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Breed-Specific Relationship Between Rebound Tonometers (TonoVet and TonoVet Plus) in Labrador Retrievers

Vet Ophthalmol. 2026 Sep;29(5):e70245. doi: 10.1111/vop.70245.

ABSTRACT

OBJECTIVE: This study aimed to characterize the relationship between intraocular pressure (IOP) measurements obtained using two rebound tonometers (TonoVet and TonoVet Plus) in Labrador retrievers and to evaluate a regression-based approximation for supporting longitudinal interpretation following device replacement.

ANIMALS STUDIED: Fifty-three clinically normal Labrador retrievers (106 eyes), including guide dog candidates and breeding dogs undergoing routine health screening in Japan, were included.

PROCEDURES: IOP was measured sequentially using the TonoVet and TonoVet Plus, both set to dog mode. The first of three readings per eye per device was used for analysis. Measurement order effects were assessed in a separate cohort. Statistical analyses included paired t-tests, Pearson’s correlation coefficient, and Bland-Altman analysis. Deming regression was used to derive a regression-based approximation accounting for measurement error in both devices.

RESULTS: Measurement order did not significantly influence IOP values. The TonoVet Plus yielded significantly higher IOP values than the TonoVet (p < 0.0001), and a moderate positive correlation was observed between the two devices (r = 0.69). Bland-Altman analysis demonstrated a systematic bias (mean difference + 4.5 mmHg; 95% limits of agreement, 1.3 to 7.7 mmHg). Deming regression yielded a slope of 1.05 and an intercept of 3.52. Age-related effects on IOP were small and not statistically significant.

CONCLUSIONS: The TonoVet Plus systematically measures higher IOP values than the TonoVet in Labrador retrievers. The derived breed-specific approximation may support longitudinal interpretation rather than precise individual-level prediction in comparable clinical settings; however, external validation in independent Labrador retriever populations is warranted.

PMID:42572116 | DOI:10.1111/vop.70245

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Tardive blepharospasm

J Neurol. 2026 Aug 10;273(9):522. doi: 10.1007/s00415-026-14038-y.

ABSTRACT

BACKGROUND: Tardive syndromes may present with variable movement disorders. Blepharospasm (BSP), while typically idiopathic in origin, may be drug-induced, but there is little information regarding frequency and phenomenology of tardive BSP.

OBJECTIVES AND METHODS: We aimed to assess the clinical features of tardive BSP and compare them with patients with idiopathic BSP. The Abnormal Involuntary Movement Scale (AIMS) was used to assess the severity of movements and the Jankovic Rating Scale (JRS) was used to evaluate the severity of BSP.

RESULTS: Among 72 consecutive patients with tardive syndromes, 15 (20.8%) were identified with BSP. Patients with tardive BSP had a younger age at onset, higher AIMS scores, and a greater frequency of associated akathisia and facial dystonia, compared with patients who had other tardive phenomena (P < 0.05, for all comparisons). Compared with 37 patients with idiopathic BSP, those with a tardive etiology were also younger and had more frequently associated orobuccolingual (OBL) stereotypy, limb/trunk stereotypies, akathisia, and facial dystonia (P ≤ 0.009), whereas apraxia of eyelid opening was only observed in patients with idiopathic BSP. Alleviating maneuvers (sensory tricks) predominated in patients with idiopathic BSP, but this difference did not reach statistical significance (P ≥ 0.05). Furthermore, there was no difference in BSP severity, as assessed by JRS, between the two groups. Comorbid limb/trunk stereotypies and OBL dyskinesia had the greatest diagnostic accuracy supporting tardive origin.

CONCLUSIONS: Tardive BSP, identified in one-fifth of patients with diverse tardive syndromes, has distinct features differing from idiopathic BSP.

PMID:42572102 | DOI:10.1007/s00415-026-14038-y

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Baseline IL-6 independently predicts severe immune-related toxicity and poor survival in advanced gastric cancer treated with immunotherapy

Gastric Cancer. 2026 Aug 9. doi: 10.1007/s10120-026-01744-9. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) improve survival in advanced gastric cancer (GC), yet predicting therapeutic benefit versus toxicity remains challenging. Elevated interleukin-6 (IL-6) is linked to poor prognosis, but whether it simultaneously influences immune-related adverse events (irAEs) and how this relationship impacts survival remains unclear.

METHODS: We retrospectively analyzed 244 patients with advanced GC treated with ICIs. Predictors of high-grade irAEs were evaluated using Firth’s penalized logistic regression to mitigate small-sample bias. Independent prognostic factors for overall survival (OS) were identified via multivariable Cox analysis and validated using propensity score matching (PSM). Causal mediation analysis was performed to assess whether the effect of IL-6 on OS was mediated through irAEs. Biological mechanisms were explored using TCGA-STAD transcriptomic data.

RESULTS: Baseline IL-6 was a strong independent predictor of high-grade irAEs (OR = 2.74, P < 0.001) and inferior OS (P = 0.019), a finding confirmed after PSM. Mediation analysis did not demonstrate a statistically significant mediating effect of irAEs on the relationship between IL-6 and survival. Bioinformatic validation linked high IL-6 expression to hyper-inflammatory signaling (TNF/IL-17 pathways) and immunosuppressive M2 macrophage infiltration.

CONCLUSION: Baseline IL-6 was independently associated with both severe immune-related toxicity and inferior overall survival, suggesting that elevated systemic IL-6 reflects an adverse inflammatory state in which toxicity does not necessarily correspond to improved therapeutic outcomes. These findings support further evaluation of IL-6 in risk stratification and warrant prospective investigation into its potential therapeutic modulation in combination with ICIs.

PMID:42572075 | DOI:10.1007/s10120-026-01744-9

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QSAR, molecular dynamics, and biological evaluation of novel myeloperoxidase inhibitors via ligand-based pharmacophore modeling as potential anticancer agents

J Comput Aided Mol Des. 2026 Aug 10;40(1):200. doi: 10.1007/s10822-026-00895-2.

ABSTRACT

Myeloperoxidase (MPO) has shown promise as a therapeutic target due to its critical role in inflammatory mechanisms and cancer progression. Despite extensive research on MPO inhibitors, the lack of integrated computational-experimental workflows constrains the efficient identification and validation of biologically relevant candidates. Hence, in this study, a ligand-based pharmacophore model of MPO inhibitors was developed to identify crucial molecular features required for inhibition. A quantitative structure-activity relationship (QSAR) model was built using the Genetic Function Approximation (GFA) algorithm, and the model statistics were found to be statistically significant (R2 = 0.765, R2_adj = 0.733, R2_Pred = 0.672, LOF = 1.2). The generated and validated pharmacophore model was used virtually to screen 53,352 compounds, yielding five structurally distinct hits. These hits were subjected to in vitro cytotoxicity analysis using two cancer cell lines. Among all the tested compounds, BTB11556 showed the strongest cytotoxic activity, with an IC50 of 12.5 μM against the Kasumi-1 leukemia cell line, and was therefore considered the lead compound. A one-way ANOVA of the IC50 values for the active compounds in Kasumi-1 cells showed a statistically significant difference in cytotoxic potency (p < 0.001). This integrated computational and experimental approach highlights the importance of pharmacophore-guided virtual screening, combined with QSAR modeling, in the development of MPO inhibitors. The findings from molecular docking, 500-ns molecular dynamics simulations, MM-GBSA calculations, and alanine scanning analyses collectively corroborate a stable binding mode of BTB11556 within the MPO active site. These results support further investigation of BTB11556 as a candidate compound associated with MPO-targeted therapeutic strategies.

PMID:42572067 | DOI:10.1007/s10822-026-00895-2

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Effect of lung volume on the apnea hypopnea index in patients with overlap syndrome: a single center study

Sleep Breath. 2026 Aug 10;30(4):235. doi: 10.1007/s11325-026-03776-y.

ABSTRACT

PURPOSE: This study aimed to evaluate the relationship between lung volume and apnea-hypopnea index (AHI) in patients with overlap syndrome (OVS).

METHODS: Chronic obstructive pulmonary disease (COPD) patients diagnosed by spirometry were recruited from Renmin Hospital of Wuhan University. They were asked to take an overnight polysomnography (PSG). Multiple regression analyses were used to assess the relationships between lung volume measures and AHI in OVS patients.

