The Impact of QT-Prolonging Medications and Drug-Drug Interactions on QTc Interval Prolongation in Hospitalized Patients: A Case-Crossover Study.

Researchers have studied potential corrected QT interval (QTc) prolongation from drug-drug interactions (DDIs), raising unresolved questions about their real-world impact. This retrospective case-crossover study investigated the effects of QT-prolonging drugs and DDIs on QTc prolongation in hospitalized patients aged 45 years and above. The cohort comprised patients who had multiple hospitalizations and developed QTc prolongation (QTc > 500 ms or an increase of >60 ms from baseline) at least 24 hours after admission between 2011 and 2019. Conditional logistic regression compared drug exposure between hospitalizations with QTc prolongation (case window) and those without (reference window). Among 2,276 patients (mean age 71; 43.8% female), the use of QT-prolonging drugs significantly increased the risk of QTc prolongation (odds ratio: 2.42 (95% confidence interval: 1.95-3.02)). The risk was higher with drugs of "known risks" (OR: 3.78 (2.91-4.90)) and "conditional risk" (OR: 2.08 (1.65-2.62)). DDIs, particularly involving multiple "known risk" drugs (OR: 7.86 (4.96-12.45)), strong cytochrome P450 enzyme inhibitors (OR: 5.57 (2.75-11.30)), or the concurrent use of ≥4 QT-prolonging drugs with any risk (OR: 5.28 (3.96-7.03)) substantially increased the risk. Cautious prescribing for patients with multiple risk factors is important to minimize the likelihood of QTc prolongation. However, when considering enhanced monitoring or drug choices, it is crucial to carefully evaluate the overall risk of QT prolongation against the benefits of treatment to ensure optimal patient care.

Duration of N1 sleep is a factor for excessive daytime sleepiness in epilepsy patients with interictal epileptiform discharges: A polysomnographic study.

Purpose: This study aimed to identify the occurrence of excessive daytime sleepiness (EDS) in epilepsy patients with interictal epileptiform discharges and to explore the impact of interictal sleep architecture and sleep-related events on EDS. Methods: This study included 101 epilepsy patients with interictal epileptiform discharges (IED) and 100 control patients who underwent simultaneous polysomnography and video ambulatory electroencephalography for >7 h throughout a single night. Multiple sleep latency tests were used to assess EDS. Comorbid EDS was present in 25 and 11 patients in the IED epilepsy and control groups, respectively. In addition, univariate and multivariate logistic regression analyses were performed to explore the factors influencing EDS. Results: The epilepsy group had a higher prevalence of comorbid EDS and shorter R sleep duration. Univariate logistic regression analysis indicated that an increased risk of EDS may be associated with prolonged N1 sleep duration, higher arousal index, lower mean saturation (mSaO2), higher oxygen desaturation index (ODI), and duration of wake after sleep onset (WASO). Multivariate logistic regression analysis revealed that N1 sleep duration was significantly correlated with EDS. Conclusion: In epilepsy patients with IED, the arousal index, mSaO2, ODI, and duration of WASO were weakly correlated with EDS, and the duration of N1 sleep demonstrated a significant positive correlation with EDS, which requires further research.

Difference of water source of two Ammopiptanthus mongolicus communities in Ulan Buh Desert, China.

To understand the adaptation of water use strategy of plant community to habitat heterogeneity, we measured the δD and δ18O values of xylem water of shrubs and potential water sources (soil water in different layers or groundwater) of Ammopiptanthus mongolicus communities on sand dune and Gobi from April to September in 2021 in the Ulan Buh Desert. Employing the MixSIAR model, we examined the seasonal dynamics of water source of each shrub by quantifying the contribution of different potential water sources. The results showed that A. mongolicus and Artemisia xerophytica on sand dune mainly used soil water of 10-25 cm in April and May after heavy rain in early spring, whereas Artemisia ordosica mainly used soil water of 10-200 cm. During the drought event within summer from June to August, A. mongolicus increasingly used soil water of 100-200 cm and groundwater, but A. xerophytica and A. ordosica increased the usage of 50-200 cm soil water. After the moderate rain in September, A. mongolicus evenly used soil water in all layers and groundwater, whereas two Artemisia shrubs preferred soil water of 10-50 cm. On Gobi, A. mongolicus and Nitraria sphaerocarpa evenly used soil water in all layers in April and May, mainly used 50-150 cm soil water from June to August and used 10-50 cm soil water in September. Convolvulus tragacanthoides mainly used soil water of 10-50 cm (from April to May), 25-150 cm (from June to August), and 10-25 cm (in September), separately. There were seasonal differences in water use of three shrubs on sand dune and Gobi A. mongolicus communities. During drought, A. mongolicus on sand dune could use deep soil water and groundwater, and that on Gobi relied only on deep soil water, which was more sensitive to rainfall.

