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OBJECTIVE: Juvenile dermatomyositis (DM) is a chronic inflammatory myopathy of childhood primarily affecting the muscles and skin. Treatment for juvenile DM is often difficult, and conventional therapies include corticosteroids and other immune suppressants. We reviewed the records of 4 patients with juvenile DM who received the B cell-depleting anti-CD20 monoclonal antibody rituximab to determine whether this therapy resulted in improved control of their juvenile DM. METHODS: This is a retrospective review of 4 pediatric patients ages 10-17 years with juvenile DM who were treated with rituximab. All patients were tested for myositis autoantibodies and received weekly rituximab infusions for a total of 4 doses. Two patients received repeat courses of rituximab 1 year after their first dose. Patients were followed up between 12 and 24 months after their first course of rituximab, and their strength, muscle enzymes, and rash were reviewed. RESULTS: One patient was positive for a myositis-specific antibody, anti-Mi-2, and demonstrated striking reductions in her muscle enzyme levels for 1 year after rituximab therapy. Following a second course of rituximab, this patient remained disease free for 14 months before requiring a third course of rituximab. Two myositis antibody-negative patients showed clinical improvement and tolerated lower doses of corticosteroids following treatment with rituximab. Finally, 1 patient had worsening of her disease following rituximab. CONCLUSION: These cases highlight the potential for anti-B cell therapies in the treatment of juvenile DM in both myositis-specific autoantibody-positive and -negative patients. [ABSTRACT FROM AUTHOR]

Background: Mass casualties caused by natural disasters and man-made events may overwhelm local emergency medical services and healthcare systems. Logistics is essential to a successful emergency medical response. Drills have been used in disaster preparedness to validate plans, policies, procedures, and agreements, and identify resource gaps. The application of the internet to facilitate the conduct of exercise was still limited. This study aimed to investigate the optimal preparation of medical supplies by medical emergency response teams (MERTs) during emergencies and disasters using an internet-based drill., Methods: An internet-based drill based on real-life mass casualty incidents (MCIs) was developed and conducted in Taiwan from June 2017 to July 2018. The drill involved an MCI with 50 events delivered under two scenarios: (1) reduced transfer capacity and well-functioning local healthcare facilities (emergency module); (2) severely reduced transfer capacity and dysfunctional local healthcare facilities (disaster module). For each event, medical supplies commonly prepared by local MERTs in Taiwan were listed in structured questionnaires and participants selected the supplies they would use., Results: Forty-three senior medical emergency responders participated in the survey (responding rate of 47.3%). Resuscitation-related supplies increased from emergency to disaster module (e.g., intubation from 9.1% to 13.9%; dopamine from 3.2% to 5.0%; all p < 0.001). In the subgroup analysis of events with life-threatening injuries, the utilization of resuscitation-related supplies (e.g., intubation from 46.6% to 65.3%; p < 0.001) remained higher in the disaster than in the emergency module. Compared to emergency medical technicians, physicians and nurses are more likely to use intravenous/intramuscular analgesics., Conclusions: The severity of scenarios and the professional background of emergency responders have a different utilization of medical supplies in the simulation drill. The internet-based drill may contribute to optimizing the preparedness of medical response to prehospital emergencies and disasters., Competing Interests: The authors report none of conflict of interests.

Aims: To determine the effect of design thinking approach in interprofessional education programme of human sexuality course., Design: A pre-test and post-test of single-group quasi-experimental study., Methods: The 35 nursing students and seven psychology students in their third year were selected by the computer randomly sampling through the lottery method. The course proceeded between September 2019 and January 2020. The participants had received an 8-week, 16-hr design thinking approach in interprofessional education programme of human sexuality course (one section per week, 2 hr per section). We used the nursing attitude toward sexual healthcare scale, nursing intervention toward sexual healthcare scale to assess students' attitude and behaviour intention toward sexual health care and competence of interprofessional education scale to assess students' competence of cooperation before and after the teaching programme. Data analysis used descriptive statistics and t-tests. A qualitative reflection log was also provided and analysed for themes. The SQUIRE-EDU checklist was followed., Results: The students' attitude and behavioural intention dimension score in the post-test is higher than those in the pre-test and reach statistically significant differences both in total and subscale. Interprofessional core competence score of Observation Experience, Reflective Feedback, Interprofessional Cooperation, Innovative Design, and Applied Technology score in the post-test is higher than those in the pre-test and reach statistically significant differences both in total and subscale. Design thinking in interprofessional education programme of human sexuality course could significantly improve both nursing and psychology students' attitude, behaviour intention of providing sexual health care and competence of interprofessional cooperation., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

To respond to patients' increasing demands and strengthen nursing professionals' capabilities, nursing students are expected to develop problem-solving skills before they enter the workforce. Problem-based learning (PBL) is expected to provide effective simulation scenarios and realistic clinical conditions to help students achieve those learning goals. This article aims to explore the effects of PBL strategies on nursing students' self-evaluation of core competencies. This longitudinal cohort survey study evaluated 322 nursing students attending Chung Shan Medical University, Taiwan, in 2013 and 2014, where PBL teaching strategies are used in all four undergraduate years from freshman to senior. Based on their undergraduate academic levels, students were categorized into three groups- one-year PBL exposure, two-year PBL exposure, and three-year exposure. A core competency questionnaire was administered twice to ask participants to self-assess five professional competencies: learning attitude, problem identification, information analysis, execution, and life-long learning. The results showed that students with the longest exposure to PBL (Group 3) had higher self-evaluated scores for all core competencies than the other groups, except for the execution competency. The mean total competency score increased by 0.12 points between the pre-and-test. In addition, the mean score increased significantly more in Group 3 than in Groups 1 and 2. These trends were consistent for the information analysis, execution, and life-long learning competencies. In conclusion, the changes in the self-evaluated scores between groups indicate PBL strategies effectively improve nursing students' core competencies. The longest exposure group reported higher self-evaluated core competency scores than the other groups, especially for the information analysis, execution, and life-long learning competencies.

Introduction: Some infertile women are eager to have children. The purpose of this study was to explore the childbearing perceptions of women who undergo in vitro fertilization (IVF) treatment., Methodology: Qualitative phenomenological data were collected from 20 infertile women who received IVF treatment in Taiwan. We conducted one-on-one in-depth interviews with the women. Audio recordings were transcribed as textual data and analyzed using Giorgi content analysis until saturation was achieved., Results: Three themes were identified: important tasks related to practicing the family life cycle, ensuring a tight circle of marriage, and the hope to change health., Discussion: Perceptions regarding childbearing in women undergoing IVF treatment in the context of the traditional Chinese fertility culture are multifaceted. To improve the overall integrity of health care provided to infertile women, nurses should be encouraged to consider the cultural connotations and needs of infertile women in the clinic.

Objectives: Stretchers are commonly used for transporting cardiac arrest patients, but their use may be limited in confined spaces, like elevators. Use of transfer sheet as an alternative has not been explored. We aimed to compare manual chest compression quality between these two methods. Methods: In this prospective, open-label, randomized cross-over manikin study, the subjects included emergency medical technicians who were assigned to 12 three-person crews. Scenarios included transport of a cardiac arrest in a high-rise building and elevator using transfer sheet (TS) and stretchers adjusted to 45° (S45) and 90° (S90). Chest compression quality was measured using a recording manikin and that before (on-scene phase) and after (transport phase) the manikin moved via transfer sheet or stretcher were compared. Results: The final analysis included 72 simulation runs. Chest compression quality did not differ among the groups in the on-scene phase. In the transport phase, the transfer sheet group provided greater mean compression depth (54.4 ± 4.2 vs 39.6 ± 7.2 mm, p < 0.01 and 54.4 ± 4.2 vs 40.6 ± 8.3 mm, p < 0.01, respectively) than stretchers of S45 and S90, and higher percentage of deep-enough compression (TS: 51.0 [23.8-74.8]% vs S45: 19.5 [5.8-29.5]%, p < 0.01) than the S45 group. Transfer sheet use showed a trend of lower percentages of full recoil (TS: 40.0 [12.8-64.5]% vs S45: 70.5 [47.0-79.8]% vs S90: 52.5 [25.3-76.0]%, p = 0.09). Chest compression fraction, compressions with correct hand position, and mean compression rates did not differ between groups in the transport phase. The TS group showed shorter time intervals of simulation start-to-first-compression (TS: 13.9 [12.4-15.1] sec vs S90: 15.9 [13.3-16.4] sec, p = 0.04) and total run time (TS: 145.7 [135.1-151.4] sec vs S90: 160.0 [151.9-175.4] sec, p < 0.01) than the S90 group. Conclusion: In this simulation, using transfer sheet outperform using stretcher for transporting cardiac arrest patients from high-rise buildings. Rescuers need to be aware of full chest recoil.

Abstract: We investigated the association between high-density lipoprotein cholesterol (HDL-C) and rs2014355 variant in the gene, short-chain acyl-coenzyme A dehydrogenase (ACADS) based on exercise habits.Data collected between 2008 and 2015 for individuals aged 30 to 70 years were available in the Taiwan Biobank (TWB) database. Backward stepwise linear regression was used to evaluate the associations of rs2014355 and exercise with HDL-C levels.We analyzed data of 5515 physically active and 4169 inactive biobank participants. The HDL-C concentrations were higher in the exercise compared to no exercise group (beta value, β = 1.79856; P < .0001). We observed that the test for interaction was significant for the ACADS rs2014355 variant and exercise (P for interaction =.0412). Multivariate analyses showed significant association between TC+CC genotype and HDL-C in the exercise (β = 1.09785; P value = .0146) compared to the no-exercise group (β = -0.03754, P = .9154).In summary, the association between HDL-C and exercise differed significantly with respect to ACADS rs2014355 genotypes. Compared to the TT genotype, the TC+CC genotype together with exercise was associated with higher levels of HDL-C., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Leptin ( LEP ) regulates glucose metabolism and energy storage in the body. Osteoarthritis (OA) is associated with the upregulation of serum LEP . LEP promoter methylation is associated with obesity. So far, few studies have explored the association of BMI and OA with LEP methylation. We assessed the interaction between body mass index (BMI) and OA on LEP promoter methylation. Data of 1114 participants comprising 583 men and 558 women, aged 30-70 years were retrieved from the Taiwan Biobank Database (2008-2015). Osteoarthritis was self-reported and cases were those who reported having ever been clinically diagnosed with osteoarthritis. BMI was categorized into underweight, normal weight, overweight, and obesity. The mean LEP promoter methylation level in individuals with osteoarthritis was 0.5509 ± 0.00437 and 0.5375 ± 0.00101 in those without osteoarthritis. The interaction between osteoarthritis and BMI on LEP promoter methylation was significant ( p -value = 0.0180). With normal BMI as the reference, the mean LEP promoter methylation level was significantly higher in obese osteoarthritic individuals ( β = 0.03696, p -value = 0.0187). However, there was no significant association between BMI and LEP promoter methylation in individuals without osteoarthritis, regardless of BMI. In conclusion, only obesity was significantly associated with LEP promoter methylation (higher levels) specifically in osteoarthritic patients.

