Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter.

The systemic complexity of a monogenic disease: the molecular network of spinal muscular atrophy.

Monogenic diseases are well-suited paradigms for the causal analysis of disease-driving molecular patterns. Spinal Muscular Atrophy (SMA) is one such monogenic model caused by mutation or deletion of the Survival of motor neuron 1 (SMN1) gene. Although several functions of the SMN protein have been studied, single functions and pathways alone do not allow to identify critical disease-driving molecules. Here, we analyzed the systemic characteristics of SMA employing proteomics, phosphoproteomics, translatomics and interactomics from two mouse models with different disease-severities and genetics. This systems approach revealed sub-networks and proteins characterizing commonalities and differences of both models. To link the identified molecular networks with the disease-causing SMN protein, we combined SMN-interactome data with both proteomes creating a comprehensive representation of SMA. By this approach, disease hubs and bottlenecks between SMN and downstream pathways could be identified. Linking a disease-causing molecule with widespread molecular dysregulations via multiomics is a concept for analyses of monogenic diseases.

A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia.

Acute myeloid leukemias (AMLs) with the NUP98-NSD1 or mixed lineage leukemia (MLL) rearrangement (MLL-r) share transcriptomic profiles associated with stemness-related gene signatures and display poor prognosis. The molecular underpinnings of AML aggressiveness and stemness remain far from clear. Studies with EZH2 enzymatic inhibitors show that polycomb repressive complex 2 (PRC2) is crucial for tumorigenicity in NUP98-NSD1+ AML, whereas transcriptomic analysis reveal that Kdm5b, a lysine demethylase gene carrying "bivalent" chromatin domains, is directly repressed by PRC2. While ectopic expression of Kdm5b suppressed AML growth, its depletion not only promoted tumorigenicity but also attenuated anti-AML effects of PRC2 inhibitors, demonstrating a PRC2-|Kdm5b axis for AML oncogenesis. Integrated RNA sequencing (RNA-seq), chromatin immunoprecipitation followed by sequencing (ChIP-seq), and Cleavage Under Targets & Release Using Nuclease (CUT&RUN) profiling also showed that Kdm5b directly binds and represses AML stemness genes. The anti-AML effect of Kdm5b relies on its chromatin association and/or scaffold functions rather than its demethylase activity. Collectively, this study describes a molecular axis that involves histone modifiers (PRC2-|Kdm5b) for sustaining AML oncogenesis.

NF-кB promotes aggresome formation via upregulating HDAC6 and in turn maintaining Vimentin cage.

Proteasome inhibitors have been applied to anticancer therapy by accumulating toxic misfolded proteins. However, chemical inactivation of proteasome generates aggresome, a Vimentin cage-enclosed subcellular structure quarantining HDAC6-Dynein-transported misfolded proteins before the protein toxicants are degraded by autophagy. Hence, aggresome may attenuate proteasome inhibitor drugs-induced cytotoxicity. To solve the problem, it is imperative to characterize how cells assemble aggresome. By examining aggresomes in six cell lines, A549 cells were selectively studied for their bigger cell size and moderate aggresome forming activity. Aggresome grew in size upon continuous exposure of A549 cells to proteasome inhibitor MG132, and reached a mature size around 16th to 24th hour of treatment. Mechanistic studies revealed that NF-кB translocated to nucleus in MG132 treated cells, and chemical activation or knockdown of NF-кB enhanced or prohibited aggresome assembly. Further analyses showed that NF-кB upregulated HDAC6, and HDAC6 maintained Vimentin cage by interacting with Vimentin p72, a key modification of the intermediate filament contributing to aggresome formation. Remarkably, chemical inactivation of NF-кB synergized MG132-induced cell mortality. All the findings suggest that NF-кB dictates aggresome assembly via upregulating HDAC6, and NF-кB inhibitor may serve as a potential drug potentiating proteasome inhibitor medicine-induced cytotoxicity during the treatment of cancer cells.

Suppression of presynaptic corticostriatal glutamate activity attenuates L-dopa-induced dyskinesia in 6-OHDA-lesioned Parkinson's disease mice.

A common adverse effect of Parkinson's disease (PD) treatment is L-dopa-induced dyskinesia (LID). This condition results from both dopamine (DA)-dependent and DA-independent mechanisms, as glutamate inputs from corticostriatal projection neurons impact DA-responsive medium spiny neurons in the striatum to cause the dyskinetic behaviors. In this study, we explored whether suppression of presynaptic corticostriatal glutamate inputs might affect the behavioral and biochemical outcomes associated with LID. We first established an animal model in which 6-hydroxydopamine (6-OHDA)-lesioned mice were treated daily with L-dopa (10 mg/kg, i.p.) for 2 weeks; these mice developed stereotypical abnormal involuntary movements (AIMs). When the mice were pretreated with the NMDA antagonist, amantadine, we observed suppression of AIMs and reductions of phosphorylated ERK1/2 and NR2B in the striatum. We then took an optogenetic approach to manipulate glutamatergic activity. Slc17a6 (vGluT2)-Cre mice were injected with pAAV5-Ef1a-DIO-eNpHR3.0-mCherry and received optic fiber implants in either the M1 motor cortex or dorsolateral striatum. Optogenetic inactivation at either optic fiber implant location could successfully reduce the intensity of AIMs after 6-OHDA lesioning and L-dopa treatment. Both optical manipulation strategies also suppressed phospho-ERK1/2 and phospho-NR2B signals in the striatum. Finally, we performed intrastriatal injections of LDN 212320 in the dyskenesic mice to enhance expression of glutamate uptake transporter GLT-1. Sixteen hours after the LDN 212320 treatment, L-dopa-induced AIMs were reduced along with the levels of striatal phospho-ERK1/2 and phospho-NR2B. Together, our results affirm a critical role of corticostriatal glutamate neurons in LID and strongly suggest that diminishing synaptic glutamate, either by suppression of neuronal activity or by upregulation of GLT-1, could be an effective approach for managing LID.

Cationic Ir(III) Complexes with 4-Fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile as the Cyclometalating Ligand: Synthesis, Characterizations, and Application to Ultrahigh-Efficiency Light-Emitting Electrochemical Cells.

Light-emitting electrochemical cells (LECs) promise low-cost, large-area luminescence applications with air-stabilized electrodes and a versatile fabrication that enables the use of solution processes. Nevertheless, the commercialization of LECs is still encountering many obstacles, such as low electroluminescence (EL) efficiencies of the ionic materials. In this paper, we propose five blue to yellow ionic Ir complexes possessing 4-fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile (ppfn) as a novel cyclometalating ligand and use them in LECs. In particular, the device within di[4-fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile]-4,4'-di-tert-butyl-2,2'-bipyridyl iridium(III) hexafluorophosphate (DTBP) shows a remarkable photoluminescence quantum yield (PLQY) of 70%, and by adjusting the emissive-layer thickness, the maximal external quantum efficiency (EQE) reaches 22.15% at 532 nm under the thickness of 0.51 µm, showing the state-of-the-art value for the reported blue-green LECs.

A comprehensive measure assessing different types of problematic use of the internet among Chinese adolescents: The Assessment of Criteria for Specific Internet-use Disorders (ACSID-11).

BACKGROUND: Problematic use of the internet (PUI) is prevalent, particularly among adolescents and young adults. Given the limited measures to assess specific types of PUI, which encompasses a broad spectrum of activities such as online gaming, social media use, pornography use, shopping, gambling, and web-streaming, Muller et al. (2022) developed the Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) to comprehensively assess different types of PUI (i.e., gaming, shopping, social media use, gambling, and pornography use). The present study aimed to validate the Chinese ACSID-11 among adolescents incorporating cross-cultural adaptations. METHODS: Using forward-backward translation method, a culturally adapted version of the ACSID-11 was prepared. Then, a cross-sectional online survey was administered between September 8 and September 26, 2023. Adolescents, using a convenience sample (N = 11,492; mean age = 16.42 years [SD ± 0.91]; 59.1% male), were recruited from six schools to complete the translated ACSID-11, Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Bergen Social Media Addiction Scale (BSMAS), and Smartphone Application Based Addiction Scale (SABAS) via an online platform. Pearson correlation coefficients assessed convergent/discriminant validity. Factor structure and measurement invariance were examined through confirmatory factor analysis (CFA) and multi-group CFA. Cronbach's alpha and McDonald's omega tested internal consistency. RESULTS: Associations between the ACSID-11 components and other scales supported convergent validity (i.e., ACSID-11 gaming scale with IGDS9-SF [0.37 ≤ r ≤ 0.41]; social networks use scale with BSMAS [0.24 ≤ r ≤ 0.31]) and discriminant validity (i.e., online gambling scale with BSMAS [0.16 ≤ r ≤ 0.19] and with SABAS [0.11 ≤ r ≤ 0.13]). A four-factor solution indicated good fit with comparative fit index (CFI) ranging from 0.982 to 0.958. The ACSID-11 was measurement invariant across sexes (∆CFI = -0.001 to 0.000) and different levels of related addictive behaviors (∆CFI = -0.001 to 0.000). Both Cronbach's alpha and McDonald's omega (0.63 to 0.97) were acceptable for both frequency and intensity of responses. CONCLUSIONS: The ACSID-11 is an appropriate scale to assess different kinds of PUI among Chinese adolescents and students. Psychometric assessment of the measure in other cultures and among clinical samples is recommended.

Diagnostic meta-analysis of the efficacy of ultrasonography for diagnosing carpal tunnel syndrome: A comparison between Asian and non-Asian populations.

BACKGROUND: Ultrasonography is used to diagnose carpal tunnel syndrome (CTS) according to various criteria. This diagnostic meta-analysis aimed to evaluate the efficacy of ultrasonography for diagnosing CTS, focusing on the cross-sectional area (CSA) of the median nerve (MN) at the inlet of the carpal tunnel and regional variations in diagnostic thresholds between Asian and non-Asian populations. METHODS: A comprehensive literature search was conducted using PubMed, Embase, and the Cochrane Library. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Patient demographic data, diagnostic "gold standards", CSA cutoff values, and diagnostic results were extracted. Meta-analysis was performed to determine the sensitivity, specificity, and optimal CSA cutoff values. RESULTS: For the 25 included studies, a combined sensitivity of 88% and specificity of 84% for CSA measurements at the carpal tunnel inlet were obtained. The Asian group had a sensitivity of 84% and specificity of 86%, while the non-Asian group had a sensitivity of 91% and specificity of 82%. The mean CSA in the Asian group was significantly lower than that in the non-Asian group (12.93 mm2 and 14.77 mm2, respectively; p = 0.042). For the Asian group, the summary receiver operating characteristic curve had an area under the curve (AUC) of 0.92 with an optimal cutoff of 10.5 mm2; for the non-Asian group, an AUC of 0.94 was obtained with a cutoff of 11.5 mm2. CONCLUSION: Ultrasonography is a reliable diagnostic method for CTS, with distinct optimal cutoff values observed between Asian and non-Asian populations. Therefore, population-specific diagnostic criteria for CTS are recommended.

[Improving the Rate of Palliative Care Completion in NICU Nurses].

BACKGROUND: Critically ill neonates receive care in the neonatal intensive care unit (NICU). Unfortunately, some neonates pass away in the NICU. Providing comprehensive neonatal palliative care and hospice services is crucial in supporting parents through the loss of their offspring. In our NICU, we identified that only 74.5% of nurses are able to properly recognize the need for palliative care and only 55% are able to implement the necessary procedures. PURPOSE: A project was designed and implemented to enhance the ability of nursing staff to recognize the need for and properly implement palliative care to improve the quality of this care in the NICU. RESOLUTIONS: We organized an on-the-job education and training program within our NICU with the goals of heightening awareness among nursing staff. In addition, a specialist palliative care operation flow chart, process preparation checklist, and palliative-care-related tools were created to facilitate the care process. RESULTS: After program implementation, among nursing staff in our NICU, the palliative care recognition accuracy rate rose to 100% (from 74.5%) and the implementation rate rose to 94.8% (from 55%). The quality of provided neonatal palliative care and hospice services was significantly improved. CONCLUSIONS: The developed program was shown to significantly improve nursing staff recognition and implementation of neonatal palliative care in our NICU. This experience provides a reference for improving palliative care quality and for helping families effectively manage end-of-life challenges.

