Search

Po-Jui Chen,1 I-Huang Lin,1 Yi-Chun Chi,2 Chun-Chieh Lai,1 Jia-Horung Hung,1 Sung-Huei Tseng,1 Yi-Hsun Huang1 1Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Yi-Hsun Huang, Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Email jackhyh@gmail.comAbstract: Purpose: This study aimed to evaluate the therapeutic efficacy and long-term outcomes of treatment with topical 2% ganciclovir solution in immunocompetent patients with aqueous humor polymerase chain reaction (PCR)-proven cytomegalovirus (CMV) anterior uveitis and corneal endotheliitis.Methods: We retrospectively reviewed the findings for immunocompetent patients diagnosed with CMV uveitis or endotheliitis based on clinical manifestations and polymerase chain reaction (PCR) examination results and treated with topical 2% ganciclovir solution at National Cheng Kung University Hospital. Clinical outcome measurements included evaluations of the response rate, relapses, resolution of anterior chamber inflammation, visual acuity, and intraocular pressure.Results: The study included 38 eyes of 32 patients. Long-term administration of topical 2% ganciclovir significantly decreased keratic precipitates (p = 0.001), anterior chamber cells (p = 0.001), and reduced intraocular pressure (p < 0.001). Only one eye was unresponsive to topical ganciclovir treatment, and the recurrence decreased to 0.13 relapses per year. The presence of keratic precipitates and higher intraocular pressure at the initial presentation were significantly associated with recurrence (p = 0.036 and p = 0.001, respectively).Conclusions:: Long-term use of topical 2% ganciclovir solution is effective, safe, and applicable when commercialized ganciclovir gel is not available.Keywords: cytomegalovirus, endotheliitis, ganciclovir, uveitis

Chun-Hwei Tai,1 Wang-Tso Lee,2 Sheng-Hong Tseng3 1Department of Neurology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 2Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Surgery, National Taiwan University Hospital, Taipei, TaiwanCorrespondence: Sheng-Hong TsengNational Taiwan University Hospital, No. 7, Zhong-Shan South Road, Taipei, 100, TaiwanTel +886 22312-3456 ext.65110Fax +886 22341-8395Email tsh5110@ntu.edu.twWang-Tso LeeNational Taiwan University Hospital, No. 7, Zhong-Shan South Road, Taipei, 100, TaiwanTel +886 22312-3456 ext.71514Fax +886 22314-7450Email leeped@hotmail.comPurpose: Dystonia type 6 (DYT6) is an autosomal dominant monogenic movement disorder that often involves craniocervical and laryngeal regions, but can in rare circumstance present as trunk dystonia or severe scoliosis. Deep brain stimulation of the globus pallidus internus (GPi-DBS) has yielded favorable results in the treatment of DYT6 patients. This report describes the case of a 14-year-old male adolescent with DYT6 dystonia and severe scoliosis who was successfully treated by GPi DBS.Patients and Methods: The diagnosis of DYT6 dystonia was made after excluding other etiologies and was confirmed by next-generation sequencing. The patient underwent bilateral GPi-DBS implantation surgery under general anesthesia.Results: The patient’s Burke–Fahn–Marsden Dystonia Rating Scale score was 24 before surgery and decreased to 13.5 at 3 months, 3 at 6 months, and 2 at 12 months after bilateral GPi-DBS, corresponding to a 91% improvement from baseline to 12 months post-surgery. The patient’s scoliosis improved significantly within 6 months after DBS. No complications occurred during surgery.Conclusion: An adolescent DYT6 patient with dystonia-related severe scoliosis was treated by bilateral GPi-DBS. The patient had an excellent outcome at 12 months after surgery, which prevented him from developing severe spinal deformity and disability. Early diagnosis of dystonia in adolescent patients can lead to timely and effective treatment. The etiology of severe scoliosis in adolescents should be carefully evaluated and differential diagnosis including dystonia should be considered. GPi-DBS in patients with DYT6 dystonia can prevent deformity.Keywords: dystonia type 6, movement disorder, spinal deformity, deep brain stimulation, globus pallidus internus

Shio-Shin Jean,1,2 Min-Chi Lu,3 Zhi-Yuan Shi,4 Shu-Hui Tseng,5 Ting-Shu Wu,6 Po-Liang Lu,7 Pei-Lan Shao,8 Wen-Chien Ko,9 Fu-Der Wang,10,11 Po-Ren Hsueh12,13 1Department of Emergency Medicine and Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 2Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Microbiology and Immunology, School of Medicine, China Medical University, Taichung, Taiwan; 4Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 5Center for Disease Control and Prevention, Ministry of Health and Welfare, Taiwan; 6Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 7Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Pediatrics, Hsin-Chu Branch, National Taiwan University Hospital, Hsin-Chu, Taiwan; 9Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan; 10Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 11School of Medicine, National Yang-Ming University, Taipei, Taiwan; 12Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 13Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: We investigated the in vitro antimicrobial susceptibilities of clinically important Gram-negative bacteria (GNB) from 16 major teaching hospitals in Taiwan in 2017. Materials and methods: Escherichia coli (n=686) and Klebsiella pneumoniae bloodstream isolates (n=673), non-typhoid Salmonella (NTS; n=221) from various sources, Shigella species (n=21) from fecal samples, and Neisseria gonorrhoeae (n=129) from the genitourinary tract were collected. Antibiotic minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Alleles encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamases (NDMs), Verona integron-encoded metallo-β-lactamase, imipenemase, OXA-48-like, and mcr-1-5 genes were detected by molecular methods in Enterobacteriaceae isolates. Results: Five (0.7%) E. coli isolates harbored mcr-1 alleles. Twenty-four (3.6%), seven (1.0%), four (0.6%), and one (0.15%) K. pneumoniae isolates contained bla KPC, bla OXA-48-like, mcr-1, and bla NDM, respectively. Three (1.4%) NTS and no Shigella isolates harbored mcr-1 genes. Seventy-one (10.5%) K. pneumoniae isolates displayed non-susceptibility (NS) to carbapenem agent(s). Phenotypically extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates showed significantly higher rates of ertapenem, tigecycline, and ceftolozane–tazobactam (CLZ–TAZ) NS (40.2%, 16.3%, and 71%–80%, respectively) than E. coli isolates exhibiting ESBL phenotypes (5.4%, 0.7%, and 18%–28%, respectively). All phenotypically ESBL-producing E. coli isolates were ceftazidime–avibactam (CAZ–AVB) susceptible. Two (8.3%) KPC-producing K. pneumoniae isolates showed CAZ–AVB NS. Hospital-acquired K. pneumoniae isolates were significantly less susceptible to ertapenem and CLZ–TAZ than hospital-acquired E. coli isolates. Conclusion: Third-generation cephalosporins remain the optimal choice for treating NTS, Shigella, and gonococcal infections in Taiwan. Hospital-acquired and phenotypically ESBL-producing K. pneumoniae are a heavy resistance burden in Taiwan. Keywords: Enterobacteriaceae, Neisseria gonorrhoeae, extended-spectrum β-lactamases, carbapenemase, ceftolozane–tazobactam, ceftazidime–avibactam

