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The Simplified Acute Physiology 3 outcome prediction model has a narrow time window for recording physiologic measurements. Our objective was to examine the prevalence and impact of missing physiologic data on the Simplified Acute Physiology 3 model's performance.Retrospective analysis of prospectively collected data.Sixty-three ICUs in the Swedish Intensive Care Registry.Patients admitted during 2011-2014 (n = 107,310).None.Model performance was analyzed using the area under the receiver operating curve, scaled Brier's score, and standardized mortality rate. We used a recalibrated Simplified Acute Physiology 3 model and examined model performance in the original dataset and in a dataset of complete records where missing data were generated (simulated dataset). One or more data were missing in 40.9% of the admissions, more common in survivors and low-risk admissions than in nonsurvivors and high-risk admissions. Discrimination did not decrease with one to two missing variables, but accuracy was highest with no missing data. Calibration was best in the original dataset with a mix of full records and records with some missing values (area under the receiver operating curve was 0.85, scaled Brier 27%, and standardized mortality rate 0.99). With zero, one, and two data missing, the scaled Brier was 31%, 26%, and 21%; area under the receiver operating curve was 0.84, 0.87, and 0.89; and standardized mortality rate was 0.92, 1.05 and 1.10, respectively. Datasets where the missing data were simulated for oxygenation or oxygenation and hydrogen ion concentration together performed worse than datasets with these data originally missing.There is a coupling between missing physiologic data, admission type, low risk, and survival. Increased loss of physiologic data reduced model performance and will deflate mortality risk, resulting in falsely high standardized mortality rates.

The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain’s intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala–parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.

Injury is an important cause of death in all age groups worldwide, and contributes to many losses of human and economic resources. Currently, we know a few data about mortality from injury, particularly among the working population. The aim of the present study was to examine death from injury over a period of 14 years (1999–2012) using the Swedish Cause of Death Registry (CDR) and the National Patient Registry, which have complete national coverage. CDR was used to identify injury-related deaths among adults (18 years or over) during the years 1999–2012. ICD-10 diagnoses from V01 to X39 were included. The significance of changes over time was analyzed by linear regression. The incidence of prehospital death decreased significantly (coefficient −0.22, r 2 = 0.30; p = 0.041) during the study period, while that of deaths in hospital increased significantly (coefficient 0.20, r 2 = 0.75; p

Background: Juvenile idiopathic arthritis (JIA) is considered to be an autoimmune disease, but the etiology is unknown. We decided to study the influence of early nutrition on later development of JIA. Methods: All parents with children born between October 1, 1997 and October 1, 1999 in Southeast Sweden were asked to participate in the ABIS prospective cohort study (All Babies in Southeast Sweden), At 1 year, questionnaires with information on breastfeeding and introduction of foods were completed by 10,565 families. We identified 32 children with JIA and 111 children with non-chronic arthritis with completed questionnaires after delivery and after 1 year. A multivariable logistic regression model, adjusted for relevant factors, was performed to calculate the association between JIA and feeding during the first year of life. Results: An increased risk for JIA was found in children who had breast fed for less than 4 months, as opposed to those who were continued on breast milk beyond 4 months of age (aOR 3.5, 95% CI 1.4-8,5; p = 0.006). A short duration of exclusive as well as total breastfeeding was associated with an increased risk of JIA (aOR 1.3, 95% CI 1.1-1.6; p = 0.008 and aOR 1.2, 95% CI 1.1-1.3; p amp;lt; 0.001). All associations between breastfeeding and JIA persisted after adjustment. There was no relationship between early nutrition and non-chronic arthritis. Conclusions: Our results indicate that there are different disease mechanisms for different types of arthritis in childhood. Longer duration of breastfeeding (both total and exclusive) may protect against development of JIA. Mothers should be encouraged to breast-feed their babies exclusively, if at all possible, for 4 months and continue partial breastfeeding for an extended time when foreign proteins are introduced. Funding Agencies|Research Unit of Kalmar County Council; Swedish Rheumatism Association; Jerring Foundation; Swedish Child Diabetes Foundation (Barndiabetesfonden); Juvenile Diabetes Research Foundation; Medical Research Council of Southeast Sweden (FORSS)

Little is known about human postprandial increase of energy expenditure and satiety-associated hormones in relation to both meal frequency and macronutrient composition.Randomized cross-over study with four conditions for each participant.Seven men and seven women (mean age 23±1.5years) were randomly assigned to the order of intake of a 750kcal drink with the same protein content while having either 20 energy-percent (E%) or 55 E% from carbohydrates and the remaining energy from fat. Participants were also randomized to consume the drinks as one large beverage or as five 150kcal portions every 30min, starting in the fasting state in the morning. Energy expenditure (EE) was determined every 30min by indirect calorimetry. Hormonal responses and suppression of hunger (by visual-analogue scales) were also studied. A p0.013 was considered statistically significant following Bonferroni-correction.The area under the curve (AUC) for EE was higher during the 2.5h after the high-carbohydrate drinks (p=0.005 by Wilcoxon) and also after ingesting one drink compared with five (p=0.004). AUC for serum active GLP-1 was higher after single drinks compared with five beverages (p=0.002). Although GLP-1 levels remained particularly high at the end of the test during the low-carbohydrate meals, the AUC did not differ compared with the high-carbohydrate occasions (low-carbohydrate: 58.9±18pg/ml/h, high-carbohydrate: 45.2±16pg/ml/h, p=0.028). Hunger sensations were suppressed more after single beverages compared with five small drinks (p=0.009).We found higher EE during 2.5h following one large drink compared with five smaller beverages. Since hunger was also suppressed more efficiently, and serum GLP-1 levels were higher after one compared with five smaller drinks, our findings do not support nibbling to avoid hunger or to keep up EE from morning to noon.

Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10min than the 6h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10min than the 6h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance.