Inhibition of ferroptosis by icariin treatment attenuates excessive ethanol consumption-induced atrial remodeling and susceptibility to atrial fibrillation, role of SIRT1.

Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study.

Chemical Redox Cycling in an Organic Photoelectrochemical Transistor: Toward Dual Chemical and Electronic Amplification for Bioanalysis.

The organic photoelectrochemical transistor (OPECT) has been proven to be a promising platform to study the rich light-matter-bio interplay toward advanced biomolecular detection, yet current OPECT is highly restrained to its intrinsic electronic amplification. Herein, this work first combines chemical amplification with electronic amplification in OPECT for dual-amplified bioanalytics with high current gain, which is exemplified by human immunoglobulin G (HIgG)-dependent sandwich immunorecognition and subsequent alkaline phosphatase (ALP)-mediated chemical redox cycling (CRC) on a metal-organic framework (MOF)-derived BiVO4/WO3 gate. The target-dependent redox cycling of ascorbic acid (AA) acting as an effective electron donor could lead to an amplified modulation against the polymer channel, as indicated by the channel current. The as-developed bioanalysis could achieve sensitive HIgG detection with a good analytical performance. This work features the dual chemical and electronic amplification for OPECT bioanalysis and is expected to stimulate further interest in the design of CRC-assisted OPECT bioassays.

Neuromuscular junction denervation and terminal Schwann cell loss in the hTDP-43 overexpression mouse model of amyotrophic lateral sclerosis.

AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with complex aetiology. Despite evidence of neuromuscular junction (NMJ) denervation and 'dying-back' pathology in models of SOD1-dependent ALS, evidence in other genetic forms of ALS is limited by a lack of suitable animal models. TDP-43, a key mediator protein in ALS, is overexpressed in neurons in Thy1-hTDP-43WT mice. We therefore aimed to comprehensively analyse NMJ pathology in this model of ALS. METHODS: Expression of TDP-43 was assessed via western blotting. Immunohistochemistry techniques, alongside NMJ-morph quantification, were used to analyse motor neuron number, NMJ denervation status and terminal Schwann cell morphology. RESULTS: We present a time course of progressive, region-specific motor neuron pathology in Thy1-hTDP-43WT mice. Thy1-driven hTDP-43 expression increased steadily, correlating with developing hindlimb motor weakness and associated motor neuron loss in the spinal cord with a median survival of 21 days. Pronounced NMJ denervation was observed in hindlimb muscles, mild denervation in cranial muscles but no evidence of denervation in either forelimb or trunk muscles. NMJ pathology was restricted to motor nerve terminals, with denervation following the same time course as motor neuron loss. Terminal Schwann cells were lost from NMJs in hindlimb muscles, directly correlating with denervation status. CONCLUSIONS: Thy1-hTDP-43WT mice represent a severe model of ALS, with NMJ pathology/denervation of distal muscles and motor neuron loss, as observed in ALS patients. This model therefore provides an ideal platform to investigate mechanisms of dying-back pathology, as well as NMJ-targeting disease-modifying therapies in ALS.

White Light-Emitting Electrochemical Cells Employing Phosphor-Sensitized Thermally Activated Delayed Fluorescence to Approach All-Phosphorescent Device Efficiencies.

Solid-state light-emitting electrochemical cells (LECs) show promising advantages of simple device architecture, low operation voltage, and insensitivity to the electrode work functions such that they have high potential in low-cost display and lighting applications. In this work, novel white LECs based on phosphor-sensitized thermally activated delayed fluorescence (TADF) are proposed. The emissive layer of these white LECs is composed of a blue-green phosphorescent host doped with a deep-red TADF guest. Efficient singlet-to-triplet intersystem crossing (ISC) on the phosphorescent host and the subsequent Förster energy transfer from the host triplet excitons to guest singlet excitons can make use of both singlet and triplet excitons on the host. With the good spectral overlap between the host emission and the guest absorption, 0.075 wt.% guest doping is sufficient to cause substantial energy transfer efficiency (ca. 40 %). In addition, such a low guest concentration also reduces the self-quenching effect and a high photoluminescence quantum yield of up to 84 % ensures high device efficiency. The phosphor-sensitized TADF white LECs indeed show a high external quantum efficiency of 9.6 %, which is comparable with all-phosphorescent white LECs. By employing diffusive substrates to extract the light trapped in the substrate, the device efficiency can be further improved by ca. 50 %. In the meantime, the intrinsic EL spectrum and device lifetime of the white LECs recover since the microcavity effect is destroyed. This work successfully demonstrates that the phosphor-sensitized TADF white LECs are potential candidates for efficient white light-emitting devices.

The crescent-like Golgi ribbon is shaped by the Ajuba/PRMT5/Aurora-A complex-modified HURP.

BACKGROUND: Golgi apparatus (GA) is assembled as a crescent-like ribbon in mammalian cells under immunofluorescence microscope without knowing the shaping mechanisms. It is estimated that roughly 1/5 of the genes encoding kinases or phosphatases in human genome participate in the assembly of Golgi ribbon, reflecting protein modifications play major roles in building Golgi ribbon. METHODS: To explore how Golgi ribbon is shaped as a crescent-like structure under the guidance of protein modifications, we identified a protein complex containing the scaffold proteins Ajuba, two known GA regulators including the protein kinase Aurora-A and the protein arginine methyltransferase PRMT5, and the common substrate of Aurora-A and PRMT5, HURP. Mutual modifications and activation of PRMT5 and Aurora-A in the complex leads to methylation and in turn phosphorylation of HURP, thereby producing HURP p725. The HURP p725 localizes to GA vicinity and its distribution pattern looks like GA morphology. Correlation study of the HURP p725 statuses and GA structure, site-directed mutagenesis and knockdown-rescue experiments were employed to identify the modified HURP as a key regulator assembling GA as a crescent ribbon. RESULTS: The cells containing no or extended distribution of HURP p725 have dispersed GA membranes or longer GA. Knockdown of HURP fragmentized GA and HURP wild type could, while its phosphorylation deficiency mutant 725A could not, restore crescent Golgi ribbon in HURP depleted cells, collectively indicating a crescent GA-constructing activity of HURP p725. HURP p725 is transported, by GA membrane-associated ARF1, Dynein and its cargo adaptor Golgin-160, to cell center where HURP p725 forms crescent fibers, binds and stabilizes Golgi assembly factors (GAFs) including TRIP11, GRASP65 and GM130, thereby dictating the formation of crescent Golgi ribbon at nuclear periphery. CONCLUSIONS: The Ajuba/PRMT5/Aurora-A complex integrates the signals of protein methylation and phosphorylation to HURP, and the HURP p725 organizes GA by stabilizing and recruiting GAFs to its crescent-like structure, therefore shaping GA as a crescent ribbon. Therefore, the HURP p725 fiber serves a template to construct GA according to its shape. Video Abstract.

Pediatric Outpatient Noncontrast Brain MRI: A Time-Driven Activity-Based Costing Analysis at Three U.S. Hospitals.

