Evaluating self-declared ancestry of U.S. Americans with autosomal, Y-chromosomal and mitochondrial DNA

The current U.S. population represents an amalgam of individuals originating mainly from four continental regions (Africa, Europe, Asia and America). To study the genetic ancestry and compare with self-declared ancestry we have analyzed paternally, maternally and bi-parentally inherited DNA markers sensitive for indicating continental genetic ancestry in all four major U.S. American groups. We found that self-declared U.S. Hispanics and U.S. African Americans tend to show variable degrees of continental genetic admixture among the three genetic systems, with evidence for a marked sex-biased admixture history. Moreover, for these two groups we observed significant regional variation across the country in genetic admixture. In contrast, self-declared U.S. European and U.S. Asian Americans were genetically more homogeneous at the continental ancestry level. Two autosomal ancestry-sensitive markers located in skin pigmentation candidate genes showed significant differences in self-declared U.S. African Americans or U.S. European Americans, relative to their assumed parental populations from Africa or Europe. This provides genetic support for the importance of skin color in the complex process of ancestry identification.     

Novelty P3 reductions in depression: Characterization using principal components analysis (PCA) of current source density (CSD) waveforms

We previously reported a novelty P3 reduction in depressed patients compared to healthy controls ( n =20 per group) in a novelty oddball task using a 31-channel montage. In an independent replication and extension using a 67-channel montage ( n =49 per group), reference-free current source density (CSD) waveforms were simplified and quantified by a temporal, covariance-based principal components analysis (PCA) (unrestricted Varimax rotation), yielding factor solutions consistent with other oddball tasks. A factor with a loadings peak at 343 ms summarized the target P3b source as well as a secondary midline frontocentral source for novels and targets. An earlier novelty vertex source (NVS) at 241 ms was present for novels, but not targets, and was reduced in patients. Compatible CSD-PCA findings were also confirmed for the original low-density sample. Results are consistent with a reduced novelty response in clinical depression, involving the early phase of the frontocentral novelty P3.     

Inferring Continental Ancestry of Argentineans from Autosomal, Y-Chromosomal and Mitochondrial DNA

We investigated the bio-geographic ancestry of Argentineans, and quantified their genetic admixture, analyzing 246 unrelated male individuals from eight provinces of three Argentinean regions using ancestry-sensitive DNA markers (ASDM) from autosomal, Y and mitochondrial chromosomes. Our results demonstrate that European, Native American and African ancestry components were detectable in the contemporary Argentineans, the amounts depending on the genetic system applied, exhibiting large inter-individual heterogeneity. Argentineans carried a large fraction of European genetic heritage in their Y-chromosomal (94.1%) and autosomal (78.5%) DNA, but their mitochondrial gene pool is mostly of Native American ancestry (53.7%); instead, African heritage was small in all three genetic systems (<4%). Population substructure in Argentina considering the eight sampled provinces was very small based on autosomal (0.92% of total variation was between provincial groups, p = 0.005) and mtDNA (1.77%, p = 0.005) data (none with NRY data), and all three genetic systems revealed no substructure when clustering the provinces into the three geographic regions to which they belong. The complex genetic ancestry picture detected in Argentineans underscores the need to apply ASDM from all three genetic systems to infer geographic origins and genetic admixture. This applies to all worldwide areas where people with different continental ancestry live geographically close together.     

Rhino-Orbitocerebral Zygomycosis Caused by Conidiobolus incongruus in an Immunocompromised Patient in Germany

Mucorales (subphylum Mucoromycotina) are well-known agents of invasive mucormycosis, whereas Entomophthorales (subphylum Entomophthoromycotina) are rarely encountered in human diseases in temperate zones. Here we report a fatal case of invasive rhino-orbitocerebral entomophthoramycosis caused by Conidiobolus incongruus in a 78-year-old woman with myelodysplastic syndrome.     

Cerebral oxygenation during the Richalet hypoxia sensitivity test and cycling time-trial performance in severe hypoxia

Background

The Richalet hypoxia sensitivity test (RT), which quantifies the cardiorespiratory response to acute hypoxia during exercise at an intensity corresponding to a heart rate of ~130 bpm in normoxia, can predict susceptibility of altitude sickness. Its ability to predict exercise performance in hypoxia is unknown.

Objectives

Investigate: (1) whether cerebral blood flow (CBF) and cerebral tissue oxygenation (O₂Hb; oxygenated hemoglobin, HHb; deoxygenated hemoglobin) responses during RT predict time-trial cycling (TT) performance in severe hypoxia; (2) if subjects with blunted cardiorespiratory responses during RT show greater impairment of TT performance in severe hypoxia.

Study design

Thirteen men [27 ± 7 years (mean ± SD), Wmax: 385 ± 30 W] were evaluated with RT and the results related to two 15 km TT, in normoxia and severe hypoxia (FIO₂ = 0.11).

Results

During RT, mean middle cerebral artery blood velocity (MCAv: index of CBF) was unaltered with hypoxia at rest (p > 0.05), while it was increased during normoxic (+22 ± 12 %, p < 0.05) and hypoxic exercise (+33 ± 17 %, p < 0.05). Resting hypoxia lowered cerebral O₂Hb by 2.2 ± 1.2 μmol (p < 0.05 vs. resting normoxia); hypoxic exercise further lowered it to ?7.6 ± 3.1 μmol below baseline (p < 0.05). Cerebral HHb, increased by 3.5 ± 1.8 μmol in resting hypoxia (p < 0.05), and further to 8.5 ± 2.9 μmol in hypoxic exercise (p < 0.05). Changes in CBF and cerebral tissue oxygenation during RT did not correlate with TT performance loss (R = 0.4, p > 0.05 and R = 0.5, p > 0.05, respectively), while tissue oxygenation and SaO₂ changes during TT did (R = ?0.76, p < 0.05). Significant correlations were observed between SaO₂, MCAv and HHb during RT (R = ?0.77, ?0.76 and 0.84 respectively, p < 0.05 in all cases).

Conclusions

CBF and cerebral tissue oxygenation changes during RT do not predict performance impairment in hypoxia. Since the changes in SaO₂ and brain HHb during the TT correlated with performance impairment, the hypothesis that brain oxygenation plays a limiting role for global exercise in conditions of severe hypoxia remains to be tested further.     

The effects of complex I function and oxidative damage on lifespan and anesthetic sensitivity in Caenorhabditis elegans

A mutation in a subunit of complex I of the mitochondrial electron transport chain (gas-1) causes Caenorhabditis elegans to be hypersensitive to volatile anesthetics and oxygen as well as shortening lifespan. We hypothesized that changes in mitochondrial respiration or reactive oxygen species production cause these changes. Therefore, we compared gas-1 to other mitochondrial mutants to identify the relative importance of these two aspects of mitochondrial function in determining longevity. Lifespans of gas-1 and mev-1 were decreased compared with N2, while that of clk-1 was increased. Rates of oxidative phosphorylation were decreased in all three mutants, but the ROS damage was decreased only in clk-1. Suppressors of gas-1 increased rates of oxidative phosphorylation, decreased oxidative damage to mitochondrial proteins and increased lifespan. Two strains containing combinations of mutations predicted to have very decreased complex I function, had unexpectedly long lifespans. We conclude that mitochondrial changes in lifespan appear to be mediated primarily by changes in oxidative damage rather than by changes in rates of oxidative phosphorylation. In contrast, the effects of mitochondrial changes on anesthetic sensitivity appear to be mediated by both altered respiration and oxidative damage.     

Farbkodierte Duplexsonographie vor und nach Lebertransplantation bei Kindern

In the current work the diagnostic value of ultrasound in infants with severe, end-stage liver disease for preoperative evaluation and for early follow-up subsequent to orthotopic liver transplantation were examined in a retrospective fashion. The nature of complications which can be judged accurately by means of ultrasound and the necessity of further tomographic imaging were assessed. A total of 43 infants who underwent liver transplantation surgery in our clinic within a period from September 2006 to June 2009 were assessed by preoperative and postoperative ultrasound. The imaging findings were analyzed in a retrospective fashion and the data were compared with the medical literature. Preoperative ultrasound examinations showed complex vascular anomalies with significance to the surgeon in 3 infants. Post-transplantation ultrasound revealed 10 vascular complications related to the transplant (2 occlusions of the hepatic artery, 2 cases of portal vein thrombosis and 6 cases with a stenosis of the portal vein anastomosis). Thus, the cumulative incidence of vascular complications was 23.3%. In conclusion ultrasound is a very sensitive modality for follow-up examinations subsequent to liver transplantation and preoperative examination. The transplant and the vasculature can be accurately judged without the need for further tomographic imaging. Thus, ultrasound is the modality of choice for preoperative evaluation and postoperative follow-up of infants receiving orthotopic liver transplants.     

Expression of neuroendocrine markers (neuronspecific enolase, synaptophysin and bombesin) in carcinoma of the lung

The value of immunoreactivity of antibodies against neuronspecific enolase (NSE), bombesin (GRP), and synaptophysin (SY 38) as markers for various human lung carcinoma has been assessed. One hundred-forty-two primary bronchus carcinomas (small cell anaplastic carcinoma, epidermoid carcinoma, adeno carcinoma, and large cell anaplastic carcinoma) were studied by the indirect immunoperoxidase method (PAP). SY 38 was found to react positively in 49/68 (79%) of the small cell anaplastic carcinoma (SCCL) and in 6/74 (8%) of the non-small cell carcinoma of the lung (NSCCL). Positive immunohistochemical data with antibody SY 38 showed in some cases an immunoreactive polypeptide of Mr = 40.000 obtained by immunoblotting similar in molecular weight as described for synaptophysin in other tumours. Reactivity of NSE was observed in 41/68 (61%) of the SCCL and in 8/74 (10%) of the NSCCL. Positive reactivity to GRP was similar to NSE in 42/68 (62%) of SCCL and in 7/74 (10%) of NSCCL. All cases of NSCCL reacting positively to SY 38 were found to react positively to NSE, and to GRP. Prognostic value of SY 38 was calculated vp = 0.71 for positive prediction and vn = 0.91 for negative prediction. The data indicate that SY 38 represents the broadest marker for neuroendocrine carcinoma of the lung since in addition to the majority of SCCL about 10% of NSCCL are recognized by the antibody SY 38.     

Triple vessel coronary artery endarterectomy and reconstruction: results in 144 patients

Coronary artery endarterectomy and reconstruction are valuable adjuncts to conventional bypass surgery when attempting to revascularize "diffusely" diseased coronary arteries. One hundred forty-four consecutive patients were operated on through February 1986, all of whom required endarterectomy and reconstruction of the left anterior descending, left circumflex and right coronary arteries. There were 130 men (90%), ranging in age from 29 to 83 years (average 55.8), whose left ventricular ejection fraction ranged from 0.20 to 0.75 (average 0.54). One hundred thirty-one patients (91%) had angina preoperatively, which was Canadian Cardiovascular Society class III or IV in 85 (59%). Fifteen operations (10%) were repeat procedures. All operations were performed using intermittent ischemic arrest. There was an average of 5.0 grafts per patient (range 3 to 8), with an average of 3.8 endarterectomized vessels per patient (range 3 to 7). There were 14 surgical deaths (10%), all cardiac in origin. Statistically significant (p less than 0.01) risk factors for increased operative mortality included repeat surgery, ejection fraction less than or equal to 0.30 and age greater than or equal to 70 years. The operative mortality rate in 106 low risk patients (male gender, age less than 70 years, ejection fraction greater than 0.30, first operation) was 3.8% (4 patients). Nonfatal complications included 13 perioperative myocardial infarctions (10%). Long-term follow-up data are available for all 102 surviving patients for an average of 30 months (range 7 to 92). There were 12 late deaths 1 to 52 months postoperatively. The 5 year actuarial survival rate is 71% for the entire group and 87% for the 106 low risk patients.(ABSTRACT TRUNCATED AT 250 WORDS)