OBJECTIVE

The purpose of this study was to create and validate a mental health subscale for the Quality of Well-Being Self-Administered (QWB-SA).

METHODS

The QWB-SA and other measures such as the Profile of Mood States (POMS), Medical Outcomes Study 36 Item Short Form (SF-36), EuroQOL 5D (EQ-5D), and Health Utilities Index Mark 2 (HUI) were administered to three samples: a general population (N = 3,844), a non-psychiatric medical population (N = 535), and a psychiatric population (N = 915). Independent expert ratings of which items represented the construct of mental health were used along with psychometric methods to develop and validate a 10-item QWB-SA mental health scale.

RESULTS

The mental health scale demonstrated high internal consistency (Cronbach's alpha = 0.827-0.842) and strong correlations with other measures of mental health, such as the POMS (r = -0.77), mental health scale from the SF-36 (r = 0.72), EQ-5D mood item (r = 0.61), and HUI Emotion Scale (r = 0.59). It was not highly correlated with measures of physical health. Among the psychiatric population, the new mental health scale was moderately correlated with indicators of psychiatric problem severity.

CONCLUSIONS

It is now possible to report outcomes and relationships with mental health in studies that use the QWB-SA. This new mental health subscale can also be used with the large volume of previously collected data using the QWB-SA to examine the impact of illnesses and interventions on mental health-related quality of life.

Inter- and intrahemispheric correlation of the EEG activity at rest was computed in two groups of men and women, between 17 and 21 years old, with extreme degrees of spatial ability (SA) evaluated by the Spatial Relations Subtest of the Differential Aptitudes Test (DAT). Interhemispheric (INTERr) and intrahemispheric (INTRAr) EEG correlations were computed by means of Pearson product-moment coefficients for 5 EEG bands after digitally filtering with an FFT. Women showed significantly higher INTERr of alpha 1 between left and right centrals, lower INTRAr between right frontal and right central regions and lower INTRAr within the left than in the right hemisphere. High SA subjects showed lower INTERr between left and right frontal derivations and higher INTRAr between frontal and parietal and between central and parietal regions of both hemispheres. Sex interacted with SA in INTRAr of alpha between right frontal and right temporal regions with high SA women showing lower INTRAr than low SA women and than men. The present results indicate a different inter- and intrahemispheric functional organization in men and women and in subjects with high and low spatial ability.

OBJECTIVE

To determine whether signs of cardiac sympathetic activation (together with vagal withdrawal) can be observed in the autonomic balance modulating the sino-atrial node as early as the initial levels of a graded light dynamic exercise.

METHODS

We studied 15 healthy ambulant subjects (mean +/- SD age 32 +/- 9 years; systolic/diastolic blood pressure 120 +/- 19/77 +/- 7 mmHg; heart rate 65 +/- 9 beats/min), who underwent a control recording of 10 min, followed by a three-step progressive (10, 20 and 30% of nominal maximum for age and sex) supine bicycle exercise. Spectral and cross-spectral analysis of RR and systolic arterial pressure variabilities were used to obtain non-invasive markers of the autonomic adjustments to exercise.

RESULTS

The low-frequency component of RR interval variability (which, in normalized units, is a marker of sympathetic modulation of the sino-atrial (SA) node) was progressively increased during all three stages of bicycle exercise. No significant changes were observed in the low-frequency component of systolic arterial pressure variability (i.e. a marker of sympathetic drive to the vasculature) in the early stages of exercise, while a significant increase was observed at 30% of maximum. The index alpha (which provides a measure of the gain of the arterial pressure-heart period baroreflex) was progressively reduced during all three stages of exercise.

CONCLUSIONS

While the sympathovagal balance modulating the SA node is immediately shifted towards sympathetic predominance (and vagal withdrawal), markers of peripheral vascular sympathetic activation appear increased only when 30% of maximum exercise is attained.

Dipeptidyl peptidase-IV (DPP-IV, CD26), a serine protease with broad distribution in mammalian tissues and known activity in serum, participates in T-cell activation and promotes a Th1-like cytokine response. Previous data on murine abortion indicate that DPP-IV may play a critical role in pregnancy failure by inducing a Th1 local response. Here, we investigated the possible participation of DPP-IV in the onset of human spontaneous abortion (SA). The systemic (peripheral blood) and local (decidua) percentages of CD4(+), CD8(+), CD26(+) and CD56(+) cells as well as the number of Th1 lymphocytes (CCR5(+) cells) were assessed in samples from women after SAs (n = 20) and from women with normally progressing pregnancies (NPs) (n = 27) using flow cytometry and immunohistochemistry. We further measured the DPP-IV activity and concentrations of Th1 (interferon-gamma and tumour necrosis factor-alpha), Th2 [interleukin-4 (IL-4), IL-10] and Th3 (transforming growth factor-beta2) cytokines in serum samples. We could not find any difference in the number of CD4(+), CD8(+), CD26(+), CD26(+)/CD4(+) or CD8(+)/CD26(+) blood cells between NP and SA patients. No differences in the Th1, Th2 or Th3 cytokine levels could be observed between both groups. However, the percentages of decidual CD26(+) lymphocytes as well as the number of decidual Th1 cells were significantly higher in SA samples compared to samples from patients with NP. Our data support the hypothesis that CD26(+) decidual lymphocytes with DPP-IV activity may play a critical role in SAs, as previously suggested in an abortion mice model. This abortive effect may be mediated by enhancing the levels of Th1 abortogenic cytokines only locally.

The interactions of human serum albumin (HSA) with sinapic acid (SA), gallic acid (GA) and shikimic acid (SI) were investigated by fluorescence and Fourier transformed infrared spectrometry. Fluorescence results showed that one molecule of protein combined with one molecule of GA at the molar ratio of drug to HSA ranging from 0.1 to 30, and their binding constant (K(A)) is 1.1x10(4) M(-1). While one HSA molecule combined with one or two molecule of SA at the molar ratio of drug to HSA ranging from 0.1 to 4.26 or 4.26 to 30, and their binding affinities (K(A)) are 1.92x10(3) M(-1) and 6.87x10(8) M(-1), respectively. There is no specific interaction between HSA and SI. Combining the curve-fitting results of infrared amide I and amide III bands, the alterations of protein secondary structures induced by drugs were estimated. The drug-protein combination brought gradual reductions of the protein alpha-helix structure with increasing the concentrations of SA and GA, but SI did not change the protein secondary structure. From the fluorescence and FT-IR results, the binding mode was discussed in relation to the structures of the organic acids.

OBJECTIVE

To examine the relationship between self-reported social anxiety and asthma in a non-clinical sample of adolescents.

METHODS

High school students (n = 765) completed the Social Anxiety Scale for Adolescents (SAS-A), the Social Phobia and Anxiety Inventory for Children (SPAI-C), and questions on asthma diagnosis, asthma symptoms, and asthma-related limitations and medical care. Relationships were examined between social anxiety symptoms and asthma, including history of diagnosis, diagnosis plus current symptoms, and severity.

RESULTS

Compared with students without an asthma diagnosis and no symptoms, students with a diagnosis and current symptoms reported heightened social anxiety symptoms related to fear of negative evaluations and generalized discomfort in social settings as measured by the SAS-A. Additionally, a greater proportion of students with an asthma diagnosis and current symptoms were in the clinical range of social anxiety on the SAS-A. Differences on the SAS-A by history of asthma diagnosis and by severity were not supported. No differences were found on the SPAI-C for history of asthma diagnosis, diagnosis plus current symptoms or severity.

CONCLUSIONS

Students with current asthma symptoms were more likely to report social anxiety, perhaps related to concerns about exhibiting symptoms or taking medication in front of peers. These findings may suggest advantages for medical providers to identify and treat social anxiety in patients with asthma.

The metabolism of praziquantel (PZQ) was studied in microsomes isolated from livers of differently pretreated rats and in the presence of various inhibitors of cytochrome P450 (P450) isoforms. Microsomes from phenobarbitone (PB)-pretreated rats metabolised PZQ to its major metabolite 4OH-praziquantel (4OH-PZQ) at a greater rate than those from 20-methylcholanthrene (MC) and saline (SA) pretreated rats. The Vmax for the PB microsomes was 600 nmol 4OH-PZQ formed/mg/min x 10(-3) compared to 91.4 nmol/mg/min x 10(-3) for MC and 238 nmol/mg/min x 10(-3) for SA microsomes. These results indicate that PZQ is metabolised by PB-inducible isoforms of P450. Inhibitor studies were conducted with microsomes from SA-pretreated animals. In these studies, caffeine, disulfuram, and tolbutamide were poor inhibitors of the metabolism of PZQ to 4OH-PZQ, with I50 values not determinable. Quinidine and quinine inhibited the hydroxylation of PZQ but with high Ki values. 17 alpha-Ethynylestradiol, cimetidine and diphenylhydramine were effective inhibitors of the formation of 4OH-PZQ, with 17 alpha-ethynylestradiol being the most potent with a Ki of 0.5 +/- 0.05 microM. From the known specificities of these P450 inhibitors, it is therefore concluded that cytochromes P450 1A2, 2E1, 2C9-10, and 2D6 probably do not contribute significantly to the metabolism of PZQ to its major metabolite in rats. It is likely that cytochromes P450 2B1 and 3A, both inducible by PB, are predominantly responsible for the formation of 4OH-PZQ.

BACKGROUND

A number of physiological factors have been suggested to participate in the alpha- Human Herpesvirus (αHHV) reactivation, such as hormonal aberration. Thyroid hormone (TH) was shown to play a suppressive role in Herpes Simplex Virus Type-1 (HSV-1) gene expression and replication in cell culture and animal models. We hypothesize that reactivation of αHHV in humans may be due to, at least in part, by TH status.

METHODS

Prior to implementing a full-scale population-based prospective inquiry into this hypothesis, a pilot study using a medical claims data base and a case-controlled, retrospective cohort investigation was conducted to develop a hypothetical link between TH complication and αHHV reactivation. Using diagnostic codes for treating thyroid disorders and αHHV infections as proxies for biologic/clinic outcomes, we queried a large, comprehensive hospital data base to construct two patient cohorts: Cohort 1 was comprised of patients receiving TH diagnoses over a twelve-year period, and Cohort 2 was composed of patients not receiving TH diagnoses during this period. Diagnoses of αHHV were recorded for each cohort and the difference in the frequency was examined for statistical significance. Demographic analyses such as age, gender, etc were also performed.

RESULTS

Using 2×2 contingency table analyses and Statistical Analysis Software (SAS), an Odds Ratio (OR) of 2.83 was observed for the total population of 21 years old and above with a chi-square of 61.55 and p < 0.001, confirming that a severe significant difference was found between these two cohorts. This result suggested that patients with αHHV diagnosis have higher chances to have TH disorders. Additional investigation revealed that female were at higher/significant probability to have both TH and αHHV diagnosis, indicating a link of αHHV reactivation to a complex hormonal profile difference between genders. Our observation indicated that female patients of 21 years of age and above exhibited a very high incidence (OR of 3.40, p < 0.001) compared to the male groups (OR of 1.91, p < 0.05), indicating the possibility that hormonal alteration in females maybe transient but robust and can lead to αHHV reactivation more often than the males.

CONCLUSIONS

These results indicated that TH dysfunction may have implication in αHHV pathogenesis and females exhibited much higher probability to suffer αHHV reactivation due to TH disruption. Although the results from this pilot study have limitations and require additional controlled clinical examination such as more detailed patient records, lab data, therapeutic outcome, etc, it provides a tool to assess the effects of hormone imbalance on virus reactivation by retrospective analyses using existing large scale data base.

BACKGROUND

Sleep-related breathing disorders occur in 20-30% of Europeans and North Americans, including 10% of sleep apnea syndrome (SAS). A preliminary study suggested that atrial overdrive pacing with a fixed heart rate might alleviate SAS. However, it is not known whether dynamic atrial overdrive pacing alleviates SAS.

METHODS

Patients with indications for a dual chamber pacemaker or implantable cardioverter-defibrillator (ICD) were screened for SAS using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. If PSQI was >5, cardio-respiratory polygraphy was performed before and 4 and 7 months after device implantation. Patients were randomized to algorithm ON-OFF (group A) or OFF-ON (group B) and the apnea-hypopnea index (AHI) was measured.

RESULTS

Out of 105 consecutive patients, 46 (44%) had a positive PSQI. This analysis included 12 patients (mean age = 61 +/- 10 years, body mass index 28.9 +/- 6.5 kg/m(2), left ventricular ejection fraction = 38.3 +/- 13.6%; 10 men). All patients suffered from obstructive or mixed SAS. There were no significant differences in PSQI or AHI between baseline and follow-up or between the two study groups. Therefore, the study was terminated ahead of schedule.

CONCLUSIONS

The prevalence of obstructive or mixed SAS was high in pacemaker or ICD recipients and reduced left ventricular ejection fraction. In these patients, long-term dynamic atrial overdrive pacing using did not improve PSQI or SAS. Therefore, patients with relevant obstructive or mixed SAS should not be offered atrial pacing therapy.

