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Background: There is increasing use of anti‐osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)‐SCAR. Objective: To characterize patients with AOA‐SCAR and investigate the HLA association and utility of in vitro diagnostic methods. Methods: We enrolled 16 cases with AOA‐cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens–Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA‐SCAR, and tolerability to alternative drugs. We further performed literature review and meta‐analysis on the HLA association of AOA‐SCAR. Results: Our data showed strontium ranelate is the most common causality of AOA‐SCAR in Asian populations. There was no cross‐hypersensitivity of SR‐SCAR with other AOA. HLA genotyping showed that SR‐SJS was most significantly associated with HLA‐A*33:03 (Pc = 5.17 × 10−3, OR: 25.97, 95% CI: 3.08–219.33). Meta‐analysis showed that HLA‐A*33:03 was associated with SR‐SJS (P = 5.01 × 10−5; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR‐SJS was 83.3%. Conclusions: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA‐A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR‐SCAR in patients whose reaction developed while taking multiple drugs. Linked Commentary: T. Shiohara. J Eur Acad Dermatol Venereol 2021; 35: 567‐568. https://doi.org/10.1111/jdv.17138. [ABSTRACT FROM AUTHOR]

To improve indoor air quality and to protect public health, Taiwan has enacted the 'Indoor Air Quality Act ( IAQ Act)' in 2012. For the general public, the indoor air quality in hair salons is important because it is a popular location that people will often visit for hair treatments. However, only a few exposure assessments regarding air pollutants have previously been performed in hair salons. To assess the air quality of hairdressing environments in Taipei, ten hairdressing salons were included for a walk-through survey in this study. In addition, the airborne concentrations of formaldehyde, volatile organic compounds ( VOCs), CO2, and phthalate esters were also determined in 5 salons. Charcoal, XAD-2, and OVS-Tenax tubes were used for the air sampling, while the samples were analyzed with gas chromatography/mass spectrometer. It was found that the products used in hair salons contained various chemicals. In fact, from the walk-through survey, a total of 387 different ingredients were found on 129 hair product labels. The hair salons were not well ventilated, with CO2 levels of 600 to 3576 ppm. The formaldehyde concentrations determined in this study ranged from 12.40 to 1.04 × 103 μg m−3, and the maximum level was above the permissible exposure limit ( PEL) of US Occupational Safety and Health Administration ( US OSHA). Additionally, 83% of the samples were with levels higher than the standard regulated by Taiwan's IAQ Act. The concentrations of VOCs and phthalate esters were below the occupational exposure limits ( OELs), but higher than what was found in general residential environments. The hair products were considered as the major source of air pollutants because significantly higher concentrations were found around the working areas. The number of perming treatments, the number of workers, and the frequency of using formaldehyde releasing products, were found to be associated with the levels of formaldehyde. This study indicates that efforts are needed to improve the indoor air quality in hairdressing salons in Taipei. [ABSTRACT FROM AUTHOR]

Researchers have indicated that the collaborative problem-solving space afforded by the collaborative systems significantly impact the problem-solving process. However, recent investigations into collaborative simulations, which allow a group of students to jointly manipulate a problem in a shared problem space, have yielded divergent results regarding their effects on collaborative learning. Hence, this study analysed how students solved a physics problem using individual-based and collaborative simulations to understand their effects on science learning. Multiple data sources including group discourse, problem-solving activities, learning test scores, and questionnaire feedback were analysed. Lag sequential analysis on the data found that students using the two simulations collaborated with peers to solve the problem in significantly different patterns. The students using the collaborative simulations demonstrated active engagement in the collaborative activity; however, they did not transform discussions into workable problem-solving activities. The students using the individual-based simulation showed a lower level of collaboration engagement, starting with individual exploration of the problem with the simulation, followed by group reflection. The two groups also showed significant differences in their learning test scores. The findings and pedagogical suggestions are discussed in the hope of addressing critical activity design issues in using computer simulations for facilitating collaborative learning. [ABSTRACT FROM AUTHOR]

