Inactivation of mouse transmembrane prolyl 4-hydroxylase increases blood brain barrier permeability and ischemia-induced cerebral neuroinflammation.

Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) regulate the hypoxic induction of >300 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-/- mice to permanent middle cerebral artery occlusion (pMCAO). Lack of P4H-TM had no effect on lesion size following pMCAO, but increased inflammatory microgliosis and neutrophil infiltration was observed in the P4htm-/- cortex. Furthermore, both the permeability of blood brain barrier and ultrastructure of cerebral tight junctions were compromised in P4htm-/- mice. At the molecular level, P4H-TM deficiency led to increased expression of proinflammatory genes and robust activation of protein kinases in the cortex, while expression of tight junction proteins and the neuroprotective growth factors erythropoietin and vascular endothelial growth factor was reduced. Our data provide the first evidence that P4H-TM inactivation has no protective effect on infarct size and increases inflammatory microgliosis and neutrophil infiltration in the cortex at early stage after pMCAO. When considering HIF-P4H inhibitors as potential therapeutics in stroke, the current data support that isoenzyme-selective inhibitors that do not target P4H-TM or HIF-P4H-3 would be preferred.

Missingness in the expanded prostate cancer index short form (EPIC-26) - prevalence, patterns, and explanatory factors.

BACKGROUND: Researchers and clinicians using common clinical assessments need to attend to the prevalence of missing data to ensure the validity of the information gathered. The Expanded Prostate Cancer Index Short Form (EPIC-26) is a commonly used measurement scale used for assessing patients' quality of life, but the measure lacks comprehensive analysis on missing data. We aimed to explore the quantity of missing answers in EPIC-26 and to characterize patterns and possible explanations of missing data in the survey. METHODS: The survey sample consisted of 625 Finnish prostate cancer patients who participated in a study with a 1-year follow-up with three measurement points (0, 6, and 12 months). Descriptive statistics were used to describe the study population and missingness level. A logistic regression was performed for each EPIC domain to study factors related to missingness during the follow-up. RESULTS: Proportions of missing answers in EPIC-26 were low (3.1-3.9%) between survey rounds. As much as 37% of patients left at least one question unanswered during their follow-up. The hormonal domain produced the most missing answers. Questions about breast tenderness/enlargement (question 13.b.), hot flashes (question 13.a.), frequency of erections (question 10.), and ability to reach orgasm (question 8.b.) were most frequently left unanswered. Higher age, lower education level, no relationship, more severe cancer, lower function scores in some EPIC domains, lower treatment satisfaction or self-rated health were associated with missingness. CONCLUSIONS: Questions 13.b. and 13.a. might be considered female-specific symptoms, thus difficult to comprehend unless patients had already experienced side effects from androgen deprivation therapy. Questions 10. and 8.b. might be difficult to answer if the patient has been sexually inactive. To improve the measure's validity, the questionnaire's hormonal section requires additional explanation that the inquired symptoms are common treatment side effects of anti-androgen therapy; questions 8-10 require a not-applicable category for sexually inactive patients.

Prostate cancer-related sexual dysfunction - the significance of social relations in men's reconstructions of masculinity.

Narrating illness experiences in a culturally acceptable manner is essential for retaining quality of life after the disruptive event of being diagnosed for prostate cancer. Psychological pressures caused by treatment side-effects such as erectile dysfunction require reinterpretation of the meanings and impacts of these side-effects on masculinity. This helps maintain coherence in men's lives. We studied how men employ culturally available discursive strategies (compensation, redefinition, recontextualisation, and normalisation) in reconstructing masculinity and sexuality. Our data consists of 22 interviews of heterosexual Finnish prostate cancer patients who had undergone surgery. The aim was to analyse the ways in which various life situations and social relations shaped and limited the use of these strategies. Discourse analysis revealed that older age, a supportive spouse, children, supportive male friends, and good health - were key elements men used in reconstructing a coherent new self-image and conception of life following cancer treatment. Men with sexually active male friends, men without families, younger men and men with new intimate relationships struggled to develop a new version of their masculinity. Being able to effectively utilise certain aspects of one's life situation in re-constructing masculinity is important in maintaining quality of life despite troublesome treatment side-effects.

