Threshold analysis of selected dose-response data for endocrine active chemicals.

Using a biologically relevant mathematical model, the Michaelis-Menten equation, we examined published data from endocrine active chemicals for evidence of no-threshold dose-response curves. Data were fit to a modified Michaelis-Menten equation which accounted for total background response. Subsequently, the data sets were analyzed using non-linear regression in order to estimate the four parameters of interest (non-hormone controlled background (Bnh), maximum response (Rmax), endogenous hormone level (D0), and the dose at which a half-maximal response was observed (ED50)) and to determine the fit to the fully modified Michaelis-Menten equation. Subsequently, response data were adjusted to account for Bnh and then normalized to Rmax, while dose data were adjusted to account for D0 and then normalized to the ED50. This data set was combined into a single, composite data set and fit to the fully modified Michaelis-Menten equation. We examined 31 data sets (24 endpoints) from studies on 9 different chemical/hormone treatments. Twenty-six of the data sets fit the modified Michaelis-Menten equation with high multiple correlation coefficients (r>0.90). The normalized data demonstrated a good fit to the modified Michaelis-Menten equation. These results indicate that a variety of biological responses fit the modified Michaelis-Menten equation, which does not have a threshold dose term.     

Inducible and endothelial nitric oxide synthase: genetic background affects ovulation in mice.

OBJECTIVE: Inducible nitric oxide synthase (NOS) and endothelial NOS are involved in female reproductive physiology. We sought to investigate the influence of the inducible (Nos2) and endothelial (Nos3) NOS genes as a function of genetic background on ovulatory capacity and early embryonic development in a mouse model. DESIGN: Observational study of genetically altered mice and their response to a superovulation protocol. SETTING: Academic research institution. ANIMALS: Wild-type mice and mice deficient for Nos2 or Nos3 were bred to C57BL/6J and 129/Sv genetic backgrounds. INTERVENTION(S): Superovulation protocol, oocyte culture. MAIN OUTCOME MEASURE(S): Number of oocytes harvested, early embryonic development of zygotes, evaluation of ovarian histology. RESULT(S): The mean number of oocytes was significantly reduced in Nos3 deficient mice on a C57BL/6J background compared with controls. Oocytes deficient for Nos3 on a C57BL/6J background also showed reduced progression to two-cell stage embryos after 24 hours, two-cell stage embryos to blastocyst stage embryos, and survival to 48 hours. Those effects were distinctly absent in mice deficient for Nos3 on a 129/Sv background and in mice deficient for Nos2 on either genetic background. CONCLUSION(S): Our data show that disruption of Nos2 had no effect on ovulation in our mice. The negative effect of Nos3 deficiency on ovulatory capacity and early embryonic development is modulated by genetic background. This suggests a role for strain-specific modifier genes in these processes.     

Influence of climatic factors in the incidence of multiple sclerosis relapses in a Portuguese population

Background and purpose:  Environmental factors are thought to be important in multiple sclerosis (MS) pathophysiology. We aimed to evaluate if there was an association between MS relapses and some climatic factors in a Portuguese population.
Methods:  Four year retrospective study analyzing 414 MS relapses in 249 consecutive relapsing–remitting patients. Non-parametric statistics were used to compare the distribution of relapses across months and seasons. Spearman's coefficient was determined to evaluate the correlation between relapses frequency and maximum and minimum atmospheric temperatures, humidity and atmospheric pressure.
Results:  The mean number of relapses was not significantly different between months or seasons. No correlation was found between relapse frequency and any climatic factor.
Conclusion:  Our series is one of the largest addressing the influence of specific climatic factors on MS relapses. The number of clinical MS relapses seems to be unrelated to climatic factors.     

Cerebral oxygen extraction fraction and cerebral venous blood volume measurements using MRI: effects of magnetic field variation.

The presence of magnetic background field inhomogeneity (DeltaB) may confound quantitative measures of cerebral venous blood volume (vCBV) and cerebral oxygen extraction fraction (MR_OEF) with T2*-based methods. The goal of this study was to correct its effect and obtain more accurate estimates of vCBV and MR_OEF. A 3D high-resolution gradient echo sequence was employed to obtain DeltaB maps by two algorithms. The DeltaB maps were then used to recover the signal loss in images acquired by a 2D multiecho gradient echo / spin echo sequence. Finally, both quantitative estimates of MR_OEF and vCBV were obtained from the DeltaB- corrected 2D multiecho gradient echo / spin echo images. A total of 12 normal subjects were studied. An overestimated vCBV was observed in the brain (4.29 +/- 0.78%) prior to DeltaB correction, while the measured vCBV was substantially reduced after DeltaB correction. Whole brain vCBV of 2.97 +/- 0.44% and 2.68 +/- 0.47% were obtained by the two different DeltaB correction methods, in excellent agreement with the reported results in the literature. Furthermore, when MR_OEF was compared with and without DeltaB correction, no significant differences (P = 0.467) were observed. The ability to simultaneously obtain vCBV and MR_OEF noninvasively may have profound clinical implications for the studies of cerebrovascular disease.     

Velocity-selective arterial spin labeling.

In pathologies in which slow or collateral flow conditions may exist, conventional arterial spin labeling (ASL) methods that apply magnetic tags based on the location of arterial spins may not provide robust measures of cerebral blood flow (CBF), as the transit delay for the delivery of blood to target tissues may far exceed the relaxation time of the tag. Here we describe current methods for ASL with velocity-selective (VS) tags (termed VSASL) that do not require spatial selectivity and can thus provide quantitative measures of CBF under slow and collateral flow conditions. The implementation of a robust multislice VSASL technique is described in detail, and data obtained with this technique are compared with those obtained with conventional pulsed ASL (PASL). The technical considerations described here include the design of VS pulses, background suppression, anisotropy with respect to velocity-encoding directions, and CBF quantitation issues.     

Communication between Parents and Deaf Children: Implications for Social-emotional Development

Parent-child communication plays a central role in social growth, as it does in other domains of development. Over 90 % of deaf children, however, have hearing parents who frequently do not have a fully effective means of communicating with them. This paper examines the role of effective parent-child communication in the social and emotional development of deaf children. Evidence concerning relations between early communication and social-emotional development of deaf children is reviewed, and superficial differences in the ways that parents interact with deaf versus hearing children are distinguished from differences that may have more significant and enduring effects. Hearing parents and their deaf children are found to develop alternative, often nonverbal, interaction strategies. Of primary interest is the extent to which those strategies have impact comparable to the strategies of hearing parents with hearing children or deaf parents with deaf children.     

试论当代生物医学中的道德选择

在当代生物医学领域中，存在诸多道德选择活动，随着科技的发展和生物医学中的众多新事物的涌理，生物医学面临的道德选择日益增多且日趋复杂，作者就当代生物医学道德选择的时代背景，基本特点及其核心原则做了初步探讨。     

The measurement of I for the cement and the paraffin solidified low and intermediate level wastes (LILWs), spent resin or evaporated bottom from the pressurized water reactor (PWR) nuclear power plants

In this paper a relatively simple and low cost analysis procedure to apply to a routine analysis of ¹²⁹I in low and intermediate level radioactive wastes (LILWs), cement and paraffin solidified evaporated bottom and spent resin, which are produced from nuclear power plants (NPPs), pressurized water reactors (PWR), is presented. The ¹²⁹I is separated from other nuclides in LILWs using an anion exchange adsorption and solvent extraction by controlling the oxidation and reduction state and is then precipitated as silver iodide for counting the beta activity with a low background gas proportional counter (GPC). The counting efficiency of GPC was varied from 4% to 8% and it was reversely proportional to the weight of AgI by a self absorption of the beta activity. Compared to a higher pH, the chemical recovery of iodide as AgI was lowered at pH 4. It was found that the chemical recovery of iodide for the cement powder showed a lower trend by increasing the cement powder weight, but it was not affected for the paraffin sample. In this experiment, the overall chemical recovery yield of the cement and paraffin solidified LILW samples and the average weight of them were 67±3% and 5.43±0.53 g, 70±7% and 10.40±1.60 g, respectively. And the minimum detectable activity (MDA) of ¹²⁹I for the cement and paraffin solidified LILW samples was calculated as 0.070 and 0.036 Bq/g, respectively. Among the analyzed cement solidified LILW samples, ¹²⁹I activity concentration of four samples was slightly higher than the MDA and their ranges were 0.076–0.114 Bq/g. Also of the analyzed paraffin solidified LILW samples, five samples contained a little higher ¹²⁹I activity concentration than the MDA and their ranges were 0.036–0.107 Bq/g.     

Endosomal toll-like receptor gene polymorphisms and susceptibility to HIV and HCV co-infection – Differential influence in individuals with distinct ethnic background

The genetic background of human populations can influence the susceptibility and outcome of infection diseases. Toll-like receptors (TLRs) have been previously associated with susceptibility to human immunodeficiency virus (HIV) infection, disease progression and hepatitis C, virus (HCV) co-infection in different populations, although mostly in Europeans. In this study, we investigated the genetic role of endosomal TLRs on susceptibility to HIV infection and HCV co-infection through the analysis of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and TLR9 rs352140 polymorphisms in 789 Brazilian individuals (374 HIV+ and 415 HIV?), taking into account their ethnic background. Amongst the 357 HIV+ individuals with available data concerning HCV infection, 98 were positive. In European descendants, the TLR9 rs5743836 C carriers displayed a higher susceptibility to HIV infection [dominant, Odds Ratio (OR) = 1.53; 95% CI: 1.05–2.23; P = 0.027]. In African descendants, TLR9 rs5743836 CT genotype was associated with protection to HIV infection (codominant, OR = 0.51; 95% CI: 0.30–0.87; P = 0.013). Also, the TLR9 rs352140 AA variant genotype was associated with susceptibility to HIV+/HCV+ co-infection in African descendants (recessive, OR = 2.92; 95% CI: 1.22–6.98, P = 0.016). These results are discussed in the context of the different ethnic background of the studied individuals highlighting the influence of this genetic/ethnic background on the susceptibility to HIV infection and HIV/HCV co-infection in Brazilian individuals.     

罗汉果三倍体雌株与二倍体雄株遗传背景的ISSR分析

目的探索罗汉果Siraitia grosvenorii三倍体雌株与二倍体雄株的遗传背景,为无籽罗汉果优良品种的选育提供分子生物学依据。方法利用ISSR分子标记对28份罗汉果种质进行遗传背景分析,用AFLP-SURV计算材料间遗传距离;用TSYS-pc和Gen AIEx分别进行聚类和主坐标分析。结果从100条ISSR引物中筛选出13条用于扩增,共获得131条清晰可辨条带,其中多态性条带99条,多态性位点百分率为75.57%。聚类和主坐标分析表明罗汉果三倍体雌株和二倍体雄株的遗传背景存在一定的丰富性,但大多遗传相似性系数较大,遗传距离较近。结论罗汉果三倍体雌株和二倍体雄株遗传背景的复杂性较低,应该尽快采取相应措施,进行种质创新,丰富无籽罗汉果亲本的遗传背景。