Search

Glaucoma is the leading cause of irreversible blindness and is characterized by slow and progressive degeneration of the optic nerve head axons and retinal ganglion cell (RGC), leading to loss of visual function. Although oxidative stress and/or alteration of mitochondrial (mt) dynamics induced by elevated intraocular pressure (IOP) are associated with this neurodegenerative disease, the mechanisms that regulate mt dysfunction-mediated glaucomatous neurodegeneration are poorly understood. Using a mouse model of glaucoma, DBA/2J (D2), which spontaneously develops elevated IOP, as well as an in vitro RGC culture system, we show here that oxidative stress, as evidenced by increasing superoxide dismutase 2 (SOD2) and mt transcription factor A (Tfam) protein expression, triggers mt fission and loss by increasing dynamin-related protein 1 (DRP1) in the retina of glaucomatous D2 mice as well as in cultured RGCs exposed to elevated hydrostatic pressure in vitro. DRP1 inhibition by overexpressing DRP1 K38A mutant blocks mt fission and triggers a subsequent reduction of oxidative stress, as evidenced by decreasing SOD2 and Tfam protein expression. DRP1 inhibition promotes RGC survival by increasing phosphorylation of Bad at serine 112 in the retina and preserves RGC axons by maintaining mt integrity in the glial lamina of glaucomatous D2 mice. These findings demonstrate an important vicious cycle involved in glaucomatous neurodegeneration that starts with elevated IOP producing oxidative stress; the oxidative stress then leads to mt fission and a specific form of mt dysfunction that generates further oxidative stress, thus perpetuating the cycle. Our findings suggest that DRP1 is a potential therapeutic target for ameliorating oxidative stress-mediated mt fission and dysfunction in RGC and its axons during glaucomatous neurodegeneration. Thus, DRP1 inhibition may provide a new therapeutic strategy for protecting both RGCs and their axons in glaucoma and other optic neuropathies.

Cyclosporin A (CsA) inhibits the opening of the mitochondrial permeability transition pore (MPTP) by interacting with cyclophilin D (CypD) and ameliorates neuronal cell death in the central nervous system against ischemic injury. However, the molecular mechanisms underlying CypD/MPTP opening-mediated cell death in ischemic retinal injury induced by acute intraocular pressure (IOP) elevation remain unknown. We observed the first direct evidence that acute IOP elevation significantly upregulated CypD protein expression in ischemic retina at 12 h. However, CsA prevented the upregulation of CypD protein expression and promoted retinal ganglion cell (RGC) survival against ischemic injury. Moreover, CsA blocked apoptotic cell death by decreasing cleaved caspase-3 protein expression in ischemic retina. Of interest, although the expression level of Bcl-xL protein did not show a significant change in ischemic retina treated with vehicle or CsA at 12 h, ischemic damage induced the reduction of Bcl-xL immunoreactivity in RGCs. More importantly, CsA preserved Bcl-xL immunoreactivity in RGCs of ischemic retina. In parallel, acute IOP elevation significantly increased phosphorylated Bad (pBad) at Ser112 protein expression in ischemic retina at 12 h. However, CsA significantly preserved pBad protein expression in ischemic retina. Finally, acute IOP elevation significantly increased mitochondrial transcription factor A (Tfam) protein expression in ischemic retina at 12 h. However, CsA significantly preserved Tfam protein expression in ischemic retina. Studies on mitochondrial DNA (mtDNA) content in ischemic retina showed that there were no statistically significant differences in mtDNA content among control and ischemic groups treated with vehicle or CsA. Therefore, these results provide evidence that the activation of CypD-mediated MPTP opening is associated with the apoptotic pathway and the mitochondrial alteration in RGC death of ischemic retinal injury. On the basis of these observations, our findings suggest that CsA-mediated CypD inhibition may provide a promising therapeutic potential for protecting RGCs against ischemic injury-mediated mitochondrial dysfunction.

Oxidative stress contributes to dysfunction of glial cells in the optic nerve head (ONH). However, the biological basis of the precise functional role of mitochondria in this dysfunction is not fully understood. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain and a potent antioxidant, acts by scavenging reactive oxygen species (ROS) for protecting neuronal cells against oxidative stress in many neurodegenerative diseases. Here, we tested whether hydrogen peroxide (100 μM H2O2)-induced oxidative stress alters the mitochondrial network, oxidative phosphorylation (OXPHOS) complex (Cx) expression and bioenergetics, as well as whether CoQ10 can ameliorate oxidative stress-mediated alterations in mitochondria of the ONH astrocytes in vitro. Oxidative stress triggered the activation of ONH astrocytes and the upregulation of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) protein expression in the ONH astrocytes. In contrast, CoQ10 not only prevented activation of ONH astrocytes but also significantly decreased SOD2 and HO-1 protein expression in the ONH astrocytes against oxidative stress. Further, CoQ10 prevented a significant loss of mitochondrial mass by increasing mitochondrial number and volume density and by preserving mitochondrial cristae structure, as well as promoted mitofilin and peroxisome-proliferator-activated receptor-γ coactivator-1 protein expression in the ONH astrocyte, suggesting an induction of mitochondrial biogenesis. Finally, oxidative stress triggered the upregulation of OXPHOS Cx protein expression, as well as reduction of cellular adeonsine triphosphate (ATP) production and increase of ROS generation in the ONH astocytes. However, CoQ10 preserved OXPHOS protein expression and cellular ATP production, as well as decreased ROS generation in the ONH astrocytes. On the basis of these observations, we suggest that oxidative stress-mediated mitochondrial dysfunction or alteration may be an important pathophysiological mechanism in the dysfunction of ONH astrocytes. CoQ10 may provide new therapeutic potentials and strategies for protecting ONH astrocytes against oxidative stress-mediated mitochondrial dysfunction or alteration in glaucoma and other optic neuropathies.

Studies examining geographic variation in care for low back pain often focus on process and outcome measures conditional on patient diagnosis but generally do not take into account a physician’s ability to diagnose the root cause of low back pain. In our case study, we used increased detection of ankylosing spondylitis—a relatively rare inflammatory back disease—as a proxy for diagnostic ability and measured the relationship between ankylosing spondylitis detection, potentially inappropriate low back pain care, and cost. Using 5 years of health insurance claims data, we found significant variation in ankylosing spondylitis detection across metropolitan statistical areas (MSAs), with 8.1% of the variation in detection explained by a region’s racial composition. Furthermore, low back pain patients in MSAs with higher ankylosing spondylitis detection had 7.9% lower use of corticosteroids, 9.0% lower use of opioids, and 8.2% lower pharmacy cost, compared with patients living in low-detection MSAs.

Objectives: To synthesize a 3D printing resin with antibacterial and long-term fluoride-releasing properties., Methods: (4,4-Bis-4-[2‑hydroxy-3-(2-methacryloyloxy)propoxy]-phenyl-pentanol-amine)-N,N-diacetic acid zirconium (IV) fluoride complex was synthesized from 4,4-bis-(4-hydroxyphenyl)-pentanoic acid and monitored using proton nuclear magnetic resonance spectroscopy. The synthesized complex was incorporated into a urethane-acrylate-based (UA) resin at 5 wt% and 10 wt% (5F-UA and 10F-UA groups, respectively). The UA resin without the synthesized complex was considered as the control group. All groups were 3D printed using a DLP printer, followed by 10 min of washing and 20 min of curing. Surface characteristics were observed using scanning electron microscopy. The mechanical properties were assessed by measuring its flexural strength and Vickers hardness. The antibacterial property was investigated with direct and indirect contact tests and a WST-8 metabolic activity assay. The suspension was fully mixed and diluted for counting the number of colony-forming units. The cell viability test was performed using a cell proliferation assay. The amount of fluoride released was measured daily for 28 days using ion chromatography. One-way analysis of variance was performed for statistical analyses using SPSS software., Results: The amount of fluoride released increased with the concentration of fluoride complex in the resin. The fluoride ions were constantly released at a low concentration from the 3D printed specimens (5F-UA: around 0.13 ppm daily; 10F-UA: around 0.22 ppm daily). The antibacterial efficacy was acceptable in both the 5F-UA and 10F-UA groups, and higher in the latter. No cytotoxicity of the resin was detected. The mechanical properties were significantly influenced by the addition of the fluoride-releasing complex., Conclusions: The present 3D printing UA resin incorporating a fluoride complex effectively inhibited the growth of S. mutans and demonstrated the ability to slowly release fluoride over an extended period of time., Clinical Significance: This study provided informative composition of a fluoride-releasing UA-based 3D printing resin, ideal for dental applications such as crowns, bridges, removable partial dentures, and orthodontic appliances, which can benefit from sustained fluoride release and antimicrobial properties. Further modifications to the resin composition can be easily achieved to enhance the resin qualities., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. All coauthors have seen and agree with the contents of the manuscript, and there is no financial interest to report. We certify that the submission is original work and is not under review by any other publication., (Copyright © 2024. Published by Elsevier Ltd.)