The expanded prostate cancer index composite short form (EPIC-26) for measuring health-related quality of life: content analysis of patients' spontaneous comments written in survey margins.

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.

COVID-19 related visiting ban in nursing homes as a source of concern for residents' family members: a cross sectional study.

BACKGROUND: Visiting a close relative who resides in a nursing home is an opportunity for family members to extend their caring roles and find reassurance that the older person's life is continuing as well as possible. At the same time, visits allow family members to observe the quality of formal care in the facility. In Finland, the COVID-19 pandemic led to the imposition of visiting bans in nursing homes in March 2020, thereby preventing customary interaction between residents and their family members. The aim of this study is to investigate family members' experiences of the visiting ban and its effects on their concern over the wellbeing of close relatives living in nursing homes. METHODS: A cross-sectional study was conducted to explore family members' self-reported concerns and the factors associated with those concerns. In the context of this unpredictable pandemic, this was considered an appropriate approach, as information at the very beginning of the visiting ban was sought, and causal relations were not investigated. The data consist of a quantitative survey (n = 366) conducted among family members in May-June 2020. Binary logistic regression analyses were performed to explore the association between the independent variables and reported concern. RESULTS: The results showed that increased concern was extremely common (79%). The factors associated with this notable increase were adequacy of contact and information, observations of changes in the wellbeing of the relative in question, and doubts over the appropriateness of the visiting restriction. CONCLUSIONS: In light of the findings, care providers should improve their information provision to residents' family members and find new ways of allowing visits to nursing homes in the future in all circumstances.

Variant in NHLRC2 leads to increased hnRNP C2 in developing neurons and the hippocampus of a mouse model of FINCA disease.

BACKGROUND: FINCA disease is a pediatric cerebropulmonary disease caused by variants in the NHL repeat-containing 2 (NHLRC2) gene. Neurological symptoms are among the first manifestations of FINCA disease, but the consequences of NHLRC2 deficiency in the central nervous system are currently unexplored. METHODS: The orthologous mouse gene is essential for development, and its complete loss leads to early embryonic lethality. In the current study, we used CRISPR/Cas9 to generate an Nhlrc2 knockin (KI) mouse line, harboring the FINCA patient missense mutation (c.442G > T, p.Asp148Tyr). A FINCA mouse model, resembling the compound heterozygote genotype of FINCA patients, was obtained by crossing the KI and Nhlrc2 knockout mouse lines. To reveal NHLRC2-interacting proteins in developing neurons, we compared cortical neuronal precursor cells of E13.5 FINCA and wild-type mouse embryos by two-dimensional difference gel electrophoresis. RESULTS: Despite the significant decrease in NHLRC2, the mice did not develop severe early onset multiorgan disease in either sex. We discovered 19 altered proteins in FINCA neuronal precursor cells; several of which are involved in vesicular transport pathways and actin dynamics which have been previously reported in other cell types including human to have an association with dysfunctional NHLRC2. Interestingly, isoform C2 of hnRNP C1/C2 was significantly increased in both developing neurons and the hippocampus of adult female FINCA mice, connecting NHLRC2 dysfunction with accumulation of RNA binding protein. CONCLUSIONS: We describe here the first NHLRC2-deficient mouse model to overcome embryonic lethality, enabling further studies on predisposing and causative mechanisms behind FINCA disease. Our novel findings suggest that disrupted RNA metabolism may contribute to the neurodegeneration observed in FINCA patients.

Personal perspectives on patient and public involvement - stories about becoming and being an expert by experience.

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.

Factors related to self-rated health and life satisfaction one year after radical prostatectomy for localised prostate cancer: a cross-sectional survey.

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.

NHLRC2 variants identified in patients with fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA): characterisation of a novel cerebropulmonary disease.

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.

Seeking certainty through narrative closure: men's stories of prostate cancer treatments in a state of liminality.

