Cytosolic nucleic acid sensing and mitochondrial transcriptomic changes as early triggers of metabolic disease in db/db mice.

Animal models of diabetes, such as db/db mice, are a useful tool for deciphering the genetic background of molecular changes at the initial stages of disease development. Our goal was to find early transcriptomic changes in three tissues involved in metabolism regulation in db/db mice: adipose tissue, muscle tissue and liver tissue. Nine animals (three per time point) were studied. Tissues were collected at 8, 12 and 16 weeks of age. Transcriptome-wide analysis was performed using mRNA-seq. Libraries were sequenced on NextSeq (Illumina). Differential expression (DE) analysis was performed with edgeR. The analysis of the gene expression profile shared by all three tissues revealed eight upregulated genes (Irf7, Sp100, Neb, Stat2, Oas2, Rtp4, H2-T24 and Oasl2) as early as between 8 and 12 weeks of age. The most pronounced differences were found in liver tissue: nine DE genes between 8 and 12 weeks of age (Irf7, Ly6a, Ly6g6d, H2-Dma, Pld4, Ly86, Fcer1g, Ly6e and Idi1) and five between 12 and 16 weeks of age (Irf7, Plac8, Ifi44, Xaf1 and Ly6a) (adj. p-value < 0.05). The mitochondrial transcriptomic profile also changed with time: we found two downregulated genes in mice between 8 and 12 weeks old (Ckmt2 and Cox6a2) and five DE genes between 12 and 16 weeks of age (Mavs, Tomm40L, Mtfp1, Ckmt2 and Cox6a2). The KEGG pathway analysis showed significant enrichment in pathways related to the autoimmune response and cytosolic DNA sensing. Our results suggest an important involvement of the immunological response, mainly cytosolic nucleic acid sensing, and mitochondrial signalling in the early stages of diabetes and obesity.

Omalizumab in the treatment of Morbihan syndrome in an adolescent girl - case report and literature review.

Morbihan syndrome (MS) is characterized by solid facial edema, usually related to rosacea or acne vulgaris. The facial edema deforms the patient's features, can impair peripheral vision, and affects quality of life. Its pathophysiology remains unclear. The disease usually has a slow and chronic course. MS most commonly affects middle-aged Caucasian men with rosacea and is rare in people below 20 years of age. MS is a diagnosis of exclusion. There is no standard treatment for MS, though systemic isotretinoin and antihistamines are mainly used. We present the case of an adolescent girl with MS nonresponding to 19 months of isotretinoin treatment with add-on antihistamines. Therapy with monthly administration of omalizumab (anti-IgE) for 6 months was an effective therapeutic option, improving the quality of life. Our case is the second description of omalizumab use in Morbihan syndrome, the first in an adolescent.

Anabolic Steroids Activate the NF-κB Pathway in Porcine Ovarian Putative Stem Cells Independently of the ZIP-9 Receptor.

Boldenone (Bdn) and nandrolone (Ndn) are anabolic androgenic steroids (AASs) that, as our previous studies have shown, may increase the risk of neoplastic transformation of porcine ovarian putative stem cells (poPSCs). The NF-κB pathway may be important in the processes of carcinogenesis and tumour progression. Therefore, in this work, we decided to test the hypothesis of whether Bdn and Ndn can activate the NF-κB pathway by acting through the membrane androgen receptor ZIP-9. For this purpose, the expression profiles of both genes involved in the NF-κB pathway and the gene coding for the ZIP-9 receptor were checked. The expression and localization of proteins of this pathway in poPSCs were also examined. Additionally, the expression of the ZIP-9 receptor and the concentration of the NF-κB1 and 2 protein complex were determined. Activation of the NF-κB pathway was primarily confirmed by an increase in the relative abundances of phosphorylated forms of RelA protein and IκBα inhibitor. Reduced quantitative profiles pinpointed not only for genes representing this pathway but also for unphosphorylated proteins, and, simultaneously, decreased concentration of the NF-κB1 and 2 complex may indicate post-activation silencing by negative feedback. However, the remarkably and sustainably diminished expression levels noticed for the SLC39A9 gene and ZIP-9 protein suggest that this receptor does not play an important role in the regulation of the NF-κB pathway.

Stinging insect identification in children with Hymenoptera venom allergy and their parents.