Objective: A burn mass casualty incident (BMCI) involving 499 patients occurred at a "color party" in Taiwan in June 27, 2015. We implemented a study to identify critical challenges regarding the prehospital emergency care in BMCIs. Methods: A 3-stage, mixed methods study was conducted in 2016. First, a statistical analysis of prehospital management using the data retrieved from the Emergency Medical Management System of the Ministry of Health and Welfare, Taiwan was performed. This was followed by a face-to-face, open-ended interview with the emergency medical technicians and the staff of the emergency operations center who responded to the incident; and the transcription of the interview data into constructed themes. Results: Our study indicated that the signs of inhalation injury needed to be incorporated in the field triage protocol for BMCIs; the collaborative utilization of regional emergency medical services may improve the surge capacity in the field; and an "island-hopping" strategy for patient transportation may allow the healthcare systems to manage the surge of burn patients more efficiently. Conclusions: Current field triage protocols may be insufficient for burn patients and should be further investigated. The practices in field triage, transport capacity, and transfer strategy can be considered as a part of an efficient prehospital emergency response to BMCIs.

Background: Women who undergo in vitro fertilization/embryo transfer (IVF/ET) face complicated psychological stress and negative emotions, which may affect health during pregnancy and the development of the fetus. The current literature does not address the question of whether women who become pregnant spontaneously and women who undergo IVF face similar levels of pregnancy stress., Purpose: This study investigates the differences in pregnancy stress between women with spontaneous pregnancy and women with IVF/ET pregnancy living in central Taiwan during their first 20 weeks of pregnancy., Methods: A prospective, longitudinal design with repeated measures, generalized estimated equations model, Wilks' λ, and Bonferroni test was used. Purposive samples of 163 women who had undergone IVF/ET and of 94 women who had undergone spontaneous pregnancy were enrolled as participants. Pregnancy stress was measured using the Chinese version of the self-administered Pregnancy Stress Scale at the 9th, 12th, and 20th weeks of pregnancy., Results: The psychological stress experienced by IVF participants significantly increased with gestational week during the first 20 weeks of pregnancy (p < .01) but did not significantly increase in spontaneous-pregnancy participants. Gestational week was the main factor found to influence stress ratings for "identifying maternal role." "Altering body structure and body function" was the main factor found to influence pregnancy stress (p < .00). The method of becoming pregnant had no significant influence on pregnancy stress during the first 20 weeks of pregnancy (p > .05)., Conclusions/implications for Practice: The results of this study provide clinical evidence that IVF/ET does not cause more stress for women than spontaneous pregnancy. However, the intensity and trend of stresses differed between these two groups. These findings suggest that nurses should consider method of pregnancy when assessing the risk of stress in expectant mothers for each gestational week and when providing appropriate care and support.

Octenyl succinic anhydride modified starch (OSA-ST) was used to encapsulate coenzyme Q10 (CoQ10). CoQ10 was dissolved in rice bran oil and incorporated into an aqueous OSA-ST solution. High pressure homogenisation of the mixture was conducted at 170 MPa for 56 cycles. The resulting emulsion had a particle size range of 200-300 nm and the absolute zeta potential varied between 8.4 and 10.6 mV. CoQ10 retention of the emulsion and freeze dried products, determined by a hexane rinse, was 98.2%. Reconstitution of the freeze dried product in Mcllvaine citrate-phosphate buffers with pH values of 3-5 and temperatures at 4 and 25 °C had very little effect on the range and distribution of the nanoparticles' size. The inflection point of the zeta potential and pH plot occurred at the first pKa of succinic acid (pH 4.2), indicating succinate as the main influence over zeta potential., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The aims of this study were to identify learning needs among traditional four-year and two-year recurrent education (RN-BSN) undergraduate nursing students in Taiwan with regard to patients' concerns about sexual health. A 24-item instrument (Learning Needs for Addressing Patients' Sexual Health Concerns) was used to collect data. Compared to RN-BSN undergraduate nursing students, traditional four-year undergraduate nursing students had more learning needs in the aspects of sexuality in health and illness (2.19 ± 0.66 vs. 1.80 ± 0.89, P = 0.005) and approaches to sexual health care (2.03 ± 0.72 vs. 1.76 ± 0.86, P = 0.033). After adjustment for other variables by the backward selection approach, those with experience in assessing patient's sexual functioning had fewer learning needs in sexuality in health and illness (β = -0.375, P = 0.001), communication about patient's intimate relationships (β = -0.242, P = 0.031), and approaches to sexual health care (β = -0.288, P = 0.013); those who agreed that sexual health care was a nursing role also expressed greater needs to learn about these 3 aspects (all P < 0.01). Content related to sexuality in health and illness and approaches to sexual health care should be strengthened in the traditional undergraduate nursing curriculum in order to support sexual health related competence, build a positive attitude regarding sexual health care as a nursing role, and strengthen the experience of assessing patient's sexual functioning. A different, simplified program may be more suitable for those with clinical experience.

