Kaposi’s Sarcoma-Associated Herpesvirus-Encoded Viral IL-6 (vIL-6) Enhances Immunoglobulin Class-Switch Recombination

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic gamma-herpesvirus that causes AIDS-associated Kaposi sarcoma (KS) and several lymphoproliferative disorders. During the humoral immune response antigen-activated mature B cells acquire functional diversification by immunoglobulin heavy chain (IgH) class-switch recombination (CSR). CSR is initiated by activation-induced cytidine deaminase (AID) which targets highly repetitive switch (S)-regions to mediate DNA double-stranded breaks (DSBs) in the IgH locus facilitating intramolecular recombination. Here we show that in the context of cytokine stimulation, CSR is enhanced in murine B cells exposed only to replication-competent KSHV in an environment of KSHV infection, which coincided with elevated AID transcripts. Using murine splenic B cells and the mouse lymphoma CH12F3-2 CSR system, we identified that vIL-6, but not murine IL-6, increased class-switching, which correlated with upregulated AID expression. Together, these data suggest a regulatory role for KSHV vIL-6 in functionally modulating B cell biology by promoting CSR, which may in part explain how KSHV infection influences humoral immunity and affect KSHV pathogenesis

High Serum Cyclophilin C levels as a risk factor marker for Coronary Artery Disease

Cyclophilins (Cyps) are ubiquitous proteins that belong to the immunophilins family consistently associated with inflammatory and cardiovascular diseases. While levels of CypA have been extensively studied, less data are available for other Cyps. The purpose of this case-control study was to determine the relationship of Cyps (A, B, C and D) with coronary artery disease (CAD) and eight inflammation markers. Serum levels of Cyps, interleukins and metalloproteinases were measured in serum collected from 84 subjects. Participants were divided into two sub-groups based on CAD diagnosis: 40 CAD patients and 44 control volunteers. Serum levels of CypA, CypB and CypC, IL-1β and IL-6 were significantly higher in CAD patients. Bivariate correlation analysis revealed a significant positive correlation between Cyps and several blood and biochemical parameters. When the ability of Cyps levels for CAD diagnosis was evaluated, higher sensitivity and selectivity values were obtained with CypC (c-statistic 0.891, p < 0.001) indicating that it is a good marker of CAD disease, while less conclusive results were obtained with CypA (c-statistic 0.748, p < 0.001) and CypB (c-statistic 0.655, p < 0.014). In addition, significant correlations of traditional CAD risk factors and CypC were observed. In summary, high levels of CypC are a risk factor for CAD and therefore it can be proposed as a new biomarker for this disease.This work could not have been done without the invaluable collaboration of the staff at the Servicio Vixilancia da Saude from Universidad de Santiago de Compostela (Andrea Vidal Dopazo) and at the Cardiology Department, Hospital Universitario Lucus Augusti (Maria Jesús Basanta-Castro, Maria del Carmen Cabarcos Leal, Clara Jimenez-Serrano, Leonor Ortega- Fernández, Maria Jesus Palacios Pool, Sofía Seco-Aldegunde). The research leading to these results has received funding from the following FEDER cofunded-grants. From Conselleria de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01). From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, AGL2016-78728-R (AEI/FEDER, UE), ISCIII/PI16/01830, ISCIII/PI16/01816 and RTC-2016-5507-2, ITC-20161072. From European Union POCTEP 0161-Nanoeaters -1-E-1, Interreg AlertoxNet EAPA-317-2016, Interreg Agritox EAPA-998-2018, and H2020 778069-EMERTOX. Sandra Gegunde was supported by a fellowship from FIDIS, Spain

H2FPEF score predicts atherosclerosis presence in patients with systemic connective tissue disease

Background: Cardiovascular diseases are common cause of morbidity and mortality in patients with systemic connective tissue diseases (SCTD) due to accelerated atherosclerosis which couldn't be explained by traditional risk factors (CVDRF). Hypothesis: We hypothesized that recently developed score predicting probability of heart failure with preserved ejection fraction (H2FPEF), as well as a measure of right ventricular-pulmonary vasculature coupling [tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio], are predictive of atherosclerosis in SCTD. Methods: 203 patients (178 females) diagnosed with SCTD underwent standard and stress-echocardiography (SE) with TAPSE/PASP and left ventricular (LV) diastolic filling pressure (E/e') measurements, carotid ultrasound and computed tomographic coronary angiography. Patients who were SE positive for ischemia underwent coronary angiography (34/203). The H2FPEF score was calculated according to age, body mass index, presence of atrial fibrillation, ≥2 antihypertensives, E/e' and PASP. Results: Mean LV ejection fraction was 66.3 ± 7.1%. Atherosclerosis was present in 150/203 patients according to: 1) intima-media thickness>0.9 mm; and 2) Agatstone score > 300 or Syntax score ≥ 1. On binary logistic regression analysis, including CVDRF prevalence, echocardiographic parameters and H2FPEF score, only H2FPEF score remained significant for the prediction of atherosclerosis presence (χ2 = 19.3, HR 2.6, CI 1.5-4.3, p < 0.001), and resting TAPSE/PASP for the prediction of a SE positive for ischemia (χ2 = 10.4, HR 0.01, CI = 0.01-0.22, p = 0.004). On ROC analysis, the optimal threshold value for identifying patients with atherosclerosis was a H2FPEF score ≥2 (Sn 60.4%, Sp 69.4%, area 0.67, SE = 0.05, p < 0.001). Conclusions: H2FPEF score and resting TAPSE/PASP demonstrated clinical value for an atherosclerosis diagnosis in patients diagnosed with SCTD

Grazing Rates of Calanus finmarchicus on Thalassiosira weissflogii Cultured under Different Levels of Ultraviolet Radiation

UVB alters photosynthetic rate, fatty acid profiles and morphological characteristics of phytoplankton. Copepods, important grazers of primary production, select algal cells based upon their size, morphological traits, nutritional status, and motility. We investigated the grazing rates of the copepod Calanus finmarchicus on the diatom Thalassiosira weissflogii cultured under 3 levels of ultraviolet radiation (UVR): photosynthetically active radiation (PAR) only (4 kJ-m−2/day), and PAR supplemented with UVR radiation at two intensities (24 kJ-m−2/day and 48 kJ-m−2/day). There was no significant difference in grazing rates between the PAR only treatment and the lower UVR treatment. However, grazing rates were significantly (∼66%) higher for copepods feeding on cells treated with the higher level of UVR. These results suggest that a short-term increase in UVR exposure results in a significant increase in the grazing rate of copepods and, thereby, potentially alters the flow rate of organic matter through this component of the ecosystem

Palynological and chemical volatile components of tipically autumnal honeys of the western Mediterranean

