Maternal Exposure to Pyrethroid Insecticides during Pregnancy and Infant Development at 18 Months of Age.

The possible association between maternal exposure to pyrethroid insecticides (PYRs) during pregnancy and infant development was explored. Levels of exposure to PYRs was assessed by metabolite (3-phenoybenzoic acid, 3-PBA) concentration in maternal spot urine sampled in the first trimester of index pregnancy, and infant development was assessed at 18 months of age using the Kinder Infants Development Scale (KIDS), which is based on a questionnaire to the caretaker. The relationship between KIDS score and maternal urinary 3-PBA levels was examined by a stepwise multiple regression analysis using biological attributes of the mother and infant, breast feeding, and nursing environment as covariates. The analysis extracted 3-PBA and the nursing environment as significant to explain the KIDS score at 18 months of age with positive partial regression coefficients. Inclusion of fish consumption frequency of the mother during pregnancy as an independent variable resulted in the selection of fish consumption as significant, while the two variables were marginally insignificant but still with a positive coefficient with the KIDS score. The result suggested a positive effect of maternal PYR exposure on infant development, the reason for which is not clear, but an unknown confounding factor is suspected.

Effect of parietal transcranial magnetic stimulation on spatial working memory in healthy elderly persons--comparison of near infrared spectroscopy for young and elderly.

In a previous study, we succeeded in improving the spatial working memory (WM) performance in healthy young persons by applying transcranial magnetic stimulation (TMS) to the parietal cortex and simultaneously measuring the oxygenated hemoglobin (oxy-Hb) level using near-infrared spectroscopy (NIRS). Since an improvement in WM was observed when TMS was applied to the right parietal cortex, the oxy-Hb distribution seemed to support a model of hemispheric asymmetry (HA). In the present study, we used the same study design to evaluate healthy elderly persons and investigated the effect of TMS on WM performance in the elderly, comparing the results with those previously obtained from young persons. The application of TMS did not affect WM performance (both reaction time and accuracy) of 38 elderly participants (mean age = 72.5 years old). To investigate the reason for this result, we conducted a three-way ANOVA examining oxy-Hb in both young and elderly participants. For the right parietal TMS site in the elderly, TMS significantly decreased the oxy-Hb level during WM performance; this result was the opposite of that observed in young participants. An additional three-way ANOVA was conducted for each of the 52 channels, and a P value distribution map was created. The P value maps for the young participants showed a clearly localized TMS effect for both the WM and control task, whereas the P map for the elderly participants showed less significant channels and localization. Further analysis following the time course revealed that right-side parietal TMS had almost no effect on the frontal cortex in the elderly participants. This result can most likely be explained by age-related differences in HA arising from the over-recruitment of oxy-Hb, differentiation in the parietal cortex, and age-related alterations of the frontal-parietal networks.

Prenatal pyrethroid insecticide exposure and thyroid hormone levels and birth sizes of neonates.

Pyrethroid insecticides have been shown to possess thyroid hormone disrupting properties in previous animal studies. In this study, the relationship between maternal exposure to pyrethroid insecticides during pregnancy and neonatal thyroid hormone status (free thyroxine (fT4) and thyroid stimulating hormone (TSH) in whole blood) and birth sizes were explored in 147 mother-neonate pairs in Tokyo. The concentration of 3-phenoxybenzoic acid (3-PBA) in maternal urine, sampled in the first trimester of gestation, was used for pyrethroid exposure assessment. Neonatal fT4 and TSH were within the normal range except for one elevated TSH (but normal fT4) in a neonate. Multiple regression analyses with stepwise variable selection did not extract maternal 3-PBA as significant for neonatal fT4 and TSH, indicating that maternal pyrethroid exposure had no apparent effect on the neonatal thyroid hormone status of the neonate subjects. For birth weight and head circumference, maternal 3-PBA was selected as significant with a positive partial regression coefficient along with other factors known to increase birth sizes of neonates (gestational weeks or maternal BMI). It was not clear if this was causal because no biological mechanism was apparent.

Associations between levels of hydroxylated PCBs and PCBs in serum of pregnant women and blood thyroid hormone levels and body size of neonates.