BACKGROUND. MRI utilization and the use of sedation or anesthesia for MRI have increased in children. Emerging alternative payment models (APMs) require a detailed understanding of the health system costs of performing these examinations. OBJECTIVE. The purpose of this study was to use time-driven activity-based costing (TDABC) to assess health system costs for outpatient noncontrast brain MRI examinations across three children's hospitals. METHODS. Direct costs for outpatient noncontrast brain MRI examinations at three academic free-standing pediatric hospitals were calculated using TDABC. Examinations were categorized as sedated MRI (i.e., sedation or anesthesia), nonsedated MRI, or limited MRI. Process maps were created to describe patient workflows based on input from key personnel and direct observation. Time durations for each process activity were determined; time stamps from retrospective EMR review were used when possible. Capacity cost rates were calculated for resource types within three cost categories (labor, equipment, and space); cost was calculated in a fourth category (supplies). Resources were allocated to each activity, and the cost of each process step was determined by multiplying step-specific capacity costs by the time required for each step. The costs of all steps were summed to yield a base-case total examination cost. Sensitivity analysis for sedated MRI was performed using minimum and maximum time duration inputs for each activity to yield minimum and maximum costs by hospital. RESULTS. The mean base-case cost for a sedated brain MRI examination was $842 (range, $775-924 across hospitals), for a nonsedated brain MRI examination was $262 (range, $240-285), and for a limited brain MRI examination was $135 (range, $127-141). For all examination types, the largest cost category as well as the largest source of difference in cost between hospitals was labor. Sensitivity analysis found that the greatest influence on overall cost at each hospital was the duration of the MRI acquisition. CONCLUSION. The health system cost of performing a sedated MRI examination was substantially greater than that of performing a nonsedated MRI examination. However, the cost of each individual examination type did not vary substantially among hospitals. CLINICAL IMPACT. Health systems operating within APMs can use this comparative cost information for purposes of cost reduction efforts and establishment of bundled prices.

Transoral endoscopic and robotic thyroidectomy for thyroid cancer: the mid-term oncological outcome.

BACKGROUND: Traditional open thyroidectomy is the surgical standard for thyroid cancer; however, it inevitably leaves a visible scar on the neck and affects the patient's quality of life. Therefore, to avoid making a neck incision, the transoral endoscopic thyroidectomy vestibular approach (TOETVA) and transoral robotic thyroidectomy (TORT) have been developed recently, and the surgical outcomes of these techniques are as favorable as open surgery for benign disease. Additionally, positive short-term surgical outcomes have also been achieved in a few patients with thyroid cancer. However, no data on the mid-to-long-term recurrence and survival rates of transoral thyroidectomy in thyroid cancer are available. Therefore, in this study, we analyzed the surgical outcomes and mid-term oncological results of the TOETVA and TORT in patients with thyroid cancer. METHODS: We reviewed patients who had received TOETVA or TORT between July 2017 and November 2021 and followed up on their oncological outcomes until December 2022. Perioperative surgical and mid-term oncological outcomes were analyzed. RESULTS: The 115 patients underwent 122 operations (57 TOETVAs and 65 TORTs), including seven complete thyroidectomies for differentiated thyroid cancer (DTC), Stage I-II, including T1-T3, N0-N1a, and initial low- to high-risk groups. There was no conversion from transoral to open surgery. TORT required a longer operating time (median [interquartile range]) than TOETVA (lobectomy: 279 [250, 318] vs. 196 [173, 253] min, p < 0.001; bilateral total thyroidectomy: 375 [309, 433] vs. 279 [238, 312] min, p < 0.001); however, no difference was found between the two groups regarding perioperative complications. Complete thyroidectomy with a second transoral approach was safe. TOETVA and TORT achieved favorable oncological outcomes with 100% survival and 98.2% acceptable response (excellent and indeterminate response) during a mean 37.88 ± 12.42 months mid-term follow-up. CONCLUSIONS: Transoral endoscopic and robotic thyroidectomy was safe and achieved favorable mid-term oncological outcomes in a selected cohort of patients with early-stage DTC.

Correlation analysis between morphologic characteristics of the thoracolumbar basivertebral foramen and Kummell's disease in patients with osteoporosis using imaging techniques.

