Damage Events Research Articles

The association between urate-lowering therapies and treatment-related adverse events, liver damage, and major adverse cardiovascular events (MACE): A network meta-analysis of randomized trials.

Hyperuricemia is a common disease that may lead to gout, renal damage, and cardiovascular events. Oral medication is the main treatment for hyperuricemia patients when lifestyle intervention fails. An evaluation of the safety of various urate-lowering therapies (ULTs) is integral to clinical decision-making. We constructed a network meta-analysis (NMA) to evaluate the safety of oral ULTs. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched up to April 1, 2021, for randomized controlled trials that examined the safety of ULTs. The language restriction was English. The three outcomes used to assess the safety of uric acid lowering medications were treatment-related adverse events, liver damage, and major adverse cardiovascular events (MACE). Thirty-two trials enrolling 23,868 individuals were included in the study. In terms of treatment-related adverse events, there were no statistically significant differences between five uric acid lowering medications and placebo: allopurinol (risk ratio (RR): 1.08; 95% credible interval (CrI): 0.91, 1.29), febuxostat (RR: 1.05; 95% CrI: 0.89, 1.25), lesinurad (RR: 1.19; 95% CrI: 0.85, 1.67), lesinurad combined with xanthine oxidase inhibitor (XOI, RR: 1.05; 95% CrI: 0.83, 1.32), and topiroxostat (RR: 1.01; 95% CrI: 0.83, 1.23). Topiroxostat likely increases risk of liver damage (RR: 2.65; 95%CI: 1.24, 5.70; NNH: 33.40) as compared with placebo. With regard to MACE, there were no statistically significant differences between three uric acid lowering medications and placebo: allopurinol (RR: 0.63; 95% CrI: 0.36, 1.34), febuxostat (RR: 0.69; 95% CrI: 0.38, 1.66), and lesinurad combined with XOI (RR: 0.56; 95% CrI: 0.23, 1.85). The rankings of different interventions were depicted by cumulative ranking curve (SUCRA). Through NMA, we provide some evidence for the safety of ULTs. We found no statistically significant differences in their effects on treatment-related adverse events and MACE. However, topiroxostat likely increases the risk of liver damage.

Evaluation of Myocardial Damage in Relation to HbA1c in Patients with Previously Unrecognized Diabetes Presenting with STEMI

Objective: The mechanisms underlying worse clinical outcomes in previously unrecognized diabetic (DM) patients in ST-elevation myocardial infarction (STEMI) are unclear. It was hypothesized that poor chronic glucose control might be related to greater myocardial damage.
 Material and Method: 51 newly diagnosed DM patients with glycated hemoglobin A1c (HbA1c) > 6.5 comprised the DM group, 54 sex- and age-matched individuals with normal glucose metabolism served as the non-DM group. Each patient underwent primary angioplasty for STEMI. The levels of cardiac specific markers before angioplasty, during angioplasty, at 6, 12, and 18 h after angioplasty were recorded. SPSS 10 package program was used to analyse data.
 Results: In both DM and non-DM groups troponin peaked at 6 h. Peak troponin levels were similar in both groups (diabetics, 22.89 ± 18.19 vs. non-diabetics, 32.67 ± 17.68 ng/ml, p=0.168).
 Conclusions: HbA1c > 6.5 is not related to extent of infarction in previously unrecognized DM patients presenting with STEMI. Future studies assessing the effects of other factors unrelated to chronic glucose control on myocardial damage and cardiovascular event rates in these patients would be of great interest.

Efficacy and safety of the application of extensive ablation in patients with atrioventricular re-entrant tachycardia (a retrospective study)

Radiofrequency catheter ablation (RFCA) has become the standard effective therapy for supraventricular tachycardia, but the reported success rates of ablation have differed across a large number of single-center studies. The main reason for tachycardia recurrence is accessory pathway (Ap)-mediated tachycardia, and the use of the RFCA strategy may be related to recurrence. This study compared the efficacy and safety of two different RFCA strategies for Ap-mediated tachycardia. We compared patients (group M) who underwent RFCA at multiple sites to patients (group S) who underwent RFCA at a single site during the index procedure for Ap-mediated tachycardia. The efficacy and safety were assessed in the two groups. Follow-up was conducted, and the main complications and the incidence of recurrence after RFCA procedures were recorded. Eight hundred eighty-two patients with 898 Aps were enrolled in group S, and 830 patients with 843 Aps were enrolled in group M. The cumulative number of recurrences (rates) in group M and group S at the 1st, 3rd, 6th, 12th, and 24th months after ablation were 4 (0.5%) and 17 (1.9%), p < 0.05; 5 (0.6%) and 27 (3.0%), p < 0.05; 6 (0.7%) and 34 (3.8%), p < 0.05; 6 (0.7%) and 43 (4.8%), p < 0.05; and 7 (0.8%) and 45 (5.0%), p < 0.05, respectively. Complications of chest pain, overactive vasovagal reaction, steam pop, and angina pectoris were rare in both groups. One patient in group M suffered from myocardial infarction before extensive ablation. No valve damage, cardiac tamponade, or other serious adverse events occurred in either group. The extensive ablation strategy reduced the recurrence rate and the need for subsequent ablation of the Ap without increasing the risk of complications.

Relationship between morning blood pressure surge and the frontal plane QRS-T angle in newly diagnosed hypertensive patients

ABSTRACT Background Morning blood pressure surge (MBPS) plays an important role in target organ damage and major adverse cardiac events. The frontal QRS-T [f(QRS-T)] angle is the electrocardiographic marker and index of ventricular arrhythmogenic events. We aimed to investigate the relationship between MBPS and the f(QRS-T) angle, which is an indicator of ventricular repolarization disorder, in patients with newly diagnosed HT. Methods Between June 2020 and March 2021, 263 patients with newly diagnosed HT who were admitted to our outpatient clinic were prospectively included in the study. According to ambulatory blood pressure monitoring (ABPM), the patients were categorized into two groups: Group-I: low-value MBPS (<37 mm Hg), and group-II: high-value MBPS (≥37 mm Hg). The f(QRS-T) angle calculated from the 12-lead electrocardiogram and all other data were compared between the groups. Results A total of 186 newly diagnosed HT patients who met the inclusion criteria were included in the study. The average f(QRS-T) angle in Groups I and 2 was 21° ± 16° and 51° ± 30°, respectively (P < .001). According to multivariate regression analysis, T peak-end and MBPS were found to be independent predictors of the f(QRS-T) angle. Conclusions As a result of our study, we found that the f(QRS-T) angle was widened in patients with exaggerated MBPS. The cause of increased cardiovascular outcomes in patients with exaggerated MBPS may be explained by widened in the f(QRS-T) angle that is a ventricular repolarization parameter.

SETD2 Non-Genomic Loss of Function and p53 Functional Inactivation in Advanced Systemic Mastocytosis (SM): Pathogenetic and Therapeutic Implications

