Development of bioactive solid-foam scaffolds from decellularized cartilage with chondrogenic and osteogenic properties.

Full osteochondral regeneration remains a major clinical challenge. Among other experimental cartilage regenerative approaches, decellularized cartilage (DCC) is considered a promising material for generating potentially implantable scaffolds useful as cartilage repair strategy. In this work, we focus on screening and comparing different decellularization methods, aiming to generate DCC potentially useful in biomedical context, and therefore, with biological activity and functional properties in terms of induction of differentiation and regeneration. Data indicates that enzymatic and detergents-based decellularization methods differentially affect ECM components, and that it has consequences in further biological behavior. SDS-treated DCC powder is not useful to be further processed in 2D or 3D structures, because these structures tend to rapidly solubilize, or disaggregate, in physiologic media conditions. Conversely, Trypsin-treated DCC powders can be processed to mechanically stable 2D films and 3D solid-foam scaffolds, presumably due to partial digestion of collagens during decellularization, which would ease crosslinking at DCC during solubilization and processing. In vitro cell culture studies indicate that these structures are biocompatible and induce and potentiate chondrogenic differentiation. In vivo implantation of DCC derived 3D porous scaffolds in rabbit osteochondral defects induce subchondral bone regeneration and fibrocartilage tissue formation after implantation. Therefore, this work defines an optimal cartilage tissue decellularization protocol able to generate DCC powders processable to biocompatible and bioactive 2D and 3D structures. These structures are useful for in vitro cartilage research and in vivo subchondral bone regeneration, while hyaline cartilage regeneration with DCC alone as implantable material remains elusive.

The MOVECLIM - AZORES project: Bryophytes from Terceira Island along an elevation gradient.

Background: Systematic studies on the biodiversity of bryophytes along elevational gradients have been conductuted within the native vegetation of the Azores, using the MOVECLIM framework. The primary objective of this study was to inventory the bryophytes present within preserved areas of native vegetation in Terceira Island (Azores). From 25 to 28 September 2012, an inventory of the bryoflora was carried out along an elevational gradient, starting near Serreta lighthouse (38.76658 Latitude; -27.37539 Longitude; 40 m a.s.l.) and culminating on the top of Santa Bárbara Mountain (38.73064 Latitude; -27.32164 Longitude; 1000 m a.s.l.). The study followed the adapted MOVECLIM standardised protocol, as follows: i) six sites were selected along an elevational transect, each site spaced at 200 m elevation intervals; ii) within each site, two 10 m x 10 m plots were established in close proximity from each other (10-15 m); iii) within these plots, three 2 m x 2 m quadrats were randomly selected and sampled for bryophytes. The following substrates were surveyed in each quadrat: rock, soil, humus, organic matter, tree bark at three different heights and leaves/fronds. For each available and bryophyte-colonised substrate, three replicate microplots of 10 cm x 5 cm were collected, resulting in a maximum of 24 microplots per quadrat. New information: Nearly three-quarters of the maximum expected number of microplots (636 out of 864; eventID) were found across the six sites on Terceira Island, resulting in a total of 3677 records (occurrenceID). A high proportion of the specimens could be identified to the species rank (n = 3661; 99.6%), representing 38 families, 60 genera and 92 species, including 58 species of liverworts (Marchantiophyta) and 34 species of mosses (Bryophyta). The inventory included several endemic species: two liverwort species endemic to the Azores, five species endemic to Macaronesia (three mosses and two liverworts) and 11 European endemic species (three mosses and eight liverworts). The elevations with the highest species richness, the highest number of endemic species and the highest number of conservation concern species, spanned between 600 and 1000 m a.s.l. above sea level, coinciding with the best preserved forest vegetation. Overall, tree-dwelling and ground-dwelling substrates showed similar levels of bryophyte occupation (75% vs. 72%). However, the 636 events were unevenly distributed across substrates: leaves and rocks had the fewest replicates (n = 54; 50.0%), while humus and the lowest tree height had the highest values (n = 106; 98.1% and n = 98; 90.7%, respectively).The study contributed to expanding knowledge about the diversity and distribution of the Azorean Bryoflora, both on a local and a regional scale.

