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Chien-Chia Huang,1,2 Po-Hung Chang,1,* Yen-Lin Huang,3– 5 Ta-Jen Lee,1,2,6 Chi-Che Huang,1,2 Pei-Wen Wu1,2,* 1Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Anatomic Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4School of Medicine, National Tsing-Hua University, Hsinchu, Taiwan; 5Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Department of Otolaryngology, Xiamen Chang Gung Hospital, Xiamen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pei-Wen Wu, Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital and Chang Gung University, No. 5, Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan, Tel +886-3-3281200 ext. 8466, Fax +886-3-3979361, Email a9665@cgmh.org.twIntroduction: Eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with greater inflammation, poorer prognosis, and a high recurrence rate after sinus surgery.Objective: This study evaluated the clinical and imaging characteristics of eosinophilic CRSwNP in patients aged 12– 17.Methods: We retrospectively enrolled 139 patients aged 12– 17 with bilateral CRSwNP. Clinical characteristics, computed tomography (CT) features, tissue eosinophil counts, and eosinophil activity were evaluated.Results: Twenty-three (16.5%) patients had recurrent nasal polyps that required revision surgery. Patients requiring revision surgery had higher tissue eosinophil infiltration in the sinus mucosa than those not requiring revision surgery. The optimal cut-off value to distinguish the need for revision surgery was a tissue eosinophil count > 21.5/high-power field determined by the receiver operating characteristic curve. The Lund-Mackay and olfactory cleft opacification scores on CT images were significant predictors of tissue eosinophil count in the univariate analysis, and only olfactory opacification scores remained statistically significant in the multivariate analysis.Conclusion: This study revealed that the CT feature of the olfactory cleft opacification score could be a significant characteristic of eosinophilic CRSwNP in adolescents.Plain Language Summary: Chronic rhinosinusitis (CRS) is an inflammation of the nasal and sinus mucosa characterized by nasal obstruction, mucopurulent rhinorrhea, facial pain/pressure, and decreased or loss of smell for over 12 weeks.CRS is classified as CRS without nasal polyps or CRS with nasal polyps (CRSwNP), depending on the presence of nasal polyps. Based on the predominance of tissue inflammatory cell infiltration by eosinophils or neutrophils, CRS can be categorized into eosinophilic and neutrophilic entities. Eosinophilic CRSwNP is clinically characterized by a greater extent of inflammation, more severe clinical symptoms and high recurrence rate after sinus surgery. Thus, early identification of the endotypes in patients with CRS is important for determining prognosis and treatment strategies.This study retrospectively enrolled 139 patients aged 12– 17 with bilateral CRSwNP. Clinical characteristics, CT features, tissue eosinophil counts, and eosinophil activity were evaluated. The results showed that patients requiring revision surgery had higher tissue eosinophil infiltration in the sinus mucosa than those not requiring revision surgery. The optimal cut-off value to distinguish the need for revision surgery was a tissue eosinophil count > 21.5/high-power field. The Lund-Mackay and olfactory cleft opacification scores on CT images were significant predictors of tissue eosinophil count in the regression analysis.Keywords: adolescent, chronic rhinosinusitis, computed tomography, eosinophil, nasal polyp

Yun-Chen Chang,1 Ta-Jen Lee,1 Chi-Che Huang,1,2 Po-Hung Chang,1,2 Yi-Wei Chen,1 Chia-Hsiang Fu1,2 1Department of Otolaryngology-Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan City, 333, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City, 333, TaiwanCorrespondence: Chia-Hsiang FuDivision of Rhinology, Department of Otolaryngology-Head and Neck Surgery, Linkou Chang Gung Memorial Hospital and Chang Gung University, No. 5 Fu-Shin Street, Guishan District, Taoyuan City, 333, TaiwanTel +886-3-3281200, ext.: 8465Fax +886-3-3979361Email fufamily@adm.cgmh.org.twBackground: Screening for the existence of aeroallergens in patients with possible allergic rhinitis using venous blood samples has become more popular, with advantages of increased convenience and less consumption of time.Objective: The aim of this study was to investigate the sensitivities and specificities of Phadiatop tests and total immunoglobulin E (IgE) levels in both adults and children.Methods: This study was conducted prospectively in a tertiary center. The process of recruitment took place from Jan 2015 to Dec 2019, and patients with clinical symptoms that suggested persistent allergic rhinitis were recruited and their serum samples collected. The results of the total IgE and Phadiatop tests as well as the positive items in the ImmunoCAP assay were recorded and analyzed.Results: A total of 9174 cases with complete data were enrolled, including 576 children and 8598 adults. A positive result in the ImmunoCAP assay was considered a positive atopic status towards aeroallergens. While using the total IgE levels to predict positive aeroallergens, the sensitivities and specificities were 65.7% and 85.7%, respectively, for adults and 86.3% and 77.4%, respectively, for children. When we used Phadiatop tests for allergy screening, the sensitivities and specificities was 94.5% and 98.2%, respectively, for the adult group and 98.5% and 96.8%, respectively, for the pediatric group.Conclusion: The Phadiatop test had better diagnostic power for aeroallergen detection than the serum total IgE levels, or even the dual test, for both the adult and pediatric groups in this hospital-based study. We suggest that the Phadiatop test is more cost-effective in aeroallergen screening for patients with suspected atopic airway diseases.Keywords: Phadiatop test, ImmunoCAP, total immunoglobulin E, IgE, aeroallergens

