Objective To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. Design National prospective cohort study. Setting 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. Participants 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants’ peripheral blood was used to assess the presence of HLA-B*58:01. Main outcome measures Incidence of allopurinol induced SCARs with and without screening. Results Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). Conclusions Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

Bind and shine: An approach for the selective detection of both enzymes and non‐enzymatic proteins using an environment‐sensitive fluorescent turn‐on probe is described (see scheme). This approach targets the hydrophobic ligand‐binding domain of the target protein to trigger the fluorescence turn‐on and was shown to be specific for the targeted protein.

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In order to investigate the effect of aging-and disease-associated deletion of mtDNA on cellular functions, we used cytoplasm fusion to construct a series of the cybrids harboring varying proportions of mtDNA with 4,977 bp deletion from skin fibroblasts of a patient with chronic progressive external ophthalmoplegia. The cybrids were grown in the Dulbecco's modified Eagle medium supplemented with 5% fetal bovine serum, 100 g/ml pyruvate and 50 g/ml uridine. The population doubling time was longer for the cybrids containing higher proportions of 4,977 bp-deleted mtDNA. In addition, we found that the respiratory function was decreased with the increase of mtDNA with 4,977 bp deletion in the cybrids. Since impairment of the respiratory system of mitochondria increases the electron leak of the respiratory chain, we further determined the oxidative stress in these cybrids. The results showed that the specific contents of 8-hydroxy 2-deoxyguanosine and lipid peroxides of the cybrids harboring > 65% of the 4,977 bp-deleted mtDNA were significantly increased as compared with those of the cybrids containing undetectable mutant mtDNA. On the other hand, we found that the mitochondrial mass and the relative content of the mitochondrial genome in the cybrids harboring 4,977 bpdeleted mtDNA were higher than those of the cybrids containing only wild type mtDNA. The relative content of mtDNA was increased 17% and 30%, respectively, in the cybrids harboring 17% and 56% of mtDNA with 4,977 bp deletion. Moreover, both mitochondrial mass and mtDNA content were concurrently increased by treatment of the cybrids with 180 M of hydrogen peroxide. Taken these findings together, we conclude that increase of mitochondrial mass and mtDNA are the molecular events associated with enhanced oxidative stress in human cells with impaired respiratory function caused by mtDNA deletion.

BackgroundDue to the rapid development of information and communication technologies, cyberbullying has emerged as a threat to adolescents. This study aimed to investigate the prevalence and correlates among profiles of traditional bullying, cyberbullying, and combined bullying among Taiwanese high school students.MethodsThis cross-sectional study employed two-stage cluster sampling in Taipei City, Taiwan. In total, 2028 high school students completed an anonymous questionnaire between March and May 2018. Nominal logistic regression analysis was performed, adjusting for clustering, to examine the correlates of each type-role category of bullying.ResultsThe prevalence rates of cyberbullying, traditional bullying, and combined bullying were 9.9, 13.3, and 9.4%, respectively, indicating that one-third of students were involved in one of these types of bullying; 48.7% of those involved in cyberbullying also experienced traditional bullying, and 41.5% of those involved in traditional bullying also experienced cyberbullying. In any type of bullying, not only being a victim but also being a bully/bully-victim was significantly associated with at least one mental health problem (serious psychological distress, self-harm, or suicidal ideation), except in the case of cyberbullying bullies/bully-victims. Internet abuse and alcohol use were more concentrated among bullies/bully-victims than victims for all types of bullying, and a similar trend was observed among types of schools and school climates, suggesting that specific behavioural circumstances or school backgrounds are associated with bullying perpetration.ConclusionsBullying is a prevalent and complex phenomenon among adolescents in Taiwan, where traditional bullying and cyberbullying frequently overlap and are likely to occur against specific backgrounds. These facts should be taken into account in future bullying prevention and support programmes in Taiwan.

Background--Ischemic stroke is a major cause of death and disability in the world. A major ischemic stroke subtype, large-vessel ischemic stroke (large artery atherosclerosis; LAA), has been shown to have some genetic components in individuals of European ancestry. However, it is not clear whether the genetic predisposition to LAA stroke varies among ethnicities. We sought to identify genetic factors that contribute to LAA stroke in 2 independent samples of Han Chinese individuals.

Background Cyberbullying is a growing public health concern threatening the well-being of adolescents in both developed and developing countries. In Taiwan, qualitative research exploring the experiences and perceptions of cyberbullying among Taiwanese young people is lacking. Methods We conducted in-depth interviews with a convenience sample of high school students (aged 16 to 18) from five schools in Taipei, Taiwan, without prior knowledge of their cyberbullying experiences. In total, 48 participants were interviewed. Results We found that the experience of cyberbullying is common, frequently occurs anonymously and publicly on unofficial school Facebook pages created by students themselves, and manifests in multiple ways, such as name-calling, uploading photos, and/or excluding victims from online groups of friends. Exclusion, which may be a type of cyberbullying unique to the Asian context, causes a sense of isolation, helplessness, or hopelessness, even producing mental health effects in the victims because people place the utmost importance on interpersonal harmony due to the Confucian values in collectivistic Asian societies. In addition, our study revealed reasons for cyberbullying that also potentially reflect the collectivistic values of Asian societies. These reasons included fun, discrimination, jealousy, revenge, and punishment of peers who broke school or social rules/norms, for example, by cheating others or being promiscuous. Conclusions Our findings reveal the pressing need for the Taiwanese school system to develop cyberbullying prevention programmes considering the nature and sociocultural characteristics of cyberbullying.

The pathogenesis of SARS-CoV remains largely unknown. To study the function of the SARS-CoV nucleocapsid protein, we have conducted a yeast two-hybrid screening experiment to identify cellular proteins that may interact with the SARS-CoV nucleocapsid protein. Pyruvate kinase (liver) was found to interact with SARS-CoV nucleocapsid protein in this experiment. The binding domains of these two proteins were also determined using the yeast two-hybrid system. The physical interaction between the SARS-CoV nucleocapsid and cellular pyruvate kinase (liver) proteins was further confirmed by GST pull-down assay, co-immunoprecipitation assay and confocal microscopy. Cellular pyruvate kinase activity in hepatoma cells was repressed by SARS-CoV nucleocapsid protein in either transiently transfected or stably transfected cells. PK deficiency in red blood cells is known to result in human hereditary non-spherocytic hemolytic anemia. It is reasonable to assume that an inhibition of PKL activity due to interaction with SARS-CoV N protein is likely to cause the death of the hepatocytes, which results in the elevation of serum alanine aminotransferase and liver dysfunction noted in most SARS patients. Thus, our results suggest that SARS-CoV could reduce pyruvate kinase activity via its nucleocapsid protein, and this may in turn cause disease.