RESULTS: Finally, 354 OVS patients and 229 patients with only COPD met the study’s entry criteria. After adjusting for age, sex, BMI, neck size, economic status, smoking, alcohol use, and hypertension, residual volume (RV), total lung capacity (TLC), and the RV/TLC ratio each had a negative link with the AHI in OVS patients (RV: exp(β) = 0.903; 95% CI, 0.852 to 0.957; P < 0.05; TLC: exp(β) = 0.947; 95% CI, 0.899 to 0.998; P < 0.05; RV/TLC: exp(β) = 0.898; 95% CI, 0.846 to 0.954; P < 0.01). However, when RV was added as a covariate in the model, forced expiratory volume in one second (FEV1) had no association with the AHI in OVS patients (P > 0.05). Also, when dividing OVS patients by lung function severity, RV had a negative correlation with the AHI in those with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 3-4 grade (exp(β) = 0.905; 95% CI, 0.835 to 0.980; P < 0.05), but in GOLD 1-2 grade patients, there was no link between RV and AHI (P > 0.05).

CONCLUSION: The higher residual volume was independently associated with lower AHI in patients with overlap syndrome, particularly among patients with GOLD 3-4 airflow limitation.

PMID:42572058 | DOI:10.1007/s11325-026-03776-y

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Beyond the incision: Does release extent matter in congenital muscular torticollis? A systematic review

Eur Spine J. 2026 Aug 10. doi: 10.1007/s00586-026-10262-2. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare clinical outcomes after unipolar versus bipolar sternocleidomastoid (SCM) release for congenital muscular torticollis (CMT), and to describe how patient age, chronicity, and postoperative rehabilitation varied across studies and may have contributed to between study differences.

METHODS: Following PRISMA guidelines, 17 observational studies were included, comprising 382 surgical procedures (unipolar 228; bipolar 154). The primary outcome was achievement of a global good-excellent clinical result using validated composite scoring systems (Lee, Cheng-Tang, Tanabe, or Lee-Kang). Secondary outcomes were recurrence and complications. Comparative quantitative synthesis was restricted to studies reporting both techniques within the same cohort and extractable technique-specific data. For recurrence, comparative quantitative synthesis was feasible in two cohorts. For global good-excellent outcome, head-to-head data were too sparse and confounded for a robust pooled comparison, and evidence remained descriptive. Heterogeneity was assessed using I².

RESULTS: Only a small number of studies provided extractable head-to-head comparisons. In these cohorts, no statistically significant difference was observed between unipolar and bipolar release in achieving a good-excellent global clinical outcome, and recurrence rates did not differ significantly between techniques, although confidence intervals were wide and events were sparse. Across single-arm cohorts, both techniques were associated with high rates of good-excellent outcomes and low recurrence, with greater variability observed in bipolar cohorts that more frequently included older or neglected cases. Complications were uncommon overall and were predominantly minor; technique-stratified reporting suggested a higher frequency of minor complications following bipolar release. Where reported, cervical alignment and range of motion improved substantially after both procedures, with no consistent radiographic advantage of one technique over the other. Across studies, postoperative rehabilitation intensity and patient chronicity appeared to influence durability of correction at least as much as release extent.

CONCLUSION: Within the limits of available observational evidence, unipolar and bipolar SCM release yield comparable global clinical outcomes with low recurrence and complication rates. No consistent comparative advantage of greater release extent was demonstrated. Between-study differences may also reflect variation in patient age, deformity chronicity, and postoperative rehabilitation. Comparative certainty remains limited by small head-to-head cohorts, heterogeneous outcome definitions, and incomplete arm-level reporting.

PMID:42572053 | DOI:10.1007/s00586-026-10262-2

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Mapping infant streptococcal mortality burden in low- and middle-income countries: temporal trends, geospatial patterns, and socioeconomic determinants

Eur J Pediatr. 2026 Aug 10;185(9):650. doi: 10.1007/s00431-026-07310-w.

