Girdling behavior of the longhorn beetle modulates the host plant to enhance larval performance.

BACKGROUND: Preingestive behavioral modulations of herbivorous insects on the host plant are abundant over insect taxa. Those behaviors are suspected to have functions such as deactivation of host plant defenses, nutrient accumulation, or modulating plant-mediated herbivore interactions. To understand the functional consequence of behavioral modulation of insect herbivore, we studied the girdling behavior of Phytoecia rufiventris Gautier (Lamiinae; Cerambycidae) on its host plant Erigeron annuus L. (Asteraceae) that is performed before endophytic oviposition in the stem. RESULTS: The girdling behavior significantly increased the larval performance in both field monitoring and lab experiment. The upper part of the girdled stem exhibited lack of jasmonic acid induction upon larval attack, lowered protease inhibitor activity, and accumulated sugars and amino acids in compared to non-girdled stem. The girdling behavior had no effect on the larval performance of a non-girdling longhorn beetle Agapanthia amurensis, which also feeds on the stem of E. annuus during larval phase. However, the girdling behavior decreased the preference of A. amurensis females for oviposition, which enabled P. rufiventris larvae to avoid competition with A. amurensis larvae. CONCLUSIONS: In conclusion, the girdling behavior modulates plant physiology and morphology to provide a modulated food source for larva and hide it from the competitor. Our study implies that the insect behavior modulations can have multiple functions, providing insights into adaptation of insect behavior in context of plant-herbivore interaction.

Ursodeoxycholic acid may protect from severe acute respiratory syndrome coronavirus 2 Omicron variant by reducing angiotensin-converting enzyme 2.

The SARS-CoV-2 caused COVID-19 pandemic has posed a global health hazard. While some vaccines have been developed, protection against viral infection is not perfect because of the urgent approval process and the emergence of mutant SARS-CoV-2 variants. Here, we employed UDCA as an FXR antagonist to regulate ACE2 expression, which is one of the key pathways activated by SARS-CoV-2 Delta variant infection. UDCA is a well-known reagent of liver health supplements and the only clinically approved bile acid. In this paper, we investigated the protective efficacy of UDCA on Omicron variation, since it has previously been verified for protection against Delta variant. When co-housing with an Omicron variant-infected hamster group resulted in spontaneous airborne transmission, the UDCA pre-supplied group was protected from weight loss relative to the non-treated group at 4 days post-infection by more than 5%-10%. Furthermore, UDCA-treated groups had a 3-fold decrease in ACE2 expression in nasal cavities, as well as reduced viral expressing genes in the respiratory tract. Here, the data show that the UDCA serves an alternative option for preventive drug, providing SARS-CoV-2 protection against not only Delta but also Omicron variant. Our results of this study will help to propose drug-repositioning of UDCA from liver health supplement to preventive drug of SARS-CoV-2 infection.

Facial Dermatoses Associated With Mask-Wearing in the COVID-19 Era: A Nationwide, Cross-Sectional, Multicenter, Questionnaire-based Study.

BACKGROUND: Daily usage of facial masks during coronavirus disease 2019 pandemic influenced on facial dermatoses. OBJECTIVE: This study investigated the impact of mask-wearing habits on facial dermatoses. METHODS: A nationwide, observational, questionnaire-based survey was conducted from July through August 2021, involving 20 hospitals in Korea. RESULTS: Among 1,958 facial dermatoses, 75.9% of patients experienced aggravation or development of new-onset facial dermatoses after wearing masks. In aggravated or newly developed acne patients (543 out of 743), associated factors were healthcare provider, female gender, and a long duration of mask-wearing. Irritating symptoms, xerosis, and hyperpigmentation were more frequently observed in this group. Aggravated or newly developed rosacea patients (515 out of 660) were likely to be female, young, and have a long duration of mask-wearing per day. Seborrheic dermatitis patients who experienced aggravation or de novo development (132 out of 184) were younger, and they more frequently involved the chin and jaw in addition to the nasolabial folds and both cheeks. Contact dermatitis patients (132 out of 147) with aggravation or de novo development tended to be female, involve both cheeks, and complain of pruritus. Aggravated or newly developed atopic dermatitis patients (165 out of 224) were more likely to be female, and had a higher baseline investigator global assessment score before mask-wearing. CONCLUSION: Clinical features and factors related to aggravation were different according to the types of facial dermatoses.

