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Aneurysmal subarachnoid hemorrhage care in a middle-income public healthcare system: A real-world neurocritical care cohort.

BACKGROUND AND PURPOSE: Although aneurysm treatment capacity has expanded worldwide, outcomes after aneurysmal subarachnoid hemorrhage (aSAH) remain strongly influenced by neurocritical care (NCC) delivery, referral pathways, and access to specialized treatment. Contemporary data describing real-world aSAH care in resource-limited healthcare systems remain scarce. We aimed to characterize treatment patterns, NCC delivery, complications, and outcomes in a large Brazilian public referral center. METHODS: This retrospective cohort study included consecutive adults with confirmed aSAH admitted between June 2018 and March 2022 to a high-volume Brazilian tertiary referral center. Only patients admitted within five days of symptom onset were included. Demographic, clinical, radiological, treatment, complication, and outcome data were extracted from institutional records. Primary outcomes were in-hospital mortality and 3-month functional outcome assessed by the modified Rankin Scale (mRS). RESULTS: Seventy-four patients were included. Disease severity was high, with 45% presenting WFNS grades 4-5, 73% modified Fisher grade 4 hemorrhage, and 64% hydrocephalus. Endovascular treatment was performed in 73% of cases, and median time from admission to aneurysm treatment was 1 day. Despite early treatment capability, only 28% of patients were admitted to an ICU within 48 h, while 38% never received ICU care. Delayed cerebral ischemia occurred in 43%, radiologic vasospasm in 58%, ventriculitis in 22%, and infectious complications in 57%. External ventricular drainage was required in 42%, and vasoactive drugs were used in 85%. In-hospital mortality was 42%, and 66% had unfavorable 3-month outcomes (mRS 4-6). CONCLUSIONS: This real-world cohort highlights the substantial neurocritical care burden of aSAH in a middle-income public healthcare system. Despite timely access to definitive aneurysm treatment, patients experienced frequent neurological and systemic complications, emphasizing that contemporary aSAH care extends well beyond aneurysm occlusion.

Humans

Efficacy of the NMIC-150 system in identifying extended-spectrum beta-lactamases in clinical isolates.

Extended-spectrum beta-lactamases (ESBLs) are significant contributors to the growing global crisis of antimicrobial resistance. This study evaluated the performance of the NMIC-150 System for susceptibility testing of third-generation cephalosporins (3GCs) and assessed whether ceftazidime-avibactam and aztreonam-avibactam could identify ESBL-producing carbapenem-resistant Enterobacterales (CREs). A total of 278 non-duplicate clinical isolates (Klebsiella pneumoniae, E. coli, and Proteus mirabilis) were analyzed. Antimicrobial susceptibility was determined using reference broth microdilution (BMD) and the NMIC-150 System. ESBL production was defined as an ≥eight-fold reduction in the minimum inhibitory concentration (MIC) of 3GCs in the presence of clavulanic acid, according to CLSI criteria. Whole-genome sequencing was performed to characterize ESBL and carbapenemase genes among 3GC-resistant isolates. A Random Forest model was used to predict ESBL-producing isolates based on MIC values. The NMIC-150 System demonstrated over 90% categorical and essential agreement with BMD for ceftazidime and ceftriaxone, along with robust predictive performance via Random Forest analysis. These findings suggest that the NMIC-150 System is a reliable platform for 3GC susceptibility testing and that an ≥eight-fold MIC reduction with ceftazidime-avibactam or aztreonam-avibactam may serve as a phenotypic indicator of ESBL production in CRE isolates. In conclusion, the NMIC-150 System shows potential for routine antimicrobial resistance surveillance and may facilitate the rapid identification of ESBL-producing CREs in clinical settings.

Microbial Sensitivity Tests

Spore-forming Clostridia as overlooked determinants of microbial risk in wastewater reuse systems.

