Carotid Reservoir Pressure Decrease After Prolonged Head Down Tilt Bed Rest in Young Healthy Subjects Is Associated With Reduction in Left Ventricular Ejection Time and Diastolic Length

BACKGROUND: The arterial pressure waveform reflects the interaction between the heart and the arterial system and carries potentially relevant information about circulatory status. According to the commonly accepted ‘wave transmission model’, the net BP waveform results from the super-position of discrete forward and backward pressure waves, with the forward wave in systole determined mainly by the left ventricular (LV) ejection function and the backward by the wave reflection from the periphery, the timing and amplitude of which depend on arterial stiffness, the wave propagation speed and the extent of downstream admittance mismatching. However, this approach obscures the ‘Windkessel function’ of the elastic arteries. Recently, a ‘reservoir-excess pressure’ model has been proposed, which interprets the arterial BP waveform as a composite of a volume-related ‘reservoir’ pressure and a wave-related ‘excess’ pressure. METHODS: In this study we applied the reservoir-excess pressure approach to the analysis of carotid arterial pressure waveforms (applanation tonometry) in 10 young healthy volunteers before and after a 5-week head down tilt bed rest which induced a significant reduction in stroke volume (SV), end-diastolic LV volume and LV longitudinal function without significant changes in central blood pressure, cardiac output, total peripheral resistance and aortic stiffness. Forward and backward pressure components were also determined by wave separation analysis. RESULTS: Compared to the baseline state, bed rest induced a significant reduction in LV ejection time (LVET), diastolic time (DT), backward pressure amplitude (bP) and pressure reservoir integral (INTPR). INTPR correlated directly with LVET, DT, time to the peak of backward wave (bT) and stroke volume, while excess pressure integral (INTXSP) correlated directly with central pressure. Furthermore, Δ.INTPR correlated directly with Δ.LVET, and Δ.DT, and in multivariate analysis INTPR was independently related to LVET and DT and INTXSP to central systolic BP. CONCLUSION: This is an hypothesis generating paper which adds support to the idea that the reservoir-wave hypothesis applied to non-invasively obtained carotid pressure waveforms is of potential clinical usefulness

Towards nZEBs : experiences in Italy

Nowadays in the European framework the good practices for high-performing buildings realization and retrofitting are copious, but what emerges is the lack of information and data sharing about them. There are indeed no official sources for notes deriving from this kind of buildings and, moreover, there is shortage of quantitative and comparable data. In a process oriented to a large-scale diffusion of nZEBs on the market, the existing good practices of actual case studies of highperforming buildings should be kept as market benchmarks and reveal to be precious sources of information. In the light of the above, the need of a harmonized database to collect and share data deriving from different building typologies and climatic zones plays a fundamental role. Due to the weakness of the existing databases and to the necessity of having practical guidelines to design nZEBs, at Italian level, an AiCARR teamwork is targeting the development of a design guide for nZEBs in Mediterranean region, based on different national experiences. In order to reach this target the workgroup has created a detailed database, useful to collect and share information about single high-performing buildings. Its main purpose is to record nZEBs, which have been already built, with available monitored data and that represent concrete models for future designing. Because of the still scarcity of monitored nZEBs, the database is suitable not only for realized monitored buildings but also for those that are still in a design phase. Actually, three different Italian case studies are catalogued in the databas

Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated Type 1 Diabetes

<p>Abstract</p> <p>Background</p> <p>Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated.</p> <p>Methods</p> <p>Sixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1%) and 26 controls (mean age 19 ± 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured.</p> <p>Results</p> <p>After adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 μm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c ≥7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP.</p> <p>Conclusions</p> <p>Our findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium-dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure.</p

Operating Parameters Optimization for the Production of Liposomes Loaded with Antibodies Using a Supercritical Fluid-Assisted Process

Encapsulation of antibodies represents a significant advance to protect and deliver these therapeutics in a controlled manner, increasing the stability requested to cover the temporal gap between particle production and their administration. Furthermore, using encapsulation, extracellular, cell surface, and intracellular targets can be reached. This work examines the feasibility of encapsulating mouse IgG isotype control antibodies within phosphatidylcholine-based liposomes using a supercritical fluid-based process called SuperLip (Supercritical-assisted Liposome formation). This process allows a continuous production of both nano- and micrometric liposomes with high encapsulation efficiency working under mild operative conditions. The effect of some operative parameters has been studied on liposome mean diameter, particle size distribution, and antibody entrapment efficiency, comparing these data with those collected working with liposomes obtained by the thin-layer hydration technique. In particular, the effect of water flow rate and of the antibody loading were studied. Antibody-loaded liposomes with mean diameters in the range between 205 and 501 nm have been obtained by using a supercritical fluid-assisted process. High entrapment efficiencies up to 94% have been calculated

Comparative expression pathway analysis of human and canine mammary tumors

<p>Abstract</p> <p>Background</p> <p>Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved.</p> <p>Results</p> <p>We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries.</p> <p>Conclusion</p> <p>Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.</p

Updated Italian Tetrapod Ichnology Reference List

We provide a list of contribution by Italian scientists to tetrapod ichnology with papers on both material from Italy and abroad. Foreign author’s contributions on tetrapod ichnology based on material from Italy are also considered. The list updates the previous one published by D’Orazi Porchetti et al. (2008) and, as a result, includes works from 1869 up to now. Following the previous reference list, papers of non-Italian researchers on foreign material are reported when the material was found on Italian territory at the time of publication

Italian recommendations on enzymatic debridement in burn surgery.

Abstract Introduction Nexobrid®, a bromelain-based type of enzymatic debridement, has become more prevalent in recent years. We present the recommendations on enzymatic debridement (Nexobrid®)'s role based on the practice knowledge of expert Italian users. Methods The Italian recommendations, endorsed by SIUST (Italian Society of Burn Surgery), on using enzymatic debridement to remove eschars for burn treatment were defined. The definition followed a process to evaluate the level of agreement (a measure of consensus) among selected experts, representing Italian burn centers, concerning defined clinical aspects of enzymatic debridement. The consensus involved a multi-phase process based on the Delphi method. Results The consensus panel included experts from Italy with a combined experience of 1068 burn patients treated with enzymatic debridement. At the end of round 3 of the Delphi method, the panel reached 100% consensus on 26 out of 27 statements. The panel achieved full, strong consensus (all respondents strongly agreed on the statement) on 24 out of 27 statements. Discussion The statements provided by the Italian consensus panel represent a "ready to use" set of recommendations for enzymatic debridement in burn surgery that both draw from and complete the existing scientific literature on the topic. These recommendations are specific to the Italian experience and are neither static nor definitive. As such, they will be updated periodically as further quality evidence becomes available