Epigenetic activation of antiviral sensors and effectors of interferon response pathways during SARS-CoV-2 infection

Recent studies have shown that methylation changes identified in blood cells of COVID-19 patients have a po-tential to be used as biomarkers of SARS-CoV-2 infection outcomes. However, different studies have reported different subsets of epigenetic lesions that stratify patients according to the severity of infection symptoms, and more importantly, the significance of those epigenetic changes in the pathology of the infection is still not clear. We used methylomics and transcriptomics data from the largest so far cohort of COVID-19 patients from four geographically distant populations, to identify casual interactions of blood cells' methylome in pathology of the COVID-19 disease. We identified a subset of methylation changes that is uniformly present in all COVID-19 patients regardless of symptoms. Those changes are not present in patients suffering from upper respiratory tract infections with symptoms similar to COVID-19. Most importantly, the identified epigenetic changes affect the expression of genes involved in interferon response pathways and the expression of those genes differs be-tween patients admitted to intensive care units and only hospitalized. In conclusion, the DNA methylation changes involved in pathophysiology of SARS-CoV-2 infection, which are specific to COVID-19 patients, can not only be utilized as biomarkers in the disease management but also present a potential treatment target

Acute and Chronic Pain Learning and Teaching in Medical School—An Observational Cross-Sectional Study Regarding Preparation and Self-Confidence of Clinical and Pre-Clinical Medical Students

Background and objectives: Adequate pain management is a major challenge of public health. The majority of students graduating from medical schools has insufficient education and experience with patients suffering pain. Not enough is being taught regarding pain in non-verbal patients (children, critically ill in the intensive care unit, demented). Chronic pain is the most difficult to optimize and requires appropriate preparation at the level of medical school. Our aim was to evaluate attitudes, expectations and the actual knowledge of medical students at different levels of their career path regarding the assessment and treatment of acute and chronic pain. Materials and Methods: We performed an observational cross-sectional study that was based on a survey distributed among medical students of pre-clinical and post-clinical years at the Pomeranian Medical University in Szczecin, Poland. The survey included: demographic data, number of hours of formal pain teaching, actual knowledge of pain assessment, and pain treatment options in adults and children. Results: We received responses from 77/364 (21.15%) students and 79.2% of them rated the need to obtain knowledge regarding pain as very important (10/10 points). Post-clinical group declared having on average 11.51 h of acute pain teaching as compared to the 7.4 h reported by the pre-clinical group (p = 0.012). Graduating students also reported having significantly more classes regarding the treatment of chronic pain (6.08 h vs. 3.79 h, p = 0.007). The average level of comfort in the post-clinical group regarding treatment of acute pain was higher than in the pre-clinical group (6.05 vs. 4.26, p = 0.006), similarly with chronic pain treatment in adults (4.33 vs. 2.97, p = 0.021) and with pain treatment in children (3.14 vs. 1.97, p = 0.026). Conclusions: This study shows that education about pain management is a priority to medical students. Despite this, there continues to be a discrepancy between students’ expectations and the actual teaching and knowledge regarding effective pain management, including the vulnerable groups: chronic pain patients, children, and critically ill people

Correction: Pollen morphology of Polish species from the genus Rubus L. (Rosaceae) and its systematic importance.

[This corrects the article DOI: 10.1371/journal.pone.0221607.]

Pollen morphology of Polish species from the genus Rubus L. (Rosaceae) and its systematic importance.

The genus Rubus L. (Rosaceae) not been investigated satisfactorily in terms of palynology. This genus is taxonomically very difficult due to the large number of species and problems with their delimitation, as well as very different distribution areas of particular species. The aim of this study was to investigate pollen morphology and for the first time the ranges of intrageneric and interspecific variability of Rubus species, as well as verify the taxonomic usefulness of these traits in distinguishing studied taxa from this genus. The selected species of the genus Rubus were analysed for 11 quantitative pollen characteristics and the following qualitative ones: exine ornamentation, pollen outline and shape, as well as bridge structure. Analyses were conducted on a total of 1740 pollen grains, which represent 58 blackberry species belonging to a majority of subgenera and all the sections and series found in Poland. The most important characters included exine ornamentation (exine ornamentation type, width and direction of grooves and striae, number and diameter of perforations) and length of the polar axis (P). The arrangement of the examined species on the dendrogram does not corroborate division of the genus Rubus into subgenera, sections and series currently adopted in taxonomy. This fact is not surprising because the taxonomy of the genus was not based on pollen characters. Pollen features should be treated in taxonomy as auxiliary, because they fail to differentiate several (10) individual species, while the other ones create groups with similar pollen traits

How Do Pollen Grains of <i>Convallaria majalis</i> L. Respond to Different Habitat Conditions?

To date, the effect of habitat conditions on the characteristics of pollen has not been extensively investigated; however, it needs to be remembered that it may be highly significant for the quality of their generative reproduction success. It was decided to conduct the analyses on Convallaria majalis as a common species, naturally found in many different forest habitats. Moreover, the investigations covered pollen morphology and for the first time also the variability of pollen grains in this species. The plant material came from 98 natural sites located in Poland, in nine differing forest habitats. In total, 2940 pollen grains were analyzed in terms of five quantitative features (i.e., the length of the longest and shortest polar axes–LA and SA, exine thickness–Ex, the LA/SA and Ex/LA ratios) as well as the following qualitative ones: pollen outline and shape, sulcus type and exine ornamentation. Our studies revealed that the most important pollen characteristics in C. majalis included sulcus type, exine ornamentation, distribution and size of perforations, LA and pollen shape. The study showed the response of pollen to different habitat conditions found in the nine investigated habitats. The Ex/LA ratio and Ex were these pollen characteristics, which exhibited the most marked response to the different habitat conditions. Pollen from two habitats, moist mixed coniferous forest and upland mesic broadleaved forest, exhibited the most distinct characteristics

Does the Reaction of Inflorescences and Flowers of the Invasive <i>Prunus serotina</i> Ehrh. to Various Herbicides Give Hope for Elimination of This Species from Polish Forests?

The North American Prunus serotina Ehrh. is an invasive neophyte widespread in Polish forests. Due to the negative impact of this species on native vegetation, the most effective methods of its removal from the stands have been searched for. Our research aimed to determine whether herbicides that were applied in spring 2020 influenced morphological features of inflorescences and flowers of P. serotina in the next year of vegetation (i.e., 2021). So far, the effects of herbicides used were analysed in the same year, no later than a few weeks after their application. The experiment was carried out on the research area of 2.7 ha located in the Zielonka Forest near Poznań in Poland (N 52.5330, E 17.1015). The response of 39 P. serotina trees to six different herbicides, containing sulfonylurea derivatives, glyphosate and phenoxy herbicides was investigated. The chemicals were applied directly to the tree, to the holes made in the trunk axis. The plant material included inflorescences from 10 control trees and 29 trees treated with different herbicides. Nine morphological inflorescence and flower features and three ratios were analysed. In total 200 inflorescences and 1000 flowers were measured. Statistically significant differences between inflorescence and flower features collected from trees treated with different herbicides were demonstrated. The largest ranges of values of the studied features were found in inflorescences and flowers collected from the control trees (C-WI, C-DWH). The greatest variability of the studied features was found for C-DWH. Compared to the control trees the reduction in inflorescence size, as well as the smaller number of flowers, were recorded in the trees treated with different herbicides, irrespective of an active substance content. The use of six different herbicides—with different active substance contents to control P. serotina proves to be effective

COVID-19: Pain Management in Patients with SARS-CoV-2 Infection—Molecular Mechanisms, Challenges, and Perspectives

Since the end of 2019, the whole world has been struggling with the pandemic of the new Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Available evidence suggests that pain is a common symptom during Coronavirus Disease 2019 (COVID-19). According to the World Health Organization, many patients suffer from muscle pain (myalgia) and/or joint pain (arthralgia), sore throat and headache. The exact mechanisms of headache and myalgia during viral infection are still unknown. Moreover, many patients with respiratory failure get admitted to the intensive care unit (ICU) for ventilatory support. Pain in ICU patients can be associated with viral disease itself (myalgia, arthralgia, peripheral neuropathies), may be caused by continuous pain and discomfort associated with ICU treatment, intermittent procedural pain and chronic pain present before admission to the ICU. Undertreatment of pain, especially when sedation and neuromuscular blocking agents are used, prone positioning during mechanical ventilation or extracorporeal membrane oxygenation (ECMO) may trigger delirium and cause peripheral neuropathies. This narrative review summarizes current knowledge regarding challenges associated with pain assessment and management in COVID-19 patients. A structured prospective evaluation should be undertaken to analyze the probability, severity, sources and adequate treatment of pain in patients with COVID-19 infection

Postoperative Delirium in Patients with Chronic Obstructive Pulmonary Disease after Coronary Artery Bypass Grafting

