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Background: Acute rhinosinusitis (ARS) is a common and well-defined disorder, primarily of viral aetiology, with rhinovirus and coronavirus accounting for more than 50% of viral ARS. The fight with COVID-19 pandemic resulted in an increased availability viral testing, which in turn allowed testing for presence of SARS-Cov-2 in all patients presenting common cold (or ARS) symptoms. The aim of this study was to assess the clinical characteristics of acute rhinosinusitis in patients diagnosed with COVID-19.Methodology/Principal: This study is a post-hoc analysis. Patients symptoms were evaluated using a structured questionnaire twice: directly after a positive SARS-Cov-2 result and 7-12 days following the first evaluation. Subjects were asked about presence of nasal and systemic symptoms as well as headache.Results: A total of 130 COVID-19 symptomatic patients were recruited into the study, 58 (45%) patients met EPOS2020 diagnostic criteria for ARS. Of all ARS patients, 72% presented with rhinorrhoea, 69% with pain perceived over paranasal sinuses, 62% with nasal congestion, 52% with cough, 45% with olfactory dysfunction, 38% with fever, 33% with facial pressure and in 22% pain was exacerbated by sinus palpation. Conclusions: Half of COVID-19 subjects has ARS. The course of SARS-Cov-2 ARS does not seem to differ significantly from ARS of other aetiologies. Since ARS in the course of COVID-19 seems to meet the definition of ARS proposed by EPOS 2020, we hypothesize that substances validated for ARS treatment, such as intranasal corticosteroids could be effective in SARS-Cov-2 ARS.

The study investigates the process of creating evaluative homogeneity within a performance-based research funding system. It does so in reference to the experience of creating a national journal ranking in Poland in 2019. It refers to the cases of two disciplines: biology and history. The use of this case is justified by its unique character, that is creating the ranking through means of both bibliometric indicators and expert panels. We therefore asked: What guided the actors who participated in the process of creating the ranking through the use of bibliometric indicators when introducing changes to its initial form? To answer this question, a mixed-methods approach was used. First, we conducted a quantitative analysis of changes made to the ranking during the consecutive steps of its creation. Second, we conducted a qualitative analysis of semi-structured interviews regarding actors’ motivations. By reflecting on the qualitative analysis along with the results of the quantitative part, this study reveals the extent to which actors impacted the form evaluative homogeneity took within the system. It further argues that this is dictated by how actors position themselves in relation to two opposing forces: those favouring the homogenization of research and those maintaining its heterogeneity. As these forces remain imbalanced, the study concludes with a call for further exploration of the interplay between the forces of homogenization and heterogenization and how the tensions between them are mediated within a performance-based research funding system.

Introduction: Surgical orbital decompression involves removal of one or more orbital bony walls in order to gain space for overgrown muscles and adipose tissue, which results in a reduction in pressure on the eye. This observational study aims to perform an endocrinological assessment of the surgical treatment outcomes of thyroid eye disease (TED) patients before and after orbital decompression. Material &Methods: This retrospective study included 51 TED patients (84 orbits) who underwent endoscopic orbital decompression (EOD) or balanced orbital decompression.The effect of surgical treatment was evaluated via the clinical activity score (CAS), modified NOSPECS and EUGOGO classification. Results: Before orbital decompression, the average CAS index was 3.83+/–1.86 points, whereas the modified NOSPECS score was 3.31+/–0.97 points. After surgical intervention, the values were as follows: 2.07+/–1.84 points for CAS and 2.5+/–0.97 points for modified NOSPECS. The EUGOGO classification before surgery showed that Graves’ orbitopathy (GO) was mild, moderate to severe and sight-threatening in 1%, 25% and 74% of the orbits, respectively. After surgery, GO was determined to be mild, moderate to severe and sight-threatening in 24%, 57% and 19% of the orbits. Statistical analysis was performed using the R 3.6.2 statistical environment. Inference about the statistical reliability of the parameter was made by calculating the mean and the 95% credibility interval (CI). Conclusions: The severity of TED decreased after orbital decompression. The CAS, modified NOSPECS and EUGOGO classification showed a statistically reliable postoperative reduction. The drop in activity of the disease after orbital surgery requires careful follow-up.

