Maksimalt oksygenopptak (VO2peak) er rekna som ein av dei viktigaste prognostiske markørane for framtidig hjarte-/karsjukdom og tidleg død. Ettersom direkte måling av VO2peak er tidkrevjande og kostbart har implementeringa i førebyggjande helsearbeid og klinisk praksis vore begrensa. Både VO2peak og ei rekkje andre sentrale helseparameter, kan betrast ved ei viss mengd fysisk aktivitet i kvardagen, og dagens globale anbefalingar er at alle vaksne bør utføre minst 150 minutt med moderat intensitet eller minst 75 minutt med høg intensitet per veke. Utforminga av anbefalingane inneber at det totale energiforbruket, og dermed helsegevinstane, kan oppnås ved ulike tilnærmingar der kortare varigheit kan kompenserast med høgare intensitet og vice versa. I dette prosjektet nytta me data på direkte målt VO2peak frå 4631 deltakarar i den siste Helseundersøkelsen i Nord-Trøndelag (HUNT 3, 2006-08) til først å utvikle ein prediksjonsmodell for å kunne estimere VO2peak og vidare undersøke om denne modellen kunne predikere framtidig hjerte-/kardødeligheit og død uansett årsak i ein stor befolkning. Me såg vidare på korleis ulike tilnærmingar til dagens anbefalingar for fysisk aktivitet var assosiert med direkte målt VO2peak i utvalet frå HUNT. Hovedfunna i avhandlinga er at VO2peak kan estimerast relativt nøyaktig ved ein regresjonsmodell med lett tilgjengelige variablar som alder, kroppssamansetning, fysisk aktivitetsnivå og kvilepuls og at modellen kan nyttast til å kategorisere personar med låg eller høg direkte målt VO2peak. Denne modellen vart nytta til å estimere VO2peak i eit stort utval friske deltakarar frå HUNT 1 (1984-86) som vart fulgt fram til registrert dødsdato eller slutten av 2010. For kvar 3,5 mL∙kg-1∙min-1 høgare estimert VO2peak var risikoen for død av hjarte- /karsjukdom 21 % lågare for personar av begge kjønn som var under 60 år ved undersøkelsen, medan risikoen uansett dødsårsak var henholdsvis 15 % og 8 % lågare for menn og kvinner. Vidare viser me at grupper som rapporterer fysisk aktivitetsvanar i tråd med dagens anbefalingar, anten ved moderat relativ intensitet over lengre tid eller høg intensitet over kortare tid, i gjennomsnitt hadde tilfredsstillande høg og tilnærma lik VO2peak. Samtidig viser me at eit relativt begrensa antal personar som rapporterte ein tidsbruk under minimum anbefaling, men med svært høg relativ intensitet, også hadde tilsvarande høg VO2peak. Også når tidsbruken eller det samla energiforbruket var konstant fann me at dei som rapporterte høg intensitet hadde høgare VO2peak enn dei som rapporterte låg eller moderate intensitet. / Directly measured peak oxygen uptake (VO2peak) is established as an important prognostic marker of cardiovascular disease and premature mortality, but is rarely evaluated for prevention purposes or in primary care settings due to costly and time-consuming procedures. Both VO2peak and several other health parameters can, however, be improved and maintained by regular exercise, and today`s recommendations suggest that all adults should do at least 150 minutes of moderate intensity or 75 minutes or vigorous intensity exercise per week. Hence, the total recommended volume or energy expenditure may be reached by strictly different approaches. In the current thesis, data on directly measured VO2peak in 4631 individuals from the third wave of the Nord-Trøndelag Health Study (HUNT 3, 2006-08), were used to first derive a simple prediction model for VO2peak that potentially could supplement direct measurements in healthcare settings and for research purposes. Next, the clinical utility of this model was examined by its ability to predict all-cause and cardiovascular mortality in a large sample of healthy men and women from the HUNT 1 (1984-86) cohort. Furthermore, we examined how different combinations of intensity and total time spent at habitual exercise were associated with VO2peak in apparently healthy, community dwelling individuals from HUNT 3. The findings in this thesis indicate that VO2peak can be predicted with reasonable accuracy by using easily available clinical and selfreported variables such as age, body composition, self-reported physical activity and resting heart rate, and that the model can be used to correctly classify subjects in the correct tail of the VO2peak distribution. For each metabolic equivalent (i.e. MET, ~3.5 mL∙kg-1∙min-1) higher CRF, the risk of CVD mortality was 21% lower in both men and women who were below 60 years at baseline, while the corresponding risk of all-cause mortality was 15% and 8% lower in men and women, respectively, for each MET higher CRF. Furthermore, we demonstrate that habitual exercise patterns of moderate intensity for a long total duration or vigorous intensity for a relatively short duration, adding up to the total volume as recommended by the health authorities, both were associated with a beneficial VO2peak –level. However, a higher VO2peak was observed among those reporting vigorous intensity compared to low and moderate intensity for a similar time spent, and energy expenditure used during exercise.

