Terebratulide brachiopod shell biomineralization by mantle epithelial cells.

To understand mineral transport pathways for shell secretion and to assess differences in cellular activity during mineralization, we imaged with TEM and FE-SEM ultrastructural characteristics of outer mantle epithelium (OME) cells. Imaging was carried out on Magellania venosa shells embedded/etched, chemically fixed/decalcified and high-pressure frozen/freeze-substituted samples from the commissure, central shell portions and from puncta. Imaging results are complemented with morphometric evaluations of volume fractions of membrane-bound organelles. At the commissure the OME consists of several layers of cells. These cells form oblique extensions that, in cross-section, are round below the primary layer and flat underneath fibres. At the commissure the OME is multi-cell layered, in central shell regions it is single-cell layered. When actively secreting shell carbonate extrapallial space is lacking, because OME cells are in direct contact with the calcite of the forming fibres. Upon termination of secretion, OME cells attach via apical hemidesmosomes to extracellular matrix membranes that line the proximal surface of fibres. At the commissure volume fractions for vesicles, mitochondria and lysosomes are higher relative to single-cell layered regions, whereas for endoplasmic-reticulum and Golgi apparatus there is no difference. FE-SEM, TEM imaging reveals the lack of extrapallial space between OME cells and developing fibres. In addition, there is no indication for an amorphous precursor within fibres when these are in active secretion mode. Accordingly, our results do not support transport of minerals by vesicles from cells to sites of mineralization, rather by transfer of carbonate ions via transport mechanisms associated with OME cell membranes.

Three-dimensional analysis of cranial growth from 6 to 12 months of age.

The aim of this study was to generate three-dimensional data of the physiological growth of the infant's cranium in the significant growth phase from 6 to 12 months of age. In a longitudinal observational study non-invasive 3D data using an optical surface scanner were generated of the entire head of 52 Caucasian infants (27 females and 25 males) between the ages of 6 (T1) and 12 (T2) months. The circumference of the head increased by 6.51 per cent (from 43.50 to 46.33cm). Analysis of width and length showed that the head grows 2.84 per cent more in length, resulting in a decrease in the cranial index of 2.52 per cent (from 83.87 to 81.76 per cent). The highest increment observed was in the total volume of the cranium, with an increase of 18.76 per cent (from 1229.01 to 1459.57cm(3)). Comparison of the left and right sides of the head by measuring the diagonal symmetry difference showed a difference of only 0.37cm. Overall, the symmetry-related parameters showed an almost symmetric development of the cranium in infants. The findings should provide valuable information on physiological growth and development of the infant's cranium. Therefore the high growth rate of the cranium in the first year of life suggests that this period is a critical period in which the disruption of developmental processes may have long-lasting effects on the morphology of the cranium with a prognostically unfavourable effect of the further growth of the viscerocranium.

Calcium isotope composition in serum and urine for the assessment of bone mineral balance (BMB) - The Osteolabs post-market follow-up study.

To further explore the clinical applicability of the calcium (Ca) isotope marker (CIM), we determined the 44Ca/42Ca isotope ratio in blood serum and urine. This ratio is expressed in the conventional δ-notation (as defined in the text below) specifically as CIM-serum for serum and as CIM-urine for urine. Our study tested the hypothesis that CIM values can differentiate between positive and negative bone mineral balance (BMB) across a diverse clinical population considering variables such as age, gender, and diet. The threshold values (CIM-serum: -0.85 ± 0.06 ‰ and CIM-urine: 0.23 ± 0.06 ‰) established in the OsteoGeo study (NCT02967978, Eisenhauer et al., 2019) were evaluated in 2320 participants as part of a surveillance study referred to as Osteolabs study. The earlier study revealed women with osteoporosis had an average CIM-serum value of -0.91 ± 0.21 ‰ (N = 24) and a CIM-urine value of 0.18 ± 0.33 ‰ (N = 71) that are significantly below the threshold values (p = 0.02 for urine, one-sided Wilcoxon rank test, p < 0.001 for serum, one-sided Student's t-test). Diseases affecting BMB such as osteoporosis, acute and chronic kidney disease (CKD), hyperthyroidism, breast cancer, prostate cancer, and myeloma were associated with significantly lower average CIM values, falling below the equilibrium thresholds and indicating negative BMB. In contrast, patients receiving osteoprotective treatments such as denosumab, Romosozumab, bisphosphonates, or hormone replacement therapy for certain diseases, had CIM values above the equilibrium thresholds indicating a positive BMB. Additionally, Ca supplements taken by some of the patients ((N = 22 (serum), N = 49 (urine), median dose: 500 mg) showed a Ca isotope composition approximately 1 ‰ higher than that from a normal diet. Consequently, their CIM values need to be adjusted to account for the amount and duration of supplementation to be comparable to those with a normal diet. Participants taking vitamin D (237 women; 58 men) showed no significant difference from the average values of the study group. Counterintuitively, the possible impact of malnutrition on individual BMB was most pronounced in vegans, who exhibited the highest average CIM-urine values compared to patients on a normal diet (p < 0.001, N = 17). The results of this study were consistent with the registered OsteoGeo study (NCT02967978) and other earlier published Ca isotope-based studies on BMB. We confirm that the CIM threshold values determined in the OsteoGeo study are generally valid for this much larger and diverse surveillance study group covering a diverse population encompassing various medical conditions and therapies.