Pharmacophore Identification and Structure-Activity Relationship Analysis of a Series of Substituted Azaindoles as Inhibitors of Trypanosoma brucei.

Human African trypanosomiasis is among the World Health Organization's designated neglected tropical diseases. Repurposing strategies are often employed in academic drug discovery programs due to financial limitations, and in this instance, we used human kinase inhibitor chemotypes to identify substituted 4-aminoazaindoles, exemplified by 1. Structure-activity and structure-property relationship analysis, informed by cheminformatics, identified 4s as a potent inhibitor of Trypanosoma brucei growth. While 4s appeared to be fast acting and cidal in the in vitro assays, it failed to cure a murine model of infection. Preliminary efforts to identify the potential mechanism of action of the series pointed to arginine kinase, though, as we demonstrate, this does not appear to be the sole target of our compounds. This comprehensive approach to drug discovery, encompassing cheminformatics, structure-potency and structure-property analysis, and pharmacophore identification, highlights our multipronged efforts to identify novel lead compounds for this deadly disease.

Origins, diversity, and adaptive evolution of DWV in the honey bees of the Azores: the impact of the invasive mite Varroa destructor.

Deformed wing virus (DWV) is a honey bee virus, whose emergence from relative obscurity is driven by the recent host-switch, adaptation, and global dispersal of the ectoparasitic mite Varroa destructor (a highly efficient vector of DWV) to reproduction on honey bees (Apis mellifera). Our study examines how varroa affects the continuing evolution of DWV, using the Azores archipelago, where varroa is present on only three out of the eight Islands, as a natural experimental system for comparing different evolutionary conditions and trajectories. We combined qPCR of 494 honey bee colonies sampled across the archipelago with amplicon deep sequencing to reveal how the DWV genetic landscape is altered by varroa. Two of the varroa-free Islands were also free of DWV, while a further two Islands were intriguingly dominated by the rare DWV-C major variant. The other four Islands, including the three varroa-infested Islands, were dominated by the common DWV-A and DWV-B variants. The varroa-infested Islands had, as expected, an elevated DWV prevalence relative to the uninfested Islands, but not elevated DWV loads, due the relatively high prevalence and loads of DWV-C on the varroa-free Islands. This establishes the Azores as a stable refuge for DWV-C and provides the most convincing evidence to date that at least some major strains of DWV may be capable of not just surviving, but actually thriving in honey bees in the absence of varroa-mediated transmission. We did not detect any change in DWV genetic diversity associated with island varroa status but did find a positive association of DWV diversity with virus load, irrespective of island varroa status.

Deciphering Host-Parasite Interplay in Leishmania Infection through a One Health View of Proteomics Studies on Drug Resistance.

Recent efforts in the study of vector-borne parasitic diseases (VBPDs) have emphasized an increased consideration for preventing drug resistance and promoting the environmental safety of drugs, from the beginning of the drug discovery pipeline. The intensive use of the few available antileishmanial drugs has led to the spreading of hyper-resistant Leishmania infantum strains, resulting in a chronic burden of the disease. In the present work, we have investigated the biochemical mechanisms of resistance to antimonials, paromomycin, and miltefosine in three drug-resistant parasitic strains from human clinical isolates, using a whole-cell mass spectrometry proteomics approach. We identified 14 differentially expressed proteins that were validated with their transcripts. Next, we employed functional association networks to identify parasite-specific proteins as potential targets for novel drug discovery studies. We used SeqAPASS analysis to predict susceptibility based on the evolutionary conservation of protein drug targets across species. MATH-domain-containing protein, adenosine triphosphate (ATP)-binding cassette B2, histone H4, calpain-like cysteine peptidase, and trypanothione reductase emerged as top candidates. Overall, this work identifies new biological targets for designing drugs to prevent the development of Leishmania drug resistance, while aligning with One Health principles that emphasize the interconnected health of people, animals, and ecosystems.

Varroa destructor shapes the unique viral landscapes of the honey bee populations of the Azores archipelago.

The worldwide dispersal of the ectoparasitic mite Varroa destructor from its Asian origins has fundamentally transformed the relationship of the honey bee (Apis mellifera) with several of its viruses, via changes in transmission and/or host immunosuppression. The extent to which honey bee-virus relationships change after Varroa invasion is poorly understood for most viruses, in part because there are few places in the world with several geographically close but completely isolated honey bee populations that either have, or have not, been exposed long-term to Varroa, allowing for separate ecological, epidemiological, and adaptive relationships to develop between honey bees and their viruses, in relation to the mite's presence or absence. The Azores is one such place, as it contains islands with and without the mite. Here, we combined qPCR with meta-amplicon deep sequencing to uncover the relationship between Varroa presence, and the prevalence, load, diversity, and phylogeographic structure of eight honey bee viruses screened across the archipelago. Four viruses were not detected on any island (ABPV-Acute bee paralysis virus, KBV-Kashmir bee virus, IAPV-Israeli acute bee paralysis virus, BeeMLV-Bee macula-like virus); one (SBV-Sacbrood virus) was detected only on mite-infested islands; one (CBPV-Chronic bee paralysis virus) occurred on some islands, and two (BQCV-Black queen cell virus, LSV-Lake Sinai virus,) were present on every single island. This multi-virus screening builds upon a parallel survey of Deformed wing virus (DWV) strains that uncovered a remarkably heterogeneous viral landscape featuring Varroa-infested islands dominated by DWV-A and -B, Varroa-free islands naïve to DWV, and a refuge of the rare DWV-C dominating the easternmost Varroa-free islands. While all four detected viruses investigated here were affected by Varroa for one or two parameters (usually prevalence and/or the Richness component of ASV diversity), the strongest effect was observed for the multi-strain LSV. Varroa unambiguously led to elevated prevalence, load, and diversity (Richness and Shannon Index) of LSV, with these results largely shaped by LSV-2, a major LSV strain. Unprecedented insights into the mite-virus relationship were further gained from implementing a phylogeographic approach. In addition to enabling the identification of a novel LSV strain that dominated the unique viral landscape of the easternmost islands, this approach, in combination with the recovered diversity patterns, strongly suggests that Varroa is driving the evolutionary change of LSV in the Azores. This study greatly advances the current understanding of the effect of Varroa on the epidemiology and adaptive evolution of these less-studied viruses, whose relationship with Varroa has thus far been poorly defined.

Effectiveness of Treatment Approaches in COVID-19 Pneumonia: A Comparative Evaluation between a Specialized Center and Conventional Hospitals.

BACKGROUND: The early stages of the COVID-19 pandemic overwhelmed general hospitals in Spain. In response, a dedicated hospital for COVID-19 care, the Hospital de Emergencias Enfermera Isabel Zendal (HEEIZ), was established. This study aimed to compare clinical outcomes of COVID-19 patients treated at the specialized HEEIZ with those at conventional general hospitals (CGHs) in Madrid, Spain. METHODS: The study was a prospective, observational cohort study including COVID-19 patients admitted to the HEEIZ and 14 CGHs (December 2020 to August 2021). Patients were assigned based on hospital preference. Clinical data were collected and analyzed using multivariate regression to assess primary and secondary outcomes, including hospital mortality, need of invasive mechanical ventilation (IMV), and pharmacological treatments. RESULTS: The HEEIZ cohort (n = 2997) was younger and had lower Charlson comorbidity scores than the CGH cohort (n = 1526). Adjusted HEEIZ hospital mortality was not significantly higher compared with CGHs (OR: 1.274; 95% CI: 0.781-2.079; p = 0.332). CONCLUSIONS: During the study period, patients admitted to the HEEIZ showed no significant differences in clinical outcomes, compared with patients admitted at CGHs. These results might support the use of specialized centers in managing pandemic surges, allowing CGHs to handle other needs.