Acquisition Time for Resting-State HbO/Hb Coupling Measured by Functional Near-Infrared Spectroscopy in Assessing Autism.

Functional near-infrared spectroscopy was used to record spontaneous hemodynamic fluctuations form the bilateral temporal lobes in 25 children with autism spectrum disorder (ASD) and 22 typically developing (TD) children. The coupling between oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (Hb) was calculated by Pearson correlation coefficient, showing significant difference between ASD and TD, thus the coupling could be a characteristic feature for ASD. To evaluate the discrimination ability of the feature obtained in different acquisition times, the receiver operating characteristic curve (ROC) was constructed and the area under curve (AUC) was calculated. The results showed AUC > 0.8 when the time duration was longer than 1.5 min, but longer than 4 min, AUC value (~0.87) hardly varied, implying the maximal discrimination ability reached. This study demonstrated the coupling could be one of characteristic features for ASD even acquired in a short measurement time.

Targeting Dual Immune Checkpoints PD-L1 and HLA-G by Trispecific T Cell Engager for Treating Heterogeneous Lung Cancer.

Immunotherapy targeting immune checkpoints (ICPs), such as programmed death-ligand-1 (PD-L1), is used as a treatment option for advanced or metastatic non-small cell lung cancer (NSCLC). However, overall response rate to anti-PD-L1 treatment is limited due to antigen heterogeneity and the immune-suppressive tumor microenvironment. Human leukocyte antigen-G (HLA-G), an ICP as well as a neoexpressed tumor-associated antigen, is previously demonstrated to be a beneficial target in combination with anti-PD-L1. In this study, a nanobody-based trispecific T cell engager (Nb-TriTE) is developed, capable of simultaneously binding to T cells, macrophages, and cancer cells while redirecting T cells toward tumor cells expressing PD-L1- and/or HLA-G. Nb-TriTE shows broad spectrum anti-tumor effects in vitro by augmenting cytotoxicity mediated by human peripheral blood mononuclear cells (PBMCs). In a humanized immunodeficient murine NSCLC model, Nb-TriTE exhibits superior anti-cancer potency compared to monoclonal antibodies and bispecific T cell engagers. Nb-TriTE, at the dose with pharmacoactivity, does not induce additional enhancement of circulating cytokines secretion from PMBCs. Nb-TriTE effectively prolongs the survival of mice without obvious adverse events. In conclusion, this study introduces an innovative therapeutic approach to address the challenges of immunotherapy and the tumor microenvironment in NSCLC through utilizing the dual ICP-targeting Nb-TriTE.

Association between methylphenidate use and long-term cardiovascular risk in paediatric patients with attention deficit and hyperactivity disorder.

BACKGROUND: There have been concerns about the potential cardiovascular (CV) adverse effects associated with methylphenidate (MTH) use. However, only limited evidence exists on the long-term safety of MTH. OBJECTIVE: To evaluate whether MTH use is associated with long-term CV risk. METHODS: This was a retrospective cohort study using 2003-2017 data from the Health and Welfare Database in Taiwan. Patients newly diagnosed with attention deficit and hyperactivity disorder (ADHD) and between 3 and 18 years of age were included. Two treatment statuses were assessed: initial treatment ≥7 days and ≥180 days. Patients treated with MTH were compared with those receiving non-medication therapy. One-to-one propensity score matching was used to balance between-group differences. Study outcomes included major CV events, chronic CV disease, cardiogenic shock and all-cause mortality. Cox proportional hazard models were used to estimate HRs between the two groups. RESULTS: We began with 307 459 patients with ADHD. After exclusion, 224 732 patients were included in the final cohort. The results showed that compared with non-ADHD medication users, patients who were treated with MTH for more than 7 days had a similar risk of major CV events (HR 0.85, 95% CI 0.72 to 0.99; p=0.040). Identical trends were found in groups who were treated for more than 180 days (HR 0.83, 95% CI 0.69 to 1.00; p=0.050). The results of the sensitivity analyses were consistent with the main analyses across all groups and individual outcomes. CONCLUSION: Short-term MTH use did not increase CV risk among patients with ADHD. More evidence on long-term MTH use and risk of cardiogenic shock and death is warranted.

