Isolation of Bordetella avium and Novel Bordetella Strain from Patients with Respiratory Disease

Bordetella avium is thought to be strictly an avian pathogen. However, 16S rRNA gene sequencing identified 2 isolates from 2 humans with respiratory disease as B. avium and a novel B. avium–like strain. Thus, B. avium and B. avium–like organisms are rare opportunistic human pathogens

The descriptive epidemiology of sitting among US adults, NHANES 2009/2010

Objectives: Using NHANES 2009/2010, to describe the amount of time a representative sample of the U.S. population spends sitting by age, sex, ethnicity, education, and body mass index. Design: Cross-sectional analysis. Methods: Participants (n= 5911, ≥20 years) self-reported demographic variables and the amount of time they spend sitting on a typical day. Body mass index was calculated from measured height and weight. Results: Mean self-reported sitting time was 285. min/day for males and 281. min/day for females. Mexican-Americans reported sitting less than both non-Hispanic Whites and non-Hispanic Blacks (all p <0.0001). Non-Hispanic White males reported sitting more than non-Hispanic Black males, while Non-Hispanic White females reported sitting more than Other Hispanic females (both p <0.0001). No significant differences were found between sexes in any age group. There was a trend for increased sitting time with increasing age for females (p for trend = 0.0045), for all Mexican-American and Hispanic participants and non-Hispanic Black males (all p ≤ 0.006) and with increasing education (p for trend <0.0001). At the College Graduate level, females reported sitting less than males (p < 0.0001). Obese females reported sitting more than normal weight and overweight females (p = 0.0008). There were no significant differences in sitting time by body mass index for males. Conclusions: Self-reported sitting time differed by ethnicity, age group, education and body mass index but there was no overall difference by sex. These results represent the most up to date prevalence of self-reported sitting for the US adult population. Certain groups should be targeted to reduce sitting time, for example those with higher educational attainment and obese females

Television, adiposity, and cardiometabolic risk in children and adolescents

Background: It is largely unknown how TV use relates to depot-specific adiposity or cardiometabolic risk in children. Purpose: To examine relationships between having a TV in the bedroom and TV viewing time with total fat mass, abdominal subcutaneous and visceral adiposity, and cardiometabolic risk in children and adolescents. Methods: A cross-sectional study of 369 children and adolescents aged 5-18 years was conducted (2010-2011; analysis 2011-2012). Waist circumference; resting blood pressure; fasting triglycerides, high-density lipoprotein cholesterol [HDL-C] and glucose; fat mass by dual-energy x-ray absorptiometry; and abdominal subcutaneous and visceral adiposity by MRI were assessed. Cardiometabolic risk was defined as three or more risk factors including adverse levels of waist circumference, blood pressure, triglycerides, HDL-C, and glucose. Logistic regression analysis was used to compute ORs of high fat mass; subcutaneous and visceral adipose tissue mass (top age-adjusted quartile); and cardiometabolic risk, based on self-reported TV present in the bedroom and TV viewing time, controlling for age, gender, ethnicity, moderate-to-vigorous physical activity level, and unhealthy diet. Results: In multivariable models, presence of a TV in the bedroom and TV viewing time were associated with (p<0.05) higher odds of high waist circumference (OR=1.9–2.1); fat mass (OR=2.0–2.5); and subcutaneous adiposity (OR=2.1–2.9), whereas viewing TV ≥5 hours/day was associated with high visceral adiposity (OR=2.0). Having a TV in the bedroom was associated with elevated cardiometabolic risk (OR=2.9) and high triglycerides (OR=2.0). Conclusions Having a bedroom TV and TV viewing time were related to high waist circumference, fat mass, and abdominal subcutaneous adiposity. TV viewing time was related to visceral adiposity, and bedroom TV was related to cardiometabolic risk in children, controlling for moderate-to-vigorous physical activity and an unhealthy diet

Gene expression profiling of whole blood: Comparison of target preparation methods for accurate and reproducible microarray analysis

<p>Abstract</p> <p>Background</p> <p>Peripheral blood is an accessible and informative source of transcriptomal information for many human disease and pharmacogenomic studies. While there can be significant advantages to analyzing RNA isolated from whole blood, particularly in clinical studies, the preparation of samples for microarray analysis is complicated by the need to minimize artifacts associated with highly abundant globin RNA transcripts. The impact of globin RNA transcripts on expression profiling data can potentially be reduced by using RNA preparation and labeling methods that remove or block globin RNA during the microarray assay. We compared four different methods for preparing microarray hybridization targets from human whole blood collected in PAXGene tubes. Three of the methods utilized the Affymetrix one-cycle cDNA synthesis/in vitro transcription protocol but varied treatment of input RNA as follows: i. no treatment; ii. treatment with GLOBINclear; or iii. treatment with globin PNA oligos. In the fourth method cDNA targets were prepared with the Ovation amplification and labeling system.</p> <p>Results</p> <p>We find that microarray targets generated with labeling methods that reduce globin mRNA levels or minimize the impact of globin transcripts during hybridization detect more transcripts in the microarray assay compared with the standard Affymetrix method. Comparison of microarray results with quantitative PCR analysis of a panel of genes from the NF-kappa B pathway shows good correlation of transcript measurements produced with all four target preparation methods, although method-specific differences in overall correlation were observed. The impact of freezing blood collected in PAXGene tubes on data reproducibility was also examined. Expression profiles show little or no difference when RNA is extracted from either fresh or frozen blood samples.</p> <p>Conclusion</p> <p>RNA preparation and labeling methods designed to reduce the impact of globin mRNA transcripts can significantly improve the sensitivity of the DNA microarray expression profiling assay for whole blood samples. While blockage of globin transcripts during first strand cDNA synthesis with globin PNAs resulted in the best overall performance in this study, we conclude that selection of a protocol for expression profiling studies in blood should depend on several factors, including implementation requirements of the method and study design. RNA isolated from either freshly collected or frozen blood samples stored in PAXGene tubes can be used without altering gene expression profiles.</p

BMI percentiles for the identification of abdominal obesity and metabolic risk in children and adolescents : evidence in support of the CDC 95th percentile

Objectives:Body mass index (BMI) percentiles have been routinely and historically used to identify elevated adiposity. The aim of this study was to investigate the optimal Centers for Disease Control and Prevention (CDC) BMI percentile that predicts elevated visceral adipose tissue (VAT), fat mass and cardiometabolic risk in a biracial sample of children and adolescents. Participants and Methods: This cross-sectional analysis included 369 white and African-American children (5-18 years). BMI was calculated using height and weight and converted to BMI percentiles based on CDC growth charts. Receiver operating characteristic curve analysis identified the optimal (balance of sensitivity and specificity) BMI percentile to predict the upper quartile of age-adjusted VAT (measured by magnetic resonance imaging), age-adjusted fat mass (measured by dual-energy X-ray absorptiometry) and elevated cardiometabolic risk (≥2 of high glucose, triglycerides and blood pressure, and low high-density lipoprotein cholesterol) for each race-by-sex group. Results: The optimal CDC BMI percentile to predict those in the top quartile of age-adjusted VAT, age-adjusted fat mass and elevated cardiometabolic risk were the 96th, the 96th and the 94th percentiles, respectively, for the sample as a whole. Sensitivity and specificity was satisfactory (>0.70) for VAT and fat mass. Compared to VAT and fat mass, there was a lower overall accuracy of the optimal percentile in identifying those with elevated cardiometabolic risk. Conclusions: The present findings support the utility of the 95th CDC BMI percentile as a useful threshold for the prediction of elevated levels of VAT, fat mass and cardiometabolic risk in children and adolescents

Congenital Cardiac Outflow Tract Abnormalities in Dogs: Prevalence and Pattern of Inheritance From 2008 to 2017

Subvalvular aortic stenosis (SAS) and valvular pulmonic stenosis (PS) are two of the most common congenital heart diseases of dogs. The aim of this study was to determine the prevalence and mode of inheritance of these congenital heart diseases in a large veterinary teaching hospital population. Case records of dogs presented to the University of California Davis, Veterinary Medical Teaching Hospital (UCD VMTH) between January 2008 to December 2017 were reviewed retrospectively and pedigree information was obtained when available. There were 259 unique SAS and 336 unique PS cases diagnosed during the study period. The prevalence of SAS was 0.3% of overall hospital admissions and 4.7% for all dogs seen by the cardiology service. The prevalence for PS was 0.41% of overall hospital admissions and 6.1% of dogs seen by the cardiology service. Bullmastiffs and Newfoundlands had the greatest prevalence (6.59 and 4.46%, respectively) and odds ratio (52.43 and 34.73, respectively) for SAS. Bulldogs and French Bulldogs had the greatest prevalence (4.8 and 2.7%, respectively) and odds ratio (13.32 and 7.52, respectively) for PS. The identified prevalence of SAS and PS is higher than previously reported. Pedigree analysis in SAS affected Bullmastiffs, Golden Retrievers, and Rottweilers suggested an autosomal recessive pattern of inheritance. The mode of inheritance for PS in Bulldogs, also appears to be autosomal recessive. The results of this study can be used to inform future selection of breeding pairs and genetic studies aimed at reducing the prevalence of these common congenital heart diseases

Cyclophosphamide Chemotherapy Sensitizes Tumor Cells to TRAIL-Dependent CD8 T Cell-Mediated Immune Attack Resulting in Suppression of Tumor Growth

Background: Anti-cancer chemotherapy can be simultaneously lymphodepleting and immunostimulatory. Pre-clinical models clearly demonstrate that chemotherapy can synergize with immunotherapy, raising the question how the immune system can be mobilized to generate anti-tumor immune responses in the context of chemotherapy. Methods and Findings: We used a mouse model of malignant mesothelioma, AB1-HA, to investigate T cell-dependent tumor resolution after chemotherapy. Established AB1-HA tumors were cured by a single dose of cyclophosphamide in a CD8 T cell- and NK cell-dependent manner. This treatment was associated with an IFN-α/β response and a profound negative impact on the anti-tumor and total CD8 T cell responses. Despite this negative effect, CD8 T cells were essential for curative responses. The important effector molecules used by the anti-tumor immune response included IFN-γ and TRAIL. The importance of TRAIL was supported by experiments in nude mice where the lack of functional T cells could be compensated by agonistic anti-TRAIL-receptor (DR5) antibodies. Conclusion: The data support a model in which chemotherapy sensitizes tumor cells for T cell-, and possibly NK cell-, mediated apoptosis. A key role of tumor cell sensitization to immune attack is supported by the role of TRAIL in tumor resolution and explains the paradox of successful CD8 T cell-dependent anti-tumor responses in the absence of CD8 T cell expansion

Measurement-induced entanglement and teleportation on a noisy quantum processor

Measurement has a special role in quantum theory: by collapsing the wavefunction it can enable phenomena such as teleportation and thereby alter the "arrow of time" that constrains unitary evolution. When integrated in many-body dynamics, measurements can lead to emergent patterns of quantum information in space-time that go beyond established paradigms for characterizing phases, either in or out of equilibrium. On present-day NISQ processors, the experimental realization of this physics is challenging due to noise, hardware limitations, and the stochastic nature of quantum measurement. Here we address each of these experimental challenges and investigate measurement-induced quantum information phases on up to 70 superconducting qubits. By leveraging the interchangeability of space and time, we use a duality mapping, to avoid mid-circuit measurement and access different manifestations of the underlying phases -- from entanglement scaling to measurement-induced teleportation -- in a unified way. We obtain finite-size signatures of a phase transition with a decoding protocol that correlates the experimental measurement record with classical simulation data. The phases display sharply different sensitivity to noise, which we exploit to turn an inherent hardware limitation into a useful diagnostic. Our work demonstrates an approach to realize measurement-induced physics at scales that are at the limits of current NISQ processors

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers