Systemic response of the GH/IGF-I axis in timely versus delayed fracture healing

The GH-IGF axis has profound effects on the local and systemic regulation of bone metabolism and may be important for quality of fracture healing. To test the hypothesis that deficiency of the GH/IGF axis may play a role in the pathogenesis of fracture non-union we investigated whether alterations of serum concentrations of the GH-IGF axis could be related to failed fracture healing compared to timely fracture healing in trauma patients. Serum probes were prospectively collected from 186 patients with surgical treatment of long bone fractures up to 6 months after surgery. Samples from 14 patients with atrophic type of non-union have been compared to 14 matched patients with normal bone healing. Postoperative time courses of serum concentrations have been analyzed using commercially available chemiluminescence sandwich assays (GH), fully automated assay systems (IGF-I, IGFBP-3) or sandwich immunometric assays (ALS). Comparison between both collectives revealed significantly lower serum concentrations of GH dependent ALS during early (1st week after surgery) and of both IGFBP-3 and ALS during late stages of fracture healing (6 and 8 weeks after surgery) in non-union patients, coinciding clinically with failed fracture healing. Tendentially lower serum levels of IGF-I in the non-union group over the entire investigation period were statistically not significant. We have been able to show time courses of serum concentrations of the GH/IGF-I axis during normal and failed fracture healing in humans. An impairment of the GH/IGF-I axis might be involved in the biochemical mechanisms determining delayed or failed fracture healing.

Transdisciplinary co-production of knowledge in the development of organic agriculture in Switzerland

The present study analyses transdisciplinary co-production of knowledge in the development of organic farming in Switzerland by using Fleck's theory of thought styles and thought collectives. Three different phases can be identified throughout the historical development. The initial phase lasting from the beginning of the 1920s to the early 1970s contains numerous characteristics of diverse well-established definitions and concepts of transdisciplinarity and represents a successful transdisciplinary process, which has not been perceived as such in the past and present scientific discussion. The second and third phases show an increasing segregation of thought collectives, caused by internal changes such as the establishment of specialised research institutions and external processes like agriculture policy and market development. These developments led to a decreasing degree of transdisciplinarity. We observe an ambiguous trend: the continuously growing and today well-established positive societal recognition of an initially rather little accepted newcomer movement is associated with the gradual loss of its very valuable forms of knowledge co-production and the related philosophical background. In order to maintain the various forms of transdisciplinary co-production of knowledge, one has to reflect not only their results or outcome but also the whole cooperation process, which has led to these results. The understanding of the historical development and characteristic features of knowledge co-production as presented in this study will help to reinforce transdisciplinary research in organic agriculture and research on transdisciplinarity in general.

Politique étrangère suisse

Le conseiller fédéral Didier Burkhalter a pris la direction du Département fédéral des affaires étrangères (DFAE). – Le parlement a octroyé un crédit de 11.35 milliards de francs pour la coopération internationale 2013-2016. – Le Conseil fédéral a activé la clause de sauvegarde envers les Etats de l’UE-8. – Les questions institutionnelles ont continué à bloquer les relations bilatérales avec l’UE. – L’Allemagne et les Etats-Unis ont maintenu la pression sur la place financière suisse lors des négociations d’accords de double-imposition. – Le peuple a refusé l’initiative de l’ASIN « La parole au peuple ! ». – La Suisse a pris position sur le conflit syrien en instaurant des sanctions contre le régime. – La Suisse a fêté ses 10 ans d’adhésion à l’ONU et a reçu son secrétaire général Ban Ki-Moon. – La Suisse a accueilli à Berne le Prix Nobel de la Paix Aung San Suu Kyi et a ouvert une ambassade au Myanmar.

Prognostic and predictive roles of MGMT protein expression and promoter methylation in sporadic pancreatic neuroendocrine neoplasms.

BACKGROUND/AIMS O(6)-methylguanine-methyltransferase (MGMT) is an important enzyme of DNA repair. MGMT promoter methylation is detectable in a subset of pancreatic neuroendocrine neoplasms (pNEN). A subset of pNEN responds to the alkylating agent temozolomide (TMZ). We wanted to correlate MGMT promoter methylation with MGMT protein loss in pNEN, correlate the findings with clinico-pathological data and determine the role of MGMT to predict response to TMZ chemotherapy. METHODS We analysed a well-characterized collective of 141 resected pNEN with median follow-up of 83 months for MGMT protein expression and promoter methylation using methylation-specific PCR (MSP). A second collective of 10 metastasized, pretreated and progressive patients receiving TMZ was used to examine the predictive role of MGMT by determining protein expression and promoter methylation using primer extension-based quantitative PCR. RESULTS In both collectives there was no correlation between MGMT protein expression and promoter methylation. Loss of MGMT protein was associated with an adverse outcome, this prognostic value, however, was not independent from grade and stage in multivariate analysis. Promoter hypermethylation was significantly associated with response to TMZ. CONCLUSION Loss of MGMT protein expression is associated with adverse outcome in a surgical series of pNET. MGMT promoter methylation could be a predictive marker for TMZ chemotherapy in pNEN, but further, favourably prospective studies will be needed to confirm this result and before this observation can influence clinical routine.

Diagnostic confidence and image quality of CT pulmonary angiography at 100 kVp in overweight and obese patients.

AIM To compare image quality and diagnostic confidence of 100 kVp CT pulmonary angiography (CTPA) in patients with body weights (BWs) below and above 100kg. MATERIALS AND METHODS The present retrospective study comprised 216 patients (BWs of 75-99kg, 114 patients; 100-125kg, 88 patients; >125kg, 14 patients), who received 100 kVp CTPA to exclude pulmonary embolism. The attenuation was measured and the contrast-to-noise ratio (CNR) was calculated in the pulmonary trunk. Size-specific dose estimates (SSDEs) were evaluated. Three blinded radiologists rated subjective image quality and diagnostic confidence. Results between the BW groups and between three body mass index (BMI) groups (BMI <25kg/m(2), BMI = 25-29.9kg/m(2), and BMI ≥30kg/m(2), i.e., normal weight, overweight, and obese patients) were compared using the Kruskal-Wallis test. RESULTS Vessel attenuation was higher and SDDE was lower in the 75-99kg group than at higher BWs (p-values between <0.001 and 0.03), with no difference between the 100-125 and >125kg groups (p = 0.892 and 1). Subjective image quality and diagnostic confidence were not different among the BW groups (p = 0.225 and 1). CNR was lower (p < 0.006) in obese patients than in normal weight or overweight subjects. Diagnostic confidence was not different in the BMI groups (p = 0.105). CONCLUSION CTPA at 100 kVp tube voltage can be used in patients weighing up to 125kg with no significant deterioration of subjective image quality and confidence. The applicability of 100 kVp in the 125-150kg BW range needs further testing in larger collectives.

Reliable LC3 and p62 autophagy marker detection in formalin fixed paraffin embedded human tissue by immunohistochemistry

Autophagy assures cellular homeostasis, and gains increasing importance in cancer, where it impacts on carcinogenesis, propagation of the malignant phenotype and development of resistance. To date, its tissue-based analysis by immunohistochemistry remains poorly standardized. Here we show the feasibility of specifically and reliably assessing the autophagy markers LC3B and p62 (SQSTM1) in formalin fixed and paraffin embedded human tissue by immunohistochemistry. Preceding functional experiments consisted of depleting LC3B and p62 in H1299 lung cancer cells with subsequent induction of autophagy. Western blot and immunofluorescence validated antibody specificity, knockdown efficiency and autophagy induction prior to fixation in formalin and embedding in paraffin. LC3B and p62 antibodies were validated on formalin fixed and paraffin embedded cell pellets of treated and control cells and finally applied on a tissue microarray with 80 human malignant and non-neoplastic lung and stomach formalin fixed and paraffin embedded tissue samples. Dot-like staining of various degrees was observed in cell pellets and 18/40 (LC3B) and 22/40 (p62) tumors, respectively. Seventeen tumors were double positive for LC3B and p62. P62 displayed additional significant cytoplasmic and nuclear staining of unknown significance. Interobserver-agreement for grading of staining intensities and patterns was substantial to excellent (kappa values 0.60 - 0.83). In summary, we present a specific and reliable IHC staining of LC3B and p62 on formalin fixed and paraffin embedded human tissue. Our presented protocol is designed to aid reliable investigation of dysregulated autophagy in solid tumors and may be used on large tissue collectives.