Périnatalité & Risques Toxiques

Microbial food cultures have directly or indirectly come under various regulatory frameworks in the course of the last decades. Several of those regulatory frameworks put emphasis on "the history of use", "traditional food", or "general recognition of safety". Authoritative lists of microorganisms with a documented use in food have therefore come into high demand. One such list was published in 2002 as a result of a joint project between the International Dairy Federation (IDF) and the European Food and Feed Cultures Association (EFFCA). The "2002 IDF inventory" has become a de facto reference for food cultures in practical use. However, as the focus mainly was on commercially available dairy cultures, there was an unmet need for a list with a wider scope. We present an updated inventory of microorganisms used in food fermentations covering a wide range of food matrices (dairy, meat, fish, vegetables, legumes, cereals, beverages, and vinegar). We have also reviewed and updated the taxonomy of the microorganisms used in food fermentations in order to bring the taxonomy in agreement with the current standing in nomenclature.

a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

Abstract We study optimal contracts in a simple model where employees are averse to inequity, as modeled by Fehr and Schmidt (1999) . A “selfish” employer can profitably exploit envy or guilt by offering contracts which create inequity off‐equilibrium, i.e., when employees do not meet his demands. Such contracts resemble team and relative performance contracts. We derive conditions for inequity aversion to be in itself a reason to form work teams of distributionally concerned employees, even in situations in which effort is contractible.

BACKGROUND: The postnatal period is a critical time window during which inflammatory events have significant and enduring effects on the brain, and as a consequence, induce alterations of emotional behavior and/or cognition later in life. However, the long-term effect of neonatal inflammation on behavior during adolescence, a sensitive period for the development of neurodevelopmental psychiatric disorders, has been little studied. In this study, we examined whether an early-life inflammatory challenge could alter emotional behaviors and spatial memory at adolescence and adulthood and whether stress axis activity, inflammatory response and neurogenesis were affected. METHODS: Lipopolysaccharide (LPS, 100 μg/kg) was administered to mice on postnatal day (PND) 14 and cytokine expression was measured in the plasma and in brain structures 3 hours later. Anxiety-like and depressive-like behavior (measured in the novelty-suppressed feeding test and the forced swim test, respectively) and spatial memory (Y-maze test) were measured at adolescence (PND30) and adulthood (PND90). Hypothalamic-pituitary-adrenal (HPA) axis activity (plasma corticosterone and glucocorticoid receptors in the hippocampus and prefrontal cortex) was measured at adulthood. In addition, the impact of a novel adult LPS challenge (100 μ/kg) was measured on spatial memory (Y-maze test), neurogenesis (doublecortin-positive cell numbers in the hippocampus) and plasma cytokine expression. RESULTS: First, we show in PND14 pups that a peripheral administration of LPS induced the expression of pro- and anti-inflammatory cytokines in the plasma and brain structures that were studied 3 hours after administration. Anxiety-like behavior was altered in adolescent, but not in adult, mice, whereas depressive-like behavior was spared at adolescence and increased at adulthood. This was accompanied by a decreased phosphorylation of the glucocorticoid receptor in the prefrontal cortex, with no effect on corticosterone levels. Second, neonatal LPS treatment had no effect on spatial memory in adolescence and adulthood. However, a second challenge of LPS in adulthood impaired spatial memory performance and neurogenesis and increased circulating levels of CCL2. CONCLUSIONS: Our study shows for the first time, in mice, that a peripheral LPS treatment at PND14 differentially alters emotional behaviors, but not spatial memory, at adolescence and adulthood. The behavioral effect of LPS at PND14 could be attributed to HPA axis deregulation and neurogenesis impairment.

The epithelium's barrier function is crucial for maintaining homeostasis and preventing the passage of food antigens and luminal bacteria. This function is essentially subserved by tight junctions (TJs), multiprotein complexes located in the most apical part of the lateral membrane. Some gastrointestinal disease states are associated with elevated intestinal permeability to macromolecules. In a study on rats, we determined the influence of chronic, daily ingestion of chlorpyrifos (CPF, a pesticide that crosses the placental barrier) during pre- and postnatal periods on intestinal permeability and TJ characteristics in the pups. Fluorescein isothiocyanate (FITC)-dextran was used as a marker of paracellular transport and mucosal barrier dysfunction. Pups were gavaged with FITC-dextran solution and blood samples were collected every 30 min for 400 min and analyzed spectrofluorimetrically. At sacrifice, different intestinal segments were resected and prepared for analysis of the transcripts (qPCR) and localization (using immunofluorescence) of ZO-1, occludin and claudins (scaffolding proteins that have a role in the constitution of TJs). In rats that had been exposed to CPF in utero and after birth, we observed a progressive increase in FITC-dextran passage across the epithelial barrier from 210 to 325 min at day 21 after birth (weaning) but not at day 60 (adulthood). At both ages, there were significant changes in intestinal TJ gene expression, with downregulation of ZO-1 and occludin and upregulation of claudins 1 and 4. In some intestinal segments, there were changes in the cellular localization of ZO-1 and claudin 4 immunostaining. Lastly, bacterial translocation to the spleen was also observed. The presence of CPF residues in food may disturb epithelial homeostasis in rats. Changes in TJ protein expression and localization may be involved in gut barrier dysfunction in this model. Uncontrolled passage of macromolecules and bacteria across the intestinal epithelium may be a risk factor for digestive inflammatory diseases.

Abstract Background Titanium dioxide (TiO 2 ) is broadly used in common consumer goods, including as a food additive (E171 in Europe) for colouring and opacifying properties. The E171 additive contains TiO 2 nanoparticles (NPs), part of them being absorbed in the intestine and accumulated in several systemic organs. Exposure to TiO 2 -NPs in rodents during pregnancy resulted in alteration of placental functions and a materno-foetal transfer of NPs, both with toxic effects on the foetus. However, no human data are available for pregnant women exposed to food-grade TiO 2 -NPs and their potential transfer to the foetus. In this study, human placentae collected at term from normal pregnancies and meconium (the first stool of newborns) from unpaired mothers/children were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and scanning transmission electron microscopy (STEM) coupled to energy-dispersive X-ray (EDX) spectroscopy for their titanium (Ti) contents and for analysis of TiO 2 particle deposition, respectively. Using an ex vivo placenta perfusion model, we also assessed the transplacental passage of food-grade TiO 2 particles. Results By ICP-MS analysis, we evidenced the presence of Ti in all placentae (basal level ranging from 0.01 to 0.48 mg/kg of tissue) and in 50% of the meconium samples (0.02–1.50 mg/kg), suggesting a materno-foetal passage of Ti. STEM-EDX observation of the placental tissues confirmed the presence of TiO 2 -NPs in addition to iron (Fe), tin (Sn), aluminium (Al) and silicon (Si) as mixed or isolated particle deposits. TiO 2 particles, as well as Si, Al, Fe and zinc (Zn) particles were also recovered in the meconium. In placenta perfusion experiments, confocal imaging and SEM-EDX analysis of foetal exudate confirmed a low transfer of food-grade TiO 2 particles to the foetal side, which was barely quantifiable by ICP-MS. Diameter measurements showed that 70 to 100% of the TiO 2 particles recovered in the foetal exudate were nanosized. Conclusions Altogether, these results show a materno-foetal transfer of TiO 2 particles during pregnancy, with food-grade TiO 2 as a potential source for foetal exposure to NPs. These data emphasize the need for risk assessment of chronic exposure to TiO 2 -NPs during pregnancy.

OBJECTIVES: Pesticide exposure via residues in food may be especially harmful when it takes place in the developing child. The present study was designed to assess the impact of perinatal exposure to chlorpyrifos (CPF, an insecticide known to cross the placental barrier). METHODS: Female rats were exposed to oral CPF (1 or 5 mg kg day vs vehicle controls) from gestation onset up to weaning of the pups that were individually gavaged (CPF or vehicle) thereafter. Two developmental time points were studied: weaning (day 21) and adulthood (day 60). After sacrifice, samples from the intestinal tract and other organs underwent microbiological and histological analyses. RESULTS: Rat pups exposed to 5 mg kg day CPF were both significantly smaller (body length) and lighter than controls. Exposure to CPF was associated with changes in the histological structures (shorter and thinner intestinal villosities), an intestinal microbial dysbiosis, and increased bacterial translocation in the spleen and liver. These significant microbial changes in the gut were associated with impaired epithelium protection (mucin-2) and microbial pattern recognition receptor (Toll-like 2 and 4) gene expression. CONCLUSIONS: Exposure to CPF during gestation and development affected the pups' intestinal development, with morphological alteration of the structures involved in nutrient absorption, intestinal microbial dysbiosis, alteration of mucosal barrier (mucin-2), stimulation of the innate immune system, and increased bacterial translocation. Perinatal exposure to CPF may therefore have short- and long-term impacts on the digestive tract.

BACKGROUND: The combination of infliximab and immunosuppressant therapy is a standard management strategy for patients with Crohn's disease. Concerns regarding the implications of long-term combination therapy provided the rationale for a formal clinical trial of treatment de-escalation. Our aim was to compare the relapse rate and the time spent in remission over 2 years between patients continuing combination therapy and those stopping infliximab or immunosuppressant therapy. METHODS: This multicentre, open-label, randomised controlled trial was performed in 64 hospitals in seven countries in Europe and Australia. Adult patients with Crohn's disease in steroid-free clinical remission for more than 6 months, on combination therapy of infliximab and immunosuppressant therapy for at least 8 months were randomly assigned (1:1:1) to either continue combination therapy (combination group), discontinue infliximab (infliximab withdrawal group), or discontinue immunosuppressant therapy (immunosuppressant withdrawal group). Randomisation was stratified according to disease duration before start of first anti-TNF treatment (≤2 or >2 years), failure of immunosuppressant therapy before start of infliximab, and presence of ulcers at baseline endoscopy. The patient number and group of each stratum were assigned by a central online randomisation website. Treatment was optimised or resumed in case of relapse in all groups. Participants, those assessing outcomes, and those analysing the data were not masked to group assignment. The coprimary endpoints were the relapse rate (superiority analysis) and time in remission over 2 years (non-inferiority analysis, non-inferiority margin 35 days). Analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT02177071, and with EU Clinical Trials Register, EUDRACT 2014-002311-41. The trial was completed in April, 2021. FINDINGS: Between Nov 2, 2015, and April 24, 2019, 254 patients were screened. Of these, 211 were randomised and 207 were included in the final analysis (n=67 in the combination group, n=71 in the infliximab withdrawal group, and n=69 in the immunosuppressant withdrawal group). 39 patients had a relapse (eight [12%] of 67 in the combination group, 25 [35%] of 71 in the infliximab withdrawal group, six [9%] of 69 in the immunosuppressant withdrawal group). 2-year relapse rates were 14% (95% CI 4-23) in the combination group, 36% (24-47) in the infliximab withdrawal group, and 10% (2-18) in the immunosuppressant withdrawal group (hazard ratio [HR] 3·45 [95% CI 1·56-7·69], p=0·003, for infliximab withdrawal vs combination, and 4·76 [1·92-11·11], p=0·0004, for infliximab withdrawal vs immunosuppressant withdrawal). Of 28 patients who had a relapse and were retreated or optimised according to protocol, remission was achieved in 25 patients (one of two in the combination group, 22 of 23 in the infliximab withdrawal group, and two of three in the immunosuppressant withdrawal group). The mean time spent in remission over 2 years was 698 days (95% CI 668-727) in the combination group, 684 days (651-717) in the infliximab withdrawal group, and 706 days (682-730) in the immunosuppressant withdrawal group. The difference in restricted mean survival time in remission was -14 days (95% CI -56 to 27) between the infliximab withdrawal group and the combination group and -22 days (-62 to 16) between the infliximab withdrawal group and the immunosuppressant withdrawal group. The 95% CIs contained the non-inferiority threshold (-35 days). We recorded 31 serious adverse events, in 20 patients, with no difference in frequency between groups. The most frequent serious adverse events were infections (four in the combination group, two in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group) and Crohn's disease exacerbation (three in the combination group, four in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group). No death nor malignancy was recorded. INTERPRETATION: In patients with Crohn's disease in sustained steroid-free remission under combination therapy with infliximab and immunosuppressant therapy, withdrawal of infliximab should only be considered after careful assessment of risks and benefits for each patient, whereas withdrawal of immunosuppressant therapy could generally represent a preferable strategy when considering treatment de-escalation. FUNDING: European Union's Horizon 2020.

