Modafinil augments brain activation associated with reward anticipation in the nucleus accumbens

Rationale

The nucleus accumbens (NAc) works as a key brain structure of the reward system, in which reward-related neural activity is well correlated with dopamine release from mesolimbic dopaminergic neurons.

Objectives

Since modafinil can modulate dopaminergic transmission through re-uptake inhibition of dopamine, we investigated whether modafinil affects the reward-related brain activity in the NAc in healthy subjects.

Methods

Twenty healthy participants underwent two series of functional magnetic resonance imaging while performing monetary incentive delay task in which they were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money, under modafinil or placebo condition. Blood oxygenation-level dependent (BOLD) activation signals during gain and loss anticipations were analyzed in the NAc as an a priori region of interest as well as the whole brain.

Results

Modafinil significantly changed subjective feelings toward positive ones. The activation of BOLD signals was observed during gain anticipation under the placebo and modafinil conditions in the left and bilateral NAc, respectively. The modafinil condition showed significantly higher BOLD signal change at the highest gain (+¥500) cue compared to the placebo condition.

Conclusions

The present study showed that modafinil affects reward processing in the NAc in healthy subjects through enhancing more positive anticipation, and it may provide a basis for the use of this drug for treating anhedonia observed in psychiatric disorders.     

Blood pressure after treatment with sodium–glucose cotransporter 2 inhibitors influences renal composite outcome: Analysis using propensity score-matched models

Aims/IntroductionSodium–glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcome in patients with type 2 diabetes mellitus, but the mechanism is not fully understood. The aim of this retrospective study was to assess the association of achieved blood pressure with renal outcomes in Japanese type 2 diabetes mellitus patients with chronic kidney disease.Materials and MethodsWe assessed 624 Japanese type 2 diabetes mellitus patients with chronic kidney disease taking SGLT2i for >1 year. The patients were classified as those with post‐treatment mean arterial pressure (MAP) of ≥92 mmHg (n = 344) and those with MAP of <92 mmHg (n = 280) for propensity score matching (1:1 nearest neighbor match with 0.04 of caliper value and no replacement). The end‐point was a composite of progression of albuminuria or a decrease in the estimated glomerular filtration rate by ≥15% per year.ResultsBy propensity score matching, a matched cohort model was constructed, including 201 patients in each group. The incidence of renal composite outcome was significantly lower among patients with MAP of <92 mmHg than among patients with MAP of ≥92 mmHg (n = 11 [6%] vs n = 26 [13%], respectively, P = 0.001). The change in estimated glomerular filtration rate was similar in the two groups; however, the change in the albumin‐to‐creatinine ratio was significantly larger in patients with MAP of <92 mmHg.ConclusionsIn Japanese type 2 diabetes mellitus patients with chronic kidney disease, blood pressure after SGLT2i administration influences the renal composite outcome. Blood pressure management is important, even during treatment with SGLT2i.     

Association between Grit Scales and adherence to regular hospital visits among Japanese patients with type 2 diabetes: Prospective observational study

This study examined the association between Grit Scales and adherence to a schedule of regular hospital visits among Japanese type 2 diabetes patients. Patients with type 2 diabetes who visited the outpatient clinic as new patients comprised the study’s participants. Self-administered Short Grit Scale data were obtained from 122 patients at the first consultation and were then observed for 1 year. As the results, 21 participants failed to attend the hospital. In a logistic regression analysis, the Grit Scale as a continuous variable was positively associated with adherence to regular clinical visits. Its odds ratio and 95% confidential interval was 9.68 and 2.87–32.65 (P = 0.0003). In conclusion, it is likely that the Grit Scale is closely associated with adherence to regular hospital visits among Japanese type 2 diabetes patients.     

PU.1 as an essential activator for the expression of gp91phox gene in human peripheral neutrophils, monocytes, and B lymphocytes

We have reported a deficiency of a 91-kDa glycoprotein component of the phagocyte NADPH oxidase (gp91^phox) in neutrophils, monocytes, and B lymphocytes of a patient with X chromosome-linked chronic granulomatous disease. Sequence analysis of his gp91^phox gene revealed a single-base mutation (C → T) at position −53. Electrophoresis mobility-shift assays showed that both PU.1 and hematopoietic-associated factor 1 (HAF-1) bound to the inverted PU.1 consensus sequence centered at position −53 of the gp91^phox promoter, and the mutation at position −53 strongly inhibited the binding of both factors. It was also indicated that a mutation at position −50 strongly inhibited PU.1 binding but hardly inhibited HAF-1 binding, and a mutation at position −56 had an opposite binding specificity for these factors. In transient expression assay using HEL cells, which express PU.1 and HAF-1, the mutations at positions −53 and −50 significantly reduced the gp91^phox promoter activity; however, the mutation at position −56 did not affect the promoter activity. In transient cotransfection study, PU.1 dramatically activated the gp91^phox promoter in Jurkat T cells, which originally contained HAF-1 but not PU.1. In addition, the single-base mutation (C → T) at position −52 that was identified in a patient with chronic granulomatous disease inhibited the binding of PU.1 to the promoter. We therefore conclude that PU.1 is an essential activator for the expression of gp91^phox gene in human neutrophils, monocytes, and B lymphocytes.     

Storage and transport of isolated M. tuberculosis at public and private health institutions in Japan

PURPOSE: To obtain basic data about the present practices on storage and transport of isolated M. tuberculosis at public and private health institutions in Japan. METHOD: Survey forms regarding the practices on storage and transport of isolated M. tuberculosis were distributed and collected by post-mail in January 2007 to 76 local public health institutions, 145 public health centres, and 150 public or private hospitals. The questionnaire was adopted from the guidelines proposed by the Ministry of Health, Labour, and Welfare in 2006 on storage and transport of isolated M. tuberculosis. RESULTS: The respondents of the survey were as follows: 96.1% (73/76) from local public health institutions, 93.8% (136/145) from public health centres, and 73.3% (110/150) from hospitals. In general, local public health institutions conformed well to the proposed standards, however public health centres and hospitals were not compliant to some standards. SUMMARY: Based on the survey conducted on the practice of storage and transport of isolated M. tuberculosis, certain discrepancy was found among public health centres and hospitals.