The first and only combination of basal and prandial insulin analogs degludec and aspart: the position of Russian endocrinologists

Insulin therapy for diabetes mellitus is the most effective way to control glycemia with the progression of the disease and the ineffectiveness of other sugar-lowering drugs. At the same time, the existing limitations of traditional insulin preparations, along with increasing attention to the individualized treatment of this disease, are pushing developers to create drugs that most closely reproduce the effect of natural human insulin. In this regard, the appearance of a combination of insulin analogs, the action profile of which practically imitates insulin secretion by a healthy pancreas, presents new possibilities in the treatment of diabetes mellitus. Insulin degludec / insulin aspart (IDegAsp, Ryzodeg®, Novo Nordisk, Denmark) is the first and only soluble combination preparation containing 70% of the ultra-long-acting insulin analogue degludec and 30% of the ultra-short-acting insulin analogue aspart in one injection, which meets the need for both basal and prandial insulin. The combined drug has nothing in common with traditional mixed insulin preparations (both human and analog) and provides doctors and patients with significant advantages over the latter. The article presents the position of Russian experts-diabetologists with extensive experience in the use of IDegAsp regarding the role and place of the drug in real clinical practice. Data from real clinical practice confirm that IDegAsp is a reasonable choice for starting and intensifying insulin therapy for type 2 diabetes mellitus when basal and prandial glycemic control is required. The use of the drug is most appropriate in patients who are on basal, biphasic, basal-plus/basal-bolus regimens and who do not achieve the goals of glycemic control during prior therapy. One of the leading reasons for choosing IDegAsp may also be a lower risk of developing hypoglycemia compared to insulin analogues of previous generations — biphasic insulin aspart and basal insulin glargine 100 U/ml. In addition, IDegAsp is a simple, flexible and safe insulin therapy for patients on premix therapy and basal-plus/basis-bolus regimens who require basal and prandial glycemic control. IDegAsp is a simple, flexible and safe insulin therapy. The greatest benefit of this drug use can be obtained by patients for whom adherence to a complex therapy regimen is difficult (the elderly, with cognitive impairment, after a stroke, with dementia), as well as patients who have an active lifestyle, accompanied by irregular food intake. It is important to note that since January 1, 2021, there is no need for a decision by a special medical commission to prescribe (IDegAsp) Ryzodeg®. This fact, as well as a significant price reduction at the end of 2020, opens up broader prospects for using the drug in the routine practice of a Russian endocrinologist

Staphylococcal Panton-Valentine Leukocidin Induces Pro-Inflammatory Cytokine Production and Nuclear Factor-Kappa B Activation in Neutrophils

Panton-Valentine leukocidin (PVL) is a cytotoxin secreted by Staphylococcus aureus and associated with severe necrotizing infections. PVL targets polymorphonuclear leukocytes, especially neutrophils, which are the first line of defense against infections. Although PVL can induce neutrophil death by necrosis or apoptosis, the specific inflammatory responses of neutrophils to this toxin are unclear. In this study, both in vivo and in vitro studies demonstrated that recombinant PVL has an important cytotoxic role in human neutrophils, leading to apoptosis at low concentrations and necrosis at high concentrations. Recombinant PVL also increased the levels of pro-inflammatory cytokine secretion from neutrophils. The up-regulation of pro-inflammatory cytokines was due to nuclear factor-kappa B (NF-κB) activation induced by PVL. Moreover, blocking NF-κB inhibited the production of inflammatory cytokines. To test the role of neutrophil immune responses during the pathogenesis of PVL-induced acute lung injury, we used immunocompetent or neutropenic rabbits to develop a model of necrotizing pneumonia. Immunocompetent rabbits challenged with PVL demonstrated increased inflammation containing neutrophilic infiltrates. In addition, there were elevated levels of inflammatory cytokines (IL-6, IL-8, TNF-α and IL-10) and NF-κB in the lung homogenate. In contrast, the lung tissues from neutropenic rabbits contained mild or moderate inflammation, and the levels of inflammatory cytokines and NF-κB increased only slightly. Data from the current study support growing evidence that neutrophils play an important role in the pathogenesis of PVL-induced tissue injury and inflammation. PVL can stimulate neutrophils to release pro-inflammatory mediators, thereby causing an acute inflammatory response. The ability of PVL to induce inflammatory cytokine release may be associated with the activation of NF-κB or its pore-forming properties

Electric-field controlled ferromagnetism in MnGe magnetic quantum dots

Electric-field control of ferromagnetism in magnetic semiconductors at room temperature has been actively pursued as one of the important approaches to realize practical spintronics and non-volatile logic devices. While Mn-doped III-V semiconductors were considered as potential candidates for achieving this controllability, the search for an ideal material with high Curie temperature (Tc>300 K) and controllable ferromagnetism at room temperature has continued for nearly a decade. Among various dilute magnetic semiconductors (DMSs), materials derived from group IV elements such as Si and Ge are the ideal candidates for such materials due to their excellent compatibility with the conventional complementary metal-oxide-semiconductor (CMOS) technology. Here, we review recent reports on the development of high-Curie temperature Mn0.05Ge0.95 quantum dots (QDs) and successfully demonstrate electric-field control of ferromagnetism in the Mn0.05Ge0.95 quantum dots up to 300 K. Upon the application of gate-bias to a metal-oxide-semiconductor (MOS) capacitor, the ferromagnetism of the channel layer (i.e. the Mn0.05Ge0.95 quantum dots) was modulated as a function of the hole concentration. Finally, a theoretical model based upon the formation of magnetic polarons has been proposed to explain the observed field controlled ferromagnetism

What EU policy framework do we need to sustain High Nature Value (HNV) farming and biodiversity? Policy Paper prepared in the framework of HNV-Link (project funded by the H2020 Research and Innovation Programme under Grant Agreement no 696391)

This policy paper builds upon the work carried out in the framework of HNV-Link (H2020 Project, 2016-2019, www.hnvlink.eu), a thematic multi-actor network on High Nature Value (HNV) Farming involving 13 partners from 10 European countries. The goal of this network is to support HNV farming systems by inspiring and sharing innovations/practices that improve their socio-economic viability while preserving their ecological value and the public services they provide. HNV-Link informs policymakers and authorities at the European and national levels of the main policy stakes around HNV farming, and to recommend adjustments of the Common Agricultural Policy (CAP) and other policies in order to adequately support HNV farming, the territories in which they are embedded, and the communities that depend on them. In Europe, farmers operate within a complex and constraining environment and policy/regulatory framework, including income support and rural development measures of the CAP, but also the numerous regulations related to agriculture, food hygiene/safety, animal health/welfare, environment protection, and climate change. This framework can provide farms with incentives or on the contrary, hinder their development, and it has consequently a major influence on their economic viability and the survival of the communities depending on farming. This institutional framework was designed to deal mainly with the problems that intensive farms face. Far less weight has been placed on designing and implementing policies adapted to the needs of HNV farms, i.e. those low-intensity farms which rely on and safeguard a rich biodiversity and associated ecosystem services made up of a variety of habitats and landscapes elements. Hence, there is a need for a creative yet thoughtful design and implementation of adapted policy measures

Standardisation of magnetic nanoparticles in liquid suspension

Suspensions of magnetic nanoparticles offer diverse opportunities for technology innovation, spanning a large number of industry sectors from imaging and actuation based applications in biomedicine and biotechnology, through large-scale environmental remediation uses such as water purification, to engineering-based applications such as position-controlled lubricants and soaps. Continuous advances in their manufacture have produced an ever-growing range of products, each with their own unique properties. At the same time, the characterisation of magnetic nanoparticles is often complex, and expert knowledge is needed to correctly interpret the measurement data. In many cases, the stringent requirements of the end-user technologies dictate that magnetic nanoparticle products should be clearly defined, well characterised, consistent and safe; or to put it another way—standardised. The aims of this document are to outline the concepts and terminology necessary for discussion of magnetic nanoparticles, to examine the current state-of-the-art in characterisation methods necessary for the most prominent applications of magnetic nanoparticle suspensions, to suggest a possible structure for the future development of standardisation within the field, and to identify areas and topics which deserve to be the focus of future work items. We discuss potential roadmaps for the future standardisation of this developing industry, and the likely challenges to be encountered along the way

Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial

Background: Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment. Methods: This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30–59 mL/min per 1·73 m2, and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete. Findings: Between Sept 20, 2016, and Sept 29, 2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA1c (estimated mean change of −1·0 percentage point (SE 0·1; −11 mmol/mol [SE 0·8]) vs −0·2 percentage points (SE 0·1; −2 mmol/mol [SE 0·8]); estimated treatment difference [ETD]: −0·8 percentage points, 95% CI −1·0 to −0·6;

Regional heterogeneity and firms’ innovation: the role of regional factors in industrial R&D in India

This study makes an early attempt to estimate the magnitude and intensity of manufacturing firms’ R&D by Indian states during the period 1991‒2008 and analyses the role of regional factors on firm-level R&D activities. As there is little research on state-wise R&D performance of firms in India, this study serves an important contribution to the academic and policy realm. It has brought out the fact the total manufacturing R&D investment in India is unevenly distributed regionally with a few states accounting for disproportionate share of it. Regional heterogeneity or inter-state disparities in R&D has increased between the 1990s and the first decade of the twenty-first century. In view of this persistent regional heterogeneity in R&D, the study has developed and estimated an empirical model for a sample of 4545 Indian manufacturing firms with R&D facilities located in single state and that explicitly includes regional factors as probable factors affecting R&D. The three-step Censored Quantitle Regression results confirm that regional factors play an important role in shaping the R&D intensity of the sample of firms. This led us to some useful policy suggestions for regional governments to promote local firms’ R&D activities

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe