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Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-function mutations in MECP2, display impaired excitatory neurotransmission, the RTT phenotype can be largely reproduced in mice simply by removing MeCP2 from inhibitory GABAergic neurons. To determine what role excitatory signaling impairment might play in RTT pathogenesis, we generated conditional mouse models with Mecp2 either removed from or expressed solely in glutamatergic neurons. MeCP2 deficiency in glutamatergic neurons leads to early lethality, obesity, tremor, altered anxiety-like behaviors, and impaired acoustic startle response, which is distinct from the phenotype of mice lacking MeCP2 only in inhibitory neurons. These findings reveal a role for excitatory signaling impairment in specific neurobehavioral abnormalities shared by RTT and other postnatal neurological disorders.DOI: http://dx.doi.org/10.7554/eLife.14199.001

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Idiopathic granulomatous lobular mastitis (IGLM) is a rare breast condition with prominent skin findings. It is typically seen in young parous women. Painful breast masses, draining sinuses, scarring, and breast atrophy are the main clinical manifestations. IGLM can resemble a variety of other inflammatory and neoplastic processes of the breast. It is thought to result from obstruction and rupture of breast lobules. Extravasated breast secretions then induce an inflammatory reaction. Corynebacteria have also been implicated in the pathogenesis. Treatment is surgical, but systemic corticosteroids, methotrexate, and antibiotics also play a role.

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Introduction: Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) are the most widely used outcome measures in clinical trials of biologics to treat psoriasis; however, these outcome measures vary in both their reliability and validity. As newer biologics approach complete clearance of psoriasis, it becomes important to have standardized, reproducible forms of measure to accurately compare treatment efficacy. The aim of this study was to evaluate the extent of and reasons for variation between PASI and PGA scores used in clinical trials. Methods: A literature search was conducted of clinical trials meeting the inclusion criteria: phase 2 or 3, evaluation of treatment efficacy in reducing psoriasis severity, and use of PASI 90/100 and sPGA or PGA 0/1 as primary end points. Results: Among the analyzed studies, 8 of 45 trials had a PASI-PGA variance of \ 5%, 4 of 45 trials had a variance of 5-10%, and 33 trials had a variance of [ 10%. The IMMvent and AMA-GINE trials were the only two trials showing 0 variation between the PASI and PGA scores, testing adalimumab and brodalumab, respectively. Ustekinumab showed the highest variance of 61.9% in the IXORA-S trial. Limitations of this paper include a relatively low number of studies assessed because of the paucity of literature available. Conclusions: The use of both PASI and PGA as equivalent assessment tools for complete clearance is redundant and subject to high variability. Novel severity assessments should be developed that reduce calculation variation and take into account patient-oriented symptoms.

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