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• A computational fluid dynamics simulation-based examination of the effect of hemolysis on thrombosis in blood contacting devices. • First of it's kind attempt to incorporate the effect of hemolysis into thrombosis in a continuum modelling framework on practical medical devices. • Modelled the interaction between hemolysis and thrombosis by modelling the chemical reaction of von Willebrand factor with extracellular hemoglobin and its hyper-adhesive form as well as ADP release from red blood cells during hemolysis. • The study quantifies the relative effect both aspects of hemolysis on thrombosis in an LVAD and finds that hyperadhesion plays a dominant role in the LVAD at higher rotor speeds. • ADP release can help initiate thrombosis at lower rotor speeds where high anticoagulation or low shear prevent full activation of platelets. Heart failure, broadly characterized by the gradual decline of the ability of the heart to maintain adequate blood flow throughout the body's vascular network of veins and arteries, is one of the leading causes of death worldwide. Mechanical Circulatory Support is one of the few available alternative interventions for late-stage heart failure with reduced ejection fraction. A ventricular assist device is surgically implanted and connected to the left and or right heart ventricles to provide additional bloodflow, off-loading the work required by the heart to maintain circulation. Modern mechanical circulatory support devices generate non-physiological flow conditions that can lead to the damage and rupture of blood cells (hemolysis), and the formation of blood clots (thrombosis), which pose severe health risks to the patient. It is essential to improve prediction tools for blood damage to reduce the risk of hemolysis and thrombosis. A simulation-based approach examines the interaction between hemolysis and thrombosis. Incompressible finite-volume computational fluid dynamics simulations are executed on an open-hub axial flow ventricular assist device. A continuum model of thrombosis and the intrinsic coagulation process is extended to include the effect of hemolysis. The model accounts for the effect of activation of platelets by shear stress, paracrine signaling, adhesion, and hemoglobin and ADP released during hemolysis. The effect of hemolysis with thrombosis is modelled by accounting for the hyper-adhesivity of von-Willebrand Factor on extracellular hemoglobin, and the increased rate of platelet activation induced by ADP release. Thrombosis is assessed at varying inflow rates and rotor speeds, and cases are executed where thrombosis is affected by ADP release and Hb-induced hyper-adhesivity. It is found that there is a non-negligible effect from hemolysis on thrombosis across a range of rotor speeds, and that hyperadhesivity plays a dominant role in thrombus formation in the presence of hemolysis. [ABSTRACT FROM AUTHOR]

Cognitive deficits are a fundamental feature of schizophrenia for which currently no effective treatments exist. This paper examines the possibility to use transcranial direct current stimulation (tDCS) to target cognitive deficits in schizophrenia as evidence from studies in healthy participants suggests that tDCS may improve cognitive functions and associated neural processes. We carried out a systematic review with the following search terms: 'tDCS', 'electric brain stimulation', 'schizophrenia', 'cognitive', 'cognition' until March 2019. 659 records were identified initially, 612 of which were excluded after abstract screening. The remaining 47 articles were assessed for eligibility based on our criteria and 26 studies were excluded. In addition, we compared several variables, such as online vs. offline-stimulation protocols, stimulation type and intensity on mediating positive vs. negative study outcomes. The majority of studies (n = 21) identified significant behavioural and neural effects on a range of cognitive functions (versus n = 11 with null results), including working memory, attention and social cognition. However, we could not identify tDCS parameters (electrode montage, stimulation protocol, type and intensity) that clearly mediated effects on cognitive deficits. There is preliminary evidence for the possibility that tDCS may improve cognitive deficits in schizophrenia. We discuss the rationale and strength of evidence for using tDCS for targeting cognitive deficits in schizophrenia as well as methodological issues and potential mechanisms of action. [ABSTRACT FROM AUTHOR]

We describe a follow-up study of a patient with a selective, progressive impairment of topographical orientation. The patient's topographical difficulties were evident only in unfamiliar surroundings at the beginning of the observation period but later on they were observed even at home. Serial neuropsychological tests demonstrated a progressive impairment of visuospatial abilities with sparing of the other cognitive domains; only at the last assessment, about six years after early disturbances and three years after the first evaluation, the patient developed the typical cognitive impairments of Alzheimer's disease (AD). This case represents a focal variant of AD not previously described and suggests that the neuronal pathways underlying spatial orientation may be selectively damaged by the degenerative process. [ABSTRACT FROM AUTHOR]

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Courtois Cardiovascular Signature Program The increasing rate of cardiovascular disease (CVD) contributes to a worsening morbidity in the general population and a socioeconomic burden on the healthcare system. Newly approved therapies present unforeseen side effects and occasionally entail adverse cardiovascular responses in patients - this issue significantly stalls efficacious pharmacological development. Indeed, modern cardiovascular treatments do not account for the variability of individual patient reactions, due to a lack of a representative in vitro cardiac model. While the use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has gained traction as a superior model for drug screening when compared to cardiac biopsies and immortalized cell lines, cardiovascular patient-specific differences remain poorly understood and understudied. We hypothesized that 1) cardiomyopathic patient-derived iPSC-CMs have differing baselines of beating rate, contractility, viability, metabolic activity and protein expression, when compared to healthy controls, and that 2) cell lines have patient-specific responses to hypoxia-induced injury. As such, the purpose of this preliminary study was two-fold: 1) to perform a characterization of patient iPSC-CM function, and 2) to study patient-specific cellular responses to hypoxia. First, we generated iPSC-CMs from the peripheral blood of donors (n=6 patients with cardiomyopathies, n=2 healthy donors). We then confirmed the expression of prominent cardiac markers connexin 43 (CXN43), sarcoendoplasmic reticulum Ca2+ ATPase (SERCA2a), GATA4 and cardiac Troponin T, as well as a lack of pluripotency markers Octamer-binding transcription factor 4 (OCT4), Nanog, Stage-specific embryonic antigen-4 (SSEA-4) and TRA-1-60 in the iPSC-CM lines, via immunocytochemistry. Preliminary assessment of iPSC-CMs (days 1-30 post-differentiation) revealed significant baseline differences in beating rate (p<0.01) and contractility amplitude (p<0.01) between iPSC-CMs derived from cardiomyopathic patients and healthy donors. We then subjected iPSC-CM lines to hypoxic conditions (24 hours), to mimic ischaemic injury. Diseased patient-derived lines had significantly decreased viability and metabolic activity when compared to the controls, under normoxic (p<0.01) and hypoxic conditions (p<0.001). Immunoblotting revealed differential expression of cardiac markers and factors implicated in cardiac function, cardioprotection and pathology. Taken together, these results suggest that the detected differences at the cellular level after hypoxia-induced injury might be translatable to the inter-individual variability currently observed in the CVD patient population. The data gathered will prove to be instrumental in future studies of iPSC-CM responses to treatment. With this preliminary study, we hope to shift the focus towards these patient-specific differences at the cellular level, in the search for tailored therapies and a higher standard of care for CVD patients. [ABSTRACT FROM AUTHOR]

Background: Chronic urticaria (CU) may affect up to 1% of the general population. Anisakis simplex hypersensitivity is frequent in areas where raw fish is consumed and A. simplex allergy represents a relevant cause of acute urticaria. We as-sessed the possible association between CU and A. simplex sensitization in an area where marinated fish is very fre-quently eaten. Methods: A thorough history of CU was sought in 919 adults seen at the Allergy Center, Bari. CU pa-tients and 187 controls underwent skin-prick testing with a commercial extract of A. simplex, and reactors were recom-mended a 6-month raw-fish-free diet regimen. Responders were followed after a further 3 months. Results: Of 919 sub-jects, 213 (23%) met the criteria for CU and 106/213 (49.7%) were sensitized to A. simplex with a significant difference be-tween patients aged >65 or <65 years (56 vs. 41%, respec-tively; p < 0.05). All patients hypersensitive to A. simplex were regular consumers of marinated fish. In a control population without CU, the prevalence of A. simplex sensitization was 16% (p < 0.001). The 6-month diet regimen led to the disap-pearance of urticaria in 82/106 cases (77%) versus 1/42 (2%) subjects who did not change their dietary habits (p < 0.001). All nonresponders were sensitized to house-dust mites. Of 75 responders who were followed-up after 3 months, CU re-lapsed In 88% of those who had reintroduced raw fish versus 14% of those who were still on the diet (p < 0.001). Conclu-sion: In areas where raw or marinated fish Is frequently eat-en, A. simplex hypersensitivity is a frequent cause of CU. [ABSTRACT FROM AUTHOR]

The guidelines for the management of urticaria in adults and children have been published in outstanding position papers. By contrast, the onset of urticaria in the elderly has not yet had a clear definition. In order to approach diagnosis and treatment in a population of elderly patients, we have performed an epidemiological study on a population of elderly people observed in the Immuno Allergology Unit in Bari University Hospital. The patients underwent skin prick test for food allergy and laboratory and instrumental tests. From the data it resulted that 49% of cases have had urticaria because of adverse drug reactions (ADRs), 16% of cases were positive to food, while in 21% of cases systemic and metabolic diseases (SMDs) have been diagnosed. If we consider the young controls, urticaria for ADR was present in 48% of cases; however, in 28% it was possible to make the diagnosis of food allergy, 12% cases had a SMD. Our results show that the main cause of urticaria in the elderly is related to drug assumption because of the high number of drugs taken, followed by internal pathologies correlated to the typical immune and metabolic changes of the elderly. Furthermore, from the observation of our data it was possible to give guidelines for the treatment of urticaria in geriatric age. [ABSTRACT FROM AUTHOR]

Physiologic changes associated with anesthesia and technical aspects of noncardiac surgical procedure expose patients with severely depressed myocardial function to an enormous risk of perioperative complications and morbidity. In cases when these patients require mechanical circulatory support while undergoing emergent or elective operations, perioparative monitoring becomes of paramount importance. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring of CsA has evolved since the introduction of CsA microemulsion. The purpose of the present review is to summarize the history of CsA concentration 2 hours postdose (C2) monitoring in heart and liver transplantation. C2 has been shown to be the best single time point that correlates with the area-under-the-curve, with a correlation coefficient (r2) ranging between .83 and .93. C2 monitoring (300 to 600 ng/mL) has resulted in a significant clinical benefit in long-term heart and liver transplant patients compared to trough level (C0) monitoring. Moreover, a C2 range of 300 to 600 ng/mL resulted in a similar calcineurin inhibition compared to a C2 range of 700 to 1000 ng/mL or a C0 range of 100 to 200 ng/mL while being less injurious to renal function. In de novo liver transplant patients not receiving induction therapy, the achievement of a target C2 of 850 to 1400 ng/mL by postoperative day 3 has resulted in a low acute rejection rate. Furthermore, C2 monitoring has been associated with a lower rejection rate in hepatitis C virus (HCV)-negative patients and with an overall lesser severity of acute rejection compared to C0 monitoring. In de novo heart transplant patients who receive antithymocyte globulin induction, a lower C2 range may be sufficient to prevent rejection and renal dysfunction. Future studies should help to fine-tune the optimal C2 range in heart or liver transplant patients receiving induction therapy and different maintenance immunosuppressive combinations. [Copyright &y& Elsevier]