The purpose of this study was to investigate possible associations between concentrations of hydroxylated PCBs (OH-PCBs) and PCBs in the serum of women in the first trimester of pregnancy and thyroid hormone levels and body size of newborn infants in 79 mother-neonate pairs. We measured 16 OH-PCB isomers and 29 PCB isomers in the serum of Japanese women sampled at 11.1±1.9 weeks of gestation. The concentrations of free thyroxine (fT4) and thyroid stimulating hormone (TSH) were measured in whole blood spots on filter papers sampled from the neonates. Dietary and lifestyle information of the mothers were obtained by self-administered questionnaires. Geometric mean (GM) concentrations of the sum of 16 OH-PCB isomers and of 29 PCB isomers were 1.2×10(2)pg/g wet wt. and 69ng/g lipid wt., respectively, in maternal serum. The GM concentrations of neonatal fT4 and TSH were 2.21ng/dL and 1.37µIU/mL, respectively. Multiple regression analysis was performed using measures of neonatal thyroid hormones as dependent variable and serum levels of OH-PCBs/PCBs and other potential covariates (age, pre-pregnancy weight, smoking status, etc.) as independent variables. The results demonstrated a significant positive association between the concentrations of some OH-PCB isomers and that of neonatal TSH. There were no significant associations between levels of PCBs and neonatal fT4, or between OH-PCBs/PCBs and body size of neonates. We conclude that exposure to/body burden of OH-PCBs, but not PCBs, at environmental levels during the first trimester of pregnancy can affect neonatal thyroid hormone status.

Exposure to pyrethroids insecticides and serum levels of thyroid-related measures in pregnant women.

Possible association between environmental exposure to pyrethroid insecticides and serum thyroid-related measures was explored in 231 pregnant women of 10-12 gestational weeks recruited at a university hospital in Tokyo during 2009-2011. Serum levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and thyroid biding globulin (TBG) and urinary pyrethroid insecticide metabolite (3-phenoxybenzoic acid, 3-PBA) were measured. Obstetrical information was obtained from medical records and dietary and lifestyle information was collected by self-administered questionnaire. Geometric mean concentration of creatinine-adjusted urinary 3-PBA was 0.363 (geometric standard deviation: 3.06) µg/g cre, which was consistent with the previously reported levels for non-exposed Japanese adult females. The range of serum fT4, TSH and TBG level was 0.83-3.41 ng/dL, 0.01-27.4 µIU/mL and 16.4-54.4 µg/mL, respectively. Multiple regression analysis was carried out by using either one of serum levels of thyroid-related measures as a dependent variable and urinary 3-PBA as well as other potential covariates (age, pre-pregnancy BMI, parity, urinary iodine, smoking and drinking status) as independent variables: 3-PBA was not found as a significant predictor of serum level of thyroid-related measures. Lack of association may be due to lower pyrethroid insecticide exposure level of the present subjects. Taking the ability of pyrethroid insecticides and their metabolite to bind to nuclear thyroid hormone (TH) receptor, as well as their ability of placental transfer, into consideration, it is warranted to investigate if pyrethroid pesticides do not have any effect on TH actions in fetus brain even though maternal circulating TH level is not affected.

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.

Cognitive-behavioral therapy modifies the naturalistic course of social anxiety disorder: findings from an ABA design study in routine clinical practices.

AIMS: While randomized evidence appears to have established efficacy of cognitive-behavioral therapy (CBT) and some pharmacotherapy for social anxiety disorder (SAD), their real-world effectiveness has been called into question by long-term naturalistic cohort studies of patients with SAD as they show very low probability of recovery and sustained social dysfunctions despite some drug and psychological therapies. METHOD: The present study examines the effectiveness of group CBT for SAD in real-world settings (n=62) by examining the course of patients' symptomatology and social functions through approximately 6 months on the waiting list, through 6 months receiving the manualized group CBT intervention consisting of 16 2-h sessions, and for 12 months after the treatment. RESULTS: We found: (i) that the patients with SAD changed little or possibly worsened through the 6 months on the waiting list, although two in three of them were on antidepressants, benzodiazepines or both; (ii) that both their symptomatology and social function improved significantly and substantively through the group CBT; and (iii) that this improvement was maintained through the 3- and 12-month follow ups. CONCLUSIONS: We can implement and must disseminate evidence-based, effective CBT for more patients with SAD to lessen their suffering and stop the perpetuation of their symptoms.

Serum levels of hydroxylated PCBs, PCBs and thyroid hormone measures of Japanese pregnant women.