Pei-Wen Wu,1,2 Ta-Jen Lee,1 Chun-Hua Wang,3 Chi-Che Huang,1,4 Po-Hung Chang,1,4 Chia-Hsiang Fu,1,4 Chien-Chia Huang1,4 1Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 2Department of Otolaryngology–Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Keelung, Taiwan; 3Department of Thoracic Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 4Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, TaiwanCorrespondence: Chien-Chia HuangDivision of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital and Chang Gung University, No. 5, Fu-Shin Street, Kweishan, Taoyuan 333, TaiwanTel +886-3-3281200 Ext 8466Fax +886-3-3979361Email agar@cgmh.org.twIntroduction: Most patients with asthma, either allergic or non-allergic, usually exhibit some level of concurrent rhinitis. Treatments for rhinitis and asthma can affect both conditions.Objective: The present study aimed to examine asthma-specific outcomes in patients with chronic rhinitis (CR) and asthma after surgery for nasal obstruction, and to identify the patient group most likely to experience improved asthma control after surgery.Methods: Asthmatic patients with CR and nasal obstruction were prospectively recruited for evaluations of nasal and asthma-specific outcomes before and after surgery for nasal obstruction.Results: Twenty-eight participants were enrolled. There was a significant association between the Asthma Control Test (ACT) and the Sino-Nasal Outcome Test-22 scores, both at the preoperative and 3-month postoperative assessments. Patients demonstrating ACT improvement after nasal surgery had worse preoperative ACT scores and predicted forced expiratory volume in 1 s.Conclusion: Nasal symptom severity was closely associated with the extent of asthma control in asthmatic patients with CR and nasal obstruction. Assessment of CR and nasal obstruction in patients with poorly controlled asthma should be considered an essential approach to improve the response to treatment and patients’ quality of life.Keywords: rhinitis, asthma, SNOT-22, quality of life, patient-reported outcome measure

Siang Fei Yeoh,1 Tae Jin Lee,2 Ka Lip Chew,3 Stephen Lin,4 Dennis Yeo,5 Sajita Setia5 1Department of Pharmacy, National University Health System, Singapore, Singapore; 2Department of Pharmacy, National University of Singapore, Singapore, Singapore; 3Department of Laboratory Medicine, National University Hospital, Singapore, Singapore; 4Global Medical Affairs, Asia-Pacific region, Pfizer, Hong Kong, People’s Republic of China; 5Medical Affairs, Pfizer Pte. Ltd., Singapore, Singapore Abstract: Candida species remains one of the most important causes of opportunistic infections worldwide. Invasive candidiasis (IC) is associated with considerable morbidity and mortality in liver disease (LD) patients if not treated promptly. Echinocandins are often recommended as a first-line empirical treatment for managing IC and can especially play a critical role in managing IC in LD patients. However, advanced LD patients are often immunocompromised and critically ill. Hence altered pharmacokinetics, drug interactions as well as tolerance issues of antifungal treatments are a concern in these patients. This comprehensive review examines the epidemiology, risk factors and diagnosis of IC in patients with LD and evaluates differences between three available echinocandins for treating this group of patients. Keywords: anidulafungin, caspofungin, candidemia, micafungin

I-Hung Shao,1,* Chia-Chen Wu,2,* Hsiao-Jung Tseng,3 Ta-Jen Lee,2 Yu-Hsiang Lin,4 Yuan-Yun Tam5 1Division of Urology, Department of Surgery, Lotung Poh-Ai Hospital, Yilan County, 2Department of Otorhinolaryngology – Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Chang Gung University, 3Biostatistical Center for Clinical Research, Chang-Gung Memorial Hospital, Taoyuan City, 4Division of Urology, Department of Surgery, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, 5Department of Otorhinolaryngology – Head and Neck Surgery, Lotung Poh-Ai Hospital, Yilan County, Taiwan *These authors contributed equally to this work Background: Pseudoephedrine is a sympathomimetic drug widely used as a nasal decongestant. However, it can cause adverse effects, such as voiding dysfunction. The risk of voiding dysfunction remains uncertain in patients without subjective voiding problems.Methodology: We prospectively enrolled patients with nasal congestion who required treatment with pseudoephedrine from May to August 2015. All patients denied concomitant subjective voiding problem. The International Prostate Symptom Score (IPSS) questionnaire was used to evaluate voiding function before and 1 week after the pseudoephedrine treatment. The results of the IPSS questionnaire were analyzed as the total (IPSS-T), voiding (IPSS-V), storage (IPSS-S), and quality of life due to urinary symptom scores.Results: We enrolled 131 males with a mean age of 42.0±14.3 years. The IPSS-T, IPSS-V, and IPSS-S scores slightly increased after the medication (IPSS-T increased from 6.49 to 6.77, IPSS-V from 3.33 to 3.53, and IPSS-S from 3.17 to 3.24). The quality of life due to urinary symptom score nonsignificantly decreased from 2.02 to 1.87. We observed that older age and a higher premedication IPSS-V score yielded significant differences (P50 years, even without subjective voiding symptoms. Keywords: pseudoephedrine, nasal congestion, voiding dysfunction, IPSS

