Role of nanostructured aggregation of chitosan derivatives on [5-methionine]enkephalin affinity

Affinities of quaternary ammonium-chitosan conjugates, their thiolated derivatives and corresponding nanostructured aggregates towards the hydrophilic drug [5-methionine]enkephalin were compared by Nuclear Magnetic Resonance (NMR) spectroscopic methods based on proton selective relaxation rate measurements. Nanoaggregates showed enhanced drug affinity in comparison with corresponding polymers, especially in the case of thiolated systems

Ergonomics and Workflow Evaluation of Automatic Doppler Angle Technology Implemented in a Diagnostic Ultrasound System

AbstractCommonly available Pulsed Wave Doppler (PW) flow velocity measurements for Ultrasound (US) investigation require the operator to manually set the direction of the flow velocity vector along the blood vessel axis on the US image, in order to determine the Doppler angle and then to estimate the real flow velocity. The present work investigates the possibility to implement on a commercially available US system an innovative Automatic Doppler Angle (ADA) Technology by analyzing the best workflow in terms of higher execution speed, lower keystrokes/adjustments helping in the prevention of Work-related Musculoskeletal Disorders (WRMSD) and a Doppler angle correction precision, comparable to the one obtained manually by expert sonographer. Ergonomics and workflow tests, then accuracy and repeatability evaluations of the Doppler velocity measurement, were performed on a portable US system (MyLabAlpha, Esaote S.p.A., Florence, Italy) by an expert sonographer. Ergonomics and workflow Tests were performed to analyze the potential of ADA in terms of reduction of muscular activation applied (by SEMG), number of activations (by cameras optoelectronic system) and time needed using ADA, in comparison to manual procedure. Accuracy and intra-operator repeatability tests of the velocity measurement were performed to evaluate the precision of the obtained PW trace velocity measurements with ADA technology, compared to manual ones. Results provided evidence that ADA tool allowed: a reduction of muscular activation (from 12% for trapezius descendens, to 25% for deltoideus anterior) a lower total number of keystrokes and a reduction of the US scan time of about 56%. The maximal variation between PW Doppler trace velocity measurement set automatically by ADA and set manually by sonographer was 11%. ADA technology can provide a Doppler angle correction precision comparable to the manual one, while decreasing the risk of WRMSD

A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices

CGRP Antagonism and Ketogenic Diet in the Treatment of Migraine

The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort. It is important to point out that this pathology not only has a decisive impact on the quality of life of those who suffer from it but also on their families and, more generally, on society as a whole. The clinical picture of migraine is complex, with debilitating unilateral or bilateral head pain, and is often associated with characteristic symptoms such as nausea, vomiting, photophobia, and phonophobia. Hormonal, environmental, psychological, dietary, or other factors can trigger it. The present review focuses on the analysis of the physiopathological and pharmacological aspects of migraine, up to the correct dietary approach, with specific nutritional interventions aimed at modulating the symptoms. Based on the symptoms that the patient experiences, targeted and specific therapy is chosen to reduce the frequency and severity of migraine attacks. Specifically, the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine is analyzed, along with the drugs that effectively target the corresponding receptor. Particularly, CGRP receptor antagonists (gepants) are very effective drugs in the treatment of migraine, given their high diffusion in the brain. Moreover, following a ketogenic diet for only one or two months has been demonstrated to reduce migraine attacks. In this review, we highlight the diverse facets of migraine, from its physiopathological and pharmacological aspects to prevention and therapy

Anti-TNF-α drugs differently affect the TNFa-sTNFR system and monocyte subsets in patients with psoriasis

TNF-a has a central role in the development and maintenance of psoriatic plaques, and its serum levels correlate with disease activity. Anti-TNF-a drugs are, however, ineffective in a relevant percentage of patients for reasons that are currently unknown. To understand whether the response to anti-TNF-a drugs is influenced by the production of anti-drug antibodies or by the modulation of the TNFa-TNFa receptor system, and to identify changes in monocyte phenotype and activity, we analysed 119 psoriatic patients who either responded or did not respond to different anti-TNF-a therapies (adalimumab, etanercept or infliximab), and measured plasma levels of TNF-a, TNF-a soluble receptors, drug and anti-drug antibodies. Moreover, we analyzed the production of TNF-a and TNF-α soluble receptors by peripheral blood mononuclear cells (PBMCs), and characterized different monocyte populations. We found that: i) the drug levels varied between responders and non-responders; ii) anti-infliximab antibodies were present in 15% of infliximab-treated patients, while anti-etanercept or anti-adalimumab antibodies were never detected; iii) plasma TNF-a levels were higher in patients treated with etanercept compared to patients treated with adalimumab or infliximab; iv) PBMCs from patients responding to adalimumab and etanercept produced more TNF-a and sTNFRII in vitro than patients responding to infliximab; v) PBMCs from patients not responding to infliximab produce higher levels of TNF-a and sTNFRII than patients responding to infliximab; vi) anti- TNF-a drugs significantly altered monocyte subsets. A complex remodelling of the TNFa-TNFa receptor system thus takes place in patients treated with anti-TNF-α drugs, that involves either the production of anti-drug antibodies or the modulation of monocyte phenotype or inflammatory activity

Natural Products for the Prevention, Treatment and Progression of Breast Cancer

In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy

2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy.

Bile duct injury (BDI) is a dangerous complication of cholecystectomy, with significant postoperative sequelae for the patient in terms of morbidity, mortality, and long-term quality of life. BDIs have an estimated incidence of 0.4-1.5%, but considering the number of cholecystectomies performed worldwide, mostly by laparoscopy, surgeons must be prepared to manage this surgical challenge. Most BDIs are recognized either during the procedure or in the immediate postoperative period. However, some BDIs may be discovered later during the postoperative period, and this may translate to delayed or inappropriate treatments. Providing a specific diagnosis and a precise description of the BDI will expedite the decision-making process and increase the chance of treatment success. Subsequently, the choice and timing of the appropriate reconstructive strategy have a critical role in long-term prognosis. Currently, a wide spectrum of multidisciplinary interventions with different degrees of invasiveness is indicated for BDI management. These World Society of Emergency Surgery (WSES) guidelines have been produced following an exhaustive review of the current literature and an international expert panel discussion with the aim of providing evidence-based recommendations to facilitate and standardize the detection and management of BDIs during cholecystectomy. In particular, the 2020 WSES guidelines cover the following key aspects: (1) strategies to minimize the risk of BDI during cholecystectomy; (2) BDI rates in general surgery units and review of surgical practice; (3) how to classify, stage, and report BDI once detected; (4) how to manage an intraoperatively detected BDI; (5) indications for antibiotic treatment; (6) indications for clinical, biochemical, and imaging investigations for suspected BDI; and (7) how to manage a postoperatively detected BDI

Shifting towards smart, connected products : a business model innovation perspective

Our everyday products become more and more digitally connected. From home appliances to toys to paper notebooks, products become embedded with sensory devices that allow them to provide more value than their predecessors. For firms, this often means to venture into activities that lie outside their core competencies. The re-orientation of some elements such as value proposition, key activities or key partnerships can instigate business model innovation. Thus, in this master thesis, we aim to give advice to managers who are challenged with the complexities that arise from the integration of smart, connected products (SCP) into their offering. Hereby, we address two pressing gaps in extant business model literature. Firstly, we investigate the opportunities and challenges that firms face when commercializing smart, connected products (SCP) and develop propositions regarding the effects of SCP on BMI. Secondly, based on three in-depth case studies of SCP sellers, we find that external partnerships, complex value chains, and new marketing strategies are common characteristics of BMI under the SCP commercialization. Further, our results indicate the necessity for firms to leverage on dynamic capabilities in order to bridge organizational challenges brought about by the integration of SCP. Finally, we find that firms seem to undergo a more radical BMI when the SCP represents a thorough change with respect to the overall product offering, and the firm does not yet have an established ecosystem of competencies to develop this new product. We suggest that an increase of radicalness of the BMI has to be supported by more agility and adaptability of the firms’ processes. Based on these findings we propose a framework, which explains SCP-driven BMI along the dimensions of agility and adaptability as capabilities of the specific firm. Finally, we offer managerial recommendations on how firms can effectively deal with the sourcing of digital know how in different way: an outsourcing, a full cooperation and an ecosystem approach.nhhma

Strangeness Enhancement in Fixed-Target Pb-Ne Collisions with LHCb SMOG Experiment

At sufficiently high temperature and energy density, nuclear matter converts to a phase where quarks and gluons are not confined: the Quark-Gluon Plasma (QGP). Such a state is produced in the laboratory with ultra-relativistic collisions of heavy nuclei, resulting in an enhanced strange hadrons' production. Strangeness enhancement has been proposed as a test of the Quark-Gluon Plasma formation due to: (i) the dominance of the $gg \rightarrow s\bar{s}$ channel and (ii) the high gluon and high strange quark densities in QGP. Here I report on the analysis of the samples related to fixed-target Pb-Ne and p-Ne collisions at $\sqrt{s_{NN}} = 68.6$ GeV collected with SMOG at LHCb