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.

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.

Pediatric patients undergoing chemotherapy may present upper airway obstruction due to severe oral mucositis. Although reversible, its clinical course correlates with the course of neutropenia and may be complicated. Thus, airway management in these patients must be determined on an individual case basis.

Facial Nerve palsy is a neurological condition that causes partial or complete impairment of the facial nerve. Bilateral facial nerve palsy is rare with an incidence of 1 per 5,000,000. We report the case of a 34-year-old gentleman who presented with sudden-onset bilateral lower motor neuron (LMN) facial weakness.

Recent taxonomic and molecular phylogenetic studies have shown that Gymnosphaera should be recognized as an independent taxonomic unit at the genus level under the family Cyatheaceae. In this study, the complete chloroplast genomes of the eight species of Cyatheaceae were sequenced, and their phylogenetic relationships were reconstructed using the maximum likelihood, Bayesian inference, maximum parsimony, and neighbor-joining methods, and the characteristics of their simple sequence repeats (SSRs) were compared and analyzed for the first time. The results showed that when Cyatheaceae was divided into three genera,the number, relative abundance, relative density, and GC content of all SSRs and of SSRs of certain unit lengths in the chloroplast genomes of the eight species of Cyatheaceae were genus specific in the whole chloroplast genomes and in their different regions (large single-copy, small single-copy, inverted repeat, intergenic spacer, intron, rRNA gene, and coding sequence regions). The SSRs overall and the single-nucleotide SSRs had significant differences in number, relative abundance, relative density, and GC content between the chloroplast genomes, their intergenic regions, and large single-copy regions. When Cyatheaceae was divided into two genera, only the difference in GC content was significant. Therefore, our results support the restoration of the hierarchical status of Gymnosphaera. This study provides an important basis for the identification of the phylogenetic relationship of Cyatheaceae plants.

Investigation of exophthalmos and blood-colored discharge from the left ventral punctum in a dog was consistent with a conjunctival cyst. 3-D prints of the cyst and surrounding facial bones identified a successful transconjunctival approach without an orbitotomy and patency of the left lacrimal duct was re-established.

BACKGROUND: Despite SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs, thus it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study seeks to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic children (SY), stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swabs samples. To define anti-SARS-CoV-2 antibodies we measured neutralization activity and total IgG load (Diasorin). We also evaluated antigen-specific B and CD8+T-cells, using a labelled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS had lower viral load at diagnosis (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Anti-SARS CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+T-cells. Whereas pro-inflammatory plasma protein profile was associated to symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regards to symptomatology, suggesting the ability of both SY and AS to contribute towards herd immunity. The virological profiling of AS suggested that they have lower virus load associated with faster virus clearance.

result shows that the blow-up is equivalent to the blow-up of the $L^r-$norms of the solutions for $r$ exceeding some critical value $r_c.$ Under very loose conditions we give the estimation of $r_c,$ relying on a variant of Gagliardo-Nirenberg inequality, and a kind of bootstrap method which is very similar to the Alikakos-Moser iteration procedure.

Miliaria crystallina is a benign skin condition that follows intense sweating due to excessive exposure to heat, hyperthermia, or humidity. Therefore, it is often observed in intensive care patients, who usually meet these conditions.

This note provides counterexamples to illustrate that Theorem 4 which is proposed by Cornejo, Lobo and Medina [M. E. Cornejo, D. Lobo, J. Medina, Bipolar fuzzy relation equations systems based on the product t-norm. Mathematical Methods in the Applied Sciences. 2019,42(17):5779-5793] is incorrect. The incorrect of Theorem 4 is due to the inaccuracy of the definition of feasible pair. Then we present the correction of the definition of feasible pair to the contention.

In this paper, we developed and studied a stochastic HIV model with nonlinear perturbation. Through a rigorous analysis, we firstly showed that the solution of the stochastic model is positive and global. Then, by employing suitable stochastic Lyapunov functions, we prove that the stochastic model admit a unique ergodic stationary distribution. In addition, sufficient conditions for the extinction of HIV infection are derived. Finally, numerical simulations are employed to confirm our theoretical results.

Lacking of systematic evaluations in soil quality and microbial community recovery after different amendments addition limits optimization of amendments combination in coal mine-soils. We performed a short-term incubation experiment over 12 weeks to assess the effects of three amendments (biochar: C; nitrogen fertilizer at three levels: N-N1~N3; microbial agent at two levels: M-M1~M2) based on C/N ratio (regulated by biochar and N level: 35:1, 25:1, 12.5:1) on soil quality and microbial community in the Qilian Mountains, China. Over the incubation period, soil pH and MBC/MBN were significantly lower than unamended treatment in N addition and C+M+N treatments, respectively. Soil organic carbon (SOC), total nitrogen (TN), available nitrogen (AN), available phosphorus (AP), available potassium (AK), microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) contents had a significant increase in all amended treatments (P<0.001). Higher AP, AK, MBC, MBN and lower MBC/MBN were observed in N2-treated soil(corresponding to C/N ratio of 25:1). Meanwhile, N2-treated soil significantly increased species richness and diversity of soil bacterial community (P<0.05). Principal coordinate analysis further showed that soil bacterial community compositions were significantly separated by N level. C-M-N treatments (especially at N2 and N1 levels) significantly increased the relative abundance (>1%) of the bacterial phyla Bacteroidetes and Firmicutes, and decreased the relative abundance of fungal phyla Chytridiomycota (P<0.05). Redundancy analysis illustrated the importance of soil nutrients in explaining variability in bacteria community composition (74.73%) than fungal (35.0%). Our results indicated that N and M addition based on biochar can improve soil quality by neutralizing soil pH and increasing soil nutrient contents, and the appropriate C/N ratio (25:1: biochar+N2-treated soil) can better promote mass, richness and diversity of soil bacterial community. Our study provided a new insight for achieving restoration of damaged habitats by changing microbial structure, diversity and mass by regulating C/N ratio of amendments

Araucaria araucana is an iconic long-lived endangered tree species exclusively distributed in Southern Chile and Argentina. Araucaria forest ecosystems provide a myriad of ecosystem benefits to local aboriginal Mapuche-Pehuenche communities. Among the main current threats for Araucaria forests are the increasing frequency and severity of wildfires and overgrazing. This study evaluates the effect of uncontrolled livestock grazing on soil quality indicators linked to critical functions relevant to forest regeneration and ecosystem service provision. We also aim to determine a set of soil quality indicators that are sensitive enough to grazing pressure, so they are useful as early indicators of degradation or the effectiveness of restoration practices. This study evaluated twenty soil quality indicators in two contiguous degraded forest areas with contrasting grazing pressure. We observed a substantial shift in forest structure, a reduction in tree coverage on the overgrazed sites. Overgrazing has produced significant deterioration of most soil physical, chemical, and biological quality indicators making soil conditions less suitable for seed germination and sapling establishment. We also observed an alteration in C, N, and P biogeochemical pools. Besides, soil physical indicators alterations suggest changes in these soils' hydrological behavior, potentially reducing water storage, availability, and increasing runoff. We show that uncontrolled grazing in native protected areas degrades soils and forest health, restricting forest regeneration and potentially accelerating erosive processes. Our results emphasized the need for an improved conservation plan for these forests that systematically evaluates and monitors livestock grazing and all its direct and indirect effects, including soil quality.

Aim: The Norwegian Association for Clinical Pharmacology in their National Guidelines decreased therapeutic range (TR) of topiramate (TPM) from 5-20 mg/L to 2-10 mg/L. The objective of this study is to ascertain which TR produces better clinical outcomes. Methods: Data source were request forms for routine therapeutic drug monitoring of TPM. Concentration dependent adverse drug reactions (ADRs) were evaluated in 1,721 samples taken pre-dose. Seizure frequency analysis was performed in 294 samples of monotherapy. Statistics: Prism 5.0, GraphPad Instatt: Mann–Whitney U test for median plasma level (PL). χ2-test for seizure frequency and for distribution of PL according to TR 5-20 mg/L and intervals <2, 2-5, 5-10, 10-20, >20 mg/L. Results: Better seizure control was found in children both in whole cohort (without seizure 49% vs 37% adults), as well as in monotherapy (56% vs 44%), in children with PL 5-20 mg/L vs 5 mg/L (65% vs 44%) and in children with PL 5-10 mg/L vs <2 mg/L. Seizure-free children had higher PL than those with seizure yearly: median (lower, upper quartile) [mg/L]: 5.5 (3.4-6.5) vs 4.7 (4.3-7.95). No difference was found in adults. Seizure control was poorer in all patients with PL <2 mg/L compared to 5-10 mg/L; and 10-20 mg/L; further in PL within 5-10 mg/L vs 10-20 mg/L; and in the period 2003-2005. ADRs reported in 38 samples (2.8%) were without relation to PL. Conclusions: Change of TR is not recommended.

Alcohol use disorder (AUD) is one of the most common but still poorly treated psychiatric conditions. Developing new treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in preclinical studies. Recent developments in our understanding of the reinforcement-based cognitive biases (RBCBs) that contribute to the development of AUD and its treatment offer new opportunities for both clinical and preclinical research. In this review, we first briefly describe psychological and cognitive theories that implicate various aspects of reinforcement sensitivity in the development, maintenance, and recurrence of alcohol addiction. Furthermore, in separate sections, we describe studies investigating RBCBs and their neural, neurochemical, and pharmacological correlates, and we discuss possible interactions between RBCBs and trajectories of AUD. Finally, we describe how recent translational studies using state-of-the-art animal models can facilitate our understanding of the role of reinforcement sensitivity and RBCBs in various aspects of AUD.