Comparison of free vascularized fibular grafts and the Masquelet technique for the treatment of segmental bone defects with open forearm fractures: a retrospective cohort study.

PURPOSE: Severe open forearm fractures commonly involve segmental bone defects. Although several methods have been proposed to treat segmental bone defects with such fractures, research comparing the radiological and clinical outcomes of free vascularized fibular grafts (FVFG) and the Masquelet technique (MT) is rare. METHODS: Data on 43 patients with open forearm fractures and segmental bone defects treated surgically in our hospital from January 2005 to January 2021 were retrospectively analyzed, and these patients were divided into an FVFG group (18 cases) and an MT group (25 cases). Clinical and radiological evaluations were performed regularly, and the minimum follow-up was 18 months. RESULTS: All 43 patients were followed up for 18 to 190 months, with a mean of 46.93 months. The mean follow-up time was significantly longer in the FVFG group than in the MT group (p = 0.000). Bone healing time was 3-16 months, with a mean of 4.67 months. The QuickDASH score at the last follow-up was 0-38.6, with a mean of 17.71, and there was no statistically significant difference between the two groups. Operative time, hospital stay, and intraoperative bleeding for bone defect reconstruction were higher in the FVFG group compared to the MT group (p = 0.000), whereas the number of procedures was lower in the FVFG group than in the MT group (p = 0.035). CONCLUSIONS: FVFG and the MT showed satisfactory clinical results for segmental bone defects of the forearm. Compared with FVFG, the MT exhibited a lower operative time, hospital stay, and intraoperative bleeding. LEVEL OF EVIDENCE: Level IV. Trial registration This study was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR2300067675; registered 17 January 2023), https://www.chictr.org.cn/showproj.html?proj=189458 .

Gα13 controls pharyngeal endoderm convergence by regulating E-cadherin expression and RhoA activation.

Pharyngeal endoderm cells undergo convergence and extension (C&E), which is essential for endoderm pouch formation and craniofacial development. Our previous work implicates Gα13/RhoA-mediated signaling in regulating this process, but the underlying mechanisms remain unclear. Here, we have used endoderm-specific transgenic and Gα13 mutant zebrafish to demonstrate that Gα13 plays a crucial role in pharyngeal endoderm C&E by regulating RhoA activation and E-cadherin expression. We showed that during C&E, endodermal cells gradually establish stable cell-cell contacts, acquire apical-basal polarity and undergo actomyosin-driven apical constriction, which are processes that require Gα13. Additionally, we found that Gα13-deficient embryos exhibit reduced E-cadherin expression, partially contributing to endoderm C&E defects. Notably, interfering with RhoA function disrupts spatial actomyosin activation without affecting E-cadherin expression. Collectively, our findings identify crucial cellular processes for pharyngeal endoderm C&E and reveal that Gα13 controls this through two independent pathways - modulating RhoA activation and regulating E-cadherin expression - thus unveiling intricate mechanisms governing pharyngeal endoderm morphogenesis.

The value of computed tomography angiography for evaluation of left atrial enlargement in patients with persistent atrial fibrillation.