I-Huang Lin,1 Sung-Huei Tseng,1 Fu-Chin Huang,1 Yi-Hsun Huang1,2 1Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; 2Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China Purpose: The aim of this study was to evaluate the long-term outcomes of ethanol pretreatment in Acanthamoeba keratitis (AK). Patients and methods: This single-center, retrospective, interventional study included 22 patients (24 eyes) who developed AK and underwent ethanol pretreatment between 2009 and 2015. Samples for smears, polymerase chain reaction, and culture for evidence of Acanthamoeba were collected. After ethanol pretreatment, the patients were treated with corneal epithelial debridement, topical 0.02% polyhexamethylene biguanide, and 0.1% propamidine isethionate. The primary outcomes were a clinically stable ocular surface, complete recovery from corneal infection, and acceptable corneal haze. The secondary outcome measure was improvement in best-corrected visual acuity. Complications and predictors of the visual outcome were also recorded. Results: Ethanol pretreatment was successful in 20 (83.3%) of the 24 eyes, and no further optical keratoplasty was required. Four eyes required rescue therapeutic keratoplasty because of rapid progression of AK. Patients in whom ethanol pretreatment was successful achieved good final visual outcomes regardless of sex, age, or causative Acanthamoeba species. Patients with worse initial best-corrected visual acuity and rigid gas permeable lens-related AK had better improvement in vision. Conclusion: Ethanol as a pretreatment for AK is safe and effective. Combined with corneal epithelial debridement, ethanol pretreatment may preclude the need for optical and therapeutic keratoplasty. This technique is suitable for all stages of AK presenting within 3 weeks of symptom onset and achieves favorable results especially in early AK. Keywords: Acanthamoeba keratitis, Acanthamoeba, ethanol pretreatment, corneal infection, corneal epithelial debridement

Shih-Heng Tseng,1,2 Min-Yuan Chou,2 I-Ming Chu1 1Department of Chemical Engineering, National Tsing Hua University, 2Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan Abstract: We have developed a theranostic nanoparticle, ie, cet-PEG-dexSPIONs, by conjugation of the anti-epidermal growth factor receptor (EGFR) monoclonal antibody, cetuximab, to dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) via periodate oxidation. Approximately 31 antibody molecules were conjugated to each nanoparticle. Cet-PEG-dexSPIONs specifically bind to EGFR-expressing tumor cells and enhance image contrast on magnetic resonance imaging. Cet-PEG-dexSPION-treated A431 cells showed significant inhibition of epidermal growth factor-induced EGFR phosphorylation and enhancement of EGFR internalization and degradation. In addition, a significant increase in apoptosis was detected in EGFR-overexpressing cell lines, A431 and 32D/EGFR, after 24 hours of incubation at 37°C with cet-PEG-dexSPIONs compared with cetuximab alone. The antibody-dependent cell-mediated cytotoxicity of cetuximab was observed in cet-PEG-dexSPIONs. The results demonstrated that cet-PEG-dexSPIONs retained the therapeutic effect of cetuximab in addition to having the ability to target and image EGFR-expressing tumors. Cet-PEG-dexSPIONs represent a promising targeted magnetic probe for early detection and treatment of EGFR-expressing tumor cells. Keywords: epidermal growth factor receptor, cetuximab, superparamagnetic iron oxide nanoparticle, magnetic resonance imaging, sodium periodate, polyethylene glycol

Currently the only method for positively identifying malignant melanoma involves invasive and often undesirable biopsy procedures. Available ex-vivo data indicates increased vascularization in the lower regions of excised melanoma, as compared to dysplastic nevi. The ability to interrogate this region of tissue in-vivo could lead to useful diagnostic information. Using a newly developed fiber based superficial probe in conjunction with a steady-state frequency-domain photon migration (SSFDPM) system, we can probe the upper 1-2 mm of tissue, extracting functional information in the near infrared (650-1000 nm) range. To test the resolution and detection range of the superficial probe in this context,deformable silicone phantoms have been fabricated that simulate normal skin with melanocytic lesions. These phantoms consist of a two-layered matrix with the optical properties of normal light skin, containing several cylindrical inclusions that simulate highly absorbing pigmented lesions such as melanoma. The e inclusions are varied in depth, diameter, and optical properties in order to fully test the probe's detection capabilities. It was found that, depending on absorption, we can typically probe to a depth of 1.0-1.5 mm in an inclusion, likely reaching the site of angiogenesis in an early-stage melanoma. Additionally, we can successfully interrogate normal tissue below lesions 1.5mm deep when absorption is about 0.4/mm or less. This data indicates that the superficial probe shows great promise for non-invasive diagnosis of pigmented lesions.© 2009 SPIE.

Meiotic disturbances in F1 hybrids and their progenies are still major problems in wide hybridization. To investigate the genome affinity reflected in chromosome pairing and segregation, we studied chromosome behaviors during meiosis in two interspecific F1 hybrids [O. minuta × O. australiensis (Om × Oa, BCE genome) and Oa × O. ridleyi (Or, EHJ genome)] by using both traditional staining methods and genomic in situ hybridization (GISH). GISH analysis has been successfully performed on mitotic chromosomes to distinguish different Oryza genomes, but relatively fewer systematic analyses of meiotic chromosomes of interspecific hybrids have been reported. In the hybrids, highly irregular chromosome behaviors through meiosis resulted in producing microspores with unbalanced genome. At diakinesis of these two hybrids, most chromosomes present as univalent, with low frequency as bivalents and occasionally as trivalents. In a pollen mother cell, 2 to 8 bivalents and 0 to 4 trivalents were observed in the hybrid Oa × Or, and 1 to 8 bivalents and 0 to 5 trivalents were observed in the hybrid Om × Oa. GISH results indicated that 51.52% bivalents in Oa × Or and 79.65% bivalents in Om × Oa involved allosyndetic association, which indicates that recombination and introgression should be possible if viable backcrosses can be recovered even from triploid hybrids. In this study, we revealed that the meiotic disturbance due to low affinities between parental genomes is the major reason for the sterility of these two triploid interspecific hybrids. The two hybrids showing vigor in reproductive growth are potential genetic resources in future breeding programs. A better understanding of genomic affinities between these distant Oryza species can facilitate planning an effective breeding program by using wide hybridization, and efficient and routine GISH analysis is helpful to monitor alien introgression in the process.

Background: Acute appendicitis is the most common acute abdomen in general surgery. Show-Chwan Memorial Hospital began an AITS/IRCAD laparoscopic training program in late May 2008. In this retrospective analysis, we surveyed the impact of the AITS training program on surgeons' preference for open appendectomy (OA) versus laparoscopic appendectomy (LA).Methods: From January 1, 2004 to July 31, 2009, patients diagnosed with acute appendicitis in Changhua Show-Chwan Memorial Hospital and Chang-Bing Show-Chwan Memorial Hospital were retrospectively analyzed. Demographic data, laboratory examinations, surgical methods, hospital stay, and complication rate data were collected and analyzed. The LA rate and effect of surgeons' preference before and after AITS were compared.Results: In all, 1,267 patients (58.2% male and 41.8% female; mean age, 36.6 years) were diagnosed with acute appendicitis during this period. Among them, 78.9% of patients had uncomplicated and 21.1% complicated appendicitis; 784 patients (61.9%) underwent OA, and 465 (36.7%) received LA. In 2004, only 8.1% of patients underwent LA, but the number increased rapidly to 90.4% in 2009 (P < 0.001). The average LA rate before AITS was 21%; however, after AITS, the LA rate increased to 84.6% (P < 0.001). The LA rate increased for all surgeons completing the training course, ranging from 16 to 83%. The overall appendectomy complication rate was 8.4%, with no significant difference between OA (9.7%) and LA (6.5%; P = 0.174). Hospital stay was shorter in the LA group (4.05 ± 1.9 days) compared with the OA group (4.55 ± 3.6; P = 0.006).Conclusions: Attending the laparoscopic training course significantly increased surgeons' preference for LA. [ABSTRACT FROM AUTHOR]

Poland achieved an excellent reputation for economic transformation during the recent global recession. The European debt crisis, however, quickly forced the reorientation of Poland’s trade outside of the European Union (EU), especially toward the dynamic region of East Asia. This study analyzes time series data from 1999 to 2013 to detect outliers in order to determine the bilateral trade paths between Poland and each East Asian country during the events of Poland’s accession to the EU in 2004, the global financial crisis from 2008 to 2009, and the European debt crisis from 2010 to 2013. From the Polish standpoint, the results showed significantly clustering outliers in the above periods and in the general trade paths from dependence through distancing and improvement to the chance of approaching East Asian partners. This study also shows that not only China but also several other countries present an excellent opportunity for boosting bilateral trade, especially with regard to Poland’s exports.

Mathematics is a very important learning subject. Mathematical knowledge can be learned by traditional or distance learning, but the mathematical problem solving ability is hard to improve without experiences through practice. Therefore, developing an interesting learning game to enhance students problem solving ability is the major concern in this paper. Since the storytelling strategy has been proved to be useful to enhance the students thinking ability, we develop a storytelling-based arithmetic card game to encourage and guide students to speak out their thinking process of problem solving, where the e-Project-Based Learning (e-PBL) platform has been applied to brainstorm the characteristics of the game and construct the storytelling script. Thus, the misconceptions can be easily diagnosed. To evaluate the performance of our approach, 40 5-grade primary school students have participated in the storytelling-based arithmetic card game experiment. The experimental result shows that the storytelling-based learning can enhance the mathematical problem solving ability via playing the game.

Abstract Some new weakly singular integral inequalities of Wendroff type are established, which generalized some known weakly singular inequalities for functions in two variables and can be used in the analysis of various problems in the theory of certain classes of integral equations and evolution equations. Application examples are also given.

A novel vardenafil analogue was discovered during adulterant screening of a dietary supplement. After extraction and purification, this analogue was identified using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) analyses. The molecular formula determined using LC-HRMS was C 24 H 34 N 6 O 5 S. Fragmentation data suggested that this unknown compound may have two modifications to vardenafil. NMR analysis confirmed the presence of a hydroxyl group on the piperazine moiety and a propyl group attached to the phenoxy group. Consequently, this compound was named 19-O-propyl hydroxy vardenafil., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rationale: Ethylene oxide (EO) sterilization is commonly employed for the sterilization of medical devices and has a very high market share. However, EO and its metabolite ethylene chlorohydrin (ECH) are toxic to humans. In compliance with the classification and residue limits of medical devices defined by ISO 10993-7, our study established two extraction methods for the testing of EO and ECH., Methods: The first method involves simulated-use extraction using water as the extraction solvent. While the second, exhaustive extraction, directly extracts sample through headspace sampling analysis. Gas chromatography-tandem mass spectrometry in multiple reaction monitoring mode was utilized, requiring only 16 min. Then, the developed method was applied to assess 10 commercially available medical devices sterilized by EO., Results: In simulated-use extraction, calibration curves were evaluated in the range of 1-100 and 5-500 μg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 85.0% to 95.2% and from 94.8% to 102.4%. In exhaustive extraction, calibration curves spanned 0.5-50 and 2-200 μg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 101.6% to 102.1% for EO and from 98.1% to 102.2% for ECH. After analysis of the 10 commercially available medical devices, two cotton swabs were found to have ECH of 35.1 and 28.4 μg per device, and four medical devices were found to have EO with concentration below the limit of quantification. Meanwhile, we found that the EO internal standard (propylene oxide) recommended by ISO 10993-7 had interference problems with other similar substances and was not suitable as an internal standard for EO., Conclusions: This study offers a sensitive and straightforward analytical approach to EO and ECH residues in a variety of medical devices. In addition, the results show that the EO or ECH content of these types of medical devices in our study falls below the regulatory limits, therefore instilling confidence among consumers regarding their safe use., (© 2024 John Wiley & Sons Ltd.)

Objectives: To develop an intrinsic capacity (IC) score and to investigate the association between IC transition with overall and cause-specific mortality, incident disability and healthcare utilization., Design: Retrospective cohort study SETTING AND PARTICIPANTS: Data from 1852 respondents aged ≥ 65 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed., Measurements: Transitions of IC score were categorized into three groups: (1) Improved IC (IC 2003-1999 >0), (2) Stable IC (IC 2003-1999 = 0), (3) Worsened IC (IC 2003-1999 <0). Cox regression and subdistribution hazard models were used to investigate IC transitions and 4-year overall and cause-specific mortality, respectively. Logistic regression were employed to develop weighted IC score (wIC, 0-16) and assess its association with incident disability and healthcare utilization. Similar analysis were repeated using non-weighted IC (nIC, 0-8) to ensure robustness., Results: Comparing to decreased wIC group, stable or increased wIC participants had significantly lower 4-year all-cause mortality, and death from infection, cardiometabolic/cerebrovascular diseases, organ failure and other causes. (Hazard ratio (HR) ranged from 0.36 to 0.56, 95% CI ranged from 0.15 to 1.00, p ≤ 0.049 in the stable wIC group; HR ranged from 0.41 to 0.51, 95% CI ranged from 0.22 to 0.94, p ≤ 0.034 in the increased wIC group). Moreover, individuals with stable or increased wIC demonstrated lower risk of incident disability and hospitalization. (Odds ratio (OR) = ranged from 0.34 to 0.70, 95% CI ranged from 0.19 to 1.00, p ≤ 0.048). Participants with stable wIC also exhibited reduced risk of emergency department visits (OR = 0.58, 95% CI = 0.41 to 0.82, p = 0.002). These results were generally consistent in the nIC model., Conclusion: Participants with stable or increased IC experienced significantly lower all-cause and most cause-specific mortality, incident disability, and healthcare utilization, which was independent of baseline IC and comorbidities. The findings remained consistent across weighted and non-weighted IC model., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Unilateral vocal fold paralysis (UVFP), characterized by immobility of one vocal fold, results from injuries of recurrent laryngeal nerves. Voice therapy is a conservative intervention aiming to address these symptoms, but standard protocols are lacking. In this study, we provided an updated review of voice therapy for UVFP over the past 3 years and analyzed the effect of voice therapy from the perspective of voice assessment recommended by the guidelines of the European Laryngological Society and the Union of the European Phoniatricians in 2023., Methods: Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 statement, we searched the databases, including PubMed, Embase, Web of Science, the Cochrane Library, and SCOPUS, from their earliest records to December 1, 2023. Quality assessment utilized Cochrane Risk of Bias and Risk Of Bias In Non-randomized Studies of Interventions tools. Data extraction encompassed study design, participant characteristics, therapy protocols, and outcome measures, including subjective and objective assessments. We performed heterogeneity analysis by calculating the I 2 statistic and meta-analysis by calculating the standardized difference of means and weighted mean differences., Results: Our systematic review and meta-analysis included 12 studies encompassing 459 patients. The review revealed a predominance of female participants across studies. Therapy protocols primarily included breathing control, laryngeal manipulation, and resonance training, often supplemented by home exercises. Outcome measures demonstrated significant improvements in subjective parameter: Voice Handicap Index ((standard mean difference) SMD = -1.51, P < 0.001), acoustic parameters: fundamental frequency (SMD = -0.38, P = 0.003), jitter (SMD = -0.97, P < 0.001), shimmer (SMD = -0.94, P < 0.001), and noise-to-harmonic ratio (SMD = -0.89, P < 0.001), and aerodynamic parameters: maximum phonation time (SMD = 1.29, P < 0.001), with early intervention yielding enhanced rate of complete glottal closure., Discussion: Two randomized controlled trials (RCTs) involved patients aware of their allocation to the treatment group, and the remaining 10 studies were retrospective, leading to bias from deviations in the intended intervention. Subjective and aerodynamic parameter inconsistency was observed, but after excluding studies with the onset of UVFP greater than 12 months, the heterogeneity of VHI scores decreased. The funnel plot was grossly symmetrical in the publication bias test. Significant improvements were noted in subjective, acoustic, and aerodynamic outcomes after intervention. Besides, there were commonalities in protocols, such as breathing control, laryngeal manipulation, and resonance training, often supplemented by home exercises., Systematic Review Registration: This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on March 28, 2024, registration number: CRD42024529750., 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 Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake., Methods: An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition., Results: In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, P for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, P for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, P for trend <0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, P for trend <0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, P for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, P for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 μg/dL, P for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, P for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (β = 0.71, 95% CI: 6.88 to 40.79, P = 0.006), five-time sit-to-stand test (β = -0.87, 95% CI: -1.59 to -0.15, P = 0.017), MNA score (β = 0.96, 95% CI: 0.20 to 1.71, P = 0.013), serum triglycerides (β = -15.01, 95% CI: -27.83 to -2.20, P = 0.022), LDL-C (β = -9.23, 95% CI: -16.98 to -1.47, P = 0.020), and DHEA-S levels (β = 9.98, 95% CI: 0.45 to 19.51, P = 0.04) than controls., Conclusions: Protein-enriched soup with weekly exercise over 12 weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

