Environmental drivers of increased ecosystem respiration in a warming tundra.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Staphylococcus aureus colonization in atopic eczema and its association with filaggrin gene mutations.

BACKGROUND: Atopic dermatitis (AD) is a prevalent disease with significant impact on physical health and quality of life. Staphylococcus aureus has been directly correlated to disease severity, and may also be a contributing causal factor in the pathogenesis of AD. OBJECTIVES: The primary aim was to assess differences in S. aureus colonization in patients with AD with and without filaggrin gene mutations. The secondary aim was to assess disease severity in relation to S. aureus colonization. Exploratory analyses were performed to investigate S. aureus genetic lineages in relation to filaggrin gene (FLG) mutations and disease severity. METHODS: Adult patients with AD (n = 101) were included in the study. Bacterial swabs were taken from lesional skin, nonlesional skin and the nose. Swabs positive for S. aureus were characterized by spa and the respective clonal complex (CC) type assigned. Patients were characterized with respect to disease severity (Scoring Atopic Dermatitis) and FLG mutations (n = 88). Fisher's exact test was used to analyse differences in S. aureus colonization in relation to FLG mutations. RESULTS: Of the 101 patients included, 74 (73%) were colonized with S. aureus. Of the colonized patients, 70 (95%) carried only one CC type in all three different sampling sites. In lesional skin, S. aureus was found in 24 of 31 patients with FLG mutations vs. 24 of 54 wild-type patients (P = 0·0004). Staphylococcus aureusCC1 clonal lineage was more prevalent in patients with FLG mutations (n = 10) than in wild-type patients (n = 2) (P = 0·003). No specific bacterial lineage was linked to disease severity. CONCLUSIONS: Increased S. aureus colonization in patients with AD with FLG mutations, and increased prevalence of CC1 in patients with FLG mutations, suggest that host-microbe interactions and clonal differences in S. aureus are important for colonization of AD skin.

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Screening and identification of small molecule inhibitors of ErbB2-induced invasion.

ERBB2 amplification and overexpression are strongly associated with invasive cancer with high recurrence and poor prognosis. Enhanced ErbB2 signaling induces cysteine cathepsin B and L expression leading to their higher proteolytic activity (zFRase activity), which is crucial for the invasion of ErbB2-positive breast cancer cells in vitro. Here we introduce a simple screening system based on zFRase activity as a primary readout and a following robust invasion assay and lysosomal distribution analysis for the identification of compounds that can inhibit ErbB2-induced invasion. With an unbiased kinase inhibitor screen, we identified Bohemine/Roscovitine, Gö6979 and JAK3 inhibitor VI as compounds that can efficiently decrease cysteine cathepsin activity. Using the well-established and clinically relevant ErbB1 and ErbB2 inhibitor lapatinib as a positive control, we studied their ability to inhibit ErbB2-induced invasion in 3-dimensional Matrigel cultures. We found one of them, JAK3 inhibitor VI, capable of inhibiting invasion of highly invasive ErbB2-positive ovarian cancer cells as efficiently as lapatinib, whereas Gö6979 and Roscovitine displayed more modest inhibition. All compounds reversed the malignant, ErbB2-induced and invasion-supporting peripheral distribution of lysosomes. This effect was most evident for lapatinib and JAK3 inhibitor VI and milder for Gö6979 and Roscovitine. Our results further showed that JAK3 inhibitor VI function was independent of JAK kinases but involved downregulation of cathepsin L. We postulate that the screening method and the verification experiments that are based on oncogene-induced changes in lysosomal hydrolase activity and lysosomal distribution could be used for identification of novel inhibitors of ErbB2-induced invasiveness. Additionally, we introduce a novel function for lapatinib in controlling malignant lysosomal distribution, that may also be involved in its capability to inhibit ErbB2-induced invasion in vivo.

Two-year follow-up survey of patients with allergic contact dermatitis from an occupational cohort: is the prognosis dependent on the omnipresence of the allergen?

BACKGROUND: Skin diseases are the most frequently recognized occupational diseases in Denmark. The prognosis for occupational contact dermatitis is often poor. OBJECTIVES: To investigate the prognosis, assessed by eczema, job status and skin-related quality of life, among patients allergic to rubber chemicals and latex (ubiquitous allergens) and epoxy (nonubiquitous allergen), 2 years after recognition of occupational allergic contact dermatitis. METHODS: From a cohort of all patients recognized as having occupational dermatitis by the Danish National Board of Industrial Injuries in 2010, 199 patients with relevant rubber allergy (contact allergy to rubber chemicals or contact urticaria from latex) or epoxy allergy were identified. Follow-up consisted of a questionnaire covering current severity of eczema, employment, exposure and quality of life. RESULTS: The response rate was 75%. Clearance of eczema was reported by 11% of patients and 67% reported improvement. Overall 22% of patients with allergy to a nonubiquitous allergen had total clearance of eczema compared with 10% of cases allergic to ubiquitous allergens and 0% of those with contact urticaria (P = 0·116). Improvement was significantly more frequent in those who had changed jobs compared with those who had not (P = 0·01). CONCLUSIONS: At follow-up, patients with contact urticaria had significantly poorer prognosis than those with contact allergy, and there was a trend towards a poorer prognosis for those with contact allergy to rubber chemicals than those with allergy to epoxy. A significant positive association between job change and improvement was found.

Roots and associated fungi drive long-term carbon sequestration in boreal forest.

Boreal forest soils function as a terrestrial net sink in the global carbon cycle. The prevailing dogma has focused on aboveground plant litter as a principal source of soil organic matter. Using (14)C bomb-carbon modeling, we show that 50 to 70% of stored carbon in a chronosequence of boreal forested islands derives from roots and root-associated microorganisms. Fungal biomarkers indicate impaired degradation and preservation of fungal residues in late successional forests. Furthermore, 454 pyrosequencing of molecular barcodes, in conjunction with stable isotope analyses, highlights root-associated fungi as important regulators of ecosystem carbon dynamics. Our results suggest an alternative mechanism for the accumulation of organic matter in boreal forests during succession in the long-term absence of disturbance.

The Danish PET/depression project: cognitive function and regional cerebral blood flow.

OBJECTIVE: To clarify the relationship between cognitive functions and regional cerebral blood flow (rCBF) in a large group of depressed patients compared with healthy controls. METHOD: A set of principal components was extracted from scores of a battery of neuropsychological tests of 40 patients suffering from major depression and 49 healthy controls. The components were correlated by multiple linear regression analyses to selected regions of interest in the brain obtained from positron emission tomography images. RESULTS: In contrast to findings in the healthy controls, cognitive functions in the depressed patients correlated significantly with rCBF in specified regions of interest in only a few instances. CONCLUSION: Our study indicates that disturbed cognitive functions in depression do not relate to specific areas of the brain in the same way as normal cognitive functioning, suggesting that the abnormalities of brain function in major depression may be qualitative, rather than quantitative, in nature.

The Danish PET/depression project: clinical symptoms and cerebral blood flow. A regions-of-interest analysis.

OBJECTIVE: We wanted to explore associations between clinical symptoms of depression and the blood flow to specific regions of the brain. Furthermore, we wanted to compare the regions-of-interest (ROI) method with the functions-of-interest (FOI) approach. METHOD: The resting blood flow to 42 ROI in the brain was obtained with positron emission tomography (PET) imaging in 42 representative in-patients with major depression and 47 matched healthy controls. RESULTS: The patients had increased blood flow to hippocampus, cerebellum, anterior cingulate gyrus, and the basal ganglia. A strong negative correlation was found between the degree of psychomotor retardation of the patients and the blood flow to the dorsolateral and supraorbital prefrontal cortices. The total Hamilton score was correlated with the blood flow to the hippocampus. CONCLUSION: Our findings support the notion that depressed patients have disturbances in the loops connecting the frontal lobes, limbic system, basal ganglia, and cerebellum.

Structural brain abnormalities in unselected in-patients with major depression.

OBJECTIVE: Several studies have indicated an increased frequency of cerebral atrophy and white matter lesions in patients with major depression, especially in older age groups. METHOD: Forty-four representative in-patients with major depression in which neurological disorders were clinically excluded, and 49 age- and gender-matched controls were MR scanned. RESULTS: Unexpectedly, two of the patients had severe brain pathology which could account for their psychiatric symptoms. Analysis of the remaining patients (mean age 42 years) did not reveal an increased frequency of cerebral atrophy. The number of white matter lesions increased with age to an odds ratio greater than 3 for patients aged 50, but this was not statistically significant. CONCLUSION: Brain atrophy and white matter lesions did not occur with significantly increased frequency in these relatively young unselected depressives, but the finding of severe brain pathology stresses the importance of brain imaging in late-onset psychiatric disorders.

Patient and relative education in community psychiatry: a randomized controlled trial regarding its effectiveness.

BACKGROUND: Family psychoeducation has a well-documented effect on the short-term prognosis in schizophrenia. Less is known about the effectiveness of shorter programmes with the main focus on information for patients (patient education) or for patients and relatives (family education). METHODS: A randomized study of the effectiveness of an eight-session psychoeducational programme for patients with schizophrenia and for their relatives was conducted in two community mental health centres, in Arhus and Viborg (Denmark). Patient outcome measures were knowledge, relapse, compliance, insight and satisfaction, and relative outcome measures were knowledge and satisfaction. Post-intervention outcome and follow-up evaluation 1 year after the start of the intervention are presented. RESULTS: A statistically significant increase in knowledge of schizophrenia in both relatives and patients was demonstrated at postintervention and a non-significant trend at 1-year follow-up. Statistically significant changes in the Verona Service Satisfaction Scale Scores in the subdimension of satisfaction with Relatives involvement were demonstrated both for patients and relatives postintervention and for patients at 1-year follow-up. There was a tendency that time-to-relapse increased in the intervention group at postintervention and that the schizophrenia subscore of the Brief Psychiatric Rating Scale was reduced in the intervention group at 1-year follow-up. No differences were found between the groups regarding compliance, insight into psychosis, psychosocial function (General Assessment of Function) or in relatives' expressed emotion scores postintervention or at 1-year follow-up. CONCLUSIONS: A short patient and relative education programme seems to be able to influence knowledge and some aspects of satisfaction, but does not seem to be sufficient to influence important variables such as relapse, compliance, psychopathology, insight or psychosocial functioning.

[Osteoporosis in unselected patients in an ambulatory clinic for pulmonary medicine. An inexpensive diagnostic possibility not requiring extra time]. / Osteoporose hos uselekterede ambulante lungemedicinske patienter. En billig diagnostisk mulighed uden brug af ekstra tid.

Patients with pulmonary and allergy-related diseases often suffer from osteoporosis. Deformities of the thoracic spine in the lateral view of a routine chest X-ray were evaluated in 1558 patients admitted to a chest clinic in a prospective, blinded and non-selected manner with various cardio-respiratory complaints. Signs of osteoporosis were found in 108 of 811 males and in 79 of 747 females. In 187 patients with thoracic spine compression a total of 106 had received corticosteroid medication. Only one received oestrogen and no one took calcium or D-vitamin supplementation. Conclusively we found that more attention should be paid to osteoporosis in patients with pulmonary disorders. An easy and cheap way is to look for fractures on a simple chest X-ray in a population of patients with cardiorespiratory complaints. We found a very high prevalence of thoracic spine deformities, especially in men.

Zinc in Danish women during late normal pregnancy and pregnancies with intra-uterine growth retardation.

Zinc and alkaline phosphatase were examined in 41 pregnant women (gestational weeks 35-41) and in 12 women within 24 h of delivery. The serum-zinc level was reduced in all the women, though to a lesser degree in women giving birth to small for gestational age (SGA) babies than in the control mothers. The difference between the two groups was significant (p = 0.019). Erythrocyte-zinc increased during pregnancy, more in control mothers than in SGA mothers (p = 0.020). Granulocyte-zinc was not significantly reduced in pregnancy and no difference was found between SGA mothers and control mothers. Alkaline phosphatase levels in serum and granulocytes were elevated equally in the two groups. These findings show that zinc level changes occur in pregnancy, but that the changes do not appear to be a dominant cause of SGA pregnancy, in Danish women.