How a group-based occupational therapy program works in woman with fibromyalgia: A process evaluation of the ADAPT program.

BACKGROUND: The ADAPT Program have improved activities of daily living (ADL) in women with fibromyalgia. To understand the functioning of the program, it is relevant to evaluate how program theory components are linked to outcomes (mechanisms) and how the randomised controlled trial (RCT) context, influenced delivery and outcomes. OBJECTIVE: To evaluate ADAPT in terms of dose, mechanisms of change and contextual factors. MATERIAL/METHODS: Dose was recorded on the n = 21 participants receiving ADAPT in the IMPROvE trial (NCT01352052). A subsample of n = 16 attended one of three 2-hour focusgroups, evaluating mechanisms of change and contextual factors. Interview questions explored participants' interaction with four program components, i.e. how the 'client-centred approach', 'group-based peer-exchange format', 'teaching-learning strategies' and 'long-term program format' triggered mechanisms facilitating/hindering outcomes. Moreover, how randomisation procedures influenced delivery and outcomes. RESULTS: Attending a long-term educational peer-exchange program, in which participants experienced met by a health professional that legitimised difficulties, facilitated participants knowledge, insights and motivation for changing habits. With time and support, participants experienced increased acceptance of their situation and began to implement more effective ways to perform ADL tasks. CONCLUSIONS/SIGNIFICANCE: Results support previous findings of improved ADL ability post-ADAPT and provide initial evidence to support the ADAPT Program theory.

Quality of ADL task performance in persons with schizophrenia: Looking beyond independence.

BACKGROUND: Persons with schizophrenia may experience decreased ability to perform activities of daily living (ADL) indicated by need for assistance in everyday life. Others are independent, but their quality of ADL task performance in terms of effort and efficiency may still be impacted. AIMS/OBJECTIVES: The overall purpose of this study was to explore the quality of ADL task performance in subgroups with schizophrenia (independent/needing assistance). MATERIALS AND METHODS: Participants were in- and outpatients at a Psychiatric Hospital diagnosed with schizophrenia (n = 83). Their quality of ADL task performance was evaluated using the Assessment of Motor and Process Skills (AMPS). Evaluations were conducted at the hospital. Two subgroups (A: independent and B: needing assistance) were created based on AMPS ADL ability measures. RESULTS: The majority in both subgroups had AMPS ADL ability measures within the risk zones. Further, the majority in subgroup A had ADL ability measures within age expectations but below mean for well persons of the same age. Both ineffective motor and process skills were identified in both subgroups. CONCLUSIONS/SIGNIFICANCE: Occupational therapy is indicated for persons with schizophrenia, both for independent persons and for persons needing assistance. This is to prevent decline in or to enhance ADL ability.

The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial.

BACKGROUND: Depression following acute coronary syndrome is prevalent and associated with increased mortality and morbidity. Melatonin may function as a primary prophylactic antidepressant substance and alleviate depressive symptoms. The study was undertaken to determine if melatonin administered following an acute coronary syndrome (ACS) could prevent development of depression. METHODS: The study was a double-blinded, placebo-controlled, multicenter, randomized clinical trial performed in five primary care cardiology departments at Zealand, Denmark. Included patients were adults patients, free of depression at baseline, included at the latest 4 weeks after acute coronary syndrome. Twenty-five mg melatonin or placebo was administered 1 h before participants' bedtime for 12 weeks. The primary outcome is Major Depression Inventory (MDI) measured every two weeks throughout the trial. Incidence of depression was apriori defined as MDI score ≥ 21 during the trial. Reported exploratory outcomes were patterns of dropout and safety outcomes. RESULTS: 1220 patients were screened and 252 participants were randomized in a 1:1 ratio. Baseline MDI score in the melatonin and placebo group were, respectively, 6.18 (CI 5.32-7.05) and 5.98 (CI 5.19-6.77). No significant intergroup differences were found during the study in the intention-to-treat analysis or per-protocol analysis. Cumulative events of depressive episodes during the 12 weeks were six in the melatonin group and four in the placebo group. A significant drop in depressive symptoms were present throughout the study period. No intergroup differences were present in dropouts or adverse events. CONCLUSIONS: Melatonin showed no prophylactic antidepressant effect following acute coronary syndrome. The non-significant results might be due to a type II error or melatonin might not be able to prevent development of depressive symptoms following ACS.

