Potential of TSPO radioligands: Bridging brain tumor diagnostics to the peripheries.

Translocator protein (TSPO) is involved in several cellular mechanisms such as steroidogenesis, immunomodulation, cell proliferation and differentiation. Overexpressed in several neurodegenerative diseases and brain cancer, TSPO radioligands have been developed over the last 20 years in positron emission tomography (PET) imaging. Recently, TSPO radioligands have extended beyond their initial application due to their specific binding to activated macrophages, making them a compelling biomarker for deciphering the intricacies of the tumor microenvironment (TME). In this review, we synthesized recent progress from the evaluation of TSPO-specific PET tracers in various peripheral tumor models and highlighted the hurdles and limitations associated with heterogeneous uptake in healthy tissue and tumor regions to achieve the clinical development of such a radiotracer.

[Pregnant women's use of tobacco and electronic cigarettes: A cross sectional survey]. / Usage du tabac et de la cigarette électronique chez la femme enceinte : une étude transversale.

OBJECTIVES: The article aims to describe tobacco and e-cigarette use among pregnant women: estimate the prevalence, identify the determinants and motivations of these behaviours. METHODS: Cross-sectional, multicentre, descriptive observational study using self-administered questionnaires for pregnant women who visited ELENA healthcare centers in May 2021. RESULTS: Of 223 patients, 38% were smokers before pregnancy and 16% continued to smoke during pregnancy. Nearly all the smokers (98%) declared that they had reduced or stopped their tobacco use, mostly without help. Young age, lack of professional activity, an unfavourable reaction to the announcement of the pregnancy, heavy smoking before the pregnancy and the presence of a smoker spouse were associated with smoking during pregnancy. Our study identified 10% of vapers before pregnancy and 7.2% during pregnancy. Of those who vaped during pregnancy, 81% were smokers before pregnancy. Most of them used a nicotine containing liquid and 38% of vapers combined smoking and e-cigarettes during pregnancy. There was no association between vaping during pregnancy and smoking cessation. A minority of women had received information about smoking during pregnancy. CONCLUSIONS: The use of electronic cigarettes by pregnant women is a poorly-known reality in France, yet it concerns approximately 7% of the women in our sample. Prospective studies on larger numbers are needed to assess the prevalence of vaping among French pregnant women and its evolution during pregnancy.

Education as a protective factor for mental health risks among youth living in highly dangerous regions in Afghanistan.

BACKGROUND: Children in Afghanistan live in dangerous areas, and have been exposed to traumatic events and chaotic education. Progress has been made on access to education for girls who were the most affected by traditional attitudes against engagement in education. OBJECTIVES: The objectives were to evaluate the mental health of Afghan children living in regions of conflict and the association of mental health with school attendance for girls and boys. METHOD: The study included 2707 school aged children in eight regions of Afghanistan (16 provinces) residing in households recruited through a multi-stage stratified cluster sampling strategy in 2017. The level of terrorist threat was evaluated by the intensity of terrorist attacks recorded that year in each province. Child mental health was assessed with the parental report Strengths and Difficulties Questionnaire (SDQ) along with information on school attendance, sociodemographic characteristics and geographic location. RESULTS: A total of 52.75% of children had scores above threshold for the SDQ total difficulties score, 39.19% for emotional difficulties, 51.98% for conduct challenges, and 15.37% for hyperactivity/inattention. Peer relationship problems were high (82.86%) and 12.38% reported that these problems impacted daily life. The level of terrorist threat was associated with SDQ total difficulties (Adjusted Odds Ratio [AOR] = 4.08, P < 0.0001), with youth in regions with high levels of terrorist threat more likely to have problems than youth in regions with low or medium levels of danger, independent of region and ethnicity. School attendance was negatively associated with emotional symptoms (AOR = 0.65, P < 0.0001) and mental health difficulties with impairment (AOR = 0.67, P = 0.007), but positively associated with peer relationships difficulties (AOR = 1.96, P > 0.0001). Conduct (AOR = 1.66, P < .0001) and SDQ total difficulties (AOR = 1.22, P = 0.019) were higher among boys. Overall, gender did not modify the relationship between school attendance and child mental health. CONCLUSION: Attending school is essential for children's mental health, across gender, and should be supported as a priority in Afghanistan despite the return of the Taliban.

Incidence and associated factors of cetuximab-induced hypersensitivity infusion reactions in 1392 cancer patients treated in four French areas: a possible association with Lyme disease?