A systematic review and meta-analysis was conducted to evaluate the relative effectiveness of different dietary macronutrient patterns on changes in resting energy expenditure (REE) in relation to weight loss, categorized as minimal (<5%) and moderate to high (>5%). Changes in REE were assessed using a DerSimonian and Laird random-effects meta-analysis. A diet lower in carbohydrates (CHO) or higher in fat and protein was associated with smaller reductions in REE, with these trends being more pronounced among participants who experienced moderate to high weight loss. Adjusted meta-regression analysis indicated that, within the participants who experienced moderate to high weight loss, each 1% increase in CHO intake was associated with a reduction of 2.30 kcal/day in REE (95% CI: -4.11 to -0.47, p = 0.013). In contrast, a 1% increase in protein and fat intake was correlated with an increase in REE by 3.00 (95% confidence interval [CI] [1.02, 5.07], p = 0.003) and 0.5 (95% CI [-2.43, 3.41], p = 0.740) kcal/day, respectively. No significant associations were found among participants who experienced minimal weight loss. These findings indicate that, under a caloric deficit, the impact of dietary macronutrient composition on REE may vary depending on the degree of weight loss and individual metabolic responses., (© 2024 World Obesity Federation.)

Aim: Chronic diseases are influential components of stroke, one of the dominant reasons for dementia and premature mortality. Environmental risks are risk factors for transitioning from stroke to dementia. This study addresses the transition behaviors in stroke and dementia development associated with chronic diseases and environmental risks., Methods: This study is an integrated survey of medical and environmental informatics concerning stroke patients' quality of life. A total of 10 627 stroke patients diagnosed in Taiwan were surveyed in this study. A covariate model and subgroup analysis were used to evaluate the influence of chronic diseases and environmental risk factors (i.e., divorce rate, unemployment rate, solitariness rate, temperature, and air pollution rate) on stroke and the corresponding dementia transition behaviors., Results: This study constructed a total of 98 covariate analysis models, consisting of 14 transition types [10 transitions from chronic diseases to stroke (5 metabolic risk states × 2 stroke states) and 4 transitions from stroke to dementia (2 stroke states × 2 dementia states)] by 7 covariates (i.e., sex, age, divorce rate, unemployment rate, temperature, air pollution, and solitariness rate). Among the 98 transitions, 26 were statistically significant., Conclusions: Sex, age, divorce rate, unemployment rate, temperature, and air pollution rate exerted a partially significant influence on the transition from chronic diseases to stroke. Sex, age, unemployment rate, and temperature partially influenced the transition from stroke to dementia. This study also considered high-risk sub-populations of stroke patients, particularly males aged 65 years and below. Geriatr Gerontol Int 2024; 24: 766-772., (© 2024 Japan Geriatrics Society.)

Ischemic stroke can lead to systemic inflammation, which can activate peripheral immune cells, causing neuroinflammation and brain injury. Meningeal lymphatics play a crucial role in transporting solutes and immune cells out of the brain and draining them into cervical lymph nodes (CLNs). However, the role of meningeal lymphatics in regulating systemic inflammation during the reperfusion stage after ischemia is not well understood. In this study, we demonstrated that brain infarct size, neuronal loss, and the effector function of inflammatory macrophage subsets were reduced after ischemia-reperfusion and disruption of meningeal lymphatics. Spatial memory function was improved in the late stage of ischemic stroke following meningeal lymphatic disruption. Brain-infiltrating immune cells, including neutrophils, monocytes, and T and natural killer cells, were reduced after cerebral ischemia-reperfusion and meningeal lymphatic disruption. Single-cell RNA sequencing analysis revealed that meningeal lymphatic disruption reprogrammed the transcriptome profile related to chemotaxis and leukocyte migration in CLN lymphatic endothelial cells (LECs), and it also decreased chemotactic CCN1 expression in floor LECs. Replenishment of CCN1 through intraventricular injection increased brain infarct size and neuronal loss, while restoring numbers of macrophages/microglia in the brains of meningeal lymphatic-disrupted mice after ischemic stroke. Blocking CCN1 in cerebrospinal fluid reduced brain infarcts and improves spatial memory function after ischemia-reperfusion injury. In summary, this study indicates that CCN1-mediated detrimental inflammation was alleviated after cerebral ischemia-reperfusion injury and meningeal lymphatic disruption. CCN1 represents a novel therapeutic target for inhibiting systemic inflammation in the brain-CLN axis after ischemia-reperfusion injury., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is an urgent unmet need for more targeted and effective treatments for advanced epithelial ovarian cancer (EOC). The emergence of drug resistance is a particular challenge, but small molecule covalent inhibitors have promise for difficult targets and appear less prone to resistance. Michael acceptors are covalent inhibitors that form bonds with cysteines or other nucleophilic residues in the target protein. However, many are categorized as pan-assay interference compounds (PAINS) and considered unsuitable as drugs due to their tendency to react non-specifically. Targeting RPN13/ADRM1-mediated substrate recognition and deubiquitination by the proteasome 19S Regulatory Particle (RP) is a promising treatment strategy. Early candidate RPN13 inhibitors (iRPN13) produced a toxic accumulation of very high molecular weight polyubiquitinated substrates, resulting in therapeutic activity in mice bearing liquid or solid tumor models, including ovarian cancer; however, they were not drug-like (PAINS) because of their central piperidone core. Up284 instead has a central spiro-carbon ring. We hypothesized that adding a guanidine moiety to the central ring nitrogen of Up284 would produce a compound, RA475, with improved drug-like properties and therapeutic activity in murine models of ovarian cancer. RA475 produced a rapid accumulation of high molecular polyubiquitinated proteins in cancer cell lines associated with apoptosis, similar to Up284 although it was 3-fold less cytotoxic. RA475 competed binding of biotinylated Up284 to RPN13. RA475 shows improved solubility and distinct pharmacodynamic properties compared to Up284. Specifically, tetraubiquitin firefly luciferase expressed in leg muscle was stabilized in mice more effectively upon IP treatment with RA475 than with Up284. However, pharmacologic analysis showed that RA475 was more rapidly cleared from the circulation, and less orally available than Up284. RA475 shows reduced ability to cross the blood-brain barrier and in vitro inhibition of HERG. Treatment of mice with RA475 profoundly inhibited the intraperitoneal growth of the ID8-luciferase ovarian tumor model. Likewise, RA475 treatment of immunocompetent mice inhibited the growth of spontaneous genetically-engineered peritoneal tumor, as did weekly cisplatin dosing. The combination of RA475 and cisplatin significantly extended survival compared to individual treatments, consistent with synergistic cytotoxicity in vitro. In sum, RA475 is a promising candidate covalent RPN13i with potential utility for treatment of patients with advanced EOC in combination with cisplatin., Competing Interests: RA475 is described in the Johns Hopkins University technology C16365 - ANTI-CANCER “SPIROCYCLIC-GUANIDINE COMPOUNDS” AND USES THERE OF, provisional application filed on May 18, 2020 as U.S. Patent Application No. 63/026,268, inventors Roden RB and Anchoori RK. The study described in this publication utilized compounds manufactured by Up Therapeutics LLC (MTA A36130) and covered by US patent US20190365726 and application 17/154,306. Dr. Roden is a consultant to Up Therapeutics LLC and owns stock in the company. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Dr. Anchoori is the founder of Up Therapeutics LLC and owns stock in the company. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Michelle Rudek reports a relationship with Geminus Therapeutics, LLC, that includes co-founder, board membership, and equity or stocks. Michelle Rudek reports a relationship with GlaxoSmithKline that includes employment (spouse). This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Anchoori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Synthetic cathinones, which are novel psychoactive substances, have caused major social problems worldwide. A substance called 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MMMP), which is employed as a commercial industrial photoinitiator for triggering polymerization, has a basic cathinone backbone; however, few reports regarding MMMP have been published. In the current study, three potential metabolites of MMMP-namely hydroxy-MMMP (HO-MMMP), HO-MMMP-sulfoxide (HO-MMMP-SO), and HO-MMMP-sulfone (HO-MMMP-SO 2 )-were successfully synthesized, and MMMP and these three potential metabolites were used as standards to establish an analytic method based on liquid chromatography-tandem mass spectrometry for the quantitative analysis of urine. This analytic method and related parameters-including dynamic range, limit of quantification, selectivity, precision, accuracy, carryover effect, matrix effect, interference, and dilution integrity-were optimized and validated. Forty urine samples from 1,691 individuals who abused drugs were determined to contain MMMP, HO-MMMP, HO-MMMP-SO, or HO-MMMP-SO 2 ; the results of this study indicate that approximately 2.37 % of drug abusers in Taiwan consumed MMMP in 2023. These 40 urine samples were analyzed to investigate the metabolism of MMMP in humans. The results indicate that HO-MMMP-SO is the main metabolite in human urine. This study recommends HO-MMMP-SO with a concentration of 2 ng/mL as a target and cutoff value, respectively, for identifying individuals who have consumed MMMP., 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. Published by Elsevier B.V.)

