development of the workshop entitled “Exploring the human body” at the Biodonostia Health Research Institute and the pilot experience of its implementation as a Service-Learning activity at the University of Málaga. Firstly, 359 secondary education students were mentored by Ph.D. students through a 5-station workshop with experiments and activities related to the physiology of the human body. Then, 301 undergraduate students of Medicine and Nursing Degrees advised 965 secondary education students. Both groups of students assessed the workshop via questionnaires and a debriefing. The data showed an overall score of 4.6 out of 5 for the workshop. Undergraduate students reported a positive impact on their academic background (4.8 out of 5), mainly due to the improvement of oral communication skills (34%). Therefore, this methodology could be a valid and applicable tool to develop the cross-disciplinary competences of undergraduate students.

Las bacterias son capaces de desarrollar mecanismos de resistencia a los antimicrobianos, aquellos adquiridos y transmisibles son los más significativos debido al potencial de diseminación. La aparición de Salmonella enterica con resistencia a C3aG, quinolonas y a colistina representa una amenaza progresiva. El objetivo fue determinar la resistencia a los antimicrobianos y la presencia de los mecanismos de resistencia plasmídicos a quinolonas, β-lactámicos y colistina en aislados de Salmonella provenientes de la vigilancia integrada de enteropatógenos. Fueron estudiadas 501 cepas de Salmonella spp. colectadas entre los años 2020 y 2021, por la red de enteropatógenos del Laboratorio Central de Salud Pública. Se investigó la resistencia a las C3aG, quinolonas y colistina, en aislamientos de humanos, alimentos, animales de consumo y ambiente. Las cepas estudiadas exhibieron resistencia a tetraciclina (32,5%), ácido nalidíxico (29%), ampicilina (13,2%), nitrofurantoína (11,6%), C3aG (7,2%), cotrimoxazol (5,8%), ciprofloxacina (2,2%). El 18% (90/501) presentaron resistencia trasferible por plásmidos, fueron detectados 111 genes (71 cepas con un gen, 17 cepas dos genes y 2 cepas tres genes diferentes). Qnr B: 41,1% (37/90), mcr-1: 38,9% (35/90), CMY: 23,3% (21/90), CTX-M: 16,7% (15/90) y Qnr S: 3,3% (3/90). Heidelberg fue el serovar predominante en muestras de pollo y el mayor portador de genes de resistencia de tipo CMY y mcr-1. La detección de genes en alimentos y animales de consumo, que pueden transmitirse fácilmente al ser humano es motivo de alerta y resalta la importancia de continuar fortaleciendo la vigilancia multisectorial y multidisciplinaria.

La comprensión de las obras audiovisuales y la calidad de la experiencia de su visionado, son dos de dos de los principales desafíos a los que se enfrentan las personas con discapacidad visual. El presente artículo aborda la importancia de los planes de alfabetización mediática para este colectivo y propone el diseño de un programa formativo que facilite el conocimiento de los códigos del lenguaje y la narrativa audiovisual como herramienta para lograr una mejora en su capacidad crítica, facilitando un aprendizaje más acorde a las transformaciones tecnológicas de la sociedad actual. Mediante una revisión de la literatura científica y un modelo metodológico mixto transversal que ha combinado el uso de encuestas, con entrevistas a expertos de la Fundación ONCE y del grupo Cinesa, se han identificado sus necesidades, intereses y demandadas formativas en relación con los medios audiovisuales, contribuyendo a optimizar el diseño del programa. El análisis de los datos obtenidos nos permite confirmar que este tipo de propuestas contribuyen a una mejora significativa en la vida de las personas en riesgo de exclusión social, facilitan su interacción con el mundo y colaboran en la eliminación de barreras que interfieren en la mejora de sus habilidades digitales y mediáticas.

Area A5 is a noradrenergic cell group in the brain stem characterised by its important role in triggering sympathetic activity, exerting a profound influence on the sympathetic outflow, which is instrumental in the modulation of cardiovascular functions, stress responses and various other physiological processes that are crucial for adaptation and survival mechanisms. Understanding the role of area A5, therefore, not only provides insights into the basic functioning of the sympathetic nervous system but also sheds light on the neuronal basis of a number of autonomic responses. In this review, we look deeper into the specifics of area A5, exploring its anatomical connections, its neurochemical properties and the mechanisms by which it influences sympathetic nervous system activity and cardiorespiratory regulation and, thus, contributes to the overall dynamics of the autonomic function in regulating body homeostasis.

