Search

Supplementary Table 2

Supplementary Table 1

Supplementary Table 5

Tumors undergo dynamic immunoediting as part of a process that balances immunologic sensing of emerging neoantigens and evasion from immune responses. Tumor-infiltrating lymphocytes (TIL) comprise heterogeneous subsets of peripheral T cells characterized by diverse functional differentiation states and dependence on T-cell receptor (TCR) specificity gained through recombination events during their development. We hypothesized that within the tumor microenvironment (TME), an antigenic milieu and immunologic interface, tumor-infiltrating peripheral T cells could reexpress key elements of the TCR recombination machinery, namely, Rag1 and Rag2 recombinases and Tdt polymerase, as a potential mechanism involved in the revision of TCR specificity. Using two syngeneic invasive breast cancer transplantable models, 4T1 and TS/A, we observed that Rag1, Rag2, and Dntt in situ mRNA expression characterized rare tumor-infiltrating T cells. In situ expression of the transcripts was increased in coisogenic Mlh1-deficient tumors, characterized by genomic overinstability, and was also modulated by PD-1 immune-checkpoint blockade. Through immunolocalization and mRNA hybridization analyses, we detected the presence of rare TDT+RAG1/2+ cells populating primary tumors and draining lymph nodes in human invasive breast cancer. Analysis of harmonized single-cell RNA-sequencing data sets of human cancers identified a very small fraction of tumor-associated T cells, characterized by the expression of recombination/revision machinery transcripts, which on pseudotemporal ordering corresponded to differentiated effector T cells. We offer thought-provoking evidence of a TIL microniche marked by rare transcripts involved in TCR shaping.

Supplementary Figures and Legends

Supplementary Table 3

Laboratory Animal Professionals experience many positive and rewarding interactions when caring for and working with research animals. However, these professionals also may experience conflicting feelings and exhaustion when the work is stressful due to factors such as limited resources, making end of life decisions, dealing with conflicting priorities, and negotiating animal care priorities with colleagues. These stresses may be further complicated by each individual's self-understanding and emotional investment in the human-animal bond. The term used for this type of complex emotional conflict and exhaustion is Compassion Fatigue. Compassion Fatigue in the Laboratory Animal Science setting is a combination of physical, emotional and psychological depletion associated with working with and caring for animals and their well-being in a research environment. The University of Washington has developed a Compassion in Science Program called Dare2Care which emphasizes self-care and helps Laboratory Animal Professionals identify stress factors and work toward a personal solution to relieve stress. The first step in developing a resiliency program is to assess the current culture and needs of the organization. At an institutional level we identified that we needed increased communication concerning study endpoints, as well as identified individuals with whom affected personnel can talk about personal concerns. We also implemented community events to reflect on the positive aspects of this field of work. We improved the physical work environment, and provided outlets established for personnel to express feelings via written word or artistically. Lastly, we started working with our Center for One Health to encompass a holisitic approach to the occupational health of our animal caregivers. One health is the relationship and interplay between people, animals and the environment and we needed to include emotional well-being in our assessment of the health of our personnel. A question was added to our occupational health screening form to include additional health or workplace concerns (e.g., Compassion Fatigue) not covered by the questionnaire, and we added a component of Compassion Fatigue awareness in our training program. Here we review the importance of identifying Compassion Fatigue in the animal research setting, focus on developing a compassion resiliency culture and provide tools and coping strategies to validate and strengthen the human-animal bond with research animals and to sustain the care that is necessary for both people and research animals.

The captive white-tailed deer industry has an estimated economic impact of $1.6 billion, annually. However, nutritional requirements for cervids are determined through research based on sheep and goats. The objective of this study was to determine the effects zinc on in vitro dry matter digestibility for white-tailed does (Odocoileus virginianus). Does (n=2) were euthanized ethically, rumens were collected, and placed into a cooler containing warm water. Rumen contents were agitated and filtered using cheesecloth while applying CO2. The fluid was placed into four separate incubator jars with filter bags containing a 1:1 alfalfa to coastal hay blend. Zinc doses of 0.073 mg/kg/d were added to two of the jars (treatments), and the additional two jars received 0.00 mg/kg/d (control). Following 48 hours of incubation, in vitro true digestibility (IVTD) showed no significant differences (P >.05) between the control and treatment groups. Average dry matter digested in vitro was 91.87% and 95.13%; respectfully. Neutral detergent fiber (NDF) was no different (P >.05) between the two groups. The average digested NDF components for the control were 56.03% and the zinc group had a mean of 57.11%. Additionally, acid detergent fiber (ADF) did not statistically differ. The control group had an average of 74.56% for digested ADF components, and the treatment had a mean of 76.90%. No significant differences were observed in digested organic matter. The control group averaged 79.51% of digested organic matter (OM), and the treatment group averaged 79.38%. This methodology did prove to be viable and functional to evaluate microbial digestion in vitro. This study can be replicated with multiple experimental units to confirm the patterns of increased digestibility. Formal nutritional guidelines can be created to allow for more efficient feeding of deer. In turn, determining nutrient requirements for deer, reducing feed costs for operations, and continue educating the captive deer industry.

BackgroundVitamin D deficiency has been shown to be associated with higher disease activity and severity of several inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and spondyloarthritis (SpA). It is, however, unknown if vitamin D level might affect the response to treatment with biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with SpA.ObjectivesTo investigate the association between vitamin D serum levels and the response to a bDMARD therapy in patients with axial SpA.MethodsPatients with a radiographic axial SpA (r-axSpA), fulfilling the modified New York criteria and starting a bDMARD therapy were recruited between 2015 and 2019 in an extension of the prospective German Spondyloarthritis Inception Cohort (GESPIC-AS). All patients were required to have at inclusion high disease activity (BASDAI >=4 and/or ASDAS >=2.1) despite previous treatment with nonsteroidal anti-inflammatory drugs. Demographics, patient clinical characteristics and vitamin D serum levels were collected at baseline. Disease activity measures (BASDAI, CRP, ASDAS) were assessed at baseline and after 6 months of bDMARD treatment. Vitamin D deficiency was defined as serum level of 25-hydroxyvitamin D < 20 ng/mL. A multivariable regression analysis was performed to determine the association between vitamin D serum level at baseline and the treatment response as defined by BASDAI and ASDAS change scores at month 6 as compared to baseline.ResultsA total of 129 patients with r-axSpA were included in the study. No patient took supplements of vitamin D at baseline. Patients had an average age (mean±SD) of 36.5±10.5 years, 64.3% were males and 86.6% were HLA-B27 positive. The prevalence of vitamin D deficiency in our cohort was 54.3%. Patient characteristics and disease activity were comparable with regard to the presence of vitamin D at baseline (Table 1); with the exception of body mass index (BMI), which was higher in patients with vitamin D deficiency. In the multivariable linear regression analysis, baseline serum level of vitamin D was independently and significantly associated with higher change in BASDAI and ASDAS (Figure 1).Table 1.Baseline characteristics of patients with radiographic axial SpA (n=129) according to vitamin D levels at baseline.Patients with vitamin D deficiency (Patients with normal levels of vitamin Dn=59Age, years36.6±11.036.3±10.0Male sex46 (65.7)37 (62.7)BMI, kg/m226.0±4.5*24.0±3.8Smoking, ever41 (58.6)29 (49.2)Winter and Spring, n (%)33 (47.1)23 (39.0)Symptom duration, years11.5±11.310.3±7.1HLA-B27 positive62 (88.6)50 (84.7)Uveitis ever17 (24.3)12 (20.3)Psoriasis ever11 (15.7)7 (11.9)IBD ever, n (%)2 (2.9)7 (11.9)CRP, mg/L12.9±19.313.9±15.3BASDAI5.7±1.45.4±1.4ASDAS3.4±0.83.5±0.8BASFI4.6±2.24.4±1.9BASMI3.1±1.52.7±1.3NSAID intake, current50 (71.4)45 (76.3)DMARDs intake, ever9 (12.9)6 (10.2)TNFi naive55 (78.6)47 (79.7)Corticoids intake, current5 (7.1)2 (3.4)*p value All numerical variables were presented as mean±SD, all categorical variables were presented as n (%).BMI, body mass index; CRP, C-reactive protein; DMARD, disease-modifying antirheumatic drug; IBD, inflammatory bowel disease; NSAID, nonsteroidal anti-inflammatory drug; TNFi, tumor necrosis factor inhibitor.Figure 1.Association between the response to bDMARDs (change in BASDAI and ASDAS after 6 months) and level of vitamin D at baseline in patients with radiographic axial SpA in the multivariable regression analysis.ConclusionHigher vitamin D levels at baseline may predict a better treatment response to bDMARDs in patients with r-axSpA. It has to be shown, however, if vitamin D supplementation might result in a better treatment response in axial SpA.Disclosure of InterestsNone declared

Symptomatic uncomplicated diverticular disease of the colon (SUDD) is generally managed by gastroenterologists rather than General Practitioners (GPs). The aim of this study was to assess the efficacy of the treatment of SUDD with rifaximin, a non-absorbable antibiotic, in a primary care setting by GPs.This retrospective, observational study investigated the use of rifaximin at a dose of 400 mg b.i.d. for 5, 7 or 10 days monthly, up to 3 months. The symptoms were reported by the patients using a visual analogic scale (VAS) of 0-10.286 SUDD patients were enrolled (44.4% of men, average age 70.92±10.98). Respectively, 15 (5.2%) patients received the treatment for 5 days, 205 (71.7%) for 7 days and 66 (23.1%) for 10 days. After three months, a significant reduction of VAS score was observed in almost all symptoms assessed: 135 (47.2%) patients reported no abdominal pain (p0.001) and 23 (8.1%) reported no symptom. Adverse events related to the treatment were recorded in 3 (1.04%) patients, all of them mild and not requiring interruption of the treatment. Acute diverticulitis occurred in 9 (3.1%) patients, but only 2 of them [0.7% (n=2)] underwent surgery due to complicated diverticulitis. Analysis within the different treatment groups (5, 7 and 10 days) shows that rifaximin treatment is effective in reducing the severity of symptoms in almost all groups except for the constipation in the 5-day group.Rifaximin can be effectively used by GPs in real-life for the management of SUDD.

Objectives: To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods: This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results: In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251 (27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions: SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. © 2020 International Society of Ultrasound in Obstetrics and Gynecology

Due to a technical error, the author list at the end of this article is unfortunately incorrect. Elif Gül Yapar Eyi is not a co-author, and therefore, his name and affiliation should not appear in the list. The correct author list and affiliations read as follows: Daniele Di Mascio, Cihat Sen, Gabriele Saccone, Alberto Galindo, Amos Grünebaum, Jun Yoshimatsu, Milan Stanojevic, AsimKurjak, Frank Chervenak, María Jos´e Rodríguez Suárez, Zita Maria Gambacorti-Passerini, María de los Angeles Anaya Baz, Esther Vanessa Aguilar Galán, Yolanda Cuñarro López, Juan Antonio De León Luis, Ignacio Cueto Hernández, Ignacio Herraiz, Cecilia Villalain, Roberta Venturella, Giuseppe Rizzo, Ilenia Mappa, Giovanni Gerosolima, Lars Hellmeyer, Josefine Königbauer, Giada Ameli, Tiziana Frusca, Nicola Volpe, Giovanni Battista Luca Schera, Stefania Fieni, Eutalia Esposito, Giuliana Simonazzi, Gaetana Di Donna, Aly Youssef, Anna Nunzia Della Gatta, Mariano Catello Di Donna, Vito Chiantera, Natalina Buono, Giulio Sozzi, Pantaleo Greco, Danila Morano, Beatrice Bianchi, Maria Giulia Lombana Marino, Federica Laraud, Arianna Ramone, Angelo Cagnacci, Fabio Barra, Claudio Gustavino, Simone Ferrero, Fabio Ghezzi, Antonella Cromi, Antonio Simone Laganá, Valentina Laurita Longo, Francesca Stollagli, Angelo Sirico, Antonio Lanzone, Lorenza Driul, Fabiana Cecchini D, Serena Xodo, Brian Rodriguez, Felipe Mercado-Olivares, Deena Elkafrawi, Giovanni Sisti, Rosanna Esposito, Antonio Coviello, Marco Cerbone, Maddalena Morlando, Antonio Schiattarella, Nicola Colacurci, Pasquale De Franciscis, Ilaria Cataneo, Marinella Lenzi, Fabrizio Sandri, Riccardo Buscemi, Giorgia Gattei, Francesca della Sala, Eleonora Valori, Maria Cristina Rovellotti, Elisa Done, Gilles Faron, Leonardo Gucciardo, Valentina Esposito, Flaminia Vena, Antonella Giancotti, Roberto Brunelli, Ludovico Muzii, Luigi Nappi, Felice Sorrentino, Lorenzo Vasciaveo, Marco Liberati, Danilo Buca, Martina Leombroni, Francesca Di Sebastiano, Luciano Di Tizio, Diego Gazzolo, Massimo Franchi, Quintino Cesare Ianniciello, Simone Garzon, Giuliano Petriglia, Leonardo Borrello, Albaro Jos´e Nieto-Calvache, Juan Manuel Burgos-Luna, Caroline Kadji, Andrew Carlin, Elisa Bevilacqua, Marina Moucho, Pedro Viana Pinto, Rita Figueiredo, Jos´e Morales Roselló, Gabriela Loscalzo, Alicia Martinez-Varea, Vincente Diago, Jesús S Jimenez Lopez, Alicia Yeliz Aykanat, Stefano Cosma, Andrea Carosso, Chiara Benedetto, Amanda Bermejo, Otto Henrique May Feuerschuette, Ozlem Uyaniklar, Sakine Rahimli Ocakouglu, Zeliha Atak, Reyhan Gündüz, Esra Tustas Haberal, Bernd Froessler, Anupam Parange, Peter Palm, Igor Samardjiski, Chiara Taccaliti, Erhan Okuyan, George Daskalakis, Renato Augusto Moreira de Sa, Alejandro Pittaro, Maria Luisa Gonzalez-Duran, Ana Concheiro Guisan, Serife Özlem Genç, Blanka Zlatohlávková, Anna Luengo Piqueras, Dolores Esteban Oliva, Aylin Pelin Cil, Olus Api, Panos Antsaklis, Liana Ples, Ioannis Kyvernitakis, Holger Maul, Marcel Malan, Albert Lila, Roberta Granese, Alfredo Ercoli, Giuseppe Zoccali, Andrea Villasco, Nicoletta Biglia, Ciuhodaru Madalina, Elena Costa, Caroline Daelemans, Axelle Pintiaux, Elisa Cueto, Eran Hadar, Sarah Dollinger, Noa A. Brzezinski Sinai, Erasmo Huertas, Pedro Arango, Amadeo Sanchez, Javier Alfonso Schvartzman, Liviu Cojocaru, Sifa Turan, Ozhan Turan, Maria Carmela Di Dedda, Rebeca Garrote Molpeceres, Snezana Zdjelar, Tanja Premru-Srsen, Lilijana Kornhauser Cerar, Mirjam Druškovic, Valentina De Robertis, Vedran Stefanovic, Irmeli Nupponen, Kaisa Nelskylä, Zulfiya Khodjaeva, Ksenia A. Gorina, Gennady T. Sukhikh, Giuseppe Maria Maruotti, Silvia Visentin, Erich Cosmi, Jacopo Ferrari, Alessandra Gatti, Daniela Luvero, Roberto Angioli, Ludovica Puri, Marco Palumbo, Giusella D’Urso, Francesco Colaleo, Agnese Maria Chiara Rapisarda, Ilma Floriana Carbone, Antonio Mollo, Giovanni Nazzaro, Mariavittoria Locci, Maurizio Guida, Attilio Di Spiezio Sardo, Pierluigi Benedetti Panici, Vincenzo Berghella, Maria Elena Flacco, Lamberto Manzoli, Giuseppe Bifulco, Giovanni Scambia, Fulvio Zullo and Francesco D’Antonio Flaminia Vena, Antonella Giancotti, Roberto Brunelli, Ludovico Muzii and Pierluigi Benedetti Panici, Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy Rosanna Esposito, Antonio Coviello, Marco Cerbone, Giuseppe Maria Maruotti, Giovanni Nazzaro, Mariavittoria Locci, Maurizio Guida, Attilio Di Spiezio Sardo, Giuseppe Bifulco and Fulvio Zullo, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy Ignacio Herraiz and Cecilia Villalain, Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, University Hospital 12 de Octubre, Complutense University of Madrid, Madrid, Spain María Jos´e Rodríguez Suárez, Hospital Universitario Central de Asturias, Asturias, Spain Zita Maria Gambacorti-Passerini, Department of Obstetrics and Gynaecology, Ciudad Real University General Hospital, Ciudad Real, Spain María de los Angeles Anaya Baz and Esther Vanessa Aguilar Galán, Department of Obstetrics and Gynaecology, Ciudad Real University General Hospital, Ciudad Real, Spain; University of Castilla-La Mancha, Ciudad Real, Spain Yolanda Cuñarro López, Juan Antonio De León Luis and Ignacio Cueto Hernández, Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, Gregorio Marañón Hospital, Complutense University of Madrid, Madrid, Spain Roberta Venturella, Department of Obstetrics and Gynaecology, School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy Giuseppe Rizzo, University of Roma Tor Vergata, Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Rome, Italy; Department of Obstetrics and Gynaecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia Ilenia Mappa, University of Roma Tor Vergata, Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Rome, Italy Giovanni Gerosolima, Department of Obstetrics and Gynaecology, Ospedale AOSG Moscati, Avellino, Italy Lars Hellmeyer, Josefine Königbauer and Giada Ameli, Department of Gynaecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany Tiziana Frusca, Nicola Volpe, Giovanni Battista Luca Schera and Stefania Fieni, Department of Obstetrics and Gynaecology, University of Parma, Parma, Italy Eutalia Esposito, Department of Obstetrics and Gynaecology, Ospedale di San Leonardo, Castellammare di Stabia, Italy Giuliana Simonazzi, Gaetana Di Donna, Aly Youssef and Anna Nunzia Della Gatta, Department of Obstetrics and Gynaecology, University of Bologna, Sant’Orsola- Malpighi University Hospital, Bologna, Italy Mariano Catello Di Donna, Vito Chiantera, Natalina Buono and Giulio Sozzi, Department of Gynaecologic Oncology, University of Palermo, Palermo, Sicilia, Italy Pantaleo Greco, Danila Morano, Beatrice Bianchi and Maria Giulia Lombana Marino, Department ofMedical Sciences, Section of Obstetrics and Gynaecology, Azienda Ospedaliera-Universitaria Sant’Anna, University of Ferrara, Ferrara, Italy Federica Laraud, Arianna Ramone, Angelo Cagnacci, Fabio Barra, Claudio Gustavino and Simone Ferrero, Academic Unit of Obstetrics and Gynaecology, IRCCS Ospedale Policlinico, San Martino, Genova, Italy Fabio Ghezzi, Antonella Cromi and Antonio Simone Laganà, Department of Obstetrics and Gynaecology, “Filippo Del Ponte” Hospita University of Insubria, Varese, Italy Valentina Laurita Longo, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy; and Queen Margaret University, Institute for Global Health and Development, Edinburgh, UK Francesca Stollagli and Ludovica Puri, Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy Angelo Sirico and Giovanni Scambia, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy Antonio Lanzone, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy Lorenza Driul, Fabiana Cecchini D and Serena Xodo, Clinic of Obstetrics and Gynaecology, University of Udine, Udine, Italy Brian Rodriguez, Felipe Mercado-Olivares, Deena Elkafrawi and Giovanni Sisti, Department of Obstetrics and Gynaecology, New York Health and Hospitals/Lincoln Bronx, The Bronx, NY, USA Maddalena Morlando, Antonio Schiattarella, Nicola Colacurci and Pasquale De Franciscis, Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy Ilaria Cataneo, Marinella Lenzi and Fabrizio Sandri, Unit of Obstetrics and Gynaecology, Ospedale Maggiore, Bologna, Italy Riccardo Buscemi, Giorgia Gattei, Francesca della Sala and Maria Cristina Rovellotti, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy Eleonora Valori, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy; Hospital Castelli, Verbania, Italy Elisa Done, Gilles Faron and Leonardo Gucciardo, UZ Brussel, Universitair Ziekenhuis, Brussel, Belgium Valentina Esposito, University of Milan, Milan, Italy Luigi Nappi, Felice Sorrentino and Lorenzo Vasciaveo, Department of Obstetrics and Gynaecology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. © 2021 De Gruyter. All rights reserved.

Background:Diet has been previously described as an impact factor on the course of rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE). It has been previously reported that dietary sugar intake may contribute to subclinical inflammation and disease activity in SLE. However, there is very little investigation on the possible association between nutritional parameters and their influence on spondyloarthritis (SpA).Objectives:To investigate the possible impact of nutritional parameters on the disease activity in patients with SpA.Methods:Patients with radiographic axial SpA and starting a biological therapy were recruited between 2015 and 2019 in an extension of the prospective German Spondyloarthritis Inception Cohort (GESPIC). Dietary habits were collected at baseline using the country-specific validated food frequency questionnaire (FFQ) developed for the use in the German Health examination Survey for Adults 2008-2011. The FFQ includes questions about the frequency and amount of 53 food items, consumed during the past 4 weeks, and enabled to compute individual mean consumptions of foods in grams per day. Total energy intake (in Kcal per day) and nutritional parameters: carbohydrates, free sugars, total fats, saturated fats, mono and poly-unsaturated fats, proteins and dietary fiber, were calculated for each patient using a nutrition organization software and the database of Federal Food Code (Bundeslebensmittelschlüssel), version 3.02. Disease activity measures (BASDAI, CRP and ASDAS), as well as height, weight and body mass index (BMI) were assessed at baseline before starting the biological treatment.Results:A total of 104 patients from 129 patients with axial SpA enrolled in the cohort were included in this nutritional analysis. The mean age (mean±SD) was 37.0±11.0 years old with symptoms duration of 11.3±9.9 years, 68.3% were males, and 86.5% were HLA-B27 positive. Patients presented BMI of 25.1±4.3 kg/m2, BASDAI 5.6±1.4, CRP 14.0±18.2 mg/l, and ASDAS 3.5±1.0.In the univariable and multivariable regression analysis, a higher energy intake and carbohydrates were associated with higher disease activity, measured by ASDAS, BASDAI and CRP. This association was attributable to the full intake of carbohydrates and specifically to the total of free sugars (monosaccharides and disaccharides) and the decrease of dietary fiber as shown in the multivariable analyses (Figure 1). This effect was independent of age, sex, smoker status and BMI.Conclusion:A higher intake of carbohydrates and a higher consumption of free sugars are associated with higher disease activity in patients with AS.Figure 1.Multivariable linear regression analysis of the association between CRP and nutritional parameters in patients with radiographic axial SpA (n=104), adjusted for age, sex, body mass index and smoker status. Model 1 included variable of total energy intake, model 2 included variable of total intake of carbohydrates (CH) and model 3 included variable of free-sugar (monosaccharides and disaccharides).B, linear regression coefficient; CH, carbohydrates; CI, confidence interval; MS-FA, monosaturated fatty acids; PuS-FA, polyunsaturated fatty acids, S-FA, saturated fatty acids.Disclosure of Interests:None declared.

An experiment was performed to determine the effects of bismuth subsalicylate (BSS) and calcium-ammonium nitrate (CAN) on in vitro fermentation of a high-concentrate (87% concentrate, DM basis) substrate. Serum bottles containing 20 mL of a 2:1 buffer:ruminal fluid inoculum and 0.2 g of substrate were incubated for 24 h. Four ruminally cannulated steers (BW = 520 ± 30 kg) were used as ruminal fluid donors and each donor was considered a block. Treatments were arranged in a 2 × 2 factorial with the following factors: BSS (0 or 0.33%, DM basis) and CAN (0 or 2.22%, DM basis). Treatments were made isonitrogenous with urea. In vitro organic matter digestibility (IVOMD) was determined in separate 100-mL centrifuge tubes. Data were analyzed using the MIXED procedure of SAS with the fixed effect of BSS, CAN, BSS × CAN, and the random effect of donor. An interaction (P < 0.01) was observed for total gas production (TGP). When CAN was included, without BSS, TGP was increased (P < 0.01); however, the combination of CAN with BSS did not affect (P = 0.85) TGP when compared to the combination of urea and BSS. Ammonia-N tended (P = 0.10) to increase when CAN was used as N source rather than urea. In vitro OM digestibility (P > 0.23) and final pH (P > 0.66) of in vitro ruminal fermentation were not affected by treatments. A tendency (P = 0.06) for an interaction regarding the production of H2S was observed; however, there were no treatment mean differences (P > 0.28). The combination of CAN and BSS did not negatively affect in vitro fermentation parameters such as OM digestion and gas production; however, a reduction in H2S with the combination of BSS and CAN may indicate potential benefits of such feeding strategies for feedlot cattle

An experiment was performed to determine the effects of bismuth subsalicylate (BSS) and calcium-ammonium nitrate (CAN) on in vitro fermentation of a high-concentrate (87% concentrate, DM basis) substrate. Serum bottles containing 20 mL of a 2:1 buffer:ruminal fluid inoculum and 0.2 g of substrate were incubated for 24 h. Four ruminally cannulated steers (BW = 520 ± 30 kg) were used as ruminal fluid donors and each donor was considered a block. Treatments were arranged in a 2 × 2 factorial with the following factors: BSS (0 or 0.33%, DM basis) and CAN (0 or 2.22%, DM basis). Treatments were made isonitrogenous with urea. In vitro organic matter digestibility (IVOMD) was determined in separate 100-mL centrifuge tubes. Data were analyzed using the MIXED procedure of SAS with the fixed effect of BSS, CAN, BSS × CAN, and the random effect of donor. An interaction (P < 0.01) was observed for total gas production (TGP). When CAN was included, without BSS, TGP was increased (P < 0.01); however, the combination of CAN with BSS did not affect (P = 0.85) TGP when compared to the combination of urea and BSS. Ammonia-N tended (P = 0.10) to increase when CAN was used as N source rather than urea. In vitro OM digestibility (P > 0.23) and final pH (P > 0.66) of in vitro ruminal fermentation were not affected by treatments. A tendency (P = 0.06) for an interaction regarding the production of H2S was observed; however, there were no treatment mean differences (P > 0.28). The combination of CAN and BSS did not negatively affect in vitro fermentation parameters such as OM digestion and gas production; however, a reduction in H2S with the combination of BSS and CAN may indicate potential benefits of such feeding strategies for feedlot cattle.