Ice sheet-free West Antarctica during peak early Oligocene glaciation.

One of Earth's most fundamental climate shifts, the greenhouse-icehouse transition 34 million years ago, initiated Antarctic ice sheet buildup, influencing global climate until today. However, the extent of the ice sheet during the Early Oligocene Glacial Maximum (~33.7 to 33.2 million years ago) that immediately followed this transition-a critical knowledge gap for assessing feedbacks between permanently glaciated areas and early Cenozoic global climate reorganization-is uncertain. In this work, we present shallow-marine drilling data constraining earliest Oligocene environmental conditions on West Antarctica's Pacific margin-a key region for understanding Antarctic ice sheet evolution. These data indicate a cool-temperate environment with mild ocean and air temperatures that prevented West Antarctic Ice Sheet formation. Climate-ice sheet modeling corroborates a highly asymmetric Antarctic ice sheet, thereby revealing its differential regional response to past and future climatic change.

[Interaction between otorhinolaryngology and orthodontics: correlation between the nasopharyngeal airway and the craniofacial complex]. / Interaktion von Hals-Nasen-Ohren-Heilkunde und Kieferorthopädie: Die Beziehung zwischen dem nasopharyngealen Luftraum und den kraniofazialen Strukturen.

In terms of pathophysiology, an anatomically narrow airway is a predisposing factor for obstruction of the upper respiratory tract. The correlation between the nasopharyngeal airway and the craniofacial structures is discussed in this context. Thus a mutual interaction between the pharynx and the mandibular position was demonstrated, whereby the transverse dimension of the nasopharynx was significantly larger in patients with prognathism than in patients with retrognathism. The influence of chronic obstruction of the nasal airway on craniofacial development was also discussed. The form-and-function interaction, which ought to explain the causal relationship between nasal obstruction and craniofacial growth, appears to be of a multifactorial rather than a one-dimensional, linear nature. It is not disputed, however, that expanding the maxilla improves not only nasal volume and nasal flow, but also the subjective sensation of patients, although it is not possible to make a prognostic statement about the extent of this improvement because of the differing reactions of individuals. Orthodontic appliances for advancing the mandible can also be successfully used in the treatment of mild obstructive sleep apnea syndrome. This treatment method should be considered particularly for patients who are unwilling to undergo or cannot tolerate CPAP treatment.

Calcium isotope ratios in blood and urine: A new biomarker for the diagnosis of osteoporosis.