To maximize therapeutic effects and minimize unwanted effects, the interest in drug targeting to the endoplasmic reticulum (ER) or Golgi apparatus (GA) has been recently growing because two organelles are distributing hubs of cellular building/signaling components (e.g., proteins, lipids, Ca 2+ ) to other organelles and the plasma membrane. Their structural or functional damages induce organelle stress (i.e., ER or GA stress), and their aggravation is strongly related to diseases (e.g., cancers, liver diseases, brain diseases). Many efforts have been developed to image (patho)physiological functions (e.g., oxidative stress, protein/lipid-related processing) and characteristics (e.g., pH, temperature, biothiols, reactive oxygen species) in the target organelles and to deliver drugs for organelle disruption using organelle-targeting moieties. Therefore, this review will overview the structure, (patho)physiological functions/characteristics, and related diseases of the organelles of interest. Future direction on ER or GA targeting will be discussed by understanding current strategies and investigations on targeting, imaging/sensing, and therapeutic systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The role of shear stress in regulating aqueous humor (AH) outflow and intraocular pressure (IOP) in the trabecular meshwork (TM) and Schlemm's canal (SC) of the eye is an emerging field. Shear stress has been shown to activate mechanosensitive ion channels in TM cells and induce nitric oxide production in SC cells, which can affect outflow resistance and lower IOP. Live-cell imaging using fluorescent protein sensors has provided real-time data to investigate the physiological relationship between fluid flow and shear stress in the outflow pathway cells. The successful application of time-lapse live-cell imaging in primary cultured cells has led to the identification of key cellular and molecular mechanisms involved in regulating AH outflow and IOP, including the role of autophagy and primary cilia as mechanosensors. This chapter presents a detailed protocol for conducting time-lapse live-cell imaging under fluid flow conditions in the outflow pathway cells., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Accurate intraoperative identification of normal parathyroid glands (PTGs) is vital to avoid hypocalcemia post total thyroidectomy. Although ultrasonography (US) has been shown to identify normal PTGs, the significance of preoperative US PTG mapping in this context is not well studied. This study evaluated the impact of preoperative US PTG mapping on intraoperative identification of normal PTGs during total thyroidectomy., Methods: The study involved 161 consecutive patients who underwent total thyroidectomy between January 2020 and June 2022. These included patients without preoperative US PTG mapping (group 1, n = 91) and those with the mapping (group 2, n = 70). Propensity score matching yielded 61 matched patients from each group. We developed a preoperative US PTG mapping technique combining US identification of normal PTGs with their localization on thyroid CT images. The intraoperative detectability of normal PTGs during thyroid surgery and detectability of normal PTGs by the preoperative US mapping were assessed by the number of PTGs identified per patient and by location., Results: In the matched cohort, group 2 demonstrated a higher median number of identified PTGs (3 vs. 2, p = 0.011), a greater proportion of patients with three or more identified PTGs (65.5% vs. 44.3%, p = 0.018), and a higher ratio of identified to expected PTGs (70.5% vs. 60.2%, p = 0.011) than group 1. In group 2, the median number of normal PTGs identified preoperatively was 3, with at least one identified in 95.7% of patients, two or more in 84.3%, three or more in 52.9%, and four or five in 24.3%., Conclusions: Preoperative US PTG mapping identified two or more normal PTGs in the majority of adult patients undergoing total thyroidectomy. Those with preoperative mapping showed a higher number of intraoperatively identified normal PTGs, including inferior PTGs, compared to those without. This technique appears to enhance the intraoperative identification of normal PTGs, thereby potentially improving surgical outcomes in total thyroidectomy., (© 2024 Wiley Periodicals LLC.)

Introduction: Delirium in neonates and infants is difficult to screen or assess because of their different developmental features and distinct delirium characteristics compared with those of older children. Some delirium management strategies, including assessment, pharmacological and non-pharmacological interventions, and prevention strategies, have been previously suggested for paediatric delirium. However, whether these strategies are effective for delirium in neonates and infants is unclear. This scoping review aims to explore comprehensive information on delirium in neonates and infants, such as the features of delirium, factors related to delirium, and current assessments and interventions in neonates and infants., Methods and Analysis: This study will be based on the Joanna Briggs Institute guidelines for scoping review protocol development and follow each stage of the framework proposed by Arksey and O'Malley. Research questions regarding delirium management in neonates and infants will be specified. A wide range of databases, including MEDLINE, EBSCO, Embase and the Cochrane Library, using optimised terms will be searched from 2004 to 2024. The summarised results will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension of the Scoping Reviews checklist., Ethics and Dissemination: Since this study will review and summarise published scientific literature, ethical approval is not required. The results of this scoping review will be disseminated through conference presentations and peer-reviewed publications. The study findings will be disseminated through seminars for experts so that they can be reflected in practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Nanoparticle (NP)-based drug delivery systems are conceived to solve poor water-solubility and chemical/physical instability, and their purpose expanded to target specific sites for maximizing therapeutic effects and minimizing unwanted events of payloads. Targeted sites are also narrowed from organs/tissues and cells to cytosol/organelles. Beyond specific site targeting, the particular release of payloads at the target sites is growing in importance. This review overviews various issues and their general strategies during multiple steps, from the preparation of drug-loaded NPs to their drug release at the target cytosol/organelles. In particular, this review focuses on current strategies for "first" delivery and "later" release of drugs to the cytosol or organelles of interest using specific stimuli in the target sites. Recognizing or distinguishing the presence/absence of stimuli or their differences in concentration/level/activity in one place from those in another is applied to stimuli-triggered release via bond cleavage or nanostructural transition. In addition, future directions on understanding the intracellular balance of stimuli and their counter-stimuli are demonstrated to synergize the therapeutic effects of payloads released from stimuli-sensitive NPs., (© 2024 The Authors. Macromolecular Bioscience published by Wiley‐VCH GmbH.)

Background: The internal mammary artery (IMA) is the most commonly used graft in coronary artery bypass grafting (CABG) because of its superior long-term patency rate. However, its small diameter poses challenges in handling, and any vascular damage that may occur during harvesting can significantly affect surgical outcomes. The primary focus during IMA harvesting is to ensure safe and effective hemostasis without direct vascular injury, while ensuring secure and reliable ligation of the vascular branches. Various methods using multiple surgical instruments have been used for this purpose. Unlike traditional instruments, the shear-tip Harmonic scalpel offers more precise vessel branching control, while minimizing damage to surrounding tissues. In this study, we assessed the utility of the shear-tip Harmonic scalpel in patients undergoing minimally invasive coronary artery bypass grafting (MICABG)., Methods: From April 2019 to May 2023, a total of 40 patients underwent MICABG. The IMA was harvested using the shear-tip Harmonic scalpel with a clipless skeletonized technique. In this cohort, 5 patients underwent complete endoscopic harvesting, while 34 patients underwent direct visualization harvesting through minimal thoracotomy. Graft patency was assessed by measuring a Doppler flowmeter in the bypass conduit., Results: Successful graft patency was achieved in all patients. The mean duration of IMA harvesting was 87 min. In total, 38 of the 40 patients underwent MICABG without the need for cardiopulmonary bypass, ensuring a stable procedure. There were no graft-related events or complications observed in any of the patients, and all were discharged without any issues. During a median follow-up period of 15.2 months, only one patient experienced graft occlusion necessitating intervention., Conclusions: The utilization of shear-tip Harmonic scalpel for IMA harvesting in MICABG is feasible and yields stable early results., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1810/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Various strategies at the microscale/nanoscale have been developed to improve oral absorption of therapeutics. Among them, gastrointestinal (GI)-transporter/receptor-mediated nanosized drug delivery systems (NDDSs) have drawn attention due to their many benefits, such as improved water solubility, improved chemical/physical stability, improved oral absorption, and improved targetability of their payloads. Their therapeutic potential in disease animal models ( e.g. , solid tumors, virus-infected lungs, metastasis, diabetes, and so on) has been investigated, and could be expanded to disease targeting after systemic/lymphatic circulation, although the detailed paths and mechanisms of endocytosis, endosomal escape, intracellular trafficking, and exocytosis through the epithelial cell lining in the GI tract are still unclear. Thus, this review summarizes and discusses potential GI transporters/receptors, their absorption and distribution, in vivo studies, and potential sequential targeting ( e.g. , oral absorption and disease targeting in organs/tissues).

