The influence of exercise intensity on comorbid anxious behavior in psychiatric conditions.

Many experts have extensively studied the potential of exercise as a treatment option for psychiatric conditions, including depression and autism spectrum disorder (ASD). Despite their core symptoms, these conditions exhibits comparable component traits, an anxiety. In this study, we explored the effect of exercise on behavioral abnormalities in psychiatric conditions, focusing on its intensity and emotional resilience. Shank3B knockout (KOSED) mice displaying self-injurious repetitive behavior and C57BL/6J mice, susceptible to stress as ASD and depression model, respectively, were subjected to moderate-intensity exercise (ME) for 2 weeks. ME mitigated the core symptoms (excessive grooming traits and behavioral despair) but did not exert a significant anxiolytic effect. Notably, exercise intensity has emerged as a critical determinant of its efficacy, as evidenced by a lower ventilation threshold and anxiolytic effect mediated by low-intensity exercise. The findings substantiate the notion that exercise is promising as a disease-modifying treatment, but intensity matters for emotional resilience.

Adequate Dose of Levothyroxine for Thyroid-Stimulating Hormone Suppression after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer.

Background: The adequate dose of levothyroxine (LT4) for patients who have undergone total thyroidectomy (TT) for differentiated thyroid cancer (DTC) is uncertain. We evaluated the LT4 dose required to achieve mild thyroid-stimulating hormone (TSH) suppression in DTC patients after TT. Methods: The electronic medical records of patients who underwent TT for DTC and received mild TSH suppression therapy were reviewed. Linear regression analysis was performed to evaluate the association between LT4 dose (µg/kg) and an ordinal group divided by body mass index (BMI). We also evaluated the trend in LT4 doses among groups divided by BMI and age. Results: In total, 123 patients achieved mild TSH suppression (0.1 to 0.5 mIU/L). The BMI variable was divided into three categories: <23 kg/m2 (n=46), ≥23 and <25 kg/m2 (n=30), and ≥25 kg/m2 (n=47). In the linear regression analysis, BMI was negatively associated with the LT4 dose after adjusting for age and sex (P<0.001). The LT4 doses required to achieve mild TSH suppression based on the BMI categories were 1.86, 1.71, and 1.71 µg/kg, respectively (P for trend <0.001). Further analysis with groups divided by age and BMI revealed that a higher BMI was related to a lower LT4 dose, especially in younger patients aged 20 to 39 (P for trend=0.011). Conclusion: The study results suggest an appropriate LT4 dose for mild TSH suppression after TT based on body weight in patients with DTC. Considering body weight, BMI, and age in estimating LT4 doses might help to achieve the target TSH level promptly.

Aqueous-Deficient Dry Eye Increases Lipid Layer Thickness Measured by Dynamic Tear Interferometry.

PURPOSE: To investigate the impact of aqueous deficiency on lipid layer thickness (LLT) measurement in dry eye disease before and after treatment of aqueous-deficient dry eye (ADDE) using dynamic tear interferometry. METHODS: This prospective comparative study included 230 eyes from 230 patients with ADDE. The treatment group with punctal plug insertion was compared with the control group. The average LLT (LLTave) was measured with a LipiView II tear interferometer at baseline and after 1 month. Correlation analyses were performed with the indices of the dynamics of the tear film lipid layer (TFLL). RESULTS: Baseline LLTave values were 116.1 ± 26.7 and 112.3 ± 27.6 nm in the treatment group (n = 121) and the control group (n = 109), respectively. At 1 month, LLTave significantly decreased in the treatment group (difference -41.8 [95% confidence interval (CI) -47.2 to -36.3], P = 0.003). The values of tear meniscus height (TMH) at baseline and 1-month follow-up were negatively correlated with LLTave (both P < 0.001). Spreading time of TFLL to equilibrium and the deviation of TFLL were positively correlated with LLTave (all P < 0.001) and negatively correlated with TMH (P < 0.001 and 0.009). In multivariate analysis (adjusted R2 = 0.411, P < 0.001), LLTave was associated with TMH (B = -1.068; P < 0.001), adjusting for age, sex, and meibomian gland expressibility. CONCLUSIONS: In ADDE, the TFLL was measured to be thicker than the normal range of 60 to 99 nm and became thinner with treatment. LLT was affected by not only meibum secretion but also aqueous status due to changes in the dynamics of TFLL.

