Crude Oil and Its Burnt Residues Induce Metamorphosis in Marine Invertebrates.

Metamorphosis is a critical process in the life cycle of most marine benthic invertebrates, determining their transition from plankton to benthos. It affects dispersal and settlement and therefore decisively influences the dynamics of marine invertebrate populations. An extended period of metamorphic competence is an adaptive feature of numerous invertebrate species that increases the likelihood of finding a habitat suitable for settlement and survival. We found that crude oil and residues of burnt oil rapidly induce metamorphosis in two different marine invertebrate larvae, a previously unknown sublethal effect of oil pollution. When exposed to environmentally realistic oil concentrations, up to 84% of tested echinoderm larvae responded by undergoing metamorphosis. Similarly, up to 87% of gastropod larvae metamorphosed in response to burnt oil residues. This study demonstrates that crude oil and its burned residues can act as metamorphic inducers in marine planktonic larvae, short-circuiting adaptive metamorphic delay. Future studies on molecular pathways and oil-bacteria-metamorphosis interactions are needed to fully understand the direct or indirect mechanisms of oil-induced metamorphosis in marine invertebrates. With 90% of chronic oiling occurring in coastal areas, this previously undescribed impact of crude oil on planktonic larvae may have global implications for marine invertebrate populations and biodiversity.

Effect of environmentally relevant concentrations of potentially toxic microplastic on coastal copepods.

Tire wear particles (TWP) are both abundant and potentially toxic types of microplastic (MP) in the coastal ocean. We tested the effects of TWP type (new tires, old tires, rubber granules from artificial turfs) and concentration (10-10,000 TWP L-1) on feeding, reproduction and fecal pellet production of two common coastal copepods at high (400 µg C L-1) and low (40 µg C L-1) food concentration consisting of a cryptophyte Rhodomonas sp. We did not observe any effect of TWP on copepods at environmentally relevant concentrations of <10 TWP L-1. At TWP concentrations that were >100 times higher than the MP concentrations measured in coastal waters, food concentration, copepod feeding mode, TWP concentration and TWP type interacted to influence copepod feeding and pellet production, while reproduction was unaffected. Our results suggest that TWP at the current measured concentrations in the ocean environment is not likely to be a threat to the common coastal copepods.

Pirouetting pigs: A large non-primate animal model based on unilateral 6-hydroxydopamine lesioning of the nigrostriatal pathway.

INTRODUCTION: The rotating 6-hydroxydopamine (6-OHDA) rat model has long been important when developing new treatment strategies for Parkinson's disease (PD). Similar non-human primate models have been developed for translational research purposes as large animal models are required by regulatory bodies as an intermediate "phase 0" trial step. However, experimental research in non-human primates encounters several economical and regulatory issues, which may be avoided by the alternative use of pigs as a large animal model for experimental brain research. OBJECTIVE: The primary aim of this study was to examine if unilateral injections of 6-OHDA into the Göttingen minipig nigrostriatal pathway would lead to dopaminergic imbalance and rotational behavior similar to the 6-OHDA unilateral symptomatic model of PD created in other species. The secondary aim was to attempt to verify the rotational behavior as a parkinsonian symptom using subthalamic deep brain stimulation (STN-DBS) to minimize the elicited rotational pattern. MATERIALS AND METHODS: Using an MRI-based stereotactic procedure, ten female Göttingen minipigs were injected unilaterally with 6-OHDA in the nigrostriatal pathway. Postoperatively, an MRI was performed, and the animals were injected with amphetamine and apomorphine and observed for rotational behavior. After a survival period of three months the brains were removed and immunohistochemically stained for tyrosine hydroxylase (TH). One week before sacrifice two animals had DBS electrodes unilaterally implanted in the subthalamic nucleus and various stimulation protocols were conducted during amphetamine challenge. RESULTS: As expected most animals rotated towards the side of the lesion when given amphetamine (3.5-4.0 mg/kg), whereas the predicted opposite response to apomorphine were much harder to reproduce. T1- and T2-weighted postoperative MRI could demonstrate the size and the location of the 6-OHDA injection. Postmortem TH-staining of the final two animals receiving a medial and a lateral injection of 25 µL of 6-OHDA (8 µg/µL, injection rate 5 µL/min) into the diencephalic nigrostriatal pathway showed a prominent unilateral decrease in TH-staining of the substantia nigra pars compacta, the ventral tegmental area and the nigrostriatal pathway on the lesioned side. These two animals displayed spontaneous rotational behavior toward the lesioned side for the first 2-3 days postoperatively, and this behavior could later on be reelicited by amphetamine and attenuated by ipsilateral STN-DBS. CONCLUSION: Female Göttingen minipigs are susceptible to unilateral dopaminergic degeneration when properly injected unilaterally with sufficient amounts of 6-OHDA in the nigrostriatal pathway. The location of the 6-OHDA injections and thus the accuracy of the employed stereotaxy can be verified in vivo using MRI postoperatively. The injected minipigs display unilateral parkinsonism with a well-defined rotational response to amphetamine that may be ameliated by STN-DBS performed on the lesioned side. The response to apomorphine was, however, not consistent, illustrating that further work on this promising non-primate large animal model is needed, before it is fully similar to the established 6-OHDA models in other species.

