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Vijaya Sarangthem,1,2,* Aena Yi,1,* Yunjae Kim,1 Alnawaz Rehemtulla,3 Byung-Heon Lee,1 Young Hyun Jeon,4 Thoudam Debraj Singh,5 Rang-Woon Park1 1Department of Biochemistry and Cell Biology, School of Medicine, and Cell & Matrix Research Institute, Kyungpook National University, Daegu, 41944, Republic of Korea; 2Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India; 3Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA; 4Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu, Republic of Korea; 5Department of Medical Oncology Laboratory, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India*These authors contributed equally to this workCorrespondence: Rang-Woon ParkDepartment of Biochemistry and Cell Biology, School of Medicine, and Cell & Matrix Research Institute, Kyungpook National University, Daegu, 41944, Republic of KoreaTel +82 53 420 4822Fax +82 53 422 1466Email nwpark@knu.ac.krThoudam Debraj SinghDepartment of Medical Oncology Laboratory, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, IndiaEmail debraj.thoudam@gmail.comBackground: Thermal-responsive self-assembled elastin-like polypeptide (ELP)-based nanoparticles are an emerging platform for controlled delivery of therapeutic peptides, proteins and small molecular drugs. The antitumor effect of bioengineered chimeric polypeptide AP1-ELP-KLAK containing an interleukin-4 receptor (IL-4R) targeting peptide and pro-apoptotic peptide (KLAKLAK) was evaluated in glioblastoma (GBM) in vitro and in vivo.Methods and Results: Herein, the therapeutic effect of AP1-ELP-KLAK was tested in advanced, and less curable glioblastoma cells with higher expression of IL-4R. Glioblastoma cell lines stably expressing different reporter systems i.e., caspase-3 sensor (surrogate marker for cellular apoptosis) or effluc/enhanced firefly luciferase (cellular viability) were established to measure cell death non-invasively. Bioluminescence imaging (BLI) of D54/effluc and U97MG/effluc treated with AP1-ELP-KLAK exhibited higher cell death up to 2∼ 3-fold than the control. Treatment with AP1-ELP-KLAK resulted in time-dependent increase of caspase-3 sensor BLI activity in D54/C cells and D54/C tumor-bearing mice. Intravenous injection of AP1-ELP-KLAK dramatically reduced tumor growth by inducing cellular apoptosis in D54/effluc tumor-bearing mice. Further, the immuno-histological examination of the excised tumor tissue confirmed the presence of apoptotic cells as well as caspase-3 activation.Conclusion: Collectively, AP1-ELP-KLAK effectively induced cellular apoptosis of glioblastoma cells and non-invasive imaging provides a window for real-time monitoring of anti-tumor effect with the provision of improving therapeutic efficacy in a glioblastoma mice model.Keywords: tumor targeting, ELP, caspase-sensor, apoptosis, IL-4 receptor, glioblastoma

Eunkyung Choi,1 Junggu Yi,1 Younghoon Jeon,2 1Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea Abstract: Postoperative negative pressure pulmonary edema (NPPE) is a rare, but well-known life-threatening complication of acute upper airway obstruction (UAO) which develops after general anesthesia. The pronounced inspiratory efforts following UAO lead to excessive negative inspiratory pressure, which may cause acute pulmonary edema. Early recognition and prompt treatment of NPPE is necessary to prevent patient morbidity and mortality. In addition, the physician should carefully manage the patient who has risk factors of UAO to prevent this situation. We experienced a case of NPPE following laryngospasm after tracheal extubation in an obese patient who underwent open reduction of orbital wall and nasal bone surgery. Keywords: airway obstruction, negative pressure pulmonary edema, laryngospasm, nasal surgery, obese

This study evaluates the effectiveness of CT and MR imaging in differentiating intradural extramedullary spinal schwannomas and meningiomas in a large group of patients. In addition, the study correlates tumour location, morphologic characteristics and enhancement pattern. From January 2000 to June 2007, we retrospectively reviewed 128 consecutive patients (51 male, 77 female; mean age at admission 53.8 years; range 17-83 years) with spinal intradural extramedullary tumours (92 schwannomas, 36 meningiomas) at our institution. Fifty-one of ninety-two schwannomas (55.4%) showed fluid signal intensity on T2-weighted MR images. Twenty-two of thirty-six meningiomas (61.1%) showed hyperintense signal intensity and thirteen of thirty-six meningiomas (36.1%) showed isointense signal on T2-weighted MR images. Fifty-four schwannomas (58.7%) showed rim enhancement and thirty-three meningiomas (91.7%) showed diffuse enhancement on contrast-enhanced T1-weighted MR imaging. Twenty-one meningiomas (58.3%) showed dural tail sign in contrast-enhanced T1-weighted MR imaging. Twenty-one meningiomas (58.3%) showed calcification on CT images. MR and CT imaging results are therefore useful for the differentiation of schwannomas from meningiomas of the spine. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to develop a Korean version of the behavior rating scale for dementia (BRSD-K) for evaluating behavioral and psychological symptoms of dementia. METHODS: The BRSD-K was administered to the informants of 268 subjects with dementia. Internal, inter-rater and test-retest reliabilities were tested. To evaluate construct validity, exploratory factor analysis was performed. To evaluate concurrent validity, Pearson correlation coefficients between BRSD-K scores and the corresponding scores of the Korean version of the neuropsychiatric inventory (NPI-K) were calculated. RESULTS: BRSD-K demonstrated substantially high levels of reliabilities. Factor analysis identified seven factors, i.e. depressive symptoms, irritability/aggression, psychotic symptoms, behavioral dysregulations, sleep disturbance, inertia, and appetite. Correlations between BRSD-K and corresponding NPI-K scores were statistically significant (p < 0.05). CONCLUSIONS: BRSD-K was found to be a reliable and valid instrument for evaluating BPSD. [ABSTRACT FROM AUTHOR]

Background: The prevalence of both chronic diseases and multi-morbidity increases with longer life spans. As Australia's population ages, the aged care sector is under increasing pressure to ensure that quality aged care is available. Key to responding to this pressure is leadership and management capability within the aged care workforce. A systematic literature review was conducted to inform the policy development necessary for the enhancement of clinical and managerial leadership skills of middle managers within residential aged care.Methods: Using scientific journal databases, hand searching of specialist journals, Google, snowballing and suggestions from experts, 4,484 papers were found. After a seven-tiered culling process, we conducted a detailed review (narrative synthesis) of 153 papers relevant to leadership and management development in aged care, incorporating expert and key stakeholder consultations.Results: * Positive staff experiences of a manager's leadership are critical to ensure job satisfaction and workforce retention, the provision of quality care and the well-being of care recipients, and potentially a reduction of associated costs.* The essential attributes of good leadership for aged care middle management are a hands-on accessibility and professional expertise in nurturing respect, recognition and team building, along with effective communication and flexibility. However, successful leadership and management outcomes depend on coherent and good organisational leadership (structural and psychological empowerment).* There is inadequate preparation for middle management leadership roles in the aged care sector and a lack of clear guidelines and key performance indicators to assess leadership and management skills.* Theory development in aged care leadership and management research is limited. A few effective generic clinical leadership programs targeting both clinical and managerial leaders exist. However, little is known regarding how appropriate and effective they are for the aged care sector.Conclusions: There is an urgent need for a national strategy that promotes a common approach to aged care leadership and management development, one that is sector-appropriate and congruent with the philosophy of person-centred care now predominant in the sector. The onus is on aged care industries as a whole and various levels of Government to make a concerted effort to establish relevant regulation, legislation and funding. [ABSTRACT FROM AUTHOR]

