Predicting the conversion of mild cognitive impairment to Alzheimer's disease based on the volumetric measurements of the selected brain structures in magnetic resonance imaging

Introduction Mild cognitive impairment (MCI) is defined as abnormal cognitive state, but does not meet the criteria for the diagnosis of dementia. According to the new guidelines Alzheimer's disease (AD) involves not only dementia's phase but also predementia phase which is asymptomatic and pathological process in the brain is already present. For this reason it is very important to determine the suitability of markers which should be positive before onset of the first symptoms. One of these biomarkers is a structural magnetic resonance imaging with hippocampal volumetric assessment. The aim of this study was to investigate the usefulness of structural brain magnetic resonance imaging with volumetric assessment of the hippocampus and entorhinal cortex, posterior cingulate gyrus, parahippocampal gyrus, temporal gyri: superior, medial and inferior, to predict the conversion of MCI to AD. Material and methods Magnetic resonance imaging of brain was performed at the baseline visit in 101 patients diagnosed with MCI. Clinic follow-ups were scheduled after 6.12 and 24 months. Results Amongst 101 patients with MCI, 17 (16.8%) converted into AD within two years of observation. All measured volumes were lower in converters than non-converters. Discriminant analysis was conducted and sensitivity for MCI conversion to AD was 64.7%, specificity 96.4%. 91% of patients were correctly classified (converter or non-converter). Conclusions Volumetric measurements may help clinicians to predict MCI conversion to AD but due to low sensitivity it cannot be use separately. The study group requires further observation

Campylobacter jejuni dsb gene expression is regulated by iron in a Fur-dependent manner and by a translational coupling mechanism

<p>Abstract</p> <p>Background</p> <p>Many bacterial extracytoplasmic proteins are stabilized by intramolecular disulfide bridges that are formed post-translationally between their cysteine residues. This protein modification plays an important role in bacterial pathogenesis, and is facilitated by the Dsb (disulfide bond) family of the redox proteins. These proteins function in two parallel pathways in the periplasmic space: an oxidation pathway and an isomerization pathway. The Dsb oxidative pathway in <it>Campylobacter jejuni </it>is more complex than the one in the laboratory <it>E. coli </it>K-12 strain.</p> <p>Results</p> <p>In the <it>C. jejuni </it>81-176 genome, the <it>dsb </it>genes of the oxidative pathway are arranged in three transcriptional units: <it>dsbA2</it>-<it>dsbB</it>-<it>astA, dsbA1 </it>and <it>dba</it>-<it>dsbI</it>. Their transcription responds to an environmental stimulus - iron availability - and is regulated in a Fur-dependent manner. Fur involvement in <it>dsb </it>gene regulation was proven by a reporter gene study in a <it>C. jejuni </it>wild type strain and its isogenic <it>fur </it>mutant. An electrophoretic mobility shift assay (EMSA) confirmed that analyzed genes are members of the Fur regulon but each of them is regulated by a disparate mechanism, and both the iron-free and the iron-complexed Fur are able to bind <it>in vitro </it>to the <it>C. jejuni </it>promoter regions. This study led to identification of a new iron- and Fur-regulated promoter that drives <it>dsbA1 </it>gene expression in an indirect way. Moreover, the present work documents that synthesis of DsbI oxidoreductase is controlled by the mechanism of translational coupling. The importance of a secondary <it>dba-dsbI </it>mRNA structure for <it>dsbI </it>mRNA translation was verified by estimating individual <it>dsbI </it>gene expression from its own promoter.</p> <p>Conclusions</p> <p>The present work shows that iron concentration is a significant factor in <it>dsb </it>gene transcription. These results support the concept that iron concentration - also through its influence on <it>dsb </it>gene expression - might control the abundance of extracytoplasmic proteins during different stages of infection. Our work further shows that synthesis of the DsbI membrane oxidoreductase is controlled by a translational coupling mechanism. The <it>dba </it>expression is not only essential for the translation of the downstream <it>dsbI </it>gene, but also Dba protein that is produced might regulate the activity and/or stability of DsbI.</p

