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The plasma–protein histidine-rich glycoprotein (HRG) is implicated in phenotypic switching of tumor-associated macrophages, regulating cytokine production and phagocytotic activity, thereby promoting vessel normalization and antitumor immune responses. To assess the therapeutic effect of HRG gene delivery on CNS tumors, we used adenovirus-encoded HRG to treat mouse intracranial GL261 glioma. Delivery of Ad5-HRG to the tumor site resulted in a significant reduction in glioma growth, associated with increased vessel perfusion and increased CD45+ leukocyte and CD8+ T-cell accumulation in the tumor. Antibody-mediated neutralization of colony-stimulating factor-1 suppressed the effects of HRG on CD45+ and CD8+ infiltration. Using a novel protein interaction–decoding technology, TRICEPS-based ligand receptor capture (LRC), we identified Stanniocalcin-2 (STC2) as an interacting partner of HRG on the surface of inflammatory cells in vitro and colocalization of HRG and STC2 in gliomas. HRG reduced the suppressive effects of STC2 on monocyte CD14+ differentiation and STC2-regulated immune response pathways. In consequence, Ad5-HRG–treated gliomas displayed decreased numbers of IL35+ Treg cells, providing a mechanistic rationale for the reduction in GL261 growth in response to Ad5-HRG delivery. We conclude that HRG suppresses glioma growth by modulating tumor inflammation through monocyte infiltration and differentiation. Moreover, HRG acts to balance the regulatory effects of its partner, STC2, on inflammation and innate and/or acquired immunity. HRG gene delivery therefore offers a potential therapeutic strategy to control antitumor immunity. Mol Cancer Ther; 17(9); 1961–72. ©2018 AACR.

Miesten yleisimmän syövän, eturauhassyövän, seulonta ei tällä hetkellä ole osa suomalaista seulontaohjelmaa. Seulonnan laajentamisesta käydään kuitenkin kiivasta keskustelua monessa maassa. Seulonta perustuu verikokeella mitattavaan PSA-arvoon, joka voi indikoida lisätestauksen tarvetta, mutta ei suoraan kerro syövän olemassaolosta. PSA-testituloksilla on kuitenkin lääketieteellinen merkitys diagnosointivaiheessa, hoitojen aikana ja niiden päätyttyä. Terveydenhuollon ammattilaisten lisäksi tuloksilla on oma merkityksensä syöpää sairastavien miesten arjessa, jossa he pyrkivät ennakoimaan sairauden puhkeamista, seuraamaan sen etenemistä ja arvioimaan hoitovastetta. Tässä tutkimuksessa kysymme: 1) Millaisia merkityksiä PSA-testitulokset saavat miesten sairauskertomuksissa? ja 2) Millä tavalla nämä merkitykset vaihtelevat sairauden eri vaiheissa? Aineistomme koostuu eturauhassyövän sairastaneiden miesten yksilöhaastatteluista (n=34). Analyysissä lähestymme haastattelukertomuksia narratiivisen lähestymistavan kautta ja tarkastelemme PSA-arvoille annettuja merkityksiä sekä testitulosten nivoutumista osaksi sairauden ajallista kulkua. Testituloksilla oli odotetusti merkittävä asema omassa kehossa tapahtuvien muutosten seuraamisessa. Tulosten seuraaminen loi kontrollin tunnetta, mutta saattoi myös aiheuttaa epävarmuutta ja ahdistusta. Tuloksia tulkitessaan miesten täytyi myös pohtia, millaiset muutokset olivat ’normaaleja’ ja mitkä puolestaan kertoivat sairauden etenemisestä tai hoitojen toimivuudesta. Testituloksilla oli merkitystä myös miesten välisessä vuorovaikutuksessa niin yhteenkuuluvuuden luojana kuin erottavana tekijänä. Lisäksi PSA-testauksessa käyminen ja omien testiarvojen tuntemus näyttäytyivät vastuullisena terveyskäyttäytymisenä. Tutkimuksen kautta pyrimme laajentamaan keskustelua seulonnoista ja niiden kautta saatavasta numeerisesta tiedosta nostamalla esiin maallikkonäkemyksiä ja tulkintoja. Tulosten pohjalta nousee esiin tarve tukea miehiä testituloksiin liittyvien epävarmuuksien käsittelyssä sekä huomioida kuinka seulontakäytännöillä on myös sosiaalisia ja moraalisia ulottuvuuksia lääketieteellisten ja taloudellisten ulottuvuuksien lisäksi.