Yuan-Yun Tam,1,* Chia-Chen Wu,2,* Ta-Jen Lee,2 Yang-Yu Lin,3 Tai-Di Chen,4 Chi-Che Huang2 1Department of Otorhinolaryngology – Head and Neck Surgery, Lotung Poh-Ai Hospital, Yilan County, 2Department of Otorhinolaryngology – Head and Neck Surgery, 3Department of Medical Imaging and Intervention, 4Department of Pathology, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan County, Taiwan *These authors contributed equally to this work Background: Sinonasal angiomatous polyp (SAP) is a rare subtype of sinonasal polyp that might be misdiagnosed as a malignant lesion due to its clinical symptoms.Methods: We retrospectively enrolled the patients who were diagnosed with SAP in our hospital during 2008–2015. We analyzed the clinical symptoms, radiological findings, and pathological features of all patients diagnosed with SAP.Results: Unilateral nasal obstruction, rhinorrhea, and epistaxis were the common symptoms. SAPs all originated from maxillary sinus and extended to nasal cavity with or without involving the nasopharynx. Expansile mass with surrounding bony destruction is typical on computed tomography imaging but specific for SAPs. The magnetic resonance revealed high signal intensity on T1-weighted images and hypointense rim on T2-weighted images.Conclusion: Computed tomography and magnetic resonance together might give rise to more accurate diagnosis of SAP. Incisional biopsy does help if the clinician suspects a malignant lesion. To treat SAP, complete removal is the optimal choice. Keywords: sinonasal angiomatous polyp, angiomatous polyp, antrochoanal polyp, angiomatous nasal polyp, infarcted nasal polyp

Hark-Soo Park,1 Seon-Ju Kim,1 Taek-Jin Lee,1 Geon-Yong Kim,1 EunHo Meang,1 Jeong-Sup Hong,1 Su-Hyon Kim,1 Sang-Bum Koh,1 Seung-Guk Hong,1 Yle-Shik Sun,1 Jin Seok Kang,2 Yu-Ri Kim,3 Meyoung-Kon Kim,3 Jayoung Jeong,4 Jong-Kwon Lee,4 Woo-Chan Son,5 Jae-Hak Park61General Toxicology Team, Korea Testing and Research Institute, Seoul, 2Department of Biomedical Laboratory Science, Namseoul University, Cheonan, 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, 4National Institute of Food and Drug Safety Evaluation, Seoul, 5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 6Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, KoreaPurpose: The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM,20(+)) nanoparticles in Sprague Dawley rats for 90 days.Methods: For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM,20(+) NPs.Results: No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with control in both 500 mg/kg groups. Total protein and albumin levels were decreased significantly in both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa, and retinal atrophy of the eye in the 500 mg/kg group.Conclusion: There were significant parameter changes in terms of anemia in the hematological and blood chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was not determined, but the lowest-observed-adverse-effect level was considered to be 125 mg/kg in both sexes and the target organs were found to be the pancreas, eye, and stomach.Keywords: positive charge, oral-toxicity study, no-observed-adverse-effect level, ZnO

Hwa Jung Ryu,1,* Mu Yeb Seo,2,* Sung Kyu Jung,1 Eun Ho Maeng,2 Seung-Young Lee,2 Dong-Hyouk Jang,2 Taek-Jin Lee,2 Ki-Yeon Jo,2 Yu-Ri Kim,3 Kyu-Bong Cho,4 Meyoung-Kon Kim,3 Beom Jun Lee,5 Sang Wook Son1 1Department of Dermatology, Korea University College of Medicine, Seoul, 2Korea Testing and Research Institute, Gyunggido, 3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 4Department of Clinical Laboratory Science, Shinheung College, Uijeongbu, 5College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea *These authors contributed equally to this work and both should be considered first authors Abstract: Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. Keywords: zinc oxide, nanoparticles, subchronic toxicity, dermal exposure

Hwa-young Lee,1 Bong-Min Yang,1 Ji-min Hong,1 Tae-Jin Lee,1 Byoung-Gie Kim,2 Jae-Weon Kim,3 Young-Tae Kim,4 Yong-Man Kim,5 Sokbom Kang61Graduate School of Public Health, Seoul National University, Seoul, South Korea; 2Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, South Korea; 3Department of Obstetrics and Gynecology, Seoul National University, Seoul, South Korea; 4Department of Obstetrics and Gynecology, Yonsei University, Seoul, South Korea; 5Department of Obstetrics and Gynecology, University of Ulsan, Ulsan, South Korea; 6Department of Obstetrics and Gynecology, National Cancer Center, Kyeonggi-do, South KoreaObjective: We performed a cost–utility analysis to assess the cost-effectiveness of a chemotherapy sequence including a combination of polyethylene glycolated liposomal doxorubicin (PLD)/carboplatin versus paclitaxel/carboplatin as a second-line treatment in women with platinum-sensitive ovarian cancer.Methods: A Markov model was constructed with a 10-year time horizon. The treatment sequence consisted of first- to sixth-line chemotherapies and best supportive care (BSC) before death. Cycle length, a time interval for efficacy evaluation of chemotherapy, was 9 weeks. The model consisted of four health states: responsive, progressive, clinical remission, and death. At any given time, a patient may have remained on a current therapy or made a transition to the next therapy or death. Median time to progressions and overall survivals data were obtained through a systematic literature review and were pooled using a meta-analytical approach. If unavailable, this was elicited from an expert panel (eg, BSC). These outcomes were converted to transition probabilities using an appropriate formula. Direct costs included drug-acquisition costs for chemotherapies, premedication, adverse-event treatment and monitoring, efficacy evaluation, BSC, drug administration, and follow-up tests during remission. Indirect costs were transportation expenses. Utilities were also derived from the literature. Costs and utilities were discounted at an annual rate of 5% per cycle.Results: PLD/carboplatin combination as the second line in the sequence is more effective and costly than paclitaxel/carboplatin combination, showing an additional US$21,658 per quality-adjusted life years. This result was robust in a deterministic sensitivity analysis except when median time to progression of second-line therapies and administration cost of PLD/carboplatin per administration cycle were varied. The probability of cost-effectiveness for PLD/carboplatin combination was 49.4% at a willingness to pay $20,000.Conclusion: A PLD/carboplatin combination is an economically valuable option as second-line chemotherapy for the treatment of platinum-sensitive ovarian cancer in South Korea.Keywords: cost, utility, Markov modeling, ovarian cancer, chemotherapy