[EN] Twenty-five samples of autumnal honeys from the western Mediterranean (Mallorca and Eivissa, Balearic Islands) were examined for pollen content (qualitative and quantitative melissopalynological analysis), moisture, electrical conductivity, colour, sensorial qualities and volatile components. Quantitative analysis showed that the honey contained Maurizio's Class II: 64%, Class III: 28%, Class IV: 4% and Class V: 4%. Fifty-four pollen types, with an average number of 16.68 per sample, were identified, belonging to 29 botanical families. Only two taxa (Ceratonia siliqua and Erica multiflora) were found in all samples. Seventeen samples were unifloral (68%) - ten (40%) of C. siliqua, six (24%) of E. multiflora and one (4%) of Hedera helix. All honeys have a low honeydew index (<?0.09%), while the values for electrical conductivity and water content were high. The major honey volatile components are: cis- and trans-linalool oxides (64.2%) and hotrienol (10.4%) for the carob (C. siliqua) and trans-linalool oxide (13.4%), p-menthane-1,8-diol (11.1%), safranal (9.7%), limonene (5,4%), -pinene (3.7%) and oxoisophorone (3.4%) for the winter heather (E. multiflora).The authors would like to extend their gratitude to the Mallorca Rural 'Leader plus' programme and the beekeepers of Mallorca and Eivissa for their support and friendly collaboration. The authors also thank an anonymous reviewer for useful comments and suggestions on an earlier version of the manuscript.Boi, M.; Llorens Molina, JA.; Cortés, L.; Lladó, G.; Llorens, L. (2013). Palynological and chemical volatile components of tipically autumnal honeys of the western Mediterranean. Grana. 52(2):93-105. doi:10.1080/00173134.2012.744774S93105522Andrade, P. B., Amaral, M. T., Isabel, P., Carvalho, J. C. M. F., Seabra, R. M., & Proença da Cunha, A. (1999). Physicochemical attributes and pollen spectrum of Portuguese heather honeys. Food Chemistry, 66(4), 503-510. doi:10.1016/s0308-8146(99)00100-4Anklam, E. (1998). A review of the analytical methods to determine the geographical and botanical origin of honey. Food Chemistry, 63(4), 549-562. doi:10.1016/s0308-8146(98)00057-0Bosch, J., Del Pino, F. G., Ramoneda, J., & Retana, J. (1996). FRUITING PHENOLOGY AND FRUIT SET OF CAROB, CERATONIA SILIQUA L. (CESALPINACEAE). Israel Journal of Plant Sciences, 44(4), 359-368. doi:10.1080/07929978.1996.10676657Bouseta, A., Collin, S., & Dufour, J.-P. (1992). Characteristic aroma profiles of unifloral honeys obtained with a dynamic headspace GC-MS system. Journal of Apicultural Research, 31(2), 96-109. doi:10.1080/00218839.1992.11101268Cajka, T., Hajslova, J., Pudil, F., & Riddellova, K. (2009). Traceability of honey origin based on volatiles pattern processing by artificial neural networks. Journal of Chromatography A, 1216(9), 1458-1462. doi:10.1016/j.chroma.2008.12.066Castro-Vázquez, L., Díaz-Maroto, M. C., González-Viñas, M. A., & Pérez-Coello, M. S. (2009). Differentiation of monofloral citrus, rosemary, eucalyptus, lavender, thyme and heather honeys based on volatile composition and sensory descriptive analysis. Food Chemistry, 112(4), 1022-1030. doi:10.1016/j.foodchem.2008.06.036Conti, M. E., Stripeikis, J., Campanella, L., Cucina, D., & Tudino, M. B. (2007). Characterization of Italian honeys (Marche Region) on the basis of their mineral content and some typical quality parameters. Chemistry Central Journal, 1(1). doi:10.1186/1752-153x-1-14Custódio, L., Serra, H., Nogueira, J. M. F., Gonçalves, S., & Romano, A. (2006). Analysis of the Volatiles Emitted by Whole Flowers and Isolated Flower Organs of the Carob Tree Using HS-SPME-GC/MS. Journal of Chemical Ecology, 32(5), 929-942. doi:10.1007/s10886-006-9044-9Cuevas-Glory, L., Ortiz-Vázquez, E., Pino, J. A., & Sauri-Duch, E. (2012). Floral classification of Yucatan Peninsula honeys by PCA & HS-SPME/GC-MS of volatile compounds. International Journal of Food Science & Technology, 47(7), 1378-1383. doi:10.1111/j.1365-2621.2012.02983.xDe Bolòs, O., & Molinier, R. (1984). Vegetation of the Pityusic Islands. Biogeography and Ecology of the Pityusic Islands, 185-221. doi:10.1007/978-94-009-6539-3_9De Maria, C. A. B., & Moreira, R. F. A. (2003). Compostos voláteis em méis florais. Química Nova, 26(1), 90-96. doi:10.1590/s0100-40422003000100016Guyot, C., Scheirman, V., & Collin, S. (1999). Floral origin markers of heather honeys: Calluna vulgaris and Erica arborea. Food Chemistry, 64(1), 3-11. doi:10.1016/s0308-8146(98)00122-8Herrera, J. (1988). Pollination Relationships in Southern Spanish Mediterranean Shrublands. The Journal of Ecology, 76(1), 274. doi:10.2307/2260469Jerković, I., & Marijanović, Z. (2010). Volatile Composition Screening of Salix spp. Nectar Honey: Benzenecarboxylic Acids, Norisoprenoids, Terpenes, and Others. Chemistry & Biodiversity, 7(9), 2309-2325. doi:10.1002/cbdv.201000021Jones, G. D., & Bryant, Jr, V. M. (2004). The use of ETOH for the dilution of honey. Grana, 43(3), 174-182. doi:10.1080/00173130410019497Kummerow, J. (1983). Comparative Phenology of Mediterranean-Type Plant Communities. Ecological Studies, 300-317. doi:10.1007/978-3-642-68935-2_17La‐Serna