We assessed the potential of Calcium (Ca) isotope fractionation measurements in blood (δ44/42CaBlood) and urine (δ44/42CaUrine) as a new biomarker for the diagnosis of osteoporosis. One hundred post-menopausal women aged 50 to 75 years underwent dual-energy X-ray absorptiometry (DXA), the gold standard for determination of bone mineral density. After exclusion of women with kidney failure and vitamin D deficiency (<25 nmol/l) 80 women remained in the study. Of these women 14 fulfilled the standard diagnostic criteria for osteoporosis based on DXA. Both the δ44/42CaBlood (p < 0.001) and δ44/42CaUrine (p = 0.004) values were significantly different in women with osteoporosis (δ44/42CaBlood: -0.99 ±â€¯0.10‰, δ 44/42CaUrine: +0.10 ±â€¯0.21‰, (Mean ±â€¯one standard deviation (SD), n = 14)) from those without osteoporosis (δ44/42CaBlood: -0.84 ±â€¯0.14‰, δ44/42CaUrine: +0.35 ±â€¯0.33‰, (SD), n = 66). This corresponded to the average Ca concentrations in morning spot urine samples ([Ca]Urine) which were higher (p = 0.041) in those women suffering from osteoporosis ([Ca]Urine-Osteoporosis: 2.58 ±â€¯1.26 mmol/l, (SD), n = 14) than in the control group ([Ca]Urine-Control: 1.96 ±â€¯1.39 mmol/l, (SD), n = 66). However, blood Ca concentrations ([Ca]Blood) were statistically indistinguishable between groups ([Ca]Blood, control: 2.39 ±â€¯0.10 mmol/l (SD), n = 66); osteoporosis group: 2.43 ±â€¯0.10 mmol/l (SD, n = 14) and were also not correlated to their corresponding Ca isotope compositions. The δ44/42CaBlood and δ44/42CaUrine values correlated significantly (p = 0.004 to p = 0.031) with their corresponding DXA data indicating that both Ca isotope ratios are biomarkers for osteoporosis. Furthermore, Ca isotope ratios were significantly correlated to other clinical parameters ([Ca]Urine, ([Ca]Urine/Creatinine)) and biomarkers (CRP, CTX/P1NP) associated with bone mineralization and demineralization. From regression analysis it can be shown that the δ44/42CaBlood values are the best biomarker for osteoporosis and that no other clinical parameters need to be taken into account in order to improve diagnosis. Cut-off values for discrimination of subjects suffering from osteoporosis were - 0.85‰ and 0.16‰ for δ44/42CaBlood and δ44/42CaUrine, respectively. Corresponding sensitivities were 100% for δ44/42CaBlood and ~79% for δ44/42CaUrine. Apparent specificities were ~55% for δ44/42CaBlood and ~71%. The apparent discrepancy in the number of diagnosed cases is reconciled by the different methodological approaches to diagnose osteoporosis. DXA reflects the bone mass density (BMD) of selected bones only (femur and spine) whereas the Ca isotope biomarker reflects bone Ca loss of the whole skeleton. In addition, the close correlation between Ca isotopes and biomarkers of bone demineralization suggest that early changes in bone demineralization are detected by Ca isotope values, long before radiological changes in BMD can manifest on DXA. Further studies are required to independently confirm that Ca isotope measurement provide a sensitive, non-invasive and radiation-free method for the diagnosis of osteoporosis.

Morphology of the sella turcica in Axenfeld-Rieger syndrome with PITX2 mutation.

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder with an incidence of 1:200 000. Genotype and phenotype are heterogeneous and clinical morphology impresses with variable expressivity. Additionally to the typical craniofacial and dental aberrations anomalies in the morphology of sella turcica are discussed. METHOD: In a multidisciplinary genetic and clinical study four patients of a family with ARS were screened by direct DNA sequencing. Radiographic analysis of the patients was performed for evaluating cranial and dental structures. Additionally, a specific analysis of the morphology of the sella turcica was made on the radiographs. RESULTS: Screening for PITX2 and FOXC1 mutations revealed a P64L missense mutation in PITX2 in all four patients. The cephalometric analysis showed a midface hypoplasia associated with a skeletal Class III. All patients showed a sella turcica bridge combined with a prominent posterior clinoid process followed by a steep clivus and an elongated sella turcica. CONCLUSION: The incidence of a sella turcica bridge in combination with a PITX2 mutation would suspect that sella turcica anomalies are typical symptoms of the syndrome. Sella turcica anomalies in association with craniofacial and dental aberrations, such as maxillary retrognathia, skeletal Class III relationship and hypoplasia of teeth, might be important indicators for ARS caused by PITX2 mutation.

Stable isotope fractionation of strontium in coccolithophore calcite: Influence of temperature and carbonate chemistry.

