Oncological therapy to Swedish men with metastatic penile cancer 2000-2015.

BACKGROUND: Penile cancer is an uncommon disease with poor prognosis when spread to more than one inguinal lymph node. Recommendations on chemo- and radiotherapy in treatment guidelines are based on low-grade evidence. There are to our knowledge no described population-based cohort with detailed information on given oncological treatment and survival data. The aim of this study is to investigate in detail how men with metastatic penile cancer have been treated with chemotherapy and radiotherapy over time, and how survival varies with N-stage and given treatment. MATERIAL AND METHODS: For this observational cohort study all men in Sweden diagnosed with penile cancer with lymph node- or distant metastases 2000-2015 were identified through the Swedish National Penile Cancer Register (NPECR). Medical records were retrieved and 325 men were confirmed to have metastatic penile cancer (Tany, c or pN1-3 and/or M1). Information on treatments was collected. Causes of death were retrieved from the National Cause of Death Register (CDR). RESULTS: Chemotherapy and/or radiotherapy were given to 172 (53%) of all men. The use of oncological treatments with curative intent increased significantly during the study period, from 30% of men with c/pN2-3 diagnosed 2000-2003 compared with 57% of men diagnosed 2012-2015. Ninety-three (29%) men received oncological treatments with curative intent of whom 85/93 (91%) had stage c/pN2-3M0. Survival decreased with higher N-stage, M1-stage, and absence of oncological treatment with curative intent. For men with c/pN3-stage, the engagement of pelvic lymph nodes was entailed with lower survival than pN3 based on extra-nodal extension (ENE). CONCLUSION: The use of oncological treatment was below recommendations in guidelines but increased during the study period. Treatment was given predominantly to men with c/pN2-3 and M1-disease. Survival was higher among men treated with curative intent; this could be due to patient selection bias.

'It depends': what 86 systematic reviews tell us about what strategies to use to support the use of research in clinical practice.

BACKGROUND: The gap between research findings and clinical practice is well documented and a range of strategies have been developed to support the implementation of research into clinical practice. The objective of this study was to update and extend two previous reviews of systematic reviews of strategies designed to implement research evidence into clinical practice. METHODS: We developed a comprehensive systematic literature search strategy based on the terms used in the previous reviews to identify studies that looked explicitly at interventions designed to turn research evidence into practice. The search was performed in June 2022 in four electronic databases: Medline, Embase, Cochrane and Epistemonikos. We searched from January 2010 up to June 2022 and applied no language restrictions. Two independent reviewers appraised the quality of included studies using a quality assessment checklist. To reduce the risk of bias, papers were excluded following discussion between all members of the team. Data were synthesised using descriptive and narrative techniques to identify themes and patterns linked to intervention strategies, targeted behaviours, study settings and study outcomes. RESULTS: We identified 32 reviews conducted between 2010 and 2022. The reviews are mainly of multi-faceted interventions (n = 20) although there are reviews focusing on single strategies (ICT, educational, reminders, local opinion leaders, audit and feedback, social media and toolkits). The majority of reviews report strategies achieving small impacts (normally on processes of care). There is much less evidence that these strategies have shifted patient outcomes. Furthermore, a lot of nuance lies behind these headline findings, and this is increasingly commented upon in the reviews themselves. DISCUSSION: Combined with the two previous reviews, 86 systematic reviews of strategies to increase the implementation of research into clinical practice have been identified. We need to shift the emphasis away from isolating individual and multi-faceted interventions to better understanding and building more situated, relational and organisational capability to support the use of research in clinical practice. This will involve drawing on a wider range of research perspectives (including social science) in primary studies and diversifying the types of synthesis undertaken to include approaches such as realist synthesis which facilitate exploration of the context in which strategies are employed.

Nationwide Data Support Centralised Decision-making in Penile Cancer Care: A Before-and-After Study on Guideline Adherence and Disease-specific survival for Patients with an Indication for Perioperative Oncological Treatment.

Background: The benefit of perioperative oncological treatment in men with penile cancer is uncertain. In 2015, treatment recommendations were centralised in Sweden and treatment guidelines were updated. Objective: To evaluate if the use of oncological treatment in men with penile cancer increased after the introduction of centralised recommendations, and whether such therapy is associated with better survival. Design setting and participants: This was a retrospective cohort study including a total of 426 men diagnosed with penile cancer with lymph node or distant metastases in Sweden during 2000-2018. Outcome measurements and statistical analysis: We first assessed the change in the proportion of patients with an indication for perioperative oncological treatment who actually received such treatment. Second, we used Cox regression to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-specific mortality associated with perioperative treatment. Comparisons were made for both all men without perioperative treatment and for those who did not receive treatment but who lacked apparent contraindications for treatment. Results and limitations: The use of perioperative oncological treatment increased from 2000 to 2018, from 32% of patients with an indication for treatment during the first 4 yr to 63% during the last 4 yr. In comparison to patients potentially eligible for oncological treatment who did not receive it, those who were treated had a 37% lower risk of disease-specific death (HR 0.63, 95% CI 0.40-0.98). Stage migration because of improvements in diagnostic tools over time may have inflated the more recent survival estimates. An influence of residual confounding due to comorbidity and other potential confounders cannot be excluded. Conclusions: The use of perioperative oncological treatment increased after the centralisation of penile cancer care in Sweden. Although the observational study design precludes causal inference, the findings suggest that perioperative treatment in patients with penile cancer eligible for treatment may be associated with better survival. Patient summary: In this study, we looked at the use of chemotherapy and radiotherapy for men with penile cancer and lymph node metastases in Sweden during 2000-2018. We found an increase in the use of cancer therapy and an increase in survival for patients who received such therapy.

Vertebral Hemangiomas: Prevalence, new classification and natural history. magnetic resonance imaging-based retrospective longitudinal study.

BACKGROUND AND PURPOSE: To determine the prevalence of vertebral hemangiomas (VHs), establish a new classification of VHs based on their MRI-signal pattern, and study their natural history. METHODS: MRI of 1000 consecutive patients who underwent at least two MRI with an interval of at least 3 years. Growth rate and change of MRI-signal pattern during the follow-up period were the parameters included in studying the natural history of VHs. RESULTS: The prevalence of VHs was 41%. VHs were classified as type I-IV with fat-rich VHs (type I), constituted 79% of all VHs. VHs were more common among females 43% versus males 39%, p = .22. The most affected vertebra was L1. Occurrence rates for cervical (1%), thoracic (7%), and lumbar spine (10%) differed significantly (p < .001). The prevalence of VHs increased with age regardless of gender or spinal part involved (p < .001). Only 26% of VHs changed their size and 4% changed their signal during the average follow-up of 7 years. All VHs were slowly growing lesions (average expected growth of <3 mm/10 years). No significant difference between growth rate of VHs type I (0.25 mm/year) and other types of VHs. None of the VHs that were initially reported as "metastases cannot be rule out" showed alarming change in signal or size. CONCLUSIONS: VH can be classified into four types based on their MRI-signal pattern. Regardless of their type, VHs are slowly growing lesions. The presence of typical morphological pattern should enable radiologists to confidently differentiate them from vertebral metastases.

Deep learning takes the pain out of back breaking work - Automatic vertebral segmentation and attenuation measurement for osteoporosis.

