Effects of Long-Acting Injectable Paliperidone Palmitate on Clinical and Functional Outcomes in Patients With Schizophrenia Based on Illness Duration.

OBJECTIVE: This study aimed to examine the degree of clinical and functional improvement after paliperidone long-acting injectable (LAI) administration according to the duration of illness. METHODS: Patients with schizophrenia diagnosed by ICD-10 criteria who were planned to start once-monthly paliperidone LAI were recruited from 2010 to 2017. Clinical and functional changes were measured every 4 weeks using the Clinical Global Impressions-Severity of Illness scale (CGI-S) and Personal and Social Performance scale (PSP), respectively, for 6 months after paliperidone LAI initiation. Improvements after starting paliperidone LAI were compared among patients with duration of illness < 3 years, ≥ 3 and < 10 years, and ≥ 10 years. RESULTS: A total of 1,166 participants (duration of illness < 3 years, n = 240; 3 ≤ duration of illness < 10 years, n = 442; duration of illness ≥ 10 years, n = 484) were enrolled. The total olanzapine-equivalent doses of antipsychotics and the LAI monotherapy proportion at the final visit were significantly different among the 3 duration of illness groups (dose: F2,1163 = 18.41, P < .001; monotherapy: χ²2 = 11.73, P = .003). The changes in CGI-S score were significantly different according to the duration of illness, and those with duration of illness < 3 years showed the best improvement (group × week: χ²12 = 25.33, P = .013). All 3 groups showed significantly improved PSP scores (week: χ²6 = 294.2, P < .001). CONCLUSIONS: Starting paliperidone LAI significantly improved clinical and functional outcomes in patients with schizophrenia, especially those with shorter duration of illness. These findings suggest that LAI antipsychotic administration may be considered in early-stage schizophrenia for improved outcomes.

Effect of Feeding High Gamma-Aminobutyric Acid-Containing Giant Embryo Black Sticky Rice (Oryza sativa L.) on Anxiety-Related Behavior of C57BL/6 Mice.

The aim of this study was to determine the effect of feeding high gamma-aminobutyric acid (GABA)-containing black sticky rice giant embryo (BSRGE, Oryza sativa L.) on anxiety-related behavior of C57BL/6 mice. Experimental feedstuff (BSRGE with high GABA+AIN-76A) and control (AIN-76A) were provided to C57BL/6 mouse for 10 days. Antianxiety effects of BSRGE with high GABA were measured using an elevated plus maze. On day 8, the number of open arm entries by GABA and control groups were 1.10 ± 1.60 (mean ± SD) and 0.00 ± 0.00 (P = .030). On day 10, the number of open arm entries by the GABA group was 2.00 ± 1.89, which was significantly (P = .025) higher than that in the control group (0.40 ± 0.84). On day 8, the time the mice spent in open arm in the GABA group and control group was 3.60 ± 7.06 and 0.00 ± 0.00 sec (P = .068), respectively. On day 10, the time the mice in the GABA and control groups spent in open arm was 6.20 ± 5.35 sec and 1.80 ± 3.82 sec (P = .042), respectively. In repeated analysis of variance for the number of entries into open arm and time spent in open arm, significant differences were found between the two groups. Therefore, BSRGE with high GABA content might have an antianxiety effect. This study can serve as a preliminary study so that further antianxiety effects of BSRGE can be determined in more extended animal or clinical research studies in the future.

Genetic localization and in vivo characterization of a Monascus azaphilone pigment biosynthetic gene cluster.

Monascus spp. produce several well-known polyketides such as monacolin K, citrinin, and azaphilone pigments. In this study, the azaphilone pigment biosynthetic gene cluster was identified through T-DNA random mutagenesis in Monascus purpureus. The albino mutant W13 bears a T-DNA insertion upstream of a transcriptional regulator gene (mppR1). The transcription of mppR1 and the nearby polyketide synthase gene (MpPKS5) was significantly repressed in the W13 mutant. Targeted inactivation of MpPKS5 also gave rise to an albino mutant, confirming that mppR1 and MpPKS5 belong to an azaphilone pigment biosynthetic gene cluster. This M. purpureus sequence was used to identify the whole biosynthetic gene cluster in the Monascus pilosus genome. MpPKS5 contains SAT/KS/AT/PT/ACP/MT/R domains, and this domain organization is preserved in other azaphilone polyketide synthases. This biosynthetic gene cluster also encodes fatty acid synthase (FAS), which is predicted to assist the synthesis of 3-oxooactanoyl-CoA and 3-oxodecanoyl-CoA. These 3-oxoacyl compounds are proposed to be incorporated into the azaphilone backbone to complete the pigment biosynthesis. A monooxygenase gene (an azaH and tropB homolog) that is located far downstream of the FAS gene is proposed to be involved in pyrone ring formation. A homology search on other fungal genome sequences suggests that this azaphilone pigment gene cluster also exists in the Penicillium marneffei and Talaromyces stipitatus genomes.

The contribution of vision, proprioception, and efference copy in storing a neural representation for guiding trail leg trajectory over an obstacle.

Stepping over obstacles requires vision to guide the leading leg, but direct visual information is not available to guide the trailing leg. The neural mechanisms for establishing a stored obstacle representation and thus facilitating the trail leg trajectory in humans are unknown. Twenty-four subjects participated in one of three experiments, which were designed to investigate the contribution of visual, proprioceptive, and efference copy signals. Subjects stepped over an obstacle with their lead leg, stopped, and straddled the obstacle for a delay period before stepping over it with their trail leg while toe elevation was recorded. Subsequently, we calculated maximum toe elevation and toe clearance. First, we found that subjects could accurately scale trail leg toe elevation and clearance, despite straddling an obstacle for up to 2 min, similar to quadrupeds. Second, we found that when the lead leg was passively moved over an obstacle (eliminating an efference copy signal and altering proprioception) without vision, trail leg toe elevation and clearance were reduced, and variability increased compared with when subjects actively moved their lead leg. Trail leg toe measures returned to normal when vision was provided during the passive manipulation. Finally, we found that altering lead leg proprioceptive feedback by adding mass to the ankle had no effect on trail leg toe measures. Taken together, our results suggest that humans can store a neural representation of obstacle properties for extended periods of time and that vision appears to be sufficient in this process to guide trail leg trajectory.