KIT constitutive activation is thought to be necessary but not sufficient for the development of aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL). The identification and dissection of cooperating pathogenetic pathways may set the basis for the development of novel therapeutic strategies.We have recently found that the HMC-1.1 and -1.2 MCL cell lines and ASM/MCL patients (pts) display histone H3 Lys36 trimethylation (H3K36Me3) deficiency as a result of non-genomic loss of function of the SETD2 methyltransferase. SETD2 plays a key role in the control of transcription and splicing fidelity, homologous recombination (HR), mismatch repair (MMR). Inhibition of proteasome-mediated degradation by bortezomib restored SETD2 protein expression and H3K36Me3. Reversing the detrimental effects of SETD2 and H36K36Me3 deficiency may be a promising therapeutic strategy.In this study, we aimed to investigate the effects of SETD2 loss of function in ASM and MCL and to assess the in vitro efficacy of second-generation proteasome inhibitors as therapeutic agents. To investigate whether increased DNA damage and reduced HR proficiency can be observed in SETD2/H3K36Me3-deficient SM, we used western blotting and immunofluorescence to assess phosphorylated histone 2A.X (γH2AX), which marks ongoing DNA damage signaling and DNA double strand breaks and Rad51, which is a surrogate for active HR. Compared to cells from healthy controls, cells from SETD2- and H3K36Me3-deficient MCL pts had significantly higher levels of γH2AX and Rad51. To assess whether the increased DNA damage may translate into a greater number of submicroscopic genomic lesions, and whether the degree of SETD2 down-modulation may be inversely correlated with the degree of genomic complexity, SNP-array data from 13 pts were examined. Structural complexity score (SCS) and genome instability index (GII) were not significantly different (SCS, 387 vs 376; GII, 0.293 vs 0.337) between pts with > or <50% residual SETD2 and H3K36Me3 levels, suggesting that the activity of HR repair may counteract DNA damage events. Moreover, SETD2 down-modulation was not associated with reduced MMR proficiency, as assessed by lack of microsatellite instability. On the other hand, RNA-seq in SETD2-deficient pts showed evidence of transcription and splicing defects like transcription-induced chimeras and intron retention not observed in healthy donors.In renal cell carcinoma cell lines, SETD2 has been shown to bind and activate p53. After proteasome inhibition, SETD2 was indeed found to immunoprecipitate with p53 in HMC-1.1 and -1.2 cells. Rescuing the interaction between SETD2 and p53 with bortezomib stabilized p53 and upregulated the expression levels of p53 targets including p21, p27, Bax and Gadd45a. This restored inhibition of cell proliferation, block of the transition towards cell cycle checkpoints and consequent activation of apoptosis. The ubiquitin E3 ligase MDM2 was also found to complex with SETD2 after proteasomal inhibition. Treatment with SP-141, a new class of MDM2 inhibitors that promote MDM2 auto-ubiquitination and degradation, also rescued SETD2 expression and H3K36Me3, suggesting that MDM2 may play a role in SETD2 degradation in ASM and MCL. Moreover, SP-141 treatment of HMC-1 cells at micromolar doses for 24-48-72-96 hours induced cytostatic but not cytotoxic effects as shown by cell growth curves. Cytostatic effects resulted from a G2/M block of cell cycle induced by Gadd45a overexpression. Clonogenic assays supported the cytostatic effects of SP141 in HMC-1.1 and -1.2 cells (LD50=0.133µM and 0.050µM respectively).Finally, treatment with the second-generation proteasome inhibitors carfilzomib and ixazomib potently induced apoptosis and reduced colony growth in HMC-1.1 (LD50=0.10nM and 0.66nM respectively) and -1.2 (LD50=0.13nM and 0.72nM respectively) cells.In conclusion: MDM2-mediated ubiquitination contributes to SETD2 non-genomic loss of function in ASM and MCL. Loss of SETD2 and H3K36Me3 is associated with increased DNA damage and transcription and splicing defects in ASM and MCL pts and is likely to afford an alternative mechanism for the inactivation of the p53-mediated checkpoint without the need for TP53 gene mutations. Approaches aimed to inhibit MDM2 activity or proteasome-mediated degradation are promising therapeutic strategies worth to be further explored.Supported by AIL and AIRC (16996) DisclosuresZanotti:Deciphera: Consultancy. Ciceri:GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Valent:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; BMS: Honoraria; Ariad: Honoraria, Research Funding; Incyte: Honoraria; Deciphera: Honoraria, Research Funding; Pfizer: Honoraria; Blueprint: Research Funding; Teva: Honoraria. Martinelli:Amgen: Consultancy; Pfizer: Consultancy; Celgene: Consultancy; Roche: Consultancy; Johnson&Johnson: Consultancy; Ariad/Incyte: Consultancy. Soverini:Incyte Biosciences: Consultancy; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy.

Demonstration of a low-cost and open-source platform for on-farm monitoring and decision support

Weather dictates farm operations including irrigation scheduling, harvesting, and protection from crop damaging events such as frost, heat waves or disease outbreaks. In a changing climate, farmers need real-time and site-specific weather data in order to better inform planning and resource allocation. Currently, public regional weather networks provide near real-time data in most locations throughout the continental United States, but these data may not represent local conditions for many locations. Commercial manufacturers provide a wide range of alternative to public weather networks that vary in quality and in usefulness for on-farm monitoring. Low-cost and open-source weather stations are an emerging alternative to public and commercially available weather networks because they are often built from components using open-source do-it-yourself (DIY) platforms and technology. For this project, we developed a Low-Cost and Open Source weather station (LOCOS) using an Arduino-based platform and deployed these systems in two field experiments. Data from four LOCOS in an Idaho vineyard showed that microclimates varied significantly across spatial scales that are relevant to disease management. In a second field experiment, data from multiple LOCOS showed significant differences in evaporative demand between two fields equipped with different center-pivot irrigation systems. The sensors used with the LOCOS showed robust results in calibration. LOCOS were capable of testing rigorous hypotheses about site-specific weather phenomena. This information supports efficient and sustainable crop production, and helps minimize consumption of available resources.

Can organic acid and sugar compositions be used to predict cell death point limits? Receptacle and pistil organs of apricot (Prunus armeniaca L.)