Marine calcifying eukaryotic phytoplankton (coccolithophores) is a major contributor to the pelagic production of CaCO3 and plays an important role in the biogeochemical cycles of C, Ca and other divalent cations present in the crystal structure of calcite. The geochemical signature of coccolithophore calcite is used as palaeoproxy to reconstruct past environmental conditions and to understand the underlying physiological mechanisms (vital effects) and precipitation kinetics. Here, we present the stable Sr isotope fractionation between seawater and calcite (Δ88/86 Sr) of laboratory cultured coccolithophores in individual dependence of temperature and seawater carbonate chemistry. Coccolithophores were cultured within a temperature and a pCO2 range from 10 to 25°C and from 175 to 1,240 µatm, respectively. Both environmental drivers induced a significant linear increase in coccolith stable Sr isotope fractionation. The temperature correlation at constant pCO2 for Emiliania huxleyi and Coccolithus braarudii is expressed as Δ88/86 Sr = -7.611 × 10-3 T + 0.0061. The relation of Δ88/86 Sr to pCO2 was tested in Emiliania huxleyi at 10 and 20°C and resulted in Δ88/86 Sr = -5.394 × 10-5 pCO2 - 0.0920 and Δ88/86 Sr = -5.742 × 10-5 pCO2 - 0.1351, respectively. No consistent relationship was found between coccolith Δ88/86 Sr and cellular physiology impeding a direct application of fossil coccolith Δ88/86 Sr as coccolithophore productivity proxy. An overall significant correlation was detected between the elemental distribution coefficient (DSr ) and Δ88/86 Sr similar to inorganic calcite with a physiologically induced offset. Our observations indicate (i) that temperature and pCO2 induce specific effects on coccolith Δ88/86 Sr values and (ii) that strontium elemental ratios and stable isotope fractionation are mainly controlled by precipitation kinetics when embedded into the crystal lattice and subject to vital effects during the transmembrane transport from seawater to the site of calcification. These results provide an important step to develop a coccolith Δ88/86 Sr palaeoproxy complementing the existing toolbox of palaeoceanography.

Ice volume and climate changes from a 6000 year sea-level record in French Polynesia.

Mid- to late-Holocene sea-level records from low-latitude regions serve as an important baseline of natural variability in sea level and global ice volume prior to the Anthropocene. Here, we reconstruct a high-resolution sea-level curve encompassing the last 6000 years based on a comprehensive study of coral microatolls, which are sensitive low-tide recorders. Our curve is based on microatolls from several islands in a single region and comprises a total of 82 sea-level index points. Assuming thermosteric contributions are negligible on millennial time scales, our results constrain global ice melting to be 1.5-2.5 m (sea-level equivalent) since ~5500 years before present. The reconstructed curve includes isolated rapid events of several decimetres within a few centuries, one of which is most likely related to loss from the Antarctic ice sheet mass around 5000 years before present. In contrast, the occurrence of large and flat microatolls indicates periods of significant sea-level stability lasting up to ~300 years.

Are cervical vertebrae suitable for age estimation?

BACKGROUND: The ability of cervical vertebrae (CV) staging to contribute in forensic age estimation is being discussed controversially. The large variability of CV geometries in the end stage of development might be the reason for not reaching a performance competitive to hand or third molar methods. Here we study the geometry of adult CV and demonstrate that the description of their "typical" appearance is often not met. MATERIALS AND METHODS: Lateral cephalograms from clinical routine of 320 subjects aged 20 years or above (median 24 years, 52% female) were evaluated. The criteria for the end stage of CV development (Hassel-Farman, Baccetti) were examined by assessing them in terms of metric measurements: (1) rectangular shape of C3/C4, (2) at least one of the height-width ratios of C3/C4 > 1 (both not <1), (3) significant concavities at the inferior margin of C2, C3 and C4. Metric data of the adults were also compared to those of 100 children aged 8-10 years (50% female). RESULTS: Adult CV often violated the criteria of rectangular shape (44% C3, 36% C4), of height-width ratio (16% C3, 35% C4) and inferior concavity (10% C2, 10% C3, 19% C4). All of the criteria for adult CV were fulfilled in only 24% of the subjects (95%CI 19-28%). The variability of measures of the CV shapes was large; e.g., the 95% reference ranges for the height-width ratios were 0.81-1.19 (C3) and 0.77-1.14 (C4). There was a material overlap of ranges of CV measures of adults and children. CONCLUSION: While hand bones and teeth have well-defined appearances in the end stage of development, adult CV have a large biological variance of shapes; it is hard to define their "typical" appearance. Moreover, measures of CV geometry do not strictly separate adults from children. These facts might reason the limited usefulness of CV in age estimation.