Although inhaled NO (iNO) therapy is often effective in treating infants with persistent pulmonary hypertension of the newborn (PPHN), up to 40% of patients fail to respond, which may be partly due to abnormal expression and function of soluble guanylate cyclase (sGC). To determine whether altered sGC expression or activity due to oxidized sGC contributes to high pulmonary vascular resistance (PVR) and poor NO responsiveness, we studied the effects of cinaciguat (BAY 58-2667), an sGC activator, on pulmonary artery smooth muscle cells (PASMC) from normal fetal sheep and sheep exposed to chronic intrauterine pulmonary hypertension (i.e., PPHN). We found increased sGC α(1)- and β(1)-subunit protein expression but lower basal cGMP levels in PPHN PASMC compared with normal PASMC. To determine the effects of cinaciguat and NO after sGC oxidation in vitro, we measured cGMP production by normal and PPHN PASMC treated with cinaciguat and the NO donor, sodium nitroprusside (SNP), before and after exposure to 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an sGC oxidizer), hyperoxia (fraction of inspired oxygen 0.50), or hydrogen peroxide (H(2)O(2)). After treatment with ODQ, SNP-induced cGMP generation was markedly reduced but the effects of cinaciguat were increased by 14- and 64-fold in PPHN fetal PASMC, respectively (P < 0.01 vs. controls). Hyperoxia or H(2)O(2) enhanced cGMP production by cinaciguat but not SNP in PASMC. To determine the hemodynamic effects of cinaciguat in vivo, we compared serial responses to cinaciguat and ACh in fetal lambs after ductus arteriosus ligation. In contrast with the impaired vasodilator response to ACh, cinaciguat-induced pulmonary vasodilation was significantly increased. After birth, cinaciguat caused a significantly greater fall in PVR than either 100% oxygen, iNO, or ACh. We conclude that cinaciguat causes more potent pulmonary vasodilation than iNO in experimental PPHN. We speculate that increased NO-insensitive sGC may contribute to the pathogenesis of PPHN, and cinaciguat may provide a novel treatment of severe pulmonary hypertension.

This study assessed sperm quality declining on relation to paternal age and its impact on in vitro fertilization (IVF) outcomes in order to estimate the APA (Advanced Paternal Age) cutoff. For this, 83 couples undergoing IVF treatment for male factor infertility were enrolled. The women age was ≤39 years, whereas the men were divided in two groups: APA (n = 41; age ≥ 40 years) and young (Y) (n = 42; age < 40 years). Conventional semen parameters (volume, concentration, motility, vitality, and morphology) were analyzed in the collected sperm samples. Furthermore, sperm genome decays (SGD) was assessed by TUNEL assay (DNA fragmentation), aniline blue staining (chromatin decondensation), and fluorescent in situ hybridization (aneuploidy). No significant difference was found concerning the conventional semen parameters between APA and Y groups. Conversely, SGD analysis showed increased DNA fragmentation; chromatin decondensation and sperm aneuploidy rates in the APA group (respectively, 41%, 43%, and 14% vs. 25%, 23%, and 4% in Y group). IVF outcomes also were affected by paternal age as indicated by the rates of cancelled embryo transfers, clinical pregnancy and miscarriage in the two groups APA and Y (29%, 17%, and 60% vs. 10%, 32%, and 42%). Finally, statistical analysis of the results suggests that the age of 40 should be considered as the APA cutoff during ART attempts.

