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Horng-Chyuan Lin,1– 3 Meng-heng Hsieh,1,2 Yu-Lun Lo,1,2 Hung-Yu Huang,1,2 Shih-Wei Huang,1,2 Chien-Da Huang,1,2 Po-Jui Chang,1,2 Chun-Yu Lo,1,2 Ting-Yu Lin,1,2 Yueh-Fu Fang,1,2 Shu-Min Lin,1,2 Chun-Yu Lin,1,2,* Ying-Huang Tsai1,2,4,* 1Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Respiratory Therapy, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 4Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital, Xiamen, 361028, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun-Yu Lin, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200 ext. 8467, Fax +886-3-3282474, Email pitiful1984@gmail.com Ying-Huang Tsai, Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation and Department of Respiratory Therapy, College of Medicine, Chang Gung University, 5 Fu-Hsing Street, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200 ext. 8470, Fax +886-3-3282474, Email chestmed@cgmh.org.twBackground: Non-cystic fibrosis bronchiectasis is associated with airway pathogen colonization. We planned to investigate the inflammatory markers in patients with different airway pathogens and their correlation with disease severity.Methods: We enrolled patients aged between 20 and 75 from October 2021 to August 2022. All patients had sputum evaluation for bacterial and fungal cultures before enrollment, and were classified into four groups according to the culture results.Results: Forty-four patients with non-CF bronchiectasis and six controls were enrolled and categorized as follows: Group 1, no pathogens identified in sputum cultures (n = 14); Group 2, positive fungal culture results (n = 18); Group 3, positive P. aeruginosa culture results (n = 7); and Group 4, positive culture results for both fungi and P. aeruginosa (n = 5). Group 4 had significantly higher serum defensin α 1, IL-6 and tissue inhibitors of MMP (TIMP)-1 levels than group 1 patients. The serum levels of IL-6 and TIMP-1 were positively correlated with the FACED score and negatively correlated with distance-saturation product.Conclusion: Significantly higher levels of serum IL-6 and TIMP-1 were found in the patients who had concomitant fungal and P. aeruginosa colonization, and were closely related to clinical severity and may have important roles in disease monitoring.Keywords: TIMP-1, non-cystic fibrosis bronchiectasis, clinical severity

Ting-Yu Lin,1,2 Firdian Makrufardi,3,4 Nguyen Thanh Tung,3,5 Amja Manullang,3 Po-Jui Chang,1,2 Chun-Yu Lo,1,2 Tzu-Hsuan Chiu,1 Pi-Hung Tung,1 Chiung-Hung Lin,1 Horng-Chyuan Lin,1,2 Chun-Hua Wang,1,2 Shu-Min Lin1,2 1Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Department of Child Health, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital, Yogyakarta, Indonesia; 5Otorhinolaryngology Department, Cho Ray Hospital, Ho Chi Minh City, VietnamCorrespondence: Shu-Min Lin, Department of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa N. Road, Taipei, Taiwan, Fax +886 33272474, Email smlin100@gmail.comBackground: Early-onset asthma (EOA) and late-onset asthma (LOA) are two distinct phenotypes. Air pollution has been associated with an increase in poorer asthma outcomes. The objective of this study was to examine the effects of traffic-related air pollution (TRAP) on asthma outcomes in EOA and LOA patients.Methods: A cross-sectional study was conducted on 675 asthma patients (LOA: 415) recruited from a major medical center in Taiwan. The land-use regression (LUR) model was used to estimate the level of exposure to PM10, PM2.5, NO2, and O3 on an individual level. We investigated the association between TRAP and asthma outcomes in EOA and LOA patients, stratified by allergic sensitization status, using a regression approach.Results: An increase in PM10 was associated with younger age of onset, increased asthma duration, and decreased lung function in EOA patients (p< 0.05). An increase in PM10 was associated with older age of onset, and decreased asthma duration, eosinophil count, and Asthma Control Test (ACT) score in LOA patients. An increase in PM2.5 was associated with younger age of onset, increased asthma duration, decreased eosinophil count, and lung function in EOA patients (p< 0.05). An increase in PM2.5 was associated with decreased lung function and ACT score in LOA patients. An increase in NO2 was associated with increased eosinophil count and decreased lung function in EOA patients (p< 0.05). An increase in O3 was associated with decreased lung function in LOA patients (p< 0.05). In addition, associations of TRAP with age of onset and eosinophil counts were mainly observed in both EOA and LOA patients with allergic sensitization, and an association with ACT was mainly observed in LOA patients without allergic sensitization.Conclusion: The impact of TRAP on age of onset, eosinophil count, and lung function in EOA patients, and ACT in LOA patients, was affected by the status of allergic sensitization.Keywords: air pollution, allergy, early-onset asthma, late-onset asthma, respiratory disease

Ting-Yu Lin,1,2 Chun-Yu Lo,1,2 Po-Jui Chang,1,2 Yu-Lun Lo,1,2 Chung-Shu Lee,1– 3 Chih-Hao Chang,1– 3 Chih-Teng Yu,1,2 Jonathan Huai Yao,1 Shu-Min Lin1,2 1Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Pulmonary and Critical Care Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City, TaiwanCorrespondence: Shu-Min Lin, Department of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa N. Road, Taipei, Taiwan, Fax + 886 33272474, Email smlin100@gmail.comBackground: The immunological features of eosinophils in early-onset asthma (EOA) differ from those in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA.Methods: Eosinophils obtained from well-controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes and specific markers related to cell functions in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function was further analyzed.Results: The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function.Conclusion: This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obesity by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.Graphical Abstract: Keywords: late-onset asthma, early-onset asthma, eosinophils, messenger RNA

Kuo-Ti Peng,1,2 Yao-Chang Chiang,3,4 Tsung-Yu Huang,5,6 Pei-Chun Chen,1 Pey-Jium Chang,6,7 Chiang-Wen Lee3,4,8,9 1Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County 61363, Taiwan; 2College of Medicine, Chang Gung University, Guishan District, Taoyuan City 33303, Taiwan; 3Department of Nursing, Chang Gung University of Science and Technology, Puzi City, Chiayi County 61363, Taiwan; 4Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City, Chiayi County 61363, Taiwan; 5Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 6Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan; 7Department of Nephrology, Chang Gung Memorial Hospital, Chiayi, Taiwan; 8Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Guishan District, Taoyuan City 33303, Taiwan; 9Department of Rehabilitation, Chang Gung Memorial Hospital, Puzi City, Chiayi County 61363, Taiwan Background: Periprosthetic joint infections (PJIs) have a high incidence of recurrence after total joint replacement and are difficult to treat by debridement or antibiotic treatment. Curcumin is a natural product with anti-inflammatory and anti-bacterial properties. The low bioactivity of curcumin in water restricts its clinical application. Curcumin nanoparticles (CURN) were developed to overcome this limitation.Methods: In this study, the therapeutic effects of CURN and their anti-inflammatory functions were investigated in a Staphylococcus aureus biofilm-induced PJIs model. Results: CURN first attenuated the biofilm-induced expansion of myeloid-derived suppressor cells (MDSCs) and then regulated M1- and M2-phenotypic MDSC expression. Down-regulation of cytokines and reactive oxygen species was considered as the mechanism of CURN in reversing the suppression of T cell proliferation. The recovery of bone permeative destruction demonstrated that CURN enhanced therapeutic potency of vancomycin in vivo. Conclusion: This is the first study to demonstrate that CURN may be useful for treating PJIs. Keywords: periprosthetic joint infections, osteomyelitis, Staphylococcus aureus, myeloid-derived suppressor cells