Introduction: The treatment of Hymenoptera venom allergy (HVA) is based among others on the proper identification of the culprit insect. Aim: To assess the accuracy in identifying stinging insects by children with HVA and their parents. Material and methods: Participants were recruited from a paediatric medical centre. The data on their demographics, sting history and ability of insect identification (based on pictures) were obtained using a questionnaire. The study sample consisted of 102 children with HVA and their parents as well as 98 children without HVA and their parents. Results: The rates of subjects correctly identifying insects in the groups were 91.2%, 92.5%, 78.8%, 82.4%, respectively. When compared to children with HVA, those without HVA were less likely to correctly identify the bee, bumblebee and hoverfly. In this group, the correct identification of the wasp was more common among children living in the countryside. The correct identification of the bee and bumblebee by children without HVA was more common among children living in the city. Conclusions: Some children with HVA and their parents cannot correctly identify stinging insects despite previous life-threatening allergic reactions. The ability to identify stinging insects may depend on the HVA diagnosis and place of residence.

Obesity aggravates contact hypersensitivity reaction in mice.

BACKGROUND: Obesity is associated with chronic, low-grade inflammation in tissues and predisposes to various complications, including inflammatory skin diseases. However, the link between obesity and contact hypersensitivity (CHS) is not fully understood. OBJECTIVES: We sought to determine the influence of obesity on T helper 1 (Th1)-mediated CHS. METHODS: The activity/phenotype/cytokine profile of the immune cells was tested in vivo and in vitro. Using quantitative polymerase chain reaction (qPCR) and fecal microbiota transplantation (FMT), we tested the role of a high-fat diet (HFD)-induced gut microbiota (GM) dysbiosis in increasing the effects of CHS. RESULTS: Exacerbated CHS correlates with an increased inflammation-inducing GM in obese mice. We showed a proinflammatory milieu in the subcutaneous adipose tissue of obese mice, accompanied by proinflammatory CD4+ T cells and dendritic cells in skin draining lymph nodes and spleen. Obese interleukin (IL)-17A-/-B6 mice are protected from CHS aggravation, suggesting the importance of IL-17A in CHS aggravation in obesity. CONCLUSIONS: Obesity creates a milieu that induces more potent CHS-effector cells but does not have effects on already activated CHS-effector cells. IL-17A is essential for the pathogenesis of enhanced CHS during obesity. Our study provides novel knowledge about antigen-specific responses in obesity, which may help with the improvement of existing treatment and/or in designing novel treatment for obesity-associated skin disorders.

Vitamin D receptor gene polymorphism influence on lumbar intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration is a multifaceted pathology that is the main morphological cause of lower back pain. This study aimed to determine the link between the vitamin D receptor gene single nucleotide polymorphisms (SNPs) and degenerative processes of the lumbar spine. The complete lumbar spinal columns were collected from 100 Caucasian cadavers via ventral dissection. The specimens for the histological analysis were harvested from the L5/S1 IVDs and endplates. Then, the tissues were cut into slices, inserted into paraffin blocks, and stained. The histology was evaluated according to the Boos' protocol. Moreover, TaqI(rs731236), FokI(rs2228570), and ApaI(rs7975232) genotyping were performed. Lastly, the histological scores for different genotypes were analyzed. The overall Boos' score in the study group was 12.49. It consisted of a mean IVD score of 7.46 and endplate score of 5.39. The determination of the SNPs was successful in 99 specimens and had a distribution of all alleles in accordance with the Hardy-Weinberg equilibrium. No significant differences in overall histological degeneration scores were found between samples from donors with different genotypes. However, in subgroup analysis of specific regions on the IVD, the significant difference was found in posterior inner anulus fibrosus for ApaI. The results of this study suggest that one must be careful when interpreting the results of the clinical and/or radiological studies on vitamin D receptor gene polymorphisms and lumbar spine degeneration risk, because such a relationship, if present, is likely to be very subtle.

Adhesion Molecule Profile and the Effect of Anti-VLA-4 mAb Treatment in Experimental Autoimmune Encephalomyelitis, a Mouse Model of Multiple Sclerosis.

In the course of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), the infiltration of lymphocytes and other inflammatory cells across the blood-brain barrier is associated with interactions between adhesion molecules expressed by infiltrating cells and vascular endothelium. Monoclonal antibodies (mAb) against the α4 subunit of α4-ß1 integrin (VLA-4) show beneficial effects in both MS and EAE. (1) Background: The aim of this study was to examine the expression of selected adhesion molecules: VLA-4, VCAM-1, LFA-1, ICAM-1 and PECAM-1 in the successive phases of EAE and the effect of anti-VLA-4 mAb treatment on that expression. (2) Methods: EAE was induced in C57BL/6 mice by immunization with MOG35-55 peptide. The animals were killed in three successive phases of the disease: onset (day 13), peak (day 18) and chronic (day 28). Frozen sections of the lumbar spinal cord were examined by quantitative immunofluorescence microscopy. The expression of the studied molecules was quantified as the percentage of the cross-sectioned spinal cord lesion area occupied by immunopositive structures. (3) Results: The expression of the studied molecules showed two temporal patterns: (1) an increase in the onset phase, a maximum in the peak phase and a decrease in the chronic phase, which corresponded to the temporal pattern of the clinical score, the number of lesions and the inflammation level (ICAM-1, LFA-1 and PECAM-1), and (2) an increase in the peak phase and no significant change or further increase in the chronic phase (VCAM-1, VLA-4). Among the molecules studied, ICAM-1 and LFA-1 exhibited the highest expression levels in the peak phase of EAE. Anti-VLA-4 mAb inhibited the expression of not only VLA-4 but also other adhesion molecules. (4) Conclusions: The interactions of adhesion molecules governing the migration of leukocytes across the blood-brain barrier change in the successive phases of EAE. The therapeutic mechanism of anti-VLA-4 mAb treatment seems to include a complex influence on a variety of adhesion molecules expressed by infiltrating cells and vascular endothelium.

Penetration of the posterior interosseous nerve fibers into the dorsal capsule of the wrist - a new perspective on wrist innervation.

The dorsal capsule of the wrist and the DCSS may play a significant role in the conduction of nerve signals transmitted from proprioceptors present in SL to PIN, which is located above the dorsal capsule. Hence, this study aimed to determine if nerve fibers of PIN penetrate inside the dorsal capsule. The dorsal capsules of the wrist were dissected from both sides from 15 cadavers. Eventually, 30 dorsal capsules were dissected. It can be concluded that the PIN nerve fibers penetrate the dorsal capsule of the wrist, as the penetration was noticeable in every part evaluated. The present study proves that afferent fibers from the mechanoreceptors of the SLIL potentially pass through the DCSS and subsequently through the dorsal capsule of the wrist to the PIN. This knowledge can surely be of great use for hand surgeons that perform procedures on the dorsal wrist.

Microanatomy of the myocardial extensions of the pulmonary valve in light of modern catheter ablation methodology.

INTRODUCTION: The muscular sleeves (or myocardial extensions) derived from the right ventricle infundibulum myocardium are considered the true anatomic substrate for right ventricular outflow tract arrhythmias. METHODS: Pulmonary valve specimens obtained from 65 donors (24.6% females, mean age 45.9 ± 15.8 years) were investigated micro-anatomically. Specimens were histologically processed, stained with Masson's Trichrome, and examined under a light microscope. RESULTS: The myocardial extensions were present in the left anterior pulmonary valve sinus in 86.2% of cases, in the right anterior sinus in 89.2% of cases and in 90.7% of cases in the posterior sinus (p = .699). In 69.2% of examined hearts, the myocardial extensions were present in all sinuses. The mean height of the extensions was 4.12 ± 1.76 (left anterior) versus 3.69 ± 1.47 (right anterior) versus 4.28 ± 1.73 mm (posterior) (p = .137). The myocardial extensions occupied an average of 28.9 ± 10.4% of the left anterior sinus, 26.7 ± 11.2% of the right anterior sinus, and 31.9 ± 11.3% of the posterior sinus (p = .044). Sleeves extending beyond the fibro-arterial transition zone were present in at least one sinus in 33.8% of hearts (in 7.7% (5/65) of the left and right anterior sinuses and 21.5% (14/65) of posterior sinus, p = .021). CONCLUSIONS: The myocardial extensions of the pulmonary valve are common anatomical entities. Although the length of the myocardial sleeves is similar in all pulmonary valve sinuses, their relative extent is greatest in the posterior sinus. Long sleeves that spread beyond the fibro-arterial transition zone were observed in one-third of hearts, predominantly in the posterior sinus. Myocardial and fibrous tissue layer thicknesses varied considerably.

Is the clinical manifestation of anaphylaxis in children influenced by the trigger of reaction?

INTRODUCTION: The number of anaphylaxis diagnoses in children is rising, being still based on the clinical picture. AIM: To determine whether triggers of anaphylaxis influence its clinical characteristics in children and adolescents. MATERIAL AND METHODS: The study group included 114 children (5 months-17 years, mean age: 8.0 ±4.8 years), (66%: boys) with the episode of anaphylaxis up to 1 year back. Medical data were entered to the NORA Registry by means of a validated structured on-line questionnaire. RESULTS: Three most frequent triggers of anaphylaxis were: insect venom (47.4%), food (35.1%), drugs (5.3%), with a predominance of food (egg white, cow's milk, nuts and peanuts) in the 0-6 years age group, while insect venom (bee predominance) in the 7-17 years age group (p = 0.016). Clinical manifestations differed between food vs. venom allergic reactions and presented as gastro-intestinal (GI) (61.4%) (p = 0.004), respiratory (RS) (93.9%) (p = 0.036), and cardiovascular (CVS) (74.6%) (p = 0.022) symptoms. Among objective symptoms, vomiting was the most common symptom in the 0-2 years age group (47.1%) (p = 0.006), while hypotension in those aged 7-12 years (40%) (p = 0.010). Severity of symptoms evaluated as Mueller's grade (IV - 74.5%) and as Ring and Messmer's grade (III - 65.8%), depended on the trigger (p = 0.028, p = 0.029, respectively). Life-threatening symptoms occurred in 26 children (fall of the blood pressure - 22%, loss of consciousness - 4.4%). CONCLUSIONS: The clinical manifestation of anaphylaxis in children is both trigger and age dependent, irrespective of the gender. A typical patient with food anaphylaxis was younger, presenting predominantly GI symptoms, while a typical patient with venom anaphylaxis was older, with mostly cardiovascular symptoms.

Intervention in anaphylaxis: the experience of one paediatric centre based on NORA reports.

Introduction: Intramuscular adrenaline administration is the primary intervention in anaphylaxis. Aim: To analyse the data on intervention in children admitted due to anaphylaxis to the tertiary paediatric centre and compare them to the data from the Network for Online-Registration of Anaphylaxis. Material and methods: A validated structured on-line questionnaire was used to collect data concerning the first and second-line intervention in anaphylaxis. The study was conducted in cooperation with the European Anaphylaxis Registry. Results: The study group comprised 114 children (76 boys, 66.87%) aged 5 months-17 years with the predominance of moderate-to-severe anaphylaxis (grade III in Ring and Messmer's, and grade IV in Mueller's scale). In 103 (90.4%) children the first line of medical intervention was provided by medical staff. In the first-line intervention 39 (34.8%) children were given adrenaline. Five (4.4%) children were given the second dose of adrenaline and were admitted to the intensive care unit. In the second-line intervention adrenaline was given to 12 (15.6%) children. In one third it was at least the second reaction to the same trigger. Children treated with adrenaline were older (9.3 ±4.8 years), in comparison to those not treated (7.3 ±4.6 years, p = 0.034). Directly after the episode of anaphylaxis the children got the prescription for the adrenaline autoinjector in 35.1%, emergency training in 7.9%, and counselling on the avoidance of the anaphylaxis trigger in 30.7%. Grade III R&M reaction increased 3-fold the odds of AAI prescription (95% CI: 1.08-8.15). Conclusions: There is a strong need to continue education on proper management of anaphylaxis in children.

Identification of CD34+/PGDFRα+ Valve Interstitial Cells (VICs) in Human Aortic Valves: Association of Their Abundance, Morphology and Spatial Organization with Early Calcific Remodeling.

