HbA1c-Variabilität in Abhängigkeit des Hämoglobins und der Erythropoietin Rezeptor stimulierenden Präparate bei Hämodialysepatienten - HESA Studie -

Der Diabetes mellitus zählt zu den Hauptursachen einer terminalen Niereninsuffizienz. Aufgrund der veränderten Erythropoiese ist die Verwendung des HbA1c für die Beurteilung der Stoffwechseleinstellung bei Diabetikern mit einer chronischen Nierenerkrankung im Stadium 5 nach KDOQI immer noch in Frage gestellt. Die vorliegende Arbeit untersuchte die HbA1c-Variabilität in Abhängigkeit der ESA-Dosis und des ESA-Präparates bei Hämodialysepatienten. Zum Einsatz kamen entweder das klassische Epoetin-Analogon Erythropoietin α oder ein Wirkstoff der neueren Generation Methoxy-Polyethylenglycol-Epoetin beta. Es wurden 102 Hämodialysepatienten, darunter 41 Diabetiker und 61 Nicht-Diabetiker, über einen Zeitraum von neun Monaten beobachtet. Von den Untersuchungsteilnehmern erhielten 48 Patienten Epoetin α und 54 Patienten Methoxy-Polyethylenglycol-Epoetin beta. Unsere Daten konnten zeigen, dass es zu einer Beeinflussung des HbA1c durch die Therapie mit ESA-Präparaten kommt. Das als alternativer Stoffwechselparameter fungierende Fructosamin unterlag keiner derartigen Beeinflussung, korrelierte jedoch nur ungenügend mit den höheren Blutzuckerwerten, sodass seine Anwendbarkeit bei Diabetikern ebenfalls erheblich einschränkt ist. In der Gegenüberstellung der beiden ESA-Präparate erzielten beide Wirkstoffe vergleichbare Ergebnisse bezüglich des Erreichens der Hämoglobin-Zielwerte. Methoxy-Polyethylenglycol-Epoetin beta zeigte im Gegensatz zu Epoetin α eine seltener notwendige Dosisanpassung und längere Applikationsintervalle. Aus der vorliegenden Arbeit geht hervor, dass bei Hämodialysepatienten das HbA1c kritisch und mit Bedacht auf mögliche Einflussfaktoren interpretiert werden sollte. Es ist dennoch derzeit der konstanteste Parameter in der Stoffwechselverlaufskontrolle bei Diabetes mellitus