Total duration of stay adjusted for percentage of the total body surface area burned (TBSA%) is a commonly used outcome measure in burn care. However, it has been criticised as it is affected by many factors, some of which are not strictly part of burn care. A division into operative stay and postoperative stay may improve this measure. The aim was to evaluate if operative stay can serve as a more standardised measure by: comparing the variation in operative stay/TBSA% with the variation in total stay/TBSA%, and to study different factors associated with operative stay and postoperative stay. Patients and methods Surgically managed burn patients admitted between 2010–14 were included. Operative stay was defined as the time from admission until the last operation, postoperative stay as the time from the last operation until discharge. The difference in variation was analysed with F-test. A retrospective review of medical records was done to explore reasons for extended postoperative stay. Multivariable regression was used to assess factors associated with operative stay and postoperative stay. Results Operative stay/TBSA% showed less variation than total duration/TBSA% (F test = 2.38, p

Purpose: To assess the independent associations between ability to cope and hopelessness with measures of health-related quality of life (HRQoL) and their effects on mortality up to 3 years after discharge in patients who have been treated in an intensive care unit (ICU). Methods: A prospective, cross-sectional multicenter study of 980 patients. Ability to cope, hopelessness, and HRQoL were evaluated using validated scales. Questionnaires were sent to patients 6, 12, 24, and 36 months after discharge from ICU. Results: After adjustment, low scores for ability to cope and high scores for hopelessness were both related to poorer HRQoL for all subscales (except for coping with bodily pain). Effects were in the same range as coexisting disease for physical subscales, and stronger for social and mental subscales. High scores for hopelessness also predicted mortality up to 3 years after discharge from ICU (p amp;lt; 0.001). Conclusions: The psychological factors ability to cope and hopelessness both strongly affected HRQoL after ICU care, and this effect was stronger than the effects of coexisting disease. Hopelessness also predicted mortality after critical illness. Awareness of the psychological state of patients after a stay in ICU is important to identify which of them are at risk. (C) 2017 Elsevier Inc. All rights reserved.

Face perception depends on activation of a core face processing network including the fusiform face area, the occipital face area and the superior temporal sulcus (STS). The medial temporal lobe (MTL) is also involved in decoding facial expression and damage to the anterior MTL, including the amygdala, generally interferes with emotion recognition. The impairment in emotion recognition following anterior MTL injury can be a direct result from injured MTL circuitry, as well as an indirect result from decreased MTL modulation of areas in the core face network. To test whether the MTL modulates activity in the core face network, we used functional magnetic resonance imaging to investigate activation in the core face processing network in patients with right or left anterior temporal lobe resections (ATR) due to intractable epilepsy. We found reductions of face-related activation in the right STS after both right and left ATR together with impaired recognition of facial expressions. Reduced activity in the fusiform and the occipital face areas was also observed in patients after right ATR suggesting widespread effects on activity in the core face network in this group. The reduction in face-related STS activity after both right and left ATR suggests that MTL modulation of the STS may facilitate recognition of facial expression.

The p53 pathway regulates stress response, and variations in p53, MDM2, and MDM4 may predispose an individual to tumor development. The aim of this study was to study the impact of genetic variation on sporadic and hereditary melanoma. We have analyzed a combination of three functionally relevant variants of the p53 pathway in 258 individuals with sporadic malignant melanomas, 50 with hereditary malignant melanomas, and 799 healthy controls. Genotyping was performed by PCR-restriction fragment length polymorphism, pyrosequencing, and allelic discrimination. We found an increased risk for hereditary melanoma in MDM2 GG homozygotes, which was more pronounced among women (P=0.035). In the event of pairwise combinations of the single nucleotide polymorphisms, a risk elevation was shown for MDM2 GG homozygotes/p53 wild-type Arg in hereditary melanoma (P=0.01). Individuals with sporadic melanomas of the superficial spreading type, including melanoma in situ, showed a slightly higher frequency of the MDM2 GG genotype compared with those with nodular melanomas (P=0.04). The dysplastic nevus phenotype, present in the majority of our hereditary melanoma cases and also in some sporadic cases, further enhanced the effect of the MDM2 GG genotype on melanoma risk (P=0.005). In conclusion, the results show an association between MDM2 SNP309 and an increased risk for hereditary melanoma, especially among women. Analysis of sporadic melanoma also shows an association between MDM2 and the superficial spreading melanoma subtype, as well as an association with the presence of dysplastic nevi in sporadic melanoma.

UNLABELLED: In patients with social anxiety disorder (SAD) it has been reported that selective serotonin reuptake inhibitors (SSRIs) and placebo induce anxiolytic effects by attenuating neural activity in overlapping amygdala subregions, i.e. left basolateral and right ventrolateral amygdala. However, it is not known whether these treatments inhibit amygdala subregions via similar or distinct brain pathways. As anxiolytic treatments may alter amygdala-frontal couplings we investigated differences and similarities in amygdala-frontal functional co-activation patterns between responders and nonresponders to SSRIs and placebo in patients with SAD. Positron emission tomography (PET) with oxygen-15-labeled water was used to measure anxiety-related regional cerebral blood flow in 72 patients with SAD before and after 6-8 wk of treatment under double-blind conditions. Functional couplings were evaluated with a seed region approach using voxel values from the left basolateral and right ventrolateral amygdala. Responders and nonresponders to SSRIs and placebo showed different treatment-induced co-activations between the left amygdala and the dorsolateral prefrontal cortex (dlPFC) as well as the rostral anterior cingulate cortex (ACC). Conjunction analysis suggested shared anxiolysis-dependent inverse co-activations in SSRI and placebo responders between the left amygdala-dlPFC and left amygdala-rostral ACC, and a shared positive co-activation between left amygdala-dorsal ACC. We demonstrate that amygdala-frontal co-activation patterns differentiate effective from ineffective anxiolytic treatments and that SSRI and placebo responders share overlapping neuromodulatory paths that may underlie improved emotion regulation and reduced expression of anxiety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00343707.

