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Building on results from the AELIX-002 trial with HIVACAT T-cell immunogen (HTI)-based vaccines, the AELIX-003 (NCT04364035) trial tested the safety of the combination of ChAdOx1.HTI (C) and MVA.HTI (M), with the TLR7 agonist vesatolimod (VES), in a double-blind, placebo-controlled, randomized clinical trial in 50 virally suppressed early-treated men with HIV-1 infection. Secondary objectives included immunogenicity and effects on viral rebound kinetics during a 24-week antiretroviral treatment interruption (ATI). The most common treatment-related adverse events were mild-to-moderate injection-site pain, influenza-like illness, headache, and fatigue. Strong, broad, and HTI-focused T-cell responses were induced by vaccination. All participants experienced viral rebound in ATI; 33.3% and 23.5% (P = 0.4494) of CCMM + VES and placebo recipients, respectively, remained off antiretroviral therapy for 24 weeks. Post hoc analysis confirmed a correlation between levels of HTI-specific T cells and prolonged time off antiretroviral therapy. The combination of HTI vaccines and VES was safe and elicited robust T-cell responses., Competing Interests: Competing interests: C.Brander and B.M. are co-inventors of the HTI immunogen (patent application PCT/EP2013/051596). C.Brander, B.M., and I.M. are co-inventors of US patent Application No. 62/935,519 and US Appl. No. 62/851,546, which have relevance to the vaccine regimen used in this study. B.M. reports consultancy, advisory, and/or speaker fees from AELIX Therapeutics, Gilead Sciences, Janssen, ViiV, and MSD. J.M. reports advisory board and speaker fees and grant support from MSD, AbbVie, Boehringer Ingelheim, Gilead Sciences, ViiV Healthcare, Janssen-Cilag, and Bristol Myers Squibb. A.C. reports advisory and speaker fees and grant support from Gilead Sciences, Janssen, MSD, and ViiV Healthcare. P.S. reports advisory and/or speaker fees and/or support for attending meetings from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, Pfizer, and ViiV Healthcare, and has received a research grant from ViiV Healthcare, all outside of the submitted work. J.B. reports speaker fees and grant support from Gilead Sciences and MSD. J.C. reports speaker fees and grant support from Gilead Sciences and MSD. J.A. reports advisory board and speaker fees and grant support from Gilead Sciences, Janssen, MSD, ViiV; data and safety monitoring board membership with Grifols and HIPRA; and is an employee of the European AIDS Clinical Society (guidelines coordinator). A.I. reports advisory and speaker fees and grant support from Gilead Sciences, Janssen, MSD, Theratechnologies, and ViiV. S.M. reports speaking fees and research grants from Gilead Sciences, Janssen-Cilag, MSD, and ViiV. P.D. reports lecture and advisory board fees from ViiV Healthcare, MSD, GSK, Roche, Theratechnologies, Janssen & Cilag, and Gilead. Y.C., Y.T., R.G., D.S., D.L. J.J.W., S.G., and E.V. are employees and stockholders of Gilead Sciences, Inc. M.F. is an employee of ClinData Insight Inc, whose services were funded by Gilead Sciences, Inc. I.M. was an employee of AELIX Therapeutics, is currently an employee of Orion Biotechnology and is a consultant for Synklino. M.G.G. was an employee of AELIX Therapeutics at the time the research was conducted. J.M.M. has received consulting honoraria and/or research grants from Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Lysovant, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work. J.N. has received honoraria and/or speaking fees and/or financial support for attending conferences from AbbVie, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dome, and ViiV Healthcare outside of the submitted work. C.Brander is the cofounder, shareholder, and CSO of AELIX. J.R.A. reports advisory and speaker fees and grant support from ViiV, Janssen, Gilead Sciences, MSD, and AELIX Therapeutics. The remaining authors declare that the research was conducted in the absence of any conflict of interest., (© 2025. The Author(s).)

Background: HCV eradication with antiviral treatment reduces hepatic disease, but some patients remain at risk of progression to cirrhosis despite HCV clearance. We aimed to examine the association between peripheral blood mononuclear cells (PBMCs) gene expression before HCV therapy and a pronounced decrease in the liver stiffness measurement (LSM) value in HIV/HCV-coinfected patients after HCV treatment and achievement of sustained virological response (SVR)., Methods: We performed a retrospective study in 48 HIV/HCV-coinfected patients who started anti-HCV treatment with at least advanced fibrosis (LSM ≥9.5). Total RNA was extracted from PBMCs at baseline, and poly(A) RNA sequencing was performed. The outcome was an LSM reduction greater than 50% (LSMred>50%) about 48 weeks after HCV treatment., Results: Seven patients (14.5%) reduced LSM by over 50%. We found 47 significant differentially expressed (SDE) genes associated with reaching an LSMred>50% after achieving HCV eradication, 42 upregulated and 5 downregulated in the LSMred>50% group. Ten and five of these upregulated genes were classified into two significantly enriched KEGG pathways: cell cycle and progesterone-mediated oocyte maturation (q-value <0.05), respectively. Two SDE genes achieved excellent discrimination ability: NCAPG had an AUROC of 0.908, NHLRC1 of 0.879, and a logistic regression model with these two genes of 0.955., Conclusion: A pre-treatment gene expression signature in PBMCs was associated with liver fibrosis regression (LSMred>50%) after achieving HCV clearing with HCV therapy in HIV/HCV-coinfected patients, where two SDE genes ( NCAPG and NHLRC1 ) showed the greatest predictive capacity, which could be used as a noninvasive marker of liver fibrosis regression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Virseda-Berdices, Brochado-Kith, Berenguer, González-García, Pérez-Latorre, Busca, Díez, Micán, Fernández-Rodríguez, Jiménez-Sousa and Resino.)