Effect of renal artery stenting on renal function and size in patients with atherosclerotic renovascular disease.

BACKGROUND: Renal artery stenting is widely performed, but little is known about its effectiveness in preserving renal function and size in patients with renovascular disease and chronic renal insufficiency. We studied the effect of renal artery stenting on renal function and size in patients with obstructive renovascular disease and chronic renal insufficiency. METHODS AND RESULTS: Stent deployment was performed in patients with chronic renal insufficiency (creatinine >1.5 mg. dL(-1)) and global renovascular obstruction (bilateral renal artery stenosis or unilateral stenosis in the presence of a solitary or single functional kidney). The effect of renal artery stenting on renal function was assessed by comparing the slopes of the regression lines derived from the reciprocal of serum creatinine versus time plotted before and after stent deployment. Renal size was assessed by serial ultrasound of pole-to-pole kidney length. Stenting was successful in all 61 vessels in 33 patients. Twenty-five patients had complete follow-up (mean 20+/-11 months). Before stent deployment, all patients exhibited a negative slope, indicating progressive renal insufficiency. After stent deployment, the slopes were positive in 18 and less negative in 7 patients. Thus, the mean slope increased from -0.0079 to 0.0043 dL. mg(-1). mo(-1) (P:<0.001). Ultrasonography on 41 kidneys revealed preservation of size, with the kidney length measuring 10.4+/-1.4 cm at baseline and 10.4+/-1.1 cm at last follow-up (P:=NS). Patient survival at 20+/-11 months was 90%. CONCLUSIONS: In patients with chronic renal insufficiency and global obstructive atherosclerotic renovascular disease, renal artery stenting improves or stabilizes renal function and preserves kidney size.

Percutaneous revascularization of atherosclerotic obstruction of aortic arch vessels.

OBJECTIVES: To compare stenting of aortic arch vessel obstruction with surgical therapy and to establish recommendations for treatment. BACKGROUND: Though surgery has been considered to be the procedure of choice for subclavian and brachiocephalic obstruction, little work has been done to compare it with stenting. METHODS: Eighteen patients with symptomatic aortic arch vessel stenosis or occlusion were treated with stenting, followed by periodic clinical follow-up and noninvasive arterial Doppler studies. Data were compared with the results as shown in a systematic review of a published series of surgery and stenting procedures which included comparison of technical success, complications, mortality and patency. RESULTS: Primary success in our series was 100% with improvement in mean stenosis from 84+/-11% to 1+/-5% and mean arm systolic blood pressure difference from 44+/-16 mm Hg to 3+/-3 mm Hg. There were no major complications (death, stroke, TIA, stent thrombosis or myocardial infarction). At follow-up (mean 17 months), all patients were asymptomatic with 100% primary patency. Literature review demonstrates equivalent patency and complications in the other published series of stenting. In contrast, there was a similar patency but overall incidence of stroke of 3+/-4% and death of 2+/-2% in the published surgical series. CONCLUSIONS: Subclavian or brachiocephalic artery obstruction can be effectively treated by primary stenting or surgery. Comparison of stenting and the surgical experience demonstrates equal effectiveness but fewer complications and suggests that stenting should be considered as first line therapy for subclavian or brachiocephalic obstruction.

Comparison of percutaneous transluminal coronary angioplasty outcome and hospital costs for low-volume and high-volume operators.

