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Objective: Electronic cigarettes (e-cigs) are popular nicotine delivery devices, yet the health effects remain unclear. To determine equivalent biomarkers, we characterized the immediate response in Apoe -/- mice exposed to tank/box-mod e-cig (e-cig tank ), pod e-cig (e-cig pod ), or cig smoke., Materials and Methods: Reproducible puff profiles were generated for each aerosol and delivered to Apoe -/- mice via a nose-only exposure system. Serum cotinine levels were quantified at various time points through ELISA and utilized to model cotinine pharmacokinetics. In addition, particle size measurements and mouse respiratory function were characterized to calculate particle dosimetry., Results and Discussion: Cig and e-cig tank particles were lognormally distributed with similar count median diameters (cig: 178 ± 2, e-cig tank : 200 ± 34nm), while e-cig pod particles were bimodally distributed and smaller (116 ± 13 and 13.3 ± 0.4 nm). Minute volumes decreased with cig exposure (5.4 ± 2.7 mL/min) compared to baseline (90.8 ± 11.6 mL/min), and less so with e-cig tank (45.2 ± 9.2 mL/min) and e-cig pod exposures (58.6 ± 6.8 mL/min), due to periods of apnea in the cig exposed groups. Cotinine was absorbed and eliminated most rapidly in the e-cig pod group ( t max = 14.5; t 1 / 2 ' = 51.9 min), whereas cotinine was absorbed (cig: 50.4, e-cig tank : 40.1 min) and eliminated (cig: 104.6, e-cig tank : 94.1 min) similarly in the cig and e-cig tank groups. For exposure times which equate the area under the cotinine-concentration curve, ∼6.4× (e-cig tank ) and 4.6× (e-cig pod ) more nicotine deposited in e-cig compared to cig exposed mice., Conclusions: This study provides a basis for incorporating cotinine pharmacokinetics into preclinical exposure studies, allowing for longitudinal studies of structural and functional changes due to exposure.

The purpose of this article is to describe the helicopter emergency medical services (HEMS) presently operating in Italy. The article details all currently operational HEMS bases and all currently used helicopters. A comparison with the HEMS situation in Italy as it was previously described in 2005 is discussed., (Copyright © 2021. Published by Elsevier Inc.)

Currently, ~ 1.5 million American deaf-blind individuals depend on the availability of interpreting services to communicate in their primary conversational language, tactile American Sign Language (ASL). In an effort to give the deaf-blind community access to a device that facilitates independent communication using tactile ASL, we developed TATUM (Tactile ASL Translational User Mechanism). TATUM employs 15 degrees of actuation in a hand-wrist system that is capable of signing the 26-letter ASL alphabet. Leveraging Interpres, an independent cloud-based service, all servo sequences that render desired fingerspelled letters and ASL words are stored in a web application programming interface (API). A validation study including both deaf and deaf-blind participants confirmed that the TATUM hand mimics a human hand both in size and feel. The current design of TATUM attained an average recognition rate of 94.7% in visual validation, indicative of the potential to support deaf and deaf-blind individuals in communicating via visual and tactile ASL.

Adventitious rooting is a de novo organogenesis process that enables plants to propagate clonally and cope with environmental stresses. Adventitious root initiation (ARI) is controlled by interconnected transcriptional and hormonal networks, but there is little knowledge of the genetic and molecular programs orchestrating these networks. Thus, we have applied genome-wide transcriptome profiling to elucidate the transcriptional reprogramming events preceding ARI. These reprogramming events are associated with the down-regulation of cytokinin (CK) signaling and response genes, which could be triggers for ARI. Interestingly, we found that CK free base (iP, tZ, cZ, and DHZ) content declined during ARI, due to down-regulation of de novo CK biosynthesis and up-regulation of CK inactivation pathways. We also found that MYC2-dependent jasmonate (JA) signaling inhibits ARI by down-regulating the expression of the CYTOKININ OXIDASE/DEHYDROGENASE1 (CKX1) gene. We also demonstrated that JA and CK synergistically activate expression of the transcription factor RELATED to APETALA2.6 LIKE (RAP2.6L), and constitutive expression of this transcription factor strongly inhibits ARI. Collectively, our findings reveal that previously unknown genetic interactions between JA and CK play key roles in ARI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Emission measurements are available in the literature for a wide variety of field burns and laboratory experiments, although previous studies do not always isolate the effect of individual features such as fuel moisture content (FMC). This study explores the effect of FMC on gaseous and particulate emissions from flaming and smouldering combustion of four different wildland fuels found across the United States. A custom linear tube-heater apparatus was built to steadily produce emissions in different combustion modes over a wide range of FMC. Results showed that when compared with flaming combustion, smouldering combustion showed increased emissions of CO, particulate matter and unburned hydrocarbons, corroborating trends in the literature. CO and particulate matter emissions in the flaming mode were also significantly correlated with FMC, which had little influence on emissions for smouldering mode combustion, when taking into account the dry mass of fuel burned. These variations occurred for some vegetative fuel species but not others, indicating that the type of fuel plays an important role. This may be due to the chemical makeup of moist and recently live fuels, which is discussed and compared with previous measurements in the literature., Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Background: High-grade gliomas are among the most aggressive central nervous system primary tumors, with a high risk of recurrence and a poor prognosis. Re-operation, re-irradiation, chemotherapy are options in this setting. No-best therapy has been established. Bevacizumab was approved on the basis of two Phase 2 trials that evaluated its efficacy in patients with recurrent glioblastoma., Materials and Methods: We have retrospectively review data of patients with high-grade glioma treated at our institution that undergone radiological or histological progression after at least one systemic treatment for recurrent disease. Bevacizumab was administered alone or in combination with chemotherapy until disease progression or unacceptable toxicity. Bevacizumab regimen was analyzed to assess PFS and OS. Histological, molecular and clinical features of the entire cohort were collected., Results: We reviewed data from 92 patients, treated from April 2009 to November 2019, with histologically confirmed diagnosis of high-grade gliomas and recurrent disease. A PFS of 55.2%, 22.9% and 9.6% was observed at 6, 12 and 24 months, respectively. Performance status, age at diagnosis (< 65 or > 65 ys.) and use of corticosteroids during bevacizumab therapy were strongly associated with PFS. The OS was 74.9% at 6 months, 31.7% at 12 months, 10.1% at 24 months. In our cohort, 51.1% were long-term responders (PFS > 6 months). Globally, bevacizumab treatment was well tolerated., Conclusion: Our analysis confirms the efficacy of bevacizumab in recurrent high-grade glioma patients with an acceptable toxicity profile, in keeping with its known safety in the literature., (© 2021. The Author(s).)

