FasL and TRAIL signaling in the skin during cutaneous leishmaniasis - implications for tissue immunopathology and infectious control

Cutaneous leishmaniasis (CL) is associated with chronic inflammation and ulceration of the skin. Tissue macrophages serve as host cells and immune activation is necessary for parasite clearance. The balance between immune-mediated tissue destruction and successful clearance of infection is delicate and ulceration has been proposed to be a result of infiltration of activated immune cells into the skin. FasL and TRAIL play a dual role in skin homeostasis through induction of apoptosis as well as proinflammatory signaling. During leishmaniasis, dysregulation of both FasL and TRAIL has been described by us and others but the resulting pathogenic effects in the skin during human leishmaniasis are not fully elucidated. Targeting disease specific immune deviations has proven to be a promising new approach for the therapy of autoimmune diseases. Potentially, targeting FasL or TRAIL in combination with microcidals could offer a future treatment strategy to reduce the disfiguring immunopathology associated with CL. In this mini review we will discuss how FasL and TRAIL-induced signaling may influence on the extent of tissue inflammation and the efficacy of parasite clearance in leishmaniasis

Språkmiljø for barn med norsk som andrespråk: Hvordan tilrettelegger en norsk barnehage språkmiljøet for barn med norsk som andrespråk

Det overordnede temaet for denne bacheloroppgaven er språkmiljø for barn med norsk som andrespråk. Jeg kom frem til dette temaet gjennom min interesse for tospråklige barn. Denne interessen startet under mitt utvekslingsopphold i sør i Europa høsten 2020, hvor jeg gjorde meg erfaringer med et barn som ikke hadde majoritetsspråket som morsmål. Dette barnet var 5 år, og hadde nylig flyttet til landet. Jeg opplevde gjennom praksisperioden at han hadde store problemer med å forstå og gjøre seg forstått på språket og at han fikk liten eller ingen støtte fra de ansatte i barnehagen. Han viste noe forståelse for engelsk og kommuniserte begrenset på engelsk med meg, men fikk beskjed av førskolelærer ved avdelingen om at i barnehagen skal man snakke majoritetsspråket. Opplevelsen med dette barnet gjennom praksis vekket en nysgjerrighet i meg for hvordan tospråklige barn opplever hverdagen i en norsk barnehage. Tall fra Utdanningsdirektoratet viser at det i 2019 gikk 275 800 barn i norske barnehager, noe som utgjør 92,2% av barn mellom 1 og 5 år. Videre viser tallene at 52 300 barn i norske barnehager er minoritetsspråklige. Dette er en økning på 2,7% fra 2018 og de siste 10 årene har det vært en nærmest dobling av minoritetsspråklige barn i norske barnehager. Totalt er 19% av barn i barnehagen minoritetsspråklige i 2019 (Utdanningsdirektoratet, 2020). Utdanningsdirektoratet definerer minoritetsspråklige barn «ved at både barnet og barnets foresatte har et annet morsmål enn norsk, samisk, svensk, dansk og engelsk» (Utdanningsdirektoratet, Barnehagespeilet 2016, s. 9), noe som betyr at antallet tospråklige barn i barnehagen er høyere enn disse tallene viser. Jeg ser derfor valgt tema som svært relevant for min fremtidige yrkeskarriere i den norske barnehagen. Rammeplanen fremmer språklig mangfold og en helhetlig språkutvikling. Den trekker også frem at personalet skal støtte flerspråklige barns morsmål og at alle barn skal få mulighet til å oppleve glede ved bruk av språk og kommunikasjon i et variert språkmiljø (Kunnskapsdepartementet, 2017). Med min interesse for flerspråklige barn og språkmiljø ønsket jeg derfor å se på hvordan dette praktiseres i barnehagen og hvilke erfaringer og tanker personalet i barnehagen har om flerspråklige barn og tilretteleggelse av språkmiljøet. Jeg endte derfor opp med problemstillingen: Hvordan tilrettelegger en norsk barnehage språkmiljøet for barn med norsk som andrespråk? Jeg har valgt å bruke begrepet en norsk barnehage for å begrense problemstillingen til en enkelt barnehage. Denne oppgaven må derfor ikke forstås som en fremstilling av hvordan det arbeides med språkmiljøet for barn med norsk som andrespråk i norske barnehager generelt, men som et innblikk i en enkelt barnehage. Det kan likevel tenkes at funnene som er gjort i denne barnehagen kan gi et innblikk i hvordan det jobbes med dette tema i flere norske barnehager. I min innsamling av data har jeg brukt pedagogiske ledere som informanter, men ved bruk av begreper som personalet og ansatte referer jeg til hele personalgruppa på avdelingen da tilretteleggelse av språkmiljøet ikke kun er pedagogisk leders ansvar. I kapittel 2 har jeg avklart min tolkning av begreper som jeg har brukt i oppgaven. I kapittel 3 presenteres teori som jeg har valgt for å belyse min problemstilling. Teorien legger vekt på språkutvikling, å lære to språk i barnehagealder og språkmiljø. Kapittel 4 omhandler hvilke metodiske valg jeg har gjort i oppgaven. Jeg gjør rede for prosessen med innhenting av informanter, intervjuene og analysen av datamaterialet, samt begrunnelse for mine metodiske valg. I kapittel 5 presenterer jeg funn og drøfting. Jeg har utført en kvalitativ studie, og ser det som mest gunstig og presentere funn og drøfting i samme kapittel. Datamaterialet i oppgaven er personsentrerte, noe som gjør det vanskelig å presentere det som meningsfulle fremstillinger uten tilhørende drøfting i lys av etablert teori. Kapittel 6 er oppgavens avslutning med en kort gjennomgang av oppgaven i sin helhet og min konklusjon på problemstillingen.publishedVersionBHBAC392

Physiological and perceptual strain of firefighters during graded exercise to exhaustion at 40 and 10°C

Purpose. To study whether perceptual identification should be included as a measure to evaluate physiological stress. Methods. Physiological variables oxygen uptake (VO2), ventilation, heart rate, blood lactate concentration, rectal temperature (Trec) and mean skin temperature, and perceptual variables rate of perceived exertion, thermal sensation and time to exhaustion, were measured at submaximal and maximal intensities during graded exercise on a treadmill to exhaustion in 12 firefighters wearing protective clothing and extra mass at 40 and 10 °C. Physiological strain index (PhSI) and perceptual strain index (PeSI) were calculated. Results. Apart from Trec, all physiological and perceptual variables were higher at submaximal intensities of 40 °C. Time to exhaustion was 16% shorter and the corresponding VO2 was reduced by 7% in the heat. A high correlation (r = 89) between PhSI and PeSI was found at both temperatures. PeSI scores were equal to PhSI at both ambient temperatures, except at the two highest intensities in the heat, where PeSI was higher. Conclusions. These findings support use of perceptual identification to evaluate physiological stress. However, at very high intensities under hot conditions the perceptual strain was estimated higher than the physiological strain. More precise indexes are needed to include perceptual measures in safety standard.publishedVersio

Safer work clothing for fishermen

The fisherman’s work environment consists of many potential risks. A study of occupational accidents in the Norwegian fishing industry in the nine-year period from 1998 to 2006 shows that more than 3/4 of the deaths were caused by loss of fishing vessel or man-overboard accidents. Furthermore, the greatest risk of drowning is found in the smallest fleet. The aim of our project was to develop safer work clothing and through this contribute to a reduction in work accidents and injuries in the fishing fleet. We considered that it is possible to produce protective work clothing that satisfies a specification of requirements covering the fishermen’s needs for protection and comfort during work. An end user-centred process including twenty-three personal interviews and a questionnaire was used to clarify the fishermen’s needs and wishes before detailed design and product development. We identified an overview of all the fishermen’s needs for protection during work, and produced a prioritised list of functional requirements for the clothing. The results show that the clothing previously preferred by fishermen does not satisfy all the users’ demands for safety, functionality and comfort. These demands have been taken into consideration when designing improved work clothing for the fishing fleet. A selected number of prototypes were developed on the basis of the established specification of requirements. The prototypes were evaluated according to the users’ requirements through tests in SINTEF’s Work Physiology Laboratory and on board fishing vessels. The results demonstrate that the new protective clothing satisfies the fishermen’s requirements