BACKGROUND: Osteoporosis is an underdiagnosed and undertreated disease worldwide. Recent studies have highlighted the use of simple vertebral trabecular attenuation values for opportunistic osteoporosis screening. Meanwhile, machine learning has been used to accurately segment large parts of the human skeleton. PURPOSE: To evaluate a fully automated deep learning-based method for lumbar vertebral segmentation and measurement of vertebral volumetric trabecular attenuation values. MATERIAL AND METHODS: A deep learning-based method for automated segmentation of bones was retrospectively applied to non-contrast CT scans of 1008 patients (mean age 57 years, 472 female, 536 male). Each vertebral segmentation was automatically reduced by 7 mm in all directions in order to avoid cortical bone. The mean and median volumetric attenuation values from Th12 to L4 were obtained and plotted against patient age and sex. L1 values were further analyzed to facilitate comparison with previous studies. RESULTS: The mean L1 attenuation values decreased linearly with age by -2.2 HU per year (age > 30, 95% CI: -2.4, -2.0, R2 = 0.3544). The mean L1 attenuation value of the entire population cohort was 140 HU ± 54. CONCLUSIONS: With results closely matching those of previous studies, we believe that our fully automated deep learning-based method can be used to obtain lumbar volumetric trabecular attenuation values which can be used for opportunistic screening of osteoporosis in patients undergoing CT scans for other reasons.

Surgeon volume and patient-reported urinary incontinence after radical prostatectomy. Population-based register study in Sweden.

OBJECTIVE: To investigate the association between surgeon volume and urinary incontinence after radical prostatectomy. METHODS: A total of 8326 men in The National Prostate Cancer Register of Sweden (NPCR) underwent robot-assisted radical prostatectomy (RARP) between 2017 and 2019 of whom 56% (4668/8 326) had responded to a questionnaire one year after RARP. The questionnaire included the question: 'How much urine leakage do you experience?' with the response alternatives 'Not at all', 'A little', defined as continence and 'Moderately', 'Much/Very much' as incontinence. Association between incontinence and mean number of RARPs/year/surgeon was analysed with multivariable logistic regression including age, Charlson Comorbidity Index (CCI), PSA, prostate volume, number of biopsy cores with cancer, cT stage, Gleason score, lymph node dissection, nerve sparing intent and response rate to the questionnaire. RESULTS: 14% (659/4 668) of the men were incontinent one year after RARP. There was no statistically significant association between surgeon volume and incontinence. Older age (>75 years vs. < 65 years, OR 2.29 [95% CI 1.48-3.53]), higher CCI (CCI 2+ vs. CCI 0, OR 1.37 [95% CI 1.04-1.80]) and no nerve sparing intent (no vs. yes OR 1.53 [95% CI 1.26-1.85]) increased risk of incontinence. There were large differences in the proportion of incontinent men between surgeons with similar annual volumes, which remained after adjustment. CONCLUSIONS: The lack of association between surgeon volume and incontinence and the wide range in outcome between surgeons with similar volumes underline the importance of individual feedback to surgeons on functional results.

On-Site X-ray Fluorescence Spectrometry Measurement Strategy for Assessing the Sulfonation to Improve Chemimechanical Pulping Processes.

Minimizing the fiber property distribution would have the potential to improve the pulp properties and the process efficiency of chemimechanical pulp. To achieve this, it is essential to improve the level of knowledge of how evenly distributed the sulfonate concentration is between the individual chemimechanical pulp fibers. Due to the variation in quality between pulpwood and sawmill chips, as well as the on-chip screening method, it is difficult to develop an impregnation system that ensures the even distribution of sodium sulfite (Na2SO3) impregnation liquid. It is, therefore, crucial to measure the distribution of sulfonate groups within wood chips and fibers on a microscale. Typically, the degree of unevenness, i.e., the amount of fiber sulfonation and softening prior to defibration, is unknown on a microlevel due to excessively robust or complex processing methods. The degree of sulfonation at the fiber level can be determined by measuring the distribution of elemental sulfur and counterions of sulfonate groups, such as sodium or calcium. A miniaturized energy-dispersive X-ray fluorescence (ED-XRF) method has been developed to address this issue, enabling the analysis of sulfur distributions. It is effective enough to be applied to industrial laboratories for further development, i.e., improved image resolution and measurement time.

Cell water dynamics on multiple time scales.

Water-biomolecule interactions have been extensively studied in dilute solutions, crystals, and rehydrated powders, but none of these model systems may capture the behavior of water in the highly organized intracellular milieu. Because of the experimental difficulty of selectively probing the structure and dynamics of water in intact cells, radically different views about the properties of cell water have proliferated. To resolve this long-standing controversy, we have measured the (2)H spin relaxation rate in living bacteria cultured in D(2)O. The relaxation data, acquired in a wide magnetic field range (0.2 mT-12 T) and analyzed in a model-independent way, reveal water dynamics on a wide range of time scales. Contradicting the view that a substantial fraction of cell water is strongly perturbed, we find that approximately 85% of cell water in Escherichia coli and in the extreme halophile Haloarcula marismortui has bulk-like dynamics. The remaining approximately 15% of cell water interacts directly with biomolecular surfaces and is motionally retarded by a factor 15 +/- 3 on average, corresponding to a rotational correlation time of 27 ps. This dynamic perturbation is three times larger than for small monomeric proteins in solution, a difference we attribute to secluded surface hydration sites in supramolecular assemblies. The relaxation data also show that a small fraction ( approximately 0.1%) of cell water exchanges from buried hydration sites on the microsecond time scale, consistent with the current understanding of protein hydration in solutions and crystals.

Synthetic Life and the Value of Life.

If humans eventually attain the ability to create new life forms, how will it affect the value of life? This is one of several questions that can be sources of concern when discussing synthetic life, but is the concern justified? In an attempt to answer this question, I have analyzed some possible reasons why an ability to create synthetic life would threaten the value of life in general (that is, not just of the synthetic creations), to see if they really give us reason to worry. The main conclusion is that it is unlikely that a future human ability to create life will really have a great negative impact on these characteristics of life. It therefore seems unlikely that the value of life will be negatively affected by the ability to create synthetic life, though it is possible that the properties in question will be less salient in the synthetic life and thus that the value of the synthetic life will be lower than that of existing life, which in turn can lead to a disturbing difference in value between different kinds of life.

Association of surgeon and hospital volume with short-term outcomes after robot-assisted radical prostatectomy: Nationwide, population-based study.

BACKGROUND AND OBJECTIVE: Few studies have investigated the association between surgical volume and outcome of robot-assisted radical prostatectomy (RARP) in an unselected cohort. We sought to investigate the association between surgical volume with peri-operative and short-term outcomes in a nation-wide, population-based study group. METHODS: 9,810 RARP's registered in the National Prostate Cancer Register of Sweden (2015-2018) were included. Associations between outcome and volume were analyzed with multivariable logistic regression including age, PSA-density, number of positive biopsy cores, cT stage, Gleason score, and extent of lymph node dissection. RESULTS: Surgeons and hospitals in the highest volume group compared to lowest group had shorter operative time; surgeon (OR 9.20, 95% CI 7.11-11.91), hospital (OR 2.16, 95% CI 1.53-3.06), less blood loss; surgeon (OR 2.58. 95% CI 2.07-3.21) hospital (no difference), more often nerve sparing intention; surgeon (OR 2.89, 95% CI 2.34-3.57), hospital (OR 2.02, 95% CI 1.66-2.44), negative margins; surgeon (OR 1.90, 95% CI 1.54-2.35), hospital (OR 1.28, 95% CI 1.07-1.53). There was wide range in outcome between hospitals and surgeons with similar volume that remained after adjustment. CONCLUSIONS: High surgeon and hospital volume were associated with better outcomes. The range in outcome was wide in all volume groups, which indicates that factors besides volume are of importance. Registration of surgical performance is essential for quality control and improvement.

Reactive oxygen species in renal vascular function.

Reactive oxygen species (ROS) are produced by the aerobic metabolism. The imbalance between production of ROS and antioxidant defence in any cell compartment is associated with cell damage and may play an important role in the pathogenesis of renal disease. NADPH oxidase (NOX) family is the major ROS source in the vasculature and modulates renal perfusion. Upregulation of Ang II and adenosine activates NOX via AT1R and A1R in renal microvessels, leading to superoxide production. Oxidative stress in the kidney prompts renal vascular remodelling and increases preglomerular resistance. These are key elements in hypertension, acute and chronic kidney injury, as well as diabetic nephropathy. Renal afferent arterioles (Af), the primary resistance vessel in the kidney, fine tune renal hemodynamics and impact on blood pressure. Vice versa, ROS increase hypertension and diabetes, resulting in upregulation of Af vasoconstriction, enhancement of myogenic responses and change of tubuloglomerular feedback (TGF), which further promotes hypertension and diabetic nephropathy. In the following, we highlight oxidative stress in the function and dysfunction of renal hemodynamics. The renal microcirculatory alterations brought about by ROS importantly contribute to the pathophysiology of kidney injury, hypertension and diabetes.

