Equianalgesic conversion tables estimate relative opioid doses expected to provide comparable analgesia, but they were not designed to predict abuse liability, reinforcement, or subjective drug-liking effects. A small number of human laboratory studies suggest that these dimensions may diverge. Oxycodone appears to produce greater psychopharmacological effects relative to morphine than would be expected from commonly used analgesic conversion ratios, whereas hydromorphone demonstrates substantially greater analgesic potency without a proportional increase in abuse-liability-related subjective potency compared with oxycodone or hydrocodone. This commentary presents an explicitly exploratory, hypothesis-generating framework that treats analgesic potency and reinforcement-related potency as distinct pharmacologic dimensions. The proposed equireinforcement ratio and reinforcement index are conceptual research tools, not validated measures or clinical conversion constants. Potential explanations include differences in absorption and onset, central nervous system exposure, receptor pharmacology, active metabolites, formulation, route, and study population. Evidence from methadone and buprenorphine treatment illustrates that receptor efficacy, pharmacokinetic stability, formulation, and treatment context can alter reinforcing effects, but it does not validate cross-opioid equireinforcement ratios. Marketing, availability, social norms, health-system structure, and cultural setting may also shape observed misuse independently of intrinsic pharmacology. The framework is intended to generate testable questions, improve interpretation of abuse-liability data, and discourage the use of equianalgesic potency as a proxy for addiction risk.

Nasal colonization by Staphylococcus aureus among healthcare professionals represents a potential risk for the spread of resistant strains in hospital settings. Thus, this cross-sectional study aimed to determine the prevalence of nasal colonization by S. aureus and to characterize the antimicrobial resistance profile of the isolated strains from professionals working in a public hospital in Caxias, Maranhão, Brazil. This study was carried out from December 2024 to February 2025. A total of 132 professionals working in a public hospital in the state of Maranhão were included. Among the participants, 36 (27.27%) were colonized by S. aureus, and 6 isolates (16.66%) were identified as methicillin-resistant S. aureus (MRSA). High resistance rates were observed to penicillin G and ampicillin (94.4%), as well as to the macrolides erythromycin (83.3%) and azithromycin (77.8%). Resistance to tetracycline was detected in 11.1% of the isolates, with 22.2% showing intermediate susceptibility. All isolates were susceptible to clindamycin, chloramphenicol, and rifampicin. Regarding risk factors, working in two healthcare locations compared to one remained significantly associated with nasal colonization after adjustment (OR = 3.15-3.50; p < 0.05), whereas longer professional experience was identified as a protective factor (OR ranging from 0.11 to 0.17; p < 0.05). These findings demonstrate the circulation of multidrug-resistant S. aureus strains among healthcare professionals and highlight the importance of active surveillance, rational antimicrobial use, and strengthened infection control strategies to reduce the spread of resistant pathogens in hospital environments.

Sepsis-associated organ injury remains a major cause of mortality in critically ill patients. Conventional assessment relies largely on physiological indicators, including lactate, mean arterial pressure (MAP), PaO2/FiO2 ratio, creatinine, urine output, and organ dysfunction scores. However, these isolated values or single-variable trends may incompletely capture the temporal instability and biological heterogeneity that characterize sepsis. Increasing evidence indicates that dynamic trajectories, variability patterns, and evolving subphenotypes may better characterize disease progression, organ recovery, and treatment responsiveness. In parallel, critical care medicine is moving from syndrome-level classification toward treatable traits, individualized treatment effects, and precision critical care. Dynamic phenotyping focuses on physiological trajectories, including lactate clearance, oxygenation evolution, hemodynamic variability, glycemic variability, and renal recovery, but its major value may lie in interpreting relationships among trajectories across organ systems. Interpretation of dynamic phenotypes therefore requires attention to cross-system temporal relationships, including coordinated recovery, coupled deterioration, and discordant recovery. From this trajectory-based perspective, sepsis-associated organ injury can be viewed as an interconnected multiorgan network involving lung-kidney, gut-lung, gut-liver, gut-kidney, and endothelial-organ cross-talk. Organ cross-talk may help explain dynamic coupling among organ systems, whereas microcirculatory-mitochondrial dysfunction may contribute to trajectory mismatch through impaired tissue perfusion, oxygen delivery-utilization uncoupling, bioenergetic failure, maladaptive metabolic reprogramming, and defective mitochondrial quality control. This trajectory-based perspective may inform future precision critical care, while most trajectory-guided strategies remain investigational and require prospective validation before routine clinical adoption.

Fermented fruit products contain diverse phytochemicals and may exert biological effects after oral intake. This study qualitatively screened for phytochemical-related signals in lung tissue after oral administration of fermented Rosa roxburghii Tratt (FRRT) and separately evaluated its preventive effects against lipopolysaccharide-induced lung injury in mice. UHPLC-MS/MS detected ten tentatively annotated phytochemical-related signals in mouse lung tissue after FRRT administration. The corresponding candidate compounds were quantified in FRRT by UHPLC-QqQ-MS/MS. FRRT preadministration attenuated bronchoalveolar protein leakage, inflammatory cytokine production, neutrophil-associated responses, epithelial barrier disruption, and histopathological injury following LPS challenge. These effects were accompanied by modulation of TLR4/MyD88/NF-κB, MAPK, JAK2/STAT3, Nrf2/HO-1, and NLRP3-related signaling. These findings document the qualitative detection of phytochemical-related signals in lung tissue under the screening conditions and support the preventive effects of FRRT against subsequent LPS-induced pulmonary injury.

Peripheral pulmonary lesions (PPLs) are increasingly detected by chest computed tomography, yet bronchoscopic diagnosis remains challenging for small and distal lesions. This prospective, single-center, randomized controlled study evaluated radial endobronchial ultrasound combined with a guide sheath (R-EBUS-GS)-assisted transbronchial cryobiopsy using a 1.1-mm ultrathin cryoprobe. Fifty patients with PPLs were randomized after successful R-EBUS-GS localization to either transbronchial cryobiopsy (TBCB) or conventional transbronchial lung biopsy with forceps (TBLB), with 25 patients in each group. The prespecified primary endpoint was pathological diagnostic yield. Pathological diagnostic yield was 84.0% in the TBCB group and 64.0% in the TBLB group; the difference was not statistically significant (p = 0.107). TBCB yielded a greater maximum total histologic tissue area than TBLB (14.6 ± 4.2 mm[2] vs. 3.1 ± 0.9 mm[2], p < 0.001) and was associated with a lower frequency of severe crush artifact (8.0% vs. 52.0%, p < 0.001). Grade 2 bleeding occurred in 32.0% and 24.0% of patients, respectively, and no Grade 3 bleeding occurred. One patient in the TBCB group developed pneumothorax and recovered with conservative treatment. These findings show that R-EBUS-GS-assisted 1.1-mm ultrathin cryobiopsy is technically feasible for PPL sampling and provides larger, better-preserved histologic specimens, while improvement in pathological diagnostic yield was not statistically demonstrated in this small randomized cohort.

Syndromic craniosynostosis (SC), such as Apert and Crouzon syndromes, causes midface hypoplasia that severely limits nasal cavity development. A computed tomography (CT)-based volumetric protocol for nasal cavity volumetry and choanal airway classification in pediatric SC patients, using landmark-based image segmentation software, is described and tested for intra-rater reproducibility. The protocol was applied to 10 SC patients (5 Apert, 5 Crouzon; 2-48 months; paired pre-/postoperative CT) and 10 reference children (60-168 months), not age-matched because CT is rarely indicated in healthy children. Intra-rater reliability was excellent (ICC = 0.987 and 0.909; 95% CI 0.934-0.997 and 0.689-0.976). Preoperative nasal cavity volume was significantly lower in SC patients (median 2,063.77 mm[3]; Q1-Q3 1,275.53-3,457.18) than in the reference group (median 35,502.13 mm[3]; Q1-Q3 28,811.21-39,167.15) (Mann-Whitney U = 0.000, Z = -3.780, p < 0.001). Nasal cavity volume increased between the paired CT scans in nine of ten patients (Wilcoxon Z = -2.701, p = 0.007; difference in medians +1,584.25 mm[3]; +76.8%), remaining at only 10.3% of the reference group median postoperatively. A weighted regression sensitivity analysis (log[Volume] vs log[Age], w = 1/Age; n = 10), accounting for the age disparity between cohorts, yielded an exploratory, model-based, non-normative estimate of 7,580 mm[3] at the SC median age (8.5 months), extrapolated below the reference group age range; the SC median represented 27.2% of this estimate. Preoperative volume varied descriptively by choanal category (normal, stenosis, atresia) without tracking narrowing severity, possibly reflecting global hypoplasia; small subgroups precluded inferential testing. Nasal cavity volume is an anatomical measure and does not by itself indicate functional airway obstruction. The protocol offers a standardized workflow for larger, age-matched multicenter studies.