Heat stress (HS) has been indicated to increase ruminal temperature, increase digestibility, and reduce ruminal pH of steers fed high concentrate diets. However, it is unclear if this effect is the result of greater fermentation rate, slower passage rate or a combination. The effect of ruminal incubation temperature on substrate digestibility and rate of fermentation were evaluated. Four cannulated British-crossbreed steers (BW = 520 kg ± 30 kg) consuming an 87% (DM) concentrate diet were utilized as rumen fluid donors in a randomized complete block design with two incubation treatments (CON=39°C and HS=42°C). Within block, duplicate 125 mL serum bottles containing 200 mg of dietary substrate were inoculated with a 2:1 buffer:ruminal fluid mixture and incubated for 24 h to measure total gas production, fermentation rate, fermentation lag, pH, and ammonia-N concentration. In vitro organic matter digestibility (IVOMD) was measured separately in 100 mL centrifuge tubes. Data were analyzed using the MIXED procedure of SAS using the fixed effect of treatment and random effect of rumen fluid donor (block). There was no treatment effect on total gas production (P = 0.92) or fermentation rate (P = 0.11); however, HS began fermenting substrate sooner than CON (P < 0.005). There was a significant effect of treatment on IVOMD where HS was greater compared to CON (79.3 vs. 70.4%; P = 0.05). Final pH and relative pH change were not different (P ≥ 0.25) likely due to buffering capacity of the in vitro technique Ammonia-N concentration was greater for HS than CON (7.92 vs. 5.33 mM; P < 0.05) and may indicate a temperature effect on ruminal nitrogen availability.In conclusion, it does not appear that incubating at a greater temperature affected the fermentation rate but likely induced a change in fermentation kinetics, which may have contributed to the greater overall IVOMD

Heat stress (HS) has been indicated to increase ruminal temperature, increase digestibility, and reduce ruminal pH of steers fed high concentrate diets. However, it is unclear if this effect is the result of greater fermentation rate, slower passage rate, or a combination. The effect of ruminal incubation temperature on substrate digestibility and rate of fermentation were evaluated. Four cannulated British-crossbreed steers (BW = 520 kg ± 30 kg) consuming an 87% (DM) concentrate diet were utilized as rumen fluid donors in a randomized complete block design with two incubation treatments (CON=39°C and HS=42°C). Within block, duplicate 125 mL serum bottles containing 200 mg of dietary substrate were inoculated with a 2:1 buffer:ruminal fluid mixture and incubated for 24 h to measure total gas production, fermentation rate, fermentation lag, pH, and ammonia-N concentration. In vitro organic matter digestibility (IVOMD) was measured separately in 100 mL centrifuge tubes. Data were analyzed using the MIXED procedure of SAS using the fixed effect of treatment and random effect of rumen fluid donor (block). There was no treatment effect on total gas production (P = 0.92) or fermentation rate (P = 0.11); however, HS began fermenting substrate sooner than CON (P < 0.005). There was a significant effect of treatment on IVOMD where HS was greater compared to CON (79.3 vs. 70.4%; P = 0.05). Final pH and relative pH change were not different (P ≥ 0.25) likely due to buffering capacity of the in vitro technique Ammonia-N concentration was greater for HS than CON (7.92 vs. 5.33 mM; P < 0.05) and may indicate a temperature effect on ruminal nitrogen availability.In conclusion, it does not appear that incubating at a greater temperature affected the fermentation rate but likely induced a change in fermentation kinetics, which may have contributed to the greater overall IVOMD

A general solution strategy for detecting faulty elements in phased arrays of arbitrary geometries is suggested. The proposed deterministic approach assumes as input data the amplitude and phase of near-field distributions and allows to determine the positions of the faulty elements. In particular, the method is founded on the well known Multiple Signal Classification (MUSIC) method, i.e., a spectral estimation technique. The proposed algorithm is also compared with a recently published method by the same authors, against experimental and numerical data. The results fully confirm the usefulness of the proposed technique, highlighting the advantages and the disadvantages of both methods.

The objective of this study was to determine if olive pomace could be supplemented at a level that increased the C18:1 concentration in blood and muscle tissue. Mature Spanish-influence goats (n=14; 41.6 kg) were fed ad libitum olive pomace mixed with molasses, starting at 2% of their BW for 28 days. Does were fed in herringbone-style runs daily with BW and blood samples collected biweekly. Biopsies were taken at d 0 and d 28 along the longissimus dorsi. FAs were extracted and measured using FAME and GC-FID, respectively; concentrations of each FA were calculated using C13:0 as an internal standard. All data were analyzed using the GLM and CORR procedure in SAS. There were significant changes in C18:1 and C18:2 in sera over time with mean consumption of 0.55 kg/d over the duration of the trial. From d 0 to d 28, the serum concentration of C18:1 increased (P

A cytogenetic monitoring study was carried out on a group of workers in clinical analysis laboratories to investigate the risk of occupational exposure to chronic low levels of chemicals.Thirty-four clinical laboratories have been involved in the study. In these laboratories, toxicants and analytical procedures utilized have been characterized. The individual occupational exposure of workers was assessed by use of a questionnaire concerning the chemical substances utilized. About 300 different chemicals have been identified. Cytogenetic analyses (chromosomal aberration and micronucleus tests) were carried out on a strictly selected group of 50 workers enrolled from these laboratories and compared to 53 controls (healthy blood donors) matched for gender and age. The exposed group shows a significantly higher frequency of genetic damage than the control group. Both chromatid and chromosome aberration frequencies in workers appear significantly higher than in controls. Similarly, comparison between micronucleated cells rates of exposed and unexposed groups show significantly higher frequencies of binucleated cells with micronucleus (BNMN) and of total micronuclei (MN tot) in workers than in controls.

This paper describes the results of a research project which is aimed at designing and realizing innovative multifunctional radar architecture based on Tile elements. In this paper we focus on the description of the design strategy of the antenna front end and on the digital beamforming architecture able to meet the performance requirements. In particular a suitable digital beamforming technique exploiting overlapped subarrays is introduced and obtained results are presented.

Resume Propos. – La frequence de l’insuffisance renale chez les patients âges pose la question d’un eventuel ajustement posologique pour les heparines de bas poids moleculaire utilisees a dose curative en pratique geriatrique. Le but de cette etude prospective etait donc de determiner si la tinzaparine, administree en une injection sous-cutanee de 175 UI anti-Xa·kg/j pendant dix jours, presentait un risque d’accumulation chez des patients de plus de 70 ans. Methodes. – L’accumulation etait evaluee par le suivi des activites anti-Xa et anti-IIa mesurees avant la premiere injection puis a j2, j5, j7 et j10. Les caracteristiques des trente patients traites par tinzaparine a dose curative et inclus (six hommes, 24 femmes) sont les suivantes en moyenne ± ecarts-types : âge = 87 ± 5,9 ans (extremes : 71 a 96) ; poids : 62,7 ± 14,6 kg (extremes :38 a 90) ; clairance de la creatinine : 40,6 ± 15,3 mL/min (extremes :20 a 72). Resultats. – La dose de tinzaparine est restee fixe pour tous les patients pendant les dix jours de traitement. Les activites anti-Xa et anti-IIa a j2 etaient respectivement de 0,66 ± 0,20 UI/mL (extremes : 0,26 a 1,04) et de 0,33 ± 0,10 UI/mL (extremes : 0,18 a 0,55). Il n’y a eu aucune accumulation, jugee sur les activites anti-Xa et anti-IIa, sur la periode de dix jours de traitement. Il n’existe aucune correlation entre les activites anti-Xa et anti-IIa, et l’âge, le poids ou la clairance de la creatinine. Un hematome au site d’injection a ete le seul effet indesirable note. Conclusion. – La tinzaparine semble donc pouvoir etre administree a la dose curative preconisee de 175 UI·kg –1 ·j –1 pendant dix jours, chez des patients âges ayant une alteration notable de la fonction renale, sans majoration du risque d’accumulation ni du risque hemorragique chez des patients dont la clairance de la creatinine est superieure a 20 mL/min.

Many efforts have been done in recent years to solve array antenna synthesis problems in a way as effective as possible. Stochastic optimization schemes have been widely applied, but useful mathematical properties of the problem, which may be useful in the synthesis process, have been neglected in many cases of interest. In this communication we show that in a number of array antenna synthesis problems proposed in the literature global optimizations are not required at all, as the problem is indeed convex with respect to all the available degrees of freedom. Then, with reference to very recent results proposed in the literature, we show how a proper exploitation of the convexity, both with respect to a part of the unknowns and derived from the exploitation of useful radiated field representations also allows to achieve design solutions significantly better than existing ones. Finally, some challenging synthesis problems which still need attention (and possibly new solutions) are discussed.

SummarySince low molecular weight heparins (LMWH) are partly eliminated by renal excretion, their pharmacodynamic profile may be modified in very elderly patients with age-related renal impairment. The aim of this prospective study was to determine whether tinzaparin (Innohep®) 175 anti-Xa IU/kg administered subcutaneously once daily over 10 days does accumulate in hospital patients greater than 70 years of age. Plasma anti-Xa and anti-IIa amidolytic levels and APTT were determined prior to the first injection (day 0), and then, at peak level i.e. 5 h after the second injection (day 2) and subsequently on days 5, 7 and 10.Thirty consecutive inpatients (6 men, 24 women) requiring LMWHs at a curative dose for acute thromboembolic disease were included. Patients’ characteristics (mean ± SD) were: age 87.0 ± 5.9 years (range 71–96), body weight 62.7 ± 14.6 kg (range 38-90) and creatinine clearance 40.6 ± 15.3 mL/min (range 20–72). The mean actual dose of tinzaparin delivered was 174.8 anti-Xa IU/kg. Since no patient had an anti-Xa activity above 1.5 IU/mL, the dose of tinzaparin remained fixed over 10 days.Anti-Xa and anti-IIa peak levels measured on day 2 were 0.66 ± 0.20 IU/mL (range 0.26–1.04) and 0.33 ± 0.10 IU/mL (range 0.18–0.55), respectively. Ex vivo anti-Xa/anti-IIa ratios were close to 2.1. APTT ratios (patient/control) were strongly correlated with anti-IIa activity (p Tinzaparin may thus be administered safely at a treatment dose (175 anti-Xa IU/kg) in older patients with age-related renal impairment. Neither dose adjustment, nor serial anti-Xa activity monitoring seems to be required in patients with creatinine clearance above 20 mL/min during the first ten day treatment.