Are values related to culture, identity, community cohesion and sense of place the values most vulnerable to climate change?

Values related to culture, identity, community cohesion and sense of place have sometimes been downplayed in the climate change discourse. However, they have been suggested to be not only important to citizens but the values most vulnerable to climate change. Here we test four empirical consequences of the suggestion: (i) at least 50% of the locations citizens' consider to be the most important locations in their municipality are chosen because they represent these values, (ii) locations representing these values have a high probability of being damaged by climate change induced sea level rise, (iii) citizens for which these values are particularly strongly held less strongly believe in the local effects of climate change, and (iv) citizens for which these values are particularly strongly held less strongly believe that they have experienced the effects of climate change. The tests were made using survey data collected in 2014 from 326 citizens owning property in Höganäs municipality, Sweden, and included values elicited using a new methodology separating instrumental values from end values, and using the former (which strictly speaking should be seen as estimates of usefulness rather than as aims in themselves) as stepping stones to pinpoint the latter, that represent the true interests of the respondents. The results provide the first evidence that, albeit frequent, values related to culture, identity, community cohesion and sense of place are not the values most vulnerable to climate change. This in turn indicates a need to further investigate the vulnerability of these values to climate change, using a methodology that clearly distinguishes between instrumental and end values.

Nanosecond to microsecond protein dynamics probed by magnetic relaxation dispersion of buried water molecules.

Large-scale protein conformational motions on nanosecond-microsecond time scales are important for many biological processes, but remain largely unexplored because of methodological limitations. NMR relaxation methods can access these time scales if protein tumbling is prevented, but the isotropy required for high-resolution solution NMR is then lost. However, if the immobilized protein molecules are randomly oriented, the water 2H and 17O spins relax as in a solution of freely tumbling protein molecules, with the crucial difference that they now sample motions on all time scales up to approximately 100 micros. In particular, the exchange rates of internal water molecules can be determined directly from the 2H or 17O magnetic relaxation dispersion (MRD) profile. This possibility opens up a new window for characterizing the motions of individual internal water molecules as well as the large-scale protein conformational fluctuations that govern the exchange rates of structural water molecules. We introduce and validate this new NMR method by presenting and analyzing an extensive set of 2H and 17O MRD data from cross-linked gels of two model proteins: bovine pancreatic trypsin inhibitor and ubiquitin. We determine residence times and order parameters of four internal water molecules in these proteins and show that they are quantitatively consistent with the information available from crystallography and solution MRD. We also show how slow motions of side-chains bearing labile hydrogens can be monitored by the same approach. Proteins of any size can be studied at physiological hydration levels with this method.

Influence of mitochondrial inhibition on global and local [Ca(2+)](I) in rat tail artery.

