Resonant micro-opto-mechanical modulators fabricated by femtosecond laser micromachining

Integrated modulators of optical phase or intensity are essential elements to reconfigure dynamically the operation of a complex waveguide circuit, or to achieve convenient optical switching within a fiber network. Thermo-optic effects are commonly exploited to achieve dynamic phase modulation in glass-based devices, since nonlinear optical effects are weak in such substrates. Thermo-optic modulators rely on electric resistive heaters patterned on top of the waveguides: they are reliable and easy to fabricate, but they suffer from slow response, dictated by the thermal diffusion dynamics. On the other hand, optically-coupled microstructures in glass, driven at their mechanical resonances, may provide interesting possibilities to achieve modulation of the optical signals in the kilohertz range and higher. In this work, we demonstrate integrated-optics intensity modulators based on micro-cantilevers with resonant oscillation frequencies in the tens-of-kilohertz range. The mechanical structures are realized in alumino-borosilicate glass substrate by water-assisted femtosecond-laser ablation. With the same femtosecond laser an optical waveguide is inscribed within the oscillating beam; a waveguide also continues in the substrate beyond the cantilever's tip. Since the entire device, with all its optical and mechanical parts, is realized in a single fabrication process, relative alignment is guaranteed. If the cantilever is at rest, light propagating in the internal waveguide yields maximum coupling to the remaining part of the waveguide. When the device is excited at resonance by means of a piezo-electric actuator, the cantilever oscillation produces periodical variations of the coupling efficiency, with an observed contrast higher than 10 dB

Squamous Cell Carcinoma and Ledderhose Disease: A Case Report

Ledderhose disease is disorder of the plantar aponeurosis. This disease is not so common and can be tackled with a surgical or conservative approach. A case of a 73-year-old man came to our attention who had a 26-year history of painless bilateral plantar nodules coalescing into an indurated mass. An ulcerative nodule had been noted in the last 16 months on the right foot, in the absence of trauma, not responsive to conservative treatment, so we decided to perform a biopsy. The histopatologic examination showed squamous cell carcinoma, with warty, well-differentiated, low-grade malignancy. Surgical treatment was suggested, so, in pneumoischemia, we made a surgical incision including the skin lesion. Then we proceeded to sculpture the anterolateral thigh fasciacutaneous flap to obtain adequate soft tissue coverage. The tumor was completely removed. Current reconstructive possibilities comprise a good anatomofunctional recovery even in the case of large demolition requests for the therapy of advanced cases of the disease described in this article. Correlation between Ledderhose disease and the formation of malignant tumors has not been made as yet, but perhaps an element that could unite these pathologies can be researched in the lively cell proliferation that characterizes both. It would be interesting to analyze the biological substrate, as well as the systemic and local levels, in patients where both diseases are manifested

Cone-beam computed tomography accuracy in pulp chamber size evaluation: An ex vivo study

This study aimed to assess ex vivo the accuracy of cone-beam computed tomography (CBCT), as compared to operative microscope, for evaluating pulp chamber size. A total of forty teeth were extracted for periodontal reasons and a horizontal section was done at the most apical level of the cement-enamel junction. The pulp chamber was photographed using a digital camera connected to an optical microscope. Then, the tooth was scanned with CBCT and the horizontal slide matching the anatomical section of pulp chamber was digitally stored. The pulp chamber section area was measured through image analysis software. The two methods provided similar results, either for monoradicular (P = 0.14) or multiradicular teeth (P = 0.93). Correlation was statistically significant (P < 0.0001), being the coefficient r = 0.89 and 0.94 for monoradicular and multiradicular teeth, respectively. Conclusively, CBCT is suitable for pulp chamber morphology evaluation. However, it has limitations in detecting the anatomical variability of small branches in root canal system

Endoscopic ultrasound-guided ablation of solid pancreatic lesions: A systematic review of early outcomes with pooled analysis

Contains fulltext : 252157.pdf (Publisher’s version ) (Open Access)BACKGROUND: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as a complementary therapeutic approach for pancreatic solid masses. However, results of published data are difficult to interpret because of a retrospective design and small sample size. AIM: To systematically review data on EUS-RFA for solid lesions and to pool the results of the different experiences in order to provide more consistent evidence in terms of safety and efficacy. METHODS: A comprehensive systematic literature search on the main databases was performed to identify articles in which patients with pancreatic solid lesions underwent EUS-RFA. The primary outcomes were procedure-related adverse events (AEs) and mortality. Secondary outcomes were the technical success rate and the effects on primary tumor growth. Statistical analyses were performed using Stata version 14.0. RESULTS: In total, 14 studies were included, with 120 patients undergoing 153 ablations of 129 solid pancreatic lesions. The STARmed technology was used in seven studies, the Habib system in six studies, and the HybridTherm probe in one study. The pooled technical success rate was 99.0% (I (2): 25.82%). The pooled overall AE rate was 8.0% (I (2): 11.46%). Excluding mild AEs, the pooled rates of serious AEs was 1.0% (I (2): 0%). No mortality related to the procedure was reported. CONCLUSION: The present pooled analysis confirms the safety and feasibility of EUS-RFA

Microbiota Gut-Brain Axis in Ischemic Stroke: A Narrative Review with a Focus about the Relationship with Inflammatory Bowel Disease.

The gut microbiota is emerging as an important player in neurodevelopment and aging as well as in brain diseases including stroke, Alzheimer's disease, and Parkinson's disease. The complex interplay between gut microbiota and the brain, and vice versa, has recently become not only the focus of neuroscience, but also the starting point for research regarding many diseases such as inflammatory bowel diseases (IBD). The bi-directional interaction between gut microbiota and the brain is not completely understood. The aim of this review is to sum up the evidencesconcerningthe role of the gut-brain microbiota axis in ischemic stroke and to highlight the more recent evidences about the potential role of the gut-brain microbiota axis in the interaction between inflammatory bowel disease and ischemic stroke

Pentraxin 3 deficiency protects from the metabolic inflammation associated to diet-induced obesity

Aims: Low-grade chronic inflammation characterizes obesity and metabolic syndrome. Here, we aim at investigating the impact of the acute-phase protein long pentraxin 3 (PTX3) on the immune-inflammatory response occurring during diet-induced obesity. Methods and results: PTX3 deficiency in mice fed a high-fat diet for 20 weeks protects from weight gain and adipose tissue deposition in visceral and subcutaneous depots. This effect is not related to changes in glucose homeostasis and lipid metabolism but is associated with an improved immune cell phenotype in the adipose tissue of Ptx3 deficient animals, which is characterized by M2-macrophages polarization and increased angiogenesis. These findings are recapitulated in humans where carriers of a PTX3 haplotype (PTX3 h2/h2 haplotype), resulting in lower PTX3 plasma levels, presented with a reduced prevalence of obesity and decreased abdominal adiposity compared with non-carriers. Conclusion: Our results support a critical role for PTX3 in the onset of obesity by promoting inflammation and limiting adipose tissue vascularization and delineate PTX3 targeting as a valuable strategy for the treatment of adipose tissue-associated inflammatory response

Gastric peroral endoscopic pyloromyotomy for refractory gastroparesis: a systematic review of early outcomes with pooled analysis

Background and Aims: Gastroparesis (GP) is a chronic debilitating condition. Prior pyloric-targeted procedures are either invasive or have questionable efficacy. Gastric peroral pyloromyotomy (G-POEM) has been proposed as a minimally invasive approach. We performed a pooled analysis to evaluate the efficacy and safety of G-POEM for GP. Methods: Electronic databases (Medline, Scopus, EMBASE) were searched up to January 2019. Studies including patients who underwent G-POEM for GP were eligible. Procedural, clinical, and safety outcomes were assessed by pooling data with a random- or fixed-effect model according to the degree of heterogeneity to obtain a proportion with a 95% confidence interval. Results: Ten studies were eligible for inclusion (292 patients), and 2 of the 10 studies were prospective. Seven studies were performed in the United States, 2 in France, and 1 in China. Endoscopic pyloromyotomy was feasible in all patients. Significant symptomatic improvement was achieved after 83.9% of procedures (mean follow-up, 7.8 ± 5.5 months). When comparing the mean values of pre- and postprocedural scintigraphic evolution, there was a significant decrease of the residual percentage at 2 and 4 hours. The overall adverse events rate was 6.8%. Conclusions: G-POEM appears to be a promising approach for GP in terms of safety and efficacy outcomes in the short term

normalization of multiple hemostatic abnormalities in uremic type 1 diabetic patients after kidney pancreas transplantation

To evaluate the effects of kidney-pancreas transplantation on hemostatic abnormalities in uremic type 1 diabetic patients, we conducted a cross-sectional study involving 12 type 1 diabetic patients, 30 uremic type 1 diabetic patients, 27 uremic type 1 diabetic patients who had a kidney-pancreas transplant, 12 uremic type 1 diabetic patients who had a kidney-alone transplant, and 13 healthy control subjects. We evaluated platelet and clotting system. Platelets in the group of uremic type 1 diabetic patients were significantly larger than platelets in the other groups. Resting calcium levels were significantly higher in the uremic type 1 diabetic patients and uremic type 1 diabetic patients who had a kidney-alone transplant than in the type 1 diabetic patients who had a kidney-pancreas transplant and control subjects. CD41 expression was significantly reduced in platelets from the uremic type 1 diabetic patients compared with the other groups. Levels of hypercoagulability markers in the type 1 diabetic patients who had a kidney-pancreas transplant and, to a lesser extent, the uremic type 1 diabetic patients who had a kidney-alone transplant but not the uremic type 1 diabetic patients were similar to those of the control subjects. A reduction in natural anticoagulants was evident in the uremic type 1 diabetic patients, whereas near-normal values were observed in the type 1 diabetic patients who had a kidney-pancreas transplant and uremic type 1 diabetic patients who had a kidney-alone transplant. Hemostatic abnormalities were not observed in type 1 diabetic patients who had a kidney-pancreas transplant. This finding might explain the lower cardiovascular death rate observed in type 1 diabetic patients who had a kidney-pancreas transplant compared with uremic type 1 diabetic patients who had a kidney-alone transplant or uremic type 1 diabetic patients

A critical role for regulatory T cells in driving cytokine profiles of Th17 cells and their modulation of glioma microenvironment.

IL-17A, produced by Th17 cells, may play a dual role in antitumor immunity. Using the GL261-glioma model, we investigated the effects of Th17 cells on tumor growth and microenvironment. Th17 cells infiltrate mouse gliomas, increase significantly in a time-dependent manner similarly to Treg and do not express Foxp3. To characterize the direct effects of Th17 cells on GL261 murine gliomas and on tumor microenvironment, we isolated IL-17-producing cells enriched from splenocytes derived from naïve (nTh17) or glioma-bearing mice (gTh17) and pre-stimulated in vitro with or without TGF-β. Spleen-derived Th17 cells co-expressing IL-17, IFN-γ and IL-10, but not Treg marker Foxp3, were co-injected intracranially with GL261 in immune-competent mice. Mice co-injected with GL261 and nTh17 survived significantly longer than gTh17 (P < 0.006) and gliomas expressed high level of IFN-γ and TNF-α, low levels of IL-10 and TGF-β. In vitro IL-17 per se did not exert effects on GL261 proliferation; in vivo gliomas grew equally well intracranially in IL-17 deficient and wild-type mice. We further analyzed relationship between Th17 cells and Treg. Treg were significantly higher in splenocytes from glioma-bearing than naïve mice (P = 0.01) and gTh17 produced more IL-10 than IFN-γ (P = 0.002). In vitro depletion of Treg using PC61 in splenocytes from glioma-bearing mice causes increased IL-17/IFN-γ cells (P = 0.007) and decreased IL-17/IL-10 cells (P = 0.03). These results suggest that Th17 polarization may be induced by Treg and that Th17 cells in gliomas modulate tumor growth depending on locally produced cytokines

PCSK9 deficiency reduces insulin secretion and promotes glucose intolerance: the role of the low-density lipoprotein receptor

Aims PCSK9 loss of function genetic variants are associated with lower low-density lipoprotein cholesterol but also with higher plasma glucose levels and increased risk of Type 2 diabetes mellitus. Here, we investigated the molecular mechanisms underlying this association. Methods and results Pcsk9 KO, WT, Pcsk9/Ldlr double KO (DKO), Ldlr KO, albumin AlbCre+/Pcsk9LoxP/LoxP (liver-selective Pcsk9 knock-out mice), and AlbCre-/Pcsk9LoxP/LoxP mice were used. GTT, ITT, insulin and C-peptide plasma levels, pancreas morphology, and cholesterol accumulation in pancreatic islets were studied in the different animal models. Glucose clearance was significantly impaired in Pcsk9 KO mice fed with a standard or a high-fat diet for 20\u2009weeks compared with WT animals; insulin sensitivity, however, was not affected. A detailed analysis of pancreas morphology of Pcsk9 KO mice vs. controls revealed larger islets with increased accumulation of cholesteryl esters, paralleled by increased insulin intracellular levels and decreased plasma insulin, and C-peptide levels. This phenotype was completely reverted in Pcsk9/Ldlr DKO mice implying the low-density lipoprotein receptor (LDLR) as the proprotein convertase subtilisin/kexin Type 9 (PCSK9) target responsible for the phenotype observed. Further studies in albumin AlbCre+/Pcsk9LoxP/LoxP mice, which lack detectable circulating PCSK9, also showed a complete recovery of the phenotype, thus indicating that circulating, liver-derived PCSK9, the principal target of monoclonal antibodies, does not impact beta-cell function and insulin secretion. Conclusion PCSK9 critically controls LDLR expression in pancreas perhaps contributing to the maintenance of a proper physiological balance to limit cholesterol overload in beta cells. This effect is independent of circulating PCSK9 and is probably related to locally produced PCSK9