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Aims: Tailored self-management support of hypertension, considering language and communication, is important for minorities, specifically in the deaf community. However, little is known about the experiences of hypertension self-management in deaf individuals who use sign language. This study aimed to explore the factors and processes of self-management in deaf sign language users with hypertension., Methods and Results: Ten men and women who used sign language participated in this study. Data were collected using in-depth personal interviews conducted in the presence of a sign language interpreter between November 2022 and February 2023. All interviews were recorded and transcribed for conventional content analysis. Qualitative analyses identified four categories related to the self-management of hypertension among participants: personal factors (chronic hand pain, unique language and communication, and efforts to turn crisis into opportunities), family and socioeconomic factors (family support and financial burden of living), challenges (limited health literacy and alienation from health education), and desire for health education considering the deaf community., Conclusion: The results of this study suggest that family support, socioeconomic status, hand pain, and health literacy should be considered for the planning and development of health education on self-management of hypertension in deaf individuals. In addition, this health education requires cooperation with qualified sign language interpreters in healthcare settings., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery., Methods: Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post-radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and progression-free survival (PFS) was evaluated using Cox regression., Results: Twenty-seven patients with 64 tumors (26% World Health Organization [WHO]-1, 41% WHO-2, 26% WHO-3, and 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT; mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (P < .0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6-44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42-44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort., Conclusions: DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post-radiosurgery. Lesion size decrease was statistically significant; however, it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery., Clinicaltrials.gov Identifier: NCT04081701., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The self-attenuation of a patient's body is an important factor in nuclear medicine for designing radiation shielding. Taiwanese reference man (TRM) and Taiwanese reference woman (TRW) were constructed to simulate the body dose rate constant and the effective body absorption factor for 18F-FDG, 131I-NaI and 99mTc-MIBI using the Monte Carlo technique. For TRM, the maximum body dose rate constants for 18F-FDG, 131I-NaI and 99mTc-MIBI were 1.26 × 10-1, 4.89 × 10-2 and 1.76 × 10-2 mSv-m2/GBq-h, respectively, at heights of 110, 110 and 100 cm. For TRW, the results were 1.23 × 10-1, 4.75 × 10-2 and 1.68 × 10-2 mSv-m2/GBq-h at heights of 100, 100 and 90 cm. The effective body absorption factors were 32.6, 36.7 and 46.2% for TRM and 34.2, 38.5 and 48.6% for TRW. Regional reference phantoms along with the derived body dose rate constant and effective body absorption factor should be used for determining regulatory secondary standards in nuclear medicine., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Although ketamine has become the second most popular recreational drug in Taiwan, there have been very few reported studies that investigated female sexual dysfunction (FSD) in ketamine abusers (KAs)., Aims: We sought to compare the difference between street and hospital KAs and explored the risk factors for FSD and lower urinary tract symptoms (LUTS) in KAs., Methods: In this cross-sectional study, female KAs aged 18 years or older were invited to complete anonymous questionnaires during an educational course provided by the departments of substance control and prevention of the local government or under the instruction of medical providers at a urology clinic. Data were reported as median (IQR) and OR and analyzed with commercial statistical software., Outcomes: Key outcome measurements were illicit drug use history, FSD symptoms, and LUTS severity., Results: We included 139 women (104 street and 35 hospital KAs) with a median age of 27.08 years. FSD was reported in 76% of all the participants (street vs hospital KAs, 68% vs 97%, P < 0.001). LUTS (Interstitial Cystitis Symptom Index [ICSI] + Interstitial Cystitis Problem Index [ICPI] ≥12) was found to be a significant risk factor for FSD in KAs. More hospital KAs (71%) reported experiencing LUTS (ICSI + ICPI ≥12) than street KAs (8%, P < 0.001). Longer duration of ketamine use (≥36 months) and mild to severe psychological symptoms (5-item Brief Symptom Rating Scale [BSRS-5] ≥6) were significant risk factors for LUTS., Clinical Implications: Sexual problems among KAs should not be overlooked since more severe sexual dysfunction was observed in patients reporting LUTS., Strengths and Limitations: To our knowledge, the present study is the largest study using validated and reliable questionnaires to examine FSD in KAs and also the first study to include street KAs. The main limitation of this study is using self-report questionnaires as they are subjective and susceptible to human errors and recall biases., Conclusions: Women who abused ketamine and reported experiencing LUTS were found to be more likely to have FSD., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The distribution and response to propranolol of problematic facial infantile haemangiomas (IHs) has rarely been described in the literature., Aim: To map problematic facial IHs and observe their response to propranolol., Methods: Eligible patients were categorized according to focal location and cohorts corresponding to these (buccal, medial, zygomatic, lateral and multiregional) were created. The primary efficacy variable was regression score ranging from 1 to 4, calculated using results of colour Doppler ultrasonography., Results: In total, 104 patients met the inclusion criteria. There were 32 (30·8%) IHs located in the buccal area, 12 (11·5%) in the medial area, 49 (47·1%) in the lateral area and 1 (1·0%) in the zygomatic area, with 10 (9·6%) IH cases having multiregional lesions. We found that the distribution pattern of most IHs matched the surface projection of the trunk of the external carotid and the facial arteries. Further analysis showed that the median regression score in the buccal and medial groups were significantly lower than those in the lateral and multiregional groups., Conclusion: Treatment of buccal and medial haemangiomas tends to be more challenging and their distribution pattern mainly reflects the direction of the facial vessels., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To identify genetic variants and polygenic risk score (PRS) relating to female gout and asymptomatic hyperuricaemia (AH) in a genome-wide association study (GWAS)., Methods: Gout, AH and normouricemia controls were included from Taiwan biobank and China Medical University Hospital. All participants were divided into discovery and replication cohorts for GWAS. PRS was estimated according to whether the variant exhibited a protective effect on the phenotypes or not. Each cohort was separated into two groups by the age of 50 years old., Results: A total of 59 472 females were enrolled, and gout and AH occupied 1.60% and 19.59%, respectively. Six variants located in genes SLC2A9, C5orf22, CNTNAP2 and GLRX5 were significantly predictors of female gout in those aged ≥50. For those aged <50 years old, only the variant rs147750368 (SPANXN1) on chromosome X was found. Most variants located in genes SLC2A9, ZNF518B, PKD2 and ABCG2 were found to be significantly related to AH in both age groups. The PRS could explain ∼0.59% to 0.89% of variance of gout in variants with protective effects, which showed 6.2 times of mean PRS in the risk variants, but only 1.2 times in the AH phenotype. Moreover, the PRS also revealed a dose-response trend between AH rates and quartile scores., Conclusion: The variants in gene SLC2A9 are the major genetic factors for females associated with gout in those aged ≥50. PRS can provide a more robust prediction of the gout/AH under a homogeneous selection of variants that show effects on the traits., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: We investigated the practice patterns of surgery for advanced ovarian cancer (AOC) through relevant international surveys., Methods: After searching for 878 studies on surgery for AOC till 2017, we extracted 18 questions with similar query and answer formats from eight studies. Among them, 5 and 13 were classified as comprehensive and procedure information., Results: In comprehensive information, there was a higher preference for optimal cytoreduction defined as no visible tumor (44%) compared with residual tumors <1 cm (38%) or <2 cm (2%) and omental disease involving the spleen or pancreas was more important as an intraoperative finding precluding optimal cytoreduction (35%) since 2010. The preference for neoadjuvant chemotherapy was the highest at its use for 1-10% (36%), which was preferred in Europe over USA. The positive expectation of preoperative determination of optimal cytoreduction was higher in Europe than in USA (44 vs. 27%; P < 0.05). In procedure information, conventional gynecological surgery was mainly performed by gynecological oncologists, whereas more than 50% of upper abdominal or urological surgeries were conducted by other surgeons. European clinicians showed a higher response rate of diaphragmatic stripping and resection than those from USA (88 vs. 60%; 69 vs. 24%; P < 0.05)., Conclusion: No visible tumor as the criterion for optimal cytoreduction was preferred in AOC, and aggressive surgery beyond conventional gynecological surgery tended to be performed by other surgeons. Moreover, the preference of neoadjuvant chemotherapy and the positive expectation of preoperative determination of optimal cytoreduction were higher in Europe than in USA.

