An observed population of intermediate-mass helium stars that have been stripped in binaries.

The hydrogen-rich outer layers of massive stars can be removed by interactions with a binary companion. Theoretical models predict that this stripping produces a population of hot helium stars of ~2 to 8 solar masses (M☉), however, only one such system has been identified thus far. We used ultraviolet photometry to identify potential stripped helium stars then investigated 25 of them using optical spectroscopy. We identified stars with high temperatures (~60,000 to 100,000 kelvin), high surface gravities, and hydrogen-depleted surfaces; 16 stars also showed binary motion. These properties match expectations for stars with initial masses of 8 to 25 M☉ that were stripped by binary interaction. Their masses fall in the gap between subdwarf helium stars and Wolf-Rayet stars. We propose that these stars could be progenitors of stripped-envelope supernovae.

Patient-specific pre-operative simulation of the surgically assisted rapid maxillary expansion using finite element method and Latin hypercube sampling: workflow and first clinical results.

Asymmetric distraction with different expansions of left and right maxillary parts is a serious complication of surgically assisted rapid maxillary expansion. An individual, highly standardized surgical intervention based on three-dimensional finite element analysis (FEA) is a new method to improve the quality of therapy. We describe a fundamental simulation-based workflow for preoperative evaluation of the osteotomies in a pilot study to achieve symmetry. A CT scan of the skull was used for analysis. Many feasible osteotomy configurations were generated and optimized using Latin hypercube sampling method and FEA choosing an individual osteotomy and maxillary movement. We successfully applied this workflow to 14 patients with symmetrical distraction.

Evaluation of symmetry behavior of surgically assisted rapid maxillary expansion with simulation-driven targeted bone weakening.

OBJECTIVES: Surgically assisted rapid maxillary expansion (SARME) is a treatment modality to overcome maxillary constrictions. During the procedure of transverse expansion, unwanted asymmetries can occur. This retrospective study investigates the transverse expansion behavior of the maxilla utilizing a simulation-driven SARME with targeted bone weakening. MATERIALS AND METHODS: Cone beam computer tomographies of 21 patients before (T1) and 4 months after treatment (T2) with simulation-driven SARME combined with a transpalatal distractor (TPD) and targeted bone weakening were superimposed. The movements of the left, right, and frontal segments were evaluated at the modified WALA ridge, mid root level, and at the root tip of all upper teeth. Linear and angular measurements were performed to detect dentoalveolar changes. RESULTS: Dentoalveolar changes were unavoidable, and buccal tipping of the premolars (6.1° ± 5.0°) was significant (p < 0.05). Transverse expansion in premolar region was higher (6.13 ± 4.63mm) than that in the molar region (4.20 ± 4.64mm). Expansion of left and right segments did not differ significantly (p > 0.05). CONCLUSION: Simulation-driven SARME with targeted bone weakening is effective to achieve symmetrical expansion in the transverse plane. CLINICAL RELEVANCE: Simulation-driven targeted bone weakening is a novel method for SARME to achieve symmetric expansion. Dental side effects cannot be prohibited.

Dissecting bipolar disorder complexity through epigenomic approach.

In recent years, numerous studies of gene regulation mechanisms have emerged in neuroscience. Epigenetic modifications, described as heritable but reversible changes, include DNA methylation, DNA hydroxymethylation, histone modifications and noncoding RNAs. The pathogenesis of psychiatric disorders, such as bipolar disorder, may be ascribed to a complex gene-environment interaction (G × E) model, linking the genome, environmental factors and epigenetic marks. Both the high complexity and the high heritability of bipolar disorder make it a compelling candidate for neurobiological analyses beyond DNA sequencing. Questions that are being raised in this review are the precise phenotype of the disorder in question, and also the trait versus state debate and how these concepts are being implemented in a variety of study designs.

[Total Pancreatectomy and Islet Autotransplantation in a Child with Recurrent Pancreatitis]. / Totale Pankreatektomie und Inselautotransplantation bei einem Kind mit chronisch rezidivierender Pankreatitis.

INTRODUCTION: Hereditary pancreatitis in children is rare. The indications for surgery in these children are complications and severe pain that cannot be managed by conservative treatment. Surgical treatment options are duodenum preserving resections as well as drainage procedures. Recurrences are common following theses surgical procedures, because usually the whole pancreas is affected. The majority of the children with symptomatic hereditary pancreatitis are free of pain after total pancreatectomy. When total pancreatectomy is combined with islet autotransplantation, pancreoprivic diabetes can be attenuated or even prevented. The principle of spleen-preserving total pancreatectomy combined with subsequent islet autotransplantation is shown in a case of a 10-year-old child with chronic recurrent pancreatitis in this video. INDICATION: Symptomatic chronic hereditary pancreatitis in children. PROCEDURE: Spleen-preserving total pancreatectomy, reconstruction with hepatico-jejunostomy and duodeno-jejunostomy, islet autotransplantation via portal vein. CONCLUSION: If the surgeon has appropriate experience, spleen-preserving total pancreatectomy is a safe procedure. In combination with islet autotransplantation, it may attenuate or prevent diabetes mellitus associated with total pancreatectomy. In highly selected pediatric patients, this surgical procedure has a major benefit compared to a purely symptomatic therapy.

Assessment of two e-learning methods teaching undergraduate students cephalometry in orthodontics.

AIM: Cephalometry is important for orthodontic diagnosis and treatment planning and is part of the core curriculum for training dentists. Training involves identifying anatomical landmarks. The aim of this investigation was to assess whether e-learning improves learning efficiency; a programme specifically designed for this purpose was compared to commercially available software. METHODS: Thirty undergraduate students underwent traditional training of cephalometry consisting of lectures and tutorials. Tracing skills were tested immediately afterwards (T0). The students were then randomly allocated to three groups: 10 students served as control (CF); they were asked to improve their skills using the material provided so far. Ten students were given a program specifically designed for this study that was based on a power point presentation (PPT). The last group was given a commercially available program that included teaching elements (SW). The groups were tested at the end the six week training (T1). The test consisted of tracing 30 points on two radiographs and a point score improvement was calculated. The students were interviewed after the second test. RESULTS: Both e-learning groups improved more than the traditional group. Improvement scores were four for CF; 8.6 for PPT and 2.8 for SW. For PPT all participants improved and the student feedback was the best compared to the other groups. For the other groups some candidates worsened. CONCLUSIONS: Blended learning produced better learning outcomes compared to using a traditional teaching method alone. The easy to use Power Point based custom software produced better results than the commercially available software.

Automatic fusion of lateral cephalograms and digital volume tomography data-perspective for combining two modalities in the future.

OBJECTIVES: This article investigates the combination of three-dimensional (3D) digital volume tomography data with two-dimensional (2D) cephalograms in dentomaxillofacial imaging. METHODS: An automatic hierarchical method to adjust the geometrical relations of these two modalities is presented. The approach is tested on phantom and patient case data, where the feasibility, usability and potential possibilities of the presented innovative method are highlighted. Digitally reconstructed radiographs are computed by casting rays through the 3D volume to get a 2D projection of the volume to produce realistic simulated cephalograms. Different similarity measures are considered based on variations of statistical and deterministic optimization procedures. Stability, precision and accuracy of the method are investigated. RESULTS: The presented algorithm demonstrates a reasonable solution of the corresponding 2D/3D registration problem. Exemplary results from phantom and patient case data are presented. Tooth movement could be determined, in contrast to the 2D lateral cephalogram, separated for each side in all three spatial directions. CONCLUSIONS: Achieved results are highlighted from a clinical point of view and demonstrate the clinical benefit in daily praxis.

Islet transplantation at the Dresden diabetes center: five years' experience.

For the majority of patients with type 1 diabetes intensive insulin therapy is effective and safe for maintaining glycemia and minimizing diabetes-associated complications. However, a rare number of patients show highly labile metabolic control and experience repeated and unpredictable hypoglycemic episodes. Such condition is often caused by defective counterregulatory mechanisms and autonomous neuropathy. Patients are at high risk for severe acute and chronic complications, and quality of life is considerably impaired. For this small subset of patients, restoration of endogenous insulin secretion can substantially improve metabolic control and quality of life. In our experience, this is irrespective of insulin independency. Here, we report on our 5 years' experience with implementing islet transplantation as a potential treatment option for type 1 diabetes. All patients were treated by long-term insulin pump therapy prior to enrolment. The main indication was severely unstable diabetes and repeated hypoglycemia. From 2008 to 2013, 10 patients have been transplanted with single islet infusion; mean follow-up time was 35 months. All patients show persistent graft function, stable glycemic control with a reduction in HbA1c in the absence of hypoglycemia. All patients are kept on minimal exogenous insulin. In conclusion, islet transplantation can be an excellent therapy for selected patients. Key prerequisite for success is a strict indication. The primary goal for islet transplantation should be stabile glycemia and prevention of hypoglycemia rather than insulin independence. In fact, maintaining minimal exogenous insulin may protect the islet graft from metabolic stress and even prolong islet graft function.

In vitro studies on the cytotoxic potential of surface sealants.

OBJECTIVE: The objective of this in vitro study was an initial screening of the cytotoxic potential of widely used smooth enamel surface sealants. MATERIALS AND METHODS: A total of 20 products were allocated to four groups based on their chemical composition: (1) filled resin-based sealants, (2) unfilled resin-based sealants, (3) a resin-modified, glass ionomer-based sealant, and (4) silicone-based sealants. All materials were applied to human enamel slices both in accordance with manufacturers' instructions and in additional experiments applying 50% undercuring and 50% overcuring. An agar overlay assay was then used to test the specimens following ISO 10933. The cytotoxic potential of each material was interpreted based on a reaction index that summarized the decolorization and lysis scores obtained. RESULTS: The cytotoxic potential decreased as follows: unfilled resin-based sealants > filled resin-based sealants > resin-modified, glass ionomer-based sealant > silicone-based sealants. In 75% of the resin-based products, deliberate undercuring was associated with more extensive decolorization zones, leading to higher rates of cytotoxic potential in two of those products. Overcuring, by contrast, was associated with a tendency for smaller decolorization zones in 50% of the resin-based products. CONCLUSION: Surface sealants derived from resin monomers exhibited cytotoxic potential in the agar overlay assay. There is also evidence of a possible association with curing, as undercuring can increase the cytotoxic potential, whereas normal curing (as per manufacturers' instructions) or overcuring may help minimize such effects. More research into the biological implications of these materials is needed, especially with regard to their potential impact on the adjacent gingiva.

Oxygen supply by photosynthesis to an implantable islet cell device.

Transplantation of islet cells is an effective treatment for type 1 diabetes with critically labile metabolic control. However, during islet isolation, blood supply is disrupted, and the transport of nutrients/metabolites to and from the islet cells occurs entirely by diffusion. Adequate oxygen supply is essential for function/survival of islet cells and is the limiting factor for graft integrity. Recently, we developed an immunoisolated chamber system for transplantation of human islets without immunosuppression. This system depended on daily oxygen supply. To provide independence from this external source, we incorporated a novel approach based on photosynthetically-generated oxygen. The chamber system was packed sandwich-like with a slab of immobilized photosynthetically active microorganisms (Synechococcus lividus) on top of a flat light source (LEDs, red light at 660 nm, intensity of 8 µE/m(2)/s). Islet cells immobilized in an alginate slab (500-1,000 islet equivalents/cm(2)) were mounted on the photosynthetic slab separated by a gas permeable silicone rubber-Teflon membrane, and the complete module was sealed with a microporous polytetrafluorethylene (Teflon) membrane (pore size: 0.4 µm) to protect the contents from the host immune cells. Upon illumination, oxygen produced by photosynthesis diffused via the silicone Teflon membrane into the islet compartment. Oxygen production from implanted encapsulated microorganisms was stable for 1 month. After implantation of the device into diabetic rats, normoglycemia was achieved for 1 week. Upon retrieval of the device, blood glucose levels returned to the diabetic state. Our results demonstrate that an implanted photosynthetic bioreactor can supply oxygen to transplanted islets and thus maintain islet viability/functionality.

Xenotransplantation of porcine islet cells as a potential option for the treatment of type 1 diabetes in the future.

