SARS-CoV-2 Transmission in Belgian French-Speaking Primary Schools: An Epidemiological Pilot Study

Schools have been a point of attention during the pandemic, and their closure one of the mitigating measures taken. A better understanding of the dynamics of the transmission of SARS-CoV-2 in elementary education is essential to advise decisionmakers. We conducted an uncontrolled non-interventional prospective study in Belgian French-speaking schools to describe the role of attending asymptomatic children and school staff in the spread of COVID-19 and to estimate the transmission to others. Each participant from selected schools was tested for SARS-CoV-2 using a polymerase chain reaction (PCR) analysis on saliva sample, on a weekly basis, during six consecutive visits. In accordance with recommendations in force at the time, symptomatic individuals were excluded from school, but per the study protocol, being that participants were blinded to PCR results, asymptomatic participants were maintained at school. Among 11 selected schools, 932 pupils and 242 school staff were included between January and May 2021. Overall, 6449 saliva samples were collected, of which 44 came back positive. Most positive samples came from isolated cases. We observed that asymptomatic positive children remaining at school did not lead to increasing numbers of cases or clusters. However, we conducted our study during a period of low prevalence in Belgium. It would be interesting to conduct the same analysis during a high prevalence period.     

Effect of Dapoxetine on Ejaculatory Performance and Related Brain Neuronal Activity in Rapid Ejaculator Rats

IntroductionA brain network specifically activated when ejaculation occurs has been described in rats. Increasing serotonin (5‐hydroxytryptamine [5‐HT]) tone impairs ejaculation and chronic 5‐HT selective serotonin reuptake inhibitors (SSRIs) are known to inhibit ejaculation. However, efficacy of acute treatment with SSRI varies from one compound to another. The SSRI dapoxetine has been reported to delay ejaculation when given on demand to men with premature ejaculation (PE), although the mechanism of action is unclear. Effects of acute SSRIs on activity of the brain ejaculation circuit in relation with ejaculation have never been examined.AimTo test the effects of acute administration of the short half‐life SSRI dapoxetine on ejaculatory performance and activity in brain ejaculation circuit in rapid ejaculator rats taken as PE model.MethodsStandard copulatory test was used to attribute one sexual category (sluggish, middle, or rapid) to male rats on the basis of their ejaculatory performance. Parameters of sexual, including ejaculatory, behavior, and Fos level of expression in discrete brain areas were assessed in the three sexual categories and in rapid category following acute oral treatment with dapoxetine.Main Outcome MeasuresEjaculation frequency (EF) and latency (EL) were measured as primary end points of ejaculatory behavior. Density of Fos‐immunopositive cells in specific brain areas of brain stem, hypothalamus, and thalamus was determined as marker of neuronal activity.ResultsEL and Fos level of expression in hypothalamic and thalamic structures were found related. Dapoxetine acute oral administration (300 mg/kg) to rapid ejaculator rats resulted in (i) diminution of ejaculatory performance (lengthened EL and decreased EF); and (ii) modulation of Fos level of expression in hypothalamic and thalamic nuclei of the brain ejaculatory circuit.ConclusionAcute treatment with dapoxetine, which reduced ejaculatory performance in rapid ejaculator rats, was also accompanied with changes in neuronal activity in components of the brain ejaculatory network. Clément P, Laurin M, Compagnie S, Facchinetti P, Bernabé J, Alexandre L, and Giuliano F. Effect of dapoxetine on ejaculatory performance and related brain neuronal activity in rapid ejaculator rats. J Sex Med **;**:**–**.     

Clear-cell Renal Cell Carcinoma: Molecular Characterization of IMDC Risk Groups and Sarcomatoid Tumors