Home Care Providers to the Rescue: A Novel First-Responder Programme.

AIM: To describe the implementation of a novel first-responder programme in which home care providers equipped with automated external defibrillators (AEDs) were dispatched in parallel with existing emergency medical services in the event of a suspected out-of-hospital cardiac arrest (OHCA). METHODS: We evaluated a one-year prospective study that trained home care providers in performing cardiopulmonary resuscitation (CPR) and using an AED in cases of suspected OHCA. Data were collected from cardiac arrest case files, case files from each provider dispatch and a survey among dispatched providers. The study was conducted in a rural district in Denmark. RESULTS: Home care providers were dispatched to 28 of the 60 OHCAs that occurred in the study period. In ten cases the providers arrived before the ambulance service and subsequently performed CPR. AED analysis was executed in three cases and shock was delivered in one case. For 26 of the 28 cases, the cardiac arrest occurred in a private home. Ninety-five per cent of the providers who had been dispatched to a cardiac arrest reported feeling prepared for managing the initial resuscitation, including use of AED. CONCLUSION: Home care providers are suited to act as first-responders in predominantly rural and residential districts. Future follow-up will allow further evaluation of home care provider arrivals and patient survival.

Elevated costs and high one-year mortality in patients with diabetic foot ulcers after surgery.

INTRODUCTION: In Denmark, approximately 300,000 patients have a diabetes mellitus diagnosis. Recently published guidelines emphasise that health-care professionals who are in direct contact with citizens should be aware of the importance of prevention and early detection of diabetic foot ulcers. The objective of this study was to evaluate the mortality, length of hospital stay and economic impact on health care in patients with acute diabetic foot ulcers who were hospitalised in the Department of Orthopaedic Surgery, Aalborg University Hospital, Denmark. METHODS: This was a prospective cohort study including all patients admitted with a diagnosis of acute foot ulcer to the Department of Orthopaedic Surgery, Aalborg, Denmark, from September 2011 to February 2012. RESULTS: A total of 48 patients were referred for surgical treatment of a diabetic foot ulcer. The average age on admission was 64 years (35-87 years). The median length of hospital stay was 17 days (3-150 days), and 14 patients were readmitted within the first year. Within the first year of enrolment, 13 patients died, corresponding to a 36% mortality rate. Based on the Danish Diagnosis-Related Groups rates, the median cost associated with a case in the study population was 133,867 DKK. CONCLUSION: Patients referred for surgical revision of diabetic foot ulcers are often severely ill, and the condition is associated with a high one-year mortality rate. Furthermore, the cost of these cases is considerable. Preventive interventions, early diagnosis and treatment and multidisciplinary interventions ­ before and during hospitalisation ­ should be implemented. FUNDING: not relevant. TRIAL REGISTRATION: The Danish Data Protection Agency (J. No. 2008-58-0028) approved the study.

ALIX and ESCRT-III coordinately control cytokinetic abscission during germline stem cell division in vivo.

