A broadly resolved molecular phylogeny of New Zealand cheilostome bryozoans as a framework for hypotheses of morphological evolution.

Larger molecular phylogenies based on ever more genes are becoming commonplace with the advent of cheaper and more streamlined sequencing and bioinformatics pipelines. However, many groups of inconspicuous but no less evolutionarily or ecologically important marine invertebrates are still neglected in the quest for understanding species- and higher-level phylogenetic relationships. Here, we alleviate this issue by presenting the molecular sequences of 165 cheilostome bryozoan species from New Zealand waters. New Zealand is our geographic region of choice as its cheilostome fauna is taxonomically, functionally and ecologically diverse, and better characterized than many other such faunas in the world. Using this most taxonomically broadly-sampled and statistically-supported cheilostome phylogeny comprising 214 species, when including previously published sequences, and 17 genes (2 nuclear and 15 mitochondrial) we tested several existing systematic hypotheses based solely on morphological observations. We find that lower taxonomic level hypotheses (species and genera) are robust while our inferred trees did not reflect current higher-level systematics (family and above), illustrating a general need for the rethinking of current hypotheses. To illustrate the utility of our new phylogeny, we reconstruct the evolutionary history of frontal shields (i.e., a calcified body-wall layer in ascus-bearing cheilostomes) and ask if its presence has any bearing on the diversification rates of cheilostomes.

Design of Bioprosthetic Aortic Valves using biaxial test data.

Bioprosthetic Aortic Valves (BAVs) do not have the serious limitations of mechanical aortic valves in terms of thrombosis. However, the lifetime of BAVs is too short, often requiring repeated surgeries. The lifetime of BAVs might be improved by using computer simulations of the structural behavior of the leaflets. The goal of this study was to develop a numerical model applicable to the optimization of durability of BAVs. The constitutive equations were derived using biaxial tensile tests. Using a Fung model, stress and strain data were computed from biaxial test data. SolidWorks was used to develop the geometry of the leaflets, and ABAQUS finite element software package was used for finite element calculations. Results showed the model is consistent with experimental observations. Reaction forces computed by the model corresponded with experimental measurements when the biaxial test was simulated. As well, the location of maximum stresses corresponded to the locations of frequent tearing of BAV leaflets. Results suggest that BAV design can be optimized with respect to durability.

Mechano-biology in the thoracic aortic aneurysm: a review and case study.

An aortic aneurysm is a permanent and localized dilatation of the aorta resulting from an irreversible loss of structural integrity of the aortic wall. The infrarenal segment of the abdominal aorta is the most common site of aneurysms; however, they are also common in the ascending and descending thoracic aorta. Many cases remain undetected because thoracic aortic aneurysms (TAAs) are usually asymptomatic until complications such as aortic dissection or rupture occurs. Clinical estimates of rupture potential and dissection risk, and thus interventional planning for TAAs, are currently based primarily on the maximum diameter and growth rate. The growth rate is calculated from maximum diameter measurements at two subsequent time points; however, this measure cannot reflect the complex changes of vessel wall morphology and local areas of weakening that underline the strong regional heterogeneity of TAA. Due to the high risks associated with both open and endovascular repair, an intervention is only justified if the risk for aortic rupture or dissection exceeds the interventional risks. Consequently, TAAs clinical management remains a challenge, and new methods are needed to better identify patients for elective repair. We reviewed the pathophysiology of TAAs and the role of mechanical stresses and mathematical growth models in TAA management; as a proof of concept, we applied a multiscale biomechanical analysis to a case study of TAA.

A microstructurally motivated model of arterial wall mechanics with mechanobiological implications.

Through mechanobiological control of the extracellular matrix, and hence local stiffness, smooth muscle cells of the media and fibroblasts of the adventitia play important roles in arterial homeostasis, including adaptations to altered hemodynamics, injury, and disease. We present a new approach to model arterial wall mechanics that seeks to define better the mechanical environments of the media and adventitia while avoiding the common prescription of a traction-free reference configuration. Specifically, we employ the concept of constituent-specific deposition stretches from the growth and remodeling literature and define a homeostatic state at physiologic pressure and axial stretch that serves as a convenient biologically and clinically relevant reference configuration. Information from histology and multiphoton imaging is then used to prescribe structurally motivated constitutive relations for a bi-layered model of the wall. The utility of this approach is demonstrated by describing in vitro measured biaxial pressure-diameter and axial force-length responses of murine carotid arteries and predicting the associated intact and radially cut traction-free configurations. The latter provides a unique validation while confirming that this constrained mixture approach naturally recovers estimates of residual stresses, which are fundamental to wall mechanics, without the usual need to prescribe an opening angle that is only defined conveniently on cylindrical geometries and cannot be measured in vivo. Among other findings, the model suggests that medial and adventitial stresses can be nearly uniform at physiologic loads, albeit at separate levels, and that the adventitia bears increasingly more load at supra-physiologic pressures while protecting the media from excessive stresses.

[Eustachian tube function tests: an update]. / Aktueller Stand der Tubenfunktionsdiagnostik: Ein Update.

There are many diverse methods for the assessment of Eustachian tube (ET) function. Clinical studies have demonstrated good results for several clinical tests, tympanometry and a number of manometric approaches, such as the nine-step test. The relevance of tubomanometry according to Estève requires further investigation. MRI studies in particular have considerably enhanced our knowledge of ET function. Endoscopy and conventional Schüller radiography are routinely employed in the clinic. The pressure chamber is ideal for simulating the most diverse test conditions, but it is only used experimentally. Sonotubometry has both the potential and the necessary level of technical advancement for a broader clinical application. The majority of investigations have demonstrated that there is no single valid method. There is currently no technique available that is capable of reflecting all aspects of ET function. Although several methods have found clinical application, a commonly accepted golden standard for ET testing still has to be established. Further clinical studies are necessary to generate an adequate amount of data pertaining to the various ET function tests.

Caloric stimulation with near infrared radiation does not induce paradoxical nystagmus.

Near infrared radiation can be used for warm stimulation in caloric irrigation of the equilibrium organ. Aim of this study was to determine whether near infrared radiation offers effective stimulation of the vestibular organ, whether it is well tolerated by the patients and especially whether it is a viable alternative to warm air stimulation in patients with defects of the tympanic membrane and radical mastoid cavities. Patients with perforations of the tympanic membrane (n = 15) and with radical mastoid cavities (n = 13) were tested both with near infrared radiation and warm dry air. A caloric-induced nystagmus could be seen equally effectively and rapidly in all patients. Contrary to stimulation with warm dry air, no paradoxical nystagmus was observed following caloric irrigation with a warm stimulus (near infrared radiation). Results of a questionnaire showed excellent patient acceptance of near infrared stimulation with no arousal effects or unpleasant feeling. In conclusion, near infrared radiation proved to be an alternative method of caloric irrigation to warm dry air in patients with tympanic membrane defects and radical mastoid cavities. Near infrared radiation is pleasant, quick, contact free, sterile and quiet. With this method an effective caloric warm stimulus is available. If near infrared radiation is used for caloric stimulus no evaporative heat loss occurs.

Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type- and mutation-specific manner.

Although activating mutations of fibroblast growth factor receptor 3 (FGFR3) are frequent in bladder tumors, little information is available on their specific effects in urothelial cells or the basis for the observed mutation spectrum. We investigated the phenotypic and signaling consequences of three FGFR3 mutations (S249C, Y375C, and K652E) in immortalized normal human urothelial cells (TERT-NHUC) and mouse fibroblasts (NIH-3T3). In TERT-NHUC, all mutant forms of FGFR3 induced phosphorylation of FRS2alpha and ERK1/2, but not AKT or SRC. PLCgamma1 phosphorylation was only observed in TERT-NHUC expressing the common S249C and Y375C mutations, and not the rare K652E mutation. Cells expressing S249C and Y375C FGFR3 displayed an increased saturation density, related to increased proliferation and viability. This effect was significantly dependent on PLCgamma1 signaling and undetectable in cells expressing K652E FGFR3, which failed to phosphorylate PLCgamma1. In contrast to TERT-NHUC, expression of mutant FGFR3 in NIH-3T3 resulted in phosphorylation of Src and Akt. In addition, all forms of mutant FGFR3 were able to phosphorylate Plcgamma1 and induce morphological transformation, cell proliferation, and anchorage-independent growth. Our results indicate that the effects of mutant FGFR3 are both cell type specific and mutation specific. Mutant FGFR3 may confer a selective advantage in the urothelium by overcoming normal contact inhibition of proliferation.

Bilateral posterior semicircular canal aplasia and atypical paroxysmal positional vertigo: a case report.

Isolated congenital malformations of semicircular canals are rare abnormalities. Most inner ear abnormalities occur in syndromes and are associated with hearing loss. Unilateral or bilateral single aplasia of one semicircular canal does not usually result in vertigo, but these become clinically important if there are clinical complaints of vertigo. Computed tomography imaging and high resolution magnetic resonance imaging may reveal inner ear abnormalities. The case is presented here of a 46-year-old male with a 10-year history of recurrent positional vertigo with strong onset when changing position to the left side. Magnetic resonance imaging of the inner ear showed a bilateral posterior semicircular canal aplasia as well as an enlarged vestibule on both sides. Dix-Hallpike positional manoeuvre revealed a positional nystagmus in the left head-hanging position of short duration and latency of a few seconds. When rising, vertigo occurred, but no nystagmus was visible. The fast phase of the nystagmus was mainly vertical down-beating with a slight torsional component to the uppermost ear. Although benign paroxysmal vertigo of the anterior canal was suspected, physical therapy was not effective using a modified liberatory manoeuvre. Brandt-Daroff therapy was effective permanently.

[Examination of the Eustachian tube activity with perfect sequences]. / Akustische Tubenfunktionsuntersuchung mit Perfekten Sequenzen--Eine neue Methode zur Beurteilung der Eustachischen Röhre.

INTRODUCTION: Sonotubometry allows an assessment of the Eustachian tube (ET) function under physiological conditions. The application of conventional sinus signals is not reliable enough for routine clinical use. The aim of this study was to investigate ET activity with so-called perfect sequences (PSEQ). PATIENTS AND METHODS: PSEQs generated by a custom-made device were applied in 25 healthy subjects. ET opening was induced by Toynbee manoeuvre, yawning, dry and water swallowing. All sonotubograms were qualitatively analysed according to their shape, and quantitatively according to increase of sound intensity, frequency of opening and opening duration. The sonotubometry results were combined with the patients' perception of tone variation. RESULTS: A number of 400 measurements were performed. In 92.75 % measurements the patients reported ET openings. These were confirmed by 81.5 % valid sonotubograms. The swallowing manoeuvres dry/water swallowing and Toynbee yielded with 94 %/90 % and 93 % valid measurements favourable results. Yawning was associated with 49 % valid measurements. Sound level increase was also significantly different in these manoeuvres when compared to yawning (p < 0.0001). Nasal decongestion had no influence on the results (p > 0.05). CONCLUSIONS: PSEQs allow an evaluation of ET function. The chosen manoeuvres trigger in healthy subjects objective ET openings with a high reliability. The application of PSEQs can detect ET activity with a high sensitivity and good specificity. By further technical refinements specificity may also be enhanced in future studies.

Prevalence of obesity in 6- and 9-year-old children living in Central-North Italy. Analysis of determinants and indicators of risk of overweight.

The objective of our article is to survey the prevalence of overweight and obesity among 6- and 9-year-old children in Emilia-Romagna, a region of Central-North Italy, and to study the eating habits and behaviours of these children and their families. During 2003 and 2005, we analysed a stratified sample of the general population of children attending pre-school (2681 children aged 6 years) and primary school (2955 children aged 9 years). Their height and weight were measured by healthcare workers. In the 6-year-old children, information concerning their eating habits was collected by means of a questionnaire completed by their parents. The prevalence of overweight was 16.5% in 6-year-old children and 20.6% in 9-year-old children. The increase of overweight from 6- to 9-year-old children was observed in males (13.5% in 6-year-old/21.3% in 9-year-old boys), but not in females. The prevalence of obesity was 8.9% in children aged 6 years and 9.0% in those aged 9 years, and it was higher in comparison with Italian surveys carried out in 1993 and in 2001: 7.5% in 6-year-old and 7.8% in 9-year-old children in 1993, and 6.6% in 6-year-old and 7.2% in 9-year-old children in 2001. In pre-school children, overweight and obesity were closely influenced by the education level, occupation and nutritional status of the parents.

Stress-modulated remodeling of a non-homogeneous body.

Many soft tissues, and arteries in primis, exhibit residual stress after unloading, a characteristic related to the ability to self-organize their own constituents (cells and extracellular matrix proteins). This behavior can be theoretically predicted in a continuum mechanics framework assuming that the body self-remodels toward a homeostatic stress state. Open questions concern the characteristics of a stationary grown state, as dictated by the mechanical properties of the material and by the specific external load. In this paper, we illustrate a mathematical framework and we perform numerical simulations for the remodeling of a two-dimensional (axisymmetric) nonlinear elastic cylinder. In particular, we address the stress-modulated remodeling of the cylinder wall when local variations in the mechanical properties of the material occur. Our main result is that, as in one spatial dimension, the tendency of the system to homeostasis generates, thanks to the remodeling process, a residual stress that homogenizes the tension in the body under load. Possible physiological implications of this result are discussed in the final section.

IGFBP-3 and IGFBP-10 (CYR61) up-regulation during the development of Barrett's oesophagus and associated oesophageal adenocarcinoma: potential biomarkers of disease risk.

Dys-regulation of the insulin-like growth factor (IGF) system increases the risk of a number of malignancies. The aim of this study was to investigate the role of members of the IGF binding protein (IGFBP) superfamily in the development of oesophageal adenocarcinoma (EAC) and their possible use as markers of disease risk. Expression of IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 was assessed using Real-Time-polymerase chain reaction (PCR) and immunohistochemistry in oesophageal tissues from Barrett's oesophagus (BE) patients with and without associated EAC, and in control subjects. IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 mRNA levels were up-regulated in Barrett's (n=17) and tumour tissue of EAC patients (n=18) compared with normal tissue of control subjects without BE or EAC (n=18) (p<0.001). Over-expression of IGFBP-3 and IGFBP-10/CYR61 proteins was observed in Barrett's, dysplastic and tumour tissue of EAC cases (n=47 for IGFBP-10; n=39 for IGFBP-3) compared with adjacent normal epithelium (p<0.050). Notably, IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 expression in Barrett's tissue of EAC cases (n=17) was significantly (p<0.001) higher than in Barrett's tissue of BE patients with no sign of progression to cancer (n=15). Overall, the results suggest that members of the IGFBP superfamily are up-regulated during oesophageal carcinogenesis and merit further investigation as markers of EAC risk.

[Bilateral tumor of the nasal vestibule--a case report]. / Bilaterale Raumforderung des Naseneingangs--ein Fallbericht.

The authors report a case of a bilateral tumor of the nasal vestibule with a six-year history of progressive impairment of nasal breathing. After microsurgical transnasal excision, the finding was diagnosed as bilateral nasolabial cyst.

[Endoscopic examinations of the eustachian tube]. / Endoskopische Untersuchungen der Eustachi-Röhre.

BACKGROUND AND OBJECTIVE: Endoscopy of the eustachian tube allows direct examination of endoluminal alterations in the course of the organ. The aim of this study was to describe anatomic and functional findings in healthy awake subjects. PATIENTS/METHODS: Ten eustachian tubes in six healthy individuals with no history of tube dysfunction were examined under local anesthesia using different types of rigid and flexible endoscopes. RESULTS: Nine of ten tubes presented with no pathologic finding. The motility of the tube cartilage could be visualized in all cases and showed a wide variety. Prior anesthesia of the mucosa with the subject in the supine position, if necessary supplemented by a tube catheter, rendered the procedure more comfortable. CONCLUSION: The eustachian tube shows a wide spectrum of anatomic and functional varieties in normal subjects. The method allows comprehensive evaluation of anatomic and functional stenoses of the eustachian tube. The transnasal-transpharyngeal approach allows only limited evaluation of the middle ear structures.

[Conservative treatment in mild obstructive sleep apnea: comparison of theophylline and nasal continous positive airway pressure ventilation]. / Konservative Behandlung bei leichtgradiger obstruktiver Schlafapnoe: Vergleich medikamentöser Therapie und nasaler Beatmung.

BACKGROUND: Comparison of theophylline and nasal continous positive airway pressure-ventilation (nCPAP) in patients non eligible for surgical treatment with obstructive sleep apnea. PATIENTS AND MATERIALS: In a prospective non-randomized study 60 patients with mild obstructive sleep apnea were investigated. All individuals were not eligible for surgery under general anaesthesia or refused surgical treatment. The efficacy of a daily single dose oral theophylline (5 - 7 mg/kg body weight, n = 30) and nCPAP ventilation (n = 30) was evaluated by apnea-hypopnea index (AHI) and Epworth Sleepiness Scale (ESS). Statistical data analysis was performed using the Wilcoxon-Test. RESULTS: In the theophylline group 4/26 patients (15 %) showed a mean AHI reduction of 42 %. The ESS-Score improved from 10.0 to 8.0. Therapy compliance was 86 %. The non-responder (22/26 patients, 85 %) group showed a mean AHI increase of 11 % (from 24.6 to 27.3). This difference was not of statistical significance (p < or = 0.878). In the CPAP group the AHI decreased from 23.3 to 2.9 (p < or = 0,0001). Mean ventilation pressure was 6.4 mbar. The ESS-Score improved from 10 to 8. Compliance was 50 %. Six of thirty patients (20 %) did not use the CPAP device regularly. During the first four weeks another nine of thirty (30.7 %) patients turned back the device. Main reasons were discomfort (61 %), noise (38 %), rhinitis, conjunctivitis and discomfort of the partner (10 %). CONCLUSIONS: None of the treatments investigated can be considered as a substantial alternative for the majority of patients non eligible for surgery. Theophylline has a high compliance but little therapeutic effect. CPAP-ventilation is more effective but has a compliance problem in the patients investigated. Both modalities may have benefit but have to be individually indicated. A multimodal approach may ease the problem.