Thermophysiological responses and work strain in fishermen on deep-sea fishing vessels

Background: Fishermen working on deep-sea vessels in the Barents and Norwegian Sea are exposed to low air temperatures, strong winds, high humidity, rain, snow and work at different intensities. Few studies have investigated the effect of environmental work factors on the physiology of this occupational group. The aim of the study was to investigate work strain and thermophysiological responses of fishermen on the trawl and factory decks of deep-sea vessels. Materials and methods: Twenty-five professional male fishermen (age 39 ± 13 years) were recruited to the study which was performed on three trawlers in the Norwegian Sea in April, June and August 2014. During a six-hour shift, heart rate (HR), core (Tc) and mean skin (Ts) temperatures were recorded, and questions about subjective thermal sensation and comfort were answered. Results: Short periods of hard (above 86% of HRmax) work raised Tc by 0.8°C to 37.8°C and decreased Ts by 2.3°C to 29.8°C during work on the trawl deck, and subjects reported being warm and sweaty. On the factory deck long periods of fairly light (between 52% and 66% HRmax) work, Tc of 37.4°C and Ts of 30.9°C were measured. Conclusions: Fishermen experience intermittent periods of heavy work on the trawl deck shown with elevated core temperature and HR. Work on the factory deck includes long periods of repetitive work with light to moderate work strain. A better understanding of work strain and environmental challenges during work on Norwegian deep-sea vessels will help identify exposure risks during work in the cold and heat.

Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis

Visceral leishmaniasis (VL) is a life-threatening disease characterized by uncontrolled parasitization of the spleen, liver, and bone marrow. Interleukin (IL)-10 has been implicated in the suppression of host immunity in human VL based on the elevated levels of IL-10 observed in plasma and lesional tissue, and its role in preventing clearance of Leishmania donovani in murine models of VL. The aim of this study was to identify the cellular source of IL-10 in human VL and determine if CD4+CD25+ (Foxp3high) regulatory T (T reg) cells are associated with active disease. We analyzed surface marker and gene expression in peripheral blood mononuclear cells and splenic aspirates from Indian VL patients before and 3–4 wk after treatment with Amphotericin B. The results did not point to an important role for natural CD4+CD25+ (Foxp3high) T reg cells in human VL. They did not accumulate in and were not a major source of IL-10 in the spleen, and their removal did not rescue antigen-specific interferon γ responses. In contrast, splenic T cells depleted of CD25+ cells expressed the highest levels of IL-10 mRNA and were the predominant lymphocyte population in the VL spleen. The elevated levels of IL-10 in VL plasma significantly enhanced the growth of L. donovani amastigotes in human macrophages. The data implicate IL-10–producing CD25−Foxp3− T cells in the pathogenesis of human VL

Sweat responses during inactive recovery after high-intensity running in hot, dry and humid conditions

