A recurrent mutation in the ARS (component B) gene encoding SLURP-1 in Turkish families with mal de Meleda: evidence of a founder effect

Mal de Meleda is a rare form of palmoplantar keratoderma, and recently mutations in the ARS (component) B gene have been identified in families with this disease. We identified a recurrent nonsense mutation, R96X, in four families of Turkish descent. In this report, we demonstrate that these families share a common ancestral haplotype at the mal de Meleda locus, suggesting a founder effect.     

Neutrophil-to-lymphocyte ratio for the assessment of hospital mortality in patients with acute pulmonary embolism

Introduction

Neutrophil-to-lymphocyte ratio (NLR), which is an essential marker of inflammation, has been shown to be associated with adverse outcomes in various cardiovascular diseases in the literature. In this study we sought to evaluate the association between NLR and prognosis of acute pulmonary embolism (APE).

Material and methods

We retrospectively evaluated blood counts and clinical data of 142 patients with the diagnosis of pulmonary embolism (PE) from Ondokuz Mayis University Hospital between January 2006 and December 2012. The patients were divided into two groups according to NLR: NLR < 4.4 (low NLR group, n = 71) and NLR ≥ 4.4 (high NLR group, n = 71).

Results

Massive embolism (66.2% vs. 36.6%, p < 0.001) and in-hospital mortality (21.1%, 1.4%, p < 0.001) were higher in the high NLR group. In multivariate regression analysis NLR ≥ 5.7, systolic blood pressure (BP) < 90 mm Hg, serum glucose > 126 mg/dl, heart rate > 110 beats/min, and PCO₂ < 35 or > 50 mm Hg were predictors of in-hospital mortality. The optimal NLR cutoff value was 5.7 for mortality in receiver operating characteristic (ROC) analysis. Having an NLR value above 5.7 was found to be associated with a 10.8 times higher mortality rate than an NLR value below 5.7.

Conclusions

In patients presenting with APE, NLR value is an independent predictor of in-hospital mortality and may be used for clinical risk classification.     

Bond strengths of brackets bonded to enamel surfaces conditioned with femtosecond and Er:YAG laser systems

The aim of this study was to compare femtosecond and Er:YAG laser systems with regard to enamel demineralization and bracket bond strength. Human-extracted premolars were randomized to three groups (n?=?17) depending on the conditioning treatment used for the buccal surfaces: 37 % orthophosphoric acid, Er:YAG laser etching (MSP mode 120 mJ, 10 Hz, 1.2 W), and femtosecond laser etching (0.4 W, 800 nm, 90 fs/pulse, 1 kHz). Metal brackets were bonded with Transbond XT to the conditioned surfaces and light cured for 20 s. The samples were thermocycled (5000 cycles, 5–55 °C) and subjected to shear bond strength (SBS) testing using a universal testing machine. Failure types were analyzed under an optical stereomicroscope and SEM. The adhesive remnant index (ARI) was evaluated to assess residual adhesive on the enamel surface. The results revealed no significant differences in SBS between the Er:YAG laser (7.2?±?3.3 MPa) and acid etching groups (7.3?±?2.7 MPa; p?<?0.05), whereas a significant difference was observed between the femtosecond laser etching group (3.3?±?1.2 MPa) and the other two groups (p?<?0.01). ARI scores were significantly different among the three groups. The results of our study suggest that laser conditioning with an Er:YAG system results in successful etching, similar to that obtained with acid. The sole use of a femtosecond laser system may not provide an adequate bond strength at the bracket–enamel interface.     

K-Ras4B/calmodulin/PI3Kα: A promising new adenocarcinoma-specific drug target?

Introduction: Decades of efforts have yet to yield a safe and effective drug to target KRAS-driven pancreatic, colorectal and lung cancers; particularly those driven by the highly oncogenic splice variant KRAS4B. K-Ras4B’s fairly smooth surface, cancer tissue/cell heterogeneity, tolerated lipid post-translational modification exchange, as well as drug-elicited toxicity present a daunting challenge.

Areas covered: Within this framework, hee we focus on a new adenocarcinoma-specific drug concept. Calmodulin (CaM) binds to K-Ras4B but not to the H-Ras or N-Ras isoforms. Physiologically, in calcium- and calmodulin-rich environments such as ductal tissues, calmodulin can sequester K-Ras4B from the membrane; in cancer, CaM/Ca²⁺ can replace the missing receptor tyrosine kinase (RTK) signal, acting to fully activate PI3Kα.

Expert opinion: An oncogenic GTP-bound K-Ras4B/CaM/PI3Kα complex is supported by available experimental and clinical data; therefore, targeting it may address a pressing therapeutic need. High resolution electron microscopy (EM) or crystal structure of the tripartite complex would allow orthosteric or allosteric drug discovery to disrupt the CaM/PI3Kα interface and thus Akt/mTOR signaling. However, since drug resistance is expected to develop, combining it with compensatory pathways, particularly those involved in cell-cycle control, appears a reasonable strategy.     

Late clinical characteristics of infants with retinopathy of prematurity and treated with cryotherapy

AIM: To describe the clinical characteristics and late results of patients with retinopathy of prematurity (ROP) treated with “6h cryotherapy”. METHODS: Out of 1252 infants screened for ROP, 52 patients were treated with temporal 6h cryotherapy from 1997 to 2005 were recalled to our clinic. Among these 23 patients were available and 46 eyes of 23 infants were included to evaluate for visual acuity, refractive error, ocular alignment, nystagmus, retinal examination (abnormal branching of retinal vessels, retinal thinning, latis degenerations, tortuosity of vessels, straightening of temporal vessels, narrowing of the angle of vessel in the juxtapapillary entrance, pigment changes, macular heterotopia), optic atrophy and optic disc cupping, axial length at birth and axial length at 1y. RESULTS: The median age at examination was 7 (5-18)y. In 32.6% of patients, the visual acuity was ≤20/200 and the mean best corrected visual acuity was 20/35 as measured with a Snellen chart. Mean spherical refractive error was -1.76±2.69 D. The degree of myopia at the last examination was found to be correlated with the elongation of the eye in the first year of life. Exotropia was present in 17.4% (n=8) of infants and esotropia in 13% (n=6). The most common retinal abnormality was abnormal branching of retinal vessels (82.6%) followed by retinal thinning (52.2%). CONCLUSION: The late clinical outcomes of infants with ROP treated in our clinic with cryotherapy seems to comparable with results of laser treatment.     

The beneficial effects of physical exercise on antioxidant status in asthmatic children

BackgroundThe pathogenesis of asthma involves both airway inflammation and an oxidant/antioxidant imbalance. It is demonstrated in asthmatic adults that exercise programmes improve lung function, a mechanism yet to be elucidated. The purpose of this study was to investigate the possible beneficial effects of physical exercise on antioxidant status in asthmatic children which may lead to ameliorated lung function.MethodsThe study enrolled thirteen control and thirty asthmatic children. The asthmatic group was subdivided into two: the first group receiving only pharmacological treatment (n = 15) and the second receiving pharmacological treatment with exercise programme (n = 15) for 8 weeks. Blood samples were drawn from the subjects before and after treatment periods. As oxidant stress markers blood levels of malondialdehyde (MDA) and total nitric oxide (NO), and as antioxidant status, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) enzyme activities were assessed.ResultsBefore any treatment was initiated, MDA and NO levels in the asthmatic group were significantly higher than the controls (3.40 ± 0.96 nmol/ml vs 2.46 ± 0.58 nmol/ml, and 12.53 ± 2.10 vs 9.40 ± 1.39 micromol/L, respectively). Both SOD (p = 0.0001) and GSH-Px (p = 0.023) activities were significantly lower in the asthmatic group. Pharmacological treatment and exercise programme together significantly improved lung performance and decreased the levels of oxidant stress markers, in concordance with a significantly increase in antioxidant enzyme activity measures when compared to the pharmacological treatment.ConclusionStructured exercise programme in asthmatic children resulted in better lung function, which may be attributed to its effect on antioxidant status.     

Propylthiouracil-induced anti-neutrophil cytoplasmic antibodies and agranulocytosis together with granulocyte colony-stimulating factor induced Sweet's syndrome in a patient with Graves' disease

Propylthiouracil (PTU) is an antithyroid drug which is known to cause drug-induced vasculitis. PTU is implicated in 80-90% of cases of anti-neutrophil cytoplasm circulating antibody (ANCA)-associated vasculitis caused by anti-thyroid drugs which induce ANCA production. Sweet's syndrome is characterized by fever, leucocytosis, neutrophilia and the sudden onset of painful skin lesions. The pathology of the disease is still unclear. Cytokine dysregulation including interleukin-6 and endogenous granulocyte colony-stimulating factor (G-CSF) are thought to play a role in the pathogenesis of Sweet's syndrome. PTU and G-CSF are known to cause Sweet's syndrome and other neutrophilic dermatosis. The presence of ANCA can have a diagnostic value in Sweet's syndrome. Systemic corticosteroids are the first-line therapy for both diseases. Here we report a female patient with Graves' disease who developed ANCA and Sweet's syndrome after using PTU and G-CSF.