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461 papers

Socioeconomic Factors and Their Role in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comprehensive Review.

Wiering L et al. · Jul 1, 2026

Metabolic dysfunction-associated steatotic liver disease (MASLD), a major public health concern, is influenced by an interplay of genetic, environmental, and lifestyle factors, with socioeconomic factors functioning as important upstream determinants whose roles remain not yet fully understood. This review synthesizes current evidence on how different indicators of socioeconomic status as well as related social determinants of health-income, poverty, food insecurity, health insurance, education, migration, and composite indices-relate to MASLD prevalence, severity, and outcomes across different world regions. Several studies associate these socioeconomic factors with an increased risk of MASLD, illustrating the disease's link with socioeconomic disadvantages. However, socioeconomic factors often lose or attenuate their independent association with MASLD once key downstream determinants-such as diet quality, physical inactivity, and metabolic comorbidities-are considered, supporting a model in which socioeconomic factors mainly shape exposure to metabolic and behavioural risk factors rather than exerting a direct causal effect. Among the factors examined, education and food insecurity demonstrate the most consistent independent associations with MASLD. Notably, the direction of socioeconomic gradients appears to differ by regional income level, with lower SES associated with higher MASLD burden in high-income countries but an inverse pattern in several middle-income settings. Evidence remains largely limited to the United States, Europe, and a small number of Asian cohorts, underscoring the need for more geographically diverse research. This review highlights the association of different socioeconomic factors with MASLD, while also revealing the need for more detailed studies which systematically disentangle individual and area-level social determinants of health, model mediating pathways and incorporate underrepresented regions and paediatric populations. A deeper understanding of how socioeconomic factors and downstream mediators jointly drive MASLD could inform targeted clinical strategies and multi-level policies aimed at mitigating the social gradient in MASLD.

Medicine

From Intention to Execution: Pre-Race Nutrition Behaviours, Influences, and Performance Outcomes in Female Endurance Athletes at the IRONMAN World Championships.

Fortis HO et al. · Jul 1, 2026

Endurance competition preparation involves complex psychological, logistical, and sociocultural factors. This study investigated the pre-race nutrition practices of female endurance athletes, by applying a newly developed extended Theory of Planned Behaviour, including behavioural execution to the framework to capture real-world influences (ETPB-X). Using a convergent mixed-methods design, 27 female triathletes competing at the 2024 IRONMAN World Championships completed questionnaires, 48-h food diaries, and semi-structured interviews before and after the race. Quantitative data (n = 23) were analysed for energy and macronutrient intake, whereas qualitative data were thematically coded using the conceptual ETPB-X framework, incorporating attitudes, subjective norms, perceived behavioural control (PBC), utilitarian drivers, and behavioural execution. Only 26% (6/23) of athletes achieved carbohydrate loading guidelines (8-12 g·kg -1 body mass (BM)·day -1 ), with an overall mean intake of 6.4 ± 2.1 g·kg -1 BM. Higher carbohydrate intake correlated with faster finish times (r = -0.50, p = 0.035), whereas fibre intake was positively associated with gastrointestinal (GI) symptom severity (r = 0.85, p < 0.001). Qualitative findings revealed that adherence to diet plans was influenced by PBC, travel logistics, emotional regulation, and athlete identity. This study provides a novel application of the ETPB-X framework to pre-race nutrition in female endurance athletes. Athletes often under-achieve carbohydrate loading targets despite awareness, with success determined as much by psychosocial and contextual factors as by knowledge. Practically, enhancing PBC, improving planning/preparation, and delivering clear goal-aligned education may bridge the intention-behaviour gap. Integrating behavioural frameworks into performance nutrition offers a pathway towards more effective athlete-centred interventions.

Biochemistry, Genetics and Molecular Biology

Longer Baseline Left Ventricular Activation Time Is Associated With Lower Mortality and Lower Risk of Heart Failure Hospitalization in Cardiac Resynchronization Therapy Recipients.

Marinko S et al. · Jul 1, 2026

Introduction Many patients do not benefit from cardiac resynchronization therapy (CRT) with current guideline parameters. The objective of this study was to examine the relationship between left ventricular activation time (LVAT) from the standard 12-lead surface electrocardiogram (ECG) and clinical outcome from CRT. Methods A retrospective study was performed on patients receiving CRT implants at a large-volume tertiary care center. Digital ECGs were collected pre- and post-implant. LVAT was defined as the time from QRS onset to maximum deflection in lead V6. The primary combined endpoint was heart failure hospitalization or all-cause mortality. Results The study group comprised 415 patients (median age [Q1-Q3] of 72.8 years [65.1-78.7], 77.3% male, median baseline LVEF 27.5% [22-30], and 43.1% with ischemic heart failure etiology) who were followed for up to 7.6 years (median 2.8). LVAT was measured pre-implant (median 78 ms [66-98]) and post-implant (median 88 ms [74-106]). In Kaplan-Meier analysis, a longer pre-implant LVAT was associated with a reduced risk of reaching the primary endpoint in patients with LBBB (log-rank p = 0.046). Post-implant LVAT was not associated with clinical outcome. Conclusion Our results show that a longer baseline LVAT is associated with a lower risk of heart failure hospitalization and all-cause mortality. This relationship was of borderline significance in multivariable analysis. Prospective trials would be useful to further explore the potential role of pre-implant LVAT in patient selection for CRT.

Medicine

Muscle fibre denervation in ageing.

Soendenbroe C. · Jul 1, 2026

Muscle fibre denervation describes the loss of effective neural input from a motor neuron to one or more muscle fibres. In ageing, denervation is increasingly recognised as an important contributor to progressive declines in muscle strength and functional capacity, yet it remains heterogeneous and difficult to define in humans. This ambiguity reflects both biological complexity and current methodological limitations. The purpose of the present review is to synthesise current human evidence for muscle fibre denervation in ageing, clarify key conceptual distinctions, and evaluate methodological approaches used to assess denervation in humans. Muscle fibre denervation can occur through structural disconnection of the motor neuron from the fibre or through functional impairment of neuromuscular transmission. Evidence for denervation in ageing is derived from histological, molecular, electrophysiological, and circulating biomarker approaches, each capturing distinct and only partially overlapping aspects of neuromuscular integrity. Importantly, no single measure provides a comprehensive assessment of denervation. Experimental models of disuse in humans reveal a functional denervation phenotype, characterised by molecular and electrophysiological changes that partially resemble those observed with ageing. Physical activity appears to mitigate against aspects of muscle fibre denervation; however, the mechanisms underlying these effects remain incompletely understood. Collectively, the available evidence indicates that denervation in ageing is a multifaceted and dynamic process that requires multimodal, longitudinal approaches to define, detect, and ultimately target denervation-related mechanisms to preserve neuromuscular function across the human lifespan.

Biochemistry, Genetics and Molecular Biology

Acute HEV Infection Is a Relevant Cause of Decompensation and ACLF in Patients With Liver Cirrhosis.

Dinkelborg K et al. · Jul 1, 2026

Background and aims Hepatitis E virus (HEV) infection is very frequent in Europe with more than 2 million annual infections. Patients with liver cirrhosis may face an increased risk of suffering from acute-on-chronic liver failure (ACLF) due to HEV infection. We explored the consequences and prevalence of HEV infection in individuals with liver cirrhosis. Methods We retrospectively analysed the clinical outcome of all consecutive patients who were hospitalized at our center due to acute HEV infection and analysed their outcome between 2014 and 2024. Next, we tested 249 sera from 184 cirrhotic patients during individual episodes of acute hepatic decompensation for anti-HEV IgM and HEV-RNA to analyse the relevance of acute HEV infection as a triggering event. Finally, we established a single center cohort of patients with advanced liver cirrhosis, and assessed the anti-HEV IgG seroprevalence (n = 332). Results Over the past decade, 32 patients with liver cirrhosis who were hospitalized due to acute HEV infection were identified. Among these patients, 16 (50%) developed ACLF, resulting in five fatalities (31.3%) and three individuals (18.8%) requiring liver transplantation for survival. Of 249 sera obtained during acute hepatic decompensation, 11 (4.4%) were either HEV-RNA positive (n = 2) and/or anti-HEV IgM positive (n = 10), linking HEV infection to these acute decompensations. Screening of patients with liver cirrhosis for anti-HEV IgG showed that 67.2% of patients (223/332) were anti-HEV negative and thus at potential risk for future HEV infection. Conclusions Patients with advanced liver cirrhosis are at risk of acute HEV infection, which is a relevant cause of hepatic decompensation and ACLF with high mortality in these patients. Trial registration DRKS00010664; NCT04801290.

Medicine

Does Speaking the Same Language With the Caretakers Associate With a Higher Neuraxial Labor Analgesia Use Rate?