To characterize the aromatizable and 5 alpha-reduced androgens produced by developing ovarian follicles, small antral (SA) and preovulatory (PO) follicles, theca and granulosa cells were incubated for 4 h with or without 8-bromo-cAMP and androstenedione. In addition, thecal explants were cultured for 10 days with or without ovine LH (oLH) to determine if the hormone-induced changes in androgen synthesis by developing follicles could be mimicked in vitro. Short term incubations of SA and PO follicles, theca and granulosa cells in medium alone resulted in limited accumulation of androgen [testosterone, 5 alpha-androstan-17 beta-ol-3-one (DHT), 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha diol), and androsterone], as determined by RIA. In the presence of 8-bromo-cAMP, PO follicles produced large quantities of testosterone (3 ng), DHT (1 ng), 3 alpha diol (15 ng), and androsterone (14 ng), while SA follicles accumulated much less androgen (0.69, 0.05, 1.23, and 1.3 ng, respectively). In the presence of androstenedione and 8-bromo-cAMP, both SA and PO follicles and theca produced large amounts of aromatizable and 5 alpha-reduced androgens. SA and PO granulosa cells required the presence of the substrate androstenedione to produce androgens, primarily testosterone and 3 alpha diol. Therefore, progesterone, androstenedione, and 5 alpha-reduced androgens were used to monitor LH action on thecal cell function in culture. Small antral theca cultured in basic culture medium alone (containing 10% fetal calf serum) displayed an increased ability to accumulate androstenedione by day 6, approximately 3 times that observed on day 2. However, a 5-fold further increase in androstenedione accumulation was observed by day 6 for SA theca cultured in the presence of oLH. Maintenance of progesterone accumulation by SA theca throughout the culture period also was dependent on the presence of LH. In contrast, androstenedione accumulation by PO theca required the presence of LH in the culture medium, while progesterone accumulation in these cultures did not. Little or no 5 alpha-reduced androgen accumulated in the media of SA and PO theca cultured in basic culture medium alone. However, SA and PO theca cultured with oLH accumulated approximately 1 ng androsterone by day 10. We conclude that 1) SA and PO follicles, theca and granulosa cells possess the enzymes required to produce large amounts of 3 alpha diol and androsterone; 2) low concentrations of oLH are required to stimulate SA thecal steroidogenesis and to maintain PO thecal androstenedione accumulation in culture.(ABSTRACT TRUNCATED AT 400 WORDS)

Myeloperoxidase (MPO) is a heme-containing glycoprotein found in the primary granules (or azurophilic granules) of human polymorphonuclear leukocytes. In the present study, cultured myeloid leukemia HL-60 cells were exposed for 0-72 h to 250 microM 4,6-dioxoheptanoic acid (succinylacetone, SA), a specific inhibitor of heme biosynthesis, and the effects were evaluated using ultrastructural, immunochemical, and cytochemical methods. En bloc peroxidase staining of glutaraldehyde-fixed cells was accomplished with a 30-min exposure to 3,3'-diaminobenzidine (DAB) tetrahydrochloride. Ultrastructural examination revealed that peroxidase reactivity in the endoplasmic reticulum (ER) was relatively unchanged for 8 h and decreased between 12 and 24 h; however, ER lacked DAB-reactive peroxidase at 48-72 h. Peroxidase reactivity in the ER reappeared within 4 h after removal of SA. Seventy-two hours after exposure to SA the number of condensed cytoplasmic granules stained with DAB was significantly decreased, and many of the granules had a "target" appearance with a central DAB-reactive dense core. Staining of mitochondria was observed with overnight exposure to DAB and persisted in HL-60 cells treated 72 h with SA. Mitochondrial and nuclear morphology appeared unaltered. Immunostaining of MPO in thin sections of paraformaldehyde/glutaraldehyde-fixed unosmicated HL-60 cells, embedded in Lowicryl K4M, was accomplished with sequential exposure to an affinity-purified monospecific rabbit antibody to HL-60-MPO and protein A conjugated to 5- or 10-nm colloidal gold. Compared to untreated control HL-60 cells, cells exposed to SA for 48 h exhibited comparable to increased immunoreactive MPO in the ER, despite the absence of heme-dependent peroxidase reactivity. The data indicate that SA inhibits formation of enzymatically active MPO and that in the presence of SA, the ER contains a form(s) of MPO that lacks enzymatic reactivity.

The adhesion of monocytes to vascular endothelium increases in the presence of high levels of low density lipoprotein (LDL). LDL changes oxidative status of endothelial cells leading to an increased expression of cell adhesion molecules. Acetylsalicylic acid (ASA) has been shown to exert antioxidant effects in high and very high concentrations. This study was designed to demonstrate the influence of acetylsalicylic acid and its major metabolite, salicylic acid (SA), on the adhesion of monocytes to LDL-stimulated endothelial cells. Monocyte adhesion to endothelial cells was concentration-dependently inhibited by both salicylates upon stimulation of endothelial cells with TNF-alpha, oxidized LDL (oxLDL), and native LDL (nLDL). The inhibitory effect of ASA was more potent than that of SA, whereas the cyclooxygenase inhibitor ibuprofen had no effect. F2-isoprostane release from LDL-stimulated endothelial cells was reduced by simultaneous incubation with ASA or SA, whereas ibuprofen had no effect. LDL-induced activation of the transcription factor NF-kappaB was inhibited by ASA, and ferritin protein was increased when endothelial cells were incubated with this drug. These results show that acetylsalicylic acid and-less potently-salicylic acid inhibit monocyte adhesion to LDL-stimulated endothelial cells by antioxidative effects. For ASA, the observed inhibition of monocyte adhesion was accomplished with concentrations that can be reached after single oral doses of 500 mg of ASA.