This study investigated the relationship between high (85%) and low (19%) relative humidity (RH) and sweat rate during inactive recovery after high-intensity work in a hot environment (30 °C). Ten male subjects performed two 20-minute run trials at 68 ± 4 % of maximal oxygen consumption (VO2max) followed by 36 minutes of inactive recovery in standing position. Regional sweat rate (RSR) was measured on the forearm and mid-central back by technical absorbent pads, and gross sweat loss was estimated from change in body weight. Core temperature (Tc) and six skin temperatures for calculation of mean skin temperature (Ts) were measured continuously together with heart rate (HR) during running and recovery. Results show that RSR was significantly (p<0.05) higher for both arm and back during running and inactive recovery in 85% RH compared to 19% RH. The highest sweat rate was observed on the back during the last five minutes of running in 85% RH (1387 g·m-2·h-1) compared to 19% RH (886 g·m-2·h-1). Gross sweat loss (GSL) was significantly higher in 85% RH (796 ± 414 g·h-1) than 19% RH (489 ± 140 g·h-1) conditions (p=0.010). Tc continued to increase for three and seven minutes post-exercise in 19% RH and 85% RH, respectively and Ts was significantly higher in 85% RH than in 19% RH (p<0.05). HR was 11 bpm higher after running in 85% RH compared to 19% RH (p=0.001). In conclusion, RSR and GSL, as well as HR, Tc and Ts was higher during post-exercise recovery in 30°C and 85% RH than in 30°C and 19% RH. This study emphasises the importance of including the effect of relative humidity in assessment of both exercise and recovery.The study was funded by the Research Council of Norway (grant no. 227107/H20)

Ten year neurocognitive trajectories in first-episode psychosis

Objective: Neurocognitive impairment is commonly reported at onset of psychotic disorders. However, the long-term neurocognitive course remains largely uninvestigated in first episode psychosis (FEP) and the relationship to clinically significant subgroups even more so. We report 10 year longitudinal neurocognitive development in a sample of FEP patients, and explore whether the trajectories of cognitive course are related to presence of relapse to psychosis, especially within the first year, with a focus on the course of verbal memory.Method: Forty-three FEP subjects (51% male, 28&#177;9 years) were followed-up neurocognitively over five assessments spanning 10 years. The test battery was divided into four neurocognitive indices; Executive Function, Verbal Learning, Motor Speed, and Verbal Fluency. The sample was grouped into those relapsing or not within the first, second and fifth year. Results: The four neurocognitive indices showed overall stability over the ten year period. Significant relapse by index interactions were found for all indices except Executive Function. Follow-up analyses identified a larger significant decrease over time for the encoding measure within Verbal Memory for patients with psychotic relapse in the first year (F (4,38)=5.8, p=0.001, η2=0.40)Conclusions: Main findings are long-term stability in neurocognitive functioning in first episode psychosis patients, with the exception of verbal memory in patients with psychotic relapse or non-remission early in the course of illness. We conclude that worsening of specific parts of cognitive function may be expected for patients with on-going psychosis, but that most patients should expect no change in cognitive performance during the first 10 years after being diagnosed

Design for end-user acceptance: requirements for work clothing for fishermen in mediterranean and northern fishing grounds

Fishing is one of the most dangerous occupations, and as many as 24,000 fishermen around the world suffer fatal injuries or drowning at sea every year. Although fishermen in the European fishing fleet work in harsh and dangerous environments, many fishermen do not use personal protective clothing and buoyancy aids due to reduced work comfort and poor functionality. This emphasizes the importance of designing work clothing and personal protective equipment (PPE) with functionality that matches the fishermen&#8217;s needs. The aim of this study was to identify the requirements for work clothing in terms of comfort, protection, and safety for fishermen operating in northern fishing grounds and in the Mediterranean. Furthermore, we investigated whether fishermen in the Mediterranean prioritize workclothing requirements differently from fishermen in northern fishing grounds. Interviews and observations of fishermen provided us with the requirements for work clothing for fishermen. A questionnaire was then distributed to a selection of European fishermen. The study showed that fishermen operating in the Mediterranean prioritized their requirements differently from fishermen in northern fishing grounds. There was good agreement on requirements regarding work comfort. Safety requirements, such as integrated buoyancy, were ranked as less important by the Mediterranean fishermen compared to fishermen in northern fishing grounds. The results of this study provide a basis for the development of work clothing and PPE for fishermen. Work clothing and PPE that fulfil the requirements are likely to obtain end-user acceptance and thus improve safety for fishermen at sea