Radical treatments of prostate cancer often lead to a pervasive liminal state that is characterised by multiple uncertainties that relate both to a possible recurrence of cancer and recovery from side effects, such as erectile and urinary dysfunctions. Liminality can make it difficult for cancer patients to narrate their experiences, as their stories lack a definite ending. After interviews with 22 Finnish men who had undergone radical prostatectomy, we analysed how men produce closure in their illness narratives. Focusing on the timelines of control visits or their anticipated recovery from side effects, these interviewees sought provisional certainty within a seemingly chaotic future. By locating erectile dysfunction in the wider context of a life-course and interpreting their fading sexuality as a 'natural' consequence of ageing, these men were adjusting to their post-operative lives. Our study further shows that the inability to adjust personal experiences to positive culturally available storylines that provide a chance for the narrative reconstruction of life, can cause materialised negative consequences, such as relationship breakdowns.

Kidney development: an overview.

BACKGROUND: Kidney diseases are worldwide public health problems with a high cost and increasing incidence. By revealing the genetic and cellular mechanism behind mammalian kidney development, better diagnostic methods and novel therapies can be expected to be developed. The mammalian kidney is a typical organ that develops on the basis of sequential and reciprocal cell and tissue interactions. Functional genetic analysis has identified that genes from different classes are involved in the construction of the kidney and the same genes are also connected to the development of diseases. SUMMARY: This review gives an overview of the basics of kidney ontogeny, from identification of the primary kidney cell to inductive signals of ureter budding and formation of the segmented nephron. We also go through some of the key factors involved in the control of morphogenesis. KEY MESSAGE: Despite the wealth of accumulated data on nephron development, including progenitor cell control factors and inductive signals, many of the detailed mechanisms remain to be revealed.

WT1 and Sox11 regulate synergistically the promoter of the Wnt4 gene that encodes a critical signal for nephrogenesis.

Wnt4, a member of the Wnt superfamily of signaling molecules, is critical for mammalian kidney development, since nephrogenesis fails in its absence, while Wnt4 signaling induces mesenchyme-to-epithelium transition and associated tubulogenesis in the uninduced mesenchymal cells in the classic transfilter model. The factors that promote Wnt4 gene expression during kidney development are largely unknown, however. We addressed the upstream regulators of the Wnt4 gene and describe here the transcription factors WT1 and Sox11 as candidate molecules in the control of gene expression. We found that WT1/Sox11 regulate Wnt4 promoter expression in a synergistic fashion in an embryonic kidney mesenchyme-derived cell line model. The transcription complex containing WT1/Sox11 was immunoprecipitated from embryonic kidney cells with Sox11 antibodies, suggesting their presence in the same complex. Dominant negative forms of WT1, namely P129L and F154S mutants, inhibited Wnt4 expression, but this inhibition was not influenced by the presence of wild-type Sox11. The mutant WT1 forms were similarly incapable of interacting with Sox11, as judged by reporter studies. The spatio-temporal expression pattern of wt1 and sox11 overlaps with that of Wnt4 in the early Xenopus pronephros. Morpholino-mediated knockdown of either wt1 or sox11 inhibited Wnt4 expression in the prospective pronephros of the Xenopus embryos. We propose that Sox11 represents a synergistic factor for WT1 in regulating the Wnt4 gene expression that is critical for nephrogenesis during kidney ontogeny.

Factors associated with living will among older persons receiving long-term care in Finland.

Background: A living will document is known to be an important tool for preparing for future care together with healthcare professionals. A living will supports an older person's self-determination and autonomy. Only a few studies have approached the underlying factors of a living will document among older long-term care recipients. Objectives: To explore how common having a living will was among older persons receiving home care or round-the-clock long-term care, as well as to evaluate associations between socio-demographical factors and functional capacity with a living will. Design: The study population consisted of older persons receiving long-term care in Finland in 2016-2017. Data were collected via individual assessments at home or at a care facility. The questions in the assessment covered health, functional capacity, service use, and social support. Methods: Primary outcome 'living will' and associated factors were identified for each person aged 65 or older from RAI-assessment data (Resident Assessment Instrument, RAI). Cross-tabulations with χ²-tests and adjusted binary logistic regression models were performed to evaluate the association between the factors and a living will. Results: Of the 10,178 participants, 21% had a living will - a greater proportion were female (22%) than male (18%), and a greater proportion of residents in assisted living (25%) and residential care homes (20%) compared with home care residents (15%) had a living will. Female gender (p < 0.001), having a proxy decision-maker (p = 0.001), increasing age (p = 0.003), impairing functional capacity (activities of daily living hierarchy p < 0.001, Cognitive Performance Scale p < 0.001), instability of health status (Changes in Health, End-Stage Disease and Signs and Symptoms p < 0.001), and closeness of death (p < 0.001) were significantly associated with a living will among older persons. Extensive differences in results were found between home care clients and clients of round-the-clock long-term care. Conclusion: Preparedness for the future with a living will varies according to services and on individual level. To reduce inequalities in end-of-life care, actions for advance care planning with appropriate timing are warranted.

No place to go? Older people reconsidering the meaning of social spaces in the context of the COVID-19 pandemic.

Under COVID-19 restrictions, older people were advised to avoid social contact and to self-isolate at home. The situation forced them to reconsider their everyday social spaces such as home and leisure time places. This study approached the meaning of social spaces for older people by examining how older people positioned themselves in relation to social spaces during the pandemic. The data were drawn from the Ageing and social well-being (SoWell) research project at Tampere University, Finland, and they consisted of phone interviews collected during the summer of 2020 with 31 older persons aged 64-96 years. The data were analysed using the frameworks of positioning analysis and environmental positioning. Results showed the positions of older people being manifold, flexible and even contradictory. Within home, the participants portrayed themselves as restricted due to limited social contact, but also as able to adapt to and content being alone. Virtual spaces were depicted as spaces for younger and healthy persons, and the participants themselves as sceptical technology users not satisfied with technology-mediated interaction. Within an assisted living facility, the participants described themselves as sensible and responsible persons who wanted to follow the facility's pandemic-related rules but also as independent persons having nothing to do with these rules. In the spaces outside the home, the participants portrayed themselves as persons who followed pandemic instructions but also as persons who were not required to follow the instructions because they could use their own judgement. These self-positions shed light on the social needs of older people in the spaces of their everyday lives. Our results provide useful insights for policy makers and professionals working with older people and will help to promote spaces of living, care and everyday life that can enhance and maintain social interaction and well-being both in times of change and in more stable times.

Temporally and spatially regulated collagen XVIII isoforms are involved in ureteric tree development via the TSP1-like domain.

Collagen XVIII (ColXVIII) is a component of the extracellular matrix implicated in embryogenesis and control of tissue homoeostasis. We now provide evidence that ColXVIII has a specific role in renal branching morphogenesis as observed in analyses of total and isoform-specific knockout embryos and mice. The expression of the short and the two longer isoforms differ temporally and spatially during renal development. The lack of ColXVIII or its specific isoforms lead to congenital defects in the 3D patterning of the ureteric tree where the short isoform plays a prominent role. Moreover, the ex vivo data suggests that ColXVIII is involved in the kidney epithelial tree patterning via its N-terminal domains, and especially the Thrombospondin-1-like domain common to all isoforms. This morphogenetic function likely involves integrins expressed in the ureteric epithelium. Altogether, the results point to an important role for ColXVIII in the matrix-integrin-mediated functions regulating renal development.

Tailoring vascular phenotype through AAV therapy promotes anti-tumor immunity in glioma.

Glioblastomas are aggressive brain tumors that are largely immunotherapy resistant. This is associated with immunosuppression and a dysfunctional tumor vasculature, which hinder T cell infiltration. LIGHT/TNFSF14 can induce high endothelial venules (HEVs) and tertiary lymphoid structures (TLS), suggesting that its therapeutic expression could promote T cell recruitment. Here, we use a brain endothelial cell-targeted adeno-associated viral (AAV) vector to express LIGHT in the glioma vasculature (AAV-LIGHT). We found that systemic AAV-LIGHT treatment induces tumor-associated HEVs and T cell-rich TLS, prolonging survival in αPD-1-resistant murine glioma. AAV-LIGHT treatment reduces T cell exhaustion and promotes TCF1+CD8+ stem-like T cells, which reside in TLS and intratumoral antigen-presenting niches. Tumor regression upon AAV-LIGHT therapy correlates with tumor-specific cytotoxic/memory T cell responses. Our work reveals that altering vascular phenotype through vessel-targeted expression of LIGHT promotes efficient anti-tumor T cell responses and prolongs survival in glioma. These findings have broader implications for treatment of other immunotherapy-resistant cancers.

