Mechanisms of Neuronal Death in a Transgenic Mouse Model for Amyotrophic Lateral Sclerosis

Neurons are large post-mitotic cells with a high metabolic activity and a highly complex morphology characterized by a dendritic tree that consists of a network of processes, and an axon that can have length of up to 104 times the diameter of the cell body. Because of this complexity the maintenance of the functional and structural integrity of neurons throughout life is a complex task that requires sophisticated transport, damage control and repair machineries. Hence, it is not surprising that aging is associated with structural and functional deterioration of the central nervous system and that neurodegenerative diseases (diseases that cause the premature loss of neurons) are among the dominant disorders associated with aging. The knowledge on processes involved in normal aging and neuronal death in neurodegerative diseases is increasing, but far from complete. Intervention in these processes is therefore not yet possible. Amyotrophic lateral sclerosis (ALS) is a fatal disease in which motoneurons in the spinal cord, brain stem and motor cortex degenerate. This disease has an incidence of 2-3 per 100.000 people, meaning that 300-450 people are diagnosed with the disease each year. The survival of ALS-patients is on average 3 years after diagnosis. The first symptoms are usually fatigue, muscle cramps, and weakness in the muscles of one of the limbs, progressing to paralysis and spreading to other parts of the body, eventually causing total body paralysis. In most patients (about 90%) no apparent genetic cause for their disease has been found, in those cases the disease is called sporadic ALS. In the other 10% a hereditary pattern has been found; familial ALS. In 1993 a mutation was found in the gene for superoxide dismutase 1 (SOD1) which causes ALS in some familial ALS families. By now more than 110 different mutations in the SOD1-gene have been linked to familial ALS and more recently mutations in 5 other genes have been found to cause familial ALS. The discovery of SOD1-mutations has enabled the production of transgenic mutant-SOD1 expressing mice that develop an ALS-like motoneuron disease. These SOD1-mutant mice develop a disease strongly resembling human ALS. These transgenic mice offer the possibility to study all stages of motoneuron death. In this thesis different aspects of ALS in the transgenic mouse model and in cultured motoneurons are studied and discussed

First records of the summerfruit tοrticid, Adoxophyes oranα F. ν .R. in Greece

Το πολυφάγο Αεπιδόπτερο Adoxophyes orana F.v.R. της οικογένειας Tortricidae παρατηρήθηκε για πρώτη φορά στην περιοχή της Νάουσας το 1985, σε μηλιές, ροδακινιές και κερασιές, όπου προσέβαλε την άνοιξη τους οφθαλμούς και αργότερα τα φύλλα και τους καρπούς. Πιθανότατα εισήλθε στην Ελλάδα από τη γειτονική Γιουγκοσλαβία, όπου ήταν γνωστό και προκαλούσε ζημιά στα οπωροφόρα δέντρα τουλάχιστον από το 1975. Το ενήλικο σε γενικό χρωματισμό και μορφή μοιάζει με το επίσης πολυφάγο φυλλοδετικό Λεπιδόπτερο.4Γί7φί rosanus L. Το άνοιγμα των πτερύγων στο ενήλικο αρσενικό είναι 15-20 mm και το θηλυκό 19-22 mm. Οι πρόσθιες πτέρυγες στο αρσενικό έχουν βασικό χρώμα κίτρινο ώχρας και στο θηλυκό σκοτεινότερο, συχνά καστανόμαυρο. Οι πτέρυγες αυτές και στα δύο φύλλα, έχουν χαρακτηριστικές κηλίδες και λωρίδες σκοτεινότερες από το βασικό χρώμα. Η πλήρως αναπτυγμένη προνύμφη είναι πράσινη και μήκους 18-20 mm.In spring 1985, buds of apple and peach trees in the Naoussa area of northern Greece were severely damaged by larvae of a tortricid moth. Adults emerged in late May and early June. Later in the season, we found larvae of the same species established and feeding on leaves and green or ripe fruits of apple and peach, as well as on ripe cherries. Larvae collected in late June were reared in the laboratory on peach leaves and on an artificial diet. The adults obtained were identified as Adoxophyes orana Fischer von Rosslerstamm (Lepidoptera. Tortricidae). A. orana is a synonym of A. reticulates Huebner, A.tripsiana Eversmann, A. fasciata Walsh., or Capua or Cacoecia reticulana Huebner and most probably, is a recent introduction to Greece. The damage it causes to fruits such as apples, peaches and cherries is such that it could not have escaped the attention of fruit growers and plant protection specialists if the insect had earlier been present in the country. A. orana has been established and caused damage to fruit trees in northwest and central Europe for approximately fifty years and in southern Yugoslavia for at least the last ten years. It is probable that it spread to northern Greece from neighboring Yugoslavia. In the Naoussa area, the moths laid their eggs in batches on fruits or leaves. On peach and cherry the eggs were laid on both sides of the leaves, whereas on apple on the upper side as was observed also in other countries. In early October, the larvae abandoned their feeding sites and went next to auxiliary buds and crevices of the bark of branches to spin their hibernating webs. The adult maleof A. orana has a wingspan of 15-20 mm and the female one of 19-22 mm. The fore wings of the male are yellow ochre reddish, and have distinct rusty-red designs. There is a basal darker (brown) area, and two large darker stripes. The median one departs from the basal third of the costa and terminates, widening or divided in two branches, at the tornus. The other stripe is preapical and may take the form of a triangular spot of which sometimes only the borders are visible. The fore wings of the female are normally darker than those of the male, often blackish-brown, and have darker and dimmer stripes and other markings. The hind wings are light grey in the male and grey-brown in the female. The ground colour in the specimens of northwestern Europe is varying from light brown to dark brown. The fully grown larva is 18-20 mm long, green, with a light brown head. It somewhat resembles the larva of another tortricid, Archipsrosanus L. which is a monovoltine polyphagous species common in Greek orchards in spring. A. orana is polyvoltine and feeds on buds, leaves and fruits of a great number of cultivated and wild plants. Among its reported many hosts are species of Betula, Crataegus, Cydonia, Gossypium, Ligustrum, Lonicera, Malus, Medicago, Pyrus, Populus, Pistacia, Parrotia, Proms,Quercus, Ribes, Rubus, Rosa, Salix, Solanum, Syringa, Tilia, Ulmus, Vaccinium and the grapevine Vitis vinifera

