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Extracellular HMGB1 protein is known to induce inflammatory responses leading to an inflammatory storm. The outbreak of the Severe Acute Respiratory Syndrome COVID-19 due to the SARS-CoV-2 virus has resulted in a huge health concern worldwide. Recent data revealed that plasma/serum HMGB1 levels of patients suffering from inflammation-mediated disorders-such as COVID-19, cancer, and autoimmune disorders-correlate positively with disease severity and vice versa. A late release of HMGB1 in sepsis suggests the existence of a wide therapeutic window for treating sepsis. Rapid and accurate methods for the detection of HMGB1 levels in plasma/serum are, therefore, of great importance for monitoring the occurrence, treatment success, and survival prediction of patients with inflammation-mediated diseases. In this review, we briefly explain the role of HMGB1 in the cell, and particularly the involvement of extracellular HMGB1 (released from the cells) in inflammation-mediated diseases, with an emphasis on COVID-19. The current assays to measure HMGB1 levels in human plasma-Western blotting, ELISA, EMSA, and a new approach based on electrochemical immunosensors, including some of our preliminary results-are presented and thoroughly discussed.
- MeSH
- biosenzitivní techniky MeSH
- COVID-19 * krev diagnóza MeSH
- imunoanalýza MeSH
- lidé MeSH
- prognóza MeSH
- protein HMGB1 * krev MeSH
- SARS-CoV-2 MeSH
- sepse * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
An enigmatic localized pneumonia escalated into a worldwide COVID-19 pandemic from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This review aims to consolidate the extensive biological minutiae of SARS-CoV-2 which requires decipherment. Having one of the largest RNA viral genomes, the single strand contains the genes ORF1ab, S, E,M, N and ten open reading frames. Highlighting unique features such as stem-loop formation, slippery frameshifting sequences and ribosomal mimicry, SARS-CoV-2 represents a formidable cellular invader. Hijacking the hosts translational engine, it produces two polyprotein repositories (pp1a and pp1ab), armed with self-cleavage capacity for production of sixteen non-structural proteins. Novel glycosylation sites on the spike trimer reveal unique SARS-CoV-2 features for shielding and cellular internalization. Affording complexity for superior fitness and camouflage, SARS-CoV-2 challenges diagnosis and vaccine vigilance. This review serves the scientific community seeking in-depth molecular details when designing drugs to curb transmission of this biological armament.
- MeSH
- COVID-19 genetika metabolismus virologie MeSH
- fylogeneze MeSH
- lidé MeSH
- otevřené čtecí rámce MeSH
- pandemie MeSH
- RNA virová genetika MeSH
- SARS-CoV-2 genetika metabolismus MeSH
- virové proteiny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Ciele. V predošlých výskumoch boli dokumentované rôzne dopady pandémie COVID-19 na mentálne zdravie. Menej pozornosti však bolo venovanej tomu, ktoré faktory tu môžu zohrávať protektívnu rolu. Otázky a hypotézy. Predkladaná štúdia sa zaoberá tým, akú rolu zohrávali tri druhy pozitívnych očakávaní (optimizmus, nádej a sebaúčinnosť) v rámci subjektívnej pohody a prežívanej úzkosti počas nástupu prvej vlny pandémie COVID-19 na Slovensku. Súbor a metódy. Výskum bol realizovaný po tom, ako bol na Slovensku vyhlásený núdzový stav (N = 1011). Autori zisťovali sme subjektívnu pohodu, aktuálne prežívanú úzkosť, tri druhy očakávaní (nádej, optimizmus a všeobecnú sebaúčinnosť) a to, do akej miery vnímali účastníci výskumu koronavírus ako nebezpečný. Druhý zber dát sa konal po celoštátnom lockdowne (N = 391). Tu sa autori zamerali na stratégie zvládania. Analýzy. V rámci analýzy dát boli využité dva postupy. Prvý bol reprezentovaný lineárnou regresiou pracujúcou s viacerými modelmi (Bayesiánsky prístup), druhý mediačnou analýzou (Frekventistický prístup). Výsledky. V hlavnej časti (N = 1011), realizovanej krátko povyhlásení núdzového stavu, sa ako dôležitý prediktor ukázal predovšetkým optimizmus. Pozitívne predikoval subjektívnu pohodu a negatívne prežívanú úzkosť. Zmienený vzťah bol sprostredkovaný tým, do akej miery považovali účastníci výskumu koronavírus za nebezpečný. Okrem toho, sebaúčinnosť negatívne predikovala prežívanú úzkosť a subškály nádeje predikovali subjektívnu pohodu. V nadväzujúcom zbere dát (N = 391), uskutočnenom po prvom lockdowne, sa autori zamerali na rolu stratégii zvládania ako potenciálneho mediátora vo vzťahu medzi očakávaniami a kritérialnými premennými. Tu sa ako jeden z potenciálne dôležitých mechanizmov ukázali predovšetkým dysfunkčné stratégie zvládania stresu. Limity. Medzi limity možno zaradiť príležitostný výber výskumného súboru a to, že otázka, týkajúca sa toho, do akej miery tu šlo o vzťah špecifický pre pandémiu, zostáva aj naďalej otvorená. Okrem toho je nevyhnutné, aby výzkumníci zostali pri vyjadrovaní sa k otázke kauzality nanajvýš opatrní.
