Molecular mimicry of NMDA receptors may contribute to neuropsychiatric symptoms in severe COVID-19 cases

Approximately 30% of individuals with severe SARS-CoV-2 infections also develop neurological and psychiatric complaints. In rare cases, the occurrence of autoimmune encephalitis has been reported after SARS-CoV-2 infection. In this systematic review, we have identified eight SARS-CoV-2-associated cases of anti-NMDA receptor encephalitis. All had cerebrospinal fluid antibodies against the NMDA receptor and a recent onset of working memory deficits, altered mental status, or psychiatric symptoms, such as confusion, agitation, auditory hallucination, catatonia and speech dysfunction. All patients received high-dose steroid and immunoglobulin therapeutics and conditions improved in each case. These findings suggest that clinical attention should be paid to warning signs of autoimmune encephalitis in severe COVID-19 cases. If characteristic features of autoimmune encephalitis are present, autoantibody diagnostics should be performed and confirmed cases should be treated with immunotherapy to minimize neurological impairments

Izloženost ambijentalnomu duhanskomu dimu na radnome mjestu u Makedoniji: kako sada stojimo?

To assess the prevalence and the level of exposure to environmental tobacco smoke (ETS) in the workplace after the enactment of the law restricting indoor smoking in Macedonia, we performed a cross-sectional, self-administered questionnaire study including 372 never-smoking workers recruited from six workplaces. We found a high prevalence of workers exposed to ETS in the workplace (27.4 %) with no significant difference between particular occupation groups. We found no significant difference in the prevalence of passive smokers in the workplace between this study and our study conducted before the law was enacted (31.5 % vs. 27.4 %, P=0.324). The prevalence of workers exposed to ETS for less than three hours a day was significantly lower than of passive smokers with longer exposure (28.4 % vs. 71.6 %, P=0.038). The prevalence of workers exposed to ETS from less than 10 cigarettes smoked by coworkers per day was lower than the prevalence of workers with higher exposure, but statistical significance was not reached (37.9 % vs. 62.1 %, P=0.087). Our findings indicate a high prevalence and a high level of exposure to ETS in the workplace, which calls for stricter adherence to smoking-free legislation or even the total ban of smoking in the workplace.Ovo je ispitivanje obuhvatilo 372 radnika na šest različitih radnih mjesta koji nikad nisu pušili kako bi se procijenila zastupljenost osoba izloženih duhanskomu dimu na radnome mjestu i razina njihove izloženosti nakon zakonskih ograničenja pušenja u zatvorenim prostorijama u Makedoniji. Ispitivanje je provedeno s pomoću upitnika koji su radnici ispunjavali sami. Utvrdili smo visoku zastupljenost radnika izloženih ambijentalnomu duhanskomu dimu na radnome mjestu (27,4 %) te nisu zamijećene statistički značajne razlike među zanimanjima. Nisu uočene značajne razlike između zastupljenosti pasivnih pušača na radnome mjestu u ovome ispitivanju i u našem ranijem ispitivanju, kada još nije na snagu stupio zakon o ograničenju pušenja (31,5 % naprema 27,4 %, P=0,324). Zastupljenost radnika izloženih ambijentalnomu duhanskomu dimu ne dulje od tri sata na dan bila je statistički značajno niža negoli onih čija je izloženost trajala duže (28,4 % naprema 71,6 %, P=0,038). Zastupljenost radnika koji su bili izloženi dimu kolega koji su pušili manje od 10 cigareta na dan bila je niža negoli onih s većom izloženosti, ali razlika nije bila statistički značajna (37,9 % naprema 62,1 %, P=0,087). Naši rezultati potvrđuju da i dalje postoje visoka zastupljenost izloženih radnika i visoke razine izloženosti ambijentalnomu duhanskomu dimu na radnome mjestu, što upućuje na potrebu uvođenja strožih zakona o zabrani pušenja

Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer

Tumor-associated macrophages (TAMs) represent a major component of the tumor microenvironment supporting tumorigenesis. TAMs re-education has been proposed as a strategy to promote tumor inhibition. However, whether this approach may work in prostate cancer is unknown. Here we find that Pten-null prostate tumors are strongly infiltrated by TAMs expressing C-X-C chemokine receptor type 2 (CXCR2), and activation of this receptor through CXCL2 polarizes macrophages toward an anti-inflammatory phenotype. Notably, pharmacological blockade of CXCR2 receptor by a selective antagonist promoted the re-education of TAMs toward a pro-inflammatory phenotype. Strikingly, CXCR2 knockout monocytes infused in Ptenpc−/−; Trp53pc−/− mice differentiated in tumor necrosis factor alpha (TNF-α)-releasing pro-inflammatory macrophages, leading to senescence and tumor inhibition. Mechanistically, PTEN-deficient tumor cells are vulnerable to TNF-α-induced senescence, because of an increase of TNFR1. Our results identify TAMs as targets in prostate cancer and describe a therapeutic strategy based on CXCR2 blockade to harness anti-tumorigenic potential of macrophages against this disease. © 2019 The Author(s) Di Mitri et al. show that CXCR2 blockade in prostate cancer triggers TAMs re-education, leading to tumor inhibition. CXCR2-KO monocytes infused in Ptenpc−/−; Trp53pc−/− tumor-bearing mice differentiate into TNFα-releasing pro-inflammatory macrophages that induce senescence in tumor cells. PTEN-null tumors display higher sensitivity to TNF-α-induced senescence because of TNFR1 upregulation

Profesionalna astma u radnika izloženih prašinama iz biljnih i voćnih čajeva

We performed a cross-sectional study to detect occupational asthma (OA) in 63 subjects occupationally exposed to herbal and fruit tea dust and in 63 corresponding controls. The evaluation included a questionnaire, skin prick tests to workplace and common inhalant allergens, spirometry, and histamine challenge test. The evaluation of the work-relatedness of asthma in the exposed workers was based on serial peak expiratory flow rate (PEFR) measurements and bronchoprovocation tests. We found a higher prevalence of respiratory symptoms in the exposed workers, whereas spirometric parameters were significantly lower. The prevalence of sensitisation to allergens and of bronchial hyperresponsivenss (BHR) did not differ significantly between the groups. The prevalence of asthma was also similar in both groups (8.0 % vs. 6.4 %; P=0.540). Work-relatedness of symptoms was reported by all asthmatic tea workers and by no control with asthma. Significant work-related changes in PEFR diurnal variations and in non-specific BHR, suggesting allergic OA, were found in one tea worker with asthma (1.6 %). No specific workplace agent causing OA in the affected subject was identified. None of the tea workers with asthma met the criteria for medical case definition of the reactive airway dysfunction syndrome (RADS). Our data confirm workplace exposure to herbal and fruit tea dust as a risk factor for OA.Svrha je ovoga presječnog ispitivanja bila otkriti profesionalnu astmu u skupini od 63 ispitanika koji su na radnome mjestu bili izloženi prašinama biljnih i voćnih čajeva. Kao kontrola uzet je jednak broj uredskih radnika koji nisu bili izloženi ovim prašinama. Ocjena izloženih i kontrolnih ispitanika obuhvatila je upitnik, skin prick testove na uobičajene i profesionalne inhalacijske alergene, spirometriju te histaminski test. Povezanost astme s profesionalnom izloženosti u radnika utvrđena je prema kriterijima Američkog kolegija pulmologa (American College of Chest Physicians, krat. ACCP), a na temelju mjerenja niza vršnih ekspiratornih protoka (engl. peak expiratory flow rate, PEFR) i niza bronhoprovokativnih testova. Izloženi su radnici iskazali veću prevalenciju respiratornih simptoma odnosno niže spirometrijske vrijednosti od kontrole. Izloženi ispitanici nisu se značajno razlikovali od kontrole u prevalenciji senzibilizacije na profesionalne i uobičajene inhalacijske alergene te prevalenciji pretjerane bronhalne reaktivnosti (engl. bronchial hyperresponsiveness, krat. BHR). Isto vrijedi i za prevalenciju astme (8,0 % u izloženih radnika prema 6,4 % u kontrola; P=0,540). Povezanost simptoma s poslom prijavili su svi radnici u obradi čaja oboljeli od astme te ni jedan kontrolni ispitanik s astmom. U jednoga astmatičnog radnika na čaju utvrđene su značajne promjene u dnevnim varijacijama PEFR-a te u nespecifičnom BHR-u koji upućuju na profesionalnu astmu (1.6 %). Nije utvrđeno koja je to tvar uzrokovala profesionalnu astmu u ovog ispitanika. Nitko od izloženih radnika s astmom nije zadovoljio sve medicinske kriterije za dijagnozu sindroma reaktivne disfunkcije dišnih putova (engl. reactive airway dysfunction syndrome, RADS). Naši podaci potvrđuju da je profesionalna izloženost prašinama iz biljnih i voćnih čajeva čimbenik rizika od profesionalne astme

High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model

Copyright: Copyright 2014 Elsevier B.V., All rights reserved.Background: The combination of virotherapy and chemotherapy may enable efficient tumor regression that would be unachievable using either therapy alone. In this study, we investigated the efficiency of transgene delivery and the cytotoxic effects of alphaviral vector in combination with 5-fluorouracil (5-FU) in a mouse mammary tumor model (4 T1).Methods: Replication-deficient Semliki Forest virus (SFV) vectors carrying genes encoding fluorescent proteins were used to infect 4 T1 cell cultures treated with different doses of 5-FU. The efficiency of infection was monitored via fluorescence microscopy and quantified by fluorometry. The cytotoxicity of the combined treatment with 5-FU and alphaviral vector was measured using an MTT-based cell viability assay. In vivo experiments were performed in a subcutaneous 4 T1 mouse mammary tumor model with different 5-FU doses and an SFV vector encoding firefly luciferase.Results: Infection of 4 T1 cells with SFV prior to 5-FU treatment did not produce a synergistic anti-proliferative effect. An alternative treatment strategy, in which 5-FU was used prior to virus infection, strongly inhibited SFV expression. Nevertheless, in vivo experiments showed a significant enhancement in SFV-driven transgene (luciferase) expression upon intratumoral and intraperitoneal vector administration in 4 T1 tumor-bearing mice pretreated with 5-FU: here, we observed a positive correlation between 5-FU dose and the level of luciferase expression.Conclusions: Although 5-FU inhibited SFV-mediated transgene expression in 4 T1 cells in vitro, application of the drug in a mouse model revealed a significant enhancement of intratumoral transgene synthesis compared with 5-FU untreated mice. These results may have implications for efficient transgene delivery and the development of potent cancer treatment strategies using alphaviral vectors and 5-FU.publishersversionPeer reviewe

Seasonal influenza vaccination of healthcare workers : Systematic review of qualitative evidence

Background Most countries recommend that healthcare workers (HCWs) are vaccinated seasonally against influenza in order to protect themselves and patients. However, in many cases coverage remains low. A range of strategies have been implemented to increase uptake. Qualitative evidence can help in understanding the context of interventions, including why interventions may fail to achieve the desired effect. This study aimed to synthesise evidence on HCWs’ perceptions and experiences of vaccination for seasonal influenza. Methods Systematic review of qualitative evidence. We searched MEDLINE, EMBASE and CINAHL and included English-language studies which reported substantive qualitative data on the vaccination of HCWs for seasonal influenza. Findings were synthesised thematically. Results Twenty-five studies were included in the review. HCWs may be motivated to accept vaccination to protect themselves and their patients against infection. However, a range of beliefs may act as barriers to vaccine uptake, including concerns about side-effects, scepticism about vaccine effectiveness, and the belief that influenza is not a serious illness. HCWs value their autonomy and professional responsibility in making decisions about vaccination. The implementation of interventions to promote vaccination uptake may face barriers both from HCWs’ personal beliefs and from the relationships between management and employees within the targeted organisations. Conclusions HCWs’ vaccination behaviour needs to be understood in the context of HCWs’ relationships with each other, with management and with patients. Interventions to promote vaccination should take into account both the individual beliefs of targeted HCWs and the organisational context within which they are implemented