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To evaluate the feasibility, safety and efficacy of the cutaneous application of Bioengineered Artificial Mesenchymal Sheet (BAMS) in venous leg ulcers (VLUs) versus conventional treatment. This protocol is based on the design of a Phase I/II, multicenter, randomized, controlled, open-label clinical trial investigating the application of a biological dressing supplemented with mesenchymal stem cells (NCT05962931). The clinical trial is being conducted in 2 primary care units within the Granada Metropolitan Health District. A total of 20 patients with VLUs are being randomized (1:1) into 2 intervention arms: a control group and a treatment group. The intervention in the treatment group consists of the local application of 4 doses of BAMS, administered once per week, while the control group receives conventional therapy. Feasibility will be assessed based on the ability to complete the administration of 4 doses in at least 80% of the patients in the treatment group. Safety will be evaluated by analyzing the incidence of adverse effects and serious adverse effects. Efficacy will be assessed in terms of the percentage of wound closure (measured by wound area reduction), macroscopic assessment of the lesion (visual macroscopic analysis and RESVECH 2.0 scale), analysis of growth factors and inflammatory cytokines (ELISA test), pain levels (VAS scale) and quality of life (CIVIQ 20). If confirmed, BAMS-based therapy may provide an effective treatment for VLUs, potentially reducing wound closure time and associated complications. This therapy could significantly enhance patients' quality of life due to the regenerative and analgesic properties of the biological dressing. Given the biological activity of mesenchymal stem cells, an accelerated healing effect is expected in the treatment group. This could lead to shorter healing times for chronic wounds, resulting in significant benefits for patients, healthcare professionals, and overall healthcare costs. NCT05962931.

Between 15% and 30% of HIV‐infected subjects fail to increase their CD4+ T‐cell counts despite continuous viral suppression (immunological nonresponders [INRs]). These subjects have a higher morbidity and mortality rate, but there are no effective treatments to reverse this situation so far. This study used data from an interrupted phase I/II clinical trial to evaluate safety and immune recovery after INRs were given four infusions, at baseline and at weeks 4, 8, and 20, with human allogeneic mesenchymal stromal cells from adipose tissue (Ad‐MSCs). Based on the study design, the first 5 out of 15 INRs recruited received unblinded Ad‐MSC infusions. They had a median CD4+ nadir count of 16/μL (range, 2‐180) and CD4+ count of 253 cells per microliter (171‐412) at baseline after 109 (54‐237) months on antiretroviral treatment and 69 (52‐91) months of continuous undetectable plasma HIV‐RNA. After a year of follow‐up, an independent committee recommended the suspension of the study because no increase of CD4+ T‐cell counts or CD4+/CD8+ ratios was observed. There were also no significant changes in the phenotype of different immunological lymphocyte subsets, percentages of natural killer cells, regulatory T cells, and dendritic cells, the inflammatory parameters analyzed, and cellular associated HIV‐DNA in peripheral blood mononuclear cells. Furthermore, three subjects suffered venous thrombosis events directly related to the Ad‐MSC infusions in the arms where the infusions were performed. Although the current study is based on a small sample of participants, the findings suggest that allogeneic Ad‐MSC infusions are not effective to improve immune recovery in INR patients or to reduce immune activation or inflammation. ClinicalTrials.gov identifier: NCT0229004. EudraCT number: 2014‐000307‐26. Between 15%‐30% of HIV‐infected subjects, do not achieve a significant immune recovery despite continuous viral suppression (immunological non‐responders). These subjects have an aberrant state of immune activation and inflammation. The treatment with adipose tissue allogeneic adult mesenchymal stromal cells does not neither improve immune recovery, nor has it succeeded in reducing the state of immune activation and inflammation.

