The Effects of Paliperidone Palmitate 1 Month on the Employment Status and Social Functioning of Patients with Schizophrenia.

Objective: We sought to evaluate the effects of a one-month paliperidone palmitate formulation (PP1M) on employment status, social function, symptomatology, and safety and conducted a two-year postmarketing surveillance study of Paliperidone Palmitate 1 Month (PP1M). Methods: Patients diagnosed with schizophrenia participated in the study. Employment status was recorded at baseline and changes were measured at one and two years. Social functioning and symptomatology were assessed using the Social and Occupational Functioning Assessment Scale (SOFAS) and the Clinical Global Impression-Schizophrenia (CGI-SCH). Data on adverse events were also collected. Results: A total of 1,319 patients were enrolled in this investigation, including 1,306 who were evaluable for safety and 1,279 who were evaluable for efficacy. The maintenance rate during the observation period was 49.4 percent. During the observation period, the percentages of patients reporting employment significantly increased: 24.3 percent of patients were employed in some capacity at baseline, 32.5 percent of patients were employed at one year, and 34.6 percent of patients were employed at two years. Significant improvements were observed in both SOFAS and CGI-SCH scores during the observation period. The percentage of patients with socially functional remission also significantly increased. A strong association between the improvement of social function, gender, and monotherapy versus polypharmacy and the improvement of employment status was observed. A total of 29.3 percent of patients experienced at least one adverse event. There were no unexpected findings from long-term treatment and a safety profile, including mortality. Conclusion: PP1M treatment appears to improve not only schizophrenic symptoms but also functional outcomes.

Difficulty Inserting Cuffed Endotracheal Tubes in a Child: A Case Report.

We experienced difficulty inserting cuffed inner diameter (ID) 4.5- and 5.0-mm endotracheal tubes (ETTs) in a 5-year-old boy. Postoperative ultrasound investigations showed that the internal transverse width of the cricoid cartilage was 8.0 mm. The maximum outer diameter (OD) of the deflated cuff portion of the cuffed ID 4.5- and 5.0-mm ETTs was 8.5 and 9.6 mm, respectively. The OD of an uncuffed ID 5.5-mm ETT was 7.6 mm; this tube passed the cricoid cartilage. Hence, the transverse width of the cricoid cartilage and ETT diameter including cuff folds should be considered when selecting cuffed ETTs.

Ultrasound detection of guidewires in-plane during pediatric central venous catheterization.

OBJECTIVE/AIM: To assess the usefulness of longitudinal ultrasound images of guidewires for pediatric central venous catheter (CVC) placement. BACKGROUND: To avoid arterial placement of a CVC, it is important to ensure that the guidewires are in the internal jugular vein (IJV) before inserting the dilators. Ultrasound confirmation of the guidewire position may eliminate accidental arterial dilation during CVC cannulation. METHODS: Fifty pediatric patients undergoing general endotracheal anesthesia for cardiovascular surgery were enrolled. The mean ± sd value for age was 14.8 ± 16.8 months; height, 69.1 ± 14.6 cm; and weight, 7.1 ± 3.2 kg. Longitudinal ultrasound images of guidewires in or around the right IJV during pediatric CVC placement were acquired using an L10-5 MHz probe (TiTAN(®); SonoSite Co., Tokyo, Japan), with the neck of the patient fully extended and the head turned 15-30 degree to the left. RESULTS: In 42 (84%) patients, guidewires were visible in the lumen of the IJV. However, in 8 (16%) patients, guidewires were not visible. Longitudinal imaging of guidewires was achieved with high probability (100%) in children in whom the distance from the clavicle to the angle of the mandible was more than 59 mm, in whom the distance from the clavicle to the puncture site was more than 30 mm, or in children taller than 65 cm. All cannulations were confirmed to be CVCs by chest radiography. CONCLUSIONS: To confirm the insertion of dilators into veins in children, we recommend that longitudinal images of the guidewires should be initially acquired.

SWAP70 functions as a Rac/Rop guanine nucleotide-exchange factor in rice.

Rho family small GTPases are involved in diverse signaling processes including immunity, growth, and development. The activity of Rho GTPases is regulated by cycling between guanosine diphosphate (GDP)-bound inactive and guanosine triphosphate (GTP)-bound active forms, in which guanine nucleotide exchange factors (GEFs) predominantly function to promote activation of the GTPases. In animals, most Rho GEFs possess a Dbl (diffuse B-cell lymphoma) homology (DH) domain which functions as a GEF-catalytic domain. However, no proteins with the DH domain have been identified in plants so far. Instead, plant-specific Rho GEFs with the PRONE domain responsible for GEF activity have been found to constitute a large family in plants. In this study, we found rice homologs of human SWAP70, Oryza sativa (Os) SWAP70A and SWAP70B, containing the DH domain. OsSWAP70A interacted with rice Rho GTPase OsRac1, an important signaling factor for immune responses. The DH domain of OsSWAP70A exhibited the GEF-catalytic activity toward OsRac1 as found in animal Rho GEFs, indicating that plants have the functional DH domains. Transient expression of OsSWAP70A enhanced OsRac1-mediated production of reactive oxygen species in planta. Reduction of OsSWAP70A and OsSWAP70B mRNA levels by RNA interference resulted in the suppression of chitin elicitor-induced defense gene expression and ROS production. Thus, it is likely that OsSWAP70 regulates immune responses through activation of OsRac1.

Tracking and visualizing the circadian ticking of the cyanobacterial clock protein KaiC in solution.

The circadian clock in cyanobacteria persists even without the transcription/translation feedbacks proposed for eukaryotic systems. The period of the cyanobacterial clock is tuned to the circadian range by the ATPase activity of a clock protein known as KaiC. Here, we provide structural evidence on how KaiC ticks away 24 h while coupling the ATPase activity in its N-terminal ring to the phosphorylation state in its C-terminal ring. During the phosphorylation cycle, the C-terminal domains of KaiC are repositioned in a stepwise manner to affect global expansion and contraction motions of the C-terminal ring. Arg393 of KaiC has a critical function in expanding the C-terminal ring and its replacement with Cys affects the temperature compensation of the period--a fundamental property of circadian clocks. The conformational ticking of KaiC observed here in solution serves as a timing cue for assembly/disassembly of other clock proteins (KaiA and KaiB), and is interlocked with its auto-inhibitory ATPase underlying circadian periodicity of cyanobacteria.

Brain cannabinoid CB2 receptor in schizophrenia.

BACKGROUND: Neural endocannabinoid function appears to be involved in schizophrenia. Two endocannabinoid receptors, CB1 and CB2, are found in the brain and elsewhere in the body. We investigated roles of CB2 in schizophrenia. MATERIALS AND METHODS: An association study was performed between tag single nucleotide polymorphisms (SNPs) in the CNR2 gene encoding the CB2 receptor and schizophrenia in two independent case-control populations. Allelic differences of associated SNPs were analyzed in human postmortem brain tissues and in cultured cells. Prepulse inhibition and locomotor activity in C57BL/6JJmsSlc mice with CB2 receptor antagonist AM630 administration was examined. RESULTS: The analysis in the first population revealed nominally significant associations between schizophrenia and two SNPs, and the associations were replicated in the second population. The R63 allele of rs2501432 (R63Q) (p = .001), the C allele of rs12744386 (p = .005) and the haplotype of the R63-C allele (p = 5 x 10(-6)) were significantly increased among 1920 patients with schizophrenia compared with 1920 control subjects in the combined population. A significantly lower response to CB2 ligands in cultured CHO cells transfected with the R63 allele compared with those with Q63, and significantly lower CB2 receptor mRNA and protein levels found in human brain with the CC and CT genotypes of rs12744386 compared with TT genotype were observed. AM630 exacerbated MK-801- or methamphetamine-induced disturbance of prepulse inhibition and hyperactivity in C57BL/6JJmsSlc mice. CONCLUSIONS: These findings indicate an increased risk of schizophrenia for people with low CB2 receptor function.

Design, synthesis, enzyme inhibition, and tumor cell growth inhibition of 2-anilinobenzamide derivatives as SIRT1 inhibitors.

A series of 2-anilinobenzamide derivatives were designed, synthesized and evaluated for their SIRT1-inhibitory activity. Among these, compounds 3 and 5 inhibited SIRT1 activity in enzyme assays and suppressed the growth of Daudi and HCT116 cells.

[Fiberscopic reduction under local anesthesia for anterior arytenoid cartilage dislocation].