A total of 28 male BALB/c mice (average weight 20.7 +/- 1.6 g) were divided into 4 treatment groups and fed a commercial diet (A), a commercial diet + induced colitis by dextran sodium sulfate (DSS) (B), Inonotus obliquus (IO) administration (C), and IO administration + induced colitis by DSS (D). IO treatment (C, D) decreased the expression of tumor necrosis factor (TNF)-alpha and signal transducers and activators of transcription (STAT)1 compared to those of the colitis induced group (B). The expressions of IL-4 and STAT6 were decreased in group D compared to the colitis induced group (B). The serum immunoglobulin (Ig)E level decreased in IO treatment groups (C, D) compared to no IO treatment groups (A and B) although there was no significant difference between the IO treatment groups. Extract from IO itself had a weak cytotoxic effect on murine macrophage cell line (RAW264.7 cells). Extract from IO inhibited lipopolysaccharide- (LPS-) induced, TNF-alpha, STAT1, pSTAT1, STAT6, and pSTAT6 production in RAW264.7 cells. [ABSTRACT FROM AUTHOR]

Iatrogenic pseudoaneurysm is a rare but potentially fatal complication of a thyroid biopsy. However, a standard management strategy has not yet been established. We aimed to evaluate the efficacy and safety of ultrasound (US)-guided thrombin injection (TI) for thyroid pseudoaneurysms. This retrospective study included 7256 patients who underwent thyroid biopsy and TI from January 2020 to January 2024. The technical success, clinical efficacy, and complication rates were evaluated. A total of 0.1% (7/7256) of pseudoaneurysms developed after thyroid biopsy. Except for 1 case that showed obliteration with manual compression, the remaining 6 refractory aneurysms (0.08%) were managed with US-guided TI. All cases (100%) were successfully occluded with US-guided TI. No major complications were observed. One patient (16.7%) developed transient loss of consciousness, which spontaneously resolved within a few seconds. US-guided TI is an effective, relatively safe, and minimally invasive method for managing pseudoaneurysms after thyroid biopsy., (© 2025 by American Journal of Neuroradiology.)

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models., Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis., Conclusions: NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation., (© 2024. The Author(s).)

Background: The health issues experienced by older people can often be severe and complex, and an increasing number are using residential aged care services to meet their care needs. High-quality nursing care is fundamental to the health and safety of aged care residents and is contingent on nurses' accurate assessment, informed decision-making, and delivery of timely interventions. However, the role of the aged care nurse is often challenging, impeded by factors such as understaffing, high workloads, and a lack of access to clinical infrastructure and resources. When these challenges mount, residents are put at greater risk of adverse outcomes, such as avoidable clinical deterioration and hospital transfers. This study describes the adaptation and implementation of the emergency nursing framework, HIRAID® (History including Infection risk, Red Flags, Assessment, Interventions, Diagnostics, reassessment, communication and plan)-a tool to assist nurses' assessment, decision-making and care in residential aged care., Methods: The HIRAID® framework will be adapted for residential aged care using a real-time Delphi and panel of aged care and nursing experts. The co-designed HIRAID® Aged Care framework will be trialled in 23 residential aged care homes in Sydney, Australia, in a modified stepped-wedge cluster randomised controlled trial design. All homes will be randomised into one of four clusters. Outcomes of interest include the rate of clinical deterioration events resulting from nurses' actions, the rate of hospital transfers determined to be inappropriate, performance against the national mandatory aged care quality indicators, resident satisfaction with care, nurse and medical staff satisfaction with communication, and the quality of nursing documentation. These outcomes will be evaluated using a combination of qualitative and quantitative analysis of routinely collected resident data, expert assessments of facility documentation events against validated criteria, and pre- and post-intervention surveys of residents, family carers, nurses, and medical staff., Discussion: This protocol describes a pragmatic trial that aims to translate an evidence-based framework from the emergency care context into residential aged care. The adapted HIRAID® Aged Care framework will be the first of its kind to standardise and guide holistic nursing assessment, decision-making, and documentation in residential aged care in Australia., Ethics and Dissemination: This research has been approved by the Western Sydney Local Health District Human Research Ethics Committee: 2023/ETH00523. A waiver of consent has been approved to access resident health data and nursing documentation at each participating site., Trial Registration: Australian and New Zealand Clinical Trial Registry, ACTRN12623000481673. Registered 12 May 2023., Protocol Version: Version 1.0 6 February 2024., (© 2024. The Author(s).)

Objectives: To estimate the national prevalence of antidementia and psychotropic medication use, and sociodemographic factors associated with their use, in Australians living with dementia., Design: Retrospective cross-sectional study., Setting and Participants: Nationwide data linkage study using 2021 Census and Pharmaceutical Benefits Scheme (PBS) data. All people aged 65 or older with dementia (self-reported in the Census or dispensed an antidementia drug subsidized by the PBS) were included., Methods: Medication use was defined as at least 1 dispensing during the 3-month period following the Census (August-October 2021). Prevalence of antidementia and psychotropic medication use, including antipsychotics, benzodiazepines and Z-drugs, antiepileptics, opioids, and psychostimulants, was calculated. Sociodemographic factors associated with medication use were explored using multivariable logistic regression models., Results: Of the 177,809 older people living with dementia included, 58.6% were using at least 1 psychotropic medication. Antidepressants were the most commonly used psychotropics (41%), followed by opioids (20%) and antipsychotics (13%). Antidementia medications were used by a quarter of people with dementia (26%). People with dementia living in the highest socioeconomic area were more likely to use antidementia medications [adjusted odds ratio (OR), 1.22; 95% CI, 1.17-1.28] and less likely to use psychotropics (OR, 0.91; 95% CI, 0.88-0.95) compared with people living in the lowest socioeconomic area. Conversely, those living in inner regional areas were more likely to use psychotropics (OR, 1.06; 95% CI, 1.03-1.10) and less likely to use antidementia medications (OR, 0.79; 95% CI, 0.77-0.82) compared with people living in metropolitan areas., Conclusions and Implications: Psychotropics were commonly used in people with dementia in Australia. Disparities in access to health care due to socioeconomic status or remoteness may have influenced the use of antidementia and psychotropic medications. Further strategies to allow more equitable access to resources and medications are needed., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Objectives: This explorative cross-country qualitative study aims to describe experiences of receiving a dementia diagnosis and experiences of support following a diagnosis in Australia, Canada, the Netherlands and Poland., Method: Qualitative study using projective techniques during online focus groups, online and telephone interviews with people with dementia and caregivers., Results: Twenty-three people with dementia and 53 caregivers participated. Qualitative content analysis revealed five themes; (1) 'Coming to terms with dementia' helped people deal with complex emotions to move forward. (3) 'The social network as a source of support' and (4) 'The challenges and realities of formal support' and impacted 'Coming to terms with dementia'. (2) 'Navigating life with dementia as a caregiver' highlights caregiver burden and was impacted by (4) 'The challenges and realities of formal support'. People were (5) 'Self-caring and preparing for tomorrow' as they focused on maintaining current health whilst planning the future. Despite differences in healthcare and post-diagnostic support systems, there were more similarities across countries than differences., Conclusion: Across countries, formal support and support from friends and family are crucial for people with dementia and caregivers to come to terms with dementia and maintain carer wellbeing to ultimately live well with dementia.

