Organ-on-a-chip: Determine feasibility of a human liver microphysiological model to assess long-term steroid metabolites in sports drug testing

A fundamental challenge in preventive doping research is the study of metabolic pathways of substances banned in sport. However, the pharmacological predictions obtained by conventional in vitro or in vivo animal studies are occasionally of limited transferability to humans according to an inability of in vitro models to mimic higher order system physiology or due to various species-specific differences using animal models. A more recently established technology for simulating human physiology is the “organ-on-a-chip” principle. In a multichannel microfluidic cell culture chip, 3-dimensional tissue spheroids, which can constitute artificial and interconnected microscale organs, imitate principles of the human physiology. The objective of this study was to determine if the technology is suitable to adequately predict metabolic profiles of prohibited substances in sport. As model compounds, the frequently misused anabolic steroids, stanozolol and dehydrochloromethyltestosterone (DHCMT) were subjected to human liver spheroids in microfluidic cell culture chips. The metabolite patterns produced and circulating in the chip media were then assessed by LC-HRMS/(MS) at different time points of up to 14 days of incubation at 37°C. The overall profile of observed glucurono-conjugated stanozolol metabolites excellently matched the commonly found urinary pattern of metabolites, including 3′OH-stanozolol-glucuronide and stanozolol-N-glucuronides. Similarly, but to a lower extent, the DHCMT metabolic profile was in agreement with phase-I and phase-II biotransformation products regularly seen in postadministration urine specimens. In conclusion, this pilot study indicates that the “organ-on-a-chip” technology provides a high degree of conformity with traditional human oral administration studies, providing a promising approach for metabolic profiling in sports drug testing.     

住院儿童死亡412例分析

０　引言　国务院下发的“九十年代中国儿童发展规划纲要”提出未来１０ａ发展战略目标中，第一位目标是到２０００年５岁以下儿童死亡率降低１／３．鉴此，我们对我科２１ａ来住院儿童死亡原因做一分析，为做好儿童保健及疾病防治工作提供依据．１　对象和方法　我院儿科１９７８～１９９８年收治住院患儿１５５１１例，死亡４１２例，其中男２７３例，女１３９例．根据死亡病例进行统计分析各年龄组的主要死因构成，死亡儿童的年龄分布、死亡患儿住院时间及死亡尸检率．２　结果　按每５ａ为一阶段统计各段死亡率，２１ａ来住院儿童死亡率…     

Quantitative ultrasound (QUS): a useful tool for monitoring bone health in preterm infants?

Preterm infants are at risk of osteopenia and metabolic bone disease (MBD) of prematurity. There is a need for simple, reliable methods to detect and monitor this condition. Aims: The aims were first to describe longitudinal changes in speed of sound (SOS) measured using quantitative ultrasound (QUS; Sunlight Omnisense, Israel) in preterm neonates: and second to determine whether SOS predicts the development of MBD. Methods: SOS was measured in the tibia in 99 preterm infants (mean (SD)) gestation 29.7 (3.6) weeks; birthweight 1340 (550) g, with longitudinal measurements in 75. SOS z‐scores were generated for gestation and sex. Clinical data were recorded. Results: Baseline SOS (but not SOS z‐score) was positively associated with gestational age. SOS and SOS z‐score fell with age. In multivariate models, peak ALP, minimum phosphate concentrations and markers of illness severity were not predictors of the fall in SOS z‐score, and baseline SOS measurements did not predict the development of high peak ALP or low phosphate. Interpretation: Speed of sound measurements fell with age in all infants, but we found no evidence that this measurement could predict biochemical indicators of MBD. We cannot exclude the possibility that this technique could be useful in monitoring the response to interventions designed to improve bone health in this population.     

The German Food Code and Nutrient Data Base (BLS II.2)

This article describes the conception and structure of the German Food Code and Nutrient Data Base (BLS). The data bank contains approx. 12,000 coded foods, menus and menu components in different stages of processing with up to 158 nutritional data for each product. Since comparatively few analytical data on the composition of foods are available, the majority of the data in the BLS are based on nutritional data calculated from recipes. Thus, a standard instrument for an uninterrupted (no missing values) evaluation of consumption surveys is made available.     

A randomized double-blind, placebo-controlled trial of the EMLA® patch for the reduction of pain associated with intramuscular injection in four to six-year-old children

The effectiveness of a eutectic mixture lidocaine-prilocaine topical anaesthetic cream (EMLA) patch compared with a placebo patch in the reduction of pain associated with intramuscular immunization was evaluated. As part of the study, 161 children (aged 4-6-y) undergoing routine diphtheria, pertussis, tetanus and polio (DPTP) immunization in five urban and five rural private office settings were randomly assigned to an EMLA patch (n = 83) or a placebo patch control group (n = 78). Pain measurements included: child's self-report on a Faces Pain Scale; facial action on the Child Facial Coding System; the Children's Hospital of Eastern Ontario Pain Scale and parent and technician ratings on a Visual Analogue Scale. Parents also rated their own and their child's immunization-related anxiety on a Visual Analogue Scale. The EMLA patch group had significantly less pain on all four pain measures compared with the placebo group. Of the children in the placebo group, 43% had clinically significant pain, compared with 17% of children in the EMLA patch group. No severe adverse symptoms occurred as a result of either EMLA or placebo patch application. CONCLUSION: The EMLA patch reduced immunization pain in 4 to 6-y-old children during needle injection.     

A pragmatic randomized controlled trial on the effectiveness of low concentrated saline spa water baths followed by ultraviolet B (UVB) compared to UVB only in moderate to severe psoriasis

OBJECTIVE: To evaluate whether low concentrated saline spa water baths followed by ultraviolet B (LC-SSW-UVB) are superior to UVB alone in moderate to severe psoriasis. BACKGROUND: There is a lack of sufficiently large randomized controlled clinical trial evaluating the additional benefit of saltwater baths followed by UVB compared to UVB only in psoriasis. STUDY DESIGN: Partly evaluator blind, multicentre, pragmatic, randomized controlled trial. SETTING: Five German spa centres. SUBJECTS: One hundred and forty-three adults with stable psoriasis during the last month and a Psoriasis Area and Severity Index (PASI) of > 10 and/or an affected body surface area of > 15%. INTERVENTIONS: LC-SSW-UVB or UVB thrice a week until remission (PASI < 5) or for a maximum of 6 weeks. Sodium chloride concentrations of natural springs varied between 4.5% and 12%. Conventional UVB (broadband UVB or selective UVB phototherapy) was used as irradiation source. MAIN OUTCOME: Reduction of PASI and/or affected body surface area of 50% at the end of the intervention period (PASI-50). Only participants receiving at least one intervention were included in the primary analysis. RESULTS: Patients allocated to LC-SSP-UVB attained a statistically significantly higher rate of PASI-50 at the end of the intervention period than patients allocated to UVB [58/79 (73%) vs. 32/64 (50%); P = 0.01; NNT, 4.3, 95% CI, 2.4-18.1]. Benefit persisted until 3 months only for one of two secondary outcomes considered. CONCLUSIONS: In routine clinical practice balneophototherapy using conventional UVB is superior to conventional UVB only at the end of a 6-week treatment course.     

Oral manifestations of human T‐cell lymphotropic virus infection in adult patients from Brazil

Oral Diseases (2010) 16 , 167–171 Objective: Human T‐cell lymphotropic virus type 1 (HTLV‐1) was the first human retrovirus discovered and its pathogenesis is related to T cells infection. This study aimed to verify the presence of oral manifestations in a Brazilian population of patients who was seropositive for HTLV, and identify risk factors for oral manifestations. Subjects and methods: An assessment was made of 139 patients at the Emilio Ribas Institute of Infectious Diseases. Results: A total of 112 (80.5%) patients were HTLV‐1, 26 (18.7%) were HTLV‐2+. About 35.2% of patients had myelopathy/tropical spastic paraparesis (HAM/TSP), with 48 of them being HTLV‐1+ and one patient was seropositive for HTLV‐1 and ‐2. The most common oral manifestations were: xerostomia (26.8%), candidiasis (20.8%), fissured tongue (17.9%), and loss of tongue papillae (10.0%). A multivariate logistic regression analysis showed that HAM/TSP is an independent risk factor for xerostomia (P = 0.02). The patients who were HAM/TSP+ were three times more likely to develop xerostomia when compared with patients without HAM/TSP (odds ratio = 2.69, 95% confidence interval = 1.17–6.17). Conclusion: Despite the fact that the findings of this study suggest a relationship between xerostomia and HAM/TSP, more studies should be developed to show what the association would be between xerostomia presented by HTLV patients and pathogenesis of the virus.     

The HIV/AIDS epidemic in eastern Europe: recent patterns and trends and their implications for policy-making.

OBJECTIVE: To describe recent patterns and trends in the HIV epidemic in eastern Europe. METHODS: AIDS programme managers and epidemiologists of 23 countries were contacted and requested to provide national HIV surveillance data. Joint United Nations Programme on HIV/AIDS/World Health Organisation country fact sheets were reviewed and analysed, and this information was supplemented with published HIV prevalence and sexually transmitted disease case reporting information, unpublished travel reports and expert evaluations. RESULTS: The cumulative number of HIV cases reported in the region increased more than fivefold between 1995 and 1997, from 9111 to 46573; Ukraine, Russia and Belarus accounted for about 90% of all new cases. Dramatic increases in the number of HIV-infected injecting drug users (IDU) were reported from these countries, and a similar pattern was emerging in Moldova, the Baltic States, the Caucasus and Kazakstan. In central Europe, the increase in the number of cases was much lower, and (with the exception of Poland) homosexual transmission was most common, whereas in the Balkan countries, cases due to heterosexual transmission were reported relatively more frequently. At the end of 1997, more than 50% of all cases region-wide had been reported from IDU. HIV prevalence data were inconclusive. The number of reported syphilis cases had risen significantly in the countries of the former Soviet Union. CONCLUSION: Our data confirm that HIV must have been rapidly spreading among IDU in several countries of the former Soviet Union, whereas central and southeast Europe have so far escaped a more extensive spread of HIV. Factors that might have fuelled a massive spread among IDU include changes in drug demand and supply, migration and specific local drug production and consumption patterns. High rates of syphilis reported in the countries of the former Soviet Union highlight that subregion's increased vulnerability with regards to a further spread of the epidemic, via heterosexual intercourse, into the general population.