Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells.

COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and injury repair. During an infection, the clearance of dead and dying cells, a process named efferocytosis, can modulate the interplay between these contrasting functions. Here, we show that engulfment of SARS-CoV-2-infected apoptotic cells exacerbates inflammatory cytokine production, inhibits the expression of efferocytic receptors, and impairs continual efferocytosis by macrophages. We also provide evidence supporting that lung monocytes and macrophages from severe COVID-19 patients have compromised efferocytic capacity. Our findings reveal that dysfunctional efferocytosis of SARS-CoV-2-infected cell corpses suppresses macrophage anti-inflammation and efficient tissue repair programs and provides mechanistic insights for the excessive production of pro-inflammatory cytokines and accumulation of tissue damage associated with COVID-19 immunopathogenesis.

Preparation, Characterization and In Vivo Biocompatibility Studies of Cotton Cellulose Nanofibers.

Cellulose nanofibers have mechanical properties that make them very attractive in a myriad of fields such as biomedicine, tissue engineering, biosensors, cosmetics and food packet products. To evaluate the potential health risks of airborne cellulose nanofibers, the cellulose nanofiber was prepared and characterized and then its pulmonary potential toxicity to a mouse model was studied. Cellulose nanofiber has been prepared by acid hydrolysis of cotton cellulose and characterized by transmission electron microscopy, zeta potential and X-ray diffraction analysis. Then, using a short-term inhalation test, the pulmonary biocompatibility of cotton cellulose nanofibers at different concentrations (0.5 mg/mL, 1 mg/mL and 2 mg/mL) were evaluated. Transmission electron images showed needle-shaped particle with a diameter of about 6-18 nm and a length of 85-225 µm. Zeta potential was -25.3±7.80 mV and the X-ray diffraction patterns indicate that cotton cellulose nanofiber has pure structural characteristics. The In Vivo results revealed that the exposure to cotton cellulose nanofiber did not alter the number of inflammatory cells or cytokine secretion by lung cells (p > 0.05). The results demonstrate that the cotton cellulose nanofiber is biocompatible and it is an environment-friendly nanomaterial with promise in various industrial sectors.

Infection of human lymphomononuclear cells by SARS-CoV-2.

Although SARS-CoV-2 severe infection is associated with a hyperinflammatory state, lymphopenia is an immunological hallmark, and correlates with poor prognosis in COVID-19. However, it remains unknown if circulating human lymphocytes and monocytes are susceptible to SARS-CoV-2 infection. In this study, SARS-CoV-2 infection of human peripheral blood mononuclear cells (PBMCs) was investigated both in vitro and in vivo . We found that in vitro infection of whole PBMCs from healthy donors was productive of virus progeny. Results revealed that monocytes, as well as B and T lymphocytes, are susceptible to SARS-CoV-2 active infection and viral replication was indicated by detection of double-stranded RNA. Moreover, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from COVID-19 patients, and less frequently in CD4 + T lymphocytes. The rates of SARS-CoV-2-infected monocytes in PBMCs from COVID-19 patients increased over time from symptom onset. Additionally, SARS-CoV-2-positive monocytes and B and CD4+T lymphocytes were detected by immunohistochemistry in post mortem lung tissue. SARS-CoV-2 infection of blood circulating leukocytes in COVID-19 patients may have important implications for disease pathogenesis, immune dysfunction, and virus spread within the host.

Enhancement of the Amazonian Açaí Waste Fibers through Variations of Alkali Pretreatment Parameters.

The açaí fruit depulping produces large amounts of long lignocellulosic fiber bundles that are disposed in the environment. Chemical pretreatments may improve açaí fibers favoring their usage in advanced materials. This work aimed to define optimal alkali reaction parameters to improve the properties of açaí fibers. Two NaOH concentrations (5 % and 10 %) and two reaction temperatures (80 °C and 100 °C) were tested. The raw and treated fibers were analyzed by scanning electron microscopy, Fourier transformed infrared spectroscopy, X-ray diffraction, and thermal analyses. All the alkali pretreatments separated fibers from the bundles, unblocked pit channels by removing silicon structures, exposed the inner lignin, partially removed non-cellulosic compounds, and raised the cellulose crystalline index. The highest temperature and NaOH content resulted in better cleaning and isolation of the fibers, while milder conditions better preserved the cellulose crystalline structure and thermal stability.

Warfarin Safety: A Cross-Sectional Study of the Factors Associated with the Consumption of Medicinal Plants in a Brazilian Anticoagulation Clinic.

OBJECTIVE: The aim of this study was to analyze factors associated with the consumption of medicinal plants by patients being treated with warfarin in a Brazilian anticoagulation clinic and to study the safety of medicinal plant use in patients on warfarin therapy. METHODS: The study was performed as an observational cross-sectional analysis. Study participants were outpatients on long-term warfarin therapy for at least 2 months for atrial fibrillation or prosthetic cardiac valves. Interviews were carried out concerning information about the habits of medicinal herb consumption, and logistic regression analysis was performed to identify factors associated with the consumption of herbs. The scientific names of the medicinal plants were identified to search for information on the effects on the hemostasis of the interactions between the medicinal herbs reported and warfarin. RESULTS: The mean age of the 273 patients included was 60.8 years; 58.7% were women. Medicinal plants were used by 67% of the participants. No association between demographic and clinical data and the use of medicinal plants was identified. Patients reported a total of 64 different plants, primarily consumed in the form of tea. The plants were mainly used to treat respiratory tract and central nervous system disorders. About 40% of the plants cited have been reported to potentially interfere with the anticoagulation therapy, principally by potentiating the effects of warfarin, which could, increase the risk of bleeding. CONCLUSION: The use of medicinal plants was highly common and widespread in patients receiving warfarin as an anticoagulation therapy. Univariate analysis of variables associated with the consumption of herbs showed no statistically significant difference in the consumption of medicinal plants for any of the sociodemographic and clinical data. The medicinal plants that were reportedly consumed by the patients could affect hemostasis. This study reinforces the need for further studies evaluating the habits of patients consuming medicinal plants and their clinical implications, and will help to design strategies to manage the risks associated with warfarin-herbal interactions.

Oral surgery in patients under antithrombotic therapy: perioperative bleeding as a significant risk factor for postoperative hemorrhage.

: To investigate perioperative and postoperative bleeding, complications in patients under therapy with anticoagulant or antiplatelet drugs submitted to oral surgery. To evaluate the risk of bleeding and safety for dental surgery, a retrospective chart review was performed. Medical and dental records of patients taking oral antithrombotic drugs undergoing dental surgery between 2010 and 2015 were reviewed. Results were statistically analyzed using Fisher's exact test, t test or the χ test. One hundred and seventy-nine patients underwent 293 surgical procedures. A total of eight cases of perioperative and 12 episodes of postoperative bleeding were documented. The complications were generally managed with local measures and did not require hospitalization. We found significant association of postoperative hemorrhage with increased perioperative bleeding (P = 0.043) and combination of anticoagulant and antiplatelet therapy (P < 0.001). The chance of postoperative hemorrhage for procedures with increased perioperative bleeding is 8.8 times bigger than procedures without perioperative bleeding. Dental surgery in patients under antithrombotic therapy might be carried out without altering the regimen because of low risk of perioperative and postoperative bleeding. However, patients with increased perioperative bleeding should be closely followed up because of postoperative complications risk.

Hydrophobic edible films made up of tomato cutin and pectin.

Cutin is the biopolyester that protects the extracellular layer of terrestrial plants against dehydration and environmental stresses. In this work, cutin was extracted from tomato processing waste and cast into edible films having pectin as a binding agent. The influences of cutin/pectin ratio (50/50 and 25/75), film-forming suspension pH, and casting method on phase dispersion, water resistance and affinity, and thermal and mechanical properties of films were investigated. Dynamic light scattering and scanning electron microscopy revealed that cutin phase aggregation was reduced by simply increasing pH. The 50/50 films obtained by casting neutral-pH suspensions presented uniform cutin dispersion within the pectin matrix. Consequently, these films exhibited lower water uptake and solubility than their acidic counterparts. The cutin/pectin films developed here were shown to mimic tomato peel itself with respect to mechanical strength and thermal stability. Such behavior was found to be virtually independent of pH and casting method.

Atrial fibrillation in women: treatment.

Sex-specific differences in the epidemiology, pathophysiology, presentation, prognosis, and treatment of atrial fibrillation (AF) are increasingly recognized. Women with AF generally experience worse symptoms, poorer quality of life, and have higher risk of stroke and death than men with AF. Effective treatment of the arrhythmia in women is critical to reduce the rate of adverse events. We review the current evidence on sex-specific differences in the utilization and outcomes of treatments for AF, including rate-control and rhythm-control strategies, and stroke-prevention therapy. In addition, we provide a critical evaluation of potential disparities and biases in health-care use that might be associated with differences in the outcomes between women and men. We underscore current knowledge gaps that need to be addressed in future studies to improve the management of AF in women. In particular, we suggest several strategies to produce high-quality evidence from randomized clinical trials for women with AF.

Rifampicin-warfarin interaction leading to macroscopic hematuria: a case report and review of the literature.

BACKGROUND: Rifampicin remains one of the first-line drugs used in tuberculosis therapy. This drug's potential to induce the hepatic cytochrome P450 oxidative enzyme system increases the risk of drug-drug interactions. Thus, although the presence of comorbidities typically necessitates the use of multiple drugs, the co-administration of rifampicin and warfarin may lead to adverse drug events. We report a bleeding episode after termination of the co-administration of rifampicin and warfarin and detail the challenges related to international normalized ratio (INR) monitoring. CASE PRESENTATION: A 59-year-old Brazilian woman chronically treated with warfarin for atrial fibrillation (therapeutic INR range: 2.0-3.0) was referred to a multidisciplinary anticoagulation clinic at a university hospital. She showed anticoagulation resistance at the beginning of rifampicin therapy, as demonstrated by repeated subtherapeutic INR values. Three months of sequential increases in the warfarin dosage were necessary to reach a therapeutic INR, and frequent visits to the anticoagulation clinic were needed to educate the patient about her pharmacotherapy and to perform the warfarin dosage adjustments. The warfarin dosage also had to be doubled at the beginning of rifampicin therapy. However, four weeks after rifampicin discontinuation, an excessively high INR was observed (7.22), with three-day macroscopic hematuria and the need for an immediate reduction in the warfarin dosage. A therapeutic and stable INR was eventually attained at 50% of the warfarin dosage used by the patient during tuberculosis therapy. CONCLUSIONS: The present case exemplifies the influence of rifampicin therapy on warfarin dosage requirements and the increased risk of bleeding after rifampicin discontinuation. Additionally, this case highlights the need for warfarin weekly monitoring after stopping rifampicin until the maintenance dose of warfarin has decreased to the amount administered before rifampicin use. In particular, patients with cardiovascular diseases and active tuberculosis represent a group with a substantial risk of drug-drug interactions. Learning how to predict and monitor drug-drug interactions may help reduce the incidence of clinically significant adverse drug events.

Agreement among four drug information sources for the occurrence of warfarin drug interactions in Brazilian heart disease patients with a high prevalence of Trypanosoma cruzi infection.

