Diphenylprolinol silyl ether catalyzed asymmetric Michael reaction of nitroalkanes and ß,ß-disubstituted α,ß-unsaturated aldehydes for the construction of all-carbon quaternary stereogenic centers.

The asymmetric Michael reaction of nitroalkanes and ß,ß-disubstituted α,ß-unsaturated aldehydes was catalyzed by diphenylprolinol silyl ether to afford 1,4-addition products with an all-carbon quaternary stereogenic center with excellent enantioselectivity. The reaction is general for ß-substituents such as ß-aryl and ß-alkyl groups, and both nitromethane and nitroethane can be employed. The addition of nitroethane is considered a synthetic equivalent of the asymmetric Michael reaction of ethyl and acetyl substituents by means of radical denitration and Nef reaction, respectively. The short asymmetric synthesis of (S)-ethosuximide with a quaternary carbon center was accomplished by using the present asymmetric Michael reaction as the key step. The reaction mechanism that involves the E/Z isomerization of α,ß-unsaturated aldehydes, the retro-Michael reaction, and the different reactivity between nitromethane and nitroethane is discussed.

In-situation safety behaviors among patients with panic disorder: descriptive and correlational study.

AIM: In-situation safety behaviors play an important role in the maintenance of anxiety because they prevent patients from experiencing unambiguous disconfirmation of their unrealistic beliefs about feared catastrophes. Strategies for identifying particular safety behaviors, however, have not been sufficiently investigated. The aims of the present study were to (i) develop a comprehensive list of safety behaviors seen in panic disorder and to examine their frequency; and (ii) correlate the safety behaviors with panic attack symptoms, agoraphobic situations and treatment response. METHODS: The subjects consisted of 46 consecutive patients who participated in group cognitive behavioral treatment (CBT) for panic disorder. All the patients completed a Safety Behavior List that was developed based on experiences with panic disorder patients. RESULTS: Carrying medications, distracting attention, carrying a plastic bottle, and drinking water were reported by more than half of the patients. The strongest correlations between panic symptoms and safety behaviors were found between symptoms of derealization and listening to music with headphones, paresthesia and pushing a cart while shopping, and nausea and squatting down. The strongest association between agoraphobic situations and safety behaviors was found between the fear of taking a bus or a train alone and moving around. Staying still predicted response to the CBT program, while concentrating on something predicted lack of response. CONCLUSION: An approximate guideline has been developed for identifying safety behaviors among patients with panic disorder and should help clinicians use CBT more effectively for these patients.

Behavior of Male Gamete Fusogen GCS1/HAP2 and the Regulation in Arabidopsis Double Fertilization.

In the sexual reproduction of flowering plants, two independent fertilization events occur almost simultaneously: two identical sperm cells fuse with either the egg cell or the central cell, resulting in embryo and endosperm development to produce a seed. GCS1/HAP2 is a sperm cell membrane protein essential for plasma membrane fusion with both female gametes. Other sperm membrane proteins, DMP8 and DMP9, are more important for egg cell fertilization than that of the central cell, suggesting its regulatory mechanism in GCS1/HAP2-driving gamete membrane fusion. To assess the GCS1/HAP2 regulatory cascade in the double fertilization system of flowering plants, we produced Arabidopsis transgenic lines expressing different GCS1/HAP2 variants and evaluated the fertilization in vivo. The fertilization pattern observed in GCS1_RNAi transgenic plants implied that sperm cells over the amount of GCS1/HAP2 required for fusion on their surface could facilitate membrane fusion with both female gametes. The cytological analysis of the dmp8dmp9 sperm cell arrested alone in an embryo sac supported GCS1/HAP2 distribution on the sperm surface. Furthermore, the fertilization failures with both female gametes were caused by GCS1/HAP2 secretion from the egg cell. These results provided a possible scenario of GCS1/HAP2 regulation, showing a potential scheme for capturing additional GCS1/HAP2-interacting proteins.

Influence of Psychotropic Pro Re Nata Drug Use on Outcomes in Hospitalized Patients with Schizophrenia.

Objective: In the treatment of patients with schizophrenia, pro re nata (PRN) drugs are commonly prescribed for medical indications such as agitation, acute psychiatric symptoms, insomnia, and anxiety. However, high-quality evidence supporting the use of PRN medications is lacking, and these drugs are administered on the basis of clinical experience and habits. Therefore, the actual use of psychotropic PRN drugs and its influence on the patients' outcomes need to be investigated. Methods: This study included 205 patients who underwent inpatient treatment for schizophrenia. We investigated the prescription of psychotropic drugs before admission and at discharge, as well as the dosing frequency of PRN drugs during hospitalization. We also examined the influence of psychotropic PRN drug use on hospitalization days, antipsychotic polypharmacy, and readmission rates. Results: Patients who used psychotropic PRN drugs during hospitalization had significantly longer hospitalization days (p = 7.5 × 10-4) and significantly higher rates of antipsychotic polypharmacy (p = 2.4 × 10-4) at discharge than those who did not use psychotropic PRN drugs. Moreover, a higher number of psychotropic PRN drugs used per day was associated with higher readmission rates within 3 months of discharge (p = 4.4 × 10-3). Conclusion: Psychotropic PRN drug use is associated with prolonged hospitalization, antipsychotic polypharmacy, and increased readmission rates in inpatients with schizophrenia. Therefore, psychiatric symptoms should be stabilized with regularly prescribed medications without the extensive use of psychotropic PRN drugs. Moreover, a system for monitoring and reexamining PRN drug use needs to be established.

Distinct neuropsychological profiles of three major symptom dimensions in obsessive-compulsive disorder.

Recent neuroimaging studies have suggested that different symptom dimensions are mediated by partially distinct neural systems in obsessive-compulsive disorder (OCD). However, the correlations between neuropsychological profiles and symptom dimensions in OCD are unknown. The aim of this study was to examine the extent to which OCD symptom dimensions were associated with episodic memory and attention and executive functions. The symptom dimensions of 63 patients with OCD were assessed using both the Padua Inventory and the Y-BOCS symptom checklist. Then, we administered the Logical Memory (LM) subset of the Wechsler Memory Scale-Revised (WMR-R) test and evaluated inhibition (Stroop test, Trail Making test) and cognitive flexibility (Digit Symbol test, Letter Fluency, and Category Fluency). While associations were observed between scores on the contamination/cleaning dimension and better performances on the LM and Trail Making tests, associations were also observed between scores on the aggressive/checking dimension and poorer performances on the Trail Making test. In addition, we found that scores on the symmetry/ordering dimension were associated with poorer performances on the LM and Trail Making tests. Our results support the hypothesis that different symptoms may represent distinct and partially overlapping neurocognitive networks in OCD patients.

Cognitive-behavior therapy for Japanese patients with panic disorder: acute phase and one-year follow-up results.

AIM: The aim of this paper is to report the outcomes and follow-up data of our cognitive behavioral therapy program for Japanese patients with panic disorder and to examine the baseline predictors of their outcomes. METHODS: Seventy outpatients with panic disorder with or without agoraphobia were treated with manualized group cognitive behavioral therapy. RESULTS: Fourteen patients (20%) did not complete the program. Among the completers, the average Panic Disorder Severity Scale score fell from 12.8 at baseline to 7.1 post-therapy (44.7% reduction). This effectiveness was sustained for 1 year. While controlling for the baseline severity, the duration of illness and the baseline social dysfunction emerged as significant predictors of the outcome. CONCLUSIONS: Our data suggest that group cognitive behavioral therapy for panic disorder can bring about as much symptom reduction among Japanese patients with panic disorder as among Western patients.

Total Synthesis of Selligueain A, a Sweet Flavan Trimer.

The first total synthesis of selligueain A (4), a plant-derived sweet polyphenol, has been achieved. The key step was the de novo synthetic approach to the selectively protected epiafzelechin unit 10, which was divergently converted to three flavan units 7, 8, and 9. These components were combined by an orthogonal activation and annulation method, enabling assembly of the characteristic trimeric structure with single and double interflavan linkages.

Sensitization of catastrophic cognition in cognitive-behavioral therapy for panic disorder.

BACKGROUND: Cognitive model of panic disorder have proposed that panic attacks result from the catastrophic misinterpretation of certain bodily sensations. Cognitive-Behavioral Therapy (CBT) for panic disorder aims to change these catastrophic cognitions. CBT intervention successfully caused reduction of catastrophic cognitions and symptomatic improvement in the majority of cases. However there are some patients who fail to modify their catastrophic cognitions or rather experience an increase in them during CBT treatment. It is clinically and theoretically important to understand about cognitive sensitization of panic disorder during CBT sessions. The purpose of the present study is 1) to clarify the baseline characteristics of panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment, and 2) to examine the course of symptomatic changes for them. METHODS: Of ninety-five outpatients with panic disorder started the group CBT program for treatment of panic disorder, seventy-nine completer were classified as "cognitively sensitized (CS)" or "cognitive responding (CR)" or "no-responder" according to the difference of the Agoraphobic Cognitions Questionnaire score across treatment. We compared the CS and CR patients in terms of their baseline clinical characteristics. Then we assessed the symptomatic and functional changes for both groups. RESULTS: At the start of the CBT program, despite of the same degree of panic disorder severity, CS scored significantly lower on ACQ score than CR. CS also showed significantly lower score on anticipatory anxiety compared to CR. At the end of treatment CS showed significant improvement in severity of panic disorder, although the degree of improvement was smaller than that for CR. Then CS would progressively reduce their agoraphobic fear and avoidance, and would improve their functional impairment up to three month of follow-up. CONCLUSION: Panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment could nonetheless gradually improve. They showed a relatively low level of catastrophic cognition and anticipatory anxiety before starting the CBT program. We might conclude that temporary sensitization of catastrophic cognition may be necessary before improvement especially among those with initially low catastrophic body sensation fears and that we need not be concerned too much with temporary increase in catastrophic cognition in the process of CBT for panic disorder.

Interoceptive hypersensitivity as prognostic factor among patients with panic disorder who have received cognitive behavioral therapy.

The efficacy of cognitive behavioral therapy (CBT) in the acute-phase treatment of panic disorder is well established. However, there are data to show CBT may not always be able to prevent recurrence after treatment. The central cognitive component of panic disorder psychopathology is thought to be hypersensitivity to physical sensations. The present study reports that some aspects of interoceptive hypersensitivity, gastrointestinal fears in particular, were predictive of the course of panic disorder after end of CBT. Clinically it is suggested that new interoceptive tasks related to gastrointestinal fears are needed.

Copper(II) and zinc(II) complexes with C-glycoside-pendant dipicolylamine (DPA)-amino acid conjugates.

A series of dipicolylamine (DPA)-functionalized amino acid ligands with a pendant C-glycosyl amide has been synthesized and complexed with Cu(II) and Zn(II). Amino acid derivatives equipped with a DPA unit were conjugated with C-glycosylamine prepared from acetobromoglucose in 4 steps. These ligands bind to metal ions as a N(3) or N(3)O chelate utilizing three DPA nitrogens and carbamoyl oxygen atoms. In the crystal structures of copper(II) and zinc(II) complexes of AcL1 (2-(N',N'-bis(2'''-pyridylmethyl)amino)-N-(2'-(2'',3'',4'',6''-tetra-O-acetyl-beta-D-glucopyranosyl)ethyl)acetamide, carbamoyl oxygen binds to the metal centre, however, NMR analysis reveals that AcL1 acts as a tridentate ligand in solution. The CD spectrum of the copper(II) complex with glycine-based AcL1 at the d-d transition region indicates that the chirality at the sugar moiety does not induce an asymmetric metal coordination environment. In contrast, the chirality at the amino acid moiety for alanine and phenylalanine derivatives, AcL2 and AcL3, respectively, induces characteristic Cotton effect in the 500-800 nm region depending on the nature of the alpha-carbon substituent of the amino acid moiety.