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Integrating renewable energies, such as wind or photovoltaic, requires an electronic power converter, the three-phase Voltage Source Inverter (VSI) the most common for such function. This paper presents a modular design of signal acquisition and control hardware (current and voltage) for the commercial SEMIKRON SKS35F VSI converter and a Texas Instruments TMS320F28335 DSP. Consequently, the proposed modular and open-source design allows its application in control systems of a VSI converter for isolated or grid-connected systems, applied to power generation based on renewable sources. The proposed scheme allows for a personalised design since it uses an open architecture to implement its own control algorithms that allow it to adapt to the application's particular needs, unlike closed-architecture commercial equipment. Detailed electronic printed circuit board designs for implementation are shown on paper. Finally, the experimental tests' results that validate the proposed design's correct functioning are presented., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Dry eye disease (DED) is a highly prevalent and debilitating condition affecting several hundred million people worldwide. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan commonly used in the treatment of DED. This review aims to critically evaluate the literature on the safety and efficacy of artificial tears containing HA used in DED treatment. Literature searches were conducted in PubMed, including MEDLINE, and in Embase via Ovid with the search term: "(hyaluronic acid OR hyaluronan OR hyaluronate) AND (dry eye OR sicca)". A total of 53 clinical trials are included in this review, including eight placebo-controlled trials. Hyaluronic acid concentrations ranged from 0.1% to 0.4%. Studies lasted up to 3 months. A broad spectrum of DED types and severities was represented in the reviewed literature. No major complications or adverse events were reported. Artificial tears containing 0.1% to 0.4% HA were effective at improving both signs and symptoms of DED. Two major gaps in the literature have been identified: 1. no study investigated the ideal drop frequency for HA-containing eyedrops, and 2. insufficient evidence was presented to recommend any specific HA formulation over another. Future investigations assessing the optimal drop frequency for different concentrations and molecular weights of HA, different drop formulations, including tonicity, and accounting for DED severity and aetiology are essential for an evidence-based, individualized approach to DED treatment., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Visual display terminal (VDT) use is a key risk factor for dry eye disease (DED). Visual display terminal (VDT) use reduces the blink rate and increases the number of incomplete blinks. However, the exact mechanisms causing DED development from VDT use have yet to be clearly described., Purpose: The purpose of the study was to conduct a review on pathophysiological mechanisms promoting VDT-associated DED., Methods: A PubMed search of the literature investigating the relationship between dry eye and VDT was performed, and relevance to pathophysiology of DED was evaluated., Findings: Fifty-five articles met the inclusion criteria. Several pathophysiological mechanisms were examined, and multiple hypotheses were extracted from the articles. Visual display terminal (VDT) use causes DED mainly through impaired blinking patterns. Changes in parasympathetic signalling and increased exposure to blue light, which could disrupt ocular homeostasis, were proposed in some studies but lack sufficient scientific support. Together, these changes may lead to a reduced function of the tear film, lacrimal gland, goblet cells and meibomian glands, all contributing to DED development., Conclusion: Visual display terminal (VDT) use appears to induce DED through both direct and indirect routes. Decreased blink rates and increased incomplete blinks increase the exposed ocular evaporative area and inhibit lipid distribution from meibomian glands. Although not adequately investigated, changes in parasympathetic signalling may impair lacrimal gland and goblet cell function, promoting tear film instability. More studies are needed to better target and improve the treatment and prevention of VDT-associated DED., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Dry eye disease (DED) is a common cause of ocular pain and discomfort. Dry eye disease (DED) stems from a loss-of-tear film homeostasis and is frequently seen in video display terminal (VDT) users. Video display terminal (VDT) use reduces blink rates and increases incomplete blinks, leading to tear film instability and ocular inflammation, promoting DED., Purpose: To assess and evaluate the methods for preventing VDT-associated DED and ocular discomfort., Methods: Studies were found using PubMed and Embase with the search terms: (digital visual terminal* OR computer use OR screen use OR smartphone OR display OR visual display terminal* OR computer vision syndrome OR tablet OR phone OR screen time) AND (dry eye OR DED)., Results: Thirty-one relevant articles were found. Ten described single-visit studies, whereas 21 had a prolonged follow-up. Most preventive measures of VDT-associated DED aimed to increase blink rate or directly prevent tear film instability, ocular inflammation, mucin loss or ocular surface damage. Using an adjustable chair and ergonomic training, blink animations and omega-3 supplementation improved signs and symptoms of VDT-associated DED. Taking frequent breaks was associated with fewer symptoms, but no study assessed the commonly suggested 20-20-20 rule., Conclusion: Preventive measures, such as blink animation programmes, oral intake of omega-3 fatty acids and improved ergonomics act on different parts of the vicious cycle of dry eye and could supplement each other. A comparison of the efficacy of the different interventions as well as more evidence of the effect of increased humidity, VDT filters and ergonomic practices, are required., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objectives: The performance of a new point-of-care CE-IVD-marked isothermal lab-on-phone COVID-19 assay was assessed in comparison to a gold standard real-time reverse transcriptase-PCR method., Methods: The study was conducted following a nonprobability sampling of ≥16-year-old volunteers from three different laboratories, using direct mouthwash (N = 24) or nasopharyngeal (N = 191) clinical samples., Results: The assay demonstrated 95.19% sensitivity and 100% specificity for detection of SARS-CoV-2 in direct nasopharyngeal crude samples and 78.95% sensitivity and 100% specificity in direct mouthwash crude samples. It also successfully detected currently predominant SARS-CoV-2 variants of concern (Beta B.1.351, Delta B.1.617.2, and Omicron B.1.1.529) and demonstrated to be inert against potential cross-reactions of other common respiratory pathogens that cause infections that present similar symptoms to COVID-19., Conclusion: This lab-on-phone pocket-sized assay relies on an isothermal amplification of SARS-CoV-2's N and E genes, taking just 50 minutes from sample to result, with only 2 minutes of hands-on time. It presents good performance when using direct nasopharyngeal crude samples, enabling a low-cost, real-time, rapid, and accurate identification of SARS-CoV-2 infections at the point of care, which is important for both clinical management and population screening, as a tool to break the chain of transmission of COVID-19 pandemic, especially in low-resources environments., Competing Interests: Conflict of interest declaration G. Doria, C. Clemente, E. Coelho, J. Colaço, R. Crespo, and O. Flores are employed by STAB VIDA Lda, the developer and manufacturer of the Doctor Vida® pocket CE-IVD system described in this manuscript., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of the present study was to evaluate the anti-glioma activity of 3-(4-fluorobenzyl)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (AV23) in a preclinical model of glioblastoma, as well as behavioral parameters and toxicological profile. The implantation of C6 cells in the left striatum of male Wistar rats was performed by stereotaxic surgery. After recovery, animals were treated with vehicle (canola oil) or AV23 (10 mg/kg/day) intragastrically for 15 days. It was found that AV23 reduced tumor volume by 90%. Serum biochemical parameters such as triglycerides, cholesterol, HDL-cholesterol, LDL-cholesterol, albumin, aspartate aminotransferase, urea, creatinine and total proteins were not changed; however, there was a slight increase in alanine aminotransferase. The compound AV23 reverted the hypoglycemia and the reduction in body weight caused by glioblastoma. Additionally, AV23 was able to revert the reduction of locomotion caused by the tumor implantation. Therefore, the compound AV23 can be considered a promising candidate in the treatment of glioblastoma., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Perioperative fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) improves prognosis in locally advanced gastric cancer (LAGC). Neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte (PLR) ratios are prognostic biomarkers but not predictive factors., Aim: To assess blood ratios' (NLR, LMR and PLR) potential predictive response to FLOT and survival outcomes in resectable LAGC patients., Methods: This was a multicentric retrospective study investigating the clinical potential of NLR, LMR, and PLR in resectable LAGC patients, treated with at least one preoperative FLOT cycle, from 12 Portuguese hospitals. Means were compared through non-parametric Mann-Whitney tests. Receiver operating characteristic curve analysis defined the cut-off values as: High PLR > 141 for progression and > 144 for mortality; high LMR > 3.56 for T stage regression (TSR). Poisson and Cox regression models the calculated relative risks/hazard ratios, using NLR, pathologic complete response, TSR, and tumor regression grade (TRG) as independent variables, and overall survival (OS) as the dependent variable., Results: This study included 295 patients (mean age, 63.7 years; 59.7% males). NLR was correlated with survival time ( r = 0.143, P = 0.014). PLR was associated with systemic progression during FLOT ( P = 0.022) and mortality ( P = 0.013), with high PLR patients having a 2.2-times higher risk of progression [95% confidence interval (CI): 0.89-5.26] and 1.5-times higher risk of mortality (95%CI: 0.92-2.55). LMR was associated with TSR, and high LMR patients had a 1.4-times higher risk of achieving TSR (95%CI: 1.01-1.99). OS benefit was found with TSR ( P = 0.015) and partial/complete TRG ( P < 0.001). Patients without TSR and with no evidence of pathological response had 2.1-times (95%CI: 1.14-3.96) and 2.8-times (95%CI: 1.6-5) higher risk of death., Conclusion: Higher NLR is correlated with longer survival time. High LMR patients have a higher risk of decreasing T stage, whereas high PLR patients have higher odds of progressing under FLOT and dying. Patients with TSR and a pathological response have better OS and lower risk of dying., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Zika is a vector-borne disease caused by an arbovirus (ZIKV) and overwhelmingly transmitted by Ae. aegypti . This disease is linked to adverse fetal outcomes, mostly microcephaly in newborns, and other clinical aspects such as acute febrile illness and neurologic complications, for example, Guillain-Barré syndrome. One of the most promising strategies to mitigate arbovirus transmission involves releasing Ae. aegypti mosquitoes carrying the maternally inherited endosymbiont bacteria Wolbachia pipientis . The presence of Wolbachia is associated with a reduced susceptibility to arboviruses and a fitness cost in mosquito life-history traits such as fecundity and fertility. However, the mechanisms by which Wolbachia influences metabolic pathways leading to differences in egg production remains poorly known. To investigate the impact of coinfections on the reproductive tract of the mosquito, we applied an isobaric labeling-based quantitative proteomic strategy to investigate the influence of Wolbachia w Mel and ZIKV infection in Ae. aegypti ovaries. To the best of our knowledge, this is the most complete proteome of Ae. aegypti ovaries reported so far, with a total of 3913 proteins identified, were also able to quantify 1044 Wolbachia proteins in complex sample tissue of Ae. aegypti ovary. Furthermore, from a total of 480 mosquito proteins modulated in our study, we discuss proteins and pathways altered in Ae. aegypti during ZIKV infections, Wolbachia infections, coinfection Wolbachia /ZIKV, and compared with no infection, focusing on immune and reproductive aspects of Ae. aegypti . The modified aspects mainly were related to the immune priming enhancement by Wolbachia presence and the modulation of the Juvenile Hormone pathway caused by both microorganism's infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ramos, Martins, Murillo, Domont, de Oliveira, Nogueira, Maciel-de-Freitas and Junqueira.)