To boost our understanding of recent frost damage events in apricot trees, we focused on estimating the cell death point in the receptacle and pistil organs of apricots by simulating the unexpected temperature changes occurring in early spring under laboratory-based freezing experiments. The hypothesis also that organic acids (oxalic, propionic, tartaric, butyric, malonic, malic, lactic, citric, maleic, fumaric and succinic acids) and soluble sugar compositions (glucose, fructose, sucrose and total sugar) may directly stimulate the change of the frost tolerance in apricot receptacle and pistil organs was investigated using two apricot (Prunus armeniaca L.) cultivars, one tolerant to frost (‘Iğdır Şalak’) and the other sensitive to frost (‘Mihralibey’). Our results indicated that the mean the cell death point (CDP) of flower pistil (from −13.26 to −14.18 °C) was at lower temperatures than those of flower receptacle (from −6.28 to −8.65 °C) in both apricot cultivars during the full blooming stage. In both apricot cultivars, receptacle organs showed more sensitive changes to the frost tolerance in response to low temperatures compared with pistil organs. In terms of organic acid and soluble sugar contents, significant differences were determined for both apricot cultivars and between the pistil and the receptacle organs of the flowers. Organic acid content was higher in the freezing-tolerant apricot cultivar (‘Iğdır Şalak’) than the freezing-sensitive apricot cultivar (‘Mihralibey’), but it was lower in the freezing-tolerant organ (pistil) in comparison with the freezing-sensitive organ (receptacle). Moreover, fructose concentrations for both ‘Mihralibey’ and ‘Iğdır Şalak’ were significantly higher in the receptacle compared to the pistil. A significant negative correlation was also observed between the mean CDP values and both all organic acids and sucrose contents in the pistil and the receptacle organs for both apricot cultivars. There was a positive relationship between the CDP values and fructose content in ‘Iğdır Şalak’. Additionally, there was a negative correlation between the CDP values and sucrose in 'Mihralibey'. Overall, the data presented suggest that the high level of sucrose and organic acid content of receptacle and pistil organs contributes to support frost tolerance of organs. The results of this study could help in the understanding of how receptacle and pistil organs of two different apricot cultivars react to frost stress, and how they modulate their soluble sugar and organic acid metabolism.Graphic abstract

Self-healing liquid metal composite for reconfigurable and recyclable soft electronics

Soft electronics and robotics are in increasing demand for diverse applications. However, soft devices typically lack rigid enclosures which can increase their susceptibility to damage and lead to failure and premature disposal. This creates a need for soft and stretchable functional materials with resilient and regenerative properties. Here we show a liquid metal-elastomer-plasticizer composite for soft electronics with robust circuitry that is self-healing, reconfigurable, and ultimately recyclable. This is achieved through an embossing technique for on-demand formation of conductive liquid metal networks which can be reprocessed to rewire or completely recycle the soft electronic composite. These skin-like electronics stretch to 1200% strain with minimal change in electrical resistance, sustain numerous damage events under load without losing electrical conductivity, and are recycled to generate new devices at the end of life. These soft composites with adaptive liquid metal microstructures can find broad use for soft electronics and robotics with improved lifetime and recyclability.

A multiscale and multiaxial model for anisotropic damage and failure of human annulus fibrosus

This article presents a multiscale model to predict deformation-induced damage and failure of human annulus fibrosus under multiaxial loading. In the modeling approach, formulated within the framework of nonlinear continuum mechanics, the hierarchical structure of the soft tissue is considered from the nano-sized collagen fibrils to the micro-sized oriented collagen fibers. At the macroscale, the multi-layered lamellar/inter-lamellar organization of the soft tissue is introduced by considering the effective interactions between adjacent layers. The stochastic process of progressive damage events operating at different scales of the solid phase is introduced for the extracellular matrix and the network of nano-sized fibrils/micro-sized fibers. The damage is made anisotropic due to lamellar oriented collagen fibers and special orientation distribution of the inter-fibrillar and inter-lamellar network of fibrils. The chemical-induced volumetric strain is also considered in our modeling approach to take into account the osmolarity effects along with the anisotropic time-dependent transversal deformations. The capacity of the model is discussed using a few available stretching datasets till failure along circumferential and radial directions. Model predictions under tilted stretching, biaxial stretching and shearing are also presented to illustrate further the efficiencies of our modeling approach. This work shows for the first time the directional effects on annulus mechanics and failure in relation to external loading mode, structure features, damage events and hydration.

