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Videotape reliability of the third revised edition of the K-SADS.

Videotaped interrater reliability was assessed with the K-SADS-III-R on 25 children with a mean age of 10:9. Kappa statistics were computed in syndromes with a frequency rate of at least 20%. The following mean kappas were obtained: major depression = 0.83; overanxious disorder = 0.85; separation anxiety = 0.85; simple phobic disorder = 0.64; oppositional disorder = 0.89; attention deficit disorder = 0.88. The mean kappa for mother derived diagnoses was 0.86; for child derived diagnoses 0.79; and, for all diagnoses combined 0.84. These reliability findings are comparable to reports with similar methodology in the child literature. The improved kappas for the anxiety disorders achieved a primary goal for this revision of the K-SADS. This study has shown that the K-SADS-III-R has sufficient reliability for research purposes.

Anxiety Disorders↗

Cardiovascular differentiation of happiness, sadness, anger, and fear following imagery and exercise.

This study examined cardiovascular patterns following happiness, sadness, anger, fear, relaxation, and control imagery in 32 subjects while they were seated and while they exercised. Affective imagery was an effective strategy for inducing reliable patterns of systolic and diastolic blood pressure and heart rate associated with particular emotional states. Anger, rather than fear, produced the greatest overall increases in cardiovascular measures and was distinctly opposite from relaxation. Anger differed from fear and all other conditions in terms of greater increases in diastolic pressure following imagery and greater increases in heart rate and slower recovery of systolic pressure following exercise. Sadness was unique in that systolic pressure and heart rate were virtually as high when subjects were still as when they were actually moving. Furthermore, sadness was the one emotional state that seemed to interfere with the cardiovascular adjustments normally associated with exercise. Implications of these findings for current biobehavioral models of emotion, including the role that specific emotions may play in the pathogenesis and treatment of cardiovascular disease, are considered.

Anger↗

Anger management style and hostility among patients with chronic pain: effects on symptom-specific physiological reactivity during anger- and sadness-recall interviews.

OBJECTIVES: We examined whether anger-in, anger-out, and hostility predicted symptom-specific muscle tension reactivity during anger induction (but not sadness induction) among patients with chronic low back pain (CLBP). For patients with CLBP, relevant muscles are the lower paraspinals (LPs). Anger-in x hostility and anger-out x hostility interactions were tested to determine whether particularly reactive groups of patients could be identified with a multivariable profile approach. METHODS: Ninety-four patients with CLBP underwent anger recall (ARI) and sadness recall (SRI) interviews, whereas LP and trapezius electromyography and systolic blood pressure, diastolic blood pressure, and heart rate were recorded. They completed anger-in, anger-out, hostility, and trait anger measures. RESULTS: Hierarchical regressions were used to test anger-in x hostility and anger-out x hostility interactions for physiological changes during the ARI and SRI. A significant anger-in x hostility interaction was found for LP change during the ARI (but not SRI) such that high anger-in/high hostility patients evinced the greatest reactivity. Effects for trapezius reactivity were nonsignificant. Significant anger-in x hostility interactions were also found for systolic blood pressure and diastolic blood pressure changes during the ARI such that high anger-in/low hostility patients showed the smallest changes. The anger-out x hostility interaction for diastolic blood pressure change during ARI was also significant such that high anger-out/low hostility patients showed the smallest changes. All effects remained significant with trait anger controlled. CONCLUSIONS: A multivariable profile approach may help identify especially vulnerable patient groups. Patients with CLBP who tend to suppress anger and are cynically hostile may be more likely to experience high levels of muscle tension near the site of pain and injury during anger, but not during sadness, than other groups.

Adaptation, Psychological↗

Away from the edge: SAD phasing from the sulfur anomalous signal measured in-house with chromium radiation.

