Work ability 8 years after breast cancer: exploring the role of social support in a nation-wide survey.

INTRODUCTION: As the 5-year survival rate after breast cancer in Norway is 92%, the population of breast cancer survivors (BCSs) is increasing. Knowledge of work ability in this population is scarce. In a population-based cohort of BCSs, we explored work ability 8 years after diagnosis and the association between work ability and social support, and cancer-related variables including late effects and lifestyle factors. METHODS: In 2019, all Norwegian women < 59 years when diagnosed with stage I-III breast cancer in 2011 or 2012, were identified by the Cancer Registry of Norway and invited to participate in a survey on work life experiences. Work ability was assessed using the Work Ability Index (scale 0-10). Factors associated with excellent work ability (score ≥ 9) were identified using univariate and multivariate logistic regression analyses, and adjusted for socioeconomic-, health- and cancer-related variables. RESULTS: Of the 1951 eligible BCSs, 1007 (52.8%) responded. After excluding survivors with relapse (n = 1), missing information on work ability score (n = 49), or work status (n = 31), the final sample comprised 926 BCSs within working age at survey (< 67 years). Mean age at survey was 56 years and 8 years (SD 0.7) had passed since diagnosis. Work ability had been reduced from 8.9 (SD 2.3) at diagnosis to 6.3 (SD 3.1). One in three BCSs reported poor work ability (WAS ≤ 5), and seven out of ten reported that their physical work ability had been reduced due to cancer. Social support from colleagues during cancer therapy was associated with excellent work ability, which was not observed for social support provided by supervisors or the general practitioner. Cognitive impairment and fatigue were inversely associated with work ability. None of the cancer-related variables, including treatment, were associated with work ability 8 years after diagnosis. CONCLUSION: In this population-based sample, one in three BCSs reported poor work ability 8 years after diagnosis. Collegial social support during cancer therapy appears to be a protective factor for sustained work ability, whilst survivors struggling with fatigue and cognitive impairments may represent a particularly vulnerable group for reduced work ability.

Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease.

Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account.

Arteriovenous Fistulae for Haemodialysis: A Systematic Review and Meta-analysis of Efficacy and Safety Outcomes.

BACKGROUND: Arteriovenous fistulae are the currently recommended gold standard vascular access modality for haemodialysis because of their prolonged patency, improved durability, and low risk of infection for those that mature. However, notable disadvantages are observed in terms of protracted maturation time, associated high rates of catheter use, and substantial abandonment rates. The aim of this study was to quantitatively summarize the outcomes of fistula patency, infection, maturation, and abandonment published in the scientific literature. METHODS: This was a systematic review and meta-analyses of studies evaluating fistula outcomes. Literature searches were conducted in multiple databases to identify observational and interventional studies of mean fistula patency rates at 1 year, infection risk, maturation time, and abandonment. Digitisation software was used to simulate individual patient level data from Kaplan-Meier survival plots. RESULTS: Over 8000 studies were reviewed, and from these, 318 studies were included comprising 62,712 accesses. For fistulas the primary unassisted, primary assisted, and secondary patency rates at one year were 64%, 73% and 79% respectively, however not all fistulas reported as patent could be confirmed as being clinically useful for dialysis (i.e. functional patency). For fistulas that were reported as mature, mean time to maturation was 3.5 months, however only 26% of created fistulas were reported as mature at 6 months and 21% of fistulas were abandoned without use. Overall risk of infection in fistula patients was 4.1% and the overall rate per 100 access days was 0.018. CONCLUSIONS: Reported fistula patency rates may overstate their potential clinical utility when time to maturation, maturation rate, abandonment and infection are considered. Protracted maturation times, abandonment and infection all have a significant impact on evaluating the clinical utility of fistula creation. A rigorous and consistent set of outcomes definitions for hemodialysis access are necessary to clarify factors contributing to fistula success and the clinical consequence of fistula failure.

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature.

Hyperargininemia is caused by deficiency of arginase 1, which catalyzes the hydrolysis of L-arginine to urea as the final enzyme in the urea cycle. In contrast to other urea cycle defects, arginase 1 deficiency usually does not cause catastrophic neonatal hyperammonemia but rather presents with progressive neurological symptoms including seizures and spastic paraplegia in the first years of life and hepatic pathology, such as neonatal cholestasis, acute liver failure, or liver fibrosis. Some patients have developed hepatocellular carcinoma. A usually mild or moderate hyperammonemia may occur at any age. The pathogenesis of arginase I deficiency is yet not fully understood. However, the accumulation of L-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. This article provides an update on the first patients ever described, gives an overview of the distinct clinical characteristics, biochemical as well as genetical background and discusses treatment options.

In situ transmission electron microscopy of light-induced photocatalytic reactions.

Transmission electron microscopy (TEM) makes it possible to obtain insight into the structure, composition and reactivity of photocatalysts, which are of fundamental interest for sustainable energy research. Such insight can be used for further material optimization. Here, we combine conventional TEM analysis of photocatalysts with environmental TEM (ETEM) and photoactivation using light. Two novel types of TEM specimen holder that enable in situ illumination are developed to study light-induced phenomena in photoactive materials, systems and photocatalysts at the nanoscale under working conditions. The technological development of the holders is described and two representative photo-induced phenomena are studied: the photodegradation of Cu2O and the photodeposition of Pt onto a GaN:ZnO photocatalyst.

[Endoscopic therapy for leaks in the gastrointestinal tract, the bile ducts and the pancreas]. / Endoskopische Therapie von Leckagen im Gastrointestinaltrakt, an den Gallenwegen und im Pankreas.

Surgery has been the mainstay of therapy in patients with gastrointestinal perforations, leakage or fistulas. New techniques for endoscopic closure of gastrointestinal perforations provide tools for an effective treatment by less invasive procedures. Temporary placement of covered self-expanding stents is an established therapy for oesophageal perforations and anastomotic leaks. Using conventional endoclips small perforations and leaks in the oesophagus and gastrointestinal tract may be closed. With the new over-the-scope-clips a more effective endoscopic full wall closure is possible in the upper gastrointestinal tract and the rectum. Endoscopically guided endoluminal vacuum therapy using polyurethane sponges is an established method for treating rectal leaks and is now increasingly used also in oesophageal leaks. Biliary leakage following endoscopic or surgical interventions is effectively treated with temporary bile stenting in most cases, but closure using metal stents or coiling may be necessary. Pancreatic leaks are a major therapeutic problem and may require multimodal therapies.

Emotional difficulties in seventh grade children in Denmark.

The present study investigates the prevalence of emotional difficulties and quality of life in a sample of 834 children from 56 seventh grade (aged 12-14 years) classes. Data was derived from a study of mental well-being developed by the National Council for Children, Denmark. The sample selection ensured that the children were nationally representative. Data was collected using the Strength and Difficulties Questionnaire (SDQ) and the Health Behaviour in School-aged Children (HBSC). Results indicated that 10.8% of children had concerns regarding emotional difficulties (6.6% definite concern; 4.2% some concern), and that significantly more girls than boys (44 girls and 10 boys) reported this concern. A novel finding was that emotional difficulties were related to children's perception of having low quality of life. Findings furthermore suggested that children's perception of a low home economy, less time spent on leisure activities, and female gender were all associated with emotional difficulties.

Integrin phosphorylation is modulated during the differentiation of F-9 teratocarcinoma stem cells.

The retinoic acid-induced differentiation of F-9 teratocarcinoma cells in monolayer culture is accompanied by the accumulation of fibrillar fibronectin deposits, the appearance of a highly structured actin cytoskeleton, and the redistribution of integrin to apparent sites of substrate contact. We have studied the 140-kD fibronectin receptor during this process and report that although the integrin molecule is present in equivalent amounts before and after differentiation, the level of integrin phosphorylation decreases dramatically as the cells differentiate. This loss of phosphorylation coincides temporally with the observed changes in actin, fibronectin, and integrin organization. The phosphorylation state of integrin thus may mediate developmentally regulated cell-matrix interactions.

Rapid capping in alpha-spectrin-deficient MEL cells from mice afflicted with hereditary hemolytic anemia.

A spectrin-based membrane skeleton is important for the stability and organization of the erythrocyte. To study the role of spectrin in cells that possess complex cytoskeletons, we have generated alpha-spectrin-deficient erythroleukemia cell lines from sph/sph mice. These cells contain beta-spectrin, but lack alpha-spectrin as determined by immunoblot and Northern blot analyses. The effects of alpha-spectrin deficiency are apparent in the cells' irregular shape and fragility in culture. Capping of membrane glycoproteins by fluorescent lectin or antibodies occurs more rapidly in sph/sph than in wild-type erythroleukemia cells, and the caps appear more concentrated. The data support the idea that spectrin plays an important role in organizing membrane structure and limiting the lateral mobility of integral membrane glycoproteins in cells other than mature erythrocytes.