Interactive regulation of immune-related resistance genes with salicylic acid and jasmonic acid signaling in systemic acquired resistance in the Xanthomonas-Brassica pathosystem.

Pathogen-responsive immune-related genes (resistance genes [R-genes]) and hormones are crucial mediators of systemic acquired resistance (SAR). However, their integrated functions in regulating SAR signaling components in local and distal leaves remain largely unknown. To characterize SAR in the Xanthomonas campestris pv. campestris (Xcc)-Brassica napus pathosystem, the responses of R-genes, (leaf and phloem) hormone levels, H2O2 levels, and Ca2+ signaling-related genes were assessed in local and distal leaves of plants exposed to four Xcc-treatments: Non-inoculation (control), only secondary Xcc-inoculation in distal leaves (C-Xcc), only primary Xcc-inoculation in local leaves (Xcc), and both primary and secondary Xcc-inoculation (X-Xcc). The primary Xcc-inoculation provoked disease symptoms as evidenced by enlarged destructive necrosis in the local leaves of Xcc and X-Xcc plants 7 days post-inoculation. Comparing visual symptoms in distal leaves 5 days post-secondary inoculation, yellowish necrotic lesions were clearly observed in non Xcc-primed plants (C-Xcc), whereas no visual symptom was developed in Xcc-primed plants (X-Xcc), demonstrating SAR. Pathogen resistance in X-Xcc plants was characterized by distinct upregulations in expression of the PAMP-triggered immunity (PTI)-related kinase-encoding gene, BIK1, the (CC-NB-LRR-type) R-gene, ZAR1, and its signaling-related gene, NDR1, with a concurrent enhancement of the kinase-encoding gene, MAPK6, and a depression of the (TIR-NB-LRR-type) R-gene, TAO1, and its signaling-related gene, SGT1, in distal leaves. Further, in X-Xcc plants, higher salicylic acid (SA) and jasmonic acid (JA) levels, both in phloem and distal leaves, were accompanied by enhanced expressions of the SA-signaling gene, NPR3, the JA-signaling genes, LOX2 and PDF1.2, and the Ca2+-signaling genes, CAS and CBP60g. However, in distal leaves of C-Xcc plants, an increase in SA level resulted in an antagonistic depression of JA, which enhanced only SA-dependent signaling, EDS1 and NPR1. These results demonstrate that primary Xcc-inoculation in local leaves induces resistance to subsequent pathogen attack by upregulating BIK1-ZAR1-mediated synergistic interactions with SA and JA signaling as a crucial component of SAR.

Complete chloroplast genome of Asarum chungbuensis (C.S. Yook & J.G. Kim) B.U. Oh 2005 (Aristolochiaceae), a Korean endemic species.

Asarum chungbuensis, a species endemic to Korea, has a limited distribution across the Korean Peninsula and is used in traditional medicine. Despite its importance, the genome structure, genetic composition, and phylogenetic relationships based on its chloroplast genome have not been documented. In this study, the complete chloroplast genome of A. chungbuensis was newly assembled. The chloroplast genome is 190,179 base pairs (bp) long, and the overall GC content (%) of the plastid was 36.8%. The chloroplast genome size of A. chungbuensis is longer than that of the normal chloroplast genome (160 kb) because of an inverted small single-copy (SSC) duplication that incorporates the SSC into an inverted repeat (IR) region. By extension, this duplication event causes this chloroplast genome to lack an SSC, unlike other formal structures. The chloroplast genome, with a tripartite structure, consisted of a single-copy region of 93,351 bp with a 34.6% GC content and two IR regions, each with a length of 48,414 bp and a 38.8% GC content. Additionally, it was found to have 113 genes, including 79 PCG genes, 30 tRNA genes, and four rRNA genes. Phylogenetic analysis revealed that A. chungbuensis was grouped with A. heterotropoides var. seoulense, which diverged from the clade comprising A. koreanum and A. patens. The newly sequenced A. chungbuensis chloroplast genome could provide valuable genomic information for determining unique genome structures, especially for the assessment of genetic diversity, phylogenetic relationships, species conservation, and biogeographic studies of the genus Asarum.

Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial.

BACKGROUND: Trastuzumab deruxtecan has shown encouraging activity in patients with treatment-refractory HER2-positive, RAS wild-type and BRAF wild-type metastatic colorectal cancer. Dose optimisation and further antitumour assessments in patients with RAS mutations and those with previous anti-HER2 therapy are warranted. We aimed to evaluate two doses of trastuzumab deruxtecan (5·4 mg/kg and 6·4 mg/kg) to establish the recommended dose in patients with pretreated HER2-positive, RAS wild-type or mutant metastatic colorectal cancer. METHODS: DESTINY-CRC02 was a multicentre, randomised, two-stage, two-arm, phase 2 study done in 53 research hospitals and medical centres in Australia, Belgium, France, Italy, Japan, South Korea, Spain, Taiwan, the UK, and the USA. Eligible patients were aged 18 years and older or 20 years and older (depending on region) with pretreated pathologically documented, unresectable, recurrent, or metastatic HER2-positive, and RAS wild-type or mutant colorectal cancer. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and have received previous chemotherapy, and anti-EGFR, anti-VEGF, or anti-PD-L1 therapy, if clinically indicated. In stage 1, patients were randomly assigned (1:1), via a secure interactive response technology system, to receive 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan administered intravenously every 21 days. Stratification factors were ECOG performance status, HER2 status, and RAS status. In stage 2, patients were assigned into the 5·4 mg/kg treatment group only. The primary endpoint was confirmed objective response rate by blinded independent central review, assessed in all patients for whom treatment was assigned (full analysis set). Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04744831, and is ongoing (not recruiting). FINDINGS: Between March 5, 2021, and March 29, 2022, 135 patients were centrally screened, 122 of whom were enrolled. In stage 1, 40 patients each were randomly assigned to receive trastuzumab deruxtecan 5·4 mg/kg and 6·4 mg/kg. In stage 2, an additional 42 patients were enrolled in the 5·4 mg/kg group. 64 (52%) participants were male and 58 (48%) were female. The median duration of follow-up was 8·9 months (IQR 6·7-10·5) in the 5·4 mg/kg group and 10·3 months (5·9-12·7) in the 6·4 mg/kg group. The confirmed objective response rate by blinded independent central review was 37·8% (31/82 [95% CI 27·3-49·2]) in the 5·4 mg/kg group and 27·5% (11/40 [14·6-43·9]) in the 6·4 mg/kg group. 34 (41%) of 83 patients in the 5·4 mg/kg group and 19 (49%) of 39 in the 6·4 mg/kg group had grade 3 or worse drug-related treatment-emergent adverse events. The most common grade 3 or worse drug-related treatment-emergent adverse events were neutrophil count decreased (13 [16%] of 83 patients), anaemia (six [7%]), nausea (six [7%]), and white blood cell count decreased (five [6%]) in the 5·4 mg/kg group; and were neutrophil count decreased (10 [26%] of 39 patients), anaemia (eight [21%]), platelet count decreased (four [10%]), and white blood cell count decreased (four [10%]) in the 6·4 mg/kg group. Drug-related serious adverse events occurred in 11 (13%) of 83 patients in the 5·4 mg/kg group and six (15%) of 39 patients in the 6·4 mg/kg group; the most common in the 5·4 mg/kg group was nausea (three [4%] patients) and the most common in the 6·4 mg/kg group were fatigue (two [5%] patients), neutropenia (two [5%]), and thrombocytopenia (two [5%]). A drug-related treatment-emergent adverse event related to death occurred in one (1%) patient in the 5·4 mg/kg group (due to hepatic failure). Adjudicated drug-related interstitial lung disease or pneumonitis events were observed in seven (8%) patients in the 5·4 mg/kg group (all grade 1 or 2) and in five (13%) patients in the 6·4 mg/kg group (four grade 1 or 2; one grade 5). INTERPRETATION: The promising antitumour activity and favourable safety profile support trastuzumab deruxtecan 5·4 mg/kg as the optimal single-agent dose for patients with pretreated HER2-positive metastatic colorectal cancer, including those with RAS mutations, previous anti-HER2 therapy, or both. FUNDING: Daiichi Sankyo and AstraZeneca.