BACKGROUND: The aging of the population is a social problem faced by many countries in the world. With the increase in the elderly population, the number of patients with Kummell's disease is also gradually increasing. No study has demonstrated that Kummell's disease has a clear correlation with the foramen of a vertebrobasilar vein. OBJECTIVES: The research was conducted to describe and evaluate the morphological characteristics of a basivertebral foramen in patients with osteoporosis and Kummell's disease by CT; to infer whether the specific morphological characteristics of basivertebral foramen may be one of the risk factors of Kummell's disease; to provide clinical suggestions for the treatment of Kummell's disease. DESIGN: Retrospective analysis from January 2020 to December 2021 on 83 patients with 83 vertebral bodies (T8-L5) diagnosed with senile osteoporosis and Kummell's disease hospitalized in our hospital due to chronic low back pain, including 57 women and 23 men. Group A was assigned for the following patients: the age ranged from 59 to 86 years old, with the average age of 67.30 ± 7.32 years old; the body mass index ranged from 20.01 to 29.46 kg/m2, with the average body mass index of 23.51 ± 3.03 kg/m2.Group B was assigned for the following patients: 83 patients diagnosed with senile osteoporosis in our outpatient department from January 2020 to December 2021, including 41 males and 42 females; the age ranged from 60 to 85 years, with an average age of 68.52 ± 4.68 years old; the height to weight ratio met the normal reference standard (except 20% above or 10% below the standard weight). Through the lanwon PACS imaging system, the related parameters of the vertebrobasilar foramen in patients with osteoporosis and Kummell's disease were measured to evaluate and analyze the correlation between the morphological characteristics of the vertebrobasilar foramen in patients with osteoporosis and Kummell's disease. RESULTS: In patients with osteoporosis, the distribution of incidence rate of Kummell's disease in the spine was consistent with that of osteoporotic compression fractures. Sagittal view of the vertebral body on CT scan and the triangular-shaped, trapezoidal-shaped, and irregular-shaped basivertebral foramen in group A accounted for 18%,57%,and 36%,respectively. In group B, triangular-shaped, trapezoidal-shaped, and irregular-shaped foramen accounted for 51%,17%,and 26%,respectively.The distribution of triangular-shaped, trapezoidal-shaped, and irregular-shaped foramen was compared between groups A and B, and the difference was recorded as statistically significant (P < 0.05). Additionally, the difference in the distribution of triangular-shaped, trapezoidal-shaped, and irregular-shaped foramen in group A was found statistically significant (P < 0.05),while that of Group B was found statistically insignificant (P > 0.05).On a horizontal CT scan of the vertebra of group A, triangles, trapezoids, and irregularities accounted for 28%, 26%, and 47%, respectively. In group B, triangles,trapezoids,and irregularities accounted for 31%, 37%, and 30%, respectively. The difference in the distribution of the triangular-shaped and trapezoidal-shaped foramen in groups A and B was statistically insignificant (P > 0.05), while that of irregular-shaped was statistically significant (P < 0.05). Additionally, there was no statistical significance (P > 0.05) in the difference in the morphological distribution of triangular-shaped and trapezoidal-shaped foramen in group A, while that of irregular-shaped was found to be statistically significant (P < 0.05). Further, the difference in the morphological distribution of triangular-shaped, trapezoidal-shaped, and irregular-shaped foramen in group B was not statistically significant (P > 0.05).In general, about 8% of the vertebral body of BF has an osseous septum. In group A, 97% are single-holed while the remaining 3% are porous; in group B, those with single holes accounted for 76%, while the remaining 24% are porous. In groups A and B, the difference in the morphological distribution of single-holed and multi-holed T8, T11, T12, L1, L2, L4, and L5 vertebral bodies was statistically significant (P < 0.05). In group A, the difference in the distribution of single-holed and multi-holed L1 and L5 vertebral bodies was statistically significant (P < 0.05). Similarly, the difference in the distribution of single-holed and multi-holed T8, T11, T12, L1, L2, and L4 basivertebral foramen was statistically significant (P < 0.05). CONCLUSIONS: In patients with osteoporosis, the incidence of vertebral Kummell's disease can be associated with the morphological characteristics of the basivertebral foramen, as observed in the CT scan. Furthermore, the vertebral body with trapezoidal-shaped and irregular-shaped basivertebral foramen and boneless septum in the foramen is highly susceptible to Kummell's disease.

Turnaround time and efficiency of pediatric outpatient brain magnetic resonance imaging: a multi-institutional cross-sectional study.