Lipid nanoparticles (LNPs) are widely recognized as crucial carriers of mRNA in therapeutic and vaccine development. The typical lipid composition of mRNA-LNP systems includes an ionizable lipid, a helper lipid, a polyethylene glycol (PEG)-lipid, and cholesterol. Concerns arise regarding cholesterol's susceptibility to oxidation, potentially leading to undesired immunological responses and toxicity. In this study, we formulated novel LNPs by replacing cholesterol with phytochemical-derived compounds, specifically ginsenoside Rg2 and its derivative phytosterol protopanaxadiol (PPD), and validated their efficacy as mRNA delivery systems. The mRNA-LNP complexes were manually prepared through a simple mixing process. The biocompatibility of these Rg2-based LNPs (Rg2-LNP) and PPD-based LNPs (PPD-LNP) was assessed through cell viability assays, while the protective function of LNPs for mRNA was demonstrated by RNase treatment. Enhanced green fluorescent protein (EGFP) mRNA delivery and expression in A549 and HeLa cells were analyzed using optical microscopy and flow cytometry. The expression efficiency of Rg2-LNP and PPD-LNP was compared with that of commercially available LNPs, with both novel formulations demonstrating superior transfection and EGFP expression. Furthermore, in vivo tests following intramuscular (I.M.) injection in hairless mice demonstrated efficient luciferase ( Luc ) mRNA delivery and effective Luc expression using Rg2-LNP and PPD-LNP compared to commercial LNPs. Results indicated that the efficiency of EGFP and Luc expression in Rg2-LNP and PPD-LNP surpassed that of the cholesterol-based LNP formulation. These findings suggest that Rg2-LNP and PPD-LNP are promising candidates for future drug and gene delivery systems.

Background: Major knowledge and practice gaps exist in aged care home services to support independence of older people with dementia. This research evaluates an adaptation of a community-based rehabilitation model for care homes, namely Interdisciplinary Care Home-bAsed Reablement Program (I-CHARP), by examining whether (and, if so, how) I-CHARP produces its intended effects and how this programme can be practicably implemented, sustained and scaled up across care homes in Australia., Methods: I-CHARP is a 4-month bio-behavioural-environmental rehabilitation model of care, integrated in care home services, supported through the deployment of an implementation strategy, the Research Enabled Aged Care Homes (REACH) network. It consists of (1) 8-12 full individual sessions and additional eight brief follow-ups per resident, tailored to the resident's needs, delivered primarily by a team of an occupational therapist, registered nurse and other allied health staff; (2) environmental modifications/assistive devices up to the value of $400 per resident; and (3) engagement of intervention care home staff, managers and regular visitors. An overarching evaluation approach is participatory action research using a cluster quasi-experimental design and mixed methods. It involves testing of the implementation strategy (REACH network and other approaches) while observing/gathering information on the intervention (I-CHARP) and related outcomes in three cycles. Participants include residents (aged ≥ 60 years with early stages of dementia) and care staff from 16 care homes. Care quality indicators, health care costs, field notes and semi-structured interviews/focus groups with intervention site staff, regular visitors and managers will provide further insights into I-CHARP processes and implementation issues., Discussion: In the final phase of the project, an Agile Implementation Playbook will be developed for the delivery of reablement care that can be used in routine practice across care homes in Australia. The study findings will also inform future policy development and strategic directions for dementia care in care homes., Trial Registration: Australian New Zealand Clinical Trial Registry, ACTRN12623000885695 Registered 16 August 2023, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386088., Protocol Version: 1.0 dated 20 July 2023., (© 2024 John Wiley & Sons Ltd.)

Objectives: To identify the prevalence of and factors associated with medication use in people living with dementia in the community., Methods: A cross-sectional study using baseline data from a randomised controlled trial known as the Interdisciplinary Home-bAsed Reablement Program (I-HARP) between 2018 and 2021 in Sydney, Australia. Participants included people with mild-moderate dementia and their carers. Medication use was classified according to the Anatomical Therapeutic Chemical codes, while potentially inappropriate medications (PIMs) were defined using 2019 Beer's Criteria and 2024 Australian list. Logistic regression models were used to identify factors associated with use of medication classes., Results: A total of 130 people with dementia and their carers were included. Of the people with dementia, 35% were using antidementia medication, 48% psychotropics, 76% PIMs and 65% polypharmacy (≥5 medications). Polypharmacy was associated with the use of psychotropics (adjusted OR [aOR]: 5.09, 95% confidence interval [CI]: 1.94-13.39) and PIMs (aOR: 17.38, 95% CI: 5.12-59.02). Higher education level was associated with lower odds of psychotropic use (aOR: .33, 95% CI: .15-.76), and age over 80 years was associated with lower odds of antidementia medication use (aOR: .29; 95% CI: .12-.72)., Conclusions: The use of PIMs, psychotropics and polypharmacy were common in this sample of people with dementia living in the community. Associations were seen between participant characteristics and medication use. Future research should focus on reviewing PIMs and polypharmacy in people with dementia living in the community to assess the impact on health outcomes., (© 2024 The Author(s). Australasian Journal on Ageing published by John Wiley & Sons Australia, Ltd on behalf of AJA Inc’.)

Introduction: The aim of this study was to examine the association of sex/gender and other factors with the perceived helpfulness of the diagnostic process and post-diagnostic services by persons with dementia and care partners. Methods: We conducted secondary cross-sectional analysis of surveys from the 'Cognisance' project. Sex/gender and other factors (e.g., demographic variables, help seeking behaviours, healthcare professional consulted) of persons with dementia and care partners from four countries were considered. Main outcomes were perceived helpfulness of diagnostic process and post-diagnostic services. We conducted descriptive and multivariate analyses. Results: Compared to men, more women with dementia perceived post-diagnostic services as helpful though not statistically significant. Sex/gender was not associated with perceived helpfulness of diagnostic process and post-diagnostic services among care partners. Satisfaction with and awareness of services were associated with perceived helpfulness among care partners. Discussion: These findings underscore the necessity for sex/gender-based research to enhance dementia care and for tailored interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with \respect to the research, authorship, and/or publication of this article.

Purpose: The time-intensive nature of acquiring 3D T1-weighted MRI and analyzing brain volumetry limits quantitative evaluation of brain atrophy. We explore the feasibility and reliability of deep learning-based accelerated MRI scans for brain volumetry., Methods: This retrospective study collected 3D T1-weighted data using 3T from 42 participants for the simulated acceleration dataset and 48 for the validation dataset. The simulated acceleration dataset consists of three sets at different simulated acceleration levels (Simul-Accel) corresponding to level 1 (65% undersampling), 2 (70%), and 3 (75%). These images were then subjected to deep learning-based reconstruction (Simul-Accel-DL). Conventional images (Conv) without acceleration and DL were set as the reference. In the validation dataset, DICOM images were collected from Conv and accelerated scan with DL-based reconstruction (Accel-DL). The image quality of Simul-Accel-DL was evaluated using quantitative error metrics. Volumetric measurements were evaluated using intraclass correlation coefficients (ICCs) and linear regression analysis in both datasets. The volumes were estimated by two software, NeuroQuant and DeepBrain., Results: Simul-Accel-DL across all acceleration levels revealed comparable or better error metrics than Simul-Accel. In the simulated acceleration dataset, ICCs between Conv and Simul-Accel-DL in all ROIs exceeded 0.90 for volumes and 0.77 for normative percentiles at all acceleration levels. In the validation dataset, ICCs for volumes > 0.96, ICCs for normative percentiles > 0.89, and R 2  > 0.93 at all ROIs except pallidum demonstrated good agreement in both software., Conclusion: DL-based reconstruction achieves clinical feasibility of 3D T1 brain volumetric MRI by up to 75% acceleration relative to full-sampled acquisition., (© 2024. The Author(s).)

