Chemical Synthesis of Truncated Capsular Oligosaccharide of Serotypes 6C and 6D of Streptococcus pneumoniae with Their Immunological Studies.

Serotypes 6C and 6D of Streptococcus pneumoniae are two major variants that cause invasive pneumococcal disease (IPD) in serogroup 6 alongside serotypes 6A and 6B. Since the introduction of the pneumococcal conjugate vaccines PCV7 and PCV13, the number of cases of IPD caused by pneumococcus in children and the elderly population has greatly decreased. However, with the widespread use of vaccines, a replacement effect has recently been observed among different serotypes and lowered the effectiveness of the vaccines. To investigate protection against the original serotypes and to explore protection against variants and replacement serotypes, we created a library of oligosaccharide fragments derived from the repeating units of the capsular polysaccharides of serotypes 6A, 6B, 6C, and 6D through chemical synthesis. The library includes nine pseudosaccharides with or without exposed terminal phosphate groups and four pseudotetrasaccharides bridged by phosphate groups. Six carbohydrate antigens related to 6C and 6D were prepared as glycoprotein vaccines for immunogenicity studies. Two 6A and two 6B glycoconjugate vaccines from previous studies were included in immunogenicity studies. We found that the conjugates containing four phosphate-bridged pseudotetrasaccharides were able to induce good immune antibodies and cross-immunogenicity by showing superior activity and broad cross-protective activity in OPKA bactericidal experiments.

Determination of doping higenamine in Chinese herbal medicines and their concentrated preparations by LC-MS/MS.

The World Anti-Doping Agency (WADA) has included higenamine in the ß2 agonist (S3) category of the Prohibited List since 2017 due to its pharmacological effects on adrenergic receptors. Although higenamine contained in Chinese herbal medicines has been identified by previous studies, comprehensive investigation on the higenamine content of Chinese herbs and their concentrated preparations is still required. This study aimed to determine the levels of higenamine in Chinese medicinal materials and their concentrated preparations used in Chinese medicine prescriptions in Taiwan. The levels of higenamine in Chinese medicinal materials, including Cortex Phellodendri, Flos Caryophylli, Fructus Euodiae, Fructus Kochiae, Plumula Nelumbinis, Radix Aconiti Preparata, Radix Aconiti Lateralis Preparata, and Radix Asari, and their concentrated preparations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Our results showed that the amounts of higenamine were detected and quantified in studied Chinese medicinal materials and their concentrated preparations, except for Flos Caryophylli, Radix Aconiti Preparata, and Radix Aconiti Lateralis Preparata. Plumula Nelumbinis and Cortex Phellodendri have higher levels of higenamine when compared to other Chinese herbs tested in the present study. The highest level of higenamine was 2100 µg/g found in the Plumula Nelumbinis medicinal material. In contrast with Plumula Nelumbinis and Cortex Phellodendri, higenamine levels below 10 µg/g were found in other most of the studied Chinese medicinal materials and their concentrated preparations. This study confirmed that various Chinese herbs and their concentrated preparations contained higenamine, and it provided more coherent and comprehensive information for reducing the potential risk of higenamine misuse in sports.

The Impact of Gut Microbiota Changes on Methotrexate-Induced Neurotoxicity in Developing Young Rats.

Methotrexate (MTX) is an essential part of therapy in the treatment of acute lymphoblastic leukemia (ALL) in children, and inferior intellectual outcomes have been reported in children who are leukemia survivors. Although several studies have demonstrated that the interaction between gut microbiota changes and the brain plays a vital role in the pathogenesis of chemotherapy-induced brain injury, preexisting studies on the effect of MTX on gut microbiota changes focused on gastrointestinal toxicity only. Based on our previous studies, which revealed that MTX treatment resulted in inferior neurocognitive function in developing young rats, we built a young rat model mimicking MTX treatment in a child ALL protocol, trying to investigate the interactions between the gut and brain in response to MTX treatment. We found an association between gut microbiota changes and neurogenesis/repair processes in response to MTX treatment, which suggest that MTX treatment results in gut dysbiosis, which is considered to be related to MTX neurotoxicity through an alteration in gut-brain axis communication.

