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To highlight the epidemiology and pathophysiology of hypertension and obesity in COVID-19 infection RECENT FINDINGS Hypertension and obesity have emerged as significant risk factors for contracting the COVID-19 virus and the subsequent severity of illness. ACE2 receptor expression and dysregulation of the RAAS pathway play important roles in the pathophysiology of these associations, as do the pro-inflammatory state and cytokine dysregulation seen in obesity. Rucaparib Some of these patterns have also been seen historically in other viral illnesses. Understanding the mechanisms behind the associations between COVID-19, hypertension, and obesity is important in developing effective targeted therapies and monitoring vaccine response and efficacy. More research is needed to apply our growing knowledge of the pathophysiology of COVID-19, hypertension, and obesity to prevention and treatment. Interventions focusing on lifestyle modification in managing hypertension and obesity can potentially have a positive impact on connd obesity can potentially have a positive impact on containing this pandemic and future viral illness outbreaks.Small heat shock proteins (SHSPs) are conserved proteins that participate in many cellular functions like preventing protein aggregation and stress response. However, their role in responding to nanoparticles (NPs) has not yet been explained. We used a chicken embryo model to investigate the effects of two different forms of iron oxide-NPs (IONPs) on the mRNA expression of HSPB1, HSPB5, HSPB8, and HSPB9 in cerebral tissue. Two hundred-ten fertilized eggs were randomly divided into seven groups (30 eggs/group; 10 eggs/replicate). Three groups received 100 ppm, 250 ppm, and 500 ppm of Fe2O3-NPs, respectively. Three other groups received 100 ppm, 250 ppm, and 500 ppm of Fe3O4-NPs, respectively, and one group remained untreated as a control. The NPs were given by in ovo method (0.3 ml/egg) only once on the first day of the embryonic period. Samples from cerebrums were collected on day 20 for gene expression analyses. HSPB1, HSPB5, HSPB8, and HSPB9 were all expressed in both normal and IONPs exposed cerebrums. SHSPs tested were differentially expressed in response to various concentrations of IONPs. The highest expression levels in response to Fe2O3-NPs and Fe3O4-NPs were observed for HSPB5 and HSPB9, respectively. The greatest gene expression changes due to the Fe2O3-NPs and Fe3O4-NPs exposure observed for HSPB1 and HSPB5, respectively. The results suggest a protective cellular mechanism against IONPs through SHSPs and recommend that expression profiling of SHSPs be included in the study of nanotoxicity.Concurrent exposure to a multitude of environmental toxicants pose serious health hazard to humans and animals. The present investigation was conceptualized to determine deleterious effects of concomitant subacute arsenic and quinalphos exposure on antioxidant responses of liver and erythrocytes of Wistar rats. Fifty-four Wistar rats were divided into nine groups with six animals in each. Animals were exposed to either quinalphos (1/100th and 1/10th of LD50) through oral gavage daily or arsenic (50 and 100 ppb) in drinking water alone and in combination for 28 days. While treatment with different toxicants alone also significantly reduced hemoglobin concentration, hepatic biomarkers and levels of antioxidant parameters as compared with control values, concomitant exposure significantly (P less then 0.05) elevated levels of hepatic transaminases and alkaline phosphatase. Moreover, along with significant depletion in activities of SOD, CAT, TTH, AChE, and enzymes of glutathione complex, a significant enhancement of lipid peroxidation was also recorded in liver and erythrocytes in co-exposed animals in a dose-dependent manner when compared with exposure to individual toxicant. More severe alterations occurred in hepatic histo-architecture of rats receiving combined treatment as compared with those treated with either toxicant. Results indicated that oxidative damage in erythrocytes was more than that of the liver of rats on concomitant exposure of arsenic and quinalphos in a dose-dependent manner. In nutshell, our results revealed that combined treatment of quinalphos with arsenic potentiated toxic effects of either toxicant on antioxidant machinery of liver and erythrocytes and hepatic histomorphology of exposed Wistar rats.
The identification of risk factors for COVID-19 adverse course in autoimmune rheumatic diseases (ARDs) is of the utmost importance when approaching patient management; however, data are scarce in relation to the Latin American population. The objective of this study was to determine predictors of hospitalization for COVID-19 patients from an ARD community cohort.
A real setting longitudinal study (March to November 2020) in an ARD community cohort was carried out. Potential predictors of hospitalization for COVID-19 examined included (1) sociodemographic variables (age, gender, education, tobacco use, socioeconomic status, and co-inhabitants), (2) comorbidities, (3) time to COVID-19 diagnosis, and (4) ARD's features clinical (disease type, disease duration, activity), treatment [corticosteroids use/doses, use of synthetic DMARDs (cDMARDs, tsDMARDs, and bDMARDs)], treatment schedule and non-adherence, and the Multidimensional Health Assessment Questionnaire (MDHAQ). Univariable and multivariable regression• Availability of diagnostic tests is of utmost importance.
We assessed the factors associated with COVID-19, clinical manifestations, and a 30-day-prognosis of COVID-19 in a cohort of rheumatoid arthritis (RA) patients compared with the index population.
In a cross-sectional study, RA patients were followed in rheumatology clinics of Tabriz University of Medical Sciences, and a group of patients diagnosed with COVID-19 from index population were recruited. Outcomes of COVID-19 were assessed by the hospitalization rate and need to intensive care unit (ICU) and mortality. During a period of 12weeks, 128 RA patients diagnosed with COVID-19, 760 RA control group, and 92 COVID-19 patients from index population were enrolled.
