RNA editing alterations define manifestation of prion diseases.

Prion diseases are fatal neurodegenerative disorders caused by misfolding of the normal prion protein into an infectious cellular pathogen. Clinically characterized by rapidly progressive dementia and accounting for 85% of human prion disease cases, sporadic Creutzfeldt-Jakob disease (sCJD) is the prevalent human prion disease. Although sCJD neuropathological hallmarks are well-known, associated molecular alterations are elusive due to rapid progression and absence of preclinical stages. To investigate transcriptome alterations during disease progression, we utilized tg340-PRNP129MM mice infected with postmortem material from sCJD patients of the most susceptible genotype (MM1 subtype), a sCJD model that faithfully recapitulates the molecular and pathological alterations of the human disease. Here we report that transcriptomic analyses from brain cortex in the context of disease progression, reveal epitranscriptomic alterations (specifically altered RNA edited pathway profiles, eg., ER stress, lysosome) that are characteristic and possibly protective mainly for preclinical and clinical disease stages. Our results implicate regulatory epitranscriptomic mechanisms in prion disease neuropathogenesis, whereby RNA-editing targets in a humanized sCJD mouse model were confirmed in pathological human autopsy material.

Contextualized Filtering for Shared Cyber Threat Information.

Cyber threat information sharing is an imperative process towards achieving collaborative security, but it poses several challenges. One crucial challenge is the plethora of shared threat information. Therefore, there is a need to advance filtering of such information. While the state-of-the-art in filtering relies primarily on keyword- and domain-based searching, these approaches require sizable human involvement and rarely available domain expertise. Recent research revealed the need for harvesting of business information to fill the gap in filtering, albeit it resulted in providing coarse-grained filtering based on the utilization of such information. This paper presents a novel contextualized filtering approach that exploits standardized and multi-level contextual information of business processes. The contextual information describes the conditions under which a given threat information is actionable from an organization perspective. Therefore, it can automate filtering by measuring the equivalence between the context of the shared threat information and the context of the consuming organization. The paper directly contributes to filtering challenge and indirectly to automated customized threat information sharing. Moreover, the paper proposes the architecture of a cyber threat information sharing ecosystem that operates according to the proposed filtering approach and defines the characteristics that are advantageous to filtering approaches. Implementation of the proposed approach can support compliance with the Special Publication 800-150 of the National Institute of Standards and Technology.

ARES: Automated Risk Estimation in Smart Sensor Environments.

Industry 4.0 adoption demands integrability, interoperability, composability, and security. Currently, integrability, interoperability and composability are addressed by next-generation approaches for enterprise systems integration such as model-based standards, ontology, business process model life cycle management and the context of business processes. Security is addressed by conducting risk management as a first step. Nevertheless, security risks are very much influenced by the assets that the business processes are supported. To this end, this paper proposes an approach for automated risk estimation in smart sensor environments, called ARES, which integrates with the business process model life cycle management. To do so, ARES utilizes standards for platform, vulnerability, weakness, and attack pattern enumeration in conjunction with a well-known vulnerability scoring system. The applicability of ARES is demonstrated with an application example that concerns a typical case of a microSCADA controller and a prototype tool called Business Process Cataloging and Classification System. Moreover, a computer-aided procedure for mapping attack patterns-to-platforms is proposed, and evaluation results are discussed revealing few limitations.

The natural history of donor hamstrings unit after anterior cruciate ligament reconstruction: a prospective MRI scan assessment.

PURPOSE: The aim of this prospective study was to assess the natural history of the donor hamstrings, compared to the contralateral knee and thigh. METHODS: In 47 patients who had ACL reconstruction (hamstrings technique), bilateral knees and thighs were investigated using MRI scans, up to 2 years post-operatively. RESULTS: Tendon regeneration below the knee joint line of the semitendinosus occurred in 30/47 (64 %) patients and of the gracilis tendon in 17/47 (36 %) patients. Insertion of both tendons at the "pes anserinus", with normal anatomic relations, was observed in 5/47 (11 %) patients. Semitendinosus and gracilis donor muscles were found retracted in 41/47 (87 %) patients. In 25/47 (53 %) patients, there was evidence of fatty infiltration of the semitendinosus muscle. All (47/47) (100 %) patients showed semitendinosus muscle atrophy and 41/47 (87 %) patients showed gracilis muscle atrophy, compared to the contralateral limb. High signal intensity on STIR images was observed in the semitendinosus in 22/47 (46 %) patients and in the gracilis muscle in 30/47 (64 %) patients, on MRI examination performed up to 24 months post-operatively. CONCLUSIONS: The "regenerated" hamstrings tendons most commonly do not regenerate fully anatomically, so they should not be considered as a first choice for re-harvesting in revision ACL reconstruction. The "donor hamstrings muscles" are found to be shorter, contracted, thinner and with a long-term abnormal MRI signal, features which are considered to be related to reduced muscle performance (knee flexion and internal rotation) post-operatively. LEVEL OF EVIDENCE: II.

