MRI biomarkers for Alzheimer's disease: the impact of functional connectivity in the default mode network and structural connectivity between lobes on diagnostic accuracy.

BACKGROUND: At present, clinical use of MRI in Alzheimer's disease (AD) is mostly focused on the assessment of brain atrophy, namely in the hippocampal region. Despite this, multiple biomarkers reflecting structural and functional brain connectivity changes have shown promising results in the assessment of AD. To help identify the most relevant ones that may stand a chance of being used in clinical practice, we compared multiple biomarker in terms of their value to discriminate AD from healthy controls and analyzed their age dependency. METHODS: 20 AD patients and 20 matched controls underwent MRI-scanning (3T GE), including T1-weighted, diffusion-MRI, and resting-state-fMRI (rsfMRI). Whole brain, white matter, gray matter, cortical gray matter and hippocampi volumes were measured using icobrain. rsfMRI between regions of the default-mode-network (DMN) was assessed using group independent-component-analysis. Median diffusivity and kurtosis were determined in gray and white-matter. DTI data was used to evaluate pairwise structural connectivity between lobar regions and the hippocampi.Logistic-Regression and Random-Forest models were trained to classify AD-status based on, respectively different isolated features and age, and feature-groups combined with age. RESULTS: Hippocampal features, features reflecting the functional connectivity between the medial-Pre-Frontal-Cortex (mPFC) and the posterior regions of the DMN, and structural interhemispheric frontal connectivity showed the strongest differences between AD-patients and controls. Structural interhemispheric parietal connectivity, structural connectivity between the parietal lobe and hippocampus in the right hemisphere, and mPFC-DMN-features, showed only an association with AD-status (p < 0.05) but not with age. Hippocampi volumes showed an association both with age and AD-status (p < 0.05).Smallest-hippocampus-volume was the most discriminative feature. The best performance (accuracy:0.74, sensitivity:0.74, specificity:0.74) was obtained with an RF-model combining the best feature from each feature-group (smallest hippocampus volume, WM volume, median GM MD, lTPJ-mPFC connectivity and structural interhemispheric frontal connectivity) and age. CONCLUSIONS: Brain connectivity changes caused by AD are reflected in multiple MRI-biomarkers. Decline in both the functional DMN-connectivity and the parietal interhemispheric structural connectivity may assist sepparating healthy-aging driven changes from AD, complementing hippocampal volumes which are affected by both aging and AD.

Altered default mode network activity and cortical thickness as vulnerability indicators for SCZ: a preliminary resting state MRI study.

OBJECTIVE: Alterations in brain function in patients with schizophrenia (SCZ) and other neuropsychiatric disorders are evident not only during specific cognitive challenges, but also from functional MRI data obtained during a resting state. Patients with chronic SCZ have shown deficits in default mood network (DMN) and gray matter volume in resting-state functional magnetic resonance imaging (rs-fMRI). However, cortical thickness and surface area in first-episode schizophrenic patients have rarely been investigated. PATIENTS AND METHODS: In the present study, we applied independent component analysis (ICA) to a series of rs-fMRIs of 15 SCZ patients and 15 matched healthy controls. The data were analyzed using MELODIC of FMRIB's Software Library (FSL version 5.9; www.fmrib.ox.ac.uk/fsl) to identify large-scale patterns of temporal signal-intensity coherence. RESULTS: Patients with SCZ showed significantly higher functional connectivity in the DMN, auditory network, and cerebellum network (p=0.049, p=0.05, and p=0.007, respectively) than matched healthy controls. The patients also exhibited significantly less cortical thickness, primarily in the bilateral prefrontal and parietal cortex, and higher thickness in the bilateral anterior temporal lobes, left medial orbitofrontal cortex, and left cuneus than the matched healthy controls. CONCLUSIONS: These results indicate that significantly abnormal DMN connectivity and cortical thickness contribute to local functional pathology in patients with SCZ.

Molecular phylogeny of Sarcocystis fayeri (Apicomplexa: Sarcocystidae) from the domestic horse Equus caballus based on 18S rRNA gene sequences and its prevalence.

Sarcocystosis is a parasitic disease caused by an intracellular protozoan parasite Sarcocystis belonging to the phylum Apicomplexa. These parasites have a requisite two-host life cycle. Recently, there are many Sarcocystis species that identified morphologically. In the present study, diaphragmatic muscle samples from the domestic horse (Equus caballus) were examined for Sarcocystis infection. The natural infection with sarcocysts was recorded to be 62·5% for only microcysts in the infected muscles. Molecular analysis using the 18S rRNA gene was conducted to swiftly and accurately identify the recovered species. Studies on the expression of the 18S rRNA gene have confirmed that the present parasite isolates belong to the Sarcocystis genus. The sequence data showed significant identities (>80%) with archived gene sequences from species within the Sarcocystidae family, and a dendrogram showing the phylogenetic relationship was constructed. The most closely related species were the previously described Sarcocystis fayeri and Sarcocystis bertrami. The current data showed that the present species was identified as S. fayeri and deposited in GenBank (accession number MF614956.1). This study highlights the importance of the genetic data in the exact taxonomy within sarcocystid species.

Long-term treatment with finasteride induces apoptosis and pathological changes in female mice.

Androgenetic alopecia is the most common type of alopecia, and it affects humans of both genders. Finasteride is a type II selective 5α-reductase inhibitor that is administered orally to treat androgenetic alopecia and benign prostatic hyperplasia in human males. However, its effect on the vital organs of females is unknown. This study was designed to investigate the effects of finasteride on the vital organs such as liver, kidney, and heart of female mice. To study the prospective effects of finasteride, female mice were orally administered two doses of finasteride (0.5 and 1.5 mg/kg) once daily for 35 days, and serum levels of various biochemical parameters and histopathology of various organs were examined. The results showed that serum levels of alkaline phosphatase were significantly increased by both high- and low-dose finasteride, whereas cholesterol was significantly increased by the high dose only. Creatine kinase was significantly increased by the high and low doses, whereas glucose was significantly decreased by both doses. Histopathological analysis and DNA damage assays showed that finasteride has adverse effects within both the short and the long periods in female mice. In addition, the proapoptotic genes Bax and caspase-3 were significantly increased by high dose finasteride, whereas the antiapoptotic gene Bcl-2 was significantly decreased by the low and high doses. In conclusion, finasteride is not currently approved for therapeutic use in females, and the findings in this study suggest caution in any future consideration of such use.

Design and control of multi-actuated atomic force microscope for large-range and high-speed imaging.

This paper presents the design and control of a high-speed and large-range atomic force microscopy (AFM). A multi-actuation scheme is proposed where several nano-positioners cooperate to achieve the range and speed requirements. A simple data-based control design methodology is presented to effectively operate the AFM scanner components. The proposed controllers compensate for the coupled dynamics and divide the positioning responsibilities between the scanner components. As a result, the multi-actuated scanner behavior is equivalent to that of a single X-Y-Z positioner with large range and high speed. The scanner of the designed AFM is composed of five nano-positioners, features 6 µm out-of-plane and 120 µm lateral ranges and is capable of high-speed operation. The presented AFM has a modular design with laser spot size of 3.5 µm suitable for small cantilever, an optical view of the sample and probe, a conveniently large waterproof sample stage and a 20 MHz data throughput for high resolution image acquisition at high imaging speeds. This AFM is used to visualize etching of calcite in a solution of sulfuric acid. Layer-by-layer dissolution and pit formation along the crystalline lines in a low pH environment is observed in real time.