Background: Cannabis use during the perinatal period is rising. Objectives: To synthesize existing knowledge on the perspectives of pregnant people and their partners about cannabis use in pregnancy and lactation. Search strategy: We searched MEDLINE, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Social Science Citation Index, Social Work Abstracts, ProQuest Sociology Collection up until April 1, 2020. Selection criteria: Eligible studies were those of any methodology which included the perspectives and experiences of pregnant or lactating people and their partners on cannabis use during pregnancy or lactation, with no time or geographical limit. Data collection and analysis: We employed a convergent integrative approach to the analysis of findings from all studies, using Sandelowski’s technique of “qualitizing statements” to extract and summarize relevant findings from inductive analysis. Main results: We identified 23 studies of pregnant people’s views about cannabis use in pregnancy. Comparative analysis revealed that whether cannabis was studied alone or grouped with other substances resulted in significant diversity in descriptions of participant decision-making priorities and perceptions of risks and benefits. Studies combining cannabis with other substance seldom addressed perceived benefits or reasons for using cannabis. Conclusions: The way cannabis is grouped with other substances influences the design and results of research. A comparative analysis emphasizes the importance of understanding why a pregnant person might choose to use cannabis in order to foster dialogue about perceptions of benefit and strategies for risk mitigation.

Introduction: Data are scarce on hs-CRP as a biomarker for airway inflammation in pediatric asthma. We aimed to examine correlation between hs-CRP and asthma control levels. Methods: Children with physician-diagnosed asthma, ages 6 to 15 years, were enrolled. Asthma control criteria of GINA-2016 were used to assess the level of asthma control. The relationships between serum hs-CRP and each of asthma control measures (Asthma control criteria, spirometry, impulse oscillometry, eosinophil counts and Fractional exhaled nitric oxide (FeNO) were assessed. Results: Out of total 150 asthmatic children; 52 (35%) had well controlled asthma, 76 (51%), and 22 (14%) children had partly controlled and uncontrolled asthma, respectively. Median (IQR) values of hs-CRP were 0.47 (0.1, 1.67) mg/L in well controlled, 0.30 (0.1, 1.83) mg/L in partly controlled, and 2.74 (0.55, 3.74) mg/L in uncontrolled asthma (p=0.029). Correlation between hs-CRP and FEV1% was significant (p=0.019). Using Receiver Operator Characteristic (ROC) analysis, area under curve for hs-CRP mg/L to discriminate between uncontrolled and (controlled + partly controlled) asthma was 0.67 (95% CI 0.55, 0.80) and a cutoff 1.1 mg/L of serum hs-CRP level had a sensitivity of 68.1% with specificity of 67.97%. In two groups of hs-CRP (< 3 mg/L) and hs-CRP (≥ 3 mg/L), high hs-CRP group had higher proportion of uncontrolled asthmatic children (p=0.03). Conclusion: Our study demonstrated higher serum hs-CRP values in uncontrolled asthma that supports the use of hs-CRP as surrogate marker of small airway inflammation. hs-CRP may be considered as a tool to predict asthma status.

Until recently many historical museum specimens were largely inaccessible to genomic inquiry, but high-throughput sequencing (HTS) approaches have allowed researchers to successfully sequence genomic DNA from dried and fluid-preserved museum specimens. In addition to preserved specimens, many museums contain large series of allozyme supernatant samples but the amenability of these samples to HTS has not yet been assessed. Here, we compared the performance of a target-capture approach using alternative sources of genomic DNA from ten specimens of spring salamanders (Plethodontidae: Gyrinophilus porphyriticus) collected 1985–1990: allozyme supernatants, allozyme homogenate pellets, and formalin-fixed tissues. We designed capture probes based on double-digest restriction-site associated (RADseq) sequencing derived loci from seven of the specimens and assessed the success and consistency of capture and RADseq technical replicates. This study design enabled direct comparisons of data quality and potential biases among the different datasets for phylogenomic and population genomic analyses. We found that in phylogenetic analyses, all replicates for a given specimen clustered together, but in principal component space, RADseq replicates did not cluster with corresponding capture-based replicates. SNP calls were on average 18.3% different between technical replicates, but these discrepancies were primarily due to differences in heterozygous/homozygous SNP calls. We demonstrate that both allozyme supernatant and formalin-fixed samples can be successfully used for population genomic analyses and we discuss ways to identify and reduce biases associated with combining capture and RADseq data.

Background & Aim: Autophagy is a cytoprotective recycling mechanism, capable of digesting dysfunctional cellular components, and this process is associated with pro-survival outcomes. Autophagy may decline in the aging myocardium, thereby contributing to cardiac dysfunction. However, it remains to be established how autophagy responds to ischemia-reperfusion stress with age. Methods: Samples from the right atrium were collected from young (≤50 years; n=5) and aged (≥70 years; n=11) patients prior to and immediately following cardioplegic arrest during coronary artery bypass grafting (CABG) surgery, a model of human ischemia-reperfusion injury. Results: Mitochondrial content did not differ between the age groups, however a 32% reduction in UQCRC2 (0.74 vs 0.53, effect of age, p=0.03) was seen with age, indicating possible compositional disruptions. In response to IR, VDAC (0.75 vs 1.05, p=0.03) and COX-I protein (0.63 vs 1.10, p=0.03) was over expressed in young, but not in aged patients. Reductions in Parkin (0.95 vs 0.49, interaction effect, p=0.04) and NIX (0.60 vs 0.21, p=0.004) protein expression with age suggest an impairment in mitochondrial recycling, which may lead to an accumulation of dysfunctional mitochondria. Following IR, our data suggest that in the young cohort, autophagy is reduced as a Beclin-1 decreased by 63% (0.95 vs 0.36, p=0.001) and no changes were observed in either p62 or LC3-II:I ratio. Conclusion: Our data demonstrate a blunted cardiac mitochondrial response to ischemia with age, accompanied by a possible impairment in mitophagy. These findings support an age-associated inability of the atrial myocardium to mount appropriate adaptive responses to stress.

Barriers to gene-flow within populations, typically in response to divergent selection, are often mediated via third-party interactions. Under these conditions speciation is inextricably linked to ecological context. We present a novel framework for studying arthropod speciation as mediated by Wolbachia, a microbial endosymbiont capable of causing host cytoplasmic incompatibility (CI) via alternative strain associations. Building on empirical findings, our model predicts that sympatric host sister-species harbour paraphyletic strains that provide CI, while well-defined congeners in ecological contact and recently diverged noninteracting congeners are uninfected due to Wolbachia redundancy. We argue that Wolbachia may provide an adaptive advantage when coupled with reduced hybrid fitness (via trait mismatching), by facilitating assortative mating between co-occurring divergent phenotypes – the contact contingency hypothesis. To test this, we applied a custom-built predictive algorithm to empirical data from host-specific pollinating fig wasps, achieving ≤88.46% accuracy. We then considered post-zygotic offspring mortality during CI matings by developing a model featuring fitness clines across oviposition resources. This oviposition trade-off model, tested through simulation, favoured CI at realistic conspecific mating frequencies despite fecundity losses. We demonstrate that a rules-based algorithm accurately predicts Wolbachia infection status. This has implications among other systems where closely-related sympatric species encounter adaptive disadvantage through hybridisation.

Concomitant thrombosis of two coronary arteries is an uncommon condition that is reported to cause sudden cardiac death. In this paper, we describe the case of a 42-year-old man who presented with simultaneous LAD and RCA occlusion causing anterior and inferior myocardial infarctions. PCI was attempted and failed, an Intra-Aortic Balloon Pump (IABP) was inserted and the patient was referred to surgery. Following surgical thrombectomy and coronary artery bypass grafting (CABG), the patient recovered with no complications.

Background: Female neonates are well-recognised to have improved outcomes compared to males. The mechanisms remain poorly understood, but hormonal influences on immune function may contribute to the female advantage during infection and inflammation. The aim of this study was to investigate the in vitro treatment effects of 17β-estradiol (E2) and its antagonism in males versus females on CD14+ monocyte cell surface receptor (TLR4, CD11b, ER-α, ER-β) expression and reactive oxygen species (ROS) production from mononuclear cells in umbilical cord blood (UCB) and adult blood. Methods: UCB samples were collected from term neonates and whole blood was collected from adults (M:F n=10 in each group). Mononuclear cells were isolated via density gradient centrifugation and flow cytometry was used to assess receptor expression and ROS production in the presence of E2, ICI 182,780 (ER antagonist), or lipopolysaccharide (LPS/endotoxin) in various combinations. Results: Basal expression of TLR4, CD11b, ER-α and ER-β did not differ on monocytes between sexes or between adults versus neonates. Treatment with E2, ICI 182,780, or LPS individually or in combination did not modulate CD11b or TLR4 expression in neonates or adults. Higher expression of monocyte ER-β expression was noted in female versus male adults following ICI 182,780 treatment alone (p<0.05). Female neonates exhibited less ROS production following LPS and E2 treatment in combination compared to male neonates (p<0.05). Conclusion: The influence of E2 on neonatal mononuclear cell ROS production provides preliminary evidence for sex-specific disparities in neonatal immune function. These responses may be amenable to immunomodulation.

To analyze the evolution of a chemical property along the reaction path, we have to extract all the necessary information from a set of electronic structure computations. However, this process is time-consuming and prone to human error. Here we introduce IRC-Analysis, a new extension in Eyringpy, to monitor the evolution of chemical properties along the intrinsic reaction coordinate, including complete reaction force analysis. IRC-Analysis collects the entire data set for each point on the reaction coordinate, eliminating human error in data capture and allowing the study of several chemical reactions in seconds, regardless of the complexity of the systems. Eyringpy has a simple input format, and no programming skills are required. A tracer has been included to visualize the evolution of a given chemical property along the reaction coordinate. Several properties can be analyzed at the same time. This version can analysis the evolution of bond distances and angles, Wiberg bond indices, natural charges, dipole moments, and orbital energies (and related properties).

Background: The effects of maternal ritodrine hydrochloride administration (MRA) during pregnancy on fetuses and offspring are not entirely clear. The present study aimed to evaluate the association between MRA and childhood wheezing using data from a nationwide Japanese birth cohort study. Methods: This study retrospectively analyzed data from the Japan Environment and Children’s Study, a nationwide birth cohort study, conducted between 2011 and 2014. Data of women with singleton births after 22 weeks of gestation were analyzed. The participants were divided according to MRA status. Considering childhood factors affecting the incidence of wheezing, a logistic regression model was used to calculate adjusted odds ratios for “wheezing ever,” diagnosis of asthma in the last 12 months, and “asthma ever” in women with MRA, with women who did not receive MRA as the reference. Participants were stratified by term births, and adjusted odds ratios for outcomes were calculated using a logistic regression model. Results: A total of 68,123 participants were analyzed. The adjusted odds ratio for wheezing ever was 1.17 (95% confidence interval, 1.12–1.22). The adjusted odds ratios for the other outcomes did not significantly increase after adjusting for childhood factors. The same tendency was confirmed after excluding women with preterm births. Conclusion: MRA was associated with an increased incidence of childhood wheezing up to three years, irrespective of term births or preterm births. It is important that perinatal physicians consider both the adverse maternal side effects of MRA and its potential effects on the offspring’s childhood.

We developed a nonbreeding period continental-scale energetics-based model of daily waterfowl movement to predict year-specific migration and overwinter occurrence. The model approximates energy-expensive movements and energy-gaining stopovers as functions of metabolism and weather, in terms of temperature and frozen precipitation (i.e., snow). The model is a Markov process operating at the population level and is parameterized through a review of literature. We examined model performance against 62 years of non-breeding period daily weather data. The average proportion of available habitat decreased as weather severity increased, with mortality decreasing as the proportion of available habitat increased. The most commonly used nodes during the course of the nonbreeding period were generally consistent across years, with the most inter-annual variation present in the overwintering area. Our model revealed that the distribution of birds on the landscape changed more dramatically when the variation in daily available habitat was greater. The main routes for avian migration in North America were predicted by our simulations: the Eastern, Central, and Western flyways. Our model predicted an average of 77.4% survivorship for the nonbreeding period across all years (range = 76.4 – 78.4%), with lowest survivorship during the fall, intermediate survivorship in the winter, and greatest survivorship in the spring. We provide the parameters necessary for exploration within and among other taxa to leverage the generalizability of this migration model to a broader expanse of bird species, and across a range of climate change and land use/land cover change scenarios.

Level: Grade 5 Lesson Duration: 2 periods (50 minutes each) Lesson Objectives: • Students will examine the heating issue in their primary building (urban heat island effect). • Students will investigate how rooftop gardens lower the maximum surface temperatures on roofs. • Students will use the information they learned to further investigate whether reducing the surface temperature of the roof results in lower temperatures in the primary building, and conserves energy. • Students will determine whether rooftop gardens can help keep buildings cool. Standards: AREO-3-LS4-4, K-ESS2-2, ESS2-2, ESS3-1 Summary of Tasks / Actions: Period 1 1. Warm-up (10 minutes) 1.1 Introduce students to the topic, refresh the class expectations and guidelines. Outline the activity and its major blocks (Defining the problem/ investigation/ problem solving, brainstorming/ planning, construction of model, test, presentation). Talk about the issues of climate change and the need to reduce carbon dioxide and conserve energy. Link this to how this effects the students and their community (e.g., our city if extremely hot in summer and our campus and building become uncomfortable resulting in increased energy use with AC units, built up cities have less gardens, or green spaces due to less space, etc.) 1.2 Have students move into their groups. 2. Groupwork: investigation, (20 minutes) 2.1. Students will use the available resources (computers, iPad's, and classroom library) to research the topic. 3. Brainstorming & Planning (20 minutes) 3.1. Students will plan how to construct their two model buildings, organise the plants to be used, and other important information found in their investigation time (with and without garden). Period 2 4. Construction (30 minutes) 4.1. Regrouping-the students will be regrouped to work on the model buildings with or without gardens. 4.2.The students will construct their models. 5. Test (10 minutes in class time but also outside class time for evening test). 5.1 The students measure how hot the inside of the buildings gets during the day and how they cool off when the Sun goes down. 6. Report (10 minutes) 6.1 The two groups of students will report their findings to the class to compare the results.

Reactor corrosion and salt deposition problems severely restrict the industrialization of supercritical water oxidation. Transpiring wall reactor can effectively weaken these two problems through a protective water film formed on its internal surface. In this work, the effects of key structural parameters on water film properties of transpiring wall reactor were explored by numerical simulation, and established models were validated by comparing simulation and experimental values. The results show that transpiration water layer, transpiring wall porosity and inner diameter hardly affected organic matter degradation. Increasing transpiration water layer and transpiring wall porosity reduced reactor center temperatures in the middle and lower zones of the reactor. Increasing transpiration water layer, transpiring wall porosity and inner diameter decreased water film temperatures but increased water film coverage rates. Increasing reactor length affected slightly on the volume of the upper supercritical oxidation zone but enlarged the subcritical zone.

We present the development and application of a two-phase stirred reactor model for heavy oil upgrading in the presence of supercritical water (SCW), with coupled phase-specific thermolysis reaction kinetics and multicomponent hydrocarbon water phase equilibrium. We demonstrate the inference of oil and water phase kinetics parameters for a compact lumped reaction kinetics model through the application of this model to two different sets of batch reactor experiments reported in the literature. We infer that, though SCW can suppress the formation of newer polynuclear aromatics (PNA) from distillate range species, it is broadly ineffective in deterring the combination of pre-existing PNA fragments in the oil feed. Quantification of the conversion to distillate liquids before the onset of coke formation helps arrive at a clearer conclusion on whether the use of SCW in the batch reactor leads to better product outcomes for different oil feeds and operating conditions.

Hereditary spherocytosis is the most common cause of hemolytic anemia due to defects in the blood cell membrane. Partial splenic embolization (PSE) might significantly improve the effects of hemolysis in HS patients while preserving partial splenic function. However, due to the poor controllability of the scope of interventional embolization, PSE in pediatric HS had not been widely studied and applied. The present study is the first to propose that optimized PSE procedure to treat pediatric HS patients, which named super-selective partial splenic embolization (SPSE). We investigated the feasibility and effectiveness of SPSE. This study was conducted by retrospectively reviewing clinical data from HS patients treated by surgical treatments who were diagnosed at children’s hospital of Chongqing medical university from January 2015 to December 2019. Patients were divided into two groups according to treatment preference: SPSE (16 patients) group and total splenectomy (41 patients) group. The data were analyzed such as preoperative and postoperative leukocytes, hemoglobin, platelets, bilirubin, immunological indicators, and postoperative complications. The success rate of two groups were 100%. The improvement of hemolysis in patients after SPSE was not different from that after total splenectomy, and the effect can be maintained for a long time. The average hemoglobin value increased significantly from 6.97g/dL before SPSE to 12.2g/dL after SPSE (P=0.000). SPSE was performed without any serious complications. SPSE is a safe and effective treatment for moderate or severe HS in children.

The first part of this study showed that the triglyceride composition of purified oils has little impact on sterol/sterol ester oleogels. Hence, changes in the gels’ properties observed in previous studies must arise from minor polar components, particularly by changing the interactions within the fibrillar network. Selected molecules (oleic acid, tocopheryl acetate, monoglycerides, and water) were added to three purified oils to unravel the individual contributions introduced by different functional groups. While all additives retarded the molecular self-assembly of sitosterol with oryzanol, distinct effects were found for gel hardness, transition temperatures and enthalpies, strain sweep responses, and microstructure. It was discovered that the maximum storage modulus in the linear viscoelastic region does not necessarily relate to the gels’ compression firmness. In samples comprising oleic acid and tocopheryl acetate, discrete interaction mechanisms with the scaffolding elements were suggested since results between the two additives developed differently and were dose-dependent. A network supporting effect was suggested at low concentrations, in line with previous results for oils comprising low levels of thermal deterioration products. The microstructure of oleogels was considerably modified with additives. Unfortunately, effects are difficult to quantify due to the packed surface observed in AFM micrographs.

Why Does Catheter Ablation of Premature Ventricular Contractions

The role of solvent composition, in particular, minor oil components on sterol/sterol ester oleogels, has been studied recently [1]. Reportedly, deterioration products hamper network formation and modify the gel’s macroscopic properties, probably due to alterations of the scaffolding elements’ interactions. However, the role of the FA composition of TAGs has not yet been addressed. In this study, minor oil components of three vegetable oils with varying degrees of unsaturation (iodine values) were removed, and the oils were chemically and physically characterized before and after the treatment. Consequently, β sitostero/γ-oryzanol oleogels were produced, and the gel-sol (DSC) and sol-gel (rheology) transitions were monitored. Moreover, large and small deformation tests were performed, and the results were linked to oil parameters. In contrast to minor oil components, the FA composition has little impact on oleogel properties. The decline in gel hardness with IV is possibly linked to a lower solvent viscosity. However, a considerable drop in gel-sol transition temperature was observed with increasing IV indicating fewer elements of scaffolding. That was linked to the rapid formation of primary oxidation products in purified flaxseed oil during oleogel preparation, impairing tube formation. Similar to previous results on deterioration products, these minor components seem to aid network strength at low concentrations resulting in similar transition enthalpies and G’. That might be due to shifted network interactions in the presence of molecular species with functional groups. In the second part of this study, these modified interactions in the presence of selected minor components will be discussed.

Brucellosis is an endemic disease in many developing countries and ranked by the World Health Organization among the top seven “neglected zoonoses”. Although a Palestinian brucellosis control program was launched in 1998, the disease reemerged after 2012. Interestingly, a similar reemerging pattern was reported in the neighboring Israeli regions. The aim of this work was to characterize the reemerging strains and delineate their genetic relatedness. During 2015-2017, blood samples from 1324 suspected patients were analyzed using two serological tests. Seropositive samples were cultured, and their DNAs were analyzed by different genetic markers to determine the involved Brucella species and rule out any possible involvement of the Rev.1 vaccine strain. The rpoB gene was sequenced from 9 isolates to screen for rifampicin-resistance mutations. Multi Locus VNTR Analysis (MLVA-16) was used for genotyping the isolates. The molecular analysis showed that all isolates were B. melitensis strains unrelated to the Rev.1 vaccine. The rpoB gene sequences showed four single nucleotide variations (SNVs) not associated with rifampicin resistance. MLVA-16 analysis clustered the isolates into 22 unique genotypes that belong to the East Mediterranean lineage. Altogether, our findings show that the reemergence of brucellosis was due to B. melitensis strains of local origin, the Palestinian and Israeli control programs’ weaknesses could be a major factor behind the reemergence of the disease. However, other socioeconomic and environmental factors must be investigated. Moreover, strengthening brucellosis control programs and enhancing cooperation between all stakeholders is essential to ensure long-term program outcomes to fight brucellosis.

José M. Carballido1 and Hergen Spits21Novartis Institutes for Biomedical Research, Translational Medicine, Preclinical Safety, Switzerland2Department of Experimental Immunology, UMC, University of Amsterdam, Amsterdam, The Netherlands.Jan Egbert de Vries (Figure 1) is a cosmopolitan immunologist and an enthralling mentor with a large track record of innovative achievements in the fields of allergy and immunology. Jan was born in Strijen (NL), a small town located in the Hollands Diep estuary in the South of The Netherlands. He spent his youth in the NL combining his studies with his passion for sports; he became Dutch champion in decathlon. Shortly after his PhD, and like his fellow countryman Erasmus of Rotterdam, he started a long journey that brought him to France, California, Austria and Switzerland, although never settling in any of the cities he worked. Like Erasmus, he has been since an insatiable scholar (“Non est ulla studiorum satietas ”) and an inspiring mentor for a large number of students and collaborators.Jan studied at the University of Utrecht (NL) and graduated from the University of Amsterdam (NL) with a PhD in Immunology in 1976. After his graduation, he spent two years in the lab of John Mendelsohn at the University of California, San Diego (US), as a recipient of an Eleanor Roosevelt fellowship. Thereafter, he returned to Amsterdam, where he became the Head of the Department of Immunology at the National Cancer Research Institute. His groundbreaking observations on the cytotoxic activity of T lymphocytes isolated from melanoma patients (1) motivated the search for tumor-specific antigens, which could be used for the development of cancer vaccines.In 1985, Jan took on the position of Director of Immunology at the UNICET- Laboratoires for Immunological Research in Dardilly, a small village near Lyon (FR). UNICET was part of Schering Plough and collaborated closely with the DNAX Research Institute of Molecular and Cellular Biology in Palo Alto (US). It was during that time when Jan became interested in allergy, gaining a notable reputation in the field. Jan made a key contribution to the elucidation of the mechanisms controlling human IgE and IgG4 switching (Figure 2), implicating IL-4 as a key regulator of these processes (2). These were the early days when mouse helper T (Th) cells were segregated as either Th1 or Th2 subsets, following the seminal work of Tim Mossman and Bob Coffman at DNAX. Jan’s team observed these distinct phenotypes in human lymphocyte populations isolated from healthy and atopic individuals. However, against the dogma, he also described additional cytokine production profiles aside of the canonical and mutually exclusive IFN-γ or IL-4 secreting types. Now, several decades later, we appreciate the diversity and plasticity of these Th cell responses. Three years in France seemed too long time for this Dutch globetrotter and thus, in 1988, he and his research team moved to DNAX to continue their work in allergy and extend their research to regulatory responses with human T cells. Jan joined DNAX as the Head of Human Immunology and his work was key in elucidating the biology of IL-10 and IL-13 following their DNA cloning at DNAX. He showed that IL-4 and IL-13 were the triggers for allergic diseases (3) such as asthma, rhinitis and atopic dermatitis, and that IL-10 was a major factor dampening immune responses (4). His team also cloned the signaling lymphocyte activation molecule (SLAM/CD150) (5), which gave name to a new family of immune receptors involved in lymphocyte activation. The in vitr o work was expanded to in vivoexperimentation using severe combined immunodeficient (SCID) mice that were reconstituted with human tissues and cells (SCID-hu mice). These studies supported many drug development projects aiming to interfere with allergic responses and/or prevent transplant rejection.In 1997, Jan was recruited by Novartis as Global Head autoimmune and inflammatory diseases and Head of the Novartis Research Institute (NFI, from its abbreviation in German) in Vienna (AT). Jan led the transition of NFI to the Novartis Institutes for Biomedical Research (NIBR), expanding its original focus on dermatology to autoimmunity and inflammation. Jan was the founder of the Novartis Immunology Platform, a multidisciplinary group focused on the discovery and early development of both therapeutic antibodies and low molecular weight drugs targeting immune checkpoints, cytokines and cytokine receptors, G-protein-coupled receptors and other targets controlling T cell activation and tolerance induction. In 2008, he became Head of NIBR Europe. During his time in Vienna and Basel, Jan was instrumental for the advancement of many projects, particularly the development of the sphingosine 1 phosphate receptor antagonists FTY720 (Fingolimod/Gilenya®) and BAF312 (Siponimod/Mayzent®) for multiple sclerosis and in championing the clinical testing of immunotherapeutics in psoriasis as early proof of concept, which led to the approval of the anti-IL-17A monoclonal antibody AIN457 (Secukinumab/Cosentyx®). Jan also nurtured the path to initiate antigen-specific immune tolerance projects at Novartis, enabling many collaborations with scientists outside of Novartis.Jan’s remarkable ability to identify transformative opportunities, together with the experience he gained in academic and industrial settings, facilitated his transition from the big pharma industry to biotech. In this new setting, he has been acting as CEO and Chairman of AIMM Therapeutics, Chairman of Cassiopea and CEO of Tr1X, where he is developing cell and gene therapies to cure autoimmune diseases.The authors of this short biography had the privilege of working with Jan for many years during different steps of his career. We, like many other colleagues who worked side by side with Jan, learned to appreciate Jan’s extraordinary scientific insights and people skills. We had the opportunity to witness his passion for science and to learn his innovative way to approach immunology challenges and we remain honored to count on him as a source for inspiration and as a good friend.Major contributionsDiscovery of cytotoxic tumor-specific cytotoxic T cell clones from melanoma patientsCloning of human IL-4 and IL-13 and elucidation of their roles in the regulation of IgE production by human B cellsCloning and characterization of human IL-10 and demonstration of its profound immune-suppressive effectsDevelopment of Gilenya® and Mayzent®, and of Cosentyx® for the treatment of multiple sclerosis and psoriasis, respectivelyReferences1. de Vries JE, Spits H. Cloned human cytotoxic T lymphocyte (CTL) lines reactive with autologous melanoma cells. I. In vitro generation, isolation, and analysis to phenotype and specificity. J Immunol1984;132 :510–519.2. Pène J, Rousset F, Briere F, Chrétien I, Bonnefoy JY, Spits H et al. IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2.Proc Natl Acad Sci USA 1988;85 :6880–6884.3. Punnonen J, Aversa G, Cocks BG, McKenzie AN, Menon S, Zurawski G et al. Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci USA 1993;90 :3730–3734.4. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med1991;174 :1209–1220.5. Cocks BG, Chang C-CJ, Carballido JM, Yssel H, de Vries JE, Aversa G. A novel receptor involved in T-cell activation. Nature1995;376 :260–263.

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Background Obstructive Sleep Apnea (OSA) is a worldwide increasing syndrome, which, by promoting endothelial dysfunction, contributes to extend the cardiovascular risk. We evaluated the cardiovascular risk in a group of OSA patients. Methods A total of 185 OSA subjects (19 normal weight, 57 overweight, 109 obeses), seen at the Ambulatory of Sleep Disorders, during one year, entered the study. We assessed anthropometric features, polysomnographic findings, cardiovascular risk factors, smoking habit, Pulmonary Function Test, Arterial Blood Gas Analysis, Epworth Questionnaire, and Charlson Co-morbidities Index (CCI). Subjects were divided into three groups, according to their BMI: individuals with BMI ≥30 Kg/m2 (Group 1 n=109, mean age 61 ± 1; 74.3 % males), individuals with BMI ranging from 25.0 to 29.9 Kg/m2 defined as overweight subjects (Group 2 n=57, mean age 58.8 ± 1.4; 77% males) and subjects with a BMI ranging from 18.5 to 24.9 Kg/m2 defined normal weight subjects (Group 3 n=19, mean age 54.2 ± 2.3; 64,2% males). Results In the whole population, the percentage cardiovascular risk was weakly related with BMI (r=0.33; P<0.001), but not with AHI. The cardiovascular risk was strictly related to the obesity (p<0.00002), while the Epworth Questionnaire score and the Charlson Co-morbidity Index were respectively statistically higher in the group of obese individuals (p=0.006, p=0.00002) than in the other 2 Groups. When AHI values were stratified in tertiles, the percentage cardiovascular risk did not vary with increasing AHI values (Figure 2). Conclusions Further studies are required to investigate the pivotal role of inflammation due to obesity, and underlying increased cardiovascular risk in OSA patients.

Background: Tailgut cysts (TGCs) are benign congenital abnormalities that usually present with non-specific symptoms, comprising a diagnostic dilemma for the physicians. The aim of this study was to systematically review the literature concerning clinical manifestations, diagnostic modalities and histologic findings of TGCs and highlight current knowledge on therapeutic management of this rare entity. Methods: PubMed and Embase databases were systematically searched by two independent investigators (last search February 18, 2021) for studies concerning TGCs published in the last two decades. Results: Totally, 144 articles, including 135 case reports and 9 case series, met our inclusion criteria. 184 patients were included (3:1/female: male) with an age of 42.3 ± 18.7 (mean, SD) years, while 5 cases concerned newborn infants. Pain was the prevailed clinical manifestation (41.8%) whereas 16.8% were asymptomatic. MRI and CT were utilized for diagnosis in 58.7% and 54.7% of cases, respectively. The majority of cysts were multilocular, while ciliated columnar epithelium and smooth muscles of the cyst wall were the prevailed histological findings. Malignant degeneration of TGCs was reported on 32.1% of cases while carcinoid tumors were the most frequent malignancies. Surgical resection was performed at 155 cases, while laparoscopic and robotic approach at 18 and 2 cases respectively. A posterior approach was implemented in 80.9%, anterior technique in 9% and combined technique in 6.7% of cases. Postoperative complications and recurrence of the cystic lesion were reported in 17.4% and 7.6% of cases, respectively. Conclusions: TGCs constitute a dilemma for the physicians. Surgical resection comprises the ultimate treatment in order to avoid complications or malignant transformation of the cyst. Further well-designed studies are needed to assess follow-up strategies and the optimal therapeutic options for TGCs.

IntroductionAnti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of necrotizing vasculitis that primarily affect small blood vessels with pauci-immune complex deposits. It was mainly divided into microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA)[1]. The positive antineutrophilic cytoplasmic antibodies (ANCA) is the hallmark of AAV, and ANCA with specificity for proteinase-3 (PR3-ANCA) is predominantly detected in GPA while ANCA against myeloperoxidase (MPO-ANCA) is the most frequent autoantibody in MPA and EGPA[2]. In China as well as in other East Asian countries, MPA with MPO-ANCA is the most common AAV whereas in western countries, GPA with PR3-ANCA positivity is the most prevalent AAV instead[3, 4]. Also, compare to GPA, MPA usually occurred in more elderly population and had higher mortality due to more severe multisystem damage [4, 5]. Of marked interest was the result from a genomewide association study, which revealed that GPA and MPA were genetically distinct and their strongest genetic associations were with the antigenic specificity of ANCA, but not with the clinical syndrome[6]. So, it would be more validate that researches on the pathogenesis of AAV should be based on MPO-AAV mainly consisted of MPA or on PR3-AAV largely composed of GPA.Although the precise cause of AAV remained elusive, studies had revealed some of factors might involve in the pathogenesis of MPO-AAV [7-9]. MPO-ANCA could activate neutrophils by combining with MPO expressed on neutrophils under the stimulation of inflammatory factors to promote inflammatory reaction[8, 10]. In addition, the complement alternative pathway (cAP) was found to be involved in the pathogenesis of MPO-AAV. The combination of fragment a of fifth complement C5 (C5a) issued from cAP with C5a receptor (C5aR) on neutrophil could improve neutrophil survival, activate its respiratory burst and phagocytosis, which would further aggravate the inflammation and clinic damages[11-13].Neutrophil extracellular traps (NETs), which was first described in 2004, is a unique innate immune defense mechanism. It is composed of DNA, histones, and granular proteins mainly including MPO, PR3, neutrophil elastase (NE), peptidylarginine deiminase 4 (PAD4) and etc[14]. Studies had revealed NETs was involved in pathogenesis of the vasculitis[15-19]. The formation of NETs was called NETosis, and PAD4 expressed in neutrophil is a critical enzyme to generate NETs by mediating histone citrullination to promote the NETosis[20]. Actually, PAD4 was found to be involved in the pathogenesis of varieties of diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and tumors[21-23]. However, to our knowledge, there is no research by now to investigated PAD4 expression in neutrophil and its possible pathogenic effect in MPO-AAV. In the present study on patients with active MPO-AAV, we explored the PAD4 expression in neutrophil, its influence on vasculitis activity and the possible mechanism via detecting the PAD4 in neutrophils, checking the NETs, C5a and MPO-ANCA in peripheral blood, and analyzing their relationships.

African swine fever (ASF) is a highly contagious viral infection of domestic and wild pigs with high mortality. First reported in East Africa in early 1900s, ASF was largely controlled in the domestic pigs of many countries. However, in recent years ASF outbreaks have been reported in several countries in Europe and Asia. The occurrence of ASF in China, the largest pork producer in the world, in 2018 and in India, the country that surrounds and shares open borders with Nepal, has increased the risk of ASF transmission to Nepal. Lately, pig farming practices is growing in Nepal overcoming traditional religious and cultural biases against it. However, emergence of viral infections like ASF can severely affect its growth and sustainability. When there are no effective vaccines available to prevent it, the government should focus on preventing entry of the virus through strict quarantine measures in the borders, controlling illegal trades, and by effective management practices including biosecurity measures.