Effacement of the fetal cisterna magna in association with myelomeningocele

The cisterna magna is effaced in association with myelomeningocele. The authors retrospectively investigated the size of the fetal cisterna magna as a predictor of fetal myelomeningocele in 67 pregnant women (17-38 menstrual weeks) referred for prenatal sonography because of an elevated serum alpha-fetoprotein level (n = 61) or a suspicion of fetal ventriculomegaly on previously obtained sonograms (n = 6). Twenty fetuses had myelomeningocele, 14 had isolated ventriculomegaly, and 33 were normal. A normal-sized cisterna magna (range, 4-9 mm in depth) was present in all normal fetuses. In 19 of 20 fetuses with myelomeningocele, the views of the posterior fossa were adequate, and in each of these the cisterna magna was effaced (n = 18) or very small (n = 1). The cisterna magna was effaced in five of 13 (38%) fetuses with isolated ventriculomegaly in whom the posterior fossa was adequately imaged. Although effacement of the cisterna magna is a nonspecific finding, the high negative predictive value of this sign is useful during routine screening of the fetal neural axis.     

Optimizing screening and mating strategies for phenotype-driven recessive N-ethyl-N-nitrosourea screens in mice.

Phenotype-driven N-ethyl-N-nitrosourea (ENU) mutagenesis screens in the mouse are being used to elucidate gene function and develop disease models. Many of the earlier screens focused on identifying dominant mutations, whereas many newer mutagenesis programs have arisen that focus on identifying recessive mutations. Recessive screens require more complex breeding and phenotyping procedures, yet little information is available on the optimal breeding and phenotyping strategies for identifying recessive mutations. Optimization involves minimizing the numbers of mice that must be bred and subjected to phenotypic screens while maximizing the number of mutant phenotypes that can be identified. Analysis of expected frequencies of mutants has been used to determine which of the typically used mating and screening strategies will produce the best returns in terms of identifying recessive phenotypes. As a general guideline, to minimize the number of mice to be screened, the optimal strategy is to mate a single generation 2 (G2) female and G1 male and screen either 11 or 17 G3 offspring to obtain at least 1 or 2 homozygous mutants, respectively. When the expense of producing and housing the mice is the greatest cost factor and the phenotype is so robust that a single outlier will suffice, then the optimal strategy is to mate 2 G2 sisters with the G1 male parent and screen a single litter from each. Intercrossing of G2 brothers and sisters is not an efficient method for maximizing returns from ENU screens.     

Ethanol consumption produces a small increase in circulating miR-122 in healthy individuals

Introduction: MicroRNA 122 (miR-122) is a new circulating biomarker for liver injury, which increases earlier than conventional markers in patients with acetaminophen hepatotoxicity. However, as co-ingestion of ethanol is common with drug overdose, a confounding effect of acute ethanol consumption on serum miR-122 must be examined. Methods: Blood was collected from healthy volunteers before and after recreational consumption of ethanol. Routine biochemistry and haematology measurements were performed, and serum miR-122 was measured by qPCR. The primary outcome was the difference in serum miR-122 with ethanol consumption. Results: We recruited 18 participants (72% male). Their mean serum ethanol concentration was 113?mg/dl (95% confidence interval [CI] 91–135?mg/dl) after consuming ethanol. Serum miR-122 increased from a mean of 71.3 million (95% CI 29.3–113.2 million) to 139.1 million (95% CI 62.6–215.7 million) copies/ml (2.2-fold increase). There was no significant difference in serum alanine aminotransferase activity before and after ethanol consumption. Conclusion: miR-122 increased with moderate ethanol consumption, but the fold change was modest. As increases with acetaminophen toxicity are 100- to 10 000-fold, moderate ethanol intoxication is unlikely to confound the use of this biomarker of hepatotoxicity.     

Demographic characteristics and prevalence of serologic markers among donors who use the confidential unit exclusion process: the Retrovirus Epidemiology Donor Study

BACKGROUND: Most blood centers utilize a confidential unit exclusion (CUE) process, intended to reduce the risk of transfusion-associated infectious diseases by allowing high-risk donors confidentially to exclude their blood from use for transfusion. The effectiveness of this method remains controversial. STUDY DESIGN AND METHODS: Confirmatory or supplemental test results for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus, as well as hepatitis B surface antigen and syphilis and screening test results for antibodies to hepatitis B core (antigen) and alanine aminotransferase levels were obtained for approximately 1.8 million units donated during 1991 and 1992 at five blood centers within the United States. The prevalences of these infectious disease markers in units that the donors confidentially excluded (CUE+) and units that the donors did not exclude (CUE-) were calculated and examined within demographic subgroups. RESULTS: Units that were CUE+ were 8 to 41 times more likely to be seropositive for antibodies to human immunodeficiency virus and hepatitis C virus, hepatitis B surface antigen, and syphilis and three to four times more likely to react for antibody to hepatitis B core (antigen) or to have elevated alanine aminotransferase levels than units that were CUE- (p < 0.001). The positive predictive value of CUE (the percentage of CUE+ units that were confirmed seropositive for any marker) was 3.5 percent, and the sensitivity of CUE (the percentage of confirmed-seropositive units that were CUE+) was 2.3 percent. CONCLUSION: The current CUE process has low sensitivity and apparently low positive predictive value, and in many cases, it appeared that donors misunderstood it. Yet, CUE was not a “random process,” as CUE+ units were more likely to be seropositive for any infectious disease marker than CUE- units. This suggests that efforts to improve the CUE system may be warranted. As risk factors for transfusion-transmitted infection become more difficult to identify by history-based screening, however, such efforts may have limited effect.     

B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen

Splenectomized individuals are prone to overwhelming infections with encapsulated bacteria and splenectomy of mice increases susceptibility to streptococcal infections, yet the exact mechanism by which the spleen protects against such infections is unknown. Using congenitally asplenic mice as a model, we show that the spleen is essential for the generation of B-1a cells, a B cell population that cooperates with the innate immune system to control early bacterial and viral growth. Splenectomy of wild-type mice further demonstrated that the spleen is also important for the survival of B-1a cells. Transfer experiments demonstrate that lack of these cells, as opposed to the absence of the spleen per se, is associated with an inability to mount a rapid immune response against streptococcal polysaccharides. Thus, absence of the spleen and the associated increased susceptibility to streptococcal infections is correlated with lack of B-1a B cells. These findings reveal a hitherto unknown role of the spleen in generating and maintaining the B-1a B cell pool.     

Total radical trapping antioxidant potential (TRAP) and exercise

The relationship between physical activity, physical fitness and total radical trapping antioxidant potential (TRAP) was examined in the Northern Ireland Health and Activity Survey. This was a cross-sectional population study (n = 1600) using a two-stage probability sample of the population. TRAP was calculated using the sum of the individual serum antioxidant concentrations (urate, protein thiols, ascorbate, alpha tocopherol and bilirubin) multiplied by their respective stoichiometric values. Physical fitness was determined by estimation of VO2max by extrapolation from submaximal oxygen uptake, and physical activity was recorded by computer-assisted interview. Mean serum TRAP concentrations were significantly higher in males (653 +/- 8.2 mumol/l, mean +/- SEM) compared to females (564 +/- 8.0 mumol/l) (p < 0.0001). Both male and female smokers had significantly lower TRAP values than non-smokers (males p < 0.0001, females p = 0.02). In females, there was a positive relationship of TRAP with age (p < 0.001) and body mass index (p < 0.001) but a negative relationship with physical fitness (p < 0.05). The known beneficial effects of exercise and activity do not appear to be directly mediated through increased antioxidant status.