Calprotectin as a new inflammatory marker of abdominal aortic aneurysm: A pilot study.

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a relevant clinical problem due to the risk of rupture of progressively dilated infrarenal aorta. It is characterized by degradation of elastic fibers, extracellular matrix, and inflammation of the arterial wall. Though neutrophil infiltration is a known feature of AAA, markers of neutrophil activation are scarcely analyzed; hence, the main objective of this study. METHODS: Plasma levels of main neutrophil activation markers were quantified in patients with AAA and a double control group (CTL) formed by healthy volunteers (HV) and patients with severe atherosclerosis submitted for carotid endarterectomy (CE). Calprotectin, a cytoplasmic neutrophil protein, was quantified, by Western blot, in arterial tissue samples from patients with AAA and organ donors. Colocalization of calprotectin and neutrophil elastase was assessed by immunofluorescence. RESULTS: Plasma calprotectin and IL-6 were both elevated in patients with AAA compared with CTL (p ⩽ 0.0001) and a strong correlation was found between both molecules (p < 0.001). This difference was maintained when comparing with HV and CE for calprotectin but only with HV for IL-6. Calprotectin was also elevated in arterial tissue samples from patients with AAA compared with organ donors (p < 0.0001), and colocalized with neutrophils in the arterial wall. CONCLUSIONS: Circulating calprotectin could be a specific AAA marker and a potential therapeutical target. Calprotectin is related to inflammation and neutrophil activation in arterial wall and independent of other atherosclerotic events.

"In Vitro" Evaluation of Energy-Based Sealing of Graft Side Branches in Bypass Surgery.

INTRODUCTION: Our objective was to compare the in vitro efficacy of electrothermal bipolar [EB] vessel sealing and ultrasonic harmonic scalpel [HS] versus mechanical interruption, with conventional ties or surgical clips (SC), in sealing saphenous vein (SV) collaterals, during its eventual preparation for bypass surgery. METHODS: Experimental in vitro study on 30 segments of SV. Each fragment included two collaterals at least 2 mm in diameter. One of them was sealed by ligation with 3/0 silk ties (control) and the other one with EB (n = 10), HS (n = 10) or medium-6 mm SC (n = 10). After incorporation in a closed circuit with pulsatile flow, the pressure was progressively increased until causing rupture. Collateral diameter, burst pressure, leak point, and histological study were recorded. RESULTS: Burst pressure was higher for SC (1320.20 ± 373.847 mmHg) as compared with EB (942.2 ± 344.9 mmHg, p = 0.065), and especially with HS (637.00 ± 320.61 mmHg, p = 0.0001). No statistically significant difference between EB and HS was found, and bursting always happened at supraphysiological pressures. The leak point for HS was always detected in the sealing zone (10/10), while for EB and SC, it occurred in the sealing zone only in 6/10(60%) and 4/10(40%), respectively (p = 0.015). CONCLUSIONS: Energy delivery devices showed similar efficacy and safety in sealing of SV side branches. Although bursting pressure was lower than with tie ligature or SC, non-inferiority efficacy was shown at the range of physiological pressures in both, EB and HS. Due to their speed and easy handling, they may be useful in the preparation of the venous graft during revascularization surgery. However, remaining questions about healing process, potential spread of tissue damage and sealing durability, will require further analysis.

New Roles for Old Friends: Involvement of the Innate Immune System in Tumor Progression.

The association between the immune system and tumor progression has attracted much interest in the research community in recent years [...].

Neutrophil Extracellular Traps and Cancer: Trapping Our Attention with Their Involvement in Ovarian Cancer.