Background: Social health in the context of dementia has recently gained interest. The development of a social health conceptual framework at the individual and social environmental levels, has revealed a critical need for a further exploration of social health markers that can be used in the development of dementia intervention and to construct social health measures., Objective: To identify social health markers in the context of dementia., Method: This international qualitative study included six countries: Australia, Germany, Indonesia, Italy, Poland, and the Netherlands. Using purposive sampling, three to five cases per country were recruited to the study, with each case consisting of a person living with dementia, a primary informal caregiver, an active network member, and a health care professional involved in the care of the person with dementia. In-depth interviews, using an agreed topic guide, and content analysis were conducted to identify known and new social health markers. The codes were then categorized against our conceptual framework of social health., Results: Sixty-seven participants were interviewed. We identified various social health markers, ranging from those that are commonly used in epidemiological studies such as loneliness to novel markers of social health at the individual and the social environmental level. Examples of novel individual-level markers were efforts to comply with social norms and making own choices in, for example, keeping contact or refusing support. At a social environmental level, examples of novel markers were proximity (physical distance) and the function of the social network of helping the person maintaining dignity., Conclusions: The current study identified both well-known and novel social health markers in the context of dementia, mapped to the social health framework we developed. Future research should focus on translating these markers into validated measures and on developing social health focused interventions for persons with dementia., Competing Interests: The 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kristanti, Vernooij-Dassen, Jeon, Verspoor, Samtani, Ottoboni, Chattat, Brodaty, Lenart-Bugla, Kowalski, Rymaszewska, Szczesniak, Gerhardus, Seifert, A’la, Effendy and Perry.)

In the Western Pacific Region, the prevalence of dementia is expected to increase, however, the diversity of the region is expected to present unique challenges. The region has varying levels of preparedness, with a limited number of countries having a specific national dementia plan and awareness campaigns. Diversity of risk and healthcare services within the region is exerting impact on diagnosis, treatment, care, and support, with most countries being under resourced. Similarly, the ability to monitor dementia-related indicators and progress research, particularly relating to treatment and clinical trial access needs to be addressed. Countries require comprehensive national plans that lay out how resources will be allocated to improve dementia literacy, train, and support carers, mobilise resources to reduce risk factors and improve research capabilities. These plans need to be informed by consumers and tailored to the region to develop an inclusive society for people living with dementia and their families., Competing Interests: ST's research is supported by an NHMRC Ideas Grant (APP2029871), FightMND, and Lenity Australia. SHK was supported by a grant of the Korea Dementia Research Project through the Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (RS-2024-00348451)”. SW is the Clinical Lead/steering committee co-chair of the ADNeT Registry and received an honorium from ROCHE and Eisai for attendance at an advisory meeting. KJA received a speaker honorarium from Roche in 2023 and is supported by ARC FL19010001. CO is supported by a University of Sydney Robinson Fellowship and an Australian National Health and Medical Research Council EL2 Fellowship (2016866). CSYL is supported by the Sydney Medical School Foundation, University of Sydney. DF is supported by the Edwards Fund for Dementia Research and has received research grants from the Dementia Australia Research Foundation, outside the work submitted. OP is supported in part by an NHMRC Leadership Fellowship and has received research grants from the NHMRC and the Australian Research Council, outside the submitted work. JCM received a speaker honorarium; investigator-initiated research grant to institution from Eisai Australia. Y-HJ has received research grants from the National Health and Medical Research Council (NHMRC) and Arcare in Australia and travel support for invited talks from Singapore Sing Health, Northern Ireland Queen’s University Belfast, Hong Kong Jockey Club, and Korea National Health Insurance Service: Long-term Care, all outside the submitted work. MCK was supported by a NHMRC Practitioner Fellowship (1156093) and National Health and Medical Research Council of Australia Partnership Project (1153439). RHT is supported by a FightMND Mid-Career Fellowship and her research is supported by NSW Health and MNDRA. GS is supported by the Japan Agency for Medical Research and Development. SN received a speaker honorarium HT, SP, DT, SM, SA, VCTM, NS, JYS, have no conflict of interests to declare., (© 2024 The Authors.)

The Western Pacific region is home to approximately 25% of the world's population. In the absence of cures for dementia, it is essential to focus on appropriate and accessible care pathways for people living with dementia and their families. This approach will ultimately result in timely diagnosis and improved care and support. Ensuring adequate dementia care and support pathways has been a longstanding issue in many developed countries and is becoming a more prominent issue in countries with rising dementia prevalence rates but comparatively limited health resources. This Viewpoint provides an overview of system-level post-diagnosis dementia care, from diagnosis to rehabilitation, across some of the region's lower (Laos, Solomon Islands, Philippines) and upper (China) middle income and high income (South Korea, Australia) countries. Gaps and challenges in post-diagnosis dementia care, as well as suggestions for optimal care, are discussed. This Viewpoint highlights highly variable system level post-diagnosis dementia care in the region., Competing Interests: Y-HJ has received research grants from the National Health and Medical Research Council (NHMRC) and Arcare in Australia and travel support for invited talks from Singapore SingHealth, Northern Ireland Queen's University Belfast, Hong Kong Jockey Club, and Korea National Health Insurance Service: Long-term Care, all outside the submitted work. DF is supported by the Edwards Fund for Dementia Research and has received research grants from the Dementia Australia Research Foundation, outside the work submitted. GHS, JCD, RM, and SK have nothing to declare and no conflict of interest. HW has received research grant from the Science and Technology Innovation 2030 and Beijing Municipal Science and Technology Commission, outside the submitted work. OP is supported in part by NHMRC Leadership Fellowship and has received research grants from the NHMRC and the Australian Research Council, outside the submitted work., (© 2024 The Authors.)

The diagnostic decision point can help diagnose food allergies while reducing the need for oral food challenge (OFC) tests. We performed a multicenter survey of children aged 0-7 years from January 1, 2018 to March 31, 2022. A total of 231 children were recruited from 18 institutions. Wheat allergy (WA) or non-wheat allergy (NWA) was determined on the basis of OFC results and symptoms. There were no differences in age, sex, family history of allergy or allergic comorbidities between the WA and NWA groups. According to receiver operating characteristic analysis for wheat-specific immunoglobulin E (IgE), the optimal cutoff value, positive decision point, and negative decision point were 10.2, 33.5, and 0.41 kU/L, respectively. For the ω-5 gliadin-specific IgE, their values were 0.69, 3.88, and 0.01 kU/L, respectively. This new diagnostic decision point may be used to diagnose WA in Korean children., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

We aimed to determine the in vitro and in vivo synergistic antiallergic effect of guaijaverin and epigallocatechin gallate (EGCG) complex (GEC), and the antiallergic rhinitis (AR) properties of guaijaverin-rich Psidium guajava and EGCG-rich Camellia sinensis (ILS-F-2301). GEC showed synergistic inhibition of β-hexosaminidase by 4.20% and interleukin (IL)-4, -5, and -13 by 4.08%, 0.67%, and 4.71%, respectively, while increasing interferon (IFN)-γ by 12.43%, compared with EGCG only. In addition, 50 μg/mL of ILS-F-2301 inhibited β-hexosaminidase release, and inhibited IL-4, -5, and -13 by 61.54%, 58.79%, and 59.25%, respectively, while increasing IFN-γ (showing 133.14% activation). Moreover, 50 μg/mL of ILS-F-2301 suppressed p-STAT6 and GATA3, while p-STAT1 and T-bet increased, and 0.039 μg/mL of guaijaverin or 5.275 μg/mL of EGCG modulated T helper (Th)1- and Th2-related proteins. These data suggested that guaijaverin and EGCG in ILS-F-2301 was the main active compound involved in Th1/Th2 modulation. In the AR mouse model, the administration of ILS-F-2301 inhibited ovalbumin (OVA)-specific IgE, histamine in serum; it also inhibited IL-4 and -5 by 28.23% and 47.15%, respectively, while increasing IFN-γ (showing 37.11% activation), compared with OVA/Alu-treated mice. Taken together, our findings suggest that ILS-F-2301 is a functional food for alleviating anti-AR.