Being female, obese, and diabetic, having pulmonary disease and chronic kidney disease (CKD), and treatment with prednisolone > 5mg/d and TNFα inhibitors (TNFis) were independent predictors of COVID-19 in RA patients. Dyspnea, anosmia, and taste loss were more common in RA patients compared with the index population. Admission in hospital, nex population, there was no significant differences in the need to ICU care and mortality between the two groups.
5 mg/d and TNFα inhibitors (TNFis) were independent predictors of COVID-19 in RA patients. • Dyspnea, anosmia and taste loss were more common in RA patients compared with the index population. • Although COVID-19 related hospitalization was higher in RA patients than in the index population, there was no significant differences in the need to ICU care and mortality between the two groups.
To evaluate the added value of whole spine magnetic resonance imaging (MRI) for disease activity assessment in ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
Spine and sacroiliac joint (SIJ) MRI scans requested by rheumatologists between 2012 and 2018 were screened retrospectively, and patients who had known diagnosis of AS or PsA were included, if the MRI was done for disease activity assessment. All MRI scans were reviewed by two experienced musculoskeletal radiologists independently, blinded to patients' diagnosis and to the other MRI. Comparisons were done for the presence of active and structural lesions. In addition, radiologists were asked to rate for "confidence level for active inflammation related to SpA." Analysis was done using the consensus scores.
Ninety patients with known diagnosis of AS (n = 55) or PsA (n = 35) were included. The frequency of active and structural lesions was not significantly different both in AS vs PsA, neither in the cervical/thoracic/lumbar spine or the assessment may be restricted to sacroiliac joint MRI, unless clinically indicated.
This meta-analysis aims to determine the association between antibodies including anti-citrullinated protein antibodies (ACPA) and rheumatoid factors (RF) and risk of rheumatoid arthritis-related interstitial lung disease (RA-ILD).
PubMed, Embase, and Cochrane were searched up to September 13, 2020, for studies investigating the risk of RA-ILD in ACPA-positive patients. The statistical meta-analysis and sensitivity analysis were performed using the Review Manager 5.4 and Stata16.0 software, respectively.
Total 1 double-blind randomized controlled study and 16 observational studies, including 992 RA-ILD patients and 2223 RA-non ILD patients, met the inclusion criteria of the meta-analysis. Compared with ACPA-negative patients, positive serum ACPA increased the risk of RA-ILD (OR = 2.51; 95% CI 1.35-4.68; P = 0.004) and serum ACPA titer was significantly correlated with risk of RA-ILD (SMD = 0.39; 95% CI 0.17-0.62; P = 0.0006). In a region-based subgroup analysis, ACPA titer in Asian, European, and African populations was significantly related to the risk of RA-ILD, while there was no significant correlation in the Americans (SMD = - 0.03; 95% CI - 0.89-0.83; P = 0.95), especially in the USA (SMD = 0.37; 95% CI - 0.26-0.99; P = 0.25). In addition, serum positive RF increased the risk of RA-ILD (OR = 2.85; 95% CI 2.19-3.71; P < 0.00001) and serum RF titer was significantly correlated with the risk of RA-ILD (SMD = 0.35; 95% CI 0.23-0.46; P < 0.00001). However, for the analysis of RF dichotomous data, the funnel shape was asymmetric and the p value of egger test was less than 0.05, which indicated potential publication bias.
ACPA and RF positive patients have greater risk of RA-ILD, and RA patients positive for ACPA should be paid more attention.
• Autoantibodies ACPA and RF increase the risk of RA-ILD. • Regions may be related to RA-ILD.
• Autoantibodies ACPA and RF increase the risk of RA-ILD. • Regions may be related to RA-ILD.Bama minipig is a unique miniature swine bred from China. Their favorable characteristics include delicious meat, strong adaptability, tolerance to rough feed, and high levels of stress tolerance. Unfavorable characteristics are their low lean meat percentage, high fat content, slow growth rate, and low feed conversion ratio. Genome-editing technology using CRISPR/Cas9 efficiently knocked out the myostatin gene (MSTN) that has a negative regulatory effect on muscle production, effectively promoting pig muscle growth and increasing lean meat percentage of the pigs. However, CRISPR/Cas9 genome editing technology is based on random mutations implemented by DNA double-strand breaks, which may trigger genomic off-target effects and chromosomal rearrangements. The application of CRISPR/Cas9 to improve economic traits in pigs has raised biosafety concerns. Base editor (BE) developed based on CRISPR/Cas9 such as cytosine base editor (CBE) effectively achieve targeted modification of a single base without relying on DNA double-strand breaks. Hence, the method has greater safety in the genetic improvement of pigs. The aim of the present study is to utilize a modified CBE to generate MSTN-knockout cells of Bama minipigs. Our results showed that the constructed "all-in-one"-modified CBE plasmid achieved directional conversion of a single C·G base pair to a T·A base pair of the MSTN target in Bama miniature pig fibroblast cells. We successfully constructed multiple single-cell colonies of Bama minipigs fibroblast cells carrying the MSTN premature termination and verified that there were no genomic off-target effects detected. This study provides a foundation for further application of somatic cell cloning to construct MSTN-edited Bama minipigs that carry only a single-base mutation and avoids biosafety risks to a large extent, thereby providing experience and a reference for the base editing of other genetic loci in Bama minipigs.
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