A document by Daniele Ronco. Click on the document to view its contents.

In conclusion, in a cohort of children with a history of severe bronchiolitis those exposed to ASM prenatally are not at increased risk of developing food or environmental allergen sensitization by early childhood. The mechanism by which ASM exposure increases risk of childhood asthma remains unclear, but alterations in the gut microbiome merit consideration.

Background Biological therapies relieve symptoms in allergic and inflammatory diseases so may also benefit people with IgE-mediated food allergy. We systematically reviewed the highest quality published evidence to inform forthcoming GA 2LEN guidelines. Methods We searched six bibliographic databases from 1946 to 30 September 2021 for randomised controlled trials, controlled clinical trials and quasi-randomised trials about biological monotherapy in people with IgE-mediated food allergy confirmed by oral food challenge. We found 3 trials with 118 participants. We used the GRADE approach. We summarised the findings narratively because studies were too heterogeneous to conduct meta-analysis. Results We included one randomised trial about etokimab, one about omalizumab and one about the discontinued TNX-901. All were in people with peanut allergy in the USA, mostly aged 13+ years. There were trends towards improved tolerance of peanut during treatment, with no increase in adverse events compared to placebo. However, we have very low certainty about the evidence. No trial reported on quality of life or cost-effectiveness. Conclusions Our review of the highest quality research found that there is not yet enough certainty of evidence to support offering etokimab or omalizumab widely for food allergy. Clinicians may consider the merits for individuals, but large randomised trials with standardised measures need to confirm the safety and efficacy and the most suitable candidates, doses and durations of treatment.

The oomycete pathogen Phytophthora capsici encodes hundreds of RXLR effectors to enter plant cells and suppress host defense responses. Only few of them are conserved across different strains and species. Such ‘core effectors’ may target hub immunity pathways that are essential during Phytophthora pathogens interacting with their hosts. However, the underlying mechanisms of core RXLRs-mediated host immunity manipulation are largely unknown. Here, we report the functional characterization of a P. capsici RXLR effector, RXLR242. RXLR242 expression is highly induced during the infection process. Its ectopic expression in Nicotiana benthamiana promotes Phytophthora infection. RXLR242 physically interacts with a group of RAB proteins, which belong to the small GTPase family and function in specifying transport pathways in the intracellular membrane trafficking system. RXLR242 impedes the secretion of PATHOGENESIS-RELATED 1 (PR1) protein to the apoplast by interfering the formation of RABE1-7-labeled vesicles. Further analysis indicated that such phenomenon is resulted from competitive binding of RXLR242 to RABE1-7. RXLR242 also interferes trafficking of the membrane-located receptor FLAGELLIN-SENSING 2 (FLS2) through competitively interacting with RABA4-3. Taken together, our work demonstrates that RXLR242 manipulates plant immunity by targeting RAB proteins and disturbing vesicle-mediated protein transporting pathway in plant hosts.

The Fourier transform of Cartesian Gaussian functions product is presented in the light of positron scattering. The calculation of this class of integrals is crucial in order to obtain the scattering amplitude in the first Born approximation framework for an _ab initio_ method recently proposed. A general solution to the scattering amplitude is given to a molecular target with no restriction due to symmetry. Moreover, symmetry relations are presented with the purpose of identifying terms that do not contribute to the calculation for the molecules in the D∞h point group optimizing the computational effort. KEYWORDS — Positron and electron scattering, Fourier transform of the Gaussian product theorem, McMurchie-Davidson procedure, Obara-Saika procedure, linear molecules .

Seed dispersal directly affects plant establishment, gene flow, and fitness. As a result, understanding patterns in seed dispersal is fundamental to understanding plant ecology and evolution, as well as addressing challenges of extinction and global change. Our ability to understand dispersal is limited because few frameworks have emerged that provide a means for predicting dispersal across time and space. We provide a novel framework that links seed dispersal to animal social status, a key component of behavior. Because social status affects individual resource access and movement, it provides a critical link to two factors that determine seed dispersal: the quantity of seeds dispersed and the spatial patterns of dispersal. Moreover, individual social status may have unappreciated effects on post-dispersal seed survival and recruitment when social status affects individual habitat use. Hence, environmental changes, such as selective harvesting and urbanization, that affect animal social structure may have unappreciated consequences for seed dispersal. The framework we present highlights these exciting new hypotheses linking environmental change, social structure, and seed dispersal. By outlining experimental approaches to test these hypotheses, we hope to facilitate studies across a wide diversity of plant-frugivore networks, which may uncover emerging hotspots or catastrophic losses of seed dispersal.