Background: Athletes have changes that can mimic pathological cardiomyopathy. Methods: Echocardiographic study of 50 male, female athletes (MA, FA) and non-athletes (MNA, FNA) age 18 to 30 years. These athletes participate in sports with predominantly endurance component. All participants exhibit no known medical illnesses or symptoms. Results: MA have thicker wall (IVSd) than MNA. No MA have IVSd > 1.2 cm and no FA have IVSd > 1.0 cm. Left ventricle internal dimension (LVIDd), left ventricle end diastolic volume index (LVEDVi) is bigger in athletes. None have LVIDd > 5.8 cm. Right ventricle fractional area change (FAC) is lower in athletes. (MA vs MNA, p = 0.013, FA vs FNA, p = 0.025). Athletes have higher septal and lateral e’ (Septal e’; MA 13.57 ± 2.66 cm/s vs MNA 11.46 ± 2.93 cm/s, p 1.2 cm and/or LVIDd > 5.8 cm. There is no difference in GLS, RVFWS and GCS but athletes have smaller LArS and LAbS.

Alternative strategies to increase access to reproductive health services among internally displaced populations are urgently needed. In eastern Burma, continuing conflict and lack of functioning health systems render the emphasis on facility-based delivery with skilled attendants unfeasible. Along the Thailand-Burma border, local organisations have implemented an innovative pilot, the Mobile Obstetric Maternal Health Workers (MOM) Project, establishing a three-tiered collaborative network of community-based reproductive health workers. Health workers from local organisations received practical training in basic emergency obstetric care plus blood transfusion, antenatal care and family planning at a central facility. After returning to their target communities inside Burma, these first-tier maternal health workers trained a second tier of local health workers and a third tier of traditional birth attendants (TBAs) to provide a limited subset of these interventions, depending on their level of training. In this ongoing project, close communication between health workers and TBAs promotes acceptance and coverage of maternity services throughout the community. We describe the rationale, design and implementation of the project and a parallel monitoring plan for evaluation of the project. This innovative obstetric health care delivery strategy may serve as a model for the delivery of other essential health services in this population and for increasing access to care in other conflict settings. [ABSTRACT FROM AUTHOR]

Background/aim: Chronic low back pain (CLBP) significantly reduces quality of life and increases reliance on healthcare resources. Despite many individuals opting for vitamin D supplementation to alleviate CLBP, its efficacy remains debatable. This meta-analysis aimed to evaluate the potential benefits of vitamin D supplementation in treating this condition., Patients and Methods: Adhering to PRISMA guidelines, we systematically reviewed the effectiveness of vitamin D supplementation in adults with CLBP, focusing exclusively on randomized controlled trials (RCTs). A comprehensive literature search was conducted up to May 2024 across multiple databases, including PubMed, Scopus, Cochrane Library, and Web of Science., Results: Ten RCTs meeting our inclusion criteria were analyzed. The results indicated that vitamin D supplementation did not significantly reduce pain scores compared to control groups (SMD: -0.130, 95%CI=-0.260 to 0.000; I 2 =0%), regardless of participants' baseline vitamin D levels. Moreover, long-term supplementation showed no notable improvement in CLBP outcomes (SMD: -0.097, 95%CI=-0.290 to -0.097; I 2 =19.878%). Additionally, supplementation with active forms of vitamin D (SMD: -0.321, 95%CI=-0.670 to 0.028; I 2 =0.000%) did not result in significant pain relief for chronic lower back pain., Conclusion: Vitamin D supplementation does not substantially alleviate CLBP. Nevertheless, it may still be considered as part of a comprehensive treatment plan. Further research is necessary to explore its long-term effects and the underlying mechanisms that may explain the observed lack of benefit., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In traditional TEMPO oxidation systems, the high cost of TEMPO catalysts has been a significant barrier to the industrialization of oxidized CNF. From an economic perspective, presenting the characteristics of various CNFs produced with the oxidation systems with reduced catalyst usage could facilitate the industrial application of CNF across a wide range of fields. In this study, it was demonstrated that reducing the amount of TEMPO catalyst used (from 0.1 to 0.05 mmol g -1 ) in a conventional oxidation system increased the carboxylate content by approximately 6.3%. Furthermore, the activation of hydroxyl amine TEMPO, which is generated after the oxidation reaction of cellulose, was enhanced by adjusting the dosage of the inexpensive oxidant NaClO, leading to a 20% improvement in carboxylate content. This suggests that controlling the amount of NaClO as an oxidant can be a key parameter in adjusting the dosage of TEMPO to achieve the targeted degree of surface substitution. Results from the dispersion stability, UV-transmittance, and morphological properties of TEMPO-oxidized CNF using microfluidizing treatment showed that high carboxylate content plays a crucial role in producing high-purity CNF suspensions, which are small, uniform, and free from microfibers. Additionally, by varying the number of mechanical treatments applied to the oxidized cellulose, various types of CNF suspensions with different mean widths were obtained. We expect that these findings offer meaningful insights to end-users seeking a breakthrough in the performance limitations of final applications using cellulose nanomaterials., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: The study compared differences in various neurocognitive characteristics across treatment modalities among schizophrenia patients recruited in one city between July 2020 and June 2023 who were on regular medication., Methods: Of the 151 participants, 113 were included in the analysis. Participants were divided into community-based and hospital-based groups, and their demographics and clinical characteristics, including insight, quality of life, positive and negative symptoms, and personal and social functioning, were examined. In addition, several aspects of cognition were assessed using neurocognitive assessments such as the Trail Making Test (TMT), Stroop test, and Wisconsin Card Sorting Test (WCST). After adjusting for age differences between groups, the final analysis included data from 42 participants in the community-based group and 33 participants in the hospital-based group., Results: Hospital-based group participants completed Stroop-W more rapidly, excelled in Rey-Osterrieth Complex Figure Test recall and recognition, and incurred fewer TMT Part B (TMT-B) and Stroop-C errors. Additionally, they outperformed in WCST total, non-persistent errors, and categories completed. Contrastingly, community-based group participants showed superior outcomes in WCST persistent responses and errors, suggesting specific neurocognitive strengths., Conclusion: We found differences in neurocognitive characteristics between the two groups. These differences were consistent across a range of cognitive domains, including attention, visual discrimination, memory, and executive functioning. Further large-scale study is needed to generalize cognitive characteristics across treatment modalities.

Background: Patient navigation interventions (PNIs) can provide personalized support and promote appropriate coordination or continuation of health and social care services. Online PNIs have demonstrated excellent potential for improving patient knowledge, transition readiness, self-efficacy, and use of services. However, the characteristics (ie, intervention type, mode of delivery, duration, frequency, outcomes and outcome measures, underlying theories or mechanisms of change of the intervention, and impact) of existing online PNIs to support the health and social needs of individuals with illness remain unclear., Objective: This scoping review of the existing literature aims to identify the characteristics of existing online PNIs reported in the literature., Methods: A scoping review based on the guidelines outlined in the Joanna Briggs Institute framework was conducted. A search for peer-reviewed literature published between 1989 and 2022 on online PNIs was conducted using MEDLINE, CINAHL, Embase, PsycInfo, and Cochrane Library databases. Two independent reviewers conducted 2 levels of screening. Data abstraction was conducted to outline key study characteristics (eg, study design, population, and intervention characteristics). The data were analyzed using descriptive statistics and qualitative content analysis., Results: A total of 100 studies met the inclusion criteria. Our findings indicate that a variety of study designs are used to describe and evaluate online PNIs, with literature being published between 2003 and 2022 in Western countries. Of these studies, 39 (39%) studies were randomized controlled trials. In addition, we noticed an increase in reported online PNIs since 2019. The majority of studies involved White females with a diagnosis of cancer and a lack of participants aged 70 years or older was observed. Most online PNIs provide support through navigation, self-management and lifestyle changes, counseling, coaching, education, or a combination of support. Variation was noted in terms of mode of delivery, duration, and frequency. Only a small number of studies described theoretical frameworks or change mechanisms to guide intervention., Conclusions: To our knowledge, this is the first review to comprehensively synthesize the existing literature on online PNIs, by focusing on the characteristics of interventions and studies in this area. Inconsistency in reporting the country of publication, population characteristics, duration and frequency of interventions, and a lack of the use of underlying theories and working mechanisms to inform intervention development, provide guidance for the reporting of future online PNIs., (©Meghan Marsh, Syeda Rafia Shah, Sarah E P Munce, Laure Perrier, Tin-Suet Joan Lee, Tracey J F Colella, Kristina Marie Kokorelias. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 19.08.2024.)

Varicella pneumonitis is typically seen in individuals with risk factors such as male gender, smoking history, and immunocompromised state and is often associated with disseminated infection, whereas primary varicella-zoster virus (VZV) infection usually involves a diffuse vesicular rash and rarely progresses to viral pneumonia. VZV pneumonitis accompanied by disseminated VZV infection is associated with a high mortality rate and may progress to diffuse alveolar hemorrhage in severe cases. In addition to cutaneous lesions, patients typically develop dyspnea, cough, tachypnea, chest pain, fever, and hemoptysis. Here, we present a rare case of disseminated VZV infection in an immunocompetent patient with pneumonitis and diffuse alveolar hemorrhage., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rao et al.)

Cerebral venous thrombosis (CVT) is an uncommon but potentially severe condition, typically affecting younger individuals, pregnant women, and those with underlying thrombophilia. We report a rare case of a 63-year-old female who presented with altered mental status, facial droop, and slurred speech and was found to have an extensive dural venous thrombosis complicated by intracerebral and subarachnoid hemorrhage due to protein S deficiency. Given her diagnosis of protein S deficiency and thrombosis, careful anticoagulation was initiated, resulting in both clinical and radiographic improvement., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rao et al.)

