Impact of pasireotide on postoperative pancreatic fistulas following distal resections

Purpose Postoperative pancreatic fistula (POPF), a difficult complication after surgery, can cause peripancreatic fluid collection and infections in the operative area. In addition, pancreatic fluid is corrosive and can lead to postoperative bleeding. Clinically significant grade B and C fistulas (CR-POPF) increase postoperative morbidity, resulting in a prolonged hospital stay. Delaying adjuvant therapy due to fistula formation in cancer patients can affect their prognosis. In this study, we aimed to determine if pasireotide affects fistula formation, and the severity of other complications in patients following pancreatic distal resections. Data and methods Between 2000 and 2016, 258 distal pancreatectomies were performed at Helsinki University Hospital and were included in our analysis. Pasireotide was administered to patients undergoing distal resections between July 2014 and December 2016. Patients received 900-mu g pasireotide administered twice daily perioperatively. Other patients who received octreotide treatment were analyzed separately. Complications such as fistulas (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), reoperations, and mortality were recorded and analyzed 90 days postoperatively. Results Overall, 47 (18%) patients received pasireotide and 31 (12%) octreotide, while 180 patients (70%) who received neither constituted the control group. There were 40 (16%) clinically relevant grade B and C POPFs: seven (15%) in the pasireotide group, three (10%) in the octreotide group, and 30 (17%) in the control group (p = 0.739). Severe complications categorized as Clavien-Dindo grade III or IV were recorded in 64 (25%) patients: 17 (27%) in the pasireotide group, 4 (6%) in the octreotide group, and 43 (67%) in the control group (p = 0.059). We found no 90-day mortality. Conclusions In this study, pasireotide did not reduce clinically relevant POPFs or severe complications following pancreatic distal resection.Peer reviewe

Tannins, flavonoids and stilbenes in extracts of African savanna woodland trees Terminalia brownii, Terminalia laxiflora and Anogeissus leiocarpus showing promising antibacterial potential

Terminalia laxiflora, Terminalia brownii and Anogeissus leiocarpus are used as decoctions, macerations, infusions and fumigations in East and West African traditional medicine for treatment of infectious diseases and their symptoms. Using this ethnopharmacological information as a guideline for our research and owing to the fact that these species have not been subjected to in depth antibacterial and phytochemical studies, thirty-nine extracts of various polarities of the stem bark, stem wood and roots were studied for growth inhibitory effects against the human pathogenic bacteria Staphylococcus epidermidis, Staphylococcus aureus, Micrococcus luteus and Pseudomonas aeruginosa. Our results indicate that the studied species contain antibacterial compounds of a wide range of polarities. All polar root extracts of T. laxiflora and various polar extracts of T. brownii roots, including hot water decoctions, gave broad-spectrum antibacterial effects and low MIC values of 39 mu g/ml. The main ellagitannins in an ethyl acetate extract of the root of T. laxiflora were found to be corilagin and its derivative and punicalagin. A methanol extract of the roots of T. brownii contained methyl-(S)-flavogallonate and its derivative as the main identified ellagitannins. Moreover, both Terminalia species were found to contain ellagic acid xylopyranoside and methyl ellagic acid xyloside and pure ellagic acid was present in T. brownii. Pure punicalagin did not give as low MIC as an ethyl acetate extract of the roots of T. laxiflora, containing punicalagin as one of its main compounds, although this ellagitannin totally inhibited the growth of S. aureus at 125 mu g/ml and P. aeruginosa at 500 mu g/ml. Similarly, pure ellagic and gallic acid gave higher MIC values than the methanolic root extract of T. brownii against S. aureus and P. aeruginosa. Moreover, a Sephadex LH-20 fraction of the methanolic extract of the roots of T. brownii, enrichedwithmethyl-(S)-flavogallonate and its isomer, gave higher MIC values than the crude methanolic extract. These results suggest that the polyphenols in the extracts might act synergistically with each other. A methanolic soxhlet extract of the roots of A. leiocarpus, containing ampelopsin, aromadendrin, taxifolin, pinosylvin and 4'-methylpinosylvin gave a low MIC value of 39 mu g/ml against all bacterial strains used in this investigation. Our results demonstrate that the roots, stem bark and stem wood of T. brownii, T. laxiflora and A. leiocarpus are rich sources of (new) antimicrobial compounds and justify the uses of these plants for treatment of infections in African traditional medicine.Peer reviewe

Visions in monochrome: Families, marriage and the individualisation thesis

This paper takes issue with the way in which the individualisation thesis – in which it is assumed that close relationships have become tenuous and fragile - has become so dominant in ‘new’ sociological theorising about family life. Although others have criticised this thesis, in this paper the main criticism derives from empirical research findings carried out with members of transnational families living in Britain whose values and practices do not fit easily with ideas of individualisation. It is argued that we need a much more complex and less linear notion of how families change across generations and in time

The BSUIN project

Baltic Sea Underground Innovation Network (BSUIN) is an European Union funded project that extends capabilities of underground laboratories. The aim of the project is to join efforts in making the underground laboratories in the Baltic Sea Region’s more accessible for innovation, business development and science by improving the availability of information about the underground facilities, service offerings, user experience, safety and marketing.The development of standards for the characterization of underground laboratories will allow to compared them with each other. This will help you choose the best places for physical measurements such as neutrino physics or searching for dark matter. The project concerns laboratories where so far no measurements have been made, and even undergrounds where there are no organized laboratories yet.The description of the BSUIN project and the first results of characterization of natural radioactive background in underground laboratories will be presented ˙ The BSUIN Project is funded by Interreg Baltic Sea funding cooperation [2]

Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss

Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 +/- 4.0 years, body mass index 23.4 +/- 1.7 kg/m(2)) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 +/- 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 +/- 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery ratePeer reviewe

Prediction of pre-eclampsia and its subtypes in high-risk cohort: hyperglycosylated human chorionic gonadotropin in multivariate models

Background: The proportion of hyperglycosylated human chorionic gonadotropin (hCG-h) to total human chorionic gonadotropin (%hCG-h) during the first trimester is a promising biomarker for prediction of early-onset pre-eclampsia. We wanted to evaluate the performance of clinical risk factors, mean arterial pressure (MAP), %hCG-h, hCG beta, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PIGF) and mean pulsatility index of the uterine artery (Uta-PI) in the first trimester in predicting pre-eclampsia (PE) and its subtypes early-onset, late-onset, severe and non-severe PE in a high-risk cohort.Methods: We studied a subcohort of 257 high-risk women in the prospectively collected Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) cohort Multivariate logistic regression was used to construct the prediction models. The first model included background variables and MAP. Additionally, biomarkers were included in the second model and mean Uta-PI was included in the third model. All variables that improved the model fit were included at each step. The area under the curve (AUC) was determined for all models.Results: We found that lower levels of serum PIGF concentration were associated with early-onset PE, whereas lower %hCG-h was associated with the late-onset PE. Serum PIGF was lower and hCG beta higher in severe PE, while %hCG-h and serum PAPP-A were lower in non-severe PE. By using multivariate regression analyses the best prediction for all PE was achieved with the third model: AUC was 0.66, and sensitivity 36% at 90% specificity. Third model also gave the highest prediction accuracy for late-onset, severe and non-severe PE: AUC 0.66 with 32% sensitivity, AUC 0.65, 24% sensitivity and AUC 0.60, 22% sensitivity at 90% specificity, respectively. The best prediction for early-onset PE was achieved using the second model: AUC 0.68 and 20% sensitivity at 90% specificity.Conclusions: Although the multivariate models did not meet the requirements to be clinically useful screening tools, our results indicate that the biomarker profile in women with risk factors for PE is different according to the subtype of PE. The heterogeneous nature of PE results in difficulty to find new, clinically useful biomarkers for prediction of PE in early pregnancy in high-risk cohorts

RAD51C Germline Mutations in Breast and Ovarian Cancer Cases from High-Risk Families

BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5′ UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001). Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene

Mutation screening of the RNF8, UBC13 and MMS2 genes in Northern Finnish breast cancer families

<p>Abstract</p> <p>Background</p> <p>Currently known susceptibility genes such as <it>BRCA1 </it>and <it>BRCA2 </it>explain less than 25% of familial aggregation of breast cancer, which suggests the involvement of additional susceptibility genes. RNF8, UBC13 and MMS2 are involved in the DNA damage response pathway and play important roles in BRCA1-mediated DNA damage recognition. Based on the evidence that several players in the ubiquitin-mediated BRCA1-dependent DDR seem to contribute to breast cancer predisposition, <it>RNF8, UBC13 </it>and <it>MMS2 </it>were considered plausible candidate genes for susceptibility to breast cancer.</p> <p>Methods</p> <p>The entire coding region and splice junctions of <it>RNF8, UBC13 </it>and <it>MMS2 </it>genes were screened for mutations in affected index cases from 123 Northern Finnish breast cancer families by using conformation sensitive gel electrophoresis, high resolution melting (HRM) analysis and direct sequencing.</p> <p>Results</p> <p>Mutation analysis revealed several changes in <it>RNF8 </it>and <it>UBC13</it>, whereas no aberrations were observed in <it>MMS2</it>. None of the found sequence changes appeared to associate with breast cancer susceptibility.</p> <p>Conclusions</p> <p>The present data suggest that mutations in <it>RNF8, UBC13 </it>and <it>MMS2 </it>genes unlikely make any sizeable contribution to breast cancer predisposition in Northern Finland.</p

Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1

Narcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated NT1 patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175-189 (NA175-189) and nucleoprotein 214-228 (NP214-228), but also respond to a NA175-189-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1675-689). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA175-189 or POMT1675-689. Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1. </p

Effect of Antihypertensive Therapy with Alpha Methyldopa on Levels of Angiogenic Factors in Pregnancies with Hypertensive Disorders

Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy