Nonliteral language in Alzheimer dementia: a review.

The use of nonliteral language in clinical assessment, especially testing the patients' ability to interpret proverbs, has a long tradition in psychiatry. However, its diagnostic sensitivity and specificity in dementias is not yet clear. The aim of this review article is to examine the current evidence on nonliteral/figurative language (proverb, metaphor, metonymy, idiom, irony, sarcasm) comprehension in Alzheimer's disease and related disorders. A comprehensive literature search identified 25 studies (16 proverb, 3 metaphor, 0 metonymy, 5 idiom, 3 sarcasm) on nonliteral language comprehension in dementia. Studies predominantly indicate a deficit. Most studies investigated Alzheimer's dementia. Applied correctly, nonliteral language is a worthwhile diagnostic tool to evaluate language and abstract thinking in dementias. During assessment, familiarity testing (e.g., by asking "are you familiar with the proverb XY") is obligatory. Still, future research is needed in several areas: evidence on decline of nonliteral language over the course of the illness is limited. So far, almost no studies delineated proverb comprehension in high risk populations such as patients with mild cognitive impairment. Currently, there is a lack of studies addressing performance in direct comparison to relevant differential diagnosis like older-age depression, delirium, brain lesion, or other psychiatric conditions.

Implementation of a manual-based training of humor abilities in patients with depression: a pilot study.

Humor and laughter can positively influence mood, promote optimism and lead to a change of perspective. Six patients with major depression participated in a group training program specifically designed to enhance humor abilities. After 8 weeks of training, short-term mood improvement was observed and the patients considered themselves more capable of using humor as a coping strategy. Acquired humor skills also helped to sustain the patients' motivation throughout the training period. In light of these encouraging findings, further studies to compare the effectiveness of the humor training with the effectiveness of other types of intervention and to assess its potential long-term effects seem warranted.

Do depressed patients lose their sense of humor?

BACKGROUND: Humor is an important coping mechanism and can improve mood. However, it is unclear whether depressed patients are able to enjoy funny material, e.g. jokes, and make use of their sense of humor for coping with adverse situations. This study aims at investigating the influence of depression on various aspects of humor abilities such as sense of humor, appraisal of funny material and exhilaration. SAMPLING AND METHODS: Nineteen patients with major depression and 18 healthy controls were examined with standardized self-assessment questionnaires to study potential group differences in humor type preferences, state and trait cheerfulness, seriousness and bad mood as well as humor coping. RESULTS: Patients and controls did not differ in their humor type preferences and the degree to which humorous stimuli were rated as being funny. The readiness to react to funny stimuli with exhilaration was significantly less pronounced in the patient group. The patients' tendency to use humor as a coping strategy was significantly lower than in the control group. CONCLUSION: The susceptibility to humorous material seems to be unaffected by the disorder. Introducing means to promote humor behavior might therefore be beneficial to depressed patients. Study limitations were that only self-rating instruments were used and that the medication was inhomogeneous.

Further evaluation of the world health organization international reference reagent for Haemoglobin A2 measurement.

INTRODUCTION: The accurate measurement of HbA2 is essential for the detection of ß-thalassaemia carriers and as no single calibrant is used by the various manufacturers of analysers, differences are seen in results obtained. The World Health Organization International Reference Reagent for HbA2 (WHO IRR 89/666) was made available to diagnostic laboratories in the 1980s and remains the only international reference material available. A previous study (2015) demonstrated that the WHO IRR remained suitable for use as an HbA2 standard as tested by 52 participants in the UK NEQAS Haematology Abnormal Haemoglobins Programme. This study was undertaken to include simultaneous analysis of three whole blood specimens over a range of HbA2 values with the WHO IRR and to include participants from laboratories outside of the UK. METHOD: Three whole blood specimens with HbA2 levels ranging from 2.4% to 5.7% and the WHO IRR were distributed to 56 laboratories located in 14 different countries. Participants were requested to test the specimens at defined intervals and return results accompanied by chromatograms or electropherograms produced. RESULTS: Differences found in results from different analyser groups reflect the bias found in the 2015 study in that bias is seen according to the methodology used and also varies in relation to the level of analyte being measured. CONCLUSION: Results of measurements from whole blood specimens and the lyophilized WHO IRR standard did not show any deterioration of the IRR, and it remains suitable for use. Linearity and calibration of analysers remain a problem.

Hemoglobin variants in Cyprus.

Cyprus, located at the eastern end of the Mediterranean region, has been a place of eastern and western civilizations, and the presence of various hemoglobin (Hb) variants can be considered a testimony to past colonizations of the island. In this study, we report the structural Hb variants identified in the Cypriot population (Greek Cypriots, Maronites, Armenians, and Latinos) during the thalassemia screening of 248,000 subjects carried out at the Thalassaemia Centre, Nicosia, Cyprus, over a period of 26 years. A sample population of 65,668 people was used to determine the frequency and localization of several of the variants identified in Cyprus. The localization of some of the variants in regions where the presence of foreign people was most prevalent provides important clues to the origin of the variants. Twelve structural variants have been identified by DNA sequencing, nine concerning the beta-globin gene and three concerning the alpha-globin gene. The most common beta-globin variants identified were Hb S (0.2%), Hb D-Punjab (0.02%), and Hb Lepore-Washington-Boston (Hb Lepore-WB) (0.03%); the most common alpha-globin variant was Hb Setif (0.1%). The presence of some of these variants is likely to be directly linked to the history of Cyprus, as archeological monuments have been found throughout the island which signify the presence for many years of the Greeks, Syrians, Persians, Arabs, Byzantines, Franks, Venetians, and Turks.

Evaluation of the suitability of the World Health Organization International Reference Reagent for Hb A2 quantitation (89/666) for continued use.

INTRODUCTION: The accurate determination of Hb A2 is a key marker when screening for a ß-thalassaemia carrier. Data from external quality assessment (EQA) exercises have shown a lack of alignment of Hb A2 quantitation both within and between methods. The only reference material available for Hb A2 quantitative assay at the time of writing is the World Health Organization International Reference Reagent (89/666; WHO IRR) prepared in the 1980s and not validated for all current methodologies. METHOD: The WHO IRR was analysed for Hb A2 concentration by 52 laboratories using a representative range of high-performance liquid chromatography and capillary electrophoresis analysers. The results of the analysis were compared to those of a whole blood EQA specimen of similar Hb A2 concentration, distributed in the same week. RESULTS: The mean Hb A2 value obtained for the WHO IRR was 5.17%, compared to the assigned value of 5.3%. The range of results returned was wide (4.0%-6.2%), with differences in the results observed by between and within analyser groups. A similar range of results was seen with the whole blood sample, although the bias observed between analyser types was different from that seen with the WHO IRR. CONCLUSION: The results may indicate a lack of commutability of the WHO IRR material, resulting from deterioration, matrix effects or changes in reagent formulation or calibration parameters. Further examination of the suitability of the WHO IRR (89/666) for continued use is required.

Trait cheerfulness modulates BOLD response in lateral cortical but not limbic brain areas--a pilot fMRI study.

Having a good "sense of humor" is an important personality characteristic that significantly influences social communication and may represent an important coping strategy. To take things "with humor" does not only represent a state characteristic but also a personality trait that can reliably be assessed with questionnaires like the "state-trait-cheerfulness-inventory" (STCI) by Ruch [Ruch et al., Assessing the "humorous temperament": construction of the facet and standard trait forms of the state-trait-cheerfulness-inventory-STCI, Humor 9 (1996) 303-339]. Substantial inter-individual differences among study subjects are a key feature of almost all functional magnetic resonance imaging studies on higher cognitive functions. Usually, they are considered as "statistical noise" and are not recommended for the data analysis, although they can have a high intra-individual stability. However, a number of recent fMRI studies found robust correlations between inter-individual differences in BOLD response and personality traits such as extraversion. The aim of this pilot exploratory study was to localise regions where the BOLD response was predicted by "humor personality" scores. 10 healthy male subjects viewed funny or non-funny versions of Gary Larson cartoons while BOLD response was measured with functional magnetic resonance imaging (fMRI). Data were collected from the whole brain (28 slices, slice thickness 4 mm, 1 mm gap, TR = 3s). SPM 99 software was used. A simple regression analysis with the sub-score cheerfulness from the STCI was applied. Higher cheerfulness in the STCI predicted brain activation in the right inferior parietal lobule (Tal X, Y, Z: 45, -77, 29), but not in limbic and prefrontal brain areas. We conclude that neural correlates of cheerfulness are correlated with BOLD response in lateral cortical rather than limbic brain areas. Likely the activated region is important for a readiness or tendency to be amused, whereas the regions previously shown to be activated in humor appreciation studies are related to the understanding of the joke and the emotional reaction.