Huang-Shen Lin,1,2 Chun-Wen Cheng,3 Ming-Shyan Lin,4 Yen-Li Chou,5 Pey-Jium Chang,2 Jing-Chi Lin,6 Jung-Jr Ye3 1Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Chia-Yi, 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 3Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, 4Division of Cardiology, Chang Gung Memorial Hospital, Yunlin, 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Chia-Yi, 6Division of Allergy and Immunology and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chia-Yi, Taiwan Objectives: To investigate the clinical characteristics, adverse drug reactions, and outcomes of the oldest old patients (aged ≥80 years) with tuberculosis (TB) treated with rifampicin, isoniazid, and pyrazinamide (RIP)-containing regimens. Design: A retrospective chart review study. Setting: A 1,200-bed tertiary teaching hospital in southwest Taiwan. Participants: We conducted a retrospective observational study between January 1, 2005 and December 31, 2011. Seven hundred adult patients (aged ≥18 years) with TB treated with RIP-containing anti-TB regimens were reviewed, including 161 oldest old patients. Outcome measures: Clinical outcomes included clinical responsiveness and microbiological eradication. Adverse outcomes included drug-induced hepatitis, and other symptoms included gastrointestinal upset (eg, abdominal pain, vomiting, diarrhea, or dyspepsia), skin rash, joint pain, and hyperuricemia. Results: Compared with the non-oldest old adult patients, the oldest old patients more frequently had hepatitis (P=0.014), gastrointestinal upset (P=0.029), and unfavorable outcomes (P

The aim of this study was to determine the biodistribution, effective retention half-time (T(eff)), and internal organ dosimetry of (131)I administered to patients with papillary thyroid cancer after a total or near total thyroidectomy, and whole-body and organ activity was measured by gamma-camera imaging at 16 time points over 5 days following the administration of 1.1 GBq of (131)I in 5 patients. Whole-body scanning was performed by using a Siemens E-CAM() gamma-camera at a fixed distance of 5 cm from the patient. (131)I activity in regions of interest (ROIs) corresponding to the bladder, heart wall, kidneys, liver, lower gastrointestinal tract, lung, stomach, and thyroid remnants were measured, with measurements in the thigh used as the background. Most activity was localized to the lower gastrointestinal tract and thyroid remnants on day 1. The longest T(eff) was in the lung and the shortest was in the bladder (34.0 and 16.8 hours, respectively). The three organs with the highest absorbed doses per unit of administered activity were the lower gastrointestinal tract (2.03 mSv/MBq), the stomach (1.32 mSv/MBq), and the heart wall (1.24 mSv/MBq). T(eff) for thyroid remnants and the whole body were also estimated. We evaluated these organ doses to determine the normal tissues most likely at risk for stochastic and deterministic effects associated with (131)I therapy for thyroid cancer and benign disease. Our results represent preliminary findings, and the study will continue to accrue a greater number of study participants. [ABSTRACT FROM AUTHOR]

Communication between clinicians, technologists, and radiologists has become more complex, with Picture Archiving and Communication Systems (PACS) now allowing the radiologist to be removed from the physical location of the patients and the site of imaging. With these changes, effective communication becomes an ongoing challenge. Efficient communication of study interpretations has also become a priority for radiologists as they struggle to maintain relevance and provide added value to patient care when clinicians have ready access to radiology images. The purpose of this paper is to share our experience in developing and implementing the Collaborative Notification System (CNS), a communication tool used to inform referring clinicians of urgent findings-a.k.a. 'wet reads.' The system utilizes a system of web pages integrated into PACS for the sending and receiving of succinct messages to provide clinical information at the point of need. A second system of pager alerts provides notification of the need for such communication through a relatively unintrusive, one-way, acknowledged alert system. The CNS provides asynchronous, integrated communication for the reporting of urgent and emergent radiology findings in a complex, geographically distributed medical environment. [ABSTRACT FROM AUTHOR]

As the use of digital image management grows, radiology systems and infrastructures have become increasingly complex. The authors describe the use of a 'digital dashboard' with real-time, context-specific information that allows for efficient system management and clinical workflow. [ABSTRACT FROM AUTHOR]

Research supports both the role of lifestyle to promote health and well-being for older adults and preventive occupational therapy lifestyle redesign to promote engagement in life activities and enhance health for 'at risk' community living elders. Occupational therapy lifestyle redesign programs seek to provide older adults with strategies and opportunities to increase participation in identified meaningful activities for life satisfaction and to positively impact physical and mental health. This article reports on a 16-week lifestyle redesign pilot study conducted within medical model adult day programs with cognitively intact frail older adults. Data analysis found that experimental group subjects showed favorable results on Role Functioning, Bodily Pain, and General Health on the 36-item Short Form Health Survey (SF-36); Social Activity on the Functional Status Questionnaire; and on the Center for Epidemiologic Studies Depression Scale (CES-D). No statistically significant differences were noted between groups upon posttests after adjusting for covariates; however, a small sample resulted in limited statistical power. Further studies with a larger sample are recommended for convincing conclusions. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study explores the roles of place attachment, nonfamily social involvement, place valuation, and individual characteristics in the process of becoming at home in assisted living residences. METHODS: Purposive sampling and cross-sectional data by means of a questionnaire completed by current assisted living residents in four states (N = 297) were used to estimate a structural equation model to explain becoming at home. RESULTS: Place attachment to town and community is a necessary but not sufficient explainer of older adults' process of becoming at home. Nonfamily social involvement plays a pivotal role through which place attachment works to explain becoming at home. Both place valuation and nonfamily social involvement exhibit direct positive effects on the outcome. DISCUSSION: Findings support a transactional interpretation of assisted living as home. The relationship between place attachment to one's community and full integration into assisted living is more complex than currently acknowledged. [ABSTRACT FROM AUTHOR]

Background: Staphylococcal enterotoxin and fungal sensitization can influence asthma severity; however, the effects on the clinical outcomes of asthma remain unclear. This study investigated the clinical outcomes of asthma in patients with or without staphylococcal enterotoxin sensitization and further analyzed the effects of fungal sensitization on the clinical outcomes of patients with staphylococcal enterotoxin sensitization., Methods: This retrospective study included patients with asthma who had undergone a staphylococcal enterotoxin-specific immunoglobulin E test at our hospital between January and August 2021. Data on clinical manifestations, medication use, pulmonary function, clinic and emergency room visits and hospitalization were collected from 106 patients., Results: The prevalence of staphylococcal enterotoxin sensitization was 27.3%. Among the patients with staphylococcal enterotoxin sensitization, 50% also presented with fungal sensitization. The risk of hospitalization and emergency room visits was higher among patients with staphylococcal enterotoxin sensitization than among those without, as was the need for high-level asthma treatment, including triple inhaler therapy and biologics. After the 12-month Program enrollment, the rates of emergency room visits and hospitalization were similar in the two cohorts. Patients with concomitant staphylococcal enterotoxin and fungal sensitization exhibited a notable post-treatment decline in pulmonary function., Conclusion: Adherence to asthma treatment protocols was shown to improve clinical outcomes in patients with or without staphylococcal enterotoxin sensitization. Among patients with staphylococcal enterotoxin sensitization, those with concomitant fungal sensitization were more likely to exhibit a rapid decline in pulmonary function during a 1-year high-level treatment program., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of the Chang Gung Memorial Foundation (permit number: 202400365B0). Participant consent was waived due to the retrospective nature of the study. Consent for publication: All authors have agreed to the publication of this manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Eosinophil activation is associated with asthma. Whether air pollution affects the activation of blood eosinophils in patients with asthma remains unknown. In this study, we investigated the correlation between transcriptional activity in eosinophils and air pollutant exposure in patients receiving different levels of Global Initiative for Asthma (GINA) treatment., Methods: We evaluated the expression levels of activation- and function-related genes in eosinophils from patients with GINA 4 or 5 (n = 20), those with GINA 3 (n = 12), and normal individuals (n = 7); the eosinophils were activated with interleukin (IL)-5 or IL-17. A land use regression model was used to estimate air pollutant exposure. The correlations between mRNA expression, lung function, and air pollutant exposure were investigated., Results: The expression levels of TGFB1, IL7R, and TLR3 were significantly higher for patients with GINA 4 or 5 than for those with GINA 3 or normal individuals. The expression of certain genes, particularly in IL-17-activated eosinophils, was correlated with lung function decline in patients with GINA 4 or 5. For patients with GINA 4 or 5, NO 2 exposure was correlated with upregulated TGFB1 expression in IL-5-activated eosinophils. For patients with GINA 3, O 3 exposure was correlated with upregulated CCR5, IL5RA, IL7R, and TGFB1 expression in IL-17-activated eosinophils and upregulated IL7R expression in IL-5-activated eosinophils., Conclusion: Patients with GINA 4 or 5 may exhibit elevated transcriptional activity in eosinophils; this elevation is correlated with lung function decline. Air pollution may affect eosinophil mRNA expression in patients with asthma., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Necrotizing soft tissue infections (NSTI) are rapidly progressing and life-threatening conditions that require prompt diagnosis. However, differentiating NSTI from other non-necrotizing skin and soft tissue infections (SSTIs) remains challenging. We aimed to evaluate the diagnostic value of the biochemical analysis of soft tissue infectious fluid in distinguishing NSTIs from non-necrotizing SSTIs., Methods: This cohort study prospectively enrolled adult patients between May 2023 and April 2024, and retrospectively included patients from April 2019 to April 2023. Patients with a clinical suspicion of NSTI in the limbs who underwent successful ultrasound-guided aspiration to obtain soft tissue infectious fluid for biochemical analysis were evaluated and classified into the NSTI and non-necrotizing SSTI groups based on their final discharge diagnosis. Common extravascular body fluid (EBF) criteria were applied., Results: Of the 72 patients who met the inclusion criteria, 10 patients with abscesses identified via ultrasound-guided aspiration were excluded. Based on discharge diagnoses, 39 and 23 patients were classified into the NSTI and non-necrotizing SSTI groups, respectively. Biochemical analysis revealed significantly higher albumin, lactate, lactate dehydrogenase (LDH), and total protein levels in the NSTI group than in the non-necrotizing SSTI group, and the NSTI group had significantly lower glucose levels and pH in soft tissue fluids. In the biochemical analysis, LDH demonstrated outstanding discrimination (area under the curve (AUC) = 0.955; p < 0.001) among the biochemical markers. Albumin (AUC = 0.884; p < 0.001), lactate (AUC = 0.891; p < 0.001), and total protein (AUC = 0.883; p < 0.001) levels also showed excellent discrimination. Glucose level (AUC = 0.774; p < 0.001) and pH (AUC = 0.780; p < 0.001) showed acceptable discrimination. When the EBF criteria were evaluated, the total scores of Light's criteria (AUC = 0.925; p < 0.001), fluid-to-serum LDH ratio (AUC = 0.929; p < 0.001), and fluid-to-serum total protein ratio (AUC = 0.927; p < 0.001) demonstrated outstanding discrimination., Conclusion: Biochemical analysis and EBF criteria demonstrated diagnostic performances ranging from acceptable to outstanding for NSTI when analyzing soft tissue infectious fluid. These findings provide valuable diagnostic insights into the recognition of NSTI. Further research is required to validate these findings., (© 2024. The Author(s).)

Background and Purpose: Stereotactic ablative body radiotherapy (SABR) is an effective treatment for localized renal cell carcinoma (RCC). However, the role of primary site SABR for locally recurrent or metastatic RCC is unclear. Here, we report outcomes of primary SABR across a diverse cohort of localized, recurrent, and metastatic RCC patients treated at our institution., Materials and Methods: RCC patients treated with SABR to lesions of the kidney or nephrectomy bed at our institution with at least 6 months of follow-up were included for analysis. Local control, overall survival, and freedom from distant failure were estimated using the Kaplan-Meier method. Estimated glomerular filtration rate (eGFR) was assessed at baseline and following SABR., Results: Fifty-three patients received primary site SABR. Thirty-seven (70 %) patients had localized RCC, and 16 (30 %) had metastatic RCC. Seven (13 %) had locally recurrent RCC after prior surgery or ablation. The median tumor size was 4.5 cm (IQR 3.7-6.3). At a median follow-up of 23 months (IQR 12-35), 2-year local control was 100 %, and 3-year local control was 94.4 % (95 % CI 84.4 %-100 %). Among patients with initially localized disease, the 2-year freedom from distant failure was 94.6 % (95 % CI 87.6 %-100 %), and the 2-year overall survival was 66.5 % (95 % CI 51.9 %-85.2 %). Twelve (23 %) patients experienced acute grade 1-2 treatment-related toxicity (nausea, vomiting, or small bowel). There were no acute grade 3-4 toxicities. Two (3.8 %) patients developed late grade 3 gastrointestinal toxicity. The median baseline eGFR was 51 mL/min/1.73 m 2 (IQR 38-77). At 1-year post-SABR, the median eGFR decline was 5 mL/min/1.73 m 2 (IQR -3 to 9). One patient required dialysis following SABR., Conclusion: This analysis demonstrates excellent local control rates across patients with localized, recurrent, and metastatic RCC treated with SABR. Treatment was associated with minimal eGFR decline., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Walter M. Stadler has acted as a member of the Data and Safety Monitoring Board for AstraZeneca, Merck, Pfizer, and Treadwell Therapeutics, and a consultant for AstraZeneca, Aveo, Caremark/CVS, EMA Wellness, Fortress Biotech, and XenCor. Sean P. Pitroda is co-founder and Chief Medical Officer of PersonaDx (including equity) and reports intellectual property unrelated to the current manuscript., (© 2024 The Author(s).)

