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Retinoid dynamics in immune cells during age-related diseases.

Retinoids comprise vitamin A and its structurally related natural and synthetic derivatives. Retinoid dynamics involves multiple retinoid forms, carrier proteins, and enzymes that orchestrate the absorption, transport, storage and biotransformation of dietary vitamin A. Beyond their canonical metabolic functions, metabolites and proteins involved in retinoid metabolism also play distinct roles in signal transduction and transcriptome reprogramming, broadening the mechanisms that influence immune cell fate decisions. Age‑related changes in retinoid bioavailability and signaling intensity alter immune cell polarization and function, thereby contributing to the pathogenesis of chronic inflammation in neurodegenerative diseases, cardiovascular diseases, osteoarthritis, and other age-related diseases. In this review, we focus on age-related alterations in the retinoid metabolic pathway and their impact on inflammation and the progression of age-related diseases. This review highlights the pivotal role of retinoid metabolism in anti-ageing interventions and considers future directions and challenges in this field.

Humans

Systems Factors Contributing to Racial/Ethnic Disparities in Maternal Health: A Systematic Review.

INTRODUCTION: Despite ongoing efforts to reduce adverse maternal outcomes, including maternal mortality and severe maternal morbidity, racial/ethnic disparities in outcomes persist in high-income countries, including the United States (US) and Canada. Limited research has examined hospital-level factors that may drive disparities and contribute to adverse outcomes. This systematic review summarizes factors within the health system contributing to adverse outcomes and racial/ethnic disparities in the US and Canada to inform future policies and practices. METHOD: We searched SCOPUS, PubMed, EBSCOhost, and ProQuest Healthcare Administration for studies that reported hospital-level factors contributing to adverse maternal outcomes and racial/ethnic disparities. The review followed a two-stage screening process. The risk of bias of the included studies was evaluated using the Mixed Methods Appraisal Tool. The System Engineering Initiative for Patient Safety (SEIPS) 2.0 framework guided the identification and categorization of factors. RESULTS: Of 2441 studies retrieved, 30 met the inclusion criteria. Twenty-eight studies were conducted in the US, and 2 were conducted in Canada. The review included 16 qualitative, 11 quantitative, and 3 mixed-methods studies. We identified 60 factors associated with different system components, including person(s) (12%), tasks (28%), tools and technology (7%), internal environment (10%), organization (28%), and external environment (15%). Shortage of resources, including staffing, poor care coordination, and discriminatory organizational practices, were key factors described in the studies. CONCLUSION: Addressing health system factors in addition to broader societal factors is important to reduce adverse outcomes and promote equity for all women and birthing persons.

Humans

Discovery of NAT-6-321056 as a novel modulator of VEGFR2 signaling to suppress tumor angiogenesis.

Vascular endothelial growth factor receptor 2 (VEGFR2) is a master regulator of angiogenesis and cancer progression. However, current VEGFR2 modulators face significant challenges, including off-target toxicity and acquired resistance, underscoring the urgent need for novel therapeutic agents with improved efficacy and safety profiles. Here, we reported that virtual screening of 39,442 natural products from the ZINC natural products-derived library, coupled with molecular docking and molecular dynamics (MD) simulations to evaluate the binding stability of candidate compounds, identified NAT-6-321056 as a highly promising modulator of VEGFR2 signaling. Biological evaluations demonstrated that NAT-6-321056 exerted potent inhibition on the growth of a broad spectrum of cancer cells, including both solid tumors and hematological malignancies. In EA.hy 926 endothelial cells and SK-N-DZ neuroblast cells, the compound significantly suppressed proliferation, migration, and invasion. Microscale thermophoresis (MST) confirmed direct binding of NAT-6-321056 to VEGFR2 with favorable affinity. Kinase profiling against a panel of 33 kinases indicated that NAT-6-321056 exhibited a multi-kinase modulation profile. Mechanistic studies revealed that NAT-6-321056 suppressed the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and was associated with reduced VEGFR2 phosphorylation and attenuation of the downstream ERK/JNK/AKT signaling pathways. Moreover, NAT-6-321056 exhibited robust in vivo anti-angiogenic effects in both the chick chorioallantoic membrane (CAM) assay and transgenic zebrafish vascular fluorescence imaging models. Computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction suggested acceptable drug-like properties. Collectively, these findings demonstrated that NAT-6-321056 is a promising modulator of VEGFR2 signaling with potent anti-angiogenic activity and represents a viable candidate for cancer therapy.