A cross-continental analysis of weight gain, psychiatric diagnoses and medication use during inpatient psychiatric treatment. The international study on physical illness in mentally ill.

Weight gain among psychiatric inpatients is a widespread phenomenon. This change in body mass index (BMI) can be caused by several factors. Based on recent research, we assume the following factors are related to weight gain during psychiatric inpatient treatment: psychiatric medication, psychiatric diagnosis, sex, age, weight on admission and geographic region of treatment. 876 of originally recruited 2328 patients met the criteria for our analysis. Patients were recruited and examined in mental health care centres in Nigeria (N = 265), Japan (N = 145) and Western-Europe (Denmark, Germany and Switzerland; N = 466). There was a significant effect of psychiatric medication, psychiatric diagnoses and geographic region, but not age and sex, on BMI changes. Geographic region had a significant effect on BMI change, with Nigerian patients gaining significantly more weight than Japanese and Western European patients. Moreover, geographic region influenced the type of psychiatric medication prescribed and the psychiatric diagnoses. The diagnoses and psychiatric medication prescribed had a significant effect on BMI change. In conclusion, we consider weight gain as a multifactorial phenomenon that is influenced by several factors. One can discuss a number of explanations for our findings, such as different clinical practices in the geographical regions (prescribing or admission strategies and access-to-care aspects), as well as socio-economic and cultural differences.

A genotype-first approach identifies an intellectual disability-overweight syndrome caused by PHIP haploinsufficiency.

Genotype-first combined with reverse phenotyping has shown to be a powerful tool in human genetics, especially in the era of next generation sequencing. This combines the identification of individuals with mutations in the same gene and linking these to consistent (endo)phenotypes to establish disease causality. We have performed a MIP (molecular inversion probe)-based targeted re-sequencing study in 3,275 individuals with intellectual disability (ID) to facilitate a genotype-first approach for 24 genes previously implicated in ID.Combining our data with data from a publicly available database, we confirmed 11 of these 24 genes to be relevant for ID. Amongst these, PHIP was shown to have an enrichment of disruptive mutations in the individuals with ID (5 out of 3,275). Through international collaboration, we identified a total of 23 individuals with PHIP mutations and elucidated the associated phenotype. Remarkably, all 23 individuals had developmental delay/ID and the majority were overweight or obese. Other features comprised behavioral problems (hyperactivity, aggression, features of autism and/or mood disorder) and dysmorphisms (full eyebrows and/or synophrys, upturned nose, large ears and tapering fingers). Interestingly, PHIP encodes two protein-isoforms, PHIP/DCAF14 and NDRP, each involved in neurodevelopmental processes, including E3 ubiquitination and neuronal differentiation. Detailed genotype-phenotype analysis points towards haploinsufficiency of PHIP/DCAF14, and not NDRP, as the underlying cause of the phenotype.Thus, we demonstrated the use of large scale re-sequencing by MIPs, followed by reverse phenotyping, as a constructive approach to verify candidate disease genes and identify novel syndromes, highlighted by PHIP haploinsufficiency causing an ID-overweight syndrome.

Trends in population blood pressure and determinant factors for population blood pressure.

