Individual Differences in Impulsive Action Reflect Variation in the Cortical Serotonin 5-HT2A Receptor System

Impulsivity is an important feature of multiple neuropsychiatric disorders, and individual variation in the degree of inherent impulsivity could play a role in the generation or exacerbation of problematic behaviors. Serotonin (5-HT) actions at the 5-HT_2AR receptor (5-HT_2AR) promote and 5-HT_2AR antagonists suppress impulsive action (the inability to withhold premature responses; motor impulsivity) upon systemic administration or microinfusion directly into the medial prefrontal cortex (mPFC), a node in the corticostriatal circuit that is thought to play a role in the regulation of impulsive action. We hypothesized that the functional capacity of the 5-HT_2AR, which is governed by its expression, localization, and protein/protein interactions (eg, postsynaptic density 95 (PSD95)), may drive the predisposition to inherent impulsive action. Stable high-impulsive (HI) and low-impulsive (LI) phenotypes were identified from an outbred rodent population with the 1-choice serial reaction time (1-CSRT) task. HI rats exhibited a greater head-twitch response following administration of the preferential 5-HT_2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and were more sensitive to the effects of the selective 5-HT_2AR antagonist M100907 to suppress impulsive action relative to LI rats. A positive correlation was observed between levels of premature responses and 5-HT_2AR binding density in frontal cortex ([³H]-ketanserin radioligand binding). Elevated mPFC 5-HT_2AR protein expression concomitant with augmented association of the 5-HT_2AR with PSD95 differentiated HI from LI rats. The observed differential sensitivity of HI and LI rats to 5-HT_2AR ligands and associated distinct 5-HT_2AR protein profiles provide evidence that spontaneously occurring individual differences in impulsive action reflect variation in the cortical 5-HT_2AR system.     

Interferon gamma release assay in the diagnosis of tuberculous mastitis

Tuberculous mastitis is rare, especially in Western countries. We describe a case where the interferon gamma release assay blood test led to diagnosis and successful treatment of the disease.     

Prostate cancer detection upon transrectal ultrasound-guided biopsy in relation to digital rectal examination and prostate-specific antigen level: what to expect in the Chinese population?

We investigated the prostate cancer detection rates upon transrectal ultrasound (TRUS)-guided biopsy in relation to digital rectal examination (DRE) and prostate-specific antigen (PSA), and risk factors of prostate cancer detection in the Chinese population. Data from all consecutive Chinese men who underwent first TRUS-guided prostate biopsy from year 2000 to 2013 was retrieved from our database. The prostate cancer detection rates with reference to DRE finding and PSA level of < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ were investigated. Multivariate logistic regression analyses were performed to investigate for potential risk factors of prostate cancer detection. A total of 2606 Chinese men were included. In patients with normal DRE, the cancer detection rates were 8.6%, 13.4%, 21.8%, 41.7% and 85.2% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. In patients with abnormal DRE, the cancer detection rates were 12.4%, 30.2%, 52.7%, 80.6% and 96.4% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. Older age, smaller prostate volume, larger number of biopsy cores, presence of abnormal DRE finding and higher PSA level were associated with increased risk of prostate cancer detection upon multivariate logistic regression analyses (P < 0.001). Chinese men appeared to have lower prostate cancer detection rates when compared to the Western population. Taking the different risk factors into account, an individualized approach to the decision of TRUS-guided biopsy can be adopted.     

Periocular Cutaneous Anaplastic Large Cell Lymphoma Clearance with Brentuximab Vedotin

The treatment options for primary cutaneous anaplastic large cell lymphoma are numerous, including excision, external beam radiation, methotrexate, and chemotherapy. In patients with recalcitrant tumors, alternative options may be necessary. The authors report a 60-year-old man with a 6cm primary cutaneous anaplastic large cell lymphoma located on the right cheek, near the eye. After failing four months of methotrexate, and due to concern for ocular radiation toxicity, the patient started brentuximab vedotin, an anti-CD30 antibody-drug conjugate. With two cycles of brentuximab vedotin, he had a complete response that was histologically confirmed. Six months after a total of four cycles, he remains clear. He experienced no side effects other than a mild infusion reaction. Brentuximab vedotin may be an effective option for primary cutaneous anaplastic large cell lymphoma in patients with large tumors in cosmetically sensitive areas, those who have not responded to conventional therapy, or those who have contraindications to radiation therapy. Optimal dosing for primary cutaneous anaplastic large cell lymphoma and long-term outcomes are not currently known.Primary cutaneous anaplastic large cell lymphomaa (pcALCL) is a subtype of cutaneous T-cell lymphoma (CTCL) histologically characterized by large, highly typical CD30+ T-cells that clinically presents as a solitary tumor. The authors report a case of a large pcALCL arising on the face with periorbital extension. The size and periorbital location were relative contraindications to radiation therapy and surgery. Oral weekly methotrexate was initiated, but the tumor enlarged in size and the growth extended near the eye despite generally adequate doses. After brief treatment with brentuximab vedotin, the tumor resolved completely.     

Gingival seal of deep Class II direct and indirect composite restorations

PURPOSE: To evaluate in vitro the gingival microleakage of Class II direct and indirect composite restorations with cervical margins 0.5 mm apical to the cemento-enamel junction (CEJ). METHODS: Mesial-occusal (MO) preparations of similar size were made in 10 homologous pairs of caries-free extracted human third molars. One specimen for each pair was prepared for a direct composite restoration and the other for an indirect composite restoration. Direct preparations were restored per manufacturer's instructions. Indirect preparations were impressed, and composite restorations were fabricated and cemented with a dual-cure cement. A total-etch technique was used for all restorations. Restorations were finished, polished, stored for 1 week in distilled water at 37 degrees C, thermocycled (5 degrees-55 degrees C x 1000), sealed with fingernail polish (leaving a 1.5 mm open periphery adjacent to the gingival margin), and placed in 0.5% basic fuchsin dye for 24 hours. Teeth were sectioned longitudinally (mesio-distally) within the restoration in two cuts and the four resulting surfaces (two inner cut surfaces, two outer cut surfaces) were evaluated for dye penetration with a x10 stereoscope using a scale of 0 (no penetration) to 4 (dye penetration involving more than half the axial wall). RESULTS: All 20 specimens had at least one score of three (dye penetration involving less than half of the axial wall) or four. Statistical analysis (Wilcoxon paired-sample test) disclosed a significant decrease in the indirect composite microleakage scores for the two outer cuts (P = 0.006, P = 0.002). No significant differences in microleakage scores were found between materials for the inner cut surfaces of the specimens. Overall, the results of die penetration showed no statistical difference between Class II direct and indirect composite restorations for microleakage.     

Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase

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