Objective: Sex-/age-differentiated cutoffs and the magnitude of serial changes in high-sensitivity cardiac troponins (hs-cTn) for acute coronary syndrome (ACS) diagnosis algorithms are still under discussion. This study presents a methodology to evaluate decision-making limits and to assess whether sex-specific cutoffs could improve diagnostic accuracy., Methods: A high-sensitivity cardiac troponin T (hs-cTnT) 0-/3-hour protocol was adopted, applying the 2015 European Society of Cardiology Guidelines. Decision-making limits (99th percentile: 14 ng/L; delta change ≥ 30%) were agreed upon with the emergency department (ED) at the University Hospital of Siena in Siena, Italy. One-year requests (5177) for hs-cTnT serial determination were compared with the final International Classification of Diseases, 9th revision, clinical modifications diagnosis (contingency tables; receiver operating characteristic curves)., Results: The algorithm's capability to exclude or confirm ACS was verified by remarkable negative predictive value (97%) and high areas under the curve for the first troponin sampling (0.712), troponin sampling at 3 hours (0.789), and delta (0.744). The clinical utility for the general population-even those with comorbidities-accessing the ED was verified. Our data did not support a sex-differentiated cutoff utility because it would not have affected patient management., Conclusion: This methodology allowed us to confirm the effectiveness of our decision-making limits., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Wildfires are now a common feature of the western US, increasing in both intensity and number of acres burned over the last three decades. The effects of this changing wildfire and smoke landscape are a critical public and occupational health issue. While respiratory morbidity due to smoke exposure is a priority, evaluating the molecular underpinnings that explain recent extrapulmonary observations is necessary. Here, we use an Apoe -/- mouse model to investigate the epigenetic impact of paternal exposure to simulated wildfire smoke. We demonstrate that 40 days of exposure to smoke from Douglas fir needles induces sperm DNA methylation changes in adult mice. DNA methylation was measured by reduced representation bisulfite sequencing and varied significantly in 3353 differentially methylated regions, which were subsequently annotated to 2117 genes. The differentially methylated regions were broadly distributed across the mouse genome, but the vast majority (nearly 80%) were hypermethylated. Pathway analyses, using gene-derived and differentially methylated region-derived gene ontology terms, point to a number of developmental processes that may warrant future investigation. Overall, this study of simulated wildfire smoke exposure suggests paternal reproductive risks are possible with prolonged exposure.

The present article shows the current neonatal air transport organization and activity in Italy. The results were obtained on the basis of a recent 2019 survey (year of activity 2018) performed by the Neonatal Transport Study Group of the Italian Society of Neonatology. The total number of newborn transports during the year 2018 was 6,464. The air-suitable transports were 512 of 5,852 (8.74%), and among them, 101 of 512 (19.72%) were performed by helicopter and 34 by airplane. Besides the availability of air transport, the interfacility distance, weather and traffic conditions, and rural mountainous roads were the main factors in determining the vehicle choice. Neonatal air transport in Italy is not homogeneously distributed and needs organizational corrections. The high density of neonatal emergency transport services on the national territory indicates the need to overcome the limits imposed by regional administrative borders, thus expanding the geographic area of competence., (Copyright © 2021. Published by Elsevier Inc.)

Despite a decline in popularity over the past several decades, cigarette smoking remains a leading cause of cardiovascular morbidity and mortality. Yet, the effects of cigarette smoking on vascular structure and function are largely unknown. To evaluate changes in the mechanical properties of the aorta that occur with chronic smoking, we exposed female apolipoprotein E-deficient mice to mainstream cigarette smoke daily for 24 wk, with room air as control. By the time of euthanasia, cigarette-exposed mice had lower body mass but experienced larger systolic/diastolic blood pressure when compared with controls. Smoking was associated with significant wall thickening, reduced axial stretch, and circumferential material softening of the aorta. Although this contributed to maintaining intrinsic tissue stiffness at control levels despite larger pressure loads, the structural stiffness became significantly larger. Furthermore, the aorta from cigarette-exposed mice exhibited decreased ability to store elastic energy and augment diastolic blood flow. Histological analysis revealed a region-dependent increase in the cross-sectional area due to smoking. Increased smooth muscle and extracellular matrix content led to medial thickening in the ascending aorta, whereas collagen deposition increased the thickness of the descending thoracic and abdominal aorta. Atherosclerotic lesions were larger in exposed vessels and featured a necrotic core overlaid by a thinned fibrous cap and macrophage infiltration, consistent with a vulnerable phenotype. Collectively, our data indicate that cigarette smoking decreases the mechanical functionality of the aorta, inflicts morphometric alterations to distinct segments of the aorta, and accelerates the progression of atherosclerosis. NEW & NOTEWORTHY We studied the effects of chronic cigarette smoking on the structure and function of the aorta in a mouse model of nose-only aerosol inhalation. Our data indicated that exposure to cigarette smoke impairs vascular function by reducing the ability of the aorta to store elastic energy and by decreasing aortic distensibility. Combined with a more vulnerable atherosclerotic phenotype, these findings reveal the biomechanical mechanisms that support the development of cardiovascular disease due to cigarette smoking.

Populus spp. are among the most economically important species worldwide. These trees are used not only for wood and fiber production, but also in the rehabilitation of degraded lands. Since they are clonally propagated, the ability of stem cuttings to form adventitious roots is a critical point for plant establishment and survival in the field, and consequently for the forest industry. Adventitious rooting in different Populus clones has been an agronomic trait targeted in breeding programs for many years, and many factors have been identified that affect this quantitative trait. A huge variation in the rooting capacity has been observed among the species in the Populus genus, and the responses to some of the factors affecting this trait have been shown to be genotype-dependent. This review analyses similarities and differences between results obtained from studies examining the role of internal and external factors affecting rooting of Populus species cuttings. Since rooting is the most important requirement for stand establishment in clonally propagated species, understanding the physiological and genetic mechanisms that promote this trait is essential for successful commercial deployment., 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 Bannoud and Bellini.)

