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Introduction Two severe acute respiratory infection (SARI) case definitions (CDs) are often used in test-negative design (TND) hospital-based vaccine effectiveness (VE) studies. SARI-CD1 requires ≥1 symptom (cough, fever, shortness of breath, anosmia, ageusia, or dysgeusia); SARI-CD2 requires both fever and cough. Using VEBIS hospital network end-of-season 2023/24 data, we compared the effect of these CDs on influenza and COVID-19 VE estimates in Europe. Methods Using the TND, we restricted analysis to seven countries recruiting patients using SARI-CD1; we created a subset of SARI patients also meeting SARI-CD2. Cases were RT-PCR-positive for influenza A(H1N1)pdm09, A(H3N2), or SARS-CoV-2; controls were influenza or SARS-CoV-2 RT-PCR-negative. We estimated VE among patients ≥65 years using logistic regression adjusted for country, onset date, age, sex, and chronic conditions. We estimated VE overall, by age group (65–79, ≥80 years) and time since vaccination (14–59, 60–119, ≥120 days). Absolute VE differences ≥10% were considered relevant. Results Patient characteristics and outcomes were similar across CDs. SARI-CD1 had slightly more vaccinated cases, with little difference in controls between the two CDs. For influenza, the absolute VE difference between SARI-CD1 and SARI-CD2 was 10% for influenza A(H1N1)pdm09 (34% vs 44%), 19% among those aged ≥80 years (21% vs 40%) and 18% at 60–119 days post-vaccination (4% vs 22%). For SARS-CoV-2, absolute VE differences were 11% overall (29% vs 40%), 11% among ≥80 years (33% vs 44%), and 12% at 60–119 days (34% vs 46%). All other absolute VE differences were < 10%. Conclusions VE was similar for influenza A(H3N2), adults 65–79 years and 14–60 days post-vaccination. We observed signals of higher VE with SARI-CD2 for influenza A(H1N1)pdm09 and SARS-CoV-2, particularly among adults ≥80 years and ≥ 60 days post-vaccination, although 95% CIs overlapped. These signals suggest CDs may contribute to VE variability and VE studies should clearly indicate CDs used.

Background: Abnormal circular smooth muscle contractility is considered a key factor in the pathogenesis of diverticular disease (DD), contributing to increased intraluminal pressure and diverticulum formation. Altered cholinergic responsiveness of colonic smooth muscle has previously been reported in DD. Although angiotensin II (Ang II) regulates gastrointestinal smooth muscle contraction through angiotensin type 1 (AT1R) and type 2 (AT2R) receptors, its role in DD remains poorly understood. The aim of the present study was to investigate alterations in contractile responses to Ang II and cholinergic stimulation in the circular muscle of the colon in DD. Methods: Colonic tissue was obtained from 16 patients with DD and 16 control patients undergoing colorectal surgery. Immunofluorescence was performed to determine the localization of AT1R and AT2R. Ang II levels in colonic muscular tissue were quantified by enzyme-linked immunosorbent assay (ELISA), AT1R and AT2R protein expression were evaluated by Western blotting, and their mRNA expression was assessed by RT-qPCR. Circular smooth muscle strips were subsequently studied using in vitro organ bath recordings to assess Ang II-induced contractile responses under basal conditions and following pharmacological blockade with losartan, tetrodotoxin (TTX), or the AT2R antagonist PD123319. Results: AT1R was predominantly localized in colonic smooth muscle cells, whereas AT2R was mainly detected in the myenteric plexus and nerve fibers. Compared with controls, DD tissues exhibited increased local Ang II levels and higher AT2R protein expression, accompanied by increased AT2R mRNA expression. Bethanechol-induced contractility was reduced in DD, whereas both peak and mean 5-min Ang II-induced contractile responses were enhanced. Losartan significantly reduced the mean 5-min Ang II-induced contractile response in both groups. However, both peak and mean responses remained significantly greater in DD than in controls following AT1R blockade. Neither TTX nor PD123319 significantly affected Ang II-induced contractions. Conclusions: The present study demonstrates altered colonic circular smooth muscle contractility in diverticular disease, characterized by enhanced responses to Ang II and reduced responses to cholinergic stimulation. The distinct muscular and neural distribution of AT1R and AT2R, respectively, suggests that altered local Ang II signaling, together with altered cholinergic regulation, may contribute to the pathogenesis of DD.

Introduction: Coccidiosis is one of the most economically important diseases in poultry production, prompting increasing interest in natural alternatives to conventional anticoccidial drugs. The aim of this study was to evaluate the biochemical and hematological response of broiler chicken serum to an herbal anticoccidial supplement during experimental Eimeria infection.

Background/Objectives: Trans-resveratrol is a bioactive polyphenol with limited pharmaceutical applicability due to poor aqueous solubility, chemical instability, and low bioavailability. This study aimed to develop trans-resveratrol-containing liposomal formulations and evaluate the influence of phospholipid composition and ultrasound-assisted processing (UAP) using a conventional ultrasonic bath on their physicochemical properties and storage behavior. Methods: Liposomes were prepared by the ethanol injection method using Lipoid® S75, Lipoid® P45, soybean lecithin, egg yolk lecithin, and selected binary phospholipid mixtures. Trans-resveratrol identity was verified by LC–MS. Particle size, polydispersity index (PDI), and zeta potential were determined before and after UAP, and physical stability was assessed after 30 days of refrigerated, light-protected storage. Results: Phospholipid composition markedly influenced liposome physicochemical characteristics. Lipoid® P45-based formulations exhibited favorable initial particle size, PDI, and zeta potential profiles. UAP generally reduced particle size and improved particle size distribution immediately after preparation, although the magnitude of the effect depended on formulation composition. During refrigerated storage, short-term physical storage behavior was strongly formulation-dependent. Selected trans-resveratrol-containing formulations, particularly Lr12, Lr13, and Lr15, exhibited marked particle growth and increased polydispersity, whereas Lr20–Lr22 exhibited the most favorable particle size and PDI profiles after 30 days. Conclusions: Phospholipid composition was a critical determinant of trans-resveratrol liposome performance. Conventional ultrasonic-bath processing provided a simple and accessible means of improving initial liposomal characteristics, but did not universally ensure short-term physical stability during 30 days of refrigerated storage. Selected binary phospholipid formulations, particularly Lr20–Lr22, showed favorable physicochemical profiles and may represent promising candidates for further formulation development.

Background/Objectives: This article examines legal and professional challenges related to legal regulation of forest therapy. It explores the legal and institutional frameworks governing professional forest therapy and their implications for professional qualifications, access to practice, and the organization of professional activities in Lithuania and the Republic of Korea. It also illustrates regulatory models and examples of certification practices for forest therapy professionals in the European Union (EU) and third countries, provided by public and private bodies. This study identifies similarities and differences in professional forest therapy training and qualification requirements, and considers their potential implications for professional responsibility and protecting service users. Methods: A structured comparative legal analysis of legal and documentary sources was conducted, complemented by a structured analysis of scientific literature. Results: Forest therapy is regulated through diverse, often non-harmonized legal and professional frameworks. Differences exist in the legal definition of the practice, practitioner qualifications and training, and certification and accreditation procedures. These differences may affect access to professional practice, professional accountability, and safeguards for users, especially where professional forest therapy is provided in a healthcare context. Conclusions: The lack of harmonized regulation may have relevance for legal uncertainty among practitioners and service users. Greater clarity on professional forest therapy standards, methodology, qualifications, and the relationship between forest therapy and healthcare regulation can be relevant to professional mobility, forest therapy service quality and consistency, and the protection of patients’ and users’ rights.

BACKGROUND: OCEANIC-STROKE (XXX) showed that asundexian added to antiplatelet therapy reduced ischemic stroke without significantly increasing bleeding in patients with noncardioembolic ischemic stroke or high-risk transient ischemic attack. We characterized bleeding categories, sites, and key subgroups. METHODS: In the safety population, 12 254 participants received at least 1 dose of asundexian (n=6124) or placebo (n=6130). Bleeding was categorized by International Society on Thrombosis and Haemostasis criteria as major, clinically relevant nonmajor (CRNM), or minor. While-on-treatment analyses included events through 2 days after the last dose, with death and permanent discontinuation as competing risks. RESULTS: Major bleeding occurred in 117 (1.9%) participants with asundexian and 107 (1.7%) with placebo (cause-specific hazard ratio [csHR], 1.10 [95% CI, 0.85–1.44]; P=0.46). Major or CRNM bleeding occurred in 339 (5.5%) and 307 (5.0%), respectively (csHR, 1.12 [95% CI, 0.96–1.30]; P=0.16), and any bleeding in 763 (12.5%) and 752 (12.3%) (csHR, 1.02 [95% CI, 0.93–1.13]; P=0.65). Treatment effects for major and major or CRNM bleeding were consistent across prespecified subgroups, including planned dual antiplatelet therapy. Symptomatic intracranial hemorrhage occurred in 41 (0.7%) and 36 (0.6%) participants. Any gastrointestinal bleeding occurred in 186 (3.0%) and 147 (2.4%) (csHR, 1.28 [95% CI, 1.03–1.59]), and lower gastrointestinal bleeding in 102 (1.7%) and 59 (1.0%) (csHR, 1.75 [95% CI, 1.27–2.41]), primarily rectal bleeding. Any procedure-related bleeding and any mucosal bleeding did not differ significantly. CONCLUSIONS: Asundexian added to antiplatelet therapy reduced ischemic stroke without significantly increasing major, major or CRNM, or any bleeding. Lower gastrointestinal bleeding was more frequent with asundexian, whereas treatment effects on major and major or CRNM bleeding were consistent across prespecified subgroups.

The formation of artefacts during the extraction and isolation of specialised metabolites is a significant issue in phytochemical research and related areas, including marine chemistry, and microbial metabolites studies. Artefacts arise when genuine natural products undergo chemical transformations induced by mechanical stress, heat, extraction, purification, storage conditions, enzymatic activity, and/or analytical procedures. Common transformation pathways include hydrolysis, oxidation, isomerisation, solvolysis, rearrangement, polymerisation, and alkylation (e.g., O-methylation). These processes are discussed using representative examples from major phytochemical classes, such as iridoids, sesquiterpene lactones, alkaloids, glucosinolates, and phenolic compounds. Considering these mechanisms of artefact formation, a best practice workflow is proposed in order to minimise artefact formation. The workflow includes systematic control strategies to reduce artefact generation and guidelines for defining appropriate control experiments prior to publishing natural products as genuine compounds. In this way, the reliability of the phytochemical literature can be enhanced. The proposed workflow covers recommendations for extraction planning, solvent selection, temperature and pH control, protection from light, oxygen and enzymes, stability testing, and transparent, systematic analytical validation. Awareness of the feasibility of artefact formation, together with transparent control experiments, will improve reproducibility, ensure structural accuracy, and facilitate more reliable interpretation of phytochemical data. Finally, guidance is provided on how to detect artefacts in previous publications and how to check for their occurrence in one's own work.

Sex disparities in ischaemic heart disease (IHD) outcomes are well documented in Western Europe, but remain poorly characterized across Eastern Europe, a region marked by substantial mortality inequalities. We aimed to determine whether population-level case fatality among individuals living with IHD differed by sex in Eastern Europe and to identify modifiable risk factors associated with disparities.

Paroxysmal dyskinesia (PD) in dogs comprises episodic, involuntary, nonepileptic movement disorders. Recent evidence suggests that PD may be associated with gluten sensitivity, paralleling human gluten-related neurologic syndromes.

In vitro embryo production (IVP) is widely used in cattle breeding, however, pregnancy outcomes remain suboptimal, primarily due to variability in oocyte and embryo quality. This study evaluated the association of donor animal category with amino acid turnover in bovine oocytes and embryos and assessed its relationship with developmental competence. Cumulus-oocyte complexes (COCs) were collected via ovum pick-up from prepubertal heifers (8.4 ± 0.5 mo of age; n = 9), pubertal heifers (16.5 ± 0.5 mo of age; n = 10), and cows (25.5 ± 0.5 mo of age; n = 10). A total of 198, 324, and 286 COCs, respectively, were subjected to in vitro maturation, fertilization, and culture. Amino acid profiles in media were quantified using gas chromatography in at least 6 independent biological replicates per experimental group, where each replicate represented a separate culture well containing pooled oocytes or embryos. Oocytes from prepubertal heifers exhibited elevated alanine and glycine levels, whereas embryos derived from these donors showed increased levels of alanine, glutamic acid, and serine, together with greater depletion of essential amino acids such as valine, isoleucine, methionine, and cystine. In contrast, oocytes and embryos from pubertal heifers and adult cows exhibited more similar amino acid profiles. These metabolic differences were associated with oocyte quality, and embryo developmental outcomes, with the highest proportion of good quality oocytes and Day 7 blastocyst formation observed in adult cows. Specific amino acids - alanine, glycine, and asparagine - showed positive associations with oocyte quality in pubertal and adult donors. These results provide insight into the developmental limitations of prepubertal oocytes and may support future efforts to refine IVM and IVC protocols. In addition, the observed amino acid profiles suggest the potential of metabolomic biomarkers for improving embryo selection and IVP efficiency in cattle, although further validation is required.