OBJECTIVES: The purpose of this study was to investigate the associations between serum concentrations of hydroxylated PCBs (OH-PCBs) and PCBs and measures of thyroid hormone status of Japanese pregnant women. METHODS: The concentrations of free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroxine binding globulin (TBG) as well as 16 OH-PCB isomers and 29 PCB isomers were analyzed in the serum of 129 women sampled in the first trimester of gestation. Dietary and lifestyle information of the subjects was obtained by self-administered questionnaire. Multiple regression analysis was performed using measures of thyroid hormones as the dependent variable and serum levels of OH-PCBs/PCBs, urinary iodine concentration, and other potential covariates (age, BMI, smoking, etc.) as independent variables. RESULTS: Geometric mean (GM) concentration of the sum of 16 isomers of OH-PCBs was 120 pg/g wet wt. and that of 29 isomers of PCBs was 68 ng/g lipid wt., respectively, in the serum of the subjects. Iodine nutrition was considered adequate to high from urinary iodine level (GM, 370 µg/g creatinine). The mean concentration of TSH, fT4 and TBG was 1.34 ± 1.37 µIU/mL, 1.22 ± 0.16 ng/dL and 33.0 ± 6.4 µg/mL, respectively, with a small number of subjects who were outside the reference range. Multiple regression analysis revealed that serum concentrations of OH-PCBs/PCBs were not significantly associated with any of the measures of thyroid hormone status. CONCLUSIONS: Exposure/body burden of OH-PCBs and PCBs at environmental levels does not have a measurable effect on thyroid hormones.

Change in quality of life and their predictors in the long-term follow-up after group cognitive behavioral therapy for social anxiety disorder: a prospective cohort study.

BACKGROUND: Social anxiety disorder (SAD) is one of the most common anxiety disorders. The efficacy of cognitive behaviour therapy (CBT) has been examined but to date its effects on Quality of Life (QoL) have not been appropriately evaluated especially in the long term.The study aimed to examine, in the long term, what aspects of Quality of Life (QoL) changed among social anxiety disorder (SAD) patients treated with group cognitive behaviour therapy (CBT) and what predictors at baseline were associated with QoL. METHODS: Outpatients diagnosed with SAD were enrolled into group CBT, and assessed at follow-ups for up to 12 months in a typical clinical setting. QoL was evaluated using the Short Form 36. Various aspects of SAD symptomatology were also assessed. Each of the QoL domains and scores on symptomatology were quantified and compared with those at baseline. Baseline predictors of QoL outcomes at follow-up were investigated. RESULTS: Fifty-seven outpatients were enrolled into group CBT for SAD, 48 completed the whole program, and 44 and 40 completed assessments at the 3-month and 12-month follow-ups, respectively. All aspects of SAD symptomatology and psychological subscales of the QoL showed statistically significant improvement throughout follow-ups for up to 12 months. In terms of social functioning, no statistically significant improvement was observed at either follow-up point except for post-treatment. No consistently significant pre-treatment predictors were observed. CONCLUSIONS: After group CBT, SAD symptomatology and some aspects of QoL improved and this improvement was maintained for up to 12 months, but the social functioning domain did not prove any significant change statistically. Considering the limited effects of CBT on QoL, especially for social functioning, more powerful treatments are needed.

Video feedback with peer ratings in naturalistic anxiety-provoking situations for social anxiety disorder: Preliminary report.

The present study aimed to examine how video feedback can affect perceived performance and anticipatory anxiety in various naturalistic social anxiety-provoking situations among clinical patients diagnosed with social anxiety disorder (SAD) and to examine predictors that might influence response to video feedback. Participants were 52 consecutive patients with DSM-IV SAD who participated in a group-based CBT program. Our results demonstrated that video feedback was associated with a decrease in the underestimation of own performance as well as the perception of feared outcomes. Moreover, anticipatory anxiety decreased after video feedback combined with peer feedback. Male sex, comorbidity with other anxiety disorders, and benzodiazepine prn, as well as patients' initial anxiety and avoidance were negative predictors of the effect of video feedback.

Videotaped experiments to drop safety behaviors and self-focused attention for patients with social anxiety disorder: do they change subjective and objective evaluations of anxiety and performance?

Safety behavior (SB) and self-focused attention (SFA) have been posited as important maintenance factors in the cognitive model of social anxiety disorder (SAD). The present study reports the results of experiments to drop SB and SFA among clinically diagnosed patients with SAD employing their own idiosyncratic anxiety-provoking situations. The ratings for observable anxiety, belief in feared outcome and overall performance were better for role plays without SB and SFA than for role plays with them. The degree of drop in SFA predicted drop in observable anxiety and belief in feared outcome. Dropping SB and SFA, however, was unable to completely correct the cognitive distortion because the subjective ratings were still significantly worse than the objective ratings.

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.

On-column electrochemical redox derivatization for enhancement of separation selectivity of liquid chromatography use of redox reaction as secondary chemical equilibrium.