Finnish governments have utilised a ‘stick and carrot’ approach to prolong work careers at the end by both increasing the official retirement age and offering financial incentives for people to work longer. This chapter explores Finnish male metalworkers’ and engineers’ thoughts regarding retirement and prolonging their careers in terms of how men’s motives change as they approach retirement age. Our interviews (conducted in 2010/2011 and 2017) indicated in both groups that the men had lost a great deal of their interest in work and most of them were ready to retire. Rather than focusing on their work ability, both metalworkers and engineers considered it important to secure sufficient health for life in retirement. Quite surprisingly, economic incentives did not seem to play a role in these men’s considerations of retirement in either of the groups, even despite the substantial income differences between them. Instead of additional money, the interviewees thought about their retirement plans in terms of health, mental wellbeing and work-related satisfaction. Our study suggests that future efforts to prolong work careers should therefore focus on improving working conditions and age-friendly work environments.

Vanhuus ei rakennu ainoastaan eletyn elämän pohjalle, vaan yhtä lailla lähestyvä kuolema määrittää vanhuutta omanlaisenaan elämänvaiheena. Kuolemaan suhtautumista vanhuudessa on tutkittu paljon ja kuolemaan asennoitumisessa on havaittu olevan tiettyjä perusmalleja, kuten kuoleman kieltäminen tai sen hyväksyminen. Tässä artikkelissa eläkeikäisten ihmisten kuolemaan valmistautumista tutkitaan toimijuuden viitekehyksestä käsin. Analysoimme tutkimusaineistona olleet vanhuuseläkkeellä olevien ihmisten haastattelut (n=36) laadullisen sisällönanalyysin menetelmin. Havaitsimme aineistossa sekä käytännöllistä että psyykkistä kuolematoimijuutta: kuolemaan valmistauduttiin niin konkreettisin toimin kuin ottamalla omaa kuolemaa haltuun. Kuoleman haltuun ottaminen tapahtui ajattelemalla sitä sekä tunnetyöskentelyn avulla. Lisäksi tavoitimme eutanasiakeskustelun ympärille rakentuvaa poliittista kuolematoimijuutta. Empiirisen tutkimuksemme perusteella esitämme, että kuolema ei ole vain jotakin väistämätöntä, vaan kuoleman läheisyys tarjoaa myös mahdollisuuksia vahvistaa omaa toimijuuttaan monella tasolla.

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Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) regulate the hypoxic induction of300 genes required for survival and adaptation under oxygen deprivation. Inhibition of HIF-P4H-2 has been shown to be protective in focal cerebral ischemia rodent models, while that of HIF-P4H-1 has no effects and inactivation of HIF-P4H-3 has adverse effects. A transmembrane prolyl 4-hydroxylase (P4H-TM) is highly expressed in the brain and contributes to the regulation of HIF, but the outcome of its inhibition on stroke is yet unknown. To study this, we subjected WT and P4htm

Introduction This study investigates comments that prostate cancer patients spontaneously write in the margins of the Expanded Prostate Cancer Index Short Form (EPIC-26) questionnaire. We aim to show the possible barriers that patients face while answering the survey, and to consider how these barriers may affect the response data generated. We investigate the kind of information patients’ comments on EPIC-26 contain, and patients’ motivations to provide this information. We also study why some EPIC domains spark more comments than others. Method We analyzed 28 pages of transcribed comments and four pages of supplementary letters from our survey participants (n = 496). Using inductive content analysis, we generated 10 categories describing the content of participants’ comments, and four themes demonstrating their motives for commenting. The comments regarding each EPIC domain were quantified to discover any differences between domains. Results The sexual domain of EPIC-26 provoked over half of all comments. Patients without recent sexual activity or desire had difficulties answering sexual function questions 8–10. The lack of instructions on whether to take erectile aid use into account when answering erectile function questions led to a diversity of answering strategies. Patients with urinary catheters could not find suitable answer options for questions 1–4. All domains sparked comments containing additional information about experienced symptoms. Conclusion Patients are mainly willing to report their symptoms, but a lack of suitable answer options causes missing data and differing answering strategies in the sexual and urinary domains of EPIC-26, weakening the quality of the response data received.

Gliomas are brain tumors characterized by an immunosuppressive microenvironment. Immunostimulatory agonistic CD40 antibodies (αCD40) are in clinical development for solid tumors, but are yet to be evaluated for glioma. Here, we demonstrate that systemic delivery of αCD40 in preclinical glioma models induces the formation of tertiary lymphoid structures (TLS) in proximity of meningeal tissue. In treatment-naïve glioma patients, the presence of TLS correlates with increased T cell infiltration. However, systemic delivery of αCD40 induces hypofunctional T cells and impairs the response to immune checkpoint inhibitors in pre-clinical glioma models. This is associated with a systemic induction of suppressive CD11b+ B cells post-αCD40 treatment, which accumulate in the tumor microenvironment. Our work unveils the pleiotropic effects of αCD40 therapy in glioma and reveals that immunotherapies can modulate TLS formation in the brain, opening up for future opportunities to regulate the immune response., Agonistic CD40 antibodies (αCD40) have broad immunostimulatory properties, however their efficacy in glioma remains unclear. Here the authors show that αCD40 promotes the formation of tertiary lymphoid structures but does not improve survival and impairs the response to immune checkpoint blockade in murine glioma models.