The recent revision of the genera Nosema and Vairimorpha (Microsporidia: Nosematidae) was flawed and misleads the bee scientific community.

The genus Vairimorpha was proposed for several species of Nosema in 1976 (Pilley, 1976), almost 70 years after Nosema apis Zander (Zander, 1909). Tokarev and colleagues proposed the redefinition of 17 microsporidian species in four genera, Nosema, Vairimorpha, Rugispora, and Oligosporidium, based on phylogenetic trees of two genetic markers (SSU rRNA and RPB1) (Tokarev et al., 2020). Several issues should invalidate this new classification, leading to the synonymization of Vairimorpha within Nosema.

A proteomic approach supports the clinical relevance of TAT-Cx43266-283 in glioblastoma.

Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43266-283, exerts antitumor effects in in vitro and in vivo models of GBM. Because addressing the mechanism of action is essential to translate these results to a clinical setting, in this study we carried out an unbiased proteomic approach. Data-independent acquisition mass spectrometry proteomics allowed the identification of 190 proteins whose abundance was modified by TAT-Cx43266-283. Our results were consistent with the inhibition of Src as the mechanism of action of TAT-Cx43266-283 and unveiled antitumor effectors, such as p120 catenin. Changes in the abundance of several proteins suggested that TAT-Cx43266-283 may also impact the brain microenvironment. Importantly, the proteins whose abundance was reduced by TAT-Cx43266-283 correlated with an improved GBM patient survival in clinical datasets and none of the proteins whose abundance was increased by TAT-Cx43266-283 correlated with shorter survival, supporting its use in clinical trials.

The Mediating Role of Exercise in Depression and Fatigue in Patients with Advanced Cancer.

This study explored the interconnections between sociodemographic elements, depression, fatigue, and exercise in patients suffering from incurable neoplasm, particularly emphasizing the mediating influence of exercise on the relationship between depression and fatigue This was a prospective, multicenter, observational study involving 15 hospitals across Spain. After three months of systemic cancer treatment, participants completed the Brief Symptom Inventory (BSI), the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ) and the Fatigue Assessment Scale (FAS) to measure levels of depression, fatigue, and exercise, respectively. A total of 616 subjects participated in this study. Activity levels differed markedly according to educational attainment, marital, and work status. There was a negative correlation between physical activity and depression, and a positive correlation between depression and fatigue (ß = -0.18, and ß = 0.46, respectively). Additionally, physical activity inversely influenced fatigue levels (ß = 0.21). Physical activity served as a partial intermediary in the link between depression and fatigue among patients with advanced, unresectable cancer. Healthcare providers are urged to consider both the physical and emotional dimensions of cancer treatment, implementing physical activity programs to enhance overall patient quality of life and mental health.

Instruments for Evaluating the Nutritional Status of Cancer Patients Undergoing Antineoplastic Treatment: A Scoping Review.

The use of validated tools to evaluate the nutritional status of the cancer patient provides guaranteed precision and reliability in their nutritional evaluation, ensuring that the information is accurate and reflects the patient's situation. The aim of this study was to identify the valid and reliable instruments in the evaluation of the nutritional status of cancer patients with a diagnosis of solid tumor undergoing antineoplastic treatment (chemotherapy and/or immunotherapy). A scoping review was conducted to search for original articles published in scientific journals in English, Spanish, or Portuguese in the past five years. In order to identify potentially relevant documents, searches were performed in the following databases: SCOPUS, WOS, CINAHL, MEDLINE, BVS, and PUBMED. DECS-MeSH descriptors and Boolean operators were used. In addition, the Arksey and O'Malley protocol, the Joanne Briggs Institute (JBI) method, and the flow chart of the Preferred Information Elements for Systematic Reviews and Meta-Analyses, known as PRISMA, were followed. The initial search strategy identified a total of 164 references, which were examined successively, leaving a final selection of ten studies. It was found that the most used instrument for nutritional evaluation was the Patient-Generated Subjective Global Assessment (PG-SGA). Other questionnaires also stood out such as the Mini Nutritional Assessment (MNA), the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Screening (NRS 2002), and the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The variation in the tools used ranges from subjective assessments to objective measurements, thus underlining the need for a comprehensive and individualized approach.

Paraneoplastic leukocytosis secondary to carcinosarcoma: a report of two cases and literature review.

BACKGROUND: Neutrophilia is an increase in the number of neutrophils over 7.5×103/µL. An increase in leukocytes over 50×103/µL is called a leukemoid reaction; and when it is associated with a solid tumor, it is considered a paraneoplastic syndrome called paraneoplastic leukemoid reaction (PLR). It is a very rare clinical condition and it is very unusual for it to be associated with carcinosarcoma. We present two cases of a leukemoid reaction observed in the Medical Oncology Department of the University Hospital of Salamanca between May and September 2023. The main objectives of our article are to describe the unusual appearance of paraneoplastic leukocytosis at the diagnosis of carcinosarcoma carcinosarcoma, explain in a detailed way its diagnostic procedure and to show the poor prognosis to which it is associated. CASE DESCRIPTION: In our presentation, we describe two similar cases: first of all, a 60-year-old woman without relevant medical history. She was referred by her primary physician to the Department of Internal Medicine in August 2023 with asthenia, lumbar pain, and weight loss of 12 kg of 3 months of evolution. The physical examination revealed a palpable hypogastric mass. An abdominal, pelvic, and thoracic computed tomography (CT) scan revealed a heterogenous solid mass with necrotic areas originating in the uterus. The anatomopathological diagnosis was carcinosarcoma. The patient showed a progressive worsening in her renal function associated with hyperviscosity secondary to hyperleukocytosis caused by 170×103/µL neutrophils. In the second case we describe the diagnosis of a PLR secondary to a kidney carcinosarcoma. When the patient started chemotherapy, he presented 55.08×103/µL leukocytes, 53.16×103/µL neutrophils. Eight days after receiving chemotherapy, the patient was admitted as an emergency with oligoanuria and decreased consciousness. He presented creatinine 6.25 mg/dL, phosphate 12.4 mg/dL, leukocytes 1.05×103/µL, and neutrophils 0.71×103/µL. The clinical diagnosis was acute exacerbation of multifactorial mixed (renal and prerenal) chronic kidney disease associated with tumor lysis syndrome and grade 3 neutropenia. The patient presented a poor evolution, dying after 2 months. CONCLUSIONS: PLR is a severe paraneoplastic syndrome associated with different types of solid tumors. Its appearance at the time of diagnosis of a tumor implies a poor vital prognosis.

Prepandemic Factors Associated With Pandemic Impact and Psychosocial Distress Among Mothers of Young Children.

OBJECTIVE: To describe the Coronovirus 19 (COVID-19) pandemic impact among mothers of young children (0-8 years) and assess prepandemic factors associated with greater pandemic impact and psychosocial distress. METHODS: Mothers from 3 US birth cohorts (n = 301, mean child age 2.4 years) reported on demographics and psychosocial distress (anxiety, perceived stress, financial stress) before the pandemic (February 2015-February 2020). During the pandemic (July 2020-June 2021), they completed a supplemental survey about the impact of the pandemic on their families (Coronavirus Impact Scale) and psychosocial distress. Multivariable linear and ordinal logistic regression were used to evaluate prepandemic factors associated with pandemic impact overall and by domain. RESULTS: Compared to prepandemic reports, maternal anxiety symptoms increased by 9.4%, perceived stress increased by 13.3%, and financial stress increased by 41.7%, of which all were statistically significant changes. Participants reported the most severe pandemic impact in family routines (72.4%), experiences of stress (40.2%), and social support (38.6%). Mothers with some college or a 4-year degree experienced higher overall pandemic impact compared to mothers with the least and highest education. Prepandemic distress was not associated with pandemic impact; however, midpandemic, all 3 distress measures were significantly positively associated with overall Coronavirus Impact Scale, with the largest effect size noted for perceived stress (B = 1.36, 95% CI: 0.90,1.82). CONCLUSIONS: While, on average, mothers of young children experienced worsening psychosocial stress during the COVID-19 pandemic, prepandemic psychosocial stress alone was not prospectively associated with greater pandemic impact, suggesting that the COVID-19 pandemic may have both elaborated existing systemic social inequalities and created new burdens.