Secondary and plantation forests are the main alternative forests remaining after the deforestation of primary forests. Understanding the conservation value of secondary and plantation forests is important for resource utilization. To explore the impact of forest conversion on biodiversity, we compared multiple diversity metrics (taxonomic, phylogenetic and functional diversity) and community structures of small mammals in the primary, secondary and plantation forests on Mt. Liangshan, Sichuan Province, China. Seven field surveys were conducted to survey local small mammal assemblages between 2016 and 2020. We found that the taxonomic, phylogenetic and functional diversity metrics of small mammals in the three forest types were similar at the landscape scale, while all diversity metrics were lowest in the plantation forest and highest in the primary forests at the site scale. The community structure analysis showed that random processes were dominant across the three forest types, and there was no difference in small mammal community structures among the three forest types. Our results indicated that secondary and plantation forests in the nature reserves, adjacent to the primary forest and exposed to little human disturbance, also can provide important habitats for small mammals.

The variable amplitude loading fatigue test with interior Inclusion-FGA-Fisheye induced failure under R = 0 was carried out on carburized 12CrNi 3 steel in very high-cycle fatigue regime. Comparing with S-N curve of constant amplitude loading, the total life is inevitably longer under variable amplitude loading. And, the surface morphology of FGA is coarser under same order of magnitude of fatigue life. Simultaneously, it can be determined that the formation micro-mechanism of FGA is caused by the continuous debondings of refined grains due to stress concentration around interior micro-defects, and variable amplitude loading will aggravate the formation of FGA. Furthermore, the life prediction model based on double nonlinear fatigue damage, which considers the coupling effect of local equivalent stress (surface residual stress, maximum stress and local stress concentration by RVE model), loading sequence and failure mechanism is established, and predicted life has good accuracy within the factor-of-three lines for experimental life.

Transition of rapid, ready-to-use, and low-cost nucleic acid-based detection technologies from laboratories to points of sample collection has drastically accelerated. However, most of these approaches are still incapable of diagnosis starting from sampling, through nucleic acid isolation and detection in the field. Here, we developed a simple, portable, low-cost, colorimetric, and remotely controllable platform for reliable, high-throughput, and rapid diagnosis using loop mediated isothermal amplification (LAMP) assays. It consists of a thermally isolated cup, low-cost electronic components, a polydimethylsiloxane sample well, and a fast prototyped case that covers electronic components. The steady-state temperature error of the system is less than 1%. We performed LAMP, Colony-LAMP, and Colony PCR reactions using the yaiO2 primer set for Escherichia coli and Pseudomonas aeruginosa samples at 65˚C and 30 min. We detected the end-point colorimetric readouts by the naked eye under day light. We confirmed the specificity and sensitivity of our approach using pure genomic DNA and crude bacterial colonies. We benchmarked our Colony-LAMP detection against Colony PCR. The number of samples tested can easily be modified for higher throughput in our system. We strongly believe that our platform can greatly contribute rapid and reliable diagnosis in versatile operational environments.

A bubble coalescence model for a solution with a nonionic surfactant and with a small bubble approach velocity was developed, in which the mechanism of how coalescence is hindered by Marangoni stress was quantitatively analyzed. The bubble coalescence time calculated for ethanol-water and MIBC-water systems were in good agreement with experimental data. At low surfactant concentrations, the Marangoni stress and bubble coalescence time increased with bulk concentration increase. Conversely, in the high concentration range, the Marangoni stress and coalescence time decreased with bulk concentration. Numerical results showed that the nonlinear relationship between coalescence time and surfactant concentration is determined by the mass transport flux between the film and its interface, which tends to diminish the spatial concentration variation of the interface, i.e., it acts as a “damper”. This damping effect increases with increased surfactant concentration, therefore decreasing the coalescence time at high concentrations.

Acting as the reactant distributor, the gas channel (GC)-gas diffusion layer (GDL) assembly is of significance to the PEM fuel cell performance and durability. In this work, an analytical flow model has been developed for the GC-GDL system. Based on the explicit expressions of the channel-porous layer flow structure, the effects of geometrical parameters are clarified and the flow effects including reactant conversion and uniformity are further derived and clarified. Results reveal that with thinner GDL or longer GC, the nonlinear decrease of axial velocity becomes faster and the decrease of transverse velocity turns from linear to nonlinear. Furthermore, the reactant conversion and uniformity are in an opposite relationship and the criterion of flow homogenization in the fuel cells is proposed to make a trade-off. Moreover, the flow non-uniformity is positively correlated with GC length, which gains insights into the fuel cell scale-up.

The famous two-balloon experiment involves two identical balloons filled up with air and connected via a hollow tube, and upon onsetting the experiment one of the balloons shrinks and the other expands. Here, we present the liquid version of that experiment. We use superhydrophobic (SHP) substrates to form spherical droplets and connect them with a capillary channel. Different droplet sizes, substrates of different hydrophobicities, and various channel pathways are investigated, and morphometric parameters of the droplets are measured through image processing. In the case of SHP substrates the pumping is from the smaller droplet to the larger one, similar to the two-balloon experiment. However, if one or both of the droplets are positioned on a normal substrate the curvature radius will indicate the direction of pumping. We interpret the results by considering the Laplace pressures and the surface tension applied by the channel at the connecting points.

Experimental results on pressure drop and gas hold-up for gas-liquid flow through packed beds obtained from a second flight on the International Space Station are presented and analyzed. It is found that the gas hold-up is a function of the bed history at low liquid and gas flow rates whereas higher gas hold-up and pressure gradients are observed for the test conditions following a liquid only pre-flow compared to the test conditions following a gas only pre-flow period. Over the range of flow rates tested, the capillary force is the dominant contributor to the pressure gradient and is found to be linear with the superficial liquid velocity but is a much weaker function of the superficial gas velocity. The capillary contribution is also a function of the particle size and varies approximately inversely with the particle diameter within the range of the test conditions.

A three-dimensional, non-isothermal and multiphase model of high temperature proton exchange membrane fuel cells is built to investigate water and phosphoric acid transportation, in which a spherical agglomerate model considering catalyst layer structure and liquid phase fraction is applied to determine the electrochemical kinetics in the cathode catalyst layer. Experimental polarization curve, water proportion in the anode outlet gas and phosphoric acid distribution are selected for validation. It is found that the simulated results can represent the experimental data with reasonable accuracy. Based on the model, the effects of current density and stoichiometry on the variable distributions are analyzed. The results show that water in anode is mainly from cathode by concentration diffusion of liquid water. A higher current density leads to a greater electro-migration of phosphoric acid from cathode to anode and a higher liquid phase fraction in anode,while a lower phosphoric acid concentration in the fuel cells.

The groundwater system is polluted by chlorinated hydrocarbon pollution in eastern Jinan, Shandong province, China, exceeding the limit of pollutants concentration in class Ⅲ of Groundwater Quality Standards (GQS, GB/T 14848-2017). In order to improve the current situation of chlorinated hydrocarbon pollutants in groundwater system of eastern Jinan, the optimization study of the pollution control is carried out. In this paper, the pollutant of carbon tetrachloride in groundwater system is taken as the main research object. By using GMS numerical simulation software to establish the solute transport model of carbon tetrachloride. The simulation results illuminate that with the passage of time, the concentration of carbon tetrachloride decreases, but the acreage of pollution plume in groundwater still has little change, and it is hard to reach the limit standard of 2.0μg/L in class Ⅲ of GQS within a short time. Sequentially, on the basis of simulation model, the optimization of pumping and injection wells is conducted in the pollution control field of research region. The results turn out that the layout of 8 pumping and 5 injection wells has the best control effect of carbon tetrachloride in groundwater system, the pollutant concentration reached the limit standard of 2.0μg/L in only 1187d, and the acreage of pollution plume in control field reduced from 21.80km2 to 12.21km2. In summary, through the optimal pollution control scheme of carbon tetrachloride, the time for pollutant concentration to reach 2.0μg/L has been reduced, and the acreage of pollution plume has been effectively controlled. This work further investigates the promoting effect of injection wells on hydraulic control of groundwater pollution, which can accelerate the circulation of the groundwater system and save the treatment time, providing a relatively practical way for the prevention and control of chlorinated hydrocarbon pollutants.

In this paper, we investigate the asymptotic stability of solutions for a class of nonlinear fractional neutral differential systems with time dependent delays when the given delays are unbounded. An example is used to show the efficacy of the theorems. The LMI tool box was used to calculate the solutions to the convex optimization problems.

