Structural analysis of peptide binding to integrins for cancer detection and treatment.

Integrins are cell receptors involved in several metabolic pathways often associated with cell proliferation. Some of these integrins are downregulated during human physical development, but when these integrins are overexpressed in adult humans, they can be associated with several diseases, such as cancer. Molecules that specifically bind to these integrins are useful for cancer detection, diagnosis, and treatment. This review focuses on the structures of integrin-peptidic ligand complexes to dissect how the binding occurs and the molecular basis of the specificity and affinity of these peptidic ligands. Understanding these interactions at the molecular level is fundamental to be able to design new peptides that are more specific and more sensitive to a particular integrin. The integrin complexes covered in this review are α5ß1, αIIbß3, αvß3, αvß6, and αvß8, because the molecular structures of the complex have been experimentally determined and their presence on tumor cancer cells are associated with a poor prognosis, making them targets for cancer detection and treatment.

Total Rehabilitation Using Adhesive Dental Restorations in Patients with Severe Tooth Wear: A 5-Year Retrospective Case Series Study.

INTRODUCTION: Currently, there is little clinical evidence to support the medium- and long-term survival and clinical performance of ultraconservative approaches using adhesive restorations in full-mouth restorations. The aim of this case series study was to evaluate the medium-term clinical performance of anterior and posterior adhesive restorations applied with direct and indirect techniques using resin composites and glass-ceramic-based materials. MATERIALS AND METHODS: The inclusion criteria were an esthetic problem as the main reason for consultation and severe generalized wear of grade 2 to 4 according to the Tooth Wear Evaluation System (TWES 2.0). In addition, at each follow-up appointment, patients were required to submit a clinical-parameter-monitoring record according to the modified United States Public Health Service (USPHS) criteria. RESULTS: Eight patients with severe tooth wear were treated through full rehabilitation in a private dental clinic in Spain by a single operator (AFC). A total of 212 restorations were performed, which were distributed as follows: 66 occlusal veneers, 26 palatal veneers and 120 vestibular veneers. No signs of marginal microleakage or postoperative sensitivity were observed in any occlusal, vestibular and/or palatal restoration after the follow-up period. The estimated survival rate of the 212 restorations was 90.1% over 60 months of observation, with a survival time of 57.6 months. Only 21 restorations had complications, which were mostly resolved with a direct composite resin. The dichotomous variables of the restoration type (posterior veneer, anterior veneer) and the type of restored tooth (anterior, posterior) were the risk predictors with statistically significant influences (p < 0.005) on the survival of the restorations. CONCLUSION: According to the results of this study, there is a significantly higher risk of restorative complications in posterior teeth compared to anterior teeth. Also, it can be concluded that the indication of adhesive anterior and posterior restorations is justified in the total oral rehabilitation of patients with severe multifactorial tooth wear, as they are associated with a low risk of failure.

Three-dimensional neuroimmune co-culture system for modeling Parkinson's disease microenvironmentsin vitro.

Parkinson's disease (PD) is a complex and multifaceted neurodegenerative disorder that results from multiple environmental factors and multicellular interactions. Although several PD neuropathologies have been identified and described, the thorough understanding of PD pathophysiology and research has been largely limited by the absence of reliablein vitromodels that truly recapitulate PD microenvironments. Here, we propose a neuroimmune co-culture system that models PD neuropathologies by combining relevant multicellular interactions with environments that mimic the brain. This system is composed of: (i) 3D bioprinted cultures of mature human dopaminergic (DA) neurons grown on extracellular matrix (ECM)-derived scaffolds doped with electroconductive nanostructures, and (ii) a direct co-culture of human astrocytes and differentiated monocytes that models neuroinflammatory responses. When co-cultured in a transwell format, these two compartments recreate relevant multicellular environments that model PD pathologies after exposure to the neurotoxin A53Tα-synuclein. With immunofluorescent staining and gene expression analyses, we show that functional and mature DA 3D networks are generated within our ECM-derived scaffolds with superior performance to standard 2D cultures. Moreover, by analyzing cytokine secretion, cell surface markers, and gene expression, we define a human monocyte differentiation scheme that allows the appearance of both monocyte-derived macrophages and dendritic cell phenotypes, as well as their optimal co-culture ratios with human astrocytes to recreate synergistic neuroinflammatory responses. We show that the combined response of both compartments to A53Tα-synuclein stimulates the formation of intracellularα-synuclein aggregates, induces progressive mitochondrial dysfunction and reactive oxygen species production, downregulates the expression of synaptic, DA, and mitophagy-related genes, and promotes the initiation of apoptotic processes within the DA networks. Most importantly, these intracellular pathologies were comparable or superior to those generated with a rotenone-stimulated 2D control that represents the current standard forin vitroPD models and showed increased resilience towards these neurotoxic insults, allowing the study of disease progression over longer time periods than current models. Taken together, these results position the proposed model as a superior alternative to current 2D models for generating PD-related pathologiesin vitro.