Arytenoid cartilage dislocation is a known complication of tracheal intubation and is also a type of laryngeal injury. Although spontaneous recovery has been reported, most patients require reduction via pharyngoscopy under general or neuroleptic anesthesia, and some must be treated by open reduction such as laryngoplasty. We report 8 cases of arytenoid cartilage dislocation between August 2003 and August 2004. Excluding 3 patients who recovered spontaneously, we conducted reduction under local anesthesia as an ambulatory procedure in the other 5 with anterior dislocation, i.e., 2 men and 3 women aged 53 to 75 years old. Of these 5, dislocation occurred after tracheal intubation in 4, and in 1 after wearing a laryngeal mask. The outcome was favorable in all 5. Surgery was conducteded after a fiberscope was inserted nasally and a urethral balloon catheter was inserted via the other nasal cavity under topical anesthesia with 4% lidocaine for both nasal cavities and the larynx. While monitoring the larynx, we expanded the balloon and pulled it away from the glottis. The expanded balloon was then placed at the arytenoid region for a few seconds. This procedure was repeated several times to achieve reduction. Three patients recovered well within 1 to 2 weeks of the first reduction, while 2 requierd a second reduction because of insufficient improvement after the first. These two both showed improved vocal cord movement and recovery from hoarseness within 1 to 2 weeks after the second reduction. We conducted 7 reductions without complications in any patient. Our approach is usable in the ambulatory setting, and is simple, minimally invasive, and effective. We consider it to be useful treatment for anterior arytenoid cartilage dislocation.

[Medical imaging: its medical economics and recent situation in Japan.].

Two fields of radiology, medical imaging and radiation therapy, are coded separately in medical fee system, and the health care statistics of 2003 shows that expenditure on the former was 5.2% of the whole medical cost and the latter 0.28%. Introduction of DPC, an abbreviation of Diagnostic Procedure Combination, was carried out in 2003, which was an essential reform of medical fee payment system that have been managed on fee-for-service base throughout, and 22% of beds for acute patients care are under the control of DPC payment in 2006. As medical imaging procedures are basically classified in inclusive payment in DPC system, their accurate statistics cannot be figured out because of the lack of description of individual procedures in DPC bills. Policy-making of medical economics will suffer a great loss from the deficiency of detailed data in published statistics. Important role in clinical diagnoses of CT and MR results an increase of fee paid for them up to more than half of total expenditure on medical imaging. So, dominant reduction of examination fee has been done for MR imaging, especially in 2002, to reduce the total cost of medical imaging. Follows could be featured as major topics of medical imaging in health insurance system, (a) fee is newly assigned for electronic handling of CT-and-MR images, and nuclear medicine, and (b) there is still a mismatch between actual payment and quality of medical facilities. As matters related to medical imaging, the followings should be stressed; (a) numbers of CT and MR units per population are dominantly high among OECD countries, but, those controlled by qualified radiologists are at the average level of those countries, (b) there is a big difference of MR examination quality among medical facilities, and (c) 76% of newly-installed high-end MR units are supplied by foreign industries. Hopefully, there will be an increase in the concern to medical fee payment system and health care cost because they possibly influence patient care, personnel affairs in clinical facilities, technological development of medical devices, and so on.

Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro.

Kai proteins globally regulate circadian gene expression of cyanobacteria. The KaiC phosphorylation cycle, which persists even without transcription or translation, is assumed to be a basic timing process of the circadian clock. We have reconstituted the self-sustainable oscillation of KaiC phosphorylation in vitro by incubating KaiC with KaiA, KaiB, and adenosine triphosphate. The period of the in vitro oscillation was stable despite temperature change (temperature compensation), and the circadian periods observed in vivo in KaiC mutant strains were consistent with those measured in vitro. The enigma of the circadian clock can now be studied in vitro by examining the interactions between three Kai proteins.

Radical scavenging activity and cytotoxicity of phenethyl ether and cinnamic amide derivatives.

Novel phenethyl ether derivatives (PhE) and cinnamic amide derivatives (CA), which have two mono- or polyphenol rings connected either by an ether (PhE) or amide bond (CA), were synthesized. We investigated their ability to scavenge the O2- and DPPH radicals in vitro, using ESR spectroscopy, in relation to their cytotoxic activity against a human oral squamous cell carcinoma (HSC-2) cell line. The radical scavenging activity was considerably influenced by the position of the hydroxyl groups in the benzene rings. Based on their radical scavenging activity and cytotoxicity, these compounds were classified into two groups: active compounds (such as catechol and hydroquinone) and inactive compounds (such as resorcin and phenol). These results suggest a close relationship between the cytotoxic activity and radical scavenging activity derived from ortho-para preference in dihydroxybenzene. PhE and CA might show potential activity in free radical mediated diseases.