Site-specific O-glycosylation on the MUC_{2} mucin protein inhibits cleavage by the porphyromonas gingivalis secreted cysteine protease (RgpB)

The colonic epithelial surface is protected by an inner mucus layer that the commensal microflora cannot penetrate. We previously demonstrated that Entamoeba histolytica secretes a protease capable of dissolving this layer that is required for parasite penetration. Here, we asked whether there are bacteria that can secrete similar proteases. We screened bacterial culture supernatants for such activity using recombinant fragments of the MUC2 mucin, the major structural component, and the only gel-forming mucin in the colonic mucus. MUC2 has two central heavily O-glycosylated mucin domains that are protease-resistant and has cysteine-rich N and C termini responsible for polymerization. Culture supernatants of Porphyromonas gingivalis, a bacterium that secretes proteases responsible for periodontitis, cleaved the MUC2 C-terminal region, whereas the N-terminal region was unaffected. The active enzyme was isolated and identified as Arg-gingipain B (RgpB). Two cleavage sites were localized to IR↓TT and NR↓QA. IR↓TT cleavage will disrupt the MUC2 polymers. Because this site has two potential O-glycosylation sites, we tested whether recombinant GalNAc-transferases (GalNAc-Ts) could glycosylate a synthetic peptide covering the IRTT sequence. Only GalNAc-T3 was able to glycosylate the second Thr in IRTT, rendering the sequence resistant to cleavage by RgpB. Furthermore, when GalNAc-T3 was expressed in CHO cells expressing the MUC2 C terminus, the second threonine was glycosylated, and the protein became resistant to RgpB cleavage. These findings suggest that bacteria can produce proteases capable of dissolving the inner protective mucus layer by specific cleavages in the MUC2 mucin and that this cleavage can be modulated by site-specific O-glycosylation

Det moderna ledarskapet : En kvalitativ studie om medarbetares uppfattning av virtuellt ledarskap ur ett genusperspektiv

The main purpose of this study is to investigate whether there is a difference between the employee's experience in virtual leadership -  in relation to female and male leadership. Distance work has existed before. But since the outbreak of the corona pandemic, distance work has become a world-famous way of working. In turn, this places higher demands on the manager's ability to guide the organization in the right direction, while maintaining the same commitment of employees. In Sweden, the number of male managers is significantly more than female managers, but according to a recently made survey, female managers perform better than male managers when distance work leading. Therefore, it is necessary to study how leadership differs by gender. We used semi-structured interviews as a method and interviewed four respondents to take part in their views on virtual leadership. The respondents are active in various industries. Two of them are women, one with a male manager, and the other with a female manager. The other two respondents are men, one with a male manager and the other with a female manager. We concluded that female managers exercise transformational leadership from a distance, while male managers exercise transactional leadership from a distance. Female managers are more committed to the personal development of their employees, are more communicative and have made greater contributions to establishing a good work culture in which everyone can participate

Ut med det gamla och in med det nya : En fallstudie om upphandling och implementering av ett nytt informationssystem inom offentlig sektor

Upphandling av informationssystem har visat sig vara ett komplext fenomen inom offentlig sektor där LOU binder upp kravställarprocessen. Studien undersöker hur ett lärosäte arbetar med utveckling och förändringsarbete inom ramen för LOU för att informationssystemet ska stödja verksamhetens behov. Detta görs genom en explorativ fallstudie med semistrukturerade intervjuer. Studien ger en förståelse för hur en verksamhet inom offentlig sektor arbetat med upphandling av system, såväl som genererar värdefulla insikter. I empirin framgår det att strategisk kommunikation bidrar till användarinvolvering och aktivt deltagande som förbättrade möjligheterna till att uppnå acceptans för systembytet. Resultaten identifierar även en konflikt mellan systemutveckling och upphandling kring balanseringen av krav där det gäller att som upphandlare ställa tillräckligt med krav men samtidigt inte göra en alltför omfattande kravspecifikation och låsa in sig utan lösningar. Resultaten mynnar ut i en modell över processen för upphandling och implementering och lämnar läsaren med en förståelse för hur upphandlings- och implementeringsarbetet kan se ut. Detta för att möta det kunskapsgap som finns om forskning kring systemutveckling, implementering och förändringsarbete kopplat till LOU. Av fallstudien kan vi dra slutsatsen att det är avgörande att en verksamhets informatik- och organisationsstrategi stödjer varandra för att verksamhetsutveckling inkluderat ett systembyte ska nå framgång

Ut med det gamla och in med det nya : En fallstudie om upphandling och implementering av ett nytt informationssystem inom offentlig sektor

Upphandling av informationssystem har visat sig vara ett komplext fenomen inom offentlig sektor där LOU binder upp kravställarprocessen. Studien undersöker hur ett lärosäte arbetar med utveckling och förändringsarbete inom ramen för LOU för att informationssystemet ska stödja verksamhetens behov. Detta görs genom en explorativ fallstudie med semistrukturerade intervjuer. Studien ger en förståelse för hur en verksamhet inom offentlig sektor arbetat med upphandling av system, såväl som genererar värdefulla insikter. I empirin framgår det att strategisk kommunikation bidrar till användarinvolvering och aktivt deltagande som förbättrade möjligheterna till att uppnå acceptans för systembytet. Resultaten identifierar även en konflikt mellan systemutveckling och upphandling kring balanseringen av krav där det gäller att som upphandlare ställa tillräckligt med krav men samtidigt inte göra en alltför omfattande kravspecifikation och låsa in sig utan lösningar. Resultaten mynnar ut i en modell över processen för upphandling och implementering och lämnar läsaren med en förståelse för hur upphandlings- och implementeringsarbetet kan se ut. Detta för att möta det kunskapsgap som finns om forskning kring systemutveckling, implementering och förändringsarbete kopplat till LOU. Av fallstudien kan vi dra slutsatsen att det är avgörande att en verksamhets informatik- och organisationsstrategi stödjer varandra för att verksamhetsutveckling inkluderat ett systembyte ska nå framgång

Air-flushing of pressure sewers as a method for hydrogen sulphide control

Luftspolning av tryckavloppsledningar har utprovats som ett alternativ för att förhindra svavelvätebildning i avloppsnätet. Syftet med luftspolningen är att tömma tryckledningen på spillvatten och på detta sätt förkorta uppehållstiden samtidigt som de sulfidbildande mikroorganismerna i ledningen får ett betydligt tuffare liv. Fullskaleförsök visar att luftspolning är ett realistiskt och fungerande alternativ för bekämpning av svavelväte i avloppsnät. Luftspolningstekniken har dock sina begränsningar, som då tryckavloppsledningen har tydliga höjdpunkter och svackor.Godkänd; 2010; 20100407 (andbra)</p

Healthcare contacts regarding circulatory conditions among swedish patients in opioid substitution treatment, with and without on-site primary healthcare

Patients in Opioid Substitution Treatment (OST) have increased mortality and morbidity, with circulatory conditions suggested to be a contributing factor. Since OST patients tend to have unmet physical healthcare needs, a small-scale intervention providing on-site primary healthcare (PHC) in OST clinics was implemented in Malmö, Sweden in 2016. In this study, we assessed registered circulatory conditions and healthcare utilization in OST patients with and without use of on-site PHC. Patients from four OST clinics in Malmö, Sweden, were recruited to a survey study in 2017–2018. Medical records for the participants were retrieved for one year prior to study participation (n = 192), and examined for circulatory diagnoses, examinations and follow-ups. Patients with and without on-site PHC were compared through descriptive statistics and univariate analyses. Eighteen percent (n = 34) of the sample had 1≤ registered circulatory condition, and 6% (n = 12) attended any clinical physiology examination or follow-up, respectively. Among patients utilizing on-site PHC (n = 26), the numbers were 27% (n = 7) for circulatory diagnosis, 15% (n = 4) for examinations, and 12% (n = 3) for follow-up. OST patients seem underdiagnosed in regard to their circulatory health. On-site PHC might be a way to diagnose and treat circulatory conditions among OST patients, although further research is needed

GR3027 reversal of neurosteroid-induced, GABA-A receptor-mediated inhibition of human brain function : an allopregnanolone challenge study

RATIONALE: GR3027 is a novel small molecule GABA-A receptor-modulating steroid antagonist, which in non-clinical studies has shown promise for treatment of human disorders due to allosteric over-activation of GABA-A receptors by neurosteroids, such as allopregnanolone. We here studied its safety, pharmacokinetics, and ability to inhibit allopregnanolone effects in humans. METHODS: Safety and pharmacokinetics were studied in healthy adult males receiving ascending single or multiple oral GR3027 vs. placebo. GR3027-mediated reversal of allopregnanolone effect on maximal saccadic eye velocity (SEV), and self-rated somnolence was studied in a double-blind, placebo-controlled, three-part cross-over study in which 3 or 30 mg oral GR3027 preceded 0.05 mg/kg of i.v. allopregnanolone. RESULTS: ]) varied linearly with dose; with dose-dependent accumulation ratios of 1.3-1.6. Allopregnanolone decreased SEV and induced somnolence in most, but not all subjects. By predefined analyses, 30 mg GR3027 significantly inhibited allopregnanolone-induced decrease in SEV (p = 0.03); 3 and 30 mg GR3027 non-significantly inhibited allopregnanolone-induced sedation. By post hoc analyses restricted to subjects with allopregnanolone-induced changes and the time period over which they occurred, GR3027 dose dependently inhibited allopregnanolone-induced decrease in SEV (p = 0.04 at 30 mg, non-significant at 3 mg) and allopregnanolone-induced sedation (p = 0.01/0.05 at 3/30 mg doses). CONCLUSION: Oral GR3027 mitigates inhibition of brain function induced by allopregnanolone at doses which are clinically well tolerated and associated with linear pharmacokinetics

Occupational therapy gender imbalance; revisiting a lingering issue

Background: Recently, it has been suggested that gender disparity in Occupational Therapy has to do with segregated gendered job norms that position female dominated professions as a ‘step down’ for many males. Interestingly, this suggestion was not underpinned by experiences of males in the profession. Aims and Methods:  Thirteen male Occupational Therapists with a variety of backgrounds were invited to this Round Table research, focussing on the broader issue of the existing gender imbalance in Occupational Therapy. Results:  Two themes emerged: ‘The core values of the profession’, and ‘Broadening the scope of the profession’; none of them suggesting that male/female imbalance was necessarily the most pressing issue. Conclusions:  A gender-unrelated approach to everyday problem-solving was put forward to achieve increased diversity in Occupational Therapists’ backgrounds, better reflecting the people they serve. By broadening the scope and the way the profession is presented, and encouraging innovative and more entrepreneurially driven approaches, diversity in the workforce could be further facilitated. These findings are discussed within the context of ‘The mutual constitution of cultures and selves’ model. Significance:  Diversity in the Occupational therapy workforce could be further facilitated with a shift in focus away from the male/female perspective to an intersectional approach.</p