Longitudinal changes and correlations of bioimpedance and anthropometric measurements in pregnancy: Simple possible bed-side tools to assess pregnancy evolution

Purpose: The aim of this study was to assess longitudinal changes of bioimpedance analysis compared with anthropometric measurements in low-risk pregnant woman recruited in the first trimester and to observe possible differences in these indices in women who developed high-risk pregnancies.

Materials and methods: Bioimpedance indices for the three trimesters of pregnancies were calculated separately for uneventful pregnancies delivered of newborns >?the 10th centile. These findings were compared with anthropometric measurements. Data of women who developed hypertensive disorders of pregnancy (HDP) or delivered SGA newborns were calculated and compared.

Results: Significantly longitudinal increases were observed in these pregnancies for total body water (TBW), free fat mass, fat mass, and extra-cellular water. These increases were paralleled body mass index (BMI), skinfolds, and waist measurements. The correlations between these two sets of findings were poor. Women who developed HDP with AGA fetuses showed significantly different bioimpedance from normal cases. TBW indices were highly significantly different since the first trimester. In pregnancies delivered of SGA newborns, these indices were opposite of the values observed in patients with HDP-AGA, TBW in these patients was significantly reduced compared with normal pregnancies.

Conclusions: The bioelectrical impedance is a fast, simple, noninvasive way to assess the TBW content in pregnancy. Our findings are in agreement with the hypothesis that bioimpedance might help to identify early in gestation patients at risk of developing different clinical phenotypes of hypertensive disease of pregnancy and SGA fetuses.     

Spinal blockade of TNF blocks spinal nerve ligation-induced increases in spinal P-p38

Although research on DNIC has revealed the inhibitory effect occurring between two remote pain stimuli, the interrelation between two adjacent painful stimuli has not yet been characterized. In the present study, we used a sample of 40 healthy volunteers to examine the effect of 30-s immersion of the fingers in water of 1 °C, as a conditioning stimulus, on pain intensities produced by conditioned mechanical punctuate stimuli, applied both adjacent and contralateral to the cooled area. There was a significant decrease in mechanical pain intensities from 17.23 ± 2.39 at baseline to 12.45 ± 2.39 when stimulating immediately after the cold immersion at an adjacent site, and from 20.00 ± 2.39 to 15.08 ± 2.39 at remote sites (F = 20.02, p < 0.0001). A significant positive correlation between the extent of pain reduction in the cooled and in the uncooled hand was found (r_s = 0.59, p = 0.0001). The extent of pain reduction following cooling in the cooled and in the uncooled hand was also found to be similar for males and for females (p = 0.63). It is concluded that under the conditions of this experiment, EA affects heterotopic and homotopic regions similarly and without gender differences.     

Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons

Slit proteins steer the migration of many cell types through their binding to Robo receptors, but how Robo controls cell motility is not clear. We describe the functional analysis of vilse, a Drosophila gene required for Robo repulsion in epithelial cells and axons. Vilse defines a conserved family of RhoGAPs (Rho GTPase-activating proteins), with representatives in flies and vertebrates. The phenotypes of vilse mutants resemble the tracheal and axonal phenotypes of Slit and Robo mutants at the CNS midline. Dosage-sensitive genetic interactions between vilse, slit, and robo mutants suggest that vilse is a component of robo signaling. Moreover, overexpression of Vilse in the trachea of robo mutants ameliorates the phenotypes of robo, indicating that Vilse acts downstream of Robo to mediate midline repulsion. Vilse and its human homolog bind directly to the intracellular domains of the corresponding Robo receptors and promote the hydrolysis of RacGTP and, less efficiently, of Cdc42GTP. These results together with genetic interaction experiments with robo, vilse, and rac mutants suggest a mechanism whereby Robo repulsion is mediated by the localized inactivation of Rac through Vilse.     

MRE11 mutations and impaired ATM-dependent responses in an Italian family with ataxia-telangiectasia-like disorder

Hypomorphic mutations of the MRE11 gene are the hallmark of the radiosensitive ataxia-telangiectasia-like disorder (ATLD). Here, we describe a new family with two affected siblings, ATLD5 and ATLD6, now aged 37 and 36, respectively. They presented with late onset cerebellar degeneration slowly progressing until puberty and absence of telangiectasias, and were cancer-free. Both patients were wild-type for ATM and NBS1, but compound heterozygotes for MRE11 gene mutations [1422C-->A, T481K; 1714C-->T, R571X]. The 1422C-->A allele was inherited from the mother, whereas the 1714C-->T, allele paternally inherited, was apparently null as a result of nonsense-mediated mRNA decay (NMD). Interestingly, the 1714C-->T mutation is the same as previously identified in an unrelated English ATLD family (probands ATLD3 and ATLD4), suggesting an important role for NMD in saving potentially lethal mutations. Lymphoblastoid cell lines (LCLs) derived from ATLD5 and ATLD6 were normal for ATM, but defective for Mre11, Rad50 and Nbs1 (the MRN complex) protein expression. Their response to gamma-radiation was abnormal, as evidenced by the enhanced radiosensitivity, attenuated autophosphorylation of ATM-S1981 and phosphorylation of the ATM targets p53-S15 and Smc1-S966, failure to form Mre11 nuclear foci and defective G1 checkpoint arrest. The fibroblasts, but not LCLs, from ATLD5 and ATLD6 showed an impaired ATM-dependent Chk2 phosphorylation. These findings further underscore the interconnection between ATM activity and MRN function, which rationalizes the clinical similarity between ataxia-telangiectasia (A-T) and ATLD.     

Direct drug susceptibility testing of Mycobacterium tuberculosis for rapid detection of multidrug resistance using the Bactec MGIT 960 system: a multicenter study

Conventional indirect drug susceptibility testing of Mycobacterium tuberculosis with liquid medium is well established and offers time-saving and reliable results. This multicenter study was carried out to evaluate if drug susceptibility testing (DST) can be successfully carried out directly from processed smear-positive specimens (direct DST) and if this approach could offer substantial time savings. Sputum specimens were digested, decontaminated, and concentrated by the laboratory routine procedure and were inoculated in Bactec MGIT 960 as well as Lowenstein-Jensen (LJ) medium for primary isolation. All the processed specimens which were acid-fast bacterium (AFB) smear positive were used for setting up direct DST for isoniazid (INH) and rifampin (RIF). After the antimicrobial mixture of polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin (PANTA) was added, the tubes were entered in the MGIT 960 instrument using the 21-day protocol (Bactec 960 pyrazinamide [PZA] protocol). Results obtained by direct DST were compared with those obtained by indirect DST to establish accuracy and time savings by this approach. Of a total of 360 AFB smear-positive sputum specimens set up for direct DST at four sites in three different countries, 307 (85%) specimens yielded reportable results. Average reporting time for direct DST was 11 days (range, 10 to 12 days). The average time savings by direct DST compared to indirect DST, which included time to isolate a culture and perform DST, was 8 days (range, 6 to 9 days). When results of direct DST were compared with those of indirect DST, there was 95.1% concordance with INH and 96.1% with rifampin. These findings indicate that direct DST with the Bactec MGIT 960 system offers further time savings and is a quick method to reliably detect multidrug resistance (MDR) cases.     

Molecular characterization and taxonomy of grapevine leafroll-associated virus 7

The complete nucleotide sequence of an Albanian isolate of grapevine leafroll-associated virus 7 (GLRaV-7-Alb) was determined. The viral genome consists of 16,404 nucleotides and has nine open reading frames (ORFs) that potentially encode proteins, most of which are typical for members of the family Closteroviridae. Only the 25-kDa (ORF8) and 27-kDa (ORF9) proteins had no apparent similarity to other viral proteins in the sequence databases. The genome structure of GLRaV-7-Alb closely resembles that of little cherry virus 1 and cordyline virus 1. In phylogenetic trees constructed with HSP70h sequences, these three viruses cluster together in a clade next to that comprising members of the genus Crinivirus, to which they are more closely related than to the clostero- and ampeloviruses. The molecular properties of these three viruses differ sufficiently from those of members of the three extant genera of the family Closteroviridae to warrant their classification in a novel genus.     

Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas

Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM. Long survival (LS) was defined as survival greater than 3 years from the time of diagnosis, and short survival was defined as less than 3 years from the time of diagnosis. Both loss of p16 protein expression by immunohistochemistry and homozygous deletion of p16 by FISH were associated with adverse prognosis. Female gender, positive p16 immunoexpression, and lack of p16/CDKN2A deletion significantly predicted the survival for the LS group. Statistical analysis showed a very strong correlation of immunohistochemistry and FISH data. Cases positive for p16 immunoexpression and negative for 9p21 deletion showed the best survival time. Our study is the first to demonstrate decreased frequency of homozygous deletion of 9p21 and loss of p16 immunoreactivity in pleural mesotheliomas from patients with long-term survival of greater than 3 years in contrast to patients with rapidly fatal mesotheliomas. A possible implementation of these tests into preoperative prognostication of MPM and therapeutic decisions should be considered.     

Startle modulation and explicit valence evaluations dissociate during backward fear conditioning

Blink startle magnitude is linearly modulated by affect such that, relative to neutral stimuli, startle magnitude is inhibited during pleasant stimuli and potentiated during unpleasant stimuli. Andreatta, Mühlberger, Yarali, Gerber, and Pauli (2010), however, report a dissociation between startle modulation and explicit valence evaluations during backward conditioning, a procedure in which the unconditional stimulus precedes the conditional stimulus (CS). Relative to controls, startles elicited during the CS were inhibited, suggesting that the CS had acquired positive valence, but participants still evaluated the CS as unpleasant after the experiment. In Experiment 1, we aimed to replicate this dissociation using a trial‐by‐trial measure of CS valence to measure startle modulation and CS valence simultaneously during forward and backward differential fear conditioning. In Experiment 2, we examined whether early and late portions of the CS could acquire differential valence by presenting startle probes at early and late probe positions during the CS. In both experiments, the dissociation between startle modulation and explicit valence evaluations in backward conditioning replicated, with CS+ evaluated as less pleasant than CS‐, but startles elicited during CS+ inhibited relative to CS‐. In Experiment 2, we provide preliminary evidence that this inhibition was present early, but not late, during the CS+. The results replicate the dissociation between implicit and explicit CS valence reported by Andreatta et al. (2010) using a trial‐by‐trial measure of valence. We also provide preliminary evidence that this dissociation may occur because the implicit and explicit measures are recorded at different times during the CS presentation.     

Kimura’s disease: case report of an Italian young male and response to oral cyclosporine A in an 8 years follow-up

Kimura’s disease is a benign chronic inflammatory disease, common in Asian males and rare in Western people. Clinically, Kimura’s disease is characterized by subcutaneous nodular lesions, usually localised in head and neck, often associated with regional lymphadenopathy. Peripheral blood eosinophilia and elevated serum IgE are often observed. We report a case of a 40-year-old Italian patient presenting with nodular subcutaneous lesions and peripheral eosinophilia. Based on clinical, histopathological and laboratory findings, a diagnosis of Kimura’s disease was made. The patient was treated with very low doses of cyclosporine A with no evidence of disease recurrence over the following 8 years. However, the discontinuation of cyclosporine A determined a relapse of the disease. The relevance of this case is due to the rarity of the disease in Italy, to its peculiar clinical presentation and, moreover, it is the first case in literature that has a good response to treatment with low doses of cyclosporine A, documented in an 8-year follow-up.