This work reports the effect of two DNA vaccines against salmonid alphavirus 3 ( SAV3) in Atlantic salmon. Presmolts were vaccinated by intramuscular injection of plasmids encoding the SAV3 structural polyprotein C-E3-E2-6K-E2 ( pCSP), E2 only ( pE2), or plasmid without insert (pc DNA3.3). E2 is expressed at the surface of cells transfected with pCSP and internally in cells transfected with pE2. A commercial vaccine based on inactivated SAV ( NCPD) was used for comparison. At 10 weeks post-vaccination, only fish vaccinated with pCSP showed antibody against E2 and virus-neutralizing activity. Vaccinated fish were infected with SAV3 to determine protection by virus quantitation in serum after 7 days and scoring of pathological changes after 21 days. Fish vaccinated with both pCSP and NCPD vaccines showed significant virus reduction in serum, while fish vaccinated with pE2 did not. All fish vaccinated with pc DNA3.3 and pE2 showed pathological changes in organs typical of PD, 60% of fish vaccinated with NCPD showed PD pathology, while fish vaccinated with pCSP did not show PD pathology. Taken together, DNA vaccination with pCSP provided strong protection for salmon against SAV3 infection, which in part may be due to production of virus-neutralizing antibodies. [ABSTRACT FROM AUTHOR]

In October 2013, a new disease affecting purple woodnettle, Oreocnide pedunculata, plants was found in Miaoli County, Taiwan. Diseased plants exhibited leaf yellowing and witches'-broom symptoms. Molecular diagnostic tools and electron microscopic cell observation were used to investigate the possible cause of the disease with a specific focus on phytoplasmas. The result of polymerase chain reaction with universal primer pairs indicated that phytoplasmas were strongly associated with the symptomatic purple woodnettles. The virtual restriction fragment length polymorphism (RFLP) patterns and phylogenetic analysis based on 16S rDNA and ribosomal protein, rplV-rpsC region revealed that purple woodnettle witches'-broom phytoplasma (PWWB) belongs to a new subgroup of 16SrI and rpI group and was designated as 16SrI-AH and rpI-Q, respectively, herein. RFLP analysis based on tuf gene region revealed that the PWWB belongs to tufI-B, but phylogenetic analysis suggested that PWWB should be delineated to a new subgroup under the tufI group. Taken together, our analyses based on 16S rRNA and rplV-rpsC region gave a finer differentiation while classifying the subgroup of aster yellows group phytoplasmas. To our knowledge, this is the first report of a Candidatus Phytoplasma asteris-related strain in 16SrI-AH, rpI-Q and tufI-B subgroup affecting purple woodnettle, and of an official documentation of purple woodnettle as being a new host of phytoplasmas. [ABSTRACT FROM AUTHOR]

Background and purpose Hepatitis C virus ( HCV) infection may cause cognitive impairment, but no studies have focused specifically on cognitive impairment stemming from HCV. The purpose of this study was to investigate the potential increased risk for dementia in HCV-infected patients. Methods A population-based cohort study based on the Taiwan National Health Insurance Research Database was conducted. From all potential participants aged 50 years or more, a total of 58 570 matched (1:1) pairs of HCV-infected patients and non- HCV-infected patients were included. Each subject was individually tracked from 1997 to 2009 to identify incident cases of dementia (onset in 1999 or later). Cox proportional hazards regressions were employed to calculate the hazard ratios ( HRs) and 95% confidence intervals ( CIs) for the association between HCV infection and dementia. Results There were 2989 dementia cases from the HCV-infected cohort during the follow-up period of 533 861.1 person-years; the overall incidence rates of dementia differed from the non- HCV cohort (56.0 vs. 47.7 cases per 10 000 person-years, P < 0.05). The adjusted HR for dementia was 1.36 (95% CI 1.27-1.42) for HCV-infected patients after adjusting for alcohol-related disease, liver cirrhosis, hepatic encephalopathy and hepatocellular carcinoma. Conclusions HCV infection may increase the risk for dementia. Further mechanistic research is needed. [ABSTRACT FROM AUTHOR]