Long-term outcomes of very low birth weight infants with intraventricular hemorrhage: a nationwide population study from 2011 to 2019.

BACKGROUND: Advancements in neonatal care have increased preterm infant survival but paradoxically raised intraventricular hemorrhage (IVH) rates. This study explores IVH prevalence and long-term outcomes of very low birth weight (VLBW) infants in Korea over a decade. METHODS: Using Korean National Health Insurance data (NHIS, 2010-2019), we identified 3372 VLBW infants with IVH among 4,129,808 live births. Health-related claims data, encompassing diagnostic codes, diagnostic test costs, and administered procedures were sourced from the NHIS database. The results of the developmental assessments  are categorized into four groups based on standard deviation (SD) scores. Neonatal characteristics and complications were compared among the groups. Logistic regression models were employed to identify significant changes in the incidence of complications and to calculate odds ratios with corresponding 95% confidence intervals for each risk factor associated with mortality and morbidity in IVH. Long-term growth and development were compared between the two groups (years 2010-2013 and 2014-2017). RESULTS: IVH prevalence was 12% in VLBW and 16% in extremely low birth weight (ELBW) infants. Over the past decade, IVH rates increased significantly in ELBW infants (P = 0.0113), while mortality decreased (P = 0.0225). Major improvements in certain neurodevelopmental outcomes and reductions in early morbidities have been observed among VLBW infants with IVH. Ten percent of the population received surgical treatments such as external ventricular drainage (EVD) or a ventriculoperitoneal (VP) shunt, with the choice of treatment methods remaining consistent over time. The IVH with surgical intervention group exhibited higher incidences of delayed development, cerebral palsy, seizure disorder, and growth failure (height, weight, and head circumference) up to 72 months of age (P < 0.0001). Surgical treatments were also significantly associated with abnormal developmental screening test results. CONCLUSIONS: The neurodevelopmental outcomes of infants with IVH, especially those subjected to surgical treatments, continue to be a matter of concern. It is imperative to prioritize specialized care for patients receiving surgical treatments and closely monitor their growth and development after discharge to improve developmental prognosis. Supplementary file2 (MP4 77987 kb).

Kinetic modeling of the plasma pharmacokinetic profiles of ADAMTS13 fragment and its Fc-fusion counterpart in mice.

Introduction: Fusion of the fragment crystallizable (Fc) to protein therapeutics is commonly used to extend the circulation time by enhancing neonatal Fc-receptor (FcRn)-mediated endosomal recycling and slowing renal clearance. This study applied kinetic modeling to gain insights into the cellular processing contributing to the observed pharmacokinetic (PK) differences between the novel recombinant ADAMTS13 fragment (MDTCS) and its Fc-fusion protein (MDTCS-Fc). Methods: For MDTCS and MDTCS-Fc, their plasma PK profiles were obtained at two dose levels following intravenous administration of the respective proteins to mice. The plasma PK profiles of MDTCS were fitted to a kinetic model with three unknown protein-dependent parameters representing the fraction recycled (FR) and the rate constants for endocytosis (kup, for the uptake into the endosomes) and for the transfer from the plasma to the interstitial fluid (kpi). For MDTCS-Fc, the model was modified to include an additional parameter for binding to FcRn. Parameter optimization was done using the Cluster Gauss-Newton Method (CGNM), an algorithm that identifies multiple sets of approximate solutions ("accepted" parameter sets) to nonlinear least-squares problems. Results: As expected, the kinetic modeling results yielded the FR of MDTCS-Fc to be 2.8-fold greater than that of MDTCS (0.8497 and 0.3061, respectively). In addition, MDTCS-Fc was predicted to undergo endocytosis (the uptake into the endosomes) at a slower rate than MDTCS. Sensitivity analyses identified the association rate constant (kon) between MDTCS-Fc and FcRn as a potentially important factor influencing the plasma half-life in vivo. Discussion: Our analyses suggested that Fc fusion to MDTCS leads to changes in not only the FR but also the uptake into the endosomes, impacting the systemic plasma PK profiles. These findings may be used to develop recombinant protein therapeutics with extended circulation time.

Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia.

Background: The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. Purpose: This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. Methods: This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. Results: A total 150 children (66 females) aged 7.7 years (6.4-9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%-75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P<0.05). The median z scores of FEV1, FEV1/ FVC, and FEF25%-75% among asymptomatic patients were also significantly lower in the severe versus non/mild BPD group (-0.82 vs. 0.09, -1.68 vs. -0.87, -1.59 vs. -0.61, respectively; all P<0.05). The severe BPD group had a higher median (range) CT score than the non/mild BPD group (6 [0-12] vs. 1 [0-10], P<0.001). Prenatal oligohydramnios was strongly associated with both low pulmonary function (FEV1/FVC

Efficacy and Safety of Fibroblast Growth Factor-21 Analogs for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis.

Fibroblast growth factor (FGF)-21 analogs are potential therapeutic candidates for metabolic dysfunction-associated steatohepatitis (MASH). This systematic review and meta-analysis aimed to assess the efficacy and safety of the FGF-21 analogs, efruxifermin, pegbelfermin, and pegozafermin for MASH treatment. A comprehensive systematic review and meta-analysis of randomized controlled trials from five major databases was conducted. Primary efficacy outcomes focused on liver histological improvement, while secondary efficacy outcomes encompassed reductions in liver fat content and improvements in biochemical parameters. Safety outcomes examined included treatment-emergent adverse events (TEAEs), treatment-related TEAEs, TEAEs leading to discontinuation, and serious TEAEs. Eight eligible studies involving 963 patients were included in this review. Compared with the placebo group, the FGF-21 analog-treated group exhibited significantly improved primary efficacy outcomes, specifically ≥1 stage improvement in fibrosis with no worsening of MASH (risk ratio [RR] = 1.83; 95% confidence interval [CI] = 1.27-2.62) and at least two-point improvement in the non-alcoholic fatty liver disease activity score with no worsening of fibrosis (RR = 2.85; 95% CI = 2.06-3.95). Despite an increased risk of TEAEs (RR = 1.17; 95% CI = 1.08-1.27) and treatment-related adverse events (RR = 1.75; 95% CI = 1.40-2.19), FGF-21 analogs exhibited an acceptable safety profile. FGF-21 analogs were significantly better in achieving liver histological improvements and beneficial biochemical outcomes compared with placebo, with a tolerable safety pattern. These findings shed light on the efficacy and safety of FGF-21 analogs and provide valuable evidence for their application as MASH therapeutics.

Aesthetic doctors' perception and attitudes toward tolerance in botulinum toxin.

BACKGROUND: Botulinum toxin is a crucial therapeutic tool with broad indications in both cosmetic and medical fields. However, the expanding cosmetic use and increased dosages of botulinum toxin have raised concerns about resistance, making it essential to study the awareness and management practices among healthcare professionals. METHODS: A survey was conducted among clinical physicians using botulinum toxin. The study investigated their experiences, awareness, and management practices related to toxin resistance. Real-time mobile app-based surveys were administered to clinicians attending the 45th International Academic Conference of the Korean Academy of Laser and Dermatology (KALDAT) on December 3, 2023. RESULTS: Among 3140 participants, 673 clinical physicians completed the survey. Of these, 363 clinicians (53.9%) reported experiencing botulinum toxin resistance. Regarding the resistance rate, 59.4% indicated less than 1%, 36% reported approximately 1%-25%, and 95.4% reported less than 25%. Efforts to prevent resistance included maintaining intervals of over 3 months (54.8%), using products with lower resistance potential (47.0%), employing minimal effective doses (28.2%), and minimizing re-administration (14.9%). CONCLUSION: In the South Korean aesthetic medicine community, a majority of clinical physician's report encountering botulinum toxin resistance. Given the potential loss of various benefits associated with resistance, there is a need to establish appropriate guidelines based on mechanistic studies and current status assessments. Educating clinicians on applicable guidelines is crucial.

Assessment of Pharmacokinetic Effects of Herbal Medicines on Escitalopram.

Purpose: Herbal medicines are occasionally used in combination with conventional antidepressants to mitigate various depression-associated symptoms. However, there is limited information on herb-antidepressant interactions. In this study, we investigated the pharmacokinetic (PK) effects of four herbal medicines (Gami-soyosan, Banhasasim-tang, Ojeok-san, and Bojungikgi-tang) on escitalopram, a commonly used antidepressant. Patients and Methods: In this open-label, fixed-sequence, three-period, crossover study, 18 participants were enrolled and divided into two groups. Each group received a 10 mg oral dose of escitalopram in period 1. Participants took escitalopram once daily and their assigned herbal medicines thrice a day for 7 d in periods 2 (group 1: Gami-soyosan, group 2: Ojeok-san) and 3 (group 1: Banhasasim-tang; group 2: Bojungikgi-tang). The primary endpoints were Cmax,ss and AUCtau,ss of escitalopram. Cmax,ss and AUCtau,ss in period 1 were obtained using nonparametric superposition from single-dose data. The PK endpoints were classified according to the CYP2C19 phenotype. Results: Of 18 participants, 16 completed the study. Systemic exposure to escitalopram resulted in a minor increase in the presence of each herbal medicine. The geometric mean ratios (GMRs, combination with herbal medicines/escitalopram monotherapy) and their 90% confidence intervals (CIs) for Cmax,ss and AUCtau,ss were as follows: Gamisoyosan- 1.1454 (0.9201, 1.4258) and 1.0749 (0.8084, 1.4291), Banhasasim-tang-1.0470 (0.7779, 1.4092) and 1.0465 (0.7035, 1.5568), Ojeok-san-1.1204 (0.8744, 1.4357) and 1.1267 (0.8466, 1.4996), and Bojungikgi-tang-1.1264 (0.8594, 1.4762) and 1.1400 (0.8515, 1.5261), respectively. Furthermore, no significant differences in the GMRs of Cmax,ss and AUCtau,ss were observed across different CYP2C19 phenotypes in any of the groups. Conclusion: The co-administration of escitalopram with Gami-soyosan, Banhasasim-tang, Ojeok-san, or Bojungikgi-tang did not exert significant PK effects on escitalopram. These findings provide valuable insights into the safe use of herbal medicines along with escitalopram.

Significant CO2 emission in the shallow inshore waters of the southeastern Yellow Sea in 2020.

This study investigated the carbonate system and air-sea CO2 exchange in the inshore waters along South Korea's western coastline in 2020. Overlooking these waters might introduce significant errors in estimating air-sea CO2 fluxes of the southeastern Yellow Sea, given their interaction with land, offshore regions, and sediments. During periods other than summer, seasonal variations in seawater CO2 partial pressure (pCO2) could be generally explained by thermal effects. Tidal mixing and shallow depths resulted in weaker stratification-induced carbon export compared to offshore regions. However, during summer, inshore waters exhibited high spatial variability in pCO2, ranging from approximately 185 to 1000 µatm. In contrast to offshore waters that modestly absorbed CO2, inshore waters shallower than 20 m emitted ∼100 Gg C yr-1 to the atmosphere. However, considering the high heterogeneity of the study area, additional observations with high spatial and temporal resolution are required to refine estimates of air-sea CO2 exchange.

Efficient Combination Chemo-Sonodynamic Cancer Therapy Using Mitochondria-Targeting Sonosensitizer-Loaded Polysorbate-Based Micelles.

Sonodynamic therapy (SDT), utilizing ultrasound (US) and sonosensitizers, holds immense potential as a noninvasive and targeted treatment for a variety of deep-seated tumors. However, the clinical translation of SDT is hampered by several key limitations in sonosensitizers, especially their low aqueous stability and poor cellular uptake. In this study, non-ionic polysorbate (Tween 80, T80) was adopted to formulate effective nanocarriers for the safe and efficient delivery of sonosensitizers to cancer cells. Mitochondria-targeting triphenylphosphonium (TPP)-conjugated chlorin e6 (Ce6) sonosensitizer was loaded into T80-based micelles for efficient SDT. Pro-oxidant piperlongumine (PL) was co-encapsulated with TPP-conjugated Ce6 (T-Ce6) in T80 micelles to enable combination chemo-SDT. T80 micelles substantially enhanced the cellular internalization of T-Ce6. As a result, T80 micelles loaded with T-Ce6 and PL [T80(T-Ce6/PL)] significantly elevated intracellular reactive oxygen species (ROS) generation in MCF-7 human breast cancer cells upon US exposure. Moreover, T-Ce6 exhibited selective accumulation within the mitochondria, leading to efficient cell death under US irradiation. Importantly, T80(T-Ce6/PL) micelles caused cancer-specific cell death by selectively triggering apoptosis in cancer cells through PL. This study demonstrated the feasibility of using T80(T-Ce6/PL) micelles for efficient and cancer-specific combination chemo-SDT.

Pharmacokinetic Modeling of Bepotastine for Determination of Optimal Dosage Regimen in Pediatric Patients with Allergic Rhinitis or Urticaria.