Defects in the phosphoinositide 3-kinase (PI3K) pathway are shared characteristics in several brain disorders, including the inherited intellectual disability and autism spectrum disorder, fragile X syndrome (FXS). PI3K signaling therefore could serve as a therapeutic target for FXS and other brain disorders. However, broad inhibition of such a central signal transduction pathway involved in essential cellular functions may produce deleterious side effects. Pharmacological strategies that selectively correct the overactive components of the PI3K pathway while leaving other parts of the pathway intact may overcome these challenges. Here, we provide the first evidence that disease mechanism-based PI3K isoform-specific inhibition may be a viable treatment option for FXS. FXS is caused by loss of the fragile X mental retardation protein (FMRP), which translationally represses specific messenger RNAs, including the PI3K catalytic isoform p110β. FMRP deficiency increases p110β protein levels and activity in FXS mouse models and in cells from subjects with FXS. Here, we show that a novel, brain-permeable p110β-specific inhibitor, GSK2702926A, ameliorates FXS-associated phenotypes on molecular, cellular, behavioral, and cognitive levels in two different FMRP-deficient mouse models. Rescued phenotypes included increased PI3K downstream signaling, protein synthesis rates, and dendritic spine density, as well as impaired social interaction and higher-order cognition. Several p110β-selective inhibitors, for example, a molecule from the same chemotype as GSK2702926A, are currently being evaluated in clinical trials to treat cancer. Our results suggest that repurposing p110β inhibitors to treat cognitive and behavioral defects may be a promising disease-modifying strategy for FXS and other brain disorders.

In this paper, we place the issue of university activism in the context of constituent and constituted power. By this we mean the ever-present danger that activists’ demands will be co-opted and concurrently deactivated. To mitigate this risk, we develop a set of conceptual tools that enables thinking about the activist university in terms of instituent praxis; that is, an open process of co-becoming of an institution and its actors through the continuous co-production of rules that drive their actions. Contrary to the view of the university as something instituted, the activist university that we propose emphasises the possibility of sustaining the process of acting and its underlying rules, rather than the result of the act. The activist university is understood here as a crack that leaves the instituted university open every time the self-production of its subject emerges by the self-transformation of the actors in the very course of their activities. We observe a chance for grounding instituent praxis in the ontological shift in thinking the activist university from being to co-becoming, as this will allow for reclaiming the future for the university and its broader ecology.

Background MORF-057 is an orally administered small molecule designed to inhibit the α 4β 7 receptor, addressing an unmet medical need in inflammatory bowel disease (IBD) patients, and avoiding the need for periodic therapeutic infusions and the risk for infusion-related reactions. This study evaluated single (SAD) and multiple ascending doses (MAD) of MORF-057 in healthy volunteers. Methods This was a randomized, double-blind, placebo-controlled, single and multiple doses, phase 1 study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MORF-057 conducted in a Phase I Unit in the USA. Subjects were randomized 3:1 to MORF-057 or placebo capsules once daily in the SAD cohorts: 25, 50, 100, 150, and 400 mg; or twice daily (BID) in the MAD cohorts: 100 and 200 mg total daily doses (dosed as 50 and 100 mg BID, respectively). In the MAD cohorts, trough PK samples were obtained premorning or pre-evening dose following administration of 50 or 100 mg BID, respectively. Blood samples to assess receptor occupancy (RO) of α 4β 7 and α 4β 1 integrins were obtained prior to the first dose and 12 hours after treatment. Results To date, 51 healthy subjects were dosed; 1 subject withdrew consent on Day 2 for personal reasons. Eleven non-serious adverse events (AEs) were reported; AEs were mild and did not result in discontinuation. Two reversible mild AEs in the 200 mg MAD cohort were possibly related to MORF-057 (macular / maculopapular rash). No safety signals were identified to date. Following dosing, MORF-057 was rapidly absorbed and systemic exposure increased approximately dose-proportionally (Fig.1). Mean α 4β 7 RO was found to be greater than 95% after each of the three highest single doses (Fig.2). In multiple dosing, mean α 4β 7 RO was greater than 90% at the lower dose, while the highest dose tested resulted in α 4β 7 RO saturation at steady state. α 4β 1 RO was below the limit of quantitation with mean trough values estimated to be Conclusion Current results demonstrated that single and multiple ascending doses of MORF-057 were well tolerated, with only mild, non-serious AEs reported that did not result in study drug discontinuation. MORF-057 demonstrated a favorable PK profile where target engagement was confirmed and resulted in α4β7 receptor saturation in many subjects receiving higher doses. These results support further investigation of MORF-057 and provide a basis for dose selection phase 2 studies in patients with IBD. (NCT04580745)