This study investigated health-related quality of life and identified factors affecting it among people with the HIV in South Korea. A total of 243 people living with HIV participated in this cross-sectional survey. Data were collected from five hospitals between November 2021 and August 2022 using structured online questionnaires. Data were analyzed using descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test, Spearman's rho analysis, and Tobit regression analysis because a significant ceiling effect was observed for the dependent variable. The mean score for the health-related quality of life was 75.74 ± 16.48. The significant factors that positively influence the health-related quality of life were "employment" (B = 4.57, p = .035), "not participating in the self-help group" (B = 6.10, p = .004), "higher self-efficacy for managing symptoms" (B = 1.32, p = .036), "higher self-efficacy for getting support/help" (B = 0.95, p = .035), and "higher self-efficacy for managing fatigue" (B = 2.80, p < .001) in the Tobit regression analysis. The results suggest that interventions to increase self-efficacy should involve developing programs and policies for people living with HIV. There is a need for efforts to provide healthcare services linked to employment support, as well as to establish a social environment in which they can work without stigma. Further, self-help groups could be utilized as intervention channels., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by the disruption of the intestinal barrier. The intestinal barrier is maintained by tight junctions (TJs), which sustain intestinal homeostasis and prevent pathogens from entering the microbiome and mucosal tissues. Ziziphus jujuba Miller ( Z. jujuba ) is a natural substance that has been used in traditional medicine as a therapy for a variety of diseases. However, in IBD, the efficacy of Z. jujuba is unknown. Therefore, we evaluated ZJB in Caco2 cells and a dextran sodium sulfate (DSS)-induced mouse model to demonstrate its efficacy in IBD. Z. jujuba extracts were prepared using 70% ethanol and were named ZJB. ZJB was found to be non-cytotoxic and to have excellent antioxidant effects. We confirmed its anti-inflammatory properties via the down-regulation of inflammatory factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). To evaluate the effects of ZJB on intestinal barrier function and TJ improvement, the trans-epithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran 4 kDa (FITC-Dextran 4) permeability were assessed. The TEER value increased by 61.389% and permeability decreased by 27.348% in the 200 μg/mL ZJB group compared with the 50 ng/mL IL-6 group after 24 h. Additionally, ZJB alleviated body weight loss, reduced the disease activity index (DAI) score, and induced colon shortening in 5% DSS-induced mice; inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were down-regulated in the serum. TJ proteins, such as Zonula occludens (ZO)-1 and occludin, were up-regulated by ZJB in an impaired Caco2 mouse model. Additionally, according to the liquid chromatography results, in tandem with mass spectrometry (LC-MS/MS) analysis, seven active ingredients were detected in ZJB. In conclusion, ZJB down-regulated inflammatory factors, protected intestinal barrier function, and increased TJ proteins. It is thus a safe, natural substance with the potential to be used as a therapeutic agent in IBD treatment.

Background: Although guidelines and protocols are available for central venous access, existing methods lack specificity and sensitivity, especially when placing peripherally inserted central catheters (PICCs). We evaluated the feasibility of catheter detection in the right atrial cavity using transthoracic echocardiography (TTE) during PICC placement., Methods: This single-center, retrospective study included consecutive patients who underwent PICC placement between January 2022 and March 2023. TTE was performed to detect the arrival of the catheter in the right atrial cavity. Catheter misplacement was defined as an aberrant catheter position on chest x-ray (CXR). The primary endpoint was predicting catheter misplacement based on catheter detection in the right atrial cavity. The secondary endpoint was optimizing catheter placement and examining catheter-associated complications., Results: Of the 110 patients identified, 10 were excluded because of poor echogenicity and vein access failure. The remaining 100 patients underwent PICC placement with TTE. The catheter was visualized in the right atrial cavity in 90 patients. CXR exams revealed catheter misplacement in seven cases. Eight patients with catheter misplacement underwent the same procedure in the other arm. In two patients, PICC placement failed due to anatomical reasons. Catheter misplacement was detected using TTE with sensitivity, specificity, positive predictive value, and negative predictive value of 97% confidence interval (CI; 91.31%-99.36%), 90% CI (55.50%-99.75%), 99%, and 75%, respectively., Conclusions: TTE is a reliable tool for detecting catheter misplacement and optimizing catheter tip positioning during PICC placement.

Objective: Employing three cycles of Design Science Research (DSR) to develop a mobile app 'ESSC (Excellent Self Supervised HIV Care)' to improve self-management among people living with HIV (PLWH)., Methods: This study is based on the DSR framework comprising three iterative cycles. In the Relevance cycle, PLWH participated in a survey of mobile health (mHealth) experiences and needs. In the Rigor cycle, the information-motivation-behavioural skills (IMB) model was applied to foundations of the app, and HIV specialists verified the contents. Experts evaluated the heuristic system and the app quality with the Mobile Application Rating Scale (MARS). In the Design cycle, ESSC was built on the findings of the other two cycles, and end-users tested the usability using uMARS., Results: The contents of the app were developed based on user requirements. The IMB model led ESSC to supplement motivational components for self-management, which built five functions: information contents; health life records including mental and sexual health; interactive counselling with healthcare providers; setting health goals after watching videos; and my page for self-reflection. To reduce social stigma and promote acceptance of the information-driven app, we created animated characters with neutral and bright features. The HIV specialists evaluated content validity as highly appropriate. The MARS score by the overall raters was between 3- acceptable and 4- good : functionality, 4.38; information, 4.12; aesthetics, 3.96; engagement, 3.37; and subjective quality, 3.25., Conclusions: The DSR approach is effective for implementing usable and useful mHealth. The ESSC app would be feasible and contribute PLWH to retention in care., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Adolescents are particularly vulnerable to smartphone overdependence. Therefore, we identified the factors influencing smartphone overdependence and risk subgroups among adolescents. The current study is a secondary analysis of nationally representative data from the 2020 Korea Youth Risk Behavior Survey. The survey targeted middle- and high-school students in South Korea aged 12-18 using stratified, clustered, multistage probability sampling, and 53,457 students from 793 schools participated in this study. Complex sample data were analyzed considering the strata, clusters, and weights. Multiple logistic regression analysis revealed age, gender, household economic status, anxiety, loneliness, depressive symptoms, and experience of violent treatment as significant predictors of smartphone overdependence. Adolescents with severe anxiety were at a 3.326 times higher risk of smartphone overdependence than adolescents with minimal anxiety. Decision tree analysis showed that anxiety, gender, loneliness, and depressive symptoms were important in differentiating risk subgroups, with anxiety being the most significant factor. Group 13, comprising girls with severe anxiety, had the highest risk at 52.9%. Thus, early detection and prevention of issues such as anxiety, loneliness, and depressive symptoms, as well as treatment for violence, can prevent smartphone overdependence among adolescents. Additionally, more thorough interventions for anxiety are warranted to prevent smartphone overdependence., (© 2024. The Author(s).)

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.

Aim: To employ network analysis to identify the central healthcare service needs of people living with HIV (PLWH) for integrated care., Design: Cross-sectional survey., Methods: A list of healthcare services was identified through literature reviews, expert workshops and validity evaluations by PLWH. A total of 243 PLWH participated at five hospitals and self-reported their need for healthcare services on a four-point Likert scale. Centrality of healthcare service needs was analysed using network analysis., Results: The mean score for 20 healthcare service needs was 3.53 out of 4. The highest scoring need, "Precaution for interaction between antiretroviral therapy and other drugs," received a rating of 3.73 but had a centrality of only 0.31. The most central node in the network of healthcare service needs, "Information and coping with opportunistic infections," had a strength centrality of 1.63 and showed significant relationships with "non-HIV-related medical services (e.g., health check-ups)" and "Regular dental services." The correlation stability coefficient, which quantifies the stability of centrality, was 0.44 with an acceptable value., Conclusions: The most central need was information on opportunistic infections that had connections with many nodes in network analysis. By interpreting the relationships between needs, healthcare providers can design interventions with an integrative perspective., Implications for Patient Care: Network visualization provides dynamic relationships between needs that are unknown from the score scale by presenting them graphically and qualitatively., Impact: Using network analysis to interpret need assessment offers an integrated nursing perspective. Coping with opportunistic infection is central to connecting the chain of healthcare. This study highlights the multifaceted understanding of patients' needs that nurses gain when they conduct network analysis., Reporting Method: We adhered to the STROBE checklist., Patient or Public Contribution: No patient or public contribution., (© 2024 John Wiley & Sons Ltd.)

Purpose: Several technical aspects of the Fick method limit its use intraoperatively. A data-driven modification of the Fick method may enable its use in intraoperative settings., Methods: This two-center retrospective observational study included 57 (28 and 29 in each center) patients who underwent off-pump coronary artery bypass graft (OPCAB) surgery. Intraoperative recordings of physiological data were obtained and divided into training and test datasets. The Fick equation was used to calculate cardiac output (CO-Fick) using ventilator-determined variables, intraoperative hemoglobin level, and SvO 2 , with continuous thermodilution cardiac output (CCO) used as a reference. A modification CO-Fick was derived and validated: CO-Fick-AD, which adjusts the denominator of the original equation., Results: Increased deviation between CO-Fick and CCO was observed when oxygen extraction was low. The root mean square error of CO-Fick was decreased from 6.07 L/min to 0.70 L/min after the modification. CO-Fick-AD showed a mean bias of 0.17 (95% CI 0.00-0.34) L/min, with a 36.4% (95% CI 30.6-44.4%) error. The concordance rates of CO-Fick-AD ranged from 73.3 to 87.1% depending on the time interval and exclusion zone., Conclusions: The original Fick method is not reliable when oxygen extraction is low, but a modification using data-driven approach could enable continuous estimation of cardiac output during the dynamic intraoperative period with minimal bias. However, further improvements in precision and trending ability are needed., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Although previous studies have shown correlation between regional cerebral oxygen saturation (rScO 2 ) and mixed venous oxygen saturation (SvO 2 ), there is a lack of pragmatic information on the clinical applicability of these findings, such as tracking ability. We retrospectively analyzed continuous intraoperative recordings of rScO 2 and SvO 2 obtained from a pulmonary artery catheter and either of two near-infrared spectroscopy (NIRS) devices (INVOS 5100C, Medtronic; O3, Masimo) during off-pump cardiopulmonary bypass (OPCAB) surgery in adult patients. The ability of rScO 2 to track SvO 2 was quantitatively evaluated with 5 min interval changes transformed into relative values. The analysis included 176 h of data acquired from 48 subjects (26 and 22 subjects for INVOS and O3 dataset, respectively). The area under ROC of the left-rScO 2 for detecting change of SvO 2  ≥ 10% in INVOS and O3 datasets were 0.919 (95% CI 0.903-0.936) and 0.852 (95% CI 0.818-0.885). The concordance rates between the interval changes of left-rScO 2 and SvO 2 in INVOS and O3 datasets were 90.6% and 91.9% with 10% exclusion zone. rScO 2 can serve as a noninvasive tool for detecting changes in SvO 2 levels, a critical hemodynamic measurement., (© 2023. The Author(s).)

Objectives: This study investigated the reciprocal longitudinal relationships between physical frailty (PF), cognitive function (CF), and falls among community-dwelling older adults, according to sex. The study proposed hypotheses that present PF and CF will affect the occurrence of falls 2 years later., Design: Secondary data analysis using the first (T1, 2016-2017) and second (T2, 2018-2019) waves of the Korean Frailty and Aging Cohort Study (KFACS)., Setting and Participants: A total of 2318 community-dwelling older adults aged 70-84 years in South Korea; mean (SD) age: 75.72 (3.83) years; 47.7% men., Methods: PF and CF were measured with the modified version of the Fried Frailty Phenotype and the Korean version of the Mini-Mental State Examination, respectively. The number of falls were assessed. Multigroup cross-lagged panel analysis was used., Results: The results showed that relationships between PF, CF, and falls were maintained over time through an autoregressive effect. PF at T1 had a statistically significant longitudinal relationship with fall experience at T2 [standardized regression coefficient (β) = 0.087, 95% CI 0.045-0.129; P < .001], and fall experience at T1 had a significant longitudinal relationship with PF at T2 (β = 0.041, 95% CI 0.006-0.076; P = .020). There was no statistically significant relationship between CF and fall experience. PF and CF had statistically significant reciprocal longitudinal relationships (all P < .001). Based on sex, there was a statistically significant longitudinal relationship between fall experience at T1 and PF at T2 for men only (β = 0.063, 95% CI 0.012-0.114; P = .015)., Conclusions and Implications: Findings highlight that health care providers should plan fall prevention programs through early intervention for PF improvement along with improvement and maintenance of CF. Specifically, even if older men are currently healthy and have a low risk of falls, it is important to prevent future fatal PF through prior interventions, such as risk activities attention and concerns about falls., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Nanocarrier-assisted sonodynamic therapy (SDT) has shown great potential for the effective and targeted treatment of deep-seated tumors by overcoming the critical limitations of sonosensitizers. However, in vivo SDT using nanocarriers is still constrained by their intrinsic toxicity and nonspecific cargo release. In this study, we developed bioreducible exosomes for the safe and tumor-specific delivery of mitochondria-targeting sonosensitizers [triphenylphosphonium-conjugated chlorin e6 (T-Ce6)] and glycolysis inhibitors (FX11). Redox-cleavable diselenide linker-bearing lipids were embedded into exosomes to trigger drug release in response to overexpressed glutathione in the tumor microenvironment. Bioreducible exosomes facilitate the cytoplasmic release of their payload in the reducing environment of tumor cells. They significantly enhance drug release and sonodynamic effects when irradiated with ultrasound (US). The mitochondria-targeted accumulation of T-Ce6 efficiently damaged the mitochondria of the cells under US irradiation, accelerating apoptotic cell death. FX11 substantially inhibited cellular energy metabolism, potentiating the antitumor efficacy of mitochondria-targeted SDT. Bioreducible exosomes effectively suppressed tumor growth in mice without significant systemic toxicity, via a combination of mitochondria-targeted SDT and energy metabolism-targeted therapy. This study offers new insights into the use of dual stimuli-responsive exosomes encapsulating sonosensitizers for safe and targeted sonodynamic cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Glioblastoma (GBM) is the most aggressive malignant brain tumor and has a high mortality rate. Photodynamic therapy (PDT) has emerged as a promising approach for the treatment of malignant brain tumors. However, the use of PDT for the treatment of GBM has been limited by its low blood‒brain barrier (BBB) permeability and lack of cancer-targeting ability. Herein, brain endothelial cell-derived extracellular vesicles (bEVs) were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB. To enhance PDT efficacy, the photosensitizer chlorin e6 (Ce6) was linked to mitochondria-targeting triphenylphosphonium (TPP) and entrapped into bEVs. TPP-conjugated Ce6 (TPP-Ce6) selectively accumulated in the mitochondria, which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation. Moreover, the encapsulation of TPP-Ce6 into bEVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6, leading to significantly enhanced PDT efficacy in U87MG GBM cells. An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that bEVs containing TPP-Ce6 [bEV(TPP-Ce6)] substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis. As such, bEV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity, suggesting that mitochondria are an effective target for photodynamic GBM therapy., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Glaucoma is a group of diseases that leads to chronic degeneration of retinal ganglion cell (RGC) axons and progressive loss of RGCs, resulting in vision loss. While aging and elevated intraocular pressure (IOP) have been identified as the main contributing factors to glaucoma, the molecular mechanisms and signaling pathways triggering RGC death and axonal degeneration are not fully understood. Previous studies in our laboratory found that overactivation of autophagy in DBA/2J::GFP-LC3 mice led to RGC death and optic nerve degeneration with glaucomatous IOP elevation. We found similar findings in aging GFP-LC3 mice subjected to chronic IOP elevation. Here, we further investigated the impact of autophagy deficiency on autophagy-deficient DBA/2J-Atg4b ko and DBA/2J-Atg4b +/- mice, generated in our laboratory via CRISPR/Cas9 technology; as well as in Atg4b ko mice subjected to the experimental TGFβ2 chronic ocular hypertensive model. Our data shows that, in contrast to DBA/2J and DBA/2J-Atg4b +/- littermates, DBA/2J-Atg4b ko mice do not develop glaucomatous IOP elevation. Atg4b deficiency also protected against glaucomatous IOP elevation in the experimental TGFβ2 chronic ocular hypertensive model. Atg4 deletion did not compromise RGC or optic nerve survival in Atg4b ko mice. Moreover, our results indicate a protective role of autophagy deficiency against RGC death and ON atrophy in the hypertensive DBA/2J-Atg4b +/- mice. Together, our data suggests a pathogenic role of autophagy activation in ocular hypertension and glaucoma., (© 2023. The Author(s).)