Drosophila beta spectrin functions independently of alpha spectrin to polarize the Na,K ATPase in epithelial cells.

Spectrin has been proposed to function as a sorting machine that concentrates interacting proteins such as the Na,K ATPase within specialized plasma membrane domains of polarized cells. However, little direct evidence to support this model has been obtained. Here we used a genetic approach to directly test the requirement for the beta subunit of the alphabeta spectrin molecule in morphogenesis and function of epithelial cells in Drosophila. beta Spectrin mutations were lethal during late embryonic/early larval development and they produced subtle defects in midgut morphology and stomach acid secretion. The polarized distributions of alphabeta(H) spectrin and ankyrin were not significantly altered in beta spectrin mutants, indicating that the two isoforms of Drosophila spectrin assemble independently of one another, and that ankyrin is upstream of alphabeta spectrin in the spectrin assembly pathway. In contrast, beta spectrin mutations had a striking effect on the basolateral accumulation of the Na,K ATPase. The results establish a role for beta spectrin in determining the subcellular distribution of the Na, K ATPase and, unexpectedly, this role is independent of alpha spectrin.

Atomic-resolution in situ transmission electron microscopy of a promoter of a heterogeneous catalyst.

Insight into the location, state, and function of a promoter in heterogeneous catalysis was obtained through atomic-resolution in situ transmission electron microscopy. In the most active ruthenium catalyst for ammonia synthesis known so far, the barium promoter is shown to be located in two different phases in the catalyst. The increased activity is suggested to be related to a two-dimensional barium-oxygen overlayer on the ruthenium crystals. The possibility for conducting such studies for other reactions could add substantially to our current understanding of heterogeneous catalysis. Heterogeneous catalysis plays an increasingly important role in environmental protection processes, in fuel upgrading, and in providing the majority of the chemical building blocks required by contemporary society. Most heterogeneous catalysts of industrial importance are multicomponent materials that are designed by trial-and-error experimentation. Application of even the most sophisticated physical-chemical characterization techniques is usually not sufficient to obtain a complete understanding of the structure of the active site, the reaction mechanism and kinetics, the structural dynamics, and the specific roles of all catalyst components.

Different dose-dependent correction of MIP-1beta and chitotriosidase during initial enzyme replacement therapy.

In tissue lesions of type I Gaucher patients, characteristic lipid-laden macrophages, 'Gaucher cells', are surrounded by inflammatory phagocytes. Gaucher cells secrete the elevated plasma chitotriosidase. The elevated plasma MIP-1beta in Gaucher patients stems from the phagocytes surrounding the Gaucher cells. Plasma chitotriosidase and MIP-1beta decrease upon successful enzyme replacement therapy (ERT) with mannose-terminated recombinant glucocerebrosidase (alglucerase). Previous histochemical analysis of Gaucher spleens revealed that Gaucher cells express little mannose receptor, in contrast to surrounding phagocytes. We therefore investigated the corrective effects of ERT on plasma MIP-1beta and chitotriosidase in more detail. We also compared effects of one year of treatment with a relatively low dose and a relatively high dose of ERT. A more rapid correction in plasma MIP-1beta, compared to chitotriosidase, was observed in most patients on low-dose ERT. Correction of plasma MIP-1beta and chitotriosidase levels was more pronounced in the higher-dosed patient group. Upon prolonged treatment, differences in the effects of enzyme dose were no longer significant. Normalization of plasma MIP-1beta and chitotriosidase levels was attained in the majority of patients. In conclusion, ERT with mannose-terminated gluocerebrosidase results in prominent corrections of plasma chitotriosidase, a marker of Gaucher cells, and in particular of plasma MIP-1beta, a marker of inflammatory phagocytes. The sharper response in plasma MIP-1beta to ERT is in line with the observation that especially phagocytes surrounding Gaucher cells express mannose-receptors.

Management of non-neuronopathic Gaucher disease with special reference to pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring.