BACKGROUND Localised prostate cancer affects patient's quality of life in many ways. The aim of this study was to explore factors related to self-rated health and life satisfaction for patients treated for prostate cancer, and to compare the results of these generic quality-of-life measures to the prostate cancer-specific quality-of-life measure (UCLA Prostate Cancer Index), which focuses on physical functioning. MATERIAL AND METHODS This cross-sectional survey was carried out among 183 men who underwent radical prostatectomy in 2012-2015 at a university hospital in Finland and were seen 1 year postsurgery. Approval from an ethics committee and written consents from participants were received. A questionnaire was used to evaluate patients' perceived quality of life. Logistic regression model, Spearman's correlation, Kruskal-Wallis test and Mann-Whitney U-test were used to analyse factors related to quality of life. RESULTS Of the 183 men in the study, 63% rated their health status as good, and 70% were satisfied with their lives after prostatectomy. Older age and better urinary function were the only factors that explained both better self-rated health and better satisfaction with life. The patients seemed not to interpret problems with sexual function as health-related problems. In our sample, sexual dysfunction was relatively severe, but patients considered them to be less harmful than urinary or bowel symptoms. Interestingly, 24% of the men with low sexual function did not find that dysfunction bothersome. CONCLUSIONS Objectively measured physical functioning is not necessarily in line with patients' experienced satisfaction with life and their self-ratings of health. More longitudinal and qualitative research is needed about the meanings that patients attach to physical treatment side effects and the extent to which they can adapt to them over time. With a bigger sample and longer follow-up time, it would be possible to identify men who particularly benefited from pretreatment counselling.

Työikäisenä muistisairauteen sairastuminen rikkoo oletetun elämänkulun, vaatien sopeutumista ja elämäntarinan uudelleenrakentamista. Tutkimuksessa selvitettiin työikäisenä sairastuneiden ja heidän läheistensä haastatteluiden (n = 26) perusteella, kuinka sairastuneet jäsentävät muistisairauden aiheuttamia elämänmuutoksia sai­rauden alkuvaiheessa ja miten läheisen tarina resonoi sairastuneen tarinan kanssa. Analyysissä havaittiin kolme erilaista tarinatyyppiä. Kaaoksen tarinaa leimasi sairas­tumisen aiheuttama elämän epävarmuus ja organisoimattomuus. Irtautumisen tari­nassa päästettiin irti turhiksi koetuista asioista, kavennettiin elämänpiiriä ja keskityt­tiin hetkessä elämiseen. Aktiivisuuden tarinassa suunniteltiin tulevaisuutta, toimittiin aktiivisesti ja vahvistettiin omaa hyvinvointia sairautta vastustamalla. Läheisten ja sairastuneiden tarinoiden yhtäläisyys vaihteli tarinatyypeittäin. Sairastamisen alkuvai­heen kokemuksia ja tilanteeseen sopeutumista peilataan tutkimuksessa kulttuurisiin sairastamisen mallitarinoihin. Tällöin tarkastellaan, kuinka tarinallisuus on osa sairas­tumisen käynnistämää elämäntarinan uudelleenrakentamisen prosessia. Lisäksi poh­ditaan, miten työikäisenä sairastuneen henkilön hyvinvointia voidaan tukea huomioi­den ihmisten erilainen suhtautuminen sairauteen. Tarvitaan ymmärrystä kulttuurisis­ta sairastamisen mallitarinoista ja muistisairauden vaikutuksista yksilön sekä perheen tilanteeseen, jotta sairastuneita ja heidän läheisiään voidaan nykyistä tehokkaammin tukea sairauteen sopeutumisessa ja sopivan arjen aktiivisuuden ylläpitämisessä.

The growing prominence of patient and public involvement in health services has led to the increased use of experiential knowledge alongside medical and professional knowledge bases. Third sector organisations, which position themselves as representatives of collective patient groups, have established channels to communicate experiential knowledge to health services. However, organisations may interpret and communicate experiential knowledge in different ways, and due to a lack of inherent authority, it can be dismissed by health professionals. Thus, drawing on individual interviews with organisation representatives, we explore the definitions and uses of as well as the ‘filters’ placed upon experiential knowledge. The analysis suggests that whilst experiential knowledge is seen as all-encompassing, practical and transformative, the organisations need to engage in actions that can tame experiential knowledge and try to balance between ensuring that the critical and authentic elements of experiential knowledge were not lost whilst retaining a position as collaborators in health care development processes.

Purpose To understand the perspectives of oncology nurses on peer support for patients with cancer and the role of oncology nurses in its provision. Method Thematic semi-structured interviews of 10 oncology nurses working in a single university hospital were conducted. The data were analysed using content analysis. Results Oncology nurses thought that peer support promotes the psychosocial wellbeing of patients with cancer by increasing their social contact and strengthening their emotional resources. In their daily work, oncology nurses engaged in several activities that promote the interactions between patients with cancer and informal forms of peer support. However, directing patients with cancer to formal peer support services outside specialised health care was not an established practice. Oncology nurses expressed several concerns about the availability of support and the coping ability of peer supporters and expressed scepticism about the reliability of information shared in peer support groups. Conclusions The awareness of oncology nurses regarding formal peer support services appears rather limited. This knowledge gap should be reduced, such as through closer collaboration between hospitals and third sector cancer organisations, which does not appear effective at present based on the results. In addition, patients with cancer should be systematically informed about peer support.

Collagen XVIII (ColXVIII) is a component of the extracellular matrix implicated in embryogenesis and control of homeostasis. We provide evidence that ColXVIII has a specific role in kidney ontogenesis by regulating the interaction between mesenchymal and epithelial tissues as observed in analyses of total and isoform-specific knockout embryos, mice, andex vivoorgan primordia. ColXVIII deficiency, both temporally and spatially, impacts the 3D pattern of ureteric tree branching morphogenesisviaits specific isoforms. Proper development of ureteric tree depends on a tight control of the nephron progenitor cells (NPCs). ColXVIII-deficient NPCs are leaving the NPC pool faster than in controls. Moreover, the data suggests that ColXVIII mediates the kidney epithelial tree patterningviaits N-terminal domains, and especially the Thrombospondin-1-like domain, and that this morphogenetic effect involves ureteric epithelial integrins. Altogether, the results propose a significant role for ColXVIII in a complex signalling network regulating renal progenitors and kidney development.

Gliomas are brain tumors characterized by immunosuppression. Immunostimulatory agonistic CD40 antibodies (αCD40) are in clinical development for solid tumors but are yet to be evaluated for glioma. Here, systemic delivery of αCD40 led to cytotoxic T cell dysfunction and impaired the response to immune checkpoint inhibitors in preclinical glioma models. This was associated with an accumulation of suppressive CD11b+ B cells. However, αCD40 also induced tertiary lymphoid structures (TLS). In human glioma, TLS correlated with increased T cell infiltration indicating enhanced immune responses. Our work unveils the pleiotropic effects of αCD40 therapy in glioma, which is of high clinical relevance.

Publisher Copyright: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Theories of inclusive masculinity and horizontal homosociality describe how previously marginalized forms of masculinity are becoming socially acceptable. Studies within these theoretical frameworks have largely focused on privileged groups of men and men’s changing attitudes towards homosexuality. This raises questions about the extent to which the theories apply to marginalized groups of men and other inequalities between men. In this article, we analyse ethnographic data from two Finnish older men’s communities that emphasize equality between men as an essential part of their ethos, and ask how inclusive practices and horizontal homosociality operate in these communities. Our intersectional analysis shows that older men’s communities may involve varying levels of inclusive practices that do not necessarily relate to sexuality but, instead, to other aspects of inequality. Future studies should consider the contextuality of men’s practices and the intersectional differences between men that are the subjects of these inclusive or exclusionary practices.

Tutkimuksessa tarkasteltiin, miten lapsia ja vanhuksia kuvataan toimijuuden näkökulmasta neljän suurimman puolueen eduskuntavaaliohjelmissa. Tutkimusmenetelmänä hyödynnettiin kriittistä diskurssianalyysiä. Aineistosta oli tunnistettavissa kaksi toimijuuden diskurssia: passiivisen ja aktiivisen toimijuuden diskurssit, joissa molemmissa puhutaan lasten ja vanhusten toimijuudesta erityisesti palvelujärjestelmän kautta. Passiivisen toimijuuden diskurssissa erilaiset yhteiskunnalliset toimijat näyttäytyivät aktiivisina toimijoina lasten ja vanhusten sijaan. Aktiivisen toimijuuden puhe kietoutui palvelujärjestelmään, joka kuvautui keskeiseksi toimijuutta tuottavaksi tekijäksi. Lisäksi lasten toimijuus rakentuu tulevaisuudessa, kun taas vanhusten toimijuus on jotakin, mitä heillä on vanhenemisestaan huolimatta vielä jäljellä. Neljä suurinta puoluetta puhuvat vaaliohjelmissaan lasten ja vanhusten toimijuudesta julkisen sektorin järjestämien palveluiden kautta yllättävänkin yhdenmukaisella tavalla. In this study we observe how the agency of children and older adults are described in programs written for parliamentary elections. The material consists of programs written for parliamentary elections between 1991 and 2019 by the four largest parties in Finland. We used critical discourse analysis as a research method. We identified two discourses concerning the agency of the children and the older adults: children and older adults as passive actors and as active actors. Within the passive actor discourse various societal actors were active but not the children nor the older adults. Children and older adults were portrayed as objects of services, activities and protection but not as actors themselves. Within the active actor discourse childrens' agency was something to be seen in the future and seniors' agency is something they still have despite their age. The four largest parties describe the agency of children and older adults surprisingly similarly in their programs. peerReviewed