Using treated municipal wastewater for crop irrigation is a key strategy to combat drought-induced water scarcity. However, current wastewater reclamation standards systematically underestimate risks from spore-forming pathogens. As highlighted in a recent minireview by A. Mrozinski, C. Le Maréchal, and E. Topp in Applied and Environmental Microbiology (92:e00173-26, 2026, https://doi.org/10.1128/aem.00173-26), Clostridioides difficile and Clostridium perfringens survive conventional disinfection, persist indefinitely in agricultural soils, and harbor critical antibiotic resistance genes. To safeguard the food supply and protect public health, regulatory frameworks must shift from relying solely on standard vegetative bacterial indicators and include monitoring resilient, spore-forming pathogens.

Clostridium

Strategy for enhanced production of A40926B0 in Nonomuraea gerenzanensis using an efficient CRISPR/AsCas12f1 system.

The global emergence of vancomycin-resistant Gram-positive pathogens underscores the urgent need for efficient production of novel lipoglycopeptide antibiotics. Dalbavancin, a last-resort therapeutic agent, relies on its key biosynthetic precursor A40926B0, whose industrial manufacture is severely limited by the low yield of wild-type Nonomuraea gerenzanensis and inefficient genetic tools for this rare actinomycete. Here, we developed a high-efficiency CRISPR/AsCas12f1 genome editing system and applied systematic metabolic engineering to boost A40926B0 biosynthesis. First, conjugation conditions were optimized to elevate the transfer efficiency in N. gerenzanensis D11. The hypercompact AsCas12f1 nuclease showed markedly lower cytotoxicity than SpCas9 and enabled 100% gene deletion efficiency with preferred PAMs (TTTG, CTTG, GTTG). Second, we strengthened the shikimate pathway via multiple genetic strategies: overexpressing feedback-resistant DAHP synthase (aroG fbr ) and chorismate mutase/prephenate dehydrogenase (tyrA fbr ), as well as knocking out pheA. This manipulation blocks the phenylalanine synthetic branch and redirects metabolic flux toward the l-tyrosine branch. Third, we engineered the branched-chain fatty acid (BCFA) pathway via promoter replacement of bkdA2B2C2, LipAB, fabF and deletion of acdH to enhance isododecanoyl side-chain supply. The combinatorial engineering yielded strain B-13, which produced 1740 mg/L A40926B0 in shake flasks. Finally, 50-L fed-batch fermentation with continuous maltodextrin feeding further increased the titer to 1817 mg/L, the highest reported titer to date. This work establishes a robust CRISPR editing tool for N. gerenzanensis and provides valuable engineering references for precursor-oriented strain improvement targeting lipoglycopeptide antibiotics, offering insights for the industrial scale production of A40926B0.

A40926B0

An individualized nomogram for predicting progression-free survival in systemic anaplastic large cell lymphoma: a multicenter, retrospective, and internally validated study.

OBJECTIVES: To develop an individualized nomogram for predicting disease progression risk in systemic anaplastic large cell lymphoma (sALCL). METHODS: Independent predictors of progression-free survival (PFS) were identified using Cox regression in a multicenter retrospective cohort of 109 sALCL patients (2010-2022). These were incorporated into a three-factor nomogram, evaluated via bootstrapped internal validation (1000 resamples), ROC analysis, C-index, decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS: A total of 29 PFS events occurred during a median follow-up of 31 months. Multivariable modelling selected serum β2-microglobulin elevation, extranodal disease, and front-line chemotherapy choice (CHOP versus CHOPE or BV+CHP) as autonomous progression drivers. Upon internal bootstrap validation, the nomogram yielded strong prognostic accuracy, achieving AUCs of 0.81, 0.85 and 0.87 for 1-, 3- and 5-year progression-free survival, alongside a corrected C-index of 0.779 (95% CI: 0.699 - 0.861). Calibration plots showed close agreement between predicted and observed outcomes, while DCA confirmed superior net clinical benefit versus conventional IPI or Ann Arbor stratification across multiple decision thresholds. CONCLUSION: This first sALCL-specific nomogram integrates clinical and treatment variables to provide personalized PFS risk estimation. While internally validated, this exploratory, observation-based tool requires external validation and recalibration in prospective cohorts before clinical implementation.

Humans

Optimization of a niosomal formulation for Quercetin delivery: Comparative effects on growth performance, antioxidant and immune responses, and disease resistance against Streptococcus iniae in rainbow trout (Oncorhynchus mykiss).

Quercetin (QUR) is a flavonoid with antibacterial and antioxidant properties that has been studied for its effects on fish health and the immune system. Due to the low bioavailability of QUR, the present study was primarily aimed at developing a niosomal formulation of QUR to enhance its bioavailability and therapeutic properties. The performance of niosomal QUR was then compared with that of its free form by evaluating their effects on the growth and immune system of rainbow trout, Oncorhynchus mykiss. For this purpose, an optimal QUR-containing niosome was formulated by testing different proportions of cholesterol, surfactant, and stabilizer, and the niosomes were then added to the fish diet. A QUR-free diet and a diet containing QUR-free niosomes (QFN) were considered control groups. Niosomes prepared at low hydrophilic-lipophilic balance (HLB) values showed higher QUR entrapment efficiency (QUR-EE%) (P&#x202f;<&#x202f;0.01). An increase in the molar ratio of cholesterol to surfactant significantly reduced QUR-EE% (P&#x202f;<&#x202f;0.05). A surfactant/cholesterol/stabilizer ratio of 1:1:0.1 increased QUR-EE% (P&#x202f;<&#x202f;0.05). The particle size of the niosomes was also affected by HLB and the surfactant/cholesterol/stabilizer ratio. Low HLB values resulted in smaller particle sizes (P&#x202f;<&#x202f;0.01). Furthermore, a surfactant/cholesterol/stabilizer ratio of 1:1:0.1 resulted in the smallest niosomal particle size (P&#x202f;<&#x202f;0.05). The presence of diacetyl phosphate as the stabilizer in the formulation improved the niosomal zeta potential to -40.55&#x202f;mV. The optimal niosomal formulation (HLB&#x202f;=&#x202f;6.6; surfactant/cholesterol/stabilizer ratio of 1:1:0.1) remained stable at 2&#x202f;&#xb0;C over 10 days of storage, as the niosomal QUR content and size did not show significant changes during this period (P&#x202f;>&#x202f;0.01). After preparation of the diets containing the optimal niosomal QUR, fish were fed the experimental diets for two months. QUR, in both niosomal and free forms, resulted in better growth performance than the QUR-free diets (P&#x202f;<&#x202f;0.01). There were no significant differences in growth performance between the free and niosomal forms of QUR; however, 500&#x202f;mg/kg QUR showed significantly better growth performance than 250&#x202f;mg/kg QUR (P&#x202f;<&#x202f;0.01). Although both the niosomal and free forms of QUR enhanced immune and antioxidant components in the fish, the effects of the niosomal form were more significant (P&#x202f;<&#x202f;0.01). In addition, QUR in both free and niosomal forms reduced fish mortality after challenge with Streptococcus iniae. In conclusion, the results of this study suggest that the niosomal form of QUR has strong potential for improving the immune system of fish and increasing resistance to S. iniae infection.

Animals

Childhood Economic Mobility and Systemic Inflammation Among Men Who Experienced Low Income in Toddlerhood: The Moderating Role of Trait Hostility.

