Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
The safety of domperidone in pregnancy remains unknown. Therefore, the study aimed to prospectively evaluate the fetal outcomes of women who were taking domperidone during pregnancy. In a prospective cohort study design, 120 1st- trimester pregnant women who were taking domperidone for controlling gastrointestinal tract symptoms and 212 age-matched pregnant women not exposed to any potential teratogenic agent, were followed-up until delivery. In the case group, domperidone was indicated for control of functional gastrointestinal disorders in 59.2%, the maximum dose was 30 mg/day and exposure occurred between 2(+4) and 20 weeks' gestation. Fetal outcomes including gestational age at birth, birth weight and length, head circumference at birth, and 1- and 5-min Apgar score were similar in the two study groups. There were three babies born with malformations in each group (OR = 0.6; 95% CI 0.1, 2.8). In conclusion, domperidone does not appear to be a major human teratogen. However, our findings require further confirmation in larger studies.
A novel imaging spectrometer can individually control spatial and spectral resolution by using zoom lenses as the foreoptics of the system and a focusing lens. By varying the focal length we can use the focusing lens to change the spatial and spectral dimensions; with the foreoptics, however, we can change only the spatial dimension. Therefore the spectral resolution and the spectral range are affected by the zoom ratio of the focusing lens, whereas the spatial resolution and the field of view are affected by the multiplication of the zoom ratios of the foreoptics and the focusing lens. By properly combining two zoom ratios, we can control the spectral resolution with a fixed spatial resolution or the spatial resolution with a fixed spectral resolution. For an imaging spectrometer with this novel zooming function, we used the lens module method and third-order aberration theory to design an initial four-group zoom system with an external entrance pupil for the focusing lens. Furthermore, using the optical design software CODE V, we obtained an optimized zoom lens with a focal-length range of 50 to 150 mm. Finally, the zoom system with its transmission grating in the Littrow configuration performs satisfactorily as the focusing lens of an imaging spectrometer in the wavelength range 450-900 nm.
Hepatobiliary and Pancreatic: Focal steatohepatitis mimicking a metastasisA woman, aged 65, was admitted to hospital for review of cancer management. Ten years previously, she had undergone a radical mastectomy for breast cancer. Bone metastases had been diagnosed 8 months prior to admission and treated with palliative radiotherapy and tamoxifen. Blood tests revealed a minor elevation of aspartate aminotransferase (133 u/l) and alanine aminotransferase (103 u/l). Serum levels of various tumor markers were within the reference range and she had negative serological tests for hepatitis B and C. An abdominal computed tomography scan showed a nodular lesion in segment 3 of the liver that showed a target-like appearance with a low-attenuation rim (Figure 1 Over recent years, there has been increasing interest in the effect of cancer therapy on the non-tumor bearing liver. These changes are more common with chemotherapy but have also been described with drugs such as tamoxifen. The most frequent change is that of a diffuse fatty liver. However, fatty change can also be focal and may mimic a metastasis as in the above patient. These areas of focal steatosis are mostly found in segments 3 and 4. This distribution has been attributed to small areas in the liver that lack portal venous inflow. However, lack of portal venous inflow has also been used to explain areas of "fat-sparing". After cessation of chemotherapy, diffuse fatty change is at least partially reversible in the majority of patients but the natural history of focal fatty change remains unclear. Images in the above patient illustrate the helpful role of CT and MRI in the differentiation of focal steatosis from liver metastases. With focal steatosis, there is a low attenuation area on unenhanced CT while, with MRI, opposed-phase T1-weighted images show signal loss when compared with the in-phase images. In contrast, there is no signal loss with opposedphase T1 images in patients with typical metastases.
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