Objective: Middle-aged women with obesity are at increased risk of iron overload and iron disorder is known to disrupt n-3 polyunsaturated fatty acid homeostasis. We evaluated relationships between pretreatment hemoglobin and n-3 polyunsaturated fatty acid levels, and tested whether pretreatment hemoglobin contributed to inter-individual variability in weight loss with special focus on changes in body weight, iron and n-3 polyunsaturated fatty acid profiles., Study Design: 117 middle and older aged women with obesity and more than two metabolic abnormalities were randomized to a 12-week hypocaloric diet without or with fish oil supplementation. Blood iron biomarker and erythrocyte membrane phospholipid profiles were evaluated., Main Outcome: The absolute change from baseline to week 12 in serum iron and erythrocyte n-3 polyunsaturated fatty acid levels according to pretreatment hemoglobin tertiles and fish oil supplementation., Results: A Pearson correlation analysis showed that pretreatment hemoglobin levels were negatively correlated with linoleic acid (r = -0.231), α-linoleic acid (r = -0.279), and n-3 polyunsaturated fatty acid (r = -0.217) (all p < 0.05). Dietary weight loss markedly enhanced erythrocyte membrane lipids of linoleic acid, α-linoleic acid, and n-6 and n-3 polyunsaturated fatty acid only in those women with the highest pretreatment hemoglobin levels (tertile 3) (all p < 0.05). Fish oil supplementation increased bioavailable iron in women with moderate pretreatment hemoglobin levels (tertile 2) (p < 0.05) and, to a lesser extent, prevented a reduction in circulating iron in those with the lowest hemoglobin levels (tertile 1)., Conclusion: Dietary weight loss is an effective treatment program to manage obesity-related iron and n-3 polyunsaturated fatty acid disorders, particularly for middle-aged women with obesity and iron overload., Competing Interests: Declaration of competing interest Dr. Shih-Yi Huang has received consulting and lecture fees from Herbalife Taiwan. No competing interests are reported by the other authors., (Copyright © 2024. Published by Elsevier B.V.)

Quantifying hemoglobin is vital yet invasive through blood draws. We developed a wearable diffuse reflectance spectroscopy device comprising control and sensor boards with photodiodes and light-emitting diodes to noninvasively determine hemoglobin. Neural networks enabled recovery of optical parameters for chromophore fitting to calculate hemoglobin. Testing healthy and elderly subjects revealed strong correlation (r=0.9) between our system and invasive methods after data conversion. Bland-Altman analysis demonstrated tight 95% limits of agreement from -1.98 to 1.98 g/dL between the DRS and invasive hemoglobin concentrations. By spectroscopically isolating hemoglobin absorption, interference from melanin was overcome. Our device has the potential for future integration into wearable technology, enabling hemoglobin level tracking., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2024 Optica Publishing Group.)

This study developed a prototype for a rotational cone-beam x-ray luminescence computed tomography (CB-XLCT) system, considering its potential application in pre-clinical theranostic imaging. A geometric calibration method applicable to both imaging chains (XL and CT) was also developed to enhance image quality. The results of systematic performance evaluations were presented to assess the feasibility of commercializing XLCT technology. Monte Carlo GATE simulation was performed to determine the optimal imaging conditions for nanophosphor particles (NPs) irradiated by 70 kV x-rays. We acquired a low-dose transmission x-ray tube and designed a prone positioning platform and a rotating gantry, using mice as targets from commercial small animal μ -CT systems. We then employed the image cross-correlation (ICC) automatic geometric calibration method to calibrate XL and CT images. The performance of the system was evaluated through a series of phantom experiments with a linearity of 0.99, and the contrast-to-noise ratio (CNR) between hydroxyl-apatite (HA) and based epoxy resin is 19.5. The XL images of the CB-XLCT prototype achieved a Dice similarity coefficient (DICE) of 0.149 for a distance of 1 mm between the two light sources. Finally, the final XLCT imaging results were demonstrated using the Letter phantoms with NPs. In summary, the CB-XLCT prototype developed in this study showed the potential to achieve high-quality imaging with acceptable radiation doses for small animals. The performance of CT images was comparable to current commercial machines, while the XL images exhibited promising results in phantom imaging, but further efforts are needed for biomedical applications., (© 2024 Institute of Physics and Engineering in Medicine.)