Acid tolerance responses and their mechanisms in Lactiplantibacillus plantarum LM1001.

This study investigated the acid tolerance responses of Lactiplantibacillus plantarum LM1001 at physiological and molecular levels. Upon exposure to low pH, L. plantarum LM1001 demonstrated increased ATPase activity and ammonia consumption, which contributed to a higher intracellular pH. Comparative analysis of cell membrane fatty acids revealed that acid-stressed cells had a significantly higher proportion of unsaturated fatty acids than those of unstressed cells. There was differential upregulation of several genes, notably those involved in alkali production (arcB, argG, and argH) and in class I and class III stress responses (clpE, clpP, hrcA, dnaK, grpE, groEL, and groES). Following 2-h exposure to pH 2.5, L. plantarum LM1001 not only exhibited enhanced survival but also showed increased auto-aggregation and improved mucin adhesion capability, albeit with a reduction in hydrophobicity. These findings indicate that acid stress induces adaptive physiological and metabolic changes in L. plantarum LM1001, enhancing its acid resistance and adherence properties. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01582-4.

Clinical application of whole-genome sequencing of solid tumors for precision oncology.

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.

Prevalence and risk factors for gallstone and renal stone formation in patients with intestinal Behçet's disease.

Background/Aims: The association between inflammatory bowel disease (IBD) and gallstone and renal stone formation has been established. However, few studies have investigated this association in patients with intestinal Behçet's disease (BD). We aimed to examine the prevalence of gallstones and renal stones in patients with intestinal BD and identify potential risk factors. Methods: We analyzed gallstone and renal stone occurrences in 553 patients diagnosed with intestinal BD who had undergone cross-sectional imaging examinations between March 2005 and April 2021 at the IBD Center, Severance Hospital, Seoul, South Korea. Logistic regression models were used to identify risk factors for gallstone and renal stone formation. Results: Of 553 patients over a mean 12.1-year duration, 141 (25.4%) patients had gallstones and 35 (6.3%) had renal stones. In multivariate logistic regression analysis, disease duration > 19 years (OR 2.91, 95% CI 1.56-5.44, 0.002). No significant correlation 0.001), prior intestinal BD-related surgery (OR 2.29, 95% CI 1.42-3.68, p < 0.001), and disease activity index for intestinal BD scores ≥ 75 (OR 2.23, 95% CI 1.12-4.45, p = 0.022) were associated with increased gallstone occurrence. A positive correlation was observed between renal stones, disease duration > 19 years (OR 5.61, 95% CI 1.98-15.90, p = 0.001) and frequent hospitalization (> 3 times) (OR 3.29, 95% CI 1.52-7.13, p = 0.002). No significant correlation was observed between gallstone and renal stone occurrence. Conclusions: These findings contribute to greater understanding concerning gallstone and renal stone prevalence and associated risk factors in patients with intestinal BD.

Prediction for Perioperative Stroke Using Intraoperative Parameters.