Vascular Endothelial Growth Factor Receptor-2

Advances in cereal protein applications for infant and Young child nutrition.

BACKGROUND: The increasing use of plant-derived proteins in infant and young child nutrition necessitates tailored amino acid profiles, high digestibility and strict safety controls. Cereal proteins, such as rice, oat, maize, millet, barley, and wheat, are widely used in complementary foods but face intrinsic limitations, notably lysine and tryptophan deficits, antinutritional factors that reduce bioavailability, gluten immunogenicity in wheat/barley, and inorganic arsenic risks in rice. SCOPE AND APPROACH: This review synthesizes recent advances in processing and formulation strategies, including enzymatic hydrolysis, fermentation, germination, extrusion, cereal-legume complementation, and micronutrient fortification. Their impacts on digestibility, techno-functionality, iron and zinc bioavailability, and protein quality, including Protein Digestibility-Corrected Amino Acid Score (PDCAAS) and Digestible Indispensable Amino Acid Score (DIAAS) are critically reviewed using data from in vitro assays, product development, and clinical trials. KEY FINDINGS AND CONCLUSIONS: Processing and blending approaches can substantially improve protein digestibility, amino acid balance and micronutrient availability, and hydrolyzed rice protein holds clinical promise for cow's milk protein allergy (CMPA). However, most evidence is preclinical, reporting of protein quality is inconsistent, and industrial translation is constrained by sensory, shelf-life, contaminant and cost issues. We recommend standardized DIAAS-based reporting, large-scale feeding trials, sensory /stability optimization, and targeted exploration of underutilized grains (e.g., oat, millet) with active allergen monitoring. Prioritizing amino acid-focused formulation coupled with strategies to enhance micronutrient bioavailability will accelerate safe adoption of cereal proteins in early-life nutrition.

Humans

Performance comparison of rapid and native barcoding methods for Oxford Nanopore sequencing of Poliovirus Viral Protein 1 (VP1) amplicons.

Accurate and timely sequencing of poliovirus is critical for global eradication efforts, particularly for molecular epidemiology based on the typing region of the genome, viral protein 1 (VP1). While Oxford Nanopore Technologies (ONT) sequencing has expanded capabilities for poliovirus surveillance, the relative performance of different ONT library preparation methods, including ligation-based (Native Barcoding) and transposase-based (Rapid Barcoding) approaches, has not been systematically evaluated. In this study, we compared rapid barcoding and native barcoding workflows for sequencing VP1 amplicons from 17 type 2 poliovirus-positive samples, each processed in triplicate. Native barcoding generated significantly more sequencing output, producing approximately 2.3-fold greater total read yield than rapid barcoding, and demonstrated higher run-to-run reproducibility (R2 = 0.979-0.998 vs. 0.847-0.929, respectively; p&#x202f;<&#x202f;0.001). In addition, native barcoding generated 80% of the total yield achieved by rapid barcoding within approximately 7&#x202f;h, whereas rapid barcoding required approximately 40&#x202f;h to reach the same output. Despite these differences, both methods produced identical VP1 consensus sequences across all samples, with comparable read quality (median per-base Q-scores of approximately Q17-Q18). Rapid barcoding provided substantial practical advantages, reducing hands-on library preparation time (55 vs. 200&#x202f;min) and per-sample cost ($12.82 vs. $16.54), while simplifying workflow and reducing technical complexity. These findings indicate that sequencing yield may not be a determinant of downstream analytical outcomes for poliovirus VP1 ONT sequencing. Rapid barcoding therefore represents a cost-effective and efficient approach for routine poliovirus surveillance, whereas native barcoding remains advantageous in applications requiring rapid data generation or maximal sequencing depth.