Pirsko L et al. · Jul 1, 2026

Use of neuraxial analgesia requires communication between the parturient and her caretakers. In this retrospective study, the use of labor analgesia is compared between parturients whose primary language is other than Finnish or Swedish and who don't communicate in these languages or English without an interpreter (Category I), who communicate in Finnish, Swedish, or English (Category II), and primary Finnish or Swedish speakers (Category III). The primary outcome of this study is the association of communication language categories with neuraxial analgesia use. The secondary outcome is the incidence of vaginal delivery without pharmacological pain relief. The parturient and labor parameters (age, body mass index (BMI), primiparity, gestational age, prior consultations for fear-of-childbirth (FOC), induction of labor, use of oxytocin, labor analgesia interventions, outcome of the attempted labor) were recorded from the electronic patient database for all 13,707 parturients that attempted vaginal delivery in the Helsinki region delivery hospitals during 2022. The distribution of parturients was 15.3%, 10.3%, and 74.4% in the language categories I, II, and III, respectively. The use rate of neuraxial analgesia was 60.8%, 65.8%, and 75.3% in the categories I, II, and III respectively. After adjustment for primiparity, maternal BMI, gestational age, FOC diagnosis, induction of labor, oxytocin use, episiotomy, and outcome of labor, the adjusted OR (aOR) for neuraxial analgesia use was (1.283 [1.093-1.506]) among parturients in Cat II compared to Cat I. Correspondingly, the ability to communicate directly (Cat II) was associated with lower use of only non-neuraxial pharmacological analgesia (aOR 0.789 [0.654-0.951]) compared to those incapable of direct communication (Cat I). No association was seen with language capability (Cat II vs. Cat I) and delivery without pharmacological pain relief (any delivery type: aOR 0.815 [0.652-1.019]; vaginal delivery: aOR 0.825 [0.645-1.055]). Ability to communicate directly with the staff is associated with shifting from non-neuraxial techniques to neuraxial analgesia but not an increase in general labor analgesia use. Cultural trends may be associated with labor analgesia choices more than language capabilities. Promotion of labor analgesia use should go beyond translation services and requires antenatal education of the available options. EDITORIAL COMMENT: This study demonstrates that language ability alone does not determine labor analgesia use but instead shapes the selection of analgesia methods. Cultural context and antenatal knowledge appear to play a central role in analgesia decision-making. Efforts to promote equitable maternity care should therefore extend beyond translation services to include culturally responsive education and communication strategies that support informed maternal choice.

Medicine

UPLC-QTOF-MS/MS and Antifungal Activity of a Fraction Enriched in Saponins From Sarcomphalus joazeiro Against Candida spp.

da Silva ARP et al. · Jul 1, 2026

The development of antifungal resistance is a complex process that involves the interaction between hosts, drugs, and microbial factors, all of which contribute to therapeutic ineffectiveness. For this reason, studies on natural products as possible therapeutic alternatives are increasingly necessary in order to gain a better understanding of plant compounds that may be more effective in treating infections caused by fungal pathogens. In this context, this study aimed to investigate the antifungal potential of the saponin-enriched fraction of the Sarcomphalus joazeiro species against the Candida albicans, Candida tropicalis, and Candida krusei strains. The selection of this species for study is due to its rich phytochemical composition and the vast traditional knowledge of its medicinal properties. The fraction obtained from the stem bark of S. joazeiro was analyzed by UPLC-QTOF-MS/MS, in which compounds such as triterpenoids, flavonoids, acids, and saponins were identified. Therefore, the results obtained in this study contribute to understanding the antifungal potential of the S. joazeiro species fraction against fungal infections, especially those caused by Candida spp.

Biochemistry, Genetics and Molecular Biology

Differential effects of lipid composition on the thermal and functional properties of membrane associated CYP2J2.