Background: MUC16 is a heavily glycosylated cell surface mucin cleaved in the tumor microenvironment to shed CA125. CA125 is a serum biomarker expressed by > 95% of non-mucinous advanced stage epithelial ovarian cancers. MUC16/CA125 contributes to the evasion of anti-tumor immunity, peritoneal spread and promotes carcinogenesis; consequently, it has been targeted with antibody-based passive and active immunotherapy. However, vaccination against this self-antigen likely requires breaking B cell tolerance and may trigger autoimmune disease. Display of self-antigens on virus-like particles (VLPs), including those produced with human papillomavirus (HPV) L1, can efficiently break B cell tolerance., Results: A 20 aa juxta-membrane peptide of the murine MUC16 (mMUC16) or human MUC16 (hMUC16) ectodomain was displayed either via genetic insertion into an immunodominant loop of HPV16 L1-VLPs between residues 136/137, or by chemical coupling using malemide to cysteine sulfhydryl groups on their surface. Female mice were vaccinated intramuscularly three times with either DNA expressing L1-MUC16 fusions via electroporation, or with alum-formulated VLP chemically-coupled to MUC16 peptides. Both regimens were well tolerated, and elicited MUC16-specific serum IgG, although titers were higher in mice vaccinated with MUC16-coupled VLP on alum as compared to L1-MUC16 DNA vaccination. Antibody responses to mMUC16-targeted vaccination cross-reacted with hMUC16 peptide, and vice versa; both were reactive with the surface of CA125+ OVCAR3 cells, but not SKOV3 that lack detectable CA125 expression. Interestingly, vaccination of mice with mMUC16 peptide mixed with VLP and alum elicited mMUC16-specific IgG, implying VLPs provide robust T help and that coupling may not be required to break tolerance to this epitope., Conclusion: Vaccination with VLP displaying the 20 aa juxta-membrane MUC16 ectodomain, which includes the membrane proximal cleavage site, is likely to be well tolerated and induce IgG targeting ovarian cancer cells, even after CA125 is shed., (© 2024. The Author(s).)

Even with the prolific clinical use of next-generation cancer therapeutics, many tumors remain unresponsive or become refractory to therapy, creating a medical need. In cancer, DCs are indispensable for T cell activation, so there is a restriction on cytotoxic T cell immunity if DCs are not present in sufficient numbers in the tumor and draining lymph nodes to take up and present relevant cancer antigens. To address this bottleneck, we developed a therapeutic based on albumin fused with FMS-related tyrosine kinase 3 ligand (Alb-Flt3L) that demonstrated superior pharmacokinetic properties compared with Flt3L, including significantly longer half-life, accumulation in tumors and lymph nodes, and cross-presenting-DC expansion following a single injection. We demonstrated that Alb-Flt3L, in combination with standard-of-care chemotherapy and radiation therapy, serves as an in situ vaccination strategy capable of engendering polyclonal tumor neoantigen-specific immunity spontaneously. In addition, Alb-Flt3L-mediated tumor control synergized with immune checkpoint blockade delivered as anti-PD-L1. The mechanism of action of Alb-Flt3L treatment revealed a dependency on Batf3, type I IFNs, and plasmacytoid DCs. Finally, the ability of Alb-Flt3L to expand human DCs was explored in humanized mice. We observed significant expansion of human cross-presenting-DC subsets, supporting the notion that Alb-Flt3L could be used clinically to modulate human DC populations in future cancer therapeutic regimens.

COVID-19 has exposed major weaknesses in the healthcare settings. The surge in COVID-19 cases increases the demands of health care, endangers vulnerable patients, and threats occupational safety. In contrast to a hospital outbreak of SARS leading to a whole hospital quarantined, at least 54 hospital outbreaks following a COVID-19 surge in the community were controlled by strengthened infection prevention and control measures for preventing transmission from community to hospitals as well as within hospitals. Access control measures include establishing triage, epidemic clinics, and outdoor quarantine stations. Visitor access restriction is applied to inpatients to limit the number of visitors. Health monitoring and surveillance is applied to healthcare personnel, including self-reporting travel declaration, temperature, predefined symptoms, and test results. Isolation of the confirmed cases during the contagious period and quarantine of the close contacts during the incubation period are critical for containment. The target populations and frequency of SARS-CoV-2 PCR and rapid antigen testing depend on the level of transmission. Case investigation and contact tracing should be comprehensive to identify the close contacts to prevent further transmission. These facility-based infection prevention and control strategies help reduce hospital transmission of SARS-CoV-2 to a minimum in Taiwan., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Universal admission screening and follow-up symptom-based testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may play critical roles in controlling nosocomial transmission. We describe the performance of test strategies for inpatients and their companions during various disease incidences in Taiwan., Design: Retrospective population-based cohort study., Setting: The study was conducted across 476 hospitals in Taiwan., Methods: The data for both testing strategies by reverse transcription-polymerase chain reaction for SARS-CoV-2 in newly admitted patients and their companions during May 2021-June 2022 were extracted and analyzed., Results: The positivity rate of universal admission screening was 0.76% (14,640 of 1,928,676) for patients and 0.37% (5,372 of 1,438,944) for companions. The weekly community incidences of period 1 (May 2021-June 2021), period 2 (July 2021-March 2022), and period 3 (April 2022-June 2022) were 6.57, 0.27, and 1,261, respectively, per 100,000 population. The positivity rates of universal admission screening for patients and companions (4.39% and 2.18%) in period 3 were higher than those in periods 1 (0.29% and 0.04%) and 2 (0.03% and 0.003%) (all P < .01). Among the 22,201 confirmed cases, 9.86% were identified by symptom-based testing. The costs and potential savings of universal admission screening for patients and companions achieved a breakeven point when the test strategy was implemented in a period with weekly community incidences of 27 and 358 per 100,000 population, respectively., Conclusions: Universal admission screening and follow-up symptom-based testing is important for reducing nosocomial transmission. Implementing universal admission screening at an appropriate time would balance the benefits with costs and potential unintended harms.

Background/purpose: Long-term care facilities (LTCFs) are high-risk settings for the novel coronavirus disease (COVID-19). The aim of the study was to describe the extent and the impacts of 2021 COVID-19 outbreaks on LTCFs in Taiwan., Methods: We retrospectively analyzed the data of each COVID-19 outbreak in LTCFs from May 15 to July 31, 2021 in Taiwan. We characterized the features of LTCFs with outbreaks and compared the characteristics of infected staff members and residents of the affected LTCFs., Results: COVID-19 outbreaks were reported in 16 LTCFs (0.9%). The outbreak was significantly associated with LTCFs with ≥50 beds [adjusted odds ratio (aOR), 6.3; 95%confidence interval [CI], 1.9-21.1] and location of Taipei metropolitan area (aOR, 4.6; 95%CI, 1.7-12.8). Resident cases accounted for 75.4% (203/269) of confirmed cases affected by outbreaks. The 30-day all-cause mortality was 24.2% for residents only and was significantly associated with age ≥65 years [adjusted hazard ratio (aHR, 4.3; 95%CI, 1.7-10.5)], presence of symptoms on diagnosis (aHR, 2.2; 95%CI, 1.3-3.7), and LTCF occupancy rate ≥80% (aHR, 3.0, 95%CI, 1.3-7.4)., Conclusion: COVID-19 outbreaks have a critical impact on residents in LTCFs owing to the advanced age and high prevalence of chronic comorbidities in this population. Multi-pronged infection control measures and mass testing are vital for mitigating COVID-19 transmission in LTCFs., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest to disclose., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

The skin is a vital organ in the human body, providing essential functions such as protection, sensation, and metabolism. Skin hydration is one of the crucial factors in maintaining normal skin function. Insufficient skin hydration can lead to dryness, shedding of the stratum corneum, a decrease in skin barrier function, and may cause skin inflammation. Therefore, maintaining or improving skin hydration is critical in promoting healthy skin. Currently, the commonly used method for measuring skin hydration is bioelectrical capacitance analysis, which is often affected by environmental humidity and can only provide limited information. To overcome these limitations, this study used diffuse reflectance spectroscopy (DRS) in the wavelength range of 400-1000 nm to quantify skin absorption and scattering modulation caused by changes in skin hydration states. The advantages of this technique include rapid measurements, non-invasiveness, a straightforward optical setup, and suitability for prolonged skin monitoring. We found that DRS-derived skin absorption coefficients had a correlation coefficient of 0.93 with the skin capacitance at various skin hydration states. In addition, our findings reveal that absorption and scattering coefficients may be useful in discerning skin hydration enhancement induced by applying soaked cotton pads or cosmeceutical facial masks, as well as evaluating skin sensation. This study verifies that the DRS method could be a convenient and effective tool for evaluating skin hydration related information., (© 2023. The Author(s).)