Anxiety reduction following repeated exposure to stressful experiences is generally held to depend on neural processes involved in extinction of conditioned fear. We predicted that repeated exposure to stressful experiences would change activity throughout the circuitry serving extinction, including ventromedial prefrontal cortex (vmPFC), the hippocampus and the amygdala. To test this prediction, 36 participants diagnosed with SAD performed two successive speeches in front of an observing audience while regional cerebral blood flow (rCBF) was recorded using positron emission tomography. To control for non-anxiolytic effects of repeated exposure, rCBF was also measured during repeated presentations of neutral and angry facial expressions. Results showed that anxiety ratings and heart rate decreased from the first to the second speech, indicating an anxiolytic effect of repeated exposure. Exposure attenuated rCBF in the amygdala whereas no change in rCBF was observed in the vmPFC or hippocampus. The rCBF-reductions in the amygdala were greater following repetition of the speech task than repetition of face exposure indicating that they were specific to anxiety attenuation and not due to a reduced novelty. Our findings suggest that amygdala-related attenuation processes are key to understanding the working mechanisms of exposure therapy.

Objectives: we assessed the incidence, risk factors and outcome of BSI over a 14-year period (2000-2013) in a Swedish county. Methods: retrospective cohort study on culture confirmed BSI among patients in the county of Östergötland, Sweden, with approximately 440,000 inhabitants. A BSI was defined as either community-onset BSI (CO-BSI) or hospital-acquired BSI (HA-BSI). Results: of a total of 11,480 BSIs, 67% were CO-BSI and 33% HA-BSI. The incidence of BSI increased by 64% from 945 to 1,546 per 100,000 hospital admissions per year during the study period. The most prominent increase, 83% was observed within the CO-BSI cohort whilst HA-BSI increased by 32%. Prescriptions of antibiotics in outpatient care decreased with 24% from 422 to 322 prescriptions dispensed/1,000 inhabitants/year, whereas antibiotics prescribed in hospital increased by 67% (from 424 to 709 DDD per 1,000 days of care). The overall 30-day mortality for HA-BSIs was 17.2%, compared to 10.6% for CO-BSIs, with an average yearly increase per 100,000 hospital admissions of 2 and 5% respectively. The proportion of patients with one or more comorbidities, increased from 20.8 to 55.3%. In multivariate analyses, risk factors for mortality within 30 days were: HA-BSI (2.22); two or more comorbidities (1.89); single comorbidity (1.56); CO-BSI (1.21); male (1.05); and high age (1.04). Conclusion: this survey revealed an alarming increase in the incidence of BSI over the 14-year study period. Interventions to decrease BSI in general should be considered together with robust antibiotic stewardship programmes to avoid both over- and underuse of antibiotics. Funding agencies: Ostergotland County Council (Hakan Hanberger ALF)

Summary Objective Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4–10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing. Methods Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale. Results During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala. Conclusion COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. When we began this project our knowledge about the outcome of COPD patients admitted to the ICU in Sweden was scarce.Aims: To investigate the characteristics, survival and health-related quality of life (HRQL) of COPD patients admitted to Swedish ICUs. To investigate how ICU personnel decide whether to use invasive or non-invasive ventilatory treatment (NIV) of the newly admitted COPD patient in need of ventilatory support. To investigate outcome according to mode of ventilation.Material and methods: Detailed data, including HRQL during recovery, from COPD patients admitted to ICUs that participated in the Swedish intensive care registry were analysed. A questionnaire was distributed to personnel in 6 of the participating ICUs in order to define factors deemed important in making the choice between invasive and non-invasive ventilation immediately after admission. The answers were analysed.Results: The proportion of COPD patients admitted to Swedish ICUs in need of ventilatory support is 1.3-1.6 % of all admissions. The patients are around 70 years-old and are severely ill on admission, with high respiratory rates and most have life-threatening disturbances in their acid-base balance and blood gases. There are more women than men. The short- and long-term mortality is high despite intensive care treatment. The majority of patients are treated with NIV. The length of stay on the ICU is shorter when NIV is used. The choice between NIV and invasive ventilation in these patients may be irrational. It is guided by current guidelines, but other non-patient-related factors seem to influence this decision. NIV seems to be preferable to invasive ventilation at admission, not only according to short-term benefits but also to long-term survival. Failure of NIV followed by invasive ventilation does not have a poorer prognosis than directly employing invasive ventilation. The health-related quality of life of COPD patients after treatment on Swedish ICUs is lower than in the general population. However it does not decline between 6 and 24 months after ICU discharge. After 24 months the HRQL is quite similar to that of COPD patients not treated on the ICU.Conclusions: COPD patients in need of ventilatory support admitted to Swedish ICUs are severely ill on admission, and their short- and long-term mortality is high despite ICU care and ventilatory treatment. Non-invasive ventilation should be the first line treatment on admission. NIV has short- and long-term benefits compared to invasive ventilation, without increasing mortality risk in case of failure. After discharge from the ICU and recovery, the HRQL of COPD patients is lower than in the general population, but comparable to COPD patients not treated on the ICU.

OBJECTIVES To examine ICU performance based on the Simplified Acute Physiology Score 3 using 30-day, 90-day, or 180-day mortality as outcome measures and compare results with 30-day mortality as reference. DESIGN Retrospective cohort study of ICU admissions from 2010 to 2014. SETTING Sixty-three Swedish ICUs that submitted data to the Swedish Intensive Care Registry. PATIENTS The development cohort was first admissions to ICU during 2011-2012 (n = 53,546), and the validation cohort was first admissions to ICU during 2013-2014 (n = 57,729). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Logistic regression was used to develop predictive models based on a first level recalibration of the original Simplified Acute Physiology Score 3 model but with 30-day, 90-day, or 180-day mortality as measures of outcome. Discrimination and calibration were excellent for the development dataset. Validation in the more recent 2013-2014 database showed good discrimination (C-statistic: 0.85, 0.84, and 0.83 for the 30-, 90-, and 180-d models, respectively), and good calibration (standardized mortality ratio: 0.99, 0.99, and 1.00; Hosmer-Lemeshow goodness of fit H-statistic: 66.4, 63.7, and 81.4 for the 30-, 90-, and 180-d models, respectively). There were modest changes in an ICU's standardized mortality ratio grouping ( 1.00) when follow-up was extended from 30 to 90 days and 180 days, respectively; about 11-13% of all ICUs. CONCLUSIONS The recalibrated Simplified Acute Physiology Score 3 hospital outcome prediction model performed well on long-term outcomes. Evaluation of ICU performance using standardized mortality ratio was only modestly sensitive to the follow-up time. Our results suggest that 30-day mortality may be a good benchmark of ICU performance. However, the duration of follow-up must balance between what is most relevant for patients, most affected by ICU care, least affected by administrative policies and practically feasible for caregivers.

Memories are not set forever, but can be altered following reactivation, which renders memories malleable, before they are again stabilized through reconsolidation. Fear memories can be attenuated by using extinction during the malleable period. The present study adopts a novel form of extinction, using verbal instructions, in order to examine whether fear memory reconsolidation can be affected by an imaginal exposure. The extinction using verbal instructions, called imaginal extinction, consists of a recorded voice encouraging participants to imagine the scene in which fear was acquired, and to envision the stimuli before their inner eye. The voice signals stimuli appearance, and identical to standard (in vivo) extinction, participants discover that the conditioned stimulus no longer is followed by unconditioned stimulus (UCS). In this way, imaginal extinction translates clinically used imaginal exposure into the standard experimental fear conditioning paradigm. Fear was acquired by pairing pictorial stimuli with an electric shock UCS. Then, both standard and imaginal extinction were given following fear memory reactivation, either after 10 min, within the reconsolidation interval, or after 6 h, outside of the reconsolidation interval. In vivo and imaginal extinction produced comparable reductions in conditioned responses during extinction and importantly, both disrupted reconsolidation of conditioned fear and abolished stimulus discrimination between reinforced and non-reinforced cues. Thus, disrupted reconsolidation of fear conditioning can be achieved without in vivo stimulus presentation, through purely cognitive means, suggesting possible therapeutic applications.

It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[β -11C]tryptophan, [11C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [11C]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.

Background: Pre-existing disease is the most important factor in the prediction of health-related quality of life (HRQoL) after intensive care. We hypothesised that the “inpatient care trajectories ...

Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.

The substance P/neurokinin 1 (SP/NK1) system has been implicated in the processing of negative affect. Its role seems complex and findings from animal studies have not been easily translated to hum ...

Colorectal tumors are continuously exposed to an inflammatory environment, which together with mitogenic signals sustain several cancer hallmarks. Nuclear factor-kappa B (NFκB) is a major regulator of inflammation and variation in NFκB-associated genes could potentially be used as biomarkers to identify patients with increased risk of colorectal cancer (CRC) development, and/or a rapidly progressing disease. In this study, 348 CRC cases and 806 randomly selected healthy individuals from southeastern Sweden were examined with regard to seven polymorphisms in NFκB pathway-associated genes. Log-rank-tests and Cox proportional hazard regression analysis examined the association between the polymorphisms and CRC-specific survival, whereas chi-square tests and logistic regression analysis were used to test for associations between the polymorphisms and CRC susceptibility. Gene expression and loss of heterozygosity analyses of TNFAIP3 were carried out in a subset of tumors to assess its role as a tumor suppressor in CRC. Heterozygous and polymorphic TNFAIP3 (rs6920220), heterozygous NLRP3 (Q705K) and polymorphic NFκB -94 ATTG ins/del genotypes were found to be associated with poorer survival in patients diagnosed with invasive CRC (aHR = 5.2, 95% CI: 2.5-10.9, P < 0.001). TNFAIP3 mRNA levels were significantly decreased in tumors compared with adjacent non-neoplastic mucosa (P < 0.0001) and loss of heterozygosity of 6q23.3 (TNFAIP3) was detected in 17% of cases, whereas only 2.5% of the investigated specimens displayed TNFAIP3 gene mutations. We propose that TNFAIP3 (rs6920220), NLRP3 (Q705K) and NFκB -94 ATTG ins/del polymorphisms are associated with poor survival in patients with advanced CRC and may be used as prognostic markers. Experimental results indicate that TNFAIP3 may act as a tumor suppressor in CRC. funding agencies|Swedish Research Council|2010-55X-20451-04-3

Genetic variants of NLRP3 and NLRP1 are known to modulate levels of pro-inflammatory cytokine interleukin (IL)-1 beta. The purpose of this study was to investigate the association of NLRP3/NLRP1 polymorphisms with susceptibility and clinical features of malignant melanoma in a Swedish casecontrol study. Common variants in NLRP3/NLRP1 were investigated in sporadic malignant melanoma patients and healthy controls followed by analysis using logistic regression. NLRP3 variant (rs35829419) was significantly more common in male patients than in controls (OR, 2.22; CI, 1.273.86). Upon stratification, significant association with nodular melanoma was observed (OR, 2.89; CI, 1.336.30), which intensified in male patients (OR 4.03, CI 1.4011.59). The NLRP1 variant (rs12150220) was significantly more common in fair-skinned female patients (OR, 1.85; CI, 1.043.33) and showed strong associations with nodular melanoma (OR, 6.03; CI, 1.3325). Our data suggest that NLRP3/NLRP1 polymorphisms are associated with melanoma susceptibility; these findings warrant validation in other independent populations.