Background and Aims: We assessed long-term clinical outcomes and prognostic factors for liver disease progression after sustained viral response with direct-acting antivirals in patients coinfected with HIV/HCV with advanced fibrosis or cirrhosis., Approach and Results: A total of 1300 patients who achieved sustained viral response with direct-acting antivirals from 2014 to 2017 in Spain were included: 1145 with compensated advanced chronic liver disease (384 advanced fibrosis and 761 compensated cirrhosis) and 155 with decompensated cirrhosis. The median follow-up was 40.9 months. Overall, 85 deaths occurred, 61 due to non-liver non-AIDS-related causes that were the leading cause of death across all stages of liver disease. The incidence (95% CI) of decompensation per 100 person-years (py) was 0 in patients with advanced fibrosis, 1.01 (0.68-1.51) in patients with compensated cirrhosis, and 8.35 (6.05-11.53) in patients with decompensated cirrhosis. The incidence (95% CI) of HCC per 100 py was 0.34 (0.13-0.91) in patients with advanced fibrosis, 0.73 (0.45-1.18) in patients with compensated cirrhosis, and 1.92 (1.00-3.70) per 100 py in patients with decompensated cirrhosis. Prognostic factors for decompensation in patients with compensated advanced chronic liver disease included serum albumin, liver stiffness measurement (LSM), and fibrosis 4. In this population, LSM and LSM-based posttreatment risk stratification models showed their predictive ability for decompensation and HCC., Conclusions: Non-liver non-AIDS-related events were the leading causes of morbidity and mortality after direct-acting antiviral cure among coinfected patients with advanced fibrosis/cirrhosis. Among those with compensated advanced chronic liver disease, baseline LSM and posttreatment LSM-based models helped to assess decompensation and HCC risk., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: In response to direct-acting antivirals (DAAs) therapy, patients who experience a decrease in hepatic venous pressure gradient (HVPG) considerably reduce liver complications and have increased survival. This study aimed to assess the metabolomic changes associated with the changes in HVPG from the start of DAA therapy until 48 weeks after effective DAA therapy in patients with advanced HCV-related cirrhosis., Methods: We carried out a multicenter longitudinal study in 31 patients with advanced hepatitis C virus (HCV)-related cirrhosis. We performed a non-targeted metabolomic analysis using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, as well as analysis of inflammation-related biomarkers using Luminex technology. The statistical analysis was performed by Generalised Linear Mixed-effects Models (GLMM), correcting for multiple testing., Results: We found that increases of 2,3-butanediol (AMR = 1.15; q-value = 0.023) and taurocholic acid (AMR = 1.06; q-value < 0.001) were significantly associated with increases in HVPG and inflammatory biomarker levels from before DAA therapy to one year after completion of successful HCV treatment., Conclusions: These metabolites have a potential role as indicators of portal hypertension evolution., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study compared the effects of a sled push priming session on performance in 20 m sprint times, vertical jump, and perceived recovery, in comparison to a control condition, during competitive microcycles. Sixteen young semi-professional football players completed two conditions: priming (heavy sled pushes and MD-1 training) and control (only MD-1 regular training), in a crossover design. Twenty-metre sprint times and countermovement jump (CMJ) were assessed 24 hours following the completion of the experimental sessions. The distribution of training load (TL) was similar between the two microcycles on each training day (p > 0.506). At 24 hours, 20 m sprint times were lower (p < 0.001; ES = -1.41), and jump height increased (p = 0.001; ES = 1.11) in the priming condition compared to the control. Individual response analysis showed that 62.5% of the participants ran faster, and 81.3% jumped higher 24 h after priming compared to the control. Furthermore, the added sled push priming exercise did not alter the recovery values perceived by players at 24 hours (p = 0.310). These findings support the use of priming exercises within competitive microcycles by incorporating these sessions on MD-1, as they appear to improve 20 m sprint time and vertical jump without impacting perceived recovery. These results contribute to the understanding of the effects of a low-volume priming session based on heavy sled push on delayed potentiation in sprint and CMJ., Competing Interests: The authors declare no conflict of interest., (Copyright © Institute of Sport – National Research Instutite.)

Acute gastric dilation and necrosis, although rare, are most commonly associated with eating disorders. We present a case of a patient with a history of prior fundoplication and complete intestinal obstruction, which led to severe gastric dilation and subsequent gastric necrosis. The condition was successfully managed through partial gastrectomy. Initial management involved gastric decompression with a nasogastric tube and fluid resuscitation. Surgical intervention remains the definitive treatment in most reported cases. Early diagnosis and timely intervention are critical to improving outcomes and minimizing morbidity and mortality., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Comité de Ética en Investigación del Hospital Regional de Alta Especialidad de Veracruz issued approval NA. This study was conducted in accordance with the ethical standards and the 1964 Helsinki Declaration, along with its later amendments or comparable ethical standards. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, González García et al.)

Creatine monohydrate supplementation is widely used by athletes in high-intensity, power-based sports due to its ability to enhance short-term performance by increasing intramuscular phosphocreatine (PCr) stores, which aid in ATP resynthesis during intense muscle contractions. However, emerging evidence suggests that creatine monohydrate offers benefits beyond athletic performance. This narrative review explores the literature supporting the advantages of creatine supplementation in women, vegans, and clinical populations. In women, who typically have lower baseline intramuscular creatine levels, supplementation may help alleviate fatigue-related symptoms associated with the menstrual cycle, particularly during the early follicular and luteal phases. For vegans and vegetarians, who often have reduced creatine stores due to the absence of creatine-rich animal products in their diet, supplementation can improve both physical and cognitive performance while supporting adherence to plant-based diets. Additionally, creatine supplementation holds potential for various clinical populations. It may mitigate muscle wasting in conditions such as sarcopenia and cachexia, support neuroprotection in neurodegenerative diseases such as Parkinson's and Huntington's, improve exercise capacity in cardiovascular diseases, and enhance energy metabolism in chronic fatigue syndrome. Creatine may also aid recovery from traumatic brain injury by promoting brain energy metabolism and reducing neuronal damage. In conclusion, creatine monohydrate supplementation can enhance physical performance, cognitive function, and overall health in women, vegans, and clinical populations by addressing creatine deficiencies, improving energy metabolism, and supporting recovery from physical and neurological challenges. Most available evidence supports the effectiveness of creatine monohydrate, which should be considered the preferred form of creatine supplementation over other variants. Additionally, proper creatine dosing is essential to maximize benefits and minimize potential adverse effects that may arise from chronic ingestion of excessively high doses.

Various immune checkpoint proteins have been linked to cirrhosis. This study aimed to explore the association between plasma levels of these proteins measured one year after successful HCV treatment and persistently liver stiffness (defined as liver stiffness measurement (LSM) ≥ 12.5 kPa) five years after HCV treatment in people with HIV (PWH). We conducted a retrospective study involving 39 patients with HIV/HCV-coinfection who had advanced fibrosis or cirrhosis and achieved sustained virologic response (SVR). Plasma samples were obtained one year after treatment, and levels of immune checkpoints along with inflammatory biomarkers were evaluated using a Luminex 200 TM analyzer. Statistical analyses were performed using Generalized Linear Models (GLMs) with a gamma distribution. Spearman correlation tests were used to analyze the correlation between significant immune checkpoints and inflammatory biomarkers. Although LSM values showed a decreasing trend over the years following successful HCV treatment, this trend was not statistically significant due to substantial variability among PWH. Persistently high liver stiffness was observed in 61.5% of patients five years after HCV treatment. Elevated plasma levels of soluble BTLA, PD-1, and TIM-3 one year after HCV treatment were associated with persistently liver stiffness five years later. These significant immune checkpoints were found to correlate with inflammatory biomarkers in PWH with persistently high liver stiffness. In conclusion, increased plasma concentrations of immune checkpoints one year after successful HCV therapy were linked to persistently high liver stiffness five years later, particularly BTLA, PD-1, and TIM-3. This suggests a potential immunopathological mechanism in ongoing liver stiffness post-HCV eradication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martín-Escolano, Virseda-Berdices, Berenguer, González-García, Brochado-Kith, Fernández-Rodríguez, Díez, Hontañon, Resino and Jiménez-Sousa.)

The interplay between polyamines and G-quadruplexes has been largely overlooked in the literature, even though polyamines are ubiquitous metabolites in living cells and G-quadruplexes are transient regulatory elements, being both of them key regulators of biological processes. Herein, we compile the investigations connecting G-quadruplexes and biogenic polyamines to understand the biological interplay between them. Moreover, we overview the main works focused on synthetic ligands containing polyamines designed to target G-quadruplexes, aiming to unravel the structural motifs for designing potent and selective G4 ligands., (© 2024 The Author(s). ChemBioChem published by Wiley-VCH GmbH.)

