Medicine and Pharmacology

Abstract: Avian viruses formed the foundation of early retrovirology. The historical line extends from the discovery of the first sarcoma virus by Peyton Rous to the quantitative determination of oncogenic activity in cell culture by the focus assay. As a viral group, avian retroviruses offered exclusive advantages that allowed the assembly of a unique and powerful tool chest for the analysis of viral activity. Among the fundamental discoveries facilitated by these tools were viral and cellular oncogenes, cell surface receptors, virus-specific detection of inapparent infection, high-frequency genetic recombination between retroviruses, and the genetic maps of simple retroviruses. The work with avian viruses was soon complemented by research on mammalian retroviruses, and several oncogenes that became the basis of successful targeted therapies were defined. The field of cancer genes is at a point of transition. Future developments will be driven by new technologies and interpretations. They will also require a more comprehensive approach.

Abstract: Background/Objectives: Previous studies have demonstrated the safety of pre-seasonal treatment with the mannan-conjugated birch pollen allergoid EP-088-T502. However, the safety of a combined pre- and co-seasonal treatment regi-men has not yet been investigated. This study aimed to compare the safety and tolera-bility of pre-seasonal versus pre- and co-seasonal treatment with EP-088-T502. Meth-ods: In this prospective, open-label, phase III trial (T502-SIT-059) (EudraCT No.:2022-004082-20), patients (N=109) who had participated in a preceding pivotal phase III study were offered continuation treatment with active EP-088-T502 (10.000 mTU/mL) across five treatment visits. For the subgroup analysis, all patients who completed their last treatment visit before 9 April 2023 (and thus before the start of the birch pollen season in Germany) were assigned to the pre-seasonal group (N=20). Those who performed the last treatment visit thereafter were assigned to the pre/co-seasonal group (N=83). Both groups were compared in terms of local and sys-temic immediate and late phase reactions and other EP-088-T502-related adverse events (AEs). Results: No deaths nor serious adverse events (SAEs) were reported during the study. No epinephrine administration was required. Systemic adverse drug reactions (SADRs, N=3) occurred in two patients who had previously received placebo. No grade III or IV systemic reactions according to the German AWMF classification were observed. Patients receiving pre- and co-seasonal treatment developed smaller wheals (mean diameter) compared with the pre-seasonal group (immediate reactions: 0.6 vs. 0.7 cm, late phase reactions: 0.3 vs. 0.4 cm at the last treatment visit). This was also reflected in the medians (immediate reactions: 0.2 cm vs. 0.4 cm, late-phase reac-tions: 0.2 vs. 0 cm at the last treatment visit). Of all AEs that were (possibly) related to EP-088-T502 (N=89), 74 (83%) occurred at the first three treatment visits (before the birch pollen season). The frequency of AEs was comparable between groups for the last two treatment visits. Patients who had received placebo in the previous trial experienced more treatment related side effects compared to patients who had already received EP-088-T502 in the previous year. Conclusions: These data suggest that EP-088-T502 is safe and well tolerated even when administered during the birch pollen season, regardless of prior exposure to EP-088-T502.

Abstract: Background/Objectives: This study evaluates the adaptation of a novel filling material (Odne®Fill, Switzerland) to the walls of the shaped root canal using micro-computed tomography. Methods: Fourteen extracted human molars (6 maxillary and 8 mandibular), comprising a total of 32 root canals, were included. After canal preparation, all canals were filled with Odne®Fill according to the manufacturer’s instructions. Periapical radiographs and micro-computed tomography were used to assess the extent of canal wall coverage by the filling material. Surface coverage was quantified by image segmentation and statistically analyzed. Results: The percentage of canal wall coverage ranged from 93.31% to 99.98%. The mean coverage rate was 97.63% (SD 1.70%) and the median was 98.23%, indicating a high degree of adaptation of the filling material to the ex vivo prepared canal walls. Conclusions: Under the conditions of this ex vivo study Odne®Fill demonstrated high canal wall adaptation values. These findings should be interpreted with caution and further com-parative and long-term studies are required before clinical relevance can be established.