PURPOSE: The aim of this study was to assess the agreement of four renowned interaction lists on potentially severe warfarin drug interactions (DI) in outpatients at a university hospital in Brazil, specifically in subgroups of Trypanosoma cruzi-infected and non-infected patients and those with previous bleeding episodes. METHODS: This was a cross-sectional study in which adult outpatients with heart disease and indications for chronic warfarin use were enrolled. The occurrence of potentially severe warfarin DI was evaluated based on the lists provided by three compendia, i.e., Drug Interaction Facts (DIF), Drug Interactions: Analysis and Management (DIAM) and DRUG-REAX, and by the World Health Organization (WHO) Model Formulary. A kappa coefficient was used to calculate the agreement among the sources. RESULTS: A total of 280 patients were studied. Most patients were female (54.6 %) with an average age of 56.8 (standard deviation 13.1) years. The agreement among the four sources was fair (Fleiss' kappa coefficient = 0.295). T. cruzi-infected individuals were less likely to have severe warfarin DI than non-infected patients (p < 0.05 for DIAM, DRUG-REAX and the WHO Model Formulary). Potentially severe DI were more frequent in patients with previous bleeding episodes, based on the DIF compendia (p = 0.007). CONCLUSIONS: This evaluation of warfarin DI revealed that the disagreement between compendia is also observed in clinical practice. T. cruzi infection is associated with a lower prevalence of potentially severe warfarin DI, but with a wider variation in its detection. Our results suggest a wide spectrum of discrepancies in detecting heart disease patients at higher risk for severe warfarin DI and a possible heterogeneity in clinical guidance.

The involvement of potassium channels in the peripheral antiedematogenic effect of intrathecally injected morphine in rats.

BACKGROUND: A previous study indicated that intrathecal administration of morphine reduces experimental inflammatory edema in rats by activating the nitric oxide/cyclic guanosine monophosphate pathway. This evidence supports the hypothesis that potassium channel opening may play an important role in mediating morphine's effect under such conditions. METHODS: Male Wistar rats received intrathecal injections of drugs (20 µL) 30 minutes before paw stimulation with carrageenan (150 µg). Edema was measured as paw volume increase (in milliliters), and plasma leakage was measured by Evans blue dye leakage. Neutrophil migration was evaluated indirectly by myeloperoxidase assay. The inflammatory infiltration and vascular congestion were observed by histologic examination. RESULTS: Morphine (37 nmol) inhibited inflammatory edema, plasma leakage, and vascular congestion but had no effect on myeloperoxidase activity or neutrophil content compared with phosphate-buffered saline. Coinjection with 4-aminopyridine (10 nmol), glibenclamide (5 nmol), and dequalinium (10 pmol) reversed, but nicorandil (0.03 nmol) enhanced the effect of morphine. CONCLUSIONS: These results support the hypothesis that the peripheral antiedematogenic effect produced by intrathecal morphine is mediated by potassium channel activation. Furthermore, this opioid effect does not involve the inhibition of acute neutrophil migration but does involve a reduction in capillary recruitment.

Warfarin drug interactions: a comparative evaluation of the lists provided by five information sources.

PURPOSE: Detecting potential drug interactions can lead to early interventions that protect patients from serious drug-related problems. The aim of this study was to evaluate the agreement among the lists of warfarin interactions provided by five information sources. METHODS: The lists of warfarin interactions and the corresponding severity ratings and documentation levels presented by the three compendia and by the World Health Organization (WHO) Model Formulary were all compared, and each list was compared to that provided on the package insert of Marevan, a brand of warfarin. The compendia used were: Drug Interaction Facts, Drug Interactions: Analysis and Management and DRUG-REAX. A kappa coefficient was used to calculate the agreement among the sources. RESULTS: A total of 537 interactions were listed. Only 13 (2.4%) were common to the five sources. The global Fleiss' kappa coefficient was -0.0080, which indicated poor agreement. Eleven warfarin interactions appeared only in the Marevan package insert. Importantly, 243 interactions (45.3% of the total) were deemed significant in at least one compendium. Only two warfarin interactions were reported as critical by all three compendia and by WHO. The most critical interactions cited by the compendia were missing from the package insert. CONCLUSIONS: Poor agreement was found among five sources listing warfarin interactions. Potentially severe clinical consequences might occur due to these discrepant recommendations. Finally, the lack of standard terminology and clinical guidance, as well as the possible inaccuracy of severity ratings and documentation might contribute to heterogeneous procedures in clinical practice.

[Post-discharge surveillance of children and adolescents treated for surgical site infections at a university hospital in Belo Horizonte, Minas Gerais State, Brazil]. / Vigilância pós-alta das infecções de sítio cirúrgico em crianças e adolescentes em um hospital universitário de Belo Horizonte, Minas Gerais, Brasil.

Hospital infections are the main complications in surgical practice. Surgical site infections are the most frequent, and can manifest after hospital discharge. In Brazil, the majority of clinical services do not maintain infection surveillance after discharge. In order to evaluate the importance of such surveillance and the profile of these post-discharge infections, a cohort of 730 child and adolescent surgical patients was followed in a teaching hospital, from 1999 to 2001. The accumulated incidence was calculated. Student's t test was used to compare mean values and the Kaplan-Meier method to analyze the period until infection, using a p value of < 0.05. A total of 87 surgical site infections were diagnosed, 37% of which after discharge. The overall surgical infection rate was 11.9%; without outpatient follow-up, the rate would have been 7.5%. Post-charge infections were diagnosed after a mean of 11.3 +/- 6.4 days, and in these patients the preoperative and postoperative hospital stays were significantly lower than in the group with in-hospital infections. The study indicates the importance of post-discharge surveillance in determining the real incidence of surgical site infections.

Vigilância pós-alta das infecções de sítio cirúrgico em crianças e adolescentes em um hospital universitário de Belo Horizonte, Minas Gerais, Brasil / Post-discharge surveillance of children and adolescents treated for surgical site infections at a university hospital in Belo Horizonte, Minas Gerais State, Brazil

As infecções hospitalares são as principais complicações na prática cirúrgica e, dentre estas, as infecções de sítio cirúrgico são as mais freqüentes. Apesar dessas infecções poderem se manifestar após a alta, no Brasil, a maioria dos serviços não faz vigilância pós-alta. Para avaliar a importância dessa vigilância e o perfil das infecções em crianças e adolescentes, acompanhou-se uma coorte de 730 pacientes cirúrgicos de um hospital universitário de Belo Horizonte, Minas Gerais, Brasil, de 1999 a 2001. Calculou-se a incidência acumulada, aplicou-se o teste t de Student na comparação de médias e o método de Kaplan-Meier na análise do tempo de ocorrência das infecções; considerou-se significativo o valor p < 0,05. Foram diagnosticadas 87 infecções de sítio cirúrgico na coorte estudada, sendo 37 por cento após a alta hospitalar. A taxa de incidência de infecções de sítio cirúrgico foi de 11,9 por cento; mas seria apenas de 7,5 por cento sem o controle pós-alta. Verificou-se no grupo dos pacientes com infecções identificadas após a alta uma média de aparecimento das infecções de 11,3 ± 6,4 dias; que os tempos de permanência pré e pós-operatórios foram significativamente menores em relação aos pacientes com infecções intra-hospitalares. O estudo indica que a vigilância pós-alta é importante para se conhecer a real incidência das infecções de sítio cirúrgico.

Hospital infections are the main complications in surgical practice. Surgical site infections are the most frequent, and can manifest after hospital discharge. In Brazil, the majority of clinical services do not maintain infection surveillance after discharge. In order to evaluate the importance of such surveillance and the profile of these post-discharge infections, a cohort of 730 child and adolescent surgical patients was followed in a teaching hospital, from 1999 to 2001. The accumulated incidence was calculated. Student's t test was used to compare mean values and the Kaplan-Meier method to analyze the period until infection, using a p value of < 0.05. A total of 87 surgical site infections were diagnosed, 37 percent of which after discharge. The overall surgical infection rate was 11.9 percent; without outpatient follow-up, the rate would have been 7.5 percent. Post-charge infections were diagnosed after a mean of 11.3 ± 6.4 days, and in these patients the preoperative and postoperative hospital stays were significantly lower than in the group with in-hospital infections. The study indicates the importance of post-discharge surveillance in determining the real incidence of surgical site infections.