This study investigated the lung-targeting characteristics, dose- and time-dependent effects, and safety of a novel engineered adeno-associated virus (AAV) vector, AAV-LungM3. In vitro, mouse primary lung organoids were transduced with AAV-LungM3 at doses of 10[3], 10[4], and 10[5] vector genomes (vg)/cell, and transduction was evaluated by fluorescence detection. For in vivo validation, C57BL/6 mice received intratracheal injection of AAV-LungM3 at doses of 0.5 × 10[11], 1.0 × 10[11], and 2.0 × 10[11] vg. Flow cytometry was performed to assess the dose-dependent transduction specificity and efficiency of AAV-LungM3 in type I alveolar epithelial cells (AT1 cells) and type II alveolar epithelial cells (AT2 cells). Using the favorable dose determined by the dose-response assay, the temporal changes in AT2 cell transduction specificity and efficiency were further monitored over a 4-week period. In addition, hematoxylin and eosin (H&E) staining, detection of peripheral blood inflammatory factors, and analysis of plasma biochemical indicators were used to evaluate early-phase safety. In vitro transduction increased in a dose-dependent manner. In vivo assays revealed that the AT2 cell transduction specificity of AAV-LungM3 decreased gradually with increasing viral dose, whereas its transduction specificity for AT1 cells increased. Nevertheless, no significant differences in the transduction efficiency of AT1 cells and AT2 cells were observed among all dose groups. Longitudinal monitoring indicated that week 2 was the preferred time point for AAV-LungM3 transduction. In conclusion, under the tested conditions, AAV-LungM3 exhibited targeting specificity to AT2 cells and favorable in vivo expression with no observed toxic effects, serving as a potential delivery platform for pulmonary gene therapy.

Obstructive airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), represent the two major chronic airway inflammatory diseases. In both conditions, the airways are exposed to a variety of microbial and environmental stimuli. A healthy airway microbiome is characterized not only by microbial diversity but also by the absence of significant quantities of pathogens, and is signified by ecological stability, functional resilience, and balanced interactions with the host immune system. Although microbial diversity is often considered a marker of respiratory health, its association with disease depends on the anatomical site, host factors, and environmental exposures. Thus, microbial diversity alone should not be used as a universal marker of airway health-the occurrence of pathogens and the organ compartment are also factors that are important to consider. Disruption of this microbial homeostasis, known as dysbiosis, may involve reduced diversity of the commensal flora as well as increased quantity of key pathogens, and this condition is believed to stimulate inflammation that is associated with the progression of asthma and COPD, including exacerbations. Environmental changes, including air pollution, climate change, and urbanization, can disrupt microbial balance by reducing diversity and increasing the prevalence of pathogens. Several mechanisms contribute to this interaction, including damage to the airway epithelium, impaired mucociliary clearance, oxidative stress, and alterations in innate and adaptive immune responses. This review examines the interplay between external environmental factors and the airway microbiome, and how they affect airway obstructive diseases, asthma, and COPD to understand their immunopathology, and to improve disease prevention and treatment approaches. This is an area of great interest, and further research is required to elucidate these interactions so we can better help our patients.