A holistic approach of a mould cheese ripening is presented. The objective was to establish relationships between the different microbiological and biochemical changes during cheese ripening. Model cheeses were prepared from pasteurized milk inoculated with Kluyveromyces lactis , Geotrichum candidum , Penicillium camemberti and Brevibacterium linens under aseptic conditions. Two cheese-making trials with efficient control of environmental parameters were carried out and showed similar ripening characteristics. K. lactis grew rapidly between days 1 and 6 (generation time around 48 h). G. candidum grew exponentially between days 4 and 10 (generation time around 4·6 d). Brevi. linens also grew exponentially but after day 6 when Pen. camemberti mycelium began developing and the pH of the rind was close to 7. Its exponential growth presented 3 phases in relation to carbon and nitrogen substrate availability. Concentrations of Pen. camemberti mycelium were not followed by viable cell count but they were evaluated visually. The viable microorganism concentrations were well correlated with the carbon substrate concentrations in the core and in the rind. The lactose concentrations were negligible after 10 d ripening, and changes in lactate quantities were correlated with fungi flora. The pH of the inner part depended on NH 3 . Surface pH was significantly related to NH 3 concentration and to fungi growth. The acid-soluble nitrogen (ASN) and non-protein nitrogen (NPN) indexes and NH 3 concentrations of the rind were low until day 6, and then increased rapidly to follow the fungi concentrations until day 45. The ASN and NPN indexes and NH 3 concentrations in the core were lower than in the rind and they showed the same evolution. G. candidum and Pen. camemberti populations have a major effect on proteolysis; nevertheless, K. lactis and Brevi. linens cell lysis also had an impact on proteolysis. Viable cell counts of K. lactis , G. candidum , Pen. camemberti and Brevi. linens were correlated with the environmental conditions, with proteolytic products and with carbon substrate assimilation. NH 3 diffusion from surface to the cheese core during ripening was highly suspected. Interaction phenomena between microorganisms are discussed.

The first months of life correspond to a key period in human life where dramatic physiological changes (establishment of microbiota, development of the immune system, etc.) occur. In order to better control these changes it is necessary to understand the behaviour of food in the gastrointestinal tract of the newborn. Infant formula is the only food for the newborn when breast-feeding is impossible. The kinetics of digestion of milk proteins and the nature of the peptides liberated in the small intestine throughout infant formula digestion have never been extensively investigated so far and were therefore studied using the piglet as a model of the newborn child. Piglets were fed infant formula by an automatic delivery system during 28 d, and slaughtered 30, 90 and 210 min after the last meal. Contents of stomach, proximal and median jejunum and ileum were collected and characterised. The extent of β-lactoglobulin (β-lg), α-lactalbumin (α-la) and casein proteolysis was monitored by inhibition ELISA, SDS-PAGE, immunoblotting and MS. At 30 min after the last meal, caseins were shown to be extensively hydrolysed in the stomach. Nevertheless, peptides originating mainly from β-caseins (from 509 to 2510 Da) were identified in the jejunum and ileum of the piglets. β-Lg partially resisted gastric digestion but completely disappeared in the stomach after 210 min. α-La had a similar behaviour to that of β-lg. Two large peptides (4276 and 2674 Da) generated from β-lg were present in the ileum after 30 and 210 min and only one (2674 Da) after 90 min.

The effects of exposure to radiofrequency electromagnetic fields (EMF), specifically related to the use of mobile telephones, on the nervous system in humans have been the subject of a large number of experimental studies in recent years. There is some evidence of an effect of exposure to a Global System for Mobile Telecommunication (GSM)-type signal on the spontaneous electroencephalogram (EEG). This is not corroborated, however, by the results from studies on evoked potentials. Although there is some evidence emerging that there may be an effect of exposure to a GSM-type signal on sleep EEG, results are still variable. In summary, exposure to a GSM-type signal may result in minor effects on brain activity, but such changes have never been found to relate to any adverse health effects. No consistent significant effects on cognitive performance in adults have been observed. If anything, any effect is small and exposure seems to improve performance. Effects in children did not differ from those in healthy adults. Studies on auditory and vestibular function are more unequivocal: neither hearing nor the sense of balance is influenced by short-term exposure to mobile phone signals. Subjective symptoms over a wide range, including headaches and migraine, fatigue, and skin itch, have been attributed to various radiofrequency sources both at home and at work. However, in provocation studies a causal relation between EMF exposure and symptoms has never been demonstrated. There are clear indications, however, that psychological factors such as the conscious expectation of effect may play an important role in this condition.