Abscission is the final step of cytokinesis that involves the cleavage of the intercellular bridge connecting the two daughter cells. Recent studies have given novel insight into the spatiotemporal regulation and molecular mechanisms controlling abscission in cultured yeast and human cells. The mechanisms of abscission in living metazoan tissues are however not well understood. Here we show that ALIX and the ESCRT-III component Shrub are required for completion of abscission during Drosophila female germline stem cell (fGSC) division. Loss of ALIX or Shrub function in fGSCs leads to delayed abscission and the consequent formation of stem cysts in which chains of daughter cells remain interconnected to the fGSC via midbody rings and fusome. We demonstrate that ALIX and Shrub interact and that they co-localize at midbody rings and midbodies during cytokinetic abscission in fGSCs. Mechanistically, we show that the direct interaction between ALIX and Shrub is required to ensure cytokinesis completion with normal kinetics in fGSCs. We conclude that ALIX and ESCRT-III coordinately control abscission in Drosophila fGSCs and that their complex formation is required for accurate abscission timing in GSCs in vivo.

Work Status and Return to the Workforce after Coronary Artery Bypass Grafting and/or Heart Valve Surgery: A One-Year-Follow Up Study.

Background. Several characteristics appear to be important for estimating the likelihood of reentering the workforce after surgery. The aim of the present study was to describe work status in a two-year time period around the time of cardiac surgery and estimate the probability of returning to the workforce. Methods. We included 681 patients undergoing coronary artery bypass grafting and/or heart valve procedures from 2003 to 2007 in the North Denmark Region. We linked hospital data to data in the DREAM database which holds information of everyone receiving social benefits. Results. At the time of surgery 17.3% were allocated disability pension and 2.3% were allocated a permanent part-time benefit. Being unemployed one year before surgery reduced the likelihood of return to the workforce (RR = 0.74 (0.60-0.92)) whereas unemployment at the time of surgery had no impact on return to the workforce (RR = 0.96 (0.78-1.18)). Sickness absence before surgery reduced the likelihood of return to the workforce. Conclusion. This study found the work status before surgery to be associated with the likelihood of return to the workforce within one year after surgery. Before surgery one-fifth of the population either was allocated disability pension or received a permanent part-time benefit.

Unemployment under the flex job scheme increases the risk of permanent social security benefits.

INTRODUCTION: In Denmark, a flex job scheme was introduced in 1998 in the expectation that more people could remain in the workforce despite a reduced working capacity. The aim of this study was to characterise the group that did not obtain a flex job after having been included in the flex job scheme. MATERIAL AND METHODS: Persons included in the flex job scheme from 1 January 2001 to 30 March 2008 were identified via the Ministry of Employment's DREAM register. Data were linked to Statistics Denmark and The Danish National Patient Registry. Among the individuals who did not obtain employment in a flex job within the first three months, we identified those who did not obtain employment before they were transferred to disability pension or flex benefit. RESULTS: A total of 74,277 persons were included in the flex job scheme. Among these persons 33% received unemployment benefit for more than three months and the rest obtained a flex job within the first three months. Overall, 23% of the unemployment benefit recipients never entered the labour market, but were awarded early retirement pension or flex benefit. This percentage varied among different socio-demographic variables and regions. CONCLUSION: The present study demonstrates that attention should be paid to the flex job scheme, especially for those who do not obtain employment within the first three months. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Modeling gradually changing seasonal variation in count data using state space models: a cohort study of hospitalization rates of stroke in atrial fibrillation patients in Denmark from 1977 to 2011.

BACKGROUND: Seasonal variation in the occurrence of cardiovascular diseases has been recognized for decades. In particular, incidence rates of hospitalization with atrial fibrillation (AF) and stroke have shown to exhibit a seasonal variation. Stroke in AF patients is common and often severe. Obtaining a description of a possible seasonal variation in the occurrence of stroke in AF patients is crucial in clarifying risk factors for developing stroke and initiating prophylaxis treatment. METHODS: Using a dynamic generalized linear model we were able to model gradually changing seasonal variation in hospitalization rates of stroke in AF patients from 1977 to 2011. The study population consisted of all Danes registered with a diagnosis of AF comprising 270,017 subjects. During follow-up, 39,632 subjects were hospitalized with stroke. Incidence rates of stroke in AF patients were analyzed assuming the seasonal variation being a sum of two sinusoids and a local linear trend. RESULTS: The results showed that the peak-to-trough ratio decreased from 1.25 to 1.16 during the study period, and that the times of year for peak and trough changed slightly. CONCLUSION: The present study indicates that using dynamic generalized linear models provides a flexible modeling approach for studying changes in seasonal variation of stroke in AF patients and yields plausible results.

Seasonality, incidence and prognosis in atrial fibrillation and stroke in Denmark and New Zealand.

OBJECTIVES: There are relatively few large studies of seasonal variation in the occurrence of stroke in patients with atrial fibrillation (AF). We investigated the seasonal variation in incidence rates of hospitalisation with stroke in patients from Denmark and New Zealand. DESIGN: Cohort study. SETTING: Nationwide hospital discharge data from Denmark and New Zealand. PARTICIPANTS: 243 381 (median age 75) subjects having a first-time hospitalisation with AF in Denmark and 51 480 (median age 76) subjects in New Zealand constituted the study population. Subjects with previous hospitalisation with stroke were excluded. PRIMARY AND SECONDARY EFFECT MEASURES: Peak-to-trough ratio of the seasonal variation in incidence rates of stroke in AF patients adjusted for an overall trend was primary effect measure and was assessed using a log-linear Poisson regression model. Secondary effect measures were incidence rate ratios of AF and 30-day case fatality for stroke patients. RESULTS: Incidence rates of AF per 1000 person-years in Denmark increased by 5.4% (95% CI 5.3% to 5.7%) for patients aged <65 and 5% (95% CI 4.9% to 5.1%) for patients aged ≥65, whereas the increase was 0.2% (95% CI -0.2% to 0.6%) for patients aged <65 and 2.6% (95% CI 2.4% to 2.8%) for patients aged ≥65 in New Zealand. In Denmark 36 088 subjects were hospitalised with stroke, and 7518 subjects in New Zealand, both showing peaks during winter with peak-to-trough ratios of 1.22 and 1.27, respectively and a decreasing trend. The 30-day case fatality risk for stroke patients having AF is now (2000-2008) about 20% in both countries. CONCLUSIONS: Although incidence rates of hospitalisation with stroke in patients with AF have decreased in recent years, stroke remains a common AF complication with a high case fatality risk. The marked winter peak in incidence rates of hospitalisation with stroke in AF patients suggests that there are opportunities to reduce this complication. Further studies are necessary to identify how to optimise treatment of AF and prevention of stroke.

Infant, obstetrical and maternal characteristics associated with thromboembolism in infancy: a nationwide population-based case-control study.

OBJECTIVES: To identify infant, obstetrical and maternal characteristics associated with arterial ischaemic stroke (AIS) and venous thromboembolism (VTE) in infancy (<1 year). DESIGN: Nationwide, population-based nested case-control study. All infants with a verified first-time diagnosis of AIS, VTE or both in Denmark through the years 1994-2006 were included, and 10 population controls were selected for each case. RESULTS: Case-infants presented with AIS (n=71) or VTE (n=38). AIS in infancy was associated with primiparity (adjusted OR 5.9 CI 95% 3.0 to 11.6)), delivery by an emergency caesarean section (adjusted OR 1.9 (CI 95% 1.0 to 3.3)), and post-term birth (adjusted OR 2.2 (CI 95% 1.1 to 4.8)). Male sex was associated with an increased risk of AIS among neonates (crude OR 1.8 (CI 95% 1.0 to 3.4)) but not among later born (crude OR 0.6 (CI 95% 0.2 to 1.4)). Risk factors for VTE in infancy included preterm birth (adjusted OR 5.5 (CI 95% 1.8 to 16.9)), low Apgar score (adjusted OR 9.2 (CI 95% 1.9 to 45.2)), and multiple births (adjusted OR 7.1 (CI 95% 1.1 to 48.1)). Previous maternal thromboembolism and pregnancy-related disorders were not associated with the risk of thromboembolism in the children. CONCLUSION: Several apparently independent infant, obstetrical and maternal characteristics were associated with thromboembolism in early life.

Body mass index and thromboembolism in children with hematological malignancies.

