A prospective longitudinal study evaluating the influence of immunosuppressives and other factors on COVID-19 in autoimmune rheumatic diseases.

BACKGROUND: We conducted this study to identify the influence of prolonged use of hydroxychloroquine (HCQ), glucocorticoids and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs). METHODS: This was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome. RESULTS: COVID-19 occurred in 314 (3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129, 219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5-20 mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence (17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh (Kerala)) and case fatality (4.1% vs 1.3% (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was significantly higher (p < 0.001) compared to the general population of the corresponding geographic region. CONCLUSIONS: Immunosuppressants have a differential impact on the risk of COVID-19 occurrence in AIRD patients. Older age, males, smokers, hypertensive, diabetic and underlying lung disease contributed to higher risk. The incidence rate and the case fatality rate in AIRD patients is much higher than that in the general population.

Medicinal Plants for Mitigating Pain and Inflammatory-Related Conditions: An Appraisal of Ethnobotanical Uses and Patterns in South Africa.

In South Africa, traditional medicine remains the first point of call for a significant proportion of the population seeking primary healthcare needs. This is particularly important for treating common conditions including pain and inflammation which are often associated with many disease conditions. This review focuses on the analysis of the trend and pattern of plants used for mitigating pain and inflammatory-related conditions in South African folk medicine. An extensive search was conducted using various scientific databases and popular ethnobotanical literature focusing on South African ethnobotany. Based on the systematic analysis, 38 sources were selected to generate the inventory of 495 plants from 99 families that are considered as remedies for pain and inflammatory-related conditions (e.g., headache, toothache, backache, menstrual pain, and rheumatism) among different ethnic groups in South Africa. The majority (55%) of the 38 studies were recorded in three provinces, namely, KwaZulu-Natal, Limpopo, and Western Cape. In terms of the number of mentions, the most popular plants used for pain and inflammatory-related conditions in South Africa were Ricinus communis L. (10), Aloe ferox Mill. (8), Pentanisia prunelloides subsp. latifolia (Hochst.) Verdc. (8), Dodonaea viscosa Jacq var. angustifolia (L.f) Benth. (8), (L.) W.T.Aiton. (7) Ruta graveolens L. (7), and Solanum aculeastrum Dunal. (7). The top five plant families represented were Asteraceae (13%), Fabaceae (8%), Apocynaceae (4.3%), Asparagaceae (4%), and Lamiaceae (4%). An estimated 54% of the recorded plants were woody (trees and shrubs) in nature, while the leaves (27%) and roots (25%) were the most dominant plant parts. The use of plants for alleviating pain and inflammatory-related conditions remains popular in South African folk medicine. The lagging ethnobotanical information from provinces such as North West, Gauteng, and Free State remains a gap that needs to be pursued meticulously in order to have a complete country-wide database.

Bioactive molecules derived from smoke and seaweed Ecklonia maxima showing phytohormone-like activity in Spinacia oleracea L.

Bioactive compounds such as karrikinolide (KAR1 from smoke) and eckol (from the seaweed Ecklonia maxima) show promising effects on several important crop plants. These plant growth-stimulating organic biomolecules, along with crude extracts (smoke-water and Kelpak® product prepared from Ecklonia maxima), were tested on spinach plants. Eckol sprayed at 10-6 M significantly increased all the growth and biochemical parameters examined compared to control spinach plants. All tested plant growth biostimulants significantly increased total chlorophyll, carotenoids and protein content of spinach leaves. The cytokinin profile of spinach plants was also determined. Cis-zeatin, dihydrozeatin and isopentenyladenine types of cytokinins were promoted by both smoke- and seaweed-based biostimulants. In comparison to the control plants, the level of free sinapic acid was greater in all spinach plants treated with these biostimulants. The application of these biostimulants can help spinach crop by improving growth, yield and nutritional quality; moreover, they are organic and cost-effective.

Identification and characterization of potential bioactive compounds from the leaves of Leucosidea sericea.

ETHNOPHARMACOLOGICAL RELEVANCE: Leucosidea sericea is a southern African tree used for treating different diseases including microbial infections and inflammatory-related conditions. AIM OF THE STUDY: To isolate and identify the chemicals in Leucosidea sericea which possibly account for the diverse therapeutic effects of the species. MATERIALS AND METHODS: Leaf material was extracted using 20% methanol and subsequently partitioned with different solvents (hexane, dichloromethane, ethyl acetate and butanol). Resultant fractions were subjected to bioactive (antimicrobial)-guided isolation and the structural elucidation was conducted using NMR (1D and 2D) spectroscopic methods. Given the broad uses of Leucosidea sericea in traditional medicine, the extract, fractions and isolated compounds were evaluated in five (5) biological assays in vitro (antimicrobial, antioxidant, acetylcholinesterase (AChE) and anti-inflammatory inhibition as well as cytotoxicity effect). RESULTS: As the most active fractions, from ethyl acetate yielded 5,7-dihydroxychromone (1); 1-hydroxy-2-oxopomolic acid (2); 3,5,7,3´,4´-pentahydroxyflavone (3) and Tiliroside (4). For the first time, these four (4) compounds were isolated from leaves of Leucosidea sericea. These aforementioned compounds demonstrated broad-spectrum antibacterial activity (1.95-125 µg/mL) and noteworthy antifungal (3.9-250 µg/mL) potential. In addition to its noteworthy antimicrobial activity, compound 3 also demonstrated significant antioxidant (EC50 = 14 µg/mL in DPPH assay) and anti-inflammatory (inhibited the level of ELAM by approximately 36% and decreased also the viability of endothelial cells) activities in vitro. Overall, AChE inhibition activity and cytotoxic response was generally weak for the extracts, fractions and isolated compounds. CONCLUSION: The pool of chemicals in Leucosidea sericea were enriched with the isolation and identification of four (4) compounds obtained from the leaf extract. Among these compounds, the significant antimicrobial activity of compound 3 provides strong evidence that support the use of Leucosidea sericea for microbial-related infections in folk medicine.

Serum Lipid Alterations in Early Rheumatoid Arthritis Patients on Disease Modifying Anti Rheumatoid Therapy.

Dyslipidaemia is a major CVD risk factor in the general population. Current evidence suggests that lipid metabolism is altered in RA due to inflammation, and that use of anti-inflammatory therapy may reverse some of these changes. The objective of our study is to compare the effect of treatment with DMARD on lipid fractions after 6 months of therapy. Forty patients who met the American College of Rheumatology, ACR/EULAR criteria for rheumatoid arthritis, with disease duration of less than 1 year and no prior treatment were included in the study. Thirty healthy volunteers were included as controls. The mean DAS-28 at disease onset was 5.15 ± 1.3. Early Rheumatoid Arthritis (ERA) patients exhibited higher serum levels of total cholesterol (TC) and lowdensity lipoprotein cholesterol (LDL-C) and lower serum high-density lipoprotein cholesterol (HDL-C) levels compared to controls. As a consequence, the atherogenic index of plasma [log (TG/HDL-C)], the atherogenic indices: TC/HDL-C as well as LDLC/HDL-C was significantly higher in ERA patients compared to controls. After 6 months of treatment, there was significant reduction of the DAS 28, HDL-C and Apo A-I improved and Lp(a) decreased significantly. All lipid ratios improved, a phenomenon primarily due to the increase in serum HDL-C levels. These changes were inversely correlated with CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves with DMARD therapy.

Enhancing growth, phytochemical constituents and aphid resistance capacity in cabbage with foliar application of eckol--a biologically active phenolic molecule from brown seaweed.

Although foliar application of seaweed extracts on plant growth and development has and is extensively studied, reliable knowledge and understanding of the mode of action of particular compound(s) responsible for enhancing plant growth is lacking. A brown seaweed Ecklonia maxima is widely used commercially as a biostimulant to improve plant growth and crop protection. Eckol, a phenolic compound isolated from E. maxima has recently shown stimulatory effects in maize, indicating its potential use as a plant biostimulant. Cabbage is a widely cultivated vegetable crop throughout the world, which requires high input of fertilizers and is susceptible to several aphid borne diseases. This study was conducted to evaluate the effect of foliar application of eckol on the growth, phytochemical constituents and myrosinase activity (aphid resistance capacity) of commercially cultivated cabbage. Foliar application of eckol (10(-6) M) significantly enhanced shoot and root length, shoot and root fresh and dry weight, leaf area and leaf number. This treatment also showed a significant increase in photosynthetic pigments (chlorophyll 'a', chlorophyll 'b', total chlorophyll and carotenoid) compared to the untreated plants. The levels of protein, proline and iridoid glycosides were significantly higher in cabbage leaves with eckol treatment. All the control plants were severely infested with cabbage aphid (Brevicoryne brassicae) but no infestation was observed on the eckol-sprayed plants, which can be attributed to an increase in myrosinase activity. This study reveals dual effects (plant growth promoting and insect repelling) of eckol on cabbage plants that need further investigations both under field conditions and in other brassicaceous species.

Challenges of the information age: the impact of false discovery on pathway identification.

BACKGROUND: Pathways with members that have known relevance to a disease are used to support hypotheses generated from analyses of gene expression and proteomic studies. Using cancer as an example, the pitfalls of searching pathways databases as support for genes and proteins that could represent false discoveries are explored. FINDINGS: The frequency with which networks could be generated from 100 instances each of randomly selected five and ten genes sets as input to MetaCore, a commercial pathways database, was measured. A PubMed search enumerated cancer-related literature published for any gene in the networks. Using three, two, and one maximum intervening step between input genes to populate the network, networks were generated with frequencies of 97%, 77%, and 7% using ten gene sets and 73%, 27%, and 1% using five gene sets. PubMed reported an average of 4225 cancer-related articles per network gene. DISCUSSION: This can be attributed to the richly populated pathways databases and the interest in the molecular basis of cancer. As information sources become enriched, they are more likely to generate plausible mechanisms for false discoveries.

Energy density, nutrient adequacy, and cost per serving can provide insight into food choices in the lower Mississippi Delta.

OBJECTIVE: To compare differences across food groups for food cost, energy, and nutrient profiles of 100 items from a cross-sectional survey of 225 stores in 18 counties across the Lower Mississippi Delta of Arkansas, Louisiana, and Mississippi. METHODS: Energy, nutrient, and cost profiles for food items were calculated by using Naturally Nutrient Rich methodology and converting price per 100 g edible portion to price per serving. Foods were grouped into 6 food groups. Mean differences were compared with ANOVA. RESULTS: Significant differences existed by food group for each measure. Energy density was highest for fats/oils/sweets, whereas nutrient density was highest for vegetables. Price per serving was lowest for fats/oils/sweets and highest for meats. CONCLUSIONS AND IMPLICATIONS: Educational messages focusing on a complete diet should consider the role of food costs and provide specific recommendations for increasing nutrient-dense foods by replacing a portion of the meat serving at meals with culturally acceptable lower-cost nutrient-dense foods.