Ramos, I. E., & GÓmez Ferreras, C. (2006). Pollen and sensorial characterization of different honeys from El Hierro (Canary Islands). Grana, 45(2), 146-159. doi:10.1080/00173130600578658Del Carmen Llasat, M., Ramis, C., & Barrantes, J. (1996). The meteorology of high‐intensity rainfall events over the west Mediterranean region. Remote Sensing Reviews, 14(1-3), 51-90. doi:10.1080/02757259609532313Louveaux, J., Maurizio, A., & Vorwohl, G. (1978). Methods of Melissopalynology. Bee World, 59(4), 139-157. doi:10.1080/0005772x.1978.11097714Martins, R. C., Lopes, V. V., Valentão, P., Carvalho, J. C. M. F., Isabel, P., Amaral, M. T., … Silva, B. M. (2008). Relevant principal component analysis applied to the characterisation of Portuguese heather honey. Natural Product Research, 22(17), 1560-1582. doi:10.1080/14786410701825004Melliou, E., & Chinou, I. (2011). Chemical constituents of selected unifloral Greek bee-honeys with antimicrobial activity. Food Chemistry, 129(2), 284-290. doi:10.1016/j.foodchem.2011.04.047Pendleton, M. (2006). Descriptions of melissopalynological methods involving centrifugation should include data for calculating Relative Centrifugal Force (RCF) or should express data in units of RCF or gravities (g). Grana, 45(1), 71-72. doi:10.1080/00173130500520479Pérez, R. A., Sánchez-Brunete, C., Calvo, R. M., & Tadeo, J. L. (2002). Analysis of Volatiles from Spanish Honeys by Solid-Phase Microextraction and Gas Chromatography−Mass Spectrometry. Journal of Agricultural and Food Chemistry, 50(9), 2633-2637. doi:10.1021/jf011551rPersano Oddo, L., Piana, L., Bogdanov, S., Bentabol, A., Gotsiou, P., Kerkvliet, J., … von der Ohe, K. (2004). Botanical species giving unifloral honey in Europe. Apidologie, 35(Suppl. 1), S82-S93. doi:10.1051/apido:2004045Persano Oddo, L., & Piro, R. (2004). Main European unifloral honeys: descriptive sheets. Apidologie, 35(Suppl. 1), S38-S81. doi:10.1051/apido:2004049Piana, M. L., Persano Oddo, L., Bentabol, A., Bruneau, E., Bogdanov, S., & Guyot Declerck, C. (2004). Sensory analysis applied to honey: state of the art. Apidologie, 35(Suppl. 1), S26-S37. doi:10.1051/apido:2004048Piasenzotto, L., Gracco, L., & Conte, L. (2003). Solid phase microextraction (SPME) applied to honey quality control. Journal of the Science of Food and Agriculture, 83(10), 1037-1044. doi:10.1002/jsfa.1502Radovic, B. S., Careri, M., Mangia, A., Musci, M., Gerboles, M., & Anklam, E. (2001). Contribution of dynamic headspace GC–MS analysis of aroma compounds to authenticity testing of honey. Food Chemistry, 72(4), 511-520. doi:10.1016/s0308-8146(00)00263-6RAMÓN-LACA, L., & MABBERLEY, D. J. (2004). The ecological status of the carob-tree (Ceratonia siliqua, Leguminosae) in the Mediterranean. Botanical Journal of the Linnean Society, 144(4), 431-436. doi:10.1111/j.1095-8339.2003.00254.xRetana, J., Ramoneda, J., Garcia Del Pino, F., & Bosch, J. (1994). Flowering phenology of carob,Ceratonia siliquaL. (Cesalpinaceae). Journal of Horticultural Science, 69(1), 97-103. doi:10.1080/14620316.1994.11515254Ricciardelli d’Albore, G. & Vorwohl, G. (1979). Mieles monoflorales en el Mediterráneo documentado con ayuda del análisis microscópico de mieles. Actas de XXVII Congreso Internacional de Apicultura, Athens, Greece, 14–20 September 1979, 201–208.Pilar de Sá‐Otero, M., Armesto‐Baztan, S., & DÍaz‐Losada, E. (2006). A study of variation in the pollen spectra of honeys sampled from the Baixa Limia‐Serra do Xurés Nature Reserve in north‐west Spain. Grana, 45(2), 137-145. doi:10.1080/00173130600708537Seijo, M. C., Jato, M. V., Aira, M. J., & Iglesias, I. (1997). Unifloral honeys of Galicia (north-west Spain). Journal of Apicultural Research, 36(3-4), 133-140. doi:10.1080/00218839.1997.11100939Terrab, A., Diez, M. J., & Heredia, F. J. (2003). Palynological, physico-chemical and colour characterization of Moroccan honeys: III. Other unifloral honey types. International Journal of Food Science and Technology, 38(4), 395-402. doi:10.1046/j.1365-2621.2003.00713.xTERRAB, A., PONTES, A., HEREDIA, F. J., & DÍEZ, M. J. (2004). A preliminary palynological characterization of Spanish thyme honeys. Botanical Journal of the Linnean Society, 146(3), 323-330. doi:10.1111/j.1095-8339.2004.00335.xTerrab, A., Valdés, B., & Josefa Díez, M. (2003). Pollen analysis of honeys from the Mamora forest region (NW Morocco). Grana, 42(1), 47-54. doi:10.1080/00173130310008580Thompson, J. D. (2005). Plant Evolution in the Mediterranean. doi:10.1093/acprof:oso/9780198515340.001.0001Von Der Ohe, W., Persano Oddo, L., Piana, M. L., Morlot, M., & Martin, P. (2004). Harmonized methods of melissopalynology. Apidologie, 35(Suppl. 1), S18-S25. doi:10.1051/apido:2004050VORWOHL, G. (1964). DIE BEZIEHUNGEN ZWISCHEN DER ELEKTRISCHEN LEITFÄHIGKEIT DER HONIGE UND IHRER TRACHTMÄSSIGEN HERKUNFT. Annales de l’Abeille, 7(4), 301-309. doi:10.1051/apido:19640403Vorwohl, G. (1967). The microscopic analysis of honey, a comparison of its methods with those of the other branches of palynology. Review of Palaeobotany and Palynology, 3(1-4), 287-290. doi:10.1016/0034-6667(67)90061-