The oral environment is an essential part of the human microbiome. The consumption of probiotic products may improve the oral microbiota and reduce the risk of diseases. This paper presents a bibliometric and critical review of randomized clinical trials (RCTs) that used probiotics to analyze oral parameters in humans. RCTs carried out with no age, gender, and ethnicity restrictions and published in the pre-COVID-19 period were included. Furthermore, the utilization of probiotic dairy products to improve oral health is discussed. The bibliometric review demonstrated that 'Microbiology,' 'Dental caries,' and 'Streptococcus mutants' were the most highlighted keywords. Furthermore, Sweden and India have the highest number of publications. The most prevalent outcomes were 'salivary parameters,' 'periodontal disease,' and 'dental caries.' The most used vehicles for probiotic administration were pharmaceutical formulas and dairy products. The administration of probiotic dairy products could modify the oral microbiota (reductions in S. mutans counts), influence the caries development and periodontal disease in children, adolescents, adults, and the elderly, and improve gingival health. The main probiotic dairy products investigated were milk, fermented milk, yogurt, kefir, curd, and cheese. Lacticaseibacillus paracasei SD1 was the most used probiotic culture. The studies demonstrated that the probiotic effect lasted 2-4 weeks after discontinuing consumption. However, the results depended on the subject type, study design, probiotic strain and concentration, and dairy product type. In conclusion, probiotic dairy products are promising alternatives to improve oral health., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Contactless vital sign monitoring systems are becoming increasing in demand for a wide range of biomedical applications. Millimetre-wave radars and embedded signal processing are the most promising technologies to enable non-contact vital signs monitoring. In this work, the challenging task of heart rate estimation from radar data has been addressed. Three different radar systems from Infineon, Texas Instruments and Acconeer, and four algorithms, FFT, Median-FFT, STFT and Median-STFT, have been analysed and compared against a reference sensor. Accuracy, as well as power figures, have been reported for all the radar systems. A dataset of 16 volunteers has been acquired, yielding a total of 400 minutes of radar-recorded vital sign data. The accuracy of the four investigated algorithms has been reported on average and per subject for every radar. The algorithm exploiting the Short Time Fourier Transform (STFT) is able to achieve an error as low as 0.02% on a single person and of 6.4% in heart rate estimation on average across the whole dataset.

Background: Dry eye disease (DED) is a multifactorial disease of the tear film and ocular surface. It causes ocular symptoms, reduced quality of life and a considerable economic burden on society. Prolonged use of visual display terminals (VDTs) has been suggested as an important risk factor for DED., Purpose: This review aims to study the association between DED and VDT use with an emphasis on the prevalence of DED among VDT users and harmful daily duration of VDT use., Methods: A PubMed search was conducted and yielded 57 relevant articles based on a set of inclusion and exclusion criteria. The studies were subclassified according to study design., Results: The far majority of the studies showed an association between VDT use and DED or DED-related signs and symptoms. The prevalence of definite or probable DED in VDT and office workers ranged from 26% to 70%, with as few as 1-2 hr of VDT exposure per day being associated with DED., Conclusion: VDT use is strongly associated with DED. VDT-associated DED is prevalent, but the exact prevalence needs to be further elucidated using standardized DED diagnosis criteria. Furthermore, a safe lower limit of daily VDT use has yet to be established. More research is needed on the effect of digitalization and digital transformation, which are particularly high during the time of the COVID-19 pandemic., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Entamoeba histolytica causes amoebiasis which is a major health concern in developing countries. E. histolytica pathogenicity has been implicated to a large repertoire of small GTPases which switch between the inactive GDP bound state and the active GTP bound state with the help of guanine nucleotide exchange factors (GEFs) and GTPase activating protein (GAPs). Rho family of small GTPases are well known to modulate the actin cytoskeletal dynamics which plays a major role in E. histolytica pathogenicity. Here, we report an atypical amoebic RhoGEF, and its preferred substrate EhRho6, which, upon overexpression abrogated the pathogenic behavior of the amoeba such as adhesion to host cell, monolayer destruction, erythrophagocytosis, and formation of actin dots. A causative immunoblot analysis revealed actin degradation in the EhRho6 overexpressing trophozoites that could be inhibited by blocking the amoebic proteasomal pathway. A careful analysis of the results from a previously published transcriptomics study, in conjunction with our observations, led to the identification of a clade of Rho GTPases in this pathogenic amoeba which we hypothesize to have implications during the amoebic encystation., (© 2022 John Wiley & Sons Ltd.)