We evaluated the impact of hepatic steatosis-insulin resistance (HS-IR) and liver fibrosis (LF) on type 2 diabetes mellitus (DM2) using triglyceride-glucose (TyG) and Fibrosis-4 (FIB-4). The incidence of DM2 was 12.9 [95% confidence interval (CI), 16.9-9.7] and 9.8 (95% CI, 6.9-13.6) per 1000 person-years in HS-IR and LF. The prevalence of HS-IR was significantly lower at 12 and 24 months with TDF + (3TC or FTC) + RPV [hazard ratio (HR) 0.5 [95% CI, 0.3-0.8], P < 0.01 at 12 months; 0.6 [0.4-0.9], P = 0.01 at 24 months]., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Understanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection., Methods: We performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index., Results: During follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG., Conclusion: We discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martín-Escolano, Virseda-Berdices, Berenguer, González-García, Brochado-Kith, Fernández-Rodríguez, Díez, Hontañon, The Marathon Study Group, Resino and Jiménez-Sousa.)

Introduction: We analyzed epidemiological, clinical characteristics, and the response to treatment in people living with HIV (PLHIV) who recently acquired hepatitis C (RAHC) in a multicentre study in Madrid (Spain)., Methods: Multicenter, ambispective, observational study of RAHC in men who have sex with men (MSM) infected with HIV. Clinical, epidemiological, and RAHC evolution were recorded prospectively in 2019 and 2020 and retrospectively in 2017 and 2018. In patients who received HCV treatment, sustained virological response (SVR) was provided 12 weeks after the end of treatment in an intention to treat analysis (ITT): all treated patients were included; and in analysis per-protocol (PP): missing patients were excluded., Results: Overall, 133 patients were included. Median (IQR) age was 40 (34.3-46.1) years, 90.9% had at least one previous sexual transmission disease (STD), and 33.6% had previously hepatitis C. More than half of the prospective sample included patients using chemsex related drugs (57.3%), 45.7% of them intravenously. The most prevalent genotype was G1a (66.2%), followed by G4 (11.3%). Ten of 90 patients evaluated for spontaneous cure (11%) cured the infection spontaneously, and 119 had treatment after a median time of 1.8 (0.7-4.6) months: sustained virological response (SVR) was achieved in 90.7% in the ITT and 94.7% in the PP analysis, with no differences regarding the direct-acting antiviral agents (DAA) combination used., Conclusions: MSM infected by HIV with a RAHC were exposed to high-risk sexual behavior. Spontaneous cure rate was low, while SVR after treatment was achieved by more than 90%., (Copyright © 2023 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Altered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis)., Methods: We conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis., Results: Patients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001)., Conclusions: Blood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests. The funding sources played no role in the study's design, collection, analysis, interpretation of the data, or manuscript writing., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Metal-modulated croconium dyes with multimodal-imaging and synergistic therapy in the tumor microenvironment have exhibited great potential in tumor theranostics. However, their unideal structure optimization always weakened the efficacy of near-infrared fluorescence-photoacoustic (NIRF/PA) imaging and photothermal therapy (PTT). Here, we screened croconium dye containing two indole groups with better NIRF/PA imaging and PTT in their family, linked to two morpholine rings, and obtained CR-736, as a lysosome-targeting and Fe 3+ -modulated agent. The established CR-736-Fe 3+ nanoplatform was accurately delivered to the breast tumor site, released CR-736 and Fe 3+ in the lower acidic lysosome microenvironment, and activated pH-responsive NIRF/PA/magnetic resonance imaging and PTT. Furthermore, ferroptosis generated hydroxyl free radicals and lipid peroxide by consuming GSH and H 2 O 2 by dint of the accumulation of Fe 3+ in tumor cells, which resulted in the inhibition of the expression of heat shock proteins and the concomitant recovery of PTT. The synergistic therapy of PTT, ferroptosis, and chemodynamics was further optimized to the maximal extent in tumor lysosome acidic microenvironment and proved both in vitro and a mouse tumor model. This study opens a new avenue in designing excellent and unique croconium-based nanoplatforms, synergizing multiple tumor theranostic methods, and further optimizing the theranostic effects in tumor microenvironment.

Background: This study evaluated titers and amplitudes of anti-E2 antibodies (anti-E2-Abs) and neutralizing antibodies against hepatitis C virus (HCV; anti-HCV-nAbs) in HIV/HCV-coinfected individuals over five years after successful HCV treatment completion. Methods: We retrospectively analyzed 76 HIV/HCV-coinfected patients achieving sustained virologic response post-HCV treatment. Plasma levels of anti-E2-Abs and anti-HCV-nAbs against five HCV genotypes (Gt1a, Gt1b, Gt2a, Gt3a, and Gt4a) were determined using ELISA and microneutralization assays, respectively. Statistical analyses comparing the three follow-up time points (baseline, one year, and five years post-HCV treatment) were performed using generalized linear mixed models, adjusting p -values with the false discovery rate ( q -value). Results: Compared to baseline, anti-E2-Abs titers decreased at one year (1.9- to 2.3-fold, q -value < 0.001) and five years (3.4- to 9.1-fold, q -value < 0.001) post-HCV treatment. Anti-HCV-nAbs decreased 2.9- to 8.4-fold ( q -value < 0.002) at one year and 17.8- to 90.4-fold ( q -value < 0.001) at five years post-HCV treatment. Anti-HCV-nAbs titers against Gt3a were consistently the lowest. Nonresponse rates for anti-E2-Abs remained low throughout the follow-up, while anti-HCV-nAbs nonresponse rates increased 1.8- to 13.5-fold ( q -value < 0.05) at five years post-HCV treatment, with Gt3a showing the highest nonresponse rate. Conclusions: Humoral immune responses against HCV decreased consistently one and five years post-HCV treatment, regardless of HCV genotype and previous HCV therapy or type of treatment (IFN- or DAA-based therapy). This decline was more pronounced for anti-HCV-nAbs, particularly against Gt3.

Background: The extensive and continuous reuse of sensitive health data could enhance the role of population health research on public decisions. This paper describes the design principles and the different building blocks that have supported the implementation and deployment of Population Health Information Research Infrastructure (PHIRI), the strengths and challenges of the approach and some future developments., Methods: The design and implementation of PHIRI have been developed upon: (i) the data visiting principle-data does not move but code moves; (ii) the orchestration of the research question throughout a workflow that ensured legal, organizational, semantic and technological interoperability and (iii) a 'master-worker' federated computational architecture that supported the development of four uses cases., Results: Nine participants nodes and 28 Euro-Peristat members completed the deployment of the infrastructure according to the expected outputs. As a consequence, each use case produced and published their own common data model, the analytical pipeline and the corresponding research outputs. All the digital objects were developed and published according to Open Science and FAIR principles., Conclusion: PHIRI has successfully supported the development of four use cases in a federated manner, overcoming limitations for the reuse of sensitive health data and providing a methodology to achieve interoperability in multiple research nodes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Liver fibrosis is a key determinant of the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Its increasing prevalence and a lack of effective treatments make it a major health problem worldwide, particularly in people living with HIV, among whom the prevalence of advanced fibrosis is higher. We have published preclinical data showing that Rilpivirine (RPV), a widely used anti-HIV drug, selectively triggers hepatic stellate cell (HSC) inactivation and apoptosis through signal transducer and activator of transcription (STAT)1-mediated pathways, effects that clearly attenuate liver fibrosis and promote regeneration. We performed a retrospective, cross-sectional study of RPV-induced effects on steatosis, inflammation, and fibrosis in liver biopsies from well-controlled HIV-infected subjects diagnosed with MASLD. Patients on RPV exhibited similar levels of HIV-related parameters to those not receiving this drug, while showing a tendency toward improved liver function and lipid profile, as well as an enhanced activation of STAT1 in hepatic non-parenchymal cells in those with identified liver injury. This protective effect, promoting STAT1-dependent HSC inactivation, was observed at different stages of MASLD. Our results suggest that RPV-based therapy is especially indicated in HIV-infected patients with MASLD-derived liver injury and highlight the potential of RPV as a new therapeutic strategy for liver diseases.

