SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among people with HIV across Europe in the multinational EuroSIDA cohort.

BACKGROUND: Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. METHODS: We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. RESULTS: Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3, and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). CONCLUSIONS: We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

The fate and transport of mercury, methylmercury, and other trace metals in Chesapeake Bay tributaries.

Six tributaries to the Chesapeake Bay were analyzed for suspended particulate matter, dissolved organic carbon, particulate organic carbon, mercury, methylmercury, lead, nickel, zinc, cadmium, chromium, and copper. This study examined the importance of flow regime, suspended particulate concentration, and watershed characteristics on the transport of mercury, methylmercury, and other trace metals. Total mercury concentrations were higher under high flow conditions which is consistent with the tendency of this metal to bind strongly to particulate matter. Methylmercury showed less flow rate dependence. Nickel, lead, and zinc concentrations responded strongly to flow rate on the Potomac River, while weaker correlations were found on the other rivers sampled. Cadmium, copper, and chromium concentrations were the least influenced by flow. Partition coefficients calculated in this study were similar to those of other estuaries and overall decreased in the order of Hg > Ni-MMHg > Cr-Pb-Zn > Cd > Cu. Watershed yield estimates and associated retention factors were calculated for the various rivers. These calculations showed that for most of the rivers, mercury was the most strongly retained within the watershed.

Cyclic AMP activates p38 mitogen-activated protein kinase in Th2 cells: phosphorylation of GATA-3 and stimulation of Th2 cytokine gene expression.

cAMP is an important second messenger with immunomodulatory properties. Elevation of intracellular cAMP in T cells, induced by agents such as IL-1alpha or PGs, inhibits T cell activation. In effector T cells, an increase in the level of intracellular cAMP inhibits cytokine production in Th1 cells but stimulates cytokine production in Th2 cells. Here we report that cAMP-induced effects in Th2 cells occur independently of the protein kinase A pathway, which is the major mediator of cAMP-induced signaling events in most cell types. Instead, cAMP stimulates activation of p38 mitogen-activated protein kinase in Th2 cells. This appears to be a Th2-selective event because cAMP barely increased p38 phosphorylation in Th1 cells. We show that in Th2 cells, cAMP promotes the production of both IL-5 and IL-13, which play distinct but critical roles in asthma pathogenesis. Our data also show that cAMP causes increased phosphorylation of the transcription factor GATA-3, which we have shown is a critical regulator of Th2 cytokine gene expression and, in turn, of airway inflammation in mice. Thus, Th2-specific GATA-3 expression and p38 mitogen-activated protein kinase activation together provide a molecular basis for the differential effects of cAMP in the two T helper cell subsets.

The figure-of-eight splint for proximal interphalangeal joint volar plate injuries.

Volar plate disruption of the proximal interphalangeal (PIP) joint is a common hand injury. Management of this injury must provide stability and motion to avoid disabling instability or stiffness. In this study, 40 patients with closed PIP joint volar plate injuries were treated with the figure-of-eight splint, a custom made, thermoplastic splint that allows protected joint motion. At two-year follow-up, 95% of these patients experienced good or excellent results. The figure-of-eight splint offers a simple and effective method of treatment for volar plate injuries of the PIP joint.

Biomechanical analysis of pin placement and pin size for external fixation of distal radius fractures.

A series of biomechanical analyses were performed to explain the recent reduction in treatment-related complications of external fixation of distal radius fractures using a limited open approach for pin placement and larger 4-mm self-tapping half pins. A comparison of pull-out strength, stress concentration effect, and inherent bending strength of 3- and 4-mm half pins was performed. The effect of proximal pin placement in the radius or in the ulna and the effect of distal pin placement in four, six, or eight metacarpal cortices were determined. These analyses demonstrate that the 4-mm self-tapping half pins result in a significantly higher pull-out strength and only a small decrease in torsional load strength of the bone. They also demonstrate that proximal pin fixation in the radius produces the most stable fixation and that distal pin fixation into six metacarpal cortices produces a strong configuration that does not violate the interosseous muscles of the second intrinsic compartment. The rate of treatment-related complications in the external fixation of distal radius fractures (specifically, pin loosening, bending and breakage, fracture through pin sites, collapse at the fracture site, and intrinsic contracture) are addressed in this study. Such complications can be minimized by using 4-mm pins after central predrilling, with proximal placement in the radius and distal placement through six cortices of the bases of the second and third metacarpals.

