The Coxiella burnetii Dot/Icm System Creates a Comfortable Home through Lysosomal Renovation

Understanding the molecular pathogenesis of Coxiella burnetii, the causative agent of human Q fever, has historically been hindered by the technical difficulties of genetically manipulating obligate intracellular bacteria. The recent development of culture conditions suitable for axenic propagation of C. burnetii has paved the way for the application of a range of genetic techniques to address key questions within the field. Recent studies using mutational analysis have revealed that the C. burnetii Dot/Icm type 4 secretion system (T4SS) is an important virulence determinant that is essential for renovation of a lysosome into a mature Coxiella-containing vacuole (CCV) permissive of intracellular replication. Interestingly, a mutant of C. burnetii deficient in Dot/Icm function was found to be capable of replicating within the parasitophorous vacuole created by Leishmania amazonensis, which indicates that C. burnetii replication is not dependent on the cohort of Dot/Icm effector proteins per se but rather that the collective actions of effectors are required to create the specialized niche supportive of replication. Thus, a role for the Dot/Icm T4SS during the intracellular life cycle of C. burnetii has been more clearly defined by these studies, which demonstrate that advances in genetic analysis should allow future studies to focus on the intricacies of Dot/Icm effector functions that facilitate development of the unique CCV

A Seat at the Table : The Norwegian Board Gender Quota: A Study on Indirect Effects

Twenty years ago, Norway led the way with the first board gender quota on ASA1 and is now considering extending the legislation to AS. This paper examines if the existing board gender quota has fulfilled one of its main objectives – increasing opportunities for all women, also those outside the boardroom. First, we find little to no evidence of an external spillover onto AS boards, as the quota had a negligible impact on increasing the gender ratio for AS. Second, we find some evidence of internal spillover from the quota onto management, causing a slight short-term boost of increased female representation in management, but with modest longterm effects. However, comparing with Sweden, neither of these findings are likely to be significant due to a probable underlying societal trend. Third, we fail to find a general internal spillover effect from boards to management or vice versa. An AS quota will undoubtingly increase the number of female seats in the boardroom. Hence, if the main objective of the quota is to increase the female share of AS boards, we recommend that the policymakers implement a quota for AS companies. However, based on our findings, we urge them not to use increased labour opportunities for women as a motivation for enacting such a quota.nhhma

Bacheloroppgave

I denne bacheloroppgaven har jeg valgt å ta for meg temaet barneskole. Oppgaven tar utgangspunkt i nye Sydskogen skole. Det gamle skolebygget ble revet for et år siden og arbeidet med den nye skolen er i full gang. Jeg ønsket å gjennomføre denne oppgaven på bakgrunn av egne erfaringer. Etter mange år bak skolebenken og ved å jobbe på skole og SFO ser jeg et behov for å endre det fysiske arbeidsmiljøet. Oppgaven tar for seg en overordnet problemstilling – hvor jeg i tillegg har underspørsmål som er tilknyttet til problemstillingen. Problemstillingen jeg endte opp med i denne oppgaven er; ”På hvilken måte påvirker rommets utforming, fleksibilitet, farger, belysning, materialer og akustikk på det fysiske- og det sosiale miljøet i skolen?” Det presenteres to av tre etasjer av skolebygget. I første etasje tar jeg for meg SFO og aula med amfi. I andre etasje har jeg valgt et klasserom med et tilhørende grupperom, bibliotek og aulaen med amfi som har tilknytning til første etasje. I oppgaven har jeg brukt forskjellige metoder for å samle informasjon og relevant teori. Jeg har brukt mye tid på fargene og gjort forsøk rundt hver enkelt farge. Intervju, observasjoner, inspirasjonsturer og befaringer har vært med på å forme oppgaven. Av disse punktene har jeg fått frem inspirasjon som jeg tok videre til idemyldringen og skisseprosessen. Gjennom denne oppgaven har jeg kommet frem til flere konklusjoner, hvor jeg vil trekke frem det fysiske læringsmiljøet og hvor individuelt det er. Fysisk læringsmiljø oppfattes forskjellig hos alle og alle mennesker har forskjellige behov. Dette gjør det ekstra viktig med fleksibilitet, som gjør at man kan tilpasse arbeidsmiljøet til hvert enkelt menneske

Estimating the future burden of hip fractures in Norway. A NOREPOS study.

Background: The incidence rate of hip fractures seems to be declining in many western countries. However, due to the ageing of the population, the number of fractures may still be on the rise. No papers so far have quantified the future burden of hip fractures in terms of both health loss (as measured in disability adjusted life years DALY) and costs. The purpose of this paper is to assess the future health and economic burden of hip fractures. Methods: We collected population projections from Statistics Norway up until the year 2040. The medium projection was used for the base case analysis. Fracture rates for 2008 were estimated based on information from the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) hip fracture database (NORHip), which includes information about all hip fractures in Norway. Future fracture rate was assumed to decline by 0.7% per year in the base case. We used the same assumptions as the global burden of disease project on years of remaining life and disability weights. Cost of hip fracture was based on the published literature. In sensitivity analyses, we assessed the impact of changing underlying assumptions on demographic change, development in hip fracture rate, assumed life expectancy and choice of disability weights. Results: Assuming a medium population growth and a continued decline in fracture rate, our estimates indicate that health lost to hip fractures will approximately double, from 32,850 DALYs in 2020 to 60,555 in 2040. Over the same period, costs are estimated to increase by 65%. Sensitivity analyses indicate that estimates are highly sensitive to assumptions on both population growth, fracture rate development, disability weights and assumed life expectancy. Conclusion: The burden of hip fractures in terms of DALYs lost and cost incurred is likely to increase even if the fracture rate continues to decline.publishedVersio

Dot/Icm Type IVB Secretion System Requirements for Coxiella burnetii Growth in Human Macrophages

Central to Q fever pathogenesis is replication of the causative agent, Coxiella burnetii, within a phagolysosome-like parasitophorous vacuole (PV) in mononuclear phagocytes. C. burnetii modulates PV biogenesis and other host cell functions, such as apoptotic signaling, presumably via the activity of proteins delivered to the host cytosol by a Dot/Icm type IVB secretion system (T4BSS). In this study, we utilized a C. burnetii strain carrying IcmD inactivated by the Himar1 transposon to investigate the requirements for Dot/Icm function in C. burnetii parasitism of human THP-1 macrophage-like cells. The icmD::Tn mutant failed to secrete characterized T4BSS substrates, a defect that correlated with deficient replication, PV development, and apoptosis protection. Restoration of type IVB secretion and intracellular growth of the icmD::Tn mutant required complementation with icmD, -J, and -B, indicating a polar effect of the transposon insertion on downstream dot/icm genes. Induction of icmDJB expression at 1 day postinfection resulted in C. burnetii replication and PV generation. Collectively, these data prove that T4BSS function is required for productive infection of human macrophages by C. burnetii. However, illustrating the metabolic flexibility of C. burnetti, the icmD::Tn mutant could replicate intracellularly when sequestered in a PV generated by wild-type bacteria, where Dot/Icm function is provided in trans, and within a phenotypically similar PV generated by the protozoan parasite Leishmania amazonensis, where host cells are devoid of Dot/Icm T4BSS effector proteins

To see the invisible - nursing for children of mentally ill parent

Bachelor sykepleie, 2018Tittel: «Å se de usynlige» «To see the invisible» Problemstilling: «Hvordan kan sykepleier gjennom kommunikasjon og samtale forebygge psykiske problemer hos barn når mor eller far har en psykisk lidelse?» Hensikt: Å øke forståelsen og få mer kunnskap om hvordan sykepleier kan ivareta barn av psykisk syke foreldre. Teori: I teoridelen tar vi for oss ulike temaer som er relevant for å kunne svare på problemstillingen. Temaer vi vektlegger er: sykepleieteoretiker Joyce Travelbee, barns psykologiske utvikling, «de usynlige barna», kommunikasjon, samtale og sykepleierens plikter og ansvar. Metode: Oppgaven er en litteraturstudie, hvor vi benytter pensum- og selvvalgt litteratur, vitenskapelige studier, samt egne erfaringer fra praksis. Konklusjon: Ved at barn blir oppdaget, sett og ivaretatt gjennom relasjonsbygging, kommunikasjon og samtale, kan sykepleier forebygge psykiske problemer hos barn med foreldre med psykisk lidelse. For å fjerne skyld og skam hos barnet, må sykepleier sørge for tilrettelagt informasjon etter barnets alder og modenhet. Dette kan fremme håp for fremtiden og betrygge barnet om at det ikke er alene om sin situasjon. Søkeord: Barn, pårørende, foreldre, psykisk lidelse, sykepleie, forebyggende arbeid, relasjon, samtale og kommunikasjon

The association between alcohol consumption and risk of hip fracture differs by age and gender in Cohort of Norway: a NOREPOS study