Purpose: Dysregulated cholesterol metabolism is critical in the pathogenesis of AMD. Cellular senescence contributes to the development of numerous age-associated diseases. In this study, we investigated the link between cholesterol burden and the cellular senescence of photoreceptors., Methods: Retinas from rod-specific ATP binding cassette subfamily A member 1 (Abca1) and G member 1 (Abcg1) (Abca1/g1-rod/-rod) knockout mice fed with a high-fat diet were analyzed for the signs of cellular senescence. Real-time quantitative PCR and immunofluorescence were used to characterize the senescence profile of the retina and cholesterol-treated photoreceptor cell line (661W). Inducible elimination of p16(Ink4a)-positive senescent cells (INK-ATTAC) mice or the administration of senolytic drugs (dasatinib and quercetin: D&Q) were used to examine the impact of senolytics on AMD-like phenotypes in Abca1/g1-rod/-rod retina., Results: Increased accumulation of senescent cells as measured by markers of cellular senescence was found in Abca1/g1-rod/-rod retina. Exogenous cholesterol also induced cellular senescence in 661W cells. Selective elimination of senescent cells in Abca1/g1-rod/-rod;INK-ATTAC mice or by administration of D&Q improved visual function, lipid accumulation in retinal pigment epithelium, and Bruch's membrane thickening., Conclusions: Cholesterol accumulation promotes cellular senescence in photoreceptors. Eliminating senescent photoreceptors improves visual function in a model of retinal neurodegeneration, and senotherapy offers a novel therapeutic avenue for further investigation.

We report a catalyst family of high-entropy alloy (HEA) atomic layers having three elements from iron-group metals (IGMs) and two elements from platinum-group metals (PGMs). Ten distinct quinary compositions of IGM-PGM-HEA with precisely controlled square atomic arrangements are used to explore their impact on hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR). The PtRuFeCoNi atomic layers perform enhanced catalytic activity and durability toward HER and HOR when benchmarked against the other IGM-PGM-HEA and commercial Pt/C catalysts. Operando synchrotron x-ray absorption spectroscopy and density functional theory simulations confirm the cocktail effect arising from the multielement composition. This effect optimizes hydrogen-adsorption free energy and contributes to the remarkable catalytic activity observed in PtRuFeCoNi. In situ electron microscopy captures the phase transformation of metastable PtRuFeCoNi during the annealing process. They transform from random atomic mixing (25°C), to ordered L1 0 (300°C) and L1 2 (400°C) intermetallic, and finally phase-separated states (500°C).

Introduction: Recent evidence recommends the use of biologics in patients with severe uncontrolled type 2 chronic rhinosinusitis with nasal polyp (CRSwNP) owing to its propensity for recurrence after functional endoscopic sinus surgery (FESS). Among the type 2 biologics used for the treatment of nasal polyps, dupilumab (Dupi, anti-IL-4) exhibited superior efficacy and safety in indirect comparison studies., Objective: This study aimed to evaluate the objective and subjective outcomes of patients with CRSwNP treated with and without adjuvant Dupi therapy after FESS., Methods: Adult patients with type 2 CRSwNP who underwent FESS with adjuvant Dupi after surgery were enrolled. A matched control group without adjuvant Dupi therapy were recruited during the same period. All patients underwent nasal endoscopy and completed the sinonasal outcome test-22 questionnaire evaluations at baseline and 3 months after surgery., Results: A total of 10 patients who received postoperative adjuvant therapy with Dupi and 20 patients who underwent surgery only were included. Patients with add-on Dupi therapy had significantly higher eosinophil cationic protein levels in the serum, eosinophil counts in peripheral blood, prevalence of asthma, and nasal polyp score at baseline. Both treatments were effective in reducing the patient's symptoms by SNOT-22 at 3 months postoperatively. However, patients with adjuvant Dupi therapy exhibited significantly better endoscopic scores than those with surgery only ( p  = .022)., Conclusion: Surgery plays an important role in treating patients with CRSwNP, and adjuvant Dupi use may facilitate objective mucosal recovery postoperatively., Level of Evidence: 4., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC. on behalf of The Triological Society.)

Laughing gas is becoming increasingly popular as a recreational drug of choice, particularly among young adults. Nitrous oxide, the toxic component of laughing gas, can cause neuronal injury when used in high doses. Through multiple mechanisms, nitrous oxide leads to B12 depletion and subsequent demyelination, particularly in the spinal cord. Here, we present the case of a 27-year-old female who presented with ataxia and was found to have laughing gas-induced subacute combined degeneration from nitrous oxide. After aggressive vitamin B12 repletion and laughing gas cessation for three months, the patient improved., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rao et al.)

Background ChatGPT is a language model that has gained widespread popularity for its fine-tuned conversational abilities. However, a known drawback to the artificial intelligence (AI) chatbot is its tendency to confidently present users with inaccurate information. We evaluated the quality of ChatGPT responses to questions pertaining to atrial fibrillation for patient education. Our analysis included the accuracy and estimated grade level of answers and whether references were provided for the answers. Methodology ChatGPT was prompted four times and 16 frequently asked questions on atrial fibrillation from the American Heart Association were asked. Prompts included Form 1 (no prompt), Form 2 (patient-friendly prompt), Form 3 (physician-level prompt), and Form 4 (prompting for statistics/references). Responses were scored as incorrect, partially correct, or correct with references (perfect). Flesch-Kincaid grade-level unique words and response lengths were recorded for answers. Proportions of the responses at differing scores were compared using the chi-square analysis. The relationship between form and grade level was assessed using the analysis of variance. Results Across all forms, scoring frequencies were one (1.6%) incorrect, five (7.8%) partially correct, 55 (85.9%) correct, and three (4.7%) perfect. Proportions of responses that were at least correct did not differ by form (p = 0.350), but perfect responses did (p = 0.001). Form 2 answers had a lower mean grade level (12.80 ± 3.38) than Forms 1 (14.23 ± 2.34), 3 (16.73 ± 2.65), and 4 (14.85 ± 2.76) (p < 0.05). Across all forms, references were provided in only three (4.7%) answers. Notably, when additionally prompted for sources or references, ChatGPT still only provided sources on three responses out of 16 (18.8%). Conclusions ChatGPT holds significant potential for enhancing patient education through accurate, adaptive responses. Its ability to alter response complexity based on user input, combined with high accuracy rates, supports its use as an informational resource in healthcare settings. Future advancements and continuous monitoring of AI capabilities will be crucial in maximizing the benefits while mitigating the risks associated with AI-driven patient education., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Lee et al.)

Vascular aging influences hemodynamics, elevating risks for vascular diseases and dementia. We recently demonstrated that knockout (KO) of Dusp5 enhances cerebral and renal hemodynamics and cognitive function. This improvement correlates with elevated pPKC and pERK1/2 levels in the brain and kidneys. Additionally, we observed that Dusp5 KO modulates the passive mechanical properties of cerebral and renal arterioles, associated with increased myogenic tone at low pressure, enhanced distensibility, greater compliance, and reduced stiffness. The present study evaluates the structural and mechanical properties of the middle cerebral artery (MCA) in Dusp5 KO rats. We found that vascular smooth muscle cell layers and the collagen content in the MCA wall are comparable between Dusp5 KO and control rats. The internal elastic lamina in the MCA of Dusp5 KO rats exhibits increased thickness, higher autofluorescence intensity, smaller fenestrae areas, and fewer fenestrations. Despite an enhanced myogenic response and tone of the MCA in Dusp5 KO rats, other passive mechanical properties, such as wall thickness, cross-sectional area, wall-to-lumen ratio, distensibility, incremental elasticity, circumferential wall stress, and elastic modulus, do not significantly differ between strains. These findings suggest that while Dusp5 KO has a limited impact on altering the structural and mechanical properties of MCA, its primary role in ameliorating hemodynamics and cognitive functions is likely attributable to its enzymatic activity on cerebral arterioles. Further research is needed to elucidate the specific enzymatic mechanisms and explore potential clinical applications in the context of vascular aging., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Although dysregulated cholesterol metabolism predisposes aging tissues to inflammation and a plethora of diseases, the underlying molecular mechanism remains poorly defined. Here, we show that metabolic and genotoxic stresses, convergently acting through liver X nuclear receptor, upregulate CD38 to promote lysosomal cholesterol efflux, leading to nicotinamide adenine dinucleotide (NAD + ) depletion in macrophages. Cholesterol-mediated NAD + depletion induces macrophage senescence, promoting key features of age-related macular degeneration (AMD), including subretinal lipid deposition and neurodegeneration. NAD + augmentation reverses cellular senescence and macrophage dysfunction, preventing the development of AMD phenotype. Genetic and pharmacological senolysis protect against the development of AMD and neurodegeneration. Subretinal administration of healthy macrophages promotes the clearance of senescent macrophages, reversing the AMD disease burden. Thus, NAD + deficit induced by excess intracellular cholesterol is the converging mechanism of macrophage senescence and a causal process underlying age-related neurodegeneration., Competing Interests: Declaration of interests R.S.A. is a co-founder of Metro Midwest Biotech. M.Y. receives patent-licensing fees from Institute for Research on Productive Aging., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction Hyperlipidemia is prevalent worldwide and affects a significant number of US adults. It significantly contributes to ischemic heart disease and millions of deaths annually. With the increasing use of the internet for health information, tools like ChatGPT (OpenAI, San Francisco, CA, USA) have gained traction. ChatGPT version 4.0, launched in March 2023, offers enhanced features over its predecessor but requires a monthly fee. This study compares the accuracy, comprehensibility, and response length of the free and paid versions of ChatGPT for patient education on hyperlipidemia. Materials and methods ChatGPT versions 3.5 and 4.0 were prompted in three different ways and 25 questions from the Cleveland Clinic's frequently asked questions (FAQs) on hyperlipidemia. Prompts included no prompting (Form 1), patient-friendly prompting (Form 2), and physician-level prompting (Form 3). Responses were categorized as incorrect, partially correct, or correct. Additionally, the grade level and word count from each response were recorded for analysis. Results Overall, scoring frequencies for ChatGPT version 3.5 were: five (6.67%) incorrect, 18 partially correct (24%), and 52 (69.33%) correct. Scoring frequencies for ChatGPT version 4.0 were: one (1.33%) incorrect, 18 (24.00%) partially correct, and 56 (74.67%) correct. Correct answers did not significantly differ between ChatGPT version 3.5 and ChatGPT version 4.0 (p = 0.586). ChatGPT version 3.5 had a significantly higher grade reading level than version 4.0 (p = 0.0002). ChatGPT version 3.5 had a significantly higher word count than version 4.0 (p = 0.0073). Discussion There was no significant difference in accuracy between the free and paid versions of hyperlipidemia FAQs. Both versions provided accurate but sometimes partially complete responses. Version 4.0 offered more concise and readable information, aligning with the readability of most online medical resources despite exceeding the National Institutes of Health's (NIH's) recommended eighth-grade reading level. The paid version demonstrated superior adaptability in tailoring responses based on the input. Conclusion Both versions of ChatGPT provide reliable medical information, with the paid version offering more adaptable and readable responses. Healthcare providers can recommend ChatGPT as a source of patient education, regardless of the version used. Future research should explore diverse question formulations and ChatGPT's handling of incorrect information., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Lee et al.)