Introducción: según estudios recientes, los Servicios Profesionales Farmacéuticos Asistenciales (SPFA) demostraron sus beneficios en la calidad de vida de pacientes y sistemas de salud. Los SPFA son actividades sanitarias prestadas desde la farmacia comunitaria (FC) para la prevención de enfermedades y la mejora de la salud mediante la optimización del uso y del resultado de los tratamientos. Sin embargo, en España existe un bajo porcentaje de farmacias comunitarias que ofrecen SPFA, a excepción de la dispensación, indicación farmacéutica, medida de parámetros clínicos, la educación/información sanitaria y la formulación magistral, ya arraigados en la profesión desde hace tiempo. Objetivo: analizar los factores facilitadores y barreras en la demanda de determinados SPFA por parte de usuarios potenciales, desde el enfoque del producto según las 4Ps del Marketing Mix. Material y métodos: estudio cualitativo de tipo explicativo-interpretativo y exploratorio basado en la teoría fundamentada, mediante análisis inductivo aplicado a entrevistas semi-estructuradas, individuales y grupales. Resultados: las barreras y facilitadores son similares en todos los SPFA analizados, salvo algunas excepciones. Estas barreras y facilitadores son multifactoriales, porque están vinculados con la farmacia, el usuario, factores externos y el farmacéutico. Conclusiones: las barreras en la demanda de los SPFA son la baja adaptación a las necesidades del usuario, los nombres poco entendibles, la falta de integración de la FC en el sistema sanitario, el desconocimiento sobre los SPFA, las insuficientes evidencias de éxito y la satisfacción en servicios percibidos como similares realizados fuera de la FC. Por el contrario, los facilitadores que ayudan al aumento de la demanda de los SPFA son la actitud y aptitud del farmacéutico, el buen trato al paciente, la accesibilidad, cercanía y confortabilidad de la FC y la necesidad del paciente por mejorar su estado de salud.

In humans, speech is a complex process that requires the coordinated involvement of various components of the phonatory system, which are monitored by the central nervous system. The larynx in particular plays a crucial role, as it enables the vocal folds to meet and converts the exhaled air from our lungs into audible sounds. Voice production requires precise and sustained exhalation, which generates an air pressure/flow that creates the pressure in the glottis required for voice production. Voluntary vocal production begins in the laryngeal motor cortex (LMC), a structure found in all mammals, although the specific location in the cortex varies in humans. The LMC interfaces with various structures of the central autonomic network associated with cardiorespiratory regulation to allow the perfect coordination between breathing and vocalization. The main subcortical structure involved in this relationship is the mesencephalic periaqueductal grey matter (PAG). The PAG is the perfect link to the autonomic pontomedullary structures such as the parabrachial complex (PBc), the Kölliker–Fuse nucleus (KF), the nucleus tractus solitarius (NTS), and the nucleus retroambiguus (nRA), which modulate cardiovascular autonomic function activity in the vasomotor centers and respiratory activity at the level of the generators of the laryngeal-respiratory motor patterns that are essential for vocalization. These cores of autonomic structures are not only involved in the generation and modulation of cardiorespiratory responses to various stressors but also help to shape the cardiorespiratory motor patterns that are important for vocal production. Clinical studies show increased activity in the central circuits responsible for vocalization in certain speech disorders, such as spasmodic dysphonia because of laryngeal dystonia.

Resumen: Introducción: Los resultados de los pacientes con diagnóstico de leucemia linfoblástica aguda con cromosoma de Philadelphia (LLA-Ph) continúan siendo desfavorables comparados con los otros tipos de leucemias linfoblásticas agudas, pese a las mejoras en los tratamientos farmacológicos y los avances del trasplante de progenitores hematopoyéticos (TPH). Pacientes y métodos: Se ha analizado el papel del TPH alogénico en pacientes diagnosticados de LLA-Ph mediante un estudio multicéntrico donde se recogen datos pertenecientes a 70 pacientes reportados por el Grupo Español de Trasplante Hematopoyético (GETH), diagnosticados de esta enfermedad trasplantados en distintos hospitales españoles entre los años 1998 y 2014. Resultados: La realización del TPH a partir del año 2004, en primera remisión completa (RC) y con el empleo de timoglobulina (ATG) como parte del acondicionamiento, impactó favorablemente en la supervivencia global (SG). El TPH a partir del año 2004 en primera RC, así como el tratamiento con ATG y el desarrollo de enfermedad de injerto contra receptor aguda (EICRa), aumentaron la supervivencia libre de eventos (SLE). La administración de imatinib, así como la ausencia de enfermedad mínima residual previas al TPH, junto con la EICRa redujeron la probabilidad de recaída. La edad del paciente inferior a 10 años, el estado de primera RC y el empleo de ATG en el acondicionamiento disminuyeron la mortalidad relacionada con el TPH. Conclusiones: Los pacientes en primera RC que han recibido ATG durante el acondicionamiento presentan mayores SG y SLE. La indicación de TPH debería considerarse en estas situaciones. Abstract: Introduction: Outcomes in patients diagnosed of acute lymphoblastic leukemia with Philadelphia chromosome (Ph-ALL) remains unfavourable compared to other subtypes of acute lymphoblastic leukemia despite improvements in drug treatments as well as advances in hematopoietic stem cell transplantation (HSCT). Patients and methods: The role of allogeneic HSCT in Ph-ALL patients has been analysed through a multicentric study where data belonging to 70 patients diagnosed of this entity in different center that received HSCT between years 1998 and 2014, were reported by the Grupo Español de Trasplante Hematopoyético (GETH). Results: The performance of HSCT from year 2004, in first complete remission (CR) status with thymoglobulin (ATG) based conditioning had a favorable impact on overall survival (OS). HSTC performance from year 2004, in first CR with ATG-based conditioning in addition to acute graft versus host disease (aGvHD) development, increased event free survival (EFS). Treatment with imatinib as well as undetectable minimal residual disease (MRD) prior to HSCT, combined with aGvHD, reduced risk of relapse (RR). Patient age less than 10 years when HSCT, first CR and ATG-based conditioning were associated to a lower transplant related mortality (TRM). Conclusions: Patients that could achieve first CR that also received ATG-based conditioning had a better OS and EFS, so HSCT should be considered for this group of patients.