OBJECTIVE: Childhood economic upward mobility (ie, increases in family income across childhood) may attenuate links between childhood poverty and systemic inflammation in adulthood, the extent of which may vary depending on inter-individual differences in personality characteristics, including hostility. METHODS: Men who experienced low income in toddlerhood (N=171) were followed prospectively into adulthood. Annual family income was collected 12 times when men were 1.5 to 17 years old. Men completed the Cook-Medley Hostility Scale and had their fasting blood drawn to measure circulating levels of C-reactive protein (CRP) at age 32. Multiple linear regression analyses examined main and moderation effects of childhood economic upward mobility and adult hostility on CRP levels adjusting for income at 1.5 years, race, parent educational attainment, and adult income, education, waist circumference, and smoking status. RESULTS: Main effects were nonsignificant, but an interaction effect emerged. Counter to expectations, childhood economic upward mobility related to greater adult CRP as trait hostility decreased ( &#x3b2; =-0.203, P =.018). Simple slope analyses further revealed that childhood economic upward mobility was positively associated with CRP among men lower in hostility ( &#x3b2; =0.23, SE=0.09, P =.020) but was unrelated to CRP among men higher in hostility. Results of post hoc sensitivity analyses are also discussed. CONCLUSIONS: Counterintuitive findings suggest that for men who experience poverty in toddlerhood, the association between childhood economic upward mobility and adult CRP may be nuanced and even in the positive direction for men low in hostility, which aligns with work on unintended health consequences of upward mobility.

Humans

Sex-stratified mortality trends in preterm birth complications in Sierra Leone: progress, persistence, and equity implications.

BACKGROUND: Preterm birth complications remain a leading cause of neonatal mortality in Sierra Leone, despite recent health system gains. Evidence on long-term sex-specific disparities in mortality due to preterm birth complications is limited, constraining equitable neonatal care planning. OBJECTIVE: To examine two&#x2011;decade trends in sex&#x2011;stratified mortality from preterm birth complications using standardized equity indicators. METHODS: We conducted a retrospective longitudinal analysis of sex-disaggregated mortality estimates from the World Health Organization (WHO) Global Health Estimates (GHE), accessed through the WHO Health Equity Assessment Toolkit (HEAT), Built-in Database Edition (Version 6.0). Mortality rates per 100,000 population were extracted for 2001, 2006, 2011, 2016, and 2021. Inequality was assessed using absolute difference (D), relative ratio (R), population attributable risk (PAR), and population attributable fraction (PAF). RESULTS: Mortality declined substantially between 2001 and 2021 for both males (85.1-49.3 per 100,000) and females (71.2-39.9 per 100,000). Male mortality remained consistently higher across all years, with relative ratios indicating approximately 20-25% excess mortality among male neonates. Absolute inequalities narrowed modestly over time, whereas relative inequalities remained largely unchanged. PAR and PAF remained close to zero throughout the study period. Wider uncertainty intervals in earlier years reflected limited empirical data availability. CONCLUSION: Although preterm mortality declined over two decades, a persistent male disadvantage remained in Sierra Leone. These findings highlight the importance of integrating sex-disaggregated equity monitoring into neonatal policies and programmes. Future research should evaluate strategies to reduce the persistent excess mortality among male neonates while sustaining overall improvements in neonatal survival and progress toward Sustainable Development Goal 3.2.

Humans

Association of time-averaged systemic immune-inflammation indices with in-hospital mortality after intracerebral hemorrhage: a retrospective study.

BACKGROUND: Systemic inflammation plays a central role in secondary brain injury following intracerebral hemorrhage (ICH). Although inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) are linked to poor outcomes, their associations with mortality are commonly assumed to be linear, potentially overlooking nonlinear patterns where mortality risk rises steeply at higher levels. METHODS: We conducted a retrospective study using the MIMIC-IV database, including 440 patients with non-traumatic ICH who were alive and remained in the ICU for at least 72&#xa0;h after admission. Mean NLR, SII, and SIRI were calculated from measurements obtained during this period. Multivariable logistic regression and restricted cubic spline (RCS) analyses were applied to assess their independent and nonlinear associations with in-hospital mortality. Model discrimination and calibration were internally validated using 1,000 bootstrap resamples. RESULTS: The in-hospital mortality rate was 26.1%. After multivariable adjustment, NLR and SIRI remained independently associated with mortality. Patients in the highest SIRI quartile had the highest risk of death (aOR&#xa0;=&#xa0;5.12; 95% CI: 2.57-12.24; p&#xa0;<&#xa0;0.001). RCS analysis revealed a significant nonlinear association between SIRI and mortality (p-nonlinearity&#xa0;<&#xa0;0.05), showing a steep risk increase at higher SIRI levels. Adding SIRI to the base model provided a modest improvement in discrimination (AUC 0.762 to 0.785, p&#xa0;=&#xa0;0.045) and significantly improved risk reclassification (cNRI&#xa0;=&#xa0;0.4778, p&#xa0;<&#xa0;0.001; IDI&#xa0;=&#xa0;0.0240, p&#xa0;=&#xa0;0.0151). CONCLUSIONS: Among patients with ICH who met the 72-hour eligibility criterion, higher 72-hour average SIRI was independently associated with in-hospital mortality. As a time-averaged measure, SIRI should be interpreted as a dynamic marker integrating the initial inflammatory state and the early clinical course rather than as a purely baseline prognostic factor. Although adding SIRI to the base model modestly improved discrimination and risk reclassification, it should be considered a candidate prognostic marker requiring external validation before clinical application.

Humans

To longevity and beyond: A systems view of aging and stress resilience.

Aging is a dynamic and time-dependent process characterized by progressive functional decline across biological systems. Key hallmarks, including genomic instability, telomere attrition, loss of proteostasis, mitochondrial dysfunction, and immunosenescence, have been widely described, each reflecting distinct yet interconnected mechanistic frameworks. Rather than acting in isolation, these processes arise from complex interactions among cellular stressors, impaired repair mechanisms, and the cumulative burden of maladaptive responses. This system-level perspective explains the inter-individual variability in aging trajectories. Centenarians represent an extreme and informative model of successful aging, in which the balance between damage accumulation and repair is shifted toward the maintenance of physiological function. Their exceptional longevity is supported by coordinated genetic, epigenetic, metabolic, and immunological adaptations that enhance resilience to age-related stressors. Here, we summarize the biological drivers and theoretical frameworks of aging within an integrative context, focusing on mechanisms associated with extended healthspan in centenarians. We also examine the contribution of major animal models, highlighting their complementary roles in elucidating conserved and species-specific aging pathways. Overall, aging outcomes reflect a dynamic equilibrium between damage and repair processes. Understanding how this balance is modulated in long-lived individuals may inform strategies to promote healthy aging and delay the onset of age-related diseases.

Humans

Recent advances in supramolecular macrocycle-based artificial light-harvesting systems.

Artificial light-harvesting systems (ALHSs) inspired by the antenna function of natural photosynthesis provide molecular platforms for collecting excitation energy and directing it to emissive or reactive acceptors. In many supramolecular ALHSs, however, practical performance is limited by poorly defined donor-acceptor orientation, aggregation-caused quenching (ACQ), interfacial defects, and limited stability in aqueous or complex media. Supramolecular macrocycles-particularly pillar[n]arenes (PAs), cucurbit[n]urils (CBs), calixarenes (CAs), cyclodextrins (CDs), and supramolecular coordination complexes (SCCs)-offer a useful design space because their cavities, pre-organized scaffolds, and reversible non-covalent interactions can confine chromophores, tune local donor/acceptor ratios, and modulate F&#xf6;rster resonance energy transfer (FRET). This Review systematically examines the unique structural advantages and assembly mechanisms of the five macrocyclic families, with an emphasis on their use in constructing ALHSs-from single-step to cascaded FRET-and in advancing aqueous photocatalysis, near-infrared bioimaging, panchromatic fluorescence modulation, and singlet oxygen generation. The resulting structure-property-application framework is intended to guide the rational design of macrocycle-assisted photofunctional materials while avoiding overextension of the photosynthesis analogy.