Abstract: Objective: Thyroid cartilage calcification and glucose metabolism may vary with age and gender. This study aimed to investigate the role of [18F]-sodium fluoride ([18F]NaF) and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT for the evaluation of physiological molecular calcification and glucose metabolism of thyroid cartilage with age. Methods: This retrospective study analyzed [18F]NaF and [¹⁸F]FDG PET/CT images from the CAMONA study (NCT01724749). Regions of interest were placed around the thyroid cartilage on CT images using OsiriX software. The mean standardized uptake value (SUVmean) was measured for [¹⁸F]NaF and [¹⁸F]FDG PET/CT images. Pearson correlation coefficients were calculated to evaluate the effects of aging on the uptake of [¹⁸F]NaF and ^[18F]FDG in the thyroid cartilage. Results: A total of 127 healthy subjects (65 females and 62 males) with a mean age of 48.46±14.13 (range 21–75) years for [¹⁸F]NaF PET/CT and a total of 114 healthy subjects (52 females and 63 males) with a mean age of 49.05±14.29 (range 21–75) years for [¹⁸F]FDG PET/CT were included. A significant positive correlation was observed between age and SUVmean of [¹⁸F]NaF in the thyroid cartilage (r=0.18, p=0.04). This result indicates that molecular calcification of this cartilage increases with aging. However, the correlation between age and SUVmean of [¹⁸F]FDG in the thyroid cartilage was not statistically significant (r=-0.09 p=0.31). Conclusion: This study presents a novel methodology for the determination of molecular calcification and glucose metabolism of laryngeal cartilage using [¹⁸F]NaF and [¹⁸F]FDG PET/CT. Molecular calcification of thyroid cartilage was found to increase with age, whereas glucose metabolism did not show a statistically significant correlation with age.

Abstract: Biofilms (BFs) bacteria are dramatically intensifying tolerance to conventional antibiotics, no longer effective. Therefore, the research for new antibiofilm (ABF) compounds are noticeably increasing the studies proliferation rate. In this regard, intriguing questions should raise to be debated. To this end, the problematics of BF, mainly in medical setting, have been afforded here in an original way, examining the tension “between efficacy and understanding”. Questions include: are BF mechanistic studies indispensable and strictly required especially at academic levels with poor economic support? When may a purely phenotypic approach still hold scientific value? Could be demonstrate empirical efficacy alone, sufficient for scientific relevance of the study? Do high costs, long times mechanistic insights, also associated to environmental issues, represent the necessary key to defeating BFs and the benchmark that determines the robustness and impact of ABF research? The state of the art of global challenge against BF, responsible for difficult-to-treat and even lethal chronic infection, has been provided. The available armamentarium of best functioning antibiotics/combinations has been discussed, while the correct way to investigate ABF mechanisms has been clarified. Among 102 studies on the ABF activity, considered, distributed in Tables and discussed, mechanistic investigations carried out correctly have been found in only 34 ones. Only efficacy screens, stopping at phenotypic descriptions, as reported in 68 out of 102 papers, are considered essential for discovering efficacious ABF compounds and are welcome by Editors and scientific community. Such approach represents the main trend of most recent literature and is strongly desirable for publication.

Abstract: Background/Objectives: Treatment decisions for elderly patients with diffuse large B-cell lymphoma (DLBCL) often rely on subjective clinical impression rather than systematic frailty assessment. We evaluated whether a modified simplified frailty score (mSFS)—a binary adaptation of the Isaksen score—predicts treatment selection, toxicity, and survival. Methods: In this retrospective study of 117 patients aged ≥65 years with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or dose-attenuated R-CHOP (R-mini-CHOP) at MedStar Health community hospitals (2000–2025), the mSFS assigned one point each for age ≥80, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, and ≥5 comorbidities; score ≥2 defined frailty. Results: Among 86 R-CHOP recipients, 17 (19.8%) were mSFS-frail; among 31 R-mini-CHOP recipients, 15 (48.4%) were mSFS-fit. In R-CHOP recipients, frailty independently predicted worse overall survival (adjusted hazard ratio [aHR] 7.67, 95% confidence interval [CI] 2.36–24.97), progression-free survival (aHR 2.90, 95% CI 1.18–7.13), grade ≥3 adverse events (adjusted odds ratio [aOR] 3.90, p = 0.035), and early discontinuation (aOR 4.41, p = 0.034). Frail R-CHOP patients had lower complete response rates (aOR 0.24, p = 0.038). Fit R-mini-CHOP patients had 88% lower odds of complete response versus fit R-CHOP patients (aOR 0.12, p = 0.003). Among R-mini-CHOP recipients, frailty was not significantly associated with outcomes. Conclusions: The mSFS revealed bidirectional discordance with oncologist-assessed frailty and independently predicted survival, toxicity, and response, supporting its integration into community oncology practice.

Abstract: Background/Objectives: Type 2 diabetes mellitus (T2DM) is a chronic multifactorial metabolic disorder requiring multi-target therapeutic strategies. This study aimed to clarify the potential material basis, key targets and molecular mechanisms by which PuRenDan (PRD) acts against T2DM through an integrated network pharmacology and molecular simulation approach. Methods: Active compounds of PRD were screened from TCMSP, HERB 2.0 and the literature, and compound-related targets were predicted using TCMSP, SwissTargetPrediction and PharmMapper. T2DM-associated targets were collected from OMIM, DrugBank, DisGeNET, HPO, ClinPGx and GeneCards to obtain drug-disease intersection targets. Cytoscape was used to construct herb-compound-target and protein-protein interaction (PPI) networks, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was performed using AutoDock Vina, and representative ligand-receptor complexes were further assessed by 100 ns molecular dynamics (MD) simulations and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) binding free-energy analysis. Results: A total of 163 active compounds, 597 PRD-related targets, 9138 T2DM-associated targets and 483 intersection targets were identified. β-sitosterol, emodin, quercetin, kaempferol and formononetin were predicted as major active compounds, whereas AKT1, TP53, SRC, IL6, TNF, EGFR and ESR1 were identified as core targets. KEGG enrichment highlighted the PI3K-Akt, MAPK, HIF-1, FoxO, mTOR, AGE-RAGE and TNF signalling pathways. Docking suggested strong multi-target binding potential for β-sitosterol. MD and MM/PBSA analyses further indicated favourable dynamic stability for β-sitosterol-TNF, β-sitosterol-AKT1, β-sitosterol-SRC and emodin-EGFR complexes, with β-sitosterol-TNF showing the lowest binding free energy. Conclusions: PRD may exert therapeutic effects against T2DM through coordinated multi-compound, multi-target and multi-pathway regulation involving inflammation, insulin signalling, oxidative stress and metabolic pathways. β-sitosterol may represent an important candidate material basis of PRD, with TNF, AKT1, SRC and EGFR as potential key targets.

Abstract: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with significant morbidity and mortality. Structural remodeling of the left atrium, particularly myocardial fibrosis, plays a key role in AF pathogenesis. Matrix metallo-proteinases (MMPs) are critical regulators of extracellular matrix remodeling and may contribute to atrial fibrosis through genetic variation. This case–control study included 179 patients with AF and 56 controls. Eight polymorphisms across five MMP genes (MMP1, MMP2, MMP3, MMP9, and MMP12) were analyzed using PCR-based methods. Associations between single nucleotide polymorphisms (SNPs), AF susceptibility, recurrence, haplotypes, and gene–gene interactions were assessed. The study population was ethnically ho-mogeneous (Polish), minimizing population stratification bias. No significant differences in allele frequencies were observed between AF and control groups in univariate analysis. However, multivariable logistic regression revealed significant associations for MMP1 rs1799750 and MMP2 rs243864 under recessive inheritance models. Haplotype analysis demonstrated a significant global association with AF (p = 0.027), with specific haplotypes showing markedly increased risk. Multifactor dimensionality reduction identified significant gene–gene interactions, particularly involving SNPs in MMP1, MMP2, MMP3, and MMP12. These findings support a polygenic model of AF susceptibility involving extra-cellular matrix remodeling pathways and highlight the importance of multi-locus genetic analyses.