INTRODUCTION: New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. METHODS: We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. RESULTS: Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. DISCUSSION: Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.

BACKGROUND: In critically ill patients at risk for organ failure, the administration of intravenous fluids has equal chances of resulting in benefit or harm. While the intent of intravenous fluid is to increase cardiac output and oxygen delivery, unwelcome results in those patients who do not increase their cardiac output are tissue edema, hypoxemia, and excess mortality. Here we briefly review bedside methods to assess fluid responsiveness, focusing upon the strengths and pitfalls of echocardiography in spontaneously breathing mechanically ventilated patients as a means to guide fluid management. We also provide new data to help clinicians anticipate bedside echocardiography findings in vasopressor-dependent, volume-resuscitated patients. OBJECTIVE: To review bedside ultrasound as a method to judge whether additional intravenous fluid will increase cardiac output. Special emphasis is placed on the respiratory effort of the patient. CONCLUSIONS: Point-of-care echocardiography has the unique ability to screen for unexpected structural findings while providing a quantifiable probability of a patient's cardiovascular response to fluids. Measuring changes in stroke volume in response to either passive leg raising or changes in thoracic pressure during controlled mechanical ventilation offer good performance characteristics but may be limited by operator skill, arrhythmia, and open lung ventilation strategies. Measuring changes in vena caval diameter induced by controlled mechanical ventilation demands less training of the operator and performs well during arrythmia. In modern delivery of critical care, however, most patients are nursed awake, even during mechanical ventilation. In patients making respiratory efforts we suggest that ventilator settings must be standardized before assessing this promising technology as a guide for fluid management.

After a short historical overview of past systematic studies on Cantharellus, discussing delimitation and species diversity of the genus as well as previous, morphology-based, infrageneric classifications, this paper presents the first molecularly-based infrageneric classification of this genus using a multigene phylogenetic approach (nucLSU, mitSSU, RPB2 and tef-1) on a dataset that covers approximately halve of the described chanterelles worldwide, including many type specimens. Six subgenera are recognized and the recognition of subgenus Afrocantharellus as a separate genus is not accepted. The taxonomic value of individual morphological features is discussed as challenged by this new multigene phylogeny which comprises five new sections, one new subgenus and many emendations for previously recognized infrageneric groups. The paper discusses the observed discrepancy in biodiversity of Cantharellus when comparing between studies that focus either on below- or above-ground presence. A preliminary biogeographic hypothesis suggests an ‘out of Africa’ Gondwanan origin as a result of vicariance and subsequent migrations.

Alcohol intake and cigarette smoking are the major lifestyle factors with negative impact on fertility. We were interested to evaluate the negative impact of these factors on oxidative stress (OS), enzymatic antioxidant activity (EAO) of spermatozoa and on its DNA damage. This study included 108 male infertile patients with normal range of sperm conventional parameters but with unexplained infertility in assisted reproductive technologies programme. Firstly, OS was analysed based on lipid peroxidation (MDA) and EAO which included catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR). Secondly, we evaluated DNA fragmentation by TUNEL assay and chromatin decondensation by aniline blue colouration. The whole lot was divided into four groups: control (nonalcoholic and nonsmoker patients), alcohol group, smoking group and alcohol-smoking group. The results showed, in three last groups compared to control an increased CAT, SOD and GR activities with high MDA level especially in smoking and alcohol-smoking group. The latter showed the highest values of DNA fragmentation and chromatin decondensation (31% and 39%) to exceed DNA damage normal range. Indeed, smoking and alcohol intake lead to increase EAO due to long-term unbalanced antioxidant/oxidation ratio with high OS which cause consequently sperm DNA damage calling in need by urgency to change the lifestyle behaviour.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic, with four million confirmed cases and 280 000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID-19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID-19 patients with vs without diabetes. METHODS: All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID-19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analysed separately in a logistic regression analysis and a Cox proportional hazards model. RESULTS: A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non-ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66-1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40-1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09-3.92, P = .027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death. CONCLUSIONS: Diabetes was prevalent in a quarter of the patients hospitalized with COVID-19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID-19 severity and diabetes is warranted.

