Anti-beta(2)-glycoprotein I antibodies in children with atopic dermatitis

beta(2)-Glycoprotein I (beta(2)GPI) appears to be the major antigen for antiphospholipid antibodies (aPL) in patients with antiphospholipid syndrome (APS). In early infancy, virtually all children initiate transient immune response to non-pathogenic nutritional antigens, which fails to terminate in children with atopic diseases. To examine the possibility that a prolonged immune response to beta(2)GPI could also spread to the human protein, antibodies against human beta(2)GPI (anti-beta(2)GPI) were determined in 93 randomly selected children with different allergic diseases. A high frequency (42%) of IgG anti-beta(2)GPI was found in children with atopic dermatitis (AD), but not in those with other allergic diseases. Anti-beta(2)GPI in children with AD were exclusively of the IgG1 subclass and bound to bovine beta(2)GPI as well, but not to either beta(2)GPI combined with the phospholipid cardiolipin. The epitopes were identified in domain V of beta(2)GPI and the antibody binding was abolished upon the specific proteolytic cleavage of the phospholipid-binding C-terminal loop in domain V of beta(2)GPI. These results indicated that the epitopes for anti-beta(2)GPI in children with AD most likely resided in close vicinity of the phospholipid-binding site of beta(2)GPI. The epitopic difference from anti-beta(2)GPI in APS may explain presumed non-thrombogenicity of anti-beta(2)GPI in children with AD.     

Estimation of hand preshaping during human grasping

A new method for evaluating hand preshaping during reaching-to-grasp movement is proposed. The method makes use of all five fingers in estimation of prehension. The investigation was performed on six healthy subjects grasping three different objects at various positions and orientations. The objects were presented to the subjects by means of a robot, which also induced perturbations in both object position and orientation. Positions of markers attached to the finger-tips and dorsum of the hand were recorded by means of a 3D optical tracking system. In the data analysis, the adjacent fingertips were interconnected, thus obtaining a planar pentagon whose various characteristics were investigated and discussed. New parameters for the evaluation of finger preshaping, such as pentagon surface area, angle between the pentagon and hand normal vectors, and the angle between the pentagon and object normal vectors were introduced. The proposed pentagon approach is expected to be useful in future work when examining grasping abilities of subjects with neuromuscular disorders.     

Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia

OBJECTIVE: Newborn screening based on measurement of 17alpha-hydroxyprogesterone (17-OHP) in a dried blood spot on filter paper is an effective tool for early diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Its most important rationale is prevention of a life-threatening salt-wasting (SW) crisis; in moderate forms of CAH, early diagnosis and treatment may prevent permanent negative effects of androgen overproduction. Our target was to analyse if all CAH patients who had been identified clinically before puberty would have been detected by the newborn screening. METHODS: Newborn screening cards of 110 CAH patients born between 1988 and 2000 in five Middle-European countries and diagnosed prior to puberty (77 SW and 33 moderate) and cards from 920 random, healthy newborn controls were analysed. CAH screening had not yet been introduced during this time. The diagnosis was based on clinical and laboratory signs and, in most cases, on CYP21 gene mutation analysis. All 17-OHP measurements in dried blood spots were carried out using a time-resolved fluoroimmunoassay kit. RESULTS: In the newborn screening blood spots, the median of 17-OHP levels was 561 nmol/l (range 91-1404 nmol/l) in subjects with the SW form and 40 nmol/l (4-247 nmol/l) in the moderate form. All 77 SW patients would have been detected by newborn screening using the recommended cut-off limits (30 nmol/l). However, 10 of 33 patients with moderate CAH would have been missed. 17-OHP levels of all controls were below the cut-off. CONCLUSION: Newborn screening is efficient for diagnosing the SW form of CAH, but is inappropriate for identifying all patients with a moderate form of CAH. It appears that the false-negative rate is at least one-third in children with the moderate form of CAH.     

Association of Average Telomere Length with Body-Mass Index and Vitamin D Status in Juvenile Population with Type 1 Diabetes

Background

Type 1 diabetes (T1D) is an autoimmune chronic disease where hyperglycemia, increased risk of oxidative stress, advanced glycation end-products and other genetic and environmental factors lead to T1D complications. Shorter telomeres are associated with hyperglycemic levels and lower serum vitamin D levels.

Methods

Average telomere length (ATL) in whole blood DNA samples was assessed with qPCR method in 53 Slovenian T1D children/adolescents (median age 8.7 years, 1:1.3 male/female ratio). Body mass index standard deviation score (BMI-SDS), glycated haemoglobin and serum level of vitamin D metabolite (25-(OH)-D3) and the age at the onset of T1D were collected from the available medical documentation.

Results

Results indicate shorter ATL in subjects with higher BMI-SDS when compared to those with longer ATL (0.455 ± 0.438, −0.63 ± 0.295; p=0.049). Subjects with higher BMI-SDS had lower serum vitamin D levels when compared to those with lower BMI-SDS (40.66 ± 3.07 vs. 52.86 ± 4.85 nmol/L; p=0.045). Vitamin D serum levels did not significantly differ between subjects with longer/shorter ATL.

Conclusion

T1D children/adolescents with shorter ATL tend to have higher BMI-SDS. Lower serum vitamin D levels were associated with higher BMI-SDS, while associations between vitamin D serum levels, age at the onset of T1D, glycated haemoglobin and ATL were not observed. Additional studies with more participants are required to clarify the role of the telomere dynamics in T1D aetiology and development of complications.     

Robustness of diffuse reflectance spectra analysis by inverse adding doubling algorithm

Analysing diffuse reflectance spectra to extract properties of biological tissue requires modelling of light transport within the tissue, considering its absorption, scattering, and geometrical properties. Due to the layered skin structure, skin tissue models are often divided into multiple layers with their associated optical properties. Typically, in the analysis, some model parameters defining these properties are fixed to values reported in the literature to speed up the fitting process and improve its performance. In the absence of consensus, various studies use different approaches in fixing the model parameters. This study aims to assess the effect of fixing various model parameters in the skin spectra fitting process on the accuracy and robustness of a GPU-accelerated two-layer inverse adding-doubling (IAD) algorithm. Specifically, the performance of the IAD method is determined for noiseless simulated skin spectra, simulated spectra with different levels of noise applied, and in-vivo measured reflectance spectra from hyperspectral images of human hands recorded before, during, and after the arterial occlusion. Our results suggest that fixing multiple parameters to a priori known values generally improves the robustness and accuracy of the IAD algorithm for simulated spectra. However, for in-vivo measured spectra, these values are unknown in advance and fixing optical parameters to incorrect values significantly deteriorates the overall performance. Therefore, we propose a method to improve the fitting performance by pre-estimating model parameters. Our findings could be considered in all future research involving the analysis of diffuse reflectance spectra to extract optical properties of skin tissue.     

Dermatome electrical stimulation as a therapeutic ambulatory aid for incomplete spinal cord injured patients

Electrical stimulation of the L-3,4 dermatome during treadmill walking is proposed as a gait training modality in incomplete spinal cord injured patients. The dermatome stimulation proved to be efficient in diminishing the extensor tone occurring after loading of the paralyzed limb during the stance phase of walking and resulting in improved flexion of the leg during the swing phase.     

Cathepsin L in glioma progression: comparison with cathepsin B

OBJECTIVE: Lysosomal cysteine cathepsins have been implicated in tumor progression. This study is aimed to reveal differential expression and compare the prognostic significance of cathepsins B and L in glioma patients. METHODS: The histological slides of 82 patients with primary astrocytic tumors were reviewed. We evaluated the immunostaining of the cathepsins in tumor and endothelial cells. RESULTS: Cathepsins B and L stained positive in 98 and 88% of cases, respectively. The total score was significantly higher in malignant than in benign tumors, both for cathepsin B (p<0.001) and for cathepsin L (p<0.01). The IHC score in endothelial cells in the malignant group was significantly higher only for cathepsin B (p<0.0001). Survival analysis indicated that in contrast to the prognostic significance of total cathepsin B and endothelial cells associated cathepsin B for shorter patients' survival, the prognostic role of cathepsin L was not confirmed. CONCLUSION: Cathepsin L is preferentially expressed in tumor cells, increasing with glioma progression, but is not significantly associated with new vasculature of glioblastoma. In contrast to cathepsin B, cathepsin L has no prognostic impact, suggesting different roles of the two cathepsins in glioma progression.