Candidate genes for obstructive sleep apnea in non-syndromic children with craniofacial dysmorphisms - a narrative review.

Pediatric obstructive sleep apnea (POSA) is a complex disease with multifactorial etiopathogenesis. The presence of craniofacial dysmorphisms influencing the patency of the upper airway is considered a risk factor for POSA development. The craniofacial features associated with sleep-related breathing disorders (SRBD) - craniosynostosis, retrognathia and micrognathia, midface and maxillary hypoplasia - have high heritability and, in a less severe form, could be also found in non-syndromic children suffering from POSA. As genetic factors play a role in both POSA and craniofacial dysmorphisms, we hypothesize that some genes associated with specific craniofacial features that are involved in the development of the orofacial area may be also considered candidate genes for POSA. The genetic background of POSA in children is less explored than in adults; so far, only one genome-wide association study for POSA has been conducted; however, children with craniofacial disorders were excluded from that study. In this narrative review, we discuss syndromes that are commonly associated with severe craniofacial dysmorphisms and a high prevalence of sleep-related breathing disorders (SRBD), including POSA. We also summarized information about their genetic background and based on this, proposed 30 candidate genes for POSA affecting craniofacial development that may play a role in children with syndromes, and identified seven of these genes that were previously associated with craniofacial features risky for POSA development in non-syndromic children. The evidence-based approach supports the proposition that variants of these candidate genes could lead to POSA phenotype even in these children, and, thus, should be considered in future research in the general pediatric population.

The use of platelet-rich fibrin in the surgical treatment of medication-related osteonecrosis of the jaw: 40 patients prospective study.

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) is defined as exposed bone in the maxillofacial region persisting for more than eight weeks in patients who are or were treated with antiresorptive or antiangiogenic agents and had no radiation therapy to the craniofacial region or obvious metastatic disease of the jaws. It is a recognised side effect of antiresorptive or antiangiogenic medication. To date, there is no specific gold standard treatment for MRONJ cases. The aim of this study was to evaluate the successful rate of surgical treatment with adjuvant local application of platelet rich fibrin. METHODS: 40 patients treated with necrotic bone resection and adjuvant local application of platelet-rich fibrin (PRF) were included. Treatment outcomes were evaluated after 12 months. RESULTS: The outcome of surgical treatment was successful in 34 of all 40 patients (85%), in 12 months follow-up. If we evaluate only cases where removal of all necrotic bone was possible the success rate was increased to 94%. A significant association between size of necrotic bone and treatment response was found (P=0.014, Wilcoxon rank sum test with continuity correction). CONCLUSIONS: Surgical treatment of MRONJ with adjuvant local PRF application proved to be very effective and safe, especially in early stages when all necrotic bone can be easily removed.

HERMES - A Software Tool for the Prediction and Analysis of Magnetic-Field-Induced Residual Dipolar Couplings in Nucleic Acids.

Field-Induced Residual Dipolar Couplings (fiRDC) are a valuable source of long-range information on structure of nucleic acids (NA) in solution. A web application (HERMES) was developed for structure-based prediction and analysis of the (fiRDCs) in NA. fiRDC prediction is based on input 3D model structure(s) of NA and a built-in library of nucleobase-specific magnetic susceptibility tensors and reference geometries. HERMES allows three basic applications: (i) the prediction of fiRDCs for a given structural model of NAs, (ii) the validation of experimental or modeled NA structures using experimentally derived fiRDCs, and (iii) assessment of the oligomeric state of the NA fragment and/or the identification of a molecular NA model that is consistent with experimentally derived fiRDC data. Additionally, the program's built-in routine for rigid body modeling allows the evaluation of relative orientation of domains within NA that is in agreement with experimental fiRDCs.

HPV, protein p16 and squamous cell carcinoma of the oral cavity.

BACKGROUND: Squamous cell carcinoma of the oral cavity is generally caused by the long-term impact of known risk factors, e.g. tobacco and alcohol, along with chronic traumatisation. A number of studies now implicate HPV infection in head and neck tumour carcinogenesis but the exact role of HPV infection in the oral cavity remains unclear. METHODS: In this study, we evaluated 78 patients with oral squamous cell carcinoma (OSCC) for the expression of protein p16 in the context of HPV positivity and its influence on the overall survival rate, disease location, staging and grading. RESULTS: Regarding the tumour location, no significant difference was found between HPV-positive and HPV-negative patients, nor between p16-positive and p16-negative patients. There was also no trend in terms of HPV status and stage, and differentiation of carcinoma. There was no effect on HPV-positive patients relative to the time to progression (P=0.84) and overall survival rate (P=0.78). P16 positivity was not found to have an effect on the overall survival rate of patients (P=0.41) and there was no correlation between p16 positivity relative to the time to progression (P=0.66). CONCLUSIONS: In summary, the data suggest that there is no effect of HPV status on the prognosis of OSCC patients compared to other HNSCC locations.

Novel simulation method of space charge effects in electron optical systems including emission of electrons.

We present a comprehensive numerical method for iterative computation of electron optical systems influenced by space charge which can accurately describe all effects in an optical system, including areas near a cathode tip and all crossovers. We use two different algorithms of evaluating the space charge distribution in different parts of the system. The Monte-Carlo based particle-in-cell method is used in the vicinity of the cathode. The algorithm based on the calculation of the current density distribution from an aberration polynomial is used for the rest of the system. We introduce a re-meshing algorithm which adapts the finite element mesh used for the field calculation in each iteration to the actual space charge distribution to keep it sufficiently fine in all areas with non-zero space charge. The algorithm is finally tested on a design of an experimental electron-welding machine developed at the ISI of the CAS.

Survival of Patients with Primary Brain Tumors: Comparison of Two Statistical Approaches.

PURPOSE: We reviewed the survival time for patients with primary brain tumors undergoing treatment with stereotactic radiation methods at the Masaryk Memorial Cancer Institute Brno. We also identified risk factors and characteristics, and described their influence on survival time. METHODS: In summarizing survival data, there are two functions of principal interest, namely, the survival function and the hazard function. In practice, both of them can depend on some characteristics. We focused on nonparametric methods, propose a method based on kernel smoothing, and compared our estimates with the results of the Cox regression model. The hazard function is conditional to age and gross tumor volume and visualized as a color-coded surface. A multivariate Cox model was also designed. RESULTS: There were 88 patients with primary brain cancer, treated with stereotactic radiation. The median survival of our patient cohort was 47.8 months. The estimate of the hazard function has two peaks (about 10 months and about 40 months). The survival time of patients was significantly different for various diagnoses (p≪0.001), KI (p = 0.047) and stereotactic methods (p = 0.033). Patients with a greater GTV had higher risk of death. The suitable threshold for GTV is 20 cm3. Younger patients with a survival time of about 50 months had a higher risk of death. In the multivariate Cox regression model, the selected variables were age, GTV, sex, diagnosis, KI, location, and some of their interactions. CONCLUSION: Kernel methods give us the possibility to evaluate continuous risk variables and based on the results offer risk-prone patients a different treatment, and can be useful for verifying assumptions of the Cox model or for finding thresholds of continuous variables.

Impact of nucleic acid self-alignment in a strong magnetic field on the interpretation of indirect spin-spin interactions.

Heteronuclear and homonuclear direct (D) and indirect (J) spin-spin interactions are important sources of structural information about nucleic acids (NAs). The Hamiltonians for the D and J interactions have the same functional form; thus, the experimentally measured apparent spin-spin coupling constant corresponds to a sum of J and D. In biomolecular NMR studies, it is commonly presumed that the dipolar contributions to Js are effectively canceled due to random molecular tumbling. However, in strong magnetic fields, such as those employed for NMR analysis, the tumbling of NA fragments is anisotropic because the inherent magnetic susceptibility of NAs causes an interaction with the external magnetic field. This motional anisotropy is responsible for non-zero D contributions to Js. Here, we calculated the field-induced D contributions to 33 structurally relevant scalar coupling constants as a function of magnetic field strength, temperature and NA fragment size. We identified two classes of Js, namely (1)JCH and (3)JHH couplings, whose quantitative interpretation is notably biased by NA motional anisotropy. For these couplings, the magnetic field-induced dipolar contributions were found to exceed the typical experimental error in J-coupling determinations by a factor of two or more and to produce considerable over- or under-estimations of the J coupling-related torsion angles, especially at magnetic field strengths >12 T and for NA fragments longer than 12 bp. We show that if the non-zero D contributions to J are not properly accounted for, they might cause structural artifacts/bias in NA studies that use solution NMR spectroscopy.

Hazard function for cancer patients and cancer cell dynamics.

The aim of the paper is to develop a procedure for an estimate of an analytical form of a hazard function for cancer patients. Although a deterministic approach based on cancer cell population dynamics yields the analytical expression, it depends on several parameters which should be estimated. On the other hand, a kernel estimate is an effective nonparametric method for estimating hazard functions. This method provides the pointwise estimate of the hazard function. Our procedure consists of two steps: in the first step we find the kernel estimate of the hazard function and in the second step the parameters in the deterministic model are obtained by the least squares method. A simulation study with different types of censorship is carried out and the developed procedure is applied to real data.

Current status of Japanese HIV-infected patients with coagulation disorders: coinfection with both HIV and HCV.

We herein report on the current status of Japanese HIV-positive patients with coagulation disorders, primarily hemophilia, based on the national survey of 31 May 2006. The total number of registered patients was 1,431 (Hemophilia A 1,086; Hemophilia B 325; von Willebrand disease 8; others 12), and 604 of these patients were deceased by 31 May 2006. The survival rate after the beginning of 1983 was evaluated by the Kaplan-Meier method. The total number of surviving patients was 827, and the survival rate on 31 May 2006 was 55.7 +/- 1.4%. Among the 827 surviving patients, HCV antibody was observed in 740, was negative in 16, and was not reported in 71 patients. Thus, the prevalence of HCV infection was 98% in the surviving patients based on the presence of HCV antibody. Among the 604 deceased patients, liver disease was reported as a cause of death in 149 cases (25%), and infection with HCV was reported as the possible cause of liver disease in 120 cases (20%). After 1997, 63 cases among the subtotal of 148 deaths had critical hepatic disease that originated from HCV infection, which accounted for 43% of the subtotal. The cumulative rate of patients who received interferon therapy was 32%. Interferon therapy should be prescribed more frequently to HIV-positive patients with coagulation disorders in order to realize the survival benefits, although clinicians should be aware of side effects and toxicities.