The contribution of arbuscular mycorrhizal fungi (AM fungi) to plant iron (Fe) acquisition has been demonstrated in several studies. A previous investigation revealed that the AM fungus Rhizophagus irregularis utilizes a high-affinity reductive pathway for Fe uptake, mediated by the Fe transporter RiFTR1. In this study, we used a genome-wide approach in R. irregularis to find genes encoding ferroxidases of the multicopper oxidase (MCO) gene family in an attempt to identify the ferroxidase partner of RiFTR1. Nine genes putatively encoding MCOs ( RiMCO1-9 ) were identified. Yeast complementation assays demonstrated that RiMCO1 and RiMCO3 can function as ferroxidases, suggesting their involvement in the reductive Fe uptake pathway. Surprisingly, RiFTR1 was capable of transporting Fe in yeast without a ferroxidase partner, resembling the Fe transport mechanism of plant IRT1-like systems. RiFTR1 exhibited increase expression in arbuscules. Overexpression of RiFTR1 in Medicago truncatula roots led to enhanced mycorrhizal colonization and arbuscule abundance, highlighting the significance of Fe for AM symbiosis.

NLR proteins contribute to antiviral immune responses. Lemon and colleagues show that NLRX1 promotes antiviral responses in hepatocytes by competing with the kinase PKR for viral double-stranded RNA, which allows accumulation of the transcription factor IRF1 for early control of viral replication. NLRX1 is unique among the nucleotide-binding-domain and leucine-rich-repeat (NLR) proteins in its mitochondrial localization and ability to negatively regulate antiviral innate immunity dependent on the adaptors MAVS and STING. However, some studies have suggested a positive regulatory role for NLRX1 in inducing antiviral responses. We found that NLRX1 exerted opposing regulatory effects on viral activation of the transcription factors IRF1 and IRF3, which might potentially explain such contradictory results. Whereas NLRX1 suppressed MAVS-mediated activation of IRF3, it conversely facilitated virus-induced increases in IRF1 expression and thereby enhanced control of viral infection. NLRX1 had a minimal effect on the transcription of IRF1 mediated by the transcription factor NF-kB and regulated the abundance of IRF1 post-transcriptionally by preventing translational shutdown mediated by the double-stranded RNA (dsRNA)-activated kinase PKR and thereby allowed virus-induced increases in the abundance of IRF1 protein.

Hepatotropic viruses are important causes of human disease, but the intrahepatic immune response to hepatitis viruses is poorly understood because of a lack of tractable smallanimal models. We describe a murine model of hepatitis A virus (HAV) infection that recapitulates critical features of type A hepatitis in humans. We demonstrate that the capacity of HAV to evade MAVS-mediated type I interferon responses defines its host species range. HAV-induced liver injury was associated with interferon-independent intrinsic hepatocellular apoptosis and hepatic inflammation that unexpectedly resulted from MAVS and IRF3/7 signaling. This murine model thus reveals a previously undefined link between innate immune responses to virus infection and acute liver injury, providing a new paradigm for viral pathogenesis in the liver.

The human concern about the effect of electromagnetic fields (EMFs) has changed over time from the effects produced by EMFs of extremely low frequencies (ELFs) to the effects produced by exposure to a radio frequency (RF), with concerns shifting toward EMFs due to the development of new technologies and forms of communication. Previous studies have analysed the effects produced at different frequencies without considering in detail the effect of the time of exposure. Therefore, in the present study, we analysed in vitro the effect produced by a 100 µT EMF at different ELFs and exposure times in glioblastomas, as well as the effect produced in a fibroblast by an RF-EMF of 2.54 GHz. Our results indicate a significant time dependence in cell viability of fibroblasts exposed to an RF-EMF of 2.54 GHz and a non-time-dependent effect in cell viability of glioblastomas exposed to an ELF-EMF, highlighting the possible relation between frequency and time of exposure.