The job of public transport, ride-hailing and delivery drivers: Conditions during the COVID-19 pandemic and implications for a post-pandemic future.

Transport workers were among the most affected by the COVID-19 crisis. In several countries, public transport and delivery drivers were considered essential workers during the pandemic, while the demand changed dramatically. In this context, little is known about the actual effects of the pandemic on the lives of drivers, and whether those effects depend on the type and formality of the corresponding job. In this paper, we analyse the impact of the pandemic on the daily jobs of public transport, ride-hailing, and delivery app drivers: we study changes on working time and income, pandemic-related concerns, and deterioration of job satisfaction, through a survey applied to drivers during the first peak of the pandemic in Santiago, Chile. Probit regressions on job satisfaction identify the main COVID-related experiences that explain variations in subjective perceptions. We then discuss the implications for post-pandemic job relationships, drivers' working conditions and urban mobility. We show that the unstable characteristics of app-based jobs sharpened during the pandemic: Public transport drivers have kept their jobs, with a similar income as in the pre-pandemic situation and keep their social security, whereas ride-hailing and delivery app drivers do not have social security. Several ride-hailing drivers lost their jobs without any compensation, while delivery drivers earn less money per hour, are more exhausted, and express the greatest concerns and largest decrease in their job satisfaction. The COVID-19 crisis has emphasized that the sustainability of post-pandemic passenger and delivery on-demand services needs to rely on formal job regulation and worker protection.

Therapies for sleep bruxism in dentistry: A critical evaluation of systematic reviews.

The aim of the study was to evaluate the methodological quality and the risk of bias of systematic reviews with regard to the literature on therapies for sleep bruxism (SB) in dentistry, applying the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews) qualitative guide, as well as the effectiveness of various kinds of treatment of SB. Initially, a total of 1,499 articles were obtained from 4 databases and 2 websites. Relevant articles were obtained from the PubMed, Scopus, Cochrane, and Embase databases as well as from Google Scholar and OpenGrey. Six systematic reviews that met the eligibility criteria were included. The methodological quality of all systematic reviews, assessed with the AMSTAR 2 tool, was critically low. Regarding treatment effectiveness, 5 systematic reviews reported on pharmacological management (botulinum toxin type A (BTX-A), clonazepam and clonidine), 2 reported on oral appliances (OAs) (stabilizing splints and mandibular advancement devices (MADs)) and 1 study addressed the effects of biofeedback (BF). The results of the therapies were diverse and confusing. The available research is not conclusive, and does not show clear evidence or a consensus on the part of researchers on the most effective treatment for the management of SB. More research of better methodological quality is needed in this area.

Correlación de la distancia recorrida en la caminata de 6 minutos y puntajes de comorbilidad Charlson y Elixhauser / Correlation of distance traveled in the 6 minute walk and Charlson and Elihauser comorbidity scores

Introduction: The walking test of 6 minutes (6MW) is a test that merges the answer of different systems (respiratory, cardiovascular, metabolic, skeletal muscle and neurosensorial) and offers an useful objective result to lead therapeutic measurements and stablish a prognosis, it's possible that the comorbid patient lowers their functional reserve and alters the result of the test not only because of the presence of pathologies cardiorespiratory, nevertheless, information about the correlation between the scores of comorbidity and the traveled distance in the 6MW is limited. Objective: Determine the correlation between the traveled distance in the 6MW and the scores of comorbidities of Charlson and Elixhauser. Methods: A cross-sectional study was made, in patients taken to the 6MW made between 2006 until March 2020, in a hospital of high complexity; there were included patients older than 18 years old, whose clinic history record and walk of 6 minutes were available. The index of Charlson and Elixhauser were calculated in the 6MW, a bivariate analysis was made between the antecedents of pathologies and the traveled distance, independently and adjusted, the spearman correlation coefficient was calculated for the different scores and the distance in meters of the 6MW, was considerate a significative p: <0,05. Results: to the final analysis 491 subjects entered, the average age was of 69 years old (sd: 14,9), 54% male, the 15,3% had an abnormal walk less than the 80% of the expected, the diseases that were considered had a statistically significant relation with the decrease of the distance in the 6MW were arterial hypertension (p: <0,001), chronic heart failure (p=0,037), heart arrhythmia (p=0,003), smoking (p=0,022), chronic pulmonary obstruction disease (p: <0,001), dementia (p=0,03diabetes mellitus with target organ damage (p=0,01), moderate to severe chronic kidney disease (p=0,012), obesity (p=0,036) y lymphoma (p=0,038 the spearman correlation coefficient between the traveled distances and Charlson was of -0,343 (IC95%:-0,420 -0,264)(p: < 0,001) and -0,213(IC95%:-0,285 -0,116)(p: <0,001) with the Elixhauser index. Conclusion: The distances walked in meters in the 6MW has a reverse low correlation with the comorbidity index, the diseases that were not cardiopulmonary and that related independently with changes in the traveled dist ance are smoking, dementia, diabetes mellitus, chronic kidney disease, obesity, and lymphoma. Key words: Comorbidities, Walk, Test, Cardiopulmonary, Charlson, Elixhauser

A facially driven complete-mouth rehabilitation with ultrathin CAD-CAM composite resin veneers for a patient with severe tooth wear: A minimally invasive approach.

The development of technologies that include face scanning and dental software has improved workflows in dentistry. Digital files make it possible to create a 3-dimensional virtual image of the patient that helps the clinician plan treatment and make decisions, reducing uncertainty and improving communication. This report describes the complete-mouth rehabilitation of a patient with severe tooth wear. The treatment adopted a minimal intervention approach, applying adhesive veneers in areas where the tooth structure was affected and used a computer-aided design and computer-aided manufacturing (CAD-CAM) workflow to prepare nanoceramic composite resin materials with a high filler loading.

Exploratory Monitoring of the Quality and Authenticity of Commercial Honey in Ecuador.

Honey is one of the oldest sweetening foods and has economic importance, making this product attractive to adulteration with cheap sugars. This can cause a critical problem in the honey industry and a possible health risk. The present work has the aim of evaluating the authenticity of honey commercialized in two different provinces of Ecuador (Pichincha and Loja) by performing physicochemical and spectroscopic analyses. For this study 25 samples were collected from different places and markets and characterized by water, sucrose, reducing sugars and electric conductivity measurement. Also, their Raman and Infrared (IR) spectra were recorded and analysed using a Principal Component Analysis (PCA) in order to verify the quality of the honeys. In addition, a screening of several pesticides was performed in order to verify possible chemical threats to human health and honey bees. It was found that 8 samples have a deviation from the Standard established parameters. Two of them have a high difference in the content of sucrose and reducing sugars, which are located deviated from all the other samples in the PCA of the applied vibrational spectroscopy (IR/Raman), shaping two clear clusters. The results show that Raman and IR spectroscopy is appropriate techniques for the quality control of honey and correlates well with the physicochemical analyses.

Interaction between leucine and palmitate catabolism in 3T3-L1 adipocytes and primary adipocytes from control and obese rats.

Metabolic profiling studies have highlighted increases in the plasma free fatty acid (FFA) and branched-chain amino acid (BCAA) concentrations, which are hallmarks of the obese and insulin-resistant phenotype. However, little is known about how the increase of the BCAA concentration modifies the metabolic fate of FFA, and vice versa, in adipocytes. Therefore, we incubated differentiated 3T3-L1 adipocytes or primary adipocytes from rats fed a control or a high-fat diet with: (1) 0, 250, 500 and 1000 µM of leucine and determined the oxidation and incorporation of [1-14C]-palmitate into lipids or proteins or (2) 0, 250, 500 or 1000 µM of palmitate and evaluated the oxidation and incorporation of [U-14C]-leucine into lipids or proteins. Leucine decreased palmitate oxidation and increased its incorporation into the lipid fraction in adipocytes; the latter was reduced in adipocytes from obese rats. However, palmitate increased leucine oxidation in adipocytes as well as reduced leucine incorporation into the protein and lipid fractions in adipocytes from obese rats. These results demonstrate that leucine modifies the metabolic fate of palmitate, and vice versa, in adipocytes and that the metabolic interaction between leucine and palmitate catabolism is altered in adipocytes from obese rats.

Correction: Mechanical properties of provisional dental materials: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0193162.].

