Mechanisms and regulation of the polyphosphate/factor XII-driven contact system in thrombosis and hemostasis

Blood coagulation leading to fibrin formation is essential to prevent loss of blood (hemostasis), but can also contribute to occlusion of vessels (thrombosis). Thrombosis causes pulmonary embolism, myocardial infarction and stroke, which are together the most common cause of death in the developed world. Current anticoagulation therapy for prevention or treatment of thromboembolic events is sufficient, however results in an increase in potentially life threatening bleedings. Two distinct pathways initiate fibrin formation: one pathway is triggered by tissue factor exposed on damaged vessel walls (extrinsic pathway) and the other by blood-borne factors (intrinsic pathway). The intrinsic pathway starts by activation of blood coagulation factor XII. The findings that factor XII appears to be involved in pathologic thrombus formation, and that factor XII deficiency is not associated with abnormal bleeding has led to a significant interest for factor XII in the scientific community. Inhibition of factor XII seemed to offer a selective and safe strategy for preventing thrombotic diseases. Coagulation factor XII becomes activated by contact with negatively charged surfaces. In previous studies it is shown that platelets initiated factor XII-driven coagulation in vivo and this activation is driven by polyphosphate. Polyphosphate is an inorganic polymer that has been identified as a potent procoagulant and proinflammatory mediator in vitro and in vivo. Polyphosphate initiated fibrin formation by the factor XII-driven intrinsic pathway of coagulation. An infusion of polyphosphate induced lethal pulmonary emboli in mice, while a deficiency in factor XII or pharmacological inhibition of factor XII activity protected animals from this pathological clot formation. These data showed that polyphosphate driven factor XII activation is a necessary mechanism in platelet-driven thrombosis in vivo. In this thesis we localize polyphosphate on activated platelets and establish and characterize recombinant tools to neutralize procoagulant polyphosphate activities based on a bacterial exopolyphosphatase. Exopolyphosphatase is an enzyme, which specifically breaks down polyphosphate. Using mutagenesis we identify a specific polyphosphate-binding mutant based on the binding domain of the exopolyphosphatase, resulting in a dual strategy of binding and degrading polyphosphate to interfere with procoagulant polyphosphate activities. Both strategies block the ability of polyphosphate to activate factor XII in different in vitro assays. Furthermore pretreatment of mice with exopolyphosphatase or the specific polyphosphate-binding mutant interferes with arterial thrombosis and protects from lethal pulmonary thromboembolism induced by platelet activity. Moreover the bleeding time of these mice are completely normal, showing that targeting of polyphosphate does not interfere with hemostasis. Finally, we use the specific polyphosphate-binding mutant as a probe to analyze polyphosphate on cells and in human samples. We present the first assay to analyze polyphosphate in human platelet-rich plasma offering the opportunity of analyzing a possible thrombotic biomarker in future clinical trials

Investigation into Feasibility of Off-grid Small Dwelling in SLO County

The trend towards green, sustainable living has grown more and more in the housing industry each year since before the turn of the century; solar in the last decade alone has grown by 60% (http://www.seia.org/research-resources/solar-industry-data). Living on a grid that runs on unclean sources of energy already has led us into an environmental disaster some call irreversible. This paper takes a detailed look into the feasibility of a small, off-grid, dwelling that utilizes modern technology in order to live more modestly. In conjunction with great advancements in solar technology along with energy storage such as deep cycle lead-acid batteries, on-site well systems with filtration can bring us to a fully self-sustaining small home

Theology, News and Notes - Vol. 60, No. 02

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1173/thumbnail.jp

Helsetjenestebehov blant flyktninger fra Ukraina som kom til Norge i 2022

This study has measured self-reported health and healthcare needs among adult refugees from Ukraine arriving in Norway during 2022. Further, we have assessed received information about, and access to, health services in Norway. Following the full-scale invasion of Ukraine, more than 35 000 Ukrainian refugees applied for protection in Norway in 2022. Most of the arrivals are women and children, and there is a lack of systematic information about the health and healthcare needs of the group, which may differ significantly from that of other refugees. Although almost half of the study participants rated their overall health as good or very good, the Ukrainian refugees rated their health poorer in several areas, when compared to the Norwegian population. The main findings show: • The refugees reported their health as poorer overall, with more long-term illnesses or health problems. • The refugees reported poorer mental health with more symptoms of psychological distress during the last week. • The refugees reported considerably poorer self-rated dental health. • Most of the refugees had received information about health services in Norway in a way they either fully or to some extent understood. The more recently arrived refugees were less likely to report having received understandable information about health services. Further, the more newly arrived were less likely to report knowing how to contact health services, or to have received the health care they felt they had needed in Norway. These findings may contribute to planning and ensuring appropriate health services for this group. Follow-up and continuity of treatment for long-term illnesses or health problems, as well as support for psychological distress and mental health care, represent important healthcare needs. Further, dental health services may also be a considerable need among the refugees. The findings suggest that information about health services in Norway can be improved, especially among the newly arrived.publishedVersio