Extreme-rainfall Data as a Basis for Landslide Warnings: a Case Study of a Road in Central Taiwan

In recent years, an increase in extreme rainfall events linked to global warming has led to increases in the number and intensity of disasters such as landslides, landslips, and debris flows in Taiwan. This study focuses on the impact of such events, especially during typhoons, on County Road 89: the main traffic artery in Renai Township, Nantou County. Specifically, it will use an inverse distance weighting method (IDW) to analyze how rainfall at the four rainfall stations in Nantou, located at Renai, Ruiyan, Cuiluan and Cuihua, may related to damage events at the 12.3k, 22.53k, 32.5k, 46.3k, and 49k points on County Road 89. Then, landslide road-damage warning ranges will be drawn up using various combinations of data, including cumulative rainfall, maximum rainfall within a 24-hour period, and I-R alert model (I: rainfall intensity, R: cumulative rainfall), with an I-T alert model (I: rainfall intensity, T: rainfall duration) for comparison. This will yield an optimal warning value for the landslide-prone area of the focal road. Finally, data from County Road 89 will be compared against data from the Lishan landslide area, to ascertain whether/how such warning values should differ across geographic areas. The results are expected to usefully inform follow-up disaster prevention planning as well as further academic research on this topic.

The effect of carbon nanotubes modified polyurethane adhesive on the impact behavior of sandwich structures

AbstractSandwich panels with aluminum honeycomb cores have emerged as an essential class of lightweight building materials in a wide variety of structural engineering areas, including marine, railway, aerospace, and automotive structures. Although sandwich structures offer remarkable mechanical properties, for instance, high specific strength and stiffness, these structures are open to the damage created by the low‐velocity impact. This study investigates the dynamic behavior of aluminum honeycomb sandwich panels with different core cell sizes based on neat and multi‐walled carbon nanotube (MWCNT) reinforced polyurethane (PU) adhesives that are aimed. The enhancement in impact performance of honeycomb sandwich structures obtained by the inclusion of MWCNTs in the PU adhesive is investigated. The effect of the MWCNT reinforcements on square sandwich panels at 50 J energy level is examined using an instrumented drop tower test setup. After acquiring load–time histories, the numerical integration method is implemented to obtain load–deflection and energy–time curves. Also, energy balance modeling (EBM) is utilized to characterize the effectualness of MWCNT reinforcement to PU adhesive on the impact behavior of sandwich panels. Theoretical EBM is confirmed that absorbed energy in the shear and bending deflections increased as the percentage of MWCNT‐added PU adhesive increases. Understanding the damage event implicated in absorbing and dissipating the impact energy is determined and compared for panels with different cell sizes, including nanoparticles, using the macroscopic optical images and microscopic scanning electron microscopy images of sandwich panels.

Grain size effect on the radiation damage tolerance of cubic zirconia against simultaneous low and high energy heavy ions: Nano triumphs bulk

Irradiation induced damage in materials is highly detrimental and is a critical issue in several vital science and technology fields, e.g., the nuclear and space industries. While the effect of dimensionality (nano/bulk) of materials on its radiation damage tolerance has been receiving tremendous interest, studies have only concentrated on low energy (nuclear energy loss (Sn) dominant) and high energy (electronic energy loss (Se) dominant) irradiations independently (wherein, interestingly, the effect is opposite). In-fact, research on radiation damage in general has almost entirely focused only on independent irradiations with low and/or high energy particles till date, and investigations under simultaneous impingement of energetic particles (which also correspond to the actual irradiation conditions during real-world applications) are very scarce. The present work elucidates, taking cubic zirconia as a model system, the effect of grain size (26 nm vs 80 nm) on the radiation tolerance against simultaneous irradiation with low energy (900 keV I) and high energy (27 meV Fe) particles/ions; and, in particular, introduces the enhancement in the radiation damage tolerance upon downsizing from bulk to nano dimension. This result is interpreted within the framework of the thermal-spike model after considering (1) the fact that there is essentially no spatial and time overlap between the damage events of the two ‘simultaneous’ irradiations, and (2) the influence of grain size on radiation damage against individual Sn and Se. The present work besides providing the first fundamental insights into how the grain size/grain boundary density inherently mediates the radiation response of a material to simultaneous Sn and Se deposition, also (1) paves the way for potential application of nano-crystalline materials in the nuclear industry (where simultaneous irradiations with low and high energy particles correspond to the actual irradiation conditions), and (2) lays the groundwork for understanding the material behaviour under other simultaneous (viz. Sn and Sn, Se and Se) irradiations.

Cost of Coexisting with a Relict Large Carnivore Population: Impact of Apennine Brown Bears, 2005-2015.