Background Local injection of darvadstrocel, a suspension of expanded adipose‐derived allogenic mesenchymal stem cells, has been used for treatment‐refractory perianal fistulas in Crohn's disease (CD). Objective This study aimed to investigate efficacy and safety of darvadstrocel for complex perianal fistulas in CD. Methods A systematic search was conducted through April 2024 in relevant databases for observational studies evaluating darvadstrocel. A random‐effects meta‐analysis model was used to calculate the pooled effect sizes (proportions or incidence rates [IRs]) with 95% confidence intervals (CIs) of effectiveness and safety outcomes. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Tool. The I2 value assessed heterogeneity. Sensitivity and subgroup analyses were also conducted. Results Twelve studies were included with 595 patients. The pooled rate of patients achieving clinical remission, defined as fistula healing, was 68.1% at month 6 (95% CI 63.4–72.7) and 77.2% (95% CI 70.1–83.8) at month 12. Combined remission, defined as clinical remission and absence of collections >2 cm confirmed by magnetic resonance imaging, was reported in 60.6% and in 69.7% of patients at months 6 and 12, respectively. The rate of patients with treatment failure, defined as no clinical remission at the last follow‐up (mean 18.7 months; SD 9.9), was 34.5%. Failure rate was independent of follow‐up time (p = 0.85). For effectiveness outcomes, between‐study heterogeneity was negligible. Subgroup analysis indicated that none of the covariates modified the treatment effect. Pooled IRs per 100 patient‐years of adverse events (AE), serious AEs, perianal abscesses, and reoperations were 19.6, 3.2, 16.9 and 7.1, respectively. Conclusion Evidence from observational studies supports the efficacy and safety of darvadstrocel for complex perianal fistulas in CD. Studies have reported high fistula healing rates that can be sustained long‐term in most patients, with negligible between‐study heterogeneity, as well as a favorable safety profile. Evidence from observational studies supports the efficacy and safety of darvadstrocel for complex perianal fistulas in Crohn's disease.

Most intervention studies investigating the effects of ergogenic aids (EAs) on sports performance have been carried out in the male population. Thus, the aim of this systematic review and meta-analysis was to summarize the effects in the existing literature of EAs used by female athletes on performance. A literature research was conducted, and a descriptive analysis of the articles included in the systematic review was carried out. Meta-analyses could be performed on 32 of the included articles, evaluating performance in strength, sprint, and cardiovascular capacity. A random-effects model and the standardized mean differences (SMD) ± 95% confidence intervals (CI) were reported. The results showed that caffeine helped to improve jumping performance, isometric strength values, and the number of repetitions until failure. Caffeine and sodium phosphate helped to improve sprint performance. Aerobic tests could be improved with the use of taurine, caffeine, and beta-alanine. No conclusive effects of beetroot juice, polyphenols, or creatine in improving aerobic performance were shown. In terms of anaerobic variables, both caffeine and sodium phosphate could help to improve repeated sprint ability. More studies are needed in female athletes that measure the effects of different EAs on sports performance, such as beetroot juice, beta-alanine or sodium phosphate, as the studies to date are scarce and there are many types of EA that need to be further considered in this population, such as creatine and taurine.

BackgroundBody Dysmorphic Disorder (BDD) is characterised by an appearance-related cognitive deficit based on distorted ideas and beliefs about one’s own body. These lead to high body dissatisfaction (BD), which affects attention, cognitive processing and behaviour.ObjectiveThe aim of this review was to systematically examine the evidence for the effectiveness of psychological interventions to improve cognitive impairments in BDD and high BD.MethodThe systematic review report followed the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement. The databases Pubmed, WOS, Scopus and EBSCO were searched, yielding a total of 2,153 records. After applying the inclusion and exclusion criteria, 10 articles, published until September 2023, were selected. Eligible studies were assessed for potential risk of bias using the Cochrane risk of bias assessment Review Manager (RevMan) tool for the Randomized Controlled Trials and ROBINS-I tool for non-randomized studies.ResultsThe results suggest that psychological interventions can reduce cognitive deficits in BDD. However, the results are supported by a limited number of very diverse studies, conducted with non-clinical, small samples, few sessions and an overall moderate risk of bias.ConclusionsFurther research is needed to confirm the efficacy of psychological interventions on cognitive deficits in BDD.