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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]

In traditional open surgery, surgeons use their fingertip palpation to investigate the hidden anatomical structures of tissue. However, in the current commercially available minimally invasive robotic surgery (MIRS) systems, while surgical instruments interact with tissues, surgeons do not sense any tactile information. Therefore, tactile sensors are required to be integrated into the tips of surgical instruments to mimic the perception of the surgeon's fingertips. The electrically based tactile sensors that exist at present cannot usually operate under static loading conditions. In addition, they are not compatible with magnetic resonance imaging (MRI) devices. Therefore, this research was aimed at restoring tactile information by developing an MRI compatible optical fiber tactile sensor. The sensor consists of only one single moving part. Thanks to this novel design, the sensor does not require the use of an array of sensors to measure the distributed tactile information. This capability simplifies the integration of the sensor into any suitable space available at the tips of surgical instruments. In addition, the sensor performs under both static and dynamic loading conditions. A theoretical model of the sensor and a finite-element model of the sensor-tissue interaction were developed. To validate the sensor, a prototype of the sensor was fabricated and tested. [ABSTRACT FROM PUBLISHER]

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]