Abstract The life histories of ectoparasites are shaped by both host and off-host environment. A suitable host is primarily needed during reproduction, whereas juvenile stages outside the host are directly exposed to environmental variability. Viviparity, i.e. the development of an embryo inside the body of the mother resulting in large offspring size, increases offspring survival. The production of large offspring has its consequences in terms of high variation in offspring age and in the environment that each young individual will face. I used a viviparous ectoparasite, the deer ked (Lipoptena cervi), to investigate the consequences of long reproductive lifespan and varying offspring environment on offspring life-histories and seasonal adaptations. Offspring life-histories varied seasonally. I showed that the resources provided by the deer ked females determine offspring performance throughout its off-host period. Offspring size increased towards the spring and the end of the reproductive period, and simultaneously offspring survival and cold tolerance increased. Seasonal variation in offspring size did not reflect the resources that would guarantee offspring survival during the longest diapause or the highest cold tolerance during the harshest winter period. Diapause intensity varies with birth time according to the expected length of the winter ahead. However, the deer ked pupae, regardless of their age, overwinter at an opportunistic diapause, which may be terminated rapidly only by an exposure to high temperature. Contrary to general observations, photoperiod has no role in regulating the seasonal shifts of the deer ked. Neither is high cold tolerance associated only with diapause, but it remains high through four seasons, also in the active developmental and adult stages. I also evaluated the effects of life-history variation on the invasion potential of the deer ked. I conducted a large-scale transplant experiment to test the survival and pupal development at and beyond the current range. I found that the lower spring and summer temperatures and the shorter growth season in the north cause a deterioration in pupal performance and shorten the flight period. However, the colder climate may not totally prevent further spread. A more important factor that will affect deer ked invasion is host availability, and especially in Finland, the density of the moose population. Seasonal variation in offspring life histories in viviparous ectoparasites differs from the variation patterns reported in most invertebrates. This may be due to the extremely large offspring size and to the fact that maternally derived resources determine offspring performance through the entire off-host period. Variation in offspring performance is thus determined by maternal resources and seasonal variation in the condition of the moose. / Tiivistelmä Useimpien ulkoloisten elinkierto on riippuvainen isännästä ja isännän ulkopuolella kasvavien jälkeläisten kohtaamista ympäristöoloista. Viviparia eli jälkeläisen kehitys naaraan sisällä ja siitä usein seuraava suuri jälkeläiskoko parantavat jälkeläisten selviytymistä. Suurten jälkeläisten tuottaminen pitkällä aikavälillä johtaa siihen, että eri-ikäiset jälkeläiset kohtaavat vuodenajasta riippuen hyvin erilaiset olosuhteet. Väitöstyössäni tarkastelin Suomessa nopeasti yleistyneen hirvieläinten ulkoloisen, hirvikärpäsen (Lipoptena cervi), avulla, mitä seurauksia viviparialla, pitkällä lisääntymiskaudella ja ympäristön vuodenaikaisvaihtelulla on jälkeläisten elinkierto-ominaisuuksiin. Väitöskirjatyössäni havaitsin, että hirvikärpäsjälkeläisten elinkiertopiirteet vaihtelevat jälkeläisen syntymäajan mukaan. Osoitin myös, että hirvikärpäsnaaraan jälkeläisilleen tarjoamat ravintovarat määrittelevät jälkeläisten isännästä riippumattoman elinkierron aikaisen menestyksen. Jälkeläisten keskimääräinen koko kasvoi lisääntymiskauden edetessä talvesta kohti kevättä, jolloin myös selviytyminen ja kylmänsietokyky paranivat. Jälkeläiskoon vuodenaikaisvaihtelu ei näin ollen vastaa jälkeläisten tarvitsemia resursseja suhteessa talvehtimisen pituuteen eikä korreloi koville talvipakkasille altistumisen todennäköisyyden kanssa. Lepotilan keston määrittelevä diapaussin syvyys vaihteli syntymävuodenaikaa vastaavasti. Diapaussin havaitsin kuitenkin olevan ensisijaisesti opportunistinen, jolloin pelkästään korkea lämpötila voi nopeasti päättää lepotilan kaikenikäisillä yksilöillä. Vastoin yleisiä käsityksiä valorytmi ei vaikuta diapaussin säätelyyn. Vastoin ennakko-odotuksia kylmänsietokyky säilyy korkeana vuoden ympäri ja kaikissa tutkituissa elinkierron vaiheissa. Sovelsin tutkimieni elinkiertopiirteiden vaikutusta myös lajin invaasiokykyyn, ja tutkin istutuskokeen avulla koteloiden selviytymistä ja kehitystä nykyisellä esiintymisalueella ja sen pohjoispuolella. Alhaisemmat kevät- ja kesälämpötilat sekä lyhyempi kasvukausi vähentävät aikuiseksi selviytymistä ja lyhentävät lentoaikaa syksyllä. Ilmastotekijöiden suhteen hirvikärpänen voisi esiintyä nykyistä pohjoisempana. Tärkein tekijä hirvikärpäsen leviämistä tarkasteltaessa on kuitenkin sopivien isäntäeläimien saatavuus ja Suomen oloissa erityisesti hirven eli hirvikärpäsen pääisännän kannan tiheys. Tutkimukseni perusteella ulkoloisten vivipariasta seuraava jälkeläisten elinkiertopiirteiden ajallinen vaihtelu eroaa muiden selkärangattomien vastaavasta vaihtelusta. Yhtenä syynä eroihin lienee se, että hirvikärpäsnaaras tuottaa erityisen suuria jälkeläisiä ja että jälkeläiset puolestaan ovat täysin riippuvaisia emon antamista resursseista. Emon lisääntymisresurssit ja hirven kunnon vuodenaikaisvaihtelu vaikuttavat mahdollisesti siihen, minkälaisia jälkeläisiä hirvikärpänen milloinkin kykenee tuottamaan.

