Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, and multi-faceted illness. Heterogenous onset and clinical presentation with additional comorbidities make it difficult to diagnose, characterize, and successfully treat. Current treatment guidelines focus on symptom management, but with no clear target or causative mechanism, remission rates are low, and fewer than 5% of patients return to their pre-morbid activity levels. Therefore, there is an urgent need to undertake robust clinical trials to identify effective treatments. This review synthesizes insights from clinical trials exploring pharmacological interventions and dietary supplements targeting immunological, metabolic, gastrointestinal, neurological, and neuroendocrine dysfunction in ME/CFS patients which require further exploration. Additionally, the trialling of alternative interventions in ME/CFS based on reported efficacy in the treatment of illnesses with overlapping symptomology is also discussed. Finally, we provide important considerations and make recommendations, focusing on outcome measures, to ensure the execution of future high-quality clinical trials to establish clinical efficacy of evidence-based interventions that are needed for adoption in clinical practice.

The subject of death has been studied since ancient times, but not from the same perspective. This article studies the change of attitude occurred in 15th-16th centuries after the council of Constance, when death came to be understood less as a source of fear than as a necessary transit. After the judgment confronting the forces of good and evil, the salvation of the soul is debated in the room of the dying. Influenced by Jean Gerson’s work, editions and translations of artes moriendi were printed in various languages,​​ sometimes including engravings to help contemplation: among them is the translation of Bernardí Vallmanya’s Cordial de l’ànima.

Exposure to stress induced by intermittent repeated social defeat (IRSD) increases vulnerability to the development of cocaine-induced conditioned place preference (CPP) among male mice; however, some defeated mice are resilient to these effects of stress. In the present study we evaluated the effects of vicarious IRSD (VIRSD) in female mice and explored behavioural traits that are potentially predictive of resilience. C57BL/6 female mice (n = 28) were exposed to VIRSD, which consisted of the animals witnessing a short experience of social defeat by a male mouse on postnatal day (PND) 47, 50, 53 and 56. The control group (n = 10) was not exposed to stress. Blood samples were collected on PND 47 and 56 for corticosterone and interleukin-6 determinations. On PND 57–58, female mice performed several behavioural tests (elevated plus maze, hole-board, object recognition, social interaction, TST and splash tests). Three weeks later, the effects of cocaine (1.5 mg/kg) on the CPP paradigm were assessed. VIRSD decreased corticosterone levels (on PND 56), increased interleukin-6 levels, enhanced novelty-seeking, improved recognition memory and induced anxiety- and depression-like symptoms. Control and VIRSD female mice did not acquire CPP, although some stressed individuals with certain behavioural traits - including a high novelty-seeking profile or the development of depression-like behaviour in the splash test shortly after VIRSD - acquired cocaine CPP. Our results confirm that some behavioural traits of female mice are associated with vulnerability or resilience to the long-term effects of social stress on cocaine reward, as previously observed in males.

The early life cycle of the Atlantic blue crab Callinectes sapidus includes seven zoeal stages that develop in coastal waters, and a later megalopal stage that colonizes estuaries. Although these stages have been largely studied in native ecosystems, very little is known about larval patterns in smaller-scale, invaded, estuarine environments such as those available in the Mediterranean Sea. The general aim of this study is to assess the distribution and abundance of early life stages of C. sapidus in the communication channels of the Albufera lagoon with the Mediterranean Sea, and in adjacent coastal waters. Different sampling methods were employed to target each life stage. (1) For zoeae, planktonic tows were conducted using a 300 μm manta net along 200 m transects parallel to the coastline at distances of 300, 1000 and 3000 m from the shore. (2) A small and manageable passive collector model was used to capture megalopae and juveniles in estuarine areas. This system was first tested from 2020 to 2021 in a single channel, with a weekly sampling frequency, and two more channels were added in 2022. Additionally, intensive daily sampling was conducted in one of the channels from September to November 2022 during the settlement peak. Results showed that zoeae of C. sapidus were more abundant in August 2021, at 1000 m from the coast, and appear to have a disjoint temporal distribution with zoeae of other crab species. Megalopae and juveniles were more abundant from September to November at all sampling sites and times. In 2022, collectors featured a dominance of megalopae at two of the sites (ca. 73%), while the site with the lowest salinity showed a dominance of juveniles (84%). For megalopae, comparative results from the intensive and the regular sampling campaigns showed that time of residence within collectors is just a single day. For juveniles, higher numbers were detected with increased deployment time, suggesting a need for enhanced habitat complexity.

BackgroundVitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). Materials and methodsA retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan–Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. ResultsOut of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5–7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0–4.8) were included in the final model. ConclusionsOur results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.

Post-transplantation cyclophosphamide (PTCy) has emerged as a promising approach for preventing graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is a lack of studies examining the impact of this GVHD prophylaxis when different donor types are used in patients with Hodgkin lymphoma (HL). This study compared the outcomes of patients with HL undergoing HSCT from HLA-matched donors, including matched sibling donors (MSDs) and matched unrelated donors (MUDs), and haploidentical donors, using PTCy as the GVHD prophylaxis approach in all cohorts. We retrospectively compared outcomes of allo-HSCT from 166 HLA-matched donors (96 sibling and 70 unrelated donors) and 694 haploidentical donors using PTCy-based GVHD prophylaxis in patients with HL registered in the European Society for Blood and Marrow Transplantation database from 2010 to 2020. Compared to HLA-matched HSCT, haploidentical donor HSCT was associated with a significantly lower rate of platelet engraftment (86% versus 94%; P < .001) and a higher rate of grade II-IV acute GVHD (34% versus 24%; P = .01). The 2-year cumulative incidence of nonrelapse mortality (NRM) was significantly lower in the HLA-matched cohort compared to the haploidentical cohort (10% versus 18%; P = .02), resulting in a higher overall survival (OS) rate (82% versus 70%; P = .002). There were no significant differences between the 2 cohorts in terms of relapse, progression-free survival, or GVHD-free relapse-free survival. In multivariable analysis, haploidentical HSCT was associated with an increased risk of grade II-IV acute GVHD and NRM and worse OS compared to HLA-matched HSCT. Our findings suggest that in the context of PTCy-based GVHD prophylaxis, transplantation from HLA-matched donors appears to be a more favorable option compared to haploidentical HSCT.

The objective of this meta-analysis was to investigate the association between hypoalbuminemia and postoperative complications in patients undergoing shoulder arthroplasty. This meta-analysis study was registered in PROSPERO (CRD42023442466) and adhered to the PRISMA guidelines. Studies focused on shoulder arthroplasty that compared hypoalbuminemia and normal albumin levels were included. A systematic literature search was conducted in PubMed, EMBASE, Scopus, and the Cochrane Collaboration database. Seven comparative studies were included, and odds ratios with a 95% confidence interval were calculated for the dichotomous variables. A fixed-effect model was used when there was no statistical evidence of heterogeneity, and a random-effect model was used when significant heterogeneity was observed. Review Manager 5.4 software was used for data analysis. The meta-analysis included a total of 20,290 patients from seven studies. Hypoalbuminemia was significantly associated with a higher risk of readmissions (OR 2.92, 95%CI 1.74 to 4.91), reoperations (OR 3.23, 95%CI 1.98 to 5.27), an increase in hospital stay duration (MD 1.59, 95%CI 0.86 to 2.32), and complications such as death (OR 5.75, 95% CI 2.98 to 11.08; studies = 4), thromboembolic events (OR 2.43, 95% CI 1.46 to 4.06; studies = 4), cardiac events (OR 2.78, 95% CI 1.07 to 7.24; studies = 3), pulmonary infections (OR 3.09, 95% CI 1.54 to 6.20; studies = 3), systemic infections (OR 2.19, 95% CI 1.51 to 3.16; studies = 3), and transfusions (OR 3.16, 95% CI 2.23 to 4.48; studies = 2). However, there was no significant association between hypoalbuminemia and renal complications, surgical site infections, urinary tract infections, wound problems, or cardiovascular events. This meta-analysis provides strong evidence that hypoalbuminemia is associated with a higher risk of postoperative complications in patients undergoing shoulder arthroplasty.

Resumen Este artículo estudia el leitmotiv del Christus medicus en los textos literarios tardomedievales. En todos los casos, la presencia de un Cristo médico se evidencia a partir de ejemplos de términos médicos y religiosos; signos de Cristo como sanador de la humanidad y taumaturgo, y en el ámbito metafórico, donde Cristo es el auténtico médico. En estas páginas analizaremos la relación que se establece entre este leitmotiv de Cristo como médico y diversos fragmentos, a través de la meditación y la reflexión por medio de la palabra alegórica.

Maralfalfa (Cenchrus purpureus (Schumach.) Morrone) is a productive fodder crop in tropical regions that has been evaluated for forage nutritional value in a Mediterranean climate. To assess the nutritional value, parameters including dry matter content (DM), ash, ether extract (EE), protein (CP), fiber contents (NDF and ADF), and the amino acids profile were determined at eight harvest times (HTs) in a non-fertilized and non-irrigated crop based in Silla (Valencia, Spain). The results showed significant differences in most of the parameters studied. While CP and ash significantly decreased over the eight HTs, NDF and ADF increased. In contrast, EE and the ratio of essential amino acids/total amino acids remained constant. Values of CP remained higher than 15% during the first two HTs (16 and 28 days). According to the analyses performed, the optimum HT can be stated at 28 days as it combines high levels of CP (including an optimal combination of essential amino acids) with low levels of fibers (NDF = 57.13%; ADF = 34.76%) and a considerable amount of dry matter (15.40%). Among the essential amino acids (EA) determined, lysine and histidine showed similar values (Lys ≈ 6%, His ≈ 1.70%) when comparing the composition of these EA to other forage species and cultivars studied, whereas methionine showed lower values. This work establishes the basis for the appropriate HT of maralfalfa according to the nutritional parameters measured. Further studies could be aimed to optimize the nutritional and phytogenic properties of maralfalfa to improve its value as a fodder crop, and to finally introduce it for sustainable livestock production in Mediterranean countries.

Extramammary Paget’s disease (EMPD) is subclinical in extent and multifocal in nature. There is no global consensus for treatment, so its management represents a challenge in clinical practice. Therefore, we conducted a systematic review through the main electronic databases to assess the effectiveness of topical imiquimod in cutaneous EMPD and to discuss its management. Finally, 24 studies involving a total of 233 EMPD patients treated with topical imiquimod were selected. The topical imiquimod response rate was 67%, and the complete response (CR) rate was 48%. Patients were treated with a three–four times a week regimen in most cases, ranging between 2 to 52 weeks. In addition, imiquimod was applied as an adjunctive treatment in 21 patients, achieving a CR rate of 71%. Consequently, imiquimod therapy could achieve a good response ratio as a first-line treatment, as adjuvant and neo-adjuvant therapy, and as a treatment for recurrent disease. The heterogeneity between studies and the lack of a control arm made it impossible to conduct a meta-analysis. To improve the quality of evidence on EMPD, multicenter studies are essential to collect a larger number of patients and, consequently, obtain high-quality evidence to standardize treatment. The Prospero registration number is CRD42023447443.