Strategies to reduce the burden of blood pressure attributable diseases require knowledge of secular trend in PBP and its determinants. The issues were investigated in the Copenhagen City Heart Study. The design of CCHS is a repeated measures study. Such designs are uniquely suited to studying changes of an outcome and what risk factors may be associated with that outcome. Repeated measures studies are very well suited for trend analysis by using mixed effect analyses. SBP decreased about 2 mmHg in 25 years. The risk factors age, gender and BMI were found valid as determinant factors for secular trends in SBP. In addition, the following factors were identified: household income and the interactions ''gender*age'' and ''survey*age''. The interaction ''gender*age'' stated that the difference between SBP in the two genders was great in the young individuals and diminished by age. The interaction ''survey*age'' stated that SBP in the young individuals decreased more with survey than SBP in the older individuals. Thus, the 20 years old subjects in survey 2, 3 and 4 have lower SBP than the 20 years old subjects in preceding surveys. The slopes were less steep in higher ages. In the group of elderly and old subjects the trend is partly explained by treatment bias because more and more subjects leave the untreated group and start treatment. The factor ''household income'' was significant only in the female population and stated that high-income women had lower SBP and a more beneficial secular trend in SBP than low-income women. Marital status, self-reported physical exercise and alcohol intake were not significant factors. A number of factors, that are interesting in relation to SBP, were not included in the CCHS and therefore not investigated. Among them are salt intake, childhood factors, genetic factors and the DASH diet. A survival study was performed to investigate the mortality rate in relation to SBP changes during the observation period. A Cox regression analysis was used in this study. The survival study demonstrated that SBP was a significant variable in survival models for all age groups. There was a decrease in mortality rate in young to middle-aged individuals. The mortality rate that is associated with a particular value of SBP did not change. Thus, it was concluded that SBP was as dangerous as it has always been and that the reduction in mortality rate was most pronounced in the age classes that also experienced the greatest reduction in blood pressure. During the observation period the number of treated individuals in the population increased from 6.5% to 18.1%. About 50% of the population was hypertensive (SBP ≥ 140 mmHg or treated with antihypertensive medication). The value of SBPtreated was used as an indicator for hypertension control in the treated population. Hypertension control is a collection of topics that includes guidelines, available medicine, physicians attitude towards hypertension treatment, systematic control, patient awareness and patient compliance. The analysis of trends in SPB in treated hypertensives showed that SBPtreated decreased 9.2 mmHg in 25 years. The result may be ascribed to improvements in treatment but may also be caused by a change in start-to-treat practice: If hypertensives start treatment at an increasingly lower SBPthreshold then SBPtreated will decrease without improvements in treatment. Therefore the start-to-treat practice was evaluated by SBPthreshold. A change in SBPthreshold was not observed. Thus, the 9.2 mmHg decrease in SBPtreated may represent improvements in treatment. ''Age'' was a significant factor for SBPtreated. This result demonstrated that elderly and old individuals were treated less successful than young and middle-aged individuals. Subjects diagnosed with ischemic heart disease constitute a group with a more advantageous slope than subjects with other diagnoses (stroke, IHD in combination with stroke, and hypertension alone). Self-reported physical exercise, gender, alcohol intake, household income and family structure were not significant as variables in the decreasing SBP among treated hypertensives. Thus, the papers in this thesis described SBP trends in the untreated and in the treated part of a population. Different patient-related factors were identified as determinant factors for trends in the two groups. The determinant factors are the explanatory variables most associated with trends in SBP. The determinant factors were different for the two groups (except for age).

The effect of MElatonin on Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome (MEDACIS): study protocol for a randomized controlled trial.

BACKGROUND: Depression following acute coronary syndrome (ACS) constitutes a serious and debilitating problem. Approximately one in five patients will develop significant depression following ACS and less severe depressive symptoms are even more frequent. Furthermore, anxiety symptoms and sleep-wake disturbances are frequent. The objective of the MEDACIS trial is to investigate whether prophylactic treatment with melatonin has a preventive effect on depression, depressive and anxiety symptoms, sleep, and circadian disturbances following ACS. METHODS/DESIGN: "The effect of MElatonin and Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome" trial (MEDACIS) is a multicenter, double-blinded, placebo-controlled, randomized clinical trial. A total of 240 patients with ACS and no depressive symptoms will be included in the trial for treatment with either 25 mg melatonin or placebo for a 12-week period. Development and severity of depressive symptoms will be evaluated using Major Depression Inventory every 2 weeks with the purpose of investigating the potential preventive effect of melatonin on depressive symptoms. DISCUSSION: Previously, only selective serotonin reuptake inhibitors (SSRIs) have been investigated in a primary preventive setup in patients following ACS. However, SSRIs are associated with several side effects. An ideal intervention would constitute the highest degree of prevention of depressive symptoms with the lowest risk of side effects. In this regard, melatonin may have advantages due to its low toxicity as well as its proven anxiolytic and hypnotic effects. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02451293 . Registered on 12 May 2015. EudraCT nr. 2015-002116-32.

The Danish Cardiac Rehabilitation Database.

AIM OF DATABASE: The Danish Cardiac Rehabilitation Database (DHRD) aims to improve the quality of cardiac rehabilitation (CR) to the benefit of patients with coronary heart disease (CHD). STUDY POPULATION: Hospitalized patients with CHD with stenosis on coronary angiography treated with percutaneous coronary intervention, coronary artery bypass grafting, or medication alone. Reporting is mandatory for all hospitals in Denmark delivering CR. The database was initially implemented in 2013 and was fully running from August 14, 2015, thus comprising data at a patient level from the latter date onward. MAIN VARIABLES: Patient-level data are registered by clinicians at the time of entry to CR directly into an online system with simultaneous linkage to other central patient registers. Follow-up data are entered after 6 months. The main variables collected are related to key outcome and performance indicators of CR: referral and adherence, lifestyle, patient-related outcome measures, risk factor control, and medication. Program-level online data are collected every third year. DESCRIPTIVE DATA: Based on administrative data, approximately 14,000 patients with CHD are hospitalized at 35 hospitals annually, with 75% receiving one or more outpatient rehabilitation services by 2015. The database has not yet been running for a full year, which explains the use of approximations. CONCLUSION: The DHRD is an online, national quality improvement database on CR, aimed at patients with CHD. Mandatory registration of data at both patient level as well as program level is done on the database. DHRD aims to systematically monitor the quality of CR over time, in order to improve the quality of CR throughout Denmark to benefit patients.

On the transition from a nurse-led hypertension clinic to hypertension control in primary care: identifying barriers to and factors acting against continuous hypertension control.

Many hypertensive patients are not treated to target and hence do not benefit fully from the blood pressure-related improvements in cardiovascular health. Hypertensive patients who had primarily been treated to a target goal in a nurse-led hypertension clinic were re-examined to evaluate whether their target goal blood pressure was maintained after their discharge from the hypertension clinic for further control in primary care, and to evaluate potential barriers to and factors acting against continuous hypertension control. The median observation time was 3.6 years (range 3 months to 7.9 years). Only 45.2% of the patients were well controlled at the time of re-examination. No patient-related factors (age, body mass index, gender, attitudes towards medication) predicted the outcome. Two factors were significant in the reduction in continuous hypertension control: the cooperation between the patient and health personnel and the shared commitment towards the target goal were discontinued; and many patients did not make control visits to the general practitioner's office. In conclusion, maintained strict control of hypertension requires both continued close collaboration between the patient and health personnel, with an emphasis on treatment goals, and systematic control visits.

Where are patients who have co-occurring mental and physical diseases located?

BACKGROUND: Patients with a psychiatric illness have a higher prevalence of physical diseases and thus a higher morbidity and mortality. AIM: The main aim was to investigate where patients with co-occurring physical diseases and mental disorders (psychotic spectrum or mood) in the health and social service system are identified most frequently before admission into psychiatry. The second aim was to compare the differences in the treatment routes taken by the patients before entry into psychiatric services in all the participating countries (Denmark, Germany, Japan, Nigeria and Switzerland). METHODOLOGY: On admission to a psychiatric service, patients diagnosed with schizophrenia, schizotypal or delusional disorders (International Classification of Diseases-10 (ICD-10) group F2) or mood (affective) disorders (ICD-10 group F3) and a co-morbid physical condition (cardiovascular disease, diabetes mellitus and overweight) were asked with which institutions or persons they had been in contact with in the previous 6 months. RESULTS: Patients from Denmark, Germany and Switzerland with mental disorders had almost the same contact pattern. Their primary contact was to public or private psychiatry, with a contact percentage of 46%-91%; in addition, general practice was a common contact, with a margin of 41%-93%. Similar tendencies are seen in Japan despite the small sample size. With regard to general practice, this is also the case with Nigerian patients. However, religious guidance or healing was rarely sought by patients in Europe and Japan, while in Nigeria about 80% of patients with mental disorders had contacted this type of service. CONCLUSION: Promoting prophylactic work between psychiatry and the general practice sector may be beneficial in diminishing physical conditions such as cardiovascular disease, diabetes mellitus and overweight in patients with mental disorders in European countries and Japan. In Nigeria (a low-to-middle-income country), religious guides or healers, along with general practitioners, are the most frequently contacted, and they therefore seem to be the most obvious partner to collaborate with.

Gram-positive siderophore-shuttle with iron-exchange from Fe-siderophore to apo-siderophore by Bacillus cereus YxeB.

Small molecule iron-chelators, siderophores, are very important in facilitating the acquisition of Fe(III), an essential element for pathogenic bacteria. Many Gram-negative outer-membrane transporters and Gram-positive lipoprotein siderophore-binding proteins have been characterized, and the binding ability of outer-membrane transporters and siderophore-binding proteins for Fe-siderophores has been determined. However, there is little information regarding the binding ability of these proteins for apo-siderophores, the iron-free chelators. Here we report that Bacillus cereus YxeB facilitates iron-exchange from Fe-siderophore to apo-siderophore bound to the protein, the first Gram-positive siderophore-shuttle system. YxeB binds ferrioxamine B (FO, Fe-siderophore)/desferrioxamine B (DFO, apo-siderophore) in vitro. Disc-diffusion assays and growth assays using the yxeB mutant reveal that YxeB is responsible for importing the FO. Cr-DFO (a FO analog) is bound by YxeB in vitro and B. cereus imports or binds Cr-DFO in vivo. In vivo uptake assays using Cr-DFO and FO and growth assays using DFO and Cr-DFO show that B. cereus selectively imports and uses FO when DFO is present. Moreover, in vitro competition assays using Cr-DFO and FO clearly demonstrate that YxeB binds only FO, not Cr-DFO, when DFO is bound to the protein. Iron-exchange from FO to DFO bound to YxeB must occur when DFO is initially bound by YxeB. Because the metal exchange rate is generally first order in replacement ligand concentration, protein binding of the apo-siderophore acts to dramatically enhance the iron exchange rate, a key component of the Gram-positive siderophore-shuttle mechanism.

Gender difference and economic gradients in the secular trend of population systolic blood pressure.

UNLABELLED: To a large extent population blood pressure (PBP) affects morbidity and mortality in the society. Reports indicated that PBP decreased in many western countries. The associations between the main cardiovascular risk factors and the changing PBP have been described. The aim of this study was to investigate association between income factors and trends in population BP and hypertension. Copenhagen City Heart Study is a prospective longitudinal epidemiological study on almost 20000 individuals through four surveys from 1976 to 2003. The BP measurement was fully standardised. Questionnaires on household income and CV risk factors were completed by the participants. After adjustment for cardiovascular risk factors there were no significant differences in systolic BP (SBP) trend associated to income among men. Among women, however, there was a reverse relationship between SBP and income. In addition, there was a trend towards a lowering of risk-factor adjusted SBP in the high income women with time. The mechanism that lies behind the associations between trend in SBP and income is not known but data suggest that poor lifestyle may explain some of the differences. The treated hypertensives are treated without income associated treatment differences. IN CONCLUSION: Women in higher income groups have lower SBP than women in low-income groups and the gap between SBP in high-income women and low-income women increased with time. There were no significant differences in SBP-trend associated to income among men. Results in treating hypertension did not differ between the income groups.

SvSXP: a Strongylus vulgaris antigen with potential for prepatent diagnosis.

BACKGROUND: Strongyle parasites are ubiquitous in grazing horses. Strongylus vulgaris, the most pathogenic of the large strongyles, is known for its extensive migration in the mesenteric arterial system. The lifecycle of S. vulgaris is characterised by a long prepatent period where the migrating larvae are virtually undetectable as there currently is no test available for diagnosing prepatent S. vulgaris infection. Presence of S. vulgaris larvae in the arterial system causes endarteritis and thrombosis with a risk of non-strangulating intestinal infarctions. Emergence of anthelmintic resistance among cyathostomins has led to recommendations of reduced treatment intensity by targeting horses that exceed a predetermined strongyle faecal egg count threshold. One study suggests an apparent increase in prevalence of S. vulgaris on farms where reduced anthelmintic treatment intensity has been implemented. These issues highlight the need for an accurate and reliable assay for diagnosing prepatent S. vulgaris infection. METHODS: Immunoscreening of a larval S. vulgaris cDNA library using hyperimmune serum raised against S. vulgaris excretory/secretory antigens was performed to identify potential diagnostic antigens. Immunoreactive clones were sequenced, one potential antigen was characterised, expressed as a recombinant protein, initially evaluated by western blot (WB) analysis, the diagnostic potential of the IgG subclasses was evaluated by ELISA, and the diagnostic accuracy evaluated using serum from 102 horses with known S. vulgaris infection status. RESULTS: The clone expressing the potential antigen encoded a S. vulgaris SXP/RAL2 homologue. The recombinant protein, rSvSXP, was shown to be a potential diagnostic antigen by WB analysis, and a target of serum IgGa, IgG(T) and total IgG in naturally infected horses, with IgG(T) antibodies being the most reliable indicator of S. vulgaris infection in horses. Evaluation of diagnostic accuracy of the ELISA resulted in a sensitivity of 73.3%, a specificity of 81.0%, a diagnostic odds ratio of 11.69; a positive likelihood ratio (LR) of 3.85 and a negative LR was 0.33. The area under the ROC curve was 0.820. CONCLUSION: IgG(T) antibodies to recombinant SvSXP show potential for use as an antigen for prepatent diagnosis of migrating stages of S. vulgaris with moderate to good diagnostic accuracy.

Cultural diversity in physical diseases among patients with mental illnesses.

OBJECTIVE: People with psychiatric diseases have a severely increased risk for physical morbidity and premature death from physical diseases. The aims of the study were to investigate the occurrence of cardiovascular diseases (CVD), diabetes (DM) and obesity in schizophrenia and depression in three different geographical areas - Asia (Japan), Africa (Nigeria) and Western Europe (Switzerland, Germany and Denmark) - and to search for possible transcultural differences in these correlations, which would also reflect the differences between low-income areas in Africa (Nigeria) and high-income areas in Europe and Japan. METHOD: Patients with International Classification of Diseases (ICD-10) F2 diseases (schizophrenia spectrum disorders) and F3 diseases (affective disorders) admitted to one Nigerian, one Japanese, two Swiss, two German and six Danish centres during 1 year were included. Physical diseases in accordance with ICD-10 were also registered. Psychiatric and physical comorbidity were calculated and standardized rate ratio incidences of background populations were our primary measures. RESULTS: Incidence rate ratios were increased for both CVD, DM and overweight in both F2 and F3 in all cultures (Western Europe, Nigeria and Japan) within the same ranges (however, the Japanese results should be interpreted conservatively owing to the limited sample size). Overweight among the mentally ill were marked in Nigeria. A parallelism of the incidence of overweight, CVD and diabetes with the occurrence in background populations was seen and was most marked in overweight. CONCLUSIONS: Overweight, CVD and DM were increased in schizophrenia spectrum disorders and affective disorders in all three cultures investigated (Western Europe, Nigeria and Japan). Lifestyle diseases were also seen in Nigeria and Japan. The results from this study indicate that cultural background might be seen as an important factor in dealing with lifestyle diseases among people with a severe mental illness, as it is in the general population.