Under embargo until: 13.07.2019Summary: The association between alcohol consumption and hip fracture differed by gender: Men aged 30–59 years drinking frequently or 14+ gl/week had higher risk than moderate drinkers. No significant association was seen in older men. Women not drinking alcohol had higher risk than those drinking moderately both regarding frequency and amount. Introduction: We aimed to examine alcohol consumption and risk of hip fracture according to age and gender in the population-based Cohort of Norway (1994–2003). Methods: Socio-demographics, lifestyle, and health were self-reported and weight and height were measured in 70,568 men and 71,357 women ≥ 30 years. Information on subsequent hip fractures was retrieved from hospitals’ electronic patient registries during 1994–2013. Frequency of alcohol consumption was categorized: never/seldom, moderate (≤ 2–3 times/week), or frequent (≥ 4 times/week), and amount as number of glasses per week: 0, 1–6, 7–13, 14–27, and 28+. Type of alcohol (wine vs. beer/hard liquor) was also examined. Cox’s proportional hazards regression was used to estimate hazard ratios (HRs) stratified on gender and baseline age < 60 and ≥ 60 years. Results: During median 15-year follow-up, 1558 men and 2511 women suffered a hip fracture. Using moderate drinkers as reference, men < 60 years drinking frequently had multivariable adjusted HR = 1.73 (CI 1.02–2.96) for hip fracture and more than 2.5 times higher risk if they consumed 14+ glasses compared to 1–6 glasses per week. In other groups of age and gender, no statistically significant increased risk was found in those consuming the highest levels of alcohol. Compared to women with moderate or frequent alcohol use, never/seldom-drinking women had the highest fracture risk. In women, use of wine was associated with lower fracture risk than other types of alcohol. Conclusions: Risk of hip fracture was highest in men < 60 years with the highest frequency and amount of alcohol consumption and in non-drinking women.acceptedVersio

Homocysteine-Lowering Treatment and the Risk of Fracture: Secondary Analysis of a Randomized Controlled Trial and an Updated Meta-Analysis

High plasma homocysteine is a risk factor for osteoporotic fractures. Several studies have assessed the possible preventive effect of homocysteine-lowering B-vitamin treatment on the risk of fracture with inconclusive results. In the current study, we include new results from the Aspirin Folate Polyp Prevention Study (AFPPS) together with an updated meta-analysis of randomized controlled trials (RCTs). Our objective was to determine whether there is an association between homocysteine-lowering B-vitamin treatment and the risk of fracture. The AFPPS trial was performed between 1994 and 2004 in nine clinical centers in the United States, and 1021 participants were randomized to a daily folic acid dose of 1 mg (n = 516) or placebo (n = 505). The main outcome was fracture of any type. In addition, we analyzed the risk of hip fracture. In the meta-analysis, studies were identified following a search strategy in electronic database and by hand searching. Risk ratio with 95% confidence interval (CI) was chosen for pooled analyses. In the AFPPS, no statistically significant association was found between folic acid treatment and fractures of any type (risk ratio [RR] = 0.95; 95% CI 0.61–1.48) or hip fracture (RR = 0.98; 95% CI 0.25–3.89). In the meta-analysis, six RCTs were included with a total of 36,527 participants. For interventions including folic acid and/or vitamin B12, the pooled RR for treatment was 0.97 (95% CI 0.87–1.09) for fractures of any type (n = 1199) and 1.00 (95% CI 0.81–1.23) for hip fractures (n = 335). In conclusion, no association was found between homocysteine-lowering treatment with B vitamins (folic acid and vitamin B12) and the risk of fracture

Tyrosine kinase inhibitors and interferon‐α increase tunneling nanotube (TNT) formation and cell adhesion in chronic myeloid leukemia (CML) cell lines (

Chronic myeloid leukemia (CML) is a stem cell disease of the bone marrow where mechanisms of inter‐leukemic communication and cell‐to‐cell interactions are proposed to be important for optimal therapy response. Tunneling nanotubes (TNTs) are novel intercellular communication structures transporting different cargos with potential implications in therapy resistance. Here, we have investigated TNTs in CML cells and following treatment with the highly effective CML therapeutics tyrosine kinase inhibitors (TKIs) and interferon‐α (IFNα). CML cells from chronic phase CML patients as well as the blast crisis phase cell lines, Kcl‐22 and K562, formed few or no TNTs. Treatment with imatinib increased TNT formation in both Kcl‐22 and K562 cells, while nilotinib or IFNα increased TNTs in Kcl‐22 cells only where the TNT increase was associated with adherence to fibronectin‐coated surfaces, altered morphology, and reduced movement involving β1integrin. Ex vivo treated cells from chronic phase CML patients showed limited changes in TNT formation similarly to bone marrow cells from healthy individuals. Interestingly, in vivo nilotinib treatment in a Kcl‐22 subcutaneous mouse model resulted in morphological changes and TNT‐like structures in the tumor‐derived Kcl‐22 cells. Our results demonstrate that CML cells express low levels of TNTs, but CML therapeutics increase TNT formation in designated cell models indicating TNT functionality in bone marrow derived malignancies and their microenvironment.publishedVersio