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In addition, fluoxetine 50 μM use-dependently inhibited Kv2.1 currents at different frequencies. In conclusion, the inhibition of Kv2.1 by fluoxetine was concentration-dependent, voltage-dependent and use-dependent. The accelerated steady-state inactivation of Kv2.1 channels induced by fluoxetine might be ascribed to the delay of the recovery process of Kv2.1. V.PURPOSE Stereotactic body radiation therapy is a therapeutic option offered to high surgical risk cancer patients with lung cancer. Focal lung irradiation in mice is a new preclinical model to help understand the development of lung damage in this context. Here we developed a mouse model of lung stereotactic therapy using arc delivery and monitored the development of lung damage while varying beam size and dose delivered. METHODS AND MATERIALS C57BL/6JRj mice were exposed to 90 Gy focal irradiation on the left lung, using 1 mm diameter, 3 x 3 mm2, 7 x 7 mm2 or 10 x 10 mm2 beam collimation for beam size effect, and using 3 x 3 mm2 beam collimation delivering 20 to 120 Gy for dose effect. Long-term lung damage was monitored with micro-CT imaging together with anatomopathological and gene expression measurements in the injured patch and the ipsilateral and contralateral lungs. RESULTS Both 1 mm diameter and 3 x 3 mm2 beam collimation allow long-term studies, but only 3 mm beam collimation generates lung fibrosis when delivering 90 Gy. Dose-effect studies with constant 3 mm beam collimation revealed a dose of 60 Gy as the minimum to obtain lung fibrosis 6 months post-exposure. Lung fibrosis development was associated with club cell depletion and increased type II pneumocyte numbers. Lung injury developed with ipsilateral and contralateral consequences such as parenchymal thickening and gene expression modifications. CONCLUSIONS Arc therapy allows long-term studies and dose escalation without lethality. In our dose-delivering conditions, dose-effect studies revealed that 3 x 3 mm2 beam collimation to a minimum single dose of 60 Gy enables preclinical models for the assessment of lung injury within a 6-month period. This model of lung tissue fibrosis in a time length compatible with mouse life span may offer good prospects for future mechanistic studies. We aimed to perform a systematic review and meta-analysis of studies examining the levels of chemokines in peripheral blood of patients with bipolar disorder (BD) and healthy controls. Meta-analysis was based on random-effects models with Hedges' g as the effect size estimate. We included 13 eligible studies (1221 BD patients and 663 controls). selleckchem The following chemokines were analysed interleukin-8 (IL-8), monocyte-chemoattractant protein-1 (MCP-1), eotaxin-1, eotaxin-2 and interferon-γ-induced protein 10 (IP-10). The levels of IL-8 (N = 8, g = 0.26, 95%CI 0.11-0.41, p less then 0.001), MCP-1 (N = 8, g = 0.40, 95%CI 0.18-0.63), eotaxin-1 (N = 3, g = 0.55, 95%CI 0.21-0.89, p = 0.001) and IP-10 (N = 4, g = 0.95, 95%CI 0.67-1.22, p less then 0.001) were significantly higher in BD patients as compared with controls. Subgroup analyses revealed that elevated levels of IL-8 (N = 5, g = 0.75, 95%CI 0.42-1.07, p less then 0.001) and MCP-1 (N = 4, g = 0.57, 95%CI 0.28-0.86, p less then 0.001) appeared only in BD patients during their depressive phase. Illness duration was associated with significantly lower levels of IL-8 in meta-regression analysis. In turn, elevated levels of IP-10 were present during euthymia (N = 2, g = 0.76, 95%CI 0.43-1.10, p less then 0.001) but not depression (N = 2, g = 1.81, 95%CI -0.16 to 3.77, p = 0.072). The analysis of eotaxin-1 levels was mainly based on studies of euthymic BD patients (N = 3). Our results suggest that chemokine alterations in BD might be related to mood state. Elevated levels of IL-8 and MCP-1 might be specific to depression. Available evidence indicates that increased levels of eotaxin-1 and IP-10 appear in euthymia; however, more studies are needed to address these alterations in other mood states. Pharmacological treatments in laboratory rodents remain a cornerstone of preclinical psychopharmacological research and drug development. There are numerous ways in which acute or chronic pharmacological treatments can be implemented, with each method having certain advantages and drawbacks. Here, we describe and validate a novel treatment method in mice, which we refer to as the micropipette-guided drug administration (MDA) procedure. This administration method is based on a sweetened condensed milk solution as a vehicle for pharmacological substances, which motivates the animals to consume vehicle and/or drug solutions voluntarily in the presence of the experimenter. In a proof-of-concept study, we show that the pharmacokinetic profiles of the atypical antipsychotic drug, risperidone, were similar whether administered via the MDA procedure or via the conventional oral gavage method. Unlike the latter, however, MDA did not induce the stress hormone, corticosterone. Furthermore, we assessed the suitability and validity of the MDA method in a mouse model of maternal immune activation, which is frequently used as a model of immune-mediated neurodevelopmental disorders. Using this model, we found that chronic treatment (>4 weeks, once per day) with risperidone via MDA led to a dose-dependent mitigation of MIA-induced social interaction deficits and amphetamine hypersensitivity. Taken together, the MDA procedure described herein represents a novel pharmacological administration method for per os treatments in mice that is easy to implement, cost effective, non-invasive, and less stressful for the animals than conventional oral gavage methods. PURPOSE To understand how breast radiologists perceive ductal carcinoma in situ (DCIS). MATERIALS AND METHODS A 19-item survey was developed by the Society of Breast Imaging Patient Care and Delivery Committee and distributed to all Society of Breast Imaging members. The survey queried respondents' demographics, knowledge of DCIS biology, language used to discuss a new diagnosis of DCIS, and perspectives on active surveillance for DCIS. Five-point Likert scales (1 = strongly disagree, 3 = neutral, 5 = strongly agree) were used. RESULTS There were 536 responses for a response rate of 41%. There was agreement that DCIS is the primary driver of overdiagnosis in breast cancer screening (median 4), and respondents provided mean and median overdiagnosis estimates of 29.7% and 25% for low-grade DCIS as well as 4.2% and 0% for high-grade DCIS, respectively. Responses varied in how to describe DCIS but most often used the word "cancer" with a qualifier such as "early" (32%) or "pre-invasive" (25%). Respondents disagreed (median 2) with removing the word "carcinoma" from DCIS.
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