The riddle of deliberate self-harm: Physiological and subjective effects of self-cutting cues in patients with borderline personality disorder and healthy controls.

Self-harming behavior is a core symptom of borderline personality disorder. Self-report studies show a correlation between a lack of self-reported negative feelings toward self-cutting cues and the likelihood of future self-destructive behavior. Despite these findings, there has so far been insufficient investigation into the implicit emotional processes evoked by this stimulus type. Forty patients with borderline personality disorder and 35 healthy controls between 20 and 50 years of age were confronted with pictures of self-cutting cues and affective reference pictures. A startle reflex paradigm was used for measuring implicit emotional responses, and the Self-Assessment Manikin was used for subjective responses. In line with previous studies, the patients rated the self-cutting pictures significantly less negatively than healthy individuals. On the physiological level, a significant startle inhibition was observed, indicating an activation of the behavioral approach system. A more detailed analysis showed that this startle inhibition effect was specific to scary pictures, whereas no such effect was observed for bloody wounds and self-cutting instruments. For pleasant standard pictures, in contrast, no startle reflex inhibition and no increase in emotional arousal parameters were found. The data replicate the findings of previous studies, demonstrating a generally diminished emotional reactivity to pleasant stimuli in patients with borderline personality disorder. In addition, a physiological approach reaction to self-cutting pictures was found, especially for the scary pictures. These results might indicate a positive identification with the long-lasting consequences of self-cutting behavior in the patients. Implications for therapy are discussed.

SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care.

Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia is associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22-2.77] adjusted for age and sex). RNAemia is comparable in performance to the best protein predictors. Mannose binding lectin 2 and pentraxin-3 (PTX3), two activators of the complement pathway of the innate immune system, are positively associated with mortality. Machine learning identified 'Age, RNAemia' and 'Age, PTX3' as the best binary signatures associated with 28-day ICU mortality. In longitudinal comparisons, COVID-19 ICU patients have a distinct proteomic trajectory associated with mortality, with recovery of many liver-derived proteins indicating survival. Finally, proteins of the complement system and galectin-3-binding protein (LGALS3BP) are identified as interaction partners of SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake and spike-induced cell-cell fusion in vitro.

Instructional Training Compared with Self-Study for Pulmonary Function Test Interpretation.

BACKGROUND: Pulmonary diseases have considerable prognostic relevance for all-cause mortality. Most patients with lung diseases such as chronic obstructive pulmonary disease are treated by general practitioners. Understanding the clinical consequences such as pulmonary hyperinflation or reduced diffusion capacity is important for the management and prognosis of patients with chronic respiratory disorders. Therefore, the interpretation of pulmonary function testing (PFT) results needs to see more emphasis in the medical education curriculum. OBJECTIVE: To develop PFT training for final-year medical students and to compare the efficacy of instructional training to self-reliant textbook study. METHODS: A two-armed randomized control trial compares learning outcomes in PFT interpretation. A total of 25 final-year medical students were selected at random into the 1) instructional training group or 2) self-reliant textbook study group on PFT interpretation. The learning time for both groups was 2 hours. The duration of the written pre- and post-training examinations was 60 minutes each. Both exams had a knowledge section (30 questions, maximum 120 points) and a skills section (11 case studies, maximum 75 points). RESULTS: The instructional training group acquired significantly more knowledge and, in particular, higher skill levels when compared with the self-reliant reading group. In the reading group, knowledge scores increased from 48 to 60% (12%) and skills scores increased from 14 to 22% (8%), whereas in the instructional group, knowledge increased from 47 to 71% (24%) and skills from 18 to 58% (40%). A multivariate analysis (Pillai's Trace: 0.633; P < 0.001) as well as follow-up univariate analyses reveal that these differences are statistically significant (knowledge: F = 8.811, df = 1, P = 0.007; skills F = 33.965, df = 1, P < 0.001). Interestingly, there was no significant group effect in the pure knowledge gain about respiratory disorders per se. CONCLUSION: The self-reliant study group was less able to translate their newly acquired knowledge into interpretation of comprehensive PFT reports. A mandatory 2-hour instructional training greatly enhances the students' knowledge and skills about PFT interpretation. Obligatory PFT instructional training should therefore be included in the students' curriculum.

Association of Hypertensive Intracerebral Hemorrhage with Left Ventricular Hypertrophy on Transthoracic Echocardiography.

INTRODUCTION: Arterial hypertension is the most frequent cause for spontaneous intracerebral hemorrhage (sICH) and may also cause left ventricular hypertrophy (LVH). We sought to analyze whether hypertensive sICH etiology is associated with LVH. METHODS: We analyzed consecutive patients with sICH who were admitted to our tertiary stroke center during a four-year period and underwent transthoracic echocardiography (TTE) as part of the diagnostic work-up. We defined hypertensive sICH as typical localization of hemorrhage in patients with arterial hypertension and no other identified sICH etiology. We defined an increased end-diastolic interventricular septal wall thickness of ≥11 mm on TTE as a surrogate parameter for LVH. RESULTS: Among 395 patients with sICH, 260 patients (65.8%) received TTE as part of their diagnostic work-up. The median age was 71 years (interquartile range (IQR) 17), 160 patients (61.5%) were male, the median baseline National Institute of Health Stroke Scale (NIHSS) score was 8 (IQR 13). Of these, 159 (61.2%) patients had a hypertensive sICH and 156 patients (60%) had LVH. In univariable (113/159 (71.1%) vs. 43/101 (42.6%); odds ratio (OR) 3.31; 95% confidence interval (CI95%) 1.97-5.62); and multivariable (adjusted OR 2.95; CI95% 1.29-6.74) analysis, hypertensive sICH was associated with LVH. CONCLUSIONS: In patients with sICH, LVH is associated with hypertensive bleeding etiology. Performing TTE is meaningful for diagnosis of comorbidities and clarification of bleeding etiology in these patients. Future studies should include long-term outcome parameters and assess left ventricular mass as main indicator for LVH.

Efficacy and safety of nasal high-flow oxygen in COPD patients.

BACKGROUND: Nasal high-flow oxygen therapy (HFOT) is a novel treatment option for patients suffering from acute or chronic respiratory failure. Aim of our study was to compare safety and efficacy of HFOT with those of conventional oxygen treatment (COT) in normo- and hypercapnic COPD patients. METHODS: A single cohort of 77 clinically stable hypoxemic patients with an indication for long-term oxygen treatment (LTOT) with or without hypercapnia successively received COT and HFOT for 60 min each, including oxygen adaption and separated by a 30 min washout phase. RESULTS: HFOT was well-tolerated in all patients. A significant decrease in PaCO2 was observed during oxygen adaption of HFOT, and increased PaO2 coincided with significantly increased SpO2 and decreased AaDO2 during both treatment phases. Even at a flow rate of 15 L/min, oxygen requirement delivered as air mixture by HFOT tended to be lower than that of COT (2.2 L/min). Not only was no increase in static or dynamic lung volumes observed during HFOT, but even was a significant reduction of residual lung volume measured in 36 patients (28%). CONCLUSIONS: Thus, short-term use of HFOT is safe in both normocapnic and hypercapnic COPD patients. Lower oxygen levels were effective in correcting hypoxemic respiratory failure and reducing hypercapnia, leading to a reduced amount of oxygen consumption. Long-term studies are needed to assess safety, tolerability, and clinical efficacy of HFOT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01686893 13.09.2012 retrospectively registered (STIT-1) and NCT01693146 14.09.2012 retrospectively registered (STIT-2). Studies were approved by the local ethics committee (Ethikkommission der Medizinischen Universität Innsbruck, Studienkennzahl UN3547, Sitzungsnummer 274/4.19).

Inflammatory processes and schizophrenia: two independent lines of evidence from a study of twins discordant and concordant for schizophrenic disorders.

