Impact of comorbidity on renal cell carcinoma prognosis: a nationwide cohort study.

BACKGROUND: Presence of comorbid diseases at time of cancer diagnosis may affect prognosis. We evaluated the impact of comorbidity on survival of patients diagnosed with renal cell carcinoma (RCC), overall and among younger (<70 years) and older (≥70 years) patients. METHODS: We established a nationwide register-based cohort of 7894 patients aged ≥18 years diagnosed with RCC in Denmark between 2006 and 2017. We computed 1- and 5-year overall survival and hazard ratios (HRs) for death according to the Charlson Comorbidity Index (CCI) score. RESULTS: Survival decreased with increasing CCI score despite an overall increase in survival over time. The 5-year survival rate of patients with no comorbidity increased from 57% among those diagnosed in 2006-2008 to 69% among those diagnosed in 2012-2014. During the same periods, the survival rate increased from 46% to 62% among patients with a CCI score of 1-2 and from 39% to 44% for those with a CCI score of ≥3. Patients with CCI scores of 1-2 and ≥3 had higher mortality rates than patients with no registered comorbidity (HR 1.15, 95% CI 1.06-1.24 and HR 1.56, 95% CI 1.40-1.73). Patterns were similar for older and younger patients. Particularly, diagnoses of liver disease (HR 2.09, 95% CI 1.53-2.84 and HR 4.01, 95% CI 2.44-6.56) and dementia (HR 2.16, 95% CI 1.34-3.48) increased mortality. CONCLUSION: Comorbidity decreased the survival of patients with RCC, irrespective of age, despite an overall increasing survival over time. These results highlight the importance of focusing on comorbidity in this group of patients.

Changes in awareness of cancer risk factors among adult New Zealanders (CAANZ): 2001 to 2015.

Behaviour change, specifically that which decreases cancer risk, is an essential element of cancer control. Little information is available about how awareness of risk factors may be changing over time. This study describes the awareness of cancer risk behaviours among adult New Zealanders in two cross-sectional studies conducted in 2001 and 2014/5.Telephone interviews were conducted in 2001 (n = 436) and 2014/5 (n = 1064). Participants were asked to recall things they can do to reduce their risk of cancer. They were then presented with a list of potential risk behaviours and asked if these could increase or decrease cancer risk.Most New Zealand adults could identify at least one action they could take to reduce their risk of cancer. However, when asked to provide specific examples, less than a third (in the 2014/5 sample) recalled key cancer risk reduction behaviours such as adequate sun protection, physical activity, healthy weight, limiting alcohol and a diet high in fruit. There had been some promising changes since the 2001 survey, however, with significant increases in awareness that adequate sun protection, avoiding sunbeds/solaria, healthy weight, limiting red meat and alcohol, and diets high in fruit and vegetables decrease the risk of developing cancer.

SunSmart Accreditation and Use of a Professional Policy Drafting Service: Both Positively and Independently Associated with High Sun Protective Hat Scores Derived from Primary School Policies.

BACKGROUND: The head and neck are exposed to the highest solar ultraviolet radiation levels and experience a disproportionate skin cancer burden. Sun protective hats can provide an effective barrier. Since early life exposure contributes to skin cancer risk, the World Health Organisation recommends prevention programmes in schools. The New Zealand SunSmart Schools programme is one example. Two criteria concern wearing hat outdoors: students are required to wear a hat providing protection for the face, neck, and ears; if a suitable hat is not worn, students must play in shaded areas. OBJECTIVES: To investigate two internationally relevant interventions as plausible statistical predictors of hat policy strength: (1) skin cancer primary prevention programme membership, (2) use of a professional policy drafting service. METHODS: Of 1,242 (62%) eligible schools participating in a 2017 national survey, 1,137 reported a sun protection policy and 842 were available for categorising and allocating protective scores (0-3). RESULTS: In multinomial (polytomous) logistic regression models of cross-sectional association, adjusted for school characteristics, SunSmart accredited schools and those utilising a policy drafting service were independently significantly more likely than their counterparts to obtain the most protective compared to the least protective hat score (respectively, RRR 6.48: 95% CI 3.66, 11.47; 7.47: 3.67, and 15.20). For the dichotomous shade measure, similar associations were found using adjusted logistic regression (OR 3.28: 95% CI 2.11, 5.09; 2.70: 1.54, 4.74). CONCLUSIONS: Our findings provide support for two plausible interventions that could potentially be implemented beneficially in primary schools via established infrastructure in any jurisdiction, internationally.