Introduction Peripartum cardiomyopathy (PPCM) is defined as an idiopathic left ventricular failure with reduced ejection fraction (EF <45%) that affects women in the last month of pregnancy or in the months after giving birth. The pathophysiology remains elusive, resulting in complications with varied severity; one of the most concerning complications is thromboembolism, specifically pulmonary embolism (PE). The purpose of this study was to characterize and evaluate the real-world prevalence, predictors, and outcomes of PE in PPCM. Methods The data were derived from the National Inpatient Sample (NIS) database from January 2016 to December 2019. The primary outcomes assessed were baseline and hospital admission characteristics and comorbidities for patients with PPCM with or without PE. Outcomes for PPCM patients with PE and predictors of mortality for PPCM were also analyzed. Results PE developed in 105 of 4,582 patients with PPCM (2.3%). Patients with PPCM and PE had longer hospital stays (10.86 days ± 1.4 vs. 5.73 ± 0.2 days, p = 0.001) and total charges ($169,487 ± $39,628 vs. $86,116 ± $3,700, p = 0.001). Patients with PE had a higher burden of coagulopathy (13.3% vs. 3.0%, p = 0.01), intracardiac thrombus (6.7% vs. 1.6%, p = 0.01), and iron deficiency anemia (21.0% vs. 12.6%, p = 0.01). Patients without PE were found to have a higher burden of preeclampsia (14.7% vs. 1.9%, p = 0.01) and obstructive sleep apnea (5.4% vs. 1.0%, p = 0.045). Predictors of mortality in patients with PPCM included cardiogenic shock (aOR 13.42, 95% CI 7.50-24.03, p = 0.05), PE (aOR 6.60, 95% CI 2.506-17.39, p = 0.05), non-ST-elevation myocardial infarction (NSTEMI; aOR 3.57, 95% CI 1.35-9.44, p = 0.05), chronic kidney disease (aOR 3.23, 95% CI 1.68-6.22, p = 0.05), and atrial fibrillation (aOR 2.57; 95% CI 1.25-5.30, p = 0.05). Conclusion Although an uncommon complication, PE in PPCM demonstrates an association with higher mortality and financial burden. Along with PE, we found predictors of mortality in PPCM to include atrial fibrillation, NSTEMI, chronic kidney disease, and cardiogenic shock., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Elkattawy et al.)

Digital PCR (dPCR) is a technique for absolute quantification of nucleic acid molecules. To develop a dPCR technique that enables more accurate nucleic acid detection and quantification, we established a novel dPCR apparatus known as centrifugal force real-time dPCR (crdPCR). This system is efficient than other systems with only 2.14% liquid loss by dispensing samples using centrifugal force. Moreover, we applied a technique for analyzing the real-time graph of the each micro-wells and distinguishing true/false positives using artificial intelligence to mitigate the rain, a persistent issue with dPCR. The limits of detection and quantification were 1.38 and 4.19 copies/μL, respectively, showing a two-fold higher sensitivity than that of other comparable devices. With the integration of this new technology, crdPCR will significantly contribute to research on next-generation PCR targeting absolute micro-analysis., (© 2024. The Author(s).)

Background Google Gemini (Google, Mountain View, CA) represents the latest advances in the realm of artificial intelligence (AI) and has garnered attention due to its capabilities similar to the increasingly popular ChatGPT (OpenAI, San Francisco, CA). Accurate dissemination of information on common conditions such as hypertension is critical for patient comprehension and management. Despite the ubiquity of AI, comparisons between ChatGPT and Gemini remain unexplored. Methods ChatGPT and Gemini were asked 52 questions derived from the American College of Cardiology's (ACC) frequently asked questions on hypertension, following a specified prompt. Prompts included: no prompting (Form 1), patient-friendly prompting (Form 2), physician-level prompting (Form 3), and prompting for statistics/references (Form 4). Responses were scored as incorrect, partially correct, or correct. Flesch-Kincaid (FK) grade level and word count were recorded. Results Across all forms, scoring frequencies were as follows: 23 (5.5%) incorrect, 162 (38.9%) partially correct, and 231 (55.5%) correct. ChatGPT showed higher rates of partially correct answers than Gemini (p = 0.0346). Physician-level prompts resulted in a higher word count across both platforms (p < 0.001). ChatGPT showed a higher FK grade level (p = 0.033) in physician-friendly prompting. Gemini exhibited a significantly higher mean word count (p < 0.001); however, ChatGPT had a higher FK grade level across all forms (p > 0.001). Conclusion To our knowledge, this study is the first to compare cardiology-related responses from ChatGPT and Gemini, two of the most popular AI chatbots. The grade level for most responses was collegiate level, which was above average for the National Institutes of Health (NIH) recommendations, but on par with most online medical information. Both chatbots responded with a high degree of accuracy, with inaccuracies being rare. Therefore, it is reasonable that cardiologists suggest either chatbot as a source of supplementary education., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Lee et al.)