Role of lysozyme inhibitors in the virulence of avian pathogenic Escherichia coli

Lysozymes are key effectors of the animal innate immunity system that kill bacteria by hydrolyzing peptidoglycan, their major cell wall constituent. Recently, specific inhibitors of the three major lysozyme families occuring in the animal kingdom (c-, g- and i-type) have been discovered in Gram-negative bacteria, and it has been proposed that these may help bacteria to evade lysozyme mediated lysis during interaction with an animal host. Escherichia coli produces two inhibitors that are specific for c-type lysozyme (Ivy, Inhibitor of vertebrate lysozyme; MliC, membrane bound lysozyme inhibitor of c-type lysozyme), and one specific for g-type lysozyme (PliG, periplasmic lysozyme inhibitor of g-type lysozyme). Here, we investigated the role of these lysozyme inhibitors in virulence of Avian Pathogenic E. coli (APEC) using a serum resistance test and a subcutaneous chicken infection model. Knock-out of mliC caused a strong reduction in serum resistance and in in vivo virulence that could be fully restored by genetic complementation, whereas ivy and pliG could be knocked out without effect on serum resistance and virulence. This is the first in vivo evidence for the involvement of lysozyme inhibitors in bacterial virulence. Remarkably, the virulence of a ivy mliC double knock-out strain was restored to almost wild-type level, and this strain also had a substantial residual periplasmic lysozyme inhibitory activity that was higher than that of the single knock-out strains. This suggests the existence of an additional periplasmic lysozyme inhibitor in this strain, and indicates a regulatory interaction in the expression of the different inhibitors

Epikrise i hånden: Bedre enn 10 i systemet?

Bakgrunn/emne: Brukermedvirkning og samhandling er viktige satsningsområder i arbeidet for å sikre god pasientsikkerhet og kvalitet i helsevesenet. Å involvere pasienten i egen sykdom og behandling, samt sikre at denne informasjonen raskt formidles mellom første- og annenlinjetjenesten, er nødvendig for å kunne bedre pasientsikkerheten. Epikrisen er et sentralt verktøy for å oppnå dette. Vi ønsker å undersøke hvordan innføring av ”epikrise i hånden” (EIH) til pasienten ved utskrivelse fra sykehusavdeling påvirker epikrisetid og pasienttilfredshet, og se på hvilke tiltak som kan være aktuelle for å gjennomføre dette. Kunnskapsgrunnlag: Ved litteratursøk fant vi gode erfaringer fra gjennomføring av EIH i Norge. Pasientene ønsker å motta informasjonen som er i epikrisen, de fleste opplever bedre egenhelse, og er mer fornøyde med behandlingen. Epikrisetiden har gjennomgående blitt betraktelig redusert og kommunikasjonen med andrelinjetjenesten har blitt styrket. Begrunnet tiltak og metode: Vi søkte i tilgjengelig litteratur, intervjuet leger i kliniske avdelinger og benyttet oss av egne erfaringer fra praksisperioden i 10.semester. Avhengig av avdelingens eksisterende rutiner og arbeidsverktøy, vil vi foreslå flere mindre tiltak. Både talegjenkjenning, digital diktering, omorganisering av sekretærtjenesten og endring av arbeidsflyten i avdelingen kan være aktuelt, sammen eller hver for seg, tilpasset de ulike avdelingers rammevilkår. Organisering: Forslaget vårt er at det i den aktuelle avdelingen nedsettes en tverrfaglig prosjektgruppe, som etter et PDSA-mønster implementerer EIH som utskrivelsespraksis i en prøveperiode. Etter prøveperioden må arbeidsgruppen vurdere effektene av tiltaket, og vurdere om det er ønskelig å implementere EIH som fast praksis. Resultater/vurdering: Målet med å innføre EIH er todelt: at pasienten blir mer involvert i egen helse og behandling, samt å øke andelen epikriser som sendes ut i løpet av den nasjonale syvdagersfristen slik at kommunikasjonen mellom ulike nivåer i helsetjenesten bedres. Begge delmål bidrar til økt pasientsikkerhet. Mål på førstnevnte vil være økt pasienttilfredshet, målt kvalitativt ved et strukturert spørreskjema. Epikrisetiden kan raskt kontrolleres ved å sjekke utsendelsesdatoen opp mot utskrivelsesdato, noe som er et indirekte mål på hvorvidt EIH er gjennomført

Hjemme, borte eller uavgjort? Kvalitet og effektivitet i pleie- og omsorgstjenestene

Hvordan organiserer norske kommuner sine pleie- og omsorgstjenester – og hvorfor? Er noen måter å organisere tjenestene på mer ressurseffektive enn andre? Hvilke kommuner produserer best kvalitet på tjenestene? Er god kvalitet kjennetegnet ved sykehjemsplass til alle som trenger det – eller til å hjelpe alle til å bli boende hjemme så lenge som mulig? Dette er noen av spørsmålene som drøftes i denne rapporten. Problemstillingene belyses ved hjelp av casestudier og registerdata. Ved hjelp av ulike analyseteknikker søker vi etter kommunetypologier – og deretter etter sammenhenger mellom typologier, effektivitet og kvalitet

Chronic obstructive pulmonary disease does not impair responses to resistance training

publishedVersio

A Radio Flare in the Long-Lived Afterglow of the Distant Short GRB 210726A: Energy Injection or a Reverse Shock from Shell Collisions?

We present the discovery of the radio afterglow of the short $\gamma$-ray burst (GRB) 210726A, localized to a galaxy at a photometric redshift of $z\sim 2.4$. While radio observations commenced $\lesssim 1~$day after the burst, no radio emission was detected until $\sim11$~days. The radio afterglow subsequently brightened by a factor of $\sim 3$ in the span of a week, followed by a rapid decay (a ``radio flare''). We find that a forward shock afterglow model cannot self-consistently describe the multi-wavelength X-ray and radio data, and underpredicts the flux of the radio flare by a factor of $\approx 5$. We find that the addition of substantial energy injection, which increases the isotropic kinetic energy of the burst by a factor of $\approx 4$, or a reverse shock from a shell collision are viable solutions to match the broad-band behavior. At $z\sim 2.4$, GRB\,210726A is among the highest redshift short GRBs discovered to date as well as the most luminous in radio and X-rays. Combining and comparing all previous radio afterglow observations of short GRBs, we find that the majority of published radio searches conclude by $\lesssim 10~$days after the burst, potentially missing these late rising, luminous radio afterglows.Comment: 28 pages, 10 figures, submitted to Ap

Genital inflammatory status and the innate immune response to contraceptive initiation

PROBLEM : Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence immune mediator changes in response to contraceptive initiation. METHODS : This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation. Women were grouped according to an overall baseline inflammatory profile. We evaluated modification of the relationships between contraceptives and immune mediators by baseline inflammation, demographic, and clinical factors. RESULTS : Overall, LNG implant and copper IUD initiation were associated with increases in inflammatory cytokines, while no changes were observed following DMPA-IM initiation. However, when stratifying by baseline inflammatory profile, women with low baseline inflammation in all groups experienced significant increases in inflammatory cytokines, while those with a high baseline inflammatory profile experienced no change or decreases in inflammatory cytokines. CONCLUSION : We conclude that pre-contraceptive initiation immune profile modifies the effect of contraceptives on the FGT innate immune response.The Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institute of Health, the Carnegie Corporation of New York, South African National Research Foundation (NRF), the Bill & Melinda Gates Foundation, the American people through the United States Agency for International Development, the Swedish International Development Cooperation Agency, the South Africa Medical Research Council and the United Nations Population Fund. Contraceptive supplies were donated by the Government of South Africa and US Agency for International Development.https://wileyonlinelibrary.com/journal/ajiam2023Medical Microbiolog

A New Family of Lysozyme Inhibitors Contributing to Lysozyme Tolerance in Gram-Negative Bacteria

Lysozymes are ancient and important components of the innate immune system of animals that hydrolyze peptidoglycan, the major bacterial cell wall polymer. Bacteria engaging in commensal or pathogenic interactions with an animal host have evolved various strategies to evade this bactericidal enzyme, one recently proposed strategy being the production of lysozyme inhibitors. We here report the discovery of a novel family of bacterial lysozyme inhibitors with widespread homologs in gram-negative bacteria. First, a lysozyme inhibitor was isolated by affinity chromatography from a periplasmic extract of Salmonella Enteritidis, identified by mass spectrometry and correspondingly designated as PliC (periplasmic lysozyme inhibitor of c-type lysozyme). A pliC knock-out mutant no longer produced lysozyme inhibitory activity and showed increased lysozyme sensitivity in the presence of the outer membrane permeabilizing protein lactoferrin. PliC lacks similarity with the previously described Escherichia coli lysozyme inhibitor Ivy, but is related to a group of proteins with a common conserved COG3895 domain, some of them predicted to be lipoproteins. No function has yet been assigned to these proteins, although they are widely spread among the Proteobacteria. We demonstrate that at least two representatives of this group, MliC (membrane bound lysozyme inhibitor of c-type lysozyme) of E. coli and Pseudomonas aeruginosa, also possess lysozyme inhibitory activity and confer increased lysozyme tolerance upon expression in E. coli. Interestingly, mliC of Salmonella Typhi was picked up earlier in a screen for genes induced during residence in macrophages, and knockout of mliC was shown to reduce macrophage survival of S. Typhi. Based on these observations, we suggest that the COG3895 domain is a common feature of a novel and widespread family of bacterial lysozyme inhibitors in gram-negative bacteria that may function as colonization or virulence factors in bacteria interacting with an animal host

Tiltak mot kjønnslemlestelse

Evalueringen vurderer om tiltakene i OK-prosjektet har bidratt til måloppnåelse, effekter og konsekvenser, om brukerperspektivet er kommet fram, og om prosjektet har nådd sine målgrupper

Ugripelig ung

Rapporten er basert på intervjuer av innvandrerorganisasjoner, menigheter og nøkkelpersoner i det somaliske og pakistanske miljøet i Oslo, samt forskning og erfaringer gjort under arbeid med prosjekter finansiert av Forskningsrådets IMER- og Velferdsprogram