Genetic Polymorphisms in Patients With Systemic Lupus Erythematosus and Jaccoud Arthropathy: A Pilot Study.

INTRODUCTION: Jaccoud arthropathy (JA) is a nonerosive and deforming arthropathy experienced frequently by patients with systemic lupus erythematosus (SLE). Although genetic polymorphisms are associated with SLE development, the association between genetic polymorphisms and JA has not been studied to date. The main objective of this study was to evaluate an association between HLA, STAT4, IRF5, and BLK polymorphisms and the presence of JA in Brazilian individuals with SLE. METHODS: Patients were selected from a cohort of individuals with SLE followed at 2 rheumatology reference centers in Salvador, Bahia, Brazil. The JA diagnosis was based on clinical and radiological criteria. The participants were genotyped for rs9271100, rs7574865, rs10488631, and rs13277113 polymorphisms in the HLA, STAT4, IRF5, and BLK genes, respectively, using real-time polymerase chain reaction. The presence of JA was correlated with allele frequencies, and clinical and laboratory data. RESULTS: One hundred forty-four individuals with SLE (38 with JA and 106 with SLE without JA) were studied. The mean age of the patients was 45 ± 12 years; the majority were women and had brown skin. Patients with JA had a longer disease duration than patients without JA. Serositis and neuropsychiatric manifestations were more frequent in the JA population. The A allele of rs13277113 in the BLK gene was associated with the presence of JA. CONCLUSIONS: The rs13277113 polymorphism in the BLK gene was found to be a possible genetic risk for JA development. However, further studies in larger populations should be performed to confirm this finding.

Factors associated with mortality of elderly people due to COVID-19: Protocol for systematic review and meta-analysis.

INTRODUCTION: The COVID-19 pandemic has become a significant health crisis, marked by high mortality rates on a global scale, with mortality from the disease being notably concentrated among the elderly due to various factors. OBJECTIVE: This study aims to investigate the biological and non-biological factors associated with COVID-19 mortality rates among the elderly worldwide. METHODS: The following databases will be consulted: PubMed, Scopus, EMBASE, Web of Science and ScienceDirect. Longitudinal observational studies (cohort and case-control-risk factors) will be included. The risk of bias, defined as low, moderate, high, will be assessed using the National Heart, Lung and Blood Institute (NHLBI) Quality Assessment Tool for observational cohort and cross-sectional studies. Two independent authors will conduct the searches, and any possible disagreements will be resolved by a third author. Heterogeneity between study results will be assessed using a standard X2 test with a significance level of 0.05, and an I2 value will be calculated to further assess heterogeneity. The random effects model for meta-analyses will be adopted to distribute the weight between the studies and standardize their contributions. The meta-analyses will be conducted using RevMan software. DISCUSSION: Despite the numerous publications on COVID-19 mortality among the elderly, there is still a gap in knowledge, as there is no systematic review and meta-analysis that summarizes the main biological and non-biological associated factors globally. CONCLUSION: The results of this study will consolidate the latest evidence and address gaps in the overall understanding of biological or non-biological associated factors. This knowledge will facilitate the development of appropriate health strategies for this demographic group and pave the way for further research. TRIAL REGISTRATION: PROSPERO (CRD42023400873).

Inactivation of SARS-CoV-2 by a chitosan/α-Ag2WO4 composite generated by femtosecond laser irradiation.

In the current COVID-19 pandemic, the next generation of innovative materials with enhanced anti-SARS-CoV-2 activity is urgently needed to prevent the spread of this virus within the community. Herein, we report the synthesis of chitosan/α-Ag2WO4 composites synthetized by femtosecond laser irradiation. The antimicrobial activity against Escherichia coli, Methicilin-susceptible Staphylococcus aureus (MSSA), and Candida albicans was determined by estimating the minimum inhibitory concentration (MIC) and minimal bactericidal/fungicidal concentration (MBC/MFC). To assess the biocompatibility of chitosan/α-Ag2WO4 composites in a range involving MIC and MBC/MFC on keratinocytes cells (NOK-si), an alamarBlue™ assay and an MTT assay were carried out. The SARS-CoV-2 virucidal effects was analyzed in Vero E6 cells through viral titer quantified in cell culture supernatant by PFU/mL assay. Our results showed a very similar antimicrobial activity of chitosan/α-Ag2WO4 3.3 and 6.6, with the last one demonstrating a slightly better action against MSSA. The chitosan/α-Ag2WO4 9.9 showed a wide range of antimicrobial activity (0.49-31.25 µg/mL). The cytotoxicity outcomes by alamarBlue™ revealed that the concentrations of interest (MIC and MBC/MFC) were considered non-cytotoxic to all composites after 72 h of exposure. The Chitosan/α-Ag2WO4 (CS6.6/α-Ag2WO4) composite reduced the SARS-CoV-2 viral titer quantification up to 80% of the controls. Then, our results suggest that these composites are highly efficient materials to kill bacteria (Escherichia coli, Methicillin-susceptible Staphylococcus aureus, and the yeast strain Candida albicans), in addition to inactivating SARS-CoV-2 by contact, through ROS production.

SARS-CoV-2: Ultrastructural Characterization of Morphogenesis in an In Vitro System.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impacted public health and the world economy and fueled a worldwide race to approve therapeutic and prophylactic agents, but so far there are no specific antiviral drugs. Understanding the biology of the virus is the first step in structuring strategies to combat it, and in this context several studies have been conducted with the aim of understanding the replication mechanism of SARS-CoV-2 in vitro systems. In this work, studies using transmission and scanning electron microscopy and 3D electron microscopy modeling were performed with the goal of characterizing the morphogenesis of SARS-CoV-2 in Vero-E6 cells. Several ultrastructural changes were observed-such as syncytia formation, cytoplasmic membrane projections, lipid droplets accumulation, proliferation of double-membrane vesicles derived from the rough endoplasmic reticulum, and alteration of mitochondria. The entry of the virus into cells occurred through endocytosis. Viral particles were observed attached to the cell membrane and in various cellular compartments, and extrusion of viral progeny took place by exocytosis. These findings allow us to infer that Vero-E6 cells are highly susceptible to SARS-CoV-2 infection as described in the literature and their replication cycle is similar to that described with SARS-CoV and MERS-CoV in vitro models.

Flavonoids from Siparuna cristata as Potential Inhibitors of SARS-CoV-2 Replication.

The novel coronavirus SARS-CoV-2 has been affecting the world, causing severe pneumonia and acute respiratory syndrome, leading people to death. Therefore, the search for anti-SARS-CoV-2 compounds is pivotal for public health. Natural products may present sources of bioactive compounds; among them, flavonoids are known in literature for their antiviral activity. Siparuna species are used in Brazilian folk medicine for the treatment of colds and flu. This work describes the isolation of 3,3',4'-tri-O-methyl-quercetin, 3,7,3',4'-tetra-O-methyl-quercetin (retusin), and 3,7-di-O-methyl-kaempferol (kumatakenin) from the dichloromethane extract of leaves of Siparuna cristata (Poepp. & Endl.) A.DC., Siparunaceae, using high-speed countercurrent chromatography in addition to the investigation of their inhibitory effect against SARS-CoV-2 viral replication. Retusin and kumatakenin inhibited SARS-CoV-2 replication in Vero E6 and Calu-3 cells, with a selective index greater than lopinavir/ritonavir and chloroquine, used as control. Flavonoids and their derivatives may stand for target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43450-021-00162-5.

Volume and Shape Assessment of Renal Radiofrequency Ablation Lesion.

OBJECTIVE: To evaluate the microscopic characteristics and quantify the volume of a radiofrequency ablation (RFA) lesion. METHODS: Ten male pigs were submitted to laparoscopic RFA. An RFA needle was introduced in the lower pole of the left kidney to create a lesion expected to be a sphere of 2.0 cm diameter. The animals were followed up for 21 days. Kidneys were weighed and the volume was assessed using Scherle's method. Cavalieri's principle was used to assess the RFA volume, and sphericity was calculated to assess RFA lesion. One sample t test was used to compare RFA volume with the volume of a sphere of 2.0 cm diameter, and sphericity to hypothetical values of a sphere and an icosahedron. Fragments of RFA region were histologically evaluated. RESULTS: Three animals developed postoperative complications and were excluded from the analyses. There was no difference in the mean weight and volume between right and left kidneys following RFA. The mean total volume of RFA injury was 3.44 cm3. There was no difference in the RFA volume in comparison with hypothetical volumes of a sphere and an icosahedron of 2.0 cm diameter. Sphericity of the RFA injury was not similar with a sphere; however, it was similar to an icosahedron. Histology revealed areas of coagulation necrosis, fibrosis, and inflammatory mononuclear infiltration. Areas with normal tissue were also observed. CONCLUSION: The volume of injury caused by RFA was as expected and its shape was comparable with an icosahedron. Microscopic evaluation revealed areas of normal-appearing tissue.