BACKGROUND: Perioperative stroke is a severe complication following surgery. To identify patients at risk for perioperative stroke, several prediction models based on the preoperative factors were suggested. Prediction models often focus on preoperative patient characteristics to assess stroke risk. However, most existing models primarily base their predictions on the patient's baseline characteristics before surgery. We aimed to develop a machine-learning model incorporating both pre- and intraoperative variables to predict perioperative stroke. METHODS AND RESULTS: This study included patients who underwent noncardiac surgery at 2 hospitals with the data of 15 752 patients from Seoul National University Hospital used for development and temporal internal validation, and the data of 449 patients from Boramae Medical Center used for external validation. Perioperative stroke was defined as a newly developed ischemic lesion on diffusion-weighted imaging within 30 days of surgery. We developed a prediction model composed of pre- and intraoperative factors (integrated model) and compared it with a model consisting of preoperative features alone (preoperative model). Perioperative stroke developed in 109 (0.69%) patients in the Seoul National University Hospital group and 11 patients (2.45%) in the Boramae Medical Center group. The integrated model demonstrated superior predictive performance with area under the curve values of 0.824 (95% CI, 0.762-0.880) versus 0.584 (95% CI, 0.499-0.667; P<0.001) in the internal validation; and 0.716 (95% CI, 0.560-0.859) versus 0.505 (95% CI, 0.343-0.654; P=0.018) in the external validation, compared to the preoperative model. CONCLUSIONS: We suggest that incorporating intraoperative factors into perioperative stroke prediction models can improve their accuracy.

Swift and precise detection of unlabeled pathogens using a nanogap electrode impedimetric sensor facilitated by electrokinetics.

For the protection of human health and environment, there is a growing demand for high-performance, user-friendly biosensors for the prompt detection of pathogenic bacteria in samples containing various substances. We present a nanogap electrode-based purely electrical impedimetric sensor that utilizes the dielectrophoresis (DEP) mechanism. Our nanogap sensor can directly and sensitively detect pathogens present at concentrations as low as 1-10 cells/assay in buffers and drinking milk without the need for separation, purification, or specific ligand binding. This is achieved by minimizing the electrical double-layer effect and electrode polarization in nanogap impedance sensors, reducing signal loss. In addition, even at low DEP voltages, nanogap sensors can quickly establish strong DEP forces between the nanogap electrodes to control the spatial concentration of pathogens around the electrodes. This activates and stabilizes inter-electrode signal transmission along the nanogap-aligned pathogens, increasing sensitivity and reducing errors during repeated measurements. The DEP-enabled nanogap impedance sensor developed in this study is valuable for a variety of pathogen detection and monitoring systems including point-of-care testing (POCT) as it can detect pathogens in diverse samples containing multiple substances quickly and with high sensitivity, is compatible with complex solutions such as food and beverages, and provides highly reproducible results without the need for separate binding and separation processes.

PD-L1 expression from surgically resected lung tumors predictive of early progression in patients previously treated with targeted therapy for initially unresectable non-small cell lung cancer.

Background: Recent evidences showed that resection of lung tumor post-targeted therapy has shown progression-free survival (PFS) benefits in initially unresectable patients. The aim of this study is to evaluate pathologic findings of resected lung tumor samples in patients who have undergone prior epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) treatment, and also to assess the prognostic factors related to outcomes after resection. Methods: The deidentified data of non-small cell lung cancer (NSCLC) patients admitted to seven university hospitals affiliated with the Catholic University of Korea were obtained from the Clinical Data Warehouse (CDW) database. Among screened patients, 40 individuals who had previously undergone targeted therapies and later received surgical resection of a primary lung tumor were evaluated for the study. Results: All 40 patients were diagnosed with adenocarcinoma. Of these, 36 with EGFR mutations received prior EGFR TKI treatment. Only one postoperative complication, atrial fibrillation, was observed. At the time of resection, 19 patients showed primary lung tumor size regressing or unchanged, while 21 patients showed primary lung tumor regrowth or new lesions being developed before the resection. The group with no programmed death-ligand 1 (PD-L1) expression from resected samples showed significantly better post-resection PFS when compared to the other group (P=0.01). In the Model II multivariate analysis for post-resection PFS, PD-L1 detection from the resected sample was significantly associated with PFS [P=0.03; hazard ratio (HR) =5.465; 95% confidence interval (CI): 1.200-24.885]. Furthermore, an increase in PD-L1 expression compared to the baseline value was associated with an increasing lung tumor burden at the time of resection (P=0.03). Conclusions: Resected specimen following targeted therapy can provide valuable clinical information that can be used to predict the prognosis of patients with initially unresectable NSCLC.

