Search

A lake-breeze and valley-wind coupled circulation system, known as Ora del Garda, typically arises in the late morning from the northern shorelines of Lake Garda (southeastern Italian Alps), and then channels into the Sarca and Lakes valleys to the north. After flowing over an elevated saddle, in the early afternoon this wind breaks out from the west into the nearby Adige Valley, hindering the regular development of the local up-valley wind by producing a strong and gusty anomalous flow in the area. Two targeted flights of an equipped motorglider were performed in the morning and afternoon of 23 August 2001 in the above valleys, exploring selected vertical slices of the atmosphere, from the lake's shore to the area where the two local airflows interact. At the same time, surface observations were collected during an intensive field measurement campaign held in the interaction area, as well as from routinely-operated weather stations disseminated along the whole study area, allowing the analysis of the different stages of the Ora del Garda development. From airborne measurements, an atmospheric boundary-layer (ABL) vertical structure, typical of deep Alpine valleys, was detected in connection with the wind flow, with rather shallow (~500 m) convective mixed layers surmounted by deeper, weakly stable layers. On the other hand, close to the lake's shoreline the ABL was found to be stabilized down to very low heights, as an effect of the onshore advection of cold air by the lake breeze. Airborne potential temperature observations were mapped over high-resolution 3-D grids for each valley section explored by the flights, using a geostatistical technique called residual kriging (RK). RK-regridded fields revealed fine-scale features and inhomogeneities of ABL thermal structures associated with the complex thermally-driven wind field developing in the valleys. The combined analysis of surface observations and RK-interpolated fields revealed an irregular propagation of the lake-breeze front in the lower part of the valley, and cross-valley thermal asymmetries amenable both to the differential solar heating of the valley slopes and to the valley curvature in its upper part. The overflowing of the potentially cooler Ora del Garda air from the Lakes Valley in the afternoon produces a strong katabatic wind at the bottom of the underlying Adige Valley, which blows in cross-valley (i.e. westerly) direction and impinges on the opposite eastern valley sidewall. RK-regridded potential temperature field highlighted that this phenomenon gives origin to a "hydraulic jump" flow structure in the urban area north of the city of Trento, leading to the down-stream formation of a ~1300 m deep well-mixed layer. The improved knowledge of the typical Ora del Garda flow patterns and associated ABL structures, deriving from the combined analysis of surface and airborne observations, has practical application in air quality forecasting for the study area, for it helps in the understanding of pollution transport and dispersion processes by thermally-driven winds in the region. Moreover, 3-D meteorological fields produced by RK are likely to be an excellent basis for comparison with results from high-resolution numerical simulations, as they provide a degree of spatial detail that is fully comparable to the spatial scales resolved by large-eddy simulations. [ABSTRACT FROM AUTHOR]

The spreading of tumor cells to secondary sites (tumor metastasis) is a complex process that involves multiple, sequential steps. Vascular adhesion and extravasation of circulating tumor cells (CTCs) is one, critical step. Curcumin, a natural compound extracted from Curcuma longa, is known to have anti-tumoral, anti-proliferative, anti-inflammatory properties and affect the expression of cell adhesion molecules, mostly by targeting the NF-κB transcription factor. Here, upon treatment with Curcumin, the vascular behavior of three different estrogen receptor negative (ER-) breast adenocarcinoma cell lines (SK-BR-3, MDA-MB-231, MDA-MB-468) is analyzed using a microfluidic system. First, the dose response to curcumin is characterized at 24, 48 and 72h using a XTT assay. For all three cell lines, an IC50 larger than 20 μM is observed at 72 h; whereas no significant reduction in cell viability is detected for curcumin concentrations up to 10 μM. Upon 24 h treatment at 10 μM of curcumin, SK-BR3 and MDA-MB-231 cells show a decrease in adhesion propensity of 40% (p = 0.02) and 47% (p = 0.001), respectively. No significant change is documented for the less metastatic MDA-MB-468 cells. All three treated cell lines show a 20% increase in rolling velocity from 48.3 to 58.7 μm/s in SK-BR-3, from 64.1 to 73.77 μm/s in MDAMB-231 and from 57.5 to 74.4 μm/s in MDA-MB-468. Collectively, these results suggest that mild curcumin treatments could limit the metastatic potential of these adenocarcinoma cell lines, possibly by altering the expression of adhesion molecules, and the organization and stiffness of the cell cytoskeleton. Future studies will elucidate the biophysical mechanisms regulating this curcumin-induced behavior and further explore the clinical relevance of these findings. [ABSTRACT FROM AUTHOR]

Purpose: The menopausal transition brings with it many physical, cognitive, and affective changes in a woman's life, impacting quality of life. Whereas prior work has examined impact on general mental health and cognitive function, research on basic affective processing during menopause remains scarce., Methods: Using a median-split procedure, this pre-registered study examined the impact of stronger (N = 46 women) vs. milder (N = 47 women) menopausal symptoms using a behavioural task of subjective emotion perception (embody) and a passive eye tracking viewing task of emotional faces in addition to self-report questionnaires. After 3 months, participants completed the questionnaires again to examine whether objective measures of emotion perception (eye tracking) might predict mental health at follow-up., Results: As anticipated, women with stronger vs. milder menopausal symptoms reported increased symptoms of anxiety, depression, stress, emotion regulation difficulties, and lower quality of life during both time points. While no evidence was found in the behavioural task, eye tracking data indicated blunted emotion perception in women with high menopausal symptoms, while women with low symptoms spent more time looking at happy faces relative to fearful or surprised faces. Although eye tracking or hormonal data did not predict mental health at follow-up, a higher estradiol/FSH ratio indicated a higher quality of life., Conclusions: This study documented an impact of the menopausal transition and strength of menopausal symptoms in particular on objective emotion perception as well as mental health and quality of life in women suffering from stronger vs. milder menopausal symptoms. Clinical implications are discussed., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: A secure attachment style could promote more intimacy in romantic relationships, while an insecure attachment style could be correlated with less positive romantic relationships in adulthood. Numerous studies have noted that a secure attachment to parents was correlated with lower levels of aggression, whereas insecure attachments were associated with higher levels of aggression. We aimed to investigate the role of the attachment system as a mediator of the expression of aggressiveness during adolescence. Specifically, we considered that the attachment to parents and peers could influence one's attachment to a romantic partner., Methods: We empirically tested whether there were relationships of parent and peer attachment on aggressiveness mediated by romantic attachment style. Participants of the study included 411 students., Results: Results indicated that for males an insecure father-child attachment style seems to be associated with higher levels of anxiety and avoidance in romantic attachments and then with aggressiveness. For females, an insecure mother-child attachment style seems to be associated with higher levels of aggressiveness., Conclusion: The attachment to parents and to peers plays a key role in defining romantic attachment according to gender, and these dimensions in turn tend to affect the levels of aggressiveness.

Cyclin-dependent kinase like-5 (CDKL5) disorder is a rare neurodevelopmental disease caused by mutations in the CDKL5 gene. The consequent misexpression of the CDKL5 protein in the nervous system leads to a severe phenotype characterized by intellectual disability, motor impairment, visual deficits and early-onset epilepsy. No therapy is available for CDKL5 disorder. It has been reported that a protein transduction domain (TAT) is able to deliver macromolecules into cells and even into the brain when fused to a given protein. We demonstrate that TAT-CDKL5 fusion protein is efficiently internalized by target cells and retains CDKL5 activity. Intracerebroventricular infusion of TAT-CDKL5 restored hippocampal development, hippocampus-dependent memory and breathing pattern in Cdkl5-null mice. Notably, systemically administered TAT-CDKL5 protein passed the blood-brain-barrier, reached the CNS, and rescued various neuroanatomical and behavioral defects, including breathing pattern and visual responses. Our results suggest that CDKL5 protein therapy may be an effective clinical tool for the treatment of CDKL5 disorder.

Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase predominantly expressed in the brain. Mutations of the CDKL5 gene lead to CDKL5 disorder, a neurodevelopmental pathology that shares several features with Rett Syndrome and is characterized by severe intellectual disability. The phosphorylation targets of CDKL5 are largely unknown, which hampers the discovery of therapeutic strategies for improving the neurological phenotype due to CDKL5 mutations. Here, we show that the histone deacetylase 4 (HDAC4) is a direct phosphorylation target of CDKL5 and that CDKL5-dependent phosphorylation promotes HDAC4 cytoplasmic retention. Nuclear HDAC4 binds to chromatin as well as to MEF2A transcription factor, leading to histone deacetylation and altered neuronal gene expression. By using a Cdkl5 knockout (Cdkl5 -/Y) mouse model, we found that hypophosphorylated HDAC4 translocates to the nucleus of neural precursor cells, thereby reducing histone 3 acetylation. This effect was reverted by re-expression of CDKL5 or by inhibition of HDAC4 activity through the HDAC4 inhibitor LMK235. In Cdkl5 -/Y mice treated with LMK235, defective survival and maturation of neuronal precursor cells and hippocampus-dependent memory were fully normalized. These results demonstrate a critical role of HDAC4 in the neurodevelopmental alterations due to CDKL5 mutations and suggest the possibility of HDAC4-targeted pharmacological interventions., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We sought to examine the efficacy in preventing surgical site infection (SSI) in cardiac surgery, using two different incise drapes (not iodine-impregnated and iodine-impregnated). A cost analysis was also considered. Between January 2008 and March 2015, 5100 consecutive cardiac surgery patients, who underwent surgery in our Institute, were prospectively collected. A total of 3320 patients received a standard not iodine-impregnated steri-drape (group A), and 1780 patients received Ioban(®) 2 drape (group B). We investigated, by a propensity matched analysis, whether the use of standard incise drape or iodine-impregnated drape would impact upon SSI rate. Totally, 808 patients for each group were matched for the available risk factors. Overall incidence of SSI was significantly higher in group A (6.5 versus 1.9 %) (p = 0.001). Superficial SSI incidence was significantly higher in group A (5.1 vs 1.6 %) (p = 0.002). Deep SSI resulted higher in group A (1.4 %) than in group B (0.4 %), although not significantly (p = 0.11). Consequently, the need for vacuum-assisted closure (VAC) therapy use resulted 4.3 % in group A versus 1.2 % in group B (p = 0.001). Overall costs for groups A and B were 12.494.912 € and 11.721.417 €, respectively. The Ioban(®) 2 offered totally 773.495 € cost savings compared to standard steri-drape. Ioban 2 drape assured a significantly lower incidence of SSI. Additionally, Ioban(®) 2 drape proved to be cost-effective in cardiac surgery.

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in a rare neurodevelopmental disorder characterized by early-onset seizures, severe developmental delay, intellectual disability and Rett syndrome-like features. CDKL5 is highly expressed in the brain during early postnatal stages, suggesting its importance for brain maturation. Using a newly-generated Cdkl5 knockout (Cdkl5 -/Y) mouse, we recently found that loss of Cdkl5 impairs postnatal hippocampal development with a reduction in neuronal precursor survival and maturation. These defects were accompanied by increased activity of the glycogen synthase kinase 3β (GSK3β) a crucial inhibitory regulator of many neurodevelopmental processes. The goal of the current study was to establish whether inhibition of GSK3β corrects hippocampal developmental defects due to Cdkl5 loss. We found that treatment with the GSK3β inhibitor SB216763 restored neuronal precursor survival, dendritic maturation, connectivity and hippocampus-dependent learning and memory in the Cdkl5 -/Y mouse. Importantly, these effects were retained one month after treatment cessation. At present, there are no therapeutic strategies to improve the neurological defects of subjects with CDKL5 disorder. Current results point at GSK3β inhibitors as potential therapeutic tools for the improvement of abnormal brain development in CDKL5 disorder., (Copyright © 2015. Published by Elsevier Inc.)

Background: The study compares the efficacy and advantages of two different drainage systems in pediatric patients during surgery for congenital heart disease (CHD)., Methods: A total of 200 consecutive pediatric patients (< 16 years) were enrolled; in 100 patients we used a polyvinyl chloride drain (PVCD) and in the other 100 we used a silicone drain (SD). Demographics, drain's technical data, and postoperative complications and costs were evaluated. A pain score was calculated in patients older than 6 years., Results: The SDs were significantly smaller when compared with PVCDs (median of 1.63 vs. 3.09 French/kg, p = 0.0006), were kept in site for a median shorter period (23 vs. 40 hours, p = 0.002), drained more thoracic spaces (median of 2 vs. 1, p < 0.0001), and were associated to a lower pain score (p = 0.01). The overall drain-related complication rate was lower for the SD group than for the PVCD group (3 vs. 9%, p = 0.1) as well as the drain-related adverse event required additional interventional maneuvers (0 vs. 6%, p = 0.04). Patients who were treated with a PVCD reported a higher perceived pain score than patients treated with a SD, both at the time when the drain was in site (p = 0.016) and during the drain's removal (p = 0.0001)., Conclusion: SDs can be used safely in pediatric patients during surgery for CHD. Sizes required are smaller than other conventional drains and multiple cavities can be drained with a single tube. The use of SD is associated to a lower complication rate, lower requirement of additional procedures, and lesser perceived pain from the patient, when compared with other more traditional drains., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: The role of extracorporeal life support (ECLS) in primary cardiogenic shock (PCS) is well established. In this study, we evaluated the impact of etiology on outcomes., Methods: Between January 2009 and March 2013, we implanted a total of 249 patients with ECLS; we focused on 64 patients for whom peripheral ECLS was the treatment for PCS. Of these, 37 cases (58%) were "acute" (mostly acute myocardial infarction: 39%); 27 (42%) had an exacerbation of "chronic" heart failure (dilated cardiomyopathy: 30%; post-ischemic cardiomyopathy: 9%; and congenital: 3%)., Results: In the group with chronic etiology, 23 patients were bridged to a left ventricular assist device (52%) or heart transplantation (33%). In the group with acute etiology, ECLS was used as a bridge-to-transplantation in 3 patients (8%), a bridge-to-bridge in 9 (24%), and a bridge-to-recovery in 18 (49%). One patient in each group was bridged to conventional surgery. Recovery of cardiac function was achieved in only the group with acute primary cardiogenic shock (18 vs 0 patients, P = .0001). A mean flow during support of ≤60% of the theoretic flow (body surface area × 2.4) was a predictor of successful weaning (P = .02). Median duration of ECLS support was 7 days (range: 2-11.5 days). Nine patients (14%) died during support; 30-day overall survival was 80% (51 of 64 patients); and 59% of patients were discharged, in whom survival at 48 months was 90%. Thirty-day survival was correlated with duration of ECLS support., Conclusions: In "chronic" heart failure, ECLS represents a bridge to a ventricular assist device or heart transplantation, whereas in "acute" settings, it offers a considerable chance of recovery, and is often the only required therapy., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Aim: Urea, the main product of protein catabolism, is a biochemical marker of renal function. Though it is known that serum urea impairs vascular health, the relationship between its concentration and vascular reactivity in vivo has not been explored. Our study was undertaken to investigate possible association between serum urea and endothelial function in subjects without chronic kidney disease (CKD)., Methods: Eighty free-living subjects with serum creatinine ≤1 mg/dL and without CKD were enrolled for the present study. Serum analyses and evaluation of endothelial function were performed in all subjects. Endothelial function was measured using the flow-mediated dilation (FMD) technique. Simple and multiple regression analyses were used to test the association between FMD and considered variables., Results: In correlation analyses FMD was found directly associated with HDL cholesterol (r=0.21; P=0.05) and eGFR (r=0.25; P=0.02) and inversely associated with age (r=-0.26; P=0.02), serum urea (r=-0.37; P<0.01), serum creatinine (r=-0.31; P<0.01) and brachial artery baseline diameter (r=-0.41; P<0.01). In multiple regression analysis only baseline artery diameter and serum urea predicted FMD; age, gender and cardiovascular risk factors did not relate with FMD., Conclusion: Our study demonstrates the association between serum urea and FMD, suggesting that the accumulation of waste products of protein metabolism may impair vascular health in subjects without CKD.

Aim: The aim of this paper was to evaluate the safety and cost-effectiveness of "2-octyl-cyanoacrylate" as skin adhesive in congenital heart surgery., Methods: From April 2010 to December 2011, we collected data from 300 patients who underwent cardiac surgery for congenital heart disease. We divided our population into 3 groups: group-1 (N.=100):"2-octyl-cyanoacrylate" has been used to replace the intra-dermal suture line; group-2 (N.=100):"2-octyl-cyanoacrylate" has been utilized as a barrier ("add-on measure") in addition to the intra-dermal suture line, group-3 (N.=100) with a standard intra-dermal suture line., Results: Median age of patients was 1.36 years. One-hundred and thirty-nine patients were younger than 12 months and 56 older than 16 years. There were 11 wound dehiscence (3.6%) (2 in group-1 and 9 in group-3, P=0.001) and 1 superficial wound infection (group-1). Six patients (2%) required surgical wound revision (2 in group-1 and 4 in group-3, P=NS). Wound complication was significantly associated to delayed sternal closure (3/12 patients, 25% versus 13/288 patients, 4.5%) (P=0.04). Median cost (intra-/postoperative) for wound treatment was lower in group-1 and 2 (19±5.5 and 23.9±7.4 € respectively) when compared to Group-3 (26.7±3.2) (P<0.0001)., Conclusion: The use of "2-octyl-cyanoacrylate" proved to be safe and effective; the "add-on measure" strategy provided the best cost-effective solution.