Journal Article

Altered reproductive hormone profiles in systemic lupus erythematosus - A systematic review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) shows a marked female predominance during reproductive years, possibly suggesting hormonal factors in its pathogenesis. However, evidence regarding reproductive hormone alterations in SLE remains inconsistent. OBJECTIVES: To systematically review studies assessing reproductive hormone levels in adult SLE patients compared with healthy controls and across disease activity states. METHODS: Following PRISMA guidelines and a pre-registered protocol (PROSPERO CRD42024544730), PubMed and Scopus were searched (May 2024). Eligible observational studies reported estradiol, testosterone, progesterone, prolactin, FSH, LH, DHEA-S, DHEA or androstenedione in SLE patients versus controls or by disease activity. Random-effects meta-analyses were conducted. RESULTS: Eighty-three studies were included (5389 individuals for SLE vs. controls; 2067 for active vs. inactive SLE). Prolactin was consistently higher in SLE (MD 8.07&#xa0;ng/mL; 95% CI 4.69-11.45; p&#xa0;<&#xa0;0.001) and even more during flare (MD 5.83&#xa0;ng/mL; 95% CI 3.88-7.78; p&#xa0;<&#xa0;0.001). Estradiol showed non-significant overall elevations but was significantly higher in women with active disease (MD 8.55&#xa0;pg/mL; 95% CI 1.37-15.73; p&#xa0;=&#xa0;0.03). DHEA-S was found to be significantly lower in SLE (MD -1.00&#xa0;&#x3bc;g/mL; 95% CI -1.5 to -0.50; p&#xa0;=&#xa0;0.002) but too few studies evaluated its dynamics during flares. FSH and LH were significantly higher in men with SLE. Other hormones were inconsistent. Only three small heterogeneous studies evaluated hormonal changes during flares. CONCLUSIONS: Prolactin excess and androgen deficiency are consistent features of SLE, particularly in women, while elevated gonadotropins are mainly seen in men. Estradiol is higher during active disease but other data are inconsistent. Longitudinal studies are limited, with prolactin the only hormone consistently linked to disease activity and full hormonal profiles during flares are largely unstudied.

Humans

Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD. OBJECTIVES: To examine baseline sex differences in ECS-related mRNA expression, DNA methylation, and single nucleotide polymorphisms (SNPs) in MDD, and associations between baseline ECS markers and antidepressant outcomes in sex-stratified analyses. METHODS: Among 178 participants with MDD from CAN-BIND-1, all received escitalopram for 8 weeks; non-responders then received adjunctive aripiprazole from Weeks 8-16.Response was defined as &#x2265;&#x2009;50% reduction in MADRS score, and remission as MADRS&#x2009;&#x2264;&#x2009;10. ANCOVAs examined baseline sex differences and sex-stratified biomarker associations with percent MADRS reduction at Weeks 8 and 16, as well as categorical response and remission outcomes. Covariates included site, baseline MADRS, age, and ethnicity. False discovery rate correction was applied. RESULTS: Baseline sex differences in methylation were observed for CACNA1H, GABRB2, MAGL, and GABRR2, though none survived correction. No baseline sex differences in mRNA expression or SNPs were detected after correction. Lower baseline DAGLA mRNA in males was associated with greater Week 8 symptom improvement (FDR corrected). This association was not observed in females. No associations with response or remission at Weeks 8 or 16 survived correction. IMPLICATIONS: Baseline sex differences in peripheral ECS-related markers were not detected in this sample. Larger studies are needed to verify whether ECS-related biomarkers, particularly DAGLA, contribute to antidepressant outcomes in a sex-specific manner.

Humans

Safety, tolerability, pharmacokinetics, and pharmacodynamics of oral JMKX003002 in Chinese healthy participants: a randomized, double-blind, placebo-controlled, single- and multiple-ascending dose, and food-effect phase I clinical trial.

OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharma-codynamics (PD) of the sodium-hydrogen exchanger 3 (NHE3) inhibitor JMKX003002 in Chinese healthy participants. PATIENTS AND METHODS: This phase I, randomized, double-blind, placebo-controlled study included a single-ascending dose (SAD) study with seven cohorts (1&#x2009;mg [n&#x2009;=&#x2009;4] and 5, 20, 50, 75, 100, or 125&#x2009;mg [n&#x2009;=&#x2009;8]), a food-effect (FE) study with six sequence groups (25&#x2009;mg twice daily, n&#x2009;=&#x2009;4), and a multiple-ascending dose (MAD) study with two cohorts (10&#x2009;mg or 20&#x2009;mg twice daily, n&#x2009;=&#x2009;10). RESULTS: JMKX003002 was well-tolerated, with mostly mild treatment-related adverse events. One Grade 3 diarrhoea occurred in each of the 50&#x2009;mg and 125&#x2009;mg groups. No serious adverse events were reported, and no participants discontinued or withdrew due to treatment-emergent adverse events. Most plasma samples were below the limit of quantification (0.2&#x2009;ng/mL), with only transient detection of low concentrations, indicating low systemic exposure. JMKX003002 was primarily excreted in&#xa0;stool (79.9% recovered) and was undetectable in urine. The PD results consistently showed decreased urinary sodium and phosphorus, along with increased stool sodium and phosphorus, compared to baseline across all three studies. One day after discontinuation, stool sodium and phosphorus remained elevated relative to baseline in the MAD study. Mixed-effects model analysis in the FE study demonstrated significant food effect on stool sodium and phosphorus excretion. CONCLUSION: JMKX003002 exhibited favorable safety and tolerability with minimal systemic exposure. It effectively increased sodium and phosphorus excretion in stool. These promising findings warrant further investigation of JMKX003002 to evaluate its clinical benefits. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300070473). Registered on April 13, 2023; prospectively registered.

Adult

Technology choice, glycemic control and patient-reported outcome measures in adults with type 1 diabetes: A randomized crossover trial comparing a smart insulin pen with an automated insulin delivery system (EBIACE-1).

AIMS: To compare glycemic outcomes and patient-reported outcome measures (PROMs) between smart insulin pens (SIP) and an automated insulin delivery (AID) system in adults with type 1 diabetes (T1D), and to identify individuals able to maintain near-optimal glycemic control using SIP. METHODS: EBIACE-1 was a randomized, open-label, crossover trial including 31 adults with T1D. Participants received SIP (InPen&#x2122;) and AID (MiniMed&#x2122; 780G) for 6&#xa0;months each. Co-primary outcomes were time in range (TIR 70-180 mg/dL) and HbA1c. Treatment effects were assessed using longitudinal models in intention-to-treat (ITT) and per-protocol (PP) analyses. Predictors of near-optimal glycemic control with SIP were evaluated using multivariable logistic regression. RESULTS: AID improved glycemic control versus SIP, with higher TIR (81&#xa0;% vs 66&#xa0;%; +15&#xa0;%, 95&#xa0;% CI 10-19; P&#xa0;<&#xa0;0.001) and lower HbA1c (6.9&#xa0;% [52&#xa0;mmol/mol] vs 7.3&#xa0;% [56&#xa0;mmol/mol]; -0.4&#xa0;%, 95&#xa0;% CI&#xa0;-&#xa0;0.6 to&#xa0;-&#xa0;0.3; P&#xa0;<&#xa0;0.001). Near-optimal glycemic control with SIP was achieved by 12 of 26 participants (46&#xa0;%). In exploratory analyses, higher baseline diabetes-related life interference was associated with a lower probability of achieving this outcome. CONCLUSIONS: AID provides superior glycemic control, although nearly half of participants achieved near-optimal control with SIP, supporting a personalized approach to technology selection.

Adult

Effect of Perioperative Sucralfate Administration on Pain Control After Tonsillectomy: A Systemic Review and Meta-Analysis.