Display of Cell Surface Sites for Fibronectin Assembly Is Modulated by Cell Adherence to 1F3 and C-Terminal Modules of Fibronectin

BACKGROUND: Fibronectin-null cells assemble soluble fibronectin shortly after adherence to a substrate coated with intact fibronectin but not when adherent to the cell-binding domain of fibronectin (modules (7)F3-(10)F3). Interactions of adherent cells with regions of adsorbed fibronectin other than modules (7)F3-(10)F3, therefore, are required for early display of the cell surface sites that initiate and direct fibronectin assembly. METHODOLOGY/PRINCIPAL FINDINGS: To identify these regions, coatings of proteolytically derived or recombinant pieces of fibronectin containing modules in addition to (7)F3-(10)F3 were tested for effects on fibronectin assembly by adherent fibronectin-null fibroblasts. Pieces as large as one comprising modules (2)F3-(14)F3, which include the heparin-binding and cell adhesion domains, were not effective in supporting fibronectin assembly. Addition of module (1)F3 or the C-terminal modules to modules (2)F3-(14)F3 resulted in some activity, and addition of both (1)F3 and the C-terminal modules resulted in a construct, (1)F3-C, that best mimicked the activity of a coating of intact fibronectin. Constructs (1)F3-C V0, (1)F3-C V64, and (1)F3-C Delta(V(15)F3(10)F1) were all able to support fibronectin assembly, suggesting that (1)F3 through (11)F1 and/or (12)F1 were important for activity. Coatings in which the active parts of (1)F3-C were present in different proteins were much less active than intact (1)F3-C. CONCLUSIONS: These results suggest that (1)F3 acts together with C-terminal modules to induce display of fibronectin assembly sites on adherent cells

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks