Antemortem differential diagnosis of dementia pathology using structural MRI: Differential-STAND

The common neurodegenerative pathologies underlying dementia are Alzheimer's disease (AD), Lewy body disease (LBD) and frontotemporal lobar degeneration (FTLD). Our aim was to identify patterns of atrophy unique to each of these diseases using antemortem structural MRI scans of pathologically confirmed dementia cases and build an MRI-based differential diagnosis system. Our approach of creating atrophy maps using structural MRI and applying them for classification of new incoming patients is labeled Differential-STAND (Differential Diagnosis Based on Structural Abnormality in Neurodegeneration). Pathologically confirmed subjects with a single dementing pathologic diagnosis who had an MRI at the time of clinical diagnosis of dementia were identified: 48 AD, 20 LBD, 47 FTLD-TDP (pathology-confirmed FTLD with TDP-43). Gray matter density in 91 regions-of-interest was measured in each subject and adjusted for head size and age using a database of 120 cognitively normal elderly. The atrophy patterns in each dementia type when compared to pathologically confirmed controls mirrored known disease-specific anatomic patterns: AD-temporoparietal association cortices and medial temporal lobe; FTLD-TDP-frontal and temporal lobes and LBD-bilateral amygdalae, dorsal midbrain and inferior temporal lobes. Differential-STAND based classification of each case was done based on a mixture model generated using bisecting k-means clustering of the information from the MRI scans. Leave-one-out classification showed reasonable performance compared to the autopsy gold standard and clinical diagnosis: AD (sensitivity: 90.7%; specificity: 84%), LBD (sensitivity: 78.6%; specificity: 98.8%) and FTLD-TDP (sensitivity: 84.4%; specificity: 93.8%). The proposed approach establishes a direct a priori relationship between specific topographic patterns on MRI and "gold standard" of pathology which can then be used to predict underlying dementia pathology in new incoming patients.     

Antemortem MRI based STructural Abnormality iNDex (STAND)-scores correlate with postmortem Braak neurofibrillary tangle stage

The clinical diagnosis of Alzheimer's disease (AD) does not exactly match the pathological findings at autopsy in every subject. Therefore, in-vivo imaging measures, such as Magnetic Resonance Imaging (MRI) that reflect underlying pathology, would be clinically useful independent supplementary measures of disease stage. We have developed an algorithm that extracts atrophy information from individual patient's 3D MRI scans and assigns a STructural Abnormality iNDex (STAND)-score to the scan based on the degree of atrophy in comparison to patterns extracted from a large library of clinically well characterized AD and CN (cognitively normal) subject's MRI scans. STAND-scores can be adjusted for demographics to give adjusted-STAND (aSTAND)-scores which are >0 for subjects with brains identified as abnormal by the algorithm. Since histopathological findings are considered to represent the "ground truth", our objective was to assess the sensitivity of aSTAND-scores to pathological AD staging. This was done by comparing antemortem MRI based aSTAND-scores with postmortem grading of disease severity in 101 subjects who had both antemortem MRI and postmortem Braak neurofibrillary tangle (NFT) staging. We found a rank correlation of 0.62 (p<0.0001) between Braak NFT stage and aSTAND-scores. The results show that optimally extracted information from MRI scans such as STAND-scores accurately capture the severity of neuronal pathology and can be used as an independent approximate surrogate marker for in-vivo pathological staging as well as for early identification of AD in individual subjects.     

Probability Mapping to Determine the Spatial Risk Pattern of Acute Gastroenteritis in Coimbatore District,India, Using Geographic Information Systems (GIS)

Background:

Maps show well the spatial configuration of information. Considerable effort is devoted to the development of geographical information systems (GIS) that increase understanding of public health problems and in particular to collaborate efforts among clinicians, epidemiologists, ecologists, and geographers to map and forecast disease risk.

Objectives:

Small populations tend to give rise to the most extreme disease rates, even if the actual rates are similar across the areas. Such situations will follow the decision-maker''s attention on these areas when they scrutinize the map for decision making or resource allocation. As an alternative, maps can be prepared using P-values (probabilistic values).

Materials and Methods:

The statistical significance of rates rather than the rates themselves are used to map the results. The incidence rates calculated for each village from 2000 to 2009 is used to estimate λ, the expected number of cases in the study area. The obtained results are mapped using Arc GIS 10.0.

Results:

The likelihood of infections from low to high is depicted in the map and it is observed that five villages namely, Odanthurai, Coimbatore Corporation, Ikkaraiboluvampatti, Puliakulam, and Pollachi Corporation are more likely to have significantly high incidences.

Conclusion:

In the probability map, some of the areas with exceptionally high or low rates disappear. These are typically small unpopulated areas, whose rates are unstable due to the small numbers problem. The probability map shows more specific regions of relative risks and expected outcomes.     

Incidence of Convexal Subarachnoid Hemorrhage in the Elderly: The Mayo Clinic Study of Aging

ObjectivesNontraumatic convexal subarachnoid hemorrhages in the elderly can be a manifestation of cerebral amyloid angiopathy associated with a high risk of future intracerebral hemorrhage. The incidence in the elderly population is unknown. Our objectives were to: 1) determine the incidence of convexal subarachnoid hemorrhage in a population-based study, and, 2) to compare apopolipoprotein-E genotype and amyloid positron emission tomographic (PET) imaging for those with versus without hemorrhage.MethodsBetween 11/29/2004 and 3/11/2017, 4462 individuals without hemorrhage at baseline participated in the population-based Mayo Clinic Study of Aging. We used the Rochester Epidemiology Project medical records-linkage system to identify intracerebral hemorrhages. Records and images were reviewed to identify convexal subarachnoid hemorrhage. Neuroimaging characteristics, demographics, medications, and apopolipoprotein-E genotype were recorded.ResultsFour cases were identified. The incidence of convexal subarachnoid hemorrhage was 14.1 per 100,000 person years. Three occurred in women, median age, 79 (range: 71-84). One patient had coexisting cerebral microbleeds. Two participants developed a subsequent lobar intracerebral hemorrhage at a median of 4.75 years after convexal subarachnoid hemorrhage. The apopolipoprotein-E -allele combinations of the 4 were: 3/3, 3/3, 2/2, and 2/3. On Pittsburgh Compound B-PET imaging, median standardized uptake value ratio with convexal subarachnoid hemorrhage was 1.86 (range: 1.38-2.34).ConclusionsConvexal subarachnoid hemorrhage is rare in the older population, occurring with an incidence of about 14 per 100,000 person years. Yet, when present, it may be associated with a high risk of future intracerebral hemorrhage.     

Vitamin D in esophageal cancer: Is there a role for chemoprevention?

Vitamin D has emerged as a promising anti-cancer agent due to its diverse biological effects on tumor differentiation, apoptosis and suppression of cellular proliferation. Current evidence suggests a protective role of vitamin D in colon cancer. The effect of vitamin D on esophageal cancer remains controversial. Multiple studies investigated the association between vitamin D and esophageal cancer, employing different modes of assessment of vitamin D status such as serum 25-hydroxyvitamin D levels, vitamin D dietary intake or exposure to ultraviolet B (UVB) radiation. Genetic variations of the vitamin D receptor (VDR) gene and VDR expression in esophageal specimens have also been investigated. Ecological studies evaluating exposure to UVB radiation yielded an inverse correlation with esophageal cancer. When vitamin D dietary intake was assessed, direct association with esophageal cancer was observed. However, circulating 25-hydroxyvitamin D concentrations showed inconsistent results. In this review article, we present a detailed summary of the current data on the effects of vitamin D on various histological subtypes of esophageal cancer and their precursor lesions. Well-powered prospective studies with accurate measurement of vitamin D status are needed before chemoprevention with vitamin D is recommended, as current evidence does not support a chemopreventive role of vitamin D against esophageal cancer. Future studies looking at the incidence of esophageal cancer in patients with pre-cancerous lesions (Barrett's esophagus and squamous cell dysplasia) receiving vitamin D supplementation are needed.     

Mining of Blast Resistance Gene,Pi2 and Its Novel Allelic Variant from Landraces of Rice from Karnataka

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Rice blast is one of the important fungal diseases of rice, caused by Magnaporthe oryzae. Rice blast can be...