Inhibition of oxidative metabolism is often found to decrease contractility of systemic vascular smooth muscle, but not to reduce global [Ca(2+)](i). In the present study, we probe the hypothesis that it is associated with an altered pattern of intracellular Ca(2+) oscillations (waves) influencing force development. In the rat tail artery, mitochondrial inhibitors (rotenone, antimycin A, and cyanide) reduced alpha(1)-adrenoceptor-stimulated force by 50% to 80%, but did not reduce global [Ca(2+)](i). Less relaxation (about 30%) was observed after inhibition of myosin phosphatase activity with calyculin A, suggesting that part of the metabolic sensitivity involves the regulation of myosin 20-kDa light chain phosphorylation, although no decrease in phosphorylation was found in freeze-clamped tissue. Confocal imaging revealed that the mitochondrial inhibitors increased the frequency but reduced the amplitude of asynchronous cellular Ca(2+) waves elicited by alpha(1) stimulation. The altered wave pattern, in association with increased basal [Ca(2+)](i), accounted for the unchanged global [Ca(2+)](i). Inhibition of glycolytic ATP production by arsenate caused similar effects on Ca(2+) waves and global [Ca(2+)](i), developing gradually in parallel with decreased contractility. Inhibition of wave activity by the InsP(3) receptor antagonist 2-APB correlated closely with relaxation. Furthermore, abolition of waves with thapsigargin in the presence of verapamil reduced force by about 50%, despite unaltered global [Ca(2+)](i), suggesting that contraction may at least partly depend on Ca(2+) wave activity. This study therefore indicates that mitochondrial inhibition influences Ca(2+) wave activity, possibly due to a close spatial relationship of mitochondria and the sarcoplasmic reticulum and that this contributes to metabolic vascular relaxation.

What are the core ideas behind the Precautionary Principle?

The Precautionary Principle is both celebrated and criticized. It has become an important principle for decision making, but it is also subject to criticism. One problem that is often pointed out with the principle is that is not clear what it actually says and how to use it. I have taken on this problem by performing an analysis of some of the most influential formulations of the principle in an attempt to identify the core ideas behind it, with the purpose of producing a formulation of the principle that is clear and practically applicable. It was found that what is called the Precautionary Principle is not a principle that tells us what do to achieve extra precaution or how to handle situations when extra precaution is called for. Instead, it was found to be a list of circumstances that each justify extra precaution. An analysis of some of the most common and influential formulations of the Precautionary Principle identified four such circumstances: (1) When we deal with important values that tend to be systematically downplayed by traditional decision methods - such as human health and the environment. (2) When we suspect that the decision might lead to irreversible and severe consequences and the values at stake are also irreplaceable, (3) When timing is at least as important as being right. (4) When it is more important to avoid false negatives than false positives. This interpretation of the Precautionary Principle does not say anything about what kind of actions to take when extra precaution is called for, but it does provide a clear and practically useful list of circumstances that call for extra precaution and that is not subject to the most common objections to the Precautionary Principle.

Understanding professional stratification and hybridisation in the medical profession: exploratory evidence from Brazilian federal university hospitals / Comprendiendo la estratificación e hibridación profesional en la profesión médica: evidencia exploratoria de los hospitales universitarios federales de Brasil / Compreendendo a estratificação profissional e hibridização na profissão médica: evidências exploratórias de hospitais universitários federais brasileiros

Abstract This paper explores drivers, implications, and trends of professional stratification and hybridisation in the medical profession employed in Brazilian substituir por: federal university hospitals (HUFs). Drawing on exploratory findings, we examine some repercussions of the migration of university hospitals to EBSERH, a public company established by the federal government to manage and organise HUFs integrated into the Unified Health System (SUS). Our research shows that transferring hospital administration to EBSERH has led to further internal stratification of the medical workforce. The shift from the logic of medical-academic professionalism to the new logic of business-like healthcare, with the adoption of distinct job contracts and more managerial logics of work and control, may well be changing subjective and formal links established between professionals, universities, and hospitals. We identify and discuss trends towards hybridisation and dehybridisation. These findings are relevant because this shift can have profound implications for the academic nature of HUFs and for the future of professionalism within these health and teaching organisations.

Resumen Este artículo explora impulsores, implicaciones y tendencias de la estratificación y la hibridación profesional en la profesión médica empleada en los hospitales universitarios federales brasileños (HUFs). A partir de hallazgos exploratorios, examinamos algunas de las repercusiones de la migración de los hospitales universitarios a la EBSERH, una empresa pública creada por el gobierno federal para administrar y organizar los HUFs integrados en el Sistema Único de Salud (SUS). Nuestra investigación muestra que la transferencia de la administración hospitalaria a la EBSERH ha llevado a una mayor estratificación interna de la fuerza laboral médica. El cambio de la lógica del profesionalismo médico-académico a una lógica empresarial en salud, con la adopción de diferentes regímenes de empleo y modos de trabajo y control más gerenciales, puede estar alterando los vínculos subjetivos y formales que se establecen entre los profesionales, las universidades y los hospitales involucrados. Se identifican y discuten tendencias hacia la hibridación y deshibridación. Estos hallazgos son relevantes porque tales cambios pueden tener profundas implicaciones para la naturaleza académica de los HUFs, así como para el futuro del profesionalismo dentro de estas organizaciones de salud y educación.

Resumo: Este artigo explora motivadores, implicações e tendências de estratificação e hibridização profissional na profissão médica atuante em hospitais universitários federais brasileiros (HUFs). Com base em achados exploratórios, examinamos algumas das repercussões da migração dos hospitais universitários para a EBSERH, uma empresa pública criada pelo governo federal para gerenciar e organizar os HUFs vinculados ao Sistema Único de Saúde (SUS). A pesquisa mostra que a transferência da administração hospitalar para a EBSERH tem acarretado maior estratificação interna da força de trabalho médica. A mudança da lógica de profissionalismo médico-acadêmico para uma nova lógica empresarial de saúde, com a adoção de distintos regimes empregatícios e formas de trabalho e controle mais gerenciais, podem estar alterando vínculos subjetivos e formais estabelecidos entre os profissionais, as universidades e os hospitais envolvidos. Tendências em direção à hibridização e desibridização foram identificadas e discutidas. Esses achados são relevantes tendo em vista que tais movimentos podem representar implicações profundas para a natureza acadêmica dos HUFs e para o futuro do profissionalismo nessas organizações de saúde e ensino.

Forest Owners' Response to Climate Change: University Education Trumps Value Profile.

Do forest owners' levels of education or value profiles explain their responses to climate change? The cultural cognition thesis (CCT) has cast serious doubt on the familiar and often criticized "knowledge deficit" model, which says that laypeople are less concerned about climate change because they lack scientific knowledge. Advocates of CCT maintain that citizens with the highest degrees of scientific literacy and numeracy are not the most concerned about climate change. Rather, this is the group in which cultural polarization is greatest, and thus individuals with more limited scientific literacy and numeracy are more concerned about climate change under certain circumstances than those with higher scientific literacy and numeracy. The CCT predicts that cultural and other values will trump the positive effects of education on some forest owners' attitudes to climate change. Here, using survey data collected in 2010 from 766 private forest owners in Sweden and Germany, we provide the first evidence that perceptions of climate change risk are uncorrelated with, or sometimes positively correlated with, education level and can be explained without reference to cultural or other values. We conclude that the recent claim that advanced scientific literacy and numeracy polarizes perceptions of climate change risk is unsupported by the forest owner data. In neither of the two countries was university education found to reduce the perception of risk from climate change. Indeed in most cases university education increased the perception of risk. Even more importantly, the effect of university education was not dependent on the individuals' value profile.

Enhanced XOR activity in eNOS-deficient mice: Effects on the nitrate-nitrite-NO pathway and ROS homeostasis.

Xanthine oxidoreductase (XOR) is generally known as the final enzyme in purine metabolism and as a source of reactive oxygen species (ROS). In addition, this enzyme has been suggested to mediate nitric oxide (NO) formation via reduction of inorganic nitrate and nitrite. This NO synthase (NOS)-independent pathway for NO generation is of particular importance during certain conditions when NO bioavailability is diminished due to reduced activity of endothelial NOS (eNOS) or increased oxidative stress, including aging and cardiovascular disease. The exact interplay between NOS- and XOR-derived NO generation is not fully elucidated yet. The aim of the present study was to investigate if eNOS deficiency is associated with changes in XOR expression and activity and the possible impact on nitrite, NO and ROS homeostasis. Plasma levels of nitrate and nitrite were similar between eNOS deficient (eNOS-/-) and wildtype (wt) mice. XOR activity was upregulated in eNOS-/- compared with wt, but not in nNOS-/-, iNOS-/- or wt mice treated with the non-selective NOS inhibitor L-NAME. Following an acute dose of nitrate, plasma nitrite increased more in eNOS-/- compared with wt, and this augmented response was abolished by the selective XOR inhibitor febuxostat. Livers from eNOS-/- displayed higher nitrite reducing capacity compared with wt, and this effect was attenuated by febuxostat. Dietary supplementation with nitrate increased XOR expression and activity, but concomitantly reduced superoxide generation. The latter effect was also seen in vitro after nitrite administration. Treatment with febuxostat elevated blood pressure in eNOS-/-, but not in wt mice. A high dose of dietary nitrate reduced blood pressure in naïve eNOS-/- mice, and again this effect was abolished by febuxostat. In conclusion, eNOS deficiency is associated with an upregulation of XOR facilitating the nitrate-nitrite-NO pathway and decreasing the generation of ROS. This interplay between XOR and eNOS is proposed to play a significant role in NO homeostasis and blood pressure regulation.

Nitric oxide generation by the organic nitrate NDBP attenuates oxidative stress and angiotensin II-mediated hypertension.

BACKGROUND AND PURPOSE: NO deficiency and oxidative stress are crucially involved in the development or progression of cardiovascular disease, including hypertension and stroke. We have previously demonstrated that acute treatment with the newly discovered organic nitrate, 2-nitrate-1,3-dibuthoxypropan (NDBP), is associated with NO-like effects in the vasculature. This study aimed to further characterize the mechanism(s) and to elucidate the therapeutic potential in a model of hypertension and oxidative stress. EXPERIMENTAL APPROACH: A combination of ex vivo, in vitro and in vivo approaches was used to assess the effects of NDBP on vascular reactivity, NO release, NADPH oxidase activity and in a model of hypertension. KEY RESULTS: Ex vivo vascular studies demonstrated NDBP-mediated vasorelaxation in mesenteric resistance arteries, which was devoid of tolerance. In vitro studies using liver and kidney homogenates revealed dose-dependent and sustained NO generation by NDBP, which was attenuated by the xanthine oxidase inhibitor febuxostat. In addition, NDBP reduced NADPH oxidase activity in the liver and prevented angiotensin II-induced activation of NADPH oxidase in the kidney. In vivo studies showed that NDBP halted the progression of hypertension in mice with chronic angiotensin II infusion. This was associated with attenuated cardiac hypertrophy, and reduced NADPH oxidase-derived oxidative stress and fibrosis in the kidney and heart. CONCLUSION AND IMPLICATIONS: The novel organic nitrate NDBP halts the progression of angiotensin II-mediated hypertension. Mechanistically, our findings suggest that NDBP treatment is associated with sustained NO release and attenuated activity of NADPH oxidase, which to some extent requires functional xanthine oxidase.

High revision rate following artificial urethral sphincter implantation.

OBJECTIVE: In severe cases of stress urinary incontinence (SUI), with sphincter dysfunction, the artificial urinary sphincter AMS 800™ may be the last solution. The purpose of this study was to evaluate the outcome of surgical intervention for SUI with the AMS 800 in patients who were treated at Sahlgrenska University Hospital, Gothenburg. The primary aim of the study was to determine the complications related to the operation. MATERIAL AND METHODS: A retrospective follow-up was done by reviewing medical records. The material comprised 97 men, who underwent their first AMS 800 implantation between May 1997 and June 2010 at Sahlgrenska University Hospital. RESULTS: The revision rate was 28%, including an infection rate of 3% and an erosion rate of 7%. The mean follow-up for revised patients was 3 years. The median time until revision was 1 year. Seventy-five per cent of all patients were satisfied with the operation at 6 months' follow-up. Radical prostatectomy was the reason behind incontinence in 84% of patients in this series. CONCLUSION: The results clearly demonstrate a need for revision procedures in a considerable proportion of patients implanted with an AMS 800 device. Patient satisfaction was high, but although this operation has extremely low mortality it has its complications and the system will need to be replaced in time.