[Elimination of various virulence plasmids by antibiotics]. / Elimination de différents plasmides de virulence par les antibiotiques.

The pathogenicity of some enterobacteria is due to a plasmid encoding for outer membrane proteins or for toxins. The elimination of the plasmid gives a non-virulent strain. We have tried to eliminate plasmids encoding for the thermostable toxin of Escherichia coli (plasmid pCSltl) or for the enteroinvasive property of Shigella (plasmids pWR24, pHW401, pWR110), of Salmonella (plasmid pSD6) and of Yersinia (plasmids pYL4 and P4). The loss of plasmid was confirmed by agarose gel electrophoresis of a crude lysate. Fourteen antibiotics belonging to different chemical families were used at subinhibitory concentration. A control experiment without antibiotic was carried out to detect spontaneous loss of plasmids. No antibiotic was able to eliminate plasmids pCSltl, pHW401, pSD6, pYL4. Novobiocin eliminated pWR24 and pWR110, rifampicin eliminated pWR110 and P4. Three other antibiotics gave a cure of bacteria harbouring plasmids pWR110 and P4 but the percentage of cure was too low for a therapeutical interest.

[The role of 4-quinolones and antibiotics in the elimination of virulence plasmids of Enterobacteriaceae]. / Rôle des 4-quinolones et des antibiotiques dans l'élimination des plasmides de virulence des entérobactéries.

Twenty-six antibiotics belonging to thirteen different chemical families had been tested on seven Enterobacteriaceae harbouring a virulence plasmid (Shigella sonnei, S. flexneri, S. dysenteriae, Escherichia coli (two plasmids). Yersinia and Salmonella dublin). Novobiocin and rifampicin were found to be most efficient eliminating three plasmids of which two come from Shigella. Clindamycin, cotrimoxazole, nifurzide, ciprofloxacin, and tilbroquinol were also efficient, but at lower rate. Four virulence plasmids (from the three Shigella sp and Y. pestis) were eliminated by one or several antibiotics. The frequency of elimination was low (at best 10% bacteria per generation). The plasmid pWR105 from S. sonnei was the less stable.

Elimination of plasmids from Enterobacteriaceae by 4-quinolone derivatives.

Twelve 4-quinolones (cinoxacin, ciprofloxacin, enoxacin, flumequin, nalidixic acid, norfloxacin, oxolinic acid, pefloxacin, pipemidic acid, rosoxacin, and piromidic and beta-hydroxypiromidic acids) and novobiocin, were used at subinhibitory concentrations to eliminate from Escherichia coli 11 antibiotic resistance plasmids belonging to different incompatibility groups. The 12 4-quinolones were also tested for their ability to cure virulence plasmids from five species of Enterobacteriaceae. All quinolones eliminated three antibiotic resistance plasmids (R446b, R386, S-a) and one virulence plasmid (pWR105), but at a low rate. Optimal curing of antibiotic resistance plasmids was obtained in human urine. Two virulence plasmids (pWR24 and pWR110) were eliminated only by flumequin and pefloxacin. Novobiocin eliminated three antibiotic resistance plasmids (R446b, R386, pIP24). The variable and low level of plasmid loss may be explained by the induction of the recA system. In addition, the inability to eliminate certain plasmids could be due to their presence in high numbers per cell.

Elimination of a virulence plasmid from Shigella sonnei and Escherichia coli by antibiotics.

Plasmid pWR105 is a non-self-conjugative plasmid conferring enteroinvasive properties on Shigella sonnei. Loss of this plasmid is accompanied by loss of the invasive phenotype as well as of the form I antigen expression. Thirteen antibiotics belonging to different chemical families were used at subinhibitory concentrations to eliminate pWR105 from S. sonnei and Escherichia coli K12. Rifampicin, novobiocin, chloramphenicol, cotrimoxazole and erythromycin eliminated the plasmid from both strains. Clindamycin eliminated pWR105 from E. coli only. Several other antibiotics gave a low rate of cure (ciprofloxacin, nalidixic acid, oxolinic acid, nifurzide, tilbroquinol, minocycline). We may expect that these antibiotics would destabilize plasmids from other Shigella species and enteroinvasive E. coli, as these extrachromosomal DNA molecules share a high degree of homology.

Inhibition of conjugal transfer of R plasmids by nitrofurans.

Nifurzide is a nitrofuran with antibacterial activity. As nitrofurans have been reported to interact with DNA, we tested the ability of nifurzide to inhibit plasmid transfer. Inhibition of plasmid transfer between Escherichia coli strains was obtained for ten plasmids belonging to nine incompatibility groups. The same effect was observed when plasmid RP4 was harboured in six different members of the Enterobacteriaceae. Inhibition depended on the reduction of the -NO2 group of nifurzide and was obtained with four other nitrofuran derivatives.

[Inhibition of the maintenance and transfer of antibiotic-resistance plasmids by quinolones]. / L'inhibition de la maintenance et du transfert des plasmides de résistance aux antibiotiques par les quinolones.

The role of quinolones in the maintenance and transfer of antibiotic resistance plasmids was investigated. Curing effect of eleven quinolones, at subinhibitory concentrations, was studied on Escherichia coli strains harbouring ten plasmids belonging to different incompatibility groups. R386, R446b and S-a were the only plasmids eliminated by all the quinolones at a rate between 0.5 to 16%. The best culture medium was human urine. A total inhibition of transfer of RP4 plasmid between two Escherichia coli strains was obtained with nalixidic and oxolinic acids and flumequin. A partial inhibition was observed with other quinolones.

[Inhibition of plasmid transfer in Escherichia coli by oxolinic acid]. / Inhibition du transfert de plasmides chez Escherichia coli, par l'acide oxolinique.

Oxolinic acid inhibits the appearance of transconjugants between Escherichia coli harbouring RP4/R6K plasmids and recipient strains. This effect is detected from 1 microgram/ml, (3, 8 microM) without loss of viability, and is not due to a curing process.

[Inhibition of the diffusion of plasmids by a nitrofuran derivative]. / Inhibition de la diffusion de plasmides par un dérivé des nitrofuranes.

Antibiotic resistance plasmids PR4, R6K, and RGN238 can transfer between Escherichia coli cells by conjugation (transfer frequency: 3 to 3.5 x 10(-4)). Nifurzide, a nitrofuran derivative, greatly depresses plasmid transfer at concentrations (59 microM) which do not affect cell viability.

[Evidence for plasmidic localization of "beta-lactamase" gene in a Pseudomonas aeruginosa strain, highly resistant to carbenicillin]. / Argument en faveur de la localisation plasmidique du gène "beta-lactamase" chez une souche de Pseudomonas aeruginosa hautement résistante à la carbénicilline.

Pseudomonas aeruginosa strain HL, isolated in Besançon (France), shows a high level of resistance for carbenicillin, as proved in preliminary studies. In this paper, we report the transfer of carbenicillin resistance from Pseudomonas aeruginosa HL1 carrying helper plasmids to other strains of the same species. Comparative study of beta-lactamase activity in the HL1 strain and in the conjugated strains allows confirmation of the transfer of an R-factor from the HL1 strain: in all these strains, the beta-lactamase has the same pI (5.3) and the same Vmax (relative to benzylpenicillin) for ampicillin, carbenicillin and cephaloridin.