RATIONALE: Methacholine (Mch) is routinely used to assess bronchial hyperreactivity; however, little is known about the differences in the lung response pattern between this provocation and that observed with ovalbumin (Ova) after allergic sensitization. OBJECTIVES: To compare (1) the central versus peripheral effects of Mch and Ova within the lung by combining measurements of airway and tissue mechanics with synchrotron radiation (SR) imaging, and (2) to assess the extent to which mechanical and imaging parameters are correlated. METHODS: We used the low-frequency forced oscillation technique and SR imaging in control (n = 12) and ovalbumin-sensitized (n = 13) rabbits, at baseline, during intravenous Mch infusion (2.5 microg/kg/min, 5.0 microg/kg/min, or 10.0 microg/kg/min), after recovery from Mch, and after intravenous Ova injection (2.0 mg). We compared intravenous Mch challenge with inhaled Mch (125 mg/ml, 90 s) in a separate group of control animals (n = 5). MEASUREMENTS AND MAIN RESULTS: Airway conductance and tissue elastance were measured by low-frequency forced oscillation technique. The central airway cross-sectional area, the ventilated alveolar area, and the heterogeneity of specific ventilation were quantified by SR imaging. Mch infusion induced constriction predominantly in the central airways, whereas Ova provocation affected mainly the peripheral airways, leading to severe ventilation heterogeneities in sensitized animals. Mch inhalation affected both conducting and peripheral airways. The correlations between airway conductance and central airway cross-sectional area (R = 0.71) and between tissue elastance and ventilated alveolar area (R = -0.72) were strong. CONCLUSIONS: The pattern of lung response caused by intravenous Mch and Ova are fundamentally different. Although inhaled Mch induces a heterogeneous lung response similar to that observed with intravenous allergen, these similar patterns are due to different mechanisms.

INTRODUCTION: High cesarean section (CS) rates are observed in patients with inflammatory bowel disease (IBD), but limited data are available to support this decision. We conducted a comprehensive review to evaluate the most appropriate mode of delivery in women with IBD according to disease phenotype and activity, as well as surgical history. MATERIALS AND METHODS: We searched MEDLINE (source PubMed) and international conference abstracts, and included all studies that evaluated digestive outcome after delivery in patients with IBD. RESULTS: A total of 41 articles or abstracts were screened, and 18 studies were considered in this review, with sample sizes ranging from 4 to 229 patients and follow-up ranging from 2 months to 7.7 years. Pooled CS rates in patients without Perianal Crohn's disease (PCD), healed PCD or active PCD, were 27%, 43%, and 46%, respectively. Regarding the median rate of new PCD (3.0% [IQR, 1.5-11.5] versus 6.5% [0-19.7]) or PCD recurrence (13.5% [3.2-32.7] versus 45% [0-58]), no increase was observed in patients with vaginal delivery compared to CS, but for patients with an active disease, worsening of symptoms was noted in two-thirds of cases. Episiotomy, perianal tears, and instrumental delivery did not influence the incidence of PCD. In patients with ileal pouch anal anastomosis, uncomplicated vaginal delivery seemed to moderately influence pouch function, with no significant difference in terms of overall continence, daytime, or night-time stool frequency, or incontinence. However, these parameters seemed negatively impacted by a complicated vaginal delivery. CONCLUSIONS: New long-term data from well-designed studies are needed, but our review suggests that systematic CS in patients suffering from IBD should probably be limited to women at risk of perineal tears and obstetric injuries, with an active PCD, or with ileal pouch anal anastomosis.