Vector-borne parasites often manipulate hosts to attract uninfected vectors. For example, parasites causing malaria alter host odor to attract mosquitoes. Here we discuss the ecology and evolution of fruit-colonizing yeast in a tripartite symbiosis – the so-called “killer yeast” system. “Killer yeast” consists of Saccharomyces cerevisiae yeast hosting two double stranded RNA viruses (M satellite dsRNAs, L-A dsRNA helper virus). When both dsRNA viruses occur in a yeast cell, the yeast converts to lethal toxin‑producing “killer yeast” phenotype that kills uninfected yeasts. Yeasts on ephemeral fruits attract insect vectors to colonize new habitats. As the viruses have no extracellular stage, they depend on the same insect vectors as yeast for their dispersal. Viruses also benefit from yeast dispersal as this promotes yeast to reproduce sexually, which is how viruses can transmit to uninfected yeast strains. We tested whether insect vectors are more attracted to killer yeasts than to non‑killer yeasts. In our field experiment, we found that killer yeasts were more attractive to Drosophila than non-killer yeasts. This suggests that vectors foraging on yeast are more likely to transmit yeast with a killer phenotype, allowing the viruses to colonize those uninfected yeast strains that engage in sexual reproduction with the killer yeast. Beyond insights into the basic ecology of the killer yeast system, our results suggest that viruses could increase transmission success by manipulating the insect vectors of their host.
The management of an unusual nasal foreign body is illustrated. A 34-year-old male presented to our outpatient clinic after inhalation of liquid cast during preparation of a plaster mask. The foreign body had solidified within the nasal cavities, causing obstruction and headache. Ambulatory removal was incomplete, therefore ESS was indicated.
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.
Background: Seasonal influenza is a burden for emergency departments. The aim of this study was to investigate whether point-of-care (POC) PCR testing can be used to reduce staff sick days and improve diagnostic and therapeutic procedures. Methods: Using a cross-over design, the cobas® Liat® Influenza A/B POC PCR test (Liat) was compared to standard clinical practice during the 2019/2020 influenza season. All adult patients (aged ≥18 years) with fever (≥38°C) and respiratory symptoms were included. Primary endpoints were prevalence of influenza infections in the ED and staff sick days. Secondary endpoints were frequency of antiviral and antibacterial therapy, time between admission and test result or treatment initiation, patient disposition, ED length of stay (LOS) and for in-patients mortality and LOS. Nurses were interviewed about handling and integration of POC testing. The occurrence of SARS-CoV-2 infections coincided with the second half of the study. Results: A total of 828 patients were enrolled in the study. All 375 patients of the intervention group were tested with Liat, 103 of them (27.6%) tested positive. During the intervention period staff sick days were reduced by 34.4% (p=0.023). Significantly more patients in the intervention group received antiviral therapy with neuraminidase-inhibitors (7.2% vs. 3.8%, p=0.028) and tested patients received antibiotics more frequently (40.0% vs. 31.6%, p=0.033). Patients with POC test were transferred to external hospitals significantly more often (5.6% vs. 1.3%, p=0.01). Conclusion: We conclude that POC testing for influenza is useful in the ED, especially if it is heavily frequented by patients with respiratory symptoms.
Vaccination against the COVID-19 virus began in December 2020 in the UK and is now running at 5% population/week. High Levels of social restrictions were implemented for the third time in January 2021 to control the second wave and resulting increases in hospitalisations and deaths. Easing those restrictions must balance multiple challenging priorities, weighing the risk of more deaths and hospitalisations against damage done to mental health, incomes and standards of living, education outcomes and provision of non-Covid-19 healthcare. Weekly and monthly officially published values in 2020/21 were used to estimate the impact of seasonality and social restrictions on the spread of COVID-19 by age group, on the economy and healthcare services. These factors were combined with the estimated impact of vaccinations and immunity from past infections into a model that retrospectively reflected the actual numbers of reported deaths closely both in 2020 and early 2021. It was applied prospectively to the next 6 months to evaluate the impact of different speeds of easing social restrictions. The results show vaccinations are significantly reducing the number of hospitalisations and deaths. The central estimate is that relative to a rapid easing, the avoided loss of 57,000 life years from a strategy of relatively slow easing over the next 4 months comes at a cost in terms of GDP reduction of around £0.4 million/life-year loss avoided. This is over 10 times higher than the usual limit the NHS uses for spending against Quality Adjusted Life Years (QALYs) saved. Alternative assumptions for key factors affecting give significantly different trade-offs between costs and benefits of different speeds of easing. Disruption of non-Covid-19 Healthcare provision also increases in times of higher levels of social restrictions. In most cases, the results favour a somewhat faster easing of restrictions in England than current policy implies.
In this study, Volterra-Fredholm integral equation is solved by Hosoya Polynomials. The solutions obtained with these methods were compared on the ﬁgure and table. And error analysis was done. Matlab programming language has been used to obtain conclusitions, tables and error analysis within a certain algorithm.
Peer-review and subject-matter editing is the backbone of scientific publishing. However, early career researchers (ECRs) are given few opportunities to participate in the editorial process beyond reviewing articles. Thus, a disconnect exists: science needs high-quality editorial talent to conduct, oversee, and improve the publishing process, yet we dedicate few resources to building editorial talent nor giving ECRs formal opportunities to influence the publishing landscape from within. Here, we describe a “two-way” fellowship model that gives ECRs a “seat” at the editorial table of a field-leading journal. We describe both the necessary framework and benefits that can stem from editorial fellowships for ECRs, editors, journals, and the scientific community.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection usually causes no or mild coryzal symptoms in the paediatric population. In this letter, we describe a 21-month-old boy infected with SARS-CoV-2 who presented atypically with features compatible with croup. With the current Coronavirus Disease 2019 (COVID-19) pandemic, infection control measures need to be appropriately heightened and early diagnostic sampling for SARS-CoV-2 should be carried out even in symptomatology that is atypical of COVID-19.
In this paper, Tetraphenyldipyranylidene (DPPh), a large quinoidal planar π-conjugated heterocyclic, was considered as primary organic molecule in organic field effect transistors (OFETs). Electron-withdrawing atoms such as F, Cl, and Br were attached to the H-atoms of four peripheral phenyl groups of para-positions relative to the O-atoms of DPPh. Density functional theory (DFT) calculations at the M06-2X/6-311G++ (d,p) level were performed. The influences of the different electron-withdrawing atoms such as F, Cl, and Br on the electronic and optical properties, charge transport parameters, and charge carrier mobility were investigated. The absorption and emission spectra of the DPPh and its derivatives were theoretically simulated in OFETs. The simulated spectra show an intense peak in the visible region (400-650 nm), in which the highest adsorption/emission intensity is related to DPPh-Br. Moreover, the charge injection energy barrier of DPPh and its derivatives were calculated by considering Pt as the source electrode. Based on the results, a greater hole transport is predicted than the electron transport. Moreover, the obtained ratio of the hole/electron mobility and the theoretical correlations between the charge transport parameters of monomers and dimers show that the insertion of the electron-withdrawing atoms in the DPPh structure is a promising strategy to have an ambipolar or n-type semiconductor, too. The obtained results show that introducing electron-withdrawing atoms at the para-position of the DPPh improves the hole/electron injection and transport process in the OFET devices. Finally, DPPh-Br shows a great performance in comparison with the substituted F and Cl atoms in the OFETs devices.
The meta-analysis by Di Tommaso et al demonstrated as elderly patients with mitral regurgitation (MR) undergoing mitral valve repair (MVr) had lower short-term mortality and higher long-term survival with respect to patients undergoing mitral valve replacement (MVR). The benefit of repair is such, that initial surgical strategy is advisable in the elderly even in case of mild symptoms if compared with conservative management. However, even if repair can be performed in presence of some specific etiologies, as degenerative MR or secondary MR, there are always cases where a replacement can be an acceptable solution compared to a repair with uncertain future, regardless of our believes and our technical ability. In this subset of patients, the literature does not show any improvement in outcome of transcatheter mitral repair. Mitral valve repair has to be always done, but look at the etiologies and to the consequences that what is done today can cause tomorrow.
Pharmaceutical industry and drugs advertisement is sometimes accused of “creating diseases”. This article assesses and describes the role of that industry in fostering medicalization. First, the notions of medicalization and pharmaceuticalization are defined. Then, the problem of distinguishing between harmful overmedicalization and well-founded medicalization is presented. Next, the phenomenon of disease mongering is explained and illustrated by the case analysis of medicalizing pain and suffering in three contexts: 1) the general idea of medicalizing physical pain, 2) the medicalization of grief, and 3) disease mongering of pseudoaddiction - a condition promoted in order to increase the demand for opioid pain relievers.
An independent 59-year-old Asian man presented with a current history of fever, left shoulder pain and unconsciousness.Contrast-enhanced computed tomography revealed mediastinitis with expansive fluid collection. During the mediastinitis treatment, huge vegetation was sequentially confirmed at the annulus of the mitral valve and was successfully treated via small right thoracotomy.