Trends in exposure to drugs and prohibited substances among sports: A nationwide analysis of 2008-2022 inquiry records.

To prevent athletes from unintentional doping, the anti-doping authorities in Taiwan have launched several sports-prohibited substances inquiry services since 2008. This study aimed to enhance the prevention of sports-prohibited substance misuse by analyzing data collected from major nationwide service systems, enabling the identification of trends in athletes' exposure to drugs and prohibited substances. The study collected over 30,000 data points from three major national anti-doping inquiry systems, spanning from 2008 to 2022. The information of the users consulted products, prohibited substances, and sports disciplines in the data were calculated and categorized. The usage of inquiry systems has shown an increasing trend from 2008 to 2022. Athletes comprised the majority of users (> 40%), significantly outnumbering other user groups (all below 20%). Among the inquiries, Western medicine accounted for the highest percentage (up to 79.6%), and it also contained the majority of the prohibited substances. Interestingly, traditional Chinese medicines had a higher chance (35.9%) of containing prohibited substances, as indicated by the mobile application. The prohibited substances mainly belonged to class S6 stimulants and S9 glucocorticoids. Among the daily medicinal products and nutritional supplements encountered by sports personnel, approximately 30% of them were found to contain prohibited substances. Future educational efforts should focus on raising awareness about traditional Chinese medicines and drugs for the common cold, ADHD, and pain relief, as well as their regulation, to prevent the misuse of prohibited substances.

The effectiveness of a transtheoretical model-based smoking cessation intervention for rural smokers: A quasi-experimental longitudinal study.

OBJECTIVE: Cigarette smoking is highly prevalent, despite being a primary preventable cause of disease and mortality. This study examined the effect of a Transtheoretical Model (TTM)-based psychoeducational intervention for smoking cessation (SC) on knowledge, SC-related parameters, and progression through the TTM stages of change among rural smokers. METHODS: This quasi-experimental study recruited 200 smokers from an outpatient clinic. The comparison group was recruited before the experimental group to address possible self-selection bias. Structured questionnaires were administered pre- and post-intervention (three months) and at follow-up (six months). RESULTS: A generalised estimation equation model indicated that the TTM-based intervention significantly increased participants' SC-knowledge and improved progression through TTM stages by the six-month follow-up. No significant group differences were found in self-efficacy and nicotine dependence scores or daily cigarette consumption. CONCLUSIONS: A TTM-based intervention enhances SC-knowledge and fosters progress through change stages. However, it does not directly impact nicotine dependence or cigarette consumption. Outpatient settings may employ TTM-based programmes for SC education and motivation. Detecting anticipated effects may require a longer intervention duration exceeding six months. PRACTICE IMPLICATIONS: Such TTM-based programmes may facilitate SC-knowledge and motivation in outpatient settings. Further research to comprehend patients' context and experiences during the stages of change is required.

Impact of pretreatment quality of life on tolerance and survival outcome in head and neck cancer patients undergoing definitive CCRT.

BACKGROUND: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. METHODS: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

Personalized Medical Terminology Learning Game: Guess the Term.

Objective: Wordbot, a chatbot designed for gamified education, transforms the process of memorizing complex medical terminology into an engaging and enjoyable activity for medical students. Taking inspiration from the "guessing words" game, Wordbot aims to improve medical students' learning outcomes by making the vocabulary memorization process more memorable. Materials and Methods: Wordbot, which can be implemented on the LINE platform, was created for this research, specifically to improve medical terminology learning. Wordbot incorporated mobile devices and personal computer-compatible flashcard games with features such as user ranking and personalization to enhance motivation and optimize learning outcomes. In the experimental research setting, half of a total of 48 nursing students were randomly assigned to use Wordbot for 4 months, and the other half were assigned to a control group relying on self-study without the help of Wordbot. Both groups received pretest and post-test to assess their respective learning of medical terminology. In this study, a statistical t-test was used to analyze the results between the two groups. In addition, user usability testing was conducted to evaluate the usability of Wordbot and gather feedback on user experience. Results: The results of this study have demonstrated that Wordbot is effective in facilitating students learning of medical terminology. Students experienced a significant improvement in their knowledge of medical terminology. An average user usability test score of 83.25 indicated that users' satisfaction with Wordbot is high. Conclusion: Incorporating gamification and personalization elements in Wordbot can significantly improve the overall enjoyment of the learning process. By participating in diverse interactive activities, users can effectively enhance their proficiency in spelling, recognition, and speaking. Wordbot utilizes sophisticated algorithms to generate customized questions based on identified mistakes, which facilitate error identification and correction. The robust findings of this study overwhelmingly support Wordbot's role as a convenient and easily accessible tool for learning medical terminology. The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Chang Gung Medical Foundation (Protocol code: 202201586B0, date of approval: 8 November 2022). We obtained informed consent from all of our study participants regarding their willingness to participate in this study.