Anomalous scattering with soft X-ray radiation opens new possibilities in phasing for macromolecular crystallography. Anomalous scattering from S atoms collected on an in-house chromium radiation source (lambda = 2.29 A) was used to phase the X-ray diffraction data of thaumatin (22 kDa) and trypsin (24 kDa) crystals. The contribution to the anomalous term, Deltaf" = 1.14 e(-), from sulfur for Cr Kalpha radiation is doubled compared with that for Cu Kalpha radiation, Deltaf" = 0.56 e(-). The direct-methods programs RANTAN or SHELXD successfully found sulfur positions using data sets with resolution limited to 3.5 A. The statistical phasing program SHARP was used to produce the electron-density maps using the sulfur anomalous signal alone at low resolution ( approximately 3.5 A). An interpretable electron-density map for each structure was obtained solely from the phases derived from single-wavelength anomalous dispersion (SAD) data obtained using Cr Kalpha radiation. Much fewer data (that is, lower redundancy) are required for this sulfur SAD phasing procedure compared with the highly redundant data reported in the sulfur SAD phasing procedure with Cu Kalpha radiation. Cr Kalpha radiation can also improve the strength of anomalous scattering of many other intrinsic elements in macromolecules, such as calcium, zinc and phosphorus, because of the increased Deltaf". Furthermore, the anomalous scattering of selenium is increased substantially from 1.14 e(-) with Cu Kalpha radiation to 2.28 e(-) with Cr Kalpha radiation. In order to measure the small Bijvoet differences accurately, several devices were developed for the experiment, including an Osmic Confocal MaxFlux optic optimized for Cr Kalpha radiation, a helium path and a beam stop. In the cases studied here, radiation damage to the samples and reduction of anomalous signal were observed in some long exposure time data sets. Therefore, an adequate data-collection strategy to maximize the completeness in a short scan range was used in subsequent data collections. The results show that the anomalous signal of S atoms can be collected quickly. Since the absorption of solvent and the loop may no longer be negligible with Cr Kalpha radiation, the orientation of the crystal and exposure time were taken into account in order to minimize the effects of radiation damage and absorption. This experimental study shows that using Cr Kalpha radiation from an in-house rotating-anode X-ray generator can provide sufficient phasing power from sulfur anomalous signals to routinely phase protein diffraction data.

Chromium↗

Is it jolly SAD?

Examples of phasing macromolecular crystal structures based on single-wavelength anomalous dispersion (SAD) have demonstrated that this approach may have general applications in structural biology. With better data-collection facilities and cryogenic techniques, combined with powerful data-processing, phasing and density-modification programs, the SAD approach may prove simpler than phasing from multi-wavelength (MAD) measurements. It can be performed at any wavelength where anomalous scattering can be observed, in many cases using laboratory X-ray sources. However, there is still a need for accurate data, successful phase improvement and a certain amount of luck. This paper extends the discussion of Jolly SAD in Dauter et al. [Dauter, Z., Dauter, M. & Dodson, E. (2002), Acta Cryst. D58, 494-506].

Cellulase↗

SAD phasing by combination of direct methods with the SOLVE/RESOLVE procedure.

In the initial stage of SAD phasing, the essential point is to break the intrinsic phase ambiguity. The presence of two kinds of phase information enables the discrimination of phase doublets from SAD data prior to density modification. One is from the heavy atoms (anomalous scatterers), while the other is from the direct-methods phase relationships. The former can be expressed by the Sim distribution, while the latter can be expressed by the Cochran distribution. Typically, only the Sim distribution has been used to yield initial phases for subsequent density modification. However, it has been demonstrated that using direct-methods phases based on the product of the Sim and Cochran distributions can lead to improved initial phases. In this paper, the direct-methods phasing procedure OASIS has been improved and combined with the SOLVE/RESOLVE procedure. Experimental SAD data from three known proteins with expected Bijvoet ratios / in the range 1.4-7.0% were used as test cases. In all cases, the phases obtained using the program RESOLVE beginning with initial phases based on experimental phases plus Sim and direct-methods information were more accurate than those based on experimental plus Sim phase information alone.

Azurin↗

SAD at home: solving the structure of oxalate decarboxylase with the anomalous signal from manganese using X-ray data collected on a home source.

Oxalate decarboxylase (OxdC) from Bacillus subtilis is a hexamer containing two manganese ions per 43.6 kDa subunit. A single highly redundant data set collected at a medium resolution of 2 A on an in-house X-ray source was sufficient to solve the structure by the single-wavelength anomalous diffraction (SAD) method using the anomalous signal from the manganese ions. The experimentally phased electron-density map was of high quality, enabling 96% of the amino-acid sequence to be automatically traced using ARP/wARP. Further analysis showed that only half of the original raw data were required for successful structure solution. Manganese currently occurs in approximately 2% of PDB entries. A brief survey suggests that several of these structures could also have been determined using manganese SAD. Moreover, the ability of manganese to substitute for other more commonly occurring divalent metal ions may indicate that the use of Mn SAD could have much wider application.

Bacillus subtilis↗

Structure determination of a novel protein by sulfur SAD using chromium radiation in combination with a new crystal-mounting method.

A novel and easy crystal-mounting technique was developed for the sulfur SAD method using Cr Kalpha radiation (2.29 A). Using this technique, the cryo-buffer and cryoloop around the protein crystal can be removed before data collection in order to eliminate their X-ray absorption. The superiority and reproducibility of the data sets with this mounting technique were demonstrated using tetragonal hen egg-white lysozyme crystals. The structure of a novel protein, PH1109, from Pyrococcus horikoshii OT3 was solved using this technique. At the wavelength of Cr Kalpha radiation, the anomalous signal |DeltaF|/|F| of PH1109 is expected to be 1.72% as this protein of 144 residues includes four methionines and two cysteines. Sulfur SAD phasing was performed using SHELXD and SHELXE. In the case of the data set obtained using this novel crystal-mounting technique, 54.9% of all residues were built with side chains automatically by RESOLVE. On the other hand, only 16.0% were built with side chains for the data set collected using the standard cryoloop. These results indicated that this crystal-mounting technique was superior to the standard loop-mounting method for the measurement of small anomalous differences at longer wavelength and yielded better results in sulfur-substructure solution and initial phasing. The present study demonstrates that the sulfur SAD method with a chromium source becomes enhanced and more practical for macromolecular structure determination using the new crystal-mounting technique.

Absorption↗

Structure determination of VEGF-E by sulfur SAD.

The crystal structure of VEGF-E was solved by the sulfur single-wavelength anomalous dispersion method (S-SAD) using highly redundant low-resolution data collected at a wavelength of lambda approximately 1.7 A with an estimated anomalous signal of 1.5%. 11 sulfur sites, nine out of 16 disulfide bonds and two out of 12 methionines could be located in the asymmetric unit using data truncated at a resolution of 4.1 A; however, none of the common diffraction data-quality indicators for SAD allowed clear discrimination between successful and unsuccessful resolution cutoffs. The high solvent content of 75% allowed efficient density modification to be performed and an unbiased electron-density map of good quality to be generated. This study demonstrates the strength of S-SAD for phasing using accurate highly redundant data at low resolution.

Crystallography, X-Ray↗

Sadness and susceptibility to judgmental bias: the case of anchoring.

In a wide range of empirical paradigms, sadness has been associated with more extensive and detail-oriented thinking than happiness, resulting in reductions in judgmental bias that arise from reliance on stereotypes and other simple decision heuristics. It was hypothesized that anchoring would constitute a significant exception to this general pattern. Recent research on anchoring indicates that an active thought process underlies the emergence of this bias. If sad people are likely to think more actively about the judgmental anchor than their neutral-mood counterparts, their subsequent judgments should be more likely to be assimilated toward this reference point. This prediction was confirmed in two experiments demonstrating that sad people are indeed more susceptible to anchoring bias than are people in a neutral mood. Moreover, this effect generalized over judgments in positive, neutral, and negative content domains.

Adult↗

Staff perceptions of sadness among people with mental handicaps.

This study investigated the use of an informant behaviour checklist to examine carestaff perceptions of sadness among a hospital population of people with mental handicaps. Using Cohen's kappa statistic there were only three checklist items which had acceptable levels of inter-rater agreement (physical aggression, crying and verbal abuse) with no significant variation in the incidence of those behaviours according to the severity of mental handicap. The findings suggest that future research might attend to concepts of sadness among carestaff and their ability to identify sad emotional states in a reliable manner.

Adolescent↗

Comparison of sadness, anger, and fear facial expressions when toddlers look at their mothers.

Research suggests that sadness expressions may be more beneficial to children than other emotions when eliciting support from caregivers. It is unclear, however, when children develop the ability to regulate their displays of distress. The current study addressed this question. Distress facial expressions (e.g., fear, anger, and sadness) were examined in 24-month-old toddlers throughout 4 episodes as well as specifically during looks to their mothers. Consistent with hypotheses and the literature, toddlers expressed sadness more frequently and with more intensity than target emotions only during looks to their mothers. These findings indicate that toddlers as young as 24 months of age are using particular emotional displays to elicit support from the social environment.

Affect↗

Cloning and expression of the Escherichia coli K-12 sad gene.

The Escherichia coli K-12 sad gene, which encodes an NAD-dependent succinic semialdehyde dehydrogenase, was cloned into a high-copy-number vector. Minicells carrying a sad+ plasmid produced a 55,000-dalton peptide, the probable sad gene product.

Bacterial Proteins↗

Neural and endocrine correlates of sadness in women: implications for neural network regulation of HPA activity.

In order to evaluate the suprahypothalamic neuroanatomical sites of relevance to adrenocorticotropic hormone (ACTH) and cortisol regulation, single photon emission computed tomography (SPECT) investigation of induced sadness was combined with a linear regression analysis of these hormone levels during mood induction. Images from eight healthy women were analyzed by statistical parametric mapping (SPM), replicating many findings from prior sadness induction studies. Statistical parametric mapping endocrine covariate analysis showed that the ventromedial prefrontal, anterior cingulate, and insular cortices may regulate ACTH and the insular cortex may be related to regulation of cortisol during sadness. Dysfunction of these sites may contribute to the cortisol dysregulation observed in some subjects with major depression.

Adolescent↗

Treatment with NS3623, a novel Cl-conductance blocker, ameliorates erythrocyte dehydration in transgenic SAD mice: a possible new therapeutic approach for sickle cell disease.

The dehydration of sickle red blood cells (RBCs) through the Ca-activated K channel depends on the parallel movement of Cl ions. To study whether Cl-conductance block might prevent dehydration of sickle RBCs, a novel Cl-conductance inhibitor (NS3623) was characterized in vitro using RBCs from healthy donors and sickle cell patients and in vivo using normal mice and a transgenic mouse model of sickle cell disease (SAD mice). In vitro, NS3623 reversibly blocked human RBC Cl-conductance (g(Cl)) with an IC(50) value of 210 nmol/L and a maximal block of 95%. In vivo, NS3623 inhibited RBC g(Cl) after oral administration to normal mice (ED(50) = 25 mg/kg). Although g(Cl), at a single dose of 100 mg/kg, was still 70% inhibited 5 hours after dosing, the inhibition disappeared after 24 hours. Repeated administration of 100 mg/kg twice a day for 10 days caused no adverse effects; therefore, this regimen was chosen as the highest dosing for the SAD mice. SAD mice were treated for 3 weeks with 2 daily administrations of 10, 35, and 100 mg/kg NS3623, respectively. The hematocrit increased, and the mean corpuscular hemoglobin concentration decreased in all groups with a concomitant increase in the intracellular cation content. A loss of the densest red cell population was observed in conjunction with a shift from a high proportion of sickled to well-hydrated discoid erythrocytes, with some echinocytes present at the highest dosage. These data indicate feasibility for the potential use of Cl-conductance blockers to treat human sickle cell disease.

Anemia, Sickle Cell↗

On assessing individual differences in rumination on sadness.

The Rumination on Sadness Scale (RSS), an individual-difference measure of rumination on sadness, was developed as an alternative to the Ruminative Responses scale of the Response Styles Questionnaire (RRRSQ; Nolen-Hoeksema & Morrow, 1991). Research has shown the RRRSQ to consist of multiple, not highly intercorrelated factors; only I factor explicitly addresses rumination. In Study 1, a 1-factor solution to a principal components analysis was shown to hold for responses to the RSS. The RSS was also shown to be reliable. In Study 2, convergent and discriminant validity of the RSS were assessed. In Study 3, individuals with high RSS scores exhibited more distress regarding current concerns with the introduction of a delay period (to allow them to ruminate) after a sad mood induction.

Adolescent↗

Anger and sadness regulation: predictions to internalizing and externalizing symptoms in children.

Examined the relation between children's self-reported anger and sadness regulation and the presence of internalizing and externalizing symptoms. Participants were 121 boys and 106 girls in the fourth and fifth grades who completed the Children's Depression Inventory (CDI), State-Trait Anxiety Inventory for Children (STAIC), Emotion Expression Scale for Children (EESC), and Children's Emotion Management Scales (CSMS, CAMS) and rated each other on aggressive behavior. Results of multiple regression analyses indicated that the inability to identify emotional states, the inhibition of anger, the dysregulation of anger and sadness, and the constructive coping with anger predicted internalizing symptoms. The dysregulated expression of sadness and constructive coping with anger were inversely related to externalizing symptoms.

Adaptation, Psychological↗

Lateralized effects of self-induced sadness and happiness on corticospinal excitability.

We studied the changes in excitability of the corticospinal projection evoked by self-induced sad and happy thoughts. Corticospinal excitability was probed using focal, single-pulse transcranial magnetic stimulation (TMS) applied to the optimal scalp position for evoking motor potentials in the contralateral first dorsal interosseus muscle. Fourteen right-handed subjects were studied while counting mentally, thinking sad thoughts, or thinking happy thoughts. In each of these three conditions TMS was applied in each subject randomly, 20 times to the right and 20 times to the left hemisphere. Sad thoughts resulted in a significant facilitation of the motor potentials evoked by left-hemispheric stimulation, while happy thoughts facilitated motor potentials evoked by right-hemispheric TMS, but decreased the amplitude of those evoked by left-hemispheric TMS. In two subjects an additional experiment using H-reflex measurements suggests that these changes are caused by changes in cortical rather than spinal excitability. These results further illustrate the lateralized control of mood in normal volunteers.

Adult↗