Agricultural exposures and DNA damage in PBMC of female farmers measured using the alkaline comet assay.

OBJECTIVE: Several studies investigated the link between agricultural occupational exposures and DNA damage, in an attempt to bring elements of biological plausibility to the increased cancer risk associated with them. However, only a few of these studies focused on females. METHODS: The comet assay was performed on PBMC (Peripheral Blood Mononuclear Cells) samples from 245 females working in open field farming and cattle raising, located in the Normandy area of France. Individual questionnaires on tasks performed were administered at the time of sampling to directly assess exposures. Environmental exposures were issued from a questionnaire assessing the farm productions. Linear regression analyses were done using the DNA damage scores. RESULTS: Regarding direct exposures, several tasks associated with exposure to potentially harmful chemicals were not associated with DNA damage, but a longer duration of use of herbicide on meadows (p = 0.05) or of cleaning and upkeep of agricultural equipment (p = 0.06) revealed higher DNA damage levels, although the number of exposed women was low. Several indirect and/or environmental exposures were associated with DNA damage in multivariate analyses: a larger surface of meadows (p = 0.006) or the presence of poultry (p = 0.03) was associated with less DNA damage, while the presence of swine (p = 0.01) was associated with higher DNA damage. Smokers and former smokers had less DNA damage than non-smokers (p = 0.0008 and p = 0.03). CONCLUSIONS: We report modified levels of DNA damage for those environmentally exposed to meadows, poultry and pig farming, underlining the need for a better knowledge of the potential health risks experienced by females in this setting.

Pesticide exposure in greenspaces: Comparing field measurement of dermal contamination with values predicted by registration models.

Since 2014, the Agricultural Operator Exposure Model (AOEM) has been the harmonised European model used for estimating non-dietary operator exposure to pesticide. It is based on studies conducted by the pesticide companies and it features 13 different crops including non-agricultural areas such as amenity grasslands. The objective of this study was to compare the dermal exposure measured during a field study conducted in a non-agricultural area with the corresponding values estimated by the model AOEM. The non-controlled field study was conducted in France in 2011 and included 24 private and public gardeners who apply glyphosate with knapsack sprayers. Dermal exposure was measured using the whole-body method and cotton gloves. Each measured value had an estimated value given by AOEM and we tested their correlation using linear regression. The model overestimated body exposure for all observations and there was no correlation between values. However, it underestimated hand exposure by 42 times and it systematically underestimated the exposure when the operators were wearing gloves, especially during the application. The model failed at being conservative regarding hand exposure and highly overestimated the protection afforded by the gloves. At a time of glyphosate renewed approval in Europe, non-controlled field studies conducted by academics are needed to improve AOEM model, especially in the non-agricultural sector. Indeed, among the 34 studies included in the model, none were conducted on a non-agricultural area and only four assessed the exposure when using a knapsack sprayer. Moreover, knapsack sprayers being the main equipment used worldwide in both agricultural and non-agricultural settings, it is also crucial to integrate new data specific to this equipment in the model. Operator exposure should be estimated with accuracy in the registration process of pesticides to ensure proper safety as well as in epidemiological studies to improve exposure assessment.

The Management of Persistent Distal Occlusions after Mechanical Thrombectomy and Thrombolysis: An Inter- and Intrarater Agreement Study.

BACKGROUND AND PURPOSE: The best management of patients with persistent distal occlusion after mechanical thrombectomy with or without IV thrombolysis remains unknown. We sought to evaluate the variability and agreement in decision-making for persistent distal occlusions. MATERIALS AND METHODS: A portfolio of 60 cases was sent to clinicians with varying backgrounds and experience. Responders were asked whether they considered conservative management or rescue therapy (stent retriever, aspiration, or intra-arterial thrombolytics) a treatment option as well as their willingness to enroll patients in a randomized trial. Agreement was assessed using κ statistics. RESULTS: The electronic survey was answered by 31 physicians (8 vascular neurologists and 23 interventional neuroradiologists). Decisions for rescue therapies were more frequent (n = 1116/1860, 60%) than for conservative management (n = 744/1860, 40%; P < .001). Interrater agreement regarding the final management decision was "slight" (κ = 0.12; 95% CI, 0.09-0.14) and did not improve when subgroups of clinicians were studied according to background, experience, and specialty or when cases were grouped according to the level of occlusion. On delayed re-questioning, 23 of 29 respondents (79.3%) disagreed with themselves on at least 20% of cases. Respondents were willing to offer trial participation in 1295 of 1860 (69.6%) cases. CONCLUSIONS: Individuals did not agree regarding the best management of patients with persistent distal occlusion after mechanical thrombectomy and IV thrombolysis. There is sufficient uncertainty to justify a dedicated randomized trial.

Diagnostic and therapeutic approach to adult central nervous system vasculitis.

The clinical manifestations of central nervous system (CNS) vasculitis are highly variable. In the absence of a positive CNS biopsy, CNS vasculitis is particularly suspected when markers of both vascular disease and inflammation are present. To facilitate the clinical and therapeutic approach to this rare condition, CNS vasculitis can be classified according to the size of the involved vessels. Vascular imaging is used to identify medium vessel disease. Small vessel disease can only be diagnosed with a CNS biopsy. Medium vessel vasculitis usually presents with focal neurological signs, while small vessel vasculitis more often leads to cognitive deficits, altered level of consciousness and seizures. Markers of CNS inflammation include cerebrospinal fluid pleocytosis or elevated protein levels, and vessel wall, parenchymal or leptomeningeal enhancement. The broad range of differential diagnoses of CNS vasculitis can be narrowed based on the disease subtype. Common mimickers of medium vessel vasculitis include intracranial atherosclerosis and reversible cerebral vasoconstriction syndrome. The diagnostic workup aims to answer two questions: is the neurological presentation secondary to a vasculitic process, and if so, is the vasculitis primary (i.e., primary angiitis of the CNS) or secondary (e.g., to a systemic vasculitis, connective tissue disorder, infection, malignancy or drug use)? In primary angiitis of the CNS, glucocorticoids and cyclophosphamide are most often used for induction therapy, but rituximab may be an alternative. Based on the available evidence, all patients should receive maintenance immunosuppression. A multidisciplinary approach is necessary to ensure an accurate and timely diagnosis and to improve outcomes for patients with this potentially devastating condition.

Health of greenspace workers: Morbidity and mortality data from the AGRICAN cohort.

INTRODUCTION: Knowledge on the health of greenspace workers is scarce, even though they are exposed to many occupational hazards. The aim of this study was to analyze mortality by cause, prevalence of some non-cancer diseases, and incidence of the main cancers among greenspace workers. METHODS: A sub-cohort of greenspace workers was formed within the AGRICAN cohort. Demographic information, health characteristics and self-reported diseases at enrollment were described separately in terms of frequencies (%), median and Interquartile Range (IQR) for greenspace workers, farmers, and other non-agricultural workers. Causes of death and cancer incidence were identified through linkage with cancer registries from enrollment (2005-2007) to 2015. Hazard ratio (HR) and 95% Confidence Intervals [95% CI] were estimated using Cox proportional hazard regression with age as the underlying timescale. RESULTS: The sub-cohort included 6247 greenspace workers who were higher proportion men, younger and more frequently smokers than farmers and non-agricultural workers. Male and female greenspace workers reported more history of allergic diseases; and males, more history of depression. Compared to other workers male greenspace workers showed a non-significant higher mortality from ischemic cardiological diseases (HR = 1.14 [0.81-1.60]). Incidence was higher in male greenspace workers than farmers for overall cancer (HR = 1.15 [1.04-1.27]), cancer of the prostate (HR = 1.21 [1.02-1.44]), thyroid (HR = 2.84 [1.26-6.41]), testis (HR = 3.98 [1.50-10.58]) and skin melanoma (HR = 2.15 [1.33-3.47]). Non-significant increased risks were also found for sarcomas, larynx and breast. In women, risk of breast cancer was higher in greenspace workers than in farmers (HR = 1.71 [1.17-2.50]). CONCLUSIONS: Whereas greenspace workers have often been included with other pesticide applicators in epidemiological studies, our analyses highlighted the differences between these two populations. They demonstrate the need to study them separately and to investigate more thoroughly the role of specific occupational exposures such as pesticides as well as the effect on women.

Occupational pesticide exposure, cancer and chronic neurological disorders: A systematic review of epidemiological studies in greenspace workers.

CONTEXT: The greenspace sector includes a broad range of occupations: gardeners, landscapers, municipal workers, maintenance operators of public facilities, golf-course employees and other sports facilities, horticulturists, plant and tree nursery workers etc. The health impact of occupational pesticide exposure has mainly been studied among farmers. Other professionals such as greenspace workers are also extremely exposed, presenting specific exposure features (practices, types of pesticide used). The aim of this review was to summarize epidemiological literature that examine the relationship between pesticide exposure and the risk of cancer and long-term health effects in greenspace workers. METHOD: Six main groups of greenspace workers were identified and examined through a systematic literature review based on PubMed and Scopus. The studies were then grouped according to their design, health outcomes and the type of population studied. RESULTS: Forty-four articles were selected among the 1679 identified. Fifteen studies were conducted exclusively among greenspace workers, while ten also studied these workers with other pesticide applicators. Six were cohorts from the general population in which greenspace workers were identified. Elevated risks were found in several studies for leukaemia, soft-tissue sarcoma, multiple myeloma, non-Hodgkin lymphoma and Parkinson's disease. DISCUSSION: The majority of studies used rough parameters for defining exposure such as job titles which could lead to the misclassification of exposure, with the risk of false or positive negative conclusions. Health outcomes were mainly collected through registries or death certificates, and information regarding potential confounders was often missing. CONCLUSION: The review identified only 15 studies conducted exclusively among greenspace workers. Elevated risk was found for several sites of cancer and Parkinson's diseases. Further epidemiological research is needed, conducted specifically on these workers, to better characterize this population, its exposure to pesticides and the related health effects.

Deep learning methods to generate synthetic CT from MRI in radiotherapy: A literature review.

PURPOSE: In radiotherapy, MRI is used for target volume and organs-at-risk delineation for its superior soft-tissue contrast as compared to CT imaging. However, MRI does not provide the electron density of tissue necessary for dose calculation. Several methods of synthetic-CT (sCT) generation from MRI data have been developed for radiotherapy dose calculation. This work reviewed deep learning (DL) sCT generation methods and their associated image and dose evaluation, in the context of MRI-based dose calculation. METHODS: We searched the PubMed and ScienceDirect electronic databases from January 2010 to March 2021. For each paper, several items were screened and compiled in figures and tables. RESULTS: This review included 57 studies. The DL methods were either generator-only based (45% of the reviewed studies), or generative adversarial network (GAN) architecture and its variants (55% of the reviewed studies). The brain and pelvis were the most commonly investigated anatomical localizations (39% and 28% of the reviewed studies, respectively), and more rarely, the head-and-neck (H&N) (15%), abdomen (10%), liver (5%) or breast (3%). All the studies performed an image evaluation of sCTs with a diversity of metrics, with only 36 studies performing dosimetric evaluations of sCT. CONCLUSIONS: The median mean absolute errors were around 76 HU for the brain and H&N sCTs and 40 HU for the pelvis sCTs. For the brain, the mean dose difference between the sCT and the reference CT was <2%. For the H&N and pelvis, the mean dose difference was below 1% in most of the studies. Recent GAN architectures have advantages compared to generator-only, but no superiority was found in term of image or dose sCT uncertainties. Key challenges of DL-based sCT generation methods from MRI in radiotherapy is the management of movement for abdominal and thoracic localizations, the standardization of sCT evaluation, and the investigation of multicenter impacts.

Pseudogap phase of cuprate superconductors confined by Fermi surface topology.

The properties of cuprate high-temperature superconductors are largely shaped by competing phases whose nature is often a mystery. Chiefly among them is the pseudogap phase, which sets in at a doping p* that is material-dependent. What determines p* is currently an open question. Here we show that the pseudogap cannot open on an electron-like Fermi surface, and can only exist below the doping p FS at which the large Fermi surface goes from hole-like to electron-like, so that p* ≤ p FS. We derive this result from high-magnetic-field transport measurements in La1.6-x Nd0.4Sr x CuO4 under pressure, which reveal a large and unexpected shift of p* with pressure, driven by a corresponding shift in p FS. This necessary condition for pseudogap formation, imposed by details of the Fermi surface, is a strong constraint for theories of the pseudogap phase. Our finding that p* can be tuned with a modest pressure opens a new route for experimental studies of the pseudogap.

Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease.

BACKGROUND: Studies have shown that lipoprotein(a) [Lp(a)], an important carrier of oxidized phospholipids, is causally related to calcific aortic valve stenosis (CAVS). Recently, we found that Lp(a) mediates the development of CAVS through autotaxin (ATX). OBJECTIVE: To determine the predictive value of circulating ATX mass and activity for CAVS. METHODS: We performed a case-control study in 300 patients with coronary artery disease (CAD). Patients with CAVS plus CAD (cases, n = 150) were age- and gender-matched (1 : 1) to patients with CAD without aortic valve disease (controls, n = 150). ATX mass and enzymatic activity and levels of Lp(a) and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) were determined in fasting plasma samples. RESULTS: Compared to patients with CAD alone, ATX mass (P < 0.0001), ATX activity (P = 0.05), Lp(a) (P = 0.003) and OxPL-apoB (P < 0.0001) levels were elevated in those with CAVS. After adjustment, we found that ATX mass (OR 1.06, 95% CI 1.03-1.10 per 10 ng mL-1 , P = 0.001) and ATX activity (OR 1.57, 95% CI 1.14-2.17 per 10 RFU min-1 , P = 0.005) were independently associated with CAVS. ATX activity interacted with Lp(a) (P = 0.004) and OxPL-apoB (P = 0.001) on CAVS risk. After adjustment, compared to patients with low ATX activity (dichotomized at the median value) and low Lp(a) (<50 mg dL-1 ) or OxPL-apoB (<2.02 nmol L-1 , median) levels (referent), patients with both higher ATX activity (≥84 RFU min-1 ) and Lp(a) (≥50 mg dL-1 ) (OR 3.46, 95% CI 1.40-8.58, P = 0.007) or OxPL-apoB (≥2.02 nmol L-1 , median) (OR 5.48, 95% CI 2.45-12.27, P < 0.0001) had an elevated risk of CAVS. CONCLUSION: Autotaxin is a novel and independent predictor of CAVS in patients with CAD.

[Oral hairy leukoplakia induced by topical steroids]. / Leucoplasie orale chevelue induite par une corticothérapie locale.

BACKGROUND: Oral hairy leukoplakia (OHL) is an EBV-associated condition of the oral mucosa, which is often painless. It is found predominantly in HIV-positive patients and is considered a clinical indicator of immunosuppression. OHL has rarely been described in HIV-negative patients, being found most often in association with iatrogenic immunosuppression. OHL induced by topical steroids remains extremely rare. PATIENTS AND METHODS: An 81-year-old HIV-negative woman, treated for 3 months with topical steroids for oral lichen planus, developed an asymptomatic white, corrugated, non-removable plaque with vertical folds on the lateral edge of the tongue. Associated oral candidiasis was noted. Based upon histological findings and in situ hybridisation showing numerous EBV-infected epithelial cells, a diagnosis of oral hairy leucoplakia was made. DISCUSSION AND CONCLUSION: To our knowledge, we report herein only the second recorded case of OHL induced strictly by topical steroids. Self-medication and poor adherence to dosage recommendations were noted in the patient's medical history. Physicians must be aware of the rare but nevertheless possible adverse events associated with topical steroid use, particularly when such medication is prescribed over a long period for inflammatory diseases of the oral mucosa.

[Systemic sclerosis and occupational exposures: About a case in a driller-powderman]. / Sclérodermie systémique et expositions professionnelles: à propos d'un cas chez un foreur-artificier.

INTRODUCTION: Erasmus' syndrome is the association between systemic sclerosis and silica exposure. CASE REPORT: We report a case of this syndrome in a driller-powderman exposed to silica and nitro compounds contained in explosives. CONCLUSION: Physiopathology and etiologies of systemic sclerosis are still not well known. However, nitric oxide, a product of nitro compounds metabolism, is involved in the physiopathology of the disease: it seems thus licit to wonder about the consequences of an uncontrolled occupational exposure to nitric oxide on the vascular function, already damaged by systemic sclerosis. To a wider extent, our report highlights the importance of a comprehensive and detailed collection of occupational exposures for patients diagnosed with systemic sclerosis.

Mothers without HLA antibodies before transplantation have a low risk of alloimmunization post-transplantation.

Human leukocyte antigen antibodies (HLA Abs) are associated with poor renal graft outcome. We selected 134 first kidney transplant recipients without HLA Ab (LABScreen® Luminex) before transplantation despite previous allogeneic exposure whether through blood transfusion (BT) and/or pregnancy (PR). We screened these patients for HLA Ab post-transplantation (yearly) and determined the risk of HLA Ab and donor-specific antibody (DSA) appearance according to BT/PR in a univariate and a multivariate model. Among the 134 patients (43 males/91 females), 56 were BT+/PR-, 41 BT-/PR+ and 37 BT+/PR+. Median delay between last PR or BT and transplantation were 25.9 years (0.5-47.8) and 8 months (0.8-128.0), respectively. Median number of PR and BT were 2 (1-11) and 3 units (1-28), respectively. After transplantation (median follow-up: 47.5 months), 13 patients (9.7%) had HLA Ab and 10 DSA, mainly directed against class II HLA (HLA Ab: 10/13, DSA: 9/10). The risk of HLA Ab and DSA appearance was significantly lower in patients with PR before transplantation (P = 0.032 and P = 0.009, respectively). The risk of DSA appearance (hazard ratio = 0.17, P = 0.027) remained significantly lower after adjustment on donor age, acute rejection and number of class I/II HLA mismatches. In conclusion, we show that parous women non-immunized are at low risk of HLA Ab production after transplantation.

Psoriasin (S100A7) associates with integrin ß6 subunit and is required for αvß6-dependent carcinoma cell invasion.

Expression of the integrin αvß6 is upregulated in a variety of carcinomas where it appears to be involved in malignant progression, although the biology of this integrin is not fully explored. We have generated oral carcinoma cells that express αvß6 composed of wild-type αv and a mutant ß6 that lacks the unique C-terminal 11 amino acids (aa). We found that these residues, although not required for αvß6-dependent adhesion or migration, are essential for αvß6-dependent invasive activity. We have used a proteomic approach to identify novel binding partners for the ß6 subunit cytoplasmic tail and report that psoriasin (Psor) (S100A7) bound preferentially to the recombinant ß6 cytoplasmic domain, though not in the absence of the unique C-terminal 11aa. Endogenous cellular Psor co-precipitated with endogenous ß6 and colocalised with αvß6 at the cell membrane and intracellular vesicles. Knockdown of Psor, with small interfering RNA, had no effect on αvß6-dependent adhesion or migration but abrogated αvß6-mediated oral carcinoma cell invasion both in Transwell and, the more physiologically relevant, organotypic invasion assays, recapitulating the behaviour of the ß6-mutant cell line. Membrane-permeant Tat-peptides encoding the unique C-terminal residues of ß6, bound directly to recombinant Psor and inhibited cellular Psor binding to ß6; this blocked αvß6-dependent, but not αvß6-independent, invasion. These data identify a novel interaction between Psor and ß6 and demonstrate that it is required for αvß6-dependent invasion by carcinoma cells. Inhibition of this interaction may represent a novel therapeutic strategy to target carcinoma invasion.

Workplace bullying and psychotropic drug use: the mediating role of physical and mental health status.

OBJECTIVES: The association between workplace bullying and psychotropic drug use is not well established. This study was aimed at exploring the association between workplace bullying, and its characteristics, and psychotropic drug use and studying the mediating role of physical and mental health. METHODS: The study population consisted of a random sample of 3132 men and 4562 women of the working population in the south-east of France. Workplace bullying, evaluated using the validated instrument elaborated by Leymann, and psychotropic drug use, as well as covariates, were measured using a self-administered questionnaire. Covariates included age, marital status, presence of children, education, occupation, working hours, night work, physico-chemical exposures at work, self-reported health, and depressive symptoms. Statistical analysis was performed using logistic regression analysis and was carried out separately for men and women. RESULTS: Workplace bullying was strongly associated with psychotropic drug use. Past exposure to bullying increased the risk for this use. The more frequent and the longer the exposure to bullying, the stronger the association with psychotropic drug use. Observing bullying on someone else at the workplace was associated with psychotropic drug use. Adjustment for covariates did not modify the results. Additional adjustment for self-reported health and depressive symptoms reduced the magnitude of the associations, especially for men. CONCLUSIONS: The association between bullying and psychotropic drug use was found to be significant and strong and was partially mediated by physical and mental health.

Workplace bullying and sleep disturbances: findings from a large scale cross-sectional survey in the French working population.

STUDY OBJECTIVES: The purpose of this study was to explore the associations between workplace bullying, the characteristics of workplace bullying, and sleep disturbances in a large sample of employees of the French working population. DESIGN: Workplace bullying, evaluated using the validated instrument developed by Leymann, and sleep disturbances, as well as covariates, were measured using a self-administered questionnaire. Covariates included age, marital status, presence of children, education, occupation, working hours, night work, physical and chemical exposures at work, self-reported health, and depressive symptoms. Statistical analysis was performed using logistic regression analysis and was carried out separately for men and women. SETTING: General working population. PARTICIPANTS: The study population consisted of a random sample of 3132 men and 4562 women of the working population in the southeast of France. RESULTS: Workplace bullying was strongly associated with sleep disturbances. Past exposure to bullying also increased the risk for this outcome. The more frequent the exposure to bullying, the higher the risk of experiencing sleep disturbances. Observing someone else being bullied in the workplace was also associated with the outcome. Adjustment for covariates did not modify the results. Additional adjustment for self-reported health and depressive symptoms diminished the magnitude of the associations that remained significant. CONCLUSIONS: The prevalence of workplace bullying (around 10%) was found to be high in this study as well was the impact of this major job-related stressor on sleep disturbances. Although no conclusion about causality could be drawn from this cross-sectional study, the findings suggest that the contribution of workplace bullying to the burden of sleep disturbances may be substantial.

[Comparison of two ELISA tests to study the seroprevalence of herpes simplex 1 et 2 infection in a maternity near Paris]. / Comparaison de deux techniques Elisa pour l'étude de la séroprévalence de l'infection à herpes simplex 1 et 2 dans une maternité de la région parisienne.

UNLABELLED: The diagnosis of herpes simplex virus (HSV) genital infection is primarily clinical. The primary indication for serodiagnosis is to detect seronegativity in pregnant women at risk of acquiring the HSV virus during the course of their pregnancy. In this study, two ELISA tests were compared for the detection of HSV infection among a population of 307 pregnant women followed at the maternity of a community-based hospital in France (Robert Ballanger hospital in the Seine-Saint-Denis department). The two tests compared were: Test Captia anti-HSV-1 and anti-HSV-2 specifics IgG of Trinity Biotech and the ELISA IgG HerpesSelect 1 and 2 of FOCUS Diagnostics distributed by Eurobio Courtaboeuf, France. RESULTS: Both tests results were similar in terms of population prevalence for HSV-1 and HSV-2 infections (respectively 86.64% and 85.99% for HSV-1; 17.59% and 15.31% for HSV-2). Whereas the prevalence of the HSV-1 virus was described in the literature as being superior to our current results, the prevalence of HSV-2 according to the results of both ELISA tests studied was similar to the one described in previous cohort studies.

Sepsis due to Clostridium perfringens after pregnancy termination with feticide by cordocentesis: a case report.

We report a case of sepsis due to Clostridium perfringens after termination of pregnancy at 22 weeks with feticide by cordocentesis. Three weeks earlier, the 41-year-old patient had undergone an amniocentesis and a full trisomy 13 karyotype had been discovered. Feticide was performed by injection of thiopental and potassium chloride after percutaneous umbilical foetal blood sampling through the same needle. The patient delivered vaginally with signs of chorioamnionitis and septicaemia. She recovered under broad-spectrum antibiotherapy. C. perfringens was present in maternal blood cultures, placental smears and foetal organs. We discuss the possible mechanisms of infection by C. perfringens, including inoculation of intestinal germs.