Enzyme replacement was introduced as treatment for non-neuronopathic Gaucher disease more than 15 years ago. To ensure the best use of this costly ultra-orphan agent, a systematic disease management approach has been proposed by an international panel; this includes the development, by consensus, of achievable treatment goals. Here we critically review these goals and monitoring guidelines and incorporate emerging experience of the disease in the therapeutic era, as well as contemporary clinical research. This review makes recommendations related specifically to the management of pregnancy; the appropriate use of splenectomy and bisphosphonate treatment; the relevance of biochemical markers to disease monitoring; and the use of semi-quantitative methods for assessing bone marrow infiltration. In addition, we identify key areas for development, including the requirement for a validated index of disease severity; the need to correlate widely used biomarkers with long-term disease outcomes, and the desirability of establishing agreed standards for monitoring of bone disease particularly in infants and children with Gaucher disease.

Minireview: molecular structure and dynamics of drug targets.

Summary of lectures presented at the Czech and Slovak Pharmacological Meeting, Prague, September 2008.

A fast sol-gel synthesis leading to highly crystalline birnessites under non-hydrothermal conditions.

Manganese oxides from the compound family of layered birnessites have attracted interest for their use as cathode materials in Li-ion batteries, as supercapacitors, and as water oxidation catalysts. Furthermore, birnessites are also excellent precursors for low-temperature syntheses of manganese oxide-based materials such as LiMn2O4 (spinel and hollandite). Most syntheses leading to highly crystalline birnessites either require hydrothermal conditions for extended periods of time ranging from days to months or a high post-treatment temperature (400-500 °C). Here, we present a novel sol-gel synthesis route leading to the formation of highly crystalline birnessites within one hour without the need for any post-treatment to enhance crystallinity. Small birnessite crystals form virtually immediately upon mixing of the reactants, albeit initially of lower crystallinity. The size of the fully developed monoclinic birnessite platelets is in the micrometer-range with a thickness of about 20-50 nm. Under the studied conditions, the presence of Li+, Na+, and K+ is necessary for the formation of well-crystallized birnessites, and the crystal size can be tuned by variation of the synthesis time. This is suggested to be linked to an increase of the Na+ content in the birnessite with increasing synthesis time.

Predicting catalysis: understanding ammonia synthesis from first-principles calculations.

Here, we give a full account of a large collaborative effort toward an atomic-scale understanding of modern industrial ammonia production over ruthenium catalysts. We show that overall rates of ammonia production can be determined by applying various levels of theory (including transition state theory with or without tunneling corrections, and quantum dynamics) to a range of relevant elementary reaction steps, such as N(2) dissociation, H(2) dissociation, and hydrogenation of the intermediate reactants. A complete kinetic model based on the most relevant elementary steps can be established for any given point along an industrial reactor, and the kinetic results can be integrated over the catalyst bed to determine the industrial reactor yield. We find that, given the present uncertainties, the rate of ammonia production is well-determined directly from our atomic-scale calculations. Furthermore, our studies provide new insight into several related fields, for instance, gas-phase and electrochemical ammonia synthesis. The success of predicting the outcome of a catalytic reaction from first-principles calculations supports our point of view that, in the future, theory will be a fully integrated tool in the search for the next generation of catalysts.

ESPEN Guidelines on Enteral Nutrition: Liver disease.

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility to increase or to insure nutrient intake in case of insufficient oral food intake. The present guideline is intended to give evidence-based recommendations for the use of ONS and TF in patients with liver disease (LD). It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. EN by means of ONS is recommended for patients with chronic LD in whom undernutrition is very common. ONS improve nutritional status and survival in severely malnourished patients with alcoholic hepatitis. In patients with cirrhosis, TF improves nutritional status and liver function, reduces the rate of complications and prolongs survival. TF commenced early after liver transplantation can reduce complication rate and cost and is preferable to parenteral nutrition. In acute liver failure TF is feasible and used in the majority of patients.

Childhood adverse life events and parental psychopathology as risk factors for bipolar disorder.

