To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended

Background  

Excess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individual's Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m². The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention.     

The phase behavior,mechanical, and rheological characteristics of blends containing nitrile polymers and poly(ethylene-co-maleic anhydride)

The phase behavior of binary blends of acrylonitrile/methyl acrylate/butadiene terpolymer (B210) and poly(ethylene-co-maleic anhydride) (PEMA) was examined based on thermal analysis and optical microscopy. Miscibility of these polymer blends was recognized over a wide range of compositions. The appearance of phase separation during subsequent heatings above the glass transition temperature (T_g) of these blends was associated with a lower critical solution temperature (LCST) behavior. Rheological characteristics such as shear storage modulus (G′), loss modulus (G″) and complex viscosity have been shown to depend on the amount of PEMA in the blend. Mechanical properties including the tensile strength and flexural modulus also were found to be related to the composition of the blend. © 1993 John Wiley & Sons, Inc.     

Motif patterns in 2D

Motif patterns consisting of sequences of intermixed solid and don’t-care characters have been introduced and studied in connection with pattern discovery problems of computational biology and other domains. In order to alleviate the exponential growth of such motifs, notions of maximal saturation and irredundancy have been formulated, whereby more or less compact subsets of the set of all motifs can be extracted, that are capable of expressing all others by suitable combinations. In this paper, we introduce the notion of maximal irredundant motifs in a two-dimensional array and develop initial properties and a combinatorial argument that poses a linear bound on the total number of such motifs. The remainder of the paper presents approaches to the discovery of irredundant motifs both by offline and incremental algorithms.     

Epigenetic and Genetic Factors Related to Curve Progression in Adolescent Idiopathic Scoliosis: A Systematic Scoping Review of the Current Literature

Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity leading, in rare cases, to a severe deformity. While the Cobb angle is a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were included; fifteen genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical applications. In contrast, nine studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic testing for AIS has the potential to significantly modify disease management. Most recent evidence suggests epigenetics as a more promising field for the identification of factors associated with AIS progression, offering a rationale for further investigation in this field.     

Cardiac Troponin Biosensor Designs: Current Developments and Remaining Challenges

Acute myocardial infarction (AMI) is considered as one of the main causes of death, threating human lives for decades. Currently, its diagnosis relies on electrocardiography (ECG), which has been proven to be insufficient. In this context, the efficient detection of cardiac biomarkers was proposed to overcome the limitations of ECG. In particular, the measurement of troponins, specifically cardiac troponin I (cTnI) and cardiac troponin T (cTnT), has proven to be superior in terms of sensitivity and specificity in the diagnosis of myocardial damage. As one of the most life-threatening conditions, specific and sensitive investigation methods that are fast, universally available, and cost-efficient to allow for early initiation of evidence-based, living-saving treatment are desired. In this review, we aim to present and discuss the major breakthroughs made in the development of cTnI and cTnT specific biosensor designs and analytical tools, highlighting the achieved progress as well as the remaining challenges to reach the technological goal of simple, specific, cheap, and portable testing chips for the rapid and efficient on-site detection of cardiac cTnI/cTnT biomarkers in order to diagnose and treat cardiovascular diseases at an incipient stage.     

A Short ERAP2 That Binds IRAP Is Expressed in Macrophages Independently of Gene Variation

The M1 zinc metalloproteases ERAP1, ERAP2, and IRAP play a role in HLA-I antigen presentation by refining the peptidome either in the ER (ERAP1 and ERAP2) or in the endosomes (IRAP). They have also been entrusted with other, although less defined, functions such as the regulation of the angiotensin system and blood pressure. In humans, ERAP1 and IRAP are commonly expressed. ERAP2 instead has evolved under balancing selection that maintains two haplotypes, one of which undergoing RNA splicing leading to nonsense-mediated decay and loss of protein. Hence, likewise in rodents, wherein the ERAP2 gene is missing, about a quarter of the human population does not express ERAP2. We report here that macrophages, but not monocytes or other mononuclear blood cells, express and secrete an ERAP2 shorter form independent of the haplotype. The generation of this “short” ERAP2 is due to an autocatalytic cleavage within a distinctive structural motif and requires an acidic micro-environment. Remarkably, ERAP2 “short” binds IRAP and the two molecules are co-expressed in the endosomes as well as in the cell membrane. Of note, the same phenomenon could be observed in some cancer cells. These data prompt us to reconsider the role of ERAP2, which might have been maintained in humans due to fulfilling a relevant function in its “short” form.     

Fighting the Huntington’s Disease with a G-Quadruplex-Forming Aptamer Specifically Binding to Mutant Huntingtin Protein: Biophysical Characterization,In Vitro and In Vivo Studies

A set of guanine-rich aptamers able to preferentially recognize full-length huntingtin with an expanded polyglutamine tract has been recently identified, showing high efficacy in modulating the functions of the mutated protein in a variety of cell experiments. We here report a detailed biophysical characterization of the best aptamer in the series, named MS3, proved to adopt a stable, parallel G-quadruplex structure and show high nuclease resistance in serum. Confocal microscopy experiments on HeLa and SH-SY5Y cells, as models of non-neuronal and neuronal cells, respectively, showed a rapid, dose-dependent uptake of fluorescein-labelled MS3, demonstrating its effective internalization, even in the absence of transfecting agents, with no general cytotoxicity. Then, using a well-established Drosophila melanogaster model for Huntington’s disease, which expresses the mutated form of human huntingtin, a significant improvement in the motor neuronal function in flies fed with MS3 was observed, proving the in vivo efficacy of this aptamer.     

Skin Inflammation Modulation via TNF-α, IL-17, and IL-12 Family Inhibitors Therapy and Cancer Control in Patients with Psoriasis

The systemic inflammatory syndrome concept is one of the foundations that stand at the basis of revolutionary modern and future therapies, based on the in-depth understanding of the delicate mechanisms that govern the collaboration between the systems and organs of the human body and, at the same time, the fine balance that ensures a reproach-free operation. An interesting concept that we propose is that of the environment-inadequacy status, a concept that non-specifically incorporates all the situations of the organism’s response disorders in the face of imprecisely defined situations of the environment. The correlation between these two concepts will define the future of modern medicine, along with the gene-adjustment mechanisms. Psoriasis is a clear example of an inadequate body response as a result of exposure to as of yet undefined triggers with an excessive systemic inflammatory reaction and hitherto insufficiently controllable. Modern biological therapies, such as TNF-α, IL-12 family, and IL-17 inhibitors, are intended to profoundly reshape the cytokine configuration of patients with inflammatory diseases such as psoriasis, with tremendous success in disease control. Yet, because of the important roles of cytokines in cancer promotion and control, concern was raised about the fact that the use of biologicals may alter immune surveillance and promote cancer progression. Both theoretical and practical data nevertheless showed that the treatment-induced control of cytokines may be beneficial for reducing the inflammatory milieu that promotes cancer and such have a beneficial role in maintaining health. We briefly present the intricate roles of those cytokine families on cancer control, with some debates on if their inhibition might or might not promote additional tumoral development.     

A posteriori optimization of parameters in stabilized methods for convection–diffusion problems – Part I

Stabilized finite element methods for convection-dominated problems require the choice of appropriate stabilization parameters. From numerical analysis, often only their asymptotic values are known. This paper presents a general framework for optimizing stabilization parameters with respect to the minimization of a target functional. Exemplarily, this framework is applied to the SUPG finite element method and the minimization of a residual-based error estimator, an error indicator, and a functional including the crosswind derivative of the computed solution. Benefits of the basic approach are demonstrated by means of numerical results.     

Integration of InGaP/GaAs/Ge triple‐junction solar cells on deeply patterned silicon substrates

We report preliminary results on InGaP/InGaAs/Ge photovoltaic cells for concentrated terrestrial applications, monolithically integrated on engineered Si(001) substrates. Cells deposited on planar Ge/Si(001) epilayers, grown by plasma‐enhanced chemical vapor deposition, provide good efficiency and spectral response, despite the small thickness of the Ge epilayers and a threading dislocation density as large as 10⁷/cm². The presence of microcracks generated by the thermal misfit is compensated by a dense collection grid that avoids insulated areas. In order to avoid the excessive shadowing introduced by the use of a dense grid, the crack density needs to be lowered. Here, we show that deep patterning of the Si substrate in blocks can be an option, provided that a continuous Ge layer is formed at the top, and it is suitably planarized before the metalorganic chemical vapor deposition. The crack density is effectively decreased, despite that the efficiency is also lowered with respect to unpatterned devices. The reasons of this efficiency reduction are discussed, and a strategy for improvement is proposed and explored. Full morphological analysis of the coalesced Ge blocks is reported, and the final devices are tested under concentrated AM1.5D spectrum. Copyright © 2016 John Wiley & Sons, Ltd.