Is there a linkage between metabolism and personality in small mammals? The root vole (Microtus oeconomus) example

Significant inter-individual variation in the rate of animal metabolism is a widespread phenomenon that has started to accumulate general interest. Here we follow recent calls to focus on linkage between the variation in energy metabolism and animal personality. By using wild caught root voles as a study species, we examined the relationship between the behavioral patterns (assessed in open field test) and resting metabolic rate (RMR), both of which are known to show large individual differences and intra-individual consistency in voles. Our results showed only a weak relationship between personality traits and metabolism, since the most parsimonious model (according to AICc) explaining RMR included only body mass and season as factors (explaining 84.8% of variation in RMR). However, the next two alternative models (within ΔAICc = 2) also included the personality trait reflecting proactive behaviors (PC1) in addition to body mass, sex and season (85.2 and 85.8% of RMR variance explained, respectively). In all, our study does not provide compelling support for recent ideas of close linkage between behavior and metabolism. Still, our study highlights that even in the case of wild caught individuals, when behavior and metabolism often carry effects of both intrinsic and extrinsic conditions, the potential metabolic effects of varying energetically costly behaviors cannot be neglected.     

Class distributions on SOM surfaces for feature extraction and object retrieval.

A Self-Organizing Map (SOM) is typically trained in unsupervised mode, using a large batch of training data. If the data contain semantically related object groupings or classes, subsets of vectors belonging to such user-defined classes can be mapped on the SOM by finding the best matching unit for each vector in the set. The distribution of the data vectors over the map forms a two-dimensional discrete probability density. Even from the same data, qualitatively different distributions can be obtained by using different feature extraction techniques. We used such feature distributions for comparing different classes and different feature representations of the data in the context of our content-based image retrieval system PicSOM. The information-theoretic measures of entropy and mutual information are suggested to evaluate the compactness of a distribution and the independence of two distributions. Also, the effect of low-pass filtering the SOM surfaces prior to the calculation of the entropy is studied.     

Budesonide reduces sensitivity and reactivity to inhaled mannitol in asthmatic subjects

OBJECTIVE: The aim of the study was to investigate whether treatment using inhaled corticosteroids decreases airway responsiveness to inhaled mannitol in asthmatic subjects. METHODOLOGY: Before treatment or a change in treatment with inhaled corticosteroids, 18 asthmatic subjects had measurements of lung function and airway sensitivity to mannitol taken and they completed a self-administered questionnaire on asthma symptoms. The procedure was repeated 6-9 weeks after taking 800-2400 microg/day of budesonide. RESULTS: There were significant reductions in airway sensitivity (provoking dose to induce a 15% fall in FEV1 (PD15)) and airway reactivity measured by the response dose ratio (RDR; final percentage fall FEV1/total dose of mannitol administered). The PD15 (Gmean (95%CI)) increased from 78 mg (51, 117) before treatment to 289 mg (202, 414) following treatment (P < 0.001). All subjects had a significant increase beyond the repeatability of 0.9 doubling doses with seven subjects becoming unresponsive. There was a 4.2 (3.4, 4.9)-fold improvement in the RDR with the value before the treatment period 0.18 (0.12, 0.28) decreasing to 0.04 (0.03, 0.08) following treatment (P < 0.001). These improvements were associated with significant improvements in lung function and symptom severity. CONCLUSION: Treatment with the inhaled corticosteroid budesonide caused a decrease in airway sensitivity and reactivity to inhaled mannitol and this was associated with expected improvements in lung function and symptoms.     

Human leucocyte antigen and TNFalpha polymorphism association in microscopic colitis

OBJECTIVES: Coeliac disease (CD) is common in patients with microscopic colitis (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated with CD, and there is evidence for an association with MC. We analysed the genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4-DQ8. In addition, TNFalpha gene polymorphism (-308) associated with susceptibility to several autoimmune diseases was studied. METHODS: Eighty patients with MC including 29 with collagenous colitis (CC) and 51 with lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule encoding genes using either an allele-specific PCR, or hybridization with sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the diagnosis of CD in 15 (18.8%) patients. TNFalpha(308) alleles were analyzed in 78 patients with MC (27 with CC and 51 with LC). A control group of 3627 patients was used in the HLA study and 178 patients in the TNFalpha study. RESULTS: HLA-DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%; P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001) and without CD (39.3%; P=0.019), compared with the controls (23%). CONCLUSION: Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele carriage. These associations are present also in MC patients without CD. The shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in patients with MC suggest an epidemiological overlap, and probably some similarities in the pathogenesis of CD and MC.     

Cerebral palsy is characterized by protein mediators in cord serum

Cerebral palsy (CP) is a major neurodevelopmental disability in childhood. An association between intrauterine infection and CP has been reported. We examined the relationship between inflammatory mediators in cord serum and CP in term and preterm children. Regional multicenter study was conducted on 19 CP children and 19 gestation-matched paired controls. CP children (n = 27) were further compared with controls of similar gestation at birth (n = 25). Serum levels of 78 protein mediators were analyzed. Eleven analytes correlated with the length of gestation both in cases and controls. In paired analysis, B-lymphocyte chemoattractant, ciliary neurotrophic factor, epidermal growth factor, interleukin (IL)-5, IL-12, IL-13, IL-15, macrophage migration inhibitory factor, monocyte chemoattractant protein-3, monokine induced by interferon gamma, and tumor necrosis factor-related apoptosis-inducing ligand were higher in children with CP (p < or = 0.05). Preterm infants with CP showed higher epidermal growth factor and lower levels of granulocyte-macrophage colony-stimulating factor, IL-2, macrophage-derived chemokine, and pulmonary and activation-regulated chemokine than their paired controls. Inflammatory mediators and growth factors serve as a footprint of the fetal response to an insult manifesting after birth as a permanent brain damage. The cytokine patterns at birth differ between premature and term infants who develop CP.     

Sensitivity and validity of three bronchial provocation tests to demonstrate the effect of inhaled corticosteroids in asthma

STUDY OBJECTIVES: To compare the sensitivity and validity of mannitol, histamine, and cold air challenges to demonstrate the effect of inhaled corticosteroids (ICS) in asthma. DESIGN: A prospective study. PARTICIPANTS: Seventeen patients with recently diagnosed, steroid-naive asthma who fulfilled the diagnostic criteria of Finnish Social Insurance Institution and were hyperresponsive to both mannitol and histamine. INTERVENTIONS: The following procedures were carried out at baseline and after 3 months and 6 months of treatment with inhaled budesonide, 800 microg/d: symptom assessment with a questionnaire, ambulatory peak expiratory flow (PEF) measurements twice daily for 2 weeks, and bronchial challenges with mannitol, histamine, and cold air. RESULTS: Budesonide decreased the sum symptom score, daily use of bronchodilating drugs, and diurnal PEF variation, but did not change FEV(1) percentage of predicted significantly. In addition, budesonide significantly decreased mannitol (p = 0.005) and histamine (p = 0.002) response dose ratios. The magnitude of the budesonide-induced change in responsiveness to these two challenges did not differ significantly. The effect of budesonide on cold air responsiveness did not reach statistical significance (p = 0.064). Change in mannitol responsiveness correlated significantly with the changes in sum symptom score and in FEV(1). Change in cold air responsiveness correlated with the changes in sum symptom score and in diurnal PEF variation. Change in histamine responsiveness correlated only with change in FEV(1). CONCLUSIONS: Mannitol challenge is both a sensitive and valid test to demonstrate the effects of ICS in asthma. Histamine challenge is equally sensitive for this purpose, but its validity may be lower than that of mannitol challenge. Cold air challenge seems to be a valid test to demonstrate the effects of ICS, but its sensitivity may be lower than that of mannitol and histamine challenges.     

The clinical utility of serum anti‐Müllerian hormone in the follow‐up of ovarian adult‐type granulosa cell tumors—A comparative study with inhibin B

Ovarian adult‐type granulosa cell tumors (AGCTs) require prolonged follow‐up, but evidence regarding the optimal follow‐up marker is lacking. The objective of our study was to validate the clinical usefulness of serum anti‐Müllerian hormone (AMH) and the current marker inhibin B as single and combined markers of AGCTs. We conducted a longitudinal, partially prospective cohort study of 123 premenopausal and postmenopausal AGCT patients with a median follow‐up time of 10.5 years (range 0.3–50.0 years). Serum AMH and inhibin B levels were measured from 560 pretreatment and follow‐up serum samples by using immunoenzymometric assays. We found that serum AMH and inhibin B levels were significantly elevated in patients with primary or recurrent AGCTs. The levels of both markers positively correlated to tumor size (p < 0.05). AMH and inhibin B performed similarly in receiving operator characteristic analyses; area under the curve (AUC) values were 0.92 [95% confidence interval (CI) 0.88–0.95] for AMH, and 0.94 (95% CI 0.90–0.96) for inhibin B. AMH was highly sensitive (92%) and specific (81%) in detecting a macroscopic AGCT. However, in AUC comparison analyses, the combination of the markers was superior to inhibin B alone. In conclusion, serum AMH is a sensitive and specific marker of AGCT, and either AMH or inhibin B can be monitored during follow‐up. However, combining AMH and inhibin B in AGCT patient follow‐up improves the detection of recurrent disease.     

Variant Bernard-Soulier syndrome due to homozygous Asn45Ser mutation in the platelet glycoprotein (GP) IX in seven patients of five unrelated Finnish families

Bernard-Soulier syndrome (BSS), a rare bleeding disorder with macrothrombocytopenia, is caused by a defect of the platelet glycoprotein (GP) Ib/IX/V complex. Here we report a variant form of BSS in eleven patients of five unrelated families who originate from a particular area of Finland. The differential diagnosis from idiopathic thrombocytopenic purpura was difficult. Bleeding symptoms were epistaxis and haematomas debuting in childhood, but no spontaneous, severe bleeding episodes were reported. The platelet count varied from 43 to 81x10(9)/l. Screening the entire GP Ibalpha, GP Ibbeta, GP IX and GP V genes revealed a recurrent homozygous Asn45Ser mutation in GP IX in all probands. Flow cytometry showed markedly reduced expression of GP Ib (<10%), and only moderately reduced expression of GP IX (24-36%) and GP V (38-49%). The expression of subunits seemed to vary independently from the normal polymorphisms. Heterozygotes did not differ significantly from controls by their GP Ib/IX/V expression. Since the Asn45Ser mutation has also been reported in three other kindreds of northern and central European origin, this study reveals that instead of being a mutation hot spot, it may be ancient and scattered in Europe. Moderate, chronic thrombocytopenia should be carefully studied to diagnose variant BSS correctly from treatment resistant idiopathic thrombocytopenia.