Cardiac malformation of partial trisomy 7p/monosomy 18p and partial trisomy 18p/monosomy 7p in siblings as a result of reciprocal unbalanced malsegregation—and review of the literature

We report two unbalanced translocations involving the short arms of chromosomes 7 and 18 due to a balanced translocation 7;18 in the mother. Karyotyping and fluorescence in situ hybridization analysis of the female fetus revealed an unbalanced subtelomeric translocation(karyotype 46,XX,der(18)t(7;18)(p22.3;p11.32)mat resulting in a partial trisomy 7p and a partial monosomy 18p.Array comparative genomic hybridization (CGH) detected a4.44-Mb heterozygous duplication at 7p22.3 to 7p22.1 and a0.178-Mb heterozygous deletion at 18p11.32. Clinical characteristics comprised a mildly stenotic bicuspid aortic valve and a small aortic arch without coarctation. The patient's older brother displayed a reciprocal version of her chromosomal aberration (46,XY,der(7)t(7;18)(p22;p11.32) resulting in a partial monosomy 7p and a partial trisomy 18p. Array CGH revealed a 4.75-Mb heterozygous deletion at 7p22.3p22.1 and a 0.579-Mb duplication at 18p11.32. He presented with tetralogy of Fallot, cleft palate, microcephalus without craniosynostosis, growth retardation, ptosis of the right eyelid, right-sided renal agenesis, unilateral cryptorchism,and mental retardation. In this report, we present the clinical phenotype in patients with aberrations of chromosomes 7p and 18p and reviewed the literature to summarize cardiovascular malformations in these patients.     

Discontinuation of HeartWare RVAD support without device removal in chronic BIVAD patients

During biventricular assist device (BVAD) support, right ventricular (RV) assistance may restore sufficient RV function after several weeks to months. Since November 2009, 10 patients (9 men and 1 woman; mean age, 49.7 ± 14.4 y) suffering from idiopathic dilatative cardiomyopathy received BVAD employing two implantable continuous-flow pumps of the HeartWare type. In three male patients, aged 53, 57, and 60 years, after a right ventricular assist device (RVAD) support time of 15.6, 11.2, and 3.6 months, respectively, the RVAD was stopped, and the percutaneous lead was surgically shortened in two cases. There were no differences in preoperative RV geometry and function or in severity of tricuspid valve regurgitation in patients with and without delayed RV recovery. Follow-up echocardiography revealed no regurgitation through the right pump in any patient. One patient died due to severe sepsis 63 days later; the other two patients are currently on left ventricular assist devices support at home, 120 and 236 days after RVAD deactivation with stable hemodynamic conditions and without any thromboembolic events. RV function may recover even after weeks or months on BVAD support. The HeartWare HVAD used as an RVAD may be stopped and left in place without complications.     

New real-time PCR assay using allelic discrimination for detection and differentiation of equine herpesvirus-1 strains with A2254 and G2254 polymorphisms

A single-nucleotide polymorphism (A(2254) or G(2254)) in open reading frame 30 (ORF30) has been linked to the neuropathogenic phenotype of equine herpesvirus-1 (EHV-1). Identification of this polymorphism led to the development of a real-time PCR (rPCR) assay using allelic discrimination (E(2)) to distinguish between potentially neuropathogenic and nonneuropathogenic EHV-1 strains (G. P. Allen, J. Vet. Diagn. Invest. 19:69-72, 2007). Although this rPCR assay can detect and genotype EHV-1 strains, subsequent studies demonstrated that it lacks the sensitivity for the routine detection of viral nucleic acid in clinical specimens. Therefore, a new allelic discrimination EHV-1 rPCR assay (E(1)) was developed by redesigning primers and probes specific to ORF30. The E(1) and E(2) rPCR assays were evaluated using 76 archived EHV isolates and 433 clinical specimens from cases of suspected EHV-1 infection. Nucleotide sequence analysis of ORF30 was used to confirm the presence of EHV-1 and characterize the genotype (A(2254) or G(2254)) in all archived isolates plus 168 of the clinical samples. The E(1) assay was 10 times more sensitive than E(2), with a lower detection limit of 10 infectious virus particles. Furthermore, all A(2254) and G(2254) genotypes along with samples from three cases of dual infection (A(2254)+G(2254)) were correctly identified by E(1), whereas E(2) produced 20 false dual positive results with only one actual mixed A(2254)+G(2254) genotype confirmed. Based on these findings, E(1) offers greater sensitivity and accuracy for the detection and A/G(2254) genotyping of EHV-1, making this improved rPCR assay a valuable diagnostic tool for investigating outbreaks of EHV-1 infection.     

