Dental anomalies and their therapeutic implications: retrospective assessment of a frequent finding in patients with cleft lip and palate.

BACKGROUND: Orofacial clefts are characterized by a frequent occurrence of dental anomalies. Numerous studies demonstrate the high prevalence of dental aplasia, supernumerary teeth, and hypoplastic teeth in patients with cleft lip with/without cleft palate (CL/P), yet the therapeutic consequences are rarely discussed. This study explores prevalence, localization, and association between primary and secondary dentition in a large European collective and begins to evaluate the significance of dental anomalies in the therapeutic course of patients with CL/P. METHODS: The medical reports of 1070 patients with different entities of CL/P who presented to our clinic within a 15-year investigation period were evaluated retrospectively. Dental anomalies were classified into three different diagnostic groups: dental aplasia, supernumerary teeth and hypoplastic teeth. The statistical analyses included studies of the frequency and localization of dental anomalies in different cleft entities as well as of the association between primary and secondary dentition and the therapeutic consequences. RESULTS: Uni- or bilateral cleft lip and palate (CLP) (47.5%) occurred most frequently, followed by cleft palate only (CPO) (32.9%) and cleft lip with or without alveolus (CL ± A) (19.6%). Dental anomalies were found significantly more often on the side of the cleft. Aplastic permanent teeth were mostly found in patients with CLP (54.8%), while supernumerary permanent teeth occurred primarily in patients with CL ± A (21.7%). Patients with CPO presented dental aplasia but no patient with CPO showed supernumerary teeth. The occurrence of dental aplasia in the primary dentition significantly increases the probability of aplastic teeth in the permanent dentition. Dental anomalies, in particular dental aplasia, significantly increase patients' need for subsequent orthodontic therapy and orthognathic surgery. CONCLUSION: Dental aplasia and hypoplasia are common in patients with CL/P not only in the cleft area but in the whole dentition. In the event of dental aplasia in the primary dentition, the frequency of aplastic teeth in the permanent dentition is significantly higher. Additionally, the need for therapeutic interventions, especially concerning orthognathic surgery, seems to be significantly higher in patients with CL/P who are affected by dental anomalies. Clinicians should take this into account when creating long-term treatment plans.

The Cleft-screen-questionnaire (CSQ) - A validated screening instrument for health-related quality of life in cleft patients.

BACKGROUND: The objective of this study is to develop and validate a specific screening instrument for assessing the quality of life (QoL) of patients with orofacial clefts. The Cleft-Screen-Questionnaire (CSQ) aims at identifying the main problematic areas and is intended for the routine use in everyday clinical practice to constantly evaluate the conditions' and treatments' effects on patients' well-being. METHODS: First, a pool of 58 questions is created by collecting items from validated questionnaires previously used for assessing the QoL in cleft populations. After the removal of duplicate questions, the questionnaires are answered by 152 patients from a tertiary care center. A factor analysis followed by the calculation of Cronbach's alpha as a reliability measurement led to the final CSQ presented here. RESULTS: The applied factor analysis resulted in five factors. Items showing low factor loadings (seen as <0.5) were excluded initially. Accordingly, factor analysis led to a preliminary number of 43 items. A reliability analysis using Cronbach's alpha and corrected alpha if item deleted showed an overall moderate to high reliability (seen as: 0.6-0.9). After excluding questions with increasing alphas if item deleted, analyses yielded in a final number of 38 questions. CONCLUSION: The final 38-item CSQ is a reliable instrument for evaluating the health-related QoL of cleft patients.

Preoperative assessment of the risk of postoperative death in patients with oral squamous cell carcinoma: a consideration beyond age, sex, and stage of cancer.

Despite improvements in the management of patients in critical care, about 3% patients who have an operation with curative intent for oral squamous cell carcinoma (SCC) do not survive their stay in hospital. Our aim was to assess the risk factors for postoperative death that were independent of the stage of the cancer, or the age and sex of the patients. We screened 4760 consecutive inpatients at a maxillofacial tertiary care centre from 2011 to 2016, and 34 of them had died within the first three months after operation. We matched them with a further 34 patients with the same TNM stage, age, and sex. General personal and clinical data and preoperative laboratory values were screened, and we applied a Charlson Comorbidity Score (for anaesthetic risk) for each group. Patients' mean (SD) age was 66 (12) years old. There was no significant difference in sex (p=1), age (p=0.718), or TNM classification. Those who died after operation had significantly more renal (p=0.027) and gastrointestinal (p=0.006) diseases, but cardiac diseases (p=0.468) and diabetes mellitus (p=1) were not significant risk factors in themselves. Patients who died postoperatively had significantly worse risk scores (p=0.001) overall. The most common causes of death were septic shock (n=10) and acute cardiac (n=9) or respiratory failure (n=7). Our findings suggested that general diseases were not intrinsically a contraindication for operation with curative intent. The Charlson Comorbidity Score helped to detect potentially fatal courses and could be useful in the preoperative assessment of patients whose general health is not good.

