Testosterone and acute stress are associated with fibrinogen and von Willebrand factor in African men: the SABPA study.

BACKGROUND Low testosterone, acute and chronic stress and hypercoagulation are all associated with hypertension and hypertension-related diseases. The interaction between these factors and future risk for coronary artery disease in Africans has not been fully elucidated. In this study, associations of testosterone, acute cardiovascular and coagulation stress responses with fibrinogen and von Willebrand factor in African and Caucasian men in a South African cohort were investigated. METHODS Cardiovascular variables were studied by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum-, salivary testosterone and citrate coagulation markers were obtained from venous blood samples. Acute mental stress responses were evoked with the Stroop test. RESULTS The African group demonstrated a higher cardiovascular risk compared to Caucasian men with elevated blood pressure, low-grade inflammation, chronic hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress responses were demonstrated in African males. In multiple regression analyses, higher circulating levels of fibrinogen and VWF in Africans were associated with a low T environment (R(2) 0.24-0.28; p≤0.01), but only circulating fibrinogen in Caucasians. Regarding endothelial function, a low testosterone environment and a profile of augmented α-adrenergic acute mental stress responses (diastolic BP, D-dimer and testosterone) were associated with circulating VWF levels in Africans (Adj R(2) 0.24; p<0.05). CONCLUSIONS An interdependence between acute mental stress, salivary testosterone, D-dimer and vascular responses existed in African males in their association with circulating VWF but no interdependence of the independent variables occurred with fibrinogen levels.

Myocardial Infarction - Stress PRevention INTervention (MI-SPRINT) to reduce the incidence of posttraumatic stress after acute myocardial infarction through trauma-focused psychological counseling: study protocol for a randomized controlled trial

BACKGROUND Posttraumatic Stress Disorder (PTSD) may occur in patients after exposure to a life-threatening illness. About one out of six patients develop clinically relevant levels of PTSD symptoms after acute myocardial infarction (MI). Symptoms of PTSD are associated with impaired quality of life and increase the risk of recurrent cardiovascular events. The main hypothesis of the MI-SPRINT study is that trauma-focused psychological counseling is more effective than non-trauma focused counseling in preventing posttraumatic stress after acute MI. METHODS/DESIGN The study is a single-center, randomized controlled psychological trial with two active intervention arms. The sample consists of 426 patients aged 18 years or older who are at 'high risk' to develop clinically relevant posttraumatic stress symptoms. 'High risk' patients are identified with three single-item questions with a numeric rating scale (0 to 10) asking about 'pain during MI', 'fear of dying until admission' and/or 'worrying and feeling helpless when being told about having MI'. Exclusion criteria are emergency heart surgery, severe comorbidities, current severe depression, disorientation, cognitive impairment and suicidal ideation. Patients will be randomly allocated to a single 45-minute counseling session targeting either specific MI-triggered traumatic reactions (that is, the verum intervention) or the general role of psychosocial stress in coronary heart disease (that is, the control intervention). The session will take place in the coronary care unit within 48 hours, by the bedside, after patients have reached stable circulatory conditions. Each patient will additionally receive an illustrated information booklet as study material. Sociodemographic factors, psychosocial and medical data, and cardiometabolic risk factors will be assessed during hospitalization. The primary outcome is the interviewer-rated posttraumatic stress level at three-month follow-up, which is hypothesized to be at least 20% lower in the verum group than in the control group using the t-test. Secondary outcomes are posttraumatic stress levels at 12-month follow-up, and psychosocial functioning and cardiometabolic risk factors at both follow-up assessments. DISCUSSION If the verum intervention proves to be effective, the study will be the first to show that a brief trauma-focused psychological intervention delivered within a somatic health care setting can reduce the incidence of posttraumatic stress in acute MI patients. TRIAL REGISTRATION ClinicalTrials.gov: NCT01781247.

Procoagulant reactivity to laboratory acute mental stress in Africans and Caucasians, and its relation to depressive symptoms: the SABPA study.