Objective To evaluate the effect of stress coping capacity in combination with mode of anaesthesia on postoperative recovery in fast-track abdominal hysterectomy. Design Prospective longitudinal st ...

a b s t r a c t The intimate connection between the brain and the heart was enunciated by Claude Bernard over 150 years ago. In our neurovisceral integration model we have tried to build on this pioneering work. In the present paper we further elaborate our model and update it with recent results. Specifically, we per- formed a meta-analysis of recent neuroimaging studies on the relationship between heart rate variability and regional cerebral blood flow. We identified a number of regions, including the amygdala and ventro- medial prefrontal cortex, in which significant associations across studies were found. We further propose that the default response to uncertainty is the threat response and may be related to the well known neg- ativity bias. Heart rate variability may provide an index of how strongly 'top-down' appraisals, mediated by cortical-subcortical pathways, shape brainstem activity and autonomic responses in the body. If the default response to uncertainty is the threat response, as we propose here, contextual information repre- sented in 'appraisal' systems may be necessary to overcome this bias during daily life. Thus, HRV may serve as a proxy for 'vertical integration' of the brain mechanisms that guide flexible control over behavior with peripheral physiology, and as such provides an important window into understanding stress and health.

Sample Size Matters : A Voxel-Based Morphometry Multi-Center Mega-Analysis of Gray Matter Volume in Social Anxiety Disorder

Background. Symptoms of late-onset hypogonadism (LOH) and concentrations of testosterone (T) and bioavailable testosterone (BT) were studied in relation to the data from the same men 5 years earlier. less thanbrgreater than less thanbrgreater thanMethods. In 2008, 282 men, aged 60-82 years, answered a questionnaire regarding demographic data, medical history, different symptoms of LOH and the 10 questions from the Androgen Decline in Aging Males (ADAM)-questionnaire. Blood samples were analysed for concentrations of T and calculations were made for BT. less thanbrgreater than less thanbrgreater thanResults. A total of 87.2% of the questionnaires were returned and analysed, and 75.2% of the responders gave blood samples. The oldest third of the men were most affected by LOH symptoms (p andlt; 0.05). Both T and BT concentrations decreased during the 5 years (p andlt; 0.05) but only the symptom less strong erections changed significantly (p andlt; 0.05). Men reporting one of the four specific symptoms from the ADAM-questionnaire for the first time in 2008 had a higher loss of T and BT than men who had unchanged or fewer symptoms than that reported in 2003. less thanbrgreater than less thanbrgreater thanConclusions. The magnitude of the decrease in concentrations is a better predictor of LOH than are the actual concentrations of T and BT. A combination of symptoms predicts LOH better than any single symptom. Funding Agencies|Swedish Medical Research Council|K2000-72X-12651-04B

Phobic fear is accompanied by intense bodily responses modulated by the amygdala. An amygdala moderated psychophysiological measure related to arousal is electrodermal activity. We evaluated the contributions of electrodermal activity to amygdala-parahippocampal regional cerebral blood flow (rCBF) during phobic memory encoding in subjects with spider or snake phobia. Recognition memory was increased for phobia-related slides and covaried with rCBF in the amygdala and the parahippocampal gyrus. The covariation between parahippocampal rCBF and recognition was related to electrodermal activity suggesting that parahippocampal memory processes were associated with sympathetic activity. Electrodermal activity further mediated the amygdala effect on parahippocampal activity. Memory encoding during phobic fear therefore seems contingent on amygdala's influence on arousal and parahippocampal activity.

Evaluate effects of electro-acupuncture (EA) and hormone therapy (HT) on health-related quality-of-life (HRQoL) and sleep in breast cancer survivors with vasomotor symptoms.Forty-five women, randomized to EA (n = 27) for 12 weeks or HT (n = 18) for 24 months, were followed for up to 2 years. Distress caused by, and numbers of, hot flushes, hours slept and times woken up/night, Psychological and General Well-being Index (PGWB) and Women's Health Questionnaire (WHQ) were registered before and during treatment and at 6, 9, 12, 18 and 24 months after start of treatment.After 12 weeks of EA (n = 19), WHQ improved from 0.32 (IQR 0.23-0.53) at baseline to 0.24 (IQR 0.12-0.39; p 0.001) and PGWB from 78 (IQR 53-89) to 79 (IQR 68-93; p = 0.002). All sleep parameters improved and Hot Flush Score (HFS) decreased by 80%. At 12 months, WHQ, PGWB and all sleep parameters remained significantly improved (n = 14) and HFS decreased by 65%. After 12 weeks of HT (n = 18), WHQ improved from 0.29 (IQR 0.15-0.44) at baseline to 0.15 (IQR 0.05-0.22; p = 0.001), PGWB from 75 (IQR 59-88) to 90 (62-97; p = 0.102) and three of five sleep parameters improved.Both EA and HT increased HRQoL and sleep, probably through decreasing numbers of and distress by hot flushes. Although flushes decreased less in the EA group than in the HT group, HRQoL improved at least to the same extent maybe due to other effects of EA, not induced by HT, e.g. on anxiety, vitality and sleep, supported by subscale analyses. EA should be further evaluated as treatment for women with breast cancer and climacteric complaints, since HT no longer can be recommended for these women.

To examine to what extent availability of social integration affects health-related quality of life (HRQoL) in former intensive care unit (ICU) patients and how it relates to corresponding findings in a general reference group. Controlled, multicenter, prospective, explorative study. HRQoL data (SF-36) were collected from three combined medical and surgical ICUs in the south-east of Sweden. Social integration was assessed by the Availability of Social Integration (AVSI) instrument (seven questions related to the social interaction of the patient). As reference group, a random sample (n = 6,093) of people from the uptake area of the hospitals was used. Social integration (AVSI), HRQoL (SF-36), and comorbidity were examined also in the reference group. None. The level of social integration significantly affected HRQoL for the former ICU patients, whereas no such effect was seen for the general reference group. For the ICU patients, social integration affected HRQoL to a larger extent than age, sex, and the ICU-related factors examined, but to a lower extent than the pre-existing diseases. For a comprehensive assessment of HRQoL in former ICU patients, it is mandatory to include the effect of social integration. The original publication is available at www.springerlink.com: Lotti Orvelius, Carl Bäckman, Mats Fredrikson, Eva Simonsson, Peter Nordlund, Anders Samuelsson and Folke Sjöberg, Social integration: an important factor for health-related quality of life after critical illness, 2011, INTENSIVE CARE MEDICINE, (37), 5, 831-838. http://dx.doi.org/10.1007/s00134-011-2137-0 Copyright: Springer Science Business Media http://www.springerlink.com/

Results of epidemiological studies on terrestrial gamma radiation (TGR) and related malignancies have not been consistent. This study is a thorough examination of this relationship. Records on all individuals living in two Swedish counties in 1973, along with their annual dwelling coordinates during the 28-year follow-up period, were retrieved from the National Archives and Statistics Sweden. We used Geographical Information System (GIS) to match the individuals' dwelling coordinates annually to the TGR given in 200×200 m grids produced by the Geological Survey of Sweden. Cases of malignancies and deaths were retrieved from the Swedish Cancer Register. During the follow-up period 61,503 incident cases were included in the analyses and in total 11 million person-years were recorded. Cox regression was used both in a linear continuous model and analyses of six exposure categories. Adjustments were made for sex, age, and population density. The hazard ratio (HR) per 100 nanoGray/hour (nGy/h) was significantly increased for total malignancies and for several sites; however, contrary to expectations, an obvious and anticipated linear exposure-response relationship could not be identified. With the lowest exposure category (0-60 nGy/h) as reference, a statistically significantly increased HR for total malignancies was seen in all exposure categories, except in the highest category 96-366 nGy/h. For breast cancer, thyroid cancer and leukaemia an obvious exposure-response could not be seen.

Symptoms of late-onset hypogonadism (LOH) are often unspecific, and the existence of a male climacteric has been much debated. In this study, we investigate aging men's thoughts about, and beliefs, in a 'male climacteric'.A questionnaire was developed including background demographic data, symptoms possibly related to LOH and questions about men's thoughts and beliefs in a 'male climacteric'. All men, 55-, 65- and 75-years old, living in Linkoping, Sweden (n=1885) received the questionnaire.One thousand three hundred fifty-six (72%) questionnaires were eligible for evaluation, 65.4% of the responders had heard of a 'male climacteric', and 42.2% believed it existed but only 3% had sought medical advice for these symptoms. More than half believed that a 'male climacteric' was related to decreased libido and less strong erections. Almost half of the men thought that decreased memory and/or dystymia and anxiousness were related to a male climacteric.The majority of men have heard of a male climacteric, but only a minority had consulted a practitioner about their symptoms. More information and knowledge are needed, for the general population to better motivate men to seek medical advice and also for the health care professionals to better deal with the symptoms of LOH.

Background: The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuate the p53 levels and associates with disease progression in several tumors. Objective: In this study, the role of the polymorphism was investigated with regard to the clinical outcome in B-cell chronic lymphocytic leukemia (B-CLL). Patients: A total of 210 patients with B-CLL were followed for up to 19 yr. Results: The overall survival (OS) of patients with at least one G-allele was significantly shorter when compared with those with two T-alleles (P = 0.024) with a more pronounced difference in patients below the median age. Age at onset of B-CLL was similar irrespective of MDM2 status. The presence of a G-allele in combination with TP53 mutations or unmutated IgVH gene status resulted in an additive risk of death. Conclusion: In this report, with a high proportion of B-CLL patients with an advanced Binet stage and with an unmutated IgVH gene, MDM2 SNP309 was found to be independently associated with OS. The survival difference was more pronounced in younger patients.

The amygdala, situated in the anterior medial temporal lobe (MTL), is involved in the emotional enhancement of memory. The present study evaluated whether anterior MTL-resections attenuated arousal induced memory enhancement for pictures. Also, the effect of MTL-resections on response latencies at retrieval was assessed. Thirty-one patients with unilateral MTL-resections (17 left, 14 right) together with 16 controls participated in a forced choice memory task with pictorial stimuli varying in arousal. Response latencies increased with stimulus arousal in controls but not in patients. This was paralleled by attenuated recognition memory for moderately and highly arousing pictures in MTL-resectioned patients as compared to healthy controls. However, patients and controls did not differ in memory performance for non-arousing pictures. These results suggest that the MTL is necessary for arousal induced memory enhancement.

Neuroticism has been linked to a functional polymorphism in the serotonin transporter gene (5-HTTLPR), with short-allele carriers being overrepresented among high-scorers on neuroticism. Studies evaluating neuroticism-related personality traits in relation to the 5-HTTLPR polymorphism among patients with premenstrual dysphoric disorder (PMDD) and are lacking. The primary aim of this study was to evaluate the relationship between PMDD and neuroticism-related personality traits, and secondly, to relate the personality trait scores of PMDD patients to experienced symptom severity and to the 5-HTTLPR short allele. Thirty PMDD patients and 55 asymptomatic healthy controls were included in the study. The Swedish Universities Scale of Personality was used to evaluate personality traits. Genotype analyses were available in 27 PMDD patients and 18 healthy controls. Women with PMDD displayed higher levels of neuroticism-related personality traits (psychic trait anxiety, somatic trait anxiety, embitterment, stress susceptibility and mistrust) than healthy controls, and these effects were most prominent in women with more severe luteal phase symptoms. Furthermore, PMDD patients with at least one copy of the short allele of the 5-HTTLPR polymorphism scored higher on psychic trait anxiety and lack of assertiveness than PMDD patients who were homozygous for the long allele. PMDD patients who suffer from more severe luteal phase symptoms also display increased scores of neuroticism-related personality traits in comparison with healthy controls. Within the group of PMDD patients, differences in certain personality trait scores are associated with the short allele of the 5-HTTLPR polymorphism.

Background Critically ill patients often spend time in the intensive care unit (ICU) either unconscious or sedated. On recovery, they are often in a state of confusion with memory loss that may be ...

This is to identify factors affecting the prevalence of Lactobacillus reuteri in maternal faeces and breast milk and infant faeces after oral supplementation with L reuteri and to assess the influence on microbial ecology, particularly Clostridium difficile and Bifidobacterium colonization.In this double-blind trial, 232 mothers with a family history of atopic disease were randomized to a daily intake of either L reuteri American-type culture collection (ATCC) 55730 (1 x 10 colony-forming units [CFU]) or placebo for the last 4 weeks of pregnancy. Their babies then continued with the same study product daily from birth until 12 months of age. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, using conventional cultivation methods.The prevalence of L reuteri was higher during the first year of life in the stool samples from infants in the active as compared with the placebo-treated group. The highest prevalence was recorded at 5 to 6 days of age (82% in the treated vs 20% in the placebo group, P0.001). Lactobacillus reuteri was isolated from 12% and 2%, respectively, in the colostrum samples (P0.05). Breast-feeding seemed to reduce faecal L reuteri counts, although antibiotics did not influence the levels of L reuteri. The administration of L reuteri did not affect bifidobacteria or C difficile colonization.Lactobacillus reuteri may be detected in breast milk after oral supplementation to the mother and in almost all infants after oral supplementation during the first year of life, as well as occasionally in many untreated infants.

Identifying brain systems that regulate or modulate autonomic nervous system functions may identify pathways through which psychosocial factors can influence health and disease. Reduced high-frequency heart rate variability (HF-HRV) characterizes anxiety disordered patients and is predictive of adverse myocardial events. Sex differences in the prevalence of anxiety disorders and cardiac diseases implicate the possibility of sex specific neural regulation of HF-HRV. We investigated the correlation between HF-HRV and regional cerebral blood flow (rCBF) in 28 subjects (15 women) with social phobia undergoing a stressful public speaking task. Regional CBF was measured with [(15)O] water positron emission tomography. Stress induced rCBF correlated positively with HF-HRV in the right supra genual anterior cingulate cortex Brodmann's area (BA) 32, the right head of the caudate nucleus and bilaterally in the medial prefrontal cortex (BA10), extending into the dorsolateral prefrontal cortex (BA46) in the left hemisphere. Men showed larger positive co-variation in the caudate than women. These findings underscore the importance of the emotional division of the anterior cingulate cortex, the prefrontal cortex and the striatum in cardiovagal activity. The study replicates and extends results from published functional neuroimaging studies on cardioregulatory or modulatory areas in healthy subjects to men and women with social phobia. Moreover, caudate functions, possibly related to dopaminergic neurotransmission, have sexually dimorphic effects on vagal modulation of the heart.

Background The aim of this investigation was to assess the incidence of elevated N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) and its relation to outcome defined as perioperative adverse cardiac events and all-cause mortality in high-risk patients undergoing non-elective surgery for hip fracture. Methods A cohort of patients with hip fractures were extracted from a prospective observational study of high-risk patients (ASA class III or IV) undergoing emergency surgery. NT-proBNP and troponin I were measured before operation. An NT-proBNP ≥3984 ng litre−1 was set as the cut-off level for significance. Perioperative adverse cardiac events and 30 day and 3 month mortality were recorded. Results Sixty-nine subjects were included. Thirty-four subjects (49%) had an NT-proBNP ≥3984 ng litre−1 before surgery. Thirty-four subjects (49%) had a perioperative adverse cardiac event. Of these, 22 subjects (65%) had NT-proBNP above the diagnostic threshold compared with 12 subjects (34%) who had an NT-proBNP below the diagnostic threshold (P=0.01). Preoperative NT-proBNP ≥3984 ng litre−1 [odds ratio (OR) 3.0; 95% confidence interval (CI) 1.0–8.9] and congestive heart failure (OR 3.0; 95% CI 1.0–9.0) were independent predictors of perioperative adverse cardiac events. A total of eight subjects (12%) died within 30 days after operation. Conclusions There is a high incidence of elevated NT-proBNP in subjects undergoing non-elective hip fracture surgery. Preoperative NT-proBNP is a valuable predictor of cardiac complications in the perioperative period.

The objective was to study effects of fear on brain activity, functional connectivity and brain-behavior relationships during symptom provocation in subjects with specific phobia. Positron emission tomography (PET) and (15)O water was used to measure regional cerebral blood flow (rCBF) in 16 women phobic of either snakes or spiders but not both. Subjects watched pictures of snakes and spiders serving either as phobic or fear-relevant, but non-phobic, control stimuli depending on phobia type. Presentation of phobic as compared with non-phobic cues was associated with increased activation of the right amygdala and cerebellum as well as the left visual cortex and circumscribed frontal areas. Activity decreased in the prefrontal, orbitofrontal and ventromedial cortices as well as in the primary somatosensory cortex and auditory cortices. Furthermore, amygdala activation correlated positively with the subjective experience of distress. Connectivity analyses of activity in the phobic state revealed increased functional couplings between voxels in the right amygdala and the periamygdaloid area, fusiform gyrus and motor cortex. During non-phobic stimulation, prefrontal activity correlated negatively with amygdala rCBF, suggesting a phobia-related functional decoupling. These results suggest that visually elicited phobic reactions activate object recognition areas and deactivate prefrontal areas involved in cognitive control over emotion-triggering areas like the amygdala, resulting in motor readiness to support fight or flight.

A positive relationship was demonstrated between the blood pressure and the fibre composition of the vastus muscle at rest in 17 hypertensive and 17 age- and sex-matched normotensive subjects. The hypertensive group had a higher proportion of fast twitch (FT) fibres (p less than 0.1). The circulatory response was measured during isometric exercise (IE) and cold pressor test (CPT). During IE the blood pressure increase was positively related to the percentage of FT fibres. No such relationship was demonstrated during CPT. It was thus found, particularly in hypertensive subjects, that an individual's muscle fibre profile is of importance for the blood pressure response during IE.

Crohn's disease (CD) is characterized by overproduction of proinflammatory cytokines like interleukin (IL)-1beta. Production of mature IL-1beta is dependent on a caspase-1-activating protein complex called the NALP3 inflammasome, composed of NALP3, ASC, and CARD8. NALP3 shares structural similarities with Nod2, and both of these proteins are required for bacteria-induced IL-1beta secretion. The combination of the polymorphisms CARD8 (C10X)and NALP3 (Q705K) was recently shown to be associated with rheumatoid arthritis.Our aim was to investigate whether these combined polymorphisms play a role in the susceptibility to CD.The study included 498 CD patients in two cohorts from different regions and 742 control individuals from a Swedish population. DNA was isolated from whole blood. Polymorphisms of (Q705K) NALP3 and (C10X) CARD8, as well as the Nod2 variants, R702W and G908R, were genotyped using the Taqman single nucleotide polymorphism assay. The Nod2 frameshift mutation, L1007fs, was detected by Megabace SNuPe genotyping.Our results show that men who have both the C10X and Q705K alleles in CARD8 and NALP3, and who express wild-type alleles of Nod2 are at an increased risk of developing CD (odds ratio, OR: 3.40 range: 1.32-8.76); P = 0.011). No association with these polymorphisms was found in women (OR: 0.89 (range: 0.44-1.77); P = 0.74).We suggest a role for combined polymorphisms in CARD8 and NALP3 in the development of CD in men, with obvious sex differences in the genetic susceptibility pattern. These findings give further support to the importance of innate immune responses in CD.

OBJECTIVE: To determine gynecologists' attitudes to mode of hysterectomy on benign indication. DESIGN: Cross-sectional study. SETTING: Sweden. POPULATION: Members of the Swedish Society of Obstetrics and Gynecology. METHODS: A postal questionnaire. Questions examined attitudes to mode of hysterectomy based on three clinical scenarios with different conditions of the uterus. Gynecologists were also asked to estimate how the distribution of the different modes of benign hysterectomy should be overall. The modes to choose were total abdominal, subtotal abdominal, laparoscopic or vaginal hysterectomy (VH). Analyses were performed with multiple logistic regression and multivariate analysis of covariance. MAIN OUTCOME MEASURES: Preferred mode of hysterectomy in the three scenarios and distribution of modes of hysterectomy. RESULTS: VH was the most preferred method in general as well as when the uterus was of normal size, whereas subtotal and total abdominal hysterectomy were the most favored methods when the uterus was enlarged. VH was more often preferred by male compared to female gynecologists as a personal preference. The choice and distribution of mode varied significantly between place of work, seniority and in the quantity of yearly performed hysterectomies. The minimal invasive methods, vaginal and laparoscopic hysterectomy, were recommended in more than 50% of the overall suggested distribution. CONCLUSION: Personal choice of mode of hysterectomy does not seem to strictly follow evidence-based recommendations, but varies significantly between gynecologist's gender, type of clinical setting in which the gynecologist works, seniority and by how many hysterectomies the gynecologist does annually.

This study investigated the effects of anxiety on nonverbal aspects of speech using data collected in the framework of a large study of social phobia treatment. The speech of social phobics (N = 71) was recorded during an anxiogenic public speaking task both before and after treatment. The speech samples were analyzed with respect to various acoustic parameters related to pitch, loudness, voice quality, and temporal aspects of speech. The samples were further content-masked by low-pass filtering (which obscures the linguistic content of the speech but preserves nonverbal affective cues) and subjected to listening tests. Results showed that a decrease in experienced state anxiety after treatment was accompanied by corresponding decreases in (a) several acoustic parameters (i.e., mean and maximum voice pitch, high-frequency components in the energy spectrum, and proportion of silent pauses), and (b) listeners’ perceived level of nervousness. Both speakers’ self-ratings of state anxiety and listeners’ ratings of perceived nervousness were further correlated with similar acoustic parameters. The results complement earlier studies on vocal affect expression which have been conducted on posed, rather than authentic, emotional speech.

Background Fear conditioning is a traditional model for the acquisition of phobias, whereas behavioral therapies use processes underlying extinction to treat phobic and other anxiety disorders. Furthermore, fear conditioning has been proposed as an endophenotype for genetic studies of anxiety disorders. Although prior studies have demonstrated that fear conditioning and self-report fears are heritable, no studies have determined whether they share a common genetic basis. Methods We obtained fear conditioning data from 173 twin pairs from the Swedish Twin Registry who also provided self-report ratings of 16 common fears. With multivariate structural equation modeling, we analyzed factor-derived scores for the subjective fear ratings together with the electrophysiologic skin conductance responses during habituation, acquisition, and extinction to determine the extent of their genetic covariation. Results Phenotypic correlations between experimental and self-report fear measures were modest and, counter-intuitively, negative (i.e., subjects who reported themselves as more fearful had smaller electrophysiologic responses). Best-fit models estimated a significant (negative) genetic correlation between them, although genetic factors underlying fear conditioning accounted for only 9% of individual differences in self-report fears. Conclusions Experimentally derived fear conditioning measures share only a small portion of the genetic factors underlying individual differences in subjective fears, cautioning against relying too heavily on the former as an endophenotype for genetic studies of phobic disorders.

Background An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants. Objective To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri . Methods Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 × 10 8 colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens. Results The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% ( P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% ( P = .02). Wheeze and other potentially allergic diseases were not affected. Conclusion Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. Clinical implication Probiotics may reduce the incidence of IgE-associated eczema in infancy.