Mechanical properties of provisional dental materials: A systematic review and meta-analysis.

Provisional restorations represent an important phase during the rehabilitation process, knowledge of the mechanical properties of the available materials allows us to predict their clinical performance. At present, there is no systematic review, which supports the clinicians' criteria, in the selection of a specific material over another for a particular clinical situation. The purpose of this systematic review and meta-analysis was to assess and compare the mechanical properties of dimethacrylates and monomethacrylates used in fabricating direct provisional restorations, in terms of flexural strength, fracture toughness and hardness. This review followed the PRISMA guidelines. The searches were conducted in PubMed, Embase, Web of Science, Scopus, the New York Academy of Medicine Grey Literature Report and were complemented by hand-searching, with no limitation of time or language up to January 10, 2017. Studies that assess and compare the mechanical properties of dimethacrylate- and monomethacrylate-based provisional restoration materials were selected. A quality assessment of full-text articles were performed according to modified ARRIVE and CONSORT criteria and modified Cochrane Collaboration's tool for in vitro studies. Initially, 256 articles were identified. After removing the duplicates and applying the selection criteria, 24 articles were included in the qualitative synthesis and 7 were included in the quantitative synthesis (meta-analysis). It may be concluded that dimethacrylate-based provisional restorations presented better mechanical behavior than monomethacrylate-based ones in terms of flexural strength and hardness. Fracture toughness showed no significant differences. Within the monomethacrylate group, polymethylmethacrylate showed greater flexural strength than polyethylmethacrylate.

Emerging perspectives on branched-chain amino acid metabolism during adipocyte differentiation.

PURPOSE OF REVIEW: Adipogenesis has been extensively studied in the context of carbohydrate and lipid metabolism. However, little information exists on the role of amino acid metabolism during adipocyte differentiation. Here, we review how branched-chain amino acid (BCAA) metabolism is modified during adipogenesis and, due to the limited information in the area, address questions that remain to be answered with further research. RECENT FINDINGS: BCAAs are rapidly consumed during adipocyte differentiation and are indispensable for this process. Furthermore, we describe how BCAA catabolic enzymes and the metabolic fate of BCAAs are modified during adipogenesis. SUMMARY: Obesity is a chronic disease characterized by increased adipose tissue due to either an increase in the size (hypertrophy) and/or number of adipocytes (hyperplasia). Hyperplasia is determined by the rate of adipogenesis. Therefore, understanding the mechanism that modulates adipogenesis in the context of amino acid metabolism will help to establish pharmacological and dietary interventions involving the type and amount of dietary protein for the treatment of obesity and its associated comorbidities.Video abstract http://links.lww.com/COCN/A11.

Metabolic Fate of Branched-Chain Amino Acids During Adipogenesis, in Adipocytes From Obese Mice and C2C12 Myotubes.

Branched-chain amino acid (BCAA) catabolism is regulated by the branched-chain aminotransferase (BCAT2) and the branched-chain α-keto acid dehydrogenase complex (BCKDH). BCAT2 and BCKDH expression and activity are modified during adipogenesis and altered in adipose tissues of mice with genetic or diet-induced obesity. However, little is known about how these modifications and alterations affect the intracellular metabolic fate of BCAAs during adipogenesis, in adipocytes from mice fed a control or high-fat diet or in C2C12 myotubes. Here, we demonstrate that BCAAs are mainly incorporated into proteins during the early stages of adipocyte differentiation. However, they are oxidized and incorporated into lipids during the late days of differentiation. Conversely, 92% and 97% of BCAA were oxidized, 1.6% and 6% were used for protein synthesis and 1.2% and 1.5% were incorporated into lipids in adipocytes from epididymal and subcutaneous adipose tissue, respectively. All three pathways were decreased in adipocytes from mice fed a high-fat diet. In C2C12 myotubes, leucine is mainly used for protein synthesis and palmitate is incorporated into lipids. Interestingly, leucine decreased both palmitate oxidation and its incorporation to lipids and proteins; and palmitate increased leucine oxidation and decreased its incorporation to lipids and proteins in a dose-dependent manner. These results demonstrate that BCAA metabolic fate differs between the early and late stages of adipocyte differentiation and in adipocytes from mice fed a control or high-fat diet; and that leucine affects the metabolic fate of palmitate and vice versa in C2C12 myotubes. J. Cell. Biochem. 118: 808-818, 2017. © 2016 Wiley Periodicals, Inc.