Thermal characteristics of fire extinguishing agents in compartment fire suppression.

Water and foam have different fire-extinguishing mechanisms. Traditional foam and compressed air foam (CAF) have different bubble structures. These differences result in different thermal characteristics, which affect the extinguishing abilities during a fire. In this study, the differences in the thermal characteristics of three different extinguishing agents (water, traditional foam, and CAF) were investigated by suppressing a compartment fire. With an ignition source in the compartment (6 m × 3 m × 3 m), the agent was preferentially applied to the outside wall of the compartment. The effects of internal cooling and burnback resistance generated from the outer wall were evaluated. The performance of each agent in shielding firefighters from radiant heat while suppressing the fire inside the compartment was evaluated. When the outside wall of the compartment was covered with each of the agents, all agents were found to reduce the room temperature. When CAF was applied, the delay time until temperature re-rise was approximately 1.76-4.5 times longer than that when water was used. In addition, foaming agents exhibited a higher heat-shielding effect than water during the initial suppression. Thus, considering the thermal characteristics of these agents, fire suppression can be more effective if foam agents are used.

Clinical effects of a home care program for patients with peritoneal dialysis in a tertiary care hospital.

Background: Digital health technologies have been rapidly adopted during the coronavirus disease 2019 pandemic. In Korea, a home care program, including face-to-face educational consultation and remote patient monitoring, was initiated to improve patients' quality of life. This study focused on patients with end-stage renal disease undergoing peritoneal dialysis to verify the long-term clinical effectiveness of this home care program. Methods: This retrospective cohort study was designed as a pre-post study to analyze the clinical impact of a home care program for patients undergoing peritoneal dialysis in a single tertiary care hospital. A total of 186 patients were selected from June 2017 to May 2022 to identify clinical changes after program implementation by analyzing changes in peritonitis incidence and laboratory test results. Interrupted time series analyses with ordinary least squares linear regression and chi-square tests were used. Results: At baseline, the incidence of peritonitis continuously increased by 0.480 cases per 1,000 patient-months (p = 0.02). After program initiation, the trend significantly decreased by 0.886 cases per 1,000 patient-months (p = 0.02). In addition, the proportion of individuals reaching the clinical target range had increased calcium levels (4.9%p, p = 0.003), stable hemoglobin (1.2%p, p = 0.477), phosphorus (2.8%p, p = 0.09), potassium (-1.6%p, p = 0.22), while parathyroid hormone levels decreased (-6.6%p, p = 0.005). Conclusion: With a reduction in peritonitis incidence and overall improvement in laboratory test results, our study suggests that conducting a home care program for patients undergoing peritoneal dialysis is clinically effective.

Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype.

Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

Estimation of Attributable Risk and Direct Medical and Non-Medical Costs of Major Mental Disorders Associated With Air Pollution Exposures Among Children and Adolescents in the Republic of Korea, 2011-2019.

BACKGROUND: Recent studies have reported the burden of attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and depressive disorder. Also, there is mounting evidence on the effects of environmental factors, such as ambient air pollution, on these disorders among children and adolescents. However, few studies have evaluated the burden of mental disorders attributable to air pollution exposure in children and adolescents. METHODS: We estimated the risk ratios of major mental disorders (ADHD, ASD, and depressive disorder) associated with air pollutants among children and adolescents using time-series data (2011-2019) obtained from a nationwide air pollution monitoring network and healthcare utilization claims data in the Republic of Korea. Based on the estimated risk ratios, we determined the population attributable fraction (PAF) and calculated the medical costs of major mental disorders attributable to air pollution. RESULTS: A total of 33,598 patients were diagnosed with major mental disorders during 9 years. The PAFs for all the major mental disorders were estimated at 6.9% (particulate matter < 10 µm [PM10]), 3.7% (PM2.5), and 2.2% (sulfur dioxide [SO2]). The PAF of PM10 was highest for depressive disorder (9.2%), followed by ASD (8.4%) and ADHD (5.2%). The direct medical costs of all major mental disorders attributable to PM10 and SO2 decreased during the study period. CONCLUSION: This study assessed the burden of major mental disorders attributable to air pollution exposure in children and adolescents. We found that PM10, PM2.5, and SO2 attributed 7%, 4%, and 2% respectively, to the risk of major mental disorders among children and adolescents.

Relationships of Jugular Bulb Parameters with Cerebral Perfusion and Metabolism After Resuscitation from Cardiac Arrest: A Post-Hoc Analysis of Experimental Studies Using a Minipig Model.

BACKGROUND: Cerebral blood flow (CBF) decreases in the first few hours or days following resuscitation from cardiac arrest, increasing the risk of secondary cerebral injury. Using data from experimental studies performed in minipigs, we investigated the relationships of parameters derived from arterial and jugular bulb blood gas analyses and lactate levels (jugular bulb parameters), which have been used as indicators of cerebral perfusion and metabolism, with CBF and the cerebral lactate to creatine ratio measured with dynamic susceptibility contrast magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. METHODS: We retrospectively analyzed 36 sets of the following data obtained during the initial hours following resuscitation from cardiac arrest: percent of measured CBF relative to that at the prearrest baseline (%CBF), cerebral lactate to creatine ratio, and jugular bulb parameters, including jugular bulb oxygen saturation, jugular bulb lactate, arterial-jugular bulb oxygen content difference, cerebral extraction of oxygen, jugular bulb-arterial lactate content difference, lactate oxygen index, estimated respiratory quotient, and arterial-jugular bulb hydrogen ion content difference. Linear mixed-effects models were constructed to examine the effects of each jugular bulb parameter on the %CBF and cerebral lactate to creatine ratio. RESULTS: The arterial-jugular bulb oxygen content difference (P = 0.047) and cerebral extraction of oxygen (P = 0.030) had a significant linear relationship with %CBF, but they explained only 12.0% (95% confidence interval [CI] 0.002-0.371) and 14.2% (95% CI 0.005-0.396) of the total %CBF variance, respectively. The arterial-jugular bulb hydrogen ion content difference had a significant linear relationship with cerebral lactate to creatine ratio (P = 0.037) but explained only 13.8% (95% CI 0.003-0.412) of the total variance in the cerebral lactate to creatine ratio. None of the other jugular bulb parameters were related to the %CBF or cerebral lactate to creatine ratio. CONCLUSIONS: In conclusion, none of the jugular bulb parameters appeared to provide sufficient information on cerebral perfusion and metabolism in this setting.

Presoaking hamstring autograft with vancomycin does not jeopardize its biomechanical properties, including graft elongation, after cyclic loading.

PURPOSE: Presoaking the graft with vancomycin before implantation has been shown to reduce the risk of postoperative infection after anterior cruciate ligament reconstruction (ACLR). However, the effects of presoaking on the graft biomechanical properties remain unclear. This study aimed to determine whether presoaking the graft with vancomycin affects the graft biomechanical properties and length after cyclic loading. METHODS: Ten paired (20 specimens) gracilis and semitendinous tendons were harvested from fresh-frozen human cadaveric specimens. Two tendons were folded in half to make four strands, and the grafts were randomized into the vancomycin and control groups. The graft was exposed to the antibiotic solution for 15 min (5 mg/mL) and prepared by mixing 1 g of vancomycin with 200 mL of normal saline (NaCl 0.9%). The control group was soaked in normal saline for 15 min. The prepared grafts were attached to the actuator of a dynamic tensile-testing machine. All grafts were tested with 3000 cycles of cyclic loading followed by a pull-to-failure. The cyclic loading protocol consisted of position and load control blocks to simulate the graft in vivo in the postoperative phase after ACLR. RESULTS: Presoaking in vancomycin did not jeopardize the biomechanical properties of the graft. In addition, presoaking with vancomycin did not elongate the grafts. No significant differences were found in the mean Young's modulus and the mean total elongation of the graft of the specimen between the vancomycin group and the control group. CONCLUSION: Presoaking the graft with vancomycin jeopardized neither its biomechanical properties nor elongation even after cyclic loading in this in vitro study. It is suggested that vancomycin presoaking could be considered a safe and effective preventive measure for postoperative infections after ACLR. LEVEL OF EVIDENCE: Not applicable.