Spinal cord infarction is a rare but severe disorder, consistently less frequent than ischemic brain injury. It constitutes only 1-2% of all neurological vascular emergencies. Here we describe a case of spinal cord infarction in a 68-year-old Caucasian man without any neurological problem in his clinical history. The patient presented to the Emergency Department complaining for sudden onset of lower limbs weakness, as well as pain and mild loss of sensitivity in both legs. These symptoms suddenly arose after a 10 minutes bicycle race. He underwent a CT angiography, which confirmed the presence of a fusiform aneurysm of infra-renal abdominal aorta with thrombotic apposition on right lateral side and some ulcerated thrombi. As such, the patient underwent a spinal cord Magnetic Resonance Imaging, that showed images compatible with an acute ischemic injury (infarction) from D11 to medullary cone. He was then treated with low molecular weight heparin, aspirin, and methylprednisolone, and was then admitted to the Stroke Unit. He gradually regained lower limbs sensitivity totally, but the strength was only partially restored. Although a rare entity, Emergency Physicians should always keep in mind this possibility when evaluating patients with sudden loss of sensitivity and/or strength in their lower limbs.

Objective: The purpose of this study was to find a predictive equation for estimating the optimal nasal endotracheal tube insertion depth in extremely low-birth weight infants (ELBWs) requiring invasive ventilation in the critical care interfacility transport setting., Methods: We retrospectively calculated the optimal tube insertion depth in a cohort of neonates ≤ 1,000 g born at our neonatal intensive care unit and nasally intubated within the first 24 hours of life from January 2019 to May 2020., Results: A total of 75 ELBW infants were included, with a median gestational age of 26.6 weeks (range, 22.1-32.6 weeks) and a median birth weight of 780 g (range, 410-990 g). The linear regression of the estimated optimal endotracheal tube insertion depth showed a good correlation when plotted against weight (R 2  = 0.491); thus, a new weight-based formula was obtained., Conclusion: The proposed weight-based formula (the "Genoa formula") may help in predicting optimal insertion depths for nasal intubation in ELBW neonates, especially when a prompt radiologic confirmation of the tube position is not available, as during neonatal critical care transport., (Copyright © 2020. Published by Elsevier Inc.)

Background: In Switzerland each year, influenza leads to between 112,000 and 275,000 medical consultations. Data on nosocomial influenza infection are limited., Aim: To describe nosocomial cases of seasonal influenza in south-western Switzerland., Methods: This study was conducted during two seasonal influenza epidemics from 2016 to 2018 in 27 acute care public hospitals in south-western Switzerland. During these two time-periods, every patient hospitalized for >72 h who was positively screened by reverse transcription-polymerase chain reaction or antigen detection for influenza was included in the survey. Characteristics of patients included age, sex, and comorbidities. Included patients were followed up until discharge or death. Complications and administration of antineuraminidases and/or antibiotics were registered., Findings: The median influenza vaccine coverage of healthcare workers was 40%. In all, 836 patients were included (98% with type A influenza virus in 2016-2017; 77% with type B virus in 2017-2018). Most patients (81%) had an unknown vaccine status. Overall, the incidence of nosocomial influenza was 0.5 per 100 admissions (0.35 per 1000 patient-days). The most frequent comorbidities were diabetes (20%), chronic respiratory diseases (19%), and malnutrition (17%). Fever (77%) and cough (66%) were the most frequent symptoms. Seventy-one percent of patients received antineuraminidases, 28% received antibiotics. Infectious complications such as pneumonia were reported in 9%. Overall, the all-cause mortality was 6%., Conclusion: The occurrence of nosocomial influenza underlines the importance of vaccinating patients and healthcare workers, rapidly recognizing community- or hospital-acquired cases, and applying adequate additional measures to prevent dissemination, including the timely administration of antineuraminidases to avoid antibiotic use (and misuse)., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Post-haemorrhagic ventricular dilatation (PHVD) still represents an important cause of brain injury in premature infants. Intervention for PHVD is recommended once Ventricular Index (VI) crosses the 97th percentile + 4 mm line according to Levene., Objectives: We aimed to compare PHVD severity, timing of intervention, and outcome between outborn infants transferred to a level IV NICU in order to be treated for PHVD and a control population of inborn infants., Methods: Preterm infants with PHVD requiring treatment were divided into: outborn infants (transferred to our NICU in order to be treated for PHVD) and inborn infants (PHVD diagnosed at our NICU). Age at intervention, difference between VI and the 97th percentile according to postmenstrual age (VI-p97), permanent shunt rate, and developmental delay rate were compared between the two groups. Neurodevelopmental outcome was assessed using the Vineland Adaptive Behavior Scales II (VABS-II), a parental questionnaire investigating four domains of adaptive behaviour and overall adaptive functioning. Developmental delay was defined as a score <70 (-2 SD or less)., Results: Twelve outborn and 15 inborn infants were included. Age at intervention (31.6 vs 17.4 days) and VI-p97 (left 10.0 vs 5.1 mm, right 7.7 vs 5.1 mm) were significantly higher among outborn infants. A permanent shunt was inserted in 66.7% of outborn and in 40.0% of inborn infants (p = 0.18). After excluding subjects with parenchymal lesions, a significantly higher rate of developmental delay was observed at 5 years in outborn patients compared to inborn patients (66.7% of outborn vs 18.2% of inborn patients with VABS-II composite score <70, p = 0.04)., Conclusions: Outborn infants reached a significantly more severe ventricular dilatation than inborn infants, largely exceeding the recommended cutoff for intervention. Our follow-up data showed a trend towards a higher rate of permanent shunt and developmental delay in outborn than in inborn patients. Infants requiring treatment should be timely transported to centres with adequate expertise in PHVD management., (©2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

The World Health Organization (WHO) herald of the "End TB Strategy" has defined goals and targets for tuberculosis prevention, care, and control to end the global tuberculosis endemic. The emergence of drug resistance and the relative dreadful consequences in treatment outcome has led to increased awareness on immunization against Mycobacterium tuberculosis ( Mtb ). However, the proven limited efficacy of Bacillus Calmette-Guérin (BCG), the only licensed vaccine against Mtb , has highlighted the need for alternative vaccines. In this review, we seek to give an overview of Mtb infection and failure of BCG to control it. Afterward, we focus on the protein- and peptide-based subunit vaccine subtype, examining the advantages and drawbacks of using this design approach. Finally, we explore the features of subunit vaccine candidates currently in pre-clinical and clinical evaluation, including the antigen repertoire, the exploited adjuvanted delivery systems, as well as the spawned immune response.

