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Safouris A.,Brugmann University Hospital | Tsivgoulis G.,National and Kapodistrian University of Athens | Tsivgoulis G.,St Annes University Hospital In Brno | Tsivgoulis G.,University of Tennessee Health Science Center | And 2 more authors.
Current Alzheimer Research | Year: 2015

Dementia is a major global health challenge, as its burden on society will increase with population aging. Given the lack of effective pharmaceutical treatment for common types of dementia including Alzheimer’s disease and vascular dementia, research interest in lifestyle modifications that could prevent, postpone the clinical syndrome or decelerate progression of dementia is growing. Among the various dietary patterns that were tested for their effects on cognition, the traditional Mediterranean diet (MeDi) has shown promising results. This review aims to summarize the epidemiological evidence on the effects of MeDi on the prevention of dementia, presenting data from cross-sectional as well as longitudinal observational studies conducted both in Mediterranean and non-Mediterranean countries. These findings have been also reproduced in the context of one recent randomizedcontrolled clinical trial. Postulated mechanisms of action that may account for the potential protective effect of MeDi on cognitive impairment will be briefly discussed. Despite the fact that the link between MeDi and cognitive decline has been only explored for less than a decade, data on efficacy is rapidly increasing and allows optimism that MeDi could emerge as an alternative prophylactic treatment for dementia. © 2015 Bentham Science Publishers.

Sarangi P.,Sloan Kettering Cancer Center | Sarangi P.,The New School | Bartosova Z.,Masaryk University | Altmannova V.,Masaryk University | And 7 more authors.
Nucleic Acids Research | Year: 2014

The Saccharomyces cerevisiae Rad1-Rad10 complex is a conserved, structure-specific endonuclease important for repairing multiple types of DNA lesions. Upon recruitment to lesion sites, Rad1-Rad10 removes damaged sequences, enabling subsequent gap filling and ligation. Acting at mid-steps of repair, the association and dissociation of Rad1-Rad10 with DNA can influence repair efficiency. We show that genotoxin-enhanced Rad1 sumoylation occurs after the nuclease is recruited to lesion sites. A single lysine outside Rad1's nuclease and Rad10-binding domains is sumoylated in vivo and in vitro. Mutation of this site to arginine abolishes Rad1 sumoylation and impairs Rad1-mediated repair at high doses of DNA damage, but sustains the repair of a single double-stranded break. The timing of Rad1 sumoylation and the phenotype bias toward high lesion loads point to a post-incision role for sumoylation, possibly affecting Rad1 dissociation from DNA. Indeed, biochemical examination shows that sumoylation of Rad1 decreases the complex's affinity for DNA without affecting other protein properties. These findings suggest a model whereby sumoylation of Rad1 promotes its disengagement from DNA after nuclease cleavage, allowing it to efficiently attend to large numbers of DNA lesions. © 2014 The Author(s) 2014.

Giannopoulos S.,University of Ioannina | Katsanos A.H.,University of Ioannina | Kosmidou M.,University of Ioannina | Tsivgoulis G.,National and Kapodistrian University of Athens | Tsivgoulis G.,St Annes University Hospital In Brno
Journal of Alzheimer's Disease | Year: 2014

The impact of statin therapy on dementia has been a hot topic of debate over the last decade and still remains highly controversial. Among all causes of dementia, vascular dementia (VaD) is the one type that is more likely to benefit from statins. To date no randomized clinical trials have been published and no systematic review has investigated a possible preventive effect of statins on the VaD subtype. In the present literature review, we tried to identify all available data on the effect of statins specifically in patients with VaD, and to further discuss this possible association. Our literature search highlighted two cross-sectional studies, two prospective cohort studies, and one retrospective cohort study. Two of the studies found a significant positive effect of statin treatment on VaD, depicted by the lower incidence of VaD in statin users, while the others reported non-significant associations. The relatively small numbers of VaD patients and statin users, as well as the presence of confounders and biases, make the interpretation of results extremely difficult. Statins may exert a benefit in the prevention of all-type dementia and VaD, through several mechanisms except for hyperlipidemia reduction. A well-designed randomized clinical trial is the ideal study design to address the effect of statin therapy in VaD and to draw final conclusions. © 2014-IOS Press and the authors.

Katsanos A.H.,University of Ioannina | Spence J.D.,University of Western Ontario | Bogiatzi C.,University of Western Ontario | Parissis J.,National and Kapodistrian University of Athens | And 6 more authors.
Stroke | Year: 2014

Background and Purpose-Recurrent cerebrovascular events are frequent in medically treated patients with patent foramen ovale (PFO), but it still remains unclear whether PFO is a causal or an incidental finding. Further uncertainty exists on whether the size of functional shunting could represent a potential risk factor. The aim of the present study was to evaluate if the presence of PFO is associated with an increased risk of recurrent stroke or transient ischemic attack and to investigate further if this relationship is related to the shunt size. Methods-We conducted a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of all available prospective studies reporting recurrent cerebrovascular events defined as cryptogenic stroke and transient ischemic attacks in medically treated patients with PFO diagnosed by echocardiography or transcranial sonography. Results-We identified 14 eligible studies including a total of 4251 patients. Patients with stroke with PFO did not have a higher risk of the combined outcome of recurrent stroke/transient ischemic attack (risk ratio=1.18; 95% confidence interval=0.78-1.79; P=0.43) or in the incidence of recurrent strokes (risk ratio =0.85; 95% confidence interval=0.59-1.22; P=0.37) in comparison with stroke patients without PFO. In addition, PFO size was not associated with the risk of recurrent stroke or transient ischemic attack. We also documented no evidence of heterogeneity across the included studies. Conclusions-Our findings indicate that medically treated patients with PFO do not have a higher risk for recurrent cryptogenic cerebrovascular events, compared with those without PFO. No relation between the degree of PFO and the risk of future cerebrovascular events was identified. © 2014 American Heart Association, Inc.

Kerasnoudis A.,St. Luke Hospital | Tsivgoulis G.,National and Kapodistrian University of Athens | Tsivgoulis G.,St Annes University Hospital In Brno
Journal of Neuroimaging | Year: 2015

Peripheral neuropathies are one of the most common reasons for seeking neurological care in everyday practice. Electrophysiological studies remain fundamental for the diagnosis and etiological classification of peripheral nerve impairment. The recent technological development though of high resolution ultrasound has allowed the clinician to obtain detailed structural images of peripheral nerves. Nerve ultrasound mainly focuses on the evaluation of the cross sectional area, cross sectional area variability along the anatomical course, echogenity, vascularity and mobility of the peripheral nerves. An increase of the cross sectional area, hypervascularity, disturbed fascicular echostructure and reduced nerve mobility are some of the most common findings of entrapments neuropathies, such as the carpal or cubital tunnel syndrome. Both the cross-sectional area increase and the hypervascularity detected with the Doppler technique seem to correlate significantly with the clinical and electrophysiological severity of the later mononeuropathies. Significantly greater cross sectional area values of the clinically affected cervical nerve root are often detected in cases of cervical radiculopathy. In such cases, the ultrasound findings seem also to correlate significantly with disease duration. On the other hand, multifocal cross sectional area enlargement of cervical roots and/or peripheral nerves is often documented in cases of immune-mediated neuropathies. None of the later pathological ultrasound findings seem to correlate significantly with the electrophysiological parameters or the functional disability. The aim of this review is to provide a timely update on the role of neuromuscular ultrasound in the diagnostic of the most common entrapment and immune-mediated peripheral neuropathies in clinical practice. © 2015 by the American Society of Neuroimaging.

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