Entwicklung der quergestreiften Ösophagusmuskulatur bei Shh-Mutantmäusen

Objectives Sonic hedgehog (Shh) is a morphogen responsible for short- or long-term regulato-ry processes during embryonic development. Shh is expressed by the endodermal epithelium of the digestive and respiratory system, whereupon it is particularly ac-tive in the esophageal tissues. Here it induces different developmental processes depending on its concentration. Atresia is a condition in which there are motility and food transport disorders in the area of the esophagus. It is believed that there is a possible link between a lack of Shh gene expression and malformations of the esophageal muscle tube, that cause the clinical symptoms. Design & Methods For the present study, breeding pairs of mice were used in which the Shh gene was heterozygous changed in both sexes. Since homozygous mutant mice are not via-ble, embryos were analyzed on the eighteenth day of development just before birth. In total, three control mice (Shh+/+), three heterozygous (Shh+/-) and three homozy-gous (Shh-/-) mutant mice were included in the study, which were from four pregnant fe-male mice. The nine esophagi of the embryos were divided into 2 mm long pieces from cranial to caudal, fixed and prepared for electron microscopy. Observations & Results While Shh(+/+) mice showed a regular transformation of smooth muscle into striated muscle in a craniocaudal sequence, the analysis of Shh(-/-) mice showed that com-plete inhibition of gene activity leads to complex morphological changes in the mouse esophagus. Although mesenchymal cells differentiated into their further de-velopmental stages, a regulated activation of proliferation and differentiation no longer took place in its conventional sequence. In addition, the amount of proliferat-ing muscle precursor cells was significantly reduced, continuity interruptions of the esophagus occurred and the stratification of the organ had been abolished. In Shh(+/-) mice there were no or no detectable developmental changes. Conclusions The results of the study suggest a link between defects in the Shh gene and mor-phological aberrations in the esophagus which are already visible in embryonic de-velopmental stages. The investigations indicate that Shh does not have any influ-ence on the actual differentiation process of mesenchymal progenitor cells but has to be involved in signal cascades that allow and control a regulated developmental sequence. The available findings are of high clinical relevance, as they are the first to show morphological changes on the electron microscopic level in the genetic mouse model, which contribute decisively to the further understanding of the patho-genesis of esophageal atresia.Hintergrund und Ziele Sonic-Hedgehog (Shh) ist ein Morphogen, welches für kurz- oder langfristige Regu-lationsprozesse während der Embryonalentwicklung zuständig ist. Shh wird vom endodermalen Epithel der Speise- und Luftwege exprimiert, worauf es unter ande-rem besonders in den Geweben des Ösophagus aktiv wird. Hier induziert es in Ab-hängigkeit von seiner Konzentration verschiedene Entwicklungsvorgänge. Die Atresie stellt ein Krankheitsbild dar, bei welchem es zu Motilitäts- und Nahrungs-transportstörungen im Bereich des Ösophagus kommt. Es wird vermutet, dass ein möglicher Zusammenhang zwischen einer ausbleibenden Shh-Genexpression und Fehlbildungen des ösophagealen Muskelschlauchs besteht, welche die klinischen Symptome verursachen. Material und Untersuchungsmethoden Für die vorliegende Untersuchung wurden Zuchtpaare von Mäusen verwendet, bei denen das Shh-Gen in beiden Geschlechtern heterozygot verändert war. Da ho-mozygote Mutantmäuse nicht überlebensfähig sind, wurden Embryonen am 18. Tag der Entwicklung kurz vor der Geburt analysiert. Insgesamt wurden jeweils drei Kon-trollmäuse (Shh+/+), drei heterozygote (Shh+/-) und drei homozygote (Shh-/-) Mu-tantmäuse in die Studie einbezogen, die von vier trächtigen weiblichen Mäusen stammten. Die neun Ösophagi der Embryonen wurden von kranial nach kaudal in 2 mm lange Stücke unterteilt, fixiert und für die Elektronenmikroskopie aufbereitet. Ergebnisse und Beobachtungen Während in Shh(+/+)-Mäusen eine regelmäßige Umwandlung der glatten in querge-streifte Muskulatur in einer kraniokaudalen Sequenz zu beobachten war, zeigte die Analyse von Shh(-/-)-Mäusen, dass eine vollständige Hemmung der Genaktivität zu komplexen morphologischen Veränderungen im Mäuseösophagus führt. Mesen-chymale Zellen differenzierten sich zwar in ihre weiteren Entwicklungsstufen, eine regulierte Aktivierung der Proliferation und Differenzierung fand jedoch nicht mehr in ihrer herkömmlichen Abfolge statt. Hinzu kommt, dass die Menge an proliferie-renden Muskelvorläuferzellen deutlich reduziert war, Kontinuitätsunterbrechungen des Ösophagus auftraten und der typische Wandaufbau des Organs aufgehoben war. In Shh(+/-)-Mäusen zeigten sich keine bzw. keine nachweisbaren Entwicklungsverän-derungen. Praktische Schlussfolgerungen Aufgrund der Untersuchungsergebnisse lässt sich auf einen Zusammenhang zwi-schen Defekten des Shh-Gens und morphologischen Aberationen im Bereich des Ösophagus schließen, die bereits in embryonalen Entwicklungsstadien sichtbar werden. Die Untersuchungen weisen darauf hin, dass Shh nicht auf die eigentliche Differenzierung der mesenchymalen Vorläuferzellen Einfluss hat, sondern an Sig-nalkaskaden beteiligt sein muss, die eine regulierte Entwicklungsabfolge zulässt und kontrolliert. Die vorliegenden Befunde haben hohe klinische Relevanz, da sie erstmalig morphologische Veränderungen auf elektronenmikroskopischer Ebene im genetischen Mäusemodell darstellen, die zum weiteren Verständnis der Patho-genese der Ösophagusatresie entscheidend beitragen

Systematische Proteomanalyse zur Optimierung des biosolaren H2-Produktionsprozesses in der einzelligen Grünalge Chlamydomonas reinhardtii

Beckmann J. Systematische Proteomanalyse zur Optimierung des biosolaren H2-Produktionsprozesses in der einzelligen Grünalge Chlamydomonas reinhardtii. Bielefeld: Universität Bielefeld; 2013

Toy for Preschoolers with Deaf-Blindness

There are approximately 70,000-100,000 people living in America that are diagnosed as deaf-blind. Since children with deaf-blindness are an extreme minority in the US, research, toys and technological advancements for these children get overlooked. As a result, the developmental processes of children with deaf-blindness are delayed by several years, compared to normal children, due to the lack of resources available to encourage learning. According to Virginia’s Department of Education standards of learning for preschoolers, development physically, mathematically,of environmental awareness and of a sense of self are core requirements for Kindergarten. Therefore, there is a need for a toy that will provide stimulation to develop physical, social, and cognitive progression to keep children with deaf-blindness on a normal learning curve. Our design consists of components each of which stimulate one of the development goals. The first component is a chair that promotes proper posture. The second component is a colored and vibrating drum game to stimulate mathematical development through pattern recognition. The third component is a Braille exposure game to stimulate literacy development, by associating a Braille word with an object or concept. The fourth component is an apparatus that can be placed over the chair that contains dangling objects where the child can reach out to explore their surrounding environment. Under the supervision and interaction of a parent/guardian, the child will develop socially through human interaction and feedback suggested in the provided instruction manual. Our team has been conducting research online and consulting professionals that have worked, or are currently working, in the deaf-blind field; therefore we gathered information on how children with deaf-blindness typically react to certain stimuli and various developmental concerns, to aid with the design of the toy components. With this foundation, our group drafted a variety of design concepts. We weighed out the positives, negatives, and overall efficiency of each concept which lead us to produce our final design. Then we presented our final design to our faculty advisor, perfect our idea and move forward with materials selection. Our next step in the design process is to test the efficiency of different materials and methods that we selected for the stimulatory components through experimentation and computation of engineering principles behind the design. Unfortunately our group encountered a problem in the design process, we are behind in the construction of the chair components due to the amount of time it took to complete the machine shop class. Once our testing is completed, we will begin to construct and complete the full prototype of our product.https://scholarscompass.vcu.edu/capstone/1003/thumbnail.jp

Personal Transparency in Perspective: The Impact of Social Networking Sites on the Recruitment Process

The “transparency trend” is hot for the summer of 2011. At least that is what they said in the fashion capitals of Milan, Paris, and London. In the new summer collections, sheer seethrough dresses reveal the beauties of the human body and leave little to the imagination. Architects too are attracted by the intriguing properties of transparent materials to create a new perception of space and boundaries, which challenges some traditional understandings of private living and daily work life. Whereas in the past, it was a Puritan statement to live without curtains at the windows, to show you had nothing to hide, today, the transparent way of life is often used to enable the owner to display their wealth and luxury. Institutions have increasingly followed this transparency trend in fashion and architecture by using glass for their buildings. Transparency is not only a fashion trend, but also a political challenge. Fashion and politics meet in the huge glass buildings of the European Union in Brussels and Strasbourg, which reflect the Union’s strategy to improve its democratic legitimacy; one of the main aims of the Lisbon Treaty (2009). In terms of adaption to this see-through trend, institutions are not only voluntarily moving towards greater transparency, they are being ambushed by those who believe that information is a public good, which should not be guarded by a few. By revealing “suppressed and censored injustices” (WikiLeaks, n.d.), WikiLeaks practices what some call “guerrilla transparency” (The Economist, 2010). When people think of transparency, the recent commotion caused by WikiLeaks’ publication of thousands of documents on nationally and internationally sensitive issues is at the forefront of their minds. This event has triggered a worldwide debate on the balance between state security and citizens’ right to know

Occupant requirements in residential buildings – an empirical study and a theoretical model

Occupant needs with regard to residential buildings are not well known due to a lack of representative scientific studies. To improve the lack of data, a large scale study was carried out using a Post Occupancy Evaluation of 1,416 building occupants. Several criteria describing the needs of occupants were evaluated with regard to their subjective level of relevance. Additionally, we investigated the degree to which deficiencies subjectively exist, and the degree to which occupants were able to accept them. From the data obtained, a hierarchy of criteria was created. It was found that building occupants ranked the physiological needs of air quality and thermal comfort the highest. Health hazards such as mould and contaminated building materials were unacceptable for occupants, while other deficiencies were more likely to be tolerated. Occupant satisfaction was also investigated. We found that most occupants can be classified as satisfied, although some differences do exist between different populations. To explain the relationship between the constructs of what we call relevance, acceptance, deficiency and satisfaction, we then created an explanatory model. Using correlation and regression analysis, the validity of the model was then confirmed by applying the collected data. The results of the study are both relevant in shaping further research and in providing guidance on how to maximize tenant satisfaction in real estate management

Occupant requirements in residential buildings – an empirical study and a theoretical model

Occupant needs with regard to residential buildings are not well known due to a lack of representative scientific studies. To improve the lack of data, a large scale study was carried out using a Post Occupancy Evaluation of 1,416 building occupants. Several criteria describing the needs of occupants were evaluated with regard to their subjective level of relevance. Additionally, we investigated the degree to which deficiencies subjectively exist, and the degree to which occupants were able to accept them. From the data obtained, a hierarchy of criteria was created. It was found that building occupants ranked the physiological needs of air quality and thermal comfort the highest. Health hazards such as mould and contaminated building materials were unacceptable for occupants, while other deficiencies were more likely to be tolerated. Occupant satisfaction was also investigated. We found that most occupants can be classified as satisfied, although some differences do exist between different populations. To explain the relationship between the constructs of what we call relevance, acceptance, deficiency and satisfaction, we then created an explanatory model. Using correlation and regression analysis, the validity of the model was then confirmed by applying the collected data. The results of the study are both relevant in shaping further research and in providing guidance on how to maximize tenant satisfaction in real estate management

Preliminary Investigation of Side Effects of Polymyxin B Administration in Hospitalized Horses

Neuro- and nephrotoxicity of polymyxins are known but clinical studies in horses are lacking. The aim of this study was to describe neurogenic and nephrogenic side effects of hospitalized horses receiving Polymyxin B (PolyB) as part of their treatment plan. Twenty horses diagnosed with surgical colic (n = 11), peritonitis (n = 5), typhlocolitis (n = 2), pneumonia, and pyometra (each n = 1) were included. Antimicrobial treatment was randomized to GENTA (gentamicin 10 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV) or NO GENTA (marbofloxacin 2 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV). The duration of PolyB treatment ranged from 1 to 4 days. Clinical and neurological examinations were performed, and serum PolyB concentrations were measured daily during and three days following PolyB treatment. Urinary analysis, plasma creatinine, urea and SDMA were assessed every other day. Video recordings of neurological examinations were graded by three blinded observers. All horses showed ataxia during PolyB treatment in both groups (median maximum ataxia score of 3/5, range 1–3/5). Weakness was detected in 15/20 (75%) horses. In 8/14 horses, the urinary γ-glutamyltransferase (GGT)/creatinine ratio was elevated. Plasma creatinine was mildly elevated in 1/16 horses, and SDMA in 2/10 horses. Mixed-model analysis showed a significant effect of time since last PolyB dose (p = 0.0001, proportional odds: 0.94) on the ataxia score. Ataxia and weakness should be considered as reversible adverse effects in hospitalized horses receiving PolyB. Signs of tubular damage occurred in a considerable number of horses; therefore, the nephrotoxic effect of polymyxins should be considered and urinary function monitored