An on-column electrochemical redox derivatization for enhancement of high-performance liquid chromatography (HPLC) separation selectivity is presented using electrochemically modulated liquid chromatography (EMLC) and porous graphitic carbon (PGC) as the packing material. PGC therefore serves two purposes: it acts both as a chromatographic stationary phase and as a working electrode. The capability of on-column electrochemical redox derivatization was evaluated using hydroquinone and catechol as model compounds. By manipulation of the applied potential, hydroquinone and catechol will migrate as equilibrium mixtures, hydroquinone and p-benzoquinone and catechol and o-benzoquinone in the potential region of 25-125 mV and 150-200 mV (vs. Ag/AgCl), respectively. These redox reactions can be used as secondary chemical equilibria so that the corresponding equilibrium mixtures elute as single peaks and their retention times can be controlled by alterations in the potential applied to the PGC stationary phase. Homogeneity of the redox activity of the PGC stationary phase applied potential was also demonstrated.

Group cognitive behavior therapy for Japanese patients with social anxiety disorder: preliminary outcomes and their predictors.

BACKGROUND: A number of studies have provided strong evidence for the use of cognitive behavior therapy (CBT) in the treatment of social anxiety disorder (SAD). However, all of the previous reports were from Europe and North America and it is unknown whether Western psychological therapies are effective for SAD in non-Western cultures. The present pilot study aimed to evaluate CBT program for SAD which was originally developed for Western patients, among Japanese patients. METHODS: Fifty-seven outpatients who participated in group CBT for SAD were evaluated using eight self-reported and one clinician-administered questionnaires to measure various aspects of SAD symptomatology at the beginning and at the end of the program. Pre- and post-treatment scores were compared and the magnitude of treatment effect was quantified as well based once on the intention-to-treat (ITT) and once among the completers only. We also examined baseline predictors of the CBT outcomes. RESULTS: Seven patients (12%) did not complete the program. For the ITT sample, the percentage of reduction was 20% to 30% and the pre to post treatment effect sizes ranged from 0.37 to 1.01. Among the completers, the respective figures were 20% to 33% and 0.41 to 1.19. We found no significant pretreatment predictor of the outcomes. CONCLUSION: Group CBT for SAD is acceptable and can bring about a similar degree of symptom reduction among Japanese patients with SAD as among Western patients.

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 and interoceptive exposure in patients with panic disorder: specificity and effectiveness.

BACKGROUND: Interoceptive exposure has been validated as an effective component of cognitive behavioral therapy (CBT) for the treatment of panic disorder but has hitherto received little research attention. We examined the effectiveness of various interoceptive exposure exercises using the Body Sensations Questionnaire (BSQ) (Chambless et al., 1984). METHODS: We first performed an exploratory principal factor analysis of all the items contained in the BSQ to obtain meaningful dimensions of interoceptive fears. Next, we examined the correlations between each interoceptive exposure task's degree of similarity to panic attacks and each BSQ factor and then examined whether the BSQ factor scores decreased in comparison with the baseline values when the corresponding exposure tasks were successfully completed by the subjects. RESULTS: The factor analyses revealed four factors, which we named "pseudoneurological fears", "gastrointestinal fears", "cardiorespiratory fears" and "fears of dissociative feelings." Among the nine interoceptive exposure tasks, 'hyperventilation', 'shaking head', 'holding breath' and 'chest breathing' were considered to reproduce pseudoneurological symptoms, 'breathing through a straw' was considered to reproduce gastrointestinal symptoms, and 'spinning' was considered to reproduce both pseudoneurological and dissociative symptoms; none of the interoceptive exercises were found to reproduce cardiorespiratory symptoms. Among each group of patients for whom 'hyperventilation', 'holding breath', 'spinning' or 'chest breathing' was effective, a significant improvement in the BSQ pseudoneurological fears factor scores was observed. On the other hand, no significant difference between the baseline and endpoint values of the BSQ gastrointestinal fears or the BSQ fears of dissociative feelings factor scores were observed among the patients for whom 'spinning' or 'breathing through a straw' was effective. CONCLUSION: Several interoceptive exposure tasks were particularly effective in reducing pseudoneurological fears. New interoceptive tasks, especially tasks related to cardiorespiratory and dissociative feelings, are needed.

Quality of life and social role functioning in Japanese patients with panic disorder.