Noncystic fibrosis bronchiectasis is a chronic respiratory disease that carries high socioeconomic and medical burdens and is caused by diverse respiratory illnesses. To improve clinical outcomes, early recognition, active treatment of exacerbations, and prevention of further exacerbations are essential. However, evidence for the treatment and prevention of acute exacerbation of noncystic fibrosis bronchiectasis, especially in children, is lacking. Therefore, the evidence- and consensus-based guidelines for medical and nonmedical treatment strategies for noncystic fibrosis bronchiectasis in children and adolescents were developed by the Korean Academy of Pediatric Allergy and Respiratory Disease using the methods recommended by the Grading of Recommendations Assessment, Development, and Evaluation working group with evidence published through July 2, 2020. This guideline encompasses evidence-based treatment recommendations as well as expert opinions, addressing crucial aspects of the treatment and management of non-cystic fibrosis bronchiectasis in children. This includes considerations for antibiotics and airway clearance strategies, particularly in areas where evidence may be limited. Large, well-designed, and controlled studies are required to accumulate further evidence of management strategies for noncystic fibrosis bronchiectasis in children and adolescents.

As a defense mechanism against deleterious stimuli, inflammation plays a vital role in the development of many disorders, including atherosclerosis, inflammatory bowel disease, experimental autoimmune encephalomyelitis, septic and non-septic shock, and non-alcoholic fatty liver disease (NAFLD). Despite the serious adverse effects of extended usage, traditional anti-inflammatory medications, such as steroidal and non-steroidal anti-inflammatory medicines (NSAIDs), are commonly used for alleviating symptoms of inflammation. The PPARδ subtype of peroxisome proliferator-activated receptors (PPARs) has attracted interest because of its potential for reducing inflammation and related disorders. In this study, a series of 1,3,4-thiadiazole derivatives were designed, synthesized, and evaluated. Compound 11 exhibited potent PPARδ agonistic activity with EC 50 values 20 nM and strong selectivity over PPARα and PPARγ. Furthermore, compound 11 demonstrated favorable in vitro and in vivo pharmacokinetic properties. In vivo experiments using labeled macrophages and paw thickness measurements confirmed compound 11's potential to reduce macrophage infiltration and alleviate inflammation. These findings highlight compound 11 as a potent and promising therapeutic candidate for the treatment of acute inflammatory diseases and warrant further investigation to explore various biological roles., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jungwook chin reports financial support was provided by National Research Foundation of Korea. Taeho Lee reports financial support was provided by National Research Foundation of Korea. Jungwook chin has patent #PCT/KR2023/003210 pending to Daegu-Gyeongbuk Medical Innovation Foundation. If there are other authors, they 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 Masson SAS. All rights reserved.)

Histone deacetylases (HDACs) are important epigenetic regulators of gene expression and various cellular processes, and are potential targets for anticancer therapy. In particular, HDAC8 is a promising therapeutic target for childhood neuroblastoma. To date, five HDAC inhibitors have been approved as anticancer drugs; however, all are non-selective HDAC inhibitors with various side effects. Furthermore, many promising HDAC inhibitors incorporate hydroxamic acid as a zinc binding group (ZBG), which may be associated with toxicity. Therefore, identification of isoform-selective HDAC inhibitors with novel ZBG is crucial. Here, a series of sulfur-based selective HDAC8 inhibitors featuring a novel ZBG were identified by modifying the early hit, ajoene, a component of garlic. Structure-activity relationship studies uncovered potent and selective HDAC8 inhibitors, and docking studies provided a structural rationale for HDAC8 inhibitory activity. One of the potent compounds, (Z)-1-phenyl-7-(4-methoxyphenyl)-2,3,7-trithiahepta-4-ene-7-oxide (15c), exhibited antiproliferative activity, with a GI 50 of 2 µM, against neuroblastoma cell lines. 15c also showed significant in vivo efficacy in a neuroblastoma BE(2)-C xenograft model., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Quality of life (QOL) is associated with mortality in dialysis patients. However, the impact of QOL index or score on elderly patients undergoing maintenance dialysis is unclear. We analyzed the relationship between QOL domains and survival in elderly end-stage renal disease (ESRD) patients on dialysis., Methods: We included 492 incident ESRD patients aged ≥65 years from a Korean nationwide prospective cohort study who were assessed for QOL with a follow-up duration of 67.3 ± 34.6 months after dialysis initiation. Their QOL was evaluated using the Kidney Disease Quality of Life (KDQOL) instrument, and the effect of each QOL domain on mortality was analyzed. Multivariable Cox regression analysis was performed to identify independent risk factors for death after adjusting for confounding factors., Results: Low physical component summary (PCS) and Short Form-36 score were significantly associated with low survival rate ( P  < .001 and P  = .017, respectively), whereas the mental component summary and ESRD-targeted item scores were not correlated with survival rate. Multivariable Cox regression analysis confirmed that only a high PCS score was associated with better survival (hazard ratio 0.71; 95% confidence interval 0.52-0.97; P  = .031). Linear regression analysis revealed that age, sex, modified Charlson comorbidity index, albumin and intact parathyroid hormone were associated with PCS. Among the PCS items, only the physical functioning score was significantly associated with mortality ( P  = .017)., Conclusion: PCS was an independent risk factor for death in elderly ESRD patients. A higher physical functioning score was associated with a better outcome, suggesting the importance of physical condition in elderly dialysis patients., Competing Interests: The authors declare no competing interests, (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Food allergies can pose significant risks and profoundly impact the quality of life of children and their families, making them a major public health concern. Allergen avoidance has been the traditional mainstay of treatment; however, recent research has focused on various approaches to food allergen immunotherapy. This review summarizes the recent advancements in oral, sublingual, and epicutaneous immunotherapies, highlighting their respective advantages and disadvantages. The ultimate goal of food allergen immunotherapy is to maximize efficacy while minimizing risks, leading to the exploration of strategies such as low-dose immunotherapy and the use of biologics. When selecting candidates for immunotherapy among patients with food allergies, factors such as allergen characteristics, the likelihood of natural resolution, age, symptom severity, and impact on quality of life require consideration, and an individualized approach should be adopted to determine the most suitable treatment method.