BACKGROUND: Previous studies have observed an increased incidence of Cetuximab-induced hypersensitivity infusion reactions (CI-IRs) in the southeastern states of the USA. Tick's bites were suspected of generating cross-reactions between cetuximab and alpha-gal. This study aims was to describe the incidence and associated risk factors of CI-IRs, in the French areas chosen according to their Lyme disease incidence. PATIENTS AND METHODS: A retrospective chart review was conducted on patients that received cetuximab infusion from January 2010 to June 2019 in 4 French areas with different Lyme disease incidence rates. RESULTS: Of 1392 patients, 117 (8.4%) experienced a CI-IR, including 68 severe (grade 3 or 4) reactions (4.9%). This CI-IR incidence was significantly higher in the Lyme disease high-risk area than in the other areas (13.2% versus 7.1%, 8.1% and 6.4%; P = 0.016). Sex (P = 0.53), premedication (P = 0.91), primary cancer location (P = 0.46) and chemotherapy regimen type (P = 0.78) had no impact on CI-IR incidence in the overall population. In the head and neck squamous cell carcinoma (HNSCC) patient subgroup, CI-IRs were significantly more frequent in the high-risk area (16.4% versus 6.7%, 7.1% and 7.0%; P = 0.0015). CONCLUSION: This study suggests that patients treated in the French area with the highest incidence of Lyme disease are at a higher risk of CI-IRs.

[Place of molecular imaging in the management of prostate cancer]. / Place de l'imagerie moléculaire dans la prise en charge du cancer de la prostate.

In the management of prostate cancer in recent years, innovative therapies have appeared requiring precise and reliable disease detection. In 2021, new generation imaging (PET/CT, multiparametric MRI, PET/MRI) have their place at all stages of the prostate cancer natural history to help target the lesion(s) and guide therapy and improve the results obtained. PSMA PET/CT is currently the leader in this type of imaging with a complete offer during the disease: both from diagnosis, to recurrence or in the oligo-metastatic and metastatic stage resistant to castration with a pivotal role in the PSMA theranostic approach. However, multiparametric MRI also has many detection advantages when the prostate is left in place, which suggests the potential major benefit of hybrid PSMA PET/MRI imaging.

[External validation of nomogram for the prediction of recurrences of pregnancy-associated breast cancer]. / Cancer du sein associé à la grossesse : validation d'un nomogramme prédictif de la récidive.

OBJECTIVE: Diagnosis and therapeutics are challenging in pregnancy-related breast cancer and a multidisciplinary approach is therefore essential. A nomogram predictive of recurrence at 36 months of PABC has recently been developed, the aim was to evaluate it on an independent cohort. PATIENTS AND METHODS: This was a monocentric retrospective study including all patients with PABC between January 2004 and March 2018. A Kaplan-Meier method was used for the analysis of recurrence-free survival. Nomogram performance was analysed on 3 indicators: discrimination by a receiver operator characteristic curve (ROC), calibration and net clinical benefit by a decision curve analysis. RESULTS: Forty-one patients have been included. The survival rate was 83 % at 3 years. The nomogram showed acceptable discrimination capacities on receiver-operator characteristic analysis (c-index: 0.78). Decision-curve analysis showed a positive net-benefit for relapse probability ranges between 5 % and 35 %. CONCLUSION: The performance of this prediction model is acceptable but the net clinical benefit low. In conclusion, prediction of recurrence remains challenging with a continued need for more precise tools.

Factors associated with time to defecate and outcomes in critically ill patients: a prospective, multicentre, observational study.

Delayed defecation is common in patients on intensive care. We aimed to determine factors associated with time to defecation after admission to intensive care and in turn its association with length of stay and mortality. We studied 396 adults admitted to one of five intensive care units in whom at least 2 days' invasive ventilation was anticipated during an expected stay of at least 3 days. The median (IQR [range]) time to defecate by the 336 out of 396 (84%) patients who did so before intensive care discharge was 6 (4-8 [1-18]) days. Defecation was independently associated with five factors, hazard ratio (95%CI), higher values indicating more rapid defecation: alcoholism, 1.32 (1.05-1.66), p = 0.02; laxatives before admission, 2.35 (1.79-3.07), p < 0.001; non-invasive ventilation, 0.54 (0.36-0.82), p = 0.004; duration of ventilation, 0.78 (0.74-0.82), p < 0.001; laxatives after admission, 1.67 (1.23-2.26), p < 0.001; and enteral nutrition within 48 h of admission, 1.43 (1.07-1.90), p = 0.01. Delayed defecation was associated with prolonged intensive care stay but not mortality.

Promising clinical performance of pretargeted immuno-PET with anti-CEA bispecific antibody and gallium-68-labelled IMP-288 peptide for imaging colorectal cancer metastases: a pilot study.

INTRODUCTION: This pilot study evaluated the imaging performance of pretargeted immunological positron emission tomography (immuno-PET) using an anti-carcinoembryonic antigen (CEA) recombinant bispecific monoclonal antibody (BsMAb), TF2 and the [68Ga]Ga-labelled HSG peptide, IMP288, in patients with metastatic colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients requiring diagnostic workup of CRC metastases or in case of elevated CEA for surveillance were prospectively studied. They had to present with elevated CEA serum titre or positive CEA tumour staining by immunohistochemistry of a previous biopsy or surgical specimen. All patients underwent endoscopic ultrasound (EUS), chest-abdominal-pelvic computed tomography (CT), abdominal magnetic resonance imaging (MRI) and positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET). For immuno-PET, patients received intravenously 120 nmol of TF2 followed 30 h later by 150 MBq of [68Ga]Ga-labelled IMP288, both I.V. The gold standard was histology and imaging after 6-month follow-up. RESULTS: Eleven patients were included. No adverse effects were reported after BsMAb and peptide injections. In a per-patient analysis, immuno-PET was positive in 9/11 patients. On a per-lesion analysis, 12 of 14 lesions were positive with immuno-PET. Median SUVmax, MTV and TLG were 7.65 [3.98-13.94, SD 3.37], 8.63 cm3 [1.98-46.64; SD 14.83] and 37.90 cm3 [8.07-127.5; SD 43.47] respectively for immuno-PET lesions. Based on a per-lesion analysis, the sensitivity, specificity, positive-predictive value and negative-predictive value were, respectively, 82%, 25%, 82% and 25% for the combination of EUS/CT/MRI; 76%, 67%, 87% and 33% for FDG-PET; and 88%, 100%, 100% and 67% for immuno-PET. Immuno-PET had an impact on management in 2 patients. CONCLUSION: This pilot study showed that pretargeted immuno-PET using anti-CEA/anti-IMP288 BsMAb and a [68Ga]Ga-labelled hapten was safe and feasible, with promising diagnostic performance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02587247 Registered 27 October 2015.

Maternal and neonatal outcomes and prognostic factors in acute fatty liver of pregnancy.

OBJECTIVE: To report complications of Acute Fatty Liver of pregnancy (AFLP), a rare liver disease of pregnancy, and identify prognostic factors for mothers and children. STUDY DESIGN: We conducted a retrospective descriptive study over 18 years in three French maternities. Demographic, clinical, biological data, and outcomes of patients and their infants were reviewed. RESULTS: 142,450 pregnancies from centers were studied. Eighteen patients with AFLP were identified The prevalence of AFLP was estimated as 1/7,914 pregnancies. Prolonged prothrombin time was identified as a risk factor of maternal complications (OR = 0.86, p = 0.0493). Gestational age at delivery was the only risk factor associated with fetal or neonate complications (OR = 0.37, p = 0.0417). One boy died of previously undiagnosed ß-oxidation deficiency at eight months. CONCLUSION: In AFLP, prothrombin time must be carefully monitored to anticipate major maternal complications. Infants born to mothers with ALFP should be screened as early as possible for mitochondrial fatty acid oxidation deficiency.

Performance comparison of modified ComBat for harmonization of radiomic features for multicenter studies.

Multicenter studies are needed to demonstrate the clinical potential value of radiomics as a prognostic tool. However, variability in scanner models, acquisition protocols and reconstruction settings are unavoidable and radiomic features are notoriously sensitive to these factors, which hinders pooling them in a statistical analysis. A statistical harmonization method called ComBat was developed to deal with the "batch effect" in gene expression microarray data and was used in radiomics studies to deal with the "center-effect". Our goal was to evaluate modifications in ComBat allowing for more flexibility in choosing a reference and improving robustness of the estimation. Two modified ComBat versions were evaluated: M-ComBat allows to transform all features distributions to a chosen reference, instead of the overall mean, providing more flexibility. B-ComBat adds bootstrap and Monte Carlo for improved robustness in the estimation. BM-ComBat combines both modifications. The four versions were compared regarding their ability to harmonize features in a multicenter context in two different clinical datasets. The first contains 119 locally advanced cervical cancer patients from 3 centers, with magnetic resonance imaging and positron emission tomography imaging. In that case ComBat was applied with 3 labels corresponding to each center. The second one contains 98 locally advanced laryngeal cancer patients from 5 centers with contrast-enhanced computed tomography. In that specific case, because imaging settings were highly heterogeneous even within each of the five centers, unsupervised clustering was used to determine two labels for applying ComBat. The impact of each harmonization was evaluated through three different machine learning pipelines for the modelling step in predicting the clinical outcomes, across two performance metrics (balanced accuracy and Matthews correlation coefficient). Before harmonization, almost all radiomic features had significantly different distributions between labels. These differences were successfully removed with all ComBat versions. The predictive ability of the radiomic models was always improved with harmonization and the improved ComBat provided the best results. This was observed consistently in both datasets, through all machine learning pipelines and performance metrics. The proposed modifications allow for more flexibility and robustness in the estimation. They also slightly but consistently improve the predictive power of resulting radiomic models.

Idiopathic pulmonary fibrosis: Significance of the usual interstitial pneumonia (UIP) CT-scan patterns defined in new international guidelines.

INTRODUCTION: The new 2018 international guidelines for diagnosing usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) by CT scan split the old pattern possible UIP (2011 IPF guidelines) into two new patterns: probable UIP and indeterminate for UIP. However, the proportions and prognoses of these new CT-scan patterns are not clear. METHODS: We used a monocentric retrospective cohort of 322 patients suspected of having IPF (University Hospital of Rennes; Competence Center for Rare Lung Diseases; 1 January 2012-31 December 2017). All patients initially diagnosed by CT scan as possible UIP were included. The chest CT-scans were then reclassified according to the new 2018 international guidelines by 3 observers. These data were then subjected to survival analysis with multivariate Cox regression using a composite endpoint of death, lung transplantation, a decline of≥10% in forced vital capacity (FVC), or hospitalization. RESULTS: Of the 89 possible UIP patients included, 74 (83%) were reclassified as probable UIP and 15 (17%) as indeterminate for UIP. Probable UIP patients were more likely to meet the composite endpoint (56/74 [75.7%] vs. 5/15 [33%] patients; HR [IC 95%] =3.12 [1.24; 7.83], P=0.015). Multivariate analysis indicated that the probable UIP pattern was associated with significantly increased risk of reaching the composite endpoint (HR [95% CI]=2.85[1.00; 8.10], P=0.049). CONCLUSION: The majority of possible UIP diagnoses corresponded to probable UIP, which was associated with a significantly worse prognosis than indeterminate for UIP. This distinction between these two CT patterns emphasizes the relevance of the new international guidelines for the diagnosis of IPF.

Activation of innate immunity by 14-3-3 ε, a new potential alarmin in osteoarthritis.

OBJECTIVE: The innate immune system plays a central role in osteoarthritis (OA). We identified 14-3-3ε as a novel mediator that guides chondrocytes toward an inflammatory phenotype. 14-3-3ε shares common characteristics with alarmins. These endogenous molecules, released into extracellular media, are increasingly incriminated in sustaining OA inflammation. Alarmins bind mainly to toll-like receptor 2 (TLR2) and TLR4 receptors and polarize macrophages in the synovium. We investigated the effects of 14-3-3ε in joint cells and tissues and its interactions with TLRs to define it as a new alarmin involved in OA. DESIGN: Chondrocyte, synoviocyte and macrophage cultures from murine or OA human samples were treated with 14-3-3ε. To inhibit TLR2/4 in chondrocytes, blocking antibodies were used. Moreover, chondrocytes and bone marrow macrophage (BMM) cultures from knockout (KO) TLRs mice were stimulated with 14-3-3ε. Gene expression and release of inflammatory mediators [interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNFα)] were evaluated via reverse transcription quantitative polymerase chain reaction (RT-qPCR) and ELISA. RESULTS: In vitro, 14-3-3ε induced gene expression and release of IL6 and MCP1 in the treated cells. The inflammatory effects of 14-3-3ε were significantly reduced following TLRs inhibition or in TLRs KO chondrocytes and BMM. CONCLUSIONS: 14-3-3ε is able to induce an inflammatory phenotype in synoviocytes, macrophages and chondrocytes in addition to polarizing macrophages. These effects seem to involve TLR2 or TLR4 to trigger innate immunity. Our results designate 14-3-3ε as a novel alarmin in OA and as a new target either for therapeutic and/or prognostic purposes.