Guarana is one of the most popular functional foods in the Amazon and widely used in the world. This work aimed to study the chemical composition of guarana produced by the main producing states and try to associate their geographical origin. We report an untargeted metabolomic analytical method performed by UHPLC-ESI-IT-MS and multivariate analysis (chemometrics) of guarana seeds, which was able to separate the samples according to their geographical origin. Previously, full chromatogram range was analyzed, and it could be observed that the two main compounds, catechin and epicatechin, have introduced large data variance in PCA analysis not related to the geographical origin of samples. After exclusion of the corresponding peaks, it was possible to obtain three main clusters corresponding to samples from Amazonas, Bahia and Mato Grosso. Thirteen dimers and trimers of procyanidins type A and B were identified by PCA and UHPLC-ESI-Q-TOF-MS/MS, as chemical markers of geographic origin., (Published by Elsevier Ltd.)

Fatty acid esters of hydroxy fatty acids (FAHFAs) represent a complex lipid class that contains both signaling mediators and structural components of lipid biofilms in humans. The majority of endogenous FAHFAs share a common chemical architecture, characterized by an estolide bond that links the hydroxy fatty acid (HFA) backbone and the fatty acid (FA). Two structurally and functionally distinct FAHFA superfamilies are recognized based on the position of the estolide bond: omega-FAHFAs and in-chain branched FAHFAs. The existing variety of possible HFAs and FAs combined with the position of the estolide bond generates a vast quantity of unique structures identified in FAHFA families. In this review, we discuss the anti-diabetic and anti-inflammatory effects of branched FAHFAs and the role of omega-FAHFA-derived lipids as surfactants in the tear film lipid layer and dry eye disease. To emphasize potential pharmacological targets, we recapitulate the biosynthesis of the HFA backbone within the superfamilies together with the degradation pathways and the FAHFA regioisomer distribution in human and mouse adipose tissue. We propose a theoretical involvement of cytochrome P450 enzymes in the generation and degradation of saturated HFA backbones and present an overview of small-molecule inhibitors used in FAHFA research. The FAHFA lipid class is huge and largely unexplored. Besides the unknown biological effects of individual FAHFAs, also the enigmatic enzymatic machinery behind their synthesis could provide new therapeutic approaches for inflammatory metabolic or eye diseases. Therefore, understanding the mechanisms of (FA)HFA synthesis at the molecular level should be the next step in FAHFA research., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Glucose tolerance represents a complex phenotype in which many tissues play important roles and interact to regulate metabolic homeostasis. Here, we perform an analysis of 13 C 6 -glucose tissue distribution, which maps the metabolome and lipidome across 12 metabolically relevant mouse organs and plasma, with integrated 13 C 6 -glucose-derived carbon tracing during oral glucose tolerance test (OGTT). We measure time profiles of water-soluble metabolites and lipids and integrate the global metabolite response into metabolic pathways. During the OGTT, glucose use is turned on with specific kinetics at the organ level, but fasting substrates like β-hydroxybutyrate are switched off in all organs simultaneously. Timeline profiling of 13 C-labeled fatty acids and triacylglycerols across tissues suggests that brown adipose tissue may contribute to the circulating fatty acid pool at maximal plasma glucose levels. The GTTAtlas interactive web application serves as a unique resource for the exploration of whole-body glucose metabolism and time profiles of tissue and plasma metabolites during the OGTT., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Irrigant solutions are used to promote dentin-growth factors (GF) release for regenerative endodontics. This review aimed to evaluate the reports comparing the release of GFs using different root canal irrigant solutions. Eligible studies compared the in vitro GF release in human teeth after the use of at least two distinct solutions. A search was conducted on Pubmed, Scopus, Web of Science, and Lilacs on 11 August 2021. Risk of bias was assessed using SciRAP. Study characteristics and quantitative data were extracted, and meta-analyses were performed for the mean difference (95% confidence interval) of the release of transforming growth factors Beta 1 (TGF-β1) by EDTA compared to other irrigants. Of sixteen eligible studies, eight were included in quantitative analysis. ELISA assays showed higher TGF-β1 release from 10% EDTA compared to 10% citric acid ( p < 0.00001). Immunogold assays showed higher levels of TGF-β1 for 17% EDTA ( p < 0.00001) compared to 10% citric acid. GRADE identified a low to very low certainty of evidence. These results point to an increased release of TGF-β1 in dentin treated with EDTA. The high heterogeneity and very low certainty of the evidence demand further studies before EDTA indication as a better irrigant for regenerative endodontics. Registration: CRD42020160871 (PROSPERO).

Wearable, intelligent, and unobtrusive sensor nodes that monitor the human body and the surrounding environment have the potential to create valuable data for preventive human-centric ubiquitous healthcare. To attain this vision of unobtrusiveness, the smart devices have to gather and analyze data over long periods of time without the need for battery recharging or replacement. This article presents a software-configurable kinetic energy harvesting and power management circuit that enables self-sustainable wearable devices. By exploiting the kinetic transducer as an energy source and an activity sensor simultaneously, the proposed circuit provides highly efficient context-aware control features. Its mixed-signal nano-power context awareness allows reaching energy neutrality even in energy-drought periods, thus significantly relaxing the energy storage requirements. Furthermore, the asynchronous sensing approach also doubles as a coarse-grained human activity recognition frontend. Experimental results, using commercial micro-kinetic generators, demonstrate the flexibility and potential of this approach: the circuit achieves a quiescent current of 57 nA and a maximum load current of 300 mA, delivered with a harvesting efficiency of 79%. Based on empirically collected motion data, the system achieves an energy surplus of over 232 mJ per day in a wrist-worn application while executing activity recognition at an accuracy of 89% and a latency of 60 s.

Low-power energy harvesting has been demonstrated as a feasible alternative for the power supply of next-generation smart sensors and IoT end devices. In many cases, the output of kinetic energy harvesters is an alternating current (AC) requiring rectification in order to supply the electronic load. The rectifier design and selection can have a considerable influence on the energy harvesting system performance in terms of extracted output power and conversion losses. This paper presents a quantitative comparison of three passive rectifiers in a low-power, low-voltage electromagnetic energy harvesting sub-system, namely the full-wave bridge rectifier (FWR), the voltage doubler (VD), and the negative voltage converter rectifier (NVC). Based on a variable reluctance energy harvesting system, we investigate each of the rectifiers with respect to their performance and their effect on the overall energy extraction. We conduct experiments under the conditions of a low-speed rotational energy harvesting application with rotational speeds of 5 rpm to 20 rpm, and verify the experiments in an end-to-end energy harvesting evaluation. Two performance metrics-power conversion efficiency (PCE) and power extraction efficiency (PEE)-are obtained from the measurements to evaluate the performance of the system implementation adopting each of the rectifiers. The results show that the FWR with PEEs of 20% at 5 rpm to 40% at 20 rpm has a low performance in comparison to the VD (40-60%) and NVC (20-70%) rectifiers. The VD-based interface circuit demonstrates the best performance under low rotational speeds, whereas the NVC outperforms the VD at higher speeds (>18 rpm). Finally, the end-to-end system evaluation is conducted with a self-powered rpm sensing system, which demonstrates an improved performance with the VD rectifier implementation reaching the system's maximum sampling rate (40 Hz) at a rotational speed of approximately 15.5 rpm.

The mitigation of rapid mass movements involves a subtle interplay between field surveys, numerical modelling, and experience. Hazard engineers rely on a combination of best practices and, if available, historical facts as a vital prerequisite in establishing reproducible and accurate hazard zoning. Full-scale field tests have been performed to reinforce the physical understanding of debris flows and snow avalanches. Rockfall dynamics are - especially the quantification of energy dissipation during the complex rock-ground interaction - largely unknown. The awareness of rock shape dependence is growing, but presently, there exists little experimental basis on how rockfall hazard scales with rock mass, size, and shape. Here, we present a unique data set of induced single-block rockfall events comprising data from equant and wheel-shaped blocks with masses up to 2670 kg, quantifying the influence of rock shape and mass on lateral spreading and longitudinal runout and hence challenging common practices in rockfall hazard assessment., (© 2021. The Author(s).)