Background: Central line-associated bloodstream infection (CLABSI) surveillance data are voluntarily submitted to the Taiwan Healthcare-associated Infection and Antimicrobial Resistance Surveillance (THAS) System. Validation of the CLABSI data is important to ensure the quality of surveillance data. We aimed to validate the CLABSI surveillance data reported to the THAS system., Methods: This study was a retrospective medical record review of patients with positive blood cultures admitted to the intensive care units (ICUs) of 13 participating hospitals between October and December 2021. An external validation team was convened to perform the validation process according to the standardised protocol and to record the reasons for misclassification., Discussion: During the study period, 688 patients with 1,238 positive blood cultures from 59 ICUs at 13 hospitals were evaluated. Among the 185 potential CLABSI events which met the THAS definition by either the external reviewers or the hospital reviewers, 24 (13.0%) events were identified by only the external reviewers, and six (3.2%) were identified by only the hospital reviewers, with an agreement rate of 83.8%. Using external reviewers as the gold standard, the pooled mean sensitivity and positive predictive value of CLABSI reporting were 86.6% (155/179) and 96.3% (155/161), respectively. Among the 37 misclassification episodes, missed case findings were the most common reason for misclassification ( N= 16, 43.2%)., Conclusions: The CLABSI data reported to the THAS system are generally reliable. This study showed the need for ongoing validation processes and quality improvement to maintain the accuracy and validity of the surveillance data., (© 2023 The Authors.)

Background: In Asian countries, such as Taiwan, social taboos regarding organ and tissue donation decreases the prevalence of organ and tissue transplants. This also applies to cornea recovery, which is a skill that requires precision and practice to perform well. In Taiwan, to ensure the maintenance of high-quality corneas, a comprehensive training program and certified examination has been implemented. This study aims to investigate the impact of these programs and examinations on cornea recovery., Methods: Researchers evaluated the efficiency of the training and certified examination process by comparing the corneoscleral rim width, Descemet's membrane folds, endothelial layer stress lines, and endothelial cell density performed by ophthalmology residents in 2018 and 2019., Results: After training and certification, the Descemet's membrane folds rate decreased from 14.3 % to 2.0 % and endothelial layer stress lines rate decreased from 22.5 % to 5.0 %. The endothelial cell density of donor grafts significantly improved from 2681.9 cells/mm 2 to 2869.7 cells/mm 2 ( p  < 0.001)., Conclusions: This study used objective data to evaluate cornea recovery quality after training and certification. The training and certified examination significantly improved the surgical skills of ophthalmology residents and could be applied in other tissue or organ recovery procedures to maintain and improve quality., Competing Interests: 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., (© 2023 The Authors.)

Accurate measurement of bilirubin concentration in adults is crucial for the diagnosis and management of liver and biliary tract diseases. Traditional methods relying on central laboratory testing pose challenges such as invasiveness, patient discomfort, and time consumption. Non-invasive alternatives have been explored, but their applicability to adult populations remains uncertain. This study aimed to develop and validate a portable non-invasive optical system based on spatially resolved diffuse reflectance spectroscopy (DRS) specifically tailored for adult transcutaneous bilirubin measurement. Forty-two adult patients with various underlying conditions were included in the study. Comparisons between transcutaneous bilirubin values measured by the DRS system and total serum bilirubin concentrations obtained through blood tests revealed strong correlations, particularly at the neck ( r  = 0.872) and the medial side of the right upper arm ( r  = 0.940). Bland-Altman analyses demonstrated substantial agreement between the transcutaneous bilirubin values and total serum bilirubin concentrations. The results highlight the potential of the non-invasive DRS system as a convenient and reliable tool for monitoring bilirubin values in adults., Competing Interests: The authors declare no conflicts of interest related to this article., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Diagnosing acute rejection after intestinal transplantation currently heavily relies on histopathological analysis of graft biopsies. However, the invasive risks associated with ileoscopic examination and the inaccessibility for biopsy after ileostomy closure hinder real-time detection of rejection responses. Molecules comprising the intestinal barrier have been identified as physiological and molecular biomarkers for various bowel conditions and systemic diseases. To investigate the potential of barrier function-related molecules in diagnosing rejection after intestinal transplantation, plasma samples were collected longitudinally from transplant recipients. The samples were categorized into "indeterminate for rejection (IND)" and "acute rejection (AR)" groups based on clinical diagnoses at each time point. The longitudinal association between plasma levels of these barrier function-related molecules and acute rejection was analyzed using the generalized estimating equations (GEE) method. Logistic GEE models revealed that plasma levels of claudin-3, occludin, sIgA, and zonulin were independent variables correlated with the clinical diagnosis of acute rejection. The subsequent prediction model demonstrated moderate ability in discriminating between IND and AR samples, with a sensitivity of 76.0%, specificity of 89.2%, and accuracy of 84.6%. In conclusion, monitoring plasma levels of claudin-3, occludin, sIgA, and zonulin shows great potential in aiding the diagnosis of acute rejection after intestinal transplantation., 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 © 2023 Chen, Tseng, Chen and Tsai.)

Background: The International Classification of Functioning, Disability and Health (ICF) core set (CS) facilitates the standardization of functioning and impairment assessment for integration of holistic care., Objective: This study developed an ICF CS for interviewing pediatric brain tumor survivors in Taiwan to help healthcare professionals in implementing disability assessment and management measures., Methods: A group of 29 experts in 10 relevant fields with at least 5 years of experience working with children with brain tumors participated in this study. The first questionnaire contained 247 second-level ICF categories. The experts rated the significance of each category by using a 5-point Likert scale. Correlations between individual and group scores were calculated to determine consensus. Categories with an average rating of higher than 4 and for which greater than or equal to 80% (23) of the participants provided a rating of 4 or higher were included in the final CS., Results: The final CS contained a total of 57 ICF categories: 20 from the Body Functions and Structures component, 36 from the Activities and Participation component, and 1 from the Environmental Factors component., Conclusion: The ICF CS for pediatric brain tumor survivors provides a framework for relevant healthcare professionals to deliver patient-centered care, ensuring that services focus on all areas of development., Implications for Practice: Patient ratings for this ICF CS may serve as a new practical and effective patient-reported information tool for acquiring patient input and for the systematic monitoring of pediatric brain tumor survivors in clinical practice. Further research should be conducted on this CS to verify our findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Bortezomib has been successful for treatment of multiple myeloma, but not against solid tumors, and toxicities of neuropathy, thrombocytopenia and the emergence of resistance have triggered efforts to find alternative proteasome inhibitors. Bis-benzylidine piperidones such as RA190 covalently bind ADRM1/RPN13, a ubiquitin receptor that supports recognition of polyubiquitinated substrates of the proteasome and their subsequent deububiqutination and degradation. While these candidate RPN13 inhibitors (iRPN13) show promising anticancer activity in mouse models of cancer, they have suboptimal drug-like properties. Here we describe Up284, a novel candidate iRPN13 possessing a central spiro-carbon ring in place of RA190's problematic piperidone core. Cell lines derived from diverse cancer types (ovarian, triple negative breast, colon, cervical and prostate cancers, multiple myeloma and glioblastoma) were sensitive to Up284, including several lines resistant to bortezomib or cisplatin. Up284 and cisplatin showed synergistic cytotoxicity in vitro. Up284-induced cytotoxicity was associated with mitochondrial dysfunction, elevated levels of reactive oxygen species, accumulation of very high molecular weight polyubiquitinated protein aggregates, an unfolded protein response and the early onset of apoptosis. Up284 and RA190, but not bortezomib, enhanced antigen presentation in vitro. Up284 cleared from plasma in a few hours and accumulated in major organs by 24 h. A single dose of Up284, when administered to mice intra peritoneally or orally, inhibited proteasome function in both muscle and tumor for >48 h. Up284 was well tolerated by mice in repeat dose studies. Up284 demonstrated therapeutic activity in xenograft, syngeneic and genetically-engineered murine models of ovarian cancer., Competing Interests: Compounds described are covered by US patent US20190365726 and application 17/154,306. The study described in this publication utilized compounds manufactured by Up Therapeutics LLC (MTA A36130). Dr. Roden is a consultant to Up Therapeutics LLC and owns stock in the company. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Dr. Anchoori is the founder of Up Therapeutics LLC and owns stock in the company. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. This does not alter our adherence to PLOS ONE policies on sharing data and materials, (Copyright: © 2023 Anchoori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Twelve Asian patients with sarcoma received interval-compressed (ic-) chemotherapy scheduled every 14 days with a regimen of vincristine (2 mg/m 2 ), doxorubicin (75 mg/m 2 ), and cyclophosphamide (1200-2200 mg/m 2 ) (VDC) alternating with a regimen of ifosfamide (9000 mg/m 2 ) and etoposide (500 mg/m 2 ) (IE), with filgrastim (5-10 mcg/kg/day) between cycles. Carboplatin (800 mg/m 2 ) was added for CIC-rearranged sarcoma. The patients were treated with 129 cycles of ic-VDC/IE with a median interval of 19 days (interquartile range [IQR], 15-24 days. Median nadirs (IQR) were neutrophil count, 134 (30-396) × 10 6 /L at day 11 (10-12), recovery by day 15 (14-17) and platelet count, 35 (23-83) × 10 9 /L at day 11 (10-13), recovery by day 17 (14-21). Fever and bacteremia were observed in 36% and 8% of cycles, respectively. The diagnoses were Ewing sarcoma (6), rhabdomyosarcoma (3), myoepithelial carcinoma (1), malignant peripheral nerve sheath tumor (1), and CIC-DUX4 Sarcoma (1). Seven of the nine patients with measurable tumors responded (one CR and six PR). Interval-compressed chemotherapy is feasible in the treatment of Asian children and young adults with sarcomas.