Solid organ and cell transplantation, including pancreatic islets constitute the treatment of choice for chronic terminal diseases. However, the clinical use of allogeneic transplantation is limited by the growing shortage of human organs. This has prompted us to initiate a unique multi-center and multi-team effort to promote translational research in xenotransplantation to bring xenotransplantation to the clinical setting. Supported by the German Research Foundation, an interdisciplinary group of surgeons, internal medicine doctors, diabetologists, material sciences experts, immunologists, cell biologists, virologists, veterinarians, and geneticists have established a collaborative research center (CRC) focusing on the biology of xenogeneic cell, tissue, and organ transplantation. A major strength of this consortium is the inclusion of members of the regulatory bodies, including the Paul-Ehrlich Institute (PEI), infection specialists from the Robert Koch Institute and PEI, veterinarians from the German Primate Center, and representatives of influential ethical and religious institutions. A major goal of this consortium is to promote islet xenotransplantation, based on the extensive expertise and experience of the existing clinical islet transplantation program. Besides comprehensive approaches to understand and prevent inflammation-mediated islet xenotransplant dysfunction [immediate blood-mediated inflammatory reaction (IBMIR)], we also take advantage of the availability of and experience with islet macroencapsulation, with the goal to improve graft survival and function. This consortium harbors a unique group of scientists with complementary expertise under a cohesive program aiming at developing new therapeutic approaches for islet replacement and solid organ xenotransplantation.

Increased gene expression of the cardiac endothelin system in obese mice.

Obesity is a well-known risk factor of atherosclerosis and heart failure. In the human heart, a local endothelin system containing prepro-endothelin-1, endothelin-converting enzyme-1, and endothelin receptors A and B has been described. The endothelin system is activated in heart failure; however, the impact of obesity on the cardiac endothelin system is unknown. In this study, 18-week-old male C57BL/6 mice fed either a control diet or a high-fat diet for 10 weeks were analyzed. High-fat diet significantly increased the body weight of the animals and augmented low-density lipoprotein, high-density lipoprotein, and cholesterol plasma levels, compared to control. The animal groups showed no significant differences in left ventricular size or function (heart rate, ejection fraction, fractional shortening, left ventricular posterior wall thickness, cardiac output) after control or high-fat diet. We did not observe signs of cardiac hypertrophy or changes in markers of cardiac fibrosis in these heart samples. The cardiac expression of prepro-endothelin-1 mRNA, endothelin-converting enzyme-1 mRNA, and protein and endothelin receptors A and B mRNA was increased in 18-week-old obese C57BL/6 mice compared to animals with normal weight (p<0.05 vs. control). Furthermore, endothelin-1 plasma levels showed an increasing trend. In conclusion, an increased expression of genes of the endothelin system was observed in the hearts of 18-week-old mice after high-fat diet, possibly contributing to later cardiovascular complications of obesity.

Treatment efficiency of mini-implant-borne distalization depending on age and second-molar eruption.

OBJECTIVE: The aim of this study was to evaluate the efficiency of molar distalization depending on age and second-molar eruption using the Beneslider. MATERIALS AND METHODS: Treatment of 51 patients (mean age 17.8 ± 9.6 years) was investigated retrospectively by means of pre- and posttreatment cephalograms. Patients were divided into three groups: 14 children with unerupted upper second molars (group 1), 23 adolescents with second molar in place (group 2), and 14 adults (group 3). The distalization forces applied were 2.4 N in group 1 and 5.0 N in groups 2 and 3. Treatment changes were evaluated and examined statistically for significant differences. RESULTS: In all patients a Class I molar relationship was achieved. All mini-implants remained stable during treatment. Mean distalization distance as measured by the displacement of the center of resistance was 3.6 ± 1.9 mm (range 1.2-8.5 mm depending on treatment needs). Since no significant tipping was detected, the type of movement can be described as bodily movement. Mean overall distalization speed was 0.6 ± 0.4 mm per month. There were no statistical differences between the groups. CONCLUSION: We found the Beneslider to be an effective appliance that enables bodily distalization in adequate treatment time. The higher resistance due to erupted second molars can be compensated by the use of higher forces without significantly reducing distalization speed.

Questionnaire study of electronic wear-time tracking as experienced by patients and parents during treatment with removable orthodontic appliances.

OBJECTIVE: To survey how patients and parents rate microelectronic wear-time tracking (TheraMon(®)) during treatment with removable orthodontic appliances. PATIENTS AND METHODS: A total of 125 patients with a mean age of 11.99 years whose treatment involved removable appliances with a built-in microsensor for wear-time documentation were enrolled in a questionnaire study addressing electronic wear-time tracking. Respondents included the patients and their parents. RESULTS: A total of 86% of the patients reported that the orthodontic appliance's comfort was unaffected by the installed sensor. A majority of respondents had a favorable impression of wear-time tracking. Printed wear-time documents from the clinician's computer were considered a "nice certificate of compliance" by 46% of patients, and 38% of them stated that they intended to improve their compliance when faced with a poor record. Indeed, 48% of parents believe that wear-time tracking can improve the therapeutic success, while 32% believe that it can reduce the duration of treatment. Around 10% of respondents felt that the sensors were unnecessary and not recommendable. CONCLUSION: These favorable ratings by patients and their parents may help future patients and users to decide for or against microelectronic wear-time tracking. Randomized studies are needed to demonstrate whether the sheer presence of a wear-time sensor stimulates compliance on its own.

A novel device for islet transplantation providing immune protection and oxygen supply.

Islet transplantation as a biological ß-cell replacement therapy has emerged as a promising option for achieving restoration of metabolic control in type 1 diabetes patients. However, partial or complete loss of islet graft function occurs in relatively short time (months to few years) after implantation. The high rate of early transplant dysfunction has been attributed to poorly viable and/or functional islets and is mediated by innate inflammatory response at the intravascular (hepatic) transplant site and critical lack of initial nutrient/oxygen supply prior to islet engraftment. In addition, the diabetogenic effect of mandatory immunosuppressive agents, limited control of alloimmunity, and the recurrence of autoimmunity limit the long-term success of islet transplantation. In order to abrogate instant blood-mediated inflammatory reaction and to provide oxygen supply for the islet graft, we have developed an extravascular (subcutaneous) transplant macrochamber (the 'ßAir' device). This device contains islets immobilized in alginate, protected from the immune system by a thin hydrophilized teflon membrane impregnated with alginate and supplied with oxygen by daily refueling with oxygen-CO (2) mixture. We have demonstrated successful utilization of the oxygen-refueling macrochamber for sustained islet viability and function as well as immunoprotection after allogeneic subcutaneous transplantation in healthy minipigs. Considering the current limitations of intraportal islet engraftment and the restricted indication for islet transplantation mainly due to necessary immunosuppressive therapy, this work could very likely lead to remarkable improvements in the procedure and moreover opens up further strategies for porcine islet cell xenotransplantation.

The JNK pathway amplifies and drives subcellular changes in tau phosphorylation.

Neurofibrillary tangles composed of hyperphosphorylated tau are a major hallmark of Alzheimer's Disease. This phosphorylated tau may be a root cause of the disorder and therefore understanding its regulation is important for therapeutic intervention. To model this pathology, Okadaic acid (OA) has been used in primary cultured hippocampal neurons to investigate effects on tau, and the role of the JNK pathway in tau phosphorylation. The use of high content screening has allowed us to quantitatively assess the profound spatiotemporal profile of these proteins, finding dramatic and inhibitable changes. Furthermore, in vitro phosphorylation experiments show that the JNK3 isoform, which is predominantly expressed in the brain, can strongly autophosphorylate itself. This has profound implications on the importance of JNK3 in the CNS and its ability to sustain signaling both towards tau and other apoptotic targets. Together these data provide novel insights into the JNK pathway and a high resolution perspective on how this pathway influences tau phosphorylation and dynamics in neurons.

An update on preventive and regenerative therapies in diabetes mellitus.

Type 1A (immune-mediated) and type 2 diabetes mellitus are two of the most common severe chronic illnesses, affecting over 230 million people worldwide with an estimated global prevalence of 5.1%. Although type 1 and type 2 diabetes differ greatly in modes of pathogenesis, these illnesses share a common pathology and consequences characterized by loss of functional beta-cell mass and subsequent dysregulation of carbohydrate and lipid metabolism. Since therapy for diabetes and the associated complications poses enormous public health and economic burdens, novel preventive and regenerative therapies have emerged in the past decade with the aim to preserve beta-cell mass and delay the onset of diabetes. The goal of this review is to provide a comprehensive overview of current efforts in the fight against diabetes, and attempts to document all strategies that have emerged in clinical studies within the past 25 years. First, strategies to identify individuals at risk, ranging from whole-genome scans to autoantibody screening, will be discussed. Second, novel approaches to prevent or delay the onset of disease will be covered. Particular focus is given on emerging strategies for individuals at risk for type 1 diabetes that target T-cell regulation and induction of tolerance, while new pharmaceutical concepts in combination with lifestyle interventions are discussed within the scope of type 2 diabetes prevention. Lastly, important efforts to halt disease progression with emphasis on beta-cell regeneration are presented.