Simple SummaryEfficiently addressing human-large carnivore conflicts is a conservation issue of increasing relevance, especially in human-dominated landscapes where impact on rural economies generates negative attitudes towards large carnivores and their conservation. We quantified patterns of bear impact on farms and the costs of compensation from 2005 to 2015 in the Abruzzo Lazio and Molise National Park (central Italy), an historical stronghold of the relict and highly imperiled Apennine brown bear population, where the park authority has been adopting conflict management approaches since the 1960s. Although the compensation program is rather costly (1490 ± 589 €/bear/year), the park policy has been increasingly integrated with prevention incentives, managing to effectively avert further increases in bear damages during the study period. Concurrently, local residents generally share a positive attitude towards bears, and the number of illegally killed bears decreased in the last decade. Despite this, our findings indicate there is still room for improvement in local conflict management, and that a more efficient use of conservation funds would benefit from increased monitoring, integrated prevention, conditional compensation, and participatory processes. Lessons learned from areas of historical coexistence between humans and large carnivores provide critical insights to design successful management strategies in areas of recent and future recolonisation by large carnivores.Human-carnivore conflicts are a major conservation issue. As bears are expanding their range in Europe’s human-modified landscapes, it is increasingly important to understand, prevent, and address human-bear conflicts and evaluate mitigation strategies in areas of historical coexistence. Based on verified claims, we assessed costs, patterns, and drivers of bear damages in the relict Apennine brown bear population in the Abruzzo Lazio and Molise National Park (PNALM), central Italy. During 2005–2015, 203 ± 71 (SD) damage events were verified annually, equivalent to 75,987 ± 30,038 €/year paid for compensation. Most damages occurred in summer and fall, with livestock depredation, especially sheep and cattle calves, prevailing over other types of damages, with apiaries ranking second in costs of compensation. Transhumant livestock owners were less impacted than residential ones, and farms that adopted prevention measures loaned from the PNALM were less susceptible to bear damages. Livestock farms chronically damaged by bears represented 8 ± 3% of those annually impacted, corresponding to 24 ± 6% of compensation costs. Further improvements in the conflict mitigation policy adopted by the PNALM include integrated prevention, conditional compensation, and participatory processes. We discuss the implications of our study for Human-bear coexistence in broader contexts.

Early Safety Warnings for Long-Distance Pipelines: A Distributed Optical Fiber Sensor Machine Learning Approach

Automated pipeline safety early warning (PSEW) systems are designed to automatically identify and locate third-party damage events on oil and gas pipelines. They are intended to replace traditional, inefficient manual inspection methods. However, current PSEW methods cannot achieve universality for various complex environments because they are sensitive to the spatiotemporal stability of the signal obtained by its distributed sensors at various locations and times. Our research aimed to improve the accuracy of long-distance oil–gas PSEW systems through machine learning. In this paper, we propose a novel real-time action recognition method for long-distance PSEW systems based on a coherent Rayleigh scattering distributed optical fiber sensor. More specifically, we put forward two complementary feature calculation methods to describe signals and build a new action recognition deep learning network based on those features. Encouraging empirical results on the data collected at a real location confirm that the features can effectively describe signals in an environment with strong noise and weak signals, and the entire approach can identify and locate third-party damage events quickly under various hardware conditions with accuracies of 99.26% (500 Hz) and 97.20% (100 Hz). More generically, our method can be applied to other fields as well.

Impact of visit-to-visit blood pressure variability on hypertensive-mediated target organ damage and future cardiovascular events: the Campania salute network.

Exaggerated variability of blood pressure (BP) poses additional stress on cardiovascular system independent of BP average value, increasing risk of target organ damage (HMOD) and cardiovascular events. We assessed the impact of visit-to-visit variability (VVV) of BP on development of cardiovascular events and HMOD. Standard deviation (SD) and coefficient of variability of mean SBP and DBP were calculated in 3555 patients from the Campania Salute Network registry, with available echocardiogram and more than six visits during follow-up. Values from the first visit were excluded. The impact of VVV of BP on cardiovascular events, and mediation of HMOD were assessed at final visit. Mean number of visits was 11 ± 6 with mean interval between visits of 9.1 ± 3.7 months. Mean visit-to-visit SD during follow-up was 13 ± 5 for systolic and 8 ± 3 mmHg for DBP; coefficients of variability were 9.7 ± 3.5 and of 9.6 ± 3.2, respectively. In multivariable analysis, left ventricular mass at follow-up was correlated with systolic VVV of BP independently of significant effect of age, BMI, mean SBP during follow-up and initial left ventricular mass. Follow-up GFR was inversely associated with systolic and diastolic VVV, independently of significant effect of age, mean glucose and SBP during follow-up, and initial GFR. In Cox regression, high VVV of BP was also associated with increased risk of cardiovascular events (hazard ratio 1.49, 95% confidence interval 1.08-2.06, P = 0.015), independently of significant effect of HMOD. VVV is associated with prevalent HMOD and development of cardiovascular events, independently of mean BP value during follow-up and HMOD.

