Characteristics of Hospitalized Cases of Pertussis in Catalonia and Navarra,Two Regions in the North of Spain

Pertussis causes a large number of cases and hospitalizations in Catalonia and Navarra. We made a study of household cases of pertussis during 2012 and 2013 in order to identify risk factors for hospitalization in pertussis cases. Each primary case reported triggered the study of their contacts. Close contacts at home and people who were in contact for >2 hours during the transmission period of cases were included. The adjusted OR and 95% confidence intervals (CI) was calculated using logistic regression. A total of 1124 pertussis cases were detected, of which 14.9% were hospitalized. Inspiratory whoop (aOR: 1.64; CI: 1.02–2.65), apnoea (aOR: 2.47; CI: 1.51–4.03) and cyanosis (aOR: 15.51; CI: 1.87–128.09) were more common in hospitalized than in outpatient cases. Hospitalization occurred in 8.7% of correctly-vaccinated cases, 41.1% of non-vaccinated cases and 9.4% of partially-vaccinated cases. In conclusion, inspiratory whoop, apnoea and cyanosis were associated factors to hospitalization while vaccination reduced hospitalizations due to pertussis.     

Individual wealth rank, community wealth inequality, and self-reported adult poor health: a test of hypotheses with panel data (2002-2006) from native Amazonians, Bolivia

Growing evidence suggests that economic inequality in a community harms the health of a person. Using panel data from a small-scale, preindustrial rural society, we test whether individual wealth rank and village wealth inequality affects self-reported poor health in a foraging-farming native Amazonian society. A person's wealth rank was negatively but weakly associated with self-reported morbidity. Each step up/year in the village wealth hierarchy reduced total self-reported days ill by 0.4 percent. The Gini coefficient of village wealth inequality bore a positive association with self-reported poor health that was large in size, but not statistically significant. We found small village wealth inequality, and evidence that individual economic rank did not change. The modest effects may have to do with having used subjective rather than objective measures of health, having small village wealth inequality, and with the possibly true modest effect of a person's wealth rank on health in a small-scale, kin-based society. Finally, we also found that an increase in mean individual wealth by village was related to worse self-reported health. As the Tsimane' integrate into the market economy, their possibilities of wealth accumulation rise, which may affect their well-being. Our work contributes to recent efforts in biocultural anthropology to link the study of social inequalities, human biology, and human-environment interactions.     

Phenotype and growth behavior of residual β-catenin-positive hepatocytes in livers of β-catenin-deficient mice

Signaling through the Wnt/β-catenin pathway is a crucial determinant of hepatic zonal gene expression, liver development, regeneration, and tumorigenesis. Transgenic mice with hepatocyte-specific knockout of Ctnnb1 (encoding β-catenin) have proven their usefulness in elucidating these processes. We now found that a small number of hepatocytes escape the Cre-mediated gene knockout in that mouse model. The remaining β-catenin-positive hepatocytes showed approximately 25% higher cell volumes compared to the β-catenin-negative cells and exhibited a marker protein expression profile similar to that of normal perivenous hepatocytes or hepatoma cells with mutationally activated β-catenin. Surprisingly, the expression pattern was observed independent of the cell's position within the liver lobule, suggesting a malfunction of physiological periportal repression of perivenously expressed genes in β-catenin-deficient liver. Clusters of β-catenin-expressing hepatocytes lacked expression of the gap junction proteins Connexin 26 and 32. Nonetheless, β-catenin-positive hepatocytes had no striking proliferative advantage, but started to grow out on treatment with phenobarbital, a tumor-promoting agent known to facilitate the formation of mouse liver adenoma with activating mutations of Ctnnb1. Progressive re-population of Ctnnb1 knockout livers with wild-type hepatocytes was seen in aged mice with a pre-cirrhotic phenotype. In these large clusters of β-catenin-expressing hepatocytes, perivenous-specific gene expression was re-established. In summary, our data demonstrate that the zone-specificity of a hepatocyte's gene expression profile is dependent on the presence of β-catenin, and that β-catenin provides a proliferative advantage to hepatocytes when promoted with phenobarbital, or in a pre-cirrhotic environment.     

Searching for DNA in museum specimens: a comparison of sources in a mammal species

The number of genetic studies that use preserved specimens as sources of DNA has been steadily increasing during the last few years. Therefore, selecting the sources that are more likely to provide a suitable amount of DNA of enough quality to be amplified and at the minimum cost to the original specimen is an important step for future research. We have compared different types of tissue (hides vs. bones) from museum specimens of Iberian lynx and multiple alternative sources within each type (skin, footpad, footpad powder, claw, diaphysis, maxilloturbinal bone, mastoid process and canine) for DNA yield and probability of amplification of both mitochondrial and nuclear targets. Our results show that bone samples yield more and better DNA than hides, particularly from sources from skull, such as mastoid process and canines. However, claws offer an amplification success as high as bone sources, which makes them the preferred DNA source when no skeletal pieces have been preserved. Most importantly, these recommended sources can be sampled incurring minimal damage to the specimens while amplifying at a high success rate for both mitochondrial and microsatellite markers.     

UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinB

DinB is the only translesion Y family DNA polymerase conserved among bacteria, archaea, and eukaryotes. DinB and its orthologs possess a specialized lesion bypass function but also display potentially deleterious -1 frameshift mutagenic phenotypes when overproduced. We show that the DNA damage-inducible proteins UmuD(2) and RecA act in concert to modulate this mutagenic activity. Structural modeling suggests that the relatively open active site of DinB is enclosed by interaction with these proteins, thereby preventing the template bulging responsible for -1 frameshift mutagenesis. Intriguingly, residues that define the UmuD(2)-interacting surface on DinB statistically covary throughout evolution, suggesting a driving force for the maintenance of a regulatory protein-protein interaction at this site. Together, these observations indicate that proteins like RecA and UmuD(2) may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution.     

Analysis of planarian Adh3 supports an intron-rich architecture and tissue-specific expression for the urbilaterian ancestral form

The alcohol dehydrogenase class 3 enzyme (ADH3) is the presumed ancestral form of the medium-chain dehydrogenase-reductase ADH family. This enzyme has been involved in formaldehyde and nitric oxide metabolism of a variety of deuterostomes and ecdysozoan protostomes. We have now characterized the structure and expression of the Adh3 gene in the lophotrochozoan Schmidtea mediterranea, a freshwater planarian. The planarian gene expands over 8.7 kb and is organized into 7 exons. The 1340 bp long Adh3cDNA contains a 1137 bp open reading frame corresponding to a deduced protein of 379 amino acids. The protein sequence is consistent with that expected for a typical class III enzyme. Twenty out of the twenty-two amino acid positions associated with enzymatic roles are strictly preserved, which suggests that the enzymatic capabilities have been conserved. In situ hybridization experiments show that Adh3 is expressed along the intestine of S. mediterranea specimens. This is consistent with the pattern observed in invertebrates and in contrast with the widespread expression of vertebrate Adh3. The comparative study across bilateria, which now includes a lophotrochozoan representative, further supports the idea that the urbilaterian Adh3 ancestor showed an intron-rich architecture and tissue-specific expression, and strengthens the view that widespread expression of Adh3 was a vertebrate innovation.     

SNP and INDEL detection in a QTL region on chicken chromosome 2 associated with muscle deposition

Genetic improvement is important for the poultry industry, contributing to increased efficiency of meat production and quality. Because breast muscle is the most valuable part of the chicken carcass, knowledge of polymorphisms influencing this trait can help breeding programs. Therefore, the complete genome of 18 chickens from two different experimental lines (broiler and layer) from EMBRAPA was sequenced, and SNPs and INDELs were detected in a QTL region for breast muscle deposition on chicken chromosome 2 between microsatellite markers MCW0185 and MCW0264 (105 849–112 649 kb). Initially, 94 674 unique SNPs and 10 448 unique INDELs were identified in the target region. After quality filtration, 77% of the SNPs (85 765) and 60% of the INDELs (7828) were retained. The studied region contains 66 genes, and functional annotation of the filtered variants identified 517 SNPs and three INDELs in exonic regions. Of these, 357 SNPs were classified as synonymous, 153 as non‐synonymous, three as stopgain, four INDELs as frameshift and three INDELs as non‐frameshift. These exonic mutations were identified in 37 of the 66 genes from the target region, three of which are related to muscle development (DTNA, RB1CC1 and MOS). Fifteen non‐tolerated SNPs were detected in several genes (MEP1B, PRKDC, NSMAF, TRAPPC8, SDR16C5, CHD7, ST18 and RB1CC1). These loss‐of‐function and exonic variants present in genes related to muscle development can be considered candidate variants for further studies in chickens. Further association studies should be performed with these candidate mutations as should validation in commercial populations to allow a better explanation of QTL effects.     

Simultaneous analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol enantiomers in rat plasma by high-performance liquid chromatography-tandem mass spectrometry: application to pharmacokinetics

Tramadol (T) is available as a racemic mixture of (+)‐trans‐T and (−)‐trans‐T. The main metabolic pathways are O‐demethylation and N‐demethylation, producing trans‐O‐desmethyltramadol ( M1 ) and trans‐N‐desmethyltramadol ( M2 ) enantiomers, respectively. The analgesic effect of T is related to the opioid activity of (+)‐trans‐T and (+)‐ M1 and to the monoaminergic action of (+/−)‐trans‐T. This is the first study using tandem mass spectrometry as a detection system for the simultaneous analysis of trans‐T, M1 , and M2 enantiomers. The analytes were resolved on a Chiralpak® AD column using hexane:ethanol (95.5:4.5, v/v) plus 0.1% diethylamine as the mobile phase. The quantitation limits were 0.5 ng/ml for trans‐T and M1 and 0.1 ng/ml for M2 . The method developed and validated here was applied to a pharmacokinetic study in rats. Male Wistar rats (n = 6 at each time point) received a single oral dose of 20 mg/kg racemic trans‐T. Blood samples were collected up to 12 h after drug administration. The kinetic disposition of trans‐T and M2 was enantioselective (AUC_(+)/(−) ratio = 4.16 and 6.36, respectively). The direction and extent of enantioselectivity in the pharmacokinetics of trans‐T and M2 in rats were comparable to data previously reported for healthy volunteers, suggesting that rats are a suitable model for enantioselective studies of trans‐T pharmacokinetics. Chirality, 2011. © 2010 Wiley‐Liss, Inc.