Publications

BACKGROUND

Mutations in ATP8B1 (FIC1) underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis) to intermittent (benign recurrent intrahepatic cholestasis). The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficiency.

METHODOLOGY/PRINCIPAL FINDINGS

We investigated the effect of genetic background on phenotypes of ATP8B1-deficient and wild-type mice, using C57Bl/6 (B6), 129, and (B6-129) F1 strain backgrounds. B6 background resulted in greater abnormalities in ATP8B1-deficient mice than did 129 and/or F1 background. ATP8B1-deficient pups of B6 background gained less weight. In adult ATP8B1-deficient mice at baseline, those of B6 background had lower serum cholesterol levels, higher serum alkaline phosphatase levels, and larger livers. After challenge with cholate-supplemented diet, these mice exhibited higher serum alkaline phosphatase and bilirubin levels, greater weight loss and larger livers. ATP8B1-deficient phenotypes in mice of F1 and 129 backgrounds are usually similar, suggesting that susceptibility to manifestations of ATP8B1 deficiency may be recessive. We also detected differences in hepatobiliary phenotypes between wild-type mice of differing strains.

CONCLUSIONS/SIGNIFICANCE

Our results indicate that the ATP8B1-deficient mouse in a B6 background may be a better model of human ATP8B1 deficiency and highlight the importance of informed background strain selection for mouse models of liver disease.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major source of morbidity and contribute significantly to healthcare costs. Although bacterial infections are implicated in nearly 50% of exacerbations, only a handful of pathogens have been consistently identified in COPD airways, primarily by culture-based methods, and the bacterial microbiota in acute exacerbations remains largely uncharacterized. The aim of this study was to comprehensively profile airway bacterial communities using a culture-independent microarray, the 16S rRNA PhyloChip, of a cohort of COPD patients requiring ventilatory support and antibiotic therapy for exacerbation-related respiratory failure. PhyloChip analysis revealed the presence of over 1,200 bacterial taxa representing 140 distinct families, many previously undetected in airway diseases; bacterial community composition was strongly influenced by the duration of intubation. A core community of 75 taxa was detected in all patients, many of which are known pathogens. Bacterial community diversity in COPD airways is substantially greater than previously recognized and includes a number of potential pathogens detected in the setting of antibiotic exposure. Comprehensive assessment of the COPD airway microbiota using high-throughput, culture-independent methods may prove key to understanding the relationships between airway bacterial colonization, acute exacerbation, and clinical outcomes in this and other chronic inflammatory airway diseases.

Modern laboratory techniques for the detection of novel human viruses are greatly needed as physicians and epidemiologists increasingly deal with infectious diseases caused by new or previously unrecognized pathogens. There are many clinical syndromes in which viruses are suspected to play a role, but for which traditional microbiology techniques routinely fail in uncovering the etiologic agent. In addition, new viruses continue to challenge the human population owing to the encroachment of human settlements into animal and livestock habitats, globalization, climate change, growing numbers of immunocompromised people and bioterrorism. Metagenomics-based tools, such as microarrays and high-throughput sequencing are ideal for responding to these challenges. Pan-viral microarrays, containing representative sequences from all known viruses, have been used to detect novel and distantly-related variants of known viruses. Sequencing-based methods have also been successfully employed to detect novel viruses and have the potential to detect the full spectrum of viruses, including those present in low numbers.

BACKGROUND

The San Joaquin Valley (SJV) in California ranks among the worst in the USA in terms of air quality, and its residents report some of the highest rates of asthma symptoms and asthma-related emergency department (ED) visits and hospitalisations in California. Using California Health Interview Survey data, the authors examined associations between air pollution and asthma morbidity in this region.

METHODS

Eligible subjects were SJV residents (2001 California Health Interview Survey) who reported physician-diagnosed asthma (n=1502, 14.6%). The authors considered two outcomes indicative of uncontrolled asthma: (1) daily or weekly asthma symptoms and (2) asthma-related ED visits or hospitalisation in the past year. Based on residential zip code, subjects were assigned annual average concentrations of ozone, PM(10) and PM(2.5) for the 1-year period prior to the interview date from their closest government air monitoring station within an 8 km (5 miles) radius.

RESULTS

Adjusting for age, gender, race/ethnicity, poverty level and insurance status, the authors observed increased odds of experiencing daily or weekly asthma symptoms for ozone, PM(10) and PM(2.5) (OR(ozone) 1.23, 95% CI 0.94 to 1.60 per 10 ppb; OR(PM10) 1.29, 95% CI 1.05 to 1.57 per 10 microg/m(3); and OR(PM2.5) 1.82; 95% CI 1.11 to 2.98 per 10 microg/m(3)). The authors also observed increased odds of asthma-related ED visits or hospitalisations for ozone (OR 1.49, 95% CI 1.05 to 2.11 per 10 ppb) and a 29% increase in odds for PM(10) (OR 1.29, 95% CI 0.99 to 1.69 per 10 microg/m(3)).

CONCLUSIONS

Overall, these findings suggest that individuals with asthma living in areas of the SJV with high ozone and particulate pollution levels are more likely to have frequent asthma symptoms and asthma-related ED visits and hospitalisations.

Epidemiological studies of biomass smoke health effects have been conducted in a variety of settings and with a variety of study designs. The Health Effects Workgroup discussed several approaches for the investigation of health effects in communities exposed to wood smoke from nearby wildland fires, intentional agricultural burning, or residential biomass burning devices such as woodstoves or cookstoves. This presentation briefly reviews observational and intervention studies that have been conducted within these exposure settings. The review is followed by a summary of discussion points among the workgroup members with particular emphasis on study design and the use of biomarkers for assessing outcomes in biomass smoke-exposed populations.

This article assesses the effect of systemic lupus erythematosus (SLE) on the shealth-related quality of life (HRQOL) and employment of persons with this condition. Far more than impaired health status can affect an individual's quality of life. The term "health-related quality of life" is used to connote the decrement in an individual's quality of life specifically attributable to a decrease in health status. The article presents evidence on employment because this plays a crucial role in determining the quality of life of most Americans of normal working age. However, evidence is also presented with respect to other domains of activity, because most people work to live but not many live to work.

Older adults often receive suboptimal care during hospitalizations and transitions to postacute settings. Inpatient geriatric services have been shown to increase care quality but have not improved patient outcomes consistently. Acute Care for the Elderly units improve patient outcomes but are resource intensive. Transitional care has been shown to reduce hospital readmissions and healthcare costs. This article describes the Geriatric Floating Interdisciplinary Transition Team (Geri-FITT), a model that combines the strengths of inpatient geriatric evaluation and comanagement and transitional care models by creating an inpatient comanagement service that also delivers transitional care. The Geri-FITT model is designed to improve the hospital care of older adults and their transitions to postacute settings. In Geri-FITT, a geriatrician-geriatric nurse practitioner team assesses patients, comanages geriatric syndromes, provides staff education, encourages patient self-management, communicates with primary care providers, and follows up with patients soon after discharge. This pilot cohort study of Geri-FITT included hospitalized patients aged 70 and older on four general medicine services (two Geri-FITT, two usual care) at an academic medical center (N=717). The study assessed the effect of Geri-FITT on patients' care transition quality (Care Transitions Measure) and their satisfaction with hospital care (four questions). The results indicate that Geri-FITT is associated with slightly higher, though not statistically significantly so, quality care transitions and greater patient satisfaction with inpatient care. Geri-FITT may be a feasible approach to enhancing inpatient management and transitional care for older adults. Further study of its effect on these and other outcomes in other healthcare settings seems warranted.