OBJECTIVE: Norepinephrine is an important chemical messenger that is involved in mood and stress in humans, and is reabsorbed by the norepinephrine transporter (NET). According to Cloninger's theory, the noradrenergic system mediates the personality trait of reward dependence. Thus far, although association studies on NET gene polymorphisms and Cloninger's personality traits have been reported, they yielded inconsistent results. Therefore, in the present study we investigated whether or not the 1287G/A, -182T/C and -3081A/T polymorphisms of the NET gene (SLC6A2) are associated with reward dependence-related traits, as assessed by the five-factor model. METHODS: After written informed consent was obtained from participants, the three NET gene polymorphisms were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), and personality was assessed by the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) in 270 Japanese university students. RESULTS: A significant relation was found between the -3081A/T functional promoter polymorphism and NEO-FFI scores: those with the T allele exhibited a lower extraversion (E) score than those without the T allele (Mann-Whitney U-test: z=-3.861, p<0.001). However, there was no correlation between the other NET gene polymorphisms and E score, and no association with other dimensions and these three polymorphisms. CONCLUSION: We conclude that the -3081A/T functional polymorphism in the NET gene may affect the extraversion of reward dependence-related traits, as measured by NEO-FFI. However, we used only the shortened version of NEO-PI-R in this study. Further investigations are necessary using the full version of self-rating personality questionnaires.
Alleles ; Asian Continental Ancestry Group* ; Extraversion (Psychology) ; Humans ; Informed Consent ; Norepinephrine ; Norepinephrine Plasma Membrane Transport Proteins* ; Polymerase Chain Reaction ; Surveys and Questionnaires ; Reward

In patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer (LC) who have acquired resistance to first and/or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), detection of EGFR T790M (T790M) mutation is essential before administration of osimertinib. Tissue sample is the main specimen used to detect the T790M mutation, and so cell block preparation using pleural or pericardial fluid should be considered. The utility of body cavity effusion cell block methods in T790M mutation detection have not yet been fully evaluated. This study aimed to evaluate the clinical background and treatment course of LC patients harboring the T790M mutation by using body cavity effusion cell block methods at our hospital. All patients were treated with first and/or second-generation EGFR-TKIs and had developed malignant pleural or pericardial fluid as a result of progressive disease. T790M mutation status was evaluated using body cavity effusion cell block method in 9 patients, from April 2016 to August 2017. We retrospectively evaluated the clinical characteristics and treatment course of these 9 patients (3 males and 6 females; median age 76 years). At the first diagnosis of LC, 7 patients had stage IV cancer; 4 patients were diagnosed by bronchial fibroscopy and 3 were diagnosed from pleural fluid examination. Regarding EGFR mutation, 3 and 6 patients carried the exon 19 deletion and L858R mutation, respectively. Median time interval between the first diagnosis of LC and T790M mutation evaluation was 30.8 months; 7 patients were diagnosed with positive T790M mutation by using body cavity effusion cell block methods. The T790M mutation was highly detected by examination of body cavity effusion cell blocks. Further evaluation is necessary with respect to variations in T790M detection rate based on the specimen collection site and/or progressive disease pattern in different patients.

Methods: This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months’ chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. Results: Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. Conclusions Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1–4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.