This review was performed to evaluate the effects of robot interventions on cognitive and psychological outcomes among older adults with cognitive impairment. Three databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) were searched for studies published in English between January 2015 and August 2021. We included studies that involved older adults with cognitive impairment, interventions using robots, outcome measures related to cognitive and psychological status, and randomized controlled trials. Ten studies included in the systematic review, and nine studies derived from these ten articles were included in the meta-analyses. The meta-analyses revealed that robot interventions significantly decreased anxiety and agitation but exerted no significant effects on cognitive function, neuropsychiatric symptoms, and quality of life. The subgroup analyses according to robot types revealed that pet-type robot interventions reduced anxiety and agitation. In addition, subgroup analysis according to the intervention format of robot interventions found that individual intervention was effective for improving agitation, but a group-based intervention was effective for improving depression. We suggest using robot interventions to improve psychological outcomes such as anxiety and agitation; however, further research is needed to determine whether robot interventions affect symptoms such as cognitive function, neuropsychiatric symptoms, and quality of life.

Cardiac angiosarcoma is a rare, malignant neoplasm affecting the heart. We present the clinical history of a 40-year-old patient diagnosed with metastatic angiosarcoma of the heart. The patient complained of shortness of breath, and a cardiac computed tomography scan revealed a mass in the right atrium and pericardial effusion. Transthoracic and transesophageal echocardiography provided detailed anatomical and functional information, and cardiac magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography/computed tomography were used to assess distant metastasis and characterize the mass in detail. Early differential diagnosis and comprehensive evaluation of a cardiac mass are vital for determining appropriate treatment strategies to improve patient outcomes. The pathological results from the endocardial biopsy confirmed the diagnosis of primary angiosarcoma. The patient underwent surgical resection of the right atrial mass but died within one month because of the locally advanced nature of the angiosarcoma and its rapid progression. The patient's medical journey sheds light on the challenges associated with diagnosing and treating this rare condition, particularly the rapid progression of its cardiac manifestations.

Aim: To understand how researchers applied the Tilburg Frailty Indicator (TFI) to older adults. The use of the TFI was examined based on the Integral Conceptual Model of Frailty (ICMF)., Design: A scoping review., Data Sources: A database search was conducted without a time limit in PubMed, CINAHL, Embase and the Cochrane library. A hand search was also conducted., Review Methods: Research questions were developed based on the population-concept-context framework suggested by the Joanna Briggs Institute (2017). Studies were included if topics were related to the use of the TFI or ICMF and designs were longitudinal studies., Results: A total of 37 studies met the inclusion criteria. Studies were reviewed according to the tested pathways of the ICMF: determinants of frailty or adverse outcomes, adverse outcomes of frailty and comparison of predictive power between frailty measures., Conclusion: The TFI is a useful tool to screen for frailty and predict health outcomes in older adults. Among the pathways of the ICMF, relationships between social factors and frailty were reported in several studies. Despite this relationship, social factors were considered as items to assess the social domain of frailty rather than determinants of frailty. The predictive power of the TFI was not superior to other frailty measures, but it had a high sensitivity., Impact: This study demonstrates the usability of the TFI in older adults living in various conditions. Further studies are required to identify more effective ways to screen frailty using the TFI., Patient or Public Contribution: No patient or public involvement in this study., (© 2023 John Wiley & Sons Ltd.)

Purpose: This study evaluated the validity and reliability of Shively and colleagues' self-efficacy for HIV disease management skills (HIV-SE) among Korean participants., Methods: The original HIV-SE questionnaire, comprising 34 items, was translated into Korean using a translation and back-translation process. To enhance clarity and eliminate redundancy, the author and expert committee engaged in multiple discussions and integrated two items with similar meanings into a single item. Further, four HIV nurse experts tested content validity. Survey data were collected from 227 individuals diagnosed with HIV from five Korean hospitals. Construct validity was verified through confirmatory factor analysis. Criterion validity was evaluated using Pearson's correlation coefficients with the new general self-efficacy scale. Internal consistency reliability and test-retest were examined for reliability., Results: The Korean version of HIV-SE (K-HIV-SE) comprises 33 items across six domains: "managing depression/mood," "managing medications," "managing symptoms," "communicating with a healthcare provider," "getting support/help," and "managing fatigue." The fitness of the modified model was acceptable (minimum value of the discrepancy function/degree of freedom = 2.49, root mean square error of approximation = .08, goodness-of-fit index = .76, adjusted goodness-of-fit index = .71, Tucker-Lewis index = .84, and comparative fit index = .86). The internal consistency reliability (Cronbach's α = .91) and test-retest reliability (intraclass correlation coefficient = .73) were good. The criterion validity of the K-HIV-SE was .59 ( p < .001)., Conclusion: This study suggests that the K-HIV-SE is useful for efficiently assessing self-efficacy for HIV disease management., Competing Interests: The authors declared no conflict of interest., (© 2023 Korean Society of Nursing Science.)

Piezoelectric nanomaterials that can generate reactive oxygen species (ROS) by piezoelectric polarization under an external mechanical force have emerged as an effective platform for cancer therapy. In this study, piezoelectric 2D WS 2 nanosheets are functionalized with mitochondria-targeting triphenylphosphonium (TPP) for ultrasound (US)-triggered, mitochondria-targeted piezodynamic cancer therapy. In addition, a glycolysis inhibitor (FX11) that can inhibit cellular energy metabolism is loaded into TPP- and poly(ethylene glycol) (PEG)-conjugated WS 2 nanosheet (TPEG-WS 2 ) to potentiate its therapeutic efficacy. Upon US irradiation, the sono-excited electrons and holes generated in the WS 2 are efficiently separated by piezoelectric polarization, which subsequently promotes the production of ROS. FX11-loaded TPEG-WS 2 (FX11@TPEG-WS 2 ) selectively accumulates in the mitochondria of human breast cancer cells. In addition, FX11@TPEG-WS 2 effectively inhibits the production of adenosine triphosphate . Thus, FX11@TPEG-WS 2 exhibits outstanding anticancer effects under US irradiation. An in vivo study using tumor-xenograft mice demonstrates that FX11@TPEG-WS 2 effectively accumulated in the tumors. Its tumor accumulation is visualized using in vivo computed tomography . Notably, FX11@TPEG-WS 2 with US irradiation remarkably suppresses the tumor growth of mice without systemic toxicity. This study demonstrates that the combination of piezodynamic therapy and energy metabolism-targeted chemotherapy using mitochondria-targeting 2D WS 2 is a novel strategy for the selective and effective treatment of tumors., (© 2023 Wiley-VCH GmbH.)