Factors affecting the crop damage by wild boar (Sus scrofa) and effects of population control in the Ticino and Lake Maggiore Park (North-western Italy)

Wild boar foraging impacts the crops, pastures, and meadows causing remarkable losses to agricultural income. Protected areas located in plains, such as the Ticino Valley Natural Park, are characterized by the coexistence of important natural habitats and intensive agricultural areas. In the Park, from 2010 to 2017, 49% of the complaints report an event of damage to maize and 43% to meadows. The total expense for reimbursements of the maize amounted to € 439,341.52, with damages concentrated in May, after sowing period and between August and September, during the milky stage of maize. For meadows reimbursements amounted to € 324,768.66, with damage events concentrated in February and March. To reduce damage to crops, the Park administration carried out lethal control of the wild boar population. From 2006 to 2017, the most used control method was culling from hunting hides. In our analysis, we did not find significant relationships between the number of shot boars and the damage amount. The factors that determine the decrease of damage probability to crops are mainly related to human disturbance and the characteristics of the fields. The predictive model of damage risk built comparing damaged and undamaged fields showed a good predictive ability. The population viability analyses showed that it is impossible to obtain a drastic reduction of population with the current harvest rate. By tripling it and focusing on the females and sub-adult a numerical reduction of 50% of the population would be achievable in 7 years and the probability of population survival would be halved in 3 years.

Safety of a New Sinus Irrigation Device in Rhinosinusitis: A Pilot Study.

Puncture and lavage of the paranasal sinuses, previously the primary treatment for unresponsive acute bacterial rhinosinusitis before surgery, has been abandoned due to procedural discomfort and advancements in antibiotic efficacy and endoscopic surgery. The rise in antibiotic-resistant bacteria has renewed the interest in minimally invasive sinus lavage to both avoid aggressive surgical interventions and identify appropriate antibiotic therapy. In this article, we describe the safety and feasibility of a new device in human patients and evaluate its efficacy as a treatment before the traditional sinus surgery in acute rhinosinusitis. The device with its seeker-shaped guiding tube and rotating wire can enter the sinus cavity through the natural ostium, pulverize the inspissated mucus, and enable lavage and culture sampling without the need for sinus puncturing. It was tested in 6 patients with chronic sinusitis under general anesthesia during endoscopic sinus surgery and in additional 10 patients with maxillary acute bacterial rhinosinusitis in outpatient settings under local anesthesia. The device enabled rapid, efficient, and atraumatic insertion of the wire into the occluded sinuses. The rotating wire permitted pulverization of the thick mucus, which enabled irrigation without mucosal damage or adverse events. Overall, 9 of 10 patients with acute bacterial rhinosinusitis demonstrated remarkable improvements and were discharged the following day with no acute symptoms. The visual analog scale score for pain dropped from 8.9 to 0.4. The remaining one patient underwent endoscopic sinus surgery subsequently. None of the patients treated during endoscopic sinus surgery developed any adverse events.

Canine Angiostrongylus vasorum-Induced Early Innate Immune Reactions Based on NETs Formation and Canine Vascular Endothelial Cell Activation In Vitro.