Background: Cervical aortic arch (CAA) is a rare anomaly that could be associated with aortic stenosis, aneurysm or heart malformations. To correct this anomaly, symptomatic patients undergo surgery, usually consisting of a prosthetic graft repair. Moreover, circulatory arrest and deep hypothermia are often needed. Case presentation: A 13-years-old patient underwent correction of an aortic arch stenosis with a post-stenotic aneurysm between the origin of the right carotid artery (RCA) and right subclavian artery (RSA) in a right CAA. A resection with direct end-to-end anastomosis was performed, with mild hypothermic cardiopulmonary by-pass. Conclusions: Surgical correction of cervical aortic arch anomalies without the use of prosthetic grafts and circulatory arrest may be a safe alternative approach, especially in the pediatric population.

Aims: Given the complexity of antithrombotic therapy guidelines especially in patients with combined antithrombotic therapy, there is a risk of inappropriate prescribing and medication errors. In order to prevent this, a multidisciplinary antithrombotic stewardship (ASP) is implemented in our hospital. The primary aim of this study is to determine the efficacy of this ASP by assessing the number of patients on combined antithrombotic therapy for whom one or more interventions are needed. Methods: A prospective cohort study in a large teaching hospital is conducted. Hospitalized patients who received combined antithrombotic therapy in which an oral anticoagulant was combined with one (double therapy) or two (triple therapy) platelet aggregation inhibitors were included. The ASP proactively evaluated the appropriateness of this combined antithrombotic therapy. If needed, ASP improved the concerned therapy. Each improvement measurement by ASP was counted as one intervention. Results: A total of 460 patients were included over a period of 12 months. 251 (54.6%) patients required at least one intervention from the ASP. The most common intervention was to define and document a maximum duration of the combined antithrombotic therapy (65.5%) instead of lifetime use of the combination, to discontinue antithrombotic therapy (19.4%) as the proper indication was lacking and to adjust the dosage (8.1%). Conclusion: As intervention was needed in more than half of the patients on combined antithrombotic therapy, it seems essential to implement an ASP that dedicated evaluates antithrombotic therapy to improve and ensure optimal use and medication safety.

Background Magnetic Resonance imaging (MRI) in patients (pts) with MRI-conditional cardiovascular implantable electronic devices (CIED) remain a logistical issue for device programming during the scan. In current practice, a trained person needs to be present on-site to program CIED for MRI scan. This can cause delay in patient care, rescheduling of tests and increase healthcare costs. A novel remote programming (RP) strategy can be utilized to reprogram the CIED remotely. We sought to explore the feasibility and safety of RP of CIED’s in pts undergoing MRI scan. Methods We implemented the Medtronic CIED RP software at our institution after ensuring HIPAA compliance. The MRI technician started the session by contacting an off-site remote operator and placing a programmer wand from 2090 Medtronic programmer over CIED. The remote operator logged into a remote access software and provided a unique access code to the MRI technician. After entering the access code into the programmer, the remote operator was able to program the device as needed. We conducted a periodic audit of the first 209 pts who underwent RP of CIED’s for MRI. Outcomes analyzed were safety parameters during RP. Results Of the 209 MRI scans, 51 scans were performed urgently. There were no connectivity and programming problems or need for MRI rescheduling. In-person reprogramming was not required for any pt. All scans were completed safely in a timely manner, and there were no reports of CIED malfunction. Conclusions Remote programming of CIED’s for MRI scans is a safe and effective strategy.

Background and Purpose T-type calcium channels, mainly the Cav3.2 subtype, are important contributors to the nociceptive signaling pathway. We investigated their involvement in inflammation and related pain-like symptoms. Experimental Approach The involvement of Cav3.2 and T-type channels was investigated using genetic and pharmacological inhibition to assess mechanical allodynia/hyperalgesia and edema development in two murine inflammatory pain models. The location of Cav3.2 involved in pain-like symptoms was studied in mice with Cav3.2 knocked out in C-low threshold mechanoreceptors (C-LTMR) and the use of ABT-639, a peripherally restricted T-type channel inhibitor. The anti-edematous effect of Cav3.2 inhibition was investigated in chimeric mice with immune cells deleted for Cav3.2. Lymphocytes and macrophages from either green fluorescent protein-targeted Cav3.2 or KO mice were used to determine the expression of Cav3.2 protein and the functional status of the cells. Key Results We showed the role of Cav3.2 channels in the development of pain-like symptoms and edema in the two murine inflammatory pain models. For the first time, we provide evidence of the involvement of Cav3.2 channels located on C-LTMRs in inflammatory pain at both peripheral and primary afferent terminals at the spinal level. We showed that Cav3.2 channels located in T cells and macrophages contribute to the inflammatory process. Conclusion and Implications This work highlights the crucial role of Cav3.2 channels in inflammation and related pain and suggests that targeting Cav3.2 channels with pharmacological agents could be an attractive and readily evaluable strategy in a clinical trial to relieve chronic inflammatory pain in affected patients.