ABSTRACT

Streptococcal mortality burden threatens children’s health in low- and middle-income countries (LMICs), yet their temporal trends, geographic disparities, and socioeconomic determinants remain unclear. Using the MICROBE database and World Bank data, we conducted a cross-sectional study to assess infant mortality burden of group A Streptococcus (GAS), group B Streptococcus (GBS), Streptococcus pneumoniae, and other streptococci in LMICs. Joinpoint regression estimated the average annual percent change (AAPC). Frontier analysis assessed the potential reduction in antimicrobial resistance (AMR) mortality burden for Streptococcus. Random forest with SHapley Additive exPlanations (SHAP) identified key socioeconomic drivers. During 1990-2021, infant streptococcal mortality burden in LMICs declined from 798.8 to 241.1 per 100,000. However, a post-2016 increase in the mortality burden of early-onset neonatal GAS and GBS bacteremia (0-6 days) was observed (annual percent change, 1.9% and 1.7%). Streptococcal mortality burden declined most slowly, or increased, among neonates in sub-Saharan Africa and South Asia (AAPC, – 5.8 to 1.6%). Multiple LMICs in sub-Saharan Africa, South Asia, and Oceania exhibited a high AMR-related mortality burden from streptococcal infections. SHAP analysis indicated that increased health expenditure was associated with lower mortality burden across most streptococcal pathogens. WASH (Water, Sanitation, and Hygiene) and skilled birth attendance were linked to lower GAS/GBS mortality burden. Complete pneumococcal vaccination was negatively associated with pneumococcal mortality burden, mainly through reduced incidence.

CONCLUSION: Infant streptococcal mortality burden persists in LMICs, especially among neonates. Increasing health investment, strengthening WASH, improving perinatal care, promoting vaccination, and enhancing antibiotic stewardship are critical.

WHAT IS KNOWN: • Infant streptococcal mortality burden in low- and middle-income countries (LMICs) constitutes a major public health concern.

WHAT IS NEW: • Infant streptococcal mortality burden in LMICs declined by 69.8% (1990-2021), but remained concentrated in neonates, with rising early-onset GAS/GBS bacteremia mortality burden. • Infant streptococcal mortality burden is predominant in sub-Saharan Africa and South Asia, where resistance to penicillin and third-generation cephalosporins is relatively high. • Government health expenditure, WASH, tailored perinatal care, full-course pneumococcal vaccination, and antibiotic stewardship are key to reducing infant streptococcal mortality burden in LMICs.

PMID:42572050 | DOI:10.1007/s00431-026-07310-w

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Recalculation of the late fetal death rate in Mexico, 2013-2023 using ICD-11 criteria applied to national vital statistics

Matern Health Neonatol Perinatol. 2026 Aug 10;12(1):36. doi: 10.1186/s40748-026-00284-5.

ABSTRACT

BACKGROUND: Cross-national comparability of fetal mortality indicators is limited by heterogeneous definitions and denominators. Mexico’s official fetal death indicators include all gestational ages and use live births as the denominator, diverging from international standards. We recalculated late fetal death rates using ICD-11 criteria and compared them with published national and international data.

METHODS: We conducted a retrospective analysis of national fetal death data from Mexico (2013-2023). Publicly available statistics on fetal deaths and registered live-birth datasets were used. All procedures followed ICD-11 recommendations for international reporting standards. Recalculated rates were compared with official Mexican publications, PAHO/WHO estimates for Mexico, and United States (US) rates.

RESULTS: From 2013 to 2023, 254,567 fetal deaths were recorded in Mexico. The recalculated ICD-11 late fetal death rate averaged 4.9 per 1,000 total births, increasing from 4.5 (2013-2015) to 5.5 (2020-2023). However, this increase should be interpreted with caution, as it is largely driven by a decline in the number of registered live births over the study period. Official Mexican fetal death rates ranged from 10.1 to 15.5 per 1,000. PAHO/WHO estimates for Mexico (2013-2023) were 7.0-7.9 per 1,000, and US rates (2014-2023) were 2.7-2.9 per 1,000. Most fetal deaths occurred before 28 weeks, with increasing proportions among cases ≤499 g. Most deaths were classified as antepartum (84%).

CONCLUSIONS: The recalculated ICD-11 late fetal death rate increased from 2013 to 2023. While national late fetal death rates were lower than historical official rates, they were nearly twice as high as US rates.

TRIAL REGISTRATION: Not applicable.

PMID:42572034 | DOI:10.1186/s40748-026-00284-5

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Extending geriatric care beyond traditional settings: lessons from a mobile assessment program

Isr J Health Policy Res. 2026 Aug 10;15(1):31. doi: 10.1186/s13584-026-00775-y.

ABSTRACT

BACKGROUND: As populations age, changing living conditions and declining self-advocacy often create barriers to essential care. Mobile Geriatric Teams (MGTs) offer a potential solution by providing assessments within a patient’s regular environment, potentially reaching underdiagnosed and undertreated individuals who struggle to access routine healthcare. The aim of this study was to evaluate the clinical impact and reach of MGTs in the Northern District of Israel. Specifically, we aimed to assess the extent of MGT-initiated Comprehensive Geriatric Assessments and compare therapeutic and diagnostic outcomes between patients seen by MGTs and those receiving standard community-based geriatric consultations.

METHODS: This is a retrospective, data-based study serving as a proof-of-concept evaluation for MGT implementation in Israel. The intervention was implemented in MHS between January 1, 2020, and December 31, 2023, and data were collected 3 and 6 months after the MGT appointment. Group comparisons were conducted using chi-square tests, Fisher’s exact tests, and Wilcoxon rank-sum tests. In addition, we performed matched logistic regression models.

RESULTS: A total of 8,152 individuals were included in the study; 4,348 were assessed by MGTs. The MGT group participants were slightly older and had a higher proportion of males and a lower SES category than the comparison group. The MGTs group had fewer diagnoses of mild cognitive impairment, dementia, and depression, compared to the comparison group. They also had more diagnoses of orthostatic hypotension, and they were more likely to be assessed for fall risk. The MGT group was also prescribed fewer medications in the months following the assessment. After the MGT intervention, we report an increase in primary care visits in the relevant population in the district where it was implemented, while the comparison group did not have a corresponding trend.

CONCLUSIONS: In this study, we demonstrated that MGTs can reach a specific subpopulation of the elderly who might not otherwise undergo a geriatric assessment, primarily males, those of low SES, and possibly those with less urgent health concerns. These findings highlight the complementary role of MGTs in increasing accessibility, promoting equity, and addressing unmet needs in populations less likely to seek care on their own.

PMID:42572029 | DOI:10.1186/s13584-026-00775-y

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Characterization of remission levels in patients with ulcerative colitis treated with 5-aminosalicylates: results of the cross-sectional CARUC-ASA study by the Belgian IBD Research and Development Group

J Crohns Colitis. 2026 Aug 5;20(8):jjag100. doi: 10.1093/ecco-jcc/jjag100.

ABSTRACT

BACKGROUND: 5-Aminosalicylic acid (5-ASA) remains the first-line therapy for mild-to-moderate ulcerative colitis (UC). Modern treatment goals extend beyond symptom control to include steroid-free remission, endoscopic healing, and biomarker normalization. Real-world evidence on 5-ASA’s ability to achieve these targets is limited. This study assessed remission levels and associated factors in Belgian UC patients in clinical remission on 5-ASA.

METHODS: This cross-sectional, multicenter, phase 4 study included UC patients in clinical remission (PRO-2 ≤ 1, no rectal bleeding) treated with 5-ASA for ≥6 months. Patients receiving corticosteroids, immunomodulators, or advanced therapies were excluded. Outcomes were complete clinical remission (PRO-2 = 0, no urgency), endoscopic remission (MES ≤ 1, UCEIS ≤ 1), complete endoscopic remission (MES = 0), histological remission (Geboes 0-1), biological remission (fecal calprotectin <150 µg/g), and deep remission (clinical, endoscopic, and histological). Adherence was assessed using MARS-5.

RESULTS: In total, 198 patients were enrolled (median age 50 years; 41% female). Treatment was oral 5-ASA only (n = 134, 68%), rectal only (n = 19, 9%), or combination (n = 45, 23%). Biological remission was observed in 78%, endoscopic remission in 87%, complete endoscopic remission in 70%, and histological remission in 80%. Deep remission occurred in 24%, limited by persistent urgency (63%). Adherence was high (median MARS-5: 24). Oral 5-ASA only was significantly associated with endoscopic remission (P < .001).

CONCLUSION: In this real-world Belgian cohort, patients in clinical remission on 5-ASA achieved high rates of objective remission, while deep remission was low because of persistent urgency. These findings confirm 5-ASA’s continued relevance in mild-to-moderate UC and highlight the importance of addressing residual symptoms despite mucosal healing.

PMID:42572012 | DOI:10.1093/ecco-jcc/jjag100