Abstract: 3,4-Methylenedioxyamphetamine (MDMA) has been shown in multiple clinical trials to greatly reduce Post-Traumatic Stress Disorder (PTSD) symptoms, with many patients experiencing lasting improvement. However, recent regulatory rejection based on problems with blinding highlights a contradiction, with regulatory agencies demanding placebo-controlled trials, yet the strong psychoactive effects of MDMA-assisted therapy make true blinding impossible.This paper examines neurofunctional mechanisms and methodological challenges relevant to MDMA-assisted therapy research. First, it introduces the Trauma-Affective Memory Loop (TAML), a simple model of how traumatic memories are stored, reactivated, and reinforced through key brain regions. Second, it explains how MDMA works on a neurofunctional level, by reducing fear signals it creates a temporary “therapeutic window”. In this state, patients can revisit trauma safely, without being overwhelmed, and reprocess the memory in a healthier way.Third, the paper proposes that different types of trauma exposures respond differently to MDMA-assisted therapy. Acute, one-time traumas may often be resolved within one to three MDMA sessions, while complex or developmental trauma, formed over years, may need repeated and carefully structured treatment.Finally, a proposed clinical-trial framework, the Brinzei MDMA-PTSD Protocol (BMPP), is presented. The framework uses a role-separated, quadruple-masked structure intended to reduce expectancy-related bias while preserving therapeutic fidelity. The aim is to move beyond debates about flawed blinding methods and instead design trials that clarify why MDMA works, for whom it works best, and how to deliver it safely and effectively.

Abstract: Background/Objectives: Celiac disease is an immune-mediated enteropathy with heterogeneous gastrointestinal and extraintestinal manifestations. Psychiatric symptoms, arthralgia, thyroid comorbidity, anemia, and abnormal liver tests can obscure recognition in primary care. Methods: We report a de-identified reflective case from routine family medicine practice, structured in accordance with CARE case-report principles. Results: A woman in her early sixties with hypothyroidism and glaucoma presented with new low mood, anhedonia, somnolence, generalized anxiety, increased alcohol intake, poor appetite, weight loss, abdominal bloating, diarrhea, flatulence, and polyarthralgia. Investigations showed mild anemia, markedly elevated ferritin and liver enzymes, uncontrolled hypothyroidism, and strongly positive tissue transglutaminase IgA (>250 kIU/L; reference 0.0-14.9). Radiographs showed mild osteoarthritis and osteopenia without erosive arthropathy. CT abdomen/pelvis excluded malignancy but showed severe diffuse hepatic steatosis and mild pancreatic atrophy. The patient declined gastroenterology referral and confirmatory endoscopy with duodenal biopsy. A working diagnosis of probable celiac disease was made; she commenced a gluten-free diet, received alcohol-cessation advice, had levothyroxine adjusted, and was followed in the community. Most symptoms improved within six months. Conclusions: Celiac serology should be considered in adults with anxiety or depressive symptoms accompanied by gastrointestinal symptoms, weight loss, arthralgia, autoimmune thyroid disease, or unexplained liver-test abnormalities. The case also highlights diagnostic uncertainty, and follow-up needs when biopsy is declined.