Childhood adverse events are risk factors for later bipolar disorder. We quantified the risks for a later diagnosis of bipolar disorder after exposure to adverse life events in children with and without parental psychopathology. This register-based population cohort study included all persons born in Denmark from 1980 to 1998 (980 554 persons). Adversities before age 15 years were: familial disruption; parental somatic illness; any parental psychopathology; parental labour market exclusion; parental imprisonment; placement in out-of-home care; and parental natural and unnatural death. We calculated risk estimates of each of these eight life events as single exposure and risk estimates for exposure to multiple life events. Main outcome variable was a diagnosis of bipolar disorder after the age of 15 years, analysed with Cox proportional hazard regression. Single exposure to most of the investigated adversities were associated with increased risk for bipolar disorder, exceptions were parental somatic illness and parental natural death. By far the strongest risk factor for bipolar disorder in our study was any mental disorder in the parent (hazard ratio 3.53; 95% confidence interval 2.73-4.53) and the additional effects of life events on bipolar risk were limited. An effect of early adverse life events on bipolar risk later in life was mainly observed in children without parental psychopathology. Our findings do not exclude early-life events as possible risk factors, but challenge the concept of adversities as important independent determinants of bipolar disorder in genetically vulnerable individuals.

Impact of voluntary vs enforced compliance of third-generation cephalosporin use in a teaching hospital.

STUDY OBJECTIVE: The purpose of this study was to assess and compare the impact of voluntary compliance and enforced compliance with institutional guidelines for initiating third-generation cephalosporin therapy. DESIGN: An audit of third-generation cephalosporin use during a 6-month period shortly after ceftriaxone and ceftazidime were added to the hospital formulary already containing cefotaxime was performed. During this period, compliance to institutional guidelines for initiating therapy was voluntary. A follow-up audit during a similar 6-month period was performed to assess compliance with institutional guidelines shortly after an enforcement policy was placed in effect. The results of these two audits were compared to assess usage patterns of these cephalosporins, compliance rates with institutional guidelines for initiating therapy, use of susceptibility testing to guide therapy, effect of use of these drugs on susceptibility patterns within the hospital, and third-generation cephalosporin costs during periods when institutional policy was unenforced and enforced. RESULTS: Only 24.2% of 66 courses of third-generation cephalosporins were initiated in compliance with institutional guidelines during the initial audit period. Susceptibility testing revealed an organism susceptible to a first-generation cephalosporin in 13 courses but in only six instances was a switch to the more narrow-spectrum antibiotic performed. At the time routine susceptibility testing to ceftazidime and ceftriaxone was instituted, 92% of Enterobacter cloacae were sensitive to ceftriaxone and 89% of Pseudomonas aeruginosa were sensitive to ceftazidime. Fifteen months later, when voluntary compliance to institutional policy was terminated, 70% of E cloacae were sensitive to ceftriaxone and 73% of P aeruginosa were sensitive to ceftazidime. During the last 6 months of this period, pharmacy expenditures totaled $50,000. The second audit revealed 85.4% of 48 courses of treatment complied with guidelines for initiating therapy. Since enforcement was instituted, sensitivity of E cloacae to ceftriaxone has risen to 88% and sensitivity of P aeruginosa to ceftazidime has increased to 80%. Pharmacy expenditures decreased to $23,000.

Consequences of crown shortening canine teeth in Greenland sled dogs.

OBJECTIVES: To evaluate the consequences of crown shortening, focusing on the prevalence of pulp exposure and periapical pathology in Greenland sled dogs that had had their canine crowns shortened at an early age. METHODS: Five cadaver heads and 54 sled dogs underwent an oral examination for dental fractures and pulp exposure of canines. All canines were radiographed and evaluated for periapical pathology. RESULTS: The prevalence of canine pulp exposure in 12 (5 heads and 7 dogs) crown shortened dogs was 91 · 7%, and 21 · 3% in 47 not-crown shortened dogs. A significant (P < 0 · 001) risk of pulp exposure of the canines in the crown shortened group compared to the not-crown shortened group was seen with a relative risk of 4 · 3 on a dog basis and a relative risk of 12 · 2 on a tooth basis. In dogs with pulp exposure of canines (n = 51) the prevalence of periapical pathology was 82 · 4%, but only 0 · 8% in dogs without pulp exposure (n = 133) resulting in a significant (relative risk, 109 · 5; P < 0 · 001) risk of periapical pathology in teeth with pulp exposure compared to teeth without pulp exposure. CLINICAL SIGNIFICANCE: The high risk of periapical pathology observed in teeth with pulp exposure confirms that these teeth should not be neglected in affected dogs.