Background: The Internet provides a plethora of information on health issues related to children's oral health., Aim: Identify online recommendations of paediatric dentistry associations of the Americas (PDAAs) regarding breastfeeding practices, weaning, sugar introduction and initiating oral hygiene., Design: Websites of PDAAs were accessed to record recommendations/questions (Q) relevant to early childhood that specifically covered issues about exclusive breastfeeding-Q1, indications of bottle feeding-Q2, when and how to start weaning-Q3 and Q4, respectively, association of breast milk and dental caries-Q5, when to start oral hygiene and how to introduce it-Q6 and Q7, respectively, and guidance on the introduction of sugar-Q8. Similarity/dissimilarity frequencies between the associations (Euclidean distances) were calculated., Results: From 35 countries on the two American continents, 21 associations were affiliated with the International Association of Paediatric Dentistry and/or the Latin American Pediatric Dentistry Association, whereas eight did not have websites. Higher (P < .05) dissimilarities for Q6 (68.2%), Q7 (72.7%), and Q8 (62.1%) were observed. Results were similar for Q1 and Q5 (P > .05). No association mentioned Q2, Q3 or Q4 responses, whereas Q7 was the most frequently discussed issue., Conclusion: Not all of the investigated issues are mentioned on websites of PDAAs, potentially stymieing efforts by both the layperson and health professional to gather information., (© 2020 BSPD, IAPD and John Wiley & Sons Ltd.)

Background: Functional acidic monomers are able to chemically interact with hydroxyapatite, and this bond appears to be very stable. Therefore, this aspect of the 10-MDP molecule made it attractive and added to self-etch adhesives., Objectives: The objective of this Systematic Review (SR) and Meta-analysis (MA) was to determine whether systems with the 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) functional monomer in their formula showed better clinical performance in restorations placed in noncarious cervical lesions (NCCL) when compared to systems without it. The PROSPERO registration number of the MA is CRD42016050538., Data and Sources: An e-search was conducted through MEDLINE via PubMed, Cochrane Library, Scopus, Web of Science, OpenGrey, Clinical Trials, Current Controlled Trials, and EU Clinical Trials Register, and a search through the references of included studies was also performed. Randomized Controlled Clinical Trials, in which the effectiveness of self-etch adhesive systems, with or without the 10-MDP functional monomer for NCCL, was discussed, were included. Risk of bias was performed according to the Cochrane Collaboration tool, and the certainty of evidence was evaluated through GRADE., Study Selection: The data were grouped, heterogeneity (I2) was tested, and after duplicate removal, 4208 manuscripts were retrieved. From these, 11 studies were included in the qualitative analysis (risk of bias), with nine classified as low risk and two unclear. GRADE analysis detected moderate-to-high certainty of evidence, so the quantitative synthesis [Meta-analysis (MA)] was performed including the 11 studies., Results and Conclusion: There were no statistical differences in the clinical performance of restorations conducted using "with or without 10-MDP" adhesive types, for all evaluated criteria (p=0.05), with heterogeneity ranging from 0% to 53%. Thus, the presence of 10-MDP functional monomer did not influence the clinical performance of restorations placed in NCCL., (©Operative Dentistry, 2021.)

This work aimed to investigate the use of Regenerative Endodontic Procedures (REP) on the treatment of pulp necrosis in mature teeth through systematic review and meta-analysis of evidence on clinical and radiographic parameters before and after REP. A search was performed in different databases on 9 September 2020, including seven clinical studies and randomized controlled trials (RCT). The methodological quality was assessed using Revised Cochrane risk-of-bias (RoB 2) and Before-and-After tools. Meta-analyses were performed to evaluate the success incidences regarding the reduction of periapical lesion and recovery of sensitivity. The certainty of the evidence was assessed using GRADE. Meta-analysis showed a high overall success of 0.95 (0.92, 0.98) I 2 = 6%, with high periapical lesion reduction at 12 months (0.93 (0.86, 0.96) I 2 = 37%) and by the end of follow-up (0.91 (0.83, 0.96) I 2 = 13%). Lower incidences of positive sensitivity response were identified for the electrical (0.58 (0.46, 0.70) I 2 = 51%) and cold tests (0.70 (0.54, 0.84) I 2 = 68%). The calculated levels of REP success were similar to those reported for immature teeth. With a very low certainty of evidence, the meta-analysis showed a high incidence of REP's success for mature teeth with necrotic pulp evidenced by periapical lesion reduction and moderate positive responses to sensitivity tests.

Introduction: Vision impairment and blindness have been significantly associated with high medical care expenditures, decrease in health utility, and loss or reduction of productivity. The objective of this study was to assess the humanistic and economic burden of blindness in a Brazilian sample from a societal perspective., Methods: Cross-sectional, observational, and multicenter study enrolling individuals with blindness (defined as the best corrected visual acuity less than 6/60 in the better-seeing eye) caused by retinal disorders. Data collection was performed between December 2012 and December 2014 through face-to-face interview using a structured questionnaire and three standardized patient-reported outcomes instruments. Direct costs were estimated by multiplying the amount of resources used (12-month recall period) by the corresponding unit cost. Productivity losses were measured using the human capital method. All data were collected in Brazilian real (BRL) and converted to United States dollar (USD), using the exchange rate of 1 USD = 3.0415 BRL (May 7, 2015)., Results: A total of 146 subjects from 17 research sites were included with a mean age of 68 (SD = 14.8) years and equal gender distribution. Blindness negatively affected both general and vision-specific health-related quality of life. One-half of patients presented some level of anxiety and depression; of these, about 50% with moderate or severe symptoms. Around one-third of subjects (34.2%) reported at least one fall in the previous 12 months due to vision impairment; of these subjects, 14% reported fractures. Emergency room visits and hospitalization were reported by around 25% and 5% of subjects, respectively. The short-term costs (annual costs) of severe vision impairment or blindness for the studied subjects was USD 128,389.09 (USD 879.37 per person). Total medical direct costs summed USD 116,182.00 (USD 795.77 per person), 61.7% of which was due to outpatient visits (with physicians and other healthcare professionals). The long-term costs (lifetime productivity loss) totalized USD 1,962,599.50 (USD 13,442.47 per person)., Conclusion: This study demonstrated that blindness imposes both humanistic and economic burden for individuals and for Brazilian society. It also pointed out that there is room to improve blindness management, especially for the poorest people, including health education for individuals, availability of services, and reduction of barriers to patients' access to healthcare assistance. This was a good starting point; however, further research is needed., (© 2021. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Axon guidance is required for the establishment of brain circuits. Whether much of the molecular basis of axon guidance is known from animal models, the molecular machinery coordinating axon growth and pathfinding in humans remains to be elucidated. The use of induced pluripotent stem cells (iPSC) from human donors has revolutionized in vitro studies of the human brain. iPSC can be differentiated into neuronal stem cells which can be used to generate neural tissue-like cultures, known as neurospheres, that reproduce, in many aspects, the cell types and molecules present in the brain. Here, we analyzed quantitative changes in the proteome of neurospheres during differentiation. Relative quantification was performed at early time points during differentiation using iTRAQ-based labeling and LC-MS/MS analysis. We identified 6438 proteins, from which 433 were downregulated and 479 were upregulated during differentiation. We show that human neurospheres have a molecular profile that correlates to the fetal brain. During differentiation, upregulated pathways are related to neuronal development and differentiation, cell adhesion, and axonal guidance whereas cell proliferation pathways were downregulated. We developed a functional assay to check for neurite outgrowth in neurospheres and confirmed that neurite outgrowth potential is increased after 10 days of differentiation and is enhanced by increasing cyclic AMP levels. The proteins identified here represent a resource to monitor neurosphere differentiation and coupled to the neurite outgrowth assay can be used to functionally explore neurological disorders using human neurospheres as a model., (Copyright © 2021. Published by Elsevier B.V.)

