Sex-specific microglia state in the Neuroligin-4 knock-out mouse model of autism spectrum disorder.

Neuroligin-4 (NLGN4) loss-of-function mutations are associated with monogenic heritable autism spectrum disorder (ASD) and cause alterations in both synaptic and behavioral phenotypes. Microglia, the resident CNS macrophages, are implicated in ASD development and progression. Here we studied the impact of NLGN4 loss in a mouse model, focusing on microglia phenotype and function in both male and female mice. NLGN4 depletion caused lower microglia density, less ramified morphology, reduced response to injury and purinergic signaling specifically in the hippocampal CA3 region predominantly in male mice. Proteomic analysis revealed disrupted energy metabolism in male microglia and provided further evidence for sexual dimorphism in the ASD associated microglial phenotype. In addition, we observed impaired gamma oscillations in a sex-dependent manner. Lastly, estradiol application in male NLGN4-/- mice restored the altered microglial phenotype and function. Together, these results indicate that loss of NLGN4 affects not only neuronal network activity, but also changes the microglia state in a sex-dependent manner that could be targeted by estradiol treatment.

T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis.

Age-related myelin damage induces inflammatory responses, yet its involvement in Alzheimer's disease remains uncertain, despite age being a major risk factor. Using a mouse model of Alzheimer's disease, we found that amyloidosis itself triggers age-related oligodendrocyte and myelin damage. Mechanistically, CD8+ T cells promote the progressive accumulation of abnormally interferon-activated microglia that display myelin-damaging activity. Thus, our data suggest that immune responses against myelinating oligodendrocytes may contribute to neurodegenerative diseases with amyloidosis.

COVID-19-induced acute kidney injury in critically ill patients: epidemiology, risk factors, and outcome.

BACKGROUND: The kidney represents a potential target for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data about acute kidney injury (AKI) during SARS-CoV-2 infection are lacking. We aimed to investigate the proportion, risk factors, and prognosis of AKI in critical patients affected with SARS-CoV-2. METHODS: A case/control study was conducted in two intensive care units of a tertiary teaching hospital. RESULTS: Among 109 patients, 75 were male (69%) with median age at 64 years and 48 (44%) developed AKI within 4 days (interquartile range [IQR], 1-9). Of them, 11 (23%), 9 (19%), and 28 (58%) were classified as stage 1, 2, and 3, respectively. AKI patients were older and presented more sepsis, acute respiratory distress syndrome, and rhabdomyolysis; higher initial urea and creatinine; more marked inflammatory syndrome and hematological disorders; and required more mechanical ventilation and vasopressors. An elevated D-dimers level (odds ratio [OR], 12.83; 95% confidence interval [CI], 1.9-85) was an independent factor of AKI. Sepsis was near to significance (OR, 5.22; 95% CI, 0.94-28; P=0.058). AKI was independently related to mortality (OR, 6.8; 95% CI, 1.49-105) and significantly reduced the survival (14.7 days; IQR, 12-17 vs. 19.9 days; IQR, 17-22.7; P=0.011) in AKI and no AKI group respectively. Hypoxemia with the ratio of the arterial partial pressure of oxygen and the inspiratory concentration of oxygen <70, and vasopressors were identified as mortality factors. CONCLUSIONS: AKI occurred in almost half the studied patients and significantly worsened their prognosis. A high D-dimers level and sepsis contributed significantly to its development.

[Corticotherapy for asthma in the child]. / La corticotherapie dans l'asthme de l'enfant.

Corticosteriods have a puissant anti-inflammatory action and enjoyment a central role in the treatment for childhood asthma. Systemic steroids are used in resistant bronchodilatator exacerbations of asthma. Usually steroids are given for short courses, rarely for long term in severe asthma with high risk of side-effects. Inhaled corticosteroids have'nt changed the treatment for childhood asthma and are recommanded in persistent asthma. Inhaled steroids are well tolerant even at high doses, but it must always research the minimal effective dose. The aim of steroid's treatment is controlling asthma with minimal side-effects to give a normal life to the asthmatic children.

[Effects of treatments on serum vitamin E levels in lung cancer]. / Effet des traitements sur les concentrations sériques de vitamine E dans le cancer bronchopulmonaire.

Previous evidence suggests that malignant tumours cause an decrease in the serum vitamin E level. We followed the serum alpha tocopherol in 55 lung cancer patients. The objective of the study was to evaluate the effects of treatments of lung cancer on serum vitamin E evolution. The vitamin E of patients symptomatically treated decreases from the first month and this decrease is significant (p < 0.001) in patients affected by SCLC and in those with NSCLC classified stage III and IV. The reduction of the vitamin E is also noted in the patients treated with chemotherapy (p < 0.001). Vitamin E levels improve gradually to reach standard values in the patients who followed a curative radiotherapy or benefited from the surgical ablation of the tumour. At 4 months after the surgical removal of the tumour, there was an increase in serum vitamin E concentrations and reached the normal values. This data indicates that surgical removal of lung cancer increases serum vitamin E concentrations compared to the baseline values possibly reflecting the relief of oxidative stress caused by malignant tumours.