The effects of two kinds of cyclodextrins (CyDs), alpha- and beta-CyD, on biological membranes were investigated by measuring changes in the absorption of a non-absorbable drug, sulfanilic acid (SA), from the rat small intestine, using in situ and in vitro experiments. After pretreatment with a mucolytic agent, N-acetyl-L-cysteine (N-Ac), only beta-CyD increased the absorption of SA significantly compared to the absorption without pretreatment. The mechanism of the enhancing effect of CyDs on the absorption of SA was discussed. Almost no morphological change in the small intestine was observed by pretreatment with N-Ac alone, N-Ac or alpha- or beta-CyD combinations. The liberation of membrane components differed among the CyDs, e.g., alpha-CyD selectively released phospholipid while beta-CyD released mainly cholesterol from the intestinal membrane. It is suggested that the interaction of membrane components with CyDs may be at least partly responsible for the enhanced absorption of SA. Moreover it was found from in vitro electrophysiological experiment, that the alteration in enhanced permeability caused by beta-CyD occurred primarily in the transcellular pathways, rather than in the paracellular pathways of the small intestine. These results suggest that the enhancement of intestinal absorption by beta-CyD, after removal of the mucin layer from the intestinal surface, is due to the interaction between the membrane components and CyD. This interaction would induce disorder in cell membrane lipid, resulting in the increased permeability of the transcellular route.

To study the mechanism of the protective effect of the spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN) against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) toxicity hydroxyl radicals and functional parameters of neuroprotection were determined. C57BL/6 mice received PBN (100 mg/kg IP) over a time period of 15 days and on day 8 MPTP (40 mg/kg SC). On day 15 striatal levels of dopamine, serotonin, and metabolites were analyzed. For radical determination mice received a single injection of salicylic acid (SA) (100 mg/kg IP) in the time period of 0.5 h before to 72 h after MPTP injection. In vivo maximum hydroxyl radical levels indicated by 2,3-dihydroxybenzoic acid/SA ratios were obtained 4 h after MPTP injection, and were not affected by PBN treatment. However, the MPTP-induced mortality, reduction of locomotor activity, continuous loss of body weight, and striatal dopamine depletion were significantly less pronounced in PBN-treated animals. These results elucidate the time course of hydroxyl free radical formation in MPTP toxicity. PBN improved the functional parameters of neuroprotection against MPTP toxicity, but there is no evidence for hydroxyl radical scavenging properties to this effect.

BACKGROUND

Chronic obstructive pulmonary disease (COPD) impairs physical status and impacts on mental health. This prospective study was designed to assess associations between mental health and systemic biomarkers, and their combined relationship with long-term survival in stable severe COPD.

METHODS

Forty-five patients with severe but stable COPD (forced expiratory volume in 1 s of 29.8 (quartiles: 22.6; 41.4) %predicted) were assessed using the Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire (PHQ), St. George's Respiratory Questionnaire and the State-Trait Anxiety Inventory (STAI). The following serum biomarkers were measured: 25-OH-cholecalciferol, C-reactive protein, erythrocyte sedimentation rate, leucocyte number, serum amyloid-A (SA-A), N-terminal pro-brain natriuretic peptide, troponin I, glycosylated haemoglobin, haemoglobin (Hb), haematocrit (Hc), creatinine and thyroid-stimulating hormone. Patients were followed-up for 36 months. Associations between aspects of mental health and biomarkers, and their utility as predictors of 3-year survival were evaluated by regression analyses.

RESULTS

The prevalence of anxiety (HADS-A: 89.9 %), depression (HADS-D: 58.8 %; PHQ: 60.6 %), somatisation (PHQ-15: 81.8 %) and psychosocial stress (PHQ-stress: 60.6 %) was high. There was a significant positive association between the leucocyte count and SA-A level with STAI-trait anxiety (p = 0.03 and p = 0.005, respectively), and between leucocytes and PHQ-stress (p = 0.043). Hb and Hc were significantly negatively associated with HADS-depression (p = 0.041 and p = 0.031, respectively). Univariate Cox regression analyses revealed that leucocyte count (hazard ratio (HR) 2.976, 95 % CI 1.059-8.358; p = 0.038), and stress (HR 4.922, 95 % CI 1.06-22.848; p = 0.042) were linked to long-term survival. In multivariate Cox regression analyses, including known risk factors for survival in COPD, PHQ-stress (HR 45.63, 95 % CI 1.72-1,208.48; p = 0.022) remained significantly associated with survival.

CONCLUSIONS

In this pilot study different dimensions of mental health were correlated to serum biomarkers, probably reflecting systemic effects of COPD. While leucocyte number and PHQ-stress were associated with long-term survival in univariate analyses, PHQ-stress remained in multivariate analyses as independent prognostic factor.

ZFY, a male-associated Zn-finger protein encoded by the human Y chromosome, exhibits a distinctive two-finger repeat: whereas odd-numbered domains fit a general consensus, even-numbered domains exhibit systematic differences. Do these odd and even sequences encode structurally distinct surfaces for DNA recognition? As a first step toward answering this question, we have recently described the sequential 1H NMR assignment of a representative nonconsensus Zn finger (designated ZFY-6T) based on 2D NMR studies of a 30-residue peptide [Kochoyan, M., Havel, T.F., Nguyen, D.T., Dahl, C.E., Keutmann, H. T., & Weiss, M.A. (1991) Biochemistry 30, 3371-3386]. Initial structural modeling by distance geometry/simulated annealing (DG/SA) demonstrated that this peptide retained the N-terminal beta-hairpin and C-terminal alpha-helix (beta beta alpha motif) observed in consensus Zn fingers. However, the precision of this initial structure was limited by resonance overlap, which led to ambiguities in the assignment of key NOEs in the hydrophobic core. In this paper these ambiguities are resolved by selective deuterium labeling, enabling a refined structure to be calculated by DG/SA and restrained molecular dynamics. These calculations provide a detailed view of the hydrophobic core and protein surface, which are analyzed in reference to previously characterized Zn fingers. Variant (even) and consensus (odd) aromatic residues Y10 and F12, shown in an "aromatic swap" analogue to provide equivalent contributions to the hydrophobic core [Weiss, M.A., & Keutmann, H.T. (1990) Biochemistry 29, 9808-9813], nevertheless exhibit striking differences in packing interactions: Y10--but not F12--contributes to a contiguous region of the protein surface defined by putative specificity-determining residues. Alternating surface architectures may have implications for the mechanism of DNA recognition by the ZFY two-finger repeat.

Little is known about the factorial invariance across gender and age for self-report measures of social anxiety in adolescence. This study examined the factorial invariance and latent mean differences of the Social Anxiety Scale for Adolescents (SAS-A) across gender and age groups in 1570 Spanish adolescents (54% girls), ranging in age from 14 to 17 years. Equality of factor structures was compared using multi-group confirmatory factor analyses. Measurement invariance for the correlated three-factor model of the SAS-A was found across gender and age samples. Analyses of latent mean differences revealed that girls exhibited higher means than boys on two SAS-A subscales, Fear of Negative Evaluation and Social Avoidance and Distress-New (SAD-New). In addition, on the SAD-New subscale, the structured means significantly diminished from 14-year olds to 16- and 17-year olds and from 15-year olds to 17-year olds. Findings are discussed in terms of the use of the SAS-A with Spanish adolescents.

The social environment plays a critical role in smoking initiation as well as relapse. We previously reported that rats acquired nicotine self-administration with an olfactogustatory cue only when another rat consuming the same cue was present during self-administration. Because carbon disulfide (CS2) mediates social learning of food preference in rodents, we hypothesized that socially acquired nicotine self-administration is also mediated by CS2. We tested this hypothesis by placing female adolescent Sprague-Dawley rats in operant chambers equipped with two lickometers. Licking on the active spout meeting a fixed-ratio 10 schedule triggered the concurrent delivery of an i.v. infusion (saline, or 30 µg/kg nicotine, free base) and an appetitive olfactogustatory cue containing CS2 (0-500 ppm). Rats that self-administered nicotine with the olfactogustatory cue alone licked less on the active spout than on the inactive spout. Adding CS2 to the olfactogustatory cue reversed the preference for the spouts. The group that received 500 ppm CS2 and the olfactogustatory cue obtained a significantly greater number of nicotine infusions than other groups. After extinction training, the original self-administration context reinstated nicotine-seeking behavior in all nicotine groups. In addition, in rats that received the olfactogustatory cue and 500 ppm CS2 during SA, a social environment where the nicotine-associated olfactory cue is present, induced much stronger drug-seeking behavior compared to a social environment lacking the olfactogustatory cue. These data established that CS2 is a critical signal that mediates social learning of nicotine self-administration with olfactogustatory cues in rodents. Additionally, these data showed that the social context can further enhance the drug-seeking behavior induced by the drug-taking environment.

OBJECTIVE

The aim of the present study was to determine the reliability and validity of the Chinese version of the Calgary Depression Scale for Schizophrenia (CDSS-C) in schizophrenia patients.

METHODS

One hundred and one inpatients from four mental health units who met DSM-IV criteria for schizophrenia were enrolled. The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS-24), Simpson-Augus Rating Scale (SAS), and Barnes Acathisia Rating Scale (BARS) were administered by the first rater, whereas the CDSS-C was assessed by a second independent rater.

RESULTS

The internal consistency (Cronbach's alpha = 0.80) and the inter-rater reliability (kappa coefficient >0.79) were good. The test-retest reliability was high (r = 0.927). The scale had good construct validity, with statistically significant correlations with the HDRS-24, G6 item (depression) of PANSS, and significant weak correlations with the general psychopathology subscale of PANSS. The CDSS-C showed no correlation with the positive and negative subscale of PANSS, the SAS and the BARS.

CONCLUSIONS

The Chinese version of CDSS is a valid and reliable instrument for the assessment of depression in schizophrenia.

The cell surface streptococcal antigen (SA) I/II of 185,000 M(r) is an immunodominant molecule that expresses one or more adhesion determinants. A series of 14 monoclonal antibodies (MAb) to defined parts of SA I/II were generated and some of these were used in passive immunization of macaques. Topical administration of selected MAb to the teeth of macaques prevented colonization of endogenous or implanted exogenous Streptococcus mutans for a period of 1 year. Significant reduction of both smooth surface and fissure caries was found in macaques who had MAb (Guy's 1) applied to their teeth, as compared with saline-treated animals. A series of in vivo passive immunization experiments was then carried out in 57 human subjects. Topical application of MAb to SA I/II prevented colonization of both artificially implanted exogenous strains of S. mutans, as well as natural recolonization by indigenous S. mutans. The properties of the protective MAb were then investigated and the epitope specificity within the SA I/II molecule was found to be essential but not the isotype specificity of the immunoglobulin (Ig). The requirement for complement activating and the phagocyte binding sites of the Fc fragment of MAb was not essential, as the F(ab')2 fragment of the MAb was as protective as the intact IgG, but the Fab fragment failed to prevent recolonization of S. mutans. Prevention of recolonization was specifically restricted to S. mutans, as the proportion of other organisms, such as S. sanguis, failed to show a significant change. The surprising feature of these experiments was that protection of re-colonization of S. mutans lasted up to 2 years, although MAb was applied for only 3 weeks and functional MAb was detected on the teeth only 3 days following application of the MAb. The long-term protection could therefore not be accounted for by a persistence of MAb on the teeth, but may be due to a shift in the microbial balance in which other bacteria occupy the ecological niche vacated by S. mutans, resulting in colonization resistance to S. mutans. Gene cloning and sequencing the SA from S. mutans, S. sobrinus and S. sanguis identified a conserved region (residues 955-1213) which on Southern hybridization and partial DNA sequence analysis was also found in 19 alpha-haemolytic oral streptococci. The results suggest that the SA molecule may constitute a family of adhesins in oral alpha haemolytic streptococci.(ABSTRACT TRUNCATED AT 400 WORDS)

OBJECTIVE

Polycystic liver disease (PCLD) may lead to extensive hepatomegaly and invalidating complaints. Therapeutic decisions, including somatostatin-analogues (SAs) and (non)-transplant surgery are besides the existence of hepatomegaly, also guided by the severity of complaints. We developed and validated a self-report instrument to capture the presence and severity of disease specific complaints for PCLD.

METHODS

The study population consisted of 129 patients. Items for the PCLD-complaint-specific assessment (POLCA) were developed based on the chart review of symptomatic PCLD patients (n=68) and literature, and discussed during expert-consensus-meetings. 61 patients who needed therapy were asked to complete the POLCA and the short form health survey version 2 (SF36V2) at baseline and after 6 months of SA-treatment. CT-scans were used to calculate liver volumes (LV). Factor analysis was conducted to identify subscales and remove suboptimal items. Reliability was assessed by Cronbach's alpha. Convergent, criterion validity and responsiveness were tested using prespecified hypotheses.