Adventitious root initiation (ARI) is a de novo organogenesis program and a key adaptive trait in plants. Several hormones regulate ARI but the underlying genetic architecture that integrates the hormonal crosstalk governing this process remains largely elusive. In this study, we use genetics, genome editing, transcriptomics, hormone profiling and cell biological approaches to demonstrate a crucial role played by the APETALA2/ETHYLENE RESPONSE FACTOR 115 transcription factor. We demonstrate that ERF115 functions as a repressor of ARI by activating the cytokinin (CK) signaling machinery. We also demonstrate that ERF115 is transcriptionally activated by jasmonate (JA), an oxylipin-derived phytohormone, which represses ARI in NINJA-dependent and independent manners. Our data indicate that NINJA-dependent JA signaling in pericycle cells blocks early events of ARI. Altogether, our results reveal a previously unreported molecular network involving cooperative crosstalk between JA and CK machineries that represses ARI., (©2020 The Authors. New Phytologist ©2020 New Phytologist Trust.)

Computational modeling of cardiovascular flows is becoming increasingly important in a range of biomedical applications, and understanding the fundamentals of computational modeling is important for engineering students. In addition to their purpose as research tools, integrated image-based computational fluid dynamics (CFD) platforms can be used to teach the fundamental principles involved in computational modeling and generate interest in studying cardiovascular disease. We report the results of a study performed at five institutions designed to investigate the effectiveness of an integrated modeling platform as an instructional tool and describe "best practices" for using an integrated modeling platform in the classroom. Use of an integrated modeling platform as an instructional tool in nontraditional educational settings (workshops, study abroad programs, in outreach) is also discussed. Results of the study show statistically significant improvements in understanding after using the integrated modeling platform, suggesting such platforms can be effective tools for teaching fundamental cardiovascular computational modeling principles., (Copyright © 2020 by ASME.)

Objective: A lack of consensus exists about the appropriate criteria to activate a helicopter during neonatal transport. The aim of the present study was to explore the possible guiding criteria to justify helicopter activation for neonatal transport (NETS)., Methods: This was a retrospective study of the Gaslini Genoa NETSs from February 1995 to December 2019. The flight and driving times and the reason for helicopter neonatal transport activation were obtained for every subject from the online NETS clinical database. Driving and flight data (mean and standard deviation [SD]) were compared using the Student t-test (P < .05)., Results: Five thousand eight hundred sixty-six transported newborn infants were identified. A significant difference emerged between the overall ground (mean = 99.2 minutes [SD = 15.7 minutes]) and overall helicopter transport times (mean = 27.8 minutes [SD = 11.9 minutes], P < .0001). Considering the "golden hour," the chance to stabilize the patient within this time frame could have been possible for 4 of 5 neonatal care centers when using a helicopter., Conclusion: On the basis of our observations, we suggest including the golden hour as 1 of the guiding criteria justifying helicopter activation, especially if applied to the reason of transport and the quality of assistance the newborn will receive while waiting for the NETS team., (Copyright © 2020. Published by Elsevier Inc.)

Vegetative propagation relies on the capacity of plants to regenerate de novo adventitious roots (ARs), a quantitative trait controlled by the interaction of endogenous factors, such as hormones and environmental cues among which light plays a central role. However, the physiological and molecular components mediating light cues during AR initiation (ARI) remain largely elusive. Here, we explored the role of red light (RL) on ARI in de-rooted Norway spruce seedlings. We combined investigation of hormone metabolism and gene expression analysis to identify potential signaling pathways. We also performed extensive anatomical characterization to investigate ARI at the cellular level. We showed that in contrast to white light, red light promoted ARI likely by reducing jasmonate (JA) and JA-isoleucine biosynthesis and repressing the accumulation of isopentyl-adenine-type cytokinins. We demonstrated that exogenously applied JA and/or CK inhibit ARI in a dose-dependent manner and found that they possibly act in the same pathway. The negative effect of JA on ARI was confirmed at the histological level. We showed that JA represses the early events of ARI. In conclusion, RL promotes ARI by repressing the accumulation of the wound-induced phytohormones JA and CK., (Copyright © 2020 Alallaq, Ranjan, Brunoni, Novák, Lakehal and Bellini.)

In response to the COVID-19 pandemic, cloth masks are being used to control the spread of virus, but the efficacy of these loose-fitting masks is not well known. Here, tools and methods typically used to assess tight-fitting respirators were modified to quantify the efficacy of community-produced and commercially produced fabric masks as personal protective equipment. Two particle counters concurrently sample ambient air and air inside the masks; mask performance is evaluated by mean particle removal efficiency and statistical variability when worn as designed and with a nylon overlayer, to independently assess fit and material. Worn as designed, both commercial surgical masks and cloth masks had widely varying effectiveness (53%-75% and 28%-91% particle removal efficiency, respectively). Most surgical-style masks improved with the nylon overlayer, indicating poor fit. This rapid testing method uses widely available hardware, requires only a few calculations from collected data, and provides both a holistic and aspect-wise evaluation of mask performance., Competing Interests: The authors declare no competing interests., (© 2020 Elsevier Inc.)

Pulmonary disease increases the risk of developing abdominal aortic aneurysms (AAA). However, the mechanism underlying the pathological dialogue between the lungs and aorta is undefined. Here, we find that inflicting acute lung injury (ALI) to mice doubles their incidence of AAA and accelerates macrophage-driven proteolytic damage of the aortic wall. ALI-induced HMGB1 leaks and is captured by arterial macrophages thereby altering their mitochondrial metabolism through RIPK3. RIPK3 promotes mitochondrial fission leading to elevated oxidative stress via DRP1. This triggers MMP12 to lyse arterial matrix, thereby stimulating AAA. Administration of recombinant HMGB1 to WT, but not Ripk3 -/- mice, recapitulates ALI-induced proteolytic collapse of arterial architecture. Deletion of RIPK3 in myeloid cells, DRP1 or MMP12 suppression in ALI-inflicted mice repress arterial stress and brake MMP12 release by transmural macrophages thereby maintaining a strengthened arterial framework refractory to AAA. Our results establish an inter-organ circuitry that alerts arterial macrophages to regulate vascular remodeling.

Background As defined by ISO 15189 competence is the "demonstrated ability to apply knowledge and skills" thus, its assessment is fundamental for ensuring the quality of the total testing process in order to reduce the risk for the patient. We have developed a functional software for the measurement of professional competences in order to standardize the procedure and to collect all the data in a single platform, avoiding redundancy and dispersion. Methods Our model objectively assesses the skills, as they become measurable and comparable with appropriate standards and involves both managers and operators, to increase their active engagement. The assessment concerns everyone, but the standards to be met (numerical values) can vary according to the responsibilities. Several subjective and objective criteria are evaluated: each parameter can contribute in a variable proportion to the total skills measured according to the needs of the organization. Results The data are automatically analyzed and can be easily monitored in real time in the form of indicators, thanks to dashboards. The comparison between the skills required and those measured allows highlighting the gap useful for planning personalized training paths. Conclusions Our tool is reliable and highly adaptable to laboratories about competences to track criteria, standards and monitored indicators. The computerized management is a strategic action as it fulfills the requirements of registration, traceability, communication, data analysis and indicators development, which are the tenets of continuous improvement, and allows planning to be made on the basis of the actual training needs.

Objectives: Increased central artery stiffness associates with cardiovascular disease. Among other factors, hypertension and aging are strong contributors to central artery stiffening, yet it has been difficult to separate their effects. Herein, we study isolated and combined effects of hypertension and aging on central artery remodeling in multiple mouse models as a function of sex., Methods: We biomechanically phenotyped the aorta as a function of two different methods of inducing hypertension [infusion of angiotensin II (AngII) or combining a high salt diet with inhibition of endothelial-derived nitric oxide synthase using L-NAME] in male and female wild-type and fibulin-5 null mice, the latter of which models aspects of aortic aging., Results: Despite increasing blood pressure similarly, salt + L-NAME led to adaptive and maladaptive remodeling in the abdominal and thoracic aorta, respectively, whereas AngII caused luminal dilatation but little remodeling of the wall. Importantly, effects of aging were more dramatic than those resulting from induced hypertension and, consequently, superimposing hypertension on aging led to modest additional changes in luminal radius and wall thickness, though wall stress and stiffness increased mainly because of the elevated pressure., Conclusion: Our results suggest that effects of hypertension on aortic remodeling are modest when superimposed on aging in mice, largely independent of sex. These findings are consistent with general observations in humans and in spontaneously hypertensive rats, though separated here for the first time in a rodent model characterized by a severe loss of elastic fiber integrity similar to that found in the aged human aorta.

Subcutaneous ( s.c. ) tumor models are widely used in pre-clinical cancer metastasis research. Despite this, the dynamics and natural progression of circulating tumor cells (CTCs) and CTC clusters (CTCCs) in peripheral blood are poorly understood in these models. In this work, we used a new technique called 'diffuse in vivo flow cytometry' (DiFC) to study CTC and CTCC dissemination in an s.c. Lewis lung carcinoma (LLC) model in mice. Tumors were grown in the rear flank and we performed DiFC up to 31 days after inoculation. At the study endpoint, lungs were excised and bioluminescence imaging (BLI) was performed to determine the extent of lung metastases. We also used fluorescence macro-cryotome imaging to visualize infiltration and growth of the primary tumor. DiFC revealed significant heterogeneity in CTC and CTCC numbers amongst all mice studied, despite using clonally identical LLC cells and tumor placement. Maximum DiFC count rates corresponded to 0.1 to 14 CTCs per mL of peripheral blood. In general, CTC numbers did not necessarily increase monotonically over time and were poorly correlated with tumor volume. However, there was a good correlation between CTC and CTCC numbers in peripheral blood and lung metastases. We attribute the differences in CTC numbers primarily due to growth patterns of the primary tumor. This study is one of the few reports of CTC shedding dynamics in sub-cutaneous metastasis models and underscores the value of in vivo methods for continuous, non-invasive CTC monitoring., Competing Interests: The authors report no conflicts of interest., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

The left atrium (LA) has a complex anatomy with heterogeneous wall thickness and curvature. The anatomy plays an important role in determining local wall stress; however, the relative contribution of wall thickness and curvature in determining wall stress in the LA is unknown. We have developed electromechanical finite element (FE) models of the LA using patient-specific anatomical FE meshes with rule-based myofiber directions. The models of the LA were passively inflated to 10mmHg followed by simulation of the contraction phase of the atrial cardiac cycle. The FE models predicted maximum LA volumes of 156.5 mL, 99.3 mL and 83.4 mL and ejection fractions of 36.9%, 32.0% and 25.2%. The median wall thickness in the 3 cases was calculated as [Formula: see text] mm, [Formula: see text] mm, and [Formula: see text] mm. The median curvature was determined as [Formula: see text] [Formula: see text], [Formula: see text], and [Formula: see text]. Following passive inflation, the correlation of wall stress with the inverse of wall thickness and curvature was 0.55-0.62 and 0.20-0.25, respectively. At peak contraction, the correlation of wall stress with the inverse of wall thickness and curvature was 0.38-0.44 and 0.16-0.34, respectively. In the LA, the 1st principal Cauchy stress is more dependent on wall thickness than curvature during passive inflation and both correlations decrease during active contraction. This emphasizes the importance of including the heterogeneous wall thickness in electromechanical FE simulations of the LA. Overall, simulation results and sensitivity analyses show that in complex atrial anatomy it is unlikely that a simple anatomical-based law can be used to estimate local wall stress, demonstrating the importance of FE analyses.

Dynamic regulation of the concentration of the natural auxin (IAA) is essential to coordinate most of the physiological and developmental processes and responses to environmental changes. Oxidation of IAA is a major pathway to control auxin concentrations in angiosperms and, along with IAA conjugation, to respond to perturbation of IAA homeostasis. However, these regulatory mechanisms remain poorly investigated in conifers. To reduce this knowledge gap, we investigated the different contributions of the IAA inactivation pathways in conifers. MS-based quantification of IAA metabolites under steady-state conditions and after perturbation was investigated to evaluate IAA homeostasis in conifers. Putative Picea abies GH3 genes (PaGH3) were identified based on a comprehensive phylogenetic analysis including angiosperms and basal land plants. Auxin-inducible PaGH3 genes were identified by expression analysis and their IAA-conjugating activity was explored. Compared to Arabidopsis, oxidative and conjugative pathways differentially contribute to reduce IAA concentrations in conifers. We demonstrated that the oxidation pathway plays a marginal role in controlling IAA homeostasis in spruce. By contrast, an excess of IAA rapidly activates GH3-mediated irreversible conjugation pathways. Taken together, these data indicate that a diversification of IAA inactivation mechanisms evolved specifically in conifers., (© 2020 The Authors New Phytologist © 2020 New Phytologist Trust.)

Objective: The rapid increase of cannabis consumption reinforces the need to elucidate the health hazards of this practice. The presence of fine particulate matter in cannabis smoke and vapor poses a major concern, as it may contribute to cardiopulmonary disease. To facilitate the assessment of risks associated with cannabis inhalation, we developed and characterized a method for exposing mice to cannabis in a way that mimics the delivery of the drug to the airways of smokers. Materials and Methods: Cannabis (10.3% THC, 0.05% CBD) was vaporized to generate aerosols with a reproducible particle profile. Aerosols were acutely delivered to male, adult C57BL/6 mice via a nose-only exposure system. Serum THC levels were measured for increasing cannabis doses. Blood pressure and heart rate were recorded at baseline and following exposure. Behavioral response to cannabis inhalation in the open field was documented. Awake neurological activity upon cannabis exposure was monitored using BOLD fMRI. Results and Discussion: Cannabis aerosols contained particles with count median diameter of 243 ± 39 nm and geometric standard deviation of 1.56 ± 0.06. Blood serum THC levels increased linearly with aerosolized mass and peaked at 136 ± 5 ng/mL. Cannabis inhalation decreased heart rate and blood pressure but promoted anxiety-like behavior. Observed differences in BOLD activation volumes linked cannabis to increased awareness to sensory stimuli and reduced behavioral arousal. Conclusions: Quantified physiological, behavioral, and neurological responses served as validation for our mouse model of cannabis inhalation. Animal models of aerosol exposure will be instrumental for uncovering the health outcomes of chronic cannabis use.

Objective: Our scope is to provide methodological elements on how to manage effectively the preanalytical phase in the laboratory testing process, by objectively measuring the risk connected to the phases handled by man with respect to those managed by machines., Background: Preanalytical errors account for most of the mistakes related to laboratory testing and can affect patient care. Hence, it is necessary to manage the risk connected to the preanalytical phase, as required by certification and accreditation bodies. The risk assessment discloses the steps at greater risk and gives indications to make decisions., Method: We have reviewed the state of art in the automation of the preanalytical phase, addressing needs and problems. We have used the proactive risk assessment methodology FMECA (Failure Mode, Effects, and Criticality Analysis) to identify the most critical phases in our preanalytical process and have calculated the risk associated., Results: The most critical phases were the human controlled ones. In particular, the highest risk indexes were associated to manual acceptance of test orders, identification of the patients, tube labeling, and sample collection., Conclusion: Automation in the preanalytical phase is fundamental to replace, support, or extend the human contribution. Nevertheless each organization is different about workloads and competencies, so the most suitable management must be tailor-made in each context., Application: We present a method by which each organization is able to find its best balance between automation and human contribution in the control of the preanalytical phase.

The root system and its architecture enormously contribute to plant survival and adaptation to the environment. Depending on the intrinsic genetic information and the surrounding rhizosphere, plants develop a highly plastic root system, which is a critical determinant for survival. Plant root system, which includes primary root (PR), lateral roots (LR) and adventitious roots (AR), is shaped by tightly controlled developmental programs. Phytohormones are the main signaling components that orchestrate and coordinate the genetic information and the external stimuli to shape the root system patterning or rhizotaxis. Besides their role in plant stress responses and defense against herbivory and pathogen attacks, jasmonic acid and its derivatives, including the receptor-active conjugate jasmonoyl-L-isoleucine (JA-Ile), emerge as potential regulators of rhizotaxis. In this chapter, we summarize and discuss the recent progress achieved during the recent years to understand the JA-mediated genetic and molecular networks guiding PR, LR, and AR initiation. We highlight the role of JAs as critical integrators in shaping rhizotaxis.

Purpose: Different authors have reported that aging could be associated with changes in obstructive sleep apnea (OSA) related parameters (apnea/hypopnea index, SpO 2 , reduction of daytime sleepiness, etc.), type of sleep and pattern of collapse. Regarding OSA severity in elderly patients, it is commonly believed that the AHI score tends to increase with aging., Methods: In this paper, we reviewed the literature regarding the studies which compared older (> 65 years old) and young (< 65 years old) OSA patients regarding the effect of aging on daytime sleepiness (ESS evaluation) and OSA severity (AHI evaluation). A meta-analysis to evaluate the effect of age on daytime sleepiness and OSAS severity was also performed to corroborate previously reported experience., Results: Meta-analysis showed no statistical (p = 0.8) differences regarding AHI differences emerged from the comparison of the two groups of patients. Elderly patients (> 65 years old) showed less daytime sleepiness, showing a statistical difference in the meta-analysis of data (p = 0.004) CONCLUSION: Although a direct correlation between aging and AHI values would seem to be present, no significant differences in baseline AHI between young (< 65-years-old) and elderly (> 65-years-old) patients emerged in this meta-analysis study. The effects of OSAS on daytime sleepiness seem to be much more prominent in young or middle-aged patients than in elderly patients.

Background: Plants rely on concentration gradients of the native auxin, indole-3-acetic acid (IAA), to modulate plant growth and development. Both metabolic and transport processes participate in the dynamic regulation of IAA homeostasis. Free IAA levels can be reduced by inactivation mechanisms, such as conjugation and degradation. IAA can be conjugated via ester linkage to glucose, or via amide linkage to amino acids, and degraded via oxidation. Members of the UDP glucosyl transferase (UGT) family catalyze the conversion of IAA to indole-3-acetyl-1-glucosyl ester (IAGlc); by contrast, IAA is irreversibly converted to indole-3-acetyl-l-aspartic acid (IAAsp) and indole-3-acetyl glutamic acid (IAGlu) by Group II of the GRETCHEN HAGEN3 (GH3) family of acyl amido synthetases. Dioxygenase for auxin oxidation (DAO) irreversibly oxidizes IAA to oxindole-3-acetic acid (oxIAA) and, in turn, oxIAA can be further glucosylated to oxindole-3-acetyl-1-glucosyl ester (oxIAGlc) by UGTs. These metabolic pathways have been identified based on mutant analyses, in vitro activity measurements, and in planta feeding assays. In vitro assays for studying protein activity are based on producing Arabidopsis enzymes in a recombinant form in bacteria or yeast followed by recombinant protein purification. However, the need to extract and purify the recombinant proteins represents a major obstacle when performing in vitro assays., Results: In this work we report a rapid, reproducible and cheap method to screen the enzymatic activity of recombinant proteins that are known to inactivate IAA. The enzymatic reactions are carried out directly in bacteria that produce the recombinant protein. The enzymatic products can be measured by direct injection of a small supernatant fraction from the bacterial culture on ultrahigh-performance liquid chromatography coupled to electrospray ionization tandem spectrometry (UHPLC-ESI-MS/MS). Experimental procedures were optimized for testing the activity of different classes of IAA-modifying enzymes without the need to purify recombinant protein., Conclusions: This new method represents an alternative to existing in vitro assays. It can be applied to the analysis of IAA metabolites that are produced upon supplementation of substrate to engineered bacterial cultures and can be used for a rapid screening of orthologous candidate genes from non-model species., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

In Arabidopsis thaliana, canonical auxin-dependent gene regulation is mediated by 23 transcription factors from the AUXIN RESPONSE FACTOR (ARF) family that interact with auxin/indole acetic acid repressors (Aux/IAAs), which themselves form co-receptor complexes with one of six TRANSPORT INHIBITOR1/AUXIN-SIGNALLING F-BOX (TIR1/AFB) proteins. Different combinations of co-receptors drive specific sensing outputs, allowing auxin to control a myriad of processes. ARF6 and ARF8 are positive regulators of adventitious root initiation upstream of jasmonate, but the exact auxin co-receptor complexes controlling the transcriptional activity of these proteins has remained unknown. Here, using loss-of-function mutants we show that three Aux/IAA genes, IAA6, IAA9, and IAA17, act additively in the control of adventitious root (AR) initiation. These three IAA proteins interact with ARF6 and/or ARF8 and likely repress their activity in AR development. We show that TIR1 and AFB2 are positive regulators of AR formation and TIR1 plays a dual role in the control of jasmonic acid (JA) biosynthesis and conjugation, as several JA biosynthesis genes are up-regulated in the tir1-1 mutant. These results lead us to propose that in the presence of auxin, TIR1 and AFB2 form specific sensing complexes with IAA6, IAA9, and/or IAA17 to modulate JA homeostasis and control AR initiation., (Copyright © 2019 The Author. Published by Elsevier Inc. All rights reserved.)

Aims: The use of electroanatomical mapping (EAM) systems can reduce radiation exposure (RX) and it can also completely eliminate the use of RX. Radiation exposure related to conventional radiofrequency ablation procedures can have a stochastic and deterministic effect on health. The main aim of this study was to evaluate the safety and feasibility of an entirely nonfluoroscopic approach to catheter ablation (CA) using EAM CARTO3., Methods: In 2011 we started an RX-minimization programme in all procedures using the CARTO system with the deliberate intention to not resort to the aid of RX unless strictly necessary. We divided procedures into two groups (group 1: from 2011 to 2013; group 2: from 2014 to 2017). The only exclusion criteria were the need for transseptal puncture, and nonidiopathic ventricular tachycardia (VT)., Results: From a total of 525 procedures, we performed CA entirely without RX in 78.5% of cases. From 2011 to 2013, we performed CA without RX in 38.5% of cases; from 2014 to 2017, we performed 96.2% of cases with zero RX. The use of RX was significantly reduced in group 2 (group 2: 1.4 ± 19.6 seconds vs group 1: 556.92 ± 520.76 seconds; P < .001). These differences were irrespective of arrhythmia treatment. There were no differences between the two groups in acute success, complications, or duration of procedures., Conclusion: CA of supraventricular tachycardia and VT entirely without RX, guided by the CARTO system, is safe, feasible, and effective. After an adequate learning curve, CA can be performed entirely without RX., (© 2019 Wiley Periodicals, Inc.)

The identification of the site in head neck unknown primary (HNUP) tumour is of utmost importance to help select best treatment while decreasing treatment-related morbidity and mortality. The primary purpose of this study is to demonstrate that TORS may be a valuable tool in detecting primary tumour. Studies were systematically searched in the PubMed, EMBASE, the Cochrane Library and CENTRAL electronic databases. A total of 12 selected studies (349 patients) were analyzed. The primary tumour detection and positive surgical margins rates were 70.8% and 19.4%, respectively. The rate of HPV-related tumour was 71.3%. The primary tumour was mainly in base of tongue (64%). In conclusion, TORS seems to be an effective surgical approach both in terms of detection of primary tumour site and in terms of therapeutic perspective for HNUP. In particular, a subset of HPV-related tumours might benefits all advantages from this surgical modality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Adventitious rooting is a post-embryonic developmental program governed by a multitude of endogenous and environmental cues. Auxin, along with other phytohormones, integrates and translates these cues into precise molecular signatures to provide a coherent developmental output. Auxin signaling guides every step of adventitious root (AR) development from the early event of cell reprogramming and identity transitions until emergence. We have previously shown that auxin signaling controls the early events of AR initiation (ARI) by modulating the homeostasis of the negative regulator jasmonate (JA). Although considerable knowledge has been acquired about the role of auxin and JA in ARI, the genetic components acting downstream of JA signaling and the mechanistic basis controlling the interaction between these two hormones are not well understood. Here we provide evidence that COI1 -dependent JA signaling controls the expression of DAO1 and its closely related paralog DAO2 . In addition, we show that the dao1-1 loss of function mutant produces more ARs than the wild type, probably due to its deficiency in accumulating JA and its bioactive metabolite JA-Ile. Together, our data indicate that DAO1 controls a sensitive feedback circuit that stabilizes the auxin and JA crosstalk during ARI.

