DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/ß-catenin signaling.

Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/ß-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls. Many of these SNVs alter Wnt/ß-catenin signaling activity of the neurally predominant DIXDC1 isoform; a subset that hyperactivate this pathway cause dominant neurodevelopmental effects. We propose that rare missense SNVs in DIXDC1 contribute to psychiatric pathogenesis by reducing spine and glutamatergic synapse density downstream of GSK3 in the Wnt/ß-catenin pathway.

Modified PIOPED criteria used in clinical practice.

UNLABELLED: To assess the use of modified PIOPED scintigraphic criteria for lung scan (V/Q) interpretation to detect pulmonary embolism (PE), we prospectively applied these criteria in suspected PE patients referred for V/Q from 9/1/92 to 2/7/94. PIOPED criteria were modified by placing a moderate segmental perfusion mismatch in the intermediate instead of low probability of PE category and using the "stripe sign." METHODS: Patients were studied by six-view V/Q imaging using 74 MBq (2 mCi) 99mTc-MAA followed by 148-370 MBq (4-10 mCi) 99mTc-DTPA aerosol, contrast pulmonary selective angiography and Doppler sonography with leg compression as needed. Patients underwent follow-up (mean 13.9 mo) to detect subsequent thromboembolic events. In this study group, 1000 patients were studied by V/Q followed by angiography in 133 patients. RESULTS: The distribution of V/Q-assigned PE probabilities was: high probability 5.7%, intermediate 17.4%, low 41.4% and normal 35.5%. Group A patients (133) underwent angiography, which resulted in the determination of a 27.1% PE prevalence. Group B patients (867) did not have angiograms; the clinical prevalence of PE was 7.5%. In the total study population, the positive predictive value of a high probability V/Q study for PE (10.1% prevalence) was 98.2%, intermediate probability V/Q study for PE was 24.1% and a low probability study for PE was only 0.5%. CONCLUSION: Modified PIOPED V/Q interpretation criteria afford better angioproven PE discrimination between intermediate (31.8% PE prevalence) and low (5.5% PE prevalence) probability V/Q results than reported for PIOPED intermediate (32.6% PE prevalence) and low (16.3% PE prevalence) probability V/Q interpretation criteria.

Thyroid and parathyroid imaging.

With the advent of better thyroid function tests, a tumor marker, and fine-needle aspiration, the role of thyroid imaging studies in the evaluation of the patients with thyroid disease has diminished. Although multimodality thyroid imaging had improved our understanding of thyroid disease, current indications for thyroid imaging are the solitary or dominant thyroid nodule, an upper mediastinal mass, differentiation of hyperthyroidism, detection and staging of postoperative thyroid cancer, neonatal hypothyroidism, thyroid developmental anomalies, and the thyroid mass post-thyroidectomy for benign disease. To provide optimal, cost-effective, care for the thyroid patient, the physician must understand the advantages and disadvantages of each imaging modality--scintigraphy, real-time sonography (RTS), computed tomography, and magnetic resonance--in specific clinical settings. Similarly, preoperative noninvasive localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism undergoing their initial neck exploration usually is not warranted. In this situation, the best localization procedure is to enlist the services of an experienced parathyroid surgeon. However, if this is not feasible because of local constraints, both sestamibi methoxy isobutyl isonitrile (MIBI) scintigraphy and magnetic resonance imaging (MRI) provide excellent localization (< 90%) of juxta-thyroidal and ectopic parathyroid adenomas. Hyperplastic glands are more difficult to detect because of their smaller size, and tandem studies (MIBI and MRI) should provide higher sensitivity before initial exploration, especially in patients with ectopic glands. In patients with persistent or recurrent disease, multimodality imaging with MIBI, MR, computed tomography and RTS in a sequential fashion is warranted to optimize two-test, site-specific localization.