[Effects of a Hybrid Health Education Program on Pain and Knee Angle in Elderly Patients After Total Knee Replacement Surgery].

BACKGROUND: Patients experience pain and limited knee angle after total knee replacement (TKR) surgery. The effectiveness of routine discharge health education remains limited. PURPOSE: This study was designed to assess the effect of hybrid health education on postoperative pain and knee angle in patients with TKR. METHODS: A single blind and randomized controlled trial study was used. Fifty-two patients with TKR were randomly assigned to either the experimental group (n = 26), which received standard care with hybrid health education and performed the multimedia-guided intervention for 30 min per day for 16 weeks, or the control group (n = 26), which received routine care only. The data collection times were at pretest (preoperative) and at the 1st week, 6th week, 12th week, 16th week after surgery. RESULTS: A total of 22 patients in the experimental group and 26 patients in the control group completed this study. After the 16-week hybrid health education intervention, the results of generalized estimating equations analysis showed that pain in the experimental and control groups differed significantly at week 12 (ß = -1.43, p = .025) and week 16 (ß = -1.52, p = .014); worst pain in the past week had significantly improved at week 12 (ß = -1.40, p = .041) and week 16 (ß = -1.55, p = .024); average pain over the past 1 week had significantly improved at week 16 (ß = -1.24, p = .035); and knee extension angle had significantly improved at week 16 (ß = -5.52, p = .033). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results of this study showed that elderly patients who received hybrid health education after TKR had significantly improved postoperative pain and knee angle and that degree of improvement in the experimental group was better than in the control group. It is recommended that the content and methods of hybrid health education developed in this study be incorporated into discharge interventions and that long-term outcomes be tracked for reference.

Stressors experienced by children with autism spectrum disorder in Taiwan: Perspectives of children and their parents.

Autism spectrum disorder has only recently been recognized as a developmental disability in Taiwan. We conducted an exploratory qualitative descriptive study with children (n = 14, mean age = 13.57 years) and their parents to understand stressors experienced by children with autism spectrum disorder in Taiwan. An analysis of face-to-face interviews revealed that children with autism spectrum disorder experienced stressors of daily living, which included environmental stimuli, academic and behavioral expectations, deviations in routine, behavioral expectations, and emotional control, and stressors of socializing, which included bullying, communication, personal interactions, conflict resolution, and difficulty understanding others' emotions. Stressors resulted from the core symptoms and characteristic behaviors of autism spectrum disorders, and also Taiwanese cultural expectations. Our findings could help develop individualized educational plans and culturally-sensitive behavioral interventions. Facilitation of these interventions could be used by nurses and health-care professionals to help facilitate problem solving and communication skills, which could reduce the stress for children with autism spectrum disorder in Taiwan.

Fetal Phagocytes Take up Allergens to Initiate T-Helper Cell Type 2 Immunity and Facilitate Allergic Airway Responses.

RATIONALE: Actively acquired tolerance occurs when foreign antigens come into contact with the immature fetal immune system. OBJECTIVES: Armed with the knowledge of actively acquired tolerance, we attempted to prenatally abolish or diminish allergic responses. METHODS: In utero injection of adjuvant-free ovalbumin (OVA) was conducted in Gestational Day 14 FVB/N mouse fetuses. Postnatally, mice were evaluated for their resistance to intraperitoneal OVA sensitization and oral or aerosolized OVA challenge, and then they were examined for humoral and cellular immunological profiles, airway hyperresponsiveness to bronchospastic stimuli, and lung histology. Fluorescent conjugates of OVA were used for further studies of mechanisms. MEASUREMENTS AND MAIN RESULTS: This presumed tolerogenic action turned out to be a sensitization process with the development of anaphylaxis or heightened recall, T-helper cell type 2-skewed responses to postnatal encounter with OVA. Further postnatal aerosolized OVA stress triggered allergic lungs with functional and structural alterations of airways. The unintended consequence resulted from macrophage-like fetal phagocytes that took up OVA and differentiated toward dendritic cells. These fetal dendritic cell progenitors attenuated proteolysis of endocytosed OVA for delayed presentation in postnatal life. This specialty of fetal phagocytes effectively retains the memory of antigens internalized early before full development of the immune system, leading to an event of in utero sensitization. CONCLUSIONS: Our results have mechanical implications for prenatal imprinting of atopy and shed light on the importance of fetal phagocytes in shaping the developing immune system and initiating allergic airway diseases.

Coping strategies of Taiwanese children with autism spectrum disorders.

AIMS AND OBJECTIVES: To explore and describe the coping experiences of children with autism spectrum disorders in Taiwan. BACKGROUND: Children with autism spectrum disorders are faced with daily social and living challenges, which can cause stress. Chinese culture emphasises discipline and obedience, which may influence coping strategies of children with autism spectrum disorders in Taiwan. DESIGN: This qualitative study employed an exploratory descriptive design. METHOD: Data were collected from in-depth, face-to-face structured interviews. Interviews explored coping strategies of Taiwanese school-aged children (aged 6-19) with autism spectrum disorders. Children (N = 17) and their caregivers were recruited by purposive sampling. Transcribed interview data were thematically analysed using the procedure of Miles and Huberman. RESULT: Five themes emerged from the analysis of the data, which described the coping strategies of the children: (1) problem-solving, (2) acting-out, (3) avoidance, (4) seeking help and (5) self-regulation. These themes included multiple coping strategies, which employed the concepts of engagement and disengagement. CONCLUSIONS: The children with autism spectrum disorder used many strategies to cope with the stresses resulting from behaviours and symptoms associated with the disorder. Most of the Taiwanese children use both problem-solving and emotional-focused coping strategies. RELEVANCE TO CLINICAL PRACTICE: Understanding coping strategies of children with autism spectrum disorder could help caregivers (parents, teachers) and medical professionals develop interventions to reduce these challenges, which could alleviate stress and improve social functioning for these children.

Reactive oxygen species modulate the differential expression of methionine sulfoxide reductase genes in Chlamydomonas reinhardtii under high light illumination.

Illumination of Chlamydomonas reinhardtii cells at 1000 (high light, HL) or 3000 (very high light, VHL) µmol photons m(-2) s(-1) intensity increased superoxide anion radical (O(2)(•-)) and hydrogen peroxide (H(2)O(2)) production, and VHL illumination also increased the singlet oxygen ((1)O(2)) level. HL and VHL illumination decreased methionine sulfoxide reductase A4 (CrMSRA4) transcript levels but increased CrMSRA3, CrMSRA5 and CrMSRB2.1 transcripts levels. CrMSRB2.2 transcript levels increased only under VHL conditions. The role of reactive oxygen species (ROS) on CrMSR expression was studied using ROS scavengers and generators. Treatment with dimethylthiourea (DMTU), a H(2)O(2) scavenger, suppressed HL- and VHL-induced CrMSRA3, CrMSRA5 and CrMSRB2.1 expression, whereas H(2)O(2) treatment stimulated the expression of these genes under 50 µmol photons m(-2) s(-1) conditions (low light, LL). Treatment with diphenylamine (DPA), a (1)O(2) quencher, reduced VHL-induced CrMSRA3, CrMSRA5 and CrMSRB2.2 expression and deuterium oxide, which delays (1)O(2) decay, enhanced these gene expression, whereas treatment with (1)O(2) (rose bengal, methylene blue and neutral red) or O(2)(•-) (menadione and methyl viologen) generators under LL conditions induced their expression. DPA treatment inhibited the VHL-induced decrease in CrMSRA4 expression, but other ROS scavengers and ROS generators did not affect its expression under LL or HL conditions. These results demonstrate that the differential expression of CrMSRs under HL illumination can be attributed to different types of ROS. H(2)O(2), O(2) (•-) and (1)O(2) modulate CrMSRA3 and CrMSRA5 expression, whereas H(2)O(2) and O(2)(•-) regulate CrMSRB2.1 and CrMSRB2.2 expression, respectively. (1)O(2) mediates the decrease of CrMSRA4 expression by VHL illumination, but ROS do not modulate its decrease under HL conditions.

Effects of a Hybrid Teaching Program on Lower Limb Muscle Strength, Knee Function, and Depression in Older Adults After Total Knee Replacement: A Randomized Controlled Trial.

The aim of the current study was to evaluate the effects of a nurse-led hybrid teaching program on lower limb strength, knee function, and depression in older adults after total knee replacement (TKR). This was a single-blind, randomized controlled trial. Fifty-two patients who underwent TKR were randomly assigned to either the experimental group (EG; n = 26), which received routine care plus 16 weeks of home rehabilitation through a hybrid teaching program, or the control group (CG; n = 26), which received routine care only. The intervention included pre-discharge face-to-face education, video instructions to follow at home after discharge, and four monthly telephone-based follow ups during the 16 weeks post-surgery. After the 16-week intervention, participants in the EG exhibited improved quadriceps strength, hamstring strength, and Knee Injury and Osteoarthritis Outcome Score (KOOS) compared to those in the CG. Generalized estimating equation analyses revealed a significant group-by-time interaction effect on quadriceps strength, overall KOOS score, and Geriatric Depression Scale-Short Form score. Findings suggest that a nurse-led hybrid teaching program enhances physical and psychological function after TKR when compared to routine care. This hybrid teaching program, involving exercise and postoperative education, proves to be a feasible and cost-effective intervention for improving outcomes in older adults following TKR. Health care teams should consider it as a viable home rehabilitation option for older adults who undergo TKR. [Research in Gerontological Nursing, 17(1), 31-40.].

Autoantigen Exposure in Murine Fetuses Elicited Nonpathogenic Autoimmunity.

BACKGROUND AND AIM: Autoimmunity refers to the presence of autoantibodies and autoreactive lymphocytes against the structural molecules of an individual's cells or tissues, known as self-antigens or autoantigens. It might exist in the absence of autoimmune disease. However, how autoimmunity develops remains a mystery, despite the discovery of autoantibodies in human cord blood. METHODS: Murine fetuses on day 14 of gestation were subjected to intraperitoneal injection of murine thyroid peroxidase (TPO) peptides or collagen type II (CII) at graded doses via transuterine approach. Postnatally, the recipients were examined for autoantibodies by ELISA and autoreactive lymphocytes by in vitro incorporation of tritium and for the development of autoimmune thyroiditis or arthritis. RESULTS: At one month of age, the recipients did not secrete significant levels of anti-TPO or CII IgG2a in sera until a dose of 0.5 µg TPO or 5.0 µg CII was injected in utero. Serum anti-TPO or CII IgG2a persisted for at least two to four months postnatally. In recipients with elevated autoantibodies, their lymphocytes also showed proliferative responses specifically to TPO or CII. However, the development of autoantibodies and autoreactive lymphocytes was not associated with inflammatory cell infiltration of thyroid glands or paw joints even though anti-TPO or CII IgG2a was enhanced by postnatal TPO or CII challenge. CONCLUSION: Fetal exposure to free autoantigens could be immunogenic, shedding new light on the in utero origin of autoantibodies and autoreactive lymphocytes. The development of autoimmunity requires a threshold intensity of autoantigen exposure in the fetus.

Nitric oxide down-regulation of carotenoid synthesis and PSII activity in relation to very high light-induced singlet oxygen production and oxidative stress in Chlamydomonas reinhardtii.

Nitric oxide (NO) was produced in Chlamydomonas reinhardtii cells 30 min after illumination at a very high light intensity of 3,000 µmol m⁻² s⁻¹ (VHL) followed by singlet oxygen (¹O2) production, lipid peroxidation, expression of oxidative stress-related genes, irreversible PSII inactivation and cell death. Treatment with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), an NO scavenger, effectively reduced ¹O2 levels and VHL damage, while treatment with diphenylamine (DPA), an ¹O2 scavenger, only slightly reduced NO levels, though VHL damage was still effectively reduced. In the presence of cPTIO, the decline in minimum (Fo, Ft) and maximum (Fm, Fm') fluorescence after 60 min of VHL illumination can be slowed, and after recovery to 50 µmol m⁻² s⁻¹ conditions, PSII activity (Fv/Fm, Fv'/Fm') and PSII donor-side and acceptor-side electron transfer were partially restored. This finding indicates that ¹O2 production is induced by NO through inhibition of PSII electron transfer under VHL conditions. VHL illumination caused a decrease in carotenoid contents but a transient increase in the transcription of two enzymes involved in carotenoid synthesis, phytoene synthase (PSY) and phytoene desaturase (PDS), at 30 min followed by a decrease at 60 min. The VHL-induced decrease in PDS transcription can be inhibited in the presence of cPTIO. The results of the present study show that NO generated in C. reinhardtii cells under VHL conditions induces ¹O2 accumulation due to a decrease in the ¹O2-scavenging capacity caused by NO-mediated inhibition of carotenoid synthesis and PSII electron transport, which, in turn, leads to oxidative damage and cell death.

Allogeneic lymphocytes exerted graft-versus-host rather than tolerogenic effects on preimmune fetuses.

BACKGROUND: Among cell suspensions from different origins, lymphocytes were reported to have the superiority of tolerance-conferring capacity in preimmune hosts. However, this belief was derived directly from murine combinations with fewer major histocompatibility complex (MHC) barriers that are exceptional in the clinical arena. Because of the potential for prenatal tolerance induction to facilitate postnatal therapies, it is important to examine the relative merits and hazards of fully MHC-mismatched naïve lymphocytes as the prenatal tolerogenic agent in the preimmune fetus to cross MHC barriers. MATERIALS AND METHODS: In utero injection of C57BL/6 splenic lymphocytes was conducted in gestational day 14 FVB/N fetuses. Then, FVB/N recipients were subjected to the evaluation of hematopoietic chimerism, donor-specific tolerance, and graft-versus-host disease (GVHD). RESULTS: With a dose of ≥ 5 × 10(5) C57BL/6 lymphocytes, the recipients born alive either died unexpectedly by maternal cannibalization or succumbed to GVHD within postnatal 1 mo. GVHD mice showed significant hematopoietic chimerism that was dominated by donor CD3 T cells. It was found that allogeneic lymphocytes could rapidly damage the fetal liver within 5 d after injection. Fetal recipients could survive a dose of ≤ 2 × 10(5) allogeneic lymphocytes beyond 1 mo of age, but at best showed microchimerism that was insufficient to confer donor-specific skin tolerance. CONCLUSIONS: Fully MHC-mismatched lymphocytes injected in utero had lethal graft-versus-host effects, which might rapidly develop within 1 wk after injection in preimmune fetuses. They were incapable of conferring significant hematopoietic chimerism and graft tolerance even at bearable doses.

Exploring Coping Strategies of Parents of Children With Autism Spectrum Disorder in Taiwan: A Qualitative Study.

BACKGROUND: Children with autism spectrum disorder (ASD) experience impairments in their social interactions, language communication, and stereotypical patterns of behavior. Parents of children with ASD experience higher levels of stress and more depression and anxiety than parents of children with other disabilities or typically developing children. Parents of children with disabilities develop coping strategies to counteract the stresses associated with raising a child with special needs. Understanding coping strategies to help counteract the stresses associated with parenting a child with ASD may enhance well-being in parents of children with ASD, improve the quality of care provided to these children, and foster better parent-child relationships. PURPOSE: The purpose of this study was to explore the coping strategies used by parents in Taiwan parenting a child with ASD. METHODS: In this descriptive qualitative study, thematic analysis was conducted on data collected during face-to-face interviews. Fourteen parents of children with ASD were recruited using purposive sampling. Researchers employed a teamwork approach for data analysis to increase the dependability and consistency of the transcribed interviews. Team members discussed coding and identified the themes collaboratively. RESULTS: Taiwanese parents of children with ASD coped with the psychological impacts of parenting by employing problem-focused and emotion-focused strategies. Problem-focused strategies included communication, support, and management, whereas emotion-focused strategies included acceptance and adaptation. Findings showed that both coping strategies were useful in addressing specific situations and circumstances. Social and clinical support improved parents' mental health and children's external behaviors. CONCLUSIONS/IMPLICATION FOR PRACTICE: Healthcare providers should evaluate how parents are coping with the stresses related to raising a child with ASD and consider the cultural factors that might influence how they accept and adapt to parenting children with ASD. Understanding these variables may be used to tailor strategies appropriate to reducing stress and improving the well-being of parents and their children. Support and resource referrals should be considered, including parent support groups, books, web-based services, and recommendations for professional consultations with social workers or therapists.

Enteric neurospheres retain the capacity to assemble neural networks with motile and metamorphic gliocytes and ganglia.

BACKGROUND: Neurosphere medium (NSM) and self-renewal medium (SRM) were widely used to isolate enteric neural stem cells (ENSCs) in the form of neurospheres. ENSCs or their neurosphere forms were neurogenic and gliogenic, but the compelling evidence for their capacity of assembling enteric neural networks remained lacking, raising the question of their aptitude for rebuilding the enteric nervous system (ENS) in ENSC therapeutics. It prompted us to explore an effective culture protocol or strategy for assembling ENS networks, which might also be employed as an in vitro model to simplify the biological complexity of ENS embedded in gut walls. METHODS: NSM and SRM were examined for their capacity to generate neurospheres in mass culture of dispersed murine fetal enterocytes at serially diluted doses and assemble enteric neural networks in two- and three-dimensional cell culture systems and ex vivo on gut explants. Time-lapse microphotography was employed to capture cell activities of assembled neural networks. Neurosphere transplantation was performed via rectal submucosal injection. RESULTS: In mass culture of dispersed enterocytes, NSM generated discrete units of neurospheres, whereas SRM promoted neural network assembly with neurospheres akin to enteric ganglia. Both were highly affected by seeding cell doses. SRM had similar ENSC mitosis-driving capacity to NSM, but was superior in driving ENSC differentiation in company with heightened ENSC apoptosis. Enteric neurospheres were motile, capable of merging together. It argued against their clonal entities. When nurtured in SRM, enteric neurospheres proved competent to assemble neural networks on two-dimensional coverslips, in three-dimensional hydrogels and on gut explants. In the course of neural network assembly from enteric neurospheres, neurite extension was preceded by migratory expansion of gliocytes. Assembled neural networks contained motile ganglia and gliocytes that constantly underwent shapeshift. Neurospheres transplanted into rectal submucosa might reconstitute myenteric plexuses of recipients' rectum. CONCLUSION: Enteric neurospheres mass-produced in NSM might assemble neural networks in SRM-immersed two- or three-dimensional environments and on gut explants, and reconstitute myenteric plexuses of the colon after rectal submucosal transplantation. Our results also shed first light on the dynamic entity of ENS and open the experimental avenues to explore cellular activities of ENS and facilitate ENS demystification.

Naturalistic exploration of the effect of osmotic release oral system-methylphenidate on remission rate and functional improvement in Taiwanese children with attention-deficit-hyperactivity disorder.

AIM: To determine the differences in the remission rate, recovery rate, functional improvement, and treatment adherence related to treatment with short-acting immediate-release methylphenidate (IR-MPH) and long-acting osmotic-release oral system-methylphenidate (OROS-MPH) in a naturalistic setting among Taiwanese children with attention-deficit-hyperactivity disorder (ADHD). METHODS: A total of 757 children with ADHD, aged 6-18 years, was evaluated using the following in order determine functional improvement and treatment adherence: the Chinese version of the Swanson, Nolan, and Pelham, version IV scale (SNAP-IV-C), Clinical Global Impression-ADHD-Severity (CGI-S) to measure remission and recovery rates, the Chinese version of the Social Adjustment Inventory for Children and Adolescents (CSAICA), and caregiver's satisfaction rate, treatment adherence, and frequency of adverse effects. RESULTS: According to the SNAP-IV-C scores, the remission rate was 30.72%, and the recovery rate was 16.38%. Compared to short-acting IR-MPH, OROS-MPH was associated with greater functional improvement and treatment adherence among children with ADHD. CONCLUSION: OROS-MPH treatment at the adequate dosage can achieve higher remission and recovery rates, produce greater functional improvement, and result in better treatment adherence than IR-MPH treatment.

Enteric Neural Network Assembly Was Promoted by Basic Fibroblast Growth Factor and Vitamin A but Inhibited by Epidermal Growth Factor.

Extending well beyond the original use of propagating neural precursors from the central nervous system and dorsal root ganglia, neurosphere medium (NSM) and self-renewal medium (SRM) are two distinct formulas with widespread popularity in enteric neural stem cell (ENSC) applications. However, it remains unknown what growth factors or nutrients are crucial to ENSC development, let alone whether the discrepancy in their components may affect the outcomes of ENSC culture. Dispersed enterocytes from murine fetal gut were nurtured in NSM, SRM or their modifications by selective component elimination or addition to assess their effects on ENSC development. NSM generated neuriteless neurospheres, whereas SRM, even deprived of chicken embryo extract, might wire ganglia together to assemble neural networks. The distinct outcomes came from epidermal growth factor, which inhibited enteric neuronal wiring in NSM. In contrast, basic fibroblast growth factor promoted enteric neurogenesis, gangliogenesis, and neuronal wiring. Moreover, vitamin A derivatives might facilitate neuronal maturation evidenced by p75 downregulation during ENSC differentiation toward enteric neurons to promote gangliogenesis and network assembly. Our results might help to better manipulate ENSC propagation and differentiation in vitro, and open a new avenue for the study of enteric neuronal neuritogenesis and synaptogenesis.

Fetal Macrophages Exposed to Salmonella Antigens Elicit Protective Immunity Against Overwhelming Salmonella Challenge in A Murine Model.

Despite the evidence for fetal immunization following maternal infection, it remained a mystery how the fetal immune system was primed by vertically-transmitted pathogens or microbial antigens, especially before its full maturation. We previously demonstrated the capacity of fetal macrophages for endocytosing oncoprotein and allergens to bridge towards adaptive immunity in postnatal life. To investigate the immunological consequences of fetal contact with microbial antigens and the role of fetal macrophages in the defense against infection before T-cell development, we exposed gestational day 14 murine fetuses and their macrophages to flagellin and heat-killed Salmonella Typhimurium. Recipients with in utero exposure to Salmonella antigens or adoptive transfer of microbial antigen-loaded fetal macrophages were examined for immune responses to Salmonella antigens and resistance to virulent Salmonella challenge. Fetal exposure to microbial antigens or adoptive transfer of microbial antigen-loaded fetal macrophages could confer antigen-specific adaptive immunity. However, protective immunity against lethal Salmonella challenge was only granted to those receiving heat-killed Salmonella antigens, presenting as heightened recall responses of serum anti-lipopolysaccharide immunoglobulins and interferon-gamma. In immunized recipients surviving Salmonella challenge, their serum transfer to succeeding recipients provided immediate protection from lethal Salmonella challenge in preference to lymphocyte transfer, indicating a more active role of humoral immunity in the prevention of Salmonella invasiveness. Our study sheds insight on the role of fetal macrophages in immunogenicity to transplacental pathogens regardless of fetal lymphocyte maturity, paving the way for fetal macrophage therapies to enhance vaccine responsiveness or increase resistance to pathogenic microorganisms in perinatal life.

Establishment of the reliability and validity of the Stress Index for Children or Adolescents with Tourette Syndrome (SICATS).

AIMS: The aim of this study was to evaluate the validity and reliability of the stress index for 10-18-years-old children or adolescents with Tourette syndrome. BACKGROUND: Tourette syndrome is a chronic tic disorder, which occurs in childhood. Children with Tourette syndrome exhibit sudden and unexpected voices or movements that may have influence on their daily activities and cause interaction barriers for children with Tourette syndrome. Therefore, a self-report stress index is necessary for children with Tourette syndrome to quickly measure the stress they have. DESIGN AND METHODS: Eight experts rated appropriateness, comprehensiveness and relevance of the questionnaire to establish content validity. A total of 116 paediatric patients filled out the stress index for 10-18-years-old children or adolescents with Tourette syndrome to evaluate its construct validity using exploratory factor analysis and internal consistency. Data from 90 pairs of paediatric patients and their caregivers were used to evaluate the inter-rater reliability. RESULT: The criterion validity index ranged from 80-98%. One item was deleted because of a small item-to-total correlation. Therefore, 26 items made up the final stress index for 10-18-years-old children or adolescents with Tourette syndrome. In exploratory factor analysis, four factors (unfairly treated, psychological, symptom control and future concern) were achieved and accounted for 52.3% of the total variance. Cronbach's alphas of the stress index for 10-18-years-old children or adolescents with Tourette syndrome were 0.89. The inter-rater reliability of stress Index for 10-18-years-old children or adolescents with Tourette syndrome (Pearson correlation coefficient between patients and their caregivers) was 0.56. CONCLUSION: The stress Index for 10-18-years-old children or adolescents with Tourette syndrome is a self-administered tool to assess the stress of children or adolescents with Tourette syndrome. Validity (content and construct) and reliability (internal consistency and inter-rater reliability) of our Stress Index for 10-18-years-old Children or Adolescents with Tourette syndrome was acceptable. RELEVANCE TO CLINICAL PRACTICE: The Stress Index for Children or Adolescents with Tourette Syndrome appears to be an ideal instrument for evaluating the stress for children with Tourette syndrome in clinical setting and finding the direction in designing an appropriate intervention programme. We welcome other researchers to use stress index for 10-18-years-old children or adolescents with Tourette syndrome so that their findings can be compared using the same measurement.

High Light-Induced Nitric Oxide Production Induces Autophagy and Cell Death in Chlamydomonas reinhardtii.

Autophagy plays a role in regulating important cellular functions in response to stress conditions. The role of nitric oxide (NO) in the regulation of autophagy in Chlamydomonas reinhardtii has been not studied. Illumination of C. reinhardtii cells under a high light (HL, 1,600 µmol m-2 s-1) condition induced a NO burst through NO synthase- and nitrate reductase-independent routes, and cell death. The abundance of CrATG8 protein, an autophagy marker of C. reinhardtii, increased after HL illumination along with a linear increase in the transcript abundance of autophagy-associated genes (CrVPS34, CrATG1, CrATG3, CrATG4, CrATG6, CrATG7, CrATG8, and CrATG12), which were suppressed in the presence of an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). The cells were treated with NO donors, S-nitroso-N-acetyl-penicillamine, and S-nitrosoglutathione, under a normal light (50 µmol m-2 s-1) condition to elucidate the role of NO in autophagy activation and cell death. Treatment with 0.05 mM or 0.1 mM NO donors increased the abundance of ATG8 protein and CrATG transcripts, which were suppressed in the presence of cPTIO. Moreover, treatment with 0.05 mM NO donors did not affect cell viability, while 0.1 mM NO donors elicited a transient decrease in cell growth and death that recovered after 12 h. The transient effect could be prevented by the presence of cPTIO. However, treatment with 1 mM H2O2 and 0.1 mM NO donors enhanced autophagy induction and resulted in cell death after 24 h. The interaction of H2O2 and NO can be prevented by cPTIO treatment. This implies that NO is critical for the interaction of H2O2 and NO that induces cell death and autophagy. Furthermore, exposure to 0.1 mM NO donors under a non-lethal HL condition (750 µmol m-2 s-1) evoked autophagy and cell death. In conclusion, the present findings demonstrated that the NO-mediated autophagy pathway is activated in C. reinhardtii under lethal high intensity illumination and may interact with H2O2 for HL-induced cell death. The relationships between autophagy and cell death are discussed.

Fetal exposure to oncoantigen elicited antigen-specific adaptive immunity against tumorigenesis.

BACKGROUND: Envisioned as a similar process to tumorigenesis in terms of biological behaviors and molecular basis, embryogenesis necessitates an immune surveillance system to eliminate erratically transformed cells. Our previous study demonstrated that fetal macrophage-like phagocytes triggered Th2-skewed immunity following endocytosing prenatally administered ovalbumin to facilitate postnatal allergic airway responses, highlighting the critical role fetal phagocytes played in dealing with antigens present in developing fetuses and shaping subsequent immune responses. It prompted us to examine whether fetuses could mount Th1 tumoricidal immunity against tumorigenesis following in utero exposure to tumor antigens. METHODS: Gestational day 14 murine fetuses underwent in utero injection of Th1-promoting human papilloma virus (HPV) E7 peptides. Postnatally, recipients were examined for immunological consequences and the resistance to TC-1 tumorigenesis. RESULTS: Fetal exposure to HPV E7 did not cause tolerance but rather immunization in the recipients, characterized by proinflammatory Th1 polarization of their lymphocytes. Fetal macrophage-like phagocytes were responsible for taking up HPV E7 and triggering HPV E7-specific T-cell cytotoxicity and humoral immunity that rendered recipients resistant to TC-1 tumorigenesis in postnatal life. Adoptive transfer of HPV E7-loaded fetal phagocytes also elicited Th1 immunity with rapid expansion of HPV E7-specific cytotoxic CD8+ T-cell clones in response to TC-1 cell challenge so as to protect the recipients from TC-1 tumorigenesis, but failed to completely eliminate pre-existing TC-1 cells despite perceptible attenuation of local TC-1 tumor growth. CONCLUSIONS: Our study revealed that Th2-biasing fetus was not immune-privileged to foreign peptides, but competent to mount Th1 cytotoxic immunity and generate immunoglobulins against tumorigenesis following in utero exposure to Th1-promoting oncoantigen. It shed light on the role of fetal macrophage-like phagocytes in bridging toward tumor antigen-specific cellular and humoral immunity potentially as an immune surveillance system to eliminate transformed cells that might be egressing during embryogenesis and leftover until postnatal life.

Protoapigenone, a novel flavonoid, induces apoptosis in human prostate cancer cells through activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase 1/2.

In this study, we investigated the anticancer effect of protoapigenone on human prostate cancer cells. Protoapigenone inhibited cell growth through arresting cancer cells at S and G(2)/M phases as well as inducing apoptosis. Blockade of cell cycle by protoapigenone was associated with an increase in the levels of inactivated phospho (p)-Cdc25C (Ser216) and a decrease in the levels of activated p-cyclin B1 (Ser147), cyclin B1, and cyclin-dependent kinase (Cdk) 2. Protoapigenone triggered apoptosis by increasing the levels of cleaved poly(ADP-ribose) polymerase and caspase-3. In addition, activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK)1/2 was a critical mediator in protoapigenone-induced cell death. Inhibition of the expression of p38 MAPK and JNK1/2 by pharmacological inhibitors or specific small interfering RNA reversed the protoapigenone-induced apoptosis through decreasing the level of cleaved caspase-3. In contrast, p38 MAPK, but not JNK1/2, was involved in the protoapigenone-mediated S and G(2)/M arrest by modulating the levels of Cdk2 and p-Cdc25C (Ser216). Moreover, in vivo xenograft study showed that protoapigenone had a significant inhibition of prostate tumor growth without major side effects on the mice we tested. This inhibition was associated with induction of apoptosis and activation of p38 MAPK and JNK1/2 in protoapigenone-treated tumor tissues. In conclusion, our results demonstrated protoapigenone suppressed prostate cancer cell growth through the activation of p38 MAPK and JNK1/2, with the potential to be developed as a chemotherapeutic agent for prostate cancer.

Protoapigenone, a novel flavonoid, inhibits ovarian cancer cell growth in vitro and in vivo.

Flavonoids are polyphenolic compounds and capable of inhibiting the growth of human cancer cells. Protoapigenone, a novel flavonoid, was isolated from the whole plant Thelypteris torresiana (Gaud), a native fern in Taiwan. In the present study, we explored the cytotoxic effects of protoapigenone on ovarian cancer cells and the immortalized ovarian epithelial cells by XTT assay. The effects of protoapigenone on cell cycle progression and apoptosis were also analyzed by FACS analysis, immunofluorescence study and immunoblotting analysis. The anti-ovarian cancer effect of protoapigenone was further examined using nude mice xenograft assay and immunohistochemistry. Our results showed that protoapigenone had a significant cytotoxicity on human ovarian cancer cells MDAH-2774 and SKOV3 but not on the immortalized non-cancer ovarian epithelial cells HOSE 6-3 and HOSE 11-12. Protoapigenone arrested MDAH-2774 and SKOV3 cells at S and G2/M phases via decreasing the expression of p-Cdk2, Cdk2, p-Cyclin B1 and Cyclin B1, as well as increasing the expression of inactive p-Cdc25C. Besides, protoapigenone had an enhanced cytotoxicity on SKOV3 cells enriched at S and G2/M phases, and ability to induce apoptosis through decreasing the protein levels of Bcl-xL and Bcl-2 and increasing the cleaved PARP by activating caspase-3. In nude mice study, protoapigenone treatment significantly suppressed the tumor growth, without major side effects. Taken together, protoapigenone showed a significant anti-ovarian cancer activity with low toxicity, suggesting its potential to be developed as a chemotherapeutic agent.

Coping mechanisms of parents of children recently diagnosed with autism in Taiwan: a qualitative study.

OBJECTIVE: To understand the coping mechanisms of Taiwanese parents whose children have recently been diagnosed with autism. BACKGROUND: When a child is diagnosed with autism, the family's life changes. Parents of a child with autism have been shown to cope with problem- or emotion-focused coping strategies. However, it is not known how parents in Taiwan adapt and cope with the stresses of taking care of an autistic child, especially in the early period after learning their child's diagnosis and while waiting for free national day care arrangements at hospital. DESIGN: A descriptive qualitative design was used, with in-depth interviews. METHODS: Parents of children diagnosed with autism (n = 17) were recruited from a children's psychiatric outpatient clinic at a medical centre in northern Taiwan. The parents were still waiting for free national day care arrangements at hospital. Data were collected through individual, tape-recorded interviews and observations, and transcripts were analysed by content analysis for emerging themes and concepts. RESULTS: The study sample of parents of children with autism described nine main coping mechanisms that fell into three core categories: adjusting to self-change, developing treatments for the autistic child and seeking support. CONCLUSIONS: The results of this study could be used by clinicians to help parents of autistic children become aware of whether or not they are using healthy coping mechanisms, and to suggest concrete and healthy coping strategies, particularly in the period after the diagnosis is confirmed and they are waiting for free national day care arrangements at hospital. RELEVANCE TO CLINICAL PRACTICE: Clinicians in child psychiatry are encouraged to become part of the social support network for parents of autistic children, thus helping them adjust to the long journey of caring for their children.