An Assessment of Dental Treatment Need: An Overview of Available Methods and Suggestions for a New, Comparative Summative Index

Objective: The aims were to give an overview and consider advantages and disadvantages of different approaches used to evaluate dental treatment need and to suggest an alternate Quantitative Summative Dental Treatment Need Index. Methods: The Medline Ovid database was searched for relevant articles published during the last three decades combining the terms "needs assessment,""dental care,""health services needs and demand." Results: There were substantial differences in methods used. Different modifications of the Decayed, Missing, Filled Teeth/Surfaces indices, complex quantitative summative indices, or simplified approaches were used to assess dental treatment need. Differing advantages and disadvantages of these methods can be identified. Previously used approaches have a common limitation for use in oral epidemiology. Conclusions: The suggested alternate Quantitative Summative Dental Treatment Needs Index focuses on an ability to compare both the total burden of treatment need as well as to make a distinction among specific treatment needs across populations. This new approach is an attempt to develop a comprehensive index for use in oral epidemiology with further revisions anticipated.     

Drug safety evaluation of lenvatinib for thyroid cancer

Introduction: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor of VEGFR1,2,3,4, FGFR1,2,3,4, PDGFR-α as well as RET and KIT signaling network. Its activity against radioiodine-resistant differentiated thyroid cancer (DTC) has been recently demonstrated. Patients, who were given lenvatinib, showed significantly longer median progression free survival than placebo group, 18.3 vs 3.6 months, respectively. This review is focused on lenvatinib safety profile in patients treated due to DTC and medullary thyroid carcinoma. Among the most frequent lenvatinib-related adverse events (AEs) were hypertension, proteinuria, diarrhea, appetite decrease, weight loss, nausea and stomatitis. Although a lot of them were manageable, in 35–68% of patients dose reduction was required. Nevertheless, only 15% of subjects withdrew the drug due to its toxicity.Areas covered: published results of clinical trials phase II and III investigating both safety and efficacy of lenvatinib in thyroid cancer.Expert opinion: Lenvatinib shows acceptable safety profile in patients with thyroid carcinoma. Treatment-related side effects are usually manageable by dose modifications or by concomitant non-pharmacological and pharmacological treatment. However, the early recognition of any potential drug toxicity is crucial to avoid serious complications as well as to keep a patient on drug as long as the treatment is beneficial.     

The Influence of Human Neutrophils on N-nitrosodimethylamine (NDMA) Synthesis

N-nitrozodimethyloamine (NDMA) is a carcinogenic compound that can be formed in vivo. NDMA is synthesized from precursors-amines and nitrosating agents. Nitrosating agents are formed through the reaction of oxide, reactive oxygen species and nitric oxide (NO). Human neutrophils (PMN) are an important source of the most reactive oxygen species as well as of the nitric oxide. The increase in oxygen metabolism of PMN can lead to the increase nitrosating agent and nitroso-forms. Inflammatory process is associated with locally decreased pH that may favor nitrosation reaction.

In the present study, we estimated the NDMA synthesis by LPS-stimulated PMN in the presence of the iNOS inhibitor – N-nitro-L-arginine methyl ester (L-NAME). In the nitrosation reaction dimethylamine (DMA) was used as substrat. The viability of the cells was measured by cytometric method. NDMA concentrations the culture media was measured by GCMS method. NO production was estimated by Griess's method. Expression of iNOS was determined by western blotting.

Results obtained showed that DMA nitrosation is most effective in pH between 3–4.5. Nonstimulated PMN produced lower concentrations of NO than LPS-stimulated cells (1.27 μg/cm³ and 1.57 μg/cm³, respectively). In the culture of nonstimulated PMN supplemented with DMA, there was NDMA (mean – 0.99 ng/cm³). In the culture of LPS-stimulated PMN in the presence of DMA, the concentration of NDMA was higher than in the culture of nonstimulated PMN (median – 1.45 ng/cm³). In the supernatants of cells incubated without DMA and with DMA, LPS and L-NAME, no NDMA was detected. These results indicate that PMN can be one of sources of nitrosating agents and can play a role in endogenous NDMA synthesis. Stimulation of PMN can lead to the increase of NDMA concentration following the increase of NO production. Different pathological conditions associated with PMN activation as well as the decreased pH may favor endogenous NDMA synthesis.     

Mandibular dental changes following serial and late extraction of mandibular second premolars

Objectives:To determine changes in occlusal curves and dental tipping occurring from mandibular second premolar serial extraction, early extraction of deciduous mandibular second molars with missing second premolars, and late second premolar extraction compared with untreated controls.Materials and Methods:Information was collected from 85 subjects at three time points: T0, prior to serial extraction; T1, after serial extraction and drift prior to orthodontic treatment, and pretreatment for the late premolar extraction patients; and T2, posttreatment. Untreated age- and gender-matched controls were used for comparison. Three occlusal curves were measured on digitized mandibular casts, and dental tipping was assessed using lateral cephalograms.Results:At T0, there were no significant differences among groups. At T1, there was significant steepening of Monson''s sphere and the curve of Wilson between early and late extraction and control groups. At T2, the differences in Monson''s sphere and the curve of Wilson were fully corrected. At T1, there were significant differences in the tipping of mandibular 6''s, 4''s, and 3''s between the early extraction groups compared with the late extraction and control groups. At T2, these differences in tipping were fully corrected. There were no differences in mandibular incisor tipping between groups at T1 or T2.Conclusions:Serial extraction produced steeper occlusal curves and significant tipping of mandibular first molars, first premolars, and canines after extraction and physiologic drift (T1). Accentuated occlusal curves and tooth tipping were fully corrected following orthodontic treatment (T2). Mandibular incisor position was unchanged by serial or late second premolar extraction.     

Temporal integration of melatonin infusion duration: signal averaging versus frequency dependence

Day length affects somatic and reproductive physiology of Siberian hamsters via regulation of the duration of nocturnal pineal melatonin secretion. Nightly 'long' (e.g. 12 hr) or 'short' (e.g. 6 hr) melatonin signals inhibit or stimulate gonadal growth, respectively. When long and short signals are presented in combination, however, neuroendocrine mechanisms exhibit a frequency-dependent response, stimulating gonadal growth only if short signals are presented every second night or more frequently. The present experiments further assessed formal models for the temporal integration of melatonin signals changing abruptly in duration from night to night. Photo-inhibited Siberian hamsters were housed in constant light and infused subcutaneously with various combinations of nightly short or long melatonin signals according to one of the several regimes that varied the frequency of short melatonin signal occurrence, average duration of the nightly melatonin signal, or both. Six weeks of nightly alternating short and long signals yielded different gonadal responses depending on the average melatonin signal duration. Moreover, when average melatonin signal duration was held constant between groups, gonadal stimulation was independent of the frequency of the constituent melatonin signals except when the duration of the short signal was reduced to 3 hr. Thus, neuroendocrine mechanisms do not solely categorize melatonin signals as either long or short but attend also to the duration of each component signal. In the majority (six of seven) of infusion regimes, reproductive responses to chimeric patterns of long and short melatonin signals were compatible with a simple signal-averaging mechanism.