We evaluated the effects of body mass index (BMI) on the risk of thromboembolism (TE) in children (<18 years) with hematological malignancies during the period 1990-2009 (n = 359). Obesity was prevalent in 12% of patients: 6% versus 17% prior to and after the year 2000 (P = 0.02). Sixty-one (17%) patients developed TE; increasing BMI was associated with increased, but statistically insignificant risk of TE [adjusted odds ratios (OR): 0.75 (95%CI 0.32-1.77), 0.93 (95%CI 0.38-2.30), and 1.01(95%CI 0.42-2.41) for underweight, overweight, and obese group]. A large prospective study is needed to define the impact of BMI on the risk of TE in children.

Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study.

OBJECTIVE: To assess the incidence rate (IR), changes in IR over time, risk factors, treatment, and outcomes of pediatric noncerebral thromboembolism (TE). STUDY DESIGN: The study included all patients aged 0 to 18 years diagnosed with first-ever noncerebral venous thromboembolism (VTE) and/or arterial TE in Denmark between 1994 and 2006. Patients were identified in national registries, followed by validation of diagnoses by medical records review. RESULTS: We confirmed 331 cases of VTE and 46 cases of arterial TE during 15.8 million person-years of observation, with corresponding IRs of 2.09 and 0.29 per 100 000 person-years. The IR peaked in infancy (age <1 year) for both VTE and arterial TE, with an additional peak among adolescents (age 15 to 18 years) for VTE. Boys predominated in IR of VTE in infancy, whereas girls did so in adolescence (P < .01). The IRs of VTE and arterial TE remained stable during the study period, but with an trend toward increasing VTE in 2001 to 2006 (P = .064). Underlying diseases/external triggers were present in 86.6% of the patients, and thrombophilia was present in 47.9% of the VTE cases. All-cause and TE-related 30-day case fatalities were 4.0% and 1.6%, respectively. CONCLUSIONS: We found age- and sex-related disparities in the IRs of pediatric VTE and arterial TE, but insignificant changes in IR from 1994 to 2006.

Do inactivated microbial preparations improve life history traits of the copepod Acartia tonsa?

We have tested a microbial preparation with probiotic effects (PSI; Sorbial A/S DANISCO) on the calanoid copepod Acartia tonsa (Dana) development time and reproduction effectiveness in culture. The hypotheses were that PSI increases the productivity and quality of copepods in culture (increased egg production and hatching success, HS). This was carried out because the use of copepods as live prey in aquaculture could increase the number of fish successfully raised through their entire life cycle. However, the availability of copepods is limited by their difficulty to be effectively raised. Our results show that the addition of PSI to the algal food increased the individual size of the adult females and their egg production. The PSI, together with Rhodomonas salina, also increased the HS of the eggs produced by PSI-treated females. These effects were observed despite that the biochemical analysis of the PSI revealed that it is a nutritionally poor food lacking essential fatty acids, and hence it cannot be used alone to raise copepods but instead as a food additive. This is the first demonstration that the effectiveness of copepod culturing can be improved using microbial preparations as a food additive.

Predictive value of pediatric thrombosis diagnoses in the Danish National Patient Registry.

Data on the validity of pediatric thrombosis diagnoses are missing. We aimed to examine the predictive value of a diagnosis of venous and arterial thrombosis using the Danish National Patient Registry (DNPR). We identified all first-time diagnoses among children and adolescents (aged 0-18 years) between 1994 and 2006 in DNPR. In total, 1138 potential cases of thrombosis were identified; the medical records were retrieved for 1112 (97.7%) and the positive predictive value (PPV) computed. Overall, the diagnosis of thrombosis was verified in 598 of the 1112 cases, corresponding to a PPV of 53.7% (95% confidence interval [CI]: 50.8-56.7). Diagnoses from wards had the PPV of 62.5% (95% CI: 59.4-65.6). The predictive value of a thrombosis diagnosis from wards was age-dependent, with a higher PPV (77.4%, 95% CI: 68.7-84.7) in neonates (<28 days) and adolescents (15-18 years) (68.2%; 95% CI: 63.2-72.5)) than in children (28 days-14 years) (51.2%; (95% CI: 46.0-56.4)). The PPV of a thrombosis diagnosis was improved by restricting the analysis to diagnoses from wards, primary diagnoses, and admissions with a length of stay of three or more days. The results indicate that an interpretation of nonvalidated hospital discharge data for pediatric thrombosis in a registry like DNPR should be made with caution.