The evaluation of the lung by ultrasound is an adjunct tool to the clinical assessment. Among different hallmarks at lung ultrasound, B-lines are well known artifacts which are not correlated to identifiable structures but can be used as an instrument for pathological classification. Multiple B-lines are the sonographic sign of lung interstitial syndrome with a direct correlation between the number of B-lines and the severity of the interstitial involvement of lung disease. In neonatology and paediatrics, the quantitative assessment of B-lines is questionable as opposed to in adult medical care. Counting B-lines is an attempt to enrich the clinical assessment and clinical information, and not simply arrive at a dichotomous answer. A semiquantitative or quantitative B-lines assessment was shown to correlate with fluid overload and demonstrated prognostic implications in specific neonatal and paediatric conditions. In neonatology, the count of B-lines is used to predict the need for admission in neonatal intensive care unit and the need for exogenous surfactant treatment. In paediatrics, the B-lines count has the role of quantifying hypervolemia in infants and children receiving dialysis. B-lines as predictors of length of stay in the paediatric intensive care unit after cardiac surgery, as a marker of disease severity in bronchiolitis, or as an indicator of lung involvement from SARS-CoV-2 infection are speculative and not yet supported by solid evidence. Lung ultrasound with the quantitative B-lines assessment is promising. The current evidence allows to use the quantification of B-lines in a limited number of neonatal and paediatric diseases.

This report presents an unusual case of multiple paraovarian cysts that required emergency surgery due to a paraovarian cyst being entrapped by another paraovarian cyst. Laparoscopic surgery is considered useful for diagnostic and therapeutic purposes and is therefore recommended owing to difficulty in differentiating paraovarian cysts from ovarian cysts.

Objectives: To compare health-related quality of life of patients primarily treated with a no-touch saphenous vein graft with that of patients who received a conventional graft. Methods: The study included all individuals treated with a percutaneous coronary intervention on a saphenous vein graft between January 2006 and June 2020. The RAND-36 health survey was used to assess health-related quality of life. The Mann–Whitney U test was used to test differences in health-related quality of life between the two groups. Effect size was estimated via Cohen’s d. The average treatment effect between the groups was tested by propensity score matching. Results: Of the 346 patients treated with a percutaneous coronary intervention in a stenosed or occluded saphenous vein graft, 165 responded to RAND-36 (no-touch: n=48; conventional: n=117). Patients with a no-touch graft reported better mean values on seven of the eight health survey domains. Statistically significant differences were observed for four of the domains, all in favour of the no-touch group. The effect size estimates indicated a small difference for five domains, with the largest values (>0.40) seen for the general health and energy/fatigue domains. Propensity score matching confirmed a statistically significant difference for the physical functioning and general health domains. Conclusions: At a mean follow-up of 5.4 years, patients who received a percutaneous coronary intervention in no-touch vein grafts showed significantly better health-related quality of life than those who received a percutaneous coronary intervention in conventional vein grafts.

Plasmid transfection of mammalian cells is the dominant platform used to produce adeno-associated virus (AAV) vectors for clinical and research applications. Low yields from this platform currently make it difficult to supply these activities with adequate material. In an effort to better understand the current limitations of transfection-based manufacturing, this study examines what proportion of cells in a model transfection produce appreciable amounts of assembled AAV capsid. Using conformation-specific antibody staining and flow cytometry we report the surprising result that despite obtaining high transfection efficiencies and nominal vector yields in our model system, only 5-10% of cells appear to produce measurable levels of assembled AAV capsids. This finding implies that considerable increases in vector titer could be realized through increasing the proportion of productive cells. Furthermore, we suggest that the flow cytometry assay used here to quantify productive cells may be a useful metric for future optimization of transfection-based AAV vector manufacturing platforms.