Carnitine is a molecule with well-documented pleiotropic functions whose biosynthesis involves four catalytic steps. Here, we report a detailed analysis of the expression and transcriptional control of TMLH gene, which codifies for the first enzyme of carnitine biosynthesis. TMLH maps at the extreme end of Xq28, a chromosomal region of high genomic instability. By 5′ and 3′ RACE, we identified and mapped two alternative 5′ TMLH first exons and seven alternative 3′-splice variants, which are spread over a genomic region of about 250 kb. While the two alternative 5′ exons have different expression profiles, all the 3′ alternative forms are ubiquitously expressed. Reporter assays revealed that the 3′-UTRs of each TMLH isoform might influence its own expression at post-transcriptional level. In addition, we identified a highly conserved promoter region of TMLH. Functional analysis of this region showed the presence of a CpG island, whose methylation-status could control the level of TMLH transcription. Finally, by mRNA in situ hybridization, we found that TMLH expression is present at E12.5 dpc in the mouse liver, lung and brain, and is then maintained in the postnatal brain with a specific neuronal pattern. Collectively, our data highlight a tight transcriptional and post-transcriptional control of TMLH expression.

Films of poly(3-hydroxybutyrate) (PHB) were crystallized from the melt by different thermal treatments and submitted to enzymatic degradation by using a PHB depolymerase purified from Aureobacterium saperdae culture. The morphology and the supermolecular structure of PHB films were investigated to explain differences in the kinetics of enzymatic degradation. Differential scanning calorimetry, optical microscopy, wide-angle X-ray diffraction and small-angle X-ray scattering were employed to characterize the PHB films. A decreasing of enzymatic degradation rate was observed with the increasing of crystallinity and crystal dimension of the PHB films. PHB samples showing the same degree of crystallinity and similar value of lamellar thickness were prepared using different isothermal crystallization and annealing temperatures. The differences in the enzymatic degradation rate of these films were explained in terms of morphological parameters.

Parturition in fingernail clams (Sphaerium spp.) can be induced by external application of serotonin and serotonergic ligands. Selective serotonin re-uptake inhibitors (SSRIs) increase neurotransmission at serotonergic synapses by blocking re-uptake transporters. We tested the efficacy of SSRIs (fluvoxamine, fluoxetine, paroxetine) at inducing parturition in the fingernail clam Sphaerium striatinum. Parturition was induced by fluvoxamine and paroxetine, but only potentiated by fluoxetine. Fluvoxamine was potent, significantly inducing parturition at concentrations from 10 nM to 100 μM compared with negative controls. Fluvoxamine also significantly potentiated a subthreshold (10 μM) concentration of serotonin. Paroxetine also induced parturition but was less potent. Only 10 μM paroxetine significantly induced parturition compared with controls. Fluoxetine (1–100 μM) did not induce any parturitions, but at 5 μM it potentiated parturition in subthreshold serotonin concentrations as low as 50 nM. These results suggest the presence of serotonin re-uptake transporters in bivalve molluscs and may provide a way of stimulating serotonergic mechanisms without using serotonin or its ligands. J. Exp. Zool. 280:260–264, 1998. © 1998 Wiley-Liss, Inc.

We have analyzed 18 families with high incidence of breast cancer or breast and ovarian cancer for the presence of BRCA1 mutations. We identified 4 mutations in the BRCA1 gene in 4 unrelated probands who belong to families with at least 1 case of breast and 1 case of ovarian cancer. Two of the mutations reported in this study are novel (GAA(1172)-->TAA in family Naples 14, GAA(1765)-->TAA in family Naples 20) whereas the others are already present in the Breast Cancer Information Core Electronic Database (http://nchgr.nih.gov/ Intramural research/Lab transfer/Bic/) (5382insC in family Naples 18 and 2080delA in family Naples 19). Conversely, no mutation in the BRCA1 gene was detected in 14 families characterized by 2 or more cases of breast cancer only, even if bilateral and with early-onset. These results indicate that germline mutations in the BRCA1 gene highly predispose for a cancer syndrome that involves the presence of both breast and ovarian cancer.

Poly(ethylene glycol)-albumin hydrogels were implanted in mice in subcutaneous position to study their biocompatibility. After one month of implantation, the fibrous capsule formed around the implant was thin and the inflammatory tissue was limited. Acid phosphatase (AP) was selected to evaluate the hydrogel as matrix for enzyme immobilization. AP-hydrogels were prepared using activated PEG (PEGa) of different molecular weights (M.W. 4,600 to 20,000) to evaluate the effect of the matrix composition on the activity of AP. The apparent Km of the immobilized AP was 16 to 20 times higher than the Km of the soluble enzyme. The apparent Km value decreases with the increase of the chain length of the PEGa used. This can be correlated to an increase in the hydrogel porosity. The operational stability of the AP was markedly improved after immobilization by 110 to 160 times according to the PEGa molecular weight involved. Also, asparaginase (ASNase) was immobilized in PEGa (M.W. 10,000)-albumin-hydrogel as a model for in vivo bioreactor. ASNase hydrogels were implanted in the peritoneal cavity of rats; 7 days later, 75% of the initial enzyme activity were retrieved.

A new and rapid method for preparing a protaneous-polymeric hydrogel is described. The gel matrix is obtained by covalent cross-linking between preactivated polyethylene glycol of 3350 molecular mass and bovine serum albumin in aqueous solution at basic pH. The polyethylene glycol-albumin hydrogel showed high protein retention and a very good swelling capacity.

International audience; This communication deals with the reconstruction of three- dimensional target from experimental multiple-frequency data measured in the anechoic chamber of the Institut Fresnel (Marseille, France). In order to take into account the random noise present in the experiments, a Bayesian approach is considered. In particular, the inversion procedure takes advantage from the joint use of the Contrast Source-Extended Born model and of a Markov Random Field regularization. We also considered a cost functional appropriately weighted by coefficients which change with the frequency, the incident angle and the receiving angle. In fact, each scattered field measurement is balanced with the noise disturbing the data.