Platelet Immobilization on Supported Phospholipid Bilayers for Single Platelet Studies.

The worldwide cardiovascular disease (CVD) epidemic is of grave concern. A major role in the etiology of CVDs is played by the platelets (thrombocytes). Platelets are anuclear cell fragments circulating in the blood. Their primary function is to catalyze clot formation, limiting traumatic blood loss in the case of injury. The same process leads to thrombosis in the case of CVDs, which are commonly managed with antiplatelet therapy. Platelets also have other, nonhemostatic functions in wound healing, inflammation, and tissue regeneration. They play a role in the early stages of atherosclerosis and the spread of cancer through metastases. Much remains to be learned about the regulation of these diverse platelet functions under physiological and pathological conditions. Breakthroughs in this regard are expected to come from single platelet studies and systems approaches. The immobilization of platelets at surfaces is advantageous for developing such approaches, but platelets are activated when they come in contact with foreign surfaces. In this work, we develop and validate a protocol for immobilizing platelets on supported lipid bilayers without activation due to immobilization. Our protocol can therefore be used for studying platelets with a wide variety of surface-sensitive techniques.

Behavioral and psychological symptoms and cognitive decline in patients with amnestic MCI and mild AD: a two-year follow-up study.

BACKGROUND: Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and dementia. In many cases, MCI represents an early stage of developing cognitive impairment. Patients diagnosed with MCI do not meet the criteria for dementia as their general intellect and everyday activities are preserved, although minor changes in instrumental activities of daily living (ADL) may occur. However, they may exhibit significant behavioral and psychological signs and symptoms (BPS), also frequently observed in patients with Alzheimer's disease (AD). Hence, we wondered to what extent specific BPS are associated with cognitive decline in participants with MCI or AD. METHODS: Our sample consisted of 164 participants, including 46 patients with amnestic (single or multi-domain) MCI and 54 patients with AD, as well as 64 control participants without cognitive disorders. Global cognitive performance, BPS, and ADL were assessed using validated clinical methods at baseline and at two-year follow-up. RESULTS: The BPS variability over the follow-up period was more pronounced in the MCI group than in patients with AD: some BPS improve, others occur newly or worsen, while others still remain unchanged. Moreover, specific changes in BPS were associated with a rapid deterioration of the global cognitive level in MCI patients. In particular, an increase of euphoria, eating disorders, and aberrant motor behavior, as well as worsened sleep quality, predicted a decline in cognitive functioning. CONCLUSIONS: Our findings confirm a higher variability of BPS over time in the MCI group than in AD patients. Moreover, our results provide evidence of associations between specific BPS and cognitive decline in the MCI group that might suggest a risk of conversion of individuals with amnestic MCI to AD.

Cognitive Empathy and the Dark Triad: A Literature Review.

This literature review aims to analyze studies published by researchers on the topic of the relationship between the psychological constructs of the Dark Triad and Cognitive Empathy. This study hypothesizes how having good cognitive empathic skills could benefit people who demonstrate Dark Triad traits, as this could facilitate the implementation of manipulative strategies. Through the process of identifying studies via databases and registers, 23 studies were included in this literature review, and the results and theories brought forward by the researchers find more agreement regarding the individual components of the Dark Triad than the whole construct: narcissism seems to have, for the most part, relatively small and typical positive correlations (more than 50% of correlations), Machiavellianism has relatively small and typical negative relationships (about 80% of correlations), and psychopathy has relatively large negative relationships (about 90% of correlations). This study conveys that Machiavellians and psychopaths, having reduced empathic abilities, use manipulation techniques that do not have to do with empathy (for example seduction, intimidation etc.), while narcissists would be, among these three dimensions, those most likely to understand others' states of mind and thus be able to use this knowledge to their advantage-although there are doubts about the veracity of the statements and answers given by narcissists in the tests administered to them. This literature review could be a valid aid to professionals dealing with people who exhibit Dark Triad traits; understanding how those exhibiting Dark Triad traits manage their empathic abilities, the areas in which the various dimensions show deficits or not, and how they act to implement their manipulative and controlling tactics could aid in the development of more effective helping strategies to be utilized in therapy settings.

Neuropsychological deficits correlate with symptoms severity and cortical thickness in Borderline Personality Disorder.

BACKGROUND: Neuropsychological abnormalities have been proposed to contribute to the development and maintenance of Borderline Personality Disorder (BPD). Previous meta-analyses and reviews confirmed deficits in a broad range of cognitive domains, including attention, cognitive flexibility, memory, executive functions, planning, information processing, and visuospatial abilities, often suggested to underlie brain abnormalities. However, no study directly explored the structural neural correlates of these deficits in BPD, also accounting for the possible confounding effect of pharmacological treatments, often used as adjunctive symptom-targeted therapy in clinical setting. METHODS: In this study we compared the performance of 24 BPD patients to 24 healthy controls obtained at the neuropsychological battery "Brief Assessment and Cognition in Schizophrenia", exploring the relationship between the cognitive impairments and current symptomatology, brain grey matter volumes and cortical thickness, controlling for medications load. RESULTS: Data revealed deficits in verbal memory and fluency, working memory, attention and speed of information processing and psychomotor speed and coordination when medication load was not in the model. Correcting for this variable, only the impairment in psychomotor abilities remained significant. A multiple regression confirmed the effect of this neuropsychological domain on the severity of BPD symptomatology (Borderline Evaluation of Severity Over Time). In BPD, the performance at psychomotor speed and coordination was also directly associated to cortical thickness in postcentral gyrus. LIMITATIONS: Relatively small sample size, especially for neuroimaging. CONCLUSIONS: Our study highlighted an influence of BPD neuropsychological impairments on symptomatology, and cortical thickness, prompting the potential clinical utility of a cognitive remediation program in BPD.

Deciphering and predicting CD4+ T cell immunodominance of influenza virus hemagglutinin.

The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry-based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance.

Early Secure Attachment as a Protective Factor Against Later Cognitive Decline and Dementia.

The etiology of neurodegenerative disorders such as dementia is complex and incompletely understood. Interest in a developmental perspective to these pathologies is gaining momentum. An early supportive social environment seems to have important implications for social, affective and cognitive abilities across the lifespan. Attachment theory may help to explain the link between these early experiences and later outcomes. This theory considers early interactions between an infant and its caregiver to be crucial to shaping social behavior and emotion regulation strategies throughout adult life. Furthermore, research has demonstrated that such early attachment experiences can, potentially through epigenetic mechanisms, have profound neurobiological and cognitive consequences. Here we discuss how early attachment might influence the development of affective, cognitive, and neurobiological resources that could protect against cognitive decline and dementia. We argue that social relations, both early and late in life, are vital to ensuring cognitive and neurobiological health. The concepts of brain and cognitive reserve are crucial to understanding how environmental factors may impact cognitive decline. We examine the role that attachment might play in fostering brain and cognitive reserve in old age. Finally, we put forward the concept of affective reserve, to more directly frame the socio-affective consequences of early attachment as protectors against cognitive decline. We thereby aim to highlight that, in the study of aging, cognitive decline and dementia, it is crucial to consider the role of affective and social factors such as attachment.

Neuroticism, depression, and anxiety traits exacerbate the state of cognitive impairment and hippocampal vulnerability to Alzheimer's disease.

INTRODUCTION: Certain personality traits are associated with higher risk of Alzheimer's disease, similar to cognitive impairment. The identification of biological markers associated with personality in mild cognitive impairment could advance the early detection of Alzheimer's disease. METHODS: We used hierarchical multivariate linear models to quantify the interaction between personality traits, state of cognitive impairment, and MRI biomarkers (gray matter brain volume, gray matter mean water diffusion) in the medial temporal lobe (MTL). RESULTS: Over and above a main effect of cognitive state, the multivariate linear model showed significant interaction between cognitive state and personality traits predicting MTL abnormality. The interaction effect was mainly driven by neuroticism and its facets (anxiety, depression, and stress) and was associated with right-left asymmetry and an anterior to posterior gradient in the MTL. DISCUSSION: Our results support the hypothesis that personality traits can alter the vulnerability and pathoplasticity of disease and therefore modulate related biomarker expression.

Subpopulations in purified platelets adhering on glass.

Understanding how platelet activation is regulated is important in the context of cardiovascular disorders and their management with antiplatelet therapy. Recent evidence points to different platelet subpopulations performing different functions. In particular, procoagulant and aggregating subpopulations have been reported in the literature in platelets treated with the GPVI agonists. How the formation of platelet subpopulations upon activation is regulated remains unclear. Here, it is shown that procoagulant and aggregating platelet subpopulations arise spontaneously upon adhesion of purified platelets on clean glass surfaces. Calcium ionophore treatment of the adhering platelets resulted in one platelet population expressing both the procoagulant and the adherent population markers phosphatidylserine and the activated form of GPIIb/IIIa, while all of the platelets expressed CD62P independently of the ionophore treatment. Therefore, all platelets have the capacity to express all three activation markers. It is concluded that platelet subpopulations observed in various studies reflect the dynamics of the platelet activation process.

Differences in intracellular calcium dynamics cause differences in α-granule secretion and phosphatidylserine expression in platelets adhering on glass and TiO2.

In this study, the activation of purified human platelets due to their adhesion on glass and TiO2 in the absence of extracellular calcium was investigated. Differences in α-granule secretion between platelets adhering on the two surfaces were detected by examining the expression and secretion of the α-granule markers P-selectin (CD62P) and ß-thromboglobulin. Similarly, differences in the expression of phosphatidylserine (PS), and in the activation of the major integrin GPIIb/IIIa, on the surfaces of the adhering platelets, were also observed. While all of these activation markers were expressed in platelets adhering on glass, the surface markers were not expressed in platelets adhering on TiO2, and ß-thromboglobulin secretion levels were substantially reduced. Differences in marker expression and secretion correlated with differences in the intracellular calcium dynamics. Calcium ionophore treatment triggered α-granule secretion and PS expression in TiO2-adhering platelets but had no effect on the activation of GPIIb/IIIa. These results demonstrate specificity in the way surfaces of artificial materials activate platelets, link differences in the intracellular calcium dynamics observed in the platelets adhering on the two surfaces to the differences in some of the platelet responses (α-granule secretion and PS expression), but also highlight the involvement of synergistic, calcium-independent pathways in platelet activation. The ability to control activation in surface-adhering platelets makes this an attractive model system for studying platelet signaling pathways and for tissue engineering applications.

Subjective cognitive decline in patients with mild cognitive impairment and healthy older adults: association with personality traits.

AIM: In normal aging, subjective cognitive decline (SCD) might reflect personality traits or affective states rather than objective cognitive decline. However, little is known on the correlates of SCD in mild cognitive impairment (MCI). The present study investigates SCD in MCI patients and healthy older adults, and explores the association of SCD with personality traits, affective states, behavioral and psychological symptoms (BPS), and episodic memory in patients with MCI as compared with healthy older adults. METHODS: A total of 55 patients with MCI and 84 healthy older adults were recruited. Standard instruments were used to evaluate SCD, episodic memory, BPS and affective states. Premorbid and current personality traits were assessed by proxies using the NEO Personality Inventory Revised. RESULTS: Patients with MCI generally reported SCD more often than healthy older adults. SCD was positively associated with depressive symptoms in both groups. With regard to personality, no significant relationship was found in the healthy older group, whereas agreeableness was significantly negatively related to SCD in the MCI group. No significant association was found between SCD and episodic memory. CONCLUSIONS: SCD is more prevalent in patients with MCI than in the healthy elderly, but it does not reflect an objective cognitive impairment. SCD rather echoes depressive symptoms in both patients with MCI and healthy subjects. The negative association of SCD with agreeableness observed in patients with MCI could indicate that MCI patients scoring high on the agreeableness trait would not report SCD in order to prevent their relatives worrying about their increasing cognitive difficulties.

Demyelination in mild cognitive impairment suggests progression path to Alzheimer's disease.

The preclinical Alzheimer's disease (AD) - amnestic mild cognitive impairment (MCI) - is manifested by phenotypes classified into exclusively memory (single-domain) MCI (sMCI) and multiple-domain MCI (mMCI). We suggest that typical MCI-to-AD progression occurs through the sMCI-to-mMCI sequence as a result of the extension of initial pathological processes. To support this hypothesis, we assess myelin content with a Magnetization Transfer Ratio (MTR) in 21 sMCI and 21 mMCI patients and in 42 age-, sex-, and education-matched controls. A conjunction analysis revealed MTR reduction shared by sMCI and mMCI groups in the medial temporal lobe and posterior structures including white matter (WM: splenium, posterior corona radiata) and gray matter (GM: hippocampus; parahippocampal and lingual gyri). A disjunction analysis showed the spread of demyelination to prefrontal WM and insula GM in executive mMCI. Our findings suggest that demyelination starts in the structures affected by neurofibrillary pathology; its presence correlates with the clinical picture and indicates the method of MCI-to-AD progression. In vivo staging of preclinical AD can be developed in terms of WM/GM demyelination.

Neuroanatomical and neuropsychological features of elderly euthymic depressed patients with early- and late-onset.

BACKGROUND: Whether or not cognitive impairment and brain structure changes are trait characteristics of late-life depression is still disputed. Previous studies led to conflicting data possibly because of the difference in the age of depression onset. In fact, several lines of evidence suggest that late-onset depression (LOD) is more frequently associated with neuropsychological deficits and brain pathology than early-onset depression (EOD). To date, no study explored concomitantly the cognitive profile and brain magnetic resonance imaging (MRI) patterns in euthymic EOD and LOD patients. METHOD: Using a cross-sectional design, 41 remitted outpatients (30 with EOD and 11 with LOD) were compared to 30 healthy controls. Neuropsychological evaluation concerned working memory, episodic memory, processing speed, naming capacity and executive functions. Volumetric estimates of the amygdala, hippocampus, entorhinal and anterior cingulate cortex were obtained using both voxel-based and region of interest morphometric methods. White matter hyperintensities were assessed semiquantitatively. RESULTS: Both cognitive performance and brain volumes were preserved in euthymic EOD patients whereas LOD patients showed a significant reduction of episodic memory capacity and a higher rate of periventricular hyperintensities compared to both controls and EOD patients. CONCLUSION: Our results support the dissociation between EOD thought to be mainly related to psychosocial factors and LOD that is characterized by increasing vascular burden and episodic memory decline.