Although a number of recent studies have shown that panic disorder is associated with deterioration in quality of life and social dysfunctions, details of these impairments and their correlates have not been well studied. The present study aims to examine which aspects of quality of life and social functioning were particularly impaired in patients with panic disorder and to search for their clinical correlates. Fifty patients with panic disorder with or without agoraphobia who participated in our group cognitive-behavioral treatment program were administered the Medical Outcomes Study Short-Form Health Survey and the Work, Home and Leisure Activities Scale. Their panic disorder symptomatology was assessed with the Panic Disorder Severity Scale and Fear Questionnaire. Compared with the population mean, the patients reported less than average quality of life in both physical and mental domains, especially in the latter domain. They also reported substantial social dysfunctions, especially in work and social leisure activities. Different aspects of patients' psychopathology were associated with these impairments. While agoraphobia appeared as a consistent predictor for most of the aspects examined, social phobia emerged as a strong predictor for mental quality of life and for work and social leisure functions. The findings suggest that we need to remain sensitive to different aspects of functional impairments of patients with panic disorder and that we may need to pay more attention to the role of social anxiety in their treatment.

Is "relationship fear" unique to Japan? Symptom factors and patient clusters of social anxiety disorder among the Japanese clinical population.

BACKGROUND: There have been only a limited number of cross-cultural studies of social anxiety disorder (SAD), especially as diagnosed with modern operationalized diagnostic criteria and as measured with recently developed assessment instruments. We examined the symptomatological structure and clinical subtypes of patients with DSM-IV SAD among the Japanese clinical population. METHODS: We performed confirmatory and exploratory factor analyses of the joint Social Interaction Anxiety Scale and Social Phobia Scale from 149 psychiatric patients diagnosed with SAD. Based on the derived symptom factors, we further ran cluster analysis to identify patient subgroups. RESULTS: Factor analyses revealed three factors which were named "scrutiny fears", "conversation fears" and "relationship fears". The first two appeared common to Western clinical populations but the third appeared unique to the Japanese. Cluster analysis based on these three factor scores yielded three subgroups, which were externally validated and which overall corresponded with mild, moderate and pervasive subtypes of social phobia. LIMITATIONS: Both factor analysis and cluster analysis employed in the present study are exploratory in nature. Further empirical examination in different settings and cultures is necessary to provide definitive answers. CONCLUSIONS: It is suggested that we may need three symptom subscales and three subtypes in order to better account for cultural variations in the presentation of SAD.

Cross-cultural evaluation of the Panic Disorder Severity Scale in Japan.

The Panic Disorder Severity Scale (PDSS) [Shear et al., 1997] is rapidly gaining world-wide acceptance as a standard global severity measure of panic disorder, however, its cross-cultural validity and reliability have not been reported yet. We developed the Japanese version of the PDSS and examined its factor structure, internal consistency and inter-rater reliability and concurrent validity among Japanese patients with panic disorder with or without agoraphobia. We also established rules of thumb for interpreting PDSS total scores, taking the Clinical Global Impression severity scale as the anchoring criterion. The identical one-factor structure of the PDSS was confirmed among the Japanese patients as among the United States patients. Both internal and inter-rater reliability was excellent (Cronbach's alpha was 0.86, and ANOVA ICCs were all above 0.90). Concurrent validity of the PDSS items with self-report questionnaires tapping similar or overlapping domains was satisfactory (Pearson correlation coefficients were mostly above 0.5). Using the anchor-based approach, the following interpretative guides are suggested: among those with established panic disorder diagnosis, PDSS total scores up to 10 correspond with "mild," those between 11 and 15 with "moderate," and those at or above 16 correspond with "severe" panic disorder. The present findings support the cross-cultural generalizability of panic disorder symptomatology and of the PDSS, in particular.

Production of a doubly chiral compound, (4R,6R)-4-hydroxy-2,2,6-trimethylcyclohexanone, by two-step enzymatic asymmetric reduction.

A practical enzymatic synthesis of a doubly chiral key compound, (4R,6R)-4-hydroxy-2,2,6-trimethylcyclohexanone, starting from the readily available 2,6,6-trimethyl-2-cyclohexen-1,4-dione is described. Chirality is first introduced at the C-6 position by a stereoselective enzymatic hydrogenation of the double bond using old yellow enzyme 2 of Saccharomyces cerevisiae, expressed in Escherichia coli, as a biocatalyst. Thereafter, the carbonyl group at the C-4 position is reduced selectively and stereospecifically by levodione reductase of Corynebacterium aquaticum M-13, expressed in E. coli, to the corresponding alcohol. Commercially available glucose dehydrogenase was also used for cofactor regeneration in both steps. Using this two-step enzymatic asymmetric reduction system, 9.5 mg of (4R,6R)-4-hydroxy-2,2,6-trimethylcyclohexanone/ml was produced almost stoichiometrically, with 94% enantiomeric excess in the presence of glucose, NAD(+), and glucose dehydrogenase. To our knowledge, this is the first report of the application of S. cerevisiae old yellow enzyme for the production of a useful compound.