The main limitation to increased rates of lung transplantation (LT) continues to be the availability of suitable donors. At present, the largest source of lung allografts is still donation after the neurologic determination of death (brain-death donors, DBD). However, only 20% of these donors provide acceptable lung allografts for transplantation. One of the proposed strategies to increase the lung donor pool is the use of donors after circulatory-determination-of-death (DCD), which has the potential to significantly alleviate the shortage of transplantable lungs. According to the Maastricht classification, there are five types of DCD donors. The first two categories are uncontrolled DCD donors (uDCD); the other three are controlled DCD donors (cDCD). Clinical experience with uncontrolled DCD donors is scarce and remains limited to small case series. Controlled DCD donation, meanwhile, is the most accepted type of DCD donation for lungs. Although the DCD donor pool has significantly increased, it is still underutilized worldwide. To achieve a high retrieval rate, experience with DCD donation, adequate management of the potential DCD donor at the intensive care unit (ICU), and expertise in combined organ procurement are critical. This review presents a concise update of lung donation after circulatory-determination-of-death and includes a step-by-step protocol of lung procurement using abdominal normothermic regional perfusion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Moreno, González-García, Ruíz-López and Alvarez.)

Background: Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed to determine whether the plasma metabolomic profile of PWH on long-term suppressive ART and immunologically recovered approximates the normality by comparison with healthy controls with similar age and gender., Methods: We carried out a cross-sectional study in 17 PWH on long-term ART (HIV-RNA <50 copies/mL, CD4 + ≥500 cells/mm 3 , and CD4 + /CD8 + ≥1) and 19 healthy controls with similar age and gender. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and Generalized Linear Models (GLM) with a gamma distribution (log-link). Significance levels (p-value) were corrected for multiple testing (q-value)., Results: PCA and PLS-DA analyses found no relevant differences between groups. Adjusted GLM showed 14 significant features (q-value<0.20), of which only three could be identified: lysophosphatidylcholine (LysoPC) (22:6) (q-value=0.148), lysophosphatidylethanolamine (LysoPE) (22:6) (q-value=0.050) and hydroperoxy-octadecatrienoic acid (HpOTrE)/dihydroperoxy-octadecatrienoic acid (DiHOTrE)/epoxy-octadecadienoic acid (EpODE) (q-value=0.136). These significant identified metabolites were directly correlated to plasma inflammatory biomarkers in PWH and negatively correlated in healthy controls., Conclusion: PWH on long-term ART have a metabolomic profile that is almost normal compared to healthy controls. Nevertheless, residual metabolic alterations linked to inflammatory biomarkers persist, which could favor the development of age-related comorbidities among this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Virseda-Berdices, Martín-Escolano, Berenguer, González-García, Brochado-Kith, Rojo, Fernández-Rodríguez, Pérez-Latorre, Hontañón, Barbas, Resino and Jiménez-Sousa.)

Objective: The incidence of type 2 diabetes mellitus (T2DM) has risen dramatically. Among people living with HIV (PLHIV), chronic disease (now >15 cases/1000 in the general population worldwide) and long-term exposure to antiretroviral therapy (ART) can alter metabolic processes early, favoring insulin resistance and T2DM. We retrospectively studied the incidence of T2DM and associated factors in the Cohort of the Spanish AIDS Research Network, a prospective cohort of PLHIV enrolled at diagnosis and before initiation of ART., Methods: PLHIV were aged >18 years and ART naive at inclusion. The incidence of new diagnoses of T2DM after initiation of ART (per 1000 person-years) was calculated. Predictors of a diagnosis of T2DM were identified by a Cox proportional hazards model adjusted for statistically significant and clinically relevant variables., Results: Cumulative incidence was 5.9 (95% CI, 5.1-6.7) per 1000 person-years, increasing significantly in persons aged >50 years to 14.4 (95% CI, 10.4-19.3). Median time to diagnosis of T2DM was 27 months. Only age and higher education were significant. Interestingly, higher education was associated with a 33% reduction in the incidence of T2DM. Having received tenofovir disoproxil fumarate + (lamivudine or emtricitabine) + rilpivirine was almost significant as a protective factor (hazard ratio, 0.49; 95% CI, .24-1.01; P = .05)., Conclusions: The incidence of T2DM in PLHIV in Spain was high, especially in persons aged >50 years. Age was the factor most closely associated with onset, and educational level was the factor most associated with reduced risk. We highlight the lack of association between HIV-related factors and T2DM and show that, within nonnucleoside reverse transcriptase inhibitors, rilpivirine could prove more benign for metabolic comorbidities., Competing Interests: Potential conflicts of interest. M. L. M. reports lecture fees from Janssen, Gilead, MSD, and ViiV-Healthcare outside the submitted work. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Rilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography., Methods: Retrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV., Results: We selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29-68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of -0.8kPa in non-RPV-exposed patients (p=0.254) and -1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, -2.8kPa [p<0.001]; non-RPV-exposed, -1.1kPa [p=0.22])., Conclusion: RPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C., (Copyright © 2022 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose of Review: The purpose of this review is to update the information about the different types of reconstruction after partial nephrectomy, with special emphasis on the new methods of suture-free hemostasis currently available., Recent Findings: The aim of renal reconstruction is to avoid bleeding and leakage of the collecting system, but now the renorrhaphy technique used is considered one of the modifiable determinants of renal function after surgery. In an attempt to avoid the loss of renal function implicit in classic reconstruction, new techniques have been described to control hemostasis and urinary leakage, which employ fewer suture layers, different suture materials and designs, and a wide range of commercially available hemostatic materials. Multiple suture characteristics have been studied as a potential factor influencing the renal function observed after partial nephrectomy. Single-plane suture techniques, the use of bearded sutures, and running sutures seem to be associated with less deterioration in postoperative renal function, and deep medullary sutures should be avoided to avoid affecting the arcuate arteries. Sutureless hemostasis systems could prevent the deterioration of renal function and complications derived from suturing, also reducing ischemia time and surgical time without increasing the risk of complications., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The diagnosis process of soft tissue sarcomas of the musculoskeletal system (SPBAL) continues to be complex, with cases of unplanned excisions ("whoops" surgeries). This study evaluates the frequency of these type of procedures, trying to indentify patient characteristics, tumors, surgical treatment and final results., Material and Methods: 131 patients treated surgically between October 2018 and December 2021 of a SPBAL were retrospectively reviewed. Patients with SPBAL located in the viscera, mediastinum, heart, retroperitoneum, peritoneum and genital tract were excluded. Differences between patients with planned and unplanned excisions were assessed with chi 2 tests and a Cox multivariate regression model., Results: Unplanned excisions of SPBAL have taken place in 18% of the patients in our área, mainly in tumors of less than 5 cm and located superficial to the fascia. 29,2% of these patients did not have a previous imaging test. It has not been shown that a "whoops" surgery can lead to a decrease in survival or a higher rate of recurrences., Conclusions: We recommend carrying out an imaging test always prior to the removal of any type of soft tissue tumor, as well as adherence to the referral guidelines to reference centers., (Copyright © 2023 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Subjective memory complaints (SMC) might be an early sign of further deterioration in cognitive functions. However, no population studies have been published covering all Spain to determine the SMC prevalence. The objective of the present study was to determine the SMC prevalence in the general population residing in Spain >50 years of age and also which related actions were done., Materials and Methods: Interviews were conducted with a nationally representative sample >50 years of age using an online/computer assisted web interview (CAWI) questionnaire. The survey consisted of 34 items divided into two blocks. Presence of SMC was considered when in question 1 the subject answered that "Yes" he had some memory problem., Results: Two thousand three hundred people (53.7% women; 23.9% ≥75 years old) were interviewed. 31% answered that they considered they had a memory problem (no differences between sexes, mean time with memory problems of 3.0 years). A higher prevalence of SMC was observed in ≥75 years old (44%). 90% did not include any specific foods in their diet for their memory problems, neither were taking any pharmaceuticals, diet supplements or nutritional supplements (92%). 78% of those interviewed with SMC have not consulted health professionals for their memory problems., Conclusions: SMC are considerably prevalent in our environment affecting almost a third of people ≥50 years of age. Most of the interviewees with SMC did not go to health professionals to manage their SMC., (Copyright © 2023 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The diagnosis process of soft tissue sarcomas of the musculoskeletal system (SPBAL) continues to be complex, with cases of unplanned excisions ("whoops" surgeries). This study evaluates the frequency of these type of procedures, trying to identify patient characteristics, tumours, surgical treatment and final results., Material and Methods: 131 patients treated surgically between October 2018 and December 2021 of a SPBAL were retrospectively reviewed. Patients with SPBAL located in the viscera, mediastinum, heart, retroperitoneum, peritoneum and genital tract were excluded. Differences between patients with planned and unplanned excisions were assessed with Chi 2 tests and a Cox multivariate regression model., Results: Unplanned excisions of SPBAL have taken place in 18% of the patients in our area, mainly in tumours of less than 5cm and located superficial to the fascia. 29.2% of these patients did not have a previous imaging test. It has not been shown that a "whoops" surgery can lead to a decrease in survival or a higher rate of recurrences., Conclusions: We recommend carrying out an imaging test always prior to the removal of any type of soft tissue tumour, as well as adherence to the referral guidelines to reference centres., (Copyright © 2023 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