Background and Aims: CT-P13 is the first biosimilar monoclonal antibody to infliximab, and was recently approved in the European Union, Japan, Korea, and USA for all six indications of infliximab. However, studies directly assessing the biologic activity of CT-P13 versus inflximab in the context of inflammatory bowel disease [IBD] are still scanty. In the present study, we aimed to compare the biological activities of CT-P13 and infliximab with specific focus on intestinal cells so as to gain insight into the potential biosimilarity of these two agents for treatment of IBD., Methods: CT-P13 and infliximab were investigated and compared by in vitro experiments for their neutralisation ability of soluble tumour necrosis factor alpha [sTNFα] and membrane-bound tumour necrosis factor alpha [mTNFα], suppression of cytokine release by reverse signalling, induction of regulatory macrophages and wound healing, and antibody-dependent cell cytotoxicity [ADCC]., Results: CT-P13 showed similar biological activities to infliximab as gauged by neutralisation of soluble TNFα, as well as blockade of apoptosis and suppression of pro-inflammatory cytokines in intestinal Caco-2 cells. Infliximab and CT-P13 equally induced apoptosis and outside-to-inside signals through transmembrane TNFα [tmTNFα]. Moreover, regulatory macrophage induction and ensuing wound healing were similarly exerted by CT-P13 and infliximab. However, neither CT-P13 nor infliximab exerted any significant ADCC of ex vivo-stimulated peripheral blood monocytes or lamina propria mononuclear cells from IBD patients., Conclusions: These findings indicate that CT-P13 and infliximab exert highly similar biological activities in intestinal cells, and further support a mechanistic comparability of these two drugs in the treatment of IBD., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

We previously presented the YM500 database, which contains >8000 small RNA sequencing (smRNA-seq) data sets and integrated analysis results for various cancer miRNome studies. In the updated YM500v3 database (http://ngs.ym.edu.tw/ym500/) presented herein, we not only focus on miRNAs but also on other functional small non-coding RNAs (sncRNAs), such as PIWI-interacting RNAs (piRNAs), tRNA-derived fragments (tRFs), small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). There is growing knowledge of the role of sncRNAs in gene regulation and tumorigenesis. We have also incorporated >10 000 cancer-related RNA-seq and >3000 more smRNA-seq data sets into the YM500v3 database. Furthermore, there are two main new sections, 'Survival' and 'Cancer', in this updated version. The 'Survival' section provides the survival analysis results in all cancer types or in a user-defined group of samples for a specific sncRNA. The 'Cancer' section provides the results of differential expression analyses, miRNA-gene interactions and cancer miRNA-related pathways. In the 'Expression' section, sncRNA expression profiles across cancer and sample types are newly provided. Cancer-related sncRNAs hold potential for both biotech applications and basic research., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Unlabelled: : Bone marrow-derived mesenchymal stem cells (BM-MSCs) are known to have an antifibrotic effect and could be used as vehicles for targeted gene delivery. Decorin plays a protective role against fibrogenesis by modulating the degradation of the extracellular matrix. The aim of this study was to determine whether the antifibrotic effect of a combination treatment consisting of BM-MSCs and decorin on hepatic fibrosis is superior to BM-MSCs alone. The effects of BM-MSCs infected with decorin-expressing adenovirus (DCN-MSCs) on hepatic fibrosis were examined in a rat model of thioacetamide (TAA)-induced cirrhosis. The effects of infection with decorin-expressing adenovirus and of incubation with the conditioned medium of DCN-MSCs on transforming growth factor-β (TGF-β) signaling were analyzed in immortalized human hepatic stellate cells (HSCs). According to the Laennec fibrosis scoring system, cirrhotic livers from rats treated with DCN-MSCs exhibited histological improvement compared with cirrhotic livers from rats treated with control adenovirus-infected MSCs (CA-MSCs). DCN-MSC treatment reduced hepatic collagen distribution, lowered the hydroxyproline content, and rescued liver function impairment in rats with TAA-induced cirrhosis. These protective effects were more potent with DCN-MSCs than with CA-MSCs. The upregulation of collagen-1, α-smooth muscle actin (α-SMA), TGF-β1, and Smad3 phosphorylation in cirrhotic livers was prevented by DCN-MSC administration. Intriguingly, medium from cultured DCN-MSCs blocked both Smad3 phosphorylation and exogenous TGF-β1 stimulated α-SMA synthesis in HSCs. DCN-MSCs exert strong protective effects against hepatic fibrosis by suppressing TGF-β/Smad signaling. Thus, treatment with DCN-MSCs is a potentially novel and efficient therapeutic approach for patients with intractable cirrhosis., Significance: A combination treatment consisting of bone marrow-derived mesenchymal stem cells (BM-MSCs) and decorin strongly inhibited the progression of thioacetamide-induced hepatic fibrosis in rats, compared with BM-MSCs alone. Furthermore, the significant inhibitory effect of BM-MSCs infected with decorin-expressing adenovirus was attributed to suppressing transforming growth factor-β (TGF-β)/Smad signaling pathway, supported by attenuation of TGF-β1 expression and inhibition of Smad3 phosphorylation. Therefore, treatment with BM-MSCs infected with decorin-expressing adenovirus could constitute a novel and efficient therapeutic approach for patients with intractable cirrhosis., (©AlphaMed Press.)

Reference man has been widely used for external and internal dose evaluation of radiation protection. The parameters of the mathematical model of organs suggested by the International Commission of Radiological Protection (ICRP) are adopted from the average data of Caucasians. However, the organ masses of Asians are significantly different from the data of Caucasians, leading to potentially dosimetric errors. In this study, a total of 40 volunteers whose heights and weights corresponded to the statistical average of Taiwanese adults were recruited. Magnetic resonance imaging was performed, and T2-weighted images were acquired. The Taiwanese reference man and woman were constructed according to the measured organ masses. The dose conversion coefficients (DCFs) for anterior-posterior (AP), posterior-anterior (PA), right lateral (RLAT) and left lateral (LLAT) irradiation geometries were simulated. For the Taiwanese reference man, the average differences of the DCFs compared with the results of ICRP-74 were 7.6, 5.1 and 11.1 % for 0.1, 1 and 10 MeV photons irradiated in the AP direction. The maximum difference reached 51.7 % for the testes irradiated by 10 MeV photons. The size of the trunk, the volume and the geometric position of organs can cause a significant impact on the DCFs for external exposure of radiation. The constructed Taiwanese reference man and woman can be used in radiation protection to increase the accuracy of dose evaluation for the Taiwanese population., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The purpose of this paper is to develop a patient-specific dose estimation system in nuclear medicine examination. A dose deposition routine to store the deposited energy of the photons during their flights was embedded in the widely used SimSET Monte Carlo code and a user-friendly interface for reading PET and CT images was developed. Dose calculated on ORNL phantom was used to validate the accuracy of this system. The ratios of S value for (99m)Tc, (18)F and (131)I computed by this system to those obtained with OLINDA for various organs were ranged from 0.93 to 1.18, which were comparable to that obtained from MCNPX2.6 code (0.88-1.22). Our system developed provides opportunity for tumor dose estimation which cannot be known from the MIRD. The radiation dose can provide useful information in the amount of radioisotopes to be administered in radioimmunotherapy.

Background: The present study investigated whether single nucleotide polymorphisms (SNPs) in the alpha-protein kinase 1 (ALPK1) gene are associated with gout in aboriginal and Han Chinese Taiwanese., Methods: A total of 1351 aborigines from the community (511 cases and 840 controls) and 511 Han people from hospital (104 cases and 407 controls) were recruited. SNPs in potentially functional regions of the 38 genes within 4q25 were identified and genotypes determined by direct sequencing. Quantitation of blood ALPK1 mRNA expression levels and luciferase assay of gout-associated rs231253 pGL3-SNP constructs cotransfected with hsa-miR-519e were examined., Results: We found that ALPK1 gene was the most determinant of gout. Three SNPs of rs11726117 M861T [C], rs231247 [G] and rs231253 [G] were most associated with gout risk [odd ratios (OR) ≥1.44, P ≤ 3.78 × 10(-6)) in aborigines. A replication set using Han people had risk at rs11726117 and rs231247 (OR ≥1.72, P ≤ 4.08 × 10(-3)). From pooled analysis (Breslow-Day test, P > 0.33) assuming an additive model, each increasing copy of the risk allele of rs11726117 [C], rs231247 [G] and rs231253 [G] showed significantly elevated OR for gout ≥1.42 (P ≥ 1.53 × 10(-6)). Consistently, the composite homozygous of linked 3 SNPs (versus wild-type, OR = 1.83, P = 8.21 × 10(-4)) had strong associations with ALPK1 mRNA expression. Luciferase showed reduced hybridization between hsa-miR-519e and construct carrying gout-associated rs231253 [G] than the wild-type [C] (P = 6.19 × 10(-4))., Conclusions: Our study found that a newly identified ALPK1 gene can effectively interfere with microRNA target recognition and modulates the mRNA expression; and the varying distribution of the implicated SNPs among cases and controls in the two studied populations suggests a significant role in gout susceptibility.

Monte Carlo (MC) simulation has been commonly used in the dose evaluation of radiation accidents and for medical purposes. The accuracy of simulated results is affected by the particle-tracking algorithm, cross-sectional database, random number generator and statistical error. The differences among MC simulation software packages must be validated. This study simulated the dose point kernel (DPK) and the cellular S-values of monoenergetic electrons ranging from 0.01 to 2 MeV and the radionuclides of (90)Y, (177)Lu and (103 m)Rh, using Fluktuierende Kaskade (FLUKA) and MC N-Particle Transport Code Version 5 (MCNP5). A 6-μm-radius cell model consisting of the cell surface, cytoplasm and cell nucleus was constructed for cellular S-value calculation. The mean absolute percentage errors (MAPEs) of the scaled DPKs, simulated using FLUKA and MCNP5, were 7.92, 9.64, 4.62, 3.71 and 3.84 % for 0.01, 0.1, 0.5, 1 and 2 MeV, respectively. For the three radionuclides, the MAPEs of the scaled DPKs were within 5 %. The maximum deviations of S(N←N), S(N←Cy) and S(N←CS) for the electron energy larger than 10 keV were 6.63, 6.77 and 5.24 %, respectively. The deviations for the self-absorbed S-values and cross-dose S-values of the three radionuclides were within 4 %. On the basis of the results of this study, it was concluded that the simulation results are consistent between FLUKA and MCNP5. However, there is a minor inconsistency for low energy range. The DPK and the cellular S-value should be used as the quality assurance tools before the MC simulation results are adopted as the gold standard.

Background: Higher cardiovascular mortality has been noted in patients with chronic kidney disease (CKD). CKD patients are also known to have impaired energy expenditure but the role of energy expenditure in cardiovascular disease is not yet known. Furthermore, the association between cold dialysis (CD) and clinical outcomes in hemodialysis patients is unclear., Methods: This was a single-center retrospective cohort study consisting of two groups: a CD group with dialyzate temperature <35.5 °C and a standard dialysis (SD) group with dialyzate temperature between 35.5 and 37 °C. The end points of the study were overall mortality, cardiac mortality and non-cardiac mortality. The study analyzed the associations between dialyzate temperature and long-term survival in CD and SD groups. Propensity score analysis was used to control for intergroup baseline differences., Results: Baseline characteristics of both groups were similar. Kaplan-Meier analysis showed that CD was significantly associated with a lower risk for overall mortality (P = 0.006) and cardiac mortality (P = 0.023) but not for non-cardiac mortality or infectious mortality. After multivariate Cox regression analysis, adjusting for propensity scores and other possible confounding factors, CD remained a significant beneficial factor for overall mortality (P = 0.030) and cardiac mortality (P = 0.034)., Conclusion: Our studies show that CD is significantly and independently associated with a lower risk for overall mortality and cardiac mortality.

Objective: To explore the causal relationship between gout and Type 2 diabetes based on genetic evidence and national outpatient database., Methods: Twenty male gout patients with early-onset, gout family history, without a habit of alcohol consumption or obesity before the first attack of gout were selected from hospital in 2010; and 42 unrelated male Chinese subjects were selected from HapMap as controls for genome-wide analysis study (GWAS). The comorbid diseases with gout were revealed by applying the significant single nucleotide polymorphisms (SNPs) to MetaCore platform, and the comorbid relationship was analysed by standardized incidence ratio (SIR) from outpatient database., Results: A total of 334 SNPs were significantly related to gout in GWAS (P < 10(-7)), and Type 2 diabetes was the most significantly associated disease with gout as recognized by 36 gene symbols correspondent to the above significant SNPs. The analysis of national outpatient database showed that the overall incident Type 2 diabetes was 1.50 cases per 1000 person-months among gout patients, which was higher than the overall incident gout (1.06 cases) among Type 2 diabetes. The age-adjusted SIR of incident Type 2 diabetes among gout was 2.59 (95% CI 2.42, 2.78), whereas the age-adjusted SIR for incident gout among Type 2 diabetes was 1.61 (95% CI 1.48, 1.74)., Conclusion: After excluding obesity and alcohol consumption behaviour, this study showed that patients with gout and Type 2 diabetes shared the common genetic factors most, and that there existed a mutual inter-dependent effect on higher incidences.

The analytical method was optimized for L-cysteine (Cys) in rat plasma with co-existing L-cystine (Cyss). We observed that more than 100% Cyss in rat plasma was converted to Cys under typical conditions for the conversion with 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F). Another conversion reagent, 4-aminosulfonyl-7-fluoro-2,1,3-benzoxadiazole (ABD-F), was then employed, with which the reaction could be carried out at a low temperature without the use of a reducing reagent. Under the optimized conditions of 4 °C and pH 8.3, the conversion ratio of Cyss to Cys in rat plasma was as low as 5-7%. We determined the Cys concentration in plasma of the portal vein of rats that had been orally administered with Cys and Cyss by applying this method. The result indicated that Cys administration and also Cyss administration effectively increased the plasma Cys level. The method developed in this study is well suited for determining the thiol compounds in biological samples.

Lesch-Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch-Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours, many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch-Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine-guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch-Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthine-guanine phosphoribosyltransferase deficiency.

Ganoderma lucidum (G. lucidum) is a medicinal mushroom having biological effects such as immunomodulation and anti-tumor actions. In China and many other Asian countries, G. lucidum is used as a folk remedy to promote health and longevity. Although many studies have shown that G. lucidum modulates the immune system, including, for example, antigen-presenting cells, natural killer (NK) cells, and the T and B lymphocytes, the effects of G. lucidum on the WEHI-3 leukemic BALB/c mice are unclear. We attempted to determine whether G. lucidum would promote immune responses in BALB/c mice injected with WEHI-3 leukemia cells. The effects of G. lucidum on the survival rate of WEHI-3 leukemia cells injected into BALB/c mice were examined. It increased the percentages of CD3 and CD19, but decreased the percentages of Mac-3 and CD11b markers, suggesting that differentiation of the precursor of T and B cells was promoted but macrophages were inhibited. It decreased the weight of spleens as compared with control mice. It also promoted phagocytosis by macrophage from peripheral blood mononuclear cell (PBMC) and it also promoted natural killer cell activity. It decreased the percentage of leukemia cells in the spleens of mice before they were injected with WEHI-3 cells. Apparently, G. lucidum affects murine leukemia WEHI-3 cells in vivo.

Introduction: Penile gangrene is a rare but troublesome problem with high mortality rates. The etiologies could be infectious, traumatic, or vasculogenic. The treatment algorithm is controversial because of limited case numbers., Aim: To describe our experiences in treating the patients with ischemic penile gangrene, to review the related literatures, and to try to summarize a practical algorithm for penile gangrene., Methods: We retrospectively reviewed the medical records of five patients with penile gangrene treated between 1996 and 2006. Data obtained include the patients' ages initial presentation, detailed histories, comorbidity, renal status, other vascular diseases, coagulation profile, treatment course, histology presentations, and prognosis were obtained., Main Outcome Measures: Comparison of the patients' ages, presentations, underlying diseases, the duration of conservative treatments, surgical options, resected penile length, and prognosis., Results: All of the five patients underwent partial penectomy. One patient underwent immediate surgery while the other four had delayed partial penectomy because of progressive distal penile gangrenous change. There was no postoperative wound infection noted in any of the five patients and all had survived after 1 year follow-up. Three of them could void independently with a neourethra meatus. Two of them kept suprapubic cystostomy as a result of bladder outlet obstruction caused by an enlarged prostate and bed-ridden status., Conclusions: Penile dry gangrene is an irreversible process. Early partial penectomy and correction of the underlying disease can prevent wound liquefaction, preserve more penile length, and improve quality of life.

Objectives: To investigate the associations between gout tophus and polymorphisms 869T/C and -509C/T in TGF-beta1 gene., Methods: The polymorphisms 869T/C and -509C/T were determined in 73 gout patients and 114 healthy controls among male Taiwanese using the PCR-restriction fragment length polymorphism method. Each patient was matched with 1-2 controls by age within 1-2 yrs. The tophus number was measured from all the patients' arms and legs., Results: Neither 869T/C nor -509C/T showed a significant association between patients and controls in the proportions of genotypes, allele frequency or dominant and recessive models. The mean number of tophi for all patients was 1.53 +/- 3.44, showing a significant difference in distribution among the genotypes at polymorphism 869T/C (P = 0.006), but not those in polymorphism -509C/T (P > 0.05). Those carrying genotype CC at polymorphism 869T/C have a mean number of tophi 0.35 (+/- 1.11), which is significantly lower than those carrying genotype TT (3.73 +/- 4.67; P < 0.05). Those with genotype TT at polymorphism 869T/C also had 11.06 times the likelihood of having at least one tophus compared with the genotype CC after adjustment of hyperuricaemia (95% CI = 1.84, 66.36; P = 0.009). However, except for the tophus number, these two polymorphisms did not show any significant association with the clinical characteristics or biochemical markers., Conclusions: The polymorphism 869T/C in TGF-beta1 gene has a significant association with the occurrence of tophus in gout patients.

Objective: To investigate the associations between polymorphisms in the promoter of the tumour necrosis factor-alpha (TNF-alpha) gene and gout., Methods: The polymorphisms -308G/A and -863C/A in the TNF-alpha gene were determined in 106 gout patients and 159 healthy controls among male Taiwanese using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The biochemical markers, including Glutamic-oxaloacetic transaminase (GOT), Glutamic-pyruvic transaminase (GPT), uric acid, creatinine, total cholesterol (TC), triglycerides (TG), body mass index (BMI) and hypertension, as well as alcohol consumption were measured., Results: The gout patients had 9.43% (10/106) with genotype AA at polymorphism -863C/A showing a significantly higher fraction than controls (0.63%; 1/159, P < 0.001). The crude results also showed that the gout patients had significantly higher portions of abnormal GOT, GPT, creatinine, TC, TG, alcohol consumption, hypertension and hyperuricaemia than controls (P < 0.05), but the -308G/A, BMI and genotype CA at -863C/A did not show the same significant difference (P > 0.05). After adjustment by a stepwise logistic regression method, the hyperuricaemia, creatinine, GPT, TG and alcohol consumption as well as genotype AA at polymorphism -863C/A were found to be significantly associated with gout., Conclusion: The genotype AA at polymorphism -863C/A in a recessive model showed a significant association with developing gout independent of hyperuricaemia, abnormal creatinine, higher TG, GPT and alcohol consumption.

Background: Acellular pertussis (aP) booster immunizations have been recommended for adolescents and older persons to enhance long-term protection and to possibly reduce community transmission of infections., Methods: This was a multicenter, randomized, double-blind vaccine trial in which one-half of the subjects received aP vaccine and one-half received hepatitis A vaccine (control subjects). All subjects were observed for almost 2 years for cough illnesses, and all underwent microbiologic and serologic studies for detection of pertussis infection. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae 2/3 were measured by enzyme-linked immunosorbent assay in serum samples obtained 1 and 12 months after immunization. Infection rates were determined with a variety of serologic criteria for control and vaccinated subjects. The incidence of prolonged cough illness was ascertained for subjects with and subjects without serologic evidence of infection., Results: Infection rates among control subjects are particularly representative of those in nonimmunized adults. Among control subjects, 0.4%-2.7% had increases in pertussis antibody of various types and degrees over 1 year, and 20%-46% had prolonged cough illnesses during this interval. Pertussis toxin antibody had the greatest specificity for detecting increases in antibody levels. Asymptomatic infections were approximately 5 times more common than clinical illnesses that met a strict clinical and microbiologic case definition. Relative to control subjects, aP-immunized subjects may have fewer increases in the antibody level (i.e., infections), especially for antibodies to fimbriae 2/3 (an antigen not in the vaccine)., Conclusions: Pertussis infections in older persons are largely asymptomatic. aP boosters confer protection for adolescents and adults against symptomatic pertussis and likely confer protection against mild and asymptomatic infections, and use of boosters may reduce transmission to others, especially infants.

Serum specimens were obtained from all subjects in the adolescent and adult acellular pertussis (aP) vaccine efficacy trial before and after immunization to study the prevalence of IgG and IgA antibody and geometric mean titers to 4 Bordetella pertussis antigens. Of 1793 adolescents and adult subjects who received aP vaccine, only 20%, 68%, 59%, and 39% had concentrations of IgG antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3, respectively, that were greater than or equal to the limit of quantitation of the enzyme-linked immunosorbent assay used in the analysis. There was minimal variation in antibody prevalence with respect to geographic area, age, sex, or race.

With the stimulation of many types of cell surface receptors, MAPKs are activated. We have previously demonstrated an effect of extracellular ATP on ERKs and gonadotropin- induced progesterone secretion, implicating the significance of ATP in the regulation of ovarian function. However, little is known about the specific role of ATP in the subsequent MAPK-induced signaling cascade in human granulosa-luteal cells (hGLCs). The present study was designed to examine the effect of ATP on the activation of the MAPK signaling pathway, including nuclear translocation and the expression of the immediate early genes in hGLCs. Western blot analysis, using a monoclonal antibody, which detected the total and phosphorylated forms of ERK1 and ERK2 (p42(mapk) and p44 (mapk), respectively), demonstrated that exogenous ATP evoked ERKs in a dose- and time-dependent manner. In contrast, p38 and JNK were not significantly activated after ATP treatment. To examine the translocation of activated ERKs, fluorescein isothiocyanate-conjugated secondary antibody was used to detect the distribution of total and phosphorylated ERKs. Immunofluorescent staining revealed that phosphorylated ERKs were translocated from cytoplasm into nucleus subsequent to 10 microm ATP treatment. To study the gene(s) induced by exogenous ATP, mRNA was extracted from hGLCs in the presence or absence of 10 microm ATP. Gene array for 23 genes associated with members of the mitogenic pathway cascade and immediate early genes revealed that the expression of early growth response 1 and c-raf-1 was increased. To our knowledge, this is the first demonstration of the ATP-induced nuclear translocation of MAPKs in the human ovary. These results suggest that the MAPK signaling pathway plays a role in mediating ATP actions in the human ovary.

As part of a prospective acellular pertussis (ACP) vaccine efficacy trial, 5 serum samples were obtained, over an 18-month period, from 101 ACP-vaccine recipients and 99 control subjects, to assess ACP antibody response and decay. Immunoglobulin (Ig) G and IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae 2/3 (FIM) were measured by enzyme-linked immunosorbant assay, and titers of agglutinin were determined. Of the subjects, 16%-19% had preimmunization values of antibodies to PT that were above the assay's limit of quantitation (LOQ); in contrast, 36%-63% of the subjects had preimmunization values of antibodies to FHA, PRN, or FIM that were above the LOQ. Substantial increases in titers of IgG and IgA antibodies to the 3 ACP antigens (PT, FHA, and PRN) were observed. Over the 18-months, the percent decay in IgG and IgA antibodies ranged from 56% to 73% and from 57% to 70%, respectively; the IgG antibody response and decay suggests that geometric mean titers likely remain above the LOQ for 2-9 years and above the threshold of detection for 4-13 years. These findings support the use of ACP booster immunizations for adolescents and adults, to provide sustained levels of antibody.

In a prospective, randomized, double-blind efficacy trial, the immunogenicity of 10 lots of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) was evaluated. More than 10,000 infants received PRP-T or hepatitis B vaccine at about 2, 4, and 6 months of age along with other childhood vaccines. In a subset of infants, geometric mean concentrations of total anticapsular antibody were 0.08, 0.79, and 5.29 micrograms/mL after the first, second, and third doses, respectively. Four lots of reconstituted lyophilized PRP-T vaccine were significantly more immunogenic than 6 lots of aqueous vaccine (P = .03). In a stepwise regression model, the most important additional factors affecting anticapsular antibody concentrations were the time between the third dose and the blood draw, race, and breast-feeding status at 6 months of age. Immune responses to diphtheria and tetanus toxoids were not significantly different for infants given PRP-T or hepatitis B vaccines along with diphtheria-tetanus toxoid-pertussis vaccine.