Diagnosed Mild Cognitive Impairment Due to Alzheimer’s Disease with PET Biomarkers of Beta Amyloid and Neuronal Dysfunction

The aim of this study is to identify mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) using amyloid imaging of beta amyloid (Aβ) deposition and FDG imaging of reflecting neuronal dysfunction as PET biomarkers. Sixty-eight MCI patients underwent cognitive testing, [11C]-PIB PET and [18F]-FDG PET at baseline and follow-up. Regions of interest were defined on co-registered MRI. PIB distribution volume ratio (DVR) was calculated using Logan graphical analysis, and the standardized uptake value ratio (SUVR) on the same regions was used as quantitative analysis for [18F]-FDG. Thirty (44.1%) of all 68 MCI patients converted to AD over 19.2±7.1 months. The annual rate of MCI conversion was 23.4%. A positive Aβ PET biomarker significantly identified MCI due to AD in individual MCI subjects with a sensitivity (SS) of 96.6% and specificity (SP) of 42.1%. The positive predictive value (PPV) was 56.8%. A positive Aβ biomarker in APOE ε4/4 carriers distinguished with a SS of 100%. In individual MCI subjects who had a prominent impairment in episodic memory and aged older than 75 years, an Aβ biomarker identified MCI due to AD with a greater SS of 100%, SP of 66.6% and PPV of 80%, compared to FDG biomarker alone or both PET biomarkers combined. In contrast, when assessed in precuneus, both Aβ and FDG biomarkers had the greatest level of certainty for MCI due to AD with a PPV of 87.8%. The Aβ PET biomarker primarily defines MCI due to AD in individual MCI subjects. Furthermore, combined FDG biomarker in a cortical region of precuneus provides an added diagnostic value in predicting AD over a short period.     

Maternal Age at First Delivery Is Associated with the Risk of Metabolic Syndrome in Postmenopausal Women: From 2008–2010 Korean National Health and Nutrition Examination Survey

BackgroundRecent cross-sectional studies demonstrated that earlier maternal age at first childbirth is correlated with a higher risk of diabetes in postmenopausal women. In this study, we evaluated whether the age at first delivery is associated with the risk of metabolic syndrome (MetS) in postmenopausal women.MethodsA total of 4,261 postmenopausal women aged 45 years or older were analyzed using data generated from Korea National Health and Nutrition Examination Surveys (2008–2010). Subjects were divided into three groups according to the maternal age at first delivery as follows: ≤ 20 years (n=878), 21-25 years (n=2314), and ≥ 26 years (n=1069).ResultsApproximately 37% of subjects had MetS. The prevalence of MetS showed a gradual increase as maternal age at first delivery decreased (≥ 26 years = 30.9% vs. 21-25 years = 39.9% vs. ≤ 20 years = 50.8%, respectively, p < 0.001). Central obesity indices such as trunk fat mass and waist circumference were significantly higher in the group aged ≤ 20 years than other groups. After adjustments for confounding factors, the odds ratios (ORs) for predicting the presence of MetS increased gradually as first delivery age decreased (≥ 26 years vs. 21-25 years vs. ≤ 20 years: OR [95% CI] = 1 vs. 1.324 [1.118-1.567] vs. 1.641 [1.322-2.036], respectively). Among components of MetS, younger maternal age at first delivery (≤ 20 years) was significantly associated with increased waist circumference (OR [95% CI] = 1.735 [1.41-2.13]), elevated blood pressure (1.261 [1.02-1.57]), high triglyceride (1.333 [1.072-1.659]), and low HDL-cholesterol (1.335[1.084-1.643]).ConclusionsOur findings suggest that younger maternal age at first delivery is independently associated with a higher risk of central obesity and MetS in postmenopausal women.     

A Multicenter,Open-Label,Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18–40 Year Old Subjects with Diagnosed Atopic Dermatitis

Background

Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.

Objective

This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects.

Methods

Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.

Results

The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.

Limitations

The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.

Conclusion

MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.

Trial Registration

ClinicalTrials.gov NCT00316602     

A molecular dynamics study on the thermal rectification effect at the solid–liquid interfaces between the face-centred cubic (FCC) of gold (Au) with the surfaces of (100), (110) and (111) crystal planes facing the liquid methane (CH4)

A molecular dynamics study on the solid–liquid (S-L) interfaces for solid wall of gold having the face-centred cubic of (100), (110) and (111) crystal planes contacting liquid methane was examined using non-equilibrium molecular dynamics simulations. An investigation on the thermal rectification effect was performed by measuring the thermal boundary conductance (TBC) at the S-L interface. Thermal rectification can be defined as the differences in the TBC at the interface between the two opposite heat flow directions; one is from the liquid to solid and vice versa. The thermal rectifications are up to 13% for (110) crystal plane, followed by 6% and 0.3% for (111) and (100) crystal planes, respectively. It was found that the TBC at the S-L interface was influenced by the magnitude of the adsorption of liquid molecules at the vicinity of the interface. The results show that due to the different temperature distribution, different magnitude of the adsorption of liquid molecules is generated for the two opposite heat flow directions. On the surface of the solid walls for (110) crystal plane, where lattice-scale corrugation exists, it was found that there exists difference in distance between the surface layers of the solid and liquid across the interface between the cases of the two opposite heat flow directions, which affects the TBC at the interface. The present results suggest that the factors that influence the thermal rectification at the S-L interface are the magnitude of the adsorption of liquid molecules and the surface structure of the solid walls that differ significantly among the three types of crystal planes.