Single-cell analysis came to change the way we look at cell populations. RNA sequencing of single cells allowed us to appreciate the diversity of cell types in the human brain in an unprecedented manner and its power to reveal cell-type specific changes in cell populations has just begun to be explored. In this context, looking at the proteome of single cells promises to bring functional information and contribute to completing the picture. The potential of single cell proteome, in developing a better understanding of the intricate connections between the very diverse cell populations in the brain, is huge. Whereas early approaches to address single-cell proteome have identified hundreds of proteins, today, techniques combining isobaric labelling and LC-MS can lead to the identification of thousands of proteins. In this review, we describe methods which have been used to identify and quantify proteins from single cells and propose that the application of isobaric labeling and label-free quantitative proteomics approach for single-cell analysis is ready to provide useful information for the neurobiology field., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Noninvasive stimulation has been widely used in the past 30 years to study and treat a large number of neurological diseases, including movement disorders., Objective: In this critical review, we illustrate the rationale for use of these techniques in movement disorders and summarize the best medical evidence based on the main clinical trials performed to date., Methods: A nationally representative group of experts performed a comprehensive review of the literature in order to analyze the key clinical decision-making factors driving transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in movement disorders. Classes of evidence and recommendations were described for each disease., Results: Despite unavoidable heterogeneities and low effect size, TMS is likely to be effective for treating motor symptoms and depression in Parkinson's disease (PD). The efficacy in other movement disorders is unclear. TMS is possibly effective for focal hand dystonia, essential tremor and cerebellar ataxia. Additionally, it is likely to be ineffective in reducing tics in Tourette syndrome. Lastly, tDCS is likely to be effective in improving gait in PD., Conclusions: There is encouraging evidence for the use of noninvasive stimulation on a subset of symptoms in selected movement disorders, although the means to optimize protocols for improving positive outcomes in routine clinical practice remain undetermined. Similarly, the best stimulation paradigms and responder profile need to be investigated in large clinical trials with established therapeutic and assessment paradigms that could also allow genuine long-term benefits to be determined.

Meibomian gland dysfunction (MGD) is a major cause of dry eye, affecting millions worldwide. Intraductal meibomian gland probing (MGP) aims to open obstructed meibomian glands using a small probe to promote meibum secretion. MGP has received increasing interest since 2010, and we critically evaluated the literature on the efficacy and safety of MGP. Despite positive results of MGP on dry eye symptoms in early single-group studies, MGP was not shown to consistently outperform controls in later controlled trials. Furthermore, MGP alone did not show improvement beyond placebo in the only placebo-controlled RCT conducted. Overall, the procedure appears safe. Self-limited intraoperative bleeding was frequent, but no major complications were reported. In conclusion, MGP has not yet been shown to be an effective treatment for MGD. Larger placebo-controlled trials need to be conducted to establish the potential effect of this novel treatment modality., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin America caused by the thermodimorphic fungi of the genus  Paracoccidioides  spp. Paracoccidioides lutzii (PL) is one of the 5 species that constitute the Paracoccidioides genus. PL expresses low amounts of glycoprotein (Gp) 43 (PLGp43) and PLGp43 displays few epitopes in common with the P. brasiliensis (PB) immunodominant antigen PBGp43, which is commonly used for serological diagnosis of PCM. This difference in structure between the glycoproteins markedly reduces the efficiency of serological diagnosis in patients infected with PL. We previously demonstrated that peptide 10 (P10) from the PBGp43 induces protective immune responses in in vitro and in vivo models of PB PCM. Since, P10 has proven to be a promising therapeutic to combat PB, we sought to identify peptides in PL that could similarly be applied for the treatment of PCM. PL yeast cell proteins were isolated from PL: dendritic cell co-cultures and subjected to immunoproteomics. This approach identified 18 PL peptides that demonstrated in silico predictions for immunogenicity. Eight of the most promising peptides were synthesized and applied to lymphocytes obtained from peptide-immunized or PL-infected mice as well as to in vitro cultures with peptides or dendritic cells pulsed the peptides. The peptides LBR5, LBR6 and LBR8 efficiently promoted CD4 + and CD8 + T cell proliferation and dendritic cells pulsed with LBR1, LBR3, LBR7 or LBR8 stimulated CD4 + T cell proliferation. We observed increases of IFN-γ in the supernatants from primed T cells for the conditions with peptides without or with dendritic cells, although IL-2 levels only increased in response to LBR8. These novel immunogenic peptides derived from PL will be employed to develop new peptide vaccine approaches and the proteins from which they are derived can be used to develop new diagnostic assays for PL and possibly other Paracoccidioides spp. These findings identify and characterize new peptides with a promising therapeutic profile for future against this important neglected systemic mycosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Silva, Taira, Cleare, Martins, Junqueira, Nosanchuk and Taborda.)

Zika virus (ZIKV) is a global public health emergency due to its association with microcephaly, Guillain-Barré syndrome, neuropathy, and myelitis in children and adults. A total of 87 countries have had evidence of autochthonous mosquito-borne transmission of ZIKV, distributed across four continents, and no antivirus therapy or vaccines are available. Therefore, several strategies have been developed to target the main mosquito vector, Aedes aegypti , to reduce the burden of different arboviruses. Among such strategies, the use of the maternally-inherited endosymbiont Wolbachia pipientis has been applied successfully to reduce virus susceptibility and decrease transmission. However, the mechanisms by which Wolbachia orchestrate resistance to ZIKV infection remain to be elucidated. In this study, we apply isobaric labeling quantitative mass spectrometry (MS)-based proteomics to quantify proteins and identify pathways altered during ZIKV infection; Wolbachia infection; co-infection with Wolbachia/ ZIKV in the A. aegypti heads and salivary glands. We show that Wolbachia regulates proteins involved in reactive oxygen species production, regulates humoral immune response, and antioxidant production. The reduction of ZIKV polyprotein in the presence of Wolbachia in mosquitoes was determined by MS and corroborates the idea that Wolbachia helps to block ZIKV infections in A. aegypti. The present study offers a rich resource of data that may help to elucidate mechanisms by which Wolbachia orchestrate resistance to ZIKV infection in A. aegypti , and represents a step further on the development of new targeted methods to detect and quantify ZIKV and Wolbachia directly in complex tissues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Martins, Ramos, Murillo, Torres, de Carvalho, Domont, de Oliveira, Mesquita, Nogueira, Maciel-de-Freitas and Junqueira.)

LoRa is popular for internet of things applications as this communication technology offers both a long range and a low power consumption. However, LoRaWAN, the standard MAC protocol that uses LoRa as physical layer, has the bottleneck of a high downlink latency to achieve energy efficiency. To overcome this drawback we explore the use of wake-up radio combined with LoRa, and propose an adequate MAC protocol that takes profit of both these heterogeneous and complementary technologies. This protocol allows an opportunistic selection of a cluster head that forwards commands from the gateway to the nodes in the same cluster. Furthermore, to achieve self-sustainability, sensor nodes might include an energy harvesting sub-system, for instance to scavenge energy from the light, and their quality of service can be tuned, according to their available energy. To have an effective self-sustaining LoRa system, we propose a new energy manager that allows less fluctuations of the quality of service between days and nights. Latency and energy are modeled in a hybrid manner, i.e., leveraging microbenchmarks on real hardware platforms, to explore the influence of the energy harvesting conditions on the quality of service of this heterogeneous network. It is clearly demonstrated that the cooperation of nodes within a cluster drastically reduces the latency of LoRa base station commands, e.g., by almost 90% compared to traditional LoRa scheme for a 10 nodes cluster.