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Eturauhassyövän seulonnan hyödyistä ja haitoista on käyty aktiivista keskustelua viime vuosina. Vaikka PSA-testi on laajasti käytössä terveydenhuollossa, väestötason seulontaa ei toistaiseksi suositella, sillä seulonnan haittoja pidetään hyötyjä suurempina. Seulonnan haittoja ovat ylidiagnostiikka ja siitä aiheutuvat ylimääräiset hoidot, jotka voivat heikentää miesten elämänlaatua. Artikkelissa tarkasteltiin paikallista eturauhassyöpää sairastavien miesten näkemyksiä seulonnan tarpeellisuudesta. Tutkimuksen aineisto koostui 28 eturauhassyöpää sairastavan miehen yksilöhaastatteluista. Analyysimenetelmänä käytettiin diskurssianalyysia. Suurin osa haastateltavista suhtautui myönteisesti väestötason seulontaan ja halusi parantaa miesten pääsyä PSA-mittauksiin. Seulonnan tarpeellisuutta perusteltiin argumenteilla, jotka liittyvät varhaisen diagnostiikan hyötyihin – kuten kustannusten säästymiseen ja kuolleisuuden vähentämiseen – tai miesten oikeuksiin ja sukupuolten tasa-arvoon. Tulostemme perusteella miehet ovat tietoisia seulontaan liittyvistä haitoista, mutta siitä huolimatta he ovat seulonnan käynnistämisen kannalla. Seulonta hahmotettiin miesten terveyden edunvalvontaan liittyvänä asiana.

Tutkimuksen tavoitteena on tehdä näkyväksi millaisia ideologisia valintoja Suomen neljä suurinta puoluetta ovat tehneet eduskuntavaaliohjelmissaan suhteessa hyvinvointivaltiokansalaisuusdiskursseihin 1991 vuodesta alkaen. Tarkastelemme erityisesti vaaliohjelmissa tuotettuja kansalaisen poliittisia ja sosiaalisia oikeuksia ja velvollisuuksia sekä kansalaisen ja valtion välistä oikeudellinen sidettä ja sen legitimointia. Tarkastelemme puolueiden hyvinvointivaltiokansalaisuusdiskursseja pohjoismaisesta hyvinvointivaltiomallista käytävän kamppailun viitekehyksessä. Kansalaisuustulkinnat ohjaavat yhteiskuntapolitiikkaa ja esimerkiksi määritelmät kansalaisten tarpeista vaikuttavat palvelurakenteeseen. Tutkimuksen aineisto koostuu Kansallinen Kokoomus r.p.:n, Perussuomalaiset r.p.:n, Suomen Keskusta r.p.:n ja Suomen Sosialidemokraattinen Puolue r.p.:n eduskuntavaaliohjelmista vuosilta 1991–2019. Perussuomalaiset r.p.:n osalta aineisto kattaa vaalivuodet 1999–2019. Tutkimuksen menetelmällinen lähestymistapa on kriittinen diskurssianalyysi ja sen avulla pyritään erityisesti löytämään argumentaatiota ja keinoja, joilla vaaliohjelmissa perustellaan kansalaisuustulkintoja. Kansalaisen poliittisiin ja sosiaalisiin oikeuksiin ja velvollisuuksiin liittyen tunnistimme kaksi diskurssia: palveluiden kohteena olevan kansalaisen ja omatoimisen kansalaisen diskurssit. Kansalaisen ja valtion oikeudelliseen siteeseen ja legitimiteettiin liittyen tunnistimme kansanvallan diskurssin. Puolueiden diskurssien välillä ei ollut löydettävissä perustavanlaatuisia näkemyseroja, vaan erot liittyivät enemmänkin painotuksiin.

Patient and public involvement activities bring 'lay participants' and their accounts of lived experiences to the centre of health service development and delivery. For individuals, these accounts can provide an important resource, offering a sense of control and an opportunity to re-frame past events. Furthermore, as involvement activities and the use of personal accounts have become more prominent, it is timely to examine the involvement process from the perspective of the 'lay participants'. Hence, the aim of this study is to explore how people become involved and how they construct the accounts of their lived experience. We analyse the stories of people with lived mental illness or caring experiences, who have become experts by experience (n = 13). We argue that becoming an expert by experience can help to re-contextualise past experiences and support the re-discovery of skills and expertise, leading experts by experience to construct both professionalised and politicised identities. The process has the potential to enforce narratives that portray illness experiences as motivators for social action and change. Additionally, we claim that the stories experts by experience share with health services and the public are not 'lay accounts' or ad hoc tales, but accounts constructed to serve specific purposes.

Peer support workers are now working with patients in a variety of settings, coming into close contact and even work alongside health professionals. Despite the potentially influential position peer support workers hold in relation to those engaged in support activities, their role, duties and their relationship to peers and health professionals lack clarity and is often defined by other actors. This study explores how peer support workers interpret and define the activities, responsibilities and knowledge associated with their work. Using methods of membership categorisation analysis, we analysed interview materials generated by conducting individual semi-structured interviews during the autumn of 2016 with prostate cancer peer support workers ( n = 11) who currently volunteer as support workers in Finland. Although the peer support workers acknowledged the psychosocial aspects of the work, we argue that their interpretations extend far beyond this and encompass expertise, advocacy and activism as central features of their work. These can be used to strengthen their position as credible commentators and educators on issues relating to cancer and men’s health; raise awareness and represent the ‘patient’s voice’ and attempt to influence both policy and clinical practice. These findings suggest that by categorising their work activities in different ways, voluntary sector actors such as peer support workers can attempt to portray themselves as legitimate authorities on a range of issues and influence decision-making ranging from individual level treatment decisions all the way to health policy.

Focal adhesion kinase (FAK) is essential for vascular endothelial growth factor-A (VEGFA)/VEGF receptor-2 (VEGFR2)-stimulated angiogenesis and vascular permeability. We have previously noted that presence of the Src homology-2 domain adapter protein B (SHB) is of relevance for VEGFA-stimulated angiogenesis in a FAK-dependent manner. The current study was conducted in order address the temporal dynamics of co-localization between these components in HEK293 and primary lung endothelial cells (EC) by total internal reflection fluorescence microscopy (TIRF). An early (

Vertaisarvioitu. English summary Psykososiaalinen tuki ei ole vakiintunut osaksi syöpäpotilaan hoitoa useista terveyspoliittisista linjauksista huolimatta. Tutkimuksessa analysoidaan, kenen tehtäväksi erikoissairaanhoidon syövänhoidossa toimivat terveydenhuollon ammattilaiset hahmottavat psykososiaalisen tuen antamisen, kuinka potilaiden tukemista tulisi heidän mukaansa kehittää sekä millaiseksi he ymmärtävät järjestöjen roolin tuen antajina. Aineisto kerättiin asiantuntijahaastatteluin syövänhoidossa työskenteleviltä terveydenhuollon ammattilaisilta (n=20). Aineiston analyysi toteutettiin aineistolähtöisellä sisällönanalyysillä. Syövänhoidossa työskentelevät terveydenhuollon ammattilaiset pitivät psykososiaalisen tuen antamista tärkeänä, mutta tuen antamisen katsottiin vaativan erityistä ammattitaitoa ja nykyistä enemmän resursseja. Haastateltavien mielestä yliopistosairaalassa on vaadittavat tukipalvelut, mutta sairaalan sisällä työnjakoa ja tuen systemaattista tarjoamista tulisi kehittää. He toivoivat sairaalaan lisää henkilökuntaa, jonka työhön tuen tarjoaminen kuuluisi. Tällöin potilaiden tuen tarpeen kartoittaminen olisi automaattisesti osa diagnoosivaiheen hoitoa. Haastateltavat kuvasivat järjestöjen tarjoamaa tukea lisänä yliopistosairaalan tukipalveluihin. He korostivat, että järjestöjen tarjoaman tuen piiriin hakeutumisen tulisi perustua potilaan vapaaehtoisuuteen ja aktiivisuuteen. Haastatteluissa tuli esiin epäilyksiä järjestöyhteistyön tiivistämistä kohtaan. Tutkimuksen tuottamaa tietoa voidaan hyödyntää kehitettäessä syöpäpotilaan kokonaisvaltaista hoitoa. Terveydenhuollon ja järjestöjen välisten raja-aitojen madaltamiseksi tarvitaan lisää tietoa järjestöjen tarjoamista tukipalveluista. Erikoissairaanhoidon henkilöstölle tarvitaan selkeämpiä ohjeita potilaiden ohjaamisesta järjestöiden palveluiden piiriin. Näiden kahden tahon välistä koulutusta syöpäpotilaan psykososiaaliseen tukemiseen liittyen tulisi lisätä. Jatkossa järjestöissä työskentelevän henkilöstön näkemyksiä erikoissairaanhoidon ja järjestöjen välisestä yhteistyöstä sekä syöpäpotilaiden psykososiaalisesta tuesta tulisi kartoittaa.