Das R et al. · Jul 1, 2026

CYP2J2 is a membrane-bound cytochrome P450 that is expressed in cardiomyocytes, where it is known to metabolize arachidonic acid into cardioprotective epoxyeicosatrienoic acids (EETs). It consists of transmembrane domains embedded in the hydrophobic segments of the cell membrane and surrounded by various lipids. Currently, we lack a detailed understanding of the role of specific lipids in mediating the physicochemical properties of CYP2J2 and the factors that govern this phenomenon. In this study, CYP2J2 was reconstituted into nanodiscs with different lipid compositions, selected to reflect those of the endoplasmic reticulum (ER) membrane, where the enzyme is expressed. Using a combination of Nano-Differential Scanning Fluorimetry (nano-DSF) and UV-Visible Spectroscopy, we demonstrate that CYP2J2 undergoes a transition in its unfolding behavior between the detergent micelle and the nanodisc environment, with the first melting transition corresponding to heme perturbation. Furthermore, we show that altering the lipid environment causes shifts of up to 3-4°C and 8-9°C in the first and second melting transition temperatures, respectively, with sphingomyelin- and POPS (1-palmitoyl-2-oleoyl-glycero-3-phosphoserine) containing nanodiscs exhibiting the highest and lowest thermal stabilities, respectively. Lipid composition was found to have no effect on substrate (ebastine) binding affinities. However, NADPH-oxidation rates showed that lipid composition directly affects CYP2J2 function in nanodiscs by altering the rate of electron transfer between the CYP and its redox partner, Cytochrome P450 Reductase (CPR). Fluorescence anisotropy measurements with DPH (1,6-Diphenyl-1,3,5-hexatriene) were also used to characterize the membrane fluidity of cholesterol- and sphingomyelin-containing nanodiscs. Together, the results show that lipid composition directly modulates the thermal stability and functional properties of CYP2J2 in nanodiscs and underscore the importance of the charge of the lipid headgroup and membrane fluidity in our understanding of the mechanism by which lipid composition exerts these effects.

Biochemistry, Genetics and Molecular Biology

Stress native mapping does not distinguish patients with previous myocardial infarction with non-obstructive coronary arteries from healthy volunteers.

Andersson DF et al. · Jul 1, 2026

Aims Patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) may be affected by coronary microvascular dysfunction with reduced stress perfusion. Changes in native T1 and T2 reflect changes in myocardial perfusion; therefore, the aim of our study was to investigate whether non-contrast, adenosine stress native T1 and T2 are affected in patients with previous suspected MINOCA. Methods and results Patients with MINOCA and a normal CMR (n = 15, 59 ± 7 years, 60% female) underwent 1.5T CMR together with age- and sex-matched volunteers. The protocol included native T1, native T2 and quantitative perfusion mapping, at rest and during adenosine stress. Myocardial stress perfusion was globally reduced, both transmurally (2.9 ± 0.9 vs. 3.6 ± 0.7 mL/min/g, p = 0.02) and in the subendocardium (2.64 ± 0.81 vs. 3.47 ± 0.78 ml/min/g, p = 0.008) in patients with MINOCA, with a reduced global ratio of subendocardial-to-transmural stress perfusion (0.921 ± 0.042 vs 0.957 ± 0.039, p = 0.021). However, there were no differences in global transmural rest native T1 or T2, stress native T1 or T2, or ΔT1- or ΔT2 values between patients and volunteers. Overall, transmural myocardial perfusion correlated with native T1 (R 2 = 0.27, p 2 = 0.48, p 2 = 0.15, p Conclusions Native T1- and T2-mapping during adenosine stress, although correlated with quantitative myocardial perfusion, are not alone sufficiently sensitive methods for distinguishing patients with MINOCA and reduced stress perfusion from healthy volunteers.

Medicine

The expanding role of protease therapeutics (2012-2026): from replacement therapies to immune system modulation and beyond.

Nelson SE et al. · Jul 1, 2026

Proteases are powerful therapeutic agents, offering unique advantages over conventional small molecules and biologics through their ability to directly and precisely cleave and (de)activate their protein targets. Since the early 1990s, FDA-approved protease therapeutics have served as replacement therapies for hematological disorders, as enzyme supplements for digestive disorders, and as treatments for neuromuscular disorders. Recent developments have expanded the use of native proteases to modulate antibody responses, improve transplant outcomes, and treat rare conditions with high unmet needs. Despite challenges such as immunogenicity and substrate specificity, the therapeutic landscape of proteases is being redefined by innovations in enzyme engineering and discovery. These advances, combined with targeted delivery strategies and improved stability, are reshaping proteases into precise and adaptable therapeutic agents. Rather than being limited to traditional uses, proteases are increasingly recognized for their potential to address complex conditions such as viral infections, neurodegeneration, and fibrosis, among others. With continued development, proteases are positioned to become a versatile and robust class of biologics with expanding clinical relevance. The present review explores the evolving landscape of protease therapeutics, focusing on their clinical applications, immune-modulatory capabilities, and future potential in precision medicine. This review provides a timely update to the comprehensive article "Proteases as Therapeutics" by Craik, Page, and Madison, published in the Biochemical Journal in 2011.

Medicine