When rational functions meet virtual elements: The lightning Virtual Element Method

We propose a lightning Virtual Element Method that eliminates the stabilisation term by actually computing the virtual component of the local VEM basis functions using a lightning approximation. In particular, the lightning VEM approximates the virtual part of the basis functions using rational functions with poles clustered exponentially close to the corners of each element of the polygonal tessellation. This results in two great advantages. First, the mathematical analysis of a priori error estimates is much easier and essentially identical to the one for any other non-conforming Galerkin discretisation. Second, the fact that the lightning VEM truly computes the basis functions allows the user to access the point-wise value of the numerical solution without needing any reconstruction techniques. The cost of the local construction of the VEM basis is the implementation price that one has to pay for the advantages of the lightning VEM method, but the embarrassingly parallelizable nature of this operation will ultimately result in a cost-efficient scheme almost comparable to standard VEM and FEM

Effect of obesity and metabolic syndrome on plasma oxysterols and fatty acids in human

BACKGROUND: Obesity and the related entity metabolic syndrome are characterized by altered lipid metabolism and associated with increased morbidity risk for cardiovascular disease and cancer. Oxysterols belong to a large family of cholesterol-derived molecules known to play crucial role in many signaling pathways underlying several diseases. Little is known on the potential effect of obesity and metabolic syndrome on oxysterols in human. OBJECTIVES: In this work, we questioned whether circulating oxysterols might be significantly altered in obese patients and in patients with metabolic syndrome. We also tested the potential correlation between circulating oxysterols and fatty acids. METHODS: 60 obese patients and 75 patients with metabolic syndrome were enrolled in the study along with 210 age- and sex-matched healthy subjects, used as control group. Plasma oxysterols were analyzed by isotope dilution GC/MS, and plasma fatty acids profiling was assessed by gas chromatography coupled with flame ionization detection. RESULTS: We found considerable differences in oxysterols profiling in the two disease groups that were gender-related. Compared to controls, males showed significant differences only in 4α- and 4β-hydroxycholesterol levels in obese and metabolic syndrome patients. In contrast, females showed consistent differences in 7-oxocholesterol, 4α-hydroxycholesterol, 25-hydroxycholesterol and triol. Concerning fatty acids, we found minor differences in the levels of these variables in males of the three groups. Significant changes were observed in plasma fatty acid profile of female patients with obesity or metabolic syndrome. We found significant correlations between various oxysterols and fatty acids. In particular, 4β-hydroxycholesterol, which is reduced in obesity and metabolic syndrome, correlated with a number of saturated and mono-unsaturated fatty acids that are end-products of de novo lipogenesis. CONCLUSIONS: Our data provide the first evidence that obesity and metabolic syndrome are associated with major, gender-specific, changes in circulating oxysterols and fatty acids. These findings suggest a metabolic link between oxysterols and fatty acids, and that oxysterols may contribute to the epidemic diseases associated with obesity and metabolic syndrome in female

Endothelial cells, endoplasmic reticulum stress and oxysterols

Oxysterols are bioactive lipids that act as regulators of lipid metabolism, inflammation, cell viability and are involved in several diseases, including atherosclerosis. Mounting evidence linked the atherosclerosis to endothelium dysfunction; in fact, the endothelium regulates the vascular system with roles in processes such as hemostasis, cell cholesterol, hormone trafficking, signal transduction and inflammation. Several papers shed light the ability of oxysterols to induce apoptosis in different cell lines including endothelial cells. Apoptotic endothelial cell and endothelial denudation may constitute a critical step in the transition to plaque erosion and vessel thrombosis, so preventing the endothelial damaged has garnered considerable attention as a novel means of treating atherosclerosis. Endoplasmic reticulum (ER) is the site where the proteins are synthetized and folded and is necessary for most cellular activity; perturbations of ER homeostasis leads to a condition known as endoplasmic reticulum stress. This condition evokes the unfolded protein response (UPR) an adaptive pathway that aims to restore ER homeostasis. Mounting evidence suggests that chronic activation of UPR leads to cell dysfunction and death and recently has been implicated in pathogenesis of endothelial dysfunction. Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation, maintaining basal levels of autophagic activity it is critical for cell survival. Several evidence suggests that persistent ER stress often results in stimulation of autophagic activities, likely as a compensatory mechanism to relieve ER stress and consequently cell death. In this review, we summarize evidence for the effect of oxysterols on endothelial cells, especially focusing on oxysterols-mediated induction of endoplasmic reticulum stress

Antimicrobial efficacy assessment and rheological investigation of two different hand sanitizers compared with the standard reference WHO formulation 1

(1) Background: recently, the use of alcohol-based hand sanitizers (ABHSs) has become very frequent, and an evaluation of the stability and effectiveness of their formulations is a critical topic which should be carefully considered. (2) Methods: starting from the characterization of the hand sanitizers object of the study, our interest was focused on their rheological behavior in order to confirm their intrinsic features, but also the stability of each formulation in different conditions of shear and temperature; the second aspect concerns the antimicrobial assessment through a panel of in vitro and in vivo experimental trials. (3) Results: rheological investigation confirmed good stability for the two hand sanitizers in gel formula with respect to the reference in liquid formula; the antimicrobial activity evaluation showed good efficacy of each formulation both in vitro and in vivo. (4) Conclusions: altogether, our overview presents a valid quality control assessment to ensure the stability and efficacy of an alcohol-based hand sanitizer

Clinical effects of Streptococcus salivarius K12 in hospitalized COVID-19 patients: results of a preliminary study

Anatomical and physiological considerations indicate that the oral cavity is a primary source of the lung microbiota community, and recent studies have shown that the microbiota in the lungs contributes to immunological homeostasis, potentially altering the organ’s susceptibility to viral infection, including SARS-CoV-2. It has been proposed that, in the case of viral infection, lung Gram-negative bacteria could promote the cytokine cascade with a better performance than a microbiota mainly constituted by Gram-positive bacteria. Recent observations also suggest that Prevotella-rich oral microbiotas would dominate the oral cavity of SARS-CoV-2-infected patients. In comparison, Streptococcus-rich microbiotas would dominate the oral cavity of healthy people. To verify if the modulation of the oral microbiota could have an impact on the current coronavirus disease, we administered for 14 days a well-recognized and oral-colonizing probiotic (S. salivarius K12) to hospitalized COVID-19 patients. The preliminary results of our randomized and controlled trial seem to prove the potential role of this oral strain in improving the course of the main markers of pathology, as well as its ability to apparently reduce the death rate from COVID-19. Although in a preliminary and only circumstantial way, our results seem to confirm the hypothesis of a direct involvement of the oral microbiota in the construction of a lung microbiota whose taxonomic structure could modulate the inflammatory processes generated at the pulmonary and systemic level by a viral infection

Physico-chemical characterization and in vitro biological evaluation of a bionic hydrogel based on hyaluronic acid and l-lysine for medical applications

Hyaluronic acid (HA) is an endogenous polysaccharide, whose hydrogels have been used in medical applications for decades. Here, we present a technology platform for stabilizing HA with a biocrosslinker, the amino acid L-Lysine, to manufacture bionic hydrogels for regenerative medicine. We synthetized bionic hydrogels with tailored composition with respect to HA concentration and degree of stabilization depending on the envisaged medical use. The structure of the hydrogels was assessed by microscopy and rheology, and the resorption behavior through enzymatic degradation with hyaluronidase. The biological compatibility was evaluated in vitro with human dermal fibroblast cell lines. HA bionic hydrogels stabilized with lysine show a 3D network structure, with a rheological profile that mimics biological matrixes, as a harmless biodegradable substrate for cell proliferation and regeneration and a promising candidate for wound healing and other medical applications

Clinical experience with pegylated hyaluronic acid fillers: A 3-year retrospective study

BACKGROUND: Hyaluronic acid fillers are the most used worldwide, thanks to the high biocompatibility and safety profile of HA and it is also the only substance that can be \u201cdissolved\u201d due to the hyaluronidase effect. AIM: A retrospective clinical evaluation of the outcomes following PEG cross-linked HA-based filler injection was performed. METHODS: Data were collected from December 2017 to June 2020. A total of 65 patients (12 M, 53 F), age ranging 28\u201362 year\u2019s old (mean age 42.3), were treated. Exclusion criteria were applied and in accord to treatment plan, were used specific site injections and fillers. Follow-up was evaluated between 6 months and 2 years. RESULTS: A total of 61 treatments using 124 vials of HA filler crosslinked with PEG were performed. CONCLUSION: In conclusion, from 2014, HA fillers having PEG as cross-linker agent have been introduced in the european market. Several papers have been published in order to evaluate the features of these fillers, although, to the best of our knowledge, this is the first clinical paper regarding their use

Polyacrylamide injection vs. Polylactic acid in hiv related lipodystrophy: A rct systematic review

Lipodystrophy is an alteration of fat metabolism that commonly affects HIV-1 positive patients treated with antiretroviral therapy (ART). The facial area is most commonly affected by peripheral lipoatrophy, thus becoming a social stigma related to chronic HIV. Several treatments have been proposed, such as modification of diet, lifestyle and both surgical and nonsurgical procedures. The goal of our systematic review is to examine published clinical studies involving the use of polyacrylamide filler for the treatment of HIV FLA, and to provide evidence-based recommendations based on published efficacy and safety data. Our research was performed on published literature until April 2021. Polyacrylamide gel is a volumetric gel that has been proven stable, nontoxic, nonallergenic, nonembryotoxic and nonabsorbable. Poly-l-lactic acid (PLA) is a biocompatible, biodegradable, synthetic polymer derived from lactic acid. We believe it is essential to draft a pre-and post-injection and operative protocol to define an even setting for the clinical condition. It is desirable that such specifications are included in a large randomized controlled trial and the follow up is longer than the studies that we found, because as we have seen in the literature there are reported adverse events even 3 or 5 years after the injections

Clinical applications of in vivo and ex vivo confocal microscopy

Confocal laser scanning microscopy (CLSM) has been introduced in clinical settings as a tool enabling a quasi-histologic view of a given tissue, without performing a biopsy. It has been applied to many fields of medicine mainly to the skin and to the analysis of skin cancers for both in vivo and ex vivo CLSM. In vivo CLSM involves reflectance mode, which is based on refractive index of cell structures serving as endogenous chromophores, reaching a depth of exploration of 200 \ub5m. It has been proven to increase the diagnostic accuracy of skin cancers, both melanoma and nonmelanoma. While histopathologic examination is the gold standard for diagnosis, in vivo CLSM alone and in addition to dermoscopy, contributes to the reduction of the number of excised lesions to exclude a melanoma, and to improve margin recognition in lentigo maligna, enabling tissue sparing for excisions. Ex vivo CLSM can be performed in reflectance and fluorescent mode. Fluorescence confocal microscopy is applied for \u201creal-time\u201d pathological examination of freshly excised specimens for diagnostic purposes and for the evaluation of margin clearance after excision in Mohs surgery. Further prospective interventional studies using CLSM might contribute to increase the knowledge about its application, reproducing real-life settings

Comparative physicochemical analysis among 1,4-butanediol diglycidyl ether cross-linked hyaluronic acid dermal fillers

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used in several chirurgical practices and in aesthetic medicine. HA filler stability can be enhanced through different cross-linking technologies; one of the most frequently cross-linker used is 1,4-butanediol diglycidyl ether (BDDE), also present in the HA-BDDE dermal filler family of the company Matex Lab S.p.A. (Brindisi, Italy). Our overview is focused on their characterization, drawing a correlation between matrix structure, rheological and physicochemical properties related to their cross-linking technologies. (2) Methods: Four different injectable HA hydrogels were characterized through optical microscopic examination and rheological behavior investigation. (3) Results: The cross-linked HA dermal fillers showed a fibrous \u201cspiderweb-like\u201d matrix structure and an elastic and solid-like profile. (4) Conclusions: The comparative analysis represents a preliminary characterization of these injectable medical devices in order to identify their best field of application