Identification of multiple system atrophy mimicking Parkinson's disease or progressive supranuclear palsy

WWe studied a subset of patients with autopsy-confirmed multiple system atrophy who presented a clinical picture that closely resembled either Parkinson’s disease or progressive supranuclear palsy. These mimics are not captured by the current diagnostic criteria for multiple system atrophy. Among 218 autopsy-proven multiple system atrophy cases reviewed, 177 (81.2%) were clinically diagnosed and pathologically confirmed as multiple system atrophy (i.e. typical cases), while the remaining 41 (18.8%) had received an alternative clinical diagnosis, including Parkinson’s disease (i.e. Parkinson’s disease mimics; n = 16) and progressive supranuclear palsy (i.e. progressive supranuclear palsy mimics; n = 17). We also reviewed the clinical records of another 105 patients with pathologically confirmed Parkinson’s disease or progressive supranuclear palsy, who had received a correct final clinical diagnosis (i.e. Parkinson’s disease, n = 35; progressive supranuclear palsy-Richardson syndrome, n = 35; and progressive supranuclear palsy-parkinsonism, n = 35). We investigated 12 red flag features that would support a diagnosis of multiple system atrophy according to the current diagnostic criteria. Compared with typical multiple system atrophy, Parkinson’s disease mimics more frequently had a good levodopa response and visual hallucinations. Vertical gaze palsy and apraxia of eyelid opening were more commonly observed in progressive supranuclear palsy mimics. Multiple logistic regression analysis revealed an increased likelihood of having multiple system atrophy [Parkinson’s disease mimic versus typical Parkinson’s disease, odds ratio (OR): 8.1; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 2.3] if a patient developed any one of seven selected red flag features in the first 10 years of disease. Severe autonomic dysfunction (orthostatic hypotension and/or urinary incontinence with the need for a urinary catheter) was more frequent in clinically atypical multiple system atrophy than other parkinsonian disorders (Parkinson’s disease mimic versus typical Parkinson’s disease, OR: 4.1; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 8.8). The atypical multiple system atrophy cases more frequently had autonomic dysfunction within 3 years of symptom onset than the pathologically confirmed patients with Parkinson’s disease or progressive supranuclear palsy (Parkinson’s disease mimic versus typical Parkinson’s disease, OR: 4.7; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 2.7). Using all included clinical features and 21 early clinical features within 3 years of symptom onset, we developed decision tree algorithms with combinations of clinical pointers to differentiate clinically atypical cases of multiple system atrophy from Parkinson’s disease or progressive supranuclear palsy

Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells

Heritability of Attractiveness to Mosquitoes

Female mosquitoes display preferences for certain individuals over others, which is determined by differences in volatile chemicals produced by the human body and detected by mosquitoes. Body odour can be controlled genetically but the existence of a genetic basis for differential attraction to insects has never been formally demonstrated. This study investigated heritability of attractiveness to mosquitoes by evaluating the response of Aedes aegypti (=Stegomyia aegypti) mosquitoes to odours from the hands of identical and non-identical twins in a dual-choice assay. Volatiles from individuals in an identical twin pair showed a high correlation in attractiveness to mosquitoes, while non-identical twin pairs showed a significantly lower correlation. Overall, there was a strong narrow-sense heritability of 0.62 (SE 0.124) for relative attraction and 0.67 (0.354) for flight activity based on the average of ten measurements. The results demonstrate an underlying genetic component detectable by mosquitoes through olfaction. Understanding the genetic basis for attractiveness could create a more informed approach to repellent development

In vitro activity of tigecycline against methicillin-resistant Staphylococcus aureus, including livestock-associated strains

The in vitro activity of tigecycline was determined using a well-defined collection of methicillin-resistant Staphylococcus aureus (MRSA) isolates (n = 202), including 33 livestock-associated strains. Susceptibility testing was performed using the Etest system. Among the 202 MRSA strains, three (1.5%) had a minimum inhibitory concentration (MIC) value for tigecycline greater than 0.5 mg/l, which are considered to be resistant. When these strains were tested using Iso-Sensitest medium, the MICs were substantially lower and no resistance was found. This discrepancy warrants further investigations into the preferred test conditions for tigecycline. In conclusion, tigecycline showed good activity against MRSA strains in vitro

Semi-automatic algorithm for construction of the left ventricular area variation curve over a complete cardiac cycle

<p>Abstract</p> <p>Background</p> <p>Two-dimensional echocardiography (2D-echo) allows the evaluation of cardiac structures and their movements. A wide range of clinical diagnoses are based on the performance of the left ventricle. The evaluation of myocardial function is typically performed by manual segmentation of the ventricular cavity in a series of dynamic images. This process is laborious and operator dependent. The automatic segmentation of the left ventricle in 4-chamber long-axis images during diastole is troublesome, because of the opening of the mitral valve.</p> <p>Methods</p> <p>This work presents a method for segmentation of the left ventricle in dynamic 2D-echo 4-chamber long-axis images over the complete cardiac cycle. The proposed algorithm is based on classic image processing techniques, including time-averaging and wavelet-based denoising, edge enhancement filtering, morphological operations, homotopy modification, and watershed segmentation. The proposed method is semi-automatic, requiring a single user intervention for identification of the position of the mitral valve in the first temporal frame of the video sequence. Image segmentation is performed on a set of dynamic 2D-echo images collected from an examination covering two consecutive cardiac cycles.</p> <p>Results</p> <p>The proposed method is demonstrated and evaluated on twelve healthy volunteers. The results are quantitatively evaluated using four different metrics, in a comparison with contours manually segmented by a specialist, and with four alternative methods from the literature. The method's intra- and inter-operator variabilities are also evaluated.</p> <p>Conclusions</p> <p>The proposed method allows the automatic construction of the area variation curve of the left ventricle corresponding to a complete cardiac cycle. This may potentially be used for the identification of several clinical parameters, including the area variation fraction. This parameter could potentially be used for evaluating the global systolic function of the left ventricle.</p

Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression

Background Besides serum levels of PSA, there is a lack of prostate cancer specific biomarkers. It is need to develop new biological markers associated with the tumor behavior which would be valuable to better individualize treatment. The aim of this study was to elucidate the relationship between single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and prostate cancer progression.Methods A total of 494 prostate cancer patients from a Spanish multicenter study were genotyped for 10 SNPs in XRCC1, ERCC2, ERCC1, LIG4, ATM and TP53 genes. The SNP genotyping was made in a Biotrove OpenArray® NT Cycler. Clinical tumor stage, diagnostic PSA serum levels, and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator.Results SNPs rs11615 (ERCC1) and rs17503908 (ATM) appeared as risk factors for prostate cancer aggressiveness. Patients wild homozygous for these SNPs (AA and TT, respectively) were at higher risk for developing cT2b – cT4 (OR = 2.21 (confidence interval (CI) 95% 1.47 – 3.31), p < 0.001) and Gleason scores ≥ 7 (OR = 2.22 (CI 95% 1.38 – 3.57), p < 0.001), respectively. Moreover, those patients wild homozygous for both SNPs had the greatest risk of presenting D’Amico high-risk tumors (OR = 2.57 (CI 95% 1.28 – 5.16)).Conclusions Genetic variants at DNA repair genes are associated with prostate cancer progression, and would be taken into account when assessing the malignancy of prostate cancer.This work was subsidized by a grant from the Instituto de Salud Carlos III (Ministerio de Economía y Competitividad from Spain), ID: PI12/01867. Almudena Valenciano has a grant from the Instituto Canario de Investigación del Cáncer (ICIC)

Improving Cry8Ka toxin activity towards the cotton boll weevil (Anthonomus grandis)

<p>Abstract</p> <p>Background</p> <p>The cotton boll weevil (<it>Anthonomus grandis</it>) is a serious insect-pest in the Americas, particularly in Brazil. The use of chemical or biological insect control is not effective against the cotton boll weevil because of its endophytic life style. Therefore, the use of biotechnological tools to produce insect-resistant transgenic plants represents an important strategy to reduce the damage to cotton plants caused by the boll weevil. The present study focuses on the identification of novel molecules that show improved toxicity against the cotton boll weevil. <it>In vitro </it>directed molecular evolution through DNA shuffling and phage display screening was applied to enhance the insecticidal activity of variants of the Cry8Ka1 protein of <it>Bacillus thuringiensis</it>.</p> <p>Results</p> <p>Bioassays carried out with <it>A. grandis </it>larvae revealed that the LC₅₀of the screened mutant Cry8Ka5 toxin was 3.15-fold higher than the wild-type Cry8Ka1 toxin. Homology modelling of Cry8Ka1 and the Cry8Ka5 mutant suggested that both proteins retained the typical three-domain Cry family structure. The mutated residues were located mostly in loops and appeared unlikely to interfere with molecular stability.</p> <p>Conclusions</p> <p>The improved toxicity of the Cry8Ka5 mutant obtained in this study will allow the generation of a transgenic cotton event with improved potential to control <it>A. grandis</it>.</p

Endocytic and Recycling Endosomes Modulate Cell Shape Changes and Tissue Behaviour during Morphogenesis in Drosophila

During development tissue deformations are essential for the generation of organs and to provide the final form of an organism. These deformations rely on the coordination of individual cell behaviours which have their origin in the modulation of subcellular activities. Here we explore the role endocytosis and recycling on tissue deformations that occur during dorsal closure of the Drosophila embryo. During this process the AS contracts and the epidermis elongates in a coordinated fashion, leading to the closure of a discontinuity in the dorsal epidermis of the Drosophila embryo. We used dominant negative forms of Rab5 and Rab11 to monitor the impact on tissue morphogenesis of altering endocytosis and recycling at the level of single cells. We found different requirements for endocytosis (Rab5) and recycling (Rab11) in dorsal closure, furthermore we found that the two processes are differentially used in the two tissues. Endocytosis is required in the AS to remove membrane during apical constriction, but is not essential in the epidermis. Recycling is required in the AS at early stages and in the epidermis for cell elongation, suggesting a role in membrane addition during these processes. We propose that the modulation of the balance between endocytosis and recycling can regulate cellular morphology and tissue deformations during morphogenesis

Transient and sustained incentive effects on electrophysiological indices of cognitive control in younger and older adults

Preparing for upcoming events, separating task-relevant from task-irrelevant information and efficiently responding to stimuli all require cognitive control. The adaptive recruitment of cognitive control depends on activity in the dopaminergic reward system as well as the frontoparietal control network. In healthy aging, dopaminergic neuromodulation is reduced, resulting in altered incentive-based recruitment of control mechanisms. In the present study, younger adults (18–28 years) and healthy older adults (66–89 years) completed an incentivized flanker task that included gain, loss, and neutral trials. Event-related potentials (ERPs) were recorded at the time of incentive cue and target presentation. We examined the contingent negative variation (CNV), implicated in stimulus anticipation and response preparation, as well as the P3, which is involved in the evaluation of visual stimuli. Both younger and older adults showed transient incentive-based modulation of CNV. Critically, cue-locked and target-locked P3s were influenced by transient and sustained effects of incentives in younger adults, while such modulation was limited to a sustained effect of gain incentives on cue-P3 in older adults. Overall, these findings are in line with an age-related reduction in the flexible recruitment of preparatory and target-related cognitive control processes in the presence of motivational incentives