IntroductionRecent trials have suggested predictive biomarkers in advanced clear-cell renal cell carcinoma (accRCC): International Metastatic RCC Database Consortium (IMDC) good risk or angiogenic gene signature for sunitinib and IMDC intermediate/poor risk for ipilimumab-nivolumab and T-effector cell signature or sarcomatoid dedifferentiation for atezolizumab-bevacizumab. We hypothesized that earlier described molecular subtypes, ccrcc1 to ccrcc4, could provide similar information as a single generic biomarker and molecularly characterize the heterogeneous intermediate-risk group.Patients and MethodsPatients with accRCC treated with systemic therapies were included. We assessed associations between the 5 biomarkers and their impact on progression-free survival (PFS) and response rate (RR) on first-line sunitinib or pazopanib. The cutoff percentage of sarcomatoid dedifferentiation with optimal discriminative value was determined.ResultsIn total, 430 patients were included (163 with molecular data). The molecular ccrcc2 subtype identified tumors with higher angiogenic gene expression across IMDC risk groups: prevalence was high in IMDC good risk and low in IMDC poor risk (P < .001). Molecular subtype, IMDC, and angiogenic gene expression had comparable C-indices to predict PFS and RR (range, 60%-66%). The ccrcc2 subtype and angiogenic gene expression were positive predictors of PFS in IMDC intermediate-risk patients (P = .006; P = .04). Immune signature did not differ between IMDC groups, but was strongly correlated with molecular subtype (P = .8 and P = .0007). A cutoff value of 25% sarcomatoid differentiation discriminated tumors with distinct molecular characteristics and therapeutic sensitivity.ConclusionIn accRCC, molecular subtypes can explain differences in IMDC risk group, expression of angiogenesis and immune response genes, and sarcomatoid dedifferentiation. They can identify molecularly different patient populations within the heterogeneous IMDC intermediate group and select patients for systemic therapies.     

Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients.

PURPOSE: Scarce information is available on the brain penetration of temozolomide (TMZ), although this novel methylating agent is mainly used for the treatment of malignant brain tumors. The purpose was to assess TMZ pharmacokinetics in plasma and cerebrospinal fluid (CSF) along with its inter-individual variability, to characterize covariates and to explore relationships between systemic or cerebral drug exposure and clinical outcomes. EXPERIMENTAL DESIGN: TMZ levels were measured by high-performance liquid chromatography in plasma and CSF samples from 35 patients with newly diagnosed or recurrent malignant gliomas. The population pharmacokinetic analysis was performed with nonlinear mixed-effect modeling software. Drug exposure, defined by the area under the concentration-time curve (AUC) in plasma and CSF, was estimated for each patient and correlated with toxicity, survival, and progression-free survival. RESULTS: A three-compartment model with first-order absorption and transfer rates between plasma and CSF described the data appropriately. Oral clearance was 10 liter/h; volume of distribution (V(D)), 30.3 liters; absorption constant rate, 5.8 h(-1); elimination half-time, 2.1 h; transfer rate from plasma to CSF (K(plasma-->CSF)), 7.2 x 10(-4)h(-1) and the backwards rate, 0.76 h(-1). Body surface area significantly influenced both clearance and V(D), and clearance was sex dependent. The AUC(CSF) corresponded to 20% of the AUC(plasma). A trend toward an increased K(plasma-->CSF) of 15% was observed in case of concomitant radiochemotherapy. No significant correlations between AUC in plasma or CSF and toxicity, survival, or progression-free survival were apparent after deduction of dose-effect. CONCLUSIONS: This is the first human pharmacokinetic study on TMZ to quantify CSF penetration. The AUC(CSF)/AUC(plasma) ratio was 20%. Systemic or cerebral exposures are not better predictors than the cumulative dose alone for both efficacy and safety.     

Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow’s milk

Background

Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy. However, its pathogenesis remains poorly understood and biomarkers are lacking. We aimed to perform in-depth characterization of humoral and cellular immune responses in children with cow’s milk (CM)-FPIES and investigated whether there is a FPIES metabolomic signature.

Methods

Children with CM-FPIES and control subjects with an IgE-mediated CM allergy (IgE-CMA), both avoiding CM, were recruited on the day of an oral food challenge. Blood samples were collected before the challenge. Total and specific levels of IgE, IgG1-4, IgA, IgM and IgD to various whey and casein allergens and to their gastroduodenal digestion products were measured in plasma, using plasma from CM-tolerant peanut allergic patients (IgE-PA, not avoiding CM) as additional controls. Cytokine secretion and cellular proliferation were analyzed after stimulation of PBMC with different CM allergens. Metabolomic profiles were obtained for plasma samples using liquid chromatography coupled to high-resolution mass spectrometry.

Results

Nine children with CM-FPIES and 12 control subjects (6 IgE-CMA and 6 IgE-PA) were included. In children with CM-FPIES, total Ig concentrations were lower than in control subjects, specific Ig against CM components were weak to undetectable, and no specific IgE against CM digestion products were detected. Moreover, in CM-FPIES patients, we did not find any Th cell proliferation or associated cytokine secretion after allergen reactivation, whereas such responses were clearly found in children with IgE-CMA. Plasma metabolic profiles were different between CM allergic patients, with significantly lower concentrations of various fatty acids and higher concentrations of primary metabolites such as amino acids in CM-FPIES compared to IgE-CMA patients.

Conclusions

In CM-FPIES, both humoral and cellular specific immune responses are weak or absent, and this is not related to CM avoidance. A metabolomic signature was identified in patients with CM-FPIES that may be useful for the diagnosis and management of this disease.

     

Dynamics of cerebral edema and the apparent diffusion coefficient of water changes in patients with severe traumatic brain injury. A prospective MRI study

The distinction between intracellular (ICE) and extracellular edema (ECE) has a crucial prognostic and therapeutic importance in patients with severe traumatic brain injury (STBI). Indeed, ICE usually leads to cellular death, and maintenance of a cerebral perfusion pressure (CPP) above 70 mmHg is still under debate since this practice may increase ECE. The purpose of this study was to describe the ECE and ICE kinetics associated with STBI using quantitative diffusion MRI. Twelve patients were prospectively studied. The initial ADC in ICE measured on day 1.3±0.7 is significantly reduced compared to normal-appearing parenchyma (0.51±0.12 * 10⁻³ mm²/s vs. 0.76±0.03 * 10⁻³ mm²/s, n=12, P<0.0001) and reaches normality on MRI 3 performed on day 14.2±3.3. In patients presenting an extension of ICE on MRI 2 performed on day 6.7±1.4 (ADC_MRI2=0.40±0.11 * 10⁻³ mm²/s), ADC values in the extension area at the first MRI were slightly, but not significantly reduced compared to normal parenchyma (0.69±0.05 * 10^-3 mm²/s, P=0.29). Normalization occurred equally by day 14. ADC in ECE (1.34±0.22 * 10⁻³ mm²/s) was elevated and stable with time under CPP therapy. Therefore, ECE is not worsened by CCP therapy, and ICE appears more relevant than ECE in STBI.     

Performances of creatinine‐based glomerular filtration rate estimating equations in simultaneous pancreas‐kidney transplant recipients: a single center cohort study

Estimating glomerular filtration rate (GFR) is important for clinical management and research studies in simultaneous pancreas‐kidney transplantation (SPK) recipients. No study has specifically investigated the reliability of recent creatinine–based GFR estimating equations in this singular population. We assessed the performances of CKD‐EPI, MDRD, Schwartz‐2009, Schwartz‐Lyon, Lund‐Malmo and Full Age Spectrum equations for estimating GFR after SPK. 126 patients were included. GFR was measured by a reference method (mGFR) one year after SPK and estimated with the different equations from a standardized measure of serum creatinine. Relative bias, precisions, 10% and 30% accuracies (P30) were used to determine equations reliability. Ages ranged from 29 to 58. Mean mGFR was 56.3 ± 13.3 [23.6–92.5] ml/min/1.73 m². In the whole population, P30 of the CKD‐EPI and MDRD equations were 42% (38.0; 46.0) and 65% (61.5; 69) respectively. As compared to the other equations, the Schwartz‐Lyon equation was significantly more accurate (P30 = 86.0% [83.5–88.0], P < 0.01) and less biased (1.13 [1.06–1.19], P < 0.01). Conclusions were similar whatever the age class (<40 or ≥40) and mGFR level (<60 or ≥60 ml/min/1.73 m²). This study suggests that the CKD‐EPI and MDRD equations have poor performances in SPK recipients and that the Schwartz‐Lyon equation is a reliable alternative.     

Facial expression and sex recognition in schizophrenia and depression.

BACKGROUND: Impaired facial expression recognition in schizophrenia patients contributes to abnormal social functioning and may predict functional outcome in these patients. Facial expression processing involves individual neural networks that have been shown to malfunction in schizophrenia. Whether these patients have a selective deficit in facial expression recognition or a more global impairment in face processing remains controversial. OBJECTIVE: To investigate whether patients with schizophrenia exhibit a selective impairment in facial emotional expression recognition, compared with patients with major depression and healthy control subjects. METHODS: We studied performance in facial expression recognition and facial sex recognition paradigms, using original morphed faces, in a population with schizophrenia (n=29) and compared their scores with those of depression patients (n=20) and control subjects (n=20). RESULTS: Schizophrenia patients achieved lower scores than both other groups in the expression recognition task, particularly in fear and disgust recognition. Sex recognition was unimpaired. CONCLUSION: Facial expression recognition is impaired in schizophrenia, whereas sex recognition is preserved, which highly suggests an abnormal processing of changeable facial features in this disease. A dysfunction of the top-down retrograde modulation coming from limbic and paralimbic structures on visual areas is hypothesized.