Pituitary abscess is a rare intracranial infection that can be life-threatening if not appropriately diagnosed and treated upon presentation. The most common presenting symptoms include headache, anterior pituitary hypofunction, and visual field disturbances. Brain imaging with either computed tomography or magnetic resonance imaging usually reveals intra- or suprasellar lesion(s). Diagnosis is typically confirmed intra- or postoperatively when pathological analysis is done. Clinicians should immediately start empiric antibiotics and request a neurosurgical consult when pituitary abscess is suspected. Escherichia coli ( E. coli ) causing intracranial infections are not well understood and are uncommon in adults. We present an interesting case of an immunocompetent male with a history of hypogonadism presenting with worsening headache and acute right eye vision loss. He was found to have a polymicrobial pituitary abscess predominantly involving E.   coli in addition to Actinomyces odontolyticus and Prevotella melaninogenica in the setting of an apoplectic pituitary prolactinoma. The definitive etiology of this infection was not determined but an odontogenic process was suspected. A chronic third molar eruption and impaction in close proximity to the pituitary gland likely led to contiguous spread of opportunistic oral microorganisms allowing for a polymicrobial pituitary abscess formation.

Background: Challenges persist in ensuring access to and optimal use of long-lasting, insecticidal bed nets (LLINs). Factors associated with ownership and use may differ depending on the history of malaria and prevention control efforts in a specific region. Understanding how the cultural and social-environmental context of bed net use may differ between high- and low-risk regions is important when identifying solutions to improve uptake and appropriate use. Methods: Community forums and a household, cross-sectional survey were used to collect information on factors related to bed net ownership and use in western Kenya. Sites with disparate levels of transmission were selected, including an endemic lowland area, Miwani, and a highland epidemic-prone area, Kapkangani. Analysis of ownership was stratified by site. A combined site analysis was conducted to examine factors associated with use of all available bed nets. Logistic regression modelling was used to determine factors associated with ownership and use of owned bed nets. Results: Access to bed nets as the leading barrier to their use was identified in community forums and cross-sectional surveys. While disuse of available bed nets was discussed in the forums, it was a relatively rare occurrence in both sites. Factors associated with ownership varied by site. Education, perceived risk of malaria and knowledge of individuals who had died of malaria were associated with higher bed net ownership in the highlands, while in the lowlands individuals reporting it was easy to get a bed net were more likely to own one. A combined site analysis indicated that not using an available bed net was associated with the attitudes that taking malaria drugs is easier than using a bed net and that use of a bed net will not prevent malaria. In addition, individuals with an unused bed net in the household were more likely to indicate that bed nets are difficult to use, that purchased bed nets are better than freely distributed ones, and that bed nets should only be used during the rainy season. Conclusion: Variations in factors associated with ownership should be acknowledged when constructing messaging and distribution campaigns. Despite reports of bed nets being used for other purposes, those in the home were rarely unused in these communities. Disuse seemed to be related to beliefs that can be addressed through education programmes. As mass distributions continue to take place, additional research is needed to determine if factors associated with LLIN ownership and use change with increasing availability of LLIN.