The aim of this study was to quantify weekly internal workload across the in-season and compare the workload variables between starter and non-starter Spanish female first league (Liga Iberdrola) football players. Twenty-six participants belonging to the same team (age, height, and mass: 25.4 ± 6.1 years, 167.4 ± 4.8 cm and 57.96 ± 6.28 kg, respectively) participated in this study. Training loads (TL) and match loads (ML) were assessed through breath-cardiovascular (RPE breath ), leg-musculature (RPE leg ) and cognitive (RPE cog ) rating of perceived exertion (RPE 0-10 ) for each training session and match during the in-season phase (35 weeks). Session-RPE (sRPE) was calculated by multiplying each RPE value by session duration (minutes). From these, total weekly TL (weekly TL+ML), weekly TL, weekly ML, chronic workload, acute:chronic workload ratio, training monotony, and training strain were calculated. Linear mixed models were used to assess differences for each dependent variable, with playing time (starter vs non-starter players) used as a fixed factor, and athlete, week, and team as random factors. The results showed that total weekly TL (d = 1.23-2.04), weekly ML (d = 4.65-5.31), training monotony (d = 0.48-1.66) and training strain (d = 0.24-1.82) for RPE breath , RPE leg and RPE cog were higher for starters in comparison with non-starters (p = 0.01). Coaches involved in elite female football should consider implementing differential sRPE monitoring strategies to optimize the weekly load distribution for starters and non-starters and to introduce compensatory strategies to equalise players' total weekly load., Competing Interests: The authors declared no conflict of interest., (Copyright © Biology of Sport 2023.)

Background: Dolutegravir (DTG) plus lamivudine (3TC) has proven highly efficacious as a switching strategy in virologically suppressed people with HIV (PWH). As this strategy was introduced relatively recently, real-world, long-term durability studies are lacking., Methods: We performed a retrospective review of treatment-experienced patients who started DTG + 3TC in a cohort of PWH. HIV-RNA <50 copies/mL was analysed at 144 weeks in an intention-to-treat (ITT) analysis (missing = failure) and a per-protocol (PP) analysis (patients with missing data or changes for reasons other than virological failure were excluded)., Results: The study population comprised 358 PWH (19% women). Median age and time with HIV infection were 51.7 and 13.4 years, respectively. The median number of previous antiretroviral combinations was three. Previous virological failure was reported in 27.1% of patients, and the M184V resistance mutation was detected in 17 patients. At 144 weeks, the percentage of individuals with HIV-RNA <50 copies/mL was 77.4% (277/358) in the ITT analysis and 95.5% (277/290) in the PP analysis. A total of 68 participants were excluded from the PP analysis (data missing, 25, discontinuation due to toxicity, 19; other, 16; death, 8). Two people with virological failure selected resistance-associated mutations (M184V and M184V + R263K). HIV-RNA remained undetectable in 17 patients with a previous history of the M184V mutation., Conclusion: Our results confirm the real-world, long-term efficacy, tolerability and high genetic barrier of DTG + 3TC in treatment-experienced PWH. Although scarce, mutations causing resistance to nucleosides and integrase can emerge., (© 2023 British HIV Association.)

Purpose: Morning priming exercise and caffeine intake have been previously suggested as an effective strategy to increase within-day performance and readiness. However, the concurrent effect of both strategies is unknown. The present research aimed to map the within-day time course of recovery and performance of countermovement jump (CMJ) outcomes, kinetics, and strategy and readiness after priming alone and in combination with caffeine. Methods: Eleven participants performed a control, a priming exercise (Priming) and a priming with concurrent caffeine intake (PrimingCaf) in a double-blind randomized, crossover design. CMJ metrics were assessed before, post, and 2 h, 4 h, and 6 h after each condition while readiness was assessed at 6 h. Results: Perceived physical, mental performance capability and activation balance were higher at 6 h after Priming and PrimingCaf conditions. Immediate reductions in jump height (5.45 to 6.25%; p < .046), concentric peak velocity (2.40 to 2.59%; p < .041) and reactive strength index-modified (RSImod) (9.06 to 9.23% p < .051) after Priming and PrimingCaf were observed, being recovered at 2 h (p > .99). Concentric impulse was restored in PrimingCaf (p > .754; d = -0.03 to-0.08) despite lower concentric mean force/BM (p < .662; d = -0.18 to -0.26) as concentric duration was increased (p > .513; d = 0.15 to 0.21). Individual analysis revealed that some participants benefit from both strategies as they showed increases in jump height over the smallest worthwhile change while others did not. Conclusions: Psychological readiness was increased after both priming conditions at 6 h; however, it seems necessary to consider individual changes to achieve the positive effects of the priming or the priming in combination with caffeine on jumping outcomes.