[Sonografic evaluation of oxygenation in head and neck cancer]. / Abschätzung der Oxygenierung von Kopf-Hals-Karzinomenmetastasen mittels Farbduplexsonographie. Ein neues nicht-invasives Verfahren.

BACKGROUND: Tumor oxygenation is an important aspect of radiosensitivity. The authors describe a new method for a non-invasive assessment of tumor oxygenation in head and neck cancer. PATIENTS AND METHODS: A group of 20 patients with neck metastases of squamous cell cancer of the head and neck region was surveyed. At first a pO (2)-polarography was performed in the metastatic cervical nodes to investigate the tissue oxygenation. In a second step, the vascularisation of these nodes was visualised by color duplex sonography. In order to evaluate the extent of vascularisation in these nodes, the density of color pixels was quantified by a custom-made software program. The color pixel density and the pO (2) values were correlated and the statistic significance was calculated by Pearson's test. RESULTS: The mean vascularisation as evaluated by the means of color duplex sonography was 7.78 % [95 % CI 6.04 - 9.51]. The interindividual pO (2) values in the stroma of metastatic lymph nodes ranged between 9.0 and 27.4 mmHg (16.6 [95 % CI 14.06 - 19.13]). The mean values of pO (2)-fractions < 2.5/< 5.0/10 mm Hg were 32.25 %, 44.25 % and 53.29 % respectively. The median value of the pO (2)-fraction was 10.49 % [95 % CI 7.13 - 13.85]. The vascularisation as evaluated by color pixel density showed a statistically significant correlation with the pO (2)-fractions < 5.0 and < 10 mmHg (p < 0.045 and < 0.0001) and with the mean (p < 0.002) and median values of tissue pO (2) values (p < 0.0001) in polarography. CONCLUSION: The results in a limited number of patients suggest, that the proposed sonographic method allows a reliable non-invasive evaluation of tissue oxygenation in cervical metastases of squamous cell head and neck cancers.

[Relevance of colour-duplex echography for detection and therapy of recurrences in the follow-up of head and neck cancer]. / Relevanz farbduplexsonographischer Untersuchungen für Rezidivdetektion und -behandlung in der Tumornachsorge von Kopf-Hals-Karzinomen.

BACKGROUND: Head and neck malignancies have a high rate of recurrences. Since the prognosis is often limited an early detection and therapy onset is essential for survival. This study surveys the relevance of regular colour-duplex echography examinations in the follow-up for detection and therapy of recurrent head and neck carcinomas. PATIENTS AND METHODS: In a prospective non-randomized study 43 patients were surveyed over a mean observation period of 28 (8-44) months. In addition to clinical and colour-duplex echography (CDS) examinations, computed tomography (CT) and positron-emission-tomography using 18fluorodeoxyglucose (PET) were performed. RESULTS: A recurrence was detected in 17/43 (39.5 %) patients. The median survival was 42 months. CDS was the most reliable procedure for the diagnosis of regional recurrences with an accuracy of 94.2 %. Sensitivity and specificity of CDS for the diagnosis of all recurrences was found to be 80 % and 78,6 % respectively. CT yielded identical results. In PET sensitivity was 82.4 % and specificity was found to be 88.4 %. In clinical examinations including panendoscopy sensitivity was 64.7 % only. In 7/17 recurrences a therapy was performed with curative intention. In 4 cases an early diagnosis by CDS contributed to a successful therapy. CONCLUSION: CDS is the imaging procedure of choice for the routine follow-up of head and neck cancer patients. In order to perform a comprehensive assessment of the head and neck region, for re-staging and to exclude second primary tumours additional (pan)endoscopy is necessary. CDS supports due to a high resolution and reliability an early therapy onset and a minimal invasive therapy. Thus, this procedure can significantly contribute to the successful treatment of recurrences in head and neck cancer.