Whether higher operator case volume is associated with improved percutaneous transluminal coronary angioplasty (PTCA) clinical and cost outcomes is the subject of this study. Hospital volume-related improvement in clinical outcomes has been shown for coronary artery bypass grafting (CABG) and PTCA. Physician case volume-related differences in clinical outcomes have not been clearly demonstrated, and differences in hospital costs have not been examined. For clinical and cost outcomes, risk-adjusted analysis of differences in PTCA outcomes has not been reported. In addition, controversy exists about the appropriate annual case volume considered adequate to maintain skills and achieve optimal clinical outcomes in performing PTCA procedures. We studied 2,350 PTCAs performed between March 1, 1991, and February 28, 1994. Physicians were divided into 2 volume groups: high (>50 cases/year) and low (<50 cases/year). The rate of emergency CABG after PTCA was 2.1% for high- and 3.9% for low-volume operators (p = 0.009). Hospital morbidity associated with PTCA was lower in high-than in low-volume operators (6.46% vs 10.73%, p <0.001). The risk-adjusted ratios for emergency CABG and morbidity were 2.05 (p = 0.005) and 1.79 (p <0.001), respectively. The length of stay averaged 4.07 +/- 4.54 days for high- and 4.49 +/- 4.33 days for low-volume operators (p = 0.003). Hospital costs averaged $7,977 +/-$7,269 for high- and $8,278 +/- $6,289 for low-volume operators (p = 0.065). The risk adjusted ratio was 1.091 (p = 0.004) for length of stay and 1.050 (p = 0.029) for cost. Thus, PTCA performed by high-volume operators is significantly less likely to require emergency CABG and is also significantly associated with lower hospital morbidity, shorter hospital length of stay, and lower hospital costs.

Angiographic and clinical outcomes following acute infarct angioplasty on saphenous vein grafts.

Acute infarct angioplasty on aortocoronary saphenous vein grafts (SVGs) poses significant challenges because of their degenerate morphology and presence of significant thrombus. Of 370 acute, primary, or rescue myocardial infarct angioplasties performed over 3 years, 21 (5.7%) were on SVGs in patients who had undergone previous coronary artery bypass grafting a mean of 7.2 years earlier. Mean duration of chest pain to start of intervention was 3.9 +/- 3.2 hours; 6 (29%) patients presented with cardiac shock and 4 had failed treatment with thrombolytic drugs. At intervention, 11 (52%) of the culprit SVGs were totally occluded. Flow was reestablished or improved in 18 (86%), but classified as Thrombolysis In Myocardial Infarction trial grade 3 in only 10 patients (48%). Distal embolization and "no reflow" occurred with a frequency of 57% and 71%, respectively. In-hospital mortality was 19%. At 6 months, freedom from death, repeat target vessel revascularization, or recurrent myocardial infarction was 55%. In 349 patients undergoing native vessel intervention, success and Thrombolysis In Myocardial Infarction trial 3 flow rates were seen in 95% and 73% of patients, respectively, and in-hospital mortality was 7.9%. This present study demonstrates that infarct angioplasty on culprit SVGs can be successful but is associated with higher rates of embolic complications and worse acute and long-term clinical outcomes compared with a parallel experience of acute infarct angioplasty on native coronary arteries.

Coronary-subclavian steal associated with severe aortic stenosis treated with combined percutaneous stenting and minimally invasive aortic valve replacement.

We describe coronary-subclavian steal restricting flow to the left internal mammary artery (LIMA) associated with critical aortic stenosis treated with combined percutaneous transluminal stenting and minimally invasive aortic valve replacement (AVR). An 86-year-old patient had coronary artery bypass graft placement (CABG) seven years prior with the LIMA anastomosed to the left anterior descending coronary artery (LAD). At the time of CABG, the patient had mild aortic stenosis and normal left ventricular function. By the time of re-presentation with refractory angina and heart failure, the patient had developed critical aortic stenosis. Because repeat CABG with median sternotomy risked damaging the LIMA, pre-operative revascularization was planned to minimize the likelihood of peri-operative ischemia. Stenting of the subclavian artery was performed prior to minimally invasive AVR.

The influence of cephalometric parameters on resonance of speech in cleft lip and palate patients. An interdisciplinary study.

There are only few studies concerning the correlation between craniofacial morphology and resonance of speech in cleft palate patients. Moreover, these investigations show a considerable inhomogeneity in material and method, their basic approach was predominantly retrospective, and the statistical methods were restricted to univariate procedures. Thus, the aim of the present study was twofold: firstly to clarify the extent to which correlations exist between craniofacial morphology and resonance of speech in cleft palate patients, subject to a sufficiently large number of patients being available to ensure differentiation with regard to age and cleft type, and secondly, within a prospective longitudinal study in juvenile cleft palate patients, to investigate whether pubertal craniofacial growth changes result in changes of resonance. The collective comprised 137 cleft palate patients. The following investigations were performed: lateral cephalometry, nasometry, and standardized speech recording. Additionally, these investigations were repeated in 51 juvenile patients after a minimum time interval of 2 years. In order to analyze the complex relations between craniofacial morphology and degree of hypernasality, multivariate statistical procedures were applied. The results of the present study indicate complex correlations between cephalometric parameters and resonance of speech, requiring age-specific differentiation. In this regard, the ratios between the length of the soft palate and the sagittal depth of the nasopharyngeal airway were of prime importance. Beyond this, significant correlations were found between craniofacial growth changes and changes of resonance during puberty which might be influenced both by dentofacial orthopedics and by maxillofacial surgery.