The concept of twin concordance involves quantifying the resemblance between co-twins in an "objective" and reproducible way. Yet, quantifying resemblance in the case of complex psychiatric traits like schizophrenic disorders leads to methodological problems, as the yes-no dichotomy of diagnostic schemata does not allow one to assess between-subject differences in psychopathology patterns sufficiently accurately. Therefore, we relied on a multidimensional, quantitative concordance measure that provided a high resolution and differentiation when assessing the resemblance of psychopathology patterns. This concordance measure was central to our investigations into the potential link between schizophrenic disorders and aberrancies of the inflammatory response system. Specifically, we aimed to determine the extent to which (1) the observed variation of between-subject psychopathology concordance among 100 schizophrenic patients and (2) the observed variation of within-pair psychopathology concordance among 71 twin pairs can be explained by immunoglobulin M (IgM) levels. To accomplish this goal, we had to "gauge" in a first step the concordance measure's performance by (1) comparing the psychopathology patterns of 269 index cases suffering from functional psychoses with the respective patterns of the 350 "affecteds" among their first-degree relatives; (2) systematically comparing the psychopathology patterns of 100 unrelated patients with a diagnosis of schizophrenic disorders with each other; and (3) detailing the within-pair concordance of elementary traits among 2734 healthy twin pairs. As to the role of active immune processes in the context of schizophrenic disorders, we found that there exists a 20-30% subgroup of patients for whom aberrancies of the inflammatory response system, as quantified through IgM levels, appeared to be linked to the pathogenesis of schizophrenic disorders (r = 0.7515/0.8184, p < 0.0001). The variation of within-pair psychopathology concordance among twins with schizophrenic disorders was found to be "explainable" in part by chronically elevated IgM levels (24.5% of observed phenotypic variance; p = 0.0434), thus suggesting that monozygotic twins concordant for schizophrenic disorders may possess a less "robust" variant of the inflammatory response system which can more easily be triggered by exogenous factors than the more "robust" variants of discordant pairs. Though the underlying biological mechanisms remain to be detected, our data have cleared the way for an early identification of patients with schizophrenic disorders for whom the inflammatory response system may be a target for therapeutic intervention. Moreover, our results will likely lead to new treatment strategies that involve elements of personalized medicine.

Assessing Chronic Stress, Coping Skills, and Mood Disorders through Speech Analysis: A Self-Assessment 'Voice App' for Laptops, Tablets, and Smartphones.

BACKGROUND: Computerized speech analysis (CSA) is a powerful method that allows one to assess stress-induced mood disturbances and affective disorders through repeated measurements of speaking behavior and voice sound characteristics. Over the past decades CSA has been successfully used in the clinical context to monitor the transition from 'affectively disturbed' to 'normal' among psychiatric patients under treatment. This project, by contrast, aimed to extend the CSA method in such a way that the transition from 'normal' to 'affected' can be detected among subjects of the general population through 10-20 self-assessments. METHODS: Central to the project was a normative speech study of 5 major languages (English, French, German, Italian, and Spanish). Each language comprised 120 subjects stratified according to gender, age, and education with repeated assessments at 14-day intervals (total n = 697). In a first step, we developed a multivariate model to assess affective state and stress-induced bodily reactions through speaking behavior and voice sound characteristics. Secondly, we determined language-, gender-, and age-specific thresholds that draw a line between 'natural fluctuations' and 'significant changes'. Thirdly, we implemented the model along with the underlying methods and normative data in a self-assessment 'voice app' for laptops, tablets, and smartphones. Finally, a longitudinal self-assessment study of 36 subjects was carried out over 14 days to test the performance of the CSA method in home environments. RESULTS: The data showed that speaking behavior and voice sound characteristics can be quantified in a reproducible and language-independent way. Gender and age explained 15-35% of the observed variance, whereas the educational level had a relatively small effect in the range of 1-3%. The self-assessment 'voice app' was realized in modular form so that additional languages can simply be 'plugged in' once the respective normative data become available. Results of the longitudinal self-assessment study in home environments demonstrated that CSA methods work well under most circumstances. CONCLUSIONS: We have successfully developed and tested a self-assessment CSA method that can monitor transitions from 'normal' to 'affected' in subjects of the general population in the broader context of mood disorders. Our easy-to-use 'voice app' evaluates sequences of 10-20 repeated assessments and watches for affect- and stress-induced deviations from baseline that exceed language-, gender-, and age-specific thresholds. Specifically, the 'voice app' provides users with stress-related 'biofeedback' and can help to identify that 10-15% subgroup of the general population that exhibits insufficient coping skills under chronic stress and may benefit from early detection and intervention prior to developing clinically relevant symptoms.

Diagnostic Impact of Transesophageal Echocardiography in Patients with Acute Cerebral Ischemia.

OBJECTIVES: Transesophageal echocardiography (TEE) is the diagnostic gold standard for the detection of structural heart diseases as potential sources of cardiac emboli in patients with acute cerebral ischemia. We sought to determine the diagnostic yield of TEE in patients with acute ischemic stroke or transient ischemic attack (TIA). METHODS: We retrospectively analyzed consecutive patients with acute cerebral ischemia who were admitted to our hospital between October 2008 and December 2011. TEE reports were screened for detection of cardiac source of embolism judged by the recommendation to change medical management. We performed univariate and multivariate analyses to identify predictors of clinically relevant TEE findings among baseline characteristics. RESULTS: Of 3314 patients with ischemic stroke or TIA, TEE was performed in 791 (24%) patients (mean age 64 ± 13 years, 589 [74%] ischemic stroke, 202 [26%] TIA). A potential cardioembolic source was found in 71 (9%) patients with patent foramen ovale with atrial septal aneurysm being the most common finding (24/71 patients, 34%). In multivariate analysis, peripheral vascular disease (OR 2.57; 95%CI 1.00-6.61), imaging evidence of infarction in multiple locations (OR 4.13; 95%CI 1.36-12.58), and infarction in the posterior circulation (OR 2.11; 95%CI 1.01-4.42) were associated with the identification of a potential cardioembolic source with TEE. CONCLUSION: TEE identified a potential structural cardioembolic source in nearly 10% of our selected patient population with acute ischemic stroke or TIA, thus underlining its diagnostic value. Our data suggest that patients with hitherto unknown stroke etiology should be considered for additional TEE.

Quantifying insufficient coping behavior under chronic stress: a cross-cultural study of 1,303 students from Italy, Spain and Argentina.

The question of how to quantify insufficient coping behavior under chronic stress is of major clinical relevance. In fact, chronic stress increasingly dominates modern work conditions and can affect nearly every system of the human body, as suggested by physical, cognitive, affective and behavioral symptoms. Since freshmen students experience constantly high levels of stress due to tight schedules and frequent examinations, we carried out a 3-center study of 1,303 students from Italy, Spain and Argentina in order to develop socioculturally independent means for quantifying coping behavior. The data analysis relied on 2 self-report questionnaires: the Coping Strategies Inventory (COPE) for the assessment of coping behavior and the Zurich Health Questionnaire which assesses consumption behavior and general health dimensions. A neural network approach was used to determine the structural properties inherent in the COPE instrument. Our analyses revealed 2 highly stable, socioculturally independent scales that reflected basic coping behavior in terms of the personality traits activity-passivity and defeatism-resilience. This replicated previous results based on Swiss and US-American data. The percentage of students exhibiting insufficient coping behavior was very similar across the study sites (11.5-18.0%). Given their stability and validity, the newly developed scales enable the quantification of basic coping behavior in a cost-efficient and reliable way, thus clearing the way for the early detection of subjects with insufficient coping skills under chronic stress who may be at risk of physical or mental health problems.

Affective state and voice: cross-cultural assessment of speaking behavior and voice sound characteristics--a normative multicenter study of 577 + 36 healthy subjects.

BACKGROUND: Human speech is greatly influenced by the speakers' affective state, such as sadness, happiness, grief, guilt, fear, anger, aggression, faintheartedness, shame, sexual arousal, love, amongst others. Attentive listeners discover a lot about the affective state of their dialog partners with no great effort, and without having to talk about it explicitly during a conversation or on the phone. On the other hand, speech dysfunctions, such as slow, delayed or monotonous speech, are prominent features of affective disorders. METHODS: This project was comprised of four studies with healthy volunteers from Bristol (English: n = 117), Lausanne (French: n = 128), Zurich (German: n = 208), and Valencia (Spanish: n = 124). All samples were stratified according to gender, age, and education. The specific study design with different types of spoken text along with repeated assessments at 14-day intervals allowed us to estimate the 'natural' variation of speech parameters over time, and to analyze the sensitivity of speech parameters with respect to form and content of spoken text. Additionally, our project included a longitudinal self-assessment study with university students from Zurich (n = 18) and unemployed adults from Valencia (n = 18) in order to test the feasibility of the speech analysis method in home environments. RESULTS: The normative data showed that speaking behavior and voice sound characteristics can be quantified in a reproducible and language-independent way. The high resolution of the method was verified by a computerized assignment of speech parameter patterns to languages at a success rate of 90%, while the correct assignment to texts was 70%. In the longitudinal self-assessment study we calculated individual 'baselines' for each test person along with deviations thereof. The significance of such deviations was assessed through the normative reference data. CONCLUSIONS: Our data provided gender-, age-, and language-specific thresholds that allow one to reliably distinguish between 'natural fluctuations' and 'significant changes'. The longitudinal self-assessment study with repeated assessments at 1-day intervals over 14 days demonstrated the feasibility and efficiency of the speech analysis method in home environments, thus clearing the way to a broader range of applications in psychiatry.

Haemoptysis due to pulmonary venous stenosis.

Haemoptysis is a potentially life-threatening condition with the need for prompt diagnosis. In about 10-20% of all cases the bleeding source remains unexplained with the standard diagnostic approach. The aim of this article is to show the necessity of widening the diagnostic approach to haemoptysis with consideration of pulmonary venous stenosis as a possible cause of even severe haemoptysis and haemoptoe. A review of the literature was performed using the Medline/PubMed database with the terms: "pulmonary venous stenosis", "pulmonary venous infarction" and "haemoptysis". Further references from the case reports were considered. 58 case reports and case collections about patients with haemoptysis due to pulmonary venous stenosis were detected. This review gives an overview about the case reports and discusses the underlying pathophysiology and the pros and cons of different imaging techniques for the detection of pulmonary venous stenosis. Several conditions predispose to the obstruction of the mediastinal pulmonary veins. Clinical findings are unspecific and may be misleading. Pulmonary venous stenosis can be detected using several imaging techniques, yet three-dimensional magnetic resonance-angiography and three-dimensional contrast-enhanced computed tomography are the most appropriate. Pulmonary venous stenosis should be considered in patients with haemoptysis.

Insufficient coping behavior under chronic stress and vulnerability to psychiatric disorders.

BACKGROUND: Epidemiological data indicate that 75% of subjects with major psychiatric disorders have their onset of illness in the age range of 17-24 years. An estimated 35-50% of college and university students drop out prematurely due to insufficient coping skills under chronic stress, while 85% of students receiving a psychiatric diagnosis withdraw from college/university prior to the completion of their education. In this study, we aimed at developing standardized means of identifying students with insufficient coping skills under chronic stress and at risk for mental health problems. SAMPLING AND METHODS: A sample of 1,217 college students from 3 different sites in the USA and Switzerland completed 2 self-report questionnaires: the Coping Strategies Inventory (COPE) and the Zurich Health Questionnaire (ZHQ), which assesses 'regular exercises', 'consumption behavior', 'impaired physical health', 'psychosomatic disturbances' and 'impaired mental health'. The data were subjected to structure analyses by means of a neural network approach. We found 2 highly stable and reproducible COPE scales that explained the observed interindividual variation in coping behavior sufficiently well and in a socioculturally independent way. The scales reflected basic coping behavior in terms of 'activity-passivity' and 'defeatism-resilience', and in the sense of stable, socioculturally independent personality traits. RESULTS: Correlation analyses carried out for external validation revealed a close relationship between high scores on the defeatism scale and impaired physical and mental health. This underlined the role of insufficient coping behavior as a risk factor for physical and mental health problems. CONCLUSION: The combined COPE and ZHQ instruments appear to constitute powerful screening tools for insufficient coping skills under chronic stress and for risks of mental health problems.

Gender and the nocebo response following conditioning and expectancy.

OBJECTIVE: To investigate the role of Pavlovian conditioning and expectancy and of gender on the nocebo effects. METHODS: Conditioning experiment: Forty-eight healthy male and female volunteers were investigated for 3 days using a standard rotation procedure. Subjects in the experimental group received a salient oral stimulus prior to rotation; subjects in the control group received the stimulus 12 h after rotations on Days 1 and 2; on Day 3, all subjects received the stimulus prior to rotation. Expectancy experiment: Another 48 healthy subjects were rotated 5 x 1 min once only. All subjects received the same oral stimulus immediately prior to rotation; subjects in the experimental group were told that the symptoms might worsen with the stimulus; controls did not receive additional information. In both experiments, symptom rating (SR) and rotation tolerance (RT) were determined. RESULTS: Conditioning significantly reduced RT (P=.015) and increased SR (P=.024). For both RT and SR, a significant "day x group x gender" effect was found (P=.044; SR: P=.011) indicating that conditioning was more effective in women. Expectancies lowered RT (P=.085) without affecting SR. There was a significant "rotation x gender" interaction on RT (P=.005) indicating that the expectancy was more effective in men. CONCLUSION: Women responded stronger to conditioning while men responded to expectancies, but to a lesser degree. It needs to be determined whether this is restricted to nausea-specific conditions or can be generalized across clinical and experimental conditions.