Cerebellar regions involved in adaptation to force field and visuomotor perturbation

Studies with patients and functional magnetic resonance imaging investigations have demonstrated that the cerebellum plays an essential role in adaptation to visuomotor rotation and force field perturbation. To identify cerebellar structures involved in the two tasks, we studied 19 patients with focal lesions after cerebellar infarction. Focal lesions were manually traced on magnetic resonance images and normalized using a new spatially unbiased template of the cerebellum. In addition, we reanalyzed data from 14 patients with cerebellar degeneration using voxel-based morphometry. We found that adjacent regions with only little overlap in the anterior arm area (lobules IV to VI) are important for adaptation in both tasks. Although adaptation to the force field task lay more anteriorly (lobules IV and V), lobule VI was more important for the visuomotor task. In addition, regions in the posterolateral cerebellum (Crus I and II) contributed to both tasks. No consistent involvement of the posterior arm region (lobule VIII) was found. Independence of the two kinds of adaptation is further supported by findings that performance in one task did not correlate to performance in the other task. Our results show that the anterior arm area of the cerebellum is functionally divided into a more posterior part of lobule VI, extending into lobule V, related to visuomotor adaption, and a more anterior part including lobules IV and V, related to force field adaption. The posterolateral cerebellum may process common aspects of both tasks.     

Applicability of two mobile analysers for mercury in urine in small-scale gold mining areas

Mercury is still used in developing countries to extract gold from the ore in small-scale gold mining areas. This is a major health hazard for people living in mining areas. The concentration of mercury in urine was analysed in different mining areas in Zimbabwe, Indonesia and Tanzania. First the urine samples were analysed by CV-AAS (cold vapour atomic absorption spectrometry) during the field projects with a mobile mercury analyser (Lumex^® or Seefelder^®) and secondly, in a laboratory with a stationary CV-AAS mercury analyser (PerkinElmer^®). Caused by the different systems (reduction agent either SnCl₂ (Lumex^® or Seefelder^®)) or NaBH₄ (PerkinElmer^®), with the mobile analysers only the inorganic mercury was obtained and with the stationary system the total mercury concentration was measured. The aims of the study were whether the results obtained in field with the mobile equipments can be compared with the stationary reference method in the laboratory and allow the application of these mobile analysers in screening studies on concerned populations to select those, who are exposed to critical mercury levels. Overall, the concentrations obtained with the two mobile systems were approximately 25% lower than determined with the stationary system. Nevertheless, both mobile systems seem to be very useful for screening of volunteers in field. Moreover, regional staff may be trained on such analysers to perform screening tests by themselves.     

Longitudinal variability of time-location/activity patterns of population at different ages: a longitudinal study in California

Background

Synoptic circulation patterns (large-scale tropospheric motion systems) affect air pollution and, potentially, air-pollution-morbidity associations. We evaluated the effect of synoptic circulation patterns (air masses) on the association between ozone and hospital admissions for asthma and myocardial infarction (MI) among adults in North Carolina.

Methods

Daily surface meteorology data (including precipitation, wind speed, and dew point) for five selected cities in North Carolina were obtained from the U.S. EPA Air Quality System (AQS), which were in turn based on data from the National Climatic Data Center of the National Oceanic and Atmospheric Administration. We used the Spatial Synoptic Classification system to classify each day of the 9-year period from 1996 through 2004 into one of seven different air mass types: dry polar, dry moderate, dry tropical, moist polar, moist moderate, moist tropical, or transitional. Daily 24-hour maximum 1-hour ambient concentrations of ozone were obtained from the AQS. Asthma and MI hospital admissions data for the 9-year period were obtained from the North Carolina Department of Health and Human Services. Generalized linear models were used to assess the association of the hospitalizations with ozone concentrations and specific air mass types, using pollutant lags of 0 to 5 days. We examined the effect across cities on days with the same air mass type. In all models we adjusted for dew point and day-of-the-week effects related to hospital admissions.

Results

Ozone was associated with asthma under dry tropical (1- to 5-day lags), transitional (3- and 4-day lags), and extreme moist tropical (0-day lag) air masses. Ozone was associated with MI only under the extreme moist tropical (5-day lag) air masses.

Conclusions

Elevated ozone levels are associated with dry tropical, dry moderate, and moist tropical air masses, with the highest ozone levels being associated with the dry tropical air mass. Certain synoptic circulation patterns/air masses in conjunction with ambient ozone levels were associated with increased asthma and MI hospitalizations.     

Missense variants in hMLH1 identified in patients from the German HNPCC consortium and functional studies

Missense mutations of the DNA mismatch repair gene MLH1 are found in a significant fraction of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) and their pathogenicity often remains unclear. We report here all 88 MLH1 missense variants identified in families from the German HNPCC consortium with clinical details of these patients/families. We investigated 23 MLH1 missense variants by two functional in vivo assays in yeast; seven map to the ATPase and 16 to the protein interaction domain. In the yeast-2-hybrid (Y2H) assay three variants in the ATPase and twelve variants in the interaction domain showed no or a reduced interaction with PMS2; seven showed a normal and one a significantly higher interaction. Using the Lys2A (14) reporter system to study the dominant negative mutator effect (DNE), 16 variants showed no or a low mutator effect, suggesting that these are nonfunctional, three were intermediate and four wild type in this assay. The DNE and Y2H results were concordant for all variants in the interaction domain, whereas slightly divergent results were obtained for variants in the ATPase domain. Analysis of the stability of the missense proteins in yeast and human embryonic kidney cells (293T) revealed a very low expression for seven of the variants in yeast and for nine in human cells. In total 15 variants were classified as deleterious, five were classified as variants of unclassified significance (VUS) and three were basically normal in the functional assays, P603R, K618R, Q689R, suggesting that these are neutral.     

Identification of intra- and inter-individual metabolite variation in plasma metabolite profiles of cats and dogs

The purpose of the present study was first to identify drivers of variance in plasma metabolite profiles of cats and dogs that may affect the interpretation of nutritional metabolomic studies. A total of fourteen cats and fourteen dogs housed in environmentally enriched accommodation were fed a single batch of diet to maintain body weight. Fasting blood samples were taken on days 14, 16 and 18 of the study. Gas chromatography-mass spectrometry (GC-MS), liquid chromatography (LC)-MS/MS and solid-phase extraction-LC-MS/MS analyses were used for metabolite profiling. Principal component (PC) analysis that indicated 31 and 27 % of the variance was explained in PC1 and PC2 for cats and dogs, respectively, with most individuals occupying a unique space. As the individual was a major driver of variance in the plasma metabolome, the second objective was to identify metabolites associated with the individual variation observed. The proportion of intra- and inter-individual variance was calculated for 109 cat and 101 dog metabolites with a low intra-individual variance (SD < 0.05). Of these, fifteen cat and six dog metabolites had inter-individual variance accounting for at least 90 % of the total variance. There were four metabolites common to both species (campesterol, DHA, a cholestenol and a sphingosine moiety). Many of the metabolites with >75 % inter-individual variance were common to both species and to similar areas of metabolism. In summary, the individual is an important driver of variance in the fasted plasma metabolome, and specific metabolites and areas of metabolism may be differentially regulated by individuals in two companion animal species.