After a stroke, sustained gait impairment can restrict participation in the activities listed in the International Classification of Functioning, Disability, and Health model and cause poor quality of life. The present study investigated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and visual feedback training (VF) training in improving lower limb motor performance, gait, and corticospinal excitability in patients with chronic stroke. Thirty patients were randomized into three groups that received either rTMS or sham stimulation over the contralesional leg region accompanied by VF training groups in addition to the conventional rehabilitation group. All participants underwent intervention sessions three times per week for four weeks. Outcome measures included the motor-evoked potential (MEP) of the anterior tibialis muscle, Berg Balance Scale (BBS) scores, Timed Up and Go (TUG) test scores, and Fugl-Meyer Assessment of Lower Extremity scores. After the intervention, the rTMS and VF group had significantly improved in MEP latency ( p = 0.011), TUG scores ( p = 0.008), and BBS scores ( p = 0.011). The sham rTMS and VF group had improved MEP latency ( p = 0.027). The rTMS and VF training may enhance the cortical excitability and walking ability of individuals with chronic stroke. The potential benefits encourage a larger trial to determine the efficacy in stroke patients.

Paclitaxel frequently induces peripheral neuropathy and myelosuppression during cancer treatment. According to the National Health Insurance Research Database of Taiwan, traditional Chinese medicine doctors widely use Xiang Sha Liu Jun Zi Tang (XSLJZT) to treat breast cancer patients who have received paclitaxel. We explored the combined therapeutic effects of XSLZJT with paclitaxel. XSLJZT did not exhibit significant cytotoxic effects on P388-D1 cells; however, the combination of XSLJZT (100 and 500 mg/kg) with paclitaxel prolonged the survival rate in P388-D1 tumor-bearing mice compared to paclitaxel-only. In addition, XSLJZT was found to enhance white blood cells (WBC) counts and promote leukocyte rebound in paclitaxel-induced leukopenia in mice. XSLJZT also reduced paclitaxel-induced mechanical pain and inhibited c-Fos protein expression in the L4-6 spinal cords of Wistar rats. Moreover, paclitaxel-induced shortening of the nerve fibers of dorsal root ganglion cells was ameliorated by pre-treatment with XSLJZT. Therefore, we suggest that XSLJZT could be used as an adjunct for cancer patients, as the formula could decrease paclitaxel-induced neuropathy and myelosuppression., 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 © 2023 Shiah, Lee, Lee, Tseng, Chen and Wang.)

The prevalence rate of neonatal jaundice can reach 80%, of which 5% may develop dangerous hemolytic jaundice. The blood test for obtaining bilirubin and hemoglobin concentration is the gold standard for diagnosing hemolytic jaundice; however, frequently drawing blood from jaundice neonates for the screening purpose is not practical. We have developed a handheld diffuse reflectance spectroscopy system to noninvasively determine the bilirubin and hemoglobin levels in neonates. Our study showed that the correlation coefficients were 0.95 and 0.80 for bilirubin and hemoglobin between the results from the blood tests and our handheld system, respectively. This handheld system could be an effective tool for screening hemolytic jaundice., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Although past research has shown an association between obesity and herpes simplex virus infection, the relationship between body mass index (BMI) and herpetic stromal keratitis (HSK) recurrence has never been investigated. In this study, we included HSK patients who received oral valacyclovir as prophylactic treatment between January 2016 and January 2021. Recurrence, possible risk factors, and the time to recurrence were recorded during follow-ups. Among the 56 patients included in this study, recurrence was reported in 21 (37.5%) patients. The age at disease onset and mean follow-up time were not significantly different in the recurrence and non-recurrence groups. However, in the Cox regression analysis, BMI ≥ 24 kg/m 2 was noted as the variable having significant correlation with recurrence ( p = 0.01 in univariate analysis and p = 0.001 in multivariate analysis). In conclusion, overweight and obesity were revealed as risk factors for HSK recurrence in patients receiving long-term antiviral prophylaxis. Further studies are needed to determine the appropriate acyclovir concentrations in the blood or aqueous humour in order to achieve desirable prophylactic effects, especially in the overweight and obese patients.

Deep brain stimulation (DBS) conventionally target at basal ganglia or thalamic structures, modulating nodal points in the cortico-basal ganglia circuit, in order to effectively treat various movement disorders, including Parkinson's disease, tremor and dystonia (especially mobile type dystonia). However, there are still some other movement disorders, such as dystonia (especially fixed type dystonia), ataxia and freezing of gait, which are not responding well to the current DBS therapy. Cerebellum, similar to basal ganglia, also plays a critical role in the pathophysiology of movement disorders. Deep cerebellar structures, such as dentate nucleus or superior cerebellar peduncle, are noticed for their potential role as treatment targets in movement disorders in recent years. With increasing evidences of animal DBS experiments, recent clinical human subject studies reported that some movement disorders patients not responding to DBS with conventional targets, may benefit significantly from cerebellar DBS. These pioneer study results are invaluable for understanding the clinical use of cerebellar DBS for treatment of movement disorders. We review the recent data of cerebellar DBS performed by different groups and summarize the indications, surgical targets, programming details and outcomes in these clinical reports. We then synthesize the current pathophysiological study of cerebellum on different movement disorders and discuss the potential mechanism of action of cerebellar DBS. In addition to basal ganglia, it is important to study new DBS targets in the cerebellum for more comprehensive treatment of movement disorders., Competing Interests: Declaration of Competing Interest The authors report no declaration of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)