Context: Pruritus is a common skin disease among older adults. With aging, there is a decrease in skin elasticity and thickness, and vascular changes occur that decrease the skin's ability to retain moisture., Objective: To investigate the effects of aromatherapy massage on pruritis and stress levels in older women., Design: This was a nonequivalence, pre-post, quasi-experimental study. To enhance the appropriateness and accuracy of the intervention, a pilot study was conducted before the main study., Setting: The participants were recruited from six senior citizens' centers in Changwon City, Gyeongnam, South Korea., Participants: The participants were 64 women ≥65 years of age with an average age of 80.7 years and 79.7 years in the intervention and the control groups, respectively., Intervention: The intervention comprised aromatherapy massage with a blend of three essential oils: 1 mL of lavender, 0.25 mL of Roman chamomile, and 0.25 mL of sandalwood diluted to 1.5% with a sweet-almond carrier oil. The control group received massages with 0.25% sandalwood oil., Outcome Measures: The symptom score table of the Pruritus Score Scale was used to measure the degree, area, and frequency of pruritus and its impact on everyday life. The study also measured skin hydration levels using moisture-measuring module sensor, skin pH using the Howskin device, and stress using the Perceived Stress Scale., Results: Of the 64 initial participants, 5 dropped out of the study, resulting in 59 being included in the analysis. A significant difference was found between the intervention and control groups regarding relief of pruritus (U = 302.5, P = .039) and stress levels (U = -6.36, P < .001). No adverse effects were observed., Conclusions: Aromatherapy massage can be an effective intervention to decrease pruritus and stress in older women. Further studies with larger samples that also include men are required to confirm the generalizability of these results.

Sonodynamic therapy (SDT) has emerged as an effective therapeutic modality as it employs ultrasound (US) to eradicate deep-seated tumors noninvasively. However, the therapeutic efficacy of SDT in clinical settings remains limited owing to the low aqueous stability and poor pharmacokinetic properties of sonosensitizers. In this study, extracellular vesicles (EVs), which have low systemic toxicity, were used as clinically available nanocarriers to effectively transfer a sonosensitizer to cancer cells. Chlorin e6 (Ce6), a sonosensitizer, was conjugated to a mitochondria-targeting triphenylphosphonium (TPP) moiety and loaded into EVs to enhance the efficacy of SDT, because mitochondria are critical subcellular organelles that regulate cell survival and death. Additionally, piperlongumine (PL), a pro-oxidant and cancer-specific chemotherapeutic agent, was co-encapsulated into EVs to achieve efficient and selective anticancer activity. The EVs substantially amplified the cellular internalization of TPP-conjugated Ce6 (TPP-Ce6), resulting in the enhanced generation of intracellular reactive oxygen species (ROS) in MCF-7 human breast cancer cells upon US exposure. Importantly, EVs encapsulating TPP-Ce6 effectively destroyed the mitochondria under irradiation with US, leading to efficient anticancer activity. The co-encapsulation of pro-oxidant PL into EVs significantly enhanced the SDT efficacy in MCF-7 cells through the excessive generation of ROS. Moreover, the EV co-encapsulating TPP-Ce6 and PL [EV(TPP-Ce6/PL)] exhibited cancer-specific cell death owing to the cancer-selective apoptosis triggered by PL. In vivo study using MCF-7 tumor-xenograft mice revealed that EV(TPP-Ce6/PL) effectively accumulated in tumors after intravenous injection. Notably, treatment with EV(TPP-Ce6/PL) and US inhibited tumor growth significantly without causing systemic toxicity. This study demonstrated the feasibility of using EV(TPP-Ce6/PL) for biocompatible and cancer-specific chemo-SDT., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Despite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive., Methods: Here, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients., Results: Differential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients., Discussion: Aberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression., Competing Interests: SL, DP and W-YP are employed by Geninus Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jeon, Kim, Kang, Park, Kim, Park, Koh, Shim, Kim, Rhee, Jeong, Lee, Park, Lim, Kim, Ha, Jo, Kim, Lee, Shon, Kim, Jeon, Choi, Kim, Lee, Choi, Park, Park, Kim and Cho.)

Background: Blood pressure measurement is an essential element during intraoperative patient management. However, errors caused by changes in transducer levels can occur during surgery., Methods: This single center, prospective, observational study enrolled 25 consecutive patients scheduled for elective cardiac surgery with invasive arterial and central venous pressure (CVP) monitoring. Hydrostatic pressures caused by level differences (leveling pressure) between a reference point (on the center of the left biceps brachii muscle) and the transducers (fixed on the right side of the operating table) for arterial and central lines were continuously measured using a leveling transducer. Adjusted pressures were calculated as measured pressure - leveling pressure. Hypotension (mean arterial pressure < 80, <70, and < 60 mmHg), and CVP (< 6, ≥6 and < 15, or ≥ 15 mmHg) and pulmonary artery pressure (PAP, mean > 20 mmHg) levels were determined using unadjusted and adjusted pressures., Results: Twenty-two patients were included in the analysis. Leveling pressure ≥ 3 mmHg and ≥ 5 mmHg observed at 46.0 and 18.7% of pooled data points, respectively. Determinations of hypotension using unadjusted and adjusted pressures showed disagreements ranging from 3.3 to 9.4% depending on the cutoffs. Disagreements in defined levels of CVP and PAP were observed at 23.0 and 17.2% of the data points, respectively., Conclusions: The errors in pressure measurement due to changes in transducer level were not trivial and caused variable disagreements in the determination of MAP, CVP, and PAP levels. To prevent distortions in intraoperative hemodynamic management, strategies should be sought to minimize or adjust for these errors in clinical practice., Trial Registration: cris.nih.go.kr (KCT0006510)., (© 2023. The Author(s).)

The Schlemm's canal (SC) is a circular, lymphatic-like vessel located at the limbus of the eye that participates in the regulation of aqueous humor drainage to control intraocular pressure (IOP). Circumferential flow of aqueous humor within the SC lumen generates shear stress, which regulates SC cell behaviour. Using biochemical analysis and real-time live cell imaging techniques, we have investigated the activation of autophagy in SC cells by shear stress. We report, for the first time, the primary cilium (PC)-dependent activation of autophagy in SC cells in response to shear stress. Moreover, we identified PC-dependent shear stress-induced autophagy to be positively regulated by phosphorylation of SMAD2 in its linker and C-terminal regions. Additionally, SMAD2/3 signaling was found to transcriptionally activate LC3B , ATG5 and ATG7 in SC cells. Intriguingly, concomitant to SMAD2-dependent activation of autophagy, we also report here the activation of mTOR pathway, a classical autophagy inhibitor, in SC cells by shear stress. mTOR activation was found to also be dependent on the PC. Moreover, pharmacological inhibition of class I PI3K increased phosphorylation of SMAD2 at the linker and activated autophagy. Together, our data indicates an interplay between PI3K and SMAD2/3 signaling pathways in the regulation of PC-dependent shear stress-induced autophagy in SC cells., Competing Interests: Disclosure statement We declare no conflict of interest, and we have no manuscripts in the press or in the submission containing the research presented here.

This study was conducted to identify fall injury patterns, the transition from the baseline to follow-up, and the factors associated with the identified fall injury patterns using data obtained from the Korean Frailty and Aging Cohort Study. The participants were 566 community-dwelling older adults with fall experience. Three fall injury patterns were identified as the baseline and follow-up periods. The probability that the participant in the "fracture injury" pattern at Time 1 transitioned to the "fracture injury" pattern at Time 2 was 0.098. The factors associated with the "bruising and/or sprain injury" pattern were education level (relative risk ratio [RRR] = 0.55, p = 0.012), alcohol consumption (RRR = 0.50, p = 0.034), and balancing in tandem position (RRR = 2.77, p < 0.001). In the "fracture injury" pattern, male (RRR = 0.22, p = 0.038), frailty score (RRR = 0.58, p = 0.042), "bruising injury" (RRR = 0.23, p = 0.007), and "sprain injury" (RRR = 0.20, p = 0.007) at the baseline were significant factors. The findings indicate that previous fall experiences, higher alcohol consumption, lower frailty scores, and poor balance levels are associated with fall injury patterns. These patterns should be considered when developing prevention interventions., (© 2022. The Author(s).)

Mulberry is a rich source of anthocyanins (ACNs) known to possess biological activities. However, these ACNs are unstable in high pH, heat, and aqueous environments with a low bioavailability. In this study, a colloidal dispersion was prepared by hot melt extrusion with proper excipients. In this process, a hydrophilic polymer matrix was used to confirm the stability of the compound in high pH, high temperature, and aqueous media. It was confirmed that the particle size and the polydispersity index value were reduced, thereby improving the solubility. In vitro release studies revealed that the extrudate had a sustained release compared to a non-extruded product. As a result of measuring changes of intestinal microorganisms ( Lacticaseibacillus rhamnosus , Pediococcus pentosaceus , Escherichia coli, Enterococcus faecalis , and Staphylococcus aureus ), contents of probiotics were found to be increased whereas contents of pathogenic microorganisms were decreased. Thus, hot-melt extrusion could enhance the stability of ACN with prolonged release. The processed formulation exhibited probiotic properties and antimicrobial activities against pathogenic intestinal microflora.

Selenophosphate synthetase (SEPHS) was originally discovered in prokaryotes as an enzyme that catalyzes selenophosphate synthesis using inorganic selenium and ATP as substrates. However, in contrast to prokaryotes, two paralogs, SEPHS1 and SEPHS2, occur in many eukaryotes. Prokaryotic SEPHS, also known as SelD, contains either cysteine (Cys) or selenocysteine (Sec) in the catalytic domain. In eukaryotes, only SEPHS2 carries out selenophosphate synthesis and contains Sec at the active site. However, SEPHS1 contains amino acids other than Sec or Cys at the catalytic position. Phylogenetic analysis of SEPHSs reveals that the ancestral SEPHS contains both selenophosphate synthesis and another unknown activity, and that SEPHS1 lost the selenophosphate synthesis activity. The three-dimensional structure of SEPHS1 suggests that its homodimer is unable to form selenophosphate, but retains ATPase activity to produce ADP and inorganic phosphate. The most prominent function of SEPHS1 is that it is implicated in the regulation of cellular redox homeostasis. Deficiency of SEPHS1 leads to the disturbance in the expression of genes involved in redox homeostasis. Different types of reactive oxygen species (ROS) are accumulated in response to SEPHS deficiency depending on cell or tissue types. The accumulation of ROS causes pleiotropic effects such as growth retardation, apoptosis, DNA damage, and embryonic lethality. SEPHS1 deficiency in mouse embryos affects retinoic signaling and other related signaling pathways depending on the embryonal stage until the embryo dies at E11.5. Dysregulated SEPHS1 is associated with the pathogenesis of various diseases including cancer, Crohn's disease, and osteoarthritis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

People living with human immunodeficiency virus (PLWH) in Korea demonstrate insufficient self-management behaviors. Especially during pandemics such as COVID-19, technology-based self-management programs are needed to overcome time and space limitations. The purpose of this study was to evaluate the effects of a self-management program using a mobile app (Health Manager) on self-management outcomes among PLWH in Korea. A randomized controlled pilot trial was performed and participants were enrolled in the infectious outpatient clinic of a single hospital. The intervention group used the mobile app for 4 weeks, while the control group received self-management education materials in a portable document format. The online self-report questionnaire assessed primary outcomes including self-efficacy for self-management, self-management behaviors, and medication adherence, and secondary outcomes including perceived health status, depression, and perceived stigma. Thirty-three participants were randomly assigned to the intervention (n = 17) or the control group (n = 16). In the intention-to-treat analysis, self-efficacy for self-management and self-management behaviors increased, while perceived stigma decreased. The app-based self-management program could be considered a helpful strategy to improve self-management outcomes among PLWH and reduce their perceived stigma during the pandemic. Further studies with larger samples and longer follow-ups are needed.Trial registration: Clinical Research Information Service, KCT0004696 [04/02/2020]., (© 2022. The Author(s).)

Background: As the life expectancy of people living with HIV increases with the advancements in antiretroviral treatment, the continuity of long-term therapy and health care for people living with HIV has gained more importance. However, the estimated proportion of people living with HIV who have access to treatment or are virally suppressed is unsatisfactory. Therefore, it is necessary to build strategies to improve treatment continuity by identifying the barriers and facilitators that affect the HIV care continuum. To enable this, we will conduct a scoping review to explore the barriers and facilitators related to the care continuum in high-income countries for adults living with HIV., Methods: The review question will be identified based on the JBI guidelines for the development of scoping review protocols. Studies exploring the barriers to and facilitators of the HIV care continuum among adults living with HIV in high-income countries will be included in this review. A literature search will be conducted on the databases (platform) of MEDLINE (Ovid), Cumulative Index to Nursing and Allied Health Literature (EBSCO), Embase (Ovid), and the Cochrane Central Register of Controlled Trials (Cochrane Library). Four researchers will screen articles for inclusion and subsequently build a charting form and collate the data to provide results., Discussion: The results of this scoping review will provide comprehensive evidence for the barriers and facilitators to be considered in the care continuum of people living with HIV. Importantly, the results will provide insight for healthcare providers and researchers to develop interventions and research the continuity in caring for people living with HIV., (© 2022. The Author(s).)

Objective: The Delirium Diagnostic Tool-Provisional (DDT-Pro) was designed to detect the presence and severity of delirium briefly and objectively regardless of psychiatric expertise. We translated the DDT-Pro into Korean and validated it in elderly Korean patients., Methods: To validate the translation and evaluate inter-rater reliability, a psychiatric trainee and a research nurse independently assessed the same patients referred to the Department of Psychiatry. The results were compared with the reference evaluations performed by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)., Results: We enrolled 42 elderly patients. The Cronbach's alpha coefficient were 0.839 (the trainee), 0.822 (the nurse). The Cohen's weighted κ between the trainee and nurse, ranged from 0.555±0.102 to 0.776±0.062. The Pearson correlation coefficients (Korean version of the DDT-Pro [K-DDT-Pro] and Korean version of the Delirium Rating Scale-Revised-98 [DRS-R98-K] total score) were γ=-0.850 (the trainee), and γ=-0.821 (the nurse). The areas under the ROC curves (AUCs) were 0.974 (the trainee) and 0.893 (the nurse)., Conclusion: The K-DDT-Pro exhibited high internal consistency and relatively substantial inter-rater reliability. The correlation with the DRS-R98-K was strongly negative. The accuracy of the K-DDT-Pro was excellent, regardless of expertise. In conclusion, the K-DDT-Pro is a brief and simple tool that usefully screens for delirium in elderly patients.

During the last few years, the autophagy lysosomal system is emerging as a central cellular pathway with roles in survival, acting as a housekeeper and stress response mechanism. Studies by our and other labs suggest that autophagy might play an essential role in maintaining aqueous humor outflow homeostasis, and that malfunction of autophagy in outflow pathway cells might predispose to ocular hypertension and glaucoma pathogenesis. In this review, we will collect the current knowledge and discuss the molecular mechanisms by which autophagy does or might regulate normal outflow pathway tissue function, and its response to different types of stressors (oxidative stress and mechanical stress). We will also discuss novel roles of autophagy and lysosomal enzymes in modulation of TGFβ signaling and ECM remodeling, and the link between dysregulated autophagy and cellular senescence. We will examine what we have learnt, using pre-clinical animal models about how dysregulated autophagy can contribute to disease and apply that to the current status of autophagy in human glaucoma. Finally, we will consider and discuss the challenges and the potential of autophagy as a therapeutic target for the treatment of ocular hypertension and glaucoma., (Copyright © 2022. Published by Elsevier Ltd.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-493/coif). The authors have no conflicts of interest to declare.

