Estimation of Nanoporous Au Young’s Modulus from Serial Block Face-SEM 3D-Characterisation

Nanoporous Au has been subjected to serial block face-scanning electron microscopy (SBF-SEM) 3D-characterisation. Corresponding sections have been digitalized and used to evaluate the associated mechanical properties. Our investigation demonstrates that the sample is homogeneous and isotropic. The effective Young’s modulus estimated by an analytical multiscale approach agrees remarkably well with the values stated in the literature.     

Comparing Digital Therapeutic Intervention with an Intensive Obesity Management Program: Randomized Controlled Trial

In this study, we evaluated whether the digital program Vitadio achieves comparable results to those of an intensive in-person lifestyle intervention in obesity management. This is a 12-month prospective, randomized controlled trial. Obese patients with insulin resistance, prediabetes or type 2 diabetes were included. The intervention group (IG) used Vitadio. The control group (CG) received a series of in-person consultations. Body weight and various metabolic parameters were observed and analyzed with ANOVA. The trial is ongoing and the presented findings are preliminary. Among 100 participants (29% men; mean age, 43 years; mean BMI, 40.1 kg/m²), 78 completed 3-month follow-up, and 51 have completed the 6-month follow-up so far. Participants significantly (p < 0.01) reduced body weight at 3 months (IG: −5.9 ± 5.0%; CG: −4.2 ± 5.0%) and 6 months (IG: −6.6±6.1%; CG: −7.1 ± 7.1%), and the difference between groups was not significant. The IG achieved favorable change in body composition; significant improvement in TAG (−0.6 ± 0.9 mmol/l, p < 0.01), HDL (0.1 ± 0.1%, p < 0.05), HbA1c (−0.2 ± 0.5%, p < 0.05) and FG (−0.5 ± 1.5 mmol/l, p < 0.05); and a superior (p = 0.02) HOMA-IR reduction (−2.5 ± 5.2, p < 0.01). The digital intervention achieved comparable results to those of the intensive obesity management program. The results suggest that Vitadio is an effective tool for supporting patients in obesity management and diabetes prevention.     

Adriamycin-induced histamine release from heart tissue in vitro

 It has been proven that the anthracyclines induce an important, noncytotoxic histamine release from rat peritoneal mast cells. As mast cells derived from different tissues exhibit marked heterogeneity, the effect of Adriamycin in comparison with other antineoplastic agents was tested on fragments of the right heart auricle, which contain a great number of mast cells. In this experimental model, Adriamycin induced a dose-dependent histamine release that was significantly limited by the antiexocytotic drug sodium cromoglycate. The antineoplastic agents cisplatin and 5-fluorouracil, in contrast, did not provoke any comparable histamine release. In the formulation employed in clinical settings, paclitaxel was also capable of inducing a histamine release comparable with that of Adriamycin; the exocytotic activity, however, was also evident when the tissue fragments were treated with Cremophor EL alone, without the addition of paclitaxel, whereas treatment of samples with paclitaxel dissolved in ethanol did not induce any releasing action. These data thus suggest that the secretory activity should be ascribed to the solvent Cremophor EL and not to paclitaxel. The release of histamine induced by paclitaxel in Cremophor EL/ethanol was also limited by sodium cromoglycate. These results again indicate that histamine release from mast cells derived not only from the peritoneal cavity but also from the cardiac tissue could play a role in the cardiotoxicity of anthracyclines and of paclitaxel in the clinically employed formulation. Received: 18 August 1996 / Accepted: 22 December 1996     

An educational approach based on a non-injury model compared with individual symptom-based physical training in chronic LBP. A pragmatic, randomised trial with a one-year follow-up

Background  

In the treatment of chronic back pain, cognitive methods are attracting increased attention due to evidence of effectiveness similar to that of traditional therapies. The purpose of this study was to compare the effectiveness of performing a cognitive intervention based on a non-injury model with that of a symptom-based physical training method on the outcomes of low back pain (LBP), activity limitation, LBP attitudes (fear-avoidance beliefs and back beliefs), physical activity levels, sick leave, and quality of life, in chronic LBP patients.     

Attenuated Purinergic Receptor Function in Patients With Type 2 Diabetes

OBJECTIVE

Extracellular nucleotides and nucleosides are involved in regulation of skeletal muscle blood flow. Diabetes induces cardiovascular dysregulation, but the extent to which the vasodilatatory capacity of nucleotides and nucleosides is affected in type 2 diabetes is unknown. The present study investigated 1) the vasodilatatory effect of ATP, uridine-triphosphate (UTP), and adenosine (ADO) and 2) the expression and distribution of P2Y² and P2X¹ receptors in skeletal muscles of diabetic subjects.

RESEARCH DESIGN AND METHODS

In 10 diabetic patients and 10 age-matched control subjects, leg blood flow (LBF) was measured during intrafemoral artery infusion of ATP, UTP, and ADO, eliciting a blood flow equal to knee-extensor exercise at 12 W (∼2.6 l/min).

RESULTS

The vasodilatatory effect of the purinergic system was 50% lower in the diabetic group as exemplified by an LBF increase of 274 ± 37 vs. 143 ± 26 ml/μmol ATP × kg, 494 ± 80 vs. 234 ± 39 ml/μmol UTP × kg, and 14.9 ± 2.7 vs. 7.5 ± 0.6 ml/μmol ADO × kg in control and diabetic subjects, respectively, thus making the vasodilator potency as follows: UTP control subjects (100) > ATP control subjects (55) > UTP diabetic subjects (47) > ATP diabetic subjects (29) > ADO control subjects (3) > ADO diabetic subjects (1.5). The distribution and mRNA expression of receptors were similar in the two groups.

CONCLUSIONS

The vasodilatatory effect of the purinergic system is severely reduced in type 2 diabetic patients. The potency of nucleotides varies with the following rank order: UTP > ATP > ADO. This is not due to alterations in receptor distribution and mRNA expression, but may be due to differences in receptor sensitivity.The net balance between vasoconstrictor and vasodilator activity in patients with type 2 diabetes is abnormal, and the ability of adjusting vascular tone during conditions with increased demands for blood flow is affected (1,2). The level of secretion and bioavailability of the potent vasodilators nitric oxide (NO) and prostacyclin (prostaglandin [PG]) are diminished, and there is an increase in the synthesis, secretion, and action of vasoconstrictors including prostanoids, angiotensin II, endothelin, and noradrenalin (3). This leads to impaired vascular reactivity, which may limit exercise capacity in patients with type 2 diabetes.In the last decade, the purinergic system and its impact on blood flow regulation have come more into focus. Several studies have shown that extracellular nucleotides and nucleosides such as ATP, uridine-triphosphate (UTP), and adenosine (ADO) are factors in the local control of vessel tone (4) and regulation of exercise-induced hyperemia (5). Interestingly, reduced ATP release has been shown in diabetic patients (6).Whereas UTP and ADO are pure vasodilators, ATP possesses the ability to induce both vasodilatation and vasoconstriction; ATP-induced vasodilatation is assumed to be a result of intravascular release of ATP from endothelial cells or erythrocytes, leading to release of NO and PG via endothelial purinergic receptors (7,8), whereas extravascular ATP leads to vasoconstriction by direct action on receptors on smooth muscle cells (9). Nucleotides and nucleosides mediate a biological response via two main categories of cell surface receptors: P1 receptor for ADO and P2 receptor recognizing primarily ATP, UTP, ADP, and uridine-diphosphate. P2 receptors are subdivided into P2X and P2Y, based on their pharmacological properties; P2Y is a family of G-protein–coupled receptors, whereas P2X is a group of ligand-gated ion channel receptors (10,11).Attenuated function of purinergic receptors is implicated in multiple diseases (12). The aim of the present study was therefore to evaluate whether the endothelial dysfunction in type 2 diabetic patients is associated with impairment of the vascular sensitivity to extracellular nucleotides and nucleosides. We hypothesized that purinergic-mediated vasodilation is diminished in type 2 diabetic patients because of decreased receptor density and/or sensitivity. We determined localization of P2Y₂ and P2X₁ receptors and measured levels of mRNA of P2Y₂ receptors to investigate potential downregulation.     

Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, does not

Metabolic effects of the glucagon-like peptide-1 analog liraglutide and the dipeptidyl peptidase-IV inhibitor vildagliptin were compared in rats made obese by supplementary candy feeding. Female Sprague-Dawley rats were randomized to 12-week diets of chow or chow plus candy. The latter were randomized for 12 further weeks to continue their diet while receiving 0.2 mg/kg liraglutide twice daily subcutaneously, 10 mg/kg vildagliptin twice daily orally, or vehicle or to revert to chow-only diet. Energy expenditure was measured, and oral glucose tolerance tests (OGTTs) were performed. Body composition was determined by dual-energy X-ray absorptiometry scanning, and pancreatic beta-cell mass was determined by histology. Candy feeding increased weight, fat mass, and feeding-associated energy expenditure. Liraglutide or reversal to chow diet fully reversed weight and fat gains. Liraglutide was associated with decreased calorie intake and shifted food preference (increased chow/decreased candy consumption). Despite weight loss, liraglutide-treated rats did not decrease energy expenditure compared with candy-fed controls. Vildagliptin affected neither weight, food intake, nor energy expenditure. OGTTs, histology, and blood analyses indirectly suggested that both drugs increased insulin sensitivity. Liraglutide and vildagliptin inhibited obesity-associated increases in beta-cell mass. This was associated with weight and fat mass normalization with liraglutide, but not vildagliptin, where the ratio of beta-cell to body mass was low.     

The neurovascular triad: mixed cavernous, capillary, and venous malformations of the brainstem

OBJECT: The four types of cerebrovascular malformations may sometimes be combined and more often occur in pairs; triads are exceptional. The authors present six patients with the clinicoradiographic profile of mixed vascular malformations of the brainstem, including cavernous malformation (CM), capillary telangiectasia, and developmental venous anomaly (DVA). METHODS: Five patients (one of whom was a child) suffered from hemorrhage, suggesting that this complex association has a high bleeding potential. Progressive growth, rebleeding, and de novo occurrence of the associated CM were documented in three cases. Magnetic resonance imaging of the brain was obtained in all patients by using one or more of the following modalities: T1-weighted sequences before and after gadolinium administration; T2-weighted sequences; T2-weighted fluid attenuated Inversion recovery; T1-weighted fast spin echo; and diffusion weighted, diffusion tensor, and perfusion imaging in three cases. RESULTS: Three patients were surgically treated with the intention of excising the hemorrhagic lesion, but only two patients had their malformations successfully removed. In the third case, diffuse pontine telangiectasia precluded the safe excision of the CM. Histological examination demonstrated a blended pathological milieu characterized by coalescent telangiectasia and venules associated with loculated endothelial chambers resembling an immature or de novo CM. Three patients were treated conservatively; recurrent minor hemorrhage occurred in one case. The authors found these malformations to be arranged in two basic relationships: CM inside the telangiectasia and CM in the radicles of the DVA. Stenosis of the main venous collector and dilation of the medullary veins were important findings. CONCLUSIONS: The pathogenesis of this malformation may be referred to a developmental deviance of the brainstem capillary-venous network associated with transitional vessels and loculated endothelial vascular spaces related to genetic and acquired origins, probably in a restrictive venous outflow milieu.     

Can rotatory knee laxity be predicted in isolated anterior cruciate ligament surgery?

Purpose

Despite the overall success of the surgical anterior cruciate ligament (ACL) reconstruction, some patients still present with instability symptoms even after the surgery, mainly due to the presence of associated lesions. At present, the pivot shift test has been reported to be the benchmark to assess rotatory knee laxity. The purpose of this study was to quantitatively evaluate rotatory knee laxity at time-zero in order to determine whether detected post-reconstruction laxity was predictable by its value measured before the reconstruction, which was hypothized to be influenced by the presence of associated lesions.

Methods

Rotatory knee laxity was retrospectively analysed in 42 patients, including two different ACL reconstructions. The maximal anterior displacement and the absolute value of the posterior acceleration reached during the reduction of the tibial lateral compartment were intra-operatively acquired by using a navigation system and identified as discriminating parameters. For each parameter, statistical linear regression analysis (line slope and intercept) was performed between pre- and post-reconstruction values.

Results

No statistically significant influence of the initial posterior acceleration on the post-reconstruction outcome was found (line slope, p > 0.05), although a statistically significant line intercept was indeed identified (p < 0.001). A statistically significant influence on the surgery outcome was instead found for the initial value of the anterior tibial displacement (line slope = 0.39, p = 0.004), meaning that, on average, about 40 % of the post-reconstruction lateral compartment displacement could be explained by the corresponding pre-reconstruction value. Both of these findings highlighted the importance of intra-operative quantification of rotatory knee laxity to identify correct indications for the surgery.

Conclusions

This study provided important implications for the future possibility of defining a quantifying tool able to assess rotatory knee laxity during ACL reconstruction. This could allow detection of additional injuries to secondary restraints by easily performing rotatory knee laxity tests, which in turn could reduce post-surgical recurrence of knee instability.