L-plastin associated syndrome of immune deficiency and hematologic cytopenia.

BACKGROUND: LCP1 encodes L-plastin, an actin-bundling protein primarily expressed in hematopoietic cells. In mouse and fish models, LCP1 deficiency has been shown to result in hematologic and immune defects. OBJECTIVE: This study aimed to determine the nature of a human inborn error of immunity resulting from a novel genetic variant of LCP1. METHODS: We performed genetic, protein, and cellular analysis of PBMCs from a kindred with apparent autosomal dominant immune deficiency. We identified a candidate causal mutation in LCP1, which we evaluated by engineering the orthologous mutation in mice and Jurkat cells. RESULTS: A splice-site variant in LCP1 segregated with lymphopenia, neutropenia, and thrombocytopenia. The splicing defect resulted in at least 2 aberrant transcripts, producing an in-frame deletion of 24 nucleotides, and a frameshift deletion of exon 8. Cellular analysis of the kindred revealed a proportionate reduction of T and B cells and a mild expansion of transitional B cells. Similarly, mice carrying the orthologous genetic variant exhibited the same in-frame aberrant transcript, reduced expression Lcp1 and gene dose-dependent leukopenia, mild thrombocytopenia, and lymphopenia, with a significant reduction of T-cell populations. Functional analysis revealed that LCP1c740-1G>A confers a defect in platelet development and function with aberrant spreading on collagen. Immunologic analysis revealed defective actin organization in T cells, reduced migration of PBMCs from patients, splenocytes from mutant mice, and a mutant Jurkat cell line in response to CXCL12; impaired germinal center B-cell expansion after immunization; and reduced cytokinesis during T cell proliferation. CONCLUSIONS: We describe a unique human hematopoietic defect affecting neutrophils, lymphocytes, and platelets arising from partial LCP1 deficiency.

Evaluation of the clinical and economic value of sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C in Spain during the last 5 years.

OBJECTIVE: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) represented a paradigm shift. In 2017, sofosbuvir/velpatasvir (SOF/VEL-Epclusa®) was approved, which showed a high cure rate in all patient, contributing to HCV elimination. The analysis aimed to quantify the clinical and economic value of SOF/VEL in HCV chronic patients since its approval in Spain. METHODS: An economic evaluation was elaborated adapting a Markov model that simulated the lifetime disease progression in of all HCV chronic patients treated with SOF/VEL (30,488 patients) since its launch (5-years), compared to previous therapies. Patients entered the model and were distributed between the fibrosis states (F0-to-F4) in treated and untreated. All patients (100%) were treated with SOF/VEL regardless of their fibrosis, and 49% with previous therapies in ≥F2. The average sustained viral response (SVR) rates 98.9% SOF/VEL versus 61.0% previous therapies. All parameters for the analysis were obtained from real-life data and literature. Only direct healthcare costs associated with disease management were included. The SOF/VEL value was measured as the number of hepatic complications avoided and their associated cost, and hepatic mortality compared to previous therapies. National Health System perspective and a 3% discount rate was applied. RESULTS: SOF/VEL decreased the number of liver complications, avoiding 92% decompensated cirrhosis, 80% hepatocellular carcinomas, and 87% liver transplants, as well as 85% liver-related mortality. Their cost associated was reduced, amounting to savings of 197M€. CONCLUSION: SOF/VEL adds relevant value to the HCV treatment, reducing the clinical and economic disease burden and contributing to HCV elimination in Spain.

rhBMP-2 induces terminal differentiation of human bone marrow mesenchymal stromal cells only by synergizing with other signals.

