Genetics of Late-Onset Alzheimer's Disease: Update from the Alzgene Database and Analysis of Shared Pathways

The genetics of late-onset Alzheimer's disease (LOAD) has taken impressive steps forwards in the last few years. To date, more than six-hundred genes have been linked to the disorder. However, only a minority of them are supported by a sufficient level of evidence. This review focused on such genes and analyzed shared biological pathways. Genetic markers were selected from a web-based collection (Alzgene). For each SNP in the database, it was possible to perform a meta-analysis. The quality of studies was assessed using criteria such as size of research samples, heterogeneity across studies, and protection from publication bias. This produced a list of 15 top-rated genes: APOE, CLU, PICALM, EXOC3L2, BIN1, CR1, SORL1, TNK1, IL8, LDLR, CST3, CHRNB2, SORCS1, TNF, and CCR2. A systematic analysis of gene ontology terms associated with each marker showed that most genes were implicated in cholesterol metabolism, intracellular transport of beta-amyloid precursor, and autophagy of damaged organelles. Moreover, the impact of these genes on complement cascade and cytokine production highlights the role of inflammatory response in AD pathogenesis. Gene-gene and gene-environment interactions are prominent issues in AD genetics, but they are not specifically featured in the Alzgene database

Isotretinoin and psychopathology: a review

Isotretinoin, a synthetic oral retinoid that is used against severe nodulocystic acne, has been associated with various psychiatric side effects such as depression, suicidality and psychotic symptoms. A great number of reports on its effects have been published since its introduction into the market. However, a causal relationship has not been established and the link between isotretinoin use and psychiatric events remains controversial. The present paper reviews the available evidence regarding the association of isotretinoin and psychiatric side effects. All published material reporting psychiatric side effects following isotretinoin treatment, including case reports, case series, reports from adverse drug event reporting systems, prospective surveys and retrospective case-control studies, are presented. In addition, the neurobiology of the retinoids and possible biological mechanisms that may lead to psychopathology are described

Abnormal auditory ERP N100 in children with dyslexia: comparison with their control siblings

<p>Abstract</p> <p>Background</p> <p>Recent research has implicated deficits of the working memory (WM) and attention in dyslexia. The N100 component of event-related potentials (ERP) is thought to reflect attention and working memory operation. However, previous studies showed controversial results concerning the N100 in dyslexia. Variability in this issue may be the result of inappropriate match up of the control sample, which is usually based exclusively on age and gender.</p> <p>Methods</p> <p>In order to address this question the present study aimed at investigating the auditory N100 component elicited during a WM test in 38 dyslexic children in comparison to those of 19 unaffected sibling controls. Both groups met the criteria of the International Classification of Diseases (ICD-10). ERP were evoked by two stimuli, a low (500 Hz) and a high (3000 Hz) frequency tone indicating forward and reverse digit span respectively.</p> <p>Results</p> <p>As compared to their sibling controls, dyslexic children exhibited significantly reduced N100 amplitudes induced by both reverse and forward digit span at Fp1, F3, Fp2, Fz, C4, Cz and F4 and at Fp1, F3, C5, C3, Fz, F4, C6, P4 and Fp2 leads respectively. Memory performance of the dyslexics group was not significantly lower than that of the controls. However, enhanced memory performance in the control group is associated with increased N100 amplitude induced by high frequency stimuli at the C5, C3, C6 and P4 leads and increased N100 amplitude induced by low frequency stimuli at the P4 lead.</p> <p>Conclusion</p> <p>The present findings are in support of the notion of weakened capture of auditory attention in dyslexia, allowing for a possible impairment in the dynamics that link attention with short memory, suggested by the anchoring-deficit hypothesis.</p

Effect of initiation-inhibition and handedness on the patterns of the P50 event-related potential component: a low resolution electromagnetic tomography study

<p>Abstract</p> <p>Background</p> <p>Recent research recognizes the association between handedness, linguistic processes and cerebral networks subserving executive functioning, but the nature of this association remains unclear. Since the P50 event related potential (ERP) is considered to reflect thalamocortical processes in association with working memory (WM) operation the present study focuses on P50 patterns elicited during the performance of a linguistic related executive functioning test in right- and left-handers.</p> <p>Methods</p> <p>In 64 young adults with a high educational level (33 left-handed) the P50 event-related potential was recorded while performing the initiation and inhibition condition of a modified version of the Hayling Sentence Completion test adjusted to induce WM. The manual preference of the participants was evaluated with the use of the Edinburgh Handedness Inventory (EHI).</p> <p>Results</p> <p>P50 showed greater amplitudes in left- than in right-handers, mainly in frontal leads, in the initiation condition. Reduced amplitudes in inhibition compared to initiation condition were observed in left-handers. Low Resolution Electromagnetic Tomography (LORETA) analysis showed lower frontal lobe activation in the inhibition than in the initiation condition in both right- and left-handers. Also, LORETA yielded that right-handers exhibited greater activation in the inhibition condition than left-handers. Additionally, LORETA showed assymetrical hemispheric activation patterns in right-handers, in contrast to symmetrical patterns observed in left-handers. Higher P50 amplitudes were recorded in right-hemisphere of right-handers in the initiation condition.</p> <p>Conclusion</p> <p>Brain activation, especially the one closely related to thalamocortical function, elicited during WM operation involving initiation and inhibition processes appears to be related to handedness.</p

Quasi-normal Modes of Electromagnetic Perturbations of Four-Dimensional Topological Black Holes with Scalar Hair

We study the perturbative behaviour of topological black holes with scalar hair. We calculate both analytically and numerically the quasi-normal modes of the electromagnetic perturbations. In the case of small black holes we find evidence of a second-order phase transition of a topological black hole to a hairy configuration.Comment: v2: 19 pages, 2 figures, added references, improved discussion, to appear in JHE

Stability Studies for Photovoltaic Integration using Power Hardware-in-the-Loop Experiments

The electrical power network is gradually migrating from a centralized generation approach to a decentralized generation with high shares of renewable energy sources (RES). However, power systems with low shares of synchronous generation and consequently low total system inertia, are vulnerable to power imbalances. Such systems can experience frequency stability problems, such as high frequency excursions and higher rates of change of frequency even under small disturbances. This phenomenon is intensified when the grid under investigation has low or no interconnections (islanded) and thus the challenge for stable operation becomes more significant for the operators. This work focuses on how the frequency stability is affected when a photovoltaic (PV) inverter is integrated into a real non-interconnected distribution grid in Cyprus. In order to capture the realistic interactions of this integration, stability experiments in a hardware-in-the-loop (HIL) environment are performed with the aim to provide insightful results for the grid operator.Comment: The 12th Mediterranean Conference on Power Generation, Transmission, Distribution and Energy Conversion (MEDPOWER 2020

Excessive weight gain after remission of depression in a schizophrenic patient treated with risperidone: case report

BACKGROUND: The use of atypical antipsychotics in schizophrenic patients has been associated with a risk of weight gain. Similarly, recovery from depression is often followed by improved appetite, greater food intake and potential increase in weight. CASE PRESENTATION: A Caucasian 33-year-old schizophrenic female patient was being treated with 6 mg/day of risperidone and 15 mg/day of clorazepate. She developed depressive symptomatology and 40 mg/day of fluoxetine was gradually added to her treatment regimen for about 9 months. After the remission of depression, and the discontinuation of fluoxetine, she experienced an increase in appetite and subsequently excessive weight gain of 52 kg. Re-administration of fluoxetine did not reverse the situation. The patient developed diabetes mellitus, which was successfully controlled with metformin 1700 mg/day. The addition at first of orlistat 360 mg/day and later of topiramate 200 mg/day has helped her to lose a significant part of the weight gained (30 kg). CONCLUSION: The case suggests a probable association between the remission of depressive symptomatology and weight gain in a schizophrenic patient