Brainstem ischemic stroke without permanent sequelae during the course of spontaneous internal carotid artery dissection : case report

Background: Internal carotid artery dissection (ICAD) is a frequent cause of a stroke in young patients. Risk factors which can lead to dissection include neck injury and diseases of the inner wall of the artery. Common symptoms in ICAD are cervical pain and headache, Horner's syndrome, paralysis of the cranial nerves and subsequently cerebral and retinal ischemia. MR angiography in TOF technique and brain MRI in T1- and T2-weighted images, FLAIR and DWI sequences are the method of choice in patients with ICAD but contrast-enhanced multislice computed tomography remains the fastest and the most available diagnostic method. Case Report: A 39-year old woman, previously healthy, presented to the Hospital Emergency Department because of increasing neck pain on the right side and difficulty in swallowing. The neurological examination revealed: drooping of the right eyelid with narrow palpebral fissure, dysarthria, anisocoria (narrower pupil on the right side), unilateral hypoesthesia on the left side, weak palatal and pharyngeal reflexes on both sides, paresthesia within the left half of the body. Seven days before, the patient felt a sudden, severe neck pain radiating to the temporal apophysis CT angiography revealed a defect in contrast filling within the left internal carotid artery and right vertebral artery. MRI of the head with MR angiography showed internal carotid artery dissection on the left side and dissection of the right vertebral artery and no ischemic changes within the brain. Conclusions: CT and MR angiography are methods characterized by high sensitivity in detecting dissection of the cervical arteries

Combined use of biochemical and volumetric biomarkers to assess the risk of conversion of mild cognitive impairment to Alzheimer’s disease

Introduction : The aim of our study was to evaluate the usefulness of several biomarkers in predicting the conversion of mild cognitive impairment (MCI) to Alzheimer’s disease (AD): β-amyloid and tau proteins in cerebrospinal fluid and the volumetric evaluation of brain structures including the hippocampus in magnetic resonance imaging (MRI). Material and methods : MRI of the brain with the volumetric assessment of hippocampus, entorhinal cortex, posterior cingulate gyrus, parahippocampal gyrus, superior, medial and inferior temporal gyri was performed in 40 patients diagnosed with mild cognitive impairment. Each patient had a lumbar puncture to evaluate β-amyloid and tau protein (total and phosphorylated) levels in the cerebrospinal fluid. The observation period was 2 years. Results : Amongst 40 patients with MCI, 9 (22.5%) converted to AD within 2 years of observation. Discriminant analysis was conducted and sensitivity for MCI conversion to AD on the basis of volumetric measurements was 88.9% and specificity 90.3%; on the basis of β-amyloid and total tau, sensitivity was 77.8% and specificity 83.9%. The combined use of the results of volumetric measurements with the results of proteins in the cerebrospinal fluid did not increase the sensitivity (88.9%) but increased specificity to 96.8% and the percentage of correct classification to 95%

Shoulder joint tuberculosis

Background: Despite the fact that joint tuberculosis is one of the most common forms of extrapulmonary tuberculosis, it is a disease entity that is very rare in Poland (less than 100 cases a year in the last 10 years). The symptoms are non-specific, and thus the disease is rarely taken into account in preliminary differential diagnosis. Case Report: A 68-year-old female patient was admitted to the Internal Diseases Clinic due to oedema and pain of the right shoulder joint. The pain has been increasing for about 8 months. Physical examination revealed increased circumference and elevated temperature of the right shoulder joint. Limb function was retained. The full range of radiological and laboratory diagnostic examinations was performed, including the biopsy of the affected tissue which revealed the presence of Mycobacterium tuberculosis in the bacterial culture. Clinical improvement was obtained after introduction of TB drugs. Conclusions: Radiological diagnostic methods (X-ray, CT scans, MRI scans) provide high precision monitoring of articular lesions. However, the decisive diagnosis requires additional laboratory tests as well as histopathological and bacteriological assays

Mitochondrial-related proteomic changes during obesity and fasting in mice are greater in the liver than skeletal muscles

Although mitochondrial dysfunction is implicated in the pathogenesis of obesity, the molecular mechanisms underlying obesity-related metabolic abnormalities are not well established. We performed mitochondrial quantitative proteomic and whole transcriptome analysis followed by functional annotations within liver and skeletal muscles, using fasted and non-fasted 16- and 48-week-old high-fat diet (HFD)-fed and normal diet-fed (control group) wild-type C56BL/6J mice, and hyperphagic ob/ob and db/db obese mice. Our study identified 1,675 and 704 mitochondria-associated proteins with at least two peptides in liver and muscle, respectively. Of these, 221 liver and 44 muscle proteins were differentially expressed (adjusted p values ≤ 0.05) between control and all obese mice, while overnight fasting altered expression of 107 liver and 35 muscle proteins. In the liver, we distinguished a network of 27 proteins exhibiting opposite direction of expression changes in HFD-fed and hyperphagic mice when compared to control. The network centered on cytochromes P450 3a11 (Cyp3a11) and 4a14 (Cyp4a14), and fructose-bisphosphate aldolase B (Aldob) proteins which bridged proteins cluster involved in Metabolism of xenobiotics with proteins engaged in Fatty acid metabolism and PPAR signaling pathways. Functional annotations revealed that most of the hepatic molecular alterations, which characterized both obesity and fasting, related to different aspects of energy metabolism (such as Fatty acid metabolism, Peroxisome, and PPAR signaling); however, only a limited number of functional annotations could be selected from skeletal muscle data sets. Thus, our comprehensive molecular overview revealed that both obesity and fasting states induce more pronounced mitochondrial proteome changes in the liver than in the muscles. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10142-013-0342-3) contains supplementary material, which is available to authorized users

Pooled sample-based GWAS: a cost-effective alternative for identifying colorectal and prostate cancer risk variants in the Polish population.

BACKGROUND: Prostate cancer (PCa) and colorectal cancer (CRC) are the most commonly diagnosed cancers and cancer-related causes of death in Poland. To date, numerous single nucleotide polymorphisms (SNPs) associated with susceptibility to both cancer types have been identified, but their effect on disease risk may differ among populations. METHODS: To identify new SNPs associated with PCa and CRC in the Polish population, a genome-wide association study (GWAS) was performed using DNA sample pools on Affymetrix Genome-Wide Human SNP 6.0 arrays. A total of 135 PCa patients and 270 healthy men (PCa sub-study) and 525 patients with adenoma (AD), 630 patients with CRC and 690 controls (AD/CRC sub-study) were included in the analysis. Allele frequency distributions were compared with t-tests and χ(2)-tests. Only those significantly associated SNPs with a proxy SNP (p<0.001; distance of 100 kb; r(2)>0.7) were selected. GWAS marker selection was conducted using PLINK. The study was replicated using extended cohorts of patients and controls. The association with previously reported PCa and CRC susceptibility variants was also examined. Individual patients were genotyped using TaqMan SNP Genotyping Assays. RESULTS: The GWAS selected six and 24 new candidate SNPs associated with PCa and CRC susceptibility, respectively. In the replication study, 17 of these associations were confirmed as significant in additive model of inheritance. Seven of them remained significant after correction for multiple hypothesis testing. Additionally, 17 previously reported risk variants have been identified, five of which remained significant after correction. CONCLUSION: Pooled-DNA GWAS enabled the identification of new susceptibility loci for CRC in the Polish population. Previously reported CRC and PCa predisposition variants were also identified, validating the global nature of their associations. Further independent replication studies are required to confirm significance of the newly uncovered candidate susceptibility loci

The GWAS-selected SNPs association with AD, CRC or PCa, considering allelic and additive models.

<p>Bold denotes significant association (<i>p</i><0.05). G1 vs. G2; compared groups of cases and controls, respectively, MA; minor allele (+) strand, F1, F2; frequency of MA in the case and control groups, respectively, OR; odds ratio, CI; confidence interval, N; control, PCa; prostate cancer, AD; adenoma, CRC; colorectal cancer, F; female, M; male.</p>a<p>^/SNP identifier based on NCBI SNP database;</p>b<p>^/NCBI ID of genes localized in proximity to the SNPs of interest (source: HapMap).</p