BACKGROUND: Recombinant human bone morphogenetic protein 2 (rhBMP-2) and human bone marrow mesenchymal stromal cells (hBM-MSCs) have been thoroughly studied for research and translational bone regeneration purposes. rhBMP-2 induces bone formation in vivo, and hBM-MSCs are its target, bone-forming cells. In this article, we studied how rhBMP-2 drives the multilineage differentiation of hBM-MSCs both in vivo and in vitro. METHODS: rhBMP-2 and hBM-MSCs were tested in an in vivo subcutaneous implantation model to assess their ability to form mature bone and undergo multilineage differentiation. Then, the hBM-MSCs were treated in vitro with rhBMP-2 for short-term or long-term cell-culture periods, alone or in combination with osteogenic, adipogenic or chondrogenic media, aiming to determine the role of rhBMP-2 in these differentiation processes. RESULTS: The data indicate that hBM-MSCs respond to rhBMP-2 in the short term but fail to differentiate in long-term culture conditions; these cells overexpress the rhBMP-2 target genes DKK1, HEY-1 and SOST osteogenesis inhibitors. However, in combination with other differentiation signals, rhBMP-2 acts as a potentiator of multilineage differentiation, not only of osteogenesis but also of adipogenesis and chondrogenesis, both in vitro and in vivo. CONCLUSIONS: Altogether, our data indicate that rhBMP-2 alone is unable to induce in vitro osteogenic terminal differentiation of hBM-MSCs, but synergizes with other signals to potentiate multiple differentiation phenotypes. Therefore, rhBMP-2 triggers on hBM-MSCs different specific phenotype differentiation depending on the signalling environment.

Clinical features and predictors of delayed neurological syndrome in carbon monoxide poisoning: the AMICO study. / Caracterización clínica y factores predictivos de desarrollo de síndrome neurológico tardío en la intoxicación por monóxido de carbono: estudio AMICO.

OBJECTIVES: To identify predictors for developing delayed neurological syndrome (DNS) after an initial episode of carbon monoxide (CO) poisoning in the interest of detecting patients most likely to develop DNS so that they can be followed. MATERIAL AND METHODS: Retrospective review of cases of CO poisoning treated in the past 10 years in the emergency departments of 4 hospitals in the AMICO study (Spanish acronym for the multicenter analysis of CO poisoning). We analyzed demographic characteristics of the patients and the clinical characteristics of the initial episode. The records of the cohort of patients with available follow-up information were reviewed to find cases of DNS. Data were analyzed by multivariant analysis to determine the relationship to characteristics of the initial exposure to CO. RESULTS: A total of 240 cases were identified. The median (interquartile range) age of the patients was 36.2 years (17.6-49.6 years); 108 patients (45.0%) were men, and the poisoning was accidental in 223 cases (92.9%). The median carboxyhemoglobin concentration on presentation was 12.7% (6.2%-18.7%). Follow-up details were available for 44 patients (18.3%). Eleven of those patients (25%) developed DNS. A low initial Glasgow Coma Scale score predicted the development of DNS with an odds ratio (OR) of 0.61 (95% CI, 0.41-0.92) and an area under the receiver operating characteristic curve of 0.876 (95% CI, 0.761-0.990) (P .001). CONCLUSION: The initial Glasgow Coma Scale score seems to be a clinical predictor of DNS after CO poisoning. We consider it important to establish follow-up protocols for patients with CO poisoning treated in hospital EDs.

OBJETIVO: Identificar factores pronósticos de desarrollo de síndrome neurológico tardío (SNT) después de un episodio inicial de intoxicación por monóxido de carbono (ICO), con el fin detectar precozmente a la población más susceptible y facilitar su acceso a un seguimiento específico. METODO: Revisión retrospectiva de todos los casos de ICO que acudieron a los servicios de urgencias (SU) de 4 hospitales durante los últimos 10 años. Se analizaron datos demográficos y características clínicas en el momento del episodio. En la cohorte de pacientes con datos de seguimiento disponibles, se evaluó la aparición de SNT y su relación con diferentes variables en la exposición inicial al CO a través de técnicas de análisis multivariante. RESULTADOS: Se identificaron 240 pacientes. La mediana de edad fue de 36,2 años (17,6-49,6). De ellos 108 (45,0%) eran hombres y 223 casos (92,9%) fueron accidentales. El nivel medio de COHb fue del 12,7% (6,2-18,7). En 44 (18,3%) episodios se disponía de datos de un seguimiento específico. En esta cohorte, 11 (25%) pacientes desarrollaron SNT. Una puntuación inicial más baja en la Escala Coma de Glasgow (GCS) (OR: 0,61, IC 95%: 0,41-0,92) fue predictor independiente del desarrollo del SNT, con un ABC en la curva COR de 0,876 (IC 95%: 0,761-0,990, p 0,001). CONCLUSIONES: Una puntuación inicial baja en la GCS parece ser un predictor clínico de desarrollo de SNT en la ICO. Dada la incidencia de SNT, consideramos fundamental establecer protocolos de seguimiento específico de estos pacientes tras su asistencia inicial en los SU.

Maternal Childhood Adversity and Infant Epigenetic Aging: Moderation by Restless Sleep During Pregnancy.

Maternal exposure to childhood adversity is associated with detrimental health outcomes throughout the lifespan and may have implications for offspring. Evidence links maternal adverse childhood experiences (ACEs) to detrimental birth outcomes, yet the impact on the infant's epigenome is unclear. Moreover, maternal sleep habits during pregnancy may influence this association. Here, we explore whether restless sleep during pregnancy moderates the association between exposure to maternal childhood adversity and infant epigenetic age acceleration in 332 mother-infant dyads (56% female; 39% Black; 25% Hispanic). During the 2nd trimester, mothers self-reported childhood adversity and past-week restless sleep; DNA methylation from umbilical vein endothelial cells was used to estimate five epigenetic clocks. Multivariable linear regression was used to test study hypotheses. Despite no evidence of main effects, there was evidence of an interaction between maternal ACEs and restless sleep in predicting infant epigenetic age acceleration using the EPIC Gestational Age clock. Only infants whose mothers reported exposure to both ACEs and restless sleep demonstrated accelerated epigenetic aging. Results provide preliminary evidence that maternal childhood adversity and sleep may influence the infant epigenome.

Influence of Age of Infection on the Gut Microbiota in Worker Honey Bees (Apis mellifera iberiensis) Experimentally Infected with Nosema ceranae.

The gut microbiota of honey bees has received increasing interest in the past decades due to its crucial role in their health, and can be disrupted by pathogen infection. Nosema ceranae is an intracellular parasite that affects the epithelial cells of the midgut, altering gut homeostasis and representing a major threat to honey bees. Previous studies indicated that younger worker bees are more susceptible to experimental infection by this parasite, although the impact of infection and of age on the gut bacterial communities remains unclear. To address this, honey bees were experimentally infected with a consistent number of N. ceranae spores at various ages post-emergence (p.e.) and the gut bacteria 7 days post-infection (p.i.) were analysed using real-time quantitative PCR, with the results compared to non-infected controls. Infected bees had a significantly higher proportion and load of Gilliamella apicola. In respect to the age of infection, the bees infected just after emergence had elevated loads of G. apicola, Bifidobacterium asteroides, Bombilactobacillus spp., Lactobacillus spp., Bartonella apis, and Bombella apis. Moreover, the G. apicola load was higher in bees infected at nearly all ages, whereas older non-infected bees had higher loads of Bifidobacterium asteroides, Bombilactobacillus spp., Lactobacillus spp., Ba. apis, and Bo apis. These findings suggest that N. ceranae infection and, in particular, the age of bees at infection modulate the gut bacterial community, with G. apicola being the most severely affected species.