Secreted Wnt antagonist Dickkopf-1 controls kidney papilla development coordinated by Wnt-7b signalling.

Wnt signalling regulates several aspects of kidney development such as nephrogenesis, ureteric bud branching and organisation of the collecting duct cells. We addressed the potential involvement of Dickkopf-1 (Dkk1), a secreted Wnt pathway antagonist. Dkk1 is expressed in the developing mouse kidney by pretubular cell aggregates and the nephrons derived from them. Besides the mesenchyme cells, the epithelial ureteric bud and more mature ureteric bud derivatives in the medulla and the papilla tip express the Dkk1 gene. To reveal the potential roles of Dkk1, we generated a floxed allele and used three Cre lines to inactivate Dkk1 function in the developing kidney. Interestingly, Dkk1 deficiency induced by Pax8Cre in the kidneys led in newborn mice to an overgrown papilla that was generated by stimulated proliferation of the collecting duct and loop of Henle cells, implying a role for Dkk1 in the collecting duct and/or loop of Henle development. Since Pax8Cre-induced Dkk1 deficiency reduced marker gene expression, Scnn1b in the collecting duct and Slc12a1 in the loop of Henle, these results together with the extended papilla phenotype are likely reasons for the decreased amount of ions and urine produced by Dkk1-deficient kidneys in the adult. Recombinant Dkk1 protein in cultured cells inhibited Wnt-7b-induced canonical Wnt signalling, which is critical for collecting duct and loop of Henle development. Moreover, Dkk1 deficiency led to an increase in the expression of canonical Wnt signalling of target Lef-1 gene expression in the stromal cells of the developing papilla. Based on the results, we propose that Dkk1 controls the degree of Wnt-7b signalling in the papilla to coordinate kidney organogenesis.

Wnt4/5a signalling coordinates cell adhesion and entry into meiosis during presumptive ovarian follicle development.

Germ cells are the foundation of an individual, since they generate the gametes and provide the unique genome established through meiosis. The sex-specific fate of the germline in mammals is thought to be controlled by somatic signals, which are still poorly characterized. We demonstrate here that somatic Wnt signalling is crucial for the control of female germline development. Wnt-4 maintains germ cell cysts and early follicular gene expression and provides a female pattern of E-cadherin and beta-catenin expression within the germ cells. In addition, we find that Stra8 expression is downregulated and the Cyp26b1 gene is expressed ectopically in the partially masculinized Wnt-4-deficient ovary. Wnt-4 may control meiosis via these proteins since the Cyp26b1 enzyme is known to degrade retinoic acid (RA) and inhibit meiosis in the male embryo, and Stra8 induces meiosis in the female through RA. Reintroduction of a Wnt-4 signal to the partially masculinized embryonic ovary, in fact, rescues the female property to a certain degree, as seen by inhibition of Cyp26b1 and induction of Irx3 gene expression. Wnt-4 deficiency allows only 20% of the germ cells to initiate meiosis in the ovary, whereas meiosis is inhibited completely in the Wnt-4/Wnt-5a double mutant. These findings indicate a critical role for Wnt signalling in meiosis. Thus, the Wnt signals are important somatic cell signals that coordinate presumptive female follicle development.

Studying constructions of aging manhood: Methodological considerations.

The study of aging masculinity benefits from theories of intersecting inequality and attention to context, and also from methodological care. Theory can help to avoid reification of naturalized distinctions by age and by sex; and methodological rigor can avoid imputations of old masculinity to activities that other people do just as much. We revisit published research to outline theory and methods that minimize risk of reification and false distinction. We review theories of intersecting inequalities (age and gender) as well as institutional context; and we focus on methods that require either explicit mention of gender by those studied or direct comparison of old men to others. We offer several examples of how we can distinguish aging masculinities by using these methods, from interview research to the study of popular culture. Comparisons of white, middle-aged men in Finland to men in the U.S., and contrast of the U.S. men to U.S. women, reveal patterns in their constructions of manhood in later life, in realms of health, anti-aging, and caregiving. We point to the importance of both intersectionality and attention to contexts, such as welfare states, which shape aging manhood.

Perspectives of oncology nurses on peer support for patients with cancer.

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.