Background: Case reports have indicated that a tropical cyclone may increase Emergency Department (ED) visits significantly., Study Objectives: To examine emergency health care demands across a series of tropical cyclones, and to build a predictive model to analyze a cyclone's potential effect., Methods: This was an observational non-concurrent prospective study performed in Taiwan. Twenty hospitals were included. The number of daily ED visits in each hospital was our primary end point, and data were retrieved from the database provided by the National Health Insurance Research Database. Our study examined the period from 2000 to 2008. A total of 22 tropical cyclones (typhoons) that had passed over eastern Taiwan and covered the area under study were included. Multiple linear regression time-series models were employed to estimate the effects of "days since typhoon landfall" and various characteristics of the typhoons on the end point of daily ED visits to each hospital., Results: The final multiple linear regression time-series model showed that the number of daily ED visits increased in areas where a strong typhoon had landed directly, with the increase being evident during the first 2 days since landfall. Our model also indicated that the three most important variables to predict a change in the pattern of daily ED visits were intensity of typhoon, simultaneous heavy rain, and direct landfall., Conclusions: During tropical cyclones, emergency services were under increased demand in selected time periods and areas. Health care authorities should collect information to build local models to optimize their resources allocation in preparation., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Heparin-induced thrombocytopenia with thrombosis (HITT) is the most severe side effect of heparin administration. Patients with HITT may die or have permanent sequelae such as stroke or limb amputation. Contaminated heparin is associated with anaphylactic reactions and deaths by activating the contact system. It is also associated with high incidence of HIT via a yet unknown mechanism. This study showed that although oversulfated heparin byproduct induced thrombin activities in both normal and HIT patient plasmas through the contact system activation, authentic heparin induced thrombin activities only in HIT patient plasmas containing autoantibodies against protein/ heparin complex. These data suggest that the negatively charged immunoglobulin G (IgG)/platelet factor 4 (PF4)/heparin complex activate the contact system and produce thrombin in human plasma, and thrombin partially activates the platelets allowing subsequent platelet activation through IgG/Fc receptor II signaling. The newly discovered mechanism of heparin-induced thrombin activity could explain the increased incidence of HIT in patients exposed to contaminated heparin. Furthermore, the assays used in these studies would be valuable for HIT diagnosis, prevention, and treatment.

Systemic lupus erythematosus (SLE), heparin-induced thrombocytopenia (HIT), rheumatoid arthritis (RA) are marked by the presence of autoantibodies against negatively changed DNA, phospholipids, heparin, and chondroitin sulfate, respectively. Heparin/protein complexes induce contact system activation in HIT patient plasmas. The activated contact system generates thrombin. Thrombin is responsible for thrombosis, a common cause of death and disabilities for both HIT and SLE. In this chapter, we analyze plasma contact system proteins, thrombin- and kallikrein-like activities, glucosamine and galactosamine content from SLE-, RA-, osteoarthritis (OA)-, and psoriasis (Ps)-patient plasmas in addition to pooled 30+ healthy patient plasmas. We found that all SLE patient plasmas exhibited abnormal contact systems marked by the absence of high molecular weight kininogen, the presence of processed C1 inhibitor (C1inh), the display of abnormal thrombin- and kallikrein-like activities, and increased levels of plasma glucosamine and galactosamine. Different patterns of contact system activation distinguish SLE, RA, and Ps whereas no contact system activation is observed in normal and OA patient plasmas. The presence of paradoxical "lupus anticoagulants" in certain thrombosis-prone SLE patient plasmas, marked by delayed clotting in clinical plasma test, was explained by the consumption of contact system proteins, especially high molecular weight kininogen. Finally, we discovered that mouse and human SLE autoantibodies bind to cell surface GAGs with structural selectivity. In conclusion, markers of abnormal contact system activation represent potential new targets for autoimmune disease diagnosis, prevention, and treatment. These markers might also be useful in monitoring SLE activity/severity and in pinpointing patients with SLE-associated arthritis and psoriasis., (Copyright © 2010 Elsevier Inc. All rights reserved.)

In the K/BxN mouse model of rheumatoid arthritis, autoantibodies specific for glucose-6-phosphate isomerase (GPI) can transfer joint-specific inflammation to most strains of normal mice. Binding of GPI and autoantibody to the joint surface is a prerequisite for joint-specific inflammation. However, how GPI localizes to the joint remains unclear. We show that glycosaminoglycans (GAGs) are the high affinity (83 nm) joint receptors for GPI. The binding affinity and structural differences between mouse paw/ankle GAGs and elbows/knee GAGs correlated with the distal to proximal disease severity in these joints. We found that cartilage surface GPI binding was greatly reduced by either chondroitinase ABC or beta-glucuronidase treatment. We also identified several inhibitors that inhibit both GPI/GAG interaction and GPI enzymatic activities, which suggests that the GPI GAG-binding domain overlaps with the active site of GPI enzyme. Our studies raise the possibility that GAGs are the receptors for other autoantigens involved in joint-specific inflammatory responses.