OBJECTIVES: This study evaluated the efficacy of perioperative intraoral sucralfate in reducing postoperative pain following tonsillectomy through a systematic review and meta-analysis. METHODS: A comprehensive search of PubMed, SCOPUS, Embase, Web of Science, and Cochrane up to September 2025 identified 13 studies comparing perioperative intraoral sucralfate with placebo or no treatment. Outcomes included throat pain, otalgia, swallowing pain, analgesic consumption, and perioperative morbidities. RESULTS: Sucralfate increased the proportion of patients reporting no or mild throat pain and otalgia, improved mucosal healing at 5 to 7&#x2009;days, and reduced throat pain, swallowing pain, otalgia, analgesic use, and time to resume&#x2009;>50% of a regular diet. No significant differences were observed in postoperative bleeding or nausea/vomiting. CONCLUSION: Perioperative intraoral sucralfate may be an effective adjuvant therapy that improves postoperative pain control, enhances wound healing, reduces analgesic requirements, and facilitates earlier dietary resumption after tonsillectomy.

Humans

Human-Centered Workspace Optimization: A 2 &#xd7; 2 Factorial Study of Adjustable Furniture and Indoor Environmental Quality.

Small workspaces function as integrated systems, yet ergonomic furniture and indoor environmental conditions are usually evaluated separately. A six-site, assessor-blinded, randomized 2 &#xd7; 2 factorial controlled study was conducted of two multicomponent packages-adjustable furniture and optimized indoor environmental quality (IEQ)-among 240 office workers for four weeks. Each group included 60 participants. Overall comfort in week 4 was highest for both packages (5.62 &#xb1; 0.53 versus 3.99 &#xb1; 0.60 with fixed furniture and basic IEQ). In a site-adjusted factorial model with HC3 robust standard errors, the adjustable-furniture effect was 0.86 points (95% confidence interval [CI], 0.62-1.09), the optimized-IEQ effect was 0.34 points (95% CI, 0.12-0.55), and their interaction was 0.44 points (95% CI, 0.14-0.74). Adjustable furniture improved postural comfort and reduced neck and lower back discomfort; optimized IEQ improved environmental comfort; both packages improved perceived productivity, satisfaction, and fatigue. The task-accuracy interaction did not remain significant after false-discovery-rate adjustment, and exploratory mediation and spline analyses did not support indirect or nonlinear effects. These results support coordinated ergonomic and environmental implementation while preserving distinct outcome pathways.

Interior Design and Furnishings

Venomous Lepidoptera: defensive toxin systems, venom composition, and clinical significance.

Venomous Lepidoptera constitute an underrecognized yet medically significant group of toxin-producing arthropods that employ contact-mediated defensive envenomation through specialized integumentary structures such as setae, spines, and scoli. Unlike actively stinging arthropods, these insects deliver venom passively upon contact, eliciting a diverse spectrum of clinical manifestations collectively termed lepidopterism. Clinical outcomes range from localized pain and dermatitis to severe systemic effects, including hemorrhagic syndromes, complement activation, and chronic inflammatory disorders. Recent advances in proteomic and transcriptomic technologies have transformed our understanding of lepidopteran venoms, revealing unexpectedly complex toxin repertoires comprising serine proteases, phospholipases, pore-forming proteins, disulfide-rich peptides, neuroactive RF-amide peptides, and immune-modulating components. These findings have provided new insights into the molecular basis of toxicity, host-pathogen interactions, and the evolutionary diversification of venom systems within Lepidoptera. This review synthesizes current knowledge on the morphology of venom-delivery structures, venom composition, mechanisms of action, and associated clinical manifestations, while highlighting medically important taxa, particularly species of the genus Lonomia. The successful development of antivenom against Lonomia envenomation underscores the translational relevance of lepidopteran toxin research and its potential for therapeutic innovation. By integrating molecular, clinical, and evolutionary perspectives, this review repositions venomous Lepidoptera as a legitimate and important component of arthropod toxinology. Furthermore, it identifies critical methodological limitations and key knowledge gaps, providing a framework for future investigations aimed at advancing our understanding of toxin biology, immunopathology, and the development of novel biomedical applications.

Animals