Neutrophils, the most abundant circulating leukocytes, play a well-known role in defense against pathogens through phagocytosis and degranulation. However, a new mechanism involving the release of neutrophil extracellular traps (NETs) composed of DNA, histones, calprotectin, myeloperoxidase, and elastase, among others, has been described. The so-called NETosis process can occur through three different mechanisms: suicidal, vital, and mitochondrial NETosis. Apart from their role in immune defense, neutrophils and NETs have been involved in physiopathological conditions, highlighting immunothrombosis and cancer. Notably, neutrophils can either promote or inhibit tumor growth in the tumor microenvironment depending on cytokine signaling and epigenetic modifications. Several neutrophils' pro-tumor strategies involving NETs have been documented, including pre-metastatic niche formation, increased survival, inhibition of the immune response, and resistance to oncologic therapies. In this review, we focus on ovarian cancer (OC), which remains the second most incidental but the most lethal gynecologic malignancy, partly due to the presence of metastasis, often omental, at diagnosis and the resistance to treatment. We deepen the state-of-the-art on the participation of NETs in OC metastasis establishment and progression and their involvement in resistance to chemo-, immuno-, and radiotherapies. Finally, we review the current literature on NETs in OC as diagnostic and/or prognostic markers, and their contribution to disease progression at early and advanced stages. The panoramic view provided in this article might pave the way for enhanced diagnostic and therapeutic strategies to improve the prognosis of cancer patients and, specifically, OC patients.

Thrombospondins in human aortic aneurysms.

Thrombospondins are a family of matricellular proteins with a multimeric structure that is known to be involved in several biological and pathological processes. Their relationship with vascular disorders has raised special interest recently. Aortic aneurysms are related to the impairment of vascular remodeling, in which extracellular matrix proteins seem to play an important role. Thus, research in thrombospondins, and their potential role in aneurysm development is progressively gaining importance. Nevertheless, studies showing thrombospondin dysregulation in human samples are still scarce. Although studies performed in vitro and in vivo models are essential to understand the molecular mechanisms and pathways underlying the disorder, descriptive studies in human samples are also necessary to ascertain their real value as biomarkers and/or novel therapeutic targets. The present article reviews the latest findings regarding the role of thrombospondins in aortic aneurysm development, paying particular attention to the studies performed in human samples.

LC-MS metabolomics of urine reveals distinct profiles for non-muscle-invasive and muscle-invasive bladder cancer.

PURPOSE: Bladder cancer (BC) is among the most frequent malignancies worldwide. Novel non-invasive markers are needed to diagnose and stage BC with more accuracy than invasive procedures like cystoscopy. To date, no study has identified urine metabolites characteristic of all BC stages. To discover novel urine metabolomic profiles to diagnose and stage non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) patients using mass spectrometry-based metabolomics. METHODS: We prospectively recruited 198 BC patients and 98 age- and sex-matched healthy volunteers without evidence of renal or bladder condition confirmed by ultrasound, from whom we collected a first morning urine sample (before surgery in patients). In a discovery stage, an untargeted metabolomic analysis was conducted in urine samples of a selection of 64 BC patients (19 TaG1, 11 TaG3, 20 T1G3, 12 T2G3, 1 T2G2, 1 T3G3) and 20 controls to identify dysregulated metabolites. Next, after exhaustive multivariate analysis, confirmed dysregulated metabolites were validated in an independent cohort of 134 BC patients (19 TaG1, 62 TaG2, 9 TaG3, 15 T1G2, 16 T1G3, 4 T2G2, 9 T2G3) and 78 controls. RESULTS: We validated p-cresol glucuronide as potential diagnostic biomarker for BC patients compared to controls (AUC = 0.79). For NMIBC, p-cresol glucuronide was valuable as staging biomarker (AUC = 0.803). And among NMIBCs, p-coumaric acid may be a potential specific staging biomarker for the TaG1 NMIBC; however, future validation experiments should be conducted once the precise version of the standard is commercially available. Remarkably, for MIBC we validated spermine as potential specific staging biomarker (AUC = 0.882). CONCLUSION: Ours is the first metabolomics study conducted in urine of a thoroughly characterized cohort comprising all stages of NMIBC, MIBC and healthy controls in which we identified non-invasive diagnostic and staging biomarkers. These may improve BC management, thus reducing the use of current harmful diagnostic techniques.

Bioprospecting of indigenous yeasts involved in cocoa fermentation using sensory and chemical strategies for selecting a starter inoculum.