Objective: CD4+CD25+FoxP3+ regulatory T (Treg) cells are critical regulators of autoimmunity. Yet the number of Treg cells is paradoxically increased in rheumatoid arthritis (RA) patients, and Treg cells show variable activity in human studies. The objective of this study was to characterize the expansion and function of Treg cells during the initiation and progression of experimental arthritis., Methods: To unequivocally identify Treg cells, we crossed FoxP3gfp mice with K/BxN mice to generate arthritic mice in which Treg cells express green fluorescence protein. We examined the expansion and function of Treg cells and effector T (Teff) cells during different stages of arthritis, using flow cytometry and cell proliferation analyses., Results: In K/BxN mice, thymic selection of KRN T cells resulted in an enrichment of forkhead box P3 (FoxP3)-positive Treg cells. Treg cell numbers increased during arthritis, with significant increases in spleens and draining lymph nodes, indicating selective tropism to sites of disease. In contrast to the in vitro unresponsiveness of Treg cells when cultured alone, substantial proportions of Treg cells proliferated in both nonarthritic and arthritic mice. However, they also underwent greater apoptosis, thereby maintaining equilibrium with Teff cells. Similarly, enhanced Treg cell-suppressive activity during arthritis was offset by greater resistance by their Teff cell counterparts and antigen-presenting cells., Conclusion: In this well-established model of RA, the interplay of Teff cells and Treg cells in K/BxN mice recapitulated many features of the human disease. We demonstrated an ordered expansion of Treg cells during arthritis and dynamic changes in Treg cell and Teff cell functions. By elucidating factors that govern Treg cell and Teff cell development in K/BxN(gfp) mice, we will gain insight into the pathophysiology of and develop novel therapeutics for human RA.

The antioxidant properties of methanolic extracts from soybean obtained with germination, wounding, and application of biotic elicitors were evaluated. Also, the relationship between observed antioxidant properties and compositional changes in isoflavone content was determined. The 2 biotic elicitors used in this study were the food-grade fungus Aspergillus sojae and A. sojae cell wall extract. Isoflavone content was determined by C(18) reverse phase high-performance chromatography coupled with a photodiode array detector. Antioxidant activities of the extracts were measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and beta-carotene cooxidation in a linoleate system. Higher antioxidant activities were observed in wounded and elicitor-treated extracts when compared with nonwounded control extracts. In addition, the phenolic content was higher in extracts from wounded and elicitor-treated soybean. Germination for 3 d slightly decreased total isoflavone content (-4.3%); however, wounding increased total isoflavone content (25.8%). The soybean extracts from seeds treated with A. sojae biotic elicitors had the highest total isoflavone contents (9.8 to 11.6 mg/g extract) and displayed the highest antioxidant activities in both the DPPH and beta-carotene assays. Also identified in the wounded and elicitor-treated extracts were the induced isoflavones glyceollins that contributed to the higher isoflavone contents observed.

Glucose-6-phosphate isomerase (GPI) is the target autoantigen recognized by KRN T cells in the K/BxN model of rheumatoid arthritis. T cell reactivity to this ubiquitous Ag results in the recruitment of anti-GPI B cells and subsequent immune complex-mediated arthritis. Because all APCs have the capacity to process and present this autoantigen, it is unclear why systemic autoimmunity with polyclonal B cell activation does not ensue. To this end, we examined how GPI is presented by B cells relative to other immunologically relevant APCs such as dendritic cells (DCs) and macrophages in the steady state, during different phases of arthritis development, and after TLR stimulation. Although all APCs can process and present the GPI:I-A(g7) complex, they do so with different efficiencies. DCs are the most potent at baseline and become progressively more potent with disease development correlating with immune complex uptake. Interestingly, in vivo and in vitro maturation of DCs did not enhance GPI presentation, suggesting that DCs use mechanisms to regulate the presentation of self-peptides. Non-GPI-specific B cells are the weakest APCs (100-fold less potent than DCs) and fail to productively engage KRN T cells at steady state and during arthritis. However, the ability to stimulate KRN T cells is strongly enhanced in B cells after TLR ligation and provides a mechanism whereby polyclonal B cells may be activated in the wake of an acute infection.

Plasma ammonia measurement is a simple yet important screening in the ED for patients with unexplained stupor or delirium. Acute hyperammonemia is a medical emergency for which immediate steps must be taken to minimize permanent brain damage. Although the most common causes of hyperammonemia are severe abnormal liver function, the absence of liver disease in some cases has been observed. This brief report describes four hyperammonemia cases with normal liver function in the ED. On careful history and speculated examinations, ornithine carbamoyltransferase (OTC) deficiency, hematologic malignancy, and the side effects of valproic acid and 5-fluorouracil (5-FU) were considered. Therapy was first aimed at correcting the hyperammonemia. Once a specific diagnosis was reached, protein restriction, essential amino acid supplementation, efficient chemotherapy, and valproic acid and 5-FU level discontinuance were instituted. In this report, the clinical presentation, pathogenesis, and diagnostic workup for various hyperammonemia causes are discussed. Every EP should understand that the clinical symptoms for hyperammonemia and prognosis are related to early diagnosis.

Incomplete deletion of KRN T cells that recognize the ubiquitously expressed self-antigen glucose-6-phosphate-isomerase (GPI) initiates an anti-GPI autoimmune cascade in K/BxN mice resulting in a humorally mediated arthritis. Transgenic (Tg) expression of a KRN T cell receptor (TCR) agonist under the major histocompatibility complex class II promoter resulted in thymic deletion with loss of anti-GPI T and B cell responses and attenuated arthritis course. However, double Tg mice succumbed to systemic autoimmunity with multiorgan inflammation and autoantibody production. Extensive thymic deletion resulted in lymphopenia and elimination of CD4+ CD25+ regulatory T cells (Tregs), but spared some CD4+ T cells expressing endogenous TCR, which oligoclonally expanded in the periphery. Disease was transferred by these T cells and prevented by cotransfer of CD4+ CD25+ Tregs. Moreover, we extended our findings to another TCR system (anti-hen egg lysozyme [HEL] TCR/HEL mice) where similarly extensive thymic deletion also resulted in disease. Thus, our studies demonstrated that central tolerance can paradoxically result in systemic autoimmunity through differential susceptibility of Tregs and autoreactive T cells to thymic deletion. Therefore, too little or too much negative selection to a self-antigen can result in systemic autoimmunity and disease.

In this review, we dissect two different antigen systems which represent the apparent extremes of T cell receptor (TCR) recognition. In the hemoglobin (Hb) system, a minor change in a single MHC anchor residue disrupts TCR recognition. In the KRN system, a single TCR shows strong reactivity to two peptides from unrelated proteins, presented by different MHC molecules. Upon closer analysis, both turn out to be specific recognition events, following set rules of engagement. Thus, although a TCR can recognize multiple ligands sharing minimal sequence homology, this recognition is still highly specific and is constrained by the same structural requirements. TCR degeneracy is therefore limited and is unlikely to be a major mechanism for autoimmunity.

The component of protein in rice, at 7-9% by weight, is relatively low, but the total amount of rice protein potentially available is significant because the production of rice worldwide, at 380 million tons annually, is huge. Rice proteins are recognized as nutritional, hypoallergenic, and healthy for human consumption, and rice protein products have been in demand in recent years. However, because of difficulties in the processing, rice protein products, particularly high-protein content ones, have not been readily available. Two of the main sources of rice protein, rice bran and, to a lesser extent, broken rice kernels, have been under-used and under-priced. This report provides an update on the processing of these sources for rice proteins. Methods of protein processing are highlighted including the traditional alkaline extraction, enzyme-assisted extraction, and the novel uses of physical treatment prior to water extraction. Also discussed are effects of processing on the functional and nutritional properties of rice protein.

Rice starch was modified with various levels of 2-octen-1-ylsuccinic anhydride (OSA). Treatments with OSA at 3, 5, and 10% resulted in starch derivatives with 0.016, 0.033, and 0.070 degrees of substitution (DS), respectively. Thermovisco properties of the derivatives were investigated by differential scanning calorimetry (DSC) and rapid visco analysis (RVA). Water content in the sample was found to have a significant effect on the characteristics of the DSC endotherm. Pasting properties of the OSA-starch and the effect of pH and salt on the RVA profiles were also studied. In general, with increased OSA-modification, the starch derivatives swelled and gelatinized at lower temperatures to achieve higher viscosities. Specifically, based on DSC analysis at 80% water, the peak temperature of gelatinization decreased from 68.5 to 63.2 degrees C as the OSA modification increased in DS from 0 (intact starch) to 0.070. On the other hand, RVA results indicate that, for samples undergoing similar increase in OSA modification, the pasting temperature decreased from 88.7 to 51.5 degrees C and the peak viscosity increased from 668 to 6822 cP.

K/BxN mice develop an inflammatory joint disease with many features characteristic of rheumatoid arthritis. In this model, the KRN transgenic T cells and nontransgenic B cells both recognize the glycolytic enzyme glucose-6-phosphate-isomerase (GPI) as an autoantigen. Here, we followed the anti-GPI B cell response that naturally arises in K/BxN mice. The anti-GPI B cell response was robust and arose at the same time as the development of serum anti-GPI autoantibody and joint inflammation. Surprisingly, although GPI was expressed systemically, the anti-GPI B cell response was focused to the lymph nodes (LN) draining the distal joints where arthritis was evident. In lymphotoxin-beta receptor-Ig-treated mice, which lack LNs, the development of arthritis was completely inhibited up to 5-6 weeks. At later times, some arthritis did develop, but at a significantly reduced level. Thus, in this spontaneous model of autoimmunity, the LNs draining the distal joints are essential for both the inhibition and amplification of the arthritogenic B cell response. These findings imply that the immune physiology of a joint is unique, resulting in a local immune response to a systemic autoantigen.

The study explores the verbal interaction relationship between therapists and members, and the interaction model of this group. Six subjects were chosen by convenience sampling from the psychiatric OPD of a medical center in the Taichung area. Subjects with informed consent participated in a 12-week course of closed group psychotherapy. All data was tape-recorded and the Hill Interaction Matrix (HIM) scale was applied for simultaneous triangulation, in order to analyze the group's dynamic development of cognitive-behavioral psychotherapy for patients with panic disorder. The results indicated that the interactive relationship between therapists and members fluctuated during the group process. Development of the group process can be subdivided into three stages: initial stage-adaptive and familiar, middle stage-explorative, and terminal stage-productive. The amount of verbal interaction was greatest in the third quadrant. In the group interaction model, the therapist tended to explore the members' problems most. Providing support was the second most frequent. Meanwhile, members also tended to discuss personal problems. It was revealed that the verbal interaction of the therapists and members were the same. The content style of this group session is member-centered, and work style is pre-worked. The results showed that the group sessions did have great therapeutic value for members.

We have examined factors governing the differentiation of autoreactive CD4+ T cells that have evaded deletion by a self peptide. Two lineages of transgenic mice (HA12 and HA104) expressing the influenza virus hemagglutinin (HA) were mated with TS1 mice that express a clonotypic T cell receptor (TCR) specific for the I-Ed-restricted determinant site 1 (S1) of HA. Thymocytes expressing high levels of the clonotypic TCR were deleted in both TS1xHA transgenic lineages. However, through allelic inclusion, thymocytes expressing low levels of the clonotypic TCR and high levels of endogenous TCR alpha-chains evaded deletion in TS1xHA12 and TS1xHA104 mice to graded degrees. When stimulated with S1 peptide in vitro, the non-autoreactive TS1 T cells were biased toward differentiation into Th2 effectors. By contrast, CD4+ T cells that evaded deletion in TS1xHA12 and TS1xHA104 mice were progressively biased toward Th1-like differentiation. Moreover, the effector cells from TS1xHA12 and TS1xHA104 mice secreted higher levels of IFN-gamma , on a per cell basis, than were secreted by their non-autoreactive counterparts. Thus, CD4+ T cells that evade deletion by a self peptide can exhibit an intrinsic bias toward differentiation into Th1 effector cells.

We have examined factors governing the negative selection of autoreactive CD4(+) T cells in transgenic mice expressing low (HA12 mice) vs. high (HA104 mice) amounts of the influenza virus hemagglutinin (HA). When mated with TS1 mice that express a transgenic TCR specific for the I-Ed-restricted determinant site 1 (S1) of HA, thymocytes expressing high levels of the clonotypic TCR were deleted in both HA-transgenic lineages. However, through allelic inclusion, thymocytes with lower levels of the clonotypic TCR evaded deletion in TS1 x HA12 and TS1 x HA104 mice to graded degrees. Moreover, in both lineages, peripheral CD4(+) T cells could be activated by the S1 peptide in vitro, and by influenza virus in vivo. These findings indicate that allelic inclusion can allow autoreactive CD4(+) thymocytes to evade thymic deletion to varying extents reflecting variation in the expression of the self peptide, and can provide a basis for the activation of autoreactive peripheral T cells by viruses bearing homologues of self peptides ("molecular mimicry").

To analyze mechanisms governing tolerance and autoimmunity to self-antigens, we have generated lineages of transgenic mice that express the influenza virus PR8 hemagglutinin (HA) as a neo-self-antigen. By comparing the HA-specific T and B cell responses that can be induced in HA Tg mice with those that are induced in non-Tg (BALB/c) mice, the specificity and genetic basis with which tolerance is induced to the HA has been examined. This article summarizes studies using lineages of HA Tg mice that express different forms and amounts of the HA under the control of the SV40 promoter/enhancer. Our studies have revealed that specific subsets of HA-specific T and B cells are negatively selected from the primary repertoires of HA Tg mice. However, substantial populations of HA-specific T and B cells evade negative selection and can be activated by virus immunization. Understanding the capacity of these autoreactive lymphocytes to differentiate and participate in antigen-specific immune responses will provide important insights into mechanisms by which autoimmunity might be induced by viruses bearing structural similarities with self-antigens.

Transgenic (Tg) mice expressing the influenza virus PR8 hemagglutinin (PR8 HA) were infected with PR8 virus and analyzed for their ability to generate T cell responses to individual MHC class II-restricted T cell determinants from the HA. HAmemb and HAtrunc mice each express HA transgene mRNA in many tissues (including the thymus), but differ in the form and amount of the HA that is expressed: HAmemb mice express the entire viral HA as a membrane-bound neo-self antigen, whereas HAtrunc mice express lower levels of a truncated HA polypeptide. HAmemb mice were found to mediate efficient negative selection of autoreactive T cells directed to the major I-Ed-restricted and I-Ad-restricted determinants from the HA (designated S1 and S2 respectively). S1-specific T cell responses were similarly undetectable in PR8-infected HAtrunc mice. However, S2-specific T cells were only partially eliminated in HAtrunc mice; indeed, even though their frequency was reduced relative to non-Tg mice, S2-specific T cells still constituted a sizable population in PR8-infected HAtrunc mice. Moreover, the S2-specific T cells from HAtrunc and non-Tg mice appeared to be equally sensitive to stimulation with S2 peptide, and in each case utilized highly diverse T cell receptors to recognize S2-I-Ad. The findings demonstrate that an individual class II-restricted T cell determinant can be recognized as a cryptic self peptide during T cell repertoire formation and as an immunodominant peptide in the context of an anti-viral T cell response, providing a basis for the induction of autoreactive T cells by viruses containing homologs of self antigens.

We have generated transgenic mouse lineages that express the influenza virus hemagglutinin in different physical forms. One kind expresses the full-length hemagglutinin molecule as a cell surface glycoprotein and can be recognized by hemagglutinin-specific B and T cells. The other expresses a truncated polypeptide corresponding to the N-terminal third of the hemagglutinin molecule. This polypeptide encodes known hemagglutinin-specific T-cell determinants; however, it contains no native B-cell epitopes, since these depend on the conformation of the fully folded protein. In each case, the hemagglutinin transgenic mice display ubiquitous expression of transgenic messenger RNA and induce T-cell tolerance to the transgene-encoded T-cell determinant site 1. Thus, the hemagglutinin is a neo-self-antigen in both kinds of hemagglutinin transgenic mice and should provide a useful system for understanding the factors and mechanisms that govern tolerance and autoimmunity to self-antigens.

We have analyzed the genetic basis for T cell recognition of an endogenous major histocompatibility complex class II-restricted self peptide. Transgenic mice expressing the influenza virus PR8 hemagglutinin I-Ed-restricted determinant S1 (HA Tg mice) mediate negative selection of PR8 S1-specific T cells, but respond to immunization with a virus containing a closely related analogue, S1(K113). Sequence analysis of S1(K113)-specific T cell receptors (TCR) from nontransgenic mice revealed a dominant TCR clonotype that cross-reacts with PR8 S1. This clonotype is eliminated by negative selection in HA Tg mice; nonetheless, modified versions of this TCR that used altered junctional sequences and a novel V alpha/V beta pairing to evade negative selection by the S1 self peptide were identified. The remaining S1(K113)-specific TCRs from HA Tg mice were highly diverse; 13 of 15 S1(K113)-specific TCRs from HA Tg mice used unique V alpha/V beta pairings. Thus, tolerance to PR8 S1 as a self peptide does not limit the diversity of the T cell response to S1(K113).

The specificity with which CD4+ T cells recognize self peptides in vivo was examined in transgenic mice that express an influenza virus PR8 hemagglutinin (HA) polypeptide in many tissues, including the thymus (HA Tg mice). HA Tg and non-Tg mice were analyzed for their T cell responses to the major PR8 HA I-E(d)-restricted CD4+ T cell determinant S1. Negative selection eliminated S1-specific T cells from HA Tg mice. Nevertheless, HA Tg mice retained the ability to mount a T cell response to a closely related analog of the S1 determinant [S1(K113)], and some S1(K113)-specific TCRs displayed a partial reactivity with S1 as indicated by their ability to transmit signals for IL-3 but not IL-2 secretion in response to the neo-self peptide. Moreover, the neo-self S1 peptide antagonized the ability of these TCRs to signal IL-2 secretion in response to the foreign S1(K113) determinant. Thus, TCRs that exhibit a partial reactivity with a self peptide are present in the peripheral T cell repertoire and can be activated by a virus containing an analog of the self peptide. These findings provide a model for the induction of autoimmunity by viruses that are close homologs of self peptides, and suggest a way in which TCRs could react with self peptides during positive selection of developing thymocytes.

An enzyme immunoassay (EIA, ELISA) using microwells coated with a flagellin-enriched fraction of B. burgdorferi and absorbent-containing sample diluent for the quantitative determination of Lyme disease (LD) IgG and IgM antibodies in human serum samples was described. This LD EIA required three 15-minute incubations at room temperature, followed by a 1-step normalization of photometer readings to EIA units (EU/ml). Compared with tests using the whole bacterial extract as antigens and a sample diluent containing 6% BSA, this new LD EIA revealed lower values for 20 syphilis (SS) and 21 normal serum samples (NS) but about the same for 21 Lyme disease (LD) samples, allowing lower cut-off points which would place almost all these SS and NS samples below while almost all LD samples above the positive cut-off point. The LD EIA results of larger numbers (67 to 291) of mixed samples correlated with results of four reference EIA. However, the LD EIA gave lower (2 to 4 fold) reactivities (index values) with SS and NS samples but higher values with positive serum samples than reference EIA. Thus, this LD EIA showed improvements in both specificity and sensitivity over other tests compared.

Studies with the T-cell antigen receptor (TCR) have shown that the endoplasmic reticulum, or an organelle closely associated with it, can retain and degrade membrane proteins selectively. The observation that only three (alpha, beta, and delta) of the six (alpha beta gamma delta epsilon zeta) subunits of the TCR are susceptible to proteolysis implies that structural features within the labile proteins mark them for degradation. The TCR beta chain is degraded in the endoplasmic reticulum, and, in this study, we have started to define the domains of the protein that make it susceptible to proteolysis. The experiments show that the transmembrane anchor and short five-amino-acid cytoplasmic tail of the protein contain a dominant determinant of proteolysis. When these residues were removed from the beta chain, the protein became resistant to proteolysis. Even though the resulting ectodomain of the beta chain lacked a transmembrane anchor, it was not secreted by cells and was retained in the endoplasmic reticulum. We conclude that retention in the endoplasmic reticulum alone does not lead to degradation. The results suggest that structural features within the membrane anchor of the protein predispose the beta chain to proteolysis. This was confirmed by replacing the membrane anchor of the interleukin 2 (IL2) receptor, a protein that was stable within the secretory pathway, with that of the TCR beta chain. The unmodified IL2 receptor was transported efficiently to the surface of cells, and an "anchor minus" construct was secreted quantitatively into the culture media. When the membrane anchor of the IL2 receptor was replaced with that of the TCR beta chain, the chimera was unable to reach the Golgi apparatus and was degraded rapidly.