Looking for landmarks in medial orbital trauma surgery.

Knowledge of the precise location of anatomical landmarks such as the anterior (AEC) and posterior ethmoid (PEC) canals facilitates medial orbital wall surgery and is of major importance for the protection of the orbital nerve. The aim of this study was to identify these anatomical structures in 100 consecutive CT scans and measure the distance between them. The authors investigated whether a predictable symmetry existed between the left and right side. The AEC was not identified unilaterally in one patient, the PEC was not identified unilaterally in six patients and not bilaterally in one patient. An additional PEC was found unilaterally in 12 and bilaterally in five patients. If an anatomical structure was found bilaterally, the authors obtained a strong Pearson's correlation between the sides (r=0.798-0.903, p<0.001). An anatomical variation was found in nearly every fourth patient. The authors think that these data call into question the use of the PEC and AEC as reliable surgical landmarks in medial orbital surgery.

Complications related to midfacial fractures: operative versus non-surgical treatment.

The treatment of midfacial fractures depends on the dislocation of the fracture and patient-related limitations. Surgical treatment risks iatrogenic complications. In 740 patients with midfacial fractures, the age, sex, fracture type, concomitant injuries, cause of accident and the decision to use operative or non-surgical treatment were recorded. Follow-up was performed 6 and 12 months after the injury. In 41% the fractures were isolated; they were multiple in 59%. Initially, hypaesthesia of the infraorbital nerve was present in 10% of the single and 16% of the multiple fracture patients. Surgical treatment was performed in 57% of the single and in 75% of the multiple fracture patients. Women underwent surgical treatment considerably less frequently than men. After 6 and 12 months, significantly more complications were present in the surgically treated cohort. Nerve disturbances and 'meteorosensitivity' were most prominent. These results, together with previous findings, indicate that there is a need for prospective clinical investigations that fulfil the criteria of evidence-based medicine to generate guidelines for decision making in trauma surgery. In the meantime, the decision to use surgical treatment for midfacial fractures has to be made carefully.

Decrease of Lp(a) during weight reduction in obese children is modified by the apo(a) kringle-IV copy number variation.

BACKGROUND: Lipoprotein(a) [Lp(a)] is considered an independent risk factor for cardiovascular disease. Its concentration is mainly determined by the kringle-IV repeat copy number variation (CNV) at the apolipoprotein(a) [apo(a)] locus. OBJECTIVE: We aimed to investigate the immediate effect of weight reduction on plasma Lp(a) levels and its dependency on the apo(a) CNV in obese children. DESIGN: We performed a prospective longitudinal intervention study of a low-fat hypocaloric diet conducted in a 3-week dietary camp for obese children. In all, 140 obese participants (54 boys and 86 girls) with a mean age of 12.5+/-1.6 years and a mean relative body mass index (BMI) before treatment of 165.6+/-24.7% were included. Body weight and plasma levels of Lp(a), lipids, apolipoproteins A-I and B, insulin, and C-reactive protein were determined before the onset and after the end of the intervention. In addition, the number of apo(a) kringle-IV repeats were determined using sodium dodecyl sulfate agarose gel electrophoresis. RESULTS: The mean loss of body weight was 5.0+/-1.3 kg (-6.6%), resulting in a mean decrease of the relative BMI of 6.6%. Blood chemistry revealed significant changes in all parameters, especially in Lp(a), with a decrease from 24.4+/-30.6 to 17.9+/-22.6 mg per 100 ml or -19% (P<0.001). The decrease of Lp(a) levels was higher in the group with low compared with high molecular weight apo(a) phenotypes (-23.9 vs -16.6%). CONCLUSIONS: Weight reduction in obese children is associated with significant changes in Lp(a) levels, especially in subjects with high pre-treatment Lp(a) concentrations. This effect is markedly influenced by the molecular phenotype at the copy-number variable apo(a) locus.

Molecular phylogeny and population structure of the codling moth (Cydia pomonella) in Central Europe: I. Ancient clade splitting revealed by mitochondrial haplotype markers.

The codling moth (Cydia pomonella L., Tortricidae, Lepidoptera) is an important pest of pome fruit with global distribution. It has adapted successfully to different habitats by forming various ecotypes and populations, often termed strains, which differ among each other in several morphological, developmental, and physiological features. Many strains of Cydia pomonella have developed resistance against a broad range of chemically different pesticides. Obviously, pesticide-resistant strains must have a genetic basis inherent to the gene pool of codling moth populations, and this deserves our particular attention. The primary intention of the present study was to contribute novel information regarding the evolutionary phylogeny and phylogeography of codling moth populations in Central Europe. In addition, we aimed at testing the hypothesis that differential biological traits and response patterns towards pesticides in codling moth populations may be reflected at a mitochondrial DNA level. In particular, we wanted to test if pesticide resistance in codling moths is associated repeatedly and independently with more than one mitochondrial haplotype. To this end, we analyzed mitochondrial DNA and constructed phylogenetic trees based on three mitochondrial genes: cytochrome oxidase I (COI), the A+T-rich region of the control region (CR), and the nicotinamide adenine dinucleotide dehydrogenase subunit 5 (ND5). The results indicate that Central European populations of Cydia pomonella are clearly divided in two ancient clades. As shown by means of a molecular clock approach, the splitting of the two clades can be dated to a time period between the lower and middle Pleistocene, about 1.29-0.20 million years ago. It is assumed that the cyclic changes of warm and cold periods during Pleistocene may have lead to the geographic separation of codling moth populations due to glaciation, giving rise to the formation of the two separate refugial clades, as already shown for many other European animal species. Due to their inclination towards developing novel detoxification gene variants, codling moth individuals from both clades independently and multifariously may have developed pesticide resistance, and this process may be ongoing. During their more recent evolutionary history, natural events such as the gradual disappearance of climate-specific geographic barriers, as well as human-aided dispersal in recent historic times, may have allowed codling moth haplotypes from the original clades to interbreed and completely merge again, creating a globally successful insect species with a gene pool capable of responding to novel selective challenges by rapid adaptation.

Molecular phylogeny and population structure of the codling moth (Cydia pomonella) in Central Europe: II. AFLP analysis reflects human-aided local adaptation of a global pest species.

Originally resident in southeastern Europe, the codling moth (Cydia pomonella L.) (Tortricidae) has achieved a nearly global distribution, being one of the most successful pest insect species known today. As shown in our accompanying study, mitochondrial genetic markers suggest a Pleistocenic splitting of Cydia pomonella into two refugial clades which came into secondary contact after de-glaciation. The actual distribution pattern shows, however, that Central European codling moths have experienced a geographic splitting into many strains and locally adapted populations, which is not reflected by their mitochondrial haplotype distribution. We therefore have applied, in addition to mitochondrial markers, an approach with a higher resolution potential at the population level, based on the analysis of amplification fragment length polymorphisms (AFLPs). As shown in the present study, AFLP markers elucidate the genetic structure of codling moth strains and populations from different Central European apple orchard sites. While individual genetic diversity within codling moth strains and populations was small, a high degree of genetic differentiation was observed between the analyzed strains and populations, even at a small geographic scale. One of the main factors contributing to local differentiation may be limited gene flow among adjacent codling moth populations. In addition, microclimatic, ecological, and geographic constraints also may favour the splitting of Cydia pomonella into many local populations. Lastly, codling moths in Central European fruit orchards may experience considerable selective pressure due to pest control activities. As a consequence of all these selective forces, today in Central Europe we see a patchy distribution of many locally adapted codling moth populations, each of them having its own genetic fingerprint. Because of the complete absence of any correlation between insecticide resistance and geographic or genetic distances among populations, AFLP markers do not have a prognostic value for predicting an outbreak of pesticide resistance in the field. By combining mitochondrial genetic data and AFLP analysis it was possible, however, to track the recent evolutionary history of Cydia pomonella on three different time scales: from population splitting in Pleistocene, to interbreeding of mitochondrial haplotypes in Holocene, to human-aided complete intermixing and splitting into many locally adapted populations in very recent times. The case of Cydia pomonella is reminiscent of examples of sympatric speciation and another example of a human-induced globally successful pest species.

Migration rates and genetic structure of two Hungarian ethnic groups in Transylvania, Romania.

Transylvania's ethnic mosaic is composed of Romanians, German Saxons and Hungarians. The ethnic groups of the Hungarian minority that settled in Romania show differences in dialects, customs and religious affiliations. In this study entire mtDNA control region sequences from 360 individuals of Hungarian ethnicity from two populations (the Csángó and the Székely), settled in the historical region of Transylvania in Romania, were generated and analyzed following high quality sequencing standards. Phylogenetic analyses were used for haplogroup determination, quasi-median network analyses were applied for the visualization of character conflicts, and median joining reconstructions were used for depicting haplotype structures. Affiliation of haplotypes to major west Eurasian haplogroups was confirmed using coding region SNPs. Gene flow between the two populations was low and biased towards a higher migration rate from the Csángó to the Székely than vice versa. Phylogeographic analyses revealed effects of genetic isolation within the Csángó population, which is, in its genetic structure, clearly different from the Székely population. The pronounced genetic divergence between the two populations is in sharp contrast to the expectation of high genetic similarity due to the close geographic proximity of their native homelands. The population data will be incorporated in the EMPOP database (http://www.empop.org).

Finnish mitochondrial DNA HVS-I and HVS-II population data.

We have analyzed the two hypervariable regions HVS-I and HVS-II of 200 Finnish male individuals for forensic purposes. The distribution of the haplotypes within Finland was determined by the geographical knowledge of the donors' maternal ancestors. In our population sample, we identified 135 different mtDNA haplotypes. Different mtDNA sequences were further divided to haplogroups using the EMPOP software. The most common haplogroups were H (40.0%) and U (27.5%). Subgroup U5b, which contains earlier described "Saami motif", consisted majority (65.5%) of the sample in the U haplogroup. Analysis of the mtDNA sequence hypervariable regions I and II showed that the mtDNA diversity within the Finnish population sample was comparable to other European populations and uniformly distributed. This is contrary to the Y-STR "minimal haplotype" diversity, which in Finland is lower than in any of the other European populations studied so far.

A study concerning the blood/breath alcohol conversion factor Q: concentration dependency and its applicability in daily routine.

The conversion factor Q, obtained by division of blood alcohol concentration (BAC) by breath alcohol concentration (BrAC) is a widely discussed topic due to its great variance. By Austrian law, regulations frequently require an estimation of a corresponding BAC by a measured BrAC. It is known that Q depends among other things, on the alcohol kinetic state of the person being tested, which mathematically can be transformed to a dependency on the BrAC. Theoretically calculated Q values per BrAC level form a hyperbola shaped curve, thus decreasing with increasing BrAC values. Applying Austrian forensic standards for BAC and BrAC measurements, these calculations were verified in a study under practical conditions with BAC and BrAC data of 390 individuals. Q decreases from 2629 (+/- 455) for BrAC levels < 0.1 mg/l to 2229 (+/- 160) for a BrAC range of 0.4-0.5 mg/l and increases again to 2428 (+/- 124) for BrAC levels > 0.6 mg/l. Since these results were obtained under realistic practical conditions they can be directly applied in routine forensic expert opinion and can eliminate avoidable variances in the calculation of Q.

Relationship between pharmacokinetics and pharmacodynamics of molsidomine and its metabolites in humans.

The pharmacokinetic properties and hemodynamic effect of molsidomine and its pharmacologically active metabolite SIN-1 were investigated in 13 healthy volunteers following single oral doses. Hemodynamic changes were measured by finger plethysmography (peripheral arterial resistance), impedance plethysmography (venous distensibility), heart rate, and blood pressure. Plasma concentrations of molsidomine, SIN-1, and SIN-1C were measured by means of high-pressure liquid chromatography. Oral administration of rapidly dissolving tablets of molsidomine (2 tablets of 4 mg), a sustained-release form of molsidomine (8 mg), and SIN-1 (4 mg) caused an increase of the a/b ratio of the finger plethysmogram and an increase of the venous distensibility. Heart rate and blood pressure remained unaffected. The time course of the peripheral arterial effect mimicked the time course of plasma concentrations of molsidomine and SIN-1. Similar to the results in animals, molsidomine was metabolized in humans to SIN-1 and subsequently degraded to the inactive metabolite SIN-1C. The kinetic profile of both metabolites could be followed in the plasma. The rate-limiting step in the metabolic sequence of molsidomine was found to be enzymatic hydrolysis and decarboxylation of molsidomine to SIN-1. Concentration-response curves of the a/b ratio of the finger plethysmogram showed that the plasma concentrations required to produce a definite effect are much higher for molsidomine than for SIN-1. This shows that the pharmacodynamically active form of molsidomine in humans is the metabolite SIN-1. The changes in the finger plethysmogram produced by SIN-1 suggest that in addition to the effect on the venous site, SIN-1 also dilates the peripheral arterial site.