Low alanine aminotransferase levels and higher number of cardiovascular events in people with Type 2 diabetes: analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS: To determine whether alanine aminotransferase or gamma-glutamyltransferase levels, as markers of liver health and non-alcoholic fatty liver disease, might predict cardiovascular events in people with Type 2 diabetes. METHODS: Data from the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed to examine the relationship between liver enzymes and incident cardiovascular events (non-fatal myocardial infarction, stroke, coronary and other cardiovascular death, coronary or carotid revascularization) over 5 years. RESULTS: Alanine aminotransferase measure had a linear inverse relationship with the first cardiovascular event occurring in participants during the study period. After adjustment, for every 1 sd higher baseline alanine aminotransferase measure (13.2 U/l), the risk of a cardiovascular event was 7% lower (95% CI 4-13; P = 0.02). Participants with alanine aminotransferase levels below and above the reference range 8-41 U/l for women and 9-59 U/l for men, had hazard ratios for a cardiovascular event of 1.86 (95% CI 1.12-3.09) and 0.65 (95% CI 0.49-0.87), respectively (P = 0.001). No relationship was found for gamma-glutamyltransferase. CONCLUSIONS: The data may indicate that in people with Type 2 diabetes, which is associated with higher alanine aminotransferase levels because of prevalent non-alcoholic fatty liver disease, a low alanine aminotransferase level is a marker of hepatic or systemic frailty rather than health.

Lower serum fibroblast activation protein shows promise in the exclusion of clinically significant liver fibrosis due to non-alcoholic fatty liver disease in diabetes and obesity.

UNLABELLED: Non-alcoholic fatty liver disease (NAFLD) is common in diabetes and obesity but few have clinically significant liver fibrosis. Improved risk-assessment is needed as the commonly used clinical-risk algorithm, the NAFLD fibrosis score (NFS), is often inconclusive. AIMS: To determine whether circulating fibroblast activation protein (cFAP), which is elevated in cirrhosis, has value in excluding significant fibrosis, particularly combined with NFS. METHODS: cFAP was measured in 106 with type 2 diabetes who had transient elastography (Cohort 1) and 146 with morbid obesity who had liver biopsy (Cohort 2). RESULTS: In Cohort 1, cFAP (per SD) independently associated with median liver stiffness (LSM) ≥ 10.3 kPa with OR of 2.0 (95% CI 1.2-3.4), p=0.006. There was 0.12 OR (95% CI 0.03-0.61) of LSM ≥ 10.3 kPa for those in the lowest compared with the highest FAP tertile (p=0.010). FAP levels below 730 pmol AMC/min/mL had 95% NPV for LSM ≥ 10.3 kPa and reclassified 41% of 64 subjects from NFS 'indeterminate-risk' to 'low-risk'. In Cohort 2, cFAP (per SD), associated with 1.7 fold (95% CI 1.1-2.8) increased odds of significant fibrosis (F ≥ 2), p=0.021, and low cFAP reclassified 49% of 73 subjects from 'indeterminate-risk' to 'low-risk'. CONCLUSIONS: Lower cFAP, when combined with NFS, may have clinical utility in excluding significant fibrosis in diabetes and obesity.

Influence of Carbon and Microbial Community Priming on the Attenuation of Uranium in a Contaminated Floodplain Aquifer.

The capacity for subsurface sediments to sequester radionuclide contaminants, such as uranium (U), and retain them after bioremediation efforts are completed is critical to the long-term stewardship of re-mediated sites. In U bioremediation strategies, carbon amendment stimulates bioreduction of U(VI) to U(IV), immobilizing it within the sediments. Sediments enriched in natural organic matter are naturally capable of sequestering significant U, but may serve as sources to the aquifer, contributing to plume persistence. Two types of organic-rich sediments were compared to better understand U release mechanisms. Sediments that were artificially primed for U removal were retrieved from an area previously biostimulated while detrital-rich sediments were collected from a location never subject to amendment. Batch incubations demonstrated that primed sediments rapidly removed uranium from the groundwater, whereas naturally reduced sediments released a sizeable portion of U before U(VI)-reduction commenced. Column experiments confirmed that U release persisted for 65 pore volumes in naturally reduced sediments, demonstrating their sink-source behavior. Acetate addition to primed sediments shifted the microbial community from sulfate-reducing bacteria within Desulfobacteraceae to the iron-reducing Geobacteraceae and Firmicutes, associated with efficient U(VI) removal and retention, respectively. In contrast, Geobacteraceae communities in naturally reduced sediments were replaced by sequences with similarity to Pseudomonas spp. during U release, while U(VI) removal only occurred with enrichment of Firmicutes. These investigations stress the importance of characterizing zones with heterogeneous carbon pools at U-contaminated sites prior to the determination of a remedial strategy to identify areas, which may contribute to long-term sourcing of the contaminants.

Diabetes and nonalcoholic Fatty liver disease: a pathogenic duo.

Recent data increasingly support a complex interplay between the metabolic condition diabetes mellitus and the pathologically defined nonalcoholic fatty liver disease (NAFLD). NAFLD predicts the development of type 2 diabetes and vice versa, and each condition may serve as a progression factor for the other. Although the association of diabetes and NAFLD is likely to be partly the result of a "common soil," it is also probable that diabetes interacts with NAFLD through specific pathogenic mechanisms. In particular, through interrelated metabolic pathways currently only partly understood, diabetes appears to accelerate the progression of NAFLD to nonalcoholic steatohepatitis, defined by the presence of necroinflammation, with varying degrees of liver fibrosis. In the research setting, obstacles that have made the identification of clinically significant NAFLD, and particularly nonalcoholic steatohepatitis, difficult are being addressed with the use of new imaging techniques combined with risk algorithms derived from peripheral blood profiling. These techniques are likely to be used in the diabetes population in the near future. This review examines the pathogenic links between NAFLD and diabetes by exploring the epidemiological evidence in humans and also through newer animal models. Emerging technology to help screen noninvasively for differing pathological forms of NAFLD and the potential role of preventive and therapeutic approaches for NAFLD in the setting of diabetes are also examined.

Molecular analysis of the metabolic rates of discrete subsurface populations of sulfate reducers.

Elucidating the in situ metabolic activity of phylogenetically diverse populations of sulfate-reducing microorganisms that populate anoxic sedimentary environments is key to understanding subsurface ecology. Previous pure culture studies have demonstrated that the transcript abundance of dissimilatory (bi)sulfite reductase genes is correlated with the sulfate-reducing activity of individual cells. To evaluate whether expression of these genes was diagnostic for subsurface communities, dissimilatory (bi)sulfite reductase gene transcript abundance in phylogenetically distinct sulfate-reducing populations was quantified during a field experiment in which acetate was added to uranium-contaminated groundwater. Analysis of dsrAB sequences prior to the addition of acetate indicated that Desulfobacteraceae, Desulfobulbaceae, and Syntrophaceae-related sulfate reducers were the most abundant. Quantifying dsrB transcripts of the individual populations suggested that Desulfobacteraceae initially had higher dsrB transcripts per cell than Desulfobulbaceae or Syntrophaceae populations and that the activity of Desulfobacteraceae increased further when the metabolism of dissimilatory metal reducers competing for the added acetate declined. In contrast, dsrB transcript abundance in Desulfobulbaceae and Syntrophaceae remained relatively constant, suggesting a lack of stimulation by added acetate. The indication of higher sulfate-reducing activity in the Desulfobacteraceae was consistent with the finding that Desulfobacteraceae became the predominant component of the sulfate-reducing community. Discontinuing acetate additions resulted in a decline in dsrB transcript abundance in the Desulfobacteraceae. These results suggest that monitoring transcripts of dissimilatory (bi)sulfite reductase genes in distinct populations of sulfate reducers can provide insight into the relative rates of metabolism of different components of the sulfate-reducing community and their ability to respond to environmental perturbations.

Feedbacks between hydrological heterogeneity and bioremediation induced biogeochemical transformations.

For guiding optimal design and interpretation of in situ treatments that strongly perturb subsurface systems, knowledge about the spatial and temporal patterns of mass transport and reaction intensities are important. Here, a procedure was developed and applied to time-lapse concentrations of a conservative tracer (bromide), an injected amendment (acetate) and reactive species (iron(II), uranium(VI) and sulfate) associated with two field scale biostimulation experiments, which were conducted successively at the same field location over two years. The procedure is based on a temporal moment analysis approach that relies on a streamtube approximation. The study shows that biostimulated reactions can be considerably influenced by subsurface hydrological and geochemical heterogeneities: the delivery of bromide and acetate and the intensity of the sulfate reduction is interpreted to be predominantly driven by the hydrological heterogeneity, while the intensity of the iron reduction is interpreted to be primarily controlled by the geochemical heterogeneity. The intensity of the uranium(VI) reduction appears to be impacted by both the hydrological and geochemical heterogeneity. Finally, the study documents the existence of feedbacks between hydrological heterogeneity and remediation-induced biogeochemical transformations at the field scale, particularly the development of precipitates that may cause clogging end flow rerouting.

Reflectance anisotropy spectra of the diamond (100)-(2x1) surface: evidence of strongly bound surface state excitons.

We compare the results of ab initio calculations with measured reflection anisotropy spectra and show that strongly bound surface-state excitons occur on the clean diamond (100) surface. These excitons are found to have a binding energy close to 1 eV, the strongest ever observed at a semiconductor surface. Important electron-hole interaction effects on the line shape of the optical transitions above the surface-state gap are also found.

Cognitive and affective responses to lithium in patients with organic brain syndrome.

The authors describe a series of patients with organic brain syndrome who showed a dramatic clinical response to lithium carbonate therapy. None of the patients had been diagnosed as manic-depressive. Most had extensive psychiatric treatment experiences and had been given both affective and cognitive diagnoses. Six of the eight patients also qualified for the diagnosis of alcoholism. They had been treated with a wide variety of psychotherapeutic medications. Lithium was found to be rapidly and dramatically effective in patients with static lesions of the central nervous system who showed a combination of dementia and agitated depression.

An outbreak in 1965 of severe respiratory illness caused by the Legionnaires' disease bacterium.

In January 1977 an unsolved outbreak of infection at St. Elizabeth's Hospital (Washington, D.C.) that occurred in 1965 was linked with Legionnaires' disease. The link was made by fluorescent antibody testing with the bacterium isolated from tissues of persons with Legionnaires' disease in the 1976 outbreak in Philadelphia. In July and August 1965, an epidemic of severe respiratory disease characterized by abrupt onset of high fever, weakness, malaise, and nonproductive cough, frequently accompanied by radiographic evidence of pneumonia, affected at least 81 patients at St. Elizabeth's Hospital, a general psychiatric hospital. Fourteen (17%) of the affected patients died. Intensive epidemiologic and laboratory investigations in 1965 did not determine the etiology. The etiologic organism may have become airborne from sites of soil excavation.

The epidemiology of St. Louis encephalitis in Corpus Christi, Texas, 1966.

In the summer of 1966, an epidemic of St. Louis encephalitis occurred in Corpus Christi, Texas, coincident with one occurring in Dallas about 563 km to the north. Among the 76 cases confirmed in Corpus Christi, there were two deaths; the attack rate was 41.0 per 100,000. In contrast with a concurrent outbreak in Dallas and the 1964 outbreak in Houston, attack rates were much higher in populations of the upper socioeconomic districts. This distribution may have resulted from the combined effects of an unusual concentration of vector mosquito breeding sites in storm sewers in the upper socioeconomic districts and a higher degree of residual immunity in the residents of the lower socioeconomic areas.