Psychosis in Alzheimer's Disease is Associated with Excitatory Neuron Vulnerability and Post-Transcriptional Mechanisms Altering Synaptic Protein Levels

Alzheimer's disease with psychosis (AD+P) is a phenotypic variant of the disease which is associated with a much more rapid deterioration compared to Alzheimer's disease without psychosis (AD-P). The neurobiological basis of AD+P is poorly understood. AD is thought to be a disease of the synapse, and our previous studies suggest that those with AD+P have a differentially affected synaptic proteome relative to those with AD-P. We previously demonstrated that multiple neuropathologies only account for approximately 18% of the variance in the occurrence of psychosis in AD. In this study, we utilized RNA-sequencing of dorsolateral prefrontal cortex (DLPFC) in a cohort of 80 AD cases to evaluate novel transcriptomic signatures that may confer risk of psychosis in AD. We found that AD+P was associated with a 9% reduction in excitatory neuron proportion compared to AD-P [Mean (SD) AD+P 0.295 (0.061); AD-P 0.324 (0.052), p = 0.026]. Network analysis identified altered expression of gene modules from protein ubiquitination, unfolded protein response, eukaryotic initiation factor 2 (EIF2) signaling and endoplasmic reticulum stress pathways in AD+P. Including cell type proportions and differentially expressed modules with neuropathology measures explained 67.5% of the variance in psychosis occurrence in our AD cohort.

Guillain-barré syndrome (GBS): acute motor axonal neuropathy (AMAN) - case report

Background: GBS is an acute inflammatory polyneuropathy resulting from an immune response after infection. Characterized as an ascetic, progressive, selflimiting flaccid tetraparesis. It has several phenotypic presentations, which one is AMAN. The treatment’s based on use of intravenous immunoglobulin (IGIV) and plasmapheresis (PLEX). Methods: A literature review of the PubMed and UpToDate databases using descriptors “GBS” and “AMAN” between 2014-2020. Objectives: Report a case of GBS, addressing AMAN variant; a literature review with therapeutic and diagnostic possibilities. Case report: DTS, 32y, male, admitted with a picture of flaccid, limp asymmetrical tetraparesis, with an asymmetrical pattern, predominant in lower limbs, without sensory symptoms. Progressive evolution, onset of motor symptoms on the 8th day after self-limited diarrhea. CSF on 3rd day of onset of motor symptoms without dissociation cytological protein - CN: 62 / Ptn: 80.1mg / dl. Repeated CSF on the 10th day with CN: 27 / Ptn: 215 mg / dl. electroneuromyography 16/04: electrophysiological examination shows motor neuropathy of axonal pattern with signs of denervation in activity, findings compatible with axonal neuropathy. IGIV was performed for 5 days, without complications. Results: The diagnosis of GBS is based on CSF clinical criteria and findings on electroneuromyography. AMAN is a phenotypic variant characterized by purely motor and axonal impairment. The therapeutic options proven effectiveness are PLEX, and IGIV. Conclusion: Studies demonstrates that there’s no difference in effectiveness between PLEX and IGIV, the choice of treatment being dependent on socioeconomic and patient-related factors.

Annotation of Human Exome Gene Variants with Consensus Pathogenicity

A novel approach is developed to address the challenge of annotating with phenotypic effects those exome variants for which relevant empirical data are lacking or minimal. The predictive annotation method is implemented as a stacked ensemble of supervised base-learners, including distributed random forest and gradient boosting machines. Ensemble models were trained and cross-validated on evidence-based categorical variant effect annotations from the ClinVar database, and were applied to 84 million non-synonymous single nucleotide variants (SNVs). The consensus model combined 39 functional mutation impacts, cross-species conservation score, and gene indispensability score. The indispensability score, accounting for differences in variant pathogenicities including in essential and mutation-tolerant genes, considerably improved the predictions. The consensus combination is consistent with as many input scores as possible while minimizing false predictions. The input scores are ranked based on their ability to predict effects. The score rankings and categorical phenotypic variant effect predictions are aimed for direct use in clinical and biological applications to prioritize human exome variants and mutations.

Gardner Syndrome: Complications/Manifestations in the Oral Cavity and Their Relationship with Oral Health

Gardner syndrome (GS) is a genetic disease, with autosomal dominant transmission, being a phenotypic variant of familial adenomatous polyposis (FAP). FAP is manifested by the development of numerous adenomas in the rectum during adolescence, and in most cases, if not identified and treated at an early stage, lead to colorectal cancer. This syndrome has several phenotypic characteristics and among them some changes in the oral cavity. Thus, the dentist has a preponderant role in the detection of lesions that may be present in the oral cavity in order to make possible an early diagnosis of the disease. Some manifestations of GS are observed at the dental level. Around 30 to 75% of GS patients present dental anomalies including dental agenesis, including teeth, delays in teeth eruption, dentigerous cysts, odontomas, supernumerary teeth, root fusion and hypercementosis. It is possible to see a significant difference in the presence of dental problems between patients with GS and the general population. In order to reduce morbidity and mortality, several types of surgery are used to eliminate the risk of colorectal cancer, preserving neighbouring anatomical functions.