Simple SummaryAngiostrongylus vasorum is a cardiopulmonary nematode that affects canids, residing in the pulmonary artery and right atrium/ventricle. Due to its location, the parasite will have a close interaction with the different components of the innate immune system, including endothelial cells and polymorphonuclear neutrophils (PMN). Here we evaluated the expression of adhesion molecules of canine aortic endothelial cells (CAEC), and NETs formation by co-culture of freshly isolated canine PMN with A. vasorum L3. Overall, we found distinct inter-donor variations in adhesion molecule expression among CAEC isolates. Additionally, PMN and A. vasorum co-culture induced NETs release without affecting larval viability.Due to its localization in the canine blood stream, Angiostrongylus vasorum is exposed to circulating polymorphonuclear neutrophils (PMN) and the endothelial cells of vessels. NETs release of canine PMN exposed to A. vasorum infective stages (third stage larvae, L3) and early pro-inflammatory immune reactions of primary canine aortic endothelial cells (CAEC) stimulated with A. vasorum L3-derived soluble antigens (AvAg) were analyzed. Expression profiles of the pro-inflammatory adhesion molecules ICAM-1, VCAM-1, P-selectin and E-selectin were analyzed in AvAg-stimulated CAEC. Immunofluorescence analyses demonstrated that motile A. vasorum L3 triggered different NETs phenotypes, with spread NETs (sprNETs) as the most abundant. Scanning electron microscopy confirmed that the co-culture of canine PMN with A. vasorum L3 resulted in significant larval entanglement. Distinct inter-donor variations of P-selectin, E-selectin, ICAM-1 and VCAM-1 gene transcription and protein expression were observed in CAEC isolates which might contribute to the high individual variability of pathological findings in severe canine angiostrongylosis. Even though canine NETs did not result in larval killing, the entanglement of L3 might facilitate further leukocyte attraction to their surface. Since NETs have already been documented as involved in both thrombosis and endothelium damage events, we speculate that A. vasorum-triggered NETs might play a critical role in disease outcome in vivo.

Impact of DNA Adduct Size, Number, and Relative Position on the Toxicity of Aromatic Amines: A Molecular Dynamics Case Study of ANdG- and APdG-Containing DNA Duplexes.

Human exposure to aromatic amines (AAs) can result in carcinogenic DNA adducts. To complement previous work geared toward understanding the mutagenicity of AA-derived adducts, which has almost exclusively studied (monoadducted) DNA containing a single lesion, the present work provides the first in-depth comparison of the structure of monoadducted and diadducted DNA duplexes. Specifically, molecular dynamics (MD) simulations were initially performed on DNA containing the nonmutagenic single-ringed N-(deoxyguanosin-8-yl)-aniline (ANdG) or the mutagenic four-ringed N-(deoxyguanosin-8-yl)-1-aminopyrene (APdG) lesion at G1, G2, or G3 in the AA deletion hotspot (5'-G1G2CG3CC) in the anti or syn glycosidic orientation (B/S duplex conformation). Subsequently, diadducted strands were assessed that span each combination of damaged sites (G1G2 (nearest neighbors), G2G3 (next-nearest neighbors), and G1G3 (two intervening nucleotides)) and anti/syn lesion glycosidic orientations. Despite other N-linked C8-dG adducts exhibiting sequence dependence conformational heterogeneity, a single ANdG or APdG lesion induces helical conformational homogeneity that is exclusively controlled by aryl moiety size. However, the preferred damaged DNA conformation can change upon the addition of a second adduct depending on lesion separation, with neighboring lesions stabilizing a nonmutagenic conformation and next-nearest damaged sites stabilizing a promutagenic conformation regardless of adduct size. As a result, diadducted DNA is found to adopt conformations that are unfavored for the corresponding monoadducted system, pointing to differential replication and repair outcomes for diadducted DNA compared to those for monoadducted DNA. Thus, although the toxicity of monoadducted DNA is most significantly dictated by lesion size, the toxicity can increase or decrease upon a second damaging event depending on lesion size and relative position. Overall, our work adds the number of lesions and their spatial separation to the growing list of factors that determine the structure and biological outcomes of adducted DNA.

Microglial Adenosine Receptors: From Preconditioning to Modulating the M1/M2 Balance in Activated Cells.

Neuronal survival depends on the glia, that is, on the astroglial and microglial support. Neurons die and microglia are activated not only in neurodegenerative diseases but also in physiological aging. Activated microglia, once considered harmful, express two main phenotypes: the pro-inflammatory or M1, and the neuroprotective or M2. When neuroinflammation, i.e., microglial activation occurs, it is important to achieve a good M1/M2 balance, i.e., at some point M1 microglia must be skewed into M2 cells to impede chronic inflammation and to afford neuronal survival. G protein-coupled receptors in general and adenosine receptors in particular are potential targets for increasing the number of M2 cells. This article describes the mechanisms underlying microglial activation and analyzes whether these cells exposed to a first damaging event may be ready to be preconditioned to better react to exposure to more damaging events. Adenosine receptors are relevant due to their participation in preconditioning. They can also be overexpressed in activated microglial cells. The potential of adenosine receptors and complexes formed by adenosine receptors and cannabinoids as therapeutic targets to provide microglia-mediated neuroprotection is here discussed.