Prenatal diagnosis of a large centromeric heteromorphism of chromosome 12: implications for genetic counseling

Chromosomal centromeric variants can be found in the course of a prenatal diagnosis. When following the discovery of fetal abnormalities at ultrasound examination, such variants may lead to some difficulties in genetic counseling. Here we describe a new heteromorphism implicating chromosome 12, found in a fetus with a suspicion of microcephaly, and we discuss its prognostic value.     

In vitro training program to improve ambidextrous skill and reduce physical fatigue during laparoscopic surgery: preliminary experience

PURPOSE: We illustrate the preliminary experience with our planned intensive in vitro training program focused on the nondominant hand and reducing physical fatigue. Apart from this, we tried to calculate how much training is required for a novice urologist to master laparoscopic freehand suturing with the dominant and nondominant hands. MATERIALS AND METHODS: Between December 2001 and May 2002, one trainee worked on a Pelvi-trainer, first with the dominant (right) hand and then with the left hand, practicing intracorporeal suturing and cutting and improving physical endurance by gradually increasing the duration of each training session. Along with the Pelvi-trainer, he worked on left-handed writing to improve wrist movements. Before starting this training, he did not have any laparoscopic experience as assistant or primary surgeon. The progress was stored in the computer prospectively to compare the results with those obtained at the end of the training. RESULTS: For the dominant hand, 30 hours over 2 months was required to master laparoscopic suturing skills. After training of the right hand, the nondominant hand required 40 hours of Pelvi-trainer work and 20 hours of handwriting during 2 months. Physical endurance for suturing in the Pelvi-trainer increased from 15 minutes to 150 minutes over 3 months. The main improvement was in the degree of pain over the right shoulder (because of the abducted position) and backache. CONCLUSION: Incorporation of sufficient in vitro training to improve nondominant hand functioning and reduce physical fatigue can make adaptation to laparoscopic surgery easier.     

Serum HBV DNA as a marker of efficacy during therapy for chronic HBV infection: analysis and review of the literature

Currently, compounds under evaluation for treatment of chronic hepatitis B virus (HBV) infection are evaluated with liver histology as the primary end point for efficacy. However, because of practical limitations in serial liver biopsies, there is a need for alternate markers to assess efficacy over shorter periods of time. Considering the direct correlation between viral replication and disease progression during human immunodeficiency virus and hepatitis C virus infection, we explored whether such a correlation exists for HBV infection. We reviewed the literature and conducted an analysis to investigate the relationship between absolute or treatment-induced changes in HBV DNA levels and other accepted markers of disease activity. A total of 26 prospective studies met our selection criteria, including 33 evaluable treatment arms. The study treatments consisted of nucleosides and/or interferon regimens and control arms. We found statistically significant and consistent correlations between viral load level or change and histologic grading and biochemical and serologic response. Our analysis suggests that a treatment-induced reduction in HBV DNA level can be used for assessing efficacy of treatment regimens. Further, we observed that quantitative HBV DNA has a broader dynamic range than histology, allowing demonstration of differences between 2 active treatments of unequal potency. The analysis showed stronger results in studies using nucleoside regimens and in hepatitis B e antigen (HBeAg)-positive patients. In conclusion, the goal of anti-HBV therapy should be profound and durable viral suppression, as defined by very sensitive assays. Additional prospective studies are needed to precisely determine the desirable level of viremia to attain.     

Nondopaminergic prefrontocortical efferent fibers modulate D1 receptor denervation supersensitivity in specific regions of the rat striatum

A unilateral injection of 6-OHDA (6 microgram/1.5 microliter) was made into the fields of Forel in order to estimate the effects of the destruction of ascending dopaminergic (DA) pathways on the denervation supersensitivity of DA D1 receptors in the rat striatum. DA-sensitive adenylate cyclase activity was markedly enhanced in the anteromedian part of the striatum 3 weeks after the lesion (+68%) and remained elevated for several weeks thereafter (+36%). A different response occurred in the laterodorsal striatum, where the increase in DA-sensitive adenylate cyclase activity was less pronounced after 3 weeks (+40%) and no longer present after 7 weeks. Estimations of catecholamine levels indicated that the lesion made destroyed not only nigrostriatal DA neurons but other ascending catecholaminergic fibers projecting into the cerebral cortex as well. In addition, retrograde transport experiments made with wheat germ agglutinin coupled to horseradish peroxidase indicated that the anteromedian part of the striatum, but not the laterodorsal one, receives both an ipsi- and contralateral cortical projection originating in the prefrontocortical DA field. When the destruction by 6-OHDA of this contralateral DA innervation was combined to the unilateral lesion of the fields of Forel, the increase in DA-sensitive adenylate cyclase activity in each striatal area 3 or 7 weeks postlesion was prevented. This effect was due to DA denervation of the prefrontal cortex since striatal D1 denervation supersensitivity was still observed when contralateral ascending noradrenergic fibers were selectively destroyed by a 6-OHDA lesion made laterally to the pedunculus cerebellaris superior. These results suggest that, by controlling the activity of corticostriatal neurons, the mesocorticoprefrontal DA neurons exert a permissive role on the development of D1-receptor denervation supersensitivity in specific areas of the striatum.     

Efficacy of live attenuated influenza vaccine against influenza illness in children as a function of illness severity

A recent study of inactivated influenza vaccine (IIV) in children aged 3–8 years demonstrated higher efficacy against moderate/severe influenza. A meta-analysis of all previous published randomized clinical trials of live attenuated influenza vaccine (LAIV) that collected information on illness severity in children aged 24–71 months was conducted. Moderate/severe influenza was defined as fever >39 °C, acute otitis media, or lower respiratory tract illness; other cases were classified as milder influenza. LAIV efficacy versus placebo was 95.4% [95% confidence interval: 88.5, 98.1] (year 1) and 88.5% [77.4, 94.9] (year 2) against moderate/severe influenza and 91.4% [77.9, 96.7] (year 1) and 84.2% [56.7, 94.3] (year 2) against milder influenza. The relative efficacy of LAIV versus IIV was 52.2% [31.6, 66.6] for moderate/severe influenza and 45.0% [28.6, 57.5] for milder influenza. Efficacy against all influenza illnesses, regardless of severity, is critical to prevent influenza illness and transmission in the community.     

Sex-related differences in frequency and perception of stressful life events during adolescence

Aim

Stressful life events and individual stress experience are important risk factors for the development of physical and mental disorders. One of the modulating factors determining interindividual differences in stress experience is the person’s gender. In the current study, we investigated sex-related differences in the frequency and perception of stressful life events during adolescence, a period characterized by particularly high stress levels.

Subject and methods

We examined 1,657 14-year-old adolescents who were recruited as part of the IMAGEN study, a European multicenter research project on mental well-being of young people. For the detection of stressful life events, we used the Life Events Questionnaire, a highly valid instrument for testing common stressful events during adolescence.

Results

Although boys and girls did not differ significantly regarding the total amount of stressful life events, girls reported more stressful events in the familial and body-related areas, whereas boys experienced more conflicts with superiors and independence-marking events. As regards valence, girls reported greater psychological distress compared to boys; however, in all significant results, the effect sizes were only small to moderate.

Conclusion

While previous research highlighted severe stressors in adult samples, we investigated for the first time adolescents with a broader scope of stressful events. The observed differences in the stress experience may contribute to explain the sex-dependent variations in the incidence of stress-related disorders.

     

An assessment of the genotoxicity and human health risk of topical use of kojic acid [5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one].

Kojic acid (KA), a natural substance produced by fungi or bacteria, such as Aspergillus, Penicillium or Acetobacter spp, is contained in traditional Japanese fermented foods and is used as a dermatological skin-lightening agent. High concentrations of KA (>or=1000 microg/plate) were mutagenic in S. typhimurium strains TA 98, TA 100, TA 1535, TA102 and E. coli WP2uvrA, but not in TA 1537. An Ames test following the "treat and plate" protocol was negative. A chromosome aberration test in V79 cells following a robust protocol showed only a marginal increase in chromosome aberrations at cytotoxic concentrations after prolonged (>or=18 h) exposure. No genotoxic activity was observed for hprt mutations either in mouse lymphoma or V79 cells, or in in vitro micronucleus tests in human keratinocytes or hepatocytes. All in vivo genotoxicity studies on KA doses were negative, including mouse bone marrow micronucleus tests after single or multiple doses, an in vivo/in vitro unscheduled DNA synthesis (UDS) test, or a study in the liver of the transgenic Muta(TM) Mouse. On the basis of pharmacokinetic studies in rats and in vitro absorption studies in human skin, the systemic exposure of KA in man following its topical application is estimated to be in the range of 0.03-0.06 mg/kg/day. Comparing these values with the NOAEL in oral subchronic animal studies (250 mg/kg/day), the calculated margin of safety would be 4200- to 8900-fold. Comparing human exposure with the doses that were negative for micronuclei, UDS and gene mutations in vivo, the margins of safety are 16000 to 26000-fold. In conclusion, the topical use of KA as a skin lightening agent results in minimal exposure that poses no or negligible risk of genotoxicity or toxicity to the consumer.