Elastic wave dispersion in layered media with suture joints: influence of structural hierarchy and viscoelasticity

Suture joints contribute to the exceptional combination of stiffness, strength, toughness and efficient load bearing and transmission of many biological structures like the cranium or ammonite fossil shells. However, their role in the attenuation of vibrations and effect on dynamic loads is less clear. Moreover, the self-similar hierarchical geometry often associated with suture joints renders its treatment with standard numerical approaches computationally prohibitive. To address this problem, this paper investigates the dynamic response of periodic layered media with suture joints using an analytical approach based on material homogenization. A general trapezoidal suture geometry is considered together with the fundamental ingredients of hierarchy and viscoelasticity. The Spectral Element Method and Bloch theorem are used to derive the dispersion relation and band diagram of the system, including propagating and evanescent dispersion modes. A strong influence of the suture morphology and material properties emerges, and the analysis reveals an important advantage of adding hierarchy, i.e. the possibility of simultaneously obtaining wider bandgaps and their shift to higher frequencies. A synergy between hierarchy and structure is also observed, providing superior levels of wave attenuation. These findings suggest a possible design concept for bioinspired devices with efficient and tailorable wave attenuation properties

Effect of atmospheric nitric oxide (NO) on measurements of exhaled NO in asthmatic children

The measurement of exhaled nitric oxide concentrations [NO] may provide a simple, noninvasive means for measuring airway inflammation. However, several measurement conditions may influence exhaled NO levels, and ambient NO may be one of these. We measured exhaled NO levels in 47 stable asthmatic children age 5 to 17 years and in 47 healthy children, gender and age matched. Exhaled [NO] in expired air was measured by a tidal breathing method with a chemiluminescence analyzer, sampling at the expiratory side of the mouthpiece. NO steady\u2010state levels were recorded. In order to keep the soft palate closed and avoid nasal contamination, the breathing circuit had a restrictor providing an expiratory pressure of 3\u20134 cm H2O at the mouthpiece. To evaluate the effect of [NO] in ambient air, measurements were randomly performed by breathing ambient air or NO\u2010free air from a closed circuit. Breathing NO\u2010free air, exhaled [NO] in asthmatics (mean \ub1 SEM) was 23.7 \ub1 1.4 ppb, significantly higher (P < 0.001) than in healthy controls (8.7 \ub1 0.4 ppb). Exhaled NO concentrations measured during ambient air breathing were higher (49 \ub1 4.6 ppb, P < 0.001) than when breathing NO\u2010free air (23.7 \ub1 1.4 ppb) and were significantly correlated (r = 0.89, P < 0.001) with atmospheric concentrations of NO (range 3\u2013430 ppb). These findings show that (1) exhaled [NO] values of asthmatic children are significantly higher than in healthy controls, and (2) atmospheric NO levels critically influence the measurement of exhaled [NO]. Therefore, using a tidal breathing method the inhalation of NO\u2010free air during the test is recommended. Pediatr Pulmonol. 1998; 26:30\u201334. \ua9 1998 Wiley\u2010Liss, Inc

Engineered membranes for residual cell trapping on microfluidic blood plasma separation systems. A comparison between porous and nanofibrous membranes

Blood-based clinical diagnostics require challenging limit-of-detection for low abundance, circulating molecules in plasma. Micro-scale blood plasma separation (BPS) has achieved remarka-ble results in terms of plasma yield or purity, but rarely achieving both at the same time. Here, we proposed the first use of electrospun polylactic-acid (PLA) membranes as filters to remove residual cell population from continuous hydrodynamic-BPS devices. The membranes hydrophilicity was improved by adopting a wet chemistry approach via surface aminolysis as demonstrated through Fourier Transform Infrared Spectroscopy and Water Contact Angle analysis. The usability of PLA-membranes was assessed through degradation measurements at extreme pH values. Plasma purity and hemolysis were evaluated on plasma samples with residual red blood cell content (1, 3, 5% hematocrit) corresponding to output from existing hydrodynamic BPS systems. Commercially available membranes for BPS were used as benchmark. Results highlighted that the electrospun membranes are suitable for downstream residual cell removal from blood, permitting the collection of up to 2 mL of pure and low-hemolyzed plasma. Fluorometric DNA quantification revealed that electrospun membranes did not significantly affect the concentration of circulating DNA. PLA-based electrospun membranes can be combined with hydrodynamic BPS in order to achieve high volume plasma separation at over 99% plasma purity

Pharmacological characterization of P2X1 and P2X3 purinergic receptors in bovine chondrocytes

SummaryObjectiveThe aim of the present study is that of characterizing, for the first time in a quantitative way, from a biochemical, physico chemical and functional point of view P2X1 and P2X3 purinergic receptors in bovine chondrocytes. The affinity and the potency of typical purinergic ligands were studied through competition binding experiments and their role in modulating chondrocyte actvities was investigated by analyzing nitric oxide (NO) and prostaglandin E2 (PGE2) release.MethodsSaturation, competition binding experiments, western blotting and immunohistochemistry assays on the P2X1 and P2X3 purinergic receptors in bovine chondrocytes were performed. Thermodynamic analysis of the P2X1 and P2X3 purinergic binding was studied to investigate the forces driving drug-receptor coupling. In the functional assays (NO and PGE2 release) the potency of purinergic agonists and antagonists was evaluated.ResultsBovine chondrocytes expressed P2X1 and P2X3 purinergic receptors and thermodynamic parameters indicated that purinergic binding is enthalpy- and entropy-driven for agonists and totally entropy-driven for antagonists. Typical purinergic agonists such as adenosine 5′-triphosphate (ATP) and α,β-methyleneATP were able to increase NO and PGE2 release. A purinergic antagonist, A317491, was able to block the stimulatory effect on functional experiments mediated by the agonists.ConclusionsThese data demonstrate for the first time the presence of functional P2X1 and P2X3 purinergic receptors in bovine chondrocytes. Agonists and antagonists are thermodynamically discriminated and are able to modulate functional responses such as NO and PGE2 release. These results suggest the potential role of novel purinergic antagonists in the treatment of pathophysiological diseases linked to the inflammation and involved in articular cartilage resorption

Improving pre-operative planning of robot assisted nephron sparing surgery using three-dimensional anatomical model

Introduction Despite the introduction of robot-assisted surgery in daily clinical practice, complex renal masses are still challenging even for expert surgeon. In this scenario 3D anatomical models and augmented reality represent valuable tools for the surgeon. Materials and methods We present a challenging case where PN was mandatory to preserve the overall renal function. The patient was 69 years old, with indwelling catheter for BPH and Parkinson disease. After a single episode of hematuria with negative cystoscopy, a cT1N0M0 renal cancer was diagnosed (38 mm maximum diameter). Pre-operative three-dimensional (3D) model was obtained. After multidisciplinary discussion robot-assisted partial nephrectomy was proposed. The surgery was planned according to the anatomical model. Results Before the procedure a 7Ch single loop ureteral stent was placed. The surgery was carried out in 220 minutes. Selective ischaemia was perfomed for 24 minutes. Estimated blood loss was 400cc. No post-operative complications were observed. Ureteral stent was removed 4 days after the surgery. Definitive histological examination described a pG2-3 T1a Nx R0 clear cell renal carcinoma. Conclusion In selected cases 3D model result to be a useful tool for the pre-operative planning of the surgery

Characterization of adenosine receptors in bovine chondrocytes and fibroblast-like synoviocytes exposed to low frequency low energy pulsed electromagnetic fields

SummaryObjectiveThe present study describes the presence and binding parameters of the A1, A2A, A2B and A3 adenosine receptors in bovine chondrocytes and fibroblast-like synoviocytes. The effect of low frequency low energy pulsed electromagnetic fields (PEMFs) on the adenosine receptor affinity and density was studied.MethodsSaturation, competition binding experiments and Western blotting assays in the absence and in the presence of PEMFs on the adenosine receptors in bovine chondrocytes or fibroblast-like synoviocytes were performed. Thermodynamic analysis of the A2A or A3 binding was studied to investigate the forces driving drug–receptor coupling. In the adenylyl cyclase and proliferation assays the potency of typical high-affinity A2A or A3 agonists in the absence and in the presence of PEMFs was evaluated.ResultsBovine chondrocytes and fibroblast-like synoviocytes expressed all adenosine receptors. PEMFs evoked an up-regulation of A2A and A3 receptors and thermodynamic parameters indicate that adenosine binding is enthalpy and entropy driven. In PEMF-treated cells the potency of typical A2A or A3 agonists on cyclic AMP assays was significantly increased when compared with the untreated cells. PEMFs potentiated the effect of A2A or A3 agonists on cell proliferation in both cell types.ConclusionsPEMFs mediate an up-regulation of A2A and A3 receptors related to an increase of their functional activities in bovine chondrocytes and fibroblast-like synoviocytes. No differences are present in adenosine affinity and in the drug–receptor interactions. Our data could be used as a trigger to future studies addressed to PEMFs and adenosine therapeutic intervention in inflammatory joint diseases

Clinical and molecular determinants of extrahepatic disease progression (ePD) in initially unresectable, liver-limited metastatic colorectal cancer (mCRC)

e15511Background: In the last years, availability of active upfront systemic regimens, development of surgical techniques and diffusion of locoregional treatments (LrTx) increased the therapeutic o..

molecular characterization of immune microenvironment in colorectal cancers with microsatellite instability by digital rna counting

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The SAFFO Study: Sex-Related Prognostic Role and Cut-Off Definition of Monocyte-to-Lymphocyte Ratio (MLR) in Metastatic Colorectal Cancer

Background: Emerging data suggest that gender-related immune system composition affects both immune response and efficacy of immunotherapy in cancer patients (pts). This study aimed to investigate the sex-related prognostic role of MLR in metastatic colorectal cancer (mCRC) pts. Methods: We analyzed a retrospective consecutive cohort of 490 mCRC patients treated from 2009 to 2018 at the Oncology Departments of Aviano and Pordenone (training set) and Udine (validation set), Italy. The prognostic impact of MLR on overall survival (OS) was evaluated with uni- and multivariable Cox regression models. The best cut-off value to predict survival was defined through ROC analyses. Results: Overall, we identified 288 males (59%) and 202 females (41%); 161 patients (33%) had a right-sided, 202 (42%) a left-sided primary, and 122 (25%) a rectal tumor. Interestingly, gender was associated with MLR (p = 0.004) and sidedness (p = 0.006). The obtained cut-off value for MLR in females and males was 0.27 and 0.49, respectively. According to univariate analysis of the training set, MLR (HR 9.07, p ≤ 0.001), MLR > 0.27 in females (HR 1.95, p = 0.003), and MLR > 0.49 in males (HR 2.65, p = 0.010) were associated with poorer OS, which was also confirmed in the validation set. In multivariate analysis, MLR > 0.27 in females (HR 2.77, p = 0.002), MLR > 0.49 in males (HR 5.39, p ≤ 0.001), BRAF mutation (HR 3.38, p ≤ 0.001), and peritoneal metastases (HR 2.50, p = 0.003) were still independently associated with worse OS. Conclusions: Males and females have a different immune response. Our study showed that high MLR, both in males and females, is an unfavorable Independent prognostic factor. Further prospective studies are needed to confirm these data