Purpose: Based on focus groups, we analyse how practical nursing students deal with being as smokers and future healthcare workers. The way they justify their smoking is discussed within a group of peers. Methods: The study has a qualitative design with an inductive approach using focus group interviews (FGIs) for data collection. A total of 29 students were interviewed in five groups of five and one group of four participants. Results: In the analysis, we found four different discursive practices the students utilized for rationalizing their own smoking and coping with the moral dilemma of smoking in a context of health care where smoking is forbidden: (1) students normalized smoking with references to its prevalence within their social circles, (2) the students asserted that their smoking was under control, (3) students considered themselves responsible smokers, and (4) students identified smoking as a part of their identity. Conclusion: Training should support the growth of professional identity and address the smoker’s identity right from the start of education. Smokers need special attention in the formulation of professional identity, however, without being stigmatized any further.

Most citations to “hegemonic masculinity” focus on gender ideals and men’s attempts to justify domination. Few scholars have tested the theory that masculinity can be hegemonic in effect by gaining the overt consent of others to their domination. We specify this largely untested theory and use data from a pilot study of middle-age men for our demonstration of how to operationalize and recognize hegemony. We argue that scholars will find that effect at intersections of gender and other inequalities such as age. We show that, in their discussion of linked ideals of gender and age, three respondents mention domination of older men by younger men, and then both consent to that domination and accept personal responsibility for forestalling it through regimens of fitness, productivity, and health. We call for further research on the hegemony of masculinity via study of intersections of gender with such understudied inequities as age.

Accessible summaryWhat is known on the subject? According to estimates more than half of adult mental health service users are parents, but their experiences are largely lacking from research literature. Parental mental illness can often be viewed from a risk perspective. Parents with mental illness and their families have unmet support needs. What this paper adds to existing knowledge? Parents with mental illness want acknowledgement that they can be able and responsible. Many parents adopt an expert by experience identity. Fathers can feel their parental role is not recognized and mothers express fears of being judged if they discuss their illness. What are the implications for practice? Adult mental health services need to recognize and support parental role of service users. Joint care planning and family oriented care should be promoted. Professionals should take advantage of the knowledge of these parents and they could be more actively engaged in service development. AbstractIntroduction Parental mental illness is often viewed from a risk perspective. Despite this, being a parent can be both valuable and motivating. Research literature lacks the perspective of mothers and fathers, who have experienced mental illness. Aim This study explores how parents with mental illness construct their identities as mothers and fathers and their experiences with health and social care services. Method Three focus groups with 19 participants were conducted in Finland and Scotland. Methods of discourse analysis have been used in to analyse the interview data. Results Adult service users want their parenting role recognized and supported. Parents have knowledge and skills which can be utilized and many have adopted an expert by experience identity. Discussion Being able to see oneself as a ‘good’ parent can be challenging but important. Parents may require support, but want to be included in the planning of their care. Services could make more use of the knowledge and skills parents and families have, and joint working could lessen parents’ anxieties. Implications for practice Mental health practitioners are in a key position in providing more family centred, resource focused care. Service user expertise should be acknowledged in clinical practice.

A novel multi-organ disease that is fatal in early childhood was identified in three patients from two non-consanguineous families. These children were born asymptomatic but at the age of 2 months they manifested progressive multi-organ symptoms resembling no previously known disease. The main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. In the affected children, neuropathology revealed increased angiomatosis-like leptomeningeal, cortical and superficial white matter vascularisation and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and previously undescribed granuloma-like lesions were observed in the lungs. Hepatomegaly, steatosis and collagen accumulation were detected in the liver. A whole-exome sequencing of the two unrelated families with the affected children revealed the transmission of two heterozygous variants in the NHL repeat-containing protein 2 (NHLRC2); an amino acid substitution p.Asp148Tyr and a frameshift 2-bp deletion p.Arg201GlyfsTer6. NHLRC2 is highly conserved and expressed in multiple organs and its function is unknown. It contains a thioredoxin-like domain; however, an insulin turbidity assay on human recombinant NHLRC2 showed no thioredoxin activity. In patient-derived fibroblasts, NHLRC2 levels were low, and only p.Asp148Tyr was expressed. Therefore, the allele with the frameshift deletion is likely non-functional. Development of the Nhlrc2 null mouse strain stalled before the morula stage. Morpholino knockdown of nhlrc2 in zebrafish embryos affected the integrity of cells in the midbrain region. This is the first description of a fatal, early-onset disease; we have named it FINCA disease based on the combination of pathological features that include fibrosis, neurodegeneration, and cerebral angiomatosis.