BACKGROUND: The post-processing technology of CTA offers significant advantages in evaluating left atrial enlargement (LAE) in patients with persistent atrial fibrillation (PAF). This study aims to identify parameters for rapidly and accurately diagnosing LAE in patients with PAF using CT cross-sections. METHODS: Left atrial pulmonary venous (PV) CT was performed to 300 PAF patients with dual-source CT, and left atrial volume (LAV), left atrial anteroposterior diameter (LAD1), left atrial transverse diameter (LAD2), and left atrial area (LAA) were measured in the ventricular end systolic (ES) and middle diastolic (MD). LA index (LAI) = LA parameter/body surface area (BSA). Left atrial volume index (LAVIES) > 77.7 ml/m2 was used as the reference standard for the LAE diagnosis. RESULTS: 227 patients were enrolled in the group, 101 (44.5%) of whom had LAE. LAVES and LAVMD (r = 0.983), LAVIES and LAVIMD (r = 0.984), LAAES and LAVIES (r = 0.817), LAAMD and LAVIES (r = 0.814) had strong positive correlations. The area under curve (AUC) showed that all measured parameters were suitable for diagnosing LAE, and the diagnostic efficacy was compared as follows: LAA/LAAI> LAD> the relative value index of LAD, LAD2> LAD1. LAA and LAAI demonstrated comparable diagnostic efficacy, with LAA being more readily available than LAAI. CONCLUSIONS: The axial LAA measured by CTA can be served as a parameter for the rapid and accurate diagnosis of LAE in patients with PAF.

Unmasking Protein Phosphatase 2A Regulatory Subunit B as a Crucial Factor in the Progression of Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is one of the major causes of heart failure. Although significant progress has been made in elucidating the underlying mechanisms, further investigation is required for clarifying molecular diagnostic and therapeutic targets. In this study, we found that the mRNA level of protein phosphatase 2 regulatory subunit B' delta (Ppp2r5d) was altered in the peripheral blood plasma of DCM patients. Knockdown of Ppp2r5d in murine cardiomyocytes increased the intracellular levels of reactive oxygen species (ROS) and inhibited adenosine triphosphate (ATP) synthesis. In vivo knockdown of Ppp2r5d in an isoproterenol (ISO)-induced DCM mouse model aggravated the pathogenesis and ultimately led to heart failure. Mechanistically, Ppp2r5d-deficient cardiomyocytes showed an increase in phosphorylation of STAT3 at Y705 and a decrease in phosphorylation of STAT3 at S727. The elevated levels of phosphorylation at Y705 in STAT3 triggered the upregulation of interleukin 6 (IL6) expression. Moreover, the decreased phosphorylation at S727 in STAT3 disrupted mitochondrial electron transport chain function and dysregulated ATP synthesis and ROS levels. These results hereby reveal a novel role for Ppp2r5d in modulating STAT3 pathway in DCM, suggesting it as a potential target for the therapy of the disease.

Enhancing Taiwan's healthcare sustainability: A Delphi study on national medicines policy reforms.

BACKGROUND/PURPOSE: The National Medicines Policy (NMP) is crucial as it sets the framework for ensuring access to affordable, high-quality medicines and promoting their rational use, which is essential for public health and the efficiency of the healthcare system. This study aims to evaluate the current state of Taiwan's NMP, identify pressing issues for improvement, and establish actionable suggestions through expert consensus to ensure the sustainable provision and use of medications. METHODS: A modified two-round Delphi technique was employed. The first-round survey identified key issues and suggestions for policy improvement, while the second-round survey evaluated the feasibility and effectiveness of these suggestions. The expert panel, consisting of 50 specialists from pharmacy, medicine, public health, and the pharmaceutical industry, evaluated key issues related to the NMP's efficacy using a 4-point Likert scale. RESULTS: The first-round survey identified 13 key issues in Taiwan's NMP, primarily focusing on the rational use and accessibility of medications. The second-round survey proposed 54 policy improvement suggestions for these issues, of which 20 were considered strong suggestions and 23 were moderate suggestions. The policy recommendations cover medication reimbursement, pharmacy professional services, administration, legislation, and education. CONCLUSION: The study highlights the urgent need for reforms in Taiwan's NMP, providing specific policy improvement suggestions to ensure high-quality medications and pharmaceutical services while supporting the sustainable operation of Taiwan's NHI system. The study underscores the significance of proactive measures to fortify healthcare sustainability in the face of evolving healthcare landscapes.

Activation of the ROCK/MYLK Pathway Affects Complex Molecular and Morphological Changes of the Trabecular Meshwork Associated With Ocular Hypertension.

Purpose: The Rho-associated protein kinase and myosin light chain kinase (ROCK/MYLK) pathway undeniably plays a pivotal role in the pathophysiology of primary open-angle glaucoma (POAG). In our study, we utilized both ocular hypertension (OHT) rabbit models and clinical investigations to gain invaluable insights that propel the development of novel treatments targeting proteins and genes associated with the trabecular meshwork (TM), thereby offering promising avenues for the management of POAG. Methods: Following microbead injections into the anterior chamber of the ocular cavity of rabbits, we observed elevated histiocyte numbers and immune scores for MYLK-4/ pMLC-2, alongside a reduction in the void space within the TM. Notably, treatment was performed with 0.1% ITRI-E-(S)-4046, a compound with dual kinase inhibitor (highly specific inhibitor of ROCK1/2 and MYLK4), significantly reduced intraocular pressure (IOP; P < 0.05) and expanded the void space within the TM (P < 0.0001) compared with OHT rabbits. In clinical investigations, we utilized whole transcriptome sequencing to analyze gene expression specifically related to the TM, obtained from patients (5 early-onset and 5 late-onset) undergoing trabeculectomy. Results: Our findings revealed 103 differential expression genes (DEGs) out of 265 molecules associated with the Rho family GTPase pathway, exhibiting a P value of 1.25E-10 and a z-score of -2.524. These results underscore significant differences between the early-onset and late-onset POAG and highlight the involvement of the ROCK/MYLK pathway. Conclusions: These findings underscore the critical involvement of the ROCK/MYLK pathway in both OHT-related and different onsets of POAG, providing valuable insights into the TM-related molecular mechanisms underlying the disease.

Exploration of the thickness-depended dynamic properties of differential phase contrast (DPC) and integrated differential phase contrast (iDPC).

A study on DPC and iDPC images of crystals is achieved with simulation. It highlights the use of electron wave intensity distribution to visualize the dynamic effect on DPC and iDPC contrasts. Electron waves near heavy atoms exhibit significant oscillations and rapid intensity decay. This oscillation causes DPC and iDPC signal inversion. Bloch wave theory is used to derive DPC and iDPC intensity distributions, elucidating the impact of dynamic effect on the contrast.

First Report of Grovesinia moricola Causing Zonate Leaf Spot on Hernandia nymphaeifolia in Taiwan.

Hernandia nymphaeifolia (C. Presl) Kubitzki, a native tree of Taiwan, is a sea drift plant (Yang and Lu 1996). It is a salt- and wind-tolerant tree (Bezona et al. 2009) and was selected for the afforestation of badlands in coastal areas of Taiwan. In December 2022, all H. nymphaeifolia seedlings at a nursery in Wu-Lai, Taiwan were diseased and wilted with a similar progression. The initial symptom was small zonate white or gray lesions with water-soaked periphery on leaves. Then, expansion and fusion of leaf spots which caused leaf blight and defoliation were observed. Seedlings eventually wilted. Sporophores found on the host were generally hypophyllous, solitary, erect, and easily detachable. The upper portion of the sporophore was considered an individual conidium and consisted of a pyramidal head that was fusiform to ventricose, 206.3 to 501.8 µm (average: 378.0 ± 75.3 µm) long, and 63.6 to 104.5 µm (average: 85.0 ± 16.2 µm) wide at the broadest point (n=30). Branches within the pyramidal head were short, compact, and di- or trichotomously branched. The central stipe was hyaline, broad, septate, tapering toward an acute apex, and sometimes constricted at the basal septum. Sclerotia were gray or black, spherical, and 1.0 to 2.5 mm (n=10) in diameter and observed on older lesions. The fungus was isolated from infected tissue and sporophores and maintained on potato dextrose agar (PDA) at 20°C in darkness. Sclerotia were produced on PDA after 4 to 5 weeks and were irregular or spherical, but no sporophore was developed. The fungus was identified as Grovesinia moricola (I. Hino) Redhead based on morphological characteristics (Tomoko et al. 2006). Three DNA samples was obtained from the cultures isolated from the diseased leaf, sporophores and sclerotia. They were then amplified by PCR with primers for the internal transcribed spacer region (ITS; primers ITS5/ITS4) and the large subunit nuclear ribosomal RNA gene (LSU; primers LR0R/LR5) (Cho et al. 2017), and then sequenced respectively. The sequences were deposited into GenBank with accession nos. PP727191 to PP727193 and PP748518 to PP748520. BLAST analysis of the three isolates showed 100% identity to the sequences of G. moricola from Taiwan (OP550202, OP550203) for the ITS region and 99.9% identity to the sequence of G. moricola from the USA (MW013804) for the LSU rRNA gene. The specimens (FS2022-140) and the culture (Asco-0109) in this study were deposited into the herbarium of Taiwan Forestry Research Institute in Taiwan. Koch's postulates were performed by inoculating four 8-month-old, asymptomatic, potted H. nymphaeifolia plants; every plant was inoculated with sporophores from infected leaves on the upper surface of each of five leaves. Four uninoculated plants were kept in separate pots and served as controls. All plants were covered with transparent plastic bags individually and incubated in a growth chamber at 18 to 20°C with 8 h of light. Similar leaf spots and sporophores were observed after 2 to 4 days and 10 days on every inoculated plant but not on uninoculated plants. The pathogen with a similar colony on PDA was reisolated from the leaf spots of the inoculated plants. Molecular identification of the reisolated pathogen by the above method was carried out. The sequences showed 99.9% identity to the sequence of G. moricola, and were deposited into GenBank with accession nos. PQ157896 to PQ157897 (ITS region) and PQ157701 to PQ157702 (LSU rRNA gene). The pathogenicity test was repeated once. G. moricola is known to cause severe defoliation on woody and annual plants, including at least 73 host species and 36 families distributed in the eastern United States and Japan (Trolinger et al. 1978). This is the first report of G. moricola on H. nymphaeifolia in the world. Control of the disease would play an important role in maintaining healthy seedlings for the afforestation in Taiwan.

Crizotinib and its enantiomer suppress ferroptosis by decreasing PE-O-PUFA content.

Ferroptosis is a specific form of cell death characterized by excessive accumulation of cellular lipid peroxides. Ferroptosis is closely associated with various diseases, inhibition of which may help alleviate multi-organ injury caused by ischemia-reperfusion and enhance the anti-tumor effect by promoting the immunity of T cells. However, clinical approved drugs targeting ferroptosis process remain rare. In this study, we unexpectedly found that (R)-crizotinib, the first-generation ALK inhibitor, has potent inhibitory activity against ferroptosis across various cell lines. Moreover, its chiral molecule (S)-crizotinib, which was considered to share no common targets with (R)-crizotinib, also suppresses ferroptosis with an efficacy similar to that of (R)-crizotinib. We further demonstrated that both crizotinib enantiomers inhibit ferroptosis independently of their known targets, but through a common mechanism involving the targeting of AGPAT3-mediated synthesis of ether-linked polyunsaturated fatty acids (PE-O-PUFA), which are known to promote lipid-ROS generation and ferroptosis. In line with their activity in cell lines, (R)-crizotinib and (S)-crizotinib effectively mitigate renal ischemia-reperfusion injury in mice. Furthermore, the two compounds also inhibit lipid-ROS accumulation in CD8+ T cells in draining lymph nodes of B16-F10 subcutaneous xenograft mice, thereby promoting anti-tumor effects. Collectively, our study firstly reports a common activity shared by (R)-crizotinib and (S)-crizotinib in ferroptosis regulation. As a clinically approved drug, (R)-crizotinib has well-established pharmacokinetics and safety, which makes it a promising candidate for repurposing. Given the current lack of FDA-approved ferroptosis inhibitors, our findings suggest therapeutically repurposing (R)-crizotinib as well as its enantiomer (S)-crizotinib for treating ferroptosis-related diseases.

Risk factors and outcome of BK polyomavirus infection in pediatric kidney transplantation.

BACKGROUND: BK polyomavirus (BKV) infection is a critical complication hindering graft survival after kidney transplantation. We aimed to investigate the risk factors and outcome of BKV infection in pediatric kidney transplantation. METHODS: The clinical and follow-up data of pediatric kidney transplant recipients at the Children's Hospital of Fudan University from Jan 2015 to June 2023 were retrospectively analyzed. RESULTS: A total of 217 patients were included in the study with mean follow-up time of 24.3 ± 19.9 months. The mean age at transplantation was 9.7 ± 4.2 years. The patient survival rate and graft survival rate were 98.2% and 96.8%, respectively. Twenty-nine patients (13.4%) developed BKV infection, which was detected at 5.8 ± 3.2 months after transplantation. Among these 29 patients with BKV infection, 8 patients (3.6%) developed BKV nephropathy (BKVN), which was diagnosed at 8.3 ± 2.9 months after transplantation, and 2 patients developed graft failure eventually. Compared with the non-BKV infection group (eGFR 76.7 ± 26.1 mL/min/1.73 m2) and BKV infection without BKVN group (eGFR 85.2 ± 23.8 mL/min/1.73 m2), BKVN group had lowest eGFR during follow-up (33.5 ± 11.0 ml/min/1.73 m2, P < 0.001). Younger age at transplant (OR 0.850, 95%CI 0.762-0.948, P = 0.005), CAKUT disease of primary etiology (OR 2.890, 95%CI 1.200-6.961, P = 0.018), and CMV negative recipient serostatus before transplantation (OR 3.698, 95%CI 1.583-8.640, P = 0.003) were independent risk factors for BKV infection. CONCLUSIONS: Incidence of BKV infection is quite high within 12 months after pediatric kidney transplantation and children with BKVN have poor graft function. Younger age at transplant, CAKUT disease, and CMV negative recipient serostatus before transplantation increase the risk of BKV infection after kidney transplantation.

Impacts and Correlations on Corneal Biomechanics, Corneal Optical Density and Intraocular Pressure after Cataract Surgery.

The study aimed to investigate the extended effects and interrelations of corneal biomechanics, corneal optical density (COD), corneal thickness (CT), and intraocular pressure (IOP) following cataract surgery. Sixteen eyes were analyzed prospectively. The Corneal Visualization Scheimpflug Technology (Corvis ST) device assessed corneal biomechanics, while the Pentacam AxL® (Pentacam) measured COD and CT. Postoperative data were collected around six months after surgery, with a subgroup analysis of data at nine months. The Pearson correlation was used to examine the relationship between surgical-induced changes in corneal biomechanics and COD. At six months, significant postoperative differences were observed in various biomechanical indices, including uncorrected IOP (IOPuct) and biomechanics-corrected IOP (bIOP). However, many indices lost statistical significance by the nine-month mark, suggesting the reversibility of postoperative corneal changes. Postoperative COD increased at the anterior layer of the 2-6 mm annulus and incision site. The changes in COD correlated with certain biomechanical indices, including maximal (Max) deformative amplitude (DA) and stiffness parameter (SP). In conclusion, despite significant immediate postoperative changes, corneal biomechanics, COD, and IOP experienced a gradual recovery process following cataract surgery. Clinicians should maintain vigilance for any unusual changes during the short-term observation period to detect abnormalities early.

Sex-specific associations between prolonged serum uric acid levels and risk of major adverse cardiovascular events.

Background: While hyperuricemia has been correlated with cardiovascular (CV) diseases, further evidence is required to evaluate the implications of stable serum uric acid (sUA) levels, especially concerning low sUA. This study aimed to investigate prolonged stable sUA levels and CV events/mortality. Methods: We conducted a retrospective cohort study at a medical center using electronic medical records linked with the national claims database. Patients with at least two sUA measurements, with intervals ranging from 6 months to 4 years, were included. The mean of the first two eligible sUA measurements were analyzed, stratified by sex. Outcomes of interest comprised major adverse cardiovascular events (MACE), heart failure hospitalization, CV and all-cause mortality. Results: This study included 33,096 patients (follow-up: men 6.6 years, women 6.4 years). After multivariable adjustment, cubic spline models showed that long-term high sUA levels were consistently associated with a higher risk of MACE, heart failure hospitalization, CV and all-cause mortality. A U-shaped association was observed between sUA levels and all-cause mortality in both sexes and between sUA levels and CV mortality in women. The impact of sUA, especially lower levels, on CV events and mortality was more pronounced in women than in men. Conclusion: Long-term high sUA levels are consistently associated with increased risk of CV events and mortality. A U-shaped association between sUA levels and all-cause mortality was observed in both men and women and was pronounced in women. The findings underscore the importance of considering sUA levels, especially in women, when assessing CV risk.

Antibiotic use and risk of autism spectrum disorder and attention-deficit/hyperactivity disorder: a population-based cohort study.

BACKGROUND: The gut microbiota is believed to influence neurodevelopment through the gut-brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD. METHODS: This was a retrospective cohort study using 2003-2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk. RESULTS: The final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04-1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01-1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90-0.94). CONCLUSIONS: The results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use.