Photodynamic therapy (PDT) is a potential therapeutic modality against cancer, resulting from the interaction of a photosensitizer (PS) and radiation that generates damage to tumor cells. The use of near-infrared radiation (IR-A) is relevant because presents recognized biological effects, such as antioxidant, neuroprotective and antitumor effects. Glioblastoma is the most aggressive central nervous system (CNS) neoplasm with high proliferation and tissue invasion capacity and is resistant to radio and chemotherapy. Here, we evaluated in vitro the possible interaction of temozolomide (TMZ) with IR-A in a glioblastoma cell line (C6) and in a human keratinocyte cell line (HaCat) how non-tumor cell model, in an attempt to search for a new treatment strategy. The effects of TMZ, IR-A and the interaction between TMZ and IR-A was evaluated by viability exclusion with trypan blue. To perform the interaction experiments, we have chosen 10 μM TMZ and 4.5 J/cm 2 of IR-A. From this, we evaluated cytotoxicity, cell proliferation, intracellular reactive oxygen species levels (ROS), as well as the process of cell migration and the P-gp and MRP-1 activity. Cell death mainly due to apoptosis, followed by necrosis, decreased cell proliferation, increased ROS levels, decreased cell migration and decreased P-gp and MRP1 activity were observed only when there was interaction between TMZ and IR-A in the C6 cell line. The interaction between TMZ and IR-A was not able to affect cell proliferation in the HaCat non-tumor cell line. Our results suggest that this interaction could be a promising approach and that in the future may serve as an antitumor strategy for PDT application.

Background: Coronary angiography and percutaneous coronary intervention are frequently and increasingly performed worldwide. Although catheters for coronary angiography are considered as single-use devices, some people still question this decision. This study evaluated the structural characteristics and thermal stability of new and reprocessed catheters., Methods: Five catheters (Judkins left) of the same brand and manufacturer were selected for each analysis. We evaluated: new catheters, catheters reprocessed once (first), twice (second), thrice (third), and seven times (seventh). The optical analyses of the proximal, middle and distal parts of the catheters were performed by magnifying glass. Besides, thermogravimetric analyses were done., Results: After reprocessing, the crushing, color changes, folds, dents, deformations, and lumen narrowing were observed; the stainless-steel framework, the external tortuosity, the interlaced mesh of stainless-steel wires and loss of polymeric material were visualized. Thermogravimetric analysis showed lost of mass of the catheters., Conclusions: This study demonstrated that the structural integrity and mass of catheters are lost with reprocessing. These findings may be caused by several steps of reprocessing; however, regardless of which step or steps were responsible, the presence of structural integrity loss leads to the recommendation of not reusing this type of device., Competing Interests: None to declare., (Copyright 2020, Oliveira et al.)

Body bio-impedance is a unique parameter to monitor changes in body composition non-invasively. Continuous measurement of bio-impedance can track changes in body fluid content and cell mass and has widespread applications for physiological monitoring. State-of-the-art implementation of bio-impedance sensor devices is still limited for continuous use, in part, due to artefacts arising at the skin-electrode (SE) interface. Artefacts at the SE interface may arise due to various factors such as motion, applied pressure on the electrode surface, changes in ambient conditions or gradual drying of electrodes. This paper presents a novel bio-impedance sensor node that includes an artefact aware method for bio-impedance measurement. The sensor node enables autonomous and continuous measurement of bio-impedance and SE contact impedance at ten frequencies between 10 kHz to 100 kHz to detect artefacts at the SE interface. Experimental evaluation with SE contact impedance models using passive 2R1C electronic circuits and also with non-invasive in vivo measurements of SE contact impedance demonstrated high accuracy (with maximum error less than 1.5%) and precision of 0.6 Ω. The ability to detect artefacts caused by motion, vertically applied pressure and skin temperature changes was analysed in proof of concept experiments. Low power sensor node design achieved with 50mW in active mode and only 143 μW in sleep mode estimated a battery life of 90 days with a 250 mAh battery and duty-cycling impedance measurements every 60 seconds. Our method for artefact aware bio-impedance sensing is a step towards autonomous and unobtrusive continuous bio-impedance measurement for health monitoring at-home or in clinical environments.

Clinical Relevance: According to the clinical and scientific evidence presented in this systematic review and meta-analysis, dental adhesives containing either organic solvent (acetone or alcohol) can be used to achieve similar clinical performance and longevity of composite restorations., Summary: Objectives: This systematic review and meta-analysis compared the clinical performance and survival rates of composite restorations placed in noncarious cervical lesions (NCCLs) using dental adhesives containing acetone or alcohol-based solvents.Methods and Materials: PubMed, Scopus, Web of Science, Virtual Health Library (VHL) LILACS, Cochrane Library, OpenGrey, Clinical Trials, and Rebec were searched. MeSH terms, supplementary concepts, synonyms, and free keywords were used in the search strategy. All references were crosschecked by two independent investigators following the PICOS strategy (population, NCCLs; intervention, acetone-based bonding agent; comparison, alcohol-based bonding agent; outcome, clinical evaluation parameters and survival rates; study design, randomized controlled clinical trials). Cochrane Collaboration's tool was used to assess risk of bias, and two distinct meta-analyses were performed using the RevMan software. The prevalence of success and the total number of restorations for each group (acetone- or alcohol-based) were used to calculate the risk difference at a confidence interval of 95%. Random-effects models were applied, and heterogeneity was assessed using the I2 index in the pooled and subgrouped meta-analyses. The certainty of evidence was evaluated through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.Results: A total of 7876 studies were retrieved, from which 27 studies were selected for the systematic review. Ten studies were classified as "low risk of bias" and included in the meta-analyses. Overall heterogeneity was not significant (I2 = 0.00%). The clinical performance of restorations placed with bonding agents based on both solvents for each of the available parameters presented no statistical significance for any of the meta-analyses (p>0.05).Conclusion: Scientific evidence suggests composite restorations placed with acetone or alcohol-based dental adhesives present similar clinical performance and survival rates in NCCLs., (© Operative Dentistry, 2020.)

Purpose: To assess the comparative diagnostic accuracy of cardiac CT and transesophageal echocardiography (TEE) in the detection of valvular and perivalvular complications in infective endocarditis., Materials and Methods: PubMed and Embase databases were systematically searched until July 2019 for original articles published in English. Studies were included if (a) they used CT and/or TEE as an index test, (b) data were provided as infective endocarditis valvular complications (classified as abscess or pseudoaneurysm, vegetation, leaflet perforation, and paravalvular leakage), and (c) they used surgical findings as the reference standard., Results: Eight studies fulfilled the inclusion criteria. The sensitivity was higher for CT than TEE for abscess or pseudoaneurysm detection, 78% (95% confidence interval [CI]: 70%, 85%) (112 of 142) versus 69% (95% CI: 62%, 76%) (94 of 135) ( P = .052) and increased to 87% (95% CI: 78%, 93%) (70 of 79) when restricted to multiphase CT studies, the difference being significant ( P = .04). The sensitivity was significantly higher for TEE than CT for vegetation detection, 94% (95% CI: 92%, 96%) (363 of 383) versus 64% (95% CI: 57%, 70%) (151 of 237) ( P < .001) and leaflet perforation detection, 81% (95% CI: 71%, 88%) (74 of 91) versus 41% (95% CI: 25%, 59%) (14 of 35) ( P = .02).The sensitivity for paravalvular leakage was 69% (95% CI: 58%, 79%) (56 of 80) versus 44% (95% CI: 30%, 59%) (21 of 48) for TEE and CT, respectively ( P = .27)., Conclusion: CT performs better than TEE in the detection of abscess or pseudoaneurysm whereas TEE gives superior results for vegetation detection, leaflet perforation, and paravalvular leakage. Supplemental material is available for this article. © RSNA, 2020., Competing Interests: Disclosures of Conflicts of Interest: M.O. disclosed no relevant relationships. L.G. disclosed no relevant relationships. Martial Hamon disclosed no relevant relationships. Michèle Hamon disclosed no relevant relationships., (2020 by the Radiological Society of North America, Inc.)