The plasma-protein histidine-rich glycoprotein (HRG) is implicated in phenotypic switching of tumor-associated macrophages, regulating cytokine production and phagocytotic activity, thereby promoting vessel normalization and antitumor immune responses. To assess the therapeutic effect of HRG gene delivery on CNS tumors, we used adenovirus-encoded HRG to treat mouse intracranial GL261 glioma. Delivery of Ad5-HRG to the tumor site resulted in a significant reduction in glioma growth, associated with increased vessel perfusion and increased CD45

Health policies and strategies promote the involvement of people with illness experiences in service development and production, integrating them into settings that have traditionally been domains of health professionals. In this study, we focus on the perspectives of people with personal illness experiences and explore how they justify involvement, position themselves as legitimate actors and forge collaborative relationships with health professionals. We have used discourse analysis in analysing individual interviews conducted with peer support workers and experts by experience (n = 17) who currently work in Finnish health services. The interviewees utilised discourses of empowerment, efficiency and patient-centeredness, aligning themselves with the justifications constructed by patient movements additionally to those found in current health policies. Both groups wanted to retain critical distance from professionals in order to voice criticisms of current care practices, yet they also frequently aligned themselves with professionals in order to gain legitimacy for their involvement. They adopted professional traits that moved them further from being lay participants sharing personal experiences and adopted an expert position. Although national-level policies provided backing and legitimacy for involvement, the lack of local-level guidance could hinder the practical implementation and make involvement largely dependent of professionals’ discretion.

The kidney plays an essential role during excretion of metabolic waste products, maintenance of key homeostasis components such as ion concentrations and hormone levels. It influences the blood pressure, composition and volume. The kidney tubule system is composed of two distinct cell populations: the nephrons forming the filtering units and the collecting duct system derived from the ureteric bud. Nephrons are composed of glomeruli that filter the blood to the Bowman’s capsule and tubular structures that reabsorb and concentrate primary urine. The collecting duct is a Wolffian duct-derived epithelial tube that concentrates and collects urine and transfers it via the renal pelvis into the bladder. The mammalian kidney function depends on the coordinated development of specific cell types within a precise architectural framework. Due to the availability of modern analysis techniques, the kidney has become a model organ defining the paradigm to study organogenesis. As kidney diseases are a problem worldwide, the understanding of mammalian kidney cells is of crucial importance to develop diagnostic tools and novel therapies. This review focuses on how the pattern of renal development is generated, how the inductive signals are regulated and what are their effects on proliferation, differentiation and morphogenesis.

Involving patients and the public in healthcare decision-making is on the policy agenda in several countries. The aim of our study was to describe and analyse the development of patient and public involvement from a policy perspective. We argue that the language of health policies can influence both the aims and the development of involvement methods. In this study health policy documents, which have guided the development of patient and public involvement in Finland have been analysed using methods of Membership Categorisation Analysis. This has enabled us to explore how health policy documents categorise patients and the wider public in relation to involvement and orientate the involvement activities in which people are able to participate. Different set of abilities, expectations, responsibilities and opportunities is attached to the categories of patient, risk group, service user, customer and expert. Health policy documents often equate involvement with choice making by service users and customers; or as involvement in service development by experts. In both of these cases, involvement is depicted as an individual activity that requires personal responsibility and specialist knowledge. Although involvement opportunities have overall increased, they are primarily available to people that are "participation ready" and able to adopt roles promoted in policies. Health policy documents produce one interpretation of involvement, nevertheless it is important that diverse groups of patients, the public and health professionals participate in the discussion and express their views, which may differ from those of policy makers.

The neo-liberal ideologies that point to individual responsibility for risks increasingly influence countries of the global North. The anti-ageing industry reflects this dictate and encourages middle-aged people to use their products and services to manage their ageing. However, given the negative connotations attached to the term ‘anti-ageing’, which is usually seen to focus on aesthetics and thus be a woman's concern, men may be likely to disavow being involved in such activities. The article uses interview data collected from men aged 42–70 from Finland and the United States of America to explore whether and how men adhere to the call to manage their ageing when such anti-ageing activities are seen to be potentially feminising. We find that these men reflected neo-liberalism in the sense that they felt that, although ageing cannot be prevented, it can be controlled. Also while they generally rejected anti-ageing products and services that they judged to affect aesthetics, they reported that they use those that they define as promoting health and performance instead. For them, masculinity is the instrumental focus on performance to the exclusion of beauty or attractiveness. Masculine anti-ageing bodily strategies must also be ‘natural’, involving hard work rather than the use of products, which they regard as never having been scientifically proven to enhance performance. Thus, in talk of their anti-ageing, men distance themselves from women.