Nanocurcumin Reduces High Glucose and Particulate Matter-Induced Endothelial Inflammation: Mitochondrial Function and Involvement of miR-221/222.

Purpose: Particulate matter (PM) 2.5, harmful air pollutants, and diabetes are associated with high morbidity and mortality from cardiovascular disease (CVD). However, the molecular mechanisms underlying the combined effects of PM and diabetes on CVD remain unclear. Methods: Endothelial cells (ECs) treated with high glucose (HG) and PM mimic hyperglycemia and air pollutant exposure in CVD. Endothelial inflammation was evaluated by Western blot and immunofluorescence of ICAM-1 expression and monocyte adhesion. The mechanisms underlying endothelial inflammation were elucidated through MitoSOX Red analysis, JC-1 staining, MitoTracker analysis, and Western blot analysis of mitochondrial fission-related, autophagy-related, and mitophagy-related proteins. Furthermore. nanocurcumin (NCur) pretreatment was used to test if it has a protective effect. Results: ECs under co-exposure to HG and PM increased ICAM-1 expression and monocyte adhesion, whereas NCur pretreatment attenuated these changes and improved endothelial inflammation. PM exposure increased mitochondrial ROS levels, worsened mitochondrial membrane potential, promoted mitochondrial fission, induced mitophagy, and aggravated inflammation in HG-treated ECs, while NCur reversed these changes. Also, HG and PM-induced endothelial inflammation is through the JNK signaling pathway and miR-221/222 specifically targeting ICAM-1 and BNIP3. PM exposure also aggravated mitochondrial ROS levels, mitochondrial fission, mitophagy, and endothelial inflammation in STZ-induced hyperglycemic mice, whereas NCur attenuated these changes. Conclusion: This study elucidated the mechanisms underlying HG and PM-induced endothelial inflammation in vitro and in vivo. HG and PM treatment increased mitochondrial ROS, mitochondrial fission, and mitophagy in ECs, whereas NCur reversed these conditions. In addition, miR-221/222 plays a role in the amelioration of endothelial inflammation through targeting Bnip3 and ICAM-1, and NCur pretreatment can modulate miR-221/222 levels. Therefore, NCur may be a promising approach to intervene in diabetes and air pollution-induced CVD.

Assessing anti-doping knowledge among Taiwanese pharmacists.

BACKGROUND: Taiwan's unique health behaviour, such as extensive exposure to Chinese Herbal Medicine (CHM), has introduced a risk of inadvertent doping among competing athletes. Pharmacy professionals have an imperative role in advising athletes on the safe use of medicines. This study provides an overview of anti-doping knowledge and educational needs among pharmacists in Taiwan and examines influencing factors. METHODS: A cross-sectional online questionnaire survey consisting of five domains, namely demographic characteristics, source of prohibited substances, identification of prohibited substances, understanding of doping control, and education needs on anti-doping, was distributed to the registered pharmacists in Taiwan. In total, 491 responses were included in the analyses. RESULTS: Respondents (65% female, aged 41.9 ± 11.4 years, with 68% having a Bachelor's degree) reported a moderate anti-doping knowledge score of 37.2 ± 4.9, ranging from 21 to 48 (out of 51). Fifteen per cent of them had the experience of being counselled about drug use in sports. Higher knowledge scores were observed in younger respondents, showing an age-dependent effect (p < 0.001). Individuals practising in southern Taiwan (compared to northern Taiwan) and those working at clinics (compared to hospitals) exhibited lower knowledge. Most of the respondents (90%) knew that stimulant ephedrine is prohibited in sports, but few had recognised diuretic furosemide (38%) and CHM (7%) containing ß2-agonist higenamine. Approximately 90% of respondents agreed with the need for anti-doping education. CONCLUSIONS: This study highlights the heterogeneity of anti-doping knowledge among pharmacy professionals and provides practical relevance in organising future educational topics and research-based activities.

Differential Effects of Clotrimazole on X-Ray Crystal Structures of Human Cytochromes P450 3A5 and 3A4.

Cytochromes P450 CYP3A5 and CYP3A4 exhibit differential plasticity that underlies differences in drug metabolism and drug-drug interactions. To extend previous studies, CYP3A4 and CYP3A5 were cocrystallized with clotrimazole, a compact ligand that binds to the heme iron in the catalytic center of the active site. Binding studies indicate that clotrimazole exhibits tight binding to CYP3A5 with a binding affinity (Kd) of <0.01 µM like that of CYP3A4. A single clotrimazole is bound to the heme iron in CYP3A4 that triggers expansion of active site cavity that reflects a loss of aromatic interactions between phenylalanine sidechains in the distal active site and increased conformational entropy for the F-F' connector due to reorientation of Phe-304 to accommodate clotrimazole. In contrast to CYP3A4, the CYP3A5 Phe-304 exhibits an induced fit along with Phe-213 to form edge-to-face aromatic interactions with heme-bound clotrimazole. These aromatic interactions between aromatic amino acids propagate by induced fits with a second clotrimazole residing in the distal active site and a third clotrimazole bound in an expanded entrance channel as well as between the three clotrimazoles. The large, expanded entrance channel surrounded by the C-terminal loop and the F' and A' helices in CYP3A5 suggests conformational selection for the binding of clotrimazole due to its large girth, which may also cause the entrance channel to remain open after the binding of the first clotrimazole to the heme iron. The additional binding sites suggest a path for sequential binding of one molecule to reach and bind to the heme iron. SIGNIFICANCE STATEMENT: Clotrimazole binds to the heme iron of CYP3A5 and CYP3A4. In CYP3A5, two clotrimazoles also bind in the distal active site and in an expanded entrance channel. Aromatic interactions between clotrimazoles and phenylalanine sidechains including Phe-304 indicate induced fits for each clotrimazole. In contrast to CYP3A5, displacement of the CYP3A4 Phe-304 rotamer by clotrimazole leads to extensive disruption of phenylalanine interactions that limit the space above the heme, to an expanded active site cavity, and to increased CYP3A4 conformational heterogeneity.

Nurse-led coaching of shared decision-making for wound treatment of pressure injury: A pilot study of a randomized trial.

Objectives: International guidelines for managing pressure injury (PI) and ulcers recommend that family members and caregivers should be involved in making decisions for appropriate wound care. However, the effect of shared decision-making (SDM) in the context of PI remains unknown. This study investigated the efficacy of nurse-led medical SDM for PI treatment. Materials and Methods: We constructed a patient decision aid (PDA) for PI treatment on the basis of nursing evidence. Subsequently, we conducted a pilot randomized controlled trial to evaluate the efficacy of SDM compared with that of usual care (control group, [CG]) for PI treatment. Participants with stage 3, stage 4, or unstageable PI were included and randomized into two groups. In the SDM group (SDMG), 10 participants received the SDM intervention for PI before treatment. All participants were followed up for 4 weeks. Primary outcomes were measured using the nine-item SDM Questionnaire (SDM-Q-9) and Decisional Conflict Scale (DCS). Secondary outcomes included wound size and cost of wound management. Results: The expert validity (medical professors and general population) of the PDA designed for PI was measured, and the content validity index was 0.96-0.97. A total of 20 participants were enrolled (10 received SDM and 10 received usual care). The mean age of the participants was 55.7 ± 8.8 years. No significant difference in baseline characteristics (sex, age, staging, or wound area) was observed between the two groups. The SDMG had higher SDM-Q-9 (P < 0.001) and DCS (P < 0.01) scores than did the CG. For the secondary outcomes, the SDMG had a decreased change of wound size and lower wound management costs than did the CG; nevertheless, the differences were not statistically significant. Conclusion: We constructed a PDA for PI treatment, which can be applied in clinical care. The pilot test results revealed that the participants had a lower cost related wound treatment and decreasing wound size in SDMG than CG after the intervention of SDM-PI for 4 weeks. In the future, clinical studies should conduct large-scale randomized trials based on the results of this pilot study.

Feasibility of ketogenic diet therapy variants for refractory epilepsy in neonates to infants under 2 years old.

BACKGROUND: Ketogenic diet Therapy (KDT) has been reported as a possible beneficial management strategy for controlling seizures in infants aged <2 years, but the safety and efficacy of this therapy remain to be investigated. We investigated the achievability, tolerability, efficacy, and safety of KDT for patients under 2 years old. MATERIALS AND METHODS: Infants younger than 2 years old with pharmacoresistant epilepsy were enrolled in this prospective study. We divided cases into three age groups: I) neonates; II) infants aged 1-12 months; III) infants aged 12-24 months. KDT initiation protocol were administration through parenteral route, enteral route or oral feeding. Seizure reduction rate, physical growth, and adverse effects were assessed at monthly visit. RESULTS: Thirteen patients who completed 6 months of KDT were recruited. There was one neonate in group I, 9 infants in group II, and 3 infants in group III. Eleven of them (11/13, 84.6%) were responders to KDT. All infants with underlying genetic etiology were seizure free after treating with KDT. The starting keto ratio was 1.1 mmol/L in group I, 2.3 mmol/L in group II, and 2.8 mmol/L in group III, which gradually approached 3:1-4:1 over 5-7 days. There were no symptomatic adverse effects or growth retardation in any of the study subjects. CONCLUSIONS: KDT is a promising alternative therapy with high feasibility, safety, and efficacy for pharmacoresistant epilepsy in infants under 2 years old, especially for those with genetic etiology. The starting keto ratio should be lower, and the keto ratio titration period should be longer than for children older than 2 years.

Increased Circulating ADMA in Young Male Rats Caused Cognitive Deficits and Increased Intestinal and Hippocampal NLRP3 Inflammasome Expression and Microbiota Composition Alterations: Effects of Resveratrol.

Endothelial dysfunction is characterized by disturbances in nitric oxide (NO) bioavailability and increased circulating asymmetric dimethylarginine (ADMA) due to the enormous release of free radicals. Increased circulating ADMA may cause endothelial dysfunction and a variety of clinical disorders, such as liver and kidney disease. Young male Sprague-Dawley rats at postnatal day 17 ± 1 received continuous ADMA infusion via an intraperitoneal pump to induce endothelial dysfunction. Four groups of rats (n = 10 per group) were allocated: control, control and resveratrol, ADMA infusion, and ADMA infusion and resveratrol groups. Spatial memory, NLR family pyrin-domain-containing 3 (NLRP3) inflammasome, cytokine expression, tight junction proteins in the ileum and dorsal hippocampus, and microbiota composition were examined. We found cognitive deficits; increased NLRP3 inflammasome in the plasma, ileum, and dorsal hippocampus; decreased ileum and dorsal hippocampal cytokine activation and tight junction proteins; and microbiota composition alterations in the ADMA-infusion young male rats. Resveratrol had beneficial effects in this context. In conclusion, we observed NLRP3 inflammasome activation in peripheral and central dysbiosis in young male rats with increased circulating ADMA, and found that resveratrol had beneficial effects. Our work adds to the mounting evidence that inhibiting systemic inflammation is a promising therapeutic avenue for cognition impairment, probably via the gut-brain axis.

Detection of emerging patterns of drug misuse in sports via wastewater monitoring: A mini-review and potential strategies.

Biological testing is a key component of the current anti-doping programme implemented by the authorities to detect doping in sports. Strategies such as longitudinal individualised data analysis and sport-specific analysis have been developed to increase the comprehensiveness of the testing. However, the trends of drug misuse in sports might not be effectively captured through today's testing plan. Wastewater testing, assembling individual-level data of a designated group to produce population-level results in one single aggregated sample, can be employed to as a complementary strategy offering added value for doping control. This paper presents an updated summary of the status of anti-doping testing and analytical methodologies for wastewater. The available literature on wastewater-based analyses of drugs prohibited in sports is reviewed. Publications surrounding sporting activities or competitions and others relevant to sports doping are selected. We debate between potential strategies and major limitations of using wastewater monitoring in anti-doping. Knowledge gaps and research directions, specifically on metabolites, stability, sensitivity, and ethical and legal considerations, are discussed. Choosing different wastewater sampling sites allows target sub-population that involved competing athletes and potentially reveal sport-specific or athlete-level-specific behaviour. Sampling from on-board toilets or athlete villages could target international-level athletes, sampling from the dormitories of national training centres allows monitoring of national-level athletes on a daily basis, and sampling from sports stadiums provides a full picture of drug use in the general population during an event. Confounding occurs as (i) the presence of non-athlete composition and the difficulty of analyses to be completely selective to the athlete population; and (ii) the identification of compounds prescribed legitimately with Therapeutic Use Exemptions, only banned in-competition, and naturally occurring. The practicalities of the approach are contextualised in monitoring the non-threshold substances such as anabolic agents, selective androgen receptor modulators, metabolic modulators, and hypoxia-inducible factor activators.

Lived Experience of Violence Perpetrated by Treated Patients and Their Visitors in Intensive Care Units: A Qualitative Study of Nurses.

BACKGROUND: Patient and visitor violence (PVV) is a widespread problem for health professionals. Nurses working in intensive care units (ICUs) face a relatively high risk of experiencing PVV, which significantly impacts both the health of nurses and the institution as a whole. The subjective perceptions of ICU nurses regarding PVV are inadequately explored in the literature. PURPOSE: The purpose of this study was to explore the perspectives, experiences, and perceptions of PVV in ICU nurses and to better understand the precipitating factors of violence. METHODS: A phenomenological qualitative design and purposive sampling were used. A semistructured interview guide was used to conduct in-depth interviews with 12 ICU nurses with PVV experiences. Giorgi's method of analysis was used to discover and identify the essential categories of experience. RESULTS: Five main experience categories were identified: family and patient factors as flashpoints, managing suppressed emotions by weathering the emotional storm, spiritual awakening after violence, and strategies for surviving further violence. The participants' experiences with PVV included a range of caring and mental health difficulties. In ICU settings, patient progress is often unpredictable, resulting in discrepancies between patient/family expectations and reality. Because feelings of frustration and powerlessness can eventually cause exhaustion in ICU nurses, implementing effective emotional management, stress adjustment, psychological counseling, team support, and violence intervention programs are crucial. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study provides new information on the process by which nurses can progress from inner trauma to self-recovery, moving from a negative affectivity disposition to a better understanding of threat appraisals and coping response options. Nurses should increase their awareness of the complexity of the phenomenon and of the interplay among the factors underlying PVV. The results of this study suggest that routine confusion and delirium assessments to rule out patients with ICU delirium in ICUs are important to preventing PVV. This study considers some of the implications of the research findings for nursing managers. Interventions, training programs, and/or management action should be used to ensure psychological and mental support is extended to all witnesses of PVV events and not only to those targeted by violence.

Annular Basal Cell Carcinoma Expanding Around Central Hypertrophic Scarring: A Case Report.

A case of annular basal cell carcinoma (BCC) with central atrophic scarring that developed secondary to spontaneous regression has been reported. We present a novel case of a large, expanding nodular and micronodular BCC with annular morphology with central hypertrophic scarring. A 61-year-old woman presented with a two-year history of a mildly itchy lesion on the right breast. Previously diagnosed as an infection, the lesion persisted after treatment with topical antifungal agents and oral antibiotics. Physical examination revealed a 5x6 cm plaque consisting of a pink-red arciform/annular edge with an overlying scale crust and a large, centrally positioned, firm, alabaster-colored portion. A punch biopsy of the pink-red rim revealed nodular and micronodular BCC features. A deep shave biopsy of the central bound-down plaque showed histopathology of scarring fibrosis with no findings of BCC regression. The malignancy was treated with two sessions of radiofrequency destruction, which led to the resolution of the tumor with no recurrence to date. Contrary to the previously reported case, BCC in our case was expanding, associated with hypertrophic scarring, and showed no signs of regression. We discuss several possible etiologies of the scarring centrally. With further awareness of this presentation, more such tumors can be detected at early stages to facilitate prompt treatment and prevent local morbidity.

