Protein expression of angiotensin-converting enzyme 2, a SARS-CoV-2-specific receptor, in fetal and placental tissues throughout gestation: new insight for perinatal counseling.

OBJECTIVE: Pregnant women can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet the incidence of perinatal infection is low. We hypothesized that this could be related to low expression of the membrane receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), in the fetoplacental unit. We evaluated protein expression of ACE2 at various gestational ages in both placentae and fetal organs from pregnancies not infected with SARS-CoV-2. METHODS: In May 2020, using samples from a registered biobank, we performed immunohistochemical analysis for ACE2 in tissue samples from fetal organs and placentae from five cases of second- or third-trimester medical termination of pregnancy in healthy women (performed between 15 and 38 weeks' gestation), as well as a further two placentae, one from a 7-week spontaneous miscarriage in a non-infected woman and one from a symptomatic pregnant woman positive for SARS-CoV-2 delivered by Cesarean section at 34 weeks. Samples were paraffin-embedded and organ tissues included kidney, brain, lung, intestinal tract, heart and testis. Matching tissues (kidney, intestinal tract, lung and testis) from autopsies of four 8-year-old children were tested as controls. Tissue sections were incubated with rabbit monoclonal anti-ACE2, and protein expression of ACE2 was detected by immunohistochemistry. RESULTS: ACE2 expression was detected in fetal kidney, rectum and ileum samples from 15 weeks onwards and in the pediatric controls. It was barely detectable in fetal lung samples at 15 + 5 weeks' gestation and not detectable thereafter, and, in the pediatric controls, ACE2 was detectable only in type-2 pneumocytes. No ACE2 expression was found in the cerebral ependymal or parenchymal tissues or in cardiac tissues. ACE2 was expressed in placental syncytiotrophoblast and cytotrophoblast samples, but not in the amnion, from 7 weeks onwards. The intensity and distribution of ACE2 staining in the placenta from the symptomatic SARS-CoV-2 woman was similar to that in the non-infected placentae. CONCLUSIONS: Marked placental expression of ACE2 provides a rationale for vertical transmission at the cellular level. Absence of ACE2 expression in the fetal brain and heart is reassuring regarding the risk of congenital malformation. Clinical follow-up of infected pregnant women and their children is needed to validate these observations. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Successful therapeutic plasma exchange in cold autoimmune hemolytic anemia in patient with disseminated tuberculosis.

An association of autoimmune hemolytic anemia with disseminated tuberculosis is an exceedingly rare entity. We describe herein a case of cold hemolytic autoimmune anemia associated with miliary tuberculosis resolved with blood transfusions, therapeutic plasma exchange, and antituberculous agents. We discuss the advantages of therapeutic plasma exchange at an early stage in the management of this condition.

[Validation of the French version of the Binge Eating Scale: Examination of its factor structure, internal consistency and construct validity in a non-clinical and a clinical population]. / Validation de la version française de la Binge Eating Scale : étude de sa structure factorielle, de sa consistance interne et de sa validité de construit en population clinique et non clinique.

OBJECTIVE: The Binge Eating Scale is a widely used scale to assess binge eating disorder in obese patients. Until now, this scale has not been validated on a French population, and no psychometrically sound tool assesses binge eating disorder in the French. This study aimed to test the psychometric properties of a French version of the Binge Eating Scale by establishing its factor structure, internal consistency, and construct validity in both a non-clinical population and a clinical population (obese patients who are candidates for bariatric surgery). METHODS: A total of 553 non-clinical subjects and 63 morbidly obese patients who were candidates for bariatric surgery were assessed with the BES and the Bulimic Investigatory Test, Edinburgh or BITE (which assesses both binge eating behaviours and use of inappropriate compensatory behaviours). We tested the factor structure of the instrument, its internal consistency, its construct validity with measures of binge eating, and its construct validity with measures of inappropriate compensatory behaviours to avoid weight gain. In 47 out of the 63 obese patients, we assessed binge eating disorder (SCID). RESULTS: In the non-clinical population, the BES had a one-factor structure (which accounted for 61% of the variance), excellent internal consistency (α=0.93), and high construct validity with measures of binge eating. In this population, construct validity with measures of inappropriate compensatory behaviours was confirmed in overweight and obese subjects (P=0.42), but not in underweight and optimal weight subjects (P<0.001). In obese patients candidates for bariatric surgery, we demonstrated that the BES had a one-factor structure (which accounted for 46% of the variance), had high internal consistency (α=0.88) and high construct validity with measures of binge eating and good construct validity with measures of inappropriate compensatory behaviours to avoid weight gain. In the subpopulation of 47 obese patients, sensitivity, specificity, positive predictive value and negative predictive value were respectively 75%, 88.4%, 37.5% and 97.4% (BES threshold=18). DISCUSSION: In this study, we validated a psychometrically sound French version of the Binge Eating Scale, both in a non-clinical and a clinical sample. The psychometric properties of the French version of the BES are comparable to its original version with a one-factor structure. The BES is a useful tool to assess binge eating disorder in obese patients (e.g., bariatric surgery candidates), but might not differentiate between binge eating disorder and bulimia nervosa in underweight and optimal weight subjects.

Evaluation of PNEC values: extrapolation from Microtox, algae, daphnid, and fish data to HC5.

In order to evaluate the risk to the environment from long term exposure of any discharged substance, toxicity thresholds are estimated, and particularly the Predicted No Effect Concentration (PNEC). This concentration can be estimated by the classic assessment factor approach or by statistical methods. These are more scientifically sound but they require several (at least 5-6) chronic ecotoxicity data, implying greater cost and time. New extrapolation methods derived from the statistical concept but requiring less data have been studied. Results show that methods based on chronic data are more reliable than methods based on acute data but the improvement is quite small. Considering the costs of chronic tests compared to acute tests, approaches based on acute data are an attractive alternative. A simple regression on the mean of the acute data gives the best results.

Statistical analysis of regulatory ecotoxicity tests.

ANOVA-type data analysis, i.e.. determination of lowest-observed-effect concentrations (LOECs), and no-observed-effect concentrations (NOECs), has been widely used for statistical analysis of chronic ecotoxicity data. However, it is more and more criticised for several reasons, among which the most important is probably the fact that the NOEC depends on the choice of test concentrations and number of replications and rewards poor experiments, i.e., high variability, with high NOEC values. Thus, a recent OECD workshop concluded that the use of the NOEC should be phased out and that a regression-based estimation procedure should be used. Following this workshop, a working group was established at the French level between government, academia and industry representatives. Twenty-seven sets of chronic data (algae, daphnia, fish) were collected and analysed by ANOVA and regression procedures. Several regression models were compared and relations between NOECs and ECx, for different values of x, were established in order to find an alternative summary parameter to the NOEC. Biological arguments are scarce to help in defining a negligible level of effect x for the ECx. With regard to their use in the risk assessment procedures, a convenient methodology would be to choose x so that ECx are on average similar to the present NOEC. This would lead to no major change in the risk assessment procedure. However, experimental data show that the ECx depend on the regression models and that their accuracy decreases in the low effect zone. This disadvantage could probably be reduced by adapting existing experimental protocols but it could mean more experimental effort and higher cost. ECx (derived with existing test guidelines, e.g., regarding the number of replicates) whose lowest bounds of the confidence interval are on average similar to present NOEC would improve this approach by a priori encouraging more precise experiments. However, narrow confidence intervals are not only linked to good experimental practices, but also depend on the distance between the best model fit and experimental data. At least, these approaches still use the NOEC as a reference although this reference is statistically not correct. On the contrary, EC50 are the most precise values to estimate on a concentration response curve, but they are clearly different from the NOEC and their use would require a modification of existing assessment factors.

[Suicidal children and adolescents]. / Enfants et adolescents suicidants.