Cobia, Rachycentron canadum L., is a very important aquatic fish that faces the risk of infection with the bacterial pathogen Photobacterium damselae ssp. piscicida, and there are few protective approaches available that use multiple antigens. In the present study, potent bivalent antigens from P. damselae ssp. piscicida showed more efficient protection than did single antigens used in isolation. In preparations of three antigens that included recombinant heat shock protein 60 ( rHSP60), recombinant α-enolase ( rENOLASE) and recombinant glyceraldehyde-3-phosphate dehydrogenase ( rGAPDH), we analysed the doses that elicited the best immune responses and found that this occurred at a total of 30 μg of antigen per fish. Subsequently, vaccination of fish with rHSP60, rENOLASE and rGAPDH achieved 46.9, 52 and 25% relative per cent survival (RPS), respectively. In addition, bivalent subunit vaccines - combination I ( rHSP60 + rENOLASE), combination II ( rENOLASE + rGAPDH) and combination III ( rHSP60 + rGAPDH) - were administered and the RPS in these groups (65.6, 64.0 and 48.4%, respectively), was higher than that achieved with single-antigen administration. Finally, in combination IV, the trivalent vaccine rHSP60 + rENOLASE + rGAPDH, the RPS was 1.6%. Taken together, our results suggest that combinations of two antigens may achieve a better efficiency than monovalent or trivalent antigens, and this may provide new insights into pathogen prevention strategies. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 295–302 (2010) Aims Cigarette smoking is a well-known risk factor associated with diabetic nephropathy. The objective of this study was to further investigate the dose–response effect of tobacco exposure on proteinuria in males with Type 2 diabetes. Methods Five hundred and nine males with Type 2 diabetes were selected from a cohort participating in a glucose control study in Taiwan. Pack-years of cigarette smoking were calculated to define tobacco exposure. Proteinuria was identified if albumin-to-creatinine ratio was ≥ 30 mg/g in at least two of three consecutive urine tests. Logistic regression and trend tests were used to delineate the association between smoking status and proteinuria. Results Compared with non-smokers, those who had smoked 15–30 or more than 30 pack-years were respectively 2.78 (95% CI 1.34–5.76, P < 0.01) and 3.20 (95% CI 1.74–5.86, P < 0.001) times more likely to develop proteinuria. The dose–response effect of tobacco exposure on the development of proteinuria is highly significant in all subjects ( P = 0.001) and in subgroups with relatively short duration of diabetes mellitus ( P < 0.001), good blood pressure control ( P = 0.001) and those of young age ( P = 0.007). Conclusions The current study shows a clear dose–response effect of cigarette smoking on development of proteinuria in male Type 2 diabetic patients. These findings reinforce the urgent need to encourage diabetic patients to stop smoking regardless of age, duration of diabetes mellitus or status of blood pressure control. [ABSTRACT FROM AUTHOR]

Background The molecular mechanisms underlying the mitogenic effect of ferulic acid (FA), an active compound derived from Angelica sinensis, have never been elucidated. It was the aim of this study to investigate the proliferative effect of FA on human breast cancer cell lines and to elucidate its modulation mechanism on HER2 expression in MCF7 line. Materials and methods By using MCF7 (oestrogen receptor-positive; ER+, HER2-low), BT474 (ER+, HER2-high), MDAMB231 (ER–, HER2-low) and SKBR3 (ER–, HER2-high) human breast cancer cell lines as in vitro models, the mitogenic effects of FA were assessed by trypan blue dye exclusion assay and DNA flow cytometry. Ferulic acid-modulated cell signalling and HER2 gene expression were evaluated in MCF7 line by Western blot and real-time RT-PCR analysis. Results Ferulic acid ER-dependently stimulated cell proliferation on MCF7 cells in a concentration-dependent manner. The HER2 oncogene (one of the prognostic factors of breast cancer) and ESR1 gene (oestrogen receptor-alpha; ERα) transcription were markedly up-regulated by FA treatment. Besides, HER2 signalling and its downstream molecules such as AKT and ERK1/2 were involved in FA-modulated ERα and cyclin D1 synthesis. Addition of anti-HER2 antibody, trastuzumab, abrogated FA-enhanced proliferative effect on MCF7 cells, indicated a positive feedback control for the action of HER2 in this setting. The fact that the ER antagonist blocked most of the FA-up-regulated HER2 expression, and that trastuzumab down-regulated ERα gene expression, suggested a cross-talk between ERα and HER2 signalling on MCF7 cells. Conclusions The authors’ conclude that FA causes human breast cancer cell proliferation by up-regulation of HER2 and ERα expression. [ABSTRACT FROM AUTHOR]

Pulse pressure (PP) has often been associated with cardiovascular morbidity and mortality. Patients with aortic regurgitation (AR) often have increased PP. The aim of this study is to investigate the associations among PP, AR and extracranial carotid artery (ECCA) carotid atherosclerosis (CA) in hypertensives and age- and sex-matched normotensives. Two hundred and sixty-three hypertensive patients and 270 normotensive subjects from the Chin-Shan Community Cardiovascular Cohort participated in this study in 1996. CA, expressed as maximal common carotid artery intima-media thickness (IMT) ≥75th percentile and ECCA plaque score >6, was measured using high-resolution B-mode ultrasonography. The presence of AR was assessed by echocardiography, and their relationships with CA were evaluated. Results showed measurements of CA significantly associated with increased PP. Presence of AR associated with CA, but this relationship was attenuated after controlling for age. Multivariate logistic regression analyses revealed that an ECCA score >6 significantly increase the risk in conjunction with PP, age and smoking in hypertensives. Correspondingly, CA increased with age, smoking and left ventricular hypertrophy on electrocardiography but not PP in normotensives. In conclusion, higher PP is strongly associated with CA in patients with hypertension. In terms of risk stratification, PP is more important in hypertensives than in normotensives which seem to imply that pulsatile haemodynamic component of BP is crucial in association with atherosclerosis. [ABSTRACT FROM AUTHOR]

To determine the clinical features, prognostic factors, and therapeutic results of Guillain–Barré syndrome (GBS) in order to improve the therapeutic strategy for this disease. We retrospectively reviewed the electrodiagnostic study and medical records of patients with GBS admitted to Chang Gung Memorial Hospital, Kaohsiung, between January 1986 and December 2000. Outcomes and prognosis were followed-up after 1 year. Ninety-six patients were enrolled in this study. According to the clinical and electrophysiological findings, 77 patients were acute inflammatory demyelinating polyradiculoneuropathy, seven were Miller Fisher syndrome, and six were axonal forms, and six were unclassified. At a follow-up of 1 year, 61 patients (64%) recovered, 30 (31%) had residua and five (5%) died. Amongst these 30 had residua, including unassisted gait in 19, assisted gait in four, and wheel/bed bound in seven. According to the statistical analysis, disabilities at the nadir ( P < 0.0001) and at admission ( P = 0.014) were significant prognostic factors. Variables used for the stepwise logistic regression, and the results revealed that after analysis for all the above variables, only disability at the nadir ( P < 0.0001) was independently associated with the treatment failure rate. Our study revealed 27% of cases in need of respiratory support during hospitalization, and 5% of hospital-treated patients die from the complications. Furthermore, 31% had residua at a follow-up of 1 year or more. If prognostic factors are considered, disability at the nadir during hospitalization demonstrates consistently poor therapeutic outcomes. Therefore, early diagnosis, choice of appropriate treatment, and preventing complications during acute stages are essential to maximize the potential for survival. [ABSTRACT FROM AUTHOR]

Abstract Pathogenic and genetic variability among seven populations of Phytophthora parasitica var. nicotianae from individual tobacco fields (Yunnan, Shandong, Henan, Heilongjiang, Shanxi, Fujian and Sichuan provinces) were investigated using pathogenicity and randomly amplified polymorphic DNA (RAPD) analyses; 63 strains were isolated from different fields of seven tobacco growing regions, using tobacco cv. Hongda as a baiting host. Pathogenic variability was evaluated in greenhouse studies using five tobacco cultivars that have different levels of resistance to tobacco black shank; 75 and 73% of the strains were pathogenic on M3 and M4, 29 and 33% on M1 and M2, and 94% were pathogenic on M5, respectively. Disease severity incited by different strains varied significantly on individual tobacco cultivars. The percentage of strains pathogenic on different cultivars varied among locations. Genotypic variation among 63 strains was evaluated by RAPD analysis. Ten primers detected 89 polymorphic bands. Cluster and principal coordinates analysed cluster groups. the minor group contained 26 strains, and major group contained 37 strains. Estimates of genetic diversity based on RAPD analysis ranged from 0.24 to 0.34 within populations to 0.36 among all strains from all populations. Phytophthora parasitica var. nicotianae populations were genotypically and phenotypically variable, but no distinct genotypic differences were identified among populations from the seven locations. [ABSTRACT FROM AUTHOR]

Phytophthora parasitica var. nicotianae is the fungal pathotype of tobacco black shank (TBS, Disease severity ≥ 2.0). Random amplified polymorphic DNA (RAPD) analysis was used to differentiate isolates which cause TBS from those which do not. Greenhouse assays combined with zoospore inoculation were performed to assess the virulence of the fungal isolates, and the results were compared with the RAPD pattern analysis. The RAPD results exhibited total correlation with the virulence assay results. Amplification patterns generated by RAPD reactions were used to generate a phenogram depicting the genetically distinct nature of the cluster defined by the TBS isolates. This cluster was exclusive and distinct from P. parasitica var. nicotianae isolates which do not cause TBS. Thus, RAPD proved to be a sensitive and highly reliable method for quickly identifying fungal pathotypes which cause TBS. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the physiologic relationship between the cardiac cycle and the nonpulsatile impeller centrifugal Taita No.1 left ventricular assist device (T-LVAD) in a chronic animal study. The relationship of the cardiac cycle, pump flow, aortic pressure, left ventricle pressure, and pump power were analyzed by 5 phases in 4 stages. The isovolumetric ventricular phase is from mitral valve closure (MVC) to aortic valve opening (AVO) and is called Stage 1. The ejection phase is from AVO to aortic valve closure (AVC) and is called Stage 2. The isovolumetric relaxation phase is from AVC to MVC and is called Stage 3. The passive filling and atrial contraction phase is from MVC to mitral valve opening (MVO) and called Stage 4. Based on evidence from the physiologic volume change of the left ventricle, the change of pump flow of the T-LVAD in a cardiac cycle by variable voltages of pump control was evaluated using animal models. After left posteriolateral thoracotomy via the fifth intercostal space under general anesthesia, the nonpulsatile centrifugal T-LVAD was implanted into 2 healthy calves. The inflow of the T-LVAD was inserted into the left ventricle through the mitral valve via the left atrial appendage. The arterial blood pressure waveform was measured and recorded on the outflow of the T-LVAD. The 4 phases of a cardiac cycle were defined as MVC-AVO (Stage 1), AVO-AVC (Stage 2), AVC-MVO (Stage 3) and MVC-MVO (Stage 4) according to the outflow pressure of the outflow of the T-LVAD and differential pressure between the outflow and inflow of the T-LVAD. We carried out the real-time waveform measurement for electrocardiogram, the outflow pressure, the T-LVAD flow and the speed, as well as open loop and constant voltage (V). In a cardiac cycle, the sensing current of the T-LVAD was inverse to the speed. The flow of the T-LVAD at the 4 stages was measured individually and analyzed with different control voltages from 10 to 18 V. The highest flow ratio of MVC-AVC/AVC-MVC was noted when the T-LVAD worked on 14 V. By using analysis methodology of the flow ratio of a cardiac cycle, the optimal physiologically effective control of the T-LVAD might be achieved.

It has been assumed that there is a relationship between periodontal diseases and diabetes mellitus, however the putative periodontal microorganisms in non-diabetes mellitus (non-DM) individuals and non-insulin-dependent diabetes mellitus (NIDDM) patients have not been well studied. In this study, the detection rates of 5 putative periodontal pathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Eikenella corrodens, Treponema denticola, and Candida albicans by polymerase chain reaction (PCR) between NIDDM and non-DM adults were compared. A total of 246 adults were randomly recruited and periodontal parameters including: plaque index (P1I), gingival index (GI), probing depth (PD) and attachment level (AL) were recorded. Subgingival plaque samples were collected by sterile curettes from the most diseased and healthy sites based on PD and AL. The differences in periodontal parameters and microbiological data in healthy and diseased sites between non-DM and NIDDM patients were compared by chi-square analysis. The results showed no significant differences in age, gender, GI, P1I, PD, and prevalence of the 5 microorganisms between the NIDDM and the non-diabetic groups. However, except for A. actinomycetemcomitans, the prevalence of the periodontal microorganisms tested was significantly higher (p <0.001) in diseased sites than in the healthy sites in both groups. The P1I, GI, PD and AL were significantly higher in T. denticola positive sites than in negative sites. The results suggested that P. gingivalis, T. denticola, E. corrodens and C. albicans may play important roles in the periodontitis of both NIDDM and non-DM individuals, however the etiology of periodontitis in both groups may not be different from each other.