Aortic valve interstitial cells (VICs) constitute a heterogeneous population involved in the maintenance of unique valvular architecture, ensuring proper hemodynamic function but also engaged in valve degeneration. Recently, cells similar to telocytes/interstitial Cajal-like cells described in various organs were found in heart valves. The aim of this study was to examine the density, distribution, and spatial organization of a VIC subset co-expressing CD34 and PDGFRα in normal aortic valves and to investigate if these cells are associated with the occurrence of early signs of valve calcific remodeling. We examined 28 human aortic valves obtained upon autopsy. General valve morphology and the early signs of degeneration were assessed histochemically. The studied VICs were identified by immunofluorescence (CD34, PDGFRα, vimentin), and their number in standardized parts and layers of the valves was evaluated. In order to show the complex three-dimensional structure of CD34+/PDGFRα+ VICs, whole-mount specimens were imaged by confocal microscopy, and subsequently rendered using the Imaris (Bitplane AG, Zürich, Switzerland) software. CD34+/PDGFRα+ VICs were found in all examined valves, showing significant differences in the number, distribution within valve tissue, spatial organization, and morphology (spherical/oval without projections; numerous short projections; long, branching, occasionally moniliform projections). Such a complex morphology was associated with the younger age of the subjects, and these VICs were more frequent in the spongiosa layer of the valve. Both the number and percentage of CD34+/PDGFRα+ VICs were inversely correlated with the age of the subjects. Valves with histochemical signs of early calcification contained a lower number of CD34+/PDGFRα+ cells. They were less numerous in proximal parts of the cusps, i.e., areas prone to calcification. The results suggest that normal aortic valves contain a subpopulation of CD34+/PDGFRα+ VICs, which might be involved in the maintenance of local microenvironment resisting to pathologic remodeling. Their reduced number in older age could limit the self-regenerative properties of the valve stroma.

Quadricuspid pulmonary valve: macroscopic and microscopic morphometric examination.

A quadricuspid pulmonary valve obtained upon autopsy of a 26-year-old male was examined. The macroscopic evaluation revealed three normal (posterior, right anterior and left anterior) leaflets and one additional leaflet of the pulmonary valve. Except that, the heart showed neither other anatomical variabilities nor any signs of heart disease. The additional leaflet was located between the left anterior and right anterior leaflets and was significantly smaller in size. Under the microscope, all leaflets showed preservation of the typical, layered structure. The thickness and extracellular matrix composition of the particular layers differed between the leaflets. Right ventricular myocardium (myocardial sleeves) exceeded the level of the hinge line in all three normal leaflets, which was not observed in the additional leaflet. Autonomic nerves and ganglia were not seen in the perivalvular epicardial adipose tissue surrounding the additional leaflet. The sinus wall of all the leaflets revealed typical organization of collagen bundles as well as elastic fibers and showed no signs of disruption. The abnormality seen in the structure of the pulmonary valve is likely to be a result of disturbed embryonic development and may affect the clinical management of patients with such variation.

Combination of ERK2 inhibitor VX-11e and voreloxin synergistically enhances anti-proliferative and pro-apoptotic effects in leukemia cells.

ERK1/2 inhibitors are new promising anticancer drugs. The aim of this study was to investigate the effect of the combination of ERK2 inhibitor VX-11e and voreloxin on MOLM-14, K562, REH and MOLT-4 leukemia cell lines. We found that VX-11e alone and in combination with voreloxin significantly decreased ERK activation in all cell lines tested. To evaluate the interactions of the drugs, cells were treated for 24 h with VX-11e or voreloxin alone and in combination at fixed ratios based on IC50 values. The combinatorial effects of both drugs were synergistic over a wide range of concentrations in MOLM-14, REH and MOLT-4 cell lines. In K562 cells, three effects were found to be additive, one antagonistic and only one synergistic. The results showed that incubation with both VX-11e and voreloxin inhibited the growth of leukemia cells, affected cell cycle and induced apoptosis. Furthermore, the molecular mechanism of these effects might be attributed to an increased expression of p21 and a decreased expression of survivin and NF-κB in all cell lines tested except from K562 cells. In conclusion, combination of VX-11e and voreloxin can exert a synergistic anticancer effect in leukemia cells.

Bronchiolitis in children - do we choose wisely?

OBJECTIVE: Aim: The aim of our study was to evaluate the adherence to the 2014 American Academy of Pediatrics guidelines for bronchiolitis. PATIENTS AND METHODS: Material and methods: The study measured the utility of diagnostic and therapeutic procedures in children with the first episode of bronchiolitis in their lives hospitalized at the University Children's Hospital in Krakow, Poland, between September 2014 and March 2015. The results were compared with the achievable benchmarks of care (ABCs) for hospitalized children with bronchiolitis. Hospital performance was measured by five clinical indicators: chest X-ray utilization, viral testing implementation, steroids, antibiotics and bronchodilator prescriptions. Odds ratios (OR) with 95% confidence intervals (95%CI) were calculated for comparisons between hospital performance and ABCs. RESULTS: Results: There were 214 children in the study group (56% were boys). Chest X-ray was performed in 95% of the children, while ABCs indicate 32.4% (OR=42; 95%CI [30-58]); viral testing in 67.9% children, whereas ABCs indicate 0.6% (OR=350; 95%CI [155-790]). Steroids were prescribed in 62% of the patients (ABCs=6.4%; OR=24; 95%CI [18-31]), similarly antibiotics in 62% (ABCs=18.5%; OR=20; 95%CI [15-25]), bronchodilators were administered in 86% patients (ABCs=18.9%; OR=27; 95%CI [21-34]). All the analyzed procedures were used dozens of times more often than suggested by ABCs (the difference is highly statistically significant). CONCLUSION: Conclusions: Overuse of ineffective procedures and therapies in bronchiolitis remains common, with overuse of chest X-rays, viral testing, prescriptions of bronchodilators, corticosteroids and antibiotics. We should focus our efforts on strategies aimed at decreasing the procedures that have no benefit for children with bronchiolitis.

Simplification of intradermal skin testing in Hymenoptera venom allergic children.

BACKGROUND: The direct comparison between children and adults with Hymenoptera venom anaphylaxis (HVA) has never been extensively reported. Severe HVA with IgE-documented mechanism is the recommendation for venom immunotherapy, regardless of age. OBJECTIVE: To determine the differences in the basic diagnostic profile between children and adults with severe HVA and its practical implications. METHODS: We reviewed the medical records of 91 children and 121 adults. RESULTS: Bee venom allergy was exposure dependent, regardless of age (P < .001). Atopy was more common in children (P = .01), whereas cardiovascular comorbidities were present almost exclusively in adults (P = .001). In the bee venom allergic group, specific IgE levels were significantly higher in children (29.5 kUA/L; interquartile range, 11.30-66.30 kUA/L) compared with adults (5.10 kUA/L; interquartile range, 2.03-8.30 kUA/L) (P < .001). Specific IgE levels for culprit insect venom were higher in bee venom allergic children compared with the wasp venom allergic children (P < .001). In adults, intradermal tests revealed higher sensitivity, accompanied by larger area of skin reactions, regardless of type of venom. At concentrations lower than 0.1 µg/mL, 16% of wasp venom allergic children and 39% of bee venom allergic children had positive intradermal test results. The median tryptase level was significantly higher in adults than in children for the entire study group (P = .002), as well as in bee (P = .002) and wasp venom allergic groups (P = .049). CONCLUSION: The basic diagnostic profile in severe HVA reactors is age dependent. Lower skin test reactivity to culprit venom in children may have practical application in starting the intradermal test procedure with higher venom concentrations.

Types of laryngomalacia in children: interrelationship between clinical course and comorbid conditions.

The aim of this study was to: (1) find out whether laryngomalacia (LM) types are related to clinical course; (2) which patients with LM are at higher risk of other airway malacia [tracheomalacia (TM) and/or bronchomalacia (BM)]; and (3) evaluate the prevalence of LM in our region. Patients with established LM diagnosis and complete clinical and endoscopy records were enrolled. They were classified into different LM types according to classification based on the side of supraglottic obstruction. One hundred ten children were included. The most common LM appearance was type I-58 children, followed by combine types (I + II and I + III)-38. The other airway malacia were found in 47 patients: TM in 31, BM in 10, and TM with BM in 6. Other comorbidities (cardiac, neurological, and genetic disorders) were identified in 30 children. Patients with combine types of LM differ from those with single type of LM in terms of prematurity (13 vs 31 %, p = 0.04) and higher weight on the examination day (p = 0.006). Patients with other airway malacia differ from children with isolated LM in terms of prematurity (40 vs 13 %, p = 0.008), comorbidities (38 vs 19 %, p = 0.024), and lower weight on the examination day (p = 0.014). The prevalence of clinically relevant LM was one in 2600-3100 newborns. Clinical course of LM cannot be anticipated on the basis of solely endoscopic evaluation of the larynx. Comorbidities and prematurity increase the risk of other airway malacia. The prevalence of LM is relatively high in the middle-south part of Poland.

Natural history of Hymenoptera venom allergy in children not treated with immunotherapy.

BACKGROUND: Differences in treatment approach still exist for children after systemic sting reactions. In addition, there are still some doubts about when systemic reactors should be treated with venom immunotherapy (VIT). OBJECTIVE: To determine the rate of sting recurrence and natural history of Hymenoptera venom allergy (HVA) in children not treated with VIT. METHODS: A total of 219 children diagnosed as having HVA who were not treated with VIT were identified in 3 pediatric allergology centers. Survey by telephone or mail with the use of a standardized questionnaire was conducted. The number of field re-stings, subsequent symptoms, and provided treatment were analyzed. RESULTS: A total of 130 of the 219 patients responded to the survey, for a response rate of 59.4%. During the median follow-up period of 72 months (interquartile range, 52-85 months), 44 children (77% boys) were stung 62 times. Normal reactions were most common, occurring in 27 patients (62%). Severe systemic reactions (SSRs) occurred in 8 (18%) of those who were re-stung. The subsequent reaction was significantly milder (P < 0.001), especially in the case of patients re-stung by the same insect (P < .001). None of the children with prediagnostic large local reactions and negative test results for venom specific IgE developed SSRs after re-sting by the culprit insect (P = .03). In children with SSRs, median time from diagnosis to re-sting was 2 times longer than that in those with large local reactions and normal reactions (P = .007). CONCLUSIONS: Most children with HVA not treated with VIT reported milder reactions after a re-sting. Probability of SSR to re-sting increases along with the severity of initial reaction.

Cardiovascular risk in chronic kidney disease patients: intima-media thickness predicts the incidence and severity of histologically assessed medial calcification in radial arteries.

BACKGROUND: The objective of the study was to determine the relationship between common carotid artery intima-media thickness (CCA-IMT) and histologically assessed calcification of radial artery in relation to clinical features and laboratory markers of bone and mineral metabolism, inflammation, and oxidative stress in patients with stage 5 chronic kidney disease (CKD). METHODS: The study comprised 59 patients (36 hemodialyzed, 23 predialysis). CCA-IMT was measured by ultrasonography; the biochemical parameters examined were assessed using routine laboratory methods, ELISA micro-plate immunoassays and spectrophotometry. Fragments of radial artery obtained during creation of hemodialysis access were cryosectioned and stained for calcifications using von Kossa method and alizarin red. RESULTS: Glucose, osteoprotegerin, pentraxin 3 and Framingham risk score significantly correlated with CCA-IMT. In multiple regression analysis, OPG positively predicted CCA-IMT. Radial artery calcifications were found in 34 patients who showed higher CCA-IMT (0.98 ± 0.13 vs 0.86 ± 0.14 mm; P = 0.006). Higher CCA-IMT values were also associated with more advanced calcifications. CCA-IMT and the presence of plaques in common carotid artery were positive predictors of radial artery calcifications, independent of dialysis status, Framingham risk score, CRP and Ca x Pi [OR for calcifications 2.19 (1.08-4.45) per 0.1 mm increase in CCA-IMT]. The presence of radial artery calcifications was a significant predictor of mortality, independent of dialysis status and Framingham risk score [HR 3.16 (1.03-9.64)]. CONCLUSIONS: In CKD patients, CCA-IMT examination can be used as a surrogate measure to assess the incidence and severity of arterial medial calcification which is associated with poor clinical outcome in these patients.

Development of Parents' of Children with Hymenoptera Venom Allergy Quality of Life Scale (PoCHVAQoLS).

INTRODUCTION: Venom allergy in children, as a potentially life-threatening disease, may have a considerable impact on the quality of life of the parents of the affected patients. AIM: To present development of the quality of life scale for such parents. MATERIAL AND METHODS: The study sample included 70 parents of children with a history of insect sting reaction, referred for consultations to the allergy centre of the University Children's Hospital of Krakow, Krakow, Poland, in 2000-2010. An initial pool of 56 items divided into 6 domains was prepared. The items with intercorrelations higher than 0.7 were removed from each domain and principal component analysis was conducted for each domain separately to provide a one-dimensional subscale for each domain. Reliability of the subscales was assessed using the Cronbach α coefficient in terms of the Classical Test Theory and with the rho coefficient in terms of the Item Response Theory. The multidimensionality of the scale was tested using multitrait scaling. RESULTS: Two to four items from each domain were selected to constitute five subscales. Both the rho and α coefficients for all the subscales were 0.75 or higher. The multitrait method showed that almost all the items indicated stronger correlations with their own subscale than with other subscales. Correlations between subscales were lower than 0.5. CONCLUSIONS: The presented scale consists of high validity and reliability subscales measuring the quality of life of parents of Hymenoptera venom allergic children. As their quality of life is strongly related to the health of their children, such information may be helpful in everyday clinical practice.