BACKGROUND: Psychiatric evaluation of suicide attempters is necessary in order to define aspects of primary and secondary prevention of suicidal behavior. POPULATION AND METHODS: All the 80 children and adolescents (66 girls and 14 boys) admitted from September 1989 to September 1992 in a pediatric hospital for suicide attempt have been included in this study. Their mean age was 13 yr 10 mo +/- 1.4 and 81% of them were more than 13 years of age. Evaluation included a structured interview and a scale assessing general psychopathology. RESULTS: Risk factors included previous psychiatric history in the patient (47%), family history of psychiatric disturbances in 33% of the mothers, 15% of the fathers and 13% in both. Recent modification in familial composition was seen in one third of cases and chronic difficulties in parent/child interaction in 92%. A relationship between the non impulsivity of the suicidal gesture, psychiatric history and depression diagnosed at the time of evaluation was also recognized. CONCLUSIONS: Knowledge of these risk factors should help to prevent and treat some aspects of suicidal behavior.

[Eating behaviors and emotional symptoms in childhood obesity: a cross-sectional exploratory study using self-report questionnaires in 63 children and adolescents]. / Conduites alimentaires et symptômes émotionnels dans l'obésité infantile : étude exploratoire transversale à partir d'autoquestionnaires chez 63 enfants et adolescents.

OBJECTIVES: The main objective was to assess emotional symptoms (anxiety and depression) and to describe eating behaviours in a population of children and adolescents consulting for obesity. The second objective was to examine the interactions between these parameters. METHOD: A cross-sectional exploratory study in obese children and adolescents was conducted using self-report questionnaires for depression (Child Depression Inventory), anxiety (State-Trait Anxiety Inventory for Children), binge eating (Binge Eating Scale adapted for children), emotional, external, and restrained eating (Dutch Eating Behaviour Questionnaire adapted for children) in obese children and adolescents, from both sexes, aged 7-15 years old. RESULTS: Fourty-one children and 22 adolescents were assessed, two-third were female, the mean age was 11 years ± 2.3 and the mean BMI z-score was 4.2 ± 0.9. Nearly half had significant anxiety, nearly one-third had depressive symptoms, and 15% had severe binge eating symptoms. Girls reported more anxiety than boys. Emotional and external eating, binge eating, and emotional symptoms were strongly associated. Binge eating was independently associated with emotional eating, depression, and anxiety (r=0.86, P<0.001). DISCUSSION: Emotional eating and emotional symptoms were strongly associated in the child and adolescent overweight population in these out-patient pediatric departments. CONCLUSION: Emotional symptoms and eating behavior assessments are needed in overweight children and adolescents in order to implement multidisciplinary treatment.

Association between symptoms of attention-deficit/hyperactivity disorder and bulimic behaviors in a clinical sample of severely obese adolescents.

OBJECTIVE: Preliminary evidence suggests a comorbidity between attention-deficit/hyperactivity disorder (ADHD) and obesity. This study was carried out to identify the clinical characteristics of obese adolescents with a higher probability of ADHD and advance the understanding of the potential factors underlying the comorbidity between obesity and ADHD. We evaluated the association between ADHD symptoms and bulimic behaviors, depressive and anxiety symptoms, degree of obesity, pubertal stage, age and gender in a clinical sample of obese adolescents. DESIGN: Cross-sectional study. SUBJECTS: Ninety-nine severely obese adolescents aged 12-17 years. MEASUREMENTS: Subjects filled out the Bulimic Investigatory Test, Edinburgh, the Beck Depression Inventory and the State-Trait Anxiety Inventory for Children. Their parents completed the Conners Parent Rating Scale, which assesses ADHD symptoms. The degree of overweight was expressed as body mass index-z score. Puberty development was clinically assessed on the basis of Tanner stages. RESULTS: Bulimic behaviors were significantly associated with ADHD symptoms after controlling for depressive and anxiety symptoms. The degree of overweight, pubertal stage, age and gender were not significantly associated with ADHD symptoms. CONCLUSION: Obese adolescents with bulimic behaviors may have a higher probability to present with ADHD symptoms independently from associated depressive or anxiety symptoms. The degree of overweight, pubertal stage, age and gender might not be useful for detecting obese adolescents with ADHD symptoms. Therefore, we suggest systematic screening for ADHD in obese adolescents with bulimic behaviors. Further studies are needed to understand which specific dimension of ADHD primarily accounts for the association with bulimic behaviors. Future research should also investigate the causal link between bulimic behaviors and ADHD and explore potential common neurobiological alterations. This may lead to a better understanding of the effectiveness of stimulants for the treatment of bulimic behaviors in obese subjects.