Less adhesiolysis and hernia repair during completion proctocolectomy after laparoscopic emergency colectomy for ulcerative colitis

The aim of this study was to determine whether the need for adhesiolysis during completion proctectomy (CP) with ileopouch anal anastomosis (IPAA) is influenced by the surgical approach of the initial emergency colectomy for ulcerative colitis and the hospital setting. One hundred consecutive patients who underwent CP with IPAA in our center between January 1999 and April 2010 were included. Emergency colectomy had been performed laparoscopically in 30 of 52 patients at the Academic Medical Center Amsterdam and in 6 of 48 patients at referring hospitals. Case files of these patients were retrospectively reviewed. Significantly more extensive adhesiolysis was performed after open compared to laparoscopic colectomy (47 vs. 6%, P <0.001). In univariate analysis, emergency colectomy at a referring hospital was also predictive for adhesiolysis (P = 0.003), but the open approach for the initial colectomy was the only independent predictive factor for the need for adhesiolysis (P <0.001) in a multivariable ordinal logistic regression analysis. Operating time of CP was significantly longer when limited [18 (95% CI = 0-36) min] or extensive [55 (35-75) min] adhesiolysis had to be performed. The interval to CP was longer after open colectomy and after colectomy performed at a referring hospital. Significantly more incisional hernia corrections during CP were performed after open emergency colectomy (14 vs. 0%, P = 0.024). Overall morbidity and postoperative hospital stay of CP were not related to the surgical approach or the hospital setting of the emergency colectomy. Laparoscopic as opposed to open emergency colectomy is associated with less adhesiolysis, fewer incisional hernias, and a shorter interval to completion proctectom

Decreased incidence of isolated tumor cells in lymph nodes after laparoscopic resection for colorectal cancer

Laparoscopic surgery has potential for less tumor cell spread because of the no-touch technique. We assessed the effect of the surgical approach (open versus no-touch laparoscopic) on the presence of tumor cells in sentinel lymph nodes (SN) of patients with stage I and II colorectal cancer. A single-center consecutive prospective series of patients operated on for colorectal cancer was analyzed. After conventional hematoxylin and eosin (H&E) staining, 107 patients without lymphatic metastases were included; 59 patients had open surgery, and 48 patients underwent laparoscopic resection. Patients in the laparoscopic group underwent a no-touch medial to lateral approach, whereas the conventional lateral to medial approach was applied in open surgery. A SN procedure was performed in all patients. The SNs were immunohistochemically analyzed for presence of occult tumor cells (OTC). According to the American Joint Committee on Cancer (AJCC) these tumor cells were divided into micrometastases (0.2-2 mm) or isolated tumor cells (ITC, 3.5 cm. Logistic regression analysis identified lymphovascular invasion as a predictor for micrometastases [odds ratio (OR) 18.4], whereas open resection was predictive for presence of ITC (OR 3.3). No-touch medial to lateral laparoscopic surgery results in less isolated tumor cells in lymph nodes compared with open lateral to medial surgery in patients with stage I and II colorectal cance