Introduction: Outcomes in patients diagnosed of acute lymphoblastic leukemia with Philadelphia chromosome (Ph-ALL) remains unfavourable compared to other subtypes of acute lymphoblastic leukemia despite improvements in drug treatments as well as advances in hematopoietic stem cell transplantation (HSCT). Patients and methods: The role of allogeneic HSCT in Ph-ALL patients has been analysed through a multicentric study where data belonging to 70 patients diagnosed of this entity in different centers that received HSCT between years 1998 and 2014, were reported by the Grupo Español de Trasplante Hematopoyético (GETH). Results: The performance of HSCT from year 2004, in first complete remission (CR) status with thymoglobulin (ATG) based conditioning had a favorable impact on overall survival (OS). HSTC performance from year 2004, in first CR with ATG-based conditioning in addition to acute graft versus host disease (aGvHD) development, increased event free survival (EFS). Treatment with imatinib as well as undetectable minimal residual disease (MRD) prior to HSCT, combined with aGvHD, reduced risk of relapse (RR). Patient age less than 10 years when HSCT, first CR and ATG-based conditioning were associated to a lower transplant related mortality (TRM). Conclusions: Patients that could achieve first CR that also received ATG-based conditioning had a better OS and EFS, so HSCT should be considered for this group of patients. Resumen: Introducción: Los resultados de los pacientes con diagnóstico de leukemia linfoblástica aguda con cromosoma de Philadelphia (LLA-Ph) continúan siendo desfavorables comparados con los otros tipos de leucemias linfoblásticas agudas, pese a las mejoras en los tratamientos farmacológicos y los avances del trasplante de progenitores hematopoyéticos (TPH). Pacientes y Métodos: Se ha analizado el papel del TPH alogénico en pacientes diagnosticados de LLA-Ph mediante un estudio multicéntrico donde se recogen datos pertenecientes a 70 pacientes reportados por el Grupo Español de Trasplante Hematopoyético (GETH ), diagnosticados de esta enfermedad trasplantados en distintos hospitales españoles entre los años 1998 y 2014. Resultados: La realización del TPH a partir del año 2004, en primera remisión completa (RC) y con el empleo de timoglobulina (ATG) como parte del acondicionamiento, impactó favorablemente en la supervivencia global (SG). El TPH a partir del año 2004 en primera RC, así como el tratamiento con ATG y el desarrollo de enfermedad de injerto contra receptor aguda (EICRa), aumentaron la supervivencia libre de eventos (SLE). La administración de imatinib así como la ausencia de enfermedad mínima residual (EMR) previas al TPH, junto con la EICRa redujeron la probabilidad de recaída (PR). La edad del paciente inferior a 10 años, el estado de primera RC y el empleo de ATG en el acondicionamiento, disminuyeron la mortalidad relacionada con el TPH (MRT). Conclusiones: Los pacientes en primera RC que han recibido ATG durante el acondicionamiento presentan mayores SG y SLE. La indicación de TPH debería considerarse en estas situaciones.

Abstract The chronic inflammatory process that characterizes inflammatory bowel diseases (IBD) is mainly driven by T-cell response to microbial and environmental antigens. Psychological stress is a potential trigger of clinical flares of IBD, and sphingosine-1-phosphate (S1P) is involved in T-cell recruitment. Hence, stress impact and the absence of sphingosine kinase 2 (Sphk2), an enzyme of S1P metabolism, were evaluated in the colon of mice after sub-chronic stress exposure. Here, we show that sub-chronic stress increased S1P in the mouse colon, possibly due to a decrease in its degradation enzymes and Sphk2. S1P accumulation could lead to inflammation and immune dysregulation reflected by upregulation of toll-like receptor 4 (TLR4) pathway, inhibition of anti-inflammatory mechanisms, cytokine-expression profile towards a T-helper lymphocyte 17 (Th17) polarization, plasmacytosis, decrease in IgA+ lymphoid lineage cells (CD45+)/B cells/plasmablasts, and increase in IgM+ B cells. Stress also enhanced intestinal permeability. Sphk2 knockout mice presented a cytokine-expression profile towards a boosted Th17 response, lower expression of claudin 3,4,7,8, and structural abnormalities in the colon. Intestinal pathophysiology should consider stress and S1P as modulators of the immune response. S1P-based drugs, including Sphk2 potentiation, represent a promising approach to treat IBD.

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker.