The role of beta-2-glycoprotein I in health and disease associating structure with function: More than just APS

Beta-2-Glycoprotein I (β2GPI) plays a number of essential roles throughout the body. β2GPI, C-reactive protein and thrombomodulin are the only three proteins that possess the dual capability to up and down regulate the complement and coagulation systems depending upon external stimulus. Clinically, β2GPI is the primary antigen in the autoimmune condition antiphospholipid syndrome (APS), which is typically characterised by pregnancy morbidity and vascular thrombosis. This protein is also capable of adopting at least two distinct structural forms, but it has been argued that several other intermediate forms may exist. Thus, β2GPI is a unique protein with a key role in haemostasis, homeostasis and immunity. In this review, we examine the genetics, structure and function of β2GPI in the body and how these factors may influence its contribution to disease pathogenesis. We also consider the clinical implications of β2GPI in the diagnosis of APS and as a potentially novel therapeutic target

Free-standing polyelectrolyte membranes made of chitosan and alginate

Free-standing films have increasing applications in the biomedical field as drug delivery systems for wound healing and tissue engineering. Here, we prepared free-standing membranes by the layer-by-layer assembly of chitosan and alginate, two widely used biomaterials. Our aim was to produce a thick membrane and to study the permeation of model drugs and the adhesion of muscle cells. We first defined the optimal growth conditions in terms of pH and alginate concentration. The membranes could be easily detached from polystyrene or polypropylene substrate without any postprocessing step. The dry thickness was varied over a large range from 4 to 35 μm. A 2-fold swelling was observed by confocal microscopy when they were immersed in PBS. In addition, we quantified the permeation of model drugs (fluorescent dextrans) through the free-standing membrane, which depended on the dextran molecular weight. Finally, we showed that myoblast cells exhibited a preferential adhesion on the alginate-ending membrane as compared to the chitosan-ending membrane or to the substrate side.This work was financially supported by Foundation for Science and Technology (FCT) through the Scholarship SFRH/BD/64601/2009 granted to S.G.C. C.M. is indebted to Grenoble INP for financial support via a postdoctoral fellowship. This work was supported by the European Commission (FP7 Program) via a European Research Council starting grant (BIOMIM, GA 259370 to C.P.). C.P. is also grateful to Institut Universitaire de France and to Grenoble Institute of Technology for financial support. We thank Isabelle Paintrand for her technical help with the confocal apparatus and Patrick Chaudouet for his help with SEM imaging

Edible bio-based nanostructures: delivery, absorption and potential toxicity

The development of bio-based nanostructures as nanocarriers of bioactive compounds to specific body sites has been presented as a hot topic in food, pharmaceutical and nanotechnology fields. Food and pharmaceutical industries seek to explore the huge potential of these nanostructures, once they can be entirely composed of biocompatible and non-toxic materials. At the same time, they allow the incorporation of lipophilic and hydrophilic bioactive compounds protecting them against degradation, maintaining its active and functional performance. Nevertheless, the physicochemical properties of such structures (e.g., size and charge) could change significantly their behavior in the gastrointestinal (GI) tract. The main challenges in the development of these nanostructures are the proper characterization and understanding of the processes occurring at their surface, when in contact with living systems. This is crucial to understand their delivery and absorption behavior as well as to recognize potential toxicological effects. This review will provide an insight into the recent innovations and challenges in the field of delivery via GI tract using bio-based nanostructures. Also, an overview of the approaches followed to ensure an effective deliver (e.g., avoiding physiological barriers) and to enhance stability and absorptive intestinal uptake of bioactive compounds will be provided. Information about nanostructures potential toxicity and a concise description of the in vitro and in vivo toxicity studies will also be given.Joana T. Martins, Oscar L. Ramos, Ana C. Pinheiro, Ana I. Bourbon, Helder D. Silva and Miguel A. Cerqueira (SFRH/BPD/89992/2012, SFRH/BPD/80766/2011, SFRH/BPD/101181/2014, SFRH/BD/73178/2010, SFRH/BD/81288/2011, and SFRH/BPD/72753/2010, respectively) are the recipients of a fellowship from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN and FSE, Portugal). The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the project "BioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes," REF.NORTE-07-0124-FEDER-000028, co-funded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDER. We also thank to the European Commission: BIOCAPS (316265, FP7/REGPOT-2012-2013.1) and Xunta de Galicia: Agrupamento INBIOMED (2012/273) and Grupo con potencial de crecimiento. The support of EU Cost Action FA1001 is gratefully acknowledged

Alpha-lipoic acid for diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is a frequent complication in people living with type 1 or type 2 diabetes. There is currently no effective treatment for DPN. Although alpha-lipoic acid (ALA, also known as thioctic acid) is widely used, there is no consensus about its benefits and harms. To assess the effects of alpha-lipoic acid as a disease-modifying agent in people with diabetic peripheral neuropathy. On 11 September 2022, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and two clinical trials registers. We also searched the reference lists of the included studies and relevant review articles for additional references not identified by the electronic searches. We included randomised clinical trials (RCTs) that compared ALA with placebo in adults (aged 18 years or older) and that applied the study interventions for at least six months. There were no language restrictions. We used standard methods expected by Cochrane. The primary outcome was change in neuropathy symptoms expressed as changes in the Total Symptom Score (TSS) at six months after randomisation. Secondary outcomes were change in neuropathy symptoms at six to 12 months and at 12 to 24 months, change in impairment, change in any validated quality of life total score, complications of DPN, and adverse events. We assessed the certainty of the evidence using GRADE. Our analysis incorporated three trials involving 816 participants. Two studies included people with type 1 or type 2 diabetes, while one study included only people with type 2 diabetes. The duration of treatment was between six months and 48 months. We judged all studies at high risk of overall bias due to attrition. ALA compared with placebo probably has little or no effect on neuropathy symptoms measured by TSS (lower score is better) after six months (mean difference (MD) -0.16 points, 95% confidence interval (CI) -0.83 to 0.51; 1 study, 330 participants; moderate-certainty evidence). The CI of this effect estimate did not contain the minimal clinically important difference (MCID) of 0.97 points. ALA compared with placebo may have little or no effect on impairment measured by the Neuropathy Impairment Score-Lower Limbs (NIS-LL; lower score is better) after six months (MD -1.02 points, 95% CI -2.93 to 0.89; 1 study, 245 participants; low-certainty evidence). However, we cannot rule out a significant benefit, because the lower limit of the CI surpassed the MCID of 2 points. There is probably little or no difference between ALA and placebo in terms of adverse events leading to cessation of treatment within six months (risk ratio (RR) 1.48, 95% CI 0.50 to 4.35; 3 studies, 1090 participants; moderate-certainty evidence). No studies reported quality of life or complications associated with DPN. Our analysis suggests that ALA probably has little or no effect on neuropathy symptoms or adverse events at six months, and may have little or no effect on impairment at six months. All the studies were at high risk of attrition bias. Therefore, future RCTs should ensure complete follow-up and transparent reporting of any participants missing from the analyses

An agent-based model for cruise ship evacuation considering the presence of smart technologies on board

The cruise ship industry has faced in recent years a continuous increase in the number of passengers, reaching 28.5 million passengers in 2018, 60.11% more than in 2009. In this context, the research literature has acknowledged the key role played by the passengers' safety and has considered different aspects when dealing with the ship evacuation process related to both environmental properties and human behavioral aspects. Cruise ship companies have manifested a real interest in offering their passengers a safe travel experience and have continuously considered and adapted their evacuation plans to support a faster evacuation process. With the enhancement of technology, cruise ship companies can contribute more to increase safety during an emergency evacuation by providing smartphone applications that can assist each passenger involved in this process. As a result, the present paper aims to measure the impact made by the use of such an application on evacuation time by considering various weather conditions, ship conditions, and different times of the day. According to this purpose, an agent-based model is created for simulating the evacuation process of a ship deck which could accommodate up to 1200 people. The results indicate that using an application reduces the average evacuation time, with a 70% increase in usage leading to a 34.5% reduction in evacuation time. The main contribution of this work is to apply agent-based modelling to analyze the evacuation behavior on cruise ships when smart technologies are available, incorporating in the analysis elements and characteristics that have been previously considered in isolation. The model can be used as a support laboratory for policy advice: it can be applied for estimating the evacuation movement time under various conditions and for different levels of application adoption, as well as for assisting the decision-makers in designing the emergency plans and making the right decisions related to cruise ship evacuation

Determinants of individuals' e-waste recycling decision: A case study from Romania

Due to the increase of the amount of electrical and electronical equipment waste (e-waste), the understanding of individual consumers' main decision triggers represents a key point in increasing the quantity of recycled e-waste. A series of studies from the literature have shown a positive relationship between the consumers' attitude, awareness, self-efficacy, social norms, and their e-waste recycling intention, as well as the positive influence between the intention and the manifested behavior. Additional to these determinants, in the present study, the influence of social media was analyzed along with the actions taken by the government and nongovernmental organizations, with the purpose to include and to capture, as much as possible, a high amount of determinants in the e-waste recycling process. Nevertheless, the demographic or socio-economic variables, such as age, gender, income, education, number of family members, etc., have shown over time to have a contribution to predicting the consumers' pro-recycling behavior. As on one side, in the research literature, the opinions related to which of the demographic or socio-economic factors can have an impact on the recycling behavior have been divided and, on another side, a series of researchers believe that the discrepancies in the findings of different studies can be due to culture in various countries, in this paper we conducted such an analysis with reference to the Romania's case. The results have shown that the demographic variables, such as age and gender, can have a contribution to predicting residents' pro-e-waste recycling behavior. Based on these findings, the policymakers can gain a better understanding of the e-waste recycling phenomenon and on its main triggers, with results in creating better policies for sustaining a proper e-waste managing system

Characterization of bonds formed between platelet factor 4 and negatively charged drugs using single molecule force spectroscopy

Immunogenicity (i.e., the ability to initiate immune reactions) is one of the major challenges for the development of new drugs, as it may turn the developed drug therapeutically ineffective or cause severe immune-related effects. Using single molecule force spectroscopy, we study rupture forces between the positively charged, endogenous protein platelet factor 4 (PF4; also known as CXC chemokine ligand 4, CXCL4) and the antithrombotic drug heparin and other negatively charged glycosaminoglycans (GAGs), which are known to form immunogenic PF4/GAG-complexes (e. g., heparin and dextran sulfate) as well as non-immunogenic complexes (e. g., chondroitin sulfate A). Our measurements suggest that the average number of sulfate groups per monosaccharide unit (i.e., the degree of sulfation DS) does not affect the unbinding characteristics of single PF4/GAG-bonds (reaction coordinate x(0) = 2.2 +/- 0.2 angstrom, energy barrier Delta G approximate to -1 k(B)T). However, the average number of GAG bonds formed to a single PF4 molecule increases with increasing DS as indicated by a rising frequency of unbinding events, suggesting a multivalent binding scheme between PF4 and GAGs. Our studies show that at least three GAG bonds have to be formed to each PF4 molecule to induce epitope formation on the PF4/GAG-complex to which PF4/GAG-complex specific antibodies bind. Hence, GAG-based drugs that form less than three bonds per PF4 molecule are unlikely to constitute PF4/drug-complexes that are of immunologic relevance

Investigating the exits' symmetry impact on the evacuation process of classrooms and lecture halls: An agent-based modeling approach

As the evacuation problem has attracted and continues to attract a series of researchers due to its high importance both for saving human lives and for reducing the material losses in such situations, the present paper analyses whether the evacuation doors configuration in the case of classrooms and lecture halls matters in reducing the evacuation time. For this aim, eighteen possible doors configurations have been considered along with five possible placements of desks and chairs. The doors configurations have been divided into symmetrical and asymmetrical clusters based on the two doors positions within the room. An agent-based model has been created in NetLogo which allows a fast configuration of the classrooms and lecture halls in terms of size, number of desks and chairs, desks and chair configuration, exits' size, the presence of fallen objects, type of evacuees and their speed. The model has been used for performing and analyzing various scenarios. Based on these results, it has been observed that, in most cases, the symmetrical doors configurations provide good/optimal results, while only some of the asymmetrical doors configurations provide comparable/better results. The model is configurable and can be used in various scenarios