The risk of cardiovascular disease is dramatically increasing in Africans (black). The prothrombotic stress response contributes to atherothrombotic disease and is modulated by depressive symptoms. We examined coagulation reactivity to acute mental stress and its relation to psychological well-being in Africans relative to Caucasians (white). A total of 102 African and 165 Caucasian school teachers underwent the Stroop Color-Word Conflict test. Circulating levels of von Willebrand factor (VWF) antigen, fibrinogen, and D-dimer were measured before and after the Stroop. Cardiovascular reactivity measures were also obtained. All participants completed the Patient Health Questionnaire-9 and the General Health Questionnaire-28 for the assessment of depressive symptoms and total psychological distress, respectively. After controlling for covariates, resting levels of VWF, fibrinogen, and D-dimer were higher in Africans than in Caucasians (all p-values ≤0.006). Depressive symptoms and psychological distress were not significantly associated with resting coagulation measures. Stress reactivity in VWF (p<0.001) and fibrinogen (p=0.016), but not in D-dimer (p=0.27), were decreased in Africans relative to Caucasians with Africans showing greater reactivity of total peripheral resistance (p=0.017). Depressive symptoms, but not general psychological distress, were associated with greater VWF increase (p=0.029) and greater fibrinogen decrease (p=0.030) in Africans relative to Caucasians. In conclusion, Africans showed greater hypercoagulability at rest but diminished procoagulant reactivity to acute mental stress when compared with Caucasians. Ethnic differences in the vascular adrenergic stress response might partially explain this finding. Depressive symptoms were associated with exaggerated VWF reactivity in Africans relative to Caucasians. The clinical implications of these findings for Africans need further study.

Nutrient additions affecting matter turnover in forest and pasture ecosystems

Nutrient inputs into ecosystems of the tropical mountain rainforest region are projected to further increase in the next decades. To investigate whether important ecosystem services such as nutrient cycling and matter turnover in native forests and pasture ecosystems show different patterns of response, two nutrient addition experiments have been established: NUMEX in the forest and FERPAST at the pasture. Both ecosystems already responded 1.5 years after the start of nutrient application (N, P, NP, Ca). Interestingly, most nutrients remained in the respective systems. While the pasture grass was co-limited by N and P, most tree species responded to P addition. Soil microbial biomass in the forest litter layer increased after NP fertilization pointing to nutrient co-limitation. In pasture soils, microorganisms were neither limited by N nor P. The results support the hypothesis that multiple and temporally variable nutrient limitations can coexist in tropical ecosystems.

Systemtheorie als Strukturwissenschaft: Vermittlerin zwischen Praxis und Forschung

Im Wettstreit systemtheoretischer Ansätze für klinische und psychotherapeutische Arbeit, sei es in Praxis oder Forschung, wird oft der synergetische Ansatz als »naturwissenschaftlich« gekennzeichnet – nicht selten mit einem pejorativen Unterton, dass er damit für nicht-naturwissenschaftliche Fragen weniger gut geeignet sei. Die Autoren zeigen hingegen auf, dass synergetische Systemtheorie als Strukturwissenschaft zu verstehen ist: Sie kann zwar auf Gegenstände des naturwissenschaftlichen Bereiches angewendet werden, genauso gut aber auch auf Prozesse, bei denen es um Sinn, Bedeutung, Narration, Interaktion etc. geht. Dialogisch erarbeiten die Autoren dabei Aspekte, die ihnen an der synergetischen Systemtheorie besonders wichtig sind, und erörtern, welche zentralen Fragen damit beantwortet bzw. untersucht werden können. Insbesondere wird diskutiert, was eine »strukturwissenschaftliche« Perspektive eigentlich meint und warum ein solcher Ansatz sowohl für Fragen der Forschung als auch der Praxis besonders geeignet erscheint.

COCAINE DEPENDENCE: THE ROLE OF SEROTONIN GENES IN

Animal studies have shown that behavioral responses to cocaine-related cues are altered by serotonergic medications. The effects of pharmacological agents on serotonin receptors 2a (5-HT2A) and 2c (5-HT2C), have yielded results suggesting that selective 5-HT2A antagonists and 5-HT2C agonists promote the disruption of cocaine-associated memories. One measure of cocaine related cues in humans is attentional bias, in which cocaine dependent individuals show greater response latency for cocaine related words than neutral words. Data from our laboratory shows that cocaine dependent subjects have altered attentional bias compared to controls. The purpose of this thesis was to investigate the role of the serotonin system in attentional bias and impulsivity in cocaine dependent individuals. We focused on the serotonin transporter, serotonin receptors 2A and 2C and tryptophan hydroxylase 1 and 2 (TPH1 and TPH2). We predicted that attentional bias and impulsivity would be higher in cocaine dependent individuals who had lower serotonin function. In the current study, we found a significant association between TPH2 genotype and attentional bias for the second block of the cocaine Stroop task. There was also a significant association between average attentional bias and HTTLPR genotype in the cocaine dependent individuals. The HT2C receptor genotype and attentional bias in our study sample also showed a significant difference. We did not find a significant difference between the serotonin 2A receptor variants or the TPH1 variants and attentional bias in the cocaine dependent group. In conclusion, the current study suggests that serotonergic medications should be utilized as pharmacotherapeutic treatment for cocaine addiction. Our results indicate that TPH2, the serotonin transporter and 2C receptor should be targeted in such a way as to modulate both, leading to increased synaptic serotonin function.

Frameless linac-based (Novalis TX) stereotactic treatment for vestibular schwannoma that extend distally into the iac (Internal Acoustic Canal): an analysis of the dose to the cochlea

Objectives: We compare the dose parameters between 3 different radiosurgery delivery techniques which may have an impact on cochlea function. Methods: Five patients with unilateral vestibular schwannoma (VS) were selected for this study. Planning procedure was carried out using the BrainLAB® iPlan planning system v. 4.5. For each patient three different planning techniques were used: dynamic arc (DA) with 5 arcs per plan, hybrid arc (HA) with 5 arcs per plan and IMRT with 8 fields per plan. For each technique, two plans were generated with different methods: with the first method (PTV coverage) it was the goal to fully cover the PTV with at least 12 Gy (normalization: 12 Gy covered 99% of the PTV) and with the second method (cochlea sparing) it was the goal to spare the cochlea (normalization: 12 Gy covers 50% of the PTV/V4Gy of cochlea lower than 1%). Plan evaluation was done considering target volume and coverage (conformity and homogeneity) and OAR constraints (mean (Dmean) and maximum dose (Dmax) to cochlea, Dmax to brainstem and cochlea). The total number of monitor units (MU) was analyzed. Results: The median tumor volume was 0.95 cm³ (range, 0.86-3 cm³). The median PTV was 1.44 cm³ (range, 1-3.5 cm³). The median distance between the tumor and the cochlea's modiulus was 2.7 mm (range, 1.8-6.3 mm). For the PTV coverage method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.872) and in Dmean (p= 0.860). We found a significant correlation (p< 0.05) between the target volume and the cochlear Dmean for all plans with Pearson's coefficient correlation of 0.90, 0.92 and 0.94 for the DA, HA and IMRT techniques, respectively. For the cochlea sparing method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.310) and in Dmean (p= 0.275). However, in this group the V4Gy of the ipsilateral cochlea represents less than 1%. When using the HA or IMRT technique, the homogeneity and conformity in the PTV, but also the number of MUs were increased in comparison to the DA technique. Conclusion: VS tumors that extend distally into the IAC had an equivalent sparing of cochlea with DA approach compared with the HA and IMRT techniques. Disclosure: No significant relationships.

Horbat Kur — 2011 Preliminary Report

Published in English and Hebrew

Report on 2010-2013 Excavations at Horvat Kur, Galilee

Four seasons of excavations at Horvat Kur in the Galilee (250570/754485) have exposed the remains of a broadhouse synagogue from the Byzantine period. The building was entered through a portico on the west or a doorway on the south. The fill beneath the portico included the discarded remains of a once colored mosaic as well as more than 1000 coins. A low bench of basalt stones (some of which were plastered) runs along the interior walls, interrupted only by a stone bemah in the center of the southern wall. The synagogue is thus oriented toward Jerusalem. Near the bemah, an ornamented limestone seat was found in situ atop the bench. The building underwent several changes and repairs in the course of its lifespan. On either side of the bemah, north-south rows of columns rested on stylobate. A basalt stone table was found in re-use in the eastern stylobate. Nicknamed “the Horvat Kur stone,” this monolith features geometric figures on three sides and figurative representations on one side. Its original function is as yet subject of research. A narrow test-trench into the sediment of a cistern located outside the northern wall of the synagogue has produced nearly thirty intact vessels of the early Byzantine period, mostly cooking pots and water jars. In addition a dense sequence of pollen samples has been taken. Preliminary interpretation of these finds indicates that the Horvat Kur synagogue illustrates Byzantine synagogue construction, decoration, and use in the setting of a Galilean village of modest economic circumstances.

