Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity.

The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β(2)-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles

Performance of Noninvasive Tests of Fibrosis Among Asians, Hispanic, and non-Hispanic Whites in the STELLAR Trials

BACKGROUND & AIMS: The effect of race on routinely available noninvasive tests of fibrosis is incompletely under stood. This study evaluated the performance of noninvasive tests among white and Asian pa tients in the STELLAR trials (NCT03053050 and NCT03053063), which evaluated selonsertib in patients with advanced (F3-F4) fibrosis due to nonalcoholic steatohepatitis (NASH). METHODS: Baseline liver biopsies were centrally read using the NASH Clinical Research Network system, and 4 noninvasive tests (Nonalcoholic fatty liver disease fibrosis score [NFS], Fibrosis-4 index [FIB-4], Enhanced Liver Fibrosis test [ELF], and liver stiffness by vibration-controlled transient elastography) were measured. The performance of these tests to discriminate advanced fibrosis was evaluated using areas under the receiver operating characteristics curves with 5-fold cross validation repeated 100 times. RESULTS: Among 3207 patients screened with evaluable liver histology, 2281 were whites and 762 were Asians. Seventy-two percent of whites and 67% of Asians had advanced fibrosis. The areas under the receiver operating characteristics curves of the noninvasive tests for advanced fibrosis were similar in whites and Asians: 0.73 and 0.75 for NFS, 0.78 and 0.80 for FIB-4, 0.79 and 0.81 for ELF, and 0.80 and 0.83 for liver stiffness, respectively. At the published cutoffs, the tests had similar sensitivities and specificities in the 2 groups. However, the sensitivities of NFS, FIB-4, and ELF were low in both white and Asian patients younger than 40 years. CONCLUSIONS: In the global phase III STELLAR trials, the diagnostic performance of routinely available noninvasive tests for the detection of advanced fibrosis due to NASH was acceptable and similar between white and Asian patients

Assessing trends and predictors of tuberculosis in Taiwan

<p>Abstract</p> <p>Background</p> <p>Variety of environmental and individual factors can cause tuberculosis (TB) incidence change. The purpose of this study was to assess the characteristics of TB trends in the period 2004 - 2008 in Taiwan by month, year, gender, age, temperature, seasonality, and aborigines.</p> <p>Methods</p> <p>The generalized regression models were used to examine the potential predictors for the monthly TB incidence in regional and national scales.</p> <p>Results</p> <p>We found that (<it>i</it>) in Taiwan the average TB incidence was 68 per 100,000 population with mortality rate of 0.036 person^-1yr^-1, (<it>ii</it>) the highest TB incidence rate was found in eastern Taiwan (116 per 100,000 population) with the largest proportion of TB relapse cases (8.17%), (<it>iii</it>) seasonality, aborigines, gender, and age had a consistent and dominant role in constructing TB incidence patterns in Taiwan, and (<it>iv</it>) gender, time trend, and 2-month lag maximum temperature showed strong association with TB trends in aboriginal subpopulations.</p> <p>Conclusions</p> <p>The proposed Poisson regression model is capable of forecasting patterns of TB incidence at regional and national scales. This study suggested that assessment of TB trends in eastern Taiwan presents an important opportunity for understanding the time-series dynamics and control of TB infections, given that this is the typical host demography in regions where these infections remain major public health problems.</p