Value of magnetic resonance imaging in diagnosis of adenomyosis and myomas of the uterus.

STUDY OBJECTIVE: To estimate the diagnostic performance of magnetic resonance imaging (MRI) in detection of myomas and adenomyosis of the uterus. DESIGN: Prospective cohort observational study (Canadian Task Force classification II-2). SETTING: Department of obstetrics and gynecology, tertiary academic hospital. PATIENTS: One hundred fifty-three consecutive women with an enlarged uterus accompanied by gynecologic symptoms and/or with an asymptomatic pelvic mass. INTERVENTION: Total abdominal hysterectomy. All patients underwent MRI before the operation. MEASUREMENTS AND MAIN RESULTS: The sensitivity, specificity, positive, and negative predictive value of MRI for the diagnosis of uterine pathology was calculated using histologic findings as the standard criterion for final diagnosis. Receiver operating characteristics curves were constructed to describe the diagnostic performance of MRI. In the diagnosis of myomas, MRI demonstrated sensitivity of 94.1%, specificity of 68.7%, PPV of 95.7%, and NPV of 61.1%. In the diagnosis of adenomyosis, MRI demonstrated sensitivity of 46.1%, specificity of 99.1%, PPV of 92.3%, and NPV of 88.5%. The area under the curve (AUC) for the diagnostic performance of MRI in the detection of myomas and adenomyosis was 0.81 and 0.73, respectively. Uterine sarcoma was diagnosed in 5 patients; in these cases, MRI demonstrated sensitivity of 60.0%, specificity of 99.2%, PPV of 75.0%, and NPV of 98.4%. The AUC for MRI in the diagnosis of uterine sarcomas was 0.80. CONCLUSIONS: MRI exhibits a high AUC for the diagnosis of both adenomyosis and myomas. The PPV of MRI in the diagnosis of adenomyosis and myomas of the uterus is high as well. MRI seems to be a useful technique in everyday clinical practice in the diagnostic approach of these common conditions, enabling clinicians to select the most appropriate management.

Prion protein gene mutation detection using long-read Nanopore sequencing.

Prion diseases are fatal neurodegenerative conditions that affect humans and animals. Rapid and accurate sequencing of the prion gene PRNP is paramount to human prion disease diagnosis and for animal surveillance programmes. Current methods for PRNP genotyping involve sequencing of small fragments within the protein-coding region. The contribution of variants in the non-coding regions of PRNP including large structural changes is poorly understood. Here, we used long-range PCR and Nanopore sequencing to sequence the full length of PRNP, including its regulatory region, in 25 samples from blood and brain of individuals with inherited or sporadic prion diseases. Nanopore sequencing detected the same variants as identified by Sanger sequencing, including repeat expansions/deletions. Nanopore identified additional single-nucleotide variants in the non-coding regions of PRNP, but no novel structural variants were discovered. Finally, we explored somatic mosaicism of PRNP's octapeptide repeat region, which is a hypothetical cause of sporadic prion disease. While we found changes consistent with somatic mutations, we demonstrate that they may have been generated by the PCR. Our study illustrates the accuracy of Nanopore sequencing for rapid and field prion disease diagnosis and highlights the need for single-molecule sequencing methods for the detection of somatic mutations.

Animal fats valorization to green transportations fuels: From concept to industrially relevant scale validation.

The potential of animal fats hydroconversion is experimentally investigated and validated in industrially relevant scale via the production of 100 L of transportation fuels. The experimental testing has indicated that mild hydrotreatment conditions are associated with low hydrogen consumption without significantly penalties in product quality. The optimal operating conditions (pressure of 6.89 MPa, H2/oil ratio of 84.95 Sm3 and LHSV of 1 hr-1) identified were also applied in the industrially relevant scale hydroprocessing pilot to validate the scale-up potential of the technology. The produced fuel is characterized by 5 wppm sulphur, 79.3 cetane index and 44.4 MJ/kg heating value, offering an advantage in compression ignition engines. The produced fuel can be blended up to 20% v/v with fossil diesel rendering a high bio-content diesel abiding by the EN 590 standard. It was found that, up to 20% per volume can be added in diesel without exceeding the requirements for CFPP standards for Greek winter diesel. Towards the commercialization of the technology with respect to the animal fats logistics, a dedicated 6-month storage stability study revealed that animal fats can be stored for up to three to four months at ambient conditions. The findings, indicate that the suggested technology is mature technology as applied successfully in the industrially-relevant-scale providing also the process data.

RNA Editing Alterations Define Disease Manifestations in the Progression of Experimental Autoimmune Encephalomyelitis (EAE).

RNA editing is an epitranscriptomic modification, leading to targeted changes in RNA transcripts. It is mediated by the action of ADAR (adenosine deaminases acting on double-stranded (ds) RNA and APOBEC (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like) deaminases and appears to play a major role in the pathogenesis of many diseases. Here, we assessed its role in experimental autoimmune encephalomyelitis (EAE), a widely used non-clinical model of autoimmune inflammatory diseases of the central nervous system (CNS), which resembles many aspects of human multiple sclerosis (MS). We have analyzed in silico data from microglia isolated at different timepoints through disease progression to identify the global editing events and validated the selected targets in murine tissue samples. To further evaluate the functional role of RNA editing, we induced EAE in transgenic animals lacking expression of APOBEC-1. We found that RNA-editing events, mediated by the APOBEC and ADAR deaminases, are significantly reduced throughout the course of disease, possibly affecting the protein expression necessary for normal neurological function. Moreover, the severity of the EAE model was significantly higher in APOBEC-1 knock-out mice, compared to wild-type controls. Our results implicate regulatory epitranscriptomic mechanisms in EAE pathogenesis that could be extrapolated to MS and other neurodegenerative disorders (NDs) with common clinical and molecular features.

D4I - Digital forensics framework for reviewing and investigating cyber attacks.

Many companies have cited lack of cyber-security as the main barrier to Industrie 4.0 or digitalization. Security functions include protection, detection, response and investigation. Cyber-attack investigation is important as it can support the mitigation of damages and maturing future prevention approaches. Nowadays, the investigation of cyber-attacks has evolved more than ever leveraging combinations of intelligent tools and digital forensics processes. Intelligent tools (e.g., YARA rules and Indicators of Compromise) are effective only when there is prior knowledge about software and mechanisms used in the cyber-attack, i.e., they are not attack-agnostic. Therefore, the effectiveness of these intelligent tools is inversely proportional to the number of the never-seen-before software and mechanisms utilized. Digital forensic processes, while not suffering from such issue, lack the ability to provide in-depth support to a cyber-attack investigation mainly due to insufficient detailed instructions in the examination and analysis phases. This paper proposes a digital forensics framework for reviewing and investigating cyber-attacks, called D4I, which focuses on enhancing the examination and analysis phases. First, the framework proposes a digital artifacts categorization and mapping to the Cyber-Kill-Chain steps of attacks. Second, it provides detailed instructing steps for the examination and analysis phases. The applicability of D4I is demonstrated with an application example that concerns a typical case of a spear phishing attack.

Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study.

BACKGROUND: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms. METHODS: We did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datasets matched for country. FINDINGS: Samples from 5208 cases were obtained between 1990 and 2014. We found 41 genome-wide significant single nucleotide polymorphisms (SNPs) and independently replicated findings at three loci associated with sCJD risk; within PRNP (rs1799990; additive model odds ratio [OR] 1·23 [95% CI 1·17-1·30], p=2·68 × 10-15; heterozygous model p=1·01 × 10-135), STX6 (rs3747957; OR 1·16 [1·10-1·22], p=9·74 × 10-9), and GAL3ST1 (rs2267161; OR 1·18 [1·12-1·25], p=8·60 × 10-10). Follow-up analyses showed that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 are associated with increased expression of the major transcripts in disease-relevant brain regions. INTERPRETATION: We present, to our knowledge, the first evidence of statistically robust genetic associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism as molecular causal mechanisms. Risk SNPs in STX6 are shared with progressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders. FUNDING: Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust.

ApoE4 lowers age at onset in patients with frontotemporal dementia and tauopathy independent of amyloid-ß copathology.

INTRODUCTION: Apolipoprotein E (ApoE) is the most important genetic risk factor for Alzheimer's disease (AD), with ApoE4 thought to enhance and accelerate amyloid-ß (Aß) pathology. ApoE4 has recently been described to increase neurodegeneration in a mouse model of frontotemporal dementia (FTD), in vitro, and in patients, demonstrating that ApoE4 modifies tauopathy independently of Aß. This raises the question whether ApoE genotype also modifies the clinical phenotype in patients with FTD with tau pathology. METHODS: We analyzed 704 patients with FTD, including a genetically and neuropathologically confirmed subset, and 452 healthy elderly controls. We compared ApoE4 genotype frequency and age at onset in tau+ or TDP43+ FTD patients with or without Aß copathology. RESULTS: The ApoE4 genotype lowered age at onset in patients with FTD and tau pathology, particularly once accounting for confounding effects of Aß pathology. DISCUSSION: We conclude that ApoE4 accelerates neurodegeneration in FTD patients with MAPT mutations or FTLD-tau pathology, independent of Aß.

MRI for the determination of pituitary iron overload in children and young adults with beta-thalassaemia major.

Hypogonadism, resulting from iron-induced pituitary dysfunction, is the most frequently reported complication in patients with beta-thalassaemia major. The aim of this study was to evaluate pituitary Magnetic Resonance Imaging (MRI) signal intensity reduction, on T2*-weighted images, as a marker of pituitary iron overload. Thirty patients (13 females and 17 males, mean age: 16.6+/-4.1) with beta-thalassaemia major on conventional treatment and 13 healthy volunteers (7 females and 6 males, mean age: 11+/-4.51 years) were studied with T2*-weighted images of the anterior pituitary using a 1.5T unit. Four thalassaemic patients (2 females and 2 males) had clinical hypogonadism and required hormonal replacement treatment. Results revealed a statistically significant reduction of pituitary signal intensity in the thalassaemia group compared to controls (p<0.001). Moreover, hypogonadal patients had significantly decreased MRI values compared to thalassaemic patients without hypogonadism (p=0.017). Relatively decreased adeno-hypophyseal MRI signal intensity was recorded in pubertal thalassaemic patients. A significant negative correlation was observed between pituitary MRI values and age (r=-0.67, r(2)=0.443, p=0.001), whereas ferritin levels and pituitary MRI values were moderately correlated (r=-0.56, r(2)=0.32, p=0.08) in adult thalassaemic patients. In conclusion, pituitary MRI indices as measured on T2*-weighted images seem to reflect pituitary iron overload and could, therefore, be used for a preclinical detection of patients who are in greater danger of developing hypogonadism.

Prognostic impact of tumor volumetry in patients with locally advanced head-and-neck carcinoma (non-nasopharyngeal) treated by radiotherapy alone or combined radiochemotherapy in a randomized trial.

PURPOSE: Tumor volume (TV) is one of the main reported factors determining the outcome of treatment in head-and-neck carcinomas. In this study, the prognostic impact of TV was explored in the context of a randomized trial with the patients assigned to receive standard radiotherapy (RT) alone or RT plus platinum compounds (RT alone, RT plus cisplatin, or RT plus carboplatin). METHODS AND MATERIALS: The tumor outlines were traced and digitized on each pretreatment CT slice for each of the 101 patients studied. Taking into account the magnification factor of the scan and CT slice thickness, a computer with specifically designed software calculated the TV in cubic centimeters. RESULTS: The median overall survival for the whole group of patients was 21.6 months (95% confidence interval, 13.0-30.2) and the 3-year survival rate was 40%. The addition of platinum compounds to RT (Groups 2 and 3) significantly improved the survival rate (RT alone vs. RT plus cisplatin, hazard ratio 0.36, p = 0.002; RT alone vs. RT plus carboplatin, hazard ratio 0.53, p = 0.029). In univariate analysis, the most significant parameters for survival were treatment group, total gross tumor volume (TGTV), complete response, nodal GTV, primary GTV, and performance status. In multivariate analysis, treatment group, TGTV, gender, and primary site were independent prognostic factors for survival. A prognostic threshold of 22.8 cm(3) was detected for TGTV. Patients with a TGTV of <22.8 cm(3) were more likely to achieve a complete response and had a median survival of 45.3 months, and those with a TGTV >22.8 cm(3) had a median survival of 12.3 months (log-rank test, p = 0.0102). CONCLUSION: The prognostic significance of the TGTV was confirmed and a cutoff value of 22.8 cm(3) derived. Our data indicated that locally advanced head-and-neck carcinomas should not be treated by standard (once-daily) RT alone. Tumor size and disease subsite should be taken into account in future randomized trials to increase their statistical power.

Model-based processing scheme for quantitative 4-D cardiac MRI analysis.

In this paper, we present an integrated model-based processing scheme for cardiac magnetic resonance imaging (MRI), embedded in an interactive computing environment suitable for quantitative cardiac analysis, which provides a set of functions for the extraction, modeling, and visualization of cardiac shape and deformation. The methods apply four-dimensional (4-D) processing (three spatial and one temporal) to multiphase multislice MRI acquisitions and produce a continuous 4-D model of the myocardial surface deformation. The model is used to measure diagnostically useful parameters, such as wall motion, myocardial thicking, and myocardial mass measurements. The proposed model-based shape extraction method has the advantage of integrating local information into an overall representation and produces a robust description of cardiac cavities. A learning segmentation process that incorporates a generating-shrinking neural network is combined with a spatiotemporal parametric modeling method through functional basis decomposition. A multiscale approach is adopted, which uses at each step a coarse-scale model defined at the previous step in order to constrain the boundary detection. The representation accuracy starts from a coarse but smooth estimation of the approximate cardiac shape and is gradually increased to the desired detail. The main advantages of the proposed methods are efficiency, lack of uncertainty about convergence, and robustness to image artifacts. Experimental results obtained from application to clinical multislice multiphase MRI examinations of normal volunteers and patients with medical record of myocardial infarction were satisfactory in terms of accuracy and robustness.

MR urography: Anatomical and quantitative information on congenital malformations in children.

BACKGROUND AND AIM: Magnetic resonance urography (MRU) is considered to be the next step in uroradiology. This technique combines superb anatomical images and functional information in a single test. In this article, we aim to present the topic of MRU in children and how it has been implemented in Northern Greece so far. The purpose of this study is to demonstrate the potential of MRU in clinical practice. We focus both on the anatomical and the quantitative information this technique can offer. MATERIALS AND METHODS: MRU was applied in 25 children (ages from 3 to 11 years) diagnosed with different types of congenital malformations. T1 and T2 images were obtained for all patients. Dynamic, contrast-enhanced data were processed and signal intensity versus time curves were created for all patients from regions of interest (ROIs) selected around the kidneys in order to yield quantitative information regarding the kidneys function. RESULTS: From the slopes of these curves we were able to evaluate which kidneys were functional and from the corticomedullary cross-over point to determine whether the renal system was obstructed or not. CONCLUSION: In all 25 cases MRU was sufficient, if not superior to other imaging modalities, to establish a complete diagnosis.

Panic Attack during Elective Gastrointestinal Endoscopy.

Background. Esophagogastroduodenoscopy (EGD) and colonoscopy (CS) can evoke anxiety, embarrassment, and discomfort. These concerns can culminate in panic attacks, which may traumatize patients and significantly decrease their compliance to the procedure. The objective of this study was to evaluate the relationship between preendoscopic anxiety and the possibility of a panic attack during an elective gastrointestinal endoscopy (EGE). Methods. The study population comprised of 79 Greek outpatients. The examination was carried out without the use of conscious sedation. Patients' anxiety levels were assessed before the procedure using the Greek version of the Spielberger State-Trait Anxiety Inventory (STAI-Y). Results. Seventy-nine patients were enrolled: 45 EGD and 34 CS. Females had higher state and trait anxiety levels than males (48.14 ± 7.94 versus 44.17 ± 7.43, P < 0.05; and 43.68 ± 6.95 versus 39.86 ± 7.46, P < 0.05). Patients who experienced panic attack had significantly higher levels of both trait and state anxiety, compared to those who were panic-free. There was no significant relationship between panic attacks and sex or type of procedure. Conclusions. Patients who experience panic attacks during endoscopic procedures appear to have significantly higher anxiety levels before the procedure. Administering the STAI questionnaire prior to the endoscopy seems to be a useful screening method for vulnerable patients.

Hydrotreating of waste cooking oil for biodiesel production. Part II: effect of temperature on hydrocarbon composition.

This study focuses on the use of waste cooking oil (WCO) as the main feedstock for hydrotreatment to evaluate the effect of temperature on the product hydrocarbon composition. A qualitative analysis was initially performed using a GC x GC-TOFMS indicating the presence of mainly paraffins of the C15-C18 range. A quantitative analysis was also performed via a GC-FID, which gave both n-paraffins and iso-paraffins in the range of C8-C29. The results indicate that hydrotreating temperature favors isomerization reactions as the amount of n-paraffins decreases while the amount of iso-paraffins increases. For all experiments the same commercial hydrotreating catalyst was utilized, while the remaining operating parameters were constant (pressure=1200 psig, LHSV=1.0 h(-1), H(2)/oil ratio=4000 scfb, liquid feed=0.33 ml/min, and gas feed=0.4 scfh).

Hydrotreating of waste cooking oil for biodiesel production. Part I: Effect of temperature on product yields and heteroatom removal.

Hydrotreating of waste cooking oil (WCO) was studied as a process for biofuels production. The hydrotreatment temperature is the most dominant operating parameter which defines catalyst performance as well as catalyst life. In this analysis, a hydrotreating temperature range of 330-398 degrees C was explored via a series of five experiments (330, 350, 370, 385 and 398 degrees C). Several parameters were considered for evaluating the effect of temperature including product yields, conversion, selectivity (diesel and gasoline), heteroatom removal (sulfur, nitrogen and oxygen) and saturation of double bonds. For all experiments the same commercial hydrotreating catalyst was utilized, while the remaining operating parameters were constant (pressure=1200 psig, LHSV=1.0 h(-1), H(2)/oil ratio=4000 scfb, liquid feed=0.33 ml/min and gas feed=0.4 scfh). It was observed that higher reactor temperatures are more attractive when gasoline production is of interest, while lower reaction temperatures are more suitable when diesel production is more important.

Brain SPECT findings of anosognosia in Alzheimer's disease.

Anosognosia is a common symptom of dementia. The aim of this study was to evaluate the contribution of different regions of the brain to anosognosia in Alzheimer's disease (AD) brains using single photon emission computed tomography (SPECT). Forty-two patients with AD were included in this study. After clinical interviews with the patients and their relatives, the patients were divided into two groups: Anosognosia and No-anosognosia. The patients were studied regarding the severity of dementia. They underwent SPECT with HMPAO and regional cerebral blood flow (rCBF) was measured. Regional CBF significantly differed between Anosognosia and No-anosognosia groups in right prefrontal (P < or = 0.02), right inferior parietal (P < or = 0.00), and right (P < or = 0.01) and left (P < or = 0.01) medial temporal cortex. There was a significant correlation between the severity of dementia and rCBF in medial temporal regions. When comparisons were made between mild and moderate stages separately, the 'right inferior parietal region' was the common region which showed hypoperfusion in both anosognosia subgroups. We conclude that anosognosia may be a reflection of functional impairment in right prefrontal, right frontal and especially right inferior parietal regions in AD.

Plasma levels of amyloid beta1-42 are independent of neuronal function in Alzheimer's disease.

The aggregation of amyloid-beta42 (Abeta42) constitutes one of the major pathogenic events in Alzheimer's disease (AD), and the study of regional cerebral blood flow (rCBF), using single photon emission computed tomography (SPECT), aids the diagnosis of AD. In this study, we evaluated whether there was a correlation between rCBF in brain regions and plasma levels of Abeta1-42 in AD. 29 patients (mean age 71 +/- 9) with a diagnosis of AD who fulfilled NINCDS-ADRDA criteria with a mean Mini-Mental Status Examination score of 15 +/- 9 and 16 normal controls (mean age 64 +/- 8) underwent SPECT brain imaging with hexamethylpropylene amine oxime, and semiquantitative analysis of rCBF was performed. Plasma samples were collected the same day of the SPECT and plasma Abeta1-42 measured by ELISA. A significant reduction of rCBF was observed in most regions in AD compared to controls, whereas mean plasma Abeta42 did not differ between the two groups. There was no correlation between rCBF in any region and plasma Abeta42 nor any correlations between gender, age, and severity with plasma levels of Abeta42. Since rCBF is coupled to neuronal activity, we conclude that plasma Abeta1-42 concentration is independent of neuronal function in every single region of the brain.