This article opens a space for dialogue between Marxism and the field of higher education research. First, it demonstrates to what extent Marx is present in the theoretical and methodological discussions within the field and it examines the reasons behind his absence, i.e., the development of two perspectives regarding capitalist transformations, namely academic capitalism and exceptionalism. Second, it introduces Marx’s method of critique, conceived as the integrity of three different analytical moments and it further explicates how those moments can be translated into the general research program. It does so in reference to a) ontological assumptions; b) sector’s political economy; c) students and academic protests; d) ideas about the alternative. Finally, it uses those four areas to reflect on the key differences between Marx’s critique and the two perspectives discussed. By doing so it opens up paths for further dialogue between Marxism and higher education research.

INTRODUCTION Granulomatosis with polyangiitis (GPA) is an autoimmune disease leading to necrotizing lesions in the affected tissues. Computed tomography (CT) of paranasal sinuses reveals multiple lesions in patients with GPA, for example, sinus opacification, bone / cartilage destruction, and neoosteogenesis. OBJECTIVES We aimed to describe and compare CT lesions found in patients with GPA and those with chronic rhinosinusitis (CRS) and to propose a new radiological marker of GPA-nasal strands. PATIENTS AND METHODS This retrospective study (2014-2019) included 53 patients with GPA (22 men, 31 women) at a median (interquartile range) age of 45 (34-60) years. Computed tomography findings of mucosal lesions in paranasal sinuses, neoosteogenesis, bony and cartilaginous lesions, and nasal strands were analyzed. Nasal strands were described as intermucosal adhesions resembling bands. A total of 71 patients with CRS (reference group) were assessed for the presence of the same parameters. RESULTS Computed tomography scans showed mucosal lesions in the sinuses of 35 patients (66%) with GPA. Nasal septum perforation was observed in 19 patients (35.8%), neoosteogenesis in 17 (32.1%), and bone damage in 14 (26.4%). External nose deformity was present in 16 patients (30.2%). Nasal strands on CT were found in 36 patients with GPA (68%) and 32 patients with CRS (45%). The presence of 5 or more strands was more characteristic of GPA than CRS (P

(1) Background: The study proposed to analyze microvessel density (MVD) in rhabdomyosarcoma (RMS) based on the expression of angiogenesis markers and define its prognostic role in this group of patients. (2) Methods: The study included forty-nine pediatric patients diagnosed with RMS. Tumor tissue expression of CD31, CD34, and CD105 was analyzed. MVD was calculated and correlated with clinical RMS prognostic parameters. (3) Results: CD31, CD34, and CD105 are expressed in all RMS cases. MVD/CD105 was significantly higher in the RMS group than in the control group. The mean and median values of MVD/CD105 in RMS were lower than MVD/CD31 and MVD/CD34. MVD/CD105 was significantly higher in patients with alveolar RMS and those with metastatic disease. Patients with higher levels of MVD/CD105 had a higher risk of death (HR = 1.009). (4) Conclusion: CD105 is a relevant angiogenesis marker in pediatric RMS, and MVD/CD105 is an independent risk factor of short overall survival in children with RMS.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com. ispartof: RHINOLOGY vol:58 issue:Suppl S29 pages:I-+ ispartof: location:Netherlands status: published

Niniejszy tekst przedstawia trzy dominujące narracje na temat uniwersytetu w kryzysie, jak również możliwe scenariusze dla przyszłego uniwersytetu, które się z nich wyłaniają. Nacisk położony zostaje na trzy różne ontologie, które podtrzymują wspominane dyskursy: indywidualną, publiczną i tego, co wspólne. W celu odsłonięcia ukrytych przesłanek, które oddziałują na wspominane dyskusje, wprowadzona zostaje metoda ontologii politycznej. Krytyczna analiza ontologicznych założeń, wspierających wizję przyszłego uniwersytetu, pokazuje, że dwa pierwsze hegemoniczne modele, choć przedstawiane jako alternatywy, w istocie wiąże założenie statyczności sektora. Dlatego też niniejszy artykuł przedstawia ontologię relacji opierającą się na tym, co wspólne, jako sposób wyrwania się z klinczu wywołanego hegemonią dyskursów o prywatnym i publicznym charakterze uniwersytetu.