The obstructive sleep apnea syndrome (OSAS) represents only part of a large group of pathologies of variable entity called respiratory sleep disorders (RSD) which include simple snoring and increased upper airway resistance syndrome (UARS). Although the etiopathogenesis of adult OSAS is well known, many aspects of this syndrome in children are still debated. Its prevalence is about 2% in children from 2 to 8 years of age, mostly related to the size of the upper airways adenoid tissue. Several risk factors linked to the development of OSAS are typical of the pediatric age. The object of this paper is to analyze the state of the art on this specific topic, discussing its implications in terms of diagnosis and management.

Objectives: This article describes the detailed project aimed to realize a dedicated ground ambulance for neonatal emergency transport service (NETS). To date, the European Community rules specify requirements for the design, testing, performance, and equipping of road ambulance used for transport and care of adult injured or ill patients, completely ignoring neonatal transport., Methods: The project consisted of electric and gas supply planning, interior design taking into account ergonomic and occupant protection principles, both during travel and during medical care performances., Results: A detailed project is presented. Main differences between European Type C ambulance and the new proposed Type D neonatal ground ambulance are the presence on board of air compressed cylinder, iNO cylinders and delivery system, phototheraphy, shock adsorbing stretcher support, cooling device, patient's placenta (refrigeration box), and transcutaneous gas analyzer., Conclusion: The European Community rules specify requirements for road ambulance used for transport and care of adult injured or ill patients, completely ignoring neonatal transport. This study describes the detailed project aimed to realize a dedicated ground ambulance for neonatal emergency transport service. This study demonstrated that it is not possible simply to adapt the currently dedicated ambulance for mobile intensive care and resuscitation services (actual type C European Community) in a modern dedicated NETS ambulance; it is of paramount importance suggesting to European Community to introduce a further ambulance type, to be identified type D, strictly reserved to neonatal transport activities.

Background: Despite regionalization of perinatal care provides for the "in utero" transfer of high-risk pregnancies, there will always be a number of neonates who undergo acute inter-facility transport. The presence of a well-organized Neonatal Emergency Transport Service (NETS) can prevent and reduce risks of transportation, especially for very preterm infants, and is therefore mandatory for any program of regionalization of perinatal care. Italian National Health System is highly decentralized and Regions are autonomous to structure, plan and delivery their regional health services. Consequently, organization models and resources available vary widely and significant regional differences in access and quality of health services have been reported in the past years. A national survey was conducted in 2015 by the neonatal transport study group of the Italian Society of Neonatology with the aim to describe neonatal transfer practices and to assess the Neonatal Emergency Transport Services (NETS) status in the 20 Italian regions., Methods: A questionnaire regarding neonatal transfer practices and NETS activity for the previous year (2014) was sent to the 44 NETS operating in the 20 Italian regions. Demographic data were obtained from the Italian National Statistical Institute (ISTAT)., Results: The overall survey response rate was 100%. In 2014, only 12 (60%) of the 20 Italian regions were fully covered by NETS, 3 (15%) regions were partially covered, while neonatal transport was not available in 5 (25%) regions. Overall, in 2014, the 44 NETS operating in Italy transported a total of 6387 infants, including 522 (8.17%) having a gestational age < 28 weeks., Conclusions: The organization of NETS in Italy is devolved on a regional basis, resulting in a large heterogeneity of access and quality to services across the country. Where available, NETS are generally well-equipped and organized but limited volume of activities often cannot guarantee adequate levels of skills of personnel or an appropriate cost-efficiency ratio. The regions reported with lack of NETS have managed, or are trying, to fill the gap, but continuing efforts to reduce regional differences in the availability and quality of services are still needed.

We recently developed an approach to characterize local nonlinear, anisotropic mechanical properties of murine arteries by combining biaxial extension-distension testing, panoramic digital image correlation, and an inverse method based on the principle of virtual power. This experimental-computational approach was illustrated for the normal murine abdominal aorta assuming uniform wall thickness. Here, however, we extend our prior approach by adding an optical coherence tomography (OCT) imaging system that permits local reconstructions of wall thickness. This multimodality approach is then used to characterize spatial variations of material and structural properties in ascending thoracic aortic aneurysms (aTAA) from two genetically modified mouse models (fibrillin-1 and fibulin-4 deficient) and to compare them with those from angiotensin II-infused apolipoprotein E-deficient and wild-type control ascending aortas. Local values of stored elastic energy and biaxial material stiffness, computed from spatial distributions of the best fit material parameters, varied significantly with circumferential position (inner vs. outer curvature, ventral vs. dorsal sides) across genotypes and treatments. Importantly, these data reveal an inverse relationship between material stiffness and wall thickness that underlies a general linear relationship between stiffness and wall stress across aTAAs. OCT images also revealed sites of advanced medial degeneration, which were captured by the inverse material characterization. Quantification of histological data further provided high-resolution local correlations among multiple mechanical metrics and wall microstructure. This is the first time that such structural defects and local properties have been characterized mechanically, which can better inform computational models of aortopathy that seek to predict where dissection or rupture may initiate.

Organic (e.g., sugars and amino acids) and inorganic (e.g., K⁺, Na⁺, PO₄ 2- , and SO₄ 2- ) solutes are transported long-distance throughout plants. Lateral movement of these compounds between the xylem and the phloem, and vice versa, has also been reported in several plant species since the 1930s, and is believed to be important in the overall resource allocation. Studies of Arabidopsis thaliana have provided us with a better knowledge of the anatomical framework in which the lateral transport takes place, and have highlighted the role of specialized vascular and perivascular cells as an interface for solute exchanges. Important breakthroughs have also been made, mainly in Arabidopsis, in identifying some of the proteins involved in the cell-to-cell translocation of solutes, most notably a range of plasma membrane transporters that act in different cell types. Finally, in the future, state-of-art imaging techniques should help to better characterize the lateral transport of these compounds on a cellular level. This review brings the lateral transport of sugars and inorganic solutes back into focus and highlights its importance in terms of our overall understanding of plant resource allocation.