Purpose: This survey aimed at assessing the clinical characteristics of patients with inflammatory reactions after intravitreal injection of antiangiogenic agents and the techniques employed by Brazilian retina specialists., Methods: We sent an 18-item questionnaire electronically to retina specialists who are using antiangiogenic agents. We got the responses between September 21 and December 23, 2018., Results: A total of 58 retina specialists participated. Most of them were from Southeastern Brazil (50%), 82.8% were dedicated to both medical and surgical practices, and 86.2% had practiced for more than 5 years. Respondents reported a mean number of 2.14 ± 1.63 patients with inflammation, 44.8% with panuveitis, and 79.3% with onset of symptoms within 72 h. Specialists used aflibercept (53.4%), bevacizumab (29.3%), and ranibizumab (27.6%). Most patients were treated with steroid drops (70.7%), and their inflammation subsided after 11.5 ± 11.5 days (86.2% lacked irreversible complications). The specialists blamed the syringe as the cause of the inflammation in 25.9% of the cases, 41.4% used Becton-Dickinson Ultra-Fine syringes, 43.1% injected the drug at room temperature, and 37.9% removed the air (53.4% by flicking the syringe). Most specialists did not detect silicone oil (67.2%), but 17.2% of them performed vitrectomies to remove vitreous opacities. Finally, 44.8% of specialists injected the same antiangiogenic agent in an eye with prior inflammatory reaction without further inflammation., Conclusions: Most specialists reported cases of early-onset inflammation after intravitreal injection of antiangiogenic agents. The incidence of irreversible complications was low. Aflibercept was the most common agent used. The causes of inflammation remain unknown, but we formulated some relevant hypotheses.

β-caryophyllene is a sesquiterpene present in the oil of many plant species, such as Copaifera sp., which has been shown to possesses potent anti-inflammatory action; however, its healing activity remains under study. The objectives of the present study were to produce a nanoemulsion containing β-caryophyllene followed by a hydrogel containing nanoemulsified β-caryophyllene, to evaluate the permeation profile in vitro, and to assess the in vivo healing activity, which is so far unexplored in the literature for pure β-caryophyllene and in pharmaceutical formulation. The nanoemulsion was obtained through high-pressure homogenization and the hydrogel by direct dispersion with hydroxyethylcellulose. Both formulations were characterized according to droplet size, polydispersity index, volume-weighted mean diameters, particle distribution, droplets diameters tracking, zeta potential, viscosity and bioadhesion behavior. β-caryophyllene content was determined by gas chromatography coupled with mass spectrometry (GC/MS). Both formulations presented a nanometric droplet size, negative zeta potential, high β-caryophyllene content, and were stable for 60 days. In agreement with the viscosity results, the hydrogel containing the β-caryophyllene nanoemulsion showed superior bioadhesiveness than the nanoemulsion. The skin permeation study in Franz cells demonstrated that isolated β-caryophyllene was unable to cross the stratum corneum and that its nanoemulsification promoted its permeation. On the other hand, in the simulated deeply wounded skin (dermis), no significant differences were observed between the formulations and isolated β-caryophyllene with respect to the amount of marker retention in the dermis, suggesting saturation of this skin layer. For the study of healing activity, the dorsal wound model was performed with an evaluation of the lesion size, anti-inflammatory markers, and antioxidant activity. The initial closure of the wound was achieved sooner in the group treated with the hydrogel containing the β-caryophyllene nanoemulsion, indicating its anti-inflammatory effect. The histological analysis indicated that on day 12 day of the lesion, the hydrogel presented similar results to those of the positive control group (Dersani® oil), proving effectiveness in cutaneous tissue repair., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Finite control set model-based predictive control techniques are distinguished by being an interesting alternative to traditional field oriented control techniques for multiphase drives due to their fast dynamic response and flexibility in the introduction of constraints. However, those predictive control techniques have some drawbacks regulating the (x-y) current components which can cause machine losses as well as a high computational burden. This paper presents a comparative study of an enhanced predictive current control technique with a conventional predictive control technique and two hybrid predictive control techniques applied to an asymmetrical six-phase induction motor drive in terms of current tracking, total harmonic distortion of stator currents and computational burden. Experimental results are reported to demonstrate the benefits of the different current control techniques by using the mean squared error and total harmonic distortion of stator currents as quality figures of merit and the number of floating point operations to measure the computational burden of each predictive control, thus concluding the advantages and limitations of each technique at transient and steady regimes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 ISA. Published by Elsevier Ltd. All rights reserved.)

Treatment-resistant epilepsy is a common and debilitating neurological condition, for which neurosurgical cure is possible. Despite undergoing nearly identical ablation procedures however, individuals with treatment-resistant epilepsy frequently exhibit heterogeneous outcomes. We hypothesized that treatment response may be related to the brain regions to which MR-guided laser ablation volumes are functionally connected. To test this, we mapped the resting-state functional connectivity of surgical ablations that either resulted in seizure freedom (N = 11) or did not result in seizure freedom (N = 16) in over 1,000 normative connectomes. There was no difference seizure outcome with respect to the anatomical location of the ablations, and very little overlap between ablation areas was identified using the Dice Index. Ablations that did not result in seizure-freedom were preferentially connected to a number of cortical and subcortical regions, as well as multiple canonical resting-state networks. In contrast, ablations that led to seizure-freedom were more functionally connected to prefrontal cortices. Here, we demonstrate that underlying normative neural circuitry may in part explain heterogenous outcomes following ablation procedures in different brain regions. These findings may ultimately inform target selection for ablative epilepsy surgery based on normative intrinsic connectivity of the targeted volume.

Optogenetics provide a potential alternative approach to the treatment of chronic pain, in which complex pathology often hampers efficacy of standard pharmacological approaches. Technological advancements in the development of thin, wireless, and mechanically flexible optoelectronic implants offer new routes to control the activity of subsets of neurons and nerve fibers in vivo . This study reports a novel and advanced design of battery-free, flexible, and lightweight devices equipped with one or two miniaturized LEDs, which can be individually controlled in real time. Two proof-of-concept experiments in mice demonstrate the feasibility of these devices. First, we show that blue-light devices implanted on top of the lumbar spinal cord can excite channelrhodopsin expressing nociceptors to induce place aversion. Second, we show that nocifensive withdrawal responses can be suppressed by green-light optogenetic (Archaerhodopsin-mediated) inhibition of action potential propagation along the sciatic nerve. One salient feature of these devices is that they can be operated via modern tablets and smartphones without bulky and complex lab instrumentation. In addition to the optical stimulation, the design enables the simultaneously wireless recording of the temperature in proximity of the stimulation area. As such, these devices are primed for translation to human patients with implications in the treatment of neurological and psychiatric conditions far beyond chronic pain syndromes.