Bepotastine, a second-generation antihistamine for allergic rhinitis and urticaria, is widely used in all age groups but lacks appropriate dosing guidelines for pediatric patients, leading to off-label prescriptions. We conducted this study to propose an optimal dosing regimen for pediatric patients based on population pharmacokinetic (popPK) and physiologically based pharmacokinetic (PBPK) models using data from two previous trials. A popPK model was built using NONMEM software. A one-compartment model with first-order absorption and absorption lag time described our data well, with body weight incorporated as the only covariate. A PBPK model was developed using PK-Sim software version 10, and the model well predicted the drug concentrations obtained from pediatric patients. Furthermore, the final PBPK model showed good concordance with the known properties of bepotastine. Appropriate pediatric doses for different weight and age groups were proposed based on the simulations. Discrepancies in recommended doses from the two models were likely due to the incorporation of age-dependent physiological factors in the PBPK model. In conclusion, our study is the first to suggest an optimal oral dosing regimen of bepotastine in pediatric patients using both approaches. This is expected to foster safer and more productive use of the drug.

Association between brain amyloid deposition and longitudinal changes of white matter hyperintensities.

BACKGROUND: Growing evidence suggests that not only cerebrovascular disease but also Alzheimer's disease (AD) pathological process itself cause cerebral white matter degeneration, resulting in white matter hyperintensities (WMHs). Some preclinical evidence also indicates that white matter degeneration may precede or affect the development of AD pathology. This study aimed to clarify the direction of influence between in vivo AD pathologies, particularly beta-amyloid (Aß) and tau deposition, and WMHs through longitudinal approach. METHODS: Total 282 older adults including cognitively normal and cognitively impaired individuals were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B PET for measuring Aß deposition, [18F] AV-1451 PET for measuring tau deposition, and MRI scans with fluid-attenuated inversion recovery image for measuring WMH volume. The relationships between Aß or tau deposition and WMH volume were examined using multiple linear regression analysis. In this analysis, baseline Aß or tau were used as independent variables, and change of WMH volume over 2 years was used as dependent variable to examine the effect of AD pathology on increase of WMH volume. Additionally, we set baseline WMH volume as independent variable and longitudinal change of Aß or tau deposition for 2 years as dependent variables to investigate whether WMH volume could precede AD pathologies. RESULTS: Baseline Aß deposition, but not tau deposition, had significant positive association with longitudinal change of WMH volume over 2 years. Baseline WMH volume was not related with any of longitudinal change of Aß or tau deposition for 2 years. We also found a significant interaction effect between baseline Aß deposition and sex on longitudinal change of WMH volume. Subsequent subgroup analyses showed that high baseline Aß deposition was associated with increase of WMH volume over 2 years in female, but not in male. CONCLUSIONS: Our findings suggest that Aß deposition accelerates cerebral WMHs, particularly in female, whereas white matter degeneration appears not influence on longitudinal Aß increase. The results also did not support any direction of influence between tau deposition and WMHs.

Effect of detrusor underactivity on surgical outcomes of holmium laser enucleation of the prostate.

OBJECTIVE: To evaluate the effect of detrusor underactivity (DUA) on the postoperative outcomes of holmium laser enucleation of the prostate (HoLEP) in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients with BPH who underwent HoLEP between January 2018 and December 2022 were enrolled in this prospective database study. Patients were divided into DUA (bladder contractility index [BCI] <100) and non-DUA (BCI ≥100) groups. Objective (maximum urinary flow rate [Qmax], post-void residual urine volume [PVR]) and subjective outcomes (International Prostate Symptom Score [IPSS], Overactive Bladder Symptom Score [OABSS], satisfaction with treatment question [STQ], overall response assessment [ORA], and willingness to undergo surgery question [WUSQ]) were compared between the two groups before surgery, and at 3 and 6 months after HoLEP. RESULTS: A total of 689 patients, with a mean (standard deviation [SD]) age of 69.8 (7.1) years, were enrolled. The mean (SD) BCI in the non-DUA (325 [47.2%]) and DUA (364 [52.8%]) groups was 123.4 (21.4) and 78.6 (14.2), respectively. Both objective (Qmax and PVR) and subjective (IPSS, IPSS-quality of life, and OABSS) outcomes after surgery significantly improved in both groups. The Qmax was lower in the DUA than in the non-DUA group postoperatively. At 6 months postoperatively, the total IPSS was higher in the DUA than in the non-DUA group. There were no significant differences in surgical complications between the two groups. Responses to the STQ, ORA, and WUSQ at 6 months postoperatively demonstrated that the patients were satisfied with the surgery (90.5% in the DUA group; 95.2% in the non-DUA group), their symptoms improved with surgery (95.9% in the DUA group; 100.0% in the non-DUA group), and they were willing to undergo surgery again (95.9% in the DUA group; 97.9% in the non-DUA group). There were no significant differences in the responses to the STQ and WUSQ between the two groups. CONCLUSION: Our midterm results demonstrated that patients with BPH and DUA showed minimal differences in clinical outcomes after HoLEP compared to those without DUA. The overall satisfaction was high in the DUA group.

Surgical quality assessment for the prospective study of oncologic outcomes after laparoscopic modified complete mesocolic excision for nonmetastatic right colon cancer (PIONEER study).

BACKGROUND: The modified complete mesocolic excision (mCME) procedure for right-sided colon cancer is a tailored approach based on the original complete mesocolic excision (CME) methodology. Limited studies evaluated the safety and feasibility of laparoscopic mCME using objective surgical quality assessments in patients with right colon cancer. The objectives of the PIONEER study were to evaluate oncologic outcomes after laparoscopic mCME and to identify optimal clinically relevant endpoints and values for standardizing laparoscopic right colon cancer surgery based on short-term outcomes of procedures performed by expert laparoscopic surgeons. MATERIALS AND METHODS: This is an ongoing prospective, multi-institutional, single-arm study conducted at five tertiary colorectal cancer centers in South Korea. Study registrants included 250 patients scheduled for laparoscopic mCME with right-sided colon adenocarcinoma (from the appendix to the proximal half of the transverse colon). The primary endpoint was 3-year disease-free survival. Secondary outcomes included 3-year overall survival, incidence of morbidity in the first 4 weeks postoperatively, completeness of mCME, central radicality, and distribution of metastatic lymph nodes. Survival data will be available after the final follow-up date (June 2024). RESULTS: The postoperative complication rate was 12.9%, with a major complication rate of 2.7%. In 87% of patients, central radicality was achieved with dissection at or beyond the level of complete exposure of the superior mesenteric vein. Mesocolic plane resection with an intact mesocolon was achieved in 75.9% of patients, as assessed through photographs. Metastatic lymph node distribution varied by tumor location and extent. Seven optimal clinically relevant endpoints and values were identified based on the analysis of complications in low-risk patients. CONCLUSIONS: Laparoscopic mCME for right-sided colon cancer produced favorable short-term postoperative outcomes. The identified optimal clinically relevant endpoints and values can serve as a reference for evaluating surgical performance of this procedure.

Combination of Superior and Posterior Capsular Release Versus Superior Capsular Release Alone in Arthroscopic Repair of Large-to-Massive Rotator Cuff Tears.

Background: Superior capsular release has been used to reduce tendon tension, especially in arthroscopic repair of large-to-massive rotator cuff tears. Some clinicians have used a more extensive release of capsules in arthroscopic cuff repair for adequate reduction of torn tendons to footprints. Purpose: To explore the effects of additional posterior capsular release for superior capsular release in arthroscopic repair of large-to-massive rotator cuff tears. Study Design: Cohort study; Level of evidence, 3. Methods: We compared 26 shoulders that underwent superior and posterior capsular release (group S&P) with 26 shoulders that underwent superior capsular release alone (group S) in arthroscopic repair of large-to-massive rotator cuff tears between January 23, 2013 and December 2, 2015. The visual analog scale for pain, American Shoulder and Elbow Surgeons score, Constant score, and range of motion (ROM) and muscle power were checked preoperatively and at 2 years postoperatively. Follow-up ultrasound was checked at 2 years postoperatively. Results: In both groups, the overall mean functional outcomes improved from preoperatively to postoperatively. Patients in group S&P showed more pre- to postoperative improvement than patients in group S with regard to internal rotation ROM (mean difference, 30.0° vs 20.6°; P < .001) and internal rotation power (3.4 vs 1.8 kgf; P = .001). Patients in group S had a higher retear rate on the follow-up ultrasound than patients in group S&P, but this difference did not reach statistical significance (23.1% vs 11.5%, respectively; P = .465). Conclusion: In the current study, patients who underwent superior and posterior capsular release in arthroscopic repair of large-to-massive rotator cuff tears had greater postoperative improvement in internal rotation ROM and power compared with patients who underwent superior capsular release alone.

Artificial intelligence predicts undiagnosed atrial fibrillation in patients with embolic stroke of undetermined source using sinus rhythm electrocardiograms.

BACKGROUND: Artificial intelligence (AI)-enabled sinus rhythm (SR) electrocardiogram (ECG) interpretation can aid in identifying undiagnosed paroxysmal atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS). OBJECTIVE: The purpose of this study was to assess the efficacy of an AI model in identifying AF based on SR ECGs in patients with ESUS. METHODS: A transformer-based vision AI model was developed using 737,815 SR ECGs from patients with and without AF to detect current paroxysmal AF or predict the future development of AF within a 2-year period. Probability of AF was calculated from baseline SR ECGs using this algorithm. Its diagnostic performance was further tested in a cohort of 352 ESUS patients from 4 tertiary hospitals, all of whom were monitored using an insertable cardiac monitor (ICM) for AF surveillance. RESULTS: Over 25.1-month follow-up, AF episodes lasting ≥1 hour were identified in 58 patients (14.4%) using ICMs. In the receiver operating curve (ROC) analysis, the area under the curve for the AI algorithm to identify AF ≥1 hour was 0.806, which improved to 0.880 after integrating the clinical parameters into the model. The AI algorithm exhibited greater accuracy in identifying longer AF episodes (ROC for AF ≥12 hours: 0.837, for AF ≥24 hours: 0.879) and a temporal trend indicating that the AI-based AF risk score increased as the ECG recording approached the AF onset (P for trend <.0001). CONCLUSIONS: Our AI model demonstrated excellent diagnostic performance in predicting AF in patients with ESUS, potentially enhancing patient prognosis through timely intervention and secondary prevention of ischemic stroke in ESUS cohorts.

Incidence and predictors of left atrial thrombus in patients with atrial fibrillation under anticoagulation therapy.

BACKGROUND: Left atrial thrombus (LAT) formation is associated with thromboembolic events. OBJECTIVE: To investigate the incidence and associated factors of LAT in patients with atrial fibrillation (AF) who had been receiving anticoagulation therapy for more than 4 weeks, and to develop a prediction model using clinical and echocardiographic features. METHODS: Medical records of 1,122 patients with AF (mean age, 59.4 ± 11.0 years, 58.3% male) who were on anticoagulation more than 4 weeks and underwent transesophageal echocardiography (TEE) were evaluated. The main outcome was the presence of LAT on TEE. RESULTS: Warfarin and non-vitamin K oral anticoagulants were used in 74.4% and 25.6% of the patients at the time of examination, respectively. LAT was present in 60 patients (5.3%). Presence of LAT on TEE was associated with age ≥ 75 years (odds ratio [OR] 2.13 [95% confidence interval, 0.94-4.58]), persistent/permanent AF (OR 2.61 [1.42-4.93]), CHA2DS2-VASc score ≥ 3 points (OR 1.91 [1.05-3.48]), left ventricular ejection fraction < 40% (OR 2.35 [1.07-4.81]), and severe left atrial enlargement (OR 3.52 [1.89-6.79]). The presence of moderate-to-severe mitral regurgitation was associated with a lower risk of LAT (OR 0.13 [0.04-0.34]). A scoring system composed of the aforementioned predictors showed excellent discrimination performance (area under the curve 0.791 [95% CI, 0.727-0.854]). CONCLUSIONS: LAT was present in a considerable number of patients who were already receiving anticoagulation therapy. A prediction model that combines clinical and echocardiographic predictors could be useful in distinguishing patients who require imaging evaluations before left atrial intervention.

Emerging role of senescent microglia in brain aging-related neurodegenerative diseases.

Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood. Cellular senescence is considered to contribute to cellular dysfunction and inflammaging. According to the threshold theory of senescent cell accumulation, the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain. Given the role of microglia in eliminating senescent cells, the accumulation of senescent microglia may lead to the acceleration of brain aging, contributing to inflammaging and increased vulnerability to neurodegenerative diseases. In this review, we propose the idea that the senescence of microglia, which is notably vulnerable to aging, could potentially serve as a central catalyst in the progression of neurodegenerative diseases. The senescent microglia are emerging as a promising target for mitigating neurodegenerative diseases.