Objectives. Although various mental health-related consequences of the COVID-19 pandemic have been documented, there has been far less attention given to potential protective factors. Questions and hypotheses. In the present study, authors examined the role of three types of positive expectancies - optimism, hope, and self-efficacy - as predictors of well-being and anxiety. Furthermore, authors examined the role of coping strategies as a potential mediator between expectancies and criterion variables. Sample and settings. The present study was conducted during the COVID-19 outbreak in Slovakia after a national emergency was declared (N=1011). Additionally, longitudinal follow up was conducted after a national lockdown (N=391). Statistical analysis. Multi-model linear regression (the Bayesian approach) and simple mediation analysis (the Frequentist approach) were used to answer research questions. Results. In the main study with N=1011 participants sampled after a national emergency was declared, the role of optimism in predicting anxiety and well-being was corroborated. Moreover, this finding was replicated after a national lockdown and the degree to which Coronavirus was considered dangerous served as a potential mediator. Besides optimism, self-efficacy negatively predicted anxiety, and subscales of hope predicted well-being. Additionally, the role of coping strategies as potential mediator was examined. In follow up with N=391 respondents who decided to participate after the national lockdown, authors found an indirect effect of optimism on well-being and anxiety through dysfunctional coping. Limitations. The present study has some limitations that should be reflected upon. For example, convenience sampling was used. Moreover, interpretations related to causality should be avoided and the specificity of the effect in relation to a pandemic situation should be further examined in future research.
Acanthamoeba spp. can cause a sight threatening disease. At present, the current treatments used to treat Acanthamoeba spp. Infections, such as biguanide-based antimicrobials, remain inefficacious, with the appearance of resistant forms and high cytotoxicity to host cells. In this study, an initial screening was conducted against Acanthamoeba castellanii Neff and murine macrophages J774A.1 using alamarBlueTM. Among the 160 compounds included in the cited box, 90% exhibited an inhibition of the parasite above 80%, while only 18.75% of the compounds inhibited the parasite with a lethality towards murine macrophage lower than 20%. Based on the amoebicidal activity, the cytotoxicity assay, and availability, Terconazole was chosen for the elucidation of the action mode in two clinical strains, Acanthamoeba culbertsoni and Acanthamoeba castellanii L10. A fluorescence image-based system and proteomic techniques were used to investigate the effect of the present azole on the cytoskeleton network and various programmed cell death features, including chromatin condensation and mitochondria dysfunction. Taking all the results together, we can suggest that Terconazole can induce programmed cell death (PCD) via the inhibition of sterol biosynthesis inhibition.
- Publikační typ
- časopisecké články MeSH
Adequate safety precautions and proper use of personal protective equipment (PPE) in hospitalized patients with health care-associated infections (HAIs) are the most effective preventions in their spread. Observational study was conducted in one inpatient facility in the Czech Republic before the COVID-19 pandemic (April 2019 to February 2020). Data were analyzed using Minitab at a significance level of .05. The execution of preventative measures in patients hospitalized with a HAI (n = 44) and the use of PPE by health care workers (n = 514) have been observed. The presence of defined PPE items usage differs on the basis of the department type (P = .0004). The correctness of PPE use differs on the basis of profession (P < .001), hand disinfection before PPE use (P < .001), use of all PPE (P < .001), and hand hygiene after PPE use (P < .001). General nurses had a higher observed frequency of hand hygiene (53.3%) than physicians (42.4%). The correct order of operations when using PPE differs on the basis of the department type (P < .001) and their architecture arrangement (open, semiopen, box) (P < .001). Critical preventative measures shortage was found at all units. Insufficient execution of the correct procedure of actions in the use of PPE was observed among health care workers. The best results have been observed among nurses.
Multiple studies have investigated bibliometric factors predictive of the citation count a research article will receive. In this article, we go beyond bibliometric data by using a range of machine learning techniques to find patterns predictive of citation count using both article content and available metadata. As the input collection, we use the CORD-19 corpus containing research articles-mostly from biology and medicine-applicable to the COVID-19 crisis. Our study employs a combination of state-of-the-art machine learning techniques for text understanding, including embeddings-based language model BERT, several systems for detection and semantic expansion of entities: ConceptNet, Pubtator and ScispaCy. To interpret the resulting models, we use several explanation algorithms: random forest feature importance, LIME, and Shapley values. We compare the performance and comprehensibility of models obtained by "black-box" machine learning algorithms (neural networks and random forests) with models built with rule learning (CORELS, CBA), which are intrinsically explainable. Multiple rules were discovered, which referred to biomedical entities of potential interest. Of the rules with the highest lift measure, several rules pointed to dipeptidyl peptidase4 (DPP4), a known MERS-CoV receptor and a critical determinant of camel to human transmission of the camel coronavirus (MERS-CoV). Some other interesting patterns related to the type of animal investigated were found. Articles referring to bats and camels tend to draw citations, while articles referring to most other animal species related to coronavirus are lowly cited. Bat coronavirus is the only other virus from a non-human species in the betaB clade along with the SARS-CoV and SARS-CoV-2 viruses. MERS-CoV is in a sister betaC clade, also close to human SARS coronaviruses. Thus both species linked to high citation counts harbor coronaviruses which are more phylogenetically similar to human SARS viruses. On the other hand, feline (FIPV, FCOV) and canine coronaviruses (CCOV) are in the alpha coronavirus clade and more distant from the betaB clade with human SARS viruses. Other results include detection of apparent citation bias favouring authors with western sounding names. Equal performance of TF-IDF weights and binary word incidence matrix was observed, with the latter resulting in better interpretability. The best predictive performance was obtained with a "black-box" method-neural network. The rule-based models led to most insights, especially when coupled with text representation using semantic entity detection methods. Follow-up work should focus on the analysis of citation patterns in the context of phylogenetic trees, as well on patterns referring to DPP4, which is currently considered as a SARS-Cov-2 therapeutic target.
- Publikační typ
- časopisecké články MeSH