Aptitude–Treatment interaction effects in psychooncological interventions

Objective: To examine aptitude–treatment interaction (ATI) effects in cancer patients receiving psychoonco- logical interventions (POIs). Method: N=36 cancer patients were treated with POI. Hierarchical linear regression was used to test two interaction effects between patient baseline characteristics (aptitudes) and process analyses of therapy sessions (treatment) on change in mental health during POI. Results: Patients with high emotional distress did best when their therapy reduced arousal, and patients with lower emotional distress benefited most if therapists emphasized arousal induction. The interaction between the coping style of the patient (internalizing vs. externalizing) and the focus of the treatment (emotion vs. behavior) did not predict POI outcomes. Conclusions: The ATI effect of patient's distress and therapist's arousal induction/reduction may help therapists to make differential treatment decisions in POI. Tailoring treatments to cancer patients based on their personal characteristics may enhance the effectiveness of POI.

Low-threshold monopolar motor mapping for resection of lesions in motor eloquent areas in children and adolescents

Object Resection of lesions close to the primary motor cortex (M1) and the corticospinal tract (CST) is generally regarded as high-risk surgery due to reported rates of postoperative severe deficits of up to 50%. The authors' objective was to determine the feasibility and safety of low-threshold motor mapping and its efficacy for increasing the extent of lesion resection in the proximity of M1 and the CST in children and adolescents. Methods The authors analyzed 8 consecutive pediatric patients in whom they performed 9 resections for lesions within or close (≤ 10 mm) to M1 and/or the CST. Monopolar high-frequency motor mapping with train-of-five stimuli (pulse duration 500 μsec, interstimulus interval 4.0 msec, frequency 250 Hz) was used. The motor threshold was defined as the minimal stimulation intensity that elicited motor evoked potentials (MEPs) from target muscles (amplitude > 30 μV). Resection was performed toward M1 and the CST at sites negative to 1- to 3-mA high-frequency train-of-five stimulation. Results The M1 was identified through high-frequency train-of-five via application of varying low intensities. The lowest motor thresholds after final resection ranged from 1 to 9 mA in 8 cases and up to 18 mA in 1 case, indicating proximity to motor neurons. Intraoperative electroencephalography documented an absence of seizures during all surgeries. Two transient neurological deficits were observed, but there were no permanent deficits. Postoperative imaging revealed complete resection in 8 patients and a very small remnant (< 0.175 cm(3)) in 1 patient. Conclusions High-frequency train-of-five with a minimal threshold of 1-3 mA is a feasible and safe procedure for resections in the proximity of the CST. Thus, low-threshold motor mapping might help to expand the area for safe resection in pediatric patients with lesions located within the precentral gyrus and close to the CST, and may be regarded as a functional navigational tool. The additional use of continuous MEP monitoring serves as a safety feedback for the functional integrity of the CST, especially because the true excitability threshold in children is unknown.

Combination of Psychological Intervention and Phosphodiesterase-5 Inhibitors for Erectile Dysfunction: A Narrative Review and Meta-Analysis

INTRODUCTION Erectile dysfunction (ED) is an increasing health problem that demands effective treatment. There is evidence that phosphodiesterase-5 inhibitors (PDE5-Is) and psychological intervention (PI) are effective treatment options; however, little is known about their comparative efficacy and the efficacy of combined treatments. AIM The aim of this systematic review and meta-analysis is to evaluate the comparative efficacy of PI, PDE5-Is, and their combination in the treatment of ED. MAIN OUTCOME MEASURES Primary outcome was ED symptoms, and secondary outcome was sexual satisfaction of the patient. METHODS A systematic literature search was conducted in order to identify relevant articles published between 1998 and 2012. We included randomized controlled trials and controlled trials comparing PI with PDE5-I treatment or one of them against a combination of both. RESULTS Eight studies with a total number of 562 patients were included in the meta-analysis. The results of the included studies are inconclusive, though they show a trend towards a larger effect of combined treatment compared with PI or PDE5-I treatment alone. The meta-analysis found that, overall, combined treatment was more efficacious for ED symptoms than PDE5-I treatment or PI alone. Combined treatment was more efficacious than PDE5-I use alone on sexual satisfaction. No differences were found between PDE5-Is and PI as stand-alone treatments. None of the moderators (treatment duration, methodological quality, or researcher allegiance) altered the effects. CONCLUSIONS The combination of PI and PDE5-Is is a promising strategy for a favorable outcome in ED and can be considered as a first-choice option for ED patients. Stronger RCTs are required to confirm this initial finding. Schmidt HM, Munder T, Gerger H, Frühauf S, and Barth J. Combination of psychological intervention and phosphodiesterase-5 inhibitors for erectile dysfunction: A narrative review and meta-analysis. J Sex Med **;**:**-**.