DWI-Based Algorithm to Predict Disability in Patients Treated with Thrombectomy for Acute Stroke.

BACKGROUND AND PURPOSE: The reasons for poor clinical outcome after thrombectomy for acute stroke, concerning around half of all patients, are misunderstood. We developed a hierarchic algorithm based on DWI to better identify patients at high risk of disability. MATERIALS AND METHODS: Our single-center, retrospective study included consecutive patients with acute ischemic stroke who underwent thrombectomy for large anterior artery occlusion and underwent pretreatment DWI. The primary outcome was the mRS at 3 months after stroke onset. Multivariable regression was used to identify independent clinical and imaging predictors of poor prognosis (mRS > 2) at 3 months, and a hierarchic algorithm predictive of disability was developed. RESULTS: A total of 149 patients were analyzed. In decreasing importance, DWI lesion volume of >80 mL, baseline NIHSS score of >14, age older than 75 years, and time from stroke onset to groin puncture of >4 hours were independent predictors of poor prognosis. The predictive hierarchic algorithm developed from the multivariate analysis predicted the risk of disability at 3 months for up to 100% of patients with a high predictive value. The area under the receiver operating characteristic curve was 0.87. CONCLUSIONS: The DWI-based hierarchic algorithm we developed is highly predictive of disability at 3 months after thrombectomy and is easy to use in routine practice.

[Facial skin cancers: Comparison of opinions in French multidisciplinary team meetings]. / Cancers cutanés de la face : avis comparés de réunions de concertation pluridisciplinaire françaises.

BACKGROUND: The aim of our study was to evaluate the diversity, or homogeneity, of recommendations made in multidisciplinary team meetings (MTM) concerning the management of facial skin cancers in France, and to analyze the determinants thereof. PATIENTS AND METHODS: We contacted a panel of dermatology and ENT multidisciplinary teams (MDT) and collected their recommendations made at meetings regarding 3 clinical cases: squamous cell carcinoma in a renal transplant patient with an incomplete excision margin (case 1), locally advanced basal cell carcinoma (case 2), and lentigo maligna (case 3). The responses were analyzed globally and then based on 2 subgroups defined by the presence or absence of a dermatologist in the MTM. The effect of the makeup of the MTM (based on the presence of a dermatologist, a plastic surgeon, an oncologist and an ENT specialist) was evaluated for the main therapeutic proposals. RESULTS: The opinions of the 45 MDMs that responded to the survey were mixed for the three cases as regards important elements such as the indication of surgical revision for case 1, the proposal of an alternative treatment to surgery for case 2, and monitoring arrangements for case 3. Certain proposals were associated with the presence of a dermatologist in the MTM, such as discussion of adaptation of immunosuppressive treatment and details of the surgical margins to be applied for case 1, as well as simple monitoring and details of monitoring arrangements in case 3. CONCLUSION: It is important to maintain dermatologists in MTMs on account of their expertise in all therapeutic areas concerning skin cancers.

Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula.

The unconventional N-methyl-d-aspartate (NMDA) receptor subunits GluN3A and GluN3B can, when associated with the other glycine-binding subunit GluN1, generate excitatory conductances purely activated by glycine. However, functional GluN1/GluN3 receptors have not been identified in native adult tissues. We discovered that GluN1/GluN3A receptors are operational in neurons of the mouse adult medial habenula (MHb), an epithalamic area controlling aversive physiological states. In the absence of glycinergic neuronal specializations in the MHb, glial cells tuned neuronal activity via GluN1/GluN3A receptors. Reducing GluN1/GluN3A receptor levels in the MHb prevented place-aversion conditioning. Our study extends the physiological and behavioral implications of glycine by demonstrating its control of negatively valued emotional associations via excitatory glycinergic NMDA receptors.

Distinct Profiles of Consumers of Psychoactive Substances in People Attending French Sexual Transmitted Infections Centers.

The objective of this cross-sectional survey was to assess the prevalence of psychoactive substance use (PSU) in people attending 11 French Sexual Transmitted Infection Centers, and to specify their profiles (PSU and link with risky sexual behaviors) using the ascending hierarchical clustering method. Among the 5220 individuals who completed the survey, 55.6% were men and the median age was 24 years [IQR: 20-31]. Among the participants, 2751 (52.7%) reported PSU at least once in their life. Ascending hierarchical clustering identified seven distinct profiles of participants based on their PSU. This study shows a high prevalence of PSU and alcohol consumption in this young population. Moreover, subgroup analysis allowed identifying groups of psychoactive substance users who presented specific risks or vulnerabilities and who should be priority targets for interventions, particularly sexual minority groups.

Safety of percutaneous renal cryoablation: an international multicentre experience from the EuRECA retrospective percutaneous database.

OBJECTIVE: To investigate the safety profile of percutaneous cryoablation of renal tumours < 7 cm, utilising data extracted from an international multicentre registry. MATERIALS AND METHODS: A retrospective review of all immediate and delayed complications from a multicentre database was performed and was categorised according to the Clavien-Dindo classification. Statistical analysis was performed for both overall complications (all Clavien-Dindo) and major complications (Clavien-Dindo 3 to 5). The following criteria were identified as potential predictive factors for complications: centre number, modality of image guidance, tumour size (≤ 4 cm vs. > 4 cm), number of tumours treated in the same session (1 vs. > 1) and tumour histology. RESULTS: A total of 713 renal tumours underwent ablation in 647 individual sessions. In 596 of the cases, one tumour was treated; in the remaining 51 cases, several tumours were treated per session. Mean lesion size was 2.8 cm. Fifty-four complications (Clavien-Dindo 1 to 5) occurred as a result of the 647 procedures, corresponding to an overall complication rate of 8.3%. The most frequent complication was bleeding (3.2%), with 9 cases (1.4%) requiring subsequent treatment. The rate of major complication was 3.4%. The only statistically significant prognostic factor for a major complication was a tumour size > 4 cm. CONCLUSION: Percutaneous renal cryoablation is associated with a low rate of complications. Tumours measuring more than 4 cm are associated with a higher risk of major complications. KEY POINTS: • Percutaneous kidney cryoablation has a low rate of complications. • Bleeding is the most frequent complication. • A tumour size superior to 4 cm is a predictive factor of major complication.

The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases.

Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions of the intestinal tract. IBD are believed to result from an inappropriate immune response against the intestinal flora in genetically predisposed patients. The precise etiology of these diseases is not fully understood, therefore treatments rely on the dampening of symptoms, essentially inflammation, rather than on the cure of the disease. Despite the availability of biologics, such as anti-TNF antibodies, some patients remain in therapeutic failure and new treatments are thus needed. The multiligand receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in inflammatory reactions and immune system activation. Here, we investigated the role of RAGE in intestinal inflammation and its potential as a therapeutic target in IBD. We showed that RAGE was upregulated in inflamed tissues from IBD patients compared to controls. Rage-/- mice were less susceptible to intestinal and colonic inflammation development than WT mice. WT mice treated with the RAGE-specific inhibitor FPS-ZM1 experienced less severe enteritis and colitis. We demonstrated that RAGE could induce intestinal inflammation by promoting oxidative stress and endothelial activation which were diminished by FPS-ZM1 treatment. Our results revealed the RAGE signaling pathway as a promising therapeutic target for IBD patients.

Case-control study found that primary language disorders were associated with screen exposure.

AIM: We explored the associations between childhood exposure to screens, including televisions, computers, game consoles, tablets and smartphones and primary language disorders. METHODS: This multi-centre case-control study comprised 167 children aged 3.5-6.5 years, who were born in 2010-2012 and diagnosed with primary language disorders, and 109 matched controls without language disorders. Questionnaires were completed by their parents who were recruited by 16 family doctors and 27 speech and language therapists in the Ille-et-Vilaine region of France. The data were analysed using a multivariate logistic regression model and presented as adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). RESULTS: We found that cases (44.3%) and controls (22.0%) exposed to screens in the morning before nursery or primary school were three times more likely to develop primary language disorders (aOR 3.40, 95% CI 1.60-7.23). When this risk was combined with rarely or never discussing screen content with their parents (aOR 2.14, 95% CI 1.01-4.54) they were six times more likely to have language problems (aOR 5.86, 95% CI 1.44-23.95). CONCLUSION: Being exposed to screens in the morning before school, and rarely or never discussing screen content with parents, meant children were six times more likely to develop primary language disorders.