Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances

Gastrointestinal disturbances are commonly reported in children with autism, complicate clinical management, and may contribute to behavioral impairment. Reports of deficiencies in disaccharidase enzymatic activity and of beneficial responses to probiotic and dietary therapies led us to survey gene expression and the mucoepithelial microbiota in intestinal biopsies from children with autism and gastrointestinal disease and children with gastrointestinal disease alone. Ileal transcripts encoding disaccharidases and hexose transporters were deficient in children with autism, indicating impairment of the primary pathway for carbohydrate digestion and transport in enterocytes. Deficient expression of these enzymes and transporters was associated with expression of the intestinal transcription factor, CDX2. Metagenomic analysis of intestinal bacteria revealed compositional dysbiosis manifest as decreases in Bacteroidetes, increases in the ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria. Expression levels of disaccharidases and transporters were associated with the abundance of affected bacterial phylotypes. These results indicate a relationship between human intestinal gene expression and bacterial community structure and may provide insights into the pathophysiology of gastrointestinal disturbances in children with autism

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

What is the concordance between the medical record and patient self-report as data sources for ambulatory care?

BackgroundThe validity of quality of care assessments relies upon data quality, yet little is known about the relative completeness and validity of data sources for evaluating the quality of care.ObjectivesWe evaluated concordance between ambulatory medical record and patient survey data. Levels of concordance, variations by type of item, sources of disagreement between data sources, and implications for quality of care assessment efforts are discussed.Design and subjectsThis was an observational study that included 1270 patients sampled from 39 West Coast medical organizations with at least 1 of the following: diabetes, ischemic heart disease, asthma or chronic obstructive pulmonary disease, or low back pain.MeasuresItems from both data sources were grouped into 4 conceptual domains: diagnosis, clinical services delivered, counseling and referral, and medication use. We present total agreement, kappa, sensitivity, and specificity at the item and domain-levels and for all items combined.ResultsWe found good concordance between survey and medical records overall, but there was substantial variation within and across domains. The worst concordance was in the counseling and referrals domain, the best in the medication use domain. Patients were able to report with good sensitivity on memorable items.ConclusionsQuality ratings are likely to vary in differing directions, depending on the data source used. The most appropriate data source for analyses of components of and overall quality of care must be considered in light of study objectives and resources. We recommend data collection from multiple sources to most accurately portray the patient and provider experience of medical care

Does ambulatory process of care predict health-related quality of life outcomes for patients with chronic disease?

ObjectiveThe validity of quality of care measurement has important implications for practicing clinicians, their patients, and all involved with health care delivery. We used empirical data from managed care patients enrolled in west coast physician organizations to test the hypothesis that observed changes in health-related quality of life across a 2.5-year window reflecting process of care.Data sources/study settingPatient self-report data as well as clinically detailed medical record review regarding 963 patients with chronic disease associated with managed care from three west coast states.Study designProspective cohort study of change in health-related quality of life scores across 30 months as measured by change in SF-12 physical component scores.Data collection/extraction methodsPatient self-report and medical record abstraction.Principal findingsWe found a positive relationship between better process scores and higher burden of illness (p<.05). After adjustment for burden of illness, using an instrumental variables approach revealed better process is associated with smaller declines in SF-12 scores across a 30-month observation window (p=.014). The application of the best quartile of process of care to patients currently receiving poor process is associated with a 4.24 increment in delta SF-12-physical component summary scores.ConclusionsThe use of instrumental variables allowed us to demonstrate a significant relationship between better ambulatory process of care and better health-related quality of life. This finding underscores the importance of efforts to improve the process of care

Immune Responses and Performance Are Influenced by Respiratory Vaccine Antigen Type and Stress in Beef Calves

The study objective was to determine if a combined weaning and transportation stress model affected performance, antibody, endocrine, or hematological responses to modified-live virus (MLV) or killed virus (KV) respiratory vaccination in beef steers. In total, 48 calves (Day 0 BW = 226 ± 6.2 kg) from a single origin were used in a 2 × 2 factorial to evaluate main effects of stress model, vaccine type, and their interaction, resulting in four treatments (n = 12/treatment) including non-stress control (C) with KV (CKV), C with MLV (CMLV), stress model implementation (S) with KV (SKV), and S with MLV (SMLV). The C calves were weaned at the origin ranch on Day −37 and transported 472 km to the study site on Day −21 to allow acclimation. The S calves were weaned on Day −3, transported 460 km to a research facility on Day −2, held overnight, and transported 164 km to the study site on Day −1 to mimic the beef cattle marketing process. Vaccines were administered on Day 0 and KV was revaccinated on Day 14. The animal was the experimental unit and dependent variables were analyzed using PROC MIXED with repeated measures (day). A stress model effect (p = 0.01) existed for DMI from Day 0 to Day 7 with greater DMI for C (6.19 vs. 4.64 kg/day) when compared to S. The MLV groups had reduced (p = 0.05) ADG from Day 0 to Day 56, compared to KV. There was a vaccine type × day (p < 0.01) interaction with increased (p ≤ 0.01) PI3V- and IBRV-specific antibody titers for KV on Day 21; conversely, MLV had increased (p ≤ 0.01) BVDV titers on Days 14, 28, 35, 42, 49, and 56. Increased (p ≤ 0.05) BRSV titers were observed in a stress model × day (p < 0.01) interaction for S on Days 21, 28, 36, and 42; however, C exceeded S in BVDV-specific antibody concentration on Days 21, 28, and 49. A day effect (p < 0.01) was observed for serum haptoglobin with the greatest (p < 0.01) concentration on Day 3. Serum cortisol concentration was greater (p ≤ 0.04) for C vs. S on Days −2, 0, 1, 3, and 5. Total leukocytes were decreased for C vs. S on Days 0, 1, 3, 5, 7, 14, and 21 (p ≤ 0.02). A reduction (p ≤ 0.04) in total leukocytes was observed for MLV on Days 5, 7, and 14 vs. KV. Neutrophils and neutrophil:lymphocyte were markedly increased (p ≤ 0.01) for S on Day −2, whereas neutrophils were decreased (p ≤ 0.01) on Days 1 and 21 for S. Monocytes were decreased on Days 1, 5 and 7 for MLV (p ≤ 0.04) and Days −2 to 14 for S (p ≤ 0.03). Eosinophils were reduced (p = 0.007) for S vs. C on Day −2, yet a distinct rebound response (p = 0.03) was noted for S on Day 0. The results indicate that S and MLV vaccination more profoundly induced immunomodulation in beef calves

The success of Acinetobacter species; genetic, metabolic and virulence attributes

An understanding of why certain Acinetobacter species are more successful in causing nosocomial infections, transmission and epidemic spread in healthcare institutions compared with other species is lacking. We used genomic, phenotypic and virulence studies to identify differences between Acinetobacter species. Fourteen strains representing nine species were examined. Genomic analysis of six strains showed that the A. baumannii core genome contains many genes important for diverse metabolism and survival in the host. Most of the A. baumannii core genes were also present in one or more of the less clinically successful species. In contrast, when the accessory genome of an individual A. baumannii strain was compared to a strain of a less successful species (A. calcoaceticus RUH2202), many operons with putative virulence function were found to be present only in the A. baumannii strain, including the csu operon, the acinetobactin chromosomal cluster, and bacterial defence mechanisms. Phenotype microarray analysis showed that compared to A. calcoaceticus (RUH2202), A. baumannii ATCC 19606(T) was able to utilise nitrogen sources more effectively and was more tolerant to pH, osmotic and antimicrobial stress. Virulence differences were also observed, with A. baumannii ATCC 19606(T), A. pittii SH024, and A. nosocomialis RUH2624 persisting and forming larger biofilms on human skin than A. calcoaceticus. A. baumannii ATCC 19606 T and A. pittii SH024 were also able to survive in a murine thigh infection model, whereas the other two species were eradicated. The current study provides important insights into the elucidation of differences in clinical relevance among Acinetobacter species

Characteristics of the bacterial strains used in this study.

<p>DE, Germany; FR, France; IT, Italy; NL, The Netherlands; SE, Sweden; US, United States.</p>1<p><i>A. baumannii</i> SDF was not included in this study due to its significantly reduced genome size and gene number compared to the <i>A. baumannii</i> isolates derived from human sources.</p>2<p>Representative strains of the <i>A. calcoaceticus</i> – <i>A. baumannii</i> complex that were analysed in detail.</p

Genetic organisation and conservation of the siderophore clusters found in <i>A. baumannii</i> ATCC 19606^T and not in <i>A. calcoaceticus</i>.

<p>(<b>A</b>) Siderophore cluster 1 (operons 36–39) is known as the acinetobactin chromosomal cluster, and (<b>B</b>) siderophore cluster 2 (operon 17) (See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046984#pone-0046984-t002" target="_blank">Table 2</a> for details about the operons). The presence of homologues for each gene in <i>A. pittii</i>, <i>A. nosocomialis</i>, and <i>A. calcoaceticus</i> is shown.</p

Metabolic diversity of specific strains of the <i>A. calcoaceticus</i> – <i>A. baumannii</i> complex.

<p>(<b>A</b>) Phenotype Microarray (PM) comparative results showing the number of compounds used (green) or not used (red) by <i>A. baumannii</i> ATCC 19606^T [A], <i>A. nosocomialis</i> [B], <i>A. pittii</i> [C] <i>and A. calcoaceticus</i> [D]. The external circle and PM number represent the Biolog plate number. (<b>B</b>) <i>A. baumannii</i> ATCC 19606^T is able to metabolise the carbon source, D–glucarate and produce α–Ketoglutarate through the functional enzymes, D–glucarate dehydrogenase and KDG dehydratase. α–Ketoglutarate is then utilized in the citrate cycle. These enzymes are not found in <i>A. calcoaceticus</i>.</p