Introduction: In the general population, nasal obstruction is a common complaint. However, an objective evaluation of nasal obstruction is difficult. Nose examination, computed tomography (CT), acoustic rhinometry, and anterior rhinomanometry do not accurately reflect the discomfort reported by patients with nasal obstruction. In patients with nasal obstruction, this study evaluated nasal breathing with a unique device for continuous nasal-oral spirometry – a nasal-oral flow analyzer (NOFA); moreover, quality of life was compared between patients with normal nasal breathing on NOFA and of those with impaired nasal breathing on NOFA. Methods: Of 181 adult patients admitted to an ENT department due to nasal obstruction that were enrolled in the study, 97 (53.6%) completed all per-protocol assessments, including the SF-36 questionnaire and 3-hour, continuous nasal-oral spirometry with NOFA. Based on the presence of normal nasal breathing defined as ≥95% of nasal flow, the 97 patients were divided into those with normal nasal breathing (n=31) and impaired nasal breathing (n=66). Results: Patients with normal nasal breathing differed from those with impaired nasal breathing with respect to all SF-36 subscales (physical functioning, p=0.004; role-physical, p=0.009; bodily pain, p

Kaszel jest najczęstszym objawem chorób układu oddechowego. Stosowane dotychczas metody leczenia przewlekłego kaszlu u dorosłych nie są w pełni skuteczne. Przewlekły kaszel o niejasnej przyczynie lub niepoddający się leczeniu może spowodować znaczne upośledzenie jakości życia. Wyniki badań dowodzą, że jedną z metod leczenia przewlekłego, uporczywego kaszlu jest terapia mowy. W pracy zaprezentowano przypadek chorej z przewlekłym kaszlem w przebiegu przewlekłego niealergicznego nieżytu nosa i choroby refluksowej przełyku, przez 18 lat leczonej nieskutecznie, u której terapia mowy istotnie zmniejszyła kaszel i poprawiła jakość życia.

Cough is the most common symptom of respiratory diseases. The results of management of chronic cough in adults are still unsatisfactory. Unexplained and difficult-to-treat chronic cough causes significant impairment in patients‘ quality of life. The results of recent studies suggest that speech therapy (speech language intervention) is one of the few methods which are usefull in management of persistent chronic cough. We present a case of a patient with chronic cough due to chronic nonallergic rhinitis and gastroesophageal reflux disease, who had been unsuccessfully treated for 18 years. In the patient speech therapy resulted in a significant decrease of cough severity and improvement of quality of life.

Epilepsy is often associated with altered expression or function of ion channels. One example of such a channelopathy is the reduction of A-type potassium currents in the hippocampal CA1 region. The underlying mechanisms of reduced A-type channel function in epilepsy are unclear. Here, we show that inhibiting a single microRNA, miR-324-5p, which targets the pore-forming A-type potassium channel subunit Kv4.2, selectively increased A-type potassium currents in hippocampal CA1 pyramidal neurons in mice. Resting membrane potential, input resistance and other potassium currents were not altered. In a mouse model of acquired chronic epilepsy, inhibition of miR-324-5p reduced the frequency of spontaneous seizures and interictal epileptiform spikes supporting the physiological relevance of miR-324-5p-mediated control of A-type currents in regulating neuronal excitability. Mechanistic analyses demonstrated that microRNA-induced silencing of Kv4.2 mRNA is increased in epileptic mice leading to reduced Kv4.2 protein levels, which is mitigated by miR-324-5p inhibition. By contrast, other targets of miR-324-5p were unchanged. These results suggest a selective miR-324-5p-dependent mechanism in epilepsy regulating potassium channel function, hyperexcitability and seizures.

Introduction: The efficacy of management of chronic cough in adults is limited. Speech therapy is one of the few therapeutic methods which seems to be useful in patients with persistent chronic cough. However, the method has not been available in Poland so far. The aim of the study was to implement speech therapy and assess its efficacy in the management of patients with difficult-to-treat chronic cough. Material and methods: Patients, who were diagnosed and managed due to difficult-to-treat chronic cough, were enrolled into the study. Speech therapy was developed on the basis of the technique described by Vertigan. The entire therapy consisted of eight weekly sessions, each lasting 45 minutes. Before and after speech therapy, cough severity and its impact on the quality of life was assessed by the Visual Analogue Scale (VAS) and Leicester Cough Questionnaire (LCQ). Additionally, cough challenge test with capsaicin was performed. Results: Eighteen women were enrolled into the study, 15 of them (83%) attended all treatment sessions (median age 66 years, median duration of cough 60 months). There was a significant decrease in cough severity measured by VAS (46 vs. 28 mm, p = 0.016) after completion of speech therapy. A significant improvement in patients’ quality of life measured by LCQ (10.7 vs. 14.6 points, p = 0.004) and an increase in the threshold of cough reflex measured by capsaicin challenge were also demonstrated. Conclusions: Speech therapy resulted in a decrease in cough severity and improvement of quality of life of females with refractory chronic cough. Our results support the use of speech therapy as add-on treatment in females with difficult-to-treat cough.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric population. In 35% of cases, RMS develops in the head and neck (H&N) region, and only combined therapy is recognized as a curative treatment. However, recent advances in skull base and reconstructive surgery, along with microsurgery and endoscopic surgery, have strengthened the role of surgery as an important part of RMS treatment. In the present study, 36 pediatric RMS cases (24 males and 12 females) were analyzed after surgical treatment. The average age at diagnosis was 7 years. In total, 67% of tumors were localized in the parameningeal region. Alveolar RMS was the most common histopathological type. A total of 16 patients were treated due to disease recurrence or a previous non-radical surgical procedure, while 19 cases had inductive chemotherapy and/or radiotherapy preceding surgical treatment due to locally advanced disease. In 1 case, only diagnostic biopsy was performed. It is recommended that the management of H&N RMS is interdisciplinary from the beginning. Extensive surgical dissection in the H&N region for RMS may result in severe cosmetic defects and functional impairment; thus, these risks should be considered during treatment planning, and the surgical approach should be based on the individual characteristics of each patient.

In the diversity of the flavor world only five basic tastes have been described. The newest one, umami, has been identified about one hundred years ago by Kikunae Ikeda but widely accepted just in the second half of the twentieth century by international scientific world. There are three umami substances: monosodium glutamate (MSG), inosine-5'-monophosphate (IMP), guanylo-5'-monophosphate (GMP). A real breakthrough in umami history concerned the finding about independent receptors for umami: T1R1 and T1R3 (taste receptors type 1 member 1 and member 3). The palatable, delicious taste of umami and its mechanism determined a lot of research studies on this highlight. Umami substances elicit salivary secretion, enhance appetite and increase food palatability. They are desirable to improve the quality of diet. Moreover, the association between umami substances and the suppression of obesity has been found. Studies suggest that umami is engaged in metabolism but also increases satiety and reduces the post-ingestive recovery of hunger.

Introduction: To evaluate the effectiveness of methylprednisolone (MP) and surgical treatment in achieving complete reversal of dysthyroid optic neuropathy (DON) and predictive factors of this therapy. Material and methods: The group consisted of 10 patients (18 eyes) with DON. The diagnosis of DON was based on at least two criteria from the following: (i) deterioration of visual acuity (VA< 1.0), (ii) loss of colour vision, (iii) optic disc swelling, and/or (iv) signs of DON in magnetic resonance imaging (presence of apical crowding and/or optic nerve stretching). A complete recovery of DON was defined as the normalisation of VA (VA = 1.0), normal colour vision, and reversal of optic disc swelling. A significant improvement was defined as improvement of VA of at least 0.2. The consecutive steps of treatment of DON consisted of: (i) first-line treatment — intravenous MP pulse therapy (3 × 1 g); (ii) second-line treatment — endoscopic intranasal orbital decompression of medial wall; (iii) additional treatment — additional MP therapy and/or surgical decompression. Results: A significant improvement in VA could be achieved in the majority of patients; a complete recovery was noted in 22.2%, 33.3%, and 66.7% of eyes after first-line, second-line, and additional treatment, respectively. Positive predictive factors were: younger age (p = 0.049), shorter duration of DON (p = 0.035), and a higher Graves’ orbitopathy clinical activity score (p = 0.035). Conclusions: By using combination therapy (intravenous MP pulse therapy and surgical decompression), a complete recovery can be achieved in the majority of patients with DON. (Endokrynol Pol 2016; 67 (2): 166–173)

In this short introduction to the thematic issue of Theoretical Practice we draw on the Marxist concept of critique to explain how Marxist higher education research could be understood as a constituting practice within-against-beyond the contemporary university in crisis.