Classification tree analysis of second neoplasms in survivors of childhood cancer

Background  

Reports on childhood cancer survivors estimated cumulative probability of developing secondary neoplasms vary from 3,3% to 25% at 25 years from diagnosis, and the risk of developing another cancer to several times greater than in the general population.     

Malignant lymphoma of the stomach in association with inflammatory myofibroblastic tumor of the spleen. A case report

We report on a case of a 40-year-old male patient who underwent a gastrectomy because of a biopsy-proven large B-cell lymphoma of the stomach. On surgery, a nodule in the spleen also was noted. Grossly and microscopically, the two lesions were different: the tumor of the stomach appeared white-gray on the cut surface and was a centroblastic variant of diffuse large B-cell lymphoma. Histologically, one perigastric lymph node was involved. Grossly, the splenic nodule was gray-yellow and had a histological appearance of an inflammatory myofibroblastic tumor (IMT). The association between malignant tumor and IMT is rare. In such an association, the latter lesion most often has been reported in the spleen. As EBV may be involved in the genesis of both lymphoma and IMT, we tested both lesions for its presence using in situ hybridization, but the tests were negative. It remains to be verified whether the association between lymphoma and IMT is more than fortuitous.     

Change of phonation control after cochlear implantation.

OBJECTIVE: To assess the influence of acquired auditory control on some voice parameters in deaf children and adults after cochlear implantation. STUDY DESIGN: Prospective clinical study. SETTING: Tertiary referral center. PATIENTS: Twenty-nine prelingually deafened children and 11 postlingually deafened adults. INTERVENTIONS: The samples of a vowel /a/ were analyzed with an Multi-Dimensional Voice Program (Kay Elemetrics Corporation, Lincoln Park, NJ) before and 6 to 12 months after the cochlear implantation. MAIN OUTCOME MEASURES: The average fundamental frequency (F0), the short-term variation of F0 (JIT) and the amplitude (SH), the very long-term variation of F0 (vF0) and the amplitude (vAm), and the noise-to-harmonic ratio (NHR) were determined and compared for both age groups. The results of the acoustic analysis performed before the implantation were compared with the results after the implantation for children and adults. RESULTS: Significantly greater JIT, SH, vF0, and vAm were detected in the children than in the adults before and after the implantation. The prelingually deafened children significantly improved the control of their phonation after 6 to 12 months' use of the cochlear implant (JIT: p=0.014, SH: p=0.011, vF0: p=0.014, vAm: p=0.031). In the postlingually deafened adults, no significant improvement was found in any of the studied voice parameters after the implantation. F0 showed little or no change after the implantation in children and adults. CONCLUSION: As expected, the voice quality of the prelingually deafened children was significantly worse than that of the postlingually deafened adults. After cochlear implantation, the children significantly improved their short-term and long-term F0 and amplitude variability. In adults, no significant improvement was detected. We suppose that the improvement is a consequence not only of the acquired hearing control but also of the adaptation ability of neuromuscular phonation control and the maturing of these control mechanisms in children. In adults, better phonation quality in general and lesser improvement after the implantation can be the results of well-developed and stable phonation patterns.     

No evidence of association of methylenetetrahydrofolate reductase polymorphism with occurrence of second neoplasms after treatment of childhood leukemia

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been associated not only with the risk for acute lymphoblastic leukemia (ALL) in adults and children, but also with increased methotrexate toxicity. The present study aimed to investigate whether MTHFR polymorphisms modify the risk for development of secondary malignancies in children treated for ALL with protocols that included high-dose methotrexate. MTHFR genotypes were determined in DNA samples isolated from archived bone marrow smears of 15 patients with a second malignancy and a matched control group of 30 patients who did not developed a second malignancy after the treatment for ALL. The frequencies of MTHFR C677T and A1298C genotypes in all patients were: C677T: CC 40%, CT 46.7% and TT 13.3% and A1298C: AA 46.7%, AC 44.4% and CC 8.9%. The relative risk for second malignancy was not significantly increased in ALL patients having at least one polymorphic C667T [odds ratio (OR) 1.51; 95% confidence interval (CI) 0.43 - 5.31] or one polymorphic A1298C allele (OR 1; 95% CI 0.29 - 3.46). Our study suggests that MTHFR polymorphisms are not associated with increased risk of second cancer in children treated with high-dose methotrexate.     

Improvement to the Corrosion Resistance of Ti-Based Implants Using Hydrothermally Synthesized Nanostructured Anatase Coatings

The electrochemical behavior of polycrystalline TiO₂ anatase coatings prepared by a one-step hydrothermal synthesis on commercially pure (CP) Ti grade 2 and a Ti13Nb13Zr alloy for bone implants was investigated in Hank’s solution at 37.5 °C. The aim was to verify to what extent the in-situ-grown anatase improved the behavior of the substrate in comparison to the bare substrates. Tafel-plot extrapolations from the potentiodynamic curves revealed a substantial improvement in the corrosion potentials for the anatase coatings. Moreover, the coatings grown on titanium also exhibited lower corrosion-current densities, indicating a longer survival of the implant. The results were explained by considering the effects of crystal morphology, coating thickness and porosity. Evidence for the existing porosity was obtained from corrosion and nano-indentation tests. The overall results indicated that the hydrothermally prepared anatase coatings, with the appropriate morphology and surface properties, have attractive prospects for use in medical devices, since better corrosion protection of the implant can be expected.     

Optodynamic energy-conversion efficiency during an Er:YAG-laser-pulse delivery into a liquid through different fiber-tip geometries

When an erbium-laser pulse is directed into water through a small-diameter fiber tip (FT), the absorption of the laser energy superheats the water and its boiling induces a vapor bubble. We present the influence of different FT geometries and pulse parameters on the vapor-bubble dynamics. In our investigation, we use a free-running erbium: yttrium aluminum garnet (Er:YAG) (λ=2.94 μm) laser that was designed for laser dentistry. Its pulse is directed into the water through FTs with a flat and conical geometry. Our results show that in the case of the conical FT, a spherical bubble is induced, while a channel-like bubble develops for the flat FT. The ratio between the mechanical energy of the liquid medium and the pulse energy, which we call the optodynamic energy-conversion efficiency, is examined using shadow photography. The results indicate that this efficiency is significantly larger when a conical FT is used and it increases with increasing pulse energy and decreasing pulse duration. The spherical bubbles are compared with the Rayleigh model in order to present the influence of the pulse duration on the dynamics of the bubble's expansion.     

Binding site comparisons for target-centered drug discovery

Introduction: The success of binding site comparisons in drug discovery is based on the recognized fact that many different proteins have similar binding sites. Indeed, binding site comparisons have found many uses in drug development and have the potential to dramatically cut the cost and shorten the time necessary for the development of new drugs.

Areas covered: The authors review recent methods for comparing protein binding sites and their use in drug repurposing and polypharmacology. They examine emerging fields including the use of binding site comparisons in precision medicine, the prediction of structured water molecules, the search for targets of natural compounds, and their application in the development of protein-based drugs by loop modeling and for comparison of RNA binding sites.

Expert opinion: Binding site comparisons have produced many interesting results in drug development, but relatively little work has been done on protein–protein interaction sites, which are particularly relevant in view of the success of biological drugs. Growth of protein loop modeling for modulating biological drugs is anticipated. The fusion of currently distinct methods for the comparison of RNA and protein binding sites into a single comprehensive approach could allow the search for new selective ribosomal antibiotics and initiate pharmaceutical research into other nucleoproteins.