Assessing the environmental impact of wastewaters.

The conventional approach for assessing the environmental impact of wastewaters uses a set of global physicochemical and ecotoxicological parameters and is well adapted to the vast majority of wastewaters. When some chemicals may be particularly harmful for the environment, a specific approach based on a comparison between the predicted environmental concentration (PEC) and the predicted no-effect concentration (PNEC) may be used. The four steps of extrapolation required for PNEC evaluation are discussed and the importance of the interspecies extrapolation is highlighted. It may also be useful to use an integrated approach relating the characteristics of the wastewater to that of specific compounds. For physicochemical parameters, a simple addition is adequate, whereas, for ecotoxicity, the problem is more complex. The toxicity of a mixture of compounds acting by the same mechanism is often described by the concentration addition model. Although this model is very useful for practical applications owing to its simplicity, a statistical evaluation of its performance indicates that it slightly over-predicts the toxicity of mixtures. A new model derived from the statistically sound "independence action" principle and based on a precise mathematical description of the dose-response relationship is proposed. Applications of this model to mixtures tested with algae demonstrate the accuracy of this model with the experimental data.

Critical analysis of methods for assessment of predicted no-effect concentration.

Current risk assessment procedures for chemical substances are based on hazard quotients and require determination of a predicted no-effect concentration (PNEC). These concentrations are usually computed by applying an assessment factor to the lowest available toxicity value. However, other approaches have also been proposed based on statistical distribution of ecotoxicity data. This paper compares the various approaches in terms of precision and robustness. When only a few data are available, an assessment factor approach can be used. However, whenever possible (i.e. for a large set of chronic data), a statistical approach like that developed by T. Aldenberg and W. Slob (1991, Confidence Limits for Hazardous Concentrations Based on Logistically Distributed NOEC Toxicity Data, RIVM Report 71902002) with a 50% confidence level is the most precise and provides a stable value with increasing confidence when the number of tests increases.

Altered lymphoid development in mice deficient for the mAF4 proto-oncogene.

Some chromosomal translocations in acute leukemias involve the fusion of the trithorax-related protein Mll (also called HRX, All1, Htrx,) with a variety of heterologous proteins. In acute lymphoblastic leukemia associated with the t(4;11)(q21;q23) translocation, the 4q21 gene that fuses with Mll is AF4. To gain insight into the potential role of AF4 in leukemogenesis and development, this gene was inactivated by homologous recombination in mice. As expected from the tissue distribution of the AF4 transcript, development of both B and T cells is affected in AF4 mutant mice. A severe reduction of the thymic double positive CD4/CD8 (CD4(+)/CD8(+)) population was observed; in addition most double- and single-positive cells expressed lower levels of CD4 and CD8 coreceptors. Most importantly, the reconstitution of the double-positive compartment by expansion of the double-negative cell compartment was severely impaired in these mutant mice. In the bone marrow pre-B and mature B-cell numbers are reduced. These results demonstrate that the function of the mAF4 gene is critical for normal lymphocyte development. This raises the possibility that the disruption of the normal AF4 gene or its association with Mll function by translocation may orient the oncogenic process toward the lymphoid lineage. This represents the first functional study using a knock-out strategy on one of the Mll partner genes in translocation-associated leukemias. (Blood. 2000;96:705-710)