Clinical efficacy and cognitive side effects of bifrontal versus right unilateral electroconvulsive therapy (ECT): a short-term randomised controlled trial in pharmaco-resistant major depression.

BACKGROUND: In most studies right unilateral electroconvulsive therapy (ECT) has been shown to cause fewer cognitive side effects but less antidepressant efficacy compared with bi(fronto)temporal ECT at certain intensities. AIMS: To compare the short-term efficacy and side effects of right unilateral ECT and bifrontal ECT. METHODS: In a double-blind randomised controlled clinical trial, 92 patients diagnosed with pharmaco-resistant major depression received either six right unilateral ECT treatments (250% stimulus intensity of titrated threshold) or six bifrontal ECT (150% of threshold) treatments over a 3-week period. Concomitant psychotropic medications were continued during ECT treatments. The severity of depression and cognitive status was assessed prior to the first ECT and one day after the sixth ECT using the 21-item Hamilton Depression Rating Scale and the modified Mini Mental State Examination. RESULTS: Eight patients did not complete the course of the study due to minor side effects or withdrawal of consent. The mean Hamilton Depression score decreased from 27 to 17 points in both groups of 46 patients, resulting in 12 responders (primary endpoint defined as a decrease >50%) in each patient group (95% confidence interval for the odds ratio from 0.35 to 2.8). There was no reduction in the modified Mini Mental State score (mean score 86 of 100 points). CONCLUSIONS: Both bifrontal and right unilateral electrode placements in ECT were reasonably safe and moderately efficacious in reducing symptoms of pharmaco-resistant major depression.

[Humor in Medicine - The Art of Leaping Over the Shadows]. / Humor in der Medizin ­ Von der Kunst, über Schatten zu springen.

Humor and laughter are integral parts of human life and communication - and so of course they occur in medical contacts.Humor is defined as a personality based cognitive emotional style of processing situations, characterized by the ability to find positive aspects even in negative situations, and the ability to communicate this point of view to others and to cheer them up. Humor can support healing processes and coping with illness. Humor and jokes reduce anxiety and stress (for patients and doctors). Humorous people have a more realistic, flexible and less fearful behaviour. Humor helps to overcome negative experience. Humor can help the patient to gain new views towards the disease and a healthy distance towards occurring symptoms. Humor improves the relationship between patient and doctor. But beware: jokes can also be used to express fears, aggression or shame. Therefore it is worthwhile to listen carefully to what patients want to express. Humor reduces the risk of burnout. In contact with patients, it is important to give their humor room, to use it and respond to it, more than making jokes. Humor can be trained. Humor training and creation of a humorous atmosphere in health care facilities should also be supported by health insurance funds, institutions' sponsors and public authorities.

Developing a reference system for the IFCC standardization of HbA2.

The importance of hemoglobin A2 (HbA2) as an indicator of the presence of ß-thalassemia was established many years ago. However, clinical application of recommended HbA2 cut off values is often hampered due to poor equivalence of HbA2 results among methods and laboratories. Thus, the IFCC standardization program for HbA2 was initiated in 2004 with the goal of achieving a complete reference system for this measurand. HbA2 standardization efforts are still in progress, including the development of a higher-order HbA2 reference measurement procedure and the preparation of a certified reference material in collaboration with the IRMM. Here, we review the past, present and future of HbA2 standardization and describe the current status of HbA2 testing.

Why are smiles contagious? An fMRI study of the interaction between perception of facial affect and facial movements.

In human communication there is often a close relationship between the perception of an emotionally expressive face and the facial response of the viewer himself. Whereas perception and generation of facial expressions have been studied separately with functional imaging methods, no studies exist on their interaction. We combined the presentation of emotionally expressive faces with the instruction to react with facial movements predetermined and assigned. fMRI was used in an event related design to examine healthy subjects while they regarded happy, sad, or neutral faces and were instructed to simultaneously move the corners of their mouths either (a). upwards or (b). downwards, or (c). to refrain from movement. The subjects' facial movements were recorded with an MR-compatible video camera. Movement latencies were shortened in congruent situations (e.g. the presentation of a happy face and combined with upward movements) and delayed in non-congruent situations. Dissonant more than congruent stimuli activated the inferior prefrontal cortex and the somatomotor cortex bilaterally. The congruent condition, in particular when seeing a happy face, activated the medial basotemporal lobes (hippocampus, amygdala, parahippocampal region). We hypothesize that this region facilitates congruent facial movements when an emotionally expressive face is perceived and that it is part of a system for non-volitional emotional facial movements.

Detection and quantitation of normal and variant haemoglobins: an analytical review.

As well as six 'normal' haemoglobins that occur at various stages of development, more than 800 abnormal or variant haemoglobins have been described. Many of these variant haemoglobins have no significant clinical consequences apart from causing confusion to clinicians and in laboratories; however, some of the variant haemoglobins result in major morbidity or mortality. The laboratory challenge is to detect these clinically significant haemoglobins and to identify them with sufficient accuracy for clinical purposes, as well as to quantitate both these and the 'normal' haemoglobins. The techniques used to detect and quantitate these haemoglobins in routine service laboratories are discussed in detail. Methods used by referral laboratories, such as mass spectrometry and DNA analysis, are briefly discussed. Haemoglobin analysis is most often undertaken as part of neonatal, antenatal or pre-anaesthetic screening; these programmes are reviewed, together with possible changes to neonatal screening and antenatal screening that may occur as part of the NHS National Plan.

Irony and proverb comprehension in schizophrenia: do female patients "dislike" ironic remarks?

Difficulties in understanding irony and sarcasm are part of the social cognition deficits in patients with schizophrenia. A number of studies have reported higher error rates during comprehension in patients with schizophrenia. However, the relationships of these impairments to schizotypal personality traits and other language deficits, such as the comprehension of proverbs, are unclear. We investigated irony and proverb comprehension in an all-female sample of 20 schizophrenia patients and 27 matched controls. Subjects indicated if a statement was intended to be ironic, literal, or meaningless and furthermore rated the meanness and funniness of the stimuli and certainty of their decision. Patients made significantly more errors than controls did. Globally, there were no overall differences in the ratings. However, patients rated the subgroup of stimuli with answers given incorrectly as having significantly less meanness and in case of an error indicated a significantly higher certainty than controls. Across all of the study participants, performances in irony (r = -0.51) and proverb (r = 0.56) comprehension were significantly correlated with schizotypal personality traits, suggesting a continuum of nonliteral language understanding. Because irony is so frequent in everyday conversations, this makes irony an especially promising candidate for social cognition training in schizophrenia.

Isn't it ironic? Neural correlates of irony comprehension in schizophrenia.

Ironic remarks are frequent in everyday language and represent an important form of social cognition. Increasing evidence indicates a deficit in comprehension in schizophrenia. Several models for defective comprehension have been proposed, including possible roles of the medial prefrontal lobe, default mode network, inferior frontal gyri, mirror neurons, right cerebral hemisphere and a possible mediating role of schizotypal personality traits. We investigated the neural correlates of irony comprehension in schizophrenia by using event-related functional magnetic resonance imaging (fMRI). In a prosody-free reading paradigm, 15 female patients with schizophrenia and 15 healthy female controls silently read ironic and literal text vignettes during fMRI. Each text vignette ended in either an ironic (n = 22) or literal (n = 22) statement. Ironic and literal text vignettes were matched for word frequency, length, grammatical complexity, and syntax. After fMRI, the subjects performed an off-line test to detect error rate. In this test, the subjects indicated by button press whether the target sentence has ironic, literal, or meaningless content. Schizotypal personality traits were assessed using the German version of the schizotypal personality questionnaire (SPQ). Patients with schizophrenia made significantly more errors than did the controls (correct answers, 85.3% vs. 96.3%) on a behavioural level. Patients showed attenuated blood oxygen level-dependent (BOLD) response during irony comprehension mainly in right hemisphere temporal regions (ironic>literal contrast) and in posterior medial prefrontal and left anterior insula regions (for ironic>visual baseline, but not for literal>visual baseline). In patients with schizophrenia, the parahippocampal gyrus showed increased activation. Across all subjects, BOLD response in the medial prefrontal area was negatively correlated with the SPQ score. These results highlight the role of the posterior medial prefrontal and right temporal regions in defective irony comprehension in schizophrenia and the mediating role of schizotypal personality traits.

Propagation lengths and group velocities of plasmons in chemically synthesized gold and silver nanowires.

Recent advances in chemical synthesis have made it possible to produce gold and silver nanowires that are free of large-scale crystalline defects and surface roughness. Surface plasmons can propagate along the wires, allowing them to serve as optical waveguides with cross sections much smaller than the optical wavelength. Gold nanowires provide improved chemical stability as compared to silver nanowires, but at the cost of higher losses for the propagating plasmons. In order to characterize this trade-off, we measured the propagation length and group velocity of plasmons in both gold and silver nanowires. Propagation lengths are measured by fluorescence imaging of the plasmonic near fields. Group velocities are deduced from the spacing of fringes in the spectrum of coherent light transmitted by the wires. In contrast to previous work, we interpret these fringes as arising from a far-field interference effect. The measured propagation characteristics agree with numerical simulations, indicating that propagation in these wires is dominated by the material properties of the metals, with additional losses due to scattering from roughness or grain boundaries providing at most a minor contribution. The propagation lengths and group velocities can also be described by a simple analytical model that considers only the lowest-order waveguide mode in a solid metal cylinder, showing that this single mode dominates in real nanowires. Comparison between experiments and theory indicates that widely used tabulated values for dielectric functions provide a good description of plasmons in gold nanowires but significantly overestimate plasmon losses in silver nanowires.

Keep smiling! Facial reactions to emotional stimuli and their relationship to emotional contagion in patients with schizophrenia.

INTRODUCTION: Emotional contagion is a common phenomenon in verbal and nonverbal communication between individuals. Perception and mimicry of facial movements play an important role in this process. Several studies have demonstrated impaired facial expression recognition in patients with schizophrenia and differences in their facial behavior compared to healthy subjects, but so far, the relationship between facial mimicry and emotional contagion has not been studied in this group. METHODS: Seventeen schizophrenic patients and an equal number of matched healthy controls were presented with digital versions of happy, sad and neutral faces from the "Pictures of facial affect" (Ekman and Friesen, Consulting Psychologists Press, Palo Alto, 1976) and were asked to pull their lip corners up or down (like in smiling or showing a sad face) according to the direction of two arrows that were presented simultaneously. In healthy subjects, congruous movements (i.e. pulling the lip corners up when seeing a happy face or pulling them down when seeing a sad face) are facilitated and dissonant movements are inhibited; these tendencies were considered as indicators of emotional contagion. RESULTS: In schizophrenic patients, these tendencies were significantly diminished. The patients were more apt to display a smile as a reaction to a sad face. We found a positive correlation between these effects and the PANSS-Scores for General Psychopathology. DISCUSSION: Patients' tendencies towards positive reactions even when a negative stimulus was presented could function as a protective mechanism against overwhelming emotional experiences.

[Insanity defense in post-traumatic stress disorder]. / Verminderte Schuldfähigkeit bei posttraumatischer Belastungsstörung (PTSD)?

We report the forensic psychiatric evaluation of a 40 year old Iraqi who suffers from a posttraumatic stress disorder (PTSD). She committed multiple non violent shopliftings. We mention criteria for a possible causal relationship between the PTSD and the crimes and discuss, why we affirm a insanity defense in this case.

Electroconvulsive therapy dosage in continuation/maintenance electroconvulsive therapy: when is a new threshold titration necessary?

Treatment effects and side effects of electroconvulsive therapy (ECT) depend on the level of applied energy in relation to the individual patient's seizure threshold. The threshold is known to increase during a course of frequently repeated ECT treatments and to return to baseline 6 months after cessation of treatment. In continuation ECT, however, as well as after early relapses, the interval between treatments is often longer than a few days but shorter than 6 months. Seizure thresholds for such cases have not been examined. We retrospectively examined 19 patients who had undergone repeated ECT treatments that had been separated by intervals of at least 14 days. We found significant changes in seizure duration, as measured by EEG and the cuff technique, when treatments were separated by durations exceeding 60 days. This is compatible with a decrease in seizure threshold or a loss of anticonvulsant action after 2 months and indicates the necessity to retitrate seizure threshold after this time.