Rheumatoid arthritis is associated with reduced adiposity but not with unfavorable major cardiovascular risk factor profiles and enhanced carotid atherosclerosis in black Africans from a developing population: a cross-sectional study

INTRODUCTION: Rheumatoid arthritis (RA) is characterized by inflamed joint-derived cytokine-mediated high-grade systemic inflammation that enhances cardiovascular metabolic risk and disease in developed populations. We investigated the potential impact of RA on cardiovascular risk factors including systemic inflammation and atherosclerosis, and their relationships in black Africans from a developing population. METHODS: We evaluated demographic features, adiposity indices, major traditional cardiovascular risk factors, circulating C-reactive protein and interleukin-6 concentrations and ultrasound determined carotid intima-media thickness (cIMT) in 274 black Africans; 115 had established RA. Data were analyzed in confounder-adjusted mixed regression models. RESULTS: The body mass index and waist-height ratio were lower in RA compared to non-RA subjects (29.2 (6.6) versus 33.7 (8.0), P < 0.0001 and 0.58 (0.09) versus 0.62 (0.1), P = 0.0003, respectively). Dyslipidemia was less prevalent in patients with RA (odds ratio (OR) (95% confidence interval (CI) = 0.54 (0.30 to1.00)); this disparity was no longer significant after further adjustment for reduced adiposity and chloroquine use. RA was also not associated with hypertension, current smoking and diabetes. The number of major traditional risk factors did not differ by RA status (1.1 (0.8) versus 1.2 (0.9), P = 0.7). Circulating C-reactive protein concentrations were similar and serum interleukin-6 concentrations reduced in RA (7.2 (3.1) versus 6.7 (3.1) mg/l, P = 0.7 and 3.9 (1.9) versus 6.3 (1.9) pg/ml, P < 0.0001, respectively). The cIMT was 0.700 (0.085) and 0.701 (0.111) mm in RA and non-RA subjects, respectively (P = 0.7). RA disease activity and severity parameters were consistently unrelated to systemic inflammation, despite the presence of clinically active disease in 82.6% of patients. In all participants, adiposity indices, smoking and converting angiotensin inhibitor non-use were associated with increased systemic inflammation, which related to more atherogenic lipid profiles, and circulating low density lipoprotein concentrations were associated with cIMT (partial R = 0.153, P = 0.032); RA did not impact on these relationships (interaction P ≥0.1). CONCLUSIONS: Among black Africans, patients with established RA experience reduced overall and abdominal adiposity but no enhanced major traditional risk factor and atherosclerosis burden. This study further suggests that an absent interleukin-6 release by inflamed RA joints into the circulation may account for this unaltered cardiovascular disease risk

Progressive in vivo development of resistance to cefiderocol in Pseudomonas aeruginosa.

We report in vivo development of cefiderocol (FDC) resistance among four sequential Pseudomonas aeruginosa clinical isolates ST244 recovered from a single patient, without exposure to FDC, which raises concern about the effectiveness of this novel drug. The first recovered P. aeruginosa isolate (P-01) was susceptible to FDC (2 μg/mL), albeit this MIC value was higher than that of a wild-type P. aeruginosa (0.12-0.25 μg/ml). The subsequent isolated strains (P-02, P-03, P-04) displayed increasing levels of FDC MICs (8, 16, and 64 μg/ml, respectively). Those isolates also showed variable and gradual increasing levels of resistance to most β-lactams tested in this study. Surprisingly, no acquired β-lactamase was identified in any of those isolates. Whole-genome sequence analysis suggested that this resistance was driven by multifactorial mechanisms including mutational changes in iron transporter proteins associated with FDC uptake, ampC gene overproduction, and mexAB-oprM overexpression. These findings highlight that a susceptibility testing to FDC must be performed prior to any prescription

Rheumatoid Arthritis Impacts on the Independent Relationships between Circulating Adiponectin Concentrations and Cardiovascular Metabolic Risk

Adiponectin and leptin are likely involved in the pathophysiology of rheumatoid arthritis (RA) and therefore potential new therapeutic targets. Adiponectin inhibition could be expected to enhance cardiovascular metabolic risk. However, it is unknown whether RA changes the influence of adipokines on cardiovascular metabolic risk. We determined whether RA impacts on the independent relationships of circulating leptin and adiponectin concentrations with cardiovascular risk factors and carotid intima-media thickness (cIMT) in 277 black African subjects from a developing population; 119 had RA. RA impacted on the relationships of adiponectin concentrations with lipid concentrations and blood pressure, independent of confounders including adiposity (interaction P < 0.05). This translated into an association of adiponectin concentrations with more favorable lipid variables including HDL cholesterol (P = 0.0005), non-HDL cholesterol (P = 0.007), and triglyceride (P = 0.005) concentrations, total cholesterol-HDL cholesterol (P = 0.0002) and triglycerides-HDL cholesterol (P = 0.0003) ratios, and higher systolic (P = 0.0006), diastolic (P = 0.0004), and mean blood pressure (P = 0.0007) in RA but not non-RA subjects. Leptin was not associated with metabolic risk after adjustment for adiposity. The cIMT did not differ by RA status, and adipokine concentrations were unrelated to atherosclerosis. This study suggests that leptin and adiponectin inhibition may not alter overall cardiovascular risk and disease in RA

Points to consider in cardiovascular disease risk management among patients with rheumatoid arthritis living in South Africa, an unequal middle income country

ABSTRACT: Background: It is plausible that optimal cardiovascular disease (CVD) risk management differs in patients with rheumatoid arthritis (RA) from low or middle income compared to high income populations. This study aimed at producing evidence-based points to consider for CVD prevention in South African RA patients. Methods: Five rheumatologists, one cardiologist and one epidemiologist with experience in CVD risk management in RA patients, as well as two patient representatives, two health professionals and one radiologist, one rheumatology fellow and 11 rheumatologists that treat RA patients regularly contributed. Systematic literature searches were performed and the level of evidence was determined according to standard guidelines. Results: Eighteen points to consider were formulated. These were grouped into 6 categories that comprised overall CVD risk assessment and management (n=4), and specific interventions aimed at reducing CVD risk including RA control with disease modifying anti-rheumatic drugs, glucocorticoids and non-steroidal anti-inflammatory drugs (n=3), lipid lowering agents (n=8), antihypertensive drugs (n=1), low dose aspirin (n=1) and lifestyle modification (n=1). Each point to consider differs partially or completely from recommendations previously reported for CVD risk management in RA patients from high income populations. Currently recommended CVD risk calculators do not reliably identify South African black RA patients with very high-risk atherosclerosis as represented by carotid artery plaque presence on ultrasound. Conclusions: Our findings indicate that optimal cardiovascular risk management likely differs substantially in RA patients from low or middle income compared to high income populations. There is an urgent need for future multicentre longitudinal studies on CVD risk in black African patients with RA.The first meeting held amongst local Rheumatologists was funded by the South African Arthritis and Rheumatology Association. The studies by Professor González-Gay have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748, PI12/00060, PI15/00525, PI18/00043, and RD12/0009/0013 and RD16/0012 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain), co-funded by FEDER funds

Does the current taxonomic delimitation of Galianthe find support in phylogenetic perspective?

Galianthe Griseb. is a neotropical genus comprising 50 species divided into two subgenera: G. subgen. Galianthe (41 spp.), characterized by homogeneous morphological traits, with species further divided into two sections (G. secc. Galianthe and G. secc. Laxae); and G. subgen. Ebelia (14 spp.) with more heterogeneous morphological characteristics. Due to its morphological similarity with other genera, Galianthe has historically been associated with Borreria, Spermacoce, Diodia (based on fruit type), as well as Denscantia and Emmeorhiza (based on inflorescence type). In recent years, molecular studies have established Galianthe as a basal genus within the Spermacoce clade, closely related to other genera such as Carajasia and Schwendenera. Despite the progress made in recent molecular studies, the studies have focused on a limited number of species within the genus, failing to encompass all infrageneric categories. Questioning of the current taxonomic delimitation of the genus, this study aims to test the monophyly of Galianthe and explore its infrageneric and interspecific phylogenetic relationships. Three markers (two nuclear: ITS, ETS, and one plastid: rps16) were utilized, encompassing 107 entities, including 42 Galianthe species, thereby representing 76% of the current genus diversity, as well as 17 closely related genera within the Spermacoce clade. The phylogenetic results confirm the monophyly of Galianthe, revealing the presence of three major subclades. Subclades I and II comprise several G. subgen. Ebelia species, whereas subclade III consists of all G. subgen. Galianthe species plus G. angulata. Regarding the sections, monophyly was not supported. Based on these findings, it can be concluded that G. subgen. Ebelia is paraphyletic, G. subgen. Galianthe is potentially paraphyletic due to G. angulata, and there is no clear distinction between the sections

Towards new insights in the phylogeny of the Spermacoce clade: an integrative taxonomic approach using morphology, anatomy, ecology and phylogenetics reveáis the new genus Leonoria

Phylogenetic inference analyses o f two nuclear and four plastid DNA markers from 82 accessions representing 19 genera o f the Spermacoce clade (Spermacoceae-Rubiaceae) confirm that the Brazilian genus Denscantia is biphyletic. By the analyses o f reproductive morphological characters, foliar morpho-anatomy and histochemical, geographical distribution ranges, and ecological niche derived from climatic space, Denscantia caldcóla is shown as a distinct lineage from the other Denscantia species, indicating its taxonomic segregation into a new monospecific genus Leonoria. Significant morphological diíferences o f Leonoria with Denscantia were found in inflorescence organization, stigma shape, fruit dehiscence, and pollen morphology. Morphoanatomical variation among leaf traits were found in epidemial cells, occurrence o f trichomes, mesophyll histochemical, and vascular organization. Analysis o f occurrence records o f 205 specimens demonstrates a clear ecological distinction between o f Denscantia s.s. and Leonoria, which is ecologically confined to limestone outcrops associated with seasonally dry forests. The current study demonstrates the importance of an integrative taxonomic approach - in which múltiple disciplines are combined - to the unravel complex taxonomic pattems within Rubiaceae. The genus Leonoria, to be newly described, is dedicated to Professor Elsa Leonor Cabral

Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice.

Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis

The Impact of Different Classification Criteria Sets on the Estimated Prevalence and Associated Risk Factors of Diastolic Dysfunction in Rheumatoid Arthritis

This study compared the estimated prevalence and potential determinants of left ventricular (LV) diastolic dysfunction upon applying different classification criteria in rheumatoid arthritis (RA). LV diastolic function was assessed echocardiographically by pulsed Doppler (E/A), tissue Doppler (E/e′, lateral and septal e′), and left atrial volume index in 176 RA patients. Relationships of traditional cardiovascular risk factors and RA characteristics with LV diastolic function and dysfunction according to previous and current criteria were determined in multivariate regression models. Waist-hip ratio was associated with E/A (standardised β (SE) = -0.28±0.09, p=0.0002) and lateral e′ (standardised β (SE) = 0.26±0.09, p=0.01); low diastolic blood pressure was related to E/e′ (standardised β (SE) = -0.16±0.08, p=0.04). Diastolic dysfunction prevalence differed upon applying previous (59%) compared to current (22%) criteria (p<0.0001). One SD increase in waist-hip ratio was associated with diastolic dysfunction when applying current criteria (OR = 2.61 (95% CI = 1.51–4.52), p=0.0006), whereas one SD increase in diastolic blood pressure was inversely related to diastolic dysfunction upon using previous criteria (OR = 0.57 (95% CI = 0.40–0.81), p=0.002). In conclusion, application of current and previous diastolic dysfunction criteria markedly alters the prevalence and risk factors associated with diastolic dysfunction in RA

Survival or Sustainability? Contributions of Innovatively-Managed News Ventures to the Future of Egyptian Journalism

In the repressive political climate prevailing in Egypt in 2013-15, news ventures aspiring to high standards of reporting were forced to innovate. This paper analyses three Egyptian start-ups that experimented with novel revenue streams and news services during that period, to gain insights into their approaches to managing journalism. In the process it compares different criteria for assessing sustainability and concludes that, in adverse political environments, narrow economic measures of profitability and survival may give a misleading picture as to the sustainability of the kind of journalism conducive to democratic practice. Operating collaboratively, transparently and ethically may slow productivity and profitability in the short term while laying stronger foundations for durable relations among media teams, as well as with readers and advertisers, in the long run