Shared Molecular Mechanisms among Alzheimer’s Disease, Neurovascular Unit Dysfunction and Vascular Risk Factors: A Narrative Review

Alzheimer’s disease (AD) is the most common type of dementia, affecting 24 million individuals. Clinical and epidemiological studies have found several links between vascular risk factors (VRF), neurovascular unit dysfunction (NVUd), blood-brain barrier breakdown (BBBb) and AD onset and progression in adulthood, suggesting a pathogenetic continuum between AD and vascular dementia. Shared pathways between AD, VRF, and NVUd/BBB have also been found at the molecular level, underlining the strength of this association. The present paper reviewed the literature describing commonly shared molecular pathways between adult-onset AD, VRF, and NVUd/BBBb. Current evidence suggests that VRF and NVUd/BBBb are involved in AD neurovascular and neurodegenerative pathology and share several molecular pathways. This is strongly supportive of the hypothesis that the presence of VRF can at least facilitate AD onset and progression through several mechanisms, including NVUd/BBBb. Moreover, vascular disease and several comorbidities may have a cumulative effect on VRF and worsen the clinical manifestations of AD. Early detection and correction of VRF and vascular disease by improving NVUd/BBBd could be a potential target to reduce the overall incidence and delay cognitive impairment in AD

MicroRNAs as potential biomarkers in pituitary adenomas

Pituitary adenomas (PAs) are one of the most common lesions of intracranial neoplasms, occurring in approximately 15% of the general population. They are typically benign, although some adenomas show aggressive behavior, exhibiting rapid growth, drug resistance, and invasion of surrounding tissues. Despite ongoing improvements in diagnostic and therapeutic strategies, late first diagnosis is common, and patients with PAs are prone to relapse. Therefore, earlier diagnosis and prevention of recurrence are of importance to improve patient care. MicroRNAs (miRNAs) are short non-coding single stranded RNAs that regulate gene expression at the post-transcriptional level. An increasing number of studies indicate that a deregulation of their expression patterns is related with pituitary tumorigenesis, suggesting that these small molecules could play a critical role in contributing to tumorigenesis and the onset of these tumors by acting either as oncosuppressors or as oncogenes, depending on the biological context. This paper provides an overview of miRNAs involved in PA tumorigenesis, which might serve as novel potential diagnostic and prognostic non-invasive biomarkers, and for the future development of miRNA-based therapeutic strategies for PAs

Are non-coding rnas useful biomarkers in parathyroid tumorigenesis?

Tumors of the parathyroid glands are common endocrine diseases almost always characterized by parathyroid hormone hypersecretion that determines the clinical manifestations of primary hyperparathyroidism, such as fatigue, kidney problems, weakness, brittle bones, and other symptoms. Most parathyroid neoplasia are benign adenomas, although rare malignant forms have been described. They are heterogeneous in terms of clinical presentation and the associated signs and symptoms overlap with those of disease and aging. Furthermore, most patients with hypercalcemia are discovered during routine blood tests for other reasons. Surgical removal is considered the main therapeutic option to cure these endocrine tumors and, therefore, innovative therapeutic approaches are actively required. Recently, a growing number of studies have suggested that alterations to the epigenetic mechanisms could play a pivotal role in parathyroid tumorigenesis. Most of the attention has been focused on non-coding RNAs (ncRNAs) (i.e., miRNAs, lncRNAs, and circRNAs) whose expression profile has been found to be deregulated in parathyroid tumors. The aim of the present paper is to give an insight into the ncRNAs involved in parathyroid tumorigenesis, which could be used in the future either as innovative diagnostic biomarkers or as therapeutic targets for the treatment of this endocrine neoplasia

Results on pre-series production and QA/QC tests of the double-ends readout panels of the new layer of trigger chambers for the ATLAS muon spectrometer phase 2 upgrade

In view of High Luminosity LHC upgrade, the ATLAS experiment will add a new layer of Resistive Plate Chambers (RPC) trigger chambers into the barrel muon spectrometer. These next-generation RPC chambers will use a 1 mm gap and a single type of readout strips coupled to front-end electronics capable of providing both coordinates in the detector plane. The procedures for assembling the readout panels and the results of Quality Assurance and Quality Control (QA/QC) tests on the pre-series panels is reported here

Impact of atrial fibrillation in critically ill patients admitted to a stepdown unit

Background: Limited data are available on the clinical course of patients with history of atrial fibrillation (AF) when admitted in an intensive care environment. We aimed to describe the occurrence of major adverse events in AF patients admitted to a stepdown care unit (SDU) and to analyse clinical factors associated with outcomes, impact of dicumarolic oral anticoagulant (OAC) therapy impact and performance of clinical risk scores in this setting. Materials and methods: Single-centre, observational retrospective analysis on a population of subjects with AF history admitted to a SDU. Therapeutic failure (composite of transfer to ICU or death) was considered the main study outcome. Occurrence of stroke and major bleeding (MH) was considered as secondary outcomes. The performance of clinical risk scores was evaluated. Results: A total of 1430 consecutive patients were enrolled. 194 (13.6%) reported the main outcome. Using multivariate logistic regression, age (odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.01-1.05), acute coronary syndrome (OR:3.10, 95% CI: 1.88-5.12), cardiogenic shock (OR:10.06, 95% CI: 5.37-18.84), septic shock (OR:5.19,95%CI:3.29-18.84), acute respiratory failure (OR:2.49, 95% CI: 1.67-3.64) and OAC use (OR: 1.61, 95% CI: 1.02-2.55) were independently associated with main outcome. OAC prescription was associated with stroke risk reduction and to both MH and main outcome risk increase. CHA2 DS2 -VASc (c-index: 0.545, P = .117 for stroke) and HAS-BLED (c-index:0.503, P = .900 for MH) did not significantly predict events occurrence. Conclusions: In critically ill AF patients admitted to a SDU, adverse outcomes are highly prevalent. OAC use is associated to an increased risk of therapeutic failure, clinical scores seem unhelpful in predicting stroke and MH, suggesting a highly individualized approach in AF management in this setting

Predictors of Peritraumatic Reactions and PTSD Following the September 11th Terrorist Attacks

In this study the authors characterize peritraumatic reactions of residents of New York City during and immediately following the September 11th terrorist attacks, identify predictors of those reactions, and identify predictors of PTSD 4 months later. A cross–sectional sample of New York residents (n = 2,001) responded to questions about sociodemographics, historical factors, event–related exposure; acute cognitive, emotional, and physiological reactions to the September 11th terrorist attacks; and current (past month) PTSD symptoms. Factor analyses of peritraumatic reactions yielded three related, but distinct, peritraumatic response patterns—dissociation, emotional reactions, and panic/physiological arousal. Several demographic, historical, and exposure–related variables predicted one or more peritraumatic reaction patterns. After controlling for demographic, historical, and exposure factors, each of the peritraumatic reactions factors, one historical factor and one event–related exposure factor remained as significant predictors of PTSD. These results support a growing literature concerning the predictive value of peritraumatic reactions in relation to PTSD. Implications for preventive efforts and suggestions for future research are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40315/2/Lawyer_Predictors of peritraumatic reactions and PTSD_2006.pd

Neural hypernetwork approach for pulmonary embolism diagnosis

Background Hypernetworks are based on topological simplicial complexes and generalize the concept of two-body relation to many-body relation. Furthermore, Hypernetworks provide a significant generalization of network theory, enabling the integration of relational structure, logic and analytic dynamics. A pulmonary embolism is a blockage of the main artery of the lung or one of its branches, frequently fatal. Results Our study uses data on 28 diagnostic features of 1427 people considered to be at risk of pulmonary embolism enrolled in the Department of Internal and Subintensive Medicine of an Italian National Hospital “Ospedali Riuniti di Ancona”. Patients arrived in the department after a first screening executed by the emergency room. The resulting neural hypernetwork correctly recognized 94 % of those developing pulmonary embolism. This is better than previous results obtained with other methods (statistical selection of features, partial least squares regression, topological data analysis in a metric space). Conclusion In this work we successfully derived a new integrative approach for the analysis of partial and incomplete datasets that is based on Q-analysis with machine learning. The new approach, called Neural Hypernetwork, has been applied to a case study of pulmonary embolism diagnosis. The novelty of this method is that it does not use clinical parameters extracted by imaging analysis