Apelin Enhances Directed Cardiac Differentiation of Mouse and Human Embryonic Stem Cells

Apelin is a peptide ligand for an orphan G-protein coupled receptor (APJ receptor) and serves as a critical gradient for migration of mesodermal cells fated to contribute to the myocardial lineage. The present study was designed to establish a robust cardiac differentiation protocol, specifically, to evaluate the effect of apelin on directed differentiation of mouse and human embryonic stem cells (mESCs and hESCs) into cardiac lineage. Different concentrations of apelin (50, 100, 500 nM) were evaluated to determine its differentiation potential. The optimized dose of apelin was then combined with mesodermal differentiation factors, including BMP-4, activin-A, and bFGF, in a developmentally specific temporal sequence to examine the synergistic effects on cardiac differentiation. Cellular, molecular, and physiologic characteristics of the apelin-induced contractile embryoid bodies (EBs) were analyzed. It was found that 100 nM apelin resulted in highest percentage of contractile EB for mESCs while 500 nM had the highest effects on hESCs. Functionally, the contractile frequency of mESCs-derived EBs (mEBs) responded appropriately to increasing concentration of isoprenaline and diltiazem. Positive phenotype of cardiac specific markers was confirmed in the apelin-treated groups. The protocol, consisting of apelin and mesodermal differentiation factors, induced contractility in significantly higher percentage of hESC-derived EBs (hEBs), up-regulated cardiac-specific genes and cell surface markers, and increased the contractile force. In conclusion, we have demonstrated that the treatment of apelin enhanced cardiac differentiation of mouse and human ESCs and exhibited synergistic effects with mesodermal differentiation factors

Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

Disentangling the relationship between cognitive estimation abilities and executive functions: a study on patients with Parkinson's disease

The cognitive estimation test (CET) measures cognitive estimation abilities: it assesses the ability to apply reasoning strategies to answer questions that usually cannot lead to a clear and exact reply. Since it requires the activation of an intricate ensemble of cognitive functions, there is an ongoing debate in the literature regarding whether the CET represents a measurement of global cognitive abilities or a pure measure of executive functions. In the present study, CET together with a neuropsychological assessment focused on executive functions was administered in thirty patients with Parkinson's disease without signs of dementia. The CET correlated with measures of verbal working memory and semantic knowledge, but not with other dimensions of executive domains, such as verbal phonemic fluency, ability to manage real-world interferences, or visuospatial reasoning. According to our results, cognitive estimation abilities appeared to trigger a defined cognitive path that includes executive functions, namely, working memory and semantic knowledge

Characteristics of anxiety and psychological well-being in chronic post-stroke patients.

BACKGROUND AND PURPOSE: Anxiety and depression are common psychological conditions in post-stroke patients. In the present study, their relation with perceived quality of life and psychophysical well-being was investigated. METHODS: In the present cross-sectional study, chronic post-stroke patients (n=81; average years from stroke=4 \ub1 4.6) were assessed with the Hospital Anxiety and Depression Scale (HADS), the 36-item Short-Form Healthy Survey (SF-36) and the Psychological General Well-Being Index (PGWBI), as well as a brief neuropsychological assessment focused on the thinking ability and executive functions. RESULTS: Higher levels of anxiety compared to depressive symptoms were found. Hierarchical multiple regressions indicated that SF-36 predicts neither anxiety nor depression, and PGWBI subscales only partially. CONCLUSION: Post-stroke anxiety can be a largely observed psychological distress in chronic patients: this pattern would be interpreted in relation to patients' expectations about their health status during a rehabilitation follow-up. SF-36 and PGWBI questionnaires did not provide satisfactory and reliable indexes: the relation between anxiety and both quality of life and psychological well-being needs further exploration

Psychological considerations in the assessment and treatment of pain in neurorehabilitation and psychological factors predictive of therapeutic response: Evidence and recommendations from the Italian consensus conference on pain in neurorehabilitation

In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) aimed to collate the evidence available across these topics