Background: The differential diagnosis of a supraventricular tachycardia (SVT) is accomplished using a number of pacing maneuvers. The incidence and mechanism of a single ventricular premature beat (VPB) on initiation and termination of tachycardia were evaluated during programmed electrical stimulation (PES) of the heart in patients with the two most common regular SVTs: atrioventricular re-entrant tachycardia (AVNRT) and orthodromic atrioventricular tachycardia (AVRT)., Methods: Three hundred and thirty-seven consecutive patients aged above 18 years with an inducible sustained AVNRT or AVRT were prospectively enrolled. Patients with more than one tachyarrhythmia mechanism were excluded. Two hundred and seventeen patients (64.4%) had typical slow/fast AVNRT and 120 (35.6%) had an orthodromic AVRT using a rapidly conducting accessory pathway for V-A conduction. In this cross-sectional study, we specifically report the analysis of tachycardia induction and termination by a single VPB., Results: Tachycardia induction with a single VPB during sinus rhythm was seen in 7 of 120 AVRT and in only one of the 217 patients with AVNRT, (5.8% vs. 0.3%, p < 0.05). When a single VPB was delivered during basic ventricular pacing these values were 28% versus 4%, respectively, (p < 0.001). Termination of tachycardia by a single VPB was observed in nine (4.1%) patients with AVNRT and in 57 (47.5%) with AVRT (p < 0.001)., Conclusion: Initiation of SVT by a single VPB during sinus rhythm was uncommon and favored AVRT. Termination of SVT by a single VPB was commonly seen in AVRT but rarely in AVNRT. These findings can be of help when interpreting a noninvasive arrhythmia event recording., (© 2019 Wiley Periodicals, Inc.)

Aims: (1) To perform a comprehensive analysis of the time elapsed between the last G-CSF injection and the PET/CT examination on the biodistribution of 18 F-FDG, with emphasis on liver, spleen, and bone marrow uptake, and (2) to investigate whether an inversion of the liver to spleen ratio affects the Deauville scoring., Materials and Methods: Retrospectively included were 74 consecutive diffuse large B cell lymphoma (DLBCL) patients referred for baseline and interim examinations and receiving immunochemotherapy with various G-CSF regimens. A comprehensive evaluation considering baseline metabolic active tumour volume (MATV), factors affecting liver uptake, the type of G-CSF, and the time elapsed between chemotherapy/G-CSF and interim PET/CTs was performed., Results: Mean (± SD) percentage variations between baseline and interim PET/CTs (i-PET/CT) for bone marrow (%Variation&#95; BONE ), liver (%Variation&#95; LIVER ) and spleen (%Variation&#95; SPLEEN ) were equal to 32.0 ± 46.9%, 16.1 ± 42.8%, and 10.6 ± 51.1 %, respectively. %Variation&#95; LIVER and %Variation&#95; SPLEEN were higher in patients using lenograstim, but this was linked to lower uptakes at baseline and was therefore likely not due to G-CSF itself. The mean delay between G-CSF injection and i-PET/CT acquisition was not an independent explanatory variable for %Variation&#95; BONE , %Variation&#95; LIVER , and %Variation&#95; SPLEEN . On the contrary, %Variation&#95; BONE and %Variation&#95; SPLEEN were negatively correlated to the time-lapse between the end of chemotherapy and i-PET/CT: ρ = - 0.342 (p = 0.010) and ρ = - 0.529 (p < 0.0001), respectively. Patients with a time-lapse since the last injection of chemotherapy < 17 days displayed higher bone and spleen SUVmax EARL . %Variation&#95; LIVER was positively correlated to baseline MATV: ρ = 0.243 (p = 0.039). Patients displaying a high baseline MATV ≥ 177 cc had significantly lower liver SUVmax EARL at baseline. This difference was no longer observed at i-PET/CT, after tumours had shrunk., Conclusions: Neither the type of G-CSF used nor the time elapsed between its last injection and i-PET/CT examination independently influences bone, hepatic, or splenic uptakes at i-PET/CT. The major determinant for the occurrence of a bone or spleen hypermetabolism on i-PET/CT is the time elapsed between the chemotherapy and the examination, which should be maintained above 15 days. Inversion of the liver to spleen ratio appeared to be due to increased spleen hypermetabolism on i-PET/CT, making unlikely an impact on the Deauville scoring.

We report on a self-sustainable, wireless accelerometer-based system for wear detection in a band saw blade. Due to the combination of low power hardware design, thermal energy harvesting with a small thermoelectric generator (TEG), an ultra-low power wake-up radio, power management and the low complexity algorithm implemented, our solution works perpetually while also achieving high accuracy. The onboard algorithm processes sensor data, extracts features, performs the classification needed for the blade's wear detection, and sends the report wirelessly. Experimental results in a real-world deployment scenario demonstrate that its accuracy is comparable to state-of-the-art algorithms executed on a PC and show the energy-neutrality of the solution using a small thermoelectric generator to harvest energy. The impact of various low-power techniques implemented on the node is analyzed, highlighting the benefits of onboard processing, the nano-power wake-up radio, and the combination of harvesting and low power design. Finally, accurate in-field energy intake measurements, coupled with simulations, demonstrate that the proposed approach is energy autonomous and can work perpetually.

Background : fMRI of mental phenomena is quite difficult to perform because lack of patient's cooperation or because the symptoms are stable. In some exceptional cases, however, fMRI and DTI are capable to provide insights on the anatomy of organic hallucinations. Methods : In this report we describe a 14-year-old boy with a left fronto-dorsal tumor who experienced chronic complex brief, frequent and repetitive complex visual and auditory hallucinations. His clinical picture included multiple and severe social and mood problems. During a presurgical fMRI mapping the patient complained of having the visual and auditory hallucinations. A block-design FMRI paradigm was obtained from the event timecourse. Deterministic DTI of the brain was obtained seeding the lesion as ROI. The patient underwent surgery and electrocorticography of the lesional area. Results : The fMRI of the hallucinations showed activation in the left inferior frontal gyrus (IFG) and the peri-lesional area. The tractography of the tumor revealed structural aberrant connectivity to occipital and temporal areas in addition to the expected connectivity with the IFG via the aslant fasciculus and homotopic contralateral areas. Intraoperative EEG demonstrated epileptic discharges in the tumor and neighboring areas. After resection, the patient's hallucinations stopped completely. He regained his normal social life and recover his normal mood. He remained asymptomatic for 90 days. Afterwards, hallucinations reappeared but with less intensity. Conclusions : To our knowledge, this is the first reported case of combined functional and structural connectivity imaging demonstrating brain regions participating in a network involved in the generation of complex auditory and visual hallucinations.

Introduction and Aims: Traumatic dental injuries (TDI), alcohol and illicit drugs consumption are highly-prevalent public health concerns. The aim of this study was to evaluate the association between alcohol and/or illicit drugs consumption and the presence of TDI., Design and Methods: This review was performed in accordance with MOOSE and PRISMA guidelines. Electronic searches were performed to found observational studies that investigated subjects that consumed alcohol and/or illicit drugs associated with TDI. Data extraction and a risk of bias assessment were performed. Three meta-analyses (MA) were performed to evaluate the association between TDI and alcohol consumption (1 st MA), subgrouping the studies into alcohol intake and binge-drinking, alcohol-related problems (2 nd MA), and drugs (3 rd MA). The odds ratio (OR) were calculated (p ≤ 0.05) for all analyses. The evidence was certainty-tested using the GRADE approach., Results: Twelve articles met the eligibility criteria. Nine studies were methodologically sound, while three had some confounding factors. In the pooled MA, an association between alcohol consumption and TDI (OR 1.57[1.33,1.85],p = 0.00001) was determined with moderate certainty of evidence, confirmed in the subgroups of alcohol intake (OR 1.49[1.17,1.90],p = 0.001) and binge-drinking (OR 1.68[1.30,2.18],p = 0.0001). No associations were found between TDI and risk for alcohol-related problems and drug use (OR 0.75[0.50,1.14],p = 0.18, and OR 1.20[0.82,1.75],p = 0.27, respectively), with both analyses having a very low certainty of evidence., Discussion and Conclusions: There is moderate evidence concerning the association between alcohol use and TDI. Despite the absence of an association between illicit drugs use, alcohol-related problems and the presence of TDI, these results should be viewed with caution, since they had very low-certainly-evidence., (Copyright © 2019 Elsevier B.V. All rights reserved.)