The Open Global Glacier Model (OGGM) v1.1

Despite their importance for sea-level rise, seasonal water availability, and as a source of geohazards, mountain glaciers are one of the few remaining subsystems of the global climate system for which no globally applicable, open source, community-driven model exists. Here we present the Open Global Glacier Model (OGGM), developed to provide a modular and open-source numerical model framework for simulating past and future change of any glacier in the world. The modeling chain comprises data downloading tools (glacier outlines, topography, climate, validation data), a preprocessing module, a mass-balance model, a distributed ice thickness estimation model, and an ice-flow model. The monthly mass balance is obtained from gridded climate data and a temperature index melt model. To our knowledge, OGGM is the first global model to explicitly simulate glacier dynamics: the model relies on the shallow-ice approximation to compute the depth-integrated flux of ice along multiple connected flow lines. In this paper, we describe and illustrate each processing step by applying the model to a selection of glaciers before running global simulations under idealized climate forcings. Even without an in-depth calibration, the model shows very realistic behavior. We are able to reproduce earlier estimates of global glacier volume by varying the ice dynamical parameters within a range of plausible values. At the same time, the increased complexity of OGGM compared to other prevalent global glacier models comes at a reasonable computational cost: several dozen glaciers can be simulated on a personal computer, whereas global simulations realized in a supercomputing environment take up to a few hours per century. Thanks to the modular framework, modules of various complexity can be added to the code base, which allows for new kinds of model intercomparison studies in a controlled environment. Future developments will add new physical processes to the model as well as automated calibration tools. Extensions or alternative parameterizations can be easily added by the community thanks to comprehensive documentation. OGGM spans a wide range of applications, from ice–climate interaction studies at millennial timescales to estimates of the contribution of glaciers to past and future sea-level change. It has the potential to become a self-sustained community-driven model for global and regional glacier evolution.</p

Functional recovery is considered the most important target: a survey of dedicated professionals

Background: The aim of this study was to survey the relative importance of postoperative recovery targets and perioperative care items, as perceived by a large group of international dedicated professionals. Methods: A questionnaire with eight postoperative recovery targets and 13 perioperative care items was mailed to participants of the first international Enhanced Recovery After Surgery (ERAS) congress and to authors of papers with a clear relevance to ERAS in abdominal surgery. The responders were divided into categories according to profession and region. Results: The recovery targets ‘To be completely free of nausea’, ‘To be independently mobile’ and ‘To be able to eat and drink as soon as possible’ received the highest score irrespective of the responder's profession or region of origin. Equally, the care items ‘Optimizing fluid balance’, ‘Preoperative counselling’ and ‘Promoting early and scheduled mobilisation’ received the highest score across all groups. Conclusions: Functional recovery, as in tolerance of food without nausea and regained mobility, was considered the most important target of recovery. There was a consistent uniformity in the way international dedicated professionals scored the relative importance of recovery targets and care items. The relative rating of the perioperative care items was not dependent on the strength of evidence supporting the items

Association of polymorphisms in the beta-2 adrenergic receptor gene with fracture risk and bone mineral density

Summary: Signaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms influence receptor function. We show that these polymorphisms are not associated with fracture risk or bone mineral density in the UCP, Rotterdam Study, and GEFOS cohorts. Introduction: Signaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms are known to influence receptor function in vitro and in vivo (rs1042713, rs1042714, and rs1800888). We examined the role of these polymorphisms in the B2AR gene on human bone metabolism. Methods: We performed nested case–control studies to determine the association of these polymorphisms with fracture risk in the Utrecht Cardiovascular Pharmacogenetics (UCP) cohort and in three cohorts of the Rotterdam Study. We also determined the association of these polymorphisms with bone mineral density (BMD) in the GEFOS Consortium. UCP contains drug-dispensing histories from community pharmacies linked to national registrations of hospital discharges in the Netherlands. The Rotterdam Study is a prospective cohort study investigating demographics and risk factors of chronic diseases. GEFOS is a large international collaboration studying the genetics of osteoporosis. Fractures were defined by ICD-9 codes 800–829 in the UCP cohort (158 cases and 2617 unmatched controls) and by regular X-ray examinations, general practitioner, and hospital records in the Rotterdam Study (2209 cases and 8559 unmatched controls). BMD was measured at the femoral neck and lumbar spine using dual-energy X-ray absorptiometry in GEFOS (N = 32,961). Results: Meta-analysis of the two nested case–control studies showed pooled odds ratios of 0.98 (0.91–1.05, p = 0.52), 1.04 (0.97–1.12, p = 0.28), and 1.16 (0.83–1.62, p = 0.38) for the associations betwee