Sorafenib (BAY 43-9006) was developed as a multi-kinase inhibitor to treat advanced renal cell, hepatocellular, and thyroid cancers. The cytotoxic effect of sorafenib on cancer cells results from not only inhibiting the MEK/ERK signaling pathway (the on-target effect) but also inducing oxidative damage (the off-target effect). The inhibitory effect of sorafenib on system Xc - (xCT), a cystine/glutamate antiporter, promotes ferroptosis induction and accounts for oxidative damage. While emerging studies on ferroptosis in cancers have garnered increasing attention, the lack of consideration for ferroptosis inducers (FINs) with favorable pharmacokinetics could be problematic. Herein, we remodeled the chemical structure of sorafenib, of which pharmacokinetics and safety are already assured, to customize the off-target effect (i.e., ferroptosis induction) to on-target by disrupting the adenine-binding motif. JB3, a sorafenib derivative (i.e., JB compounds), with a tenfold higher IC 50 toward RAF1 because of chemical remodeling, induced strong cytotoxicity in the elastin-sensitive lung cancer cells, while it was markedly reduced by ferrostatin-1. The 24% oral bioavailability of JB3 in rats accounted for a significant anti-tumor effect of orally administrated JB3 in xenograft models. These results indicate that JB3 could be further developed as an orally bioavailable FIN in novel anti-cancer therapeutics., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study aimed to evaluate the effect of micelle silymarin (MS) supplementation on productive performance, egg quality, and blood biochemical parameters in laying hens. A total of 384 (Hy-Line brown, 28-week-old) laying hens were randomly distributed into one of four dietary treatment groups (eight replication per treatment; 12 hens per replicate) for a 12-week long feeding trial. Hens were fed a basal diet with the addition of 0%, 0.02%, 0.04%, and 0.06% of MS respectively. The results expressed that egg production percentage and egg weight were linearly (p < 0.05) enhanced at Weeks 0-6, 7-12, and 0-12, when 0%, 0.02%, 0.04%, and 0.06% of MS were added to laying hen diets. The feed conversion ratio and feed intake improved (p < 0.05) linearly at Weeks 0-6, 7-12, and 0-12 with increasing levels of MS supplementation in laying hens. The eggshell thickness and eggshell strength were linearly (p < 0.05) improved at weeks 4, 8, and 12 with an MS-supplemented diet. Additionally, eggshell colour, Haugh unit, and albumin height had no significant (p > 0.05) difference throughout the experimental period with different levels of MS-supplemented diet. The yolk colour of eggs showed significant (p < 0.05) differences at weeks 8 and 12 with levels of the MS-supplemented diet. However, at the end of the trial, the blood profile indicated that cholesterol levels decreased (p < 0.05) linearly, and triglyceride levels showed a tendency to decrease (p < 0.10) with MS supplementation. In conclusion, increasing the level of MS addition in the laying hen diet improved the egg production percentage and egg quality, reducing cholesterol levels in Hy-Line brown hens. However, this study indicates that MS can be added to the diet of laying hens up to 0.06% for improved egg production and egg quality., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Advances in functional studies on epigenetic regulators have disclosed the vital roles played by diverse histone lysine demethylases (KDMs), ranging from normal development to tumorigenesis. Most of the KDMs are Jumonji C domain-containing (JMJD) proteins. Many of these KDMs remove methyl groups from histone tails to regulate gene transcription. There are more than 30 known KDM proteins, which fall into different subfamilies. Of the many KDM subfamilies, KDM3 (JMJD1) proteins specifically remove dimethyl and monomethyl marks from lysine 9 on histone H3 and other non-histone proteins. Dysregulation of KDM3 proteins leads to infertility, obesity, metabolic syndromes, heart diseases, and cancers. Among the KDM3 proteins, KDM3A has been largely studied in cancers. However, despite a number of studies pointing out their importance in tumorigenesis, KDM3B and KDM3C are relatively overlooked. KDM3B and KDM3C show context-dependent functions, showing pro- or anti-tumorigenic abilities in different cancers. Thus, this review provides a thorough understanding of the involvement of KDM3B and KDMC in oncology that should be helpful in determining the role of KDM3 proteins in preclinical studies for development of novel pharmacological methods to overcome cancer., (© 2024. The Author(s).)

Background: Efforts to profile atopic dermatitis (AD) tissues have intensified, yet comprehensive analysis of systemic immune landscapes in severe AD remains crucial., Methods: Employing single-cell RNA sequencing, we analyzed over 300,000 peripheral blood mononuclear cells from 12 severe AD patients (Eczema area and severity index (EASI) > 21) and six healthy controls., Results: Results revealed significant immune cell shifts in AD patients, including increased Th2 cell abundance, reduced NK cell clusters with compromised cytotoxicity, and correlated Type 2 innate lymphoid cell proportions with disease severity. Moreover, unique monocyte clusters reflecting activated innate immunity emerged in very severe AD (EASI > 30). While overall dendritic cells (DCs) counts decreased, a distinct Th2-priming subset termed "Th2&#95;DC" correlated strongly with disease severity, validated across skin tissue data, and flow cytometry with additional independent severe AD samples. Beyond the recognized role of Th2 adaptive immunity, our findings highlight significant innate immune cell alterations in severe AD, implicating their roles in disease pathogenesis and therapeutic potentials., Conclusion: Apart from the widely recognized role of Th2 adaptive immunity in AD pathogenesis, alterations in innate immune cells and impaired cytotoxic cells have also been observed in severe AD. The impact of these alterations on disease pathogenesis and the effectiveness of potential therapeutic targets requires further investigation., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: To investigate the incidence of implant-related pain after medial opening wedge high tibial osteotomy (MOWHTO) using a locking plate, to determine whether implant removal provides pain relief and functional improvement, and to evaluate bone healing and loss of correction after implant removal., Methods: Between March 2014 and September 2017, MOWHTO was performed without bone graft. The inclusion criteria were patients who underwent implant removal after MOWHTO and were followed up for a minimum of 2 years. Patients were evaluated for implant removal 1 and 2 years after surgery. Clinical and functional evaluations were conducted to investigate implant-related pain using the visual analog scale, Lysholm score, and Tegner score. The radiographic indices measured were the gap-filling rate, weightbearing line (WBL) ratio, hip-knee-ankle angle (HKAA), medial proximal tibial angle (MPTA), and posterior tibial slope angle (PTSA)., Results: A total of 55 patients were enrolled. Fifty-one (92.7%) patients experienced implant-related pain prior to implant removal, with 43 and 8 patients reporting mild pain and moderate pain, respectively. At 1 and 2 years after implant removal, mild pain occurred in 6 (10.9%) and 5 (9.1%) patients, respectively. The remaining patients reported no implant-related pain. Prior to implant removal and 1 year after implant removal, the Lysholm score improved from 77.0 ± 5.6 to 86.8 ± 5.7 (P < .001), and the Tegner score improved from 3.3 ± 1.2 to 3.9 ± 1.3 (P < .001). The mean gap-filling rate was 84.4% ± 9.6% at implant removal, and it significantly increased to 93.7% ± 5.4% and 97.4% ± 2.6% at 1 and 2 years after implant removal, respectively (P < .001). For the WBL ratio, HKAA, MPTA, and PTSA, no statistically significant differences were found after implant removal., Conclusions: The incidence of implant-related pain after MOWHTO using the medial proximal tibial locking plate was high. Implant removal provides pain relief and functional improvement (met minimal clinically important differences). Even after implant removal, bone healing progressed gradually without a loss of correction in all patients., Level of Evidence: Level IV, case series., Competing Interests: Disclosures The authors report the following potential conflicts of interest or sources of funding: This research was supported by grant 2020-01 from the Kangdong Sacred Heart Hospital Fund, Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2022R1I1A1A01071458), and Hallym University Research Fund. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Personal care interactions can provide vital opportunities for caregivers to engage with a person living with advanced dementia. However, interactions may also be a contentious experience, what makes this so is not fully understood. We aimed to examine features of personal care interactions between caregivers and people with advanced dementia to understand how care may be improved., Research Design and Methods: This was a naturalistic observation study using one-off video-recorded observations of personal care interactions between 14 people with advanced dementia and 12 caregivers (n = 7 care-home staff, n = 5 family carers) in the United Kingdom (total observation time 03:01:52). Observations were analyzed with observational video coding to determine the frequency of actions of people with dementia and qualitative content analysis for in-depth examination., Results: Refusals of care were present in 32% of video sections. Active engagement of people with dementia was observed in 66% of sections. Rare contentious interactional components were characterized by the person with dementia appearing to show uneasiness and caregivers being flustered and uncertain. However, caregivers typically emanated a nurturing attentiveness, were attuned to the person, and skilled in seamlessly supporting them through care activities., Discussion and Implications: Findings draw on real-world empirical evidence to reinvigorate the notion of person-centeredness in dementia care. The findings provide much needed insight into practical ways to improve care interactions for people with advanced dementia and enhance their personhood. Appropriate training/guidance for caregivers could support positive personal care experiences for both the person with dementia and caregiver., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Venoarterial extracorporeal membrane oxygenation (ECMO) is a key treatment method used with patients in cardiac arrest who do not respond to medical treatment. A critical step in initiating therapy is the insertion of ECMO cannulas. Peripheral ECMO cannulation methods have been preferred for extracorporeal cardiopulmonary resuscitation (ECPR)., Methods: Patients who underwent ECPR at Daegu Catholic University Medical Center between January 2017 and May 2023 were included in this study. We analyzed the impact of 2 different peripheral cannulation strategies (surgical cutdown vs. percutaneous cannulation) on various factors, including survival rate., Results: Among the 99 patients included in this study, 66 underwent surgical cutdown, and 33 underwent percutaneous insertion. The survival to discharge rates were 36.4% for the surgical cutdown group and 30.3% for the percutaneous group (p=0.708). The ECMO insertion times were 21.3 minutes for the surgical cutdown group and 10.3 minutes for the percutaneous group (p<0.001). The factors associated with overall mortality included a shorter low-flow time (hazard ratio [HR], 1.045; 95% confidence interval [CI], 1.019-1.071; p=0.001) and whether return of spontaneous circulation was achieved (HR, 0.317; 95% CI, 0.127-0.787; p=0.013). Low-flow time was defined as the time from the start of cardiopulmonary resuscitation to the completion of ECMO cannula insertion., Conclusion: No statistically significant difference in in-hospital mortality was observed between the surgical and percutaneous groups. However, regardless of the chosen cannulation strategy, reducing ECMO cannulation time was beneficial, as a shorter low-flow time was associated with significant benefits in terms of survival.

Purpose: This study explores the usability, usefulness and user experience of the Forward with Dementia website for people with dementia and family carers, and identifies strategies to improve web design for this population., Methods: The website was iteratively user-tested by 12 participants (five people with dementia, seven carers) using the Zoom platform. Data collection involved observations, semi-structured interviews and questionnaires. Integrative mixed-method data analysis was used, informed by inductive thematic qualitative analysis., Results: Users of Version 1 of the website experienced web functionality, navigation and legibility issues. Strategies for desirable web design were identified as simplifying functions, streamlining navigation and decluttering page layouts. Implementation of strategies produced improvements in usability, user experience and usefulness in Version 2, with mean System Usability Scale scores improving from 15 to 84, and mean task completion improving from 55% to 89%. The user journey for people with dementia and carers overlapped, but each group had their own unique needs in the context of web design., Conclusions: The interplay between a website's content, functionality, navigation and legibility can profoundly influence user perceptions of a website. Dementia-related websites play an important role in informing audiences of management strategies, service availability and planning for the progression of dementia. Findings of this study may assist in guiding future web development targeting this population.

Micelle silymarin (MS) is known for its various beneficial properties, including antiswelling, antioxidant, hepatoprotective and antidiabetic effects. The primary goal of this research was to investigate how MS impacts the performance, egg quality, water loss and blood profile of laying hens. 288 Hy-Line brown laying hens, 28 weeks in age, were utilized for this experiment. The hens were randomly allocated into three dietary treatment groups, with each group comprising eight replicates of 12 hens, each housed in individual pens with access to feed and water. Over a 12-week feeding trial, the hens were provided with a basal diet supplemented with different levels of MS: 0%, 0.03% and 0.06%. The results indicated that the inclusion of MS in the hens' diet did not have a significant impact on their performance (p > 0.05). However, Haugh units, egg weight and eggshell strength showed a linear improvement (p < 0.05) throughout the entire trial period with MS supplementation. Furthermore, there was a linear decrease in egg yolk colour and eggshell thickness showed linear improvements (p < 0.05), particularly during Week 8, with MS supplementation. Moreover, layers fed diet supplemented with MS showed a linear increased (p < 0.05) in albumen height and eggshell thickness in Week 12. In addition, egg water loss during Week 12, the third day of incubation, linearly decreased as an effect of the increasing level of the MS in the laying hen's diet (p < 0.05). Regarding blood profile parameters, the study revealed a tendency for alkaline phosphatase to decrease, whereas aspartate aminotransferase and cholesterol levels were linearly decreased (p < 0.05). In summary, increasing the level of MS supplementation in the diet of laying hens appeared to be beneficial in improving egg quality, slight improvement for egg water loss and certain aspects of blood profile parameters, without adversely affecting the hens' growth performance., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Rat animal models are widely used owing to their relatively superior cognitive abilities and higher similarity compared with mouse models to human physiological characteristics. However, their use is limited because of difficulties in establishing embryonic stem cells and performing genetic modifications, and insufficient embryological research. In this study, we established optimal superovulation and fertilized-egg transfer conditions, including optimal hormone injection concentration (≥150 IU/kg of PMSG and hCG) and culture medium (mR1ECM), to obtain high-quality zygotes and establish in vitro fertilization conditions for rats. Next, sgRNA with optimal targeting activity was selected by performing PCR analysis and the T7E1 assay, and the CRISPR/Cas9 system was used to construct a rat model for muscular dystrophy by inducing a deficiency in the fukutin gene without any off-target effect detected. The production of fukutin knockout rats was phenotypically confirmed by observing a drop-in body weight to one-third of that of the control group. In summary, we succeeded in constructing the first muscular dystrophy disease rat model using the CRISPR/CAS9 system for increasing future prospects of producing various animal disease models and encouraging disease research using rats.

Background Blood-brain barrier (BBB) permeability change is a possible pathologic mechanism of autoimmune encephalitis. Purpose To evaluate the change in BBB permeability in patients with autoimmune encephalitis as compared with healthy controls by using dynamic contrast-enhanced (DCE) MRI and to explore its predictive value for treatment response in patients. Materials and Methods This single-center retrospective study included consecutive patients with probable or possible autoimmune encephalitis and healthy controls who underwent DCE MRI between April 2020 and May 2021. Automatic volumetric segmentation was performed on three-dimensional T1-weighted images, and volume transfer constant ( K trans ) values were calculated at encephalitis-associated brain regions. K trans values were compared between the patients and controls, with adjustment for age and sex with use of a nonparametric approach. The Wilcoxon rank sum test was performed to compare K trans values of the good (improvement in modified Rankin Scale [mRS] score of at least two points or achievement of an mRS score of  ≤2) and poor (improvement in mRS score of less than two points and achievement of an mRS score >2) treatment response groups among the patients. Results Thirty-eight patients with autoimmune encephalitis (median age, 38 years [IQR, 29-59 years]; 20 [53%] female) and 17 controls (median age, 71 years [IQR, 63-77 years]; 12 [71%] female) were included. All brain regions showed higher K trans values in patients as compared with controls ( P < .001). The median difference in K trans between the patients and controls was largest in the right parahippocampal gyrus (25.1 × 10 -4 min -1 [95% CI: 17.6, 43.4]). Among patients, the poor treatment response group had higher baseline K trans values in both cerebellar cortices ( P = .03), the left cerebellar cortex ( P = .02), right cerebellar cortex ( P = .045), left cerebral cortex ( P = .045), and left postcentral gyrus ( P = .03) than the good treatment response group. Conclusion DCE MRI demonstrated that BBB permeability was increased in all brain regions in patients with autoimmune encephalitis as compared with controls, and baseline K trans values were higher in patients with poor treatment response in the cerebellar cortex, left cerebral cortex, and left postcentral gyrus as compared with the good response group. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Filippi and Rocca in this issue.

Objectives: To evaluate the need and feasibility of a nurse-led antimicrobial stewardship (AMS) programme in two Australian residential aged care homes (RACHs) to inform a stepped-wedged, cluster randomized controlled trial (SW-cRCT)., Methods: A mixed-methods pilot study of a nurse-led AMS programme was performed in two RACHs in Victoria, Australia (July-December 2019). The AMS programme comprised education, infection assessment and management guidelines, and documentation to support appropriate antimicrobial use in urinary, lower respiratory and skin/soft tissue infections. The programme was implemented over three phases: (i) pre-implementation education and integration (1 month); (ii) implementation of the intervention (3 months); and (iii) post-intervention evaluation (1 month). Baseline RACH and resident data and weekly infection and antimicrobial usage were collected and analysed descriptively to evaluate the need for AMS strategies. Feedback on intervention resources and implementation barriers were identified from semi-structured interviews, an online staff questionnaire and researcher field notes., Results: Six key barriers to implementation of the intervention were identified and used to refine the intervention: aged care staffing and capacity; access to education; resistance to practice change; role of staff in AMS; leadership and ownership of the intervention at the RACH and organization level; and family expectations. A total of 61 antimicrobials were prescribed for 40 residents over the 3 month intervention. Overall, 48% of antibiotics did not meet minimum criteria for appropriate initiation (respiratory: 73%; urinary: 54%; skin/soft tissue: 0%)., Conclusions: Several barriers and opportunities to improve implementation of AMS in RACHs were identified. Findings were used to inform a revised intervention to be evaluated in a larger SW-cRCT., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Targeted protein degradation (TPD) technology, such as proteolysis-targeting chimera (PROTAC), has become a new therapeutic modality. However, the degradation of undruggable proteins, such as those involved in protein-protein interactions (PPIs), using PROTAC is still limited owing to the difficulties in finding small-molecule binders of these proteins. To identify new chemical moieties that bind to the target sites of the protein of interest (POI), we conducted a site-specific and fragment-based covalent ligand screening using liquid chromatography-tandem mass spectrometry (LC-MS/MS). To apply the selected hits to the PROTAC approach, two-dimensional (2D) nuclear magnetic resonance (NMR) experiments were performed to evaluate the reversible binding of their analogs without covalent warheads. To proof the proposed approach, human mouse double minute (MDM)2 was selected as a model system since it is involved in PPIs and is known to be a degradable target protein. Western blot analysis showed that newly synthesized PROTACs, incorporated reversible analogs of screening hits, affected degradation in a dose- and time-dependent manner. This methodology makes it possible to use PROTAC technology to exploit previously undruggable proteins for TPD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Young Ho Jeon has patent #Pharmaceutical composition for preventing or treating hyper-proliferative disease including new small molecules inhibiting MDM2 protein pending to Korea University Sejong Campus. H.L., J.Y.L., H.J., H.Y.C., M.K., S.H.B., J.J., J.Y.K., and Y.H.J. have filled a provisional patent in the Korea related to this work., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objectives: To describe the development and use of an Evidence to Decision (EtD) framework when formulating recommendations for the Evidence-Based Clinical Practice Guideline for Deprescribing Opioid Analgesics., Study Design and Setting: Evidence was derived from an overview of systematic reviews and qualitative studies conducted with healthcare professionals and people who take opioids for pain. A multidisciplinary guideline development group conducted extensive EtD framework review and iterative refinement to ensure that guideline recommendations captured contextual factors relevant to the guideline target setting and audience., Results: The guideline development group considered and accounted for the complexities of opioid deprescribing at the individual and health system level, shaping recommendations and practice points to facilitate point-of-care use. Stakeholders exhibited diverse preferences, beliefs, and values. This variability, low certainty of evidence, and system-level policies and funding models impacted the strength of the generated recommendations, resulting in the formulation of four 'conditional' recommendations., Conclusion: The context within which evidence-based recommendations are considered, as well as the political and health system environment, can contribute to the success of recommendation implementation. Use of an EtD framework allowed for the development of implementable recommendations relevant at the point-of-care through consideration of limitations of the evidence and relevant contextual factors., Competing Interests: Declaration of competing interest Dr Reeve receives royalties from UpToDate (Wolters Kluwer) for writing a chapter on deprescribing. Professor Nielsen has received untied educational grants from Seqirus to study prescription opioid poisoning and was a named investigator on a buprenorphine depot implementation trial funded by Indivior, both unrelated to this work. Dr Holliday received an honorarium for two presentations from Indivior unrelated to this work. The University of Colorado receives remuneration for Professor Bero's work as Senior Research Integrity Editor for Cochrane. This is not related to the current work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The Carer Assessment of medicaTion management guidanCe for people with dementia at Hospital discharge (CATCH) tool was developed to examine the carer's experiences of medication management guidance delivery at discharge. This study explored its factor structure, characterized carers' experiences at discharge, and identified predictors of carer preparedness to manage medications at discharge., Methods: A cross-sectional survey of carers across Australia was distributed. Survey responses were analyzed descriptively, and exploratory factor and regression analyses were performed., Results: A total of 185 survey responses were completed. Exploratory factor analysis revealed 2 factors in the CATCH tool: (1) shared and supported decision-making in medication management (16 items loading 0.47 to 0.93); 2) provision of medication management guidance that is easy to understand (4 items loading (0.48 to 0.82). Internal consistency was acceptable (Cronbach alpha >0.8). Almost 18% of participants stated that they were not included in decisions about medications for people with dementia. The carer reported that the measure of how guidance is provided was positively related to their confidence in the management of medications postdischarge and satisfaction ( P < 0.05 for both)., Conclusions: The CATCH tool can give the patient and carer an opportunity to provide feedback on key elements of medication management guidance delivered at discharge., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: C-reactive protein-to-albumin ratio (CAR) is a prognostic marker in various diseases that represents patients' inflammation and nutritional status. Here, we aimed to investigate the prognostic value of CAR in critically ill patients with severe acute kidney injury requiring continuous renal replacement therapy (CRRT)., Methods: We retrospectively collected data from eight tertiary hospitals in Korea from 2006-2021. The patients were divided into quartiles according to CAR levels at the time of CRRT initiation. Cox regression analyses were performed to investigate the effect of CAR on in-hospital mortality. The mortality prediction performance of CAR was evaluated using the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI)., Results: In total, 3,995 patients who underwent CRRT were included, and the in-hospital mortality rate was 67.3% during the follow-up period. The 7-day, 30-day, and in-hospital mortality rates increased toward higher CAR quartiles (all p &lt; 0.001). After adjusting for confounding variables, the higher quartile groups had an increased risk of in-hospital mortality (quartile 3: adjusted hazard ratio [aHR], 1.26, 95% confidence interval [CI], 1.10-1.43, p &lt; 0.001; quartile 4: aHR, 1.22, 95% CI, 1.07-1.40, p = 0.003). CAR combined with Acute Physiology and Chronic Health Evaluation II or Sequential Organ Failure Assessment scores significantly increased the predictive power compared to each severity score alone for AUC, NRI, and IDI (all p &lt; 0.05)., Conclusions: A high CAR is associated with increased in-hospital mortality in critically ill patients requiring CRRT. The combined use of CAR and severity scores provides better predictive performance for mortality than the severity score alone., (© 2023 S. Karger AG, Basel.)

Background: Forward with Dementia is a co-designed campaign to improve communication of dementia diagnosis and post-diagnostic support., Methods: Webinars, a website, social and traditional media, and promotions through project partners were used to disseminate campaign messages to health and social care professionals (primary audience) and people with dementia and carers (secondary audience). The campaign ran between October 2021 and June 2022, with 3-months follow-up. The RE-AIM framework was used for process evaluation. Measurements included surveys and interviews, a log of activities (e.g. webinars, social media posts) and engagements (e.g. attendees, reactions to posts), and Google Analytics., Results: There were 29,053 interactions with campaign activities. More than three-quarters of professionals (n = 63/81) thought webinars were very or extremely helpful. Professionals and people with dementia and carers reported that the website provided appropriate content, an approachable tone, and was easy to use. Following campaign engagement, professionals planned to (n = 77/80) or had modified (n = 29/44) how they communicated the diagnosis and/or provided post-diagnostic information and referrals. Qualitative data suggested that the campaign may have led to benefits for some people with dementia and carers., Conclusions: Forward with Dementia was successful in terms of reach, appropriateness, adoption and maintenance for professionals, however flow-through impacts on people with dementia are not clear. Targeted campaigns can potentially change health professionals' communication and support around chronic diseases such as dementia., (© 2023. The Author(s).)