Abstract: Chronic migraine affects 1–2% of the global population and is the leading cause of neurological disability among women under 50 years of age. The advent of calcitonin gene–related peptide (CGRP)-targeting monoclonal antibodies and small-molecule receptor antagonists has constituted the first disease-specific preventive paradigm; nonetheless, real-world registries demonstrate that 30–50% of treated patients fail to revert to an episodic phenotype, with medication-overuse headache further complicating clinical management. The therapeutic ceiling observed with single-target CGRP pharmacology implies that chronification is governed by mechanisms operating upstream of, in parallel with, and beyond the trigeminovascular neuropeptide loop. The present narrative review synthesises converging evidence from 2020 to 2026 and advances a multi-stratum model in which chronic migraine is conceptualised as an emergent systems failure. Within the trigeminocervical complex, the alarmin high-mobility group box 1 (HMGB1) is proposed to function as an upstream catalyst of the Toll-like receptor 4 (TLR4)–NF-κB–CGRP signalling axis; murine nitroglycerin models indicate that HMGB1 silencing attenuates neuroinflammation and central sensitisation. Clinical data obtained from patients with medication-overuse headache reveal elevated circulating concentrations of lipopolysaccharide, HMGB1, and hypoxia-inducible factor 1-alpha, consistent with intestinal-barrier compromise driving sustained systemic neuroinflammation. Preclinical findings from 2026 document sex-specific perturbations of the gut microbiota and faecal metabolome, together with augmented allodynia in female chronic-migraine models; complementary work demonstrates that sleep restriction and caffeine synergistically reduce the trigeminovascular activation threshold in a sex-dependent manner. Functional neuroimaging implicates sustained decoupling of the salience, default-mode, and central-executive networks as the putative neural substrate of interictal cognitive morbidity. A complementary computational account, grounded in the Free Energy Principle, conceptualises chronification as the consolidation of pathologically rigid prior beliefs—a hypothesis amenable to falsification via task-based contingent-negative-variation, mismatch-negativity, and Hierarchical Gaussian Filter modelling of probabilistic-learning paradigms. It is concluded that progress in chronic-migraine research requires a transition from single-target optimisation toward multi-stratum intervention, anchored in a longitudinal transitional cohort with integrated neuroimaging, electrophysiological, microbial, and ecological-momentary endpoints.

Abstract: Introduction- Undergoing drastic metabolic and behavioral transformations, carcinogenesis is a cumulative process which leads to excessive proliferation in an unusual manner, camouflage to escape surveillance by the immune system. Aim-The aim of this review is to provide an in-depth exploration of immunology of cancer, highlighting the mechanisms and various aspects immune system, how it interacts with cancer cells and the challenges coming in its way due to tumor cell immune evasion. Method-A comprehensive literature survey and search was made across major electronic databases, which include PubMed, Scopus, and Web of Science, covering publications up to June 2025. The search strategy employed combinations of keywords and medical terms relevant to tumors. Conclusion-Representing one of the most significant advances in the field of oncology the evolving field of cancer immunotherapy offers promising treatment options thereby harnessing the body’s immune system to target cancer cells. Justification-it is not our intention to revisit many of the issues relating to tumor immunology, which have already been covered in detail previously in the literature. Rather this article focuses on the aspects that by compiling desperate foundational knowledge and parallel newer advances in this rapidly evolving field, the review offers a holistic framework of worth to our researchers, clinicians, and students working in the area of cancer immunology and oncology.

Abstract: Long‑acting injectable (LAI) formulations have transformed adherence in several psychiatric conditions, yet no depot antidepressant currently exists. People with major depressive disorder (MDD) remain at risk of accidental overdose from prescribed oral medications, particularly during periods of cognitive impairment or crisis. Artificial intelligence (AI)–driven molecular modelling now enables the design of antidepressant compounds optimised for slow‑release, water‑based depot systems that avoid the fibromas and granulomatous reactions associated with oil‑based injectables. This study outlines an AI‑enabled workflow for generating a novel antidepressant molecule with favourable receptor‑binding properties, low toxicity, and compatibility with biodegradable, aqueous depot carriers. The resulting formulation has the potential to reduce overdose risk, improve adherence, and decrease the burden of frequent GP prescribing.