Preparing electrospun fibers by applying a potential difference between a polymeric solution and a contacting substrate is increasingly attracting attention in tissue engineering applications. Among the numerous polymers, polycaprolactone (PCL) bioscaffold has been widely investigated due to its biocompatibility and biodegradability. Bioactive powder can be added to further improve its performance. In the present study, bioactive glass powder modified by adding 0-6 wt.% antibacterial zinc element (coded as ZBG) was prepared through the sol-gel process. Furthermore, PCL bioscaffolds with various ZBG additions were prepared using the electrospinning technique. The zinc-doped bioactive glass powder and electrospun PCL/ZBG bioscaffolds were evaluated using scanning electron microscopy, X-ray diffraction and Fourier-transform infrared spectroscopy to determine their structural properties. Additionally, in vitro bioactivity, biocompatibility and antibacterial performance were investigated. Experimental results showed that sol-gelled ZBG powder possessed superior bioactivity and 0.8 g ZBG was the optimal addition to prepare PCL/ZBG bioscaffolds with. All the electrospun PCL/ZBG bioscaffolds were biocompatible and their antibacterial performance against two S. aureus strains (SA133 and Newman) improved with increasing zinc concentration. Electrospun PCL/ZBG bioscaffolds exhibited excellent bioactivity and have great potential for biomedical application.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 45 is a globally disseminated MRSA lineage. Herein, we investigated whether MRSA ST45 isolates from cellulitis and from osteomyelitis display distinctive phenotypic and genomic characteristics., Methods: A total of 15 MRSA ST45 isolates from cellulitis (CL-MRSA; n = 6) or osteomyelitis (OM-MRSA; n = 9) were collected in a Taiwan hospital. These MRSA ST45 isolates were characterized for their antimicrobial susceptibility, biofilm-forming ability, cellular infectivity in vitro, and pathogenicity in vivo. Four CL-MRSA and 6 OM-MRSA ST45 isolates were selected for whole-genome sequencing (WGS)., Results: Antibiotic resistance tests showed that all OM-MRSA ST45 strains, but not CL-MRSA ST45 strains, were resistant to ciprofloxacin, levofloxacin, gentamicin, and doxycycline. Compared to the CL-MRSA ST45 isolates, the OM-MRSA ST45 isolates had stronger biofilm-forming ability and cellular infectivity and caused more severe disease in mice. WGS analysis revealed that these OM-MRSA ST45 isolates carry multiple common mutations or polymorphisms in genes associated with antibiotic resistance and virulence. Moreover, the transposable elements IS256 and IS257R2 were found only in the OM-MRSA ST45 isolates., Conclusions: The emergence and spread of the highly pathogenic and multidrug-resistant ST45 MRSAs identified from osteomyelitis may pose a serious threat on public health., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Carburized steel shafts are commonly used in industry due to their good wear resistance and fatigue life. If the surface of carburized shafts exhibits an undesired tensile stress, shot peening treatment may be required to alter the stress condition on the surface. In the present study, the effects of shot peening pressure (3-5 kg/cm 2 ), time (32-64 s), and material (stainless steel, carbon steel, and glass) on the residual stress, retained austenite, microhardness, and surface roughness of the carburized shafts were investigated. The experimental results showed that the surface residual tensile stress was changed into compressive stress after the shot peening treatment. The shot peening effects increased with the increasing peening pressure and time. In addition, a significant decrease in the amount of retained austenite in the subsurface region was observed. Peening with different materials can affect the peening effect. Using glass pellets exhibited the best shot peening effect but suffered massive pellet fracture during processing. In overall consideration, the optimal peening parameters for carburized steel shafts for practical industrial applications involved using the stainless-steel pellets with a peening pressure of 5 kg/cm 2 and a peening time of 64 s. The maximum residual stress was -779 MPa at a depth of 0.02 mm, while the highest surface microhardness was 827 HV 0.1 .

Although all herpesviruses utilize a highly conserved replication machinery to amplify their viral genomes, different members may have unique strategies to modulate the assembly of their replication components. Herein, we characterize the subcellular localization of seven essential replication proteins of varicella-zoster virus (VZV) and show that several viral replication enzymes such as the DNA polymerase subunit ORF28, when expressed alone, are localized in the cytoplasm. The nuclear import of ORF28 can be mediated by the viral DNA polymerase processivity factor ORF16. Besides, ORF16 could markedly enhance the protein abundance of ORF28. Noteworthily, an ORF16 mutant that is defective in nuclear transport still retained the ability to enhance ORF28 abundance. The low abundance of ORF28 in transfected cells was due to its rapid degradation mediated by the ubiquitin-proteasome system. We additionally reveal that radicicol, an inhibitor of the chaperone Hsp90, could disrupt the interaction between ORF16 and ORF28, thereby affecting the nuclear entry and protein abundance of ORF28. Collectively, our findings imply that the cytoplasmic retention and rapid degradation of ORF28 may be a key regulatory mechanism for VZV to prevent untimely viral DNA replication, and suggest that Hsp90 is required for the interaction between ORF16 and ORF28., 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 B.V. All rights reserved.)

Barium zirconate (BaZrO 3 , BZO), which exhibits superior mechanical, thermal, and chemical stability, has been widely used in many applications. In dentistry, BZO is used as a radiopacifier in mineral trioxide aggregates (MTAs) for endodontic filling applications. In the present study, BZO was prepared using the sol-gel process, followed by calcination at 700-1000 °C. The calcined BZO powders were investigated using X-ray diffraction and scanning electron microscopy. Thereafter, MTA-like cements with the addition of calcined BZO powder were evaluated to determine the optimal composition based on radiopacity, diametral tensile strength (DTS), and setting times. The experimental results showed that calcined BZO exhibited a majority BZO phase with minor zirconia crystals. The crystallinity, the percentage, and the average crystalline size of BZO increased with the increasing calcination temperature. The optimal MTA-like cement was obtained by adding 20% of the 700 °C-calcined BZO powder. The initial and final setting times were 25 and 32 min, respectively. They were significantly shorter than those (70 and 56 min, respectively) prepared with commercial BZO powder. It exhibited a radiopacity of 3.60 ± 0.22 mmAl and a DTS of 3.02 ± 0.18 MPa. After 28 days of simulated oral environment storage, the radiopacity and DTS decreased to 3.36 ± 0.53 mmAl and 2.84 ± 0.27 MPa, respectively. This suggests that 700 °C-calcined BZO powder has potential as a novel radiopacifier for MTAs.

Barium titanate (BaTiO 3 , BTO), conventionally used for dielectric and ferroelectric applications, has been assessed for biomedical applications, such as its utilization as a radiopacifier in mineral trioxide aggregates (MTA) for endodontic treatment. In the present study, BTO powders were prepared using the sol-gel process, followed by calcination at 400-1100 °C. The X-ray diffraction technique was then used to examine the as-prepared powders to elucidate the effect of calcination on the phase composition and crystalline size of BTO. Calcined BTO powders were then used as radiopacifiers for MTA. MTA-like cements were investigated to determine the optimal calcination temperature based on the radiopacity and diametral tensile strength (DTS). The experimental results showed that the formation of BTO phase was observed after calcination at temperatures of 600 °C and above. The calcined powders were a mixture of BaTiO 3 phase with residual BaCO 3 and/or Ba 2 TiO 4 phases. The performance of MTA-like cements with BTO addition increased with increasing calcination temperature up to 1000 °C. The radiopacity, however, decreased after 7 days of simulated oral environmental storage, whereas an increase in DTS was observed. Optimal MTA-like cement was obtained by adding 40 wt.% 1000 °C-calcined BTO powder, with its resulting radiopacity and DTS at 4.83 ± 0.61 mmAl and 2.86 ± 0.33 MPa, respectively. After 7 days, the radiopacity decreased slightly to 4.69 ± 0.51 mmAl, accompanied by an increase in DTS to 3.13 ± 0.70 MPa. The optimal cement was biocompatible and verified using MG 63 and L929 cell lines, which exhibited cell viability higher than 95%.

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO 3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases., (© 2024 Wiley‐VCH GmbH.)

The (pro)renin receptor ((P)RR) is an essential component of the renin-angiotensin system (RAS) as a specific single-pass transmembrane receptor for prorenin and renin and has now emerged as a multifunctional protein implicated in a wide variety of developmental and physio-pathological processes and pathways. The (P)RR may be of pathological significance in metabolic syndrome. The (P)RR has received much consideration; substantial efforts have been made to understand the localization, regulation, and function of the (P)RR at both a molecular and system level. (P)RR regulation of cell function depends on whether it is intact or cleaved into its constituent forms. Therefore, the present chapter describes immunohistochemical approaches to examine the expression of (P)RR in various organs. It was shown that different molecular forms of (P)RR could be present in different tissue compartments in almost all organs. Among them, the liver has high PRR activity. Our findings could elucidate more detailed distribution of different (P)RR molecular forms in different organs, which could provide useful information to further investigate the pathophysiological mechanisms of the development of various diseases in the future.

Mineral trioxide aggregates (MTA) are commonly used as endodontic filling materials but suffer from a long setting time and tooth discoloration. In the present study, the feasibility of using barium titanate (BTO) for discoloration and a calcium chloride (CaCl 2 ) solution to shorten the setting time was investigated. BTO powder was prepared using high-energy ball milling for 3 h, followed by sintering at 700-1300 °C for 2 h. X-ray diffraction was used to examine the crystallinity and crystalline size of the as-milled and heat-treated powders. MTA-like cements were then prepared using 20-40 wt.% BTO as a radiopacifier and solidified using a 0-30% CaCl 2 solution. The corresponding radiopacity, diametral tensile strength (DTS), initial and final setting times, and discoloration performance were examined. The experimental results showed that for the BTO powder prepared using a combination of mechanical milling and heat treatment, the crystallinity and crystalline size increased with the increasing sintering temperature. The BTO sintered at 1300 °C (i.e., BTO-13) exhibited the best radiopacity and DTS. The MTA-like cement supplemented with 30% BTO-13 and solidified with a 10% CaCl 2 solution exhibited a radiopacity of 3.68 ± 0.24 mmAl and a DTS of 2.54 ± 0.28 MPa, respectively. In the accelerated discoloration examination using UV irradiation, the color difference was less than 1.6 and significantly lower than the clinically perceptible level (3.7). This novel MTA exhibiting a superior color stability, shortened setting time, and excellent biocompatibility has potential for use in endodontic applications.

Purpose: To address the contentious data sharing across hospitals, this study adopted a novel approach, federated learning (FL), to establish an aggregate model for acute kidney injury (AKI) prediction in critically ill patients in Taiwan., Methods: This study used data from the Critical Care Database of Taichung Veterans General Hospital (TCVGH) from 2015 to 2020 and electrical medical records of the intensive care units (ICUs) between 2018 and 2020 of four referral centers in different areas across Taiwan. AKI prediction models were trained and validated thereupon. An FL-based prediction model across hospitals was then established., Results: The study included 16,732 ICU admissions from the TCVGH and 38,424 ICU admissions from the other four hospitals. The complete model with 60 features and the parsimonious model with 21 features demonstrated comparable accuracies using extreme gradient boosting, neural network (NN), and random forest, with an area under the receiver-operating characteristic (AUROC) curve of approximately 0.90. The Shapley Additive Explanations plot demonstrated that the selected features were the key clinical components of AKI for critically ill patients. The AUROC curve of the established parsimonious model for external validation at the four hospitals ranged from 0.760 to 0.865. NN-based FL slightly improved the model performance at the four centers., Conclusion: A reliable prediction model for AKI in ICU patients was developed with a lead time of 24 h, and it performed better when the novel FL platform across hospitals was implemented., Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00248-5., Competing Interests: Conflict of interestWe declare no competing interests., (© The Author(s) 2023.)

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitations, occurring mainly in the small airways. Weakness in the respiratory muscles contributes to dyspnea and a decreased exercise capacity in COPD patients. This study aimed to investigate the effectiveness of home-based inspiratory muscle training (IMT) on small airway function and symptoms in COPD patients. This research adopted a non-randomized controlled-study quasi-experimental design. The IMT program consisted of two 15 min sessions·d -1 , 5 d·wk -1 , with 40% of the maximal inspiratory pressure (PI max ) on each participant's assessment results and lasted for 12 weeks. Small airway function was assessed using plethysmography at baseline and after 12 weeks. The modified British Medical Research Council (mMRC), COPD assessment test (CAT), PI max , and 6 min walking distance (6MWD) were recorded at baseline as well as four, eight, and twelve weeks. Twenty-three participants with at least moderate COPD were enrolled in IMT ( n = 16) or in the control group ( n = 7) in this study. The study participants were mostly male (82.6%), and the average age was 68.29 ± 10.87 years, with a mean body mass index (BMI) of 23.54 ± 4.79. After 12 weeks, the ratios of the first second of forced expiration to the forced vital capacity (FEV 1 /FVC%) ( B coefficient [95% Wald confidence interval] of 5.21 [0.46 to 9.96], p = 0.032), forced expiratory flow (FEF 25-75% ) (0.20 [0.04 to 0.35] L/s, p = 0.012), and FEF 50% (0.26 [0.08 to 0.43] L/s, p = 0.004) in the IMT group were significantly better than in the control group. The IMT group showed significantly lower CAT scores at week 8 (-5.50 [-10.31 to -0.695] scores, p = 0.025) than the control group. The mMRC grade, CAT score, PI max , and 6MWD were significantly improved compared to their values at baseline in the IMT group. Home-based IMT effectively improved post-bronchodilator small airway function and disease-associated symptoms in COPD patients.

Background: To assess the effect of a commercial artificial intelligence (AI) solution implementation in the emergency department on clinical outcomes in a single level 1 trauma center., Methods: A retrospective cohort study for two time periods-pre-AI (1.1.2017-1.1.2018) and post-AI (1.1.2019-1.1.2020)-in a level 1 trauma center was performed. The ICH algorithm was applied to 587 consecutive patients with a confirmed diagnosis of ICH on head CT upon admission to the emergency department. Study variables included demographics, patient outcomes, and imaging data. Participants admitted to the emergency department during the same time periods for other acute diagnoses (ischemic stroke (IS) and myocardial infarction (MI)) served as control groups. Primary outcomes were 30- and 120-day all-cause mortality. The secondary outcome was morbidity based on Modified Rankin Scale for Neurologic Disability (mRS) at discharge., Results: Five hundred eighty-seven participants (289 pre-AI-age 71 ± 1, 169 men; 298 post-AI-age 69 ± 1, 187 men) with ICH were eligible for the analyzed period. Demographics, comorbidities, Emergency Severity Score, type of ICH, and length of stay were not significantly different between the two time periods. The 30- and 120-day all-cause mortality were significantly reduced in the post-AI group when compared to the pre-AI group (27.7% vs 17.5%; p = 0.004 and 31.8% vs 21.7%; p = 0.017, respectively). Modified Rankin Scale (mRS) at discharge was significantly reduced post-AI implementation (3.2 vs 2.8; p = 0.044)., Conclusion: The added value of this study emphasizes the introduction of artificial intelligence (AI) computer-aided triage and prioritization software in an emergent care setting that demonstrated a significant reduction in a 30- and 120-day all-cause mortality and morbidity for patients diagnosed with intracranial hemorrhage (ICH). Along with mortality rates, the AI software was associated with a significant reduction in the Modified Ranking Scale (mRs)., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Supine position reduces nasal patency compared with that in the sitting position; however, data on the effects of prone position on nasal patency is lacking., Methods: We assessed the nasal patency of 30 healthy individuals without upper respiratory tract disorders by using visual analog scale (VAS) score and acoustic rhinometry in 7 positions: sitting; frontal, right, and left supine; and frontal, right, and left prone., Results: According to the VAS scores, compared with that in the sitting position, both the supine and prone positions significantly increased subjective nasal obstruction ( P < .001). The prone position had a more significant effect than did the supine position ( P = .017). The results of minimal cross-sectional area measured through acoustic rhinometry demonstrated that both the supine and prone positions reduced the nasal patency significantly, but without significant differences between the effects of prone and supine positions ( P = .794)., Conclusion: This is the first study to elucidate that the prone position can significantly reduce the nasal patency in healthy individuals through subjective and objective assessments., Level of Evidence: IV.

Aim: To evaluate optic nerve head (ONH) vessel density (VD) changes after cataract surgery using optical coherence tomography angiography (OCTA)., Methods: This was a prospective observational study. Thirty-four eyes with mild/moderate cataracts were included. ONH scans were obtained before and 3mo after cataract surgery using OCTA. Radial peripapillary capillary (RPC) density, all VD, large VD and retinal nerve fiber layer thickness (RNFLT) in total disc, inside disc, and different peripapillary sectors were assessed and analyzed. Image quality score (QS), fundus photography grading and best-corrected visual acuity (BCVA) were also collected, and correlation analyses were performed between VD change and these parameters., Results: Compared with baseline, both RPC and all VD increased in inside disc area 3mo postoperatively (from 47.5%±5.3% to 50.2%±3.7%, and from 57.87%±4.30% to 60.47%±3.10%, all P <0.001), but no differences were observed in peripapillary area. However, large VD increased from 5.63%±0.77% to 6.47%±0.72% in peripapillary ONH region ( P <0.001). RPC decreased in inferior and superior peripapillary ONH parts ( P =0.019, <0.001 respectively). There were obvious negative correlations between RPC change and large VD change in inside disc, superior-hemi, and inferior-hemi ( r =-0.419, -0.370, and -0.439, P =0.017, 0.044, and 0.015, respectively). No correlations were found between VD change and other parameters including QS change, fundus photography grading, postoperative BCVA, and postoperative peripapillary RNFLT., Conclusion: RPC density and all VD in the inside disc ONH region increase 3mo after surgery in patients with mild to moderate cataract. No obvious VD changes are found in peripapillary area postoperatively., (International Journal of Ophthalmology Press.)

Chronic kidney disease (CKD) is a serious public health problem. Due to a high variability in the speed of CKD progression to end-stage renal disease (ESRD) and the critical involvement of Wnt/β-catenin signaling in CKD, we investigated the role of the Wnt antagonist Dickkopf-1 (DKK1) in CKD progression. Our data revealed that patients with CKD stages 4-5 had higher DKK1 levels in their serum and renal tissues than the control subjects. In an 8-year follow-up, the serum DKK1-high group in the enrolled CKD patients showed a faster progression to ESRD than the serum DKK1-low group. Using a rat model of 5/6 nephrectomy (Nx)-induced CKD, we consistently detected elevated serum levels and renal production of DKK1 in 5/6 Nx rats compared to sham-operated rats. Importantly, the knockdown of the DKK1 levels in the 5/6 Nx rats markedly attenuated the CKD-associated phenotypes. Mechanistically, we demonstrated that the treatment of mouse mesangial cells with recombinant DKK1 protein induced not only the production of multiple fibrogenic proteins, but also the expression of endogenous DKK1. Collectively, our findings suggest that DKK1 acts as a profibrotic mediator in CKD, and elevated levels of serum DKK1 may be an independent predictor of faster disease progression to ESRD in patients with advanced CKD.

Background: Dying at home accompanied by loved-ones is regarded favorably and brings good luck in Taiwan. This study aimed to examine the relevant factors affecting whether an individual dies at home or not in a group of terminal patients receiving palliative home care service., Methods: The patients who were admitted to a palliative home care service at a hospital-affiliated home health care agency were consecutively enrolled between March 1, 2021 and March 31, 2022. During the period of care, the instruments of the palliative care outcomes collaboration was used to assess patients in each home visit twice a week, including symptom assessment scale, palliative care problem severity score, Australia-modified Karnofsky performance status, resource utilization groups-activities of daily living, and palliative care phase., Results: There were 56 participants (53.6% female) with a median age of 73.0 years (interquartile range (IQR) 61.3-80.3 y/o), of whom 51 (91.1%) patients were diagnosed with cancer and 49 (96.1%) had metastasis. The number of home visits was 3.5 (IQR 2.0-5.0) and the average number of days under palliative home care service was 31 (IQR 16.3-51.5) before their death. After the end of the study, there was a significant deterioration of sleeping, appetite, and breathing problems in the home-death group, and appetite problems in the non-home death patients. However, physician-reported psychological/spiritual problems improved in the home-death group, and pain improved in the non-home death patients. Physical performance deteriorated in both groups, and more resource utilization of palliative care was needed. The 44 patients who died at home had greater cancer disease severity, fewer admissions, and the proportion of families desiring a home death for the patient was higher., Conclusions: Although the differences in palliative outcome indicators were minor between patients who died at home and those who died in the hospital, understanding the determinants and change of indicators after palliative care service at different death places may be helpful for improving the quality of end-of-life care., (© 2023. The Author(s).)

Human noroviruses (HuNVs) are the leading cause of gastroenteritis worldwide. NS1.2 is critical for HuNV pathogenesis, but the function is still unclear. The GII NS1.2 of HuNVs, unlike GI NS1.2, was localized to the endoplasmic reticulum (ER) and lipid droplets (LDs) and is accompanied by a distorted-filamentous ER morphology and aggregated-enlarged LDs. LC3 was recruited to the NS1.2-localized membrane through an autophagy-independent pathway. NS1.2, expressed from a cDNA clone of GII.4 norovirus, formed complexes with NTPase and NS4, which exhibited aggregated vesicle-like structures that were also colocalized with LC3 and LDs. NS1.2 is structurally divided into three domains from the N terminus: an inherently disordered region (IDR), a region that contains a putative hydrolase with the H-box/NC catalytic center (H-box/NC), and a C-terminal 251-330 a.a. region containing membrane-targeting domain. All three functional domains of NS1.2 were required for the induction of the filamentous ER. The IDR was essential for LC3 recruitment by NS1.2. Both the H-Box/NC and membrane-targeting domains are required for the induction of aggregated-enlarged LDs, NS1.2 self-assembly, and interaction with NTPase. The membrane-targeting domain was sufficient to interact with NS4. The study characterized the NS1.2 domain required for membrane targeting and protein-protein interactions, which are crucial for forming a viral replication complex.

Hydrogel-based microspheres prepared by emulsification have been widely used as drug carriers, but biocompatibility remains a challenging issue. In this study, gelatin was used as the water phase, paraffin oil was used as the oil phase, and Span 80 was used as the surfactant. Microspheres were prepared using a water-in-oil (W/O) emulsification. Diammonium phosphate (DAP) or phosphatidylcholine (PC) were further used to improve the biocompatibility of post-crosslinked gelatin microspheres. The biocompatibility of DAP-modified microspheres (0.5-10 wt.%) was better than that of PC (5 wt.%). The microspheres soaked in phosphate-buffered saline (PBS) lasted up to 26 days before fully degrading. Based on microscopic observation, the microspheres were all spherical and hollow inside. The particle size distribution ranged from 19 μm to 22 μm in diameter. The drug release analysis showed that the antibiotic gentamicin loaded on the microspheres was released in a large amount within 2 h of soaking in PBS. It was stabilized until the amount of microspheres integrated was significantly reduced after soaking for 16 days and then released again to form a two-stage drug release curve. In vitro experiments showed that DAP-modified microspheres at concentrations less than 5 wt.% had no cytotoxicity. Antibiotic-impregnated and DAP-modified microspheres had good antibacterial effects against Staphylococcus aureus and Escherichia coli , but these drug-impregnated groups hinder the biocompatibility of hydrogel microspheres. The developed drug carrier can be combined with other biomaterial matrices to form a composite for delivering drugs directly to the affected area in the future to achieve local therapeutic effects and improve the bioavailability of drugs.

This is a case of an innovative method of continuous irrigation approach for wound care following surgical drainage. Compared with the traditional labor-intensive irrigation, this novel handy method is not only reducing the workload but is also less time-consuming and inexpensive. This continuous irrigation approach is an efficient alternative approach for wound care in deep infection of the head and neck.

The outbreak of severe acute respiratory syndrome (SARS) in 2003 in Taiwan impacted Taiwanese society. However, the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan and spread around the world. During these outbreaks, nursing staff experienced different levels of pressure. Studies have explored the stress and adjustment of nurses during these periods, but studies describing the feelings of nurses during both SARS and COVID-19 outbreaks are lacking. The aim of this study was to explore the experiences of nurses who had cared for both SARS and COVID-19 patients. A qualitative study combined with snowball sampling was applied. Semi-structured questions were used to interview 10 nurses who had experienced both SARS and COVID-19. Two themes and four sub-themes were analyzed, which were: facing the epidemic from the unknown to known; and the experiences from ignorance to proficiency. The sub-themes were: the feeling of frustration and concern; bottlenecks and pressures in my work; my mission and support; and positive energy and camaraderie. The results showed that the media acts as an important resource during disease outbreaks; therefore, government departments have to use their wisdom to make good use of the media. Secondly, understanding the general public's response to the disease is also important for first-line nurses. Finally, on-the-job education and guidelines for first-line nurses are necessary, and support from the administration is also important.

Background: Chest compressions are the basis of cardiopulmonary resuscitation (CPR), and high-quality chest compressions can improve survival rate in patients with out-of-hospital cardiac arrest. Although many efforts have been made to improve the quality of CPR in inexperienced adults, the results are still not high, especially during emergencies. The primary purpose of this study is to investigate whether a brief instructional chest compression-only CPR video could improve chest compression quality in inexperienced adults. Methods: One hundred adults with no CPR experience (age: 20.28 ± 2.28 years; women: 50, men: 50) participated in this study. Participants completed body composition and handgrip strength measurements, and performed two CPR quality tests on the Laerdal ® Little Anne QCPR Manikin, namely without video-CPR (WV-CPR) and video-CPR (V-CPR). The WV-CPR quality test was performed first. After 2 minutes of continuous chest compression, the participants rested for 10 seconds and repeated 3 cycles (phase 1, phase 2, and phase 3). After resting for more than 72 hours, V-CPR quality test was conducted. During the V-CPR with video intervention, the participants also continued to compress the chest for 2 minutes, and then rested for 10 seconds, repeating 3 cycles. Results: In phase 1, compared with WV-CPR, the V-CPR has a significant increase ( p < 0.001) in chest compression fraction (CCF) (56.31 ± 33.22% vs. 41.82 ± 32.30%) and percent of correct compression rate (PCCR) (96.17 ± 8.45% vs. 26.31 ± 37.55%). In addition, the V-CPR has significantly lower ( p < 0.001) chest compression rate (CCR) (110.85 ± 2.40 cpm vs. 128.86 ± 24.52 cpm) and rating of perceived exertion (RPE) (11.89 ± 2.25 vs. 12.87 ± 2.25). For phases 2 through 3, V-CPR and WV-CPR achieved significant differences in CCF, CCD, CCR, PCCR, and RPE ( p < 0.01). There were significant differences ( p < 0.05) in CCF, CCD, chest compression rebound rate, and RPE among the different administration stages of both WV-CPR and V-CPR. Conclusions: The results of this study revealed that a brief instructional chest compression-only CPR video could improve chest compression quality for inexperienced adults by reducing fatigue and CCR, and increasing CCF and PCCR., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Late-onset asthma (LOA) differs from early-onset asthma (EOA) in terms of prognosis and the treatment response because it has a much worse prognosis and a poorer response to standard asthma treatment. This study sought to investigate the characteristics and clinical outcomes of asthma patients with phenotypes distinguished by age at onset and atopy status. We prospectively recruited patients with asthma who were registered in a pay-for-performance program operated by Taiwan’s National Health Insurance Administration (NHIA). These patients received regular outpatient treatment for at least 1 year at every outpatient clinic visit since 2019. Baseline characteristics and clinical outcomes were compared between patients with LOA (≥40 years) and those with EOA (<40 years). Of the consecutive 101 patients with asthma, 21 patients (20.7%) had EOA and 80 (79.3%) had LOA. In the 12-month period, patients with EOA had higher declines in forced expiratory volume in one second (FEV1; −2.1 ± 8.4 vs. 6.8 ± 13.1, % of predicted value, p = 0.037) and forced vital capacity (FVC; −4.6 ± 12.0 vs. 6.1 ± 13.6, % of predicted value, p = 0.023) than patients with LOA. Patients with nonatopic EOA had a significantly higher exacerbation rate at 12 months than patients with nonatopic LOA (50% vs. 11.8%, p = 0.012). Identification of different phenotypes of asthma is important in clinical practice because treatment responses may differ.

Background: To date, treating nasal polyps (NPs) is still a medical challenge. However, we have developed an innovative therapy using licorice extract (LE: Glycyrrhiza glabra) to treat rhinitis and sinusitis via nasal irrigation and have discovered that it significantly affects treatment of NPs., Hypothesis/purpose: This study investigated the mechanism of LE on NPs., Study Design: NPs were collected from three patients using tissue biopsies before and 2 weeks after nasal irrigation with licorice for histopathological analysis. Additionally, NPs from two patients were collected, and nasal polyp-derived fibroblasts (NPDF) were isolated and cultured., Methods: The TGF-β1-stimulated NPDF model was used to examine the effect of LE on fibroblast differentiation (biomarker: α-SMA), the consequent production of extracellular matrix (ECM; biomarkers: fibronectin, FBN), and the functional signaling pathway., Results: Immunohistochemistry (IHC) revealed that the number of eosinophils and the expression of α-SMA and interstitial collagen of polyps after licorice treatment significantly decreased. Additionally, RT-PCR, western blotting, and immunofluorescence (IF) showed that α-SMA and FBN expressions were significantly increased in the NPDF, which was stimulated by TGF-β1, and LE dose-dependently could effectively reduce this effect. Furthermore, western blotting showed that LE could attenuate α-SMA and FBN expressions by preventing the signaling pathway of MAPK/ERK-1/2, which IHC and IF further confirmed. In addition, LE effectively suppressed the cell migration of NPDF, which is related to polyp expansion., Conclusion: LE is clinically used to treat sinusitis with NPs through nasal irrigation, which significantly reduces the size of NPs. This effect could attenuate fibroblast differentiation, ECM production and cell migration, and one of the functional mechanisms may be through inhibition of the MAPK/ERK-1/2 signaling pathway., Trial Registration: ISRCTN (No. 51425529) registered on 17/04/2020 (retrospectively registered) - http://www.isrctn.com/ISRCTN51425529., (© 2022. The Author(s).)

Mineral trioxide aggregates (MTA) have been widely used in endodontic treatments, but after some time, patients suffer tooth discoloration due to the use of bismuth oxide (Bi2O3) as a radiopacifier. Replacement of Bi2O3 with high energy ball-milled single (zirconia ZrO2; hafnia, HfO2; or tantalum pentoxide, Ta2O5) or binary oxide powder was attempted, and corresponding discoloration improvement was investigated in the present study. Bi2O3-free MTA is expected to exhibit superior discoloration. The radiopacity, diametral tensile strength, and discoloration of MTA-like cements prepared from the as-milled powder were investigated. Experimental results showed that MTA-like cements prepared using Ta2O5 exhibited a slightly higher radiopacity than that of HfO2 but had a much higher radiopacity than ZrO2. Milling treatment (30 min to 3 h) did not affect the radiopacities significantly. These MTA-like cements exhibited superior color stability (all measured ΔE00 < 1.0) without any perceptible differences after UV irradiation. MTA-like cements prepared using ZrO2 exhibited the best color stability but the lowest radiopacity, which can be improved by introducing binary oxide. Among the investigated samples, MTA-like cement using (ZrO2)50(Ta2O5)50 exhibited excellent color stability and the best overall performance with a radiopacity of 3.25 mmAl and a diametral tensile strength of 4.39 MPa.

The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded ORF50 protein is a potent transcriptional activator essential for triggering KSHV lytic reactivation. Despite extensive studies, little is known about whether ORF50 possesses the ability to repress gene expression or has an antagonistic action to cellular transcription factors. Previously, we demonstrated that human oncoprotein MDM2 can promote the degradation of ORF50 protein. Herein, we show that abundant ORF50 expression in cells can conversely downregulate MDM2 expression via repressing both the upstream (P1) and internal (P2) promoters of the MDM2 gene. Deletion analysis of the MDM2 P1 promoter revealed that there were two ORF50-dependent negative response elements located from -102 to -63 and from -39 to +1, which contain Sp1-binding sites. For the MDM2 P2 promoter, the ORF50-dependent negative response element was identified in the region from -110 to -25, which is coincident with the location of two known p53-binding sites. Importantly, we further demonstrated that overexpression of Sp1 or p53 in cells indeed upregulated MDM2 expression; however, coexpression with ORF50 protein remarkably reduced the Sp1- or p53-mediated MDM2 upregulation. Collectively, our findings propose a reciprocal negative regulation between ORF50 and MDM2 and uncover that ORF50 decreases MDM2 expression through repressing Sp1- and p53-mediated transactivation.

Background: Chronic rhinosinusitis (CRS) affects the quality of life of many people worldwide and can cause comorbidities. Our previous research proved that Sjogren's syndrome (SS) is a predisposing factor for CRS, with a 2.5-fold associated risk. Antibiotics are important in CRS treatment; however, there is a paucity of research on the pathogenic bacteria of SS-CRS in the past. We conducted this study to investigate the pathogenic difference of SS-CRS and non-SS-CRS and aimed to give clinicians references when selecting antibiotics to treat SS-CRS., Materials and Methods: A total of 14,678 patients hospitalized for CRS operation from 2004 to 2018 were identified from the Chang Gung Research Database. These CRS cases were classified as either SS-CRS or non-SS-CRS. We analyzed their bacterial distribution by studying the results of the pus cultures performed alongside surgery., Results: The top three facultative anaerobic or aerobic isolated bacteria in the SS-CRS group were coagulase-negative Staphylococcus (CoNS: 34.3%), Pseudomonas aeruginosa (28.6%), methicillin-sensitive Staphylococcus aureus (MSSA: 20%), and Staphylococcus epidermidis (20%). In the non-SS-CRS group, S. epidermidis (29.3%), CoNS (25.7%), and MSSA (14.2%) were identified. The top three anaerobic bacterial genera were Cutibacterium (54.3%), Peptostreptococcus (11.4%), and Fusobacterium (11.4%) in the SS-CRS group and Cutibacterium (53.8%), Peptostreptococcus (25%), and Prevotella (12.9%) in the non-SS-CRS group., Conclusions: P. aeruginosa is a major pathogen in SS-CRS patients. In addition, physicians should be aware of potential Fusobacterium and antibiotic-resistant bacterial infection in patients with SS-CRS., (© 2022. The Author(s).)

Background: Treatment responsiveness to corticosteroids is excellent for cryptogenic organizing pneumonia (COP) and sarcoidosis, but suboptimal for idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP). We hypothesise that the differential expression of IL-17 contributes to variable corticosteroid sensitivity in different interstitial lung diseases., Objective: To determine the associations among expression of IL-17, glucocorticoid receptor-β and responsiveness to corticosteroid treatment in interstitial lung diseases., Methods: Immunohistochemical (IHC) staining was performed on formalin-fixed paraffin-embedded (FFPE) lung tissues obtained by bronchoscopic, CT-guided or surgical biopsies, and quantified by both cell counting (% positive cells) by individuals and by software IHC Profiler plugin of ImageJ (opacity density score). We studied the effect of IL-17 on corticosteroid sensitivity in human fibroblast MRC5 cell line., Results: Compared with specimens from patients with COP (n =13) and sarcoidosis (n =13), those from IPF patients (n = 21) had greater GR-β and IL-17 expression and neutrophil infiltration. Radiographic progression after oral corticosteroid treatment was positively correlated with the expression in IL-17 and GR-β/GR-α ratio in all patients (COP, sarcoidosis and IPF) and also within the IPF subgroup only. IL-17 expression level was positively associated with GR-β and GR-β/GR-α ratio. In MRC5 cells, exogenous IL-17 increased the production of collagen I and up-regulated GR-β expression and dexamethasone's suppressive effect on collagen I production was impaired by IL-17, and silencing IL-17 receptor A gene attenuated the effect of IL-17., Conclusion: Up-regulation of GR-β/GR-α ratio by IL-17 could be associated with the relative corticosteroid-insensitivity of IPF., 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., (Copyright © 2022 Lo, Wang, Wang, Chen, Huang, Chung, Huang, Lin, Lee, Lin, Lin, Chang, Lin, Heh, He and Chung.)

Objectives/hypothesis: To examine the pathogenic bacterial spectra and prognosis of deep neck infection (DNI) in end-stage renal disease (ESRD) patients., Study Design: Retrospective study., Methods: Patients diagnosed with DNI between 2004 and 2015 in Chang Gung Memorial Hospital were enrolled and divided into three groups, namely ESRD-DNI, chronic kidney disease (CKD)-DNI, and non-CKD-DNI. Differences in pathogenic bacteria, treatment, and prognosis were compared across the three groups., Results: The bacterial spectra differed among the three groups. The main three facultative anaerobic or aerobic bacteria causing ESRD-DNIs were methicillin-resistant Staphylococcus aureus (MRSA; 25.4%), methicillin-susceptible S. aureus (MSSA; 14.1%), and Klebsiella pneumoniae (KP; 12.7%). For CKD-DNIs, they were KP (23.5%), Viridans streptococci (VS; 23.5%), and MSSA (14.7%). For non-CKD-DNIs, they were VS (31.7%), KP (17.2%), and coagulase-negative staphylococci (8.0%). Compared with the other groups, the ESRD-DNI group had higher white blood cell and C-reactive protein levels, longer hospital stays, more frequent admissions to the intensive care unit, more mediastinal complications, and a significantly higher mortality rate., Conclusions: The ESRD-DNI group exhibited more severe disease activity and higher mortality compared with those of the CKD-DNI and non-CKD-DNI groups. MRSA was the leading pathogen for patients with ESRD-DNI. Physicians must implement strategies for the early detection of MRSA to accurately prescribe antibiotics and prevent nosocomial transmission., Level of Evidence: 4 Laryngoscope, 132:1403-1409, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)