Automated localisation and boundary identification of superficial femoral artery on MRI sequences

In this paper, an automated method to localise the right superficial femoral artery (SFA) and identify its boundary on magnetic resonance imaging (MRI) sequences without contrast medium injection is proposed. Some anatomical knowledge combined with the mathematical morphology is used to distinguish SFA from other vessels. Afterwards, the directional gradient, continuity and the local contrast are applied as features to identify the artery's boundary using dynamic programming. The accuracy analysis shows that the system has average unsigned errors 3.1 ± 3.1% on five sequences compared to experts' manual tracings.     

Effect of tocilizumab on haematological markers implicates interleukin-6 signalling in the anaemia of rheumatoid arthritis

Introduction

Our objective was to determine the interrelationships of interleukin (IL)-6 receptor inhibition with haemoglobin, acute-phase reactants and iron metabolism markers (including hepcidin) in patients with rheumatoid arthritis (RA).

Methods

Data of patients receiving tocilizumab or placebo in the MEASURE study were analysed. We investigated associations at baseline and during tocilizumab treatment among haemoglobin, parameters of haemoglobin and iron homeostasis [ferritin, total iron-binding capacity (TIBC), hepcidin, haptoglobin], IL-6 and acute-phase reactants [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] to identify statistical correlates of rise in haemoglobin level.

Results

At baseline, CRP and haptoglobin were inversely correlated (modestly) with haemoglobin levels. After treatment with tocilizumab, CRP, hepcidin, ferritin and haptoglobin levels fell alongside increases in TIBC and haemoglobin. The falls in CRP, hepcidin and haptoglobin levels in the first 2 weeks correlated with a week 12 rise in TIBC and haemoglobin.

Conclusions

Inflammatory anaemia improves in patients with RA treated with tocilizumab. This improvement correlates with the degree of suppression of systemic inflammation, reduction in hepcidin and haptoglobin and increase in iron-binding capacity. These clinical data provide evidence of a role for IL-6 signalling in the inflammatory anaemia of RA.     

Review of the Palaearctic Acomopterella Zaitzev (Diptera,Sciaroidea, Mycetophilidae)

The distribution of Acomopterella species in the Palaearctic region has been re-examined in this study, using recently collected material. The European species was found to be distributed in the eastern Palaearctic as well. A second Palaearctic species from Honshu (Japan) is herein described. The morphology of adult specimens was studied by light microscopy and scanning electron microscopy. The shape of functional specialized setae on mid tibiae in Acomopterella and seven further fungus gnat genera is described and the suitability of this character for systematic studies is discussed. Details of a “hind tibial organ” are described.The position of Acomopterella in the tribe Gnoristini is briefly discussed. Acomopterella is found to be more closely related to Speolepta Edwards, 1925, than to any other recent genus.     

Distinct composition of human fetal HDL attenuates its anti-oxidative capacity

In human high-density lipoprotein (HDL) represents the major cholesterol carrying lipoprotein class in cord blood, while cholesterol is mainly carried by low-density lipoprotein in maternal serum. Additionally, to carrying cholesterol, HDL also associates with a range of proteins as cargo. We tested the hypothesis that fetal HDL carries proteins qualitatively and quantitatively different from maternal HDL. These differences then contribute to distinct HDL functionality in both circulations. Shotgun proteomics and biochemical analyses were used to assess composition/function of fetal and maternal HDL isolated from uncomplicated human pregnancies at term of gestation. The pattern of analyzed proteins that were statistically elevated in fetal HDL (apoE, proteins involved in coagulation, transport processes) suggests a particle characteristic for the light HDL₂ sub-fraction. In contrast, proteins that were enriched in maternal HDL (apoL, apoF, PON1, apoD, apoCs) have been described almost exclusively in the dense HDL₃ fraction and relevant to its anti-oxidative function and role in innate immunity. Strikingly, PON1 mass and activity were 5-fold lower (p < 0.01) in the fetus, which was accompanied by attenuation of anti-oxidant capacity of fetal HDL. Despite almost equal quantity of CETP in maternal and fetal HDL, its enzymatic activity was 55% lower (p < 0.001) in the fetal circulation, whereas LCAT activity was not altered. These findings indicate that maternally derived HDL differs from fetal HDL with respect to its proteome, size and function. Absence of apoA-1, apoL and PON1 on fetal HDL is associated with decreased anti-oxidative properties together with deficiency in innate immunity collectively indicating distinct HDLs in fetuses.     

Cognitive Factors Mediate Placebo Responses in Patients with House Dust Mite Allergy

Background

Placebo effects have been reported in type I allergic reactions. However the neuropsychological mechanisms steering placebo responses in allergies are largely unknown. The study analyzed whether and to what extend a conditioned placebo response is affecting type I allergic reactions and whether this response can be reproduced at multiple occasions.

Methods

62 patients with house dust mite allergy were randomly allocated to either a conditioned (n = 25), sham-conditioned (n = 25) or natural history (n = 12) group. During the learning phase (acquisition), patients in the conditioned group received the H₁-receptor antagonist desloratadine (5mg) (unconditioned stimulus/US) together with a novel tasting gustatory stimulus (conditioned stimulus/CS). Patients in the sham-conditioned control group received the CS together with a placebo pill. After a wash out time of 9 days patients in the conditioned and sham-conditioned group received placebo pills together with the CS during evocation. Allergic responses documented by wheal size after skin prick test and symptom scores after nasal provocation were analyzed at baseline, after last desloratadine treatment and after the 1^st and 5^th CS re-exposure.

Results

Both conditioned and sham-conditioned patients showed significantly decreased wheal sizes after the 1^st CS-evocation and significantly decreased symptom scores after the 1^st as well as after the 5^th evocation compared to the natural history control group.

Conclusions

These results indicate that placebo responses in type I allergy are not primarily mediated by learning processes, but seemed to be induced by cognitive factors such as patients’ expectation, with these effects not restricted to a single evocation.     

Alterations of Red Cell Membrane Properties in Nneuroacanthocytosis

Neuroacanthocytosis (NA) refers to a group of heterogenous, rare genetic disorders, namely chorea acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington’s disease-like 2 (HDL2) and pantothenate kinase associated neurodegeneration (PKAN), that mainly affect the basal ganglia and are associated with similar neurological symptoms. PKAN is also assigned to a group of rare neurodegenerative diseases, known as NBIA (neurodegeneration with brain iron accumulation), associated with iron accumulation in the basal ganglia and progressive movement disorder. Acanthocytosis, the occurrence of misshaped erythrocytes with thorny protrusions, is frequently observed in ChAc and MLS patients but less prevalent in PKAN (about 10%) and HDL2 patients. The pathological factors that lead to the formation of the acanthocytic red blood cell shape are currently unknown. The aim of this study was to determine whether NA/NBIA acanthocytes differ in their functionality from normal erythrocytes. Several flow-cytometry-based assays were applied to test the physiological responses of the plasma membrane, namely drug-induced endocytosis, phosphatidylserine exposure and calcium uptake upon treatment with lysophosphatidic acid. ChAc red cell samples clearly showed a reduced response in drug-induced endovesiculation, lysophosphatidic acid-induced phosphatidylserine exposure, and calcium uptake. Impaired responses were also observed in acanthocyte-positive NBIA (PKAN) red cells but not in patient cells without shape abnormalities. These data suggest an “acanthocytic state” of the red cell where alterations in functional and interdependent membrane properties arise together with an acanthocytic cell shape. Further elucidation of the aberrant molecular mechanisms that cause this acanthocytic state may possibly help to evaluate the pathological pathways leading to neurodegeneration.     

Isolation and characterization of isochorismate synthase and cinnamate 4-hydroxylase during salinity stress,wounding, and salicylic acid treatment in Carthamus tinctorius

Salicylic acid (SA) is a prominent signaling molecule during biotic and abiotic stresses in plants biosynthesized via cinnamate and isochorismate pathways. Cinnamate 4-hydroxylase (C4H) and isochorismate synthase (ICS) are the main enzymes in phenylpropanoid and isochorismate pathways, respectively. To investigate the actual roles of these genes in resistance mechanism to environmental stresses, here, the coding sequences of these enzymes in safflower (Carthamus tinctorius), as an oilseed industrial medicinal plant, were partially isolated and their expression profiles during salinity stress, wounding, and salicylic acid treatment were monitored. As a result, safflower ICS (CtICS) and C4H (CtC4H) were induced in early time points after wounding (3–6 h). Upon salinity stress, CtICS and CtC4H were highly expressed for the periods of 6–24 h and 3–6 h after treatment, respectively. It seems evident that ICS expression level is SA concentration dependent as if safflower treatment with 1 mM SA could induce ICS much stronger than that with 0.1 mM, while C4H is less likely to be so. Based on phylogenetic analysis, safflower ICS has maximum similarity to its ortholog in Vitis vinifera up to 69%, while C4H shows the highest similarity to its ortholog in Echinacea angustifolia up to 96%. Overall, the isolated genes of CtICS and CtC4H in safflower could be considered in plant breeding programs for salinity tolerance as well as for pathogen resistance.