Cocoa fermentation is the key and most relevant process in the synthesis of aroma and flavor precursor molecules in dry beans or raw material for producing chocolate. Because this process occurs in an uncontrolled manner, the chemical and sensory quality of beans can vary and be negatively affected. One of the strategies for the standardization and improvement of the sensory quality of chocolate is the introduction of microbial starter cultures. Among these, yeasts involved in fermentation have been studied because of their pectinolytic and metabolic potential in the production of volatile compounds. This study was aimed at isolating and characterizing, both sensory and chemically, yeasts involved in cocoa fermentation that could be used as starter cultures from two agro-ecological regions for the cultivation of cocoa in Colombia. The microbiological analyses identified 22 species represented mostly by Saccharomyces cerevisiae, Wickerhamomyces anomalus and Pichia sp. The preliminary sensory analysis of eight of these species showed that Hanseniaspora thailandica and Pichia kluyveri presented sensory profiles characterized by high intensity levels of fruity notes, which could be ascribed to the production of ethyl acetate, isoamyl acetate, and 2-phenylethyl acetate.

Identification of miR-20a-5p as Robust Normalizer for Urine microRNA Studies in Renal Cell Carcinoma and a Profile of Dysregulated microRNAs.

Renal cell carcinoma (RCC) is the third most frequent urinary malignancy and one of the most lethal. Current diagnostic and follow-up techniques are harmful and unspecific in low-grade tumors. Novel minimally invasive markers such as urine microRNAs (miRNAs) are under study. However, discrepancies arise among studies in part due to lack of consent regarding normalization. We aimed to identify the best miRNA normalizer for RCC studies performed in urine samples together with a miRNA profile with diagnostic value and another for follow-up. We evaluated the performance of 120 candidate miRNAs in the urine of 16 RCC patients and 16 healthy controls by RT-qPCR followed by a stability analysis with RefFinder. In this screening stage, miR-20a-5p arose as the most stably expressed miRNA in RCC and controls, with a good expression level. Its stability was validated in an independent cohort of 51 RCC patients and 32 controls. Using miR-20a-5p as normalizer, we adjusted and validated a diagnostic model for RCC with three miRNAs (miR-200a-3p, miR-34a-5p and miR-365a-3p) (AUC = 0.65; Confidence Interval 95% [0.51, 0.79], p = 0.043). let-7d-5p and miR-205-5p were also upregulated in patients compared to controls. Comparing RCC samples before surgery and fourteen weeks after, we identified let-7d-5p, miR-152-3p, miR-30c-5p, miR-362-3p and miR-30e-3p as potential follow-up profile for RCC. We identified validated targets of most miRNAs in the renal cell carcinoma pathway. This is the first study that identifies a robust normalizer for urine RCC miRNA studies, miR-20a-5p, which may allow the comparison of future studies among laboratories. Once confirmed in a larger independent cohort, the miRNAs profiles identified may improve the non-invasive diagnosis and follow-up of RCC.

Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer.

PURPOSE OF REVIEW: Renal cell carcinoma (RCC) is the third most common urologic malignancy. First symptoms are usually unspecific and belated causing the stages to be high when diagnosed. As compensation, incidental detection of RCC by abdominal imaging techniques for other medical purposes is a reality that favours a decrease in the stage of new diagnosed tumours. Therefore, identifying novel predictive biomarkers for diagnosis, progression and prognosis of RCC is fundamental. RECENT FINDINGS: To date, several studies have demonstrated that microRNAs (miRNAs) play a role in the particular scenario of urologic tumors, and alterations at miRNA level are involved in the initiation, progression and metastases formation of renal cancer. In the present review, we have summarized the up­to­date preliminary clinical works on the role of urinary miRNA profiling in RCC, including an evaluation of its value as a potential biomarker for diagnosis, prognosis and follow up of RCC patients.

Side effects of a mixture of essential oils on Psyttalia concolor.

Integrated Pest Management programs do not always prioritize natural enemies when selecting control methods; too often these important pest reducing agents are negatively affected by the action of other methods in agroecosystems. The aim of this research was to evaluate side effects of a bioinsecticide, developed from the mixture of cedar (Cedrus atlantica), eucalyptus (Corymbia citriodora) and lemon grass (Cymbopogon citratus) essential oils (EOs), in a ratio of 1:1:1, on Psyttalia concolor (Szèpligeti) (Hymenoptera: Braconidae) which is a parasitoid of some pests of the Tephritidae family, as Ceratitis capitata. The LD50 of the EOs mixture for C. capitata females was 3.09 µl/g, whereas the LD50 for P. concolor females was 20.45 µl/g which suggests the natural enemy is more tolerant to the EOs mixture. P. concolor parasitized L3 larvae of C. capitata through a voile treated with the mixture of EOs at 1.8% without causing any deleterious effects neither on the percentage of attacked hosts nor on the emergence rate, whereas at the highest concentration tested, 4.8%, decreased both parameters during the 2 first days after treatment. Semi-field assays showed that mixture of EOs was harmless to P. concolor when released 4 h after treatment whereas killed 55 ± 3.9% males and 37.5 ± 1.6% females of C. capitata. The mixture of EOs used jointly with lambda-cyhalothrin or kaolin, both compounds applied against C. capitata in conventional and organic farming, respectively, did not increase the toxicity and/or persistence against the pest.

Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients.

microRNAs (miRNAs) are small RNAs that regulate different biological processes. Our objective was to identify miRNAs dysregulated in plasma and tissue of patients with abdominal aortic aneurysm (AAA) and explore new potential targets involved in AAA. Fifty-seven subjects were recruited for a plasma study (30 AAA patients, 16 healthy volunteers and 11 patients with atherosclerosis). The expression level of 179 miRNAs was screened in plasma from a subset of samples, and dysregulated miRNAs were validated in the entire study population. Dysregulated miRNAs were also quantified in aortic tissue of 21 AAA patients and 8 organ donors. Applying a gene set enrichment analysis, an interaction map of dysregulated miRNAs and their targets was built, and selected targets were quantified in tissue samples. miR-27b-3p and miR-221-3p were overexpressed in plasma of AAA patients compared with healthy controls, 1.6 times and 1.9 times, respectively. In AAA tissue, six miRNAs (miR-1, miR-27b-3p, miR-29b-3p, miR-133a-3p, miR-133b, and miR-195-5p) were underexpressed from 1.6 to 4.8 times and four miRNAs (miR-146a-5p, miR-21-5p, miR-144-3p, and miR-103a-3p) were overexpressed from 1.3 to 7.2 times. Thrombospondin-2, a target of miR-195-5p, was increased in AAA tissue and negatively correlated with the expression of miR-195-5p, suggesting their involvement in a common regulatory mechanism.

Increase of Neutrophil Activation Markers in Venous Thrombosis-Contribution of Circulating Activated Protein C.

Upon activation, neutrophils release their content through different mechanisms like degranulation and NETosis, thus prompting thrombosis. The natural anticoagulant activated protein C (APC) inhibits neutrophil NETosis and, consequently, this may lower the levels of neutrophil activation markers in plasma, further diminishing the thrombotic risk exerted by this anticoagulant. We aimed to describe the status of markers of neutrophil activation in plasma of patients with venous thrombosis, their association with the thrombotic risk and the potential contribution of APC. We quantified three markers of neutrophil activation (cell-free DNA, calprotectin, and myeloperoxidase) in 253 patients with venous thromboembolism (VTE) in a stable phase (192 lower extremity VTE and 61 splanchnic vein thrombosis) and in 249 healthy controls. In them, we also quantified plasma APC, soluble endothelial protein C receptor (EPCR), and soluble thrombomodulin (TM), and we genotyped two genetic regulators of APC: the EPCR gene (PROCR) haplotypes (H) and the TM gene (THBD) c.1418C>T polymorphism. We found a significant increase in plasma cell-free DNA (p < 0.0001), calprotectin (p = 0.0001) and myeloperoxidase (p = 0.005) in VTE patients compared to controls. Furthermore, all three neutrophil activation markers were associated with an increase in the thrombotic risk. Cell-free DNA and calprotectin plasma levels were significantly correlated (Spearman r = 0.28; p < 0.0001). As expected, the natural anticoagulant APC was significantly decreased in VTE patients (p < 0.0001) compared to controls, what was mediated by its genetic regulators PROCR-H1, PROCR-H3, and THBD-c.1418T, and inversely correlated with cell-free DNA levels. This is the largest case-control study that demonstrates the increase in markers of neutrophil activation in vivo in VTE patients and their association with an increased thrombotic risk. This increase could be mediated by low APC levels and its genetic regulators, which could also increase NETosis, further enhancing thrombosis and inflammation.

MicroRNAs and Neutrophil Activation Markers Predict Venous Thrombosis in Pancreatic Ductal Adenocarcinoma and Distal Extrahepatic Cholangiocarcinoma.

Cancer-associated venous thrombosis (VTE) increases mortality and morbidity. However, limited tools are available to identify high risk patients. Upon activation, neutrophils release their content through different mechanisms, thereby prompting thrombosis. We explored plasma microRNAs (miRNAs) and neutrophil activation markers to predict VTE in pancreatic ductal adenocarcinoma (PDAC) and distal extrahepatic cholangiocarcinoma (DECC). Twenty-six PDAC and 6 DECC patients recruited at cancer diagnosis, were examined for deep vein thrombosis and pulmonary embolisms, and were then followed-up with clinical examinations, blood collections, and biCUS. Ten patients developed VTE and were compared with 22 age- and sex-matched controls. miRNA expression levels were measured at diagnosis and right before VTE, and neutrophil activation markers (cell-free DNA, nucleosomes, calprotectin, and myeloperoxidase) were measured in every sample obtained during follow-up. We obtained a profile of 7 miRNAs able to estimate the risk of future VTE at diagnosis (AUC = 0.95; 95% Confidence Interval (CI) (0.987, 1)) with targets involved in the pancreatic cancer and complement and coagulation cascades pathways. Seven miRNAs were up- or down-regulated before VTE compared with diagnosis. We obtained a predictive model of VTE with calprotectin as predictor (AUC = 0.77; 95% CI (0.57, 0.95)). This is the first study that addresses the ability of plasma miRNAs and neutrophil activation markers to predict VTE in PDAC and DECC.

Communication Channels Used by Women to Contact a Population-Based Breast Cancer Screening Program in Catalonia, Spain.

Communication is a corner stone of population-based breast cancer screening programs that need to invite all the women from their target population and provide them with balanced information on screening to guaranty informed participation. Invited women also need to be able to contact screening programs to get further information on screening procedures and/or cancel and reschedule appointments. This study describes the communication channels used by women invited for breast cancer screening to contact the program. The study population consisted of 141,684 women, aged 50-69 years, who were invited during 2015-2016 for screening by the Catalan Breast Cancer Screening Program (Spain). Multiple logistic regression models were performed to assess the association between age, screening history, socioeconomic status and reasons for contacting the program and the outcome variables (contact with the program; contact through information and communication technology (ICT) channels). Among the 141,684 women invited for BC screening, 22.5% contacted the screening office mainly to reschedule (42.2%) and cancel (29.2%) appointments. While the communication channel mostly used was the telephone, 24.8% of the women used ICT. ICT was more frequently used by women who had never been screened. Women who wanted to change their appointment were 65% (OR 1.65, 95%CI 1.54-1.76) more likely to use ICT than women who wanted to cancel it. This study showed the need to reinforce communication between women and breast cancer screening programs and the importance of offering communication channels suiting all women's needs to facilitate appointments' rescheduling and cancelling and therefore improve screening programs' efficiency.

Characterization of a new toxin from the entomopathogenic fungus Metarhizium anisopliae: the ribotoxin anisoplin.

Metarhizium anisopliae is an entomopathogenic fungus relevant in biotechnology with applications like malaria vector control. Studies of its virulence factors are therefore of great interest. Fungal ribotoxins are toxic ribonucleases with extraordinary efficiency against ribosomes and suggested as potential insecticides. Here we describe this ribotoxin characteristic activity in M. anisopliae cultures. Anisoplin has been obtained as a recombinant protein and further characterized. It is structurally similar to hirsutellin A, the ribotoxin from the entomopathogen Hirsutella thompsonii. Moreover, anisoplin shows the ribonucleolytic activity typical of ribotoxins and cytotoxicity against insect cells. How Metarhizium uses this toxin and possible applications are of interest.

Occupation and mammographic density: A population-based study (DDM-Occup).

INTRODUCTION: High mammographic density is one of the main risk factors for breast cancer. Although several occupations have been associated with breast cancer, there are no previous occupational studies exploring the association with mammographic density. Our objective was to identify occupations associated with high mammographic density in Spanish female workers. METHODS: We conducted a population-based cross-sectional study of occupational determinants of high mammographic density in Spain, based on 1476 women, aged 45-68 years, recruited from seven screening centers within the Spanish Breast Cancer Screening Program network. Reproductive, family, personal, and occupational history data were collected. The latest occupation of each woman was collected and coded according to the 1994 National Classification of Occupations. Mammographic density was assessed from the cranio-caudal mammogram of the left breast using a semi-automated computer-assisted tool. Association between mammographic density and occupation was evaluated by using mixed linear regression models, using log-transformed percentage of mammographic density as dependent variable. Models were adjusted for age, body mass index, menopausal status, parity, smoking, alcohol intake, educational level, type of mammography, first-degree relative with breast cancer, and hormonal replacement therapy use. Screening center and professional reader were included as random effects terms. RESULTS: Mammographic density was higher, although non-statistically significant, among secondary school teachers (eß = 1.41; 95%CI = 0.98-2.03) and nurses (eß = 1.23; 95%CI = 0.96-1.59), whereas workers engaged in the care of people (eß = 0.81; 95%CI = 0.66-1.00) and housewives (eß = 0.87; 95%CI = 0.79-0.95) showed an inverse association with mammographic density. A positive trend for every 5 years working as secondary school teachers was also detected (p-value = 0.035). CONCLUSIONS: Nurses and secondary school teachers were the occupations with the highest mammographic density in our study, showing the latter a positive trend with duration of employment. Future studies are necessary to confirm if these results are due to chance or are the result of a true association whose causal hypothesis is, for the moment, unknown.

Lethal and sublethal effects of pesticides on Chrysoperla carnea larvae (Neuroptera: Chrysopidae) and the influence of rainfastness in their degradation pattern over time.

The predator Chrysoperla carnea is a model species for the study of non-target effects of pesticides under different scenarios: registration of plant protection products under the European Union and effects of the Bt toxin. Laboratory and persistence studies were carried out with six pesticides currently used in corn crops in Spain that were applied at their maximum field recommended concentrations. The assessed end-points were larval mortality, survivorship until adult stage, duration of the larval and pupal periods, fecundity, fertility and sex ratio of the emerged adults. Based on the total effect (lethal and sublethal) caused to L3 larvae in contact with fresh residues in the laboratory, pendimethalin was harmless (IOBC 1), lambda-cyhalothrin, abamectin, and hexythiazox were slightly harmful (IOBC 2), deltamethrin was moderately harmful (IOBC 3) and chlorpyrifos was harmful (IOBC 4). Afterwards, the residues of the two most toxic pesticides in the lab (deltamethrin and chlorpyrifos) were aged under greenhouse conditions (22 ± 2 °C, 40 ± 10 % R.H., 16.9 µmol m(-2) s(-1) UV radiation) in the presence and absence of artificial rainfall (10 l m(-2) h(-1), applied 24 h after pesticide application). Deltamethrin was classified as short lived (IOBC A) in both cases. However, degradation of chlorpyrifos residues was accelerated in the presence of rainfall, leading to the classification as slightly persistent (IOBC B), while in absence of rainfall it behaved as persistent (IOBC D). Every pesticide can be recommended for inclusion in corn IPM programs where the predator is present except chlorpyrifos that exhibited high direct toxicity in the lab and prolonged residual action even in the presence of rainfall.

Impact of Feeding on Contaminated Prey on the Life Parameters of Nesidiocoris Tenuis (Hemiptera: Miridae) Adults.

Insecticide selectivity to natural enemies is an important concern in integrated pest management programs. Although there is a wide range of information concerning pesticide lethal and sublethal effects on contaminated surfaces, little is known when the route of exposure occurs at a trophic level. This study evaluates this route of pesticide intake on the omnivorous predator Nesidiocoris tenuis (Reuter) (Hemiptera: Miridae) for the first time. Under laboratory conditions, prey treated with six insecticides (flubendiamide, spirotetramat, deltamethrin, flonicamid, metaflumizone, and sulfoxaflor) were offered to N. tenuis adults for 3 days. Mortality (24, 48, and 72 h after treatment), offspring production (third until eighth day) and longevity were documented. Metaflumizone and sulfoxaflor were classified as moderately harmful products because although the percentage of mortality was only 28 and 36%, respectively, both products caused a severe decrease in offspring production and longevity. Flonicamid and flubendiamide were classified as slightly harmful products; although they did not have a lethal effect, sublethal impact was important on the parameters studied. Spirotetramat and deltamethrin were insecticides categorized as harmless. This information could be useful for selecting the most appropriate insecticides to control pests in tomato crops in which N. tenuis is a relevant biological control agent.

Are Mummies and Adults of Eretmocerus mundus (Hymenoptera: Aphelinidae) Compatible With Modern Insecticides?

The parasitic wasp Eretmocerus mundus (Mercet) is an important natural enemy of the widespread key pest Bemisia tabaci (Gennadius). The toxicity of 11 modern insecticides applied at their maximum field recommended rate in Spain was tested in two life stages of E. mundus: adults and mummies. Laboratory and persistence tests were conducted and effects assessed not only in terms of mortality but on reproductive performance as well. Some insecticides caused the same effect to both life stages: flubendiamide, methoxyfenozide, spiromesifen, and flonicamid were harmless, while spinosad and sulfoxaflor were harmful. The last two insecticides cannot be used jointly with E. mundus under any condition because they were highly persistent. The rest of tested insecticides (spirotetramat, metaflumizone, deltamethrin, abamectin, and emamectin) caused some direct mortality to one or both life stages and/or affected reproduction of the parasitic wasp and their harmful effect in the field ranged from short lived (metaflumizone and spirotetramat) to slightly persistent (emamectin) and to moderately persistent (abamectin and deltamethrin). Therefore, they could be recommended for use in integrated pest management programs together with the natural enemy if appropriate safety intervals after insecticide application are observed.

Association of the thrombomodulin gene c.1418C>T polymorphism with thrombomodulin levels and with venous thrombosis risk.

OBJECTIVE: To investigate the association of the THBD c.1418C>T polymorphism, which encodes for the replacement of Ala455 by Val in thrombomodulin (TM), with venous thromboembolism (VTE), plasma soluble TM, and activated protein C levels. In addition, human umbilical vein endothelial cells (HUVEC) isolated from 100 umbilical cords were used to analyze the relation between this polymorphism and THBD mRNA and TM protein expression. APPROACH AND RESULTS: The THBD c.1418C>T polymorphism was genotyped in 1173 patients with VTE and 1262 control subjects. Levels of soluble TM and activated protein C were measured in 414 patients with VTE (not on oral anticoagulants) and 451 controls. HUVECs were genotyped for the polymorphism and analyzed for THBD mRNA and TM protein expression and for the ability to enhance protein C activation by thrombin. The 1418T allele frequency was lower in patients than in controls (P<0.001), and its presence was associated with a reduced VTE risk, reduced soluble TM levels, and increased circulating activated protein C levels (P<0.001). In cultured HUVEC, the 1418T allele did not influence THBD expression but was associated with increased TM in cell lysates, increased rate of protein C activation, and reduced soluble TM levels in conditioned medium. CONCLUSIONS: The THBD 1418T allele is associated with lower soluble TM, both in plasma and in HUVEC-conditioned medium, and with an increase in functional membrane-bound TM in HUVEC, which could explain the increased activated protein C levels and the reduced VTE risk observed in individuals carrying this allele.