Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats

Recent advances in deriving induced pluripotent stem (iPS) cells from patients offer new possibilities for biomedical research and clinical applications, as these cells could be used for autologous transplantation. We differentiated iPS cells from patients with Parkinson''s disease (PD) into dopaminergic (DA) neurons and show that these DA neurons can be transplanted without signs of neurodegeneration into the adult rodent striatum. The PD patient iPS (PDiPS) cell-derived DA neurons survived at high numbers, showed arborization, and mediated functional effects in an animal model of PD as determined by reduction of amphetamine- and apomorphine-induced rotational asymmetry, but only a few DA neurons projected into the host striatum at 16 wk after transplantation. We next applied FACS for the neural cell adhesion molecule NCAM on differentiated PDiPS cells before transplantation, which resulted in surviving DA neurons with functional effects on amphetamine-induced rotational asymmetry in a 6-OHDA animal model of PD. Morphologically, we found that PDiPS cell-derived non-DA neurons send axons along white matter tracts into specific close and remote gray matter target areas in the adult brain. Such findings establish the transplantation of human PDiPS cell-derived neurons as a long-term in vivo method to analyze potential disease-related changes in a physiological context. Our data also demonstrate proof of principle of survival and functional effects of PDiPS cell-derived DA neurons in an animal model of PD and encourage further development of differentiation protocols to enhance growth and function of implanted PDiPS cell-derived DA neurons in regard to potential therapeutic applications.     

Costs and Health Utilities Associated with Extremely Preterm Birth: Evidence from the EPICure Study

ObjectiveTo estimate costs and health utilities associated with extremely preterm birth at approximately 11 years of age using evidence from a whole population study (the EPICure study).MethodsThe study population comprised surviving children born at 20 through 25 completed weeks of gestation in all 276 maternity units in the United Kingdom and Republic of Ireland from March through December 1995 and a control group of classmates born at full term, matched for age, sex, and ethnic group. Estimates of utilization of health, social, and education services were combined with unit costs derived from primary and secondary sources. Generalized liner regression was used to estimate the impact of extremely preterm birth on public sector costs during the 11th year of life. Suboptimal levels of function for each of the eight attributes of the Health Utilities Index Mark III (cognition, vision, hearing, speech, ambulation, dexterity, emotion, and pain) and multiplicative multi-attribute utility scores were compared between the extremely preterm children and their classmates. Tobit regressions were performed to explore the effects of gestational age at birth on the Health Utilities Index Mark III multiattribute utility score.ResultsMean (standard deviation [SD]) public sector costs over the 12-month period were £6484 (£5548) for the combined extremely preterm group and £4007 (£2537) for their classmates, generating a mean cost difference of £2477 (bootstrap 95% confidence interval [CI] £1605, £3360) that was statistically significant (P < 0.001). The generalized linear models revealed that compared to birth at term, birth at ≤23 completed weeks, 24⁺⁰–24⁺⁶ weeks and 25⁺⁰–25⁺⁶ weeks gestation increased public sector costs by an average of £2417 (95% CI £60, £4774; P = 0.044), £1528 (95% CI £129, £2927; P = 0.032) and £1501 (95% CI £428, £2574; P = 0.006), respectively. In all eight attributes of the Health Utilities Index Mark III, there were significantly higher proportions of suboptimal levels of function among the extremely preterm children (P ≤ 0.05). The mean (SD) multiattribute utility score for the extremely preterm children as a cohort was 0.789 (0.264), compared to 0.956 (0.102) for the classmates born at term, a mean difference in utility score of 0.167 (95% CI 0.124, 0.209) that was statistically significant (P < 0.001). The Tobit regressions revealed that, compared to birth at term, birth at ≤23 completed weeks, 24⁺⁰–24⁺⁶ weeks and 25⁺⁰–25⁺⁶ weeks gestation reduced the Health Utilities Index Mark III multi-attribute utility score by an average of 0.312 (95% CI 0.169, 0.455; P < 0.001), 0.337 (95% CI 0.235, 0.439; P < 0.001) and 0.243 (95% CI 0.159, 0.327; P < 0.001), respectively.ConclusionsThe results of this study should be used to inform the development of future economic evaluations of interventions aimed at preventing extremely preterm birth or alleviating its effects.     

The Hong Kong Society of Rheumatology consensus recommendations for the management of gout

Clinical Rheumatology - Gout is one of the most common noncommunicable diseases in Hong Kong. Although effective treatment options are readily available, the management of gout in Hong Kong remains...     

Developmental assessment of preterm infants at 2 years: validity of parent reports

Parental questionnaires are inexpensive alternatives to standardized testing for outcome measurement. The Parent Report of Children's Abilities has previously been revised (PARCA-R) and validated for use with very-preterm infants at 2 years of age. This study revalidated the PARCA-R for assessing cognition in a larger and more inclusive sample of preterm infants. One hundred and sixty-four children (82 males, 82 females) of <32 weeks' gestation (median 29wks, interquartile range [IQR] 28-30wks); and median birthweight 1200g (IQR 925-1463g) were evaluated using the Mental Development Index (MDI) of the Bayley Scales of Infant Development - 2nd edition (BSID-II) at 2 years' corrected age. Parents completed the PARCA-R questionnaire. Significant correlations between PARCA-R Parent Report Composite (PRC) scores and MDI scores (r=0.77, 95% confidence interval [CI] 0.69-0.82, p<0.01) demonstrated concurrent validity. A receiver operating characteristic-determined PRC cut-off of <44 had optimal discriminatory power (area under curve 0.92) for identifying MDI <70, with 85% sensitivity (95% CI 0.58-0.96), 87% specificity (95% CI 0.81-0.92), 98% negative predictive value (95% CI 0.95-1), and 37% positive predictive value (95% CI 0.22-0.54). The PARCA-R has good concurrent validity and diagnostic utility for identifying cognitive delay in very-preterm infants at 2 years of age. It is useful for outcome measurement, developmental screening, and facilitating parental involvement at follow-up.     

克泻灵片中苦参碱类生物碱的HPLC分析

目的:对克泻灵片中主要有效生物碱定性、定量。完善产品的质量控制及评价手段。方法:采用HPLC,紫外测定波长:220nm。结果:片剂中有有效生物碱以苦参碱类生物碱为主,其中苦参碱和槐定碱含量高,分别占总生物碱的14.2％～31.6％和22.6％～62.7％,其次为槐颗碱和槐胺碱,氧化苦参碱的含量很低。结论:建立了HPLC测定克泻灵片中主要生物碱,方法简便快捷,精密度好,回收率高,可用于制剂及原料的质量控制。     

Complementary medicine: use and attitudes among GPs

BACKGROUND: Information about use and attitudes of GPs towards complementary medicine is required in order to inform the debate about its place within mainstream medicine. There is evidence that public use of complementary medicine is particularly high in the South-West of England. OBJECTIVE: This study aimed to determine the use of, and attitudes towards, complementary medicine among GPs. METHODS: A questionnaire survey was performed of all primary care physicians working in the health service in Devon and Cornwall. RESULTS: Replies were received from 461 GPs, a response rate of 47%. A total of 314 GPs (68%, range 32-85%) had been involved in complementary medicine in some way during the previous week. One or other form of complementary medicine was practised by 74 of the respondents (16%), the two most common being homoeopathy (5.9%) and acupuncture (4.3%). In addition, 115 of the respondents (25%) had referred at least one patient to a complementary therapist in the previous week, and 253 (55%) had endorsed or recommended treatment with complementary medicine. Chiropractic, acupuncture and osteopathy were rated as the three most effective therapies, and the majority of respondents believed that these three therapies should be funded by the health service. A total of 176 (38%) of respondents reported adverse effects, most commonly after manipulation. CONCLUSION: Over two-thirds of the GPs in Devon and Cornwall who responded to the survey had been involved with complementary medicine in some way during the previous week. This figure is higher than the national average. The majority of respondents believed that acupuncture, chiropractic and osteopathy were effective and should be funded by the NHS.