Labour induces increased concentrations of biglycan and hyaluronan in human fetal membranes.

OBJECTIVE: The proteoglycan decorin stabilizes collagen whereas biglycan and hyaluronan disrupt well-organized collagen. The aim was to compare hyaluronan and proteoglycans in human fetal membranes obtained before and after spontaneous labour at term. STUDY DESIGN: Prelabour samples of fetal membranes (N=9) were obtained from elective caesarean sections and regionally sampled from over the cervix (cervical membranes) and mid-zone samples between this area and the placental edge. Postlabour samples (N=11) were obtained from spontaneous vaginal delivery and also regionally sampled. Amnion and chorio-decidua were analysed separately. The proteoglycans decorin and biglycan were analysed using alcian blue precipitation, SDS polyacrylamide gel electrophoresis and immunostaining. Hyaluronan was analysed using a radioimmunoassay and by histochemistry. Collagen was measured by estimating hydroxyproline content. RESULTS: In prelabour membranes the biglycan concentration (microg/mg wtw) in the cervical amnion was 40% lower than in the mid-zone amnion (P<0.05). After delivery the cervical amnion showed a twofold increase in biglycan (P<0.05), a 30% decrease in collagen (P<0.05), and a 50% decrease in decorin concentration (P<0.05). In mid-zone samples after delivery the concentrations of hyaluronan showed an increase form 1.0 to 4.9 microg/mg wtw (P<0.05). Histology demonstrated a gelatinous substance, which separated amnion and chorio-decidua, in particular at the cervical site. This gelatinous substance contained hyaluronan at a concentration of 3.0 microg/mg wtw. CONCLUSION: It is well established that prelabour fetal membranes are considerably stronger than postlabour fetal membranes. Two features may explain this; a weakening of the amnion combined with a separation of amnion and chorio-decidua. The biomechanical changes are consistent with the decrease in collagen and decorin, and the increase in hyaluronan and biglycan demonstrated in this study. The separation of the membranes is caused by the formation of a gelatinous substance, rich in hyaluronan. The results indicate that the biomechanical changes are not merely secondary to the stress of labour but that an active maturation process is involved.

Chronic intermittent hypoxia and incremental cycling exercise independently depress muscle in vitro maximal Na+-K+-ATPase activity in well-trained athletes.

Athletes commonly attempt to enhance performance by training in normoxia but sleeping in hypoxia [live high and train low (LHTL)]. However, chronic hypoxia reduces muscle Na(+)-K(+)-ATPase content, whereas fatiguing contractions reduce Na(+)-K(+)-ATPase activity, which each may impair performance. We examined whether LHTL and intense exercise would decrease muscle Na(+)-K(+)-ATPase activity and whether these effects would be additive and sufficient to impair performance or plasma K(+) regulation. Thirteen subjects were randomly assigned to two fitness-matched groups, LHTL (n = 6) or control (Con, n = 7). LHTL slept at simulated moderate altitude (3,000 m, inspired O(2) fraction = 15.48%) for 23 nights and lived and trained by day under normoxic conditions in Canberra (altitude approximately 600 m). Con lived, trained, and slept in normoxia. A standardized incremental exercise test was conducted before and after LHTL. A vastus lateralis muscle biopsy was taken at rest and after exercise, before and after LHTL or Con, and analyzed for maximal Na(+)-K(+)-ATPase activity [K(+)-stimulated 3-O-methylfluorescein phosphatase (3-O-MFPase)] and Na(+)-K(+)-ATPase content ([(3)H]ouabain binding sites). 3-O-MFPase activity was decreased by -2.9 +/- 2.6% in LHTL (P < 0.05) and was depressed immediately after exercise (P < 0.05) similarly in Con and LHTL (-13.0 +/- 3.2 and -11.8 +/- 1.5%, respectively). Plasma K(+) concentration during exercise was unchanged by LHTL; [(3)H]ouabain binding was unchanged with LHTL or exercise. Peak oxygen consumption was reduced in LHTL (P < 0.05) but not in Con, whereas exercise work was unchanged in either group. Thus LHTL had a minor effect on, and incremental exercise reduced, Na(+)-K(+)-ATPase activity. However, the small LHTL-induced depression of 3-O-MFPase activity was insufficient to adversely affect either K(+) regulation or total work performed.

A guidance for assessing and communicating uncertainties.

In the daily practice of science for policy, as experienced by governmental agencies which inform the policy and the public on the state and outlook of the environment, there is a pressing need for guidance in assessing and communicating uncertainties. This need extends beyond the quantitative assessment of uncertainties in model results, and focuses on the entire process of environmental assessment, running from problem framing towards reporting the results of the study. Using the Netherlands Environmental Assessment Agency (RIVM/MNP) as a case, the development, structure and content of such a guidance system is highlighted. Conditions for a successful implementation of the guidance system are discussed, and some prospects for future work are outlined.

Cortisol reactivity and anxiety and depression in pregnant adolescents: a longitudinal perspective.

The purpose of this investigation was to examine: (1) the relations among cortisol reactivity (short term changes in cortisol concentration) and anxiety and depression symptoms in adolescents during pregnancy and early postpartum, and (2) cortisol reactivity and psychosocial variables as predictors of anxiety and depression symptoms in pregnancy and early postpartum. Cortisol reactivity, an index of hypothalamic-pituitary-adrenal activity, was hypothesized to be a vulnerability factor for poor physical and mental health outcomes in adolescents. Forty adolescents aged 14 to 19 years (M = 17.3, SD = 1.3) were enrolled in the study and were seen at < 20 weeks gestation (T1), 34-36 weeks gestation (T2), and 2-3 weeks postpartum (T3). Blood was drawn for cortisol at T1 and T3. Psychological assessments of anxiety and depression symptoms, life optimism, and self-worth were administered at T1, T2, and T3. There were significant correlations among cortisol reactivity and anxiety and depression symptoms at T1 and T3, but the correlations were the reverse of the hypothesized direction. Pregnant adolescents with increased cortisol reactivity (cortisol concentrations that increased across a 40-min period) had fewer symptoms of anxiety and depression than other adolescents. Longitudinal analyses showed that anxiety and depression symptoms at T1 were a stronger predictor of postpartum anxiety and depression than was cortisol reactivity, life optimism, self-worth, or age at pregnancy.

PIP: The authors hypothesized cortisol reactivity to be a vulnerability factor for poor physical and mental health outcomes in adolescents. This paper reports findings from a study of the relations among cortisol reactivity and anxiety and depression symptoms in pregnancy and early postabortion. 40 adolescents aged 14-19 years were enrolled in the study and seen at less than 20 weeks gestation, 34-36 weeks gestation, and 2-3 weeks postpartum. Blood was drawn for cortisol at the 1st and 3rd time indexes. At all times, psychological assessments of anxiety and depression symptoms, life optimism, and self-worth were administered. Significant correlations were found among cortisol reactivity and anxiety and depression symptoms at T1 and T3, but in a direction opposite of that which was hypothesized. Pregnant adolescents with increased cortisol reactivity had fewer symptoms of anxiety and depression than other adolescents. Longitudinal analyses further demonstrated that anxiety and depression symptoms at T1 were stronger predictors of postpartum anxiety and depression than were cortisol reactivity, life optimism, self worth, or age at pregnancy.

N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals.

The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated the effects of the antioxidant compound N-acetylcysteine (NAC) on muscle cysteine, cystine, and glutathione and on time to fatigue during prolonged, submaximal exercise in endurance athletes. Eight men completed a double-blind, crossover study, receiving NAC or placebo before and during cycling for 45 min at 71% peak oxygen consumption (VO2 peak) and then to fatigue at 92% VO2 peak. NAC was intravenously infused at 125 mg.kg(-1).h(-1) for 15 min and then at 25 mg.kg(-1).h(-1) for 20 min before and throughout exercise. Arterialized venous blood was analyzed for NAC, glutathione status, and cysteine concentration. A vastus lateralis biopsy was taken preinfusion, at 45 min of exercise, and at fatigue and was analyzed for NAC, total glutathione (TGSH), reduced glutathione (GSH), cysteine, and cystine. Time to fatigue at 92% VO2 peak was reproducible in preliminary trials (coefficient of variation 5.6 +/- 0.6%) and with NAC was enhanced by 26.3 +/- 9.1% (NAC 6.4 +/- 0.6 min vs. Con 5.3 +/- 0.7 min; P <0.05). NAC increased muscle total and reduced NAC at both 45 min and fatigue (P <0.005). Muscle cysteine and cystine were unchanged during Con, but were elevated above preinfusion levels with NAC (P <0.001). Muscle TGSH (P <0.05) declined and muscle GSH tended to decline (P=0.06) during exercise. Both were greater with NAC (P <0.05). Neither exercise nor NAC affected whole blood TGSH. Whereas blood GSH was decreased and calculated oxidized glutathione increased with exercise (P <0.05), both were unaffected by NAC. In conclusion, NAC improved performance in well-trained individuals, with enhanced muscle cysteine and GSH availability a likely mechanism.

Depression in adolescence.

Adolescence is an important developmental period for understanding the nature, course, and treatment of depression. Recent research concerned with depressive mood, syndromes, and disorders during adolescence is reviewed, including investigations of the prevalence, course, risk factors, and prevention and treatment programs for each of these three levels of depressive phenomena in adolescence. A broad biopsychosocial perspective on adolescent depression is recommended, and possible directions for future integrative research are proposed. Based on current research and knowledge, implications for research, program, and national policy are considered.

An interlaboratory study to find an alternative to the MPN technique for enumerating Escherichia coli in shellfish.

Nine laboratories in eight countries tested 16 batches of common mussels (Mytilus edulis) over a 32 week period in order to find an alternative to the Most Probable Number (MPN) technique to enumerate E. coli. The alternatives investigated included the 3M Petrifilm system, the Merck Chromocult agar method and a Malthus conductance technique. The Petrifilm was found to be unsuitable and was subsequently dropped from the trial. After 669 analyses, a correlation of 0.83 was observed for log E. coli counts between the MPN and Chromocult methods and there was no significant evidence that either method tended to give higher readings than the other. The MPN was slightly better than the Chromocult method for repeatability but the Chromocult was slightly better for reproducibility. However, the observed differences are probably too small to be of practical importance. On the basis of these data therefore, the two methods appear equally suitable for E. coli enumeration in shellfish. There were poor correlations between these methods and the Malthus technique. A small but significant number of samples tested positive on the Malthus instrument but were recorded negative on the MPN and Chromocult tests. Subsequent analysis positively identified E. coli from these Malthus assays. After statistical analysis, errors were noted in both the MPN and Chromocult methods but it was found that there would be no statistical differences if the Chromocult agar were used as an alternative to the MPN technique.

Developmental issues influencing guidelines for adolescent health research: a review.

Adolescent development brings many opportunities to adolescents as research participants. They may be enthusiastic participants, especially if the focus of the research is of interest to the adolescents. Their increasing sense of self and development of autonomy may yield open, thoughtful responses less likely with older research participants. At the same time, the researcher must be aware of particular vulnerabilities of adolescents. Cognitive and reasoning capacity emerges gradually over the adolescent decade, making younger adolescents less capable than older adolescents of effective reasoning. The researcher can adjust materials to be understandable to the younger adolescent but should also recognize that inexperience could increase anxiety or emotionality about an issue not problematic to an older adolescent or adult. Making clear the right of the adolescent to refuse to discuss particular issues usually permits more honest responses, and increases the likelihood of consent to research or parts of research. Especially stressful circumstances may cause degradation of reasoning capacity suggesting that the researcher needs to assess whether the adolescent is able to make a wise decision about participation, as well as about particular responses. The researcher can usually identify ways to alleviate stress in the study situation and should take all steps necessary to obtain both informed consent and valid responses. Existing research provides clear evidence that most adolescents, at least past age 14 or 15 years, are able to function as well as adults research participants under most circumstances. With younger adolescents and under stressful situations, the researcher can find ways to minimize risk from research and increase the likelihood of valid responses.

Social changes among youth: the United States experience.

The tremendous increase in research on adolescence over the past 20 years, and especially the last decade, has produced a great deal of knowledge about adolescent development and the development of problems during adolescence. This new knowledge should lead to more effective interventions. Although more research is needed on basic developmental processes and context influences, this is especially the case in the area of effective interventions. The next decade may bring significant new knowledge that will dramatically improve the lives of young people in the United States. This is desperately needed as the current status of youth must change.

Prevention of high-risk behaviors in adolescent women.

PURPOSE: To better delineate the impact of health risk behaviors on adolescent women's current and future health and development. METHOD: The Commonwealth Fund Survey of Adolescent Health, a national survey of adolescents in Grades 5-12 designed to better understand their health and health care needs, was used as the basis for this study. Survey data were collected in 1997 from a total of 6730 adolescents (3568 females, 3162 males). Areas examined include smoking, drinking, use of other drugs, violence, safety, reproductive risks, and the prevention of risk behaviors in adolescent women. RESULTS: Adolescent women are almost equally likely to smoke, drink, and engage in other substance use as their male counterparts, but with increased health risks. Different motivations for engaging in risk behavior also are evident. Adolescent women are also more likely than adolescent men to experience physical abuse, and they are twice as likely to be sexually abused. CONCLUSIONS: Effective prevention programs need to recognize that the motivations for engaging in risk behaviors may differ by gender. Developmental awareness, proper assessment, and pivotal institutions can provide and shape what is needed for healthy development.

Adolescent development and the emergence of sexuality.

Adolescence is a time of significant opportunity and significant challenge. Challenges can be difficult for some adolescents, which may result in problems that are expressed as affective disturbances or by the adolescent's participation in risk-taking behaviors. This review emphasizes the changes in biopsychosocial development during adolescence. We specifically address aspects of individual change during the adolescent decade (e.g., biological, cognitive, psychosocial, and sexual development) as well as the effects of context on normal development and responses to challenges during this period. Predispositions or vulnerabilities present prior to a developmental transition may be exacerbated by the transition. Adolescents can become healthy adults with the encouragement to develop gradually by limiting the simultaneous changes they experience, where possible, and by supporting healthy development through developmentally appropriate activities and supportive relationships with adults and peers.

[Pyometra without accompanying malignant uterine disease]. / Pyometra uden ledsagende malign lidelse i uterus.

Twenty-two cases of non-malignant pyometra which were observed during a period of 15 years are described. 22% were recurrences. All of the women were postmenopausal with discharge and haemorrhage as the commonest symptoms. Pyrexia was rare. Pyometra cannot be excluded or diagnosed by means of gynaecological examination. In cases of suspected pyometra, thorough cervical dilatation and curettage are recommended. Antibiotics should only be administered if there is evidence of invasive infection, in the form of pyrexia, generalised malaise or altered laboratory parameters. In cases such as these, preparations which are effective for aerobic and also anaerobic bacteria should be employed. Follow-up control every six months is recommended on account of the great tendency to recur.

[Granulosa cell tumor. A 30-year material from a central hospital]. / Granulosacelletumor. Et 30-års materiale fra et centralsygehus.

During a 30-years period seventeen women were correctly diagnosed as having a granulosa cell tumour. Two died of the tumour, while six women died of other causes. No pathological features correlated to prognosis. A conservative surgical approach to preserve fertility is not recommended; of the three fertile women in our group one died of the disease and another one had two relapses within three years. Eleven tumours showed evidence of increased oestradiol production, and this proved useful as a tumour marker. Follow up is rarely performed unless relapse occurs.

Chorioamniontis in preterm delivery is associated with degradation of decorin and biglycan and depletion of hyaluronan in fetal membranes.

OBJECTIVE: The proteoglycan decorin stabilizes collagen whereas biglycan and hyaluronan disrupt well-organized collagen. The aim was to determine the concentrations of these constituents in fetal membranes in relation to gestational age, preterm labour, PPROM and chorioamnionitis. STUDY DESIGN: Preterm fetal membranes (24-34 weeks gestation) were obtained from elective caesarean deliveries (N = 4), from PPROM (N = 14), and from preterm labour (N = 14). Term fetal membranes from elective caesarean deliveries (N = 9) and spontaneous vaginal deliveries (N = 11) were used for comparison. Chorioamnionitis was assessed histologically. The proteoglycans were analysed using alcian blue precipitation, SDS-PAGE and immunostaining. Hyaluronan was estimated by a radioimmunoassay. RESULTS: Preterm amniotic membranes with chorioamnionitis displayed a 8-fold decrease in hyaluronan concentration as well as a pronounced (88%) degradation of decorin and biglycan (p < 0.05). The amnion from preterm elective caesarean sections had higher decorin (3.2 vs. 1.7 µg/mg, p < 0.05) and lower biglycan (0.4 vs. 1.0 µg/mg, p < 0.05) concentrations as compared to similar term amnion (p < 0.05), whereas the hyaluronan concentrations were not associated with gestational age. Also the chorio-decidua from preterm caesarean sections had higher decorin concentrations (1.8 vs. 1.0 µg/mg, p < 0.05) whereas the biglycan concentration was unchanged. Labour (term as well as preterm) was characterized by increased hyaluronan and biglycan concentrations in the amnion (not statistically significant). CONCLUSION: The biglycan/decorin balance increases during third trimester of pregnancy and during active labour. This relation might contribute to mechanical weakening of the membranes. Chorioamnionitis induces dramatic degradation of both proteoglycans and hyaluronan, which can explain the decreased biomechanical strength.

Infusion with the antioxidant N-acetylcysteine attenuates early adaptive responses to exercise in human skeletal muscle.

AIM: Production of reactive oxygen species (ROS) in skeletal muscle is markedly increased during exercise and may be essential for exercise adaptation. We, therefore, investigated the effects of infusion with the antioxidant N-acetylcysteine (NAC) on exercise-induced activation of signalling pathways and genes involved in exercise adaptation in human skeletal muscle. METHODS: Subjects completed two exercise tests, 7 days apart, with saline (control, CON) or NAC infusion before and during exercise. Exercise tests comprised of cycling at 71% VO(2peak) for 45 min, and then 92% VO(2peak) to fatigue, with vastus lateralis biopsies at pre-infusion, after 45-min cycling and at fatigue. RESULTS: Analysis was conducted on the mitogen-activated protein kinase signalling pathways, demonstrating that NAC infusion blocked the exercise-induced increase in JNK phosphorylation, but not ERK1/2, or p38 MAPK. Nuclear factor-κB p65 phosphorylation was unaffected by exercise; however, it was reduced in NAC at fatigue by 14% (P < 0.05) compared with pre-infusion. Analysis of exercise and/or ROS-sensitive genes demonstrated that exercise-induced mRNA expression is ROS dependent of MnSOD, but not PGC-1α, interleukin-6, monocyte chemotactic protein-1, or heat-shock protein 70. CONCLUSION: These results suggest that inhibition of ROS attenuates some skeletal muscle cell signalling pathways and gene expression involved in adaptations to exercise.