Background and Objectives: The incidence of postoperative delirium (POD) in patients with chronic obstructive pulmonary disease (COPD) is unclear. It seems that postoperative respiratory problems that may occur in COPD patients, including prolonged mechanical ventilation or respiratory-tract infections, may contribute to the development of delirium. The aim of the study was to identify a relationship between COPD and the occurrence of delirium after cardiac surgery and the impact of these combined disorders on postoperative mortality. Materials and Methods: We performed an analysis of data collected from 4151 patients undergoing isolated coronary artery bypass grafting (CABG) in a tertiary cardiac-surgery center between 2012 and 2018. We included patients with a clinical diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. The primary endpoint was postoperative delirium; Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) was used for delirium assessment. Results: Final analysis included 283 patients with COPD, out of which 65 (22.97%) were diagnosed with POD. Delirious COPD patients had longer intubation time (p = 0.007), more often required reintubation (p = 0.019), had significantly higher levels of C-reactive protein (CRP) three days after surgery (p = 0.009) and were more often diagnosed with pneumonia (p &lt; 0.001). The CRP rise on day three correlated positively with the occurrence of postoperative pneumonia (r = 0.335, p = 0.005). The probability of survival after CABG was significantly lower in COPD patients with delirium (p &lt; 0.001). Conclusions: The results of this study confirmed the relationship between chronic obstructive pulmonary disease and the incidence of delirium after cardiac surgery. The probability of survival in COPD patients undergoing CABG who developed postoperative delirium was significantly decreased

The Effect of Potassium Canrenoate (Mineralocorticoid Receptor Antagonist) on the Markers of Inflammation in the Treatment of COVID-19 Pneumonia and Fibrosis—A Secondary Analysis of Randomized Placebo-Controlled Clinical Trial

In March 2020, the World Health Organization (WHO) announced a global pandemic of coronavirus disease 2019 (COVID-19) that presented mainly as an acute infection of the lower respiratory tract (pneumonia), with multiple long-term consequences, including lung fibrosis. The aim of this study was to evaluate the influence of potassium canrenoate on inflammatory markers in the treatment of COVID-19 pneumonia. A randomized clinical trial (RCT) of intravenous potassium canrenoate vs. placebo was performed between December 2020 and November 2021. This study is a secondary analysis of that RCT. In the final analysis, a total of 49 hospitalized patients were included (24 allocated to the potassium canrenoate group and 25 to the placebo group). Patients were assessed by serum testing and blood cell cytometry on day 1 and day 7 of the intervention. Age, sex, and body mass index were not significantly different between the placebo group and intervention group. Although there was a significantly higher rate of ischemic heart disease in the placebo group, rates of other preexisting comorbidities were not significantly different. There were no significant differences in the inflammatory parameters between the potassium canrenoate and placebo groups on day 1 and day 7. However, the intragroup comparisons using Wilcoxon’s test showed significant differences between day 1 and day 7. The CD3% for potassium canrenoate increased significantly between day 1 and day 7 (12.85 ± 9.46; 11.55 vs. 20.50 ± 14.40; 17.80; p = 0.022), while the change in the placebo group was not significant (15.66 ± 11.39; 12.65 vs. 21.16 ± 15.37; 16.40; p = 0.181). The IL-1ß total count [%] increased over time for both potassium canrenoate (0.68 ± 0.58; 0.45 vs. 1.27 ± 0.83; 1.20; p = 0.004) and placebo (0.61 ± 0.59; 0.40 vs. 1.16 ± 0.91; 1.00; p = 0.016). The TNF-α total count (%) decreased significantly between day 1 and day 7 for potassium canrenoate (0.54 ± 0.45; 0.40 vs. 0.25 ± 0.23; 0.10; p = 0.031), but not for placebo (0.53 ± 0.47; 0.35 vs. 0.26 ± 0.31; 0.20; p = 0.056). Interleukin-6 (pg/mL) showed a significant decrease between day 1 and day 7 for potassium canrenoate (64.97 ± 72.52; 41.00 vs. 24.20 ± 69.38; 5.30; p = 0.006), but not the placebo group. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19-induced pneumonia may be associated with significant changes in certain inflammatory markers (interleukin-6, CD3%, TNF-α), potentially related to pulmonary fibrosis. Although some positive trends were observed in the potassium canrenoate group, none of these observations reached statistical significance. Any possible benefits from the use of potassium canrenoate as an anti-inflammatory or antifibrotic drug in COVID-19 patients require further investigation