Poliovirus

Selective and sensitive colorimetric sensing of carbosulfan based on BiO2-x/Bi2O2.75 nanosheets with excellent haloperoxidase-like activity.

The development of colorimetric methods based on directly inhibiting nanozyme activity for pesticide detection has attracted considerable attention. In this study, we report a novel colorimetric sensing strategy utilizing BiO2-x/Bi2O2.75 nanosheets (BiO2-x/Bi2O2.75 NSs) with haloperoxidase (HPO)-like activity for the rapid and sensitive detection of carbosulfan (CBS) in foods. Oxygen-vacancy-rich BiO2-x/Bi2O2.75 NSs with HPO-like activity were rationally constructed. Kinetic studies revealed a remarkable Michaelis-Menten constant (Km) of 0.014&#xa0;mM for I-, indicating a higher affinity for iodide ions than other reported HPO-like nanozymes, as evidenced by its lower Km. Under acidic conditions, CBS tends to be hydrolyzed to produce reductive sulfide species, which directly inhibit the iodoperoxidase-like activity of BiO2-x/Bi2O2.75 NSs, enabling selective detection with a limit of detection (LOD) of 0.18&#xa0;&#x3bc;g/mL and a linear range of 0.20-100&#xa0;&#x3bc;g/mL. When the concentration of interfering pesticides and substances was 5 times that of CBS, the sensor remained unaffected, exhibiting excellent stability and specificity. This work contributes to the detection of CBS in complex food matrices, bridging the application gap of HPO-like nanozymes in pesticide detection and providing a promising method for food safety detection.

Colorimetry

Psychotherapy training in psychiatry: a systematic review and narrative synthesis on the supervision experiences of early-career psychiatrists.

BACKGROUND: Supervision is a fundamental component of psychotherapy training, transforming theoretical knowledge into clinical skills through real-world practice. Psychotherapy training practices vary widely between countries, training programs, and over time, including supervision. Our systematic review aimed to investigate and describe the experiences of psychotherapy supervision through early-career psychiatrists' (ECPs) views. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and PubPsych for survey-based studies on ECPs' experiences of psychotherapy supervision during or after their psychiatry training and reported our findings according to the PRISMA guidelines. Of 32,877 articles screened, 29 articles were included. Each article underwent quality assessment, and results were synthesized narratively. RESULTS: Included articles published between 2000 and 2025, were from Europe (N = 16, 55.1%), the Americas (N = 5, 17.2%), Western Pacific (N = 4, 13.7%), South-East Asia (N = 2, 7%), Eastern Mediterranean (N = 1, 3.5%), and Africa (N = 1, 3.5%), with a total of 4691 participants. Supervision access rates ranged from 26.2% in Nigeria to 85.5% in Russia, with significant variation across countries and psychotherapy modalities. Most ECPs received 50-100 total hours of supervision, frequently delivered in weekly sessions. While formats, individual, group, or mixed, varied by country and training scheme, supervision was generally provided by a psychiatrist-psychotherapist. Common learning techniques included oral consultations and case discussions, followed by audio recordings or transcripts. The need to self-fund psychotherapy supervision costs was identified as a prominent barrier. CONCLUSIONS: Psychotherapy supervision is inconsistent globally, with barriers including supervisor availability and cost. There is a large implementation gap between recommendations and evaluated practice. Digital tools and competency-based frameworks may improve access and quality.

Humans

The genomic origins and evolutionary path to a key innovation in the world's most venomous snakes.

Evolutionary innovation is a catalyst for the colonization of new environments and the adaptive radiations of major groups. Novel traits typically evolve through the modification of preexisting characters, but the genetic paths underlying their origin have been challenging to trace, and the general requirements for and relative order of different kinds of gene mutations have been difficult to assess. Here, we trace the genomic origins of four procoagulant venom toxins (factor X, factor V, group I phospholipase A2, and Kunitz-type toxins) that collectively underlie a novel, especially potent blood-clotting venom type in the recently evolved Australian brown snake and taipan clade. We find evidence for a previously unknown fifth toxin, coagulation factor VII, and show that the toxins evolved through two distinct genetic paths. The factor X and factor V toxins evolved through the sequential de novo co-option of ancestral clotting factor proteins that entailed their heterotopic expression in the venom gland, the fixation of segmental duplications containing each locus, and subsequent gain-of-function mutations that rendered factor X and factor V constitutively active. In contrast, the phospholipase A2 and Kunitz-type toxins evolved by modifying the functions of neurotoxins that were part of the venom arsenal. Our findings support models in which innovative mutations in single-copy genes precede gene duplication in the evolution of novel proteins and offer a rare view into the genesis of a complex trait that has played a central role in a major adaptive radiation.

Animals

Prenatal exome sequencing of fetuses with central nervous system anomalies based on prenatal ultrasound and magnetic resonance imaging diagnosis: A retrospective cohort study with a systematic review and meta-analysis.

INTRODUCTION: Fetal central nervous system (CNS) abnormalities have diverse etiologies, with genetic factors as a major contributor. Prenatal exome sequencing (ES) is a powerful tool for precise molecular diagnosis of CNS anomalies, but its diagnostic yield varies among studies. This study aimed to evaluate the additional diagnostic yield of prenatal ES compared with chromosomal microarray analysis (CMA) in fetuses with CNS anomalies detected by prenatal imaging. MATERIAL AND METHODS: We collected ES results from fetuses diagnosed with CNS anomalies by prenatal imaging (2019-2024) who had negative results. Subgroup analyses assessed phenotype-specific ES diagnostic yield for associated genes and variants. A systematic review and meta-analysis incorporating our data and published studies further explored the association between phenotype and diagnostic yield. RESULTS: In the cohort study of 219 cases, ES identified pathogenic/likely pathogenic single nucleotide variations in 36 cases (16%). The highest diagnostic yield of ES was in cases with multisystem malformations (25%, 14/55), followed by multiple CNS anomalies (15%, 2/13) and isolated CNS anomalies (13%, 20/151). The most commonly identified isolated CNS anomaly was agenesis of the corpus callosum (31%, 5/16). Neural tube defects with urogenital anomalies were associated with a positive ES finding in 57% (4/7) of cases. The meta-analysis of 989 cases from 22 studies showed a pooled diagnostic yield of ES of 27% (95% CI, 21%-34%). The highest diagnostic yield of ES was in cases of corpus callosum anomalies with facial abnormalities (75%, 8/11) and neural tube defects with urogenital malformations (80%, 12/15). The diagnostic yield of ES for three or more CNS abnormalities was 43% (95% CI, 31%-58%), significantly higher than that for only two abnormalities (10%, 95% CI, 4%-18%). No significant difference in diagnostic yield was found between cases identified by prenatal MRI combined with ultrasound (27%, 95% CI, 20%-36%) and those identified by ultrasound alone (25%, 95% CI, 17%-35%). CONCLUSIONS: ES provided a significantly higher diagnostic yield than CMA for fetal CNS abnormalities, with diagnostic yields varying by phenotype. The systematic review and meta-analysis confirmed that the complexity and combination of malformations are key factors associated with differences in ES diagnostic yield.

Humans

Siglec-7 orchestrates mitochondrial dynamics and metabolic reprogramming to restrain human NK cell cytotoxic function.

Natural killer (NK) cells are innate lymphocytes that directly eliminate tumor and virus-infected cells by integrating signals from activating and inhibitory receptors, and their effector functions are tightly coupled to cellular metabolism. Given that the inhibitory receptor PD-1 reprograms T cell metabolism to shape functional fate, the bioenergetic consequences of inhibitory receptor engagement on human NK cells remain largely unexplored, particularly for sialic acid-binding immunoglobulin-like lectin (Siglec-7), a glyco-immune checkpoint receptor. Here, we investigated metabolic programs and effector functions associated with Siglec-7 expression and antibody-mediated Siglec-7 ligation in primary NK cells and NK-92MI cells. Siglec-7POS NK cells exhibited selectively impaired CD107a degranulation under glycolytic and oxidative phosphorylation inhibition, whereas Siglec-7NEG cells remained relatively resistant, indicating distinct energetic wiring between these subsets. Engagement of Siglec-7 by an agonistic antibody induced mitochondrial fission with altered Drp1 phosphorylation, transient mitochondrial depolarization, and broadly suppressed mitochondrial respiration, while concurrently enhancing glycolytic capacity, consistent with a dual metabolic shift upon Siglec-7 ligation. In contrast, sustained Siglec-7 expression in NK-92MI-S cells was associated with globally enhanced mitochondrial respiratory capacity, indicating that sustained Siglec-7 expression and short-term treatment with an agonistic anti-Siglec-7 antibody were associated with distinct metabolic profiles in NK cells. Furthermore, Siglec-7POS NK cells showed increased accumulation of autophagic vacuole, reduced proliferation, and heightened apoptotic susceptibility compared with Siglec-7NEG counterparts. Collectively, these findings support an association between Siglec-7 status, mitochondrial homeostasis, and metabolic fitness in NK cells, with Siglec-7NEG cells retaining a metabolically robust, cytotoxic phenotype.

Journal Article

Faster N1 latency in response to homeostatic-like plasticity of PREPs is impaired during pain: A randomized-placebo capsaicin-pain study.

INTRODUCTION: Homeostatic-like plasticity (HP-like) stabilizes cortical excitability through long-term potentiation and depression-like mechanisms. The efficacy of homeostatic regulation in the corticomotor system is impaired during pain, which may have functional relevance for chronic pain. This study investigated whether a cortical HP-like response could be assessed by nociceptive stimulation, and if such response was impaired by experimental tonic pain. METHODS: Twenty-eight healthy participants completed placebo and capsaicin sessions, with 11 sham controls for time and design. HP-like plasticity was induced with two blocks of anodal tDCS over the primary motor cortex. The N1 (TP7) and N2P2 (Cz) components of electrically induced pain-related evoked potentials (PREPs) were assessed from the volar forearm before and after patch application, and again immediately and 20&#xa0;min after HP-like induction. An HP-like response was defined by PREP decrease after induction, and further normalization to baseline. RESULTS: Anodal tDCS did not induce an HP-like regulation of PREP amplitudes. Interestingly, an HP-like response was observed as a fastening of N1 latency after HP-like induction, which returned to baseline values after 20&#xa0;min. The latter effect was impaired during capsaicin-induced pain, where N1 was slower. The N2P2 component showed habituation over time in all sessions. CONCLUSION: This is the first study that investigates the HP-like regulation of nociceptive-evoked responses. An HP-like response was observed as a shortening of N1 latency, suggesting that early nociceptive processing may be susceptible to homeostatic regulation. In contrast, the later component, N2P2, showed habituation over time, which prevented evaluation of HP-like effects.

Humans

Exploring precision risk in pediatric vesicoureteral reflux: Innate immune gene variations and reflux outcomes in the RIVUR cohort.

INTRODUCTION: Children with vesicoureteral reflux (VUR) are at increased risk for morbidity from recurrent urinary tract infections (UTIs), yet the factors influencing spontaneous VUR resolution remain poorly defined. This study evaluates whether genetic variations in key urinary innate immune effectors (DEFA1A3, DMBT1, and RNASE7) influences VUR resolution and interacts with prophylaxis to alter clinical response. METHODS: We conducted a secondary analysis of 303 RIVUR participants with available DEFA1A3 and DMBT1 copy number variation (CNV) data and RNASE7 rs1263872 genotype. Primary outcomes were (1) VUR improvement (decrease in grade) and (2) VUR resolution at study exit. Multivariable logistic regression models included genotype, treatment, and their interactions, adjusting for age, sex, baseline grade (high vs low), laterality, bowel/bladder dysfunction, and any UTI. Internal validation used 2000-sample bootstrap with bias-corrected and accelerated confidence intervals and influence diagnostics. RESULTS: Clinical covariates did not significantly predict VUR improvement. Children with DEFA1A3 CNV >5 had higher odds of improvement (OR 2.36, 95% CI 1.12-4.96, p = 0.023), an effect that remained significant in bootstrap analyses. High-grade VUR was associated with lower odds of resolution (OR 0.34, 95% CI 0.12-0.94, p = 0.038). A significant interaction was observed between prophylaxis and high DMBT1 copy number for VUR resolution (interaction OR 2.99, 95% CI 1.11-8.04, p = 0.031); no interaction was seen for improvement. RNASE7 rs1263872 was not associated with either outcome. CONCLUSION: Innate immune gene variation may contribute to heterogeneity in VUR outcomes. High DEFA1A3 copy number was associated with reflux improvement and a DMBT1-prophylaxis interaction was associated with reflux resolution. The results of this study is hypothesis-generating and prompt further evaluation to assess whether a subset of children may experience structural benefit from prophylaxis or have a more favorable natural history based on their innate immune genotype.

Humans

The composition of the periostracum in the razor clam Sinonovacula constricta and the mantle's response to sulfide.

The razor clam Sinonovacula constricta inhabits sulfide-rich intertidal sediments and exhibits remarkable tolerance to this toxicant, yet the role of its periostracum in sulfide adaptation remains poorly understood. In this study, we investigated the composition and structure of the periostracum proteins, and the response of the mantle to sulfide stress. Scanning electron microscopy and energy-dispersive X-ray spectroscopy revealed that the periostracum is approximately 10&#xa0;&#x3bc;m thick and contains 1.43&#xa0;wt% sulfur, and proteomic analysis further confirmed the presence of organic sulfur (Cys/Met-rich proteins), suggesting its involvement in sulfur deposition. Using LC-MS/MS, we identified 77 high-confidence proteins from the periostracum, which were classified into six functional categories: enzymes, framework proteins, immune-related proteins, calcium ion-related proteins, other proteins, and proteins with unknown functions. Phylogenetic analyses of representative proteins revealed bivalve-specific evolutionary patterns, with several proteins exclusively present in Bivalvia, such as Unknown protein 2 and 7, which possess signal peptides and low-complexity domains. For the sulfide exposure experiment, razor clams were subjected to three Na2S concentrations (0, 10, and 100&#xa0;&#x3bc;M). qPCR analysis showed that, compared with the control group, Chitin-binding protein 3 and Tyrosinase were significantly upregulated in the mantle, peaking in the 100&#xa0;&#x3bc;M group at 48&#xa0;h (5677.84-fold and 157.20-fold, respectively), whereas Collagen and Cadherin 3 were generally suppressed. This study represents one of the most comprehensive proteomic profiles of the razor clam periostracum and highlights the mantle's potential role in sulfide tolerance, offering insights for sulfur-tolerant aquaculture breeding and bioremediation applications.

Animals

Low-salinity stress alters growth, histology, physiology, and transcriptomic profiles of the gills and antennal glands in Macrobrachium rosenbergii.

Salinity is a major abiotic constraint in freshwater aquaculture of the giant freshwater prawn Macrobrachium rosenbergii, yet the coordinated roles of the gills and antennal glands, the two primary osmoregulatory organs in decapod crustaceans, under low-salinity stress remain poorly characterized. Here, we integrated histological, physiological, and transcriptomic analyses to characterize the adaptive responses of M. rosenbergii to acute (96&#xa0;h) and chronic (8&#xa0;weeks) exposure to salinity 5. Chronic low-salinity stress significantly impaired growth performance and decreased the survival rate. Acute stress induced thinning of the gill filaments, partial disorganization of pillar cells, and dilation of the intermicrovillar space in the antennal glands, whereas chronic stress caused gill vacuolization, cuticle thinning, and adaptive folding of antennal gland microvilli. In parallel, acute exposure significantly decreased hemolymph sodium and potassium ion concentrations but increased magnesium ion concentration, whereas chronic exposure increased hemolymph sodium and potassium ion concentrations, upregulated gill Na+/K+-ATPase activity, and enhanced hepatopancreatic antioxidant capacity. Transcriptomic analyses revealed distinct tissue-specific responses. Under acute stress, the gills preferentially activated pathways associated with cytoskeletal remodeling, motor proteins, and tight junctions, whereas chronic acclimation shifted the transcriptional response toward the renin-angiotensin system and glutathione metabolism. In the antennal glands, acute stress rapidly activated the renin secretion pathway, whereas chronic exposure promoted membrane remodeling by enriching pathways related to lipid and glycan metabolism. These findings reveal tissue-specific functional differentiation and synergistic coordination between the gills and antennal glands that underpin M. rosenbergii's adaptive response to low-salinity stress.

Animals

Impact of a thermal care bundle on peri-operative hypothermia, surgical site infection, and readmissions in osteosynthesis patients: A randomised controlled trial.

BACKGROUND: Maintaining normothermia throughout the peri-operative period prevents the occurrence of complications related to hypothermia. OBJECTIVE: To determine the effect of a thermal care bundle with a short prewarming period on inadvertent peri-operative hypothermia (IPH), surgical site infection (SSI), and unplanned readmission among osteosynthesis patients, and to identify associated variables. DESIGN: Open-label, randomised controlled trial. SETTING: University hospital. PATIENTS: One hundred and forty-eight patients who underwent osteosynthesis surgery. INTERVENTION: The intervention group received the thermal care bundle, which consisted in prewarming patients 10&#x200a;min before anaesthesia delivery and maintaining body temperature with a forced air device during surgery and the immediate postoperative period; in addition, the operating room environmental temperature was kept at 21&#x200a;&#xb0;C, and fluids were warmed to 38&#x200a;&#xb0;C. MAIN OUTCOME MEASURES: For the primary objective, hypothermia was defined as core body temperature below 36&#x200a;&#xb0;C and measured using the 3M Spot On zero heat flux sensor. Core temperature was recorded upon admission to the pre-operative holding area and subsequently every 30&#x200a;min until postanaesthesia care unit (PACU) discharge. Secondary objectives were SSI and readmissions: a follow-up at 30 to 60 and 90&#x200a;days was performed by the principal investigator. RESULTS: All 148 patients completed the study, and there were no significant differences between the groups at baseline. At the start of surgery, the incidence of hypothermia was significantly lower in the bundle group (1.3 vs. 9.9% among controls; odds ratio&#x200a;=&#x200a;7.59, P &#x200a;=&#x200a;0.021). A significantly lower incidence of hypothermia was also observed at admission to the PACU (14.3% in the bundle group vs. 29.6% among controls; odds ratio&#x200a;=&#x200a;2.07; P &#x200a;=&#x200a;0.024). Application of the bundle increased patients' core body temperature by 0.13&#x200a;&#xb0;C (95% confidence interval (CI), 0.003 to 0.254; P &#x200a;=&#x200a;0.045). Patients in the bundle group had a slightly lower observed incidence of wound infections requiring readmission (odds ratio&#x200a;=&#x200a;0.35; 95% CI, 0.04 to 2.92), although this difference was not statistically significant ( P &#x200a;=&#x200a;0.332). CONCLUSIONS: The bundle reduces peri-operative hypothermia by up to 59%, but does not affect on SSI; factors like presurgery hospital stay, operating room and PACU occupancy were identified as risk factors for SSI. REGISTRATION: 21 July 2022: NCT05469958 (Clinical Trials.gov), first recruitment 15 August 2022.