Abstract: Mitochondria regulate cellular energetics, redox balance, apoptosis, and inflammatory signaling in oral, airway, and systemic tissues. Hypoxia is a powerful modulator of mitochondrial function, with effects ranging from adaptive hormesis to overt injury. Cyclic altitude training, most delivered as intermittent hypoxic exposure or intermittent hypoxia training (IHT), has been proposed as a strategy to improve mitochondrial efficiency and exercise performance. By contrast, obstructive sleep apnea (OSA) exposes patients to uncontrolled chronic intermittent hypoxia (CIH), a pattern increasingly linked to endothelial dysfunction, ceramide-mediated mitochondrial dysfunction, insulin resistance, systemic inflammation, oral dysbiosis, and periodontitis. This narrative review covers intermittent hypoxia, mitochondrial biogenesis, hypoxia-inducible factor signaling, OSA, periodontitis, oral microbiome shifts, nitric oxide biology, and smoke-related mitochondrial injury. Appropriately dosed IHT can increase mitochondrial biogenesis, improve mitochondrial morphology, and augment oxidative capacity through pathways involving PGC-1alpha, hypoxia-inducible signaling, mitochondrial dynamics, and reactive oxygen species-dependent hormesis. In contrast, CIH in OSA promotes oxidative stress, sympathetic activation, endothelial injury, and inflammatory signaling and is associated with worse periodontal status and altered salivary microbiome profiles. Controlled IHT and OSA-related CIH, therefore, represent opposite ends of a hypoxia continuum, and mitochondrial health connects sleep-disordered breathing, periodontal inflammation, environmental exposures, and systemic cardiometabolic risk within a single conceptual frame. Sphingolipid signaling—particularly hypoxia- and toxicant-driven ceramide accumulation—connects CIH, inhaled environmental exposures, mitochondrial fragmentation, and the development of insulin resistance.

Abstract: Amplification of the mesenchymal–epithelial transition factor protooncogene (MET), fibroblast growth factor receptor 2 (FGFR2), and epidermal growth factor receptor (EGFR) genes has been identified in 2–24%, 2–9%, and 27–64% of patients with gastric cancer (GC), respectively. This study characterised carcinogenesis-related alterations and copy number variation (CNV) in 286 genes from four human GC cell lines and analysed differences in the susceptibility of these cells to treatment with pelitinib, tepotinib, and docetaxel. Using a targeted DNA sequencing, we evaluated alterations and CNV in 286 genes from four GC cell lines. We assessed the antitumour activity of pelitinib, tepotinib, and docetaxel in these GC cell lines and in a xenograft model. Docetaxel is a drug commonly used to treat gastric cancer and was used as a positive control in this study. The effects of pelitinib, tepotinib, and docetaxel on cell viability (half-maximal inhibitory concentration), apoptotic cell death, tumour volume, and hematoxylin and eosin staining were evaluated using MTS cell proliferation assays and flow cytometry. Antitumour efficacy was assessed in xenograft mice. Compared to tepotinib, pelitinib inhibited the growth of GC cells, showing dose-dependent amplification of EGFR (CNV > 3, without HRAS, KRAS, or NRAS mutations), MET (CNV > 30), and FGFR2 (CNV = 87), with concomitant cell death induction. In the murine xenograft model, tumour volumes were significantly reduced in the pelitinib, tepotinib, and docetaxel-treated groups when administered by daily oral gavage at doses of 10, 10, and 5 mg/kg/day, respectively. Histologically, necrosis was more pronounced in the pelitinib, tepotinib, and docetaxel groups than in the control group. Pelitinib demonstrated anti-tumour activity, with MET and FGFR2 amplified in all tested GCs and EGFR amplified in GCs without HRAS, KRAS, or NRAS mutations.