Differential diagnosis of primary failure of eruption (PFE) with and without evidence of pathogenic mutations in the PTHR1 gene.

BACKGROUND: Primary failure of eruption (PFE) may be associated with pathogenic mutations in the PTHR1 gene. It has numerous manifestations and is characterized by severe posterior open bite. However, there are also phenotypically similar types of eruption anomalies not associated with a known pathogenic PTHR1 mutation. The purpose of this study was to evaluate whether a distinction can be made between PTHR1-mutation carriers and noncarriers based on clinical and radiological findings. PATIENTS AND METHODS: A total of 36 patients with suspected PFE diagnoses were included and analyzed in accordance with specific clinical and radiographic criteria. In addition, all patients underwent Sanger DNA sequencing analysis of all coding sequences (and the immediate flanking intronic sequences) of the PTHR1 gene. RESULTS: Of these patients, 23 exhibited a heterozygous pathogenic mutation in the PTHR1 gene (PTHR1-mutation carriers), while molecular genetic analysis revealed nosequence alteration in the other 13 patients (non-PTHR1-mutation carriers). Relevant family histories were obtained from 5 patients in the carrier group; hence, this group included a total of 13 familial and 10 simplex cases. The group of noncarriers revealed no relevant family histories. All patients in the carrier group met six of the clinical and radiographic criteria explored in this study: (1) posterior teeth more often affected; (2) eruption disturbance of an anterior tooth in association with additional posterior-teeth involvement; (3) affected teeth resorbing the alveolar bone located coronal to them; (4) involvement of both deciduous and permanent teeth; (5) impaired vertical alveolar-process growth; and (6) severe subsequent finding of posterior open bite. None of the analyzed criteria were, by contrast, met by all patients in the noncarrier group. All patients in the carrier group could be assigned to one of three classifications indicating the extent of eruption disturbance, whereas 4 of the 13 noncarriers presented none of these three patterns. The clinical and radiographic criteria employed in this study would have correctly identified 10 of the 13 PFE patients in the noncarrier group as possessing no detectable PTHR1 mutation. CONCLUSION: The evaluation of clinical and radiographic characteristics can heighten the specificity of ruling out suspected PTHR1 involvement in PFE patients. A hereditary element of PTHR1-associated PFE is clearly identifiable. More studies with more patients are needed to optimize the sensitivity of this preliminary approach on the differential identification of PTHR1-mutation carriers versus noncarriers by multivariate analysis.

Three-dimensional investigation of facial surface asymmetries in skeletal malocclusion patients before and after orthodontic treatment combined with orthognathic surgery.

OBJECTIVES: The goal of the following study was to quantify facial soft-tissue asymmetry in patients with pronounced skeletal malocclusion anomalies before and after orthodontic treatment combined with orthognathic surgery. In addition, the facial attractiveness of these patients was rated by dental specialists and laypersons both before and after treatment based on the three-dimensional (3D) data. PATIENTS AND METHODS: An optical sensor was used to noninvasively capture the 3D facial surface data of 60 adult patients including two groups of 20 patients with skeletal Class II or III anomalies and a control group of another 20 subjects with Class I relationships. Facial surface asymmetries were evaluated immediately before the surgical procedure and 1 year thereafter. In addition, subjective ratings of facial attractiveness were obtained based on a questionnaire from orthodontists, maxillofacial surgeons, and laypersons. RESULTS: No differences in facial soft-tissue asymmetry were observed between the Class II and III patients either pre- or postoperatively, but asymmetry was found to be more pronounced in the skeletal malocclusion groups than in the Class I control group both pre- and postoperatively. The subjective ratings of facial attractiveness by the various rater groups yielded more favorable results for the post- than preoperative patient images, reflecting differences that reached overall statistical significance. CONCLUSION: Quantitative analysis of facial soft-tissue asymmetry and calculating a cutoff value allowed us to distinguish patients with skeletal malocclusion from a control group solely on the basis of asymmetry. Combined regimens of orthodontic treatment and orthognathic surgery go some way in reducing asymmetry toward the levels seen in untreated control subjects, while the asymmetry pattern characteristic of this type of malocclusion will persist. Nevertheless, the asymmetry reduction is noticeable enough to result in more favorable ratings of attractiveness.