Anal Sac Adenocarcinoma with Vertebromedullary Metastasis in a Cocker Spaniel

Background: Several neoplasms can affect the perianal region, being the hepatic adenoma and the anal sac adenocarcinoma (ASAC), which is considered the most frequent. The ASAC is a malignant neoplasm originating from the secretory epithelium of the perianal apocrine glands and is rarely seen in veterinary medicine. The ASAC occurs mainly in adult to elderly canines with high metastasis rates. Patients may be asymptomatic or manifest discomfort and behavioral changes. In the presence of metastasis, the most frequent clinical signs are inappetence, coughing, dyspnea, and colorectal obstruction. Given this scenario, this paper aims to describe the clinical presentation, diagnostic examination, and necropsy findings of a Cocker Spaniel with ASAC and metastasis in the vertebral body, spinal cord, and cauda equina. Case: A 8-year-old neutered male Cocker Spaniel (12 kg of body mass) with a clinical history of non-ambulatory paraparesis was evaluated. The patient also presented tenesmus, difficulty to defecate, and the presence of nodules in the anal sac area. On the neurological examination, asymmetrical changes compatible with injury between L4-S3 were found. A complete blood count, serum biochemistry, and imaging exams such as plain radiography, abdominal ultrasonography (US), and magnetic resonance imaging (MRI) were requested. Blood count revealed anemia and neutrophilic leukocytosis and hypercalcemia. The liver showed increased echogenicity and thickened pancreas in the abdominal US scan. A slightly heterogeneous, vascularized mass with irregular borders was identified in the topographic region of the sublumbar lymph nodes; MRI images demonstrated an expansile formation in the ventral region of the lumbosacral spine, corresponding to the sublumbar lymph nodes and interruption of the cerebrospinal fluid at L5, suggestive of compression of the spinal cord and cauda equina. A presumptive diagnosis of perianal neoplasm with metastasis was made based on the complementary exams. The dog was referred to necropsy, which revealed a 4 cm tumor in the perianal region that invaded the pelvic canal. Multifocal nodules were present on the lung surface, liver, and kidneys, suggesting metastasis. On the cross-section of the spine, one could note the presence of the tumor in the vertebral bodies, spinal cord, and cauda equina from L5 to S3. Even with histopathological evaluation of the tumor, only the immunohistochemical analysis allowed us to confirm the anal sac adenocarcinoma. Discussion: Adenomas and carcinomas are perianal gland neoplasms common in adult and elderly male dogs; the Cocker Spaniel breed is among the most affected. The clinical signs presented by the patient, such as tenesmus and difficulty in adopting the posture of defecation, are common, although neurological changes are rare. As for metastasis, carcinomas of the perianal region present high chances of metastasis to organs including the liver, kidneys, and lungs, both lymphatically and hematogenously, but few studies have related these factors to neurological alterations  due to metastasis. We concluded that metastases from carcinomas to the spine must be considered a possible differential diagnosis in cases of patients presenting clinical signs that are compatible with spinal cord compression and a history of previous neoplasm. Keywords: canine perianal carcinoma, neoplasm, spinal cord metastasis. Título: Adenocarcinoma de saco anal com metástase vertebro-medular em um Cocker Spaniel Descritores: carcinoma perianal canino, neoplasma, metástase medula espinhal.Introdução: Diversas neoplasias podem acometer a região perianal, sendo o adenoma hepático e o adenocarcinoma do saco anal (ASA), considerados os mais frequentes. O ASAC é uma neoplasia maligna originada do epitélio secretor das glândulas apócrinas perianais e raramente é visto na medicina veterinária. O ASA ocorre principalmente em cães adultos a idosos com altas taxas de metástase. Os pacientes podem ser assintomáticos ou manifestar desconforto e alterações comportamentais. Na presença de metástase, os sinais clínicos mais frequentes são inapetência, tosse, dispneia e obstrução colorretal. Diante desse cenário, este trabalho tem como objetivo descrever a apresentação clínica, exame diagnóstico e achados de necropsia de um Cocker Spaniel com ASAC e metástase no corpo vertebral, medula espinhal e cauda equina.Caso: Foi avaliado um macho castrado da raça Cocker Spaniel (12 kg de massa corporal) de oito anos de idade com história clínica de paraparesia não deambulatória. A paciente também apresentava tenesmo, dificuldade para defecar e presença de nódulos na região do saco anal. Ao exame neurológico, foram encontradas alterações assimétricas compatíveis com lesão entre L4-S3. Foram solicitados hemograma completo, bioquímica sérica e exames de imagem como radiografia simples, ultrassonografia (US) abdominal e ressonância magnética (RM). O hemograma revelou anemia e leucocitose neutrofílica e hipercalcemia. O fígado mostrou ecogenicidade aumentada e pâncreas espessado na US abdominal. Identificou-se massa pouco heterogênea, vascularizada e de contornos irregulares na região topográfica dos linfonodos sublombares; As imagens de RM demonstraram formação expansiva na região ventral da coluna lombossacral, correspondendo aos linfonodos sublombares e interrupção do líquido cefalorraquidiano em L5, sugestiva de compressão da medula espinhal e cauda equina. O diagnóstico presuntivo de neoplasia perianal com metástase foi feito com base nos exames complementares. A cadela foi encaminhada para necropsia, que revelou tumoração de 4 cm na região perianal que invadia o canal pélvico. Nódulos multifocais estavam presentes na superfície pulmonar, fígado e rins, sugerindo metástase. No corte transversal da coluna, notou-se a presença do tumor nos corpos vertebrais, medula espinhal e cauda equina de L5 a S3. Mesmo com a avaliação histopatológica do tumor, apenas a análise imuno-histoquímica permitiu confirmar o adenocarcinoma do saco anal.Discussão: Adenomas e carcinomas são neoplasias das glândulas perianais comuns em cães machos adultos e idosos; a raça Cocker Spaniel está entre as mais afetadas. Os sinais clínicos apresentados pelo paciente, como tenesmo e dificuldade em adotar a postura de defecar, são comuns, embora alterações neurológicas sejam raras. Quanto à metástase, os carcinomas da região perianal apresentam grandes chances de metástase para órgãos como fígado, rins e pulmões, tanto por via linfática quanto hematogênica, porém poucos estudos relacionam esses fatores às alterações neurológicas decorrentes da metástase. Concluímos que metástases de carcinomas para a coluna devem ser consideradas um possível diagnóstico diferencial em pacientes que apresentam sinais clínicos compatíveis com compressão medular e história de neoplasia prévia

Flotillins Are Involved in the Polarization of Primitive and Mature Hematopoietic Cells

BACKGROUND: Migration of mature and immature leukocytes in response to chemokines is not only essential during inflammation and host defense, but also during development of the hematopoietic system. Many molecules implicated in migratory polarity show uniform cellular distribution under non-activated conditions, but acquire a polarized localization upon exposure to migratory cues. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present evidence that raft-associated endocytic proteins (flotillins) are pre-assembled in lymphoid, myeloid and primitive hematopoietic cells and accumulate in the uropod during migration. Furthermore, flotillins display a polarized distribution during immunological synapse formation. Employing the membrane lipid-order sensitive probe Laurdan, we show that flotillin accumulation in the immunological synapse is concomittant with membrane ordering in these regions. CONCLUSIONS: Together with the observation that flotillin polarization does not occur in other polarized cell types such as polarized epithelial cells, our results suggest a specific role for flotillins in hematopoietic cell polarization. Based on our results, we propose that in hematopoietic cells, flotillins provide intrinsic cues that govern segregation of certain microdomain-associated molecules during immune cell polarization