BACKGROUND: Aside from single-center reports, few data exist across pediatric institutions that examine overall MRI turnaround time (TAT) and the determinants of variability. OBJECTIVE: To determine average duration and determinants of a brain MRI examination at academic pediatric institutions and compare the duration to those used in practice expense relative value units (RVUs). MATERIALS AND METHODS: This multi-institutional cross-sectional investigation comprised four academic pediatric hospitals. We included children ages 0 to < 18 years who underwent an outpatient MRI of the brain without contrast agent in 2019. Our outcome of interest was the overall MRI TAT derived by time stamps. We estimated determinants of overall TAT using an adjusted log-transformed multivariable linear regression model with robust standard errors. RESULTS: The average overall TAT significantly varied among the four hospitals. A sedated brain MRI ranged from 158 min to 224 min, a non-sedated MRI from 70 min to 112 min, and a limited MRI from 44 min to 70 min. The most significant predictor of a longer overall TAT was having a sedated MRI (coefficient = 0.71, 95% confidence interval [CI]: 0.66-0.75; P < 0.001). The median MRI scan time for a non-sedated exam was 38 min and for a sedated exam, 37 min, approximately double the duration used by the Relative Value Scale (RVS) Update Committee (RUC). CONCLUSION: We found considerable differences in the overall TAT across four pediatric academic institutions. Overall, the significant predictors of turnaround times were hospital site and MRI pathway (non-sedated versus sedated versus limited MRI).

Shared decision making for anticoagulation reduces anxiety and improves adherence in patients with atrial fibrillation.

BACKGROUND: Treatment with oral anticoagulants (OACs) could prevent stroke in atrial fibrillation (AF), but side effects developed due to OACs may cause patients anxiety during decision making. This study aimed to investigate whether shared decision making (SDM) reduces anxiety and improves adherence to stroke prevention measures in patients with AF. METHODS: A one-group pretest-posttest design using a questionnaire survey was applied at the outpatient cardiology clinic between July 2019 until September 2020. A Patient Decision Aid (PDA) tool was used for the completion of the questionnaire survey after health education and counseling. Ten questions were included for patients' recognition of SDM, and a 5-point scoring method was used, where "very much" was scored as 5 points, and "totally not" was scored as 1 point. RESULTS: Fifty-two patients with AF were enrolled. In terms of patients' recognition of SDM, points of more than 4.17 out of 5 were noted, indicating recognition above the level of "very much." The patients' anxiety scores before SDM were 3.56 (1.2), with a decrease of 0.64 points (p < 0.001) to 2.92 (1.3) after SDM. After SDM, the number of patients who decided to take OAC increased from 76.9% to 88.5%, and the 15.4% answering "unclear" decreased to 1.9% (p = 0.006). The patients' anxiety levels after SDM were associated with gender (p = 0.025). CONCLUSIONS: The approach using SDM enhanced our understanding of the pros and cons of OAC treatment and, in patients with AF, decreased anxiety about therapeutic decisions and increased willingness to accept treatment options.

Sesamin suppresses angiotensin-II-enhanced oxidative stress and hypertrophic markers in H9c2 cells.

Myocardial hypertrophy plays a crucial role in cardiovascular disease (CVD) development. Myocardial hypertrophy is an adaptive response by myocardial cells to stress after cardiac injury to maintain cardiac output and function. Angiotensin II (Ang-II) regulates CVD through the renin-angiotensin-aldosterone system, and its signaling in cardiac myocytes leads to excessive reactive oxygen species (ROS) production, oxidative stress, and inflammation. Sesamin (SA), a natural compound in sesame seeds, has anti-inflammatory and anti-apoptotic effects. This study investigated whether SA could attenuate hypertrophic damage and oxidative injuries in H9c2 cells under Ang-II stimulation. We found that SA decreased the cell surface area. Furthermore, Ang-II treatment reduced Ang-II-increased ANP, BNP, and ß-MHC expression. Ang-II enhanced NADPH oxidase activity, ROS formation, and decreased Superoxide Dismutase (SOD) activity. SA treatment reduces Ang-II-caused oxidative injuries. We also found that SA mitigates Ang-II-induced apoptosis and pro-inflammatory responses. In conclusion, SA could attenuate Ang-II-induced cardiac hypertrophic injuries by inhibiting oxidative stress, apoptosis, and inflammation in H9c2 cells. Therefore, SA might be a potential supplement for CVD management.