Abstract: Gender role beliefs shape healthcare interactions, particularly in societies with deeply rooted traditional norms. This study examined discrepancies between culturally inherited gender role ideologies and actual behavioural patterns within a diverse cohort involved in medical training and practice. Participants, aged 20–52, represented a wide range of clinical exposure, employment status and personal life circumstances, offering a complex sociocultural spectrum rather than a uniform academic group. Using an interpretative phenomenological approach, participants provided written and oral reflections on widely known Romanian gender role axioms. Results revealed endorsement of traditional beliefs—like male authority and female domestic responsibility—yet these convictions frequently contrasted with participants’ lived behaviours, including women serving as primary earners, engaging in advanced studies and balancing multiple roles, and men in caregiving professions. This misalignment suggests unconscious bias and limited self-awareness of one’s own nonconforming practices. These discrepancies have implications for clinical care, as rigid gender role beliefs may influence communication, empathy, the ability to provide equitable healthcare to gender-diverse patients. Findings indicate the need for structured gender-diversity education, reflexivity training and cultural competence development across medical curricula, workplace settings and continuing professional education. Overall, the study demonstrates how traditional gender representations persist despite behavioural change, potentially shaping healthcare attitudes and reinforcing bias unless explicitly addressed.

Abstract: Background: Skin grafts including split-thickness skin grafts (SSG) and full-thickness skin grafts (FTSG) are widely used in reconstructive surgery. Infection following grafting can compromise graft take and prolong hospitalisation, yet contemporary cohort data describing incidence, microbiology and graft-specific risk factors remain limited. Methods: We conducted a retrospective observational cohort study of 977 consecutive skin graft procedures performed in 116 patients at two hospitals in New South Wales, Australia, between 1 July 2021 and 13 August 2024. Post-graft infection was defined as a clinician-diagnosed graft site infection with microbiological confirmation. Infection incidence was estimated with exact 95% confidence intervals. Associations between graft characteristics and infection were explored using chi-square testing and binomial regression to estimate relative risks. Length of stay (LOS) was assigned to the index admission corresponding to each procedure and analysed using negative binomial regression to account for overdispersion. Results: Among 977 graft procedures, 66 infections occurred, giving an overall infection incidence of 6.8% (95% CI 5.3–8.5%). Median LOS was substantially longer in infected cases than non-infected cases (34 vs 3 days, p < 0.001). Full-thickness grafts to the face (RR 0.083, 95% CI 0.008–0.827) and nose (RR 0.038, 95% CI 0.004–0.378) were associated with a reduced incidence of infection, although estimates were imprecise because of sparse data. Among infections, Staphylococcus aureus accounted for approximately 47% of cases and Pseudomonas aeruginosa for approximately 20%. In a nested antimicrobial audit cohort of 111 split-thickness skin graft procedures, peri-operative prophylaxis was common, postoperative antibiotics were frequently prescribed, and postoperative antibiotic prescribing was not associated with reduced infection, although the analysis was underpowered. Conclusions: Post-graft infection occurred in 6.8% of procedures. This rate is comparable with contemporary literature and was associated with substantial morbidity. S. aureus and P. aeruginosa predominated. These findings support consideration of targeted preventive strategies, microbiology-informed empiric therapy and antimicrobial stewardship, while highlighting the need for prospective studies with more comprehensive risk adjustment.

Abstract: Point-of-care testing (POCT) for cardiac troponin is increasingly used to support rapid clinical decision-making, particularly in resource-limited settings. However, while many central laboratories, including those in Sri Lanka, now use high-sensitivity cardiac troponin I (hs-cTnI) assays, commonly available POCT platforms continue to use conventional methodologies with different analytical characteristics and decision thresholds. We evaluated the analytical agreement and clinical concordance of two POCT troponin assays against a central laboratory hs-cTnI assay using paired samples obtained during routine clinical care in a Sri Lankan hospital. Both POCT devices demonstrated strong correlation with the laboratory assay (Pearson r ≈ 0.90). However, Bland–Altman analysis showed substantial positive bias and wide limits of agreement, indicating poor interchangeability at the individual sample level, with proportional bias observed in one device. Clinically relevant discordance was also identified, with 26.9% and 30.4% of samples classified as negative by POCT despite being positive by the reference assay. Regression-based recalibration did not significantly improve concordance. These findings highlight that strong correlation does not ensure diagnostic agreement, emphasizing the need for local validation before integrating POCT troponin assays into established hs-cTnI diagnostic pathways.

Abstract: Background: Neuroinflammation contributes to etiopathology and symptom severity in neurodegenerative and neuropsychiatric disorders. Glial cells, especially microglia and astrocytes, play a crucial role in neuroinflammation. It has been reported that ginseng and its bioactive component ginsenoside Rg1 exhibit anti-inflammatory effects and improve cognitive performance in various models. However, the exact underlying mechanisms remain unclear. Methods: An astrocyte-microglia co-culture model simulating physiological (M5, 5-10% microglia) and pathological/inflammatory (M30, 30-40% microglia) conditions was treated with different concentrations of ginsenoside Rg1 (15, 30, 45 µM), ginseng extract (derived from Korean red ginseng) at low-dose (12.5, 25, 37.5 µg/ml) or high-dose (125, 250, 375 µg/ml) for 24 hours. Cell viability was assessed by MTT assay. Microglial reactivity was examined by immunocytochemistry. Astrocytic gap-junctional coupling was investigated using scrape loading method and connexin 43 (Cx43) expression was analyzed by immunocytochemistry and Western blot. Results: Both Rg1 and low-dose ginseng extract reduced microglial activation under inflammatory conditions by promoting a phenotypic shift from activated to homeostatic (resting) microglia. Rg1 preserved astrocytic gap-junctional function by preventing the inflammation-induced downregulation of Cx43 expression and enhancing Cx43-mediated gap-junctional intercellular communication. Rg1 caused a significant reduction of glial cell viability only at high concentrations (30 and 45 µM) under inflammatory conditions. High-dose ginseng extract showed significant concentration-dependent cytotoxicity, reducing glial cell viability under physiological and pathological conditions, without comparable anti-inflammatory benefits. Conclusions: This study suggests that low-dose ginseng and its active compound Rg1 exert anti-inflammatory effects by modulation of astrocytic coupling and microglial reactivity. These results provide a novel therapeutic perspective for ginseng in the treatment of neurodegenerative and neuropsychiatric diseases related to neuroinflammation.

Abstract: Localized lower respiratory tract infection including unilobar and round pneumonia can be associated with hypoxia and oxygen requirements. Previous explanations include shunting of deoxygenated blood, a systemic inflammatory response syndrome and vasoconstriction.This is unexplained.The alternative hypothesis is that spread of fluid absorption inhibiting cytokines in the alveolar spaces of the inflamed lung is cause of hypoxia in localized lower respiratory tract infection by spread of Cystic Fibrosis Transmembrane Conductance (CFTR) dysfunction in alveolar epithelial cells to more areas including those not infected. There is no evidence of pulmonary shunting to explain hypoxia in localized pneumonia. Systemic inflammatory response syndrome (SIRS) related generalized increase in alveolar capillary barrier or pulmonary vasoconstriction not visible on a chest x-ray cannot explain the hypoxia detected in most patients. Confirmation of the hypothesis could be achieved using pulmonary MRI or high resolution CT to confirm spread of alveolar fluid accumulation from the localized pneumonia focus as opposed to generalized SIRS related pulmonary oedema together with cytokine and chloride measurement in bronchoalveolar lavage samples from the lung segments near the affected lung segment and unaffected contralateral lung. Ventilation/perfusion scintigraphy could investigate for involvement of vasoconstriction or micro-emboli from intravascular coagulation.Should the posed hypothesis be confirmed adjuvant strategies including small molecule CFTR activators, CFTR activating combination of beta-agonists, phosphodiesterase inhibitors and steroids could be used to treat hypoxia and CFTR activating low-intensity ultrasound explored.