Effectiveness of bionator therapy for Class II malocclusions: a comparative long-term study.

OBJECTIVE: The goal of this retrospective study was to examine the effectiveness of isolated bionator therapy in Class II patients both longitudinally and over the long term. We aimed to determine whether skeletal and/or dentoalveolar reactions differ in relationship to the Angle Class (II, Division 1 vs. II, Division 2). PATIENTS AND METHODS: A total of 50 juvenile patients with Class II malocclusion (♀ n = 26, ♂ n = 24) were included. A total of 24 patients presented an Angle Class II, Division 1 and 26 an Angle Class II, Division 2. We compared the patients' lateral cephalograms taken at the beginning of treatment (t1: 10.1 years), after active therapy (t2: 13.8 years), and at the end of retention (t3: 16.4 years) analyzing the following cephalometric parameters: SNA, SNB, ANB, ANB(ind), SNPog, Wits appraisal, U1-SN, U1-SpP, L1-MeGo, interincisal angle. Mean and standard deviations of each of the variables were calculated. Differences between t1-t2 and t2-t3 were tested for statistical significance. Changes in the variables were then analyzed biometrically for specific differences in terms of Angle Class (II, Division 1 vs. II, Division 2). RESULTS: Between t1 and t2, SNB (p = 0.000) and SNPog (p = 0.000) increased significantly, as did ANB (p = 0.000), while the difference between ANB and ANB(ind) (p = 0.000) and Wits appraisal (p = 0.000) decreased significantly. The dentoalveolar variables U1-SN, U1-SpP, and the interincisal angle changed significantly in both groups. The inclination of the upper incisors was corrected by retrusion in the Class II, Division 1 and by protrusion in the Class II, Division 2 group. Only marginal changes in all variables between t2 and t3 were observed. CONCLUSION: A significant skeletal effect (even in long-time stability) through bionator treatment could be confirmed in this study of Class II, Divisions 1 and 2 patients. The desired effect on the upper front teeth was realized, and there was no appreciable dentoalveolar compensation in the mandible.

Head orthesis therapy in infants with unilateral positional plagiocephaly: an interdisciplinary approach to broadening the range of orthodontic treatment.

OBJECTIVE: Unilateral positional plagiocephaly is the most common deformity of the head in infants. As part of a prospective controlled clinical study, the pathomorphology of the positional plagiocephaly in early infancy was examined. The goal was to use noninvasive three-dimensional (3D) imaging to generate, for the first time ever, a standard database of infants without head deformities, to quantify the asymmetry of the positional plagiocephaly, and to evaluate the effectiveness of functional growth control using head orthesis. PATIENTS AND METHODS: In the present study, 3D soft-tissue data of the entire head were collected from a total of 40 infants: 20 with positional plagiocephaly (6.0 ± 0.97 months) and 20 infants without a head deformity (6.4 ± 0.3 months). Functional growth was controlled using a custom-made head orthesis. To evaluate the therapy, pre- and posttherapeutic scans were evaluated in three dimensions. RESULTS: Compared with the control group, infants with positional plagiocephaly demonstrated a reduced maximum length of the head, an increased head height, a shift in the ear axis as well as asymmetric anterior and posterior volumes of the neurocranium in lateral comparisons. Therapy using head orthesis led to a significant improvement of the asymmetry, with a reduction of the diagonal difference and an adjustment of the posterior volumes. CONCLUSION: Conservative growth control of extrinsically deformed infant skulls represents an interdisciplinary medical expansion of the orthodontic therapeutic spectrum. To prevent potential effects of positional plagiocephaly on the viscerocranium, head orthesis therapy is advisable in infancy.