Background: Several factors impact the preservation of renal function after partial nephrectomy. Warm ischemia time is the main modifiable surgical factor. Renorrhaphy represents the key of hemostasia, but it is associated with increase of warm ischemia time and complications. The aim of this study was to describe our initial surgical experience with a new surgical technique for sutureless partial nephrectomy, based on the application of our own developed renal-sutureless-device-RSD., Methods: Between 2020-2021, 10 patients diagnosed with renal cell carcinoma stage cT1a-b cN0M0 with an exophytic component were operated using renal-sutureless-device-RSD. Surgical technique of sutureless partial nephrectomy with renal-sutureless-device-RSD is described in a step-by-step fashion. Clinical data was collected in a dedicated database. Presurgical, intraoperative, postoperative variables, pathology and functional results were evaluated. Medians and ranges of values for selected variables were reported as descriptive statistics., Results: Partial nephrectomy was carried out with the use of renal-sutureless-device-RSD without renorrhaphy in all cases (70%cT1a-30%cT1b). Median tumor size was 3.15 cm (IQR: 2.5-4.5). R.E.N.A.L Score had a range between 4a-10. Median surgical time was 97.5 minutes (IQR 75-105). Renal artery clamping was only required in 4 cases, with a median warm ischemia time of 12.5 minutes (IQR 10-15). No blood transfusion, intraoperative and postoperative complications were noted. Free-of-disease margin rate achieved was 90%. Median length of stay was 2 days (IQR 2-2). Laboratory data on hemoglobin and hematocrit levels, as well as renal function tests, remained stable after partial nephrectomy., Conclusions: Our initial experience suggests that a sutureless PN using the RSD device is feasible and safe. Further investigation is needed to determine the clinical benefit of this technique.

Hepatic steatosis is a common condition found in the liver of hepatitis C virus (HCV)-infected patients, contributing to more severe forms of liver disease. In addition, the human immunodeficiency virus (HIV) may accelerate this process. Alternatively, several immune checkpoint proteins have been reported to be upregulated and correlated with disease progression during HCV and HIV infections. In steatosis, a detrimental immune system activation has been established; however, the role of the immune checkpoints has not been addressed so far. Thus, this study aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before antiviral therapy) with hepatic steatosis index (HSI) increase at the end of follow-up (∼ five years after sustained virologic response (SVR)). We performed a multicenter retrospective study in 62 patients coinfected with HIV/HCV who started antiviral therapy. Immune checkpoint proteins were analyzed at baseline using a Luminex 200TM analyzer. The statistical association analysis was carried out using Generalized Linear Models (GLM) and Partial Least Squares Discriminant Analysis (PLS-DA). Fifty-three percent of the patients showed HSI increase from baseline to the end of follow-up. Higher immune checkpoint protein levels of BTLA, CD137(4-1BB), CD80, GITR, LAG-3, and PD-L1 before HCV therapy were associated with a long-term increase in HSI after successful HCV therapy, suggesting a potential predictive role for early detection of progression towards steatosis in HIV/HCV-coinfected patients., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Metallo-phthalocyanines (MPc) are common photosensitizers with ideal photophysical and photochemical properties. Also, these molecules have shown to interact with non-canonical nucleic acid structures, such as G-quadruplexes, and modulate oncogenic expression in cancer cells. Herein, we report the synthesis and characterisation of two metallo-phthalocyanines containing either zinc (ZnPc) or nickel (NiPc) in the central aromatic core and four alkyl ammonium lateral chains. The interaction of both molecules with G-quadruplex DNA was assessed by UV-Vis, fluorescence and FRET melting experiments. Both molecules bind strongly to G-quadruplexes and stabilise these structures, being NiPc the most notable G-quadruplex stabiliser. In addition, the photosensitizing ability of both metal complexes was explored by the evaluation of the singlet oxygen generation and their photoactivation in cells. Only ZnPc showed a high singlet oxygen generation either by direct observation or by indirect evaluation using a DPBF dye. The cellular evaluation showed mainly cytoplasmic localization of ZnPc and a decrease of the IC 50 values of the cell viability of ZnPc upon light activation of two orders of magnitude. Two metallo-phthalocyanines containing zinc and nickel within the aromatic core have been investigated as G-quadruplex stabilizers and photosensitizers. NiPc shows a high G4 binding but negligible photosensitizing ability while ZnPc exhibits a moderate binding to G-quadruplex together with a high potency to generate singlet oxygen and photocytotoxicity. The interaction with G4s and capacity to be photosensitized is associated with the geometry adopted by the central metal core of the phthalocyanine scaffold., (© 2023. The Author(s).)

The study presents 'G4-QuadScreen', a user-friendly computational tool for identifying MTDLs against G4s. Also, it offers a few hit MTDLs based on in silico and in vitro approaches. Multi-tasking QSAR models were developed using linear discriminant analysis and random forest machine learning techniques for predicting the responses of interest (G4 interaction, G4 stabilization, G4 selectivity, and cytotoxicity) considering the variations in the experimental conditions (e.g., G4 sequences, endpoints, cell lines, buffers, and assays). A virtual screening with G4-QuadScreen and molecular docking using YASARA (AutoDock-Vina) was performed. G4 activities were confirmed via FRET melting, FID, and cell viability assays. Validation metrics demonstrated the high discriminatory power and robustness of the models (the accuracy of all models is ~>90% for the training sets and ~>80% for the external sets). The experimental evaluations showed that ten screened MTDLs have the capacity to selectively stabilize multiple G4s. Three screened MTDLs induced a strong inhibitory effect on various human cancer cell lines. This pioneering computational study serves a tool to accelerate the search for new leads against G4s, reducing false positive outcomes in the early stages of drug discovery. The G4-QuadScreen tool is accessible on the ChemoPredictionSuite website.

The purpose of this paper was to conduct a systematic review and meta-analysis of studies examining the differences in the mean propulsive velocities between men and women in the different exercises studied (squat, bench press, inclined bench press and military press). Quality Assessment and Validity Tool for Correlational Studies was used to assess the methodological quality of the included studies. Six studies of good and excellent methodological quality were included. Our meta-analysis compared men and women at the three most significant loads of the force-velocity profile (30, 70 and 90% of 1RM). A total of six studies were included in the systematic review, with a total sample of 249 participants (136 men and 113 women). The results of the main meta-analysis indicated that the mean propulsive velocity is lower in women than men in 30% of 1RM (ES = 1.30 ± 0.30; CI: 0.99-1.60; p < 0.001) and 70% of 1RM (ES = 0.92 ± 0.29; CI: 0.63, 1.21; p < 0.001). In contrast, for the 90% of the 1RM (ES = 0.27 ± 0.27; CI: 0.00, 0.55), we did not find significant differences ( p = 0.05). Our results support the notion that prescription of the training load through the same velocity could cause women to receive different stimuli than men.

Aim: To describe and compare the peak physical demands through the worst-case scenario method (WCS), according to different rolling average (RA) time epochs (i.e. 1 min, 3 min, and 5 min) and contextual variables in women soccer players. Methods: Using an observational-comparative study design, an elite women soccer team from the Spanish 1 st league division was monitored during 27 matches. Nine WCS-dependent variables were assessed, including total distance (TD), high-speed running distance (HSR), sprint distance (SP), acceleration, and deceleration distance at different intensities by players position (i.e., central defenders [CD], wide defenders [WD], central midfielders [CM], wide midfielders [WM], forwards [F]), match half, location, and match outcome. Results: The 1-min RA showed the lowest variability (CV = 9.8-65.8%) for all nine dependent variables. The WD presented the highest TD (168 ± 15.71 m/min). Differences between positions were observed for: CM

Introduction: Inborn errors of immunity (IEI) are a heterogeneous group of diseases caused by intrinsic defects of the immune system. Estimating the immune competence of immunocompromised patients for an infection risk assessment or after SARS-CoV-2 vaccination constituted a challenge., Methods: The aim of this study was to determine the humoral responses of patients with IEI through a comprehensive analysis of specific receptor-binding domain-positive (RBD+) IgG+ memory B cells (MBCs) by flow cytometry, together with routine S-specific IgG antibodies and QuantiFERON SARS-CoV-2 (T-cell response), before the vaccine and 3 weeks after a second dose., Results and Discussion: We first analyzed the percentage of specific RBD+ IgG+ MBCs in healthy healthcare workers. Within the control group, there was an increase in the percentage of specific IgG+ RBD+ MBCs 21 days after the second dose, which was consistent with S-specific IgG antibodies.Thirty-one patients with IEI were included for the pre- and post-vaccination study; IgG+ RBD+ MBCs were not evaluated in 6 patients due to an absence of B cells in peripheral blood. We detected various patterns among the patients with IEI with circulating B cells (25, 81%): an adequate humoral response was observed in 12/25, consider by the detection of positive S-specific IgG antibodies and the presence of specific IgG+ RBD+ MBCs, presenting a positive T-cell response; in 4/25, very low S-specific IgG antibody counts correlated with undetectable events in the IgG+ RBD+ MBC compartment but with positive cellular response. Despite the presence of S-specific IgG antibodies, we were unable to detect a relevant percentage of IgG+ RBD+ MBCs in 5/25; however, all presented positive T-cell response. Lastly, we observed a profound failure of B and T-cell response in 3 (10%) patients with IEI, with no assessment of S-specific IgG antibodies, IgG+ RBD+ MBCs, and negative cellular response. The identification of specific IgG+ RBD+ MBCs by flow cytometry provides information on different humoral immune response outcomes in patients with IEI and aids the assessment of immune competence status after SARS-CoV-2 mRNA vaccine (BNT162b2), together with S-specific IgG antibodies and T-cell responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 del Pino Molina, Bravo Gallego, Nozal, Soto-Serrano, Martínez-Feito, Reche-Yebra, González-Torbay, Cuesta-Martín de la Cámara, Gianelli, Cámara, González-García, González-Muñoz, Rodríguez-Pena and López Granados.)

Metal complexes have gained a huge interest in the biomedical research in the last decade because of the access to unexplored chemical space with regards to organic molecules and to present additional functionalities to act simultaneously as diagnostic and therapeutic agents. Herein, we evaluated the interaction of two polytopic polyaza ligands and their zinc complexes with DNA and RNA by UV thermal denaturation, fluorescence and circular dichroism spectroscopic assays. The zinc coordination was investigated by X-ray diffraction and afforded the structure of the binuclear zinc complex of PYPOD. Thermal denaturation of DNA and RNA and fluorimetry analysis revealed preferential binding of the zinc-PHENPOD complexes towards GC-containing DNA in contrast to the free ligands. On the other hand, PYPOD metal complexes, compared to the free ligand, stabilized AT-based DNA (B-form) better than AU-RNA (A-form). With regards to single stranded RNA, the binuclear complex of PHENPOD and the free ligand can efficiently identify polyadenylic acid (poly A) among other RNA sequences by circular dichroism spectroscopy. The antimicrobial activity in S. aureus and E. coli bacteria showed the highest activity for the free ligands and their trinuclear zinc complexes. This work can provide valuable insights into the impact of the nuclearity of polytopic polyaza ligands in the binding to DNA/RNA and the antimicrobial effect.

Introduction: Kidney procurement procedure must be carried out following a standardized technique in order to optimize kidney grafts for their subsequent implantation., Objectives: Review of the available literature on kidney procurement procedure., Material and Methods: Narrative review of the available evidence on deceased donor kidney procurement technique after a search of relevant manuscripts indexed in PubMed, EMBASE and Scielo written in English and Spanish., Results: Deceased donor kidney procurement can be divided into two groups, donation after brain death (DBD) and donation after circulatory death (DCD). Kidney procurement in DBD frequently includes other chest and/or abdominal organs, requiring multidisciplinary surgical coordination. During the harvesting procedure, the renal vascular pedicle must remain intact for subsequent implantation and reduced ischemia time., Conclusions: Adequate execution and perfect knowledge of the technique for surgical removal and anatomy reduces the rate of graft losses associated to inadequate harvesting techniques., (Copyright © 2022 AEU. Published by Elsevier España, S.L.U. All rights reserved.)

Background: We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH)., Methods: Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models., Results: A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020)., Conclusions: Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context., Competing Interests: Potential conflicts of interest. J. B. reports honoraria for advice or public speaking from Gilead Sciences, Inc, GSK, Janssen Pharmaceuticals, MSD, and ViiV Healthcare; grants from Gilead Sciences, Inc, MSD, and ViiV Healthcare; and support for attending meetings and/or travel from MSD, ViiV Healthcare, and Janssen Pharmaceuticals. I. J. reports honoraria for advice or public speaking from GILEAD, and ViiV Healthcare; honoraria for performing statistical analyses from Fundación Investigación Biomédica Hospital Gregorio Marañón and grants from MSD. J. G.-G. reports honoraria for advice or public speaking from Gilead Sciences, Inc, Janssen Pharmaceuticals, MSD, and ViiV Healthcare; grants or contracts from MSD, ViiV Healthcare, and Gilead Sciences, Inc; support for attending meetings and/or travel from Gilead Sciences, Inc (paid to author); and participation on a DSMB or advisory board for ViiV Healthcare and Janssen-Cilag, S.A. D. D. reports honoraria for public speaking from Gilead Sciences, Inc, Janssen Pharmaceuticals, and ViiV Healthcare (some of this payment was made to author's institution); support for attending meetings and/or travel from Gilead Sciences, Inc; and plays a role in the Spanish AIDS Society and Spanish HIV/AIDS Research Network of Excellence. J. O. reports honoraria for advice or public speaking from Gilead Sciences, Inc, Janssen Pharmaceuticals, MSD, ViiV Healthcare, Pfizer, and GSK; grants from Gilead Sciences, Inc, MSD, and ViiV Healthcare, including consulting fees from Janssen, ViiV, MSD, Gilead Sciences, Inc, and Pfizer; and support for attending meetings and/or travel from Gilead Sciences, Inc, and ViiV. P. D. reports honoraria for advice or public speaking or grants and participation on a DSMB or advisory board from AbbVie, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Inc, GSK, MSD, Janssen Pharmaceuticals, Pfizer, Theratechnologies, and ViiV Healthcare. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Through the methodology of optical surface design based on concentric rings, this paper proposes the design of freeform mirrors, initially by employing segmented rings, each of them with different spherical radii of curvature, and then by employing segmented conic rings with different conic constants in each of the segments. These surfaces will then produce the desired images. For the case of segmented spherical rings, mathematical expressions were deduced to obtain the image points as a function of the radii of curvature. Furthermore, it is shown that in the case where conic rings were used, there is a decrease in spherical aberration, which allows the manipulation of the generated image. Finally, several proposals are presented for the design of mirrors to generate both the desired size of the image and the desired distribution of energy, together with their analyses., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Background: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH., Methods: We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 - 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46)., Results: We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021))., Conclusions: A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patients., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

An exact equation to relate the optical path differences (OPD) with its transversal aberration components (TAC) is determined. The OPD-TAC equation reproduces the Rayces formula and introduces the coefficient for the longitudinal aberration. The defocus orthonormal Zernike polynomial ( Z DF ) is not a solution for the OPD-TAC equation since the obtained longitudinal defocus depends on the ray height on the exit pupil, meaning that it cannot be interpreted as a defocus. In order to find an exact expression for OPD defocus, first, a general relationship between the wavefront shape and its OPD is established. Second, an exact formula for the defocus OPD is established. Finally, it is proved that only the exact defocus OPD is an exact solution of the exact OPD-TAC equation.

Two new ligands (TPB3P and TPB3Py) showing a strong stabilisation effect and good selectivity for G4 over duplex DNAs have been synthesised. The ligands hold three analogous polyamine pendant arms (TPA3P and TPA3Py) but differ in the central aromatic core, which is a triphenylbenzene moiety instead of a triphenylamine moiety. Both TPB3P and TPB3Py exhibit high cytotoxicity in MCF-7, LN229 and HeLa cancer cells in contrast to TPA-based ligands, which exhibit no significant cytotoxicity. Moreover, the most potent G4 binders have been encapsulated in liposomes and AS1411 aptamer-targeted liposomes reaching nanomolar IC 50 values for the most cytotoxic systems.

Two fluorescent and non-toxic spirobifluorene molecules bearing either positive (Spiro-NMe3) or negative (Spiro-SO3) charged moieties attached to the same aromatic structure have been investigated as binders for DNA. The novel Spiro-NMe3 containing four alkylammonium substituents interacts with G-quadruplex (G4) DNA structures and shows preference for G4s over duplex by means of FRET melting and fluorescence experiments. The interaction is governed by the charged substituents of the ligands as deduced from the lower binding of the sulfonate analogue (Spiro-SO3). On the contrary, Spiro-SO3 exhibits higher binding affinity to duplex DNA structure than to G4. Both molecules show a moderate quenching of the fluorescence upon DNA binding. The confocal microscopy evaluation shows the internalization of both molecules in HeLa cells and their lysosomal accumulation., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background: Beetroot juice is a sport supplement with a high level of evidence on the physical performance enhancement. However, in swimming, there is no clear data about the effects of beetroot juice on performance. Objective: To investigate whether an acute intake of beetroot juice (BJ) improves the performance of competitive swimmers in a repeated maximum swimming effort. Method: Thirteen national-level swimmers (six females and seven males), participated in this randomized, double-blind crossover study. In two different trials, swimmers ingested a 70-mL placebo shot (.04 mmol NO 3 - ; PLA) or a 70-mL Beet-It shot (6.4 mmol of NO 3 - beet juice [BJ]) 3 h before undergoing a 6 × 100-m front-crawl maximal effort test with 7 min rest between each 100 m. Results: Overall, 100-m times showed no difference between the BJ and PLA groups ( p = .364), although a possibly shorter time was observed for BJ in the last repetition ( p = .104; mean difference [MD] = -.99 s, mean-based inference [MBI] = 49/51/0). Participants in the BJ condition showed a possibly lower rate of perceived exertion in the first ( p = .242, MD = -.85, MBI = 70/28/2) and second repetitions ( p = .165, MD = 1.15, MBI = 83/16/1), whereas Total Quality Recovery scale scores were likely higher in the first ( p = .110, MD = 1.15, MBI = 83/16/1) and third ( p = .082, MD = -.77, MBI = 70/29/1) repetitions compared with those in the PLA group. Blood lactate concentration [La + ] levels showed no differences between groups in any of the repetitions ( p > .05, unclear), and we observed an increase in 100-m times for both BJ and PLA (BJ: p = .014, MD = -1.51 s; PLA: p = .029, MD = -1.57 s) after the fifth repetition. Conclusion: No clear differences in performance were observed in a 6 × 100-m repeated sprint test by competitive swimmers when supplementing (or not) with BJ. However, there was a trend toward a better recovery between efforts and a better tolerance of fatigue when swimmers ingested BJ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Moreno, Morencos, Vicente-Campos, Muñoz, González-García and Veiga.)

This study aimed to identify the effects of same-day resistance priming exercise on countermovement jump parameters and subjective readiness, and to identify whether baseline strength level influenced these outcomes. Fourteen participants performed two separate conditions (Priming [2 sets high-load parallel squats with a 20% velocity loss cut-off] and Control) in a randomized, counterbalanced crossover design. Countermovement jump was assessed at pre, post and 6 h while readiness was assessed at pre and at 6 h only. All countermovement jump force-time metrics were similar between conditions ( p >0.05), but different individual responses were noted 6 h after priming. Jump height was increased for 4/14, decreased for another 4/14, and maintained for 6/14 participants at 6 h. Higher perceived physical performance capability ( p <0.001) and activation balance ( p =0.005) were observed after priming only. Positive relationships were observed between strength and the percentage change in jump height (r=0.47-0.50; p =0.033-0.042), concentric peak velocity (r=0.48-0.51; p =0.030-0.041) and im p ulse (r=0.47; p =0.030-0.045) at post and 6 h after priming exercise. These findings suggest that velocity-based high-load low-volume priming exercise has potential to positively impact jump performance and subjective readiness later that day in certain individuals. Participant absolute strength level may influence this response but should be confirmed in subsequent studies., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: The addition of imatinib to the therapeutic arsenal for chronic myeloid leukaemia (CML) has changed the natural course of the disease, in such a way that it is now considered a chronic pathology. However, to achieve therapeutic success, it is necessary to reach adequate plasma concentrations to ensure efficacy and safety.In this study, we aimed to evaluate the plasma concentration of imatinib, analysing its influence on effectiveness and safety in patients with CML., Methods: We performed a descriptive, multicentre study in which imatinib plasma levels from patients diagnosed with CML between 2019-2020 were analysed. An optimal therapeutic range of 750-1500 ng/mL was established for the stratification of patients, according to their minimum plasma concentrations measured at steady state (Cssmin)., Results: A total of 28 patients were included, of whom only 39.3% (n = 11) showed Cssmin within the therapeutic range. 100% of patients with Cssmin >750 ng/mL achieved an optimal molecular response, while only 50% of patients with Cssmin <750 ng/mL achieved an optimal molecular response ( p  = 0.0004). The toxicity rate was 36.4% for patients with Cssmin >1500 ng/mL and 5.9% for those with Cssmin <1500 ng/mL ( p  = 0.039)., Conclusions: This study aimed to describe the correlation between the toxicity and effectiveness of imatinib according to its Cssmin in routine clinical practice conditions. Based on our findings, it would be certainly justified to monitor patient plasma concentrations of imatinib on a daily routine basis in our hospitals.