WHAT IS KNOWN ON THE SUBJECT?: Internally displaced persons (IDPs) in Myanmar have been exposed to conflict and violence for a long time and experience physical, psychological and social problems. Post-traumatic stress symptoms (PTSS) are more prevalent among IDPs than among general populations and refugees, and limited research is available on this topic among IDPs in Myanmar. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: More than one-third of the IDPs in our sample from Myanmar camps had a high PTSS score. More than two-thirds experienced traumatic events and left home after age 18. The overall functional health of IDPs was poor, and the presence or absence of PTSS led to differences in the factors associated with functional health in each group. Resilience and PTSS were associated with the functional health of IDPs in Myanmar. Further, functional health was positively correlated with levels of resilience among those relatively low in PTSS. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health nurses need to assess IDPs' health status and PTSS by first performing health screening at camps in Myanmar. Subsequently, tailored interventions can be provided according to individual health conditions and PTSS severity. IDPs in Myanmar need psychological first aid to cope with the ongoing conflict and violence, and further mental health nurse training is necessary to implement this aid and tailored interventions for PTSS., Abstract: INTRODUCTION: Internally displaced persons (IDPs) are individuals forced to leave their homes and move within their country. Post-traumatic stress symptoms (PTSS) are prevalent in this population., Aim: To investigate trauma symptoms and functional health of IDPs in Myanmar and identify the factors associated with their functional health according to the presence/absence of PTSS., Method: This cross-sectional study included 201 IDPs who completed a questionnaire on functional health, PTSS, resilience, social support and hope. The analysis included descriptive statistics, t-tests, Pearson's correlation coefficients and multiple linear regression with interaction analyses., Results: Over one-third of the participants had PTSS, with low functional health scores. The greater the resilience, the better the functional health. The higher participants' PTSS, the poorer their functional health. There was a significant interaction between resilience and PTSS., Discussion: Tailored resilience-building programs, as well as health policies and services, are needed to enhance IDPs' functional health and help them overcome PTSS., Implications for Practice: Psychological first aid should be provided to minimize PTSS experienced in situations of ongoing conflict and violence. Mental health nurses should be trained to assess IDPs' health status and tailor interventions accordingly., (© 2022 John Wiley & Sons Ltd.)

There is a lack of evidence regarding the effects of exercise on older individuals living with HIV. This systematic review and meta-analysis examined previous studies on physical activity interventions for people living with HIV aged ≥50 years. The effectiveness of the interventions on various physical and psychological health outcomes was evaluated. Databases used for this review included PubMed, EMBASE, CINAHL, and Cochrane Library CENTRAL. Twelve randomized controlled trials on physical activity interventions for people ≥50 years and living with HIV were included. Standardized mean differences were calculated using random-effect models. All effect sizes were expressed using Cohen's d values and their 95% confidence intervals (CIs). Physical activity interventions had a significant effect on walking capacity (Cohen's d : 0.467; 95% CI [0.069, 0.865]). The effect sizes on cardiorespiratory fitness, weight, and health-related quality of life were not significant. These findings suggest that physical activity interventions for people living with HIV aged ≥50 years are effective for the improvement of walking capacity. Further larger and higher-quality studies are required to determine the full effects of physical activity interventions on various health outcomes among older adults with HIV.

Extracellular vesicles (EVs) have emerged as biocompatible nanocarriers for efficient delivery of various therapeutic agents, with intrinsic long-term blood circulatory capability and low immunogenicity. Here, indocyanine green (ICG)- and paclitaxel (PTX)-loaded EVs [EV(ICG/PTX)] were developed as a biocompatible nanoplatform for safe and efficient cancer treatment through near-infrared (NIR) light-triggered combination chemo/photothermal/photodynamic therapy. High dual drug encapsulation in EVs was achieved for both the hydrophilic ICG and hydrophobic PTX by simple incubation. The EVs substantially improved the photostability and cellular internalization of ICG, thereby augmenting the photothermal effects and reactive oxygen species production in breast cancer cells upon NIR light irradiation. Hence, ICG-loaded EVs activated by NIR light irradiation showed greater cytotoxic effects than free ICG. EV(ICG/PTX) showed the highest anticancer activity owing to the simultaneous chemo/photothermal/photodynamic therapy when compared with EV(ICG) and free ICG. In vivo study revealed that EV(ICG/PTX) had higher accumulation in tumors and improved pharmacokinetics compared to free ICG and PTX. In addition, a single intravenous administration of EV(ICG/PTX) exhibited a considerable inhibition of tumor proliferation with negligible systemic toxicity. Thus, this study demonstrates the potential of EV(ICG/PTX) for clinical translation of combination chemo-phototherapy.

Disclosure of human immunodeficiency virus (HIV) infection status improves treatment adherence and HIV prevention. Social networks influence such disclosure by people living with HIV/AIDS (PLWH). This study aimed to investigate the disclosure status of Korean PLWH and determine the social network characteristics associated with disclosure. A cross-sectional study design was used, and 148 Korean PLWH answered self-report questionnaires that included items on the characteristics of social networks and disclosure. Logistic regression and decision tree analysis were performed. In total, 81 participants (54.7%) reported disclosing HIV status to the most important supporter. Five factors were found to influence disclosure: age, self-help group participation, living arrangement, social network relationship, and tie strength; three groups had higher percentages of nondisclosure. The findings suggest that healthcare practitioners should provide adequate counseling by considering the characteristics of social networks and disclosure status of PLWH. Researchers should identify high-risk populations using decision tree analysis.

Due to increasing safety and intracellular delivery concerns about hydrophilic polymers in amphiphilic polymer-based nanoparticles (NPs), this study investigates small hydrophilic molecule-stabilized NPs for effective intracellular delivery with multiorganelle targetability and dual responsiveness to acidic pH/glutathione (GSH). In the construction of small hydrophilic molecule-stabilized NP (MSPCL-NP), the A-B-A-type amphiphilic polymer (MSPCL-P) is composed of two short hydrophilic carboxylate-capped disulfide derivatives (A) that replace hydrophilic polymers and assist in providing colloidal stability and preventing antibody (e.g., at least anti-PEG antibody)-mediated specific interactions and complement activation in the plasma and a hydrophobic multiple disulfide-containing poly(ε-caprolactone) block (B) that carries hydrophobic drugs. The carboxylates on the surface of MSPCL-NP target the acidic extratumoral/endolysosomal milieu by sensing and buffering acidic pH values, and the hydrophobic carboxylic acids improve adsorptive endocytosis and effective endosomal escape. Multiple disulfide linkages selectively target cytosolic GSH, resulting in rapid drug release from the destroyed MSPCL-NP via the cleavage of disulfide bonds in MSPCL-P. Doxorubicin (DOX)-loaded NP (DOX@MSPCL-NP) exerts strong effects on killing cells in vitro and inhibits tumor growth in HCT116 xenograft tumor-bearing mice. In conclusion, the multifunctionality and multispatial targetability of MSPCL-NP might effectively overcome various sequential drug delivery hurdles, ranging from blood circulation to drug release. Furthermore, the introduction of small hydrophilic molecules represents a potential strategy to make self-assembled NPs without the use of hydrophilic polymers., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Sonodynamic therapy has shown promise as an effective alternative to conventional photodynamic therapy owing to its ability to treat deep-seated tumors. However, the development of stimuli-responsive sonosensitizers with high biocompatibility faces a significant challenge. Methods: In this study, we developed dual stimuli-responsive sonosensitizers with desirable biosafety using extracellular vesicles (EVs), a class of naturally occurring nanoparticles. Indocyanine green (ICG), which functions as both a sonosensitizer and photoacoustic (PA) imaging agent, was loaded into EVs, together with paclitaxel (PTX) and sodium bicarbonate (SBC), to achieve pH-responsive PA imaging-guided chemo-sonodynamic combination therapy. Results: The EVs significantly improved the cellular uptake of ICG, thus triggering enhanced sonodynamic effects in breast cancer cells. SBC-, ICG-, and PTX-loaded EV [SBC-EV(ICG/PTX)] efficiently released the PTX in response to acidic pH in the endo/lysosomes because CO 2 bubbles generated from the SBC caused the EV membranes to burst. The drug release was further facilitated by ultrasound (US) treatment, demonstrating dual pH/US-responsive drug release. The ICG- and PTX-loaded EVs exhibited efficient anticancer activity against breast tumor cells owing to the combination of chemo-sonodynamic therapy. High-resolution PA imaging visualized the preferential tumor accumulation of SBC-EV(ICG/PTX) in tumor-bearing mice. Notably, a single intravenous injection of SBC-EV(ICG/PTX) with US irradiation significantly suppressed tumor growth in mice without systemic toxicity. Conclusions: Our findings demonstrate that dual stimuli-responsive SBC-EV(ICG/PTX) are promising sonotheranostic nanoplatforms for safe and efficient chemo-sonodynamic combination cancer therapy and photoacoustic imaging., Competing Interests: Competing Interests: Chulhong Kim has financial interests in OPTICHO, which, however, did not support this study., (© The author(s).)