Bacillus cereus iron uptake protein fishes out an unstable ferric citrate trimer.

Citrate is a common biomolecule that chelates Fe(III). Many bacteria and plants use ferric citrate to fulfill their nutritional requirement for iron. Only the Escherichia coli ferric citrate outer-membrane transport protein FecA has been characterized; little is known about other ferric citrate-binding proteins. Here we report a unique siderophore-binding protein from the gram-positive pathogenic bacterium Bacillus cereus that binds multinuclear ferric citrate complexes. We have demonstrated that B. cereus ATCC 14579 takes up (55)Fe radiolabeled ferric citrate and that a protein, BC_3466 [renamed FctC (ferric citrate-binding protein C)], binds ferric citrate. The dissociation constant (K(d)) of FctC at pH 7.4 with ferric citrate (molar ratio 1:50) is 2.6 nM. This is the tightest binding observed of any B. cereus siderophore-binding protein. Nano electrospray ionization-mass spectrometry (nano ESI-MS) analysis of FctC and ferric citrate complexes or citrate alone show that FctC binds diferric di-citrate, and triferric tricitrate, but does not bind ferric di-citrate, ferric monocitrate, or citrate alone. Significantly, the protein selectively binds triferric tricitrate even though this species is naturally present at very low equilibrium concentrations.

Population blood pressure and low to moderate alcohol intake in an untreated population followed over 20years. Copenhagen City heart study.

UNLABELLED: The aim of this study is to evaluate whether a changing population alcohol intake is capable of setting off a shift in the blood pressure distribution in the untreated part of a population. The focus is on subjects with an alcohol intake well below the limits of alcoholism because these subjects make out the majority of the population. The Copenhagen City Heart Study is a prospective longitudinal epidemiological study. The untreated study population was followed over 20years. Specially trained technicians using a blinded sphygmomanometer measured BP once with the subject in the sitting position. The BP measurement was fully standardised and the measurement method was unchanged throughout the observation period. A questionnaire concerning drinking habits was completed by the participants and double-checked by the technicians. The results were a decreasing population systolic BP and an increasing self-reported alcohol intake. The population increase was based on an increasing proportion of light to moderate drinkers. There was no effect of a moderately increasing alcohol intake as a covariate in a multivariate analysis of population systolic BP. CONCLUSION: A moderately increasing population alcohol intake cannot explain the observed changes in population systolic blood pressure.

Decreasing systolic blood pressure and declining mortality rates in an untreated population: results from the Copenhagen City Heart Study.

OBJECTIVE: The aim of the present study was to evaluate developments in 30 years mortality risk that may be associated with developments in population systolic blood pressure (SBP) and to evaluate possible secular trends in BP-associated mortality risk in the untreated population. DESIGN: The Copenhagen City Heart Study is a prospective longitudinal epidemiological study. The present analysis comprised participants from survey 1 (1976-78) and 3 (1991-94). METHODS: BP measurements and other methods were fully standardized and unchanged throughout the observation period. Questionnaires were completed by the participants and double checked by the technicians while they were interviewing the participants. RESULTS: 18 077 persons participated. Age, systolic BP, diastolic BP, cholesterol, BMI, diabetes, gender and habitual physical activity were significant predictors of all-cause death in all age groups. Risk factor adjusted risk for all-cause death was significantly lower in survey 3 compared with survey 1. Among elderly people, there was no development in mortality risk. In the age groups 40-49 years and 50-59 years there were survey differences indicating a significant trend towards longer life expectancy compared with their age-matched counterparts in survey 1. The association between BP and mortality remained unchanged. CONCLUSION: A declining risk of all-cause death was observed in the younger and middle-aged cohorts of the population. The decrease in systolic BP and decline in mortality risk in the same age groups points to a role of systolic BP in age-cohort differentiated improvements of life expectancy. The effect of systolic BP on mortality did not change during follow-up.

Trends and determinant factors for population blood pressure with 25 years of follow-up: results from the Copenhagen City Heart Study.

OBJECTIVE: This study aimed to evaluate within-population trends in population blood pressure (BP) over 25 years and to identify important determinants for a changing population BP. DESIGN: Copenhagen City Heart Study is a prospective longitudinal epidemiological study. The study population (15 508) did not receive antihypertensive therapy. METHODS: The BP measurement was fully standardized and measurement method was unchanged throughout the observation period. A questionnaire concerning drinking habits, smoking, medical therapy and physical exercise was completed by the participants and double checked by the technicians. RESULTS: After an initial increase, population systolic BP (SBP) decreased. All risk factors were tested in the longitudinal model by means of a residual likelihood ratio test. The final model included sex, age and body mass index as significant factors and covariates. Two interactions were included. The first interaction 'age×sex' showed that the sex differences diminished with age. The second interaction 'age×survey' showed that the value of SBP in the young generations decreased survey by survey. SBP in the elderly also decreased survey by survey, but to a lesser degree. Diastolic BP (DBP) increased to a peak value in survey 3 and hereafter decreased. CONCLUSION: SBP decreased. body mass index, sex and age have an effect on population BP. A decreasing trend in SBP among new entrants is responsible for (part of) the observed decrease in population SBP. The decreasing SBP among the elderly was affected by the fact that an increasing number of the elderly population started antihypertensive medication. DBP decreased, but none of the investigated factors affected DBP.

The Rut pathway for pyrimidine degradation: novel chemistry and toxicity problems.

The Rut pathway is composed of seven proteins, all of which are required by Escherichia coli K-12 to grow on uracil as the sole nitrogen source. The RutA and RutB proteins are central: no spontaneous suppressors arise in strains lacking them. RutA works in conjunction with a flavin reductase (RutF or a substitute) to catalyze a novel reaction. It directly cleaves the uracil ring between N-3 and C-4 to yield ureidoacrylate, as established by both nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. Although ureidoacrylate appears to arise by hydrolysis, the requirements for the reaction and the incorporation of (18)O at C-4 from molecular oxygen indicate otherwise. Mass spectrometry revealed the presence of a small amount of product with the mass of ureidoacrylate peracid in reaction mixtures, and we infer that this is the direct product of RutA. In vitro RutB cleaves ureidoacrylate hydrolytically to release 2 mol of ammonium, malonic semialdehyde, and carbon dioxide. Presumably the direct products are aminoacrylate and carbamate, both of which hydrolyze spontaneously. Together with bioinformatic predictions and published crystal structures, genetic and physiological studies allow us to predict functions for RutC, -D, and -E. In vivo we postulate that RutB hydrolyzes the peracid of ureidoacrylate to yield the peracid of aminoacrylate. We speculate that RutC reduces aminoacrylate peracid to aminoacrylate and RutD increases the rate of spontaneous hydrolysis of aminoacrylate. The function of RutE appears to be the same as that of YdfG, which reduces malonic semialdehyde to 3-hydroxypropionic acid. RutG appears to be a uracil transporter.