Risk of Somatic Diagnoses in Specialist Health Care Among Norwegian-Born Youth and Young Adults with Immigrant Parents

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Diagnoses of infectious diseases among Norwegian-born children to immigrant parents – the role of parental socioeconomic position

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Covid-19: personer testet, påviste smittetilfeller og relaterte innleggelser etter utdanning og inntekt

Executive summary Introduction Reports from several countries indicate that people with low education and income are more likely to be affected by COVID-19. In this report we investigate how education level and household income are related to test activity, confirmed cases, hospitalizations, invasive ventilation, and death related to COVID-19 in Norway. Methods We have utilized the nation-wide emergency preparedness register, BeredtC19, which contains individual-level data covering the entire Norwegian population. The study population consists of individuals with a personal identification number, alive and registered as residents per 1st March 2020 and are aged 25 years or older. The study period was February 2020 to May 2021. The exposure variables, highest attained education and household income after tax (equivalent income), are operationalised, respectively, into five categories for education, and into deciles for household income. Outcomes studied were test activity (being tested and share of positive tests among those tested), laboratory confirmed cases, related hospitalizations, use of invasive ventilation and death. We have used both descriptive analyses and linear regressions. For the outcomes test activity, confirmed cases, and hospitalization, we adjust for age, sex, municipality of residence and country of birth. Results DiscussionThe sample comprised 3 882 249 persons, of which 1 864 860 were tested at least once, 75 698 were confirmed cases, 8 222 hospitalizations, 821 received invasive ventilation, and 710 died. In total, 20 % had attained below upper secondary education and 37 % university or college education. The median household income was 644 143 NOK. The lowest income decile and the undisclosed/no education group were on average younger compared to the other categories. Immigrants made up 93 % of those in the undisclosed/no education group and 40 % of the 1st (lowest) income decile. There was a positive correlation between increasing education from below upper secondary education to university/college education and test rate, which remained after adjustments. For household income, the relationship after 15th June 2020 was slightly S-shaped, with generally higher testing rates in the higher income deciles compared to the lower income deciles. After adjustment there was a clear positive relationship between household income and testing rate. Both lower education level and household income were associated with elevated risk of infection and with more severe disease (hospitalization, invasive ventilation, and death). Persons in the three lowest household income deciles and those with a below upper secondary education or undisclosed/no education have been hit hardest. The differences between the different education and income groups in confirmed cases and related hospitalizations decrease when we adjust for age, sex, municipality of residence and country of birth. For confirmed cases, the differences between household income deciles were fully attenuated. For other outcomes, differences were somewhat decreased, however there were still clear trends even after adjustment. Adjusting for immigrant status (country of birth) made the largest impact overall, especially for the category undisclosed/no education, which was predominantly immigrants. Discussion These findings correspond with other reports and studies on the relationship between COVID-19 (and health in general) and education and income. This report does not empirically examine why people with low education and low household income have been disproportionally affected, but factors such as working conditions, living conditions, health literacy, delayed access to health services or underlying diseases are suggested as possible mechanisms. Conclusion Individuals with lower education and household income have had higher rates of confirmed cases, hospitalization, invasive ventilation and deaths related to COVID-19. When we adjust for age, sex, municipality of residence and country of birth, differences between the groups are reduced, but rarely eliminated. Of the factors included, country of birth had the largest impact in accounting for the differences between the education and income groups. Going forward, it will be important to obtain more knowledge about the causes and mechanisms behind the observed overrepresentation.Sammendrag Innledning Rapporter fra flere land tyder på at personer med lav utdanning og inntekt har større sannsynlighet for å bli rammet av covid-19 enn andre. I denne rapporten undersøker vi hvordan utdanningsnivået og husholdningsinntekt er relatert til testaktivitet, påviste smittetilfeller, sykehusinnleggelser, respiratorbruk og død knyttet til covid-19 i Norge. Metode Vi har brukt det nasjonale beredskapsregisteret “BeredtC19” med data på individnivå over hele den norske befolkningen. Studiepopulasjon består av hver person med personnummer, registrert som bosatt 1. mars 2020 og er 25 år eller eldre. Studieperioden var fra februar 2020 til mai 2021. Forklaringsvariablene, høyeste oppnådde utdanning og husholdningsinntekt etter skatt (ekvivalentinntekt), er operasjonalisert i fem utdanningskategorier og ti inntektsdesiler. Utfallene vi har studert er testaktivitet (andel testede og andel av positive tester av de testede), påviste smittetilfeller (med PCR-test), relatert sykehusinnleggelser, respiratorbruk og død. Vi har både brukt deskriptive analyser og lineær regresjon. For utfallsvariablene andel testede, påvist smitte og innleggelser justerer vi for alder, kjønn, bostedskommune og fødeland. Resultat Utvalget besto av 3 882 249 personer, hvor 1 864 860 var testet minst en gang, 75 698 fikk påvist smitte, 8 222 var innlagt på sykehus, 821 trengte respiratorbehandling og 710 har dødd. Totalt hadde 20 % oppnådd grunnskole som høyest utdanning, mens 37 % hadde universitet- eller høgskoleutdanning. Median-husholdningsinntekten var 644 143 kr. Den laveste inntektsdesilen og gruppen med uoppgitt eller uten utdanning var i gjennomsnitt yngre enn de andre gruppene. Innvandrere utgjorde 93 % av gruppen med uoppgitt eller uten utdanning, og 40 % av den laveste inntektsdesilen. Det var en positiv sammenheng mellom økende utdanning (fra grunnskole til universitet/høgskole) og andel testede, som besto også etter justering. For husholdningsinntekt var sammenhengen svakt S-formet etter 15. juni 2020, med generelt høyere andel testede i de øvre inntektsdesilene sammenlignet med de nedre. Etter justering var det en klar positiv sammenheng mellom husholdningsinntekt og andel testede. Generelt var både lavere utdanning og lavere husholdningsinntekt tettere forbundet med en forhøyet risiko for å bli smittet og mer alvorlig sykdom (sykehusinnleggelse, respiratorbruk og død). Personer i de tre laveste inntektsdesilene og de med grunnskole eller uoppgitt/ingen utdanning har blitt rammet hardest. Forskjellene i påviste tilfeller og relaterte innleggelser minsker mellom de ulike inntekts- og utdanningsgruppene når vi justerer for alder, kjønn, bostedskommune og fødeland. For påviste tilfeller er forskjellene mellom inntektsdesilene borte. For de andre utfallene er forskjellene svekket, men det er fortsatt klare mønstre etter justering. Fødeland var den faktoren som generelt hadde mest betydning for endringene mellom modellene, spesielt for gruppen uoppgitt/uten utdanning som hovedsakelig består av innvandrere. Diskusjon Disse funnene sammenfaller med andre rapporter og studier over relasjonen mellom covid-19 (og helse generelt) og inntekt og utdanning. Denne rapport undersøker ikke empirisk hvorfor personer med lav utdanning og lav husholdningsinntekt er hardest rammet, men faktorer som familie- og husholdningsstørrelse og sammensetning, arbeidsforhold, boforhold, helsekompetanse, forsinket tilgang til helsetjenester eller underliggende sykdommer er foreslått som mulige mekanismer. Konklusjon Personer i den lavere enden av utdannings- og inntektsskalaen er overrepresentert i påviste smittetilfeller, relaterte innleggelser, respiratorbruk og død. Når vi justerer for alder, kjønn, bostedskommune og fødeland reduseres overrepresentasjonen mellom gruppene, men mønstrene forblir de samme. Av faktorene som er inkludert er det fødeland som har den største betydningen i å forstå forskjellene mellom personer med ulike utdanninger og husholdningsinntekter. Fremover vil det være viktig å skaffe mer kunnskap om årsakene og mekanismene bak denne overrepresentasjonen.publishedVersio

Активность микрофлоры как показатель токсичности морских донных отложений шельфовой зоны Черного моря и Керченского пролива

Изучена потенциальная активность донной микрофлоры в местах утечки остатков химических токсикантов, затопленных в период Второй Мировой войны ХХ в. Отмечены особенности восстановления жизнедеятельности микрофлоры при различных уровнях загрязнения донных отложений мышьяком и хлорированными органическими сульфидами. Полученные результаты перспективно использовать при оценке экологического состояния донных отложений в загрязненных прибрежных акваториях

Variation in disease in childhood according to immigrant background

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Obesity diagnoses in children and adolescents in Norway by immigrant background

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