RESULTS

In the validation group (n=61), 47 received lanreotide (LAN) and 14 were offered LAN as bridge to liver transplantation (LTx). Factor analysis identified four subscales, which correlated with the physical component summary (PCS). Baseline POLCA scores were significantly higher in LTx-listed patients. In contrast to SF36V2, POLCA-paired observations in 47 patients demonstrated that 2 subscales were lowered significantly and 2 borderline. LV reduction of ⩾ 120 ml resulted in a numerical, more pronounced relative decrease of all scores.

CONCLUSIONS

In contrast to SF36V2, the POLCA shows good validity and responsiveness to measure complaint severity in PCLD.

Sleep apnea (SA) is a common sleep disorder increasingly recognized as a risk for cardiovascular disease. Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with significant morbidity and mortality. An increasing number of investigations in recent years have linked SA to AF. In this review, we aim to provide a critical overview of the existing evidence in a question and answer format by addressing the following: What is the prevalent association between the two conditions (separating nocturnally detected AF episodes from AF as a prevalent condition)? Is SA a risk factor for incident AF? Is SA a risk factor for recurrence of AF following cardioversion/catheter-based ablation? What is the association between SA and AF in patients with heart failure? Are there signature electrocardiographic markers of AF found in patients with SA? Are there electrophysiology-based studies supporting the link between SA and AF? What other sleep characteristics (beyond SA) are found in patients with AF? What is the impact of SA treatment on AF? What is the effect of AF treatment on sleep? Finally, we address unsolved questions and suggest future directions to enhance our understanding of the AF-SA relationship.

To determine the genotype distributions of the polymorphisms in platelet glycoproteins (GP) Ib-alpha, Ia/IIa and IIb/IIIa and their association with clinical arterial thrombosis and preclinical carotid atherosclerosis in type 2 diabetes we studied 229 patients with type 2 diabetes and 229 controls matched by age, gender and ethnicity. Biochemical and haemostasis analyses were performed. The GP Ib-alpha VNTR, GP Ia 807 C/T and GP IIIa Pl(A) polymorphisms were determined by PCR. Thrombotic events were registered and carotid atherosclerosis was evaluated by ultrasound examination. A total of 107 patients had clinical atherothrombosis (CA), 65 subclinical atherosclerosis (SA), and 57 had no evidence of atherosclerosis (NA). There were no differences in allele frequencies and the genotype distribution of platelet GP polymorphisms between diabetic patients and controls. The VNTR Ib-alpha polymorphism was not associated with CA. We found a significant association between CA and the 807T (odds ratio [OR]: 2.86, confidence interval [CI]: 1.65-4.93; p<0.001) and PlA2 (OR: 2.03, CI: 1.13-3.65; p=0.03) alleles (in GP Ia and GP IIIa, respectively) in comparison to SA and NA group. Diabetic patients with the coexistence of the 807T and PlA2 alleles presented the highest risk of CA (OR: 3.59, CI: 1.64-7.8; p<0.001). The coexistence of both 807T and PlA2 alleles was also associated with the presence of SA (OR: 9.00, CI: 1.10-73.42; p=0.04). In conclusion, the 807T allele of GP Ia and the PlA2 allele of GP IIIa, and specially its combination, may confer an additional risk for development of carotid atherosclerosis and arterial thrombosis in type 2 diabetes.

BACKGROUND

Plasmodium falciparum placental malaria (PM) contributes to 10,000 maternal deaths due to severe anemia (SA) each year in Africa, primarily among primigravid women who are most susceptible. Increased levels of proinflammatory cytokines like TNF-alpha are associated with maternal anemia in first time mothers but not in other women. Here we aimed to identify additional changes in the plasma proteome associated with pregnancy malaria that may contribute to the development of malaria-related maternal anemia.

RESULTS

A semi-quantitative mass spectrometry approach was used to compare the relative abundance of plasma proteins in anemic versus non-anemic women with PM. Levels of 24 proteins differed significantly between anemic and non-anemic primigravidae, including several lipid metabolism proteins and molecular transport proteins involved in the acute phase response signaling network. These differences were not observed in multigravid women who enjoy specific immunity that protect them from PM. In a confirmatory study of a larger cohort of primigravid women, levels of the lipid metabolism protein Apolipoprotein (Apo)-AI were significantly lower in PM+ women with SA.

CONCLUSIONS

Apo-AI levels are significantly lower in severely anemic primigravidae with PM, and ApoA1 levels positively correlate with hemoglobin levels in primigravid but not multigravid women. Apo-AI is known to have anti-inflammatory effects, and thus Apo-AI reductions may contribute to the inflammatory processes that result in SA.