Women with advanced ovarian cancer generally have a poor prognosis but there is significant variability in survival despite similar disease characteristics and treatment regimens. The aim of this study was to determine whether psychosocial factors predict survival in women with ovarian cancer, controlling for potential confounders.

There is considerable evidence that cigarette smoking is the primary etiology of chronic obstructive pulmonary disease (COPD), and that oxidative stress occurs in COPD with the family of tissue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzymes playing a significant role in lung pathogenesis. The purpose of this study was to determine the effects of cigarette smoke extract (CSE) on Nox signaling to epithelial sodium channels (ENaCs). Pre-treatment with diphenyleneiodonium (DPI), a pan-Nox inhibitor, prevented stimulatory effects of CSE on ENaC activity; open probability (Po) changed from 0.36 +/- 0.09 to 0.11 +/- 0.02; n=10, p=0.01 following CSE and DPI exposure. Likewise, Fulvene-5 (which inhibits Nox2 and Nox4 isoforms) decreased the number of ENaC per patch (from 2.75 +/- 0.25 to 1 +/- 0.5, n=9, p=0.002) and open probability (0.18 +/- 0.08 to 0.02 +/- 0.08, p=0.04). Cycloheximide chase assays show that CSE exposure prevented alpha-ENaC subunit degradation, whereas concurrent CSE exposure in the presence of Nox inhibitor, Fulvene 5, resulted in normal proteolytic degradation of alpha-ENaC protein in primary isolated lung cells. In vivo, co-instillation of CSE and Nox inhibitor promoted alveolar flooding in C57Bl6 mice compared to accelerated rates of fluid clearance observed in CSE alone instilled lungs. Real-time PCR indicates that mRNA levels of Nox2 were unaffected by CSE treatment while Nox4 transcript levels significantly increased 3.5 fold in response to CSE. Data indicate that CSE is an agonist of Nox4 enzymatic activity, and that CSE-mediated Nox4 plays an important role in altering lung ENaC activity.

Recently, the layering of augmented reality information on top of smartphone applications has created unprecedented user engagement and popularity. One augmented reality-based entertainment application, Pokemon Go (Pokemon Company, Tokyo, Japan) has become the most rapidly downloaded in history. This technology holds tremendous promise to promote ambulatory activity. However, there exists the obvious potential for distraction-related morbidity. We report two cases, presenting simultaneously to our trauma center, with injuries sustained secondary to gameplay with this augmented reality-based application.

Background Diastolic dysfunction is common in sickle cell disease (SCD), and is associated with an increased risk of mortality. However, the molecular pathogenesis underlying this development is poorly understood. The aim of this study was to identify a gene expression profile that is associated with diastolic function in SCD, potentially elucidating molecular mechanisms behind diastolic dysfunction development. Methods Diastolic function was measured via echocardiography in 65 patients with SCD from two independent study populations. Gene expression microarray data was compared with diastolic function in both study cohorts. Candidate genes that associated in both analyses were tested for validation in a murine SCD model. Lastly, genotyping array data from the replication cohort was used to derive cis-expression quantitative trait loci (cis-eQTLs) and genetic associations within the candidate gene regions. Results Transcriptome data from both patient cohorts implicated 7 genes associated with diastolic function, and mouse SCD myocardial expression validated 3 of these genes. Genetic associations and eQTLs were detected in 2 of the 3 genes, FUCA2 and IL18. Conclusions FUCA2 and IL18 are associated with diastolic function in SCD patients, and may be involved in the pathogenesis of the disease. Genetic polymorphisms within the FUCA2 and IL18 gene regions are also associated with diastolic function in SCD, likely by affecting expression levels of the genes.

Pulmonary hypertension (PH), when it complicates sarcoidosis, carries a poor prognosis, in part because it is difficult to detect early in patients with worsening respiratory symptoms. Pathogenesis of sarcoidosis occurs via incompletely characterized mechanisms that are distinct from the mechanisms of pulmonary vascular remodeling well known to occur in conjunction with other chronic lung diseases. To address the need for a biomarker to aid in early detection as well as the gap in knowledge regarding the mechanisms of PH in sarcoidosis, we used genome-wide peripheral blood gene expression analysis and identified an 18-gene signature capable of distinguishing sarcoidosis patients with PH (n = 8), sarcoidosis patients without PH (n = 17), and healthy controls (n = 45). The discriminative accuracy of this 18-gene signature was 100% in separating sarcoidosis patients with PH from those without it. If validated in a large replicate cohort, this signature could potentially be used as a diagnostic molecular biomarker for sarcoidosis-associated PH.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.