Adult

Barriers to physical activity in patients with systemic lupus erythematosus in the UK.

INTRODUCTION: Physical activity (PA) may play an important role as a non-pharmacological addition to the management of SLE for disease control and reduction of cardiovascular risk factors. Those with SLE have been reported to engage in PA less than the general population. OBJECTIVE: To describe PA patterns and patient-reported barriers to PA for people with SLE in the UK. METHODS: An online survey was conducted of adults aged&#x2009;&#x2265;&#x2009;18 years. Participants were recruited from posters in outpatient clinics, newsletters and Lupus UK social media platforms. Survey questions included demographic information, perception of disease activity, the International Physical Activity Questionnaire (IPAQ) and specific leisure time questions. RESULTS: Two hundred sixty-eight patients participated, with a median (IQR) age of 51 (39-59) years and SLE disease duration of 10 (4-20) years&#xa0;were included. SLE-diagnosis was collected by self-report. In those with complete IPAQ data, 178/228 (79.1%) were in a moderate/high activity group. Participants in this group were more likely to be in employment and had lower levels of fatigue and pain. Fatigue was the most reported barrier to PA, irrespective of activity levels. Participants in the low PA group were more likely to have SLE-specific barriers such as higher disease activity and higher pain scores. CONCLUSIONS: Perceptions and preferences in relation to PA differ greatly between individuals with SLE. The most common self-reported barrier to PA was fatigue. Exploration of individual perceptions of PA should form part of consultations, to address perceived barriers. Key Points &#x2022; Some patients with self-reported SLE can meet WHO physical activity targets, especially those who remain in work. &#x2022; Fatigue is the most frequently reported barrier to physical activity for patients, irrespective of their activity levels. &#x2022; People are less likely to engage in PA if they believe it will negatively affect their SLE.

Humans

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7&#xa0;days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals

Single antiplatelet therapy and tirofiban bridged with surface modified flow diverters for ruptured blood blister-like aneurysms: single center experience and systematic review.

BACKGROUND: Blood blister-like aneurysms (BBAs) of the internal carotid artery are rare but high risk lesions that frequently re-rupture due to their fragile structure and dissecting pathology. Treatment is particularly challenging in ruptured cases, given the risks associated with dual antiplatelet therapy. Recent advancements in flow diverter stents (FDSs) with surface modifications, and the use of single antiplatelet therapy (SAPT), offer a potential alternative strategy. METHODS: We conducted a retrospective review of 17 patients with ruptured internal carotid artery BBAs treated with surface modified FDS under SAPT (ticagrelor or prasugrel) bridged periprocedurally with intravenous tirofiban. All procedures were performed within the acute phase of subarachnoid hemorrhage. Clinical, radiographic outcomes, and procedure related complications were evaluated. RESULTS: Among 17 patients, 94.1% achieved complete angiographic occlusion, and 76.5% attained favorable clinical outcomes (modified Rankin Scale score &#x2264;2). No aneurysm rebleeding or device related ischemic events occurred. A total of 11 patients underwent external ventricular drainage or ventriculoperitoneal shunting without discontinuing SAPT, and no hemorrhagic complications were observed. A literature review incorporating seven additional series identified a total of 42 FDS plus SAPT treated BBA cases, with similar safety and efficacy profiles. CONCLUSIONS: Surface modified FDS with SAPT and tirofiban bridging appears to be a promising treatment option for ruptured BBAs, offering high occlusion rates with minimal thromboembolic and hemorrhagic complications. Larger prospective studies are needed to validate these findings.

Humans