Surgical Results with Low-Grade Arteriovenous Malformations : A Single Center 14-Year Experience.

Objective: Advancements in surgical techniques for cerebral arteriovenous malformation (AVM) underscore its efficacy. Our research aims to showcase the positive outcomes of treating low-grade AVMs surgically, focusing on safety and effectiveness. Methods: We retrospectively reviewed 55 patients (36 males, 19 females, and average age 37.4 years) with Spetzler-Martin (S-M) grade 1 and 2 AVMs who underwent surgical resection between January 2009 and December 2022. Results: In our study, 55 patients with S-M grade 1 and 2 AVMs underwent surgical resection, evenly divided between grades 1 (50.9%) and 2 (49.1%). Intracranial hemorrhage was the primary symptom in 74.5% of cases. Pre-operative Glasgow Coma Scale (GCS) scores revealed 69.1% of patients scored above 13, with 18% below 8. Successful resection was achieved in 87.3%. Postoperatively, 95.5% of ruptured and 90.9% of unruptured AVM patients showed lower or same modified Rankin Scale scores. Poorer outcomes were significantly linked to lower GCS scores and intranidal/flow-related aneurysms through multivariate logistic regression. Postoperative seizures noted in 9 patients, were exclusive to the ruptured AVM group. Conclusion: Our findings indicate surgical resection as a beneficial treatment for low-grade AVMs, yielding high cure rates and positive functional outcomes in both ruptured and unruptured cases. Preoperative GCS scores and the presence of associated aneurysms are predictive of postoperative functional status. Additionally, managing postoperative seizures effectively is key to enhancing prognosis.

Effects of antiarrhythmic drug responsiveness and diagnosis-to-ablation time on outcomes after catheter ablation for persistent atrial fibrillation.

Background: The impact of delaying atrial fibrillation catheter ablation (AFCA) for antiarrhythmic drug (AAD) management on the disease course remains unclear. This study investigated AFCA rhythm outcomes based on the diagnosis-to-ablation time (DAT) and AAD responsiveness in participants with persistent AF (PeAF). Methods: We included data from 1038 AAD-resistant PeAF participants, all of whom had a clear time point for AF diagnosis, especially PeAF at diagnosis time, and had undergone an AFCA for the first time. Participants who experienced recurrences of paroxysmal type on AAD therapy were analyzed as a cohort of AAD-partial responders; those maintaining PeAF on AAD were AAD-non-responders. We determined the DAT cutoff for best discriminating long-term rhythm outcomes using a maximum log-likelihood estimation method based on the Cox proportional hazard regression model. Results: Of the participants (79.8% male; median age 61), 806 (77.6%) were AAD-non-responders. AAD-non-responders had a higher body mass index and a larger left atrial diameter than AAD-partial-responders. They also had a higher incidence of AF recurrence after AFCA (adjusted hazard ratio 1.75, 95% confidence interval 1.33-2.30; log-rank p < .001) compared to AAD-partial-responders. The maximum log-likelihood estimation showed bimodal cutoffs at 22 and 40 months. The optimal DAT cutoff rhythm outcome was 22 months, which discriminated better in the AAD-partial-responders than in the AAD-non-responders. Conclusions: Both DAT and AAD responsiveness influenced AFCA rhythm outcomes. Delaying AFCA to a DAT of longer than 22 months was inadvisable, particularly in the participants in whom PeAF was changed to paroxysmal AF during AAD therapy.