Termbot: A Chatbot-Based Crossword Game for Gamified Medical Terminology Learning.

Medical terminology can be challenging for healthcare students due to its unfamiliar and lengthy terms. Traditional methods such as flashcards and memorization can be ineffective and require significant effort. To address this, an online chatbot-based learning model called Termbot was designed to provide an engaging and convenient method for enhancing medical terminology learning. Termbot, accessible through the LINE platform, offers crossword puzzles that turn boring medical terms into a fun learning experience. An experimental study was conducted, which showed that students who trained with Termbot made significant progress in learning medical terms, demonstrating the potential of chatbots to improve learning outcomes. Termbot's gamified approach to learning can also be applied to other fields, making it a useful tool for students to learn medical terminology conveniently and enjoyably.

Lymphocyte disturbance and functional assessment of the [Asp521Asn] ZAP70 mutation.

Activated zeta-chain-associated protein kinase 70 (ZAP70) phosphorylates the TCRαß:CD3:zeta complex to diversify and amplify TCR signaling. Patients with ZAP70 mutations can present with phenotypes of immune dysregulation as well as infection. We identified the first Taiwanese boy with the [Asp521Asn] ZAP70 mutation who presented with recurrent pneumonia, inflammatory bowel disease-like diarrhea, transient hematuria and autoimmune hepatitis. He had isolated CD8 lymphopenia, eosinophilia, hypogammaglobulinemia, and impaired lymphocyte proliferation. Downstream CD3/CD28 signaling, phosphorylation of AKT, ZAP70 and Ca2+ influx were decreased in [Asp521Asn] ZAP70 lymphocytes. Immunophenotyping analysis revealed expansion of transitional B and CD21-low B cells, Th2-skewing T follicular helper cells, but lower Treg cells. The Asp521Asn-ZAP70 hindered TCR-CD3 downstream phosphorylation and disturbed lymphocyte subgroup "profiles" leading to autoimmunity/autoinflammation. Further large-scale studies are warranted to clarify this lymphocyte disturbance. The prognosis significantly depends on hematopoietic stem cell transplantation, but not the genotype, the presence of opportunistic infections or immune dysregulation.

Children's perceptions of interactive virtual-reality interventions implemented before and after intravenous cannulation.

BACKGROUND: Although some studies have reported evidence of the effectiveness of virtual-reality interventions implemented for children undergoing intravenous (IV) cannulation, children's perceptions of virtual-reality interventions implemented during IV cannulation warrant further exploration. AIMS: To explore the school-aged children's perceptions of interactive virtual-reality interventions implemented before and after IV cannulation. METHODS: A qualitative descriptive study was adopted. Sixty-nine children aged 6-12 years from two medical centers were recruited and interviewed from June to September 2020. After the completion of the immersive virtual-reality scene of IV cannulation before undergoing actual IV cannulation and the emotionally cathartic virtual-reality play after the placement process, individual interviews were conducted with the children in the paediatric wards. Inductive content analysis was performed to analyse children's perceptions. The study complied with the Consolidated Criteria for Reporting Qualitative Research. RESULTS: Three categories related to children's perception of interactive virtual-reality interventions implemented before and after IV cannulation were identified: (1) feelings towards and coping strategies employed during IV cannulation; (2) mental preparation through immersion in the virtual-reality scene; and (3) healing effects of immersive cathartic play. CONCLUSIONS: The findings indicate that interactive virtual-reality interventions can help hospitalised children mentally prepare for medical procedures, obtain knowledge regarding such procedures, and overcome their fear of needles. The children's reported perceptions of the virtual-reality interventions indicated that the interventions were age-appropriate, safe and fun. The results of this study highlight the need to more thoroughly understand the perceptions of hospitalised children and may serve as a reference for designing child-friendly care interventions for nursing practice.