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In the Federal Republic of Germany about 3 million people suffer from tinnitus/are hit by tinnitus, numerous of them depend on intensive medical care. The repetitive transcranial magnetic stimulation is considered to be an innovative and promising therapy in tinnitus treatment. Low frequency stimulation is meant to reduce the abnormal neural activity in the auditory cortex. This study focuses on the efficacy of rTMS with tinnitus patients in the course of a multi disciplinary / an interdisciplinary therapy concept.
From November 2008 to June 2009 29 outpatients with chronic tinnitus were treated by low frequency rTMS (1 Hz frequency, 2000 impulses, intensity 110%) for 10 proceedings, stimulating the sinistral auditory cortex with a figure-of-eight-coil. Prior to and afterwards the proceedings questionnaires and assessments of a psychologist took place, afterwards statistical analyses were conducted, the data was explored and systematically discussed.
The severity index of the tinnitus as well as the depression symptoms of the subjects improved significantly. The average reduction rate of the tinnitus score is set at 7 points. With a response criterion at the minimum of 5 points, 57% were declared as responder, 29% as non-responder and 4 patients (14%) described an increase of the tinnitus loudness/annoyance.
The results show that the rTMS works as a helpful treatment tool with tinnitus patients and should be considered as an option in the routine tinnitus treatment.
Functional Transcranial Doppler sonography (fTCD) has been applied to assess peak mean cerebral blood flow velocity (MFV) with a high temporal resolution during cognitive activation. Yet, little attention has been devoted to gender-related alterations of MFV, including spectral analysis. In healthy subjects, fTCD was used to investigate a series of cerebral hemodynamic parameters in the middle cerebral arteries (MCA) during the Trail Making Tests (TMT), a means of selective attention and complex cognitive functioning. After the initial peak, there was an MFV decline during complex functioning. Further, in females, we observed a dynamic shift in hemispheric dominance during that condition and there was a frequency peak at 0.375 Hz in both MCA. These novel results suggest condition-specific features of cerebral hemodynamics in females, and it adds to the notion that gender is a fundamental confounder of brain physiology. It is intriguing to speculate whether condition-related alterations of spectral frequencies in females represent a marker of increased vulnerability for psychiatric diseases such as depression.
Acid sphingomyelinase (A-SMase) is a glycoprotein that functions as a lysosomal hydrolase, catalysing the degradation of sphyngomyelin to phosphorylcholine and ceramide. Several lines of evidence suggest its central role in all three types of apoptosis. The activation of neuronal A-SMase has been shown to be important in the stress-induced apoptotic death of hippocampal neurons. The aim of the present study was to investigate the association between the activity of A-SMase, hippocampal volume and memories function in healthy young volunteers.
Materials and Methods:
The activity of A-SMase was measured in peripheral blood mononuclear cells of 19 healthy female students of the University of Erlangen- Nuernberg (26,32 ± 3,95 years old, Body mass: 22,29 ± 2,63 kgr/m2). The hippocampal formation was outlined in high-resolution anatomical magnetic resonance imaging data. The memory function was assessed with the Inventory for Memory diagnostics (Inventar zur Gedaechtnisdiagnostik). Correlations between continuous variables were examined, using Spearman's rank correlation coefficient.
The activity of A-SMase did not correlate with hippocampal volume and memory performance.
These findings indicate that the activity of the A-SMase influences neither the brain hippocampal volume of young healthy females, nor their memory performance.
To evaluate the safety of phosphatidylserine (PS) enriched with omega3 fatty acids, mainly eicosapentaenoic (PS-Omega3) in children with attention-deficit hyperactivity disorder (ADHD).
Two hundred children diagnosed with ADHD were randomised to receive either PS-Omega3 (300 mg PS-Omega3/day) or placebo for 15 weeks. One hundred and fifty children continued into an open-label extension for an additional 15 weeks in which they all consumed PS-Omega3 (150 mg PS-Omega3/day). Standard blood biochemical and haematological safety parameters, blood pressure, heart rate, weight and height were evaluated. Adverse events and the Side Effect Rating Scale were also assessed.
One hundred and sixty-two participants completed the double-blind phase. No significant differences were noted between the two study groups in any of the safety parameters evaluated. One hundred and forty participants completed the open-label phase. At the end of this phase, no significant changes from baseline were observed in any of the studied parameters among participants who consumed PS-Omega3 for 30 weeks.
Study results demonstrate that consumption of PS-Omega3 by children with ADHD, as indicated in a 30-week evaluation period, is safe and well tolerated, without any negative effect on body weight or growth.
To study the efficacy and safety of phosphatidylserine (PS) containing Omega3 long-chain polyunsaturated fatty acids attached to its backbone (PS-Omega3) in reducing attention-deficit/ hyperactivity disorder (ADHD) symptoms in children.
A 15-week, double-blind, placebo-controlled phase followed by an open-label extension of additional 15 weeks. Two hundred ADHD children were randomized to receive either PS-Omega3 or placebo, out of them, 150 children continued into the extension. Efficacy was assessed using Conners’ parent and teacher rating scales (CRS-P,T), Strengths and Difficulties Questionnaire (SDQ), and Child Health Questionnaire (CHQ). Safety evaluation included adverse events monitoring.
The key finding of the double-blind phase was the significant reduction in the Global:Restless/impulsive subscale of CRS-P and the significant improvement in Parent impact-emotional (PE) subscale of the CHQ, both in the PS-Omega3 group. Exploratory subgroup analysis of children with a more pronounced hyperactive/impulsive behavior, as well as mood and behavior-dysregulation, revealed a significant reduction in the ADHD-Index and hyperactive components. Data from the open-label extension indicated sustained efficacy for children who continued to receive PS-Omega3. Children that switched to PS-Omega3 treatment from placebo showed a significant reduction in subscales scores of both CRS-P and the CRS-T, as compare to baseline scores. The treatment was well tolerated.
The results of this 30-week study suggest that PS-Omega3 may reduce ADHD symptoms in children. Preliminary analysis suggests that this treatment may be especially effective in a subgroup of hyperactive-impulsive, emotionally and behaviorally-dysregulated ADHD children.
It is frequently suggested that gender role norms influence certain expectations towards a child's gender related behavior and that deviations are perceived negatively by the social environment. Gender-dysphoric individuals experience a strong and persistent cross-gender identification and discomfort about the assigned sex and the associated gender role behaviors.
The objective of this study was to investigate how adult gender dysphoric individuals recall play and peer-group preferences in childhood according to stereotypical expectations regarding the assigned sex.
Differences between individuals who transition from female to male (FtMs) and those who transition from male to female (MtFs) as well as differences with regard to subgroups based on the age of onset (early onset: during childhood, EO; late onset: with begin of puberty development, LO) are tested.
Data collection took place as part of the European network for the investigation of gender incongruence (ENIGI), a multicenter cooperation between European gender clinics in Amsterdam (NL), Ghent (BE), Hamburg (GER) and Oslo (NO). Play behavior and peer preferences were measured as part of the Biographic Questionnaire on Transsexualism.
The total sample of N=634 participants was collected between 2006 and 2012. Participants were prescribed a diagnosis according to DSM-IV-TR criteria of Gender Identity Disorder.
The results show, that cross-gender behavior was more frequently recalled in FtMS than MtFs. Within the gender-groups, individuals who were assessed as having an early onset recalled cross-gender behaviors more frequently than individuals who were assessed as having a late-onset.
The results will be discussed in line with actual research findings.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Pressure ridges impact the mass, energy and momentum budgets of the sea-ice cover and present an obstacle to transportation through ice-infested waters. Quantifying ridge characteristics is important for understanding total sea-ice mass and for improving the representation of sea-ice dynamics in high-resolution models. Multi-sensor measurements collected during annual Operation IceBridge (OIB) airborne surveys of the Arctic provide new opportunities to assess the sea ice at the end of winter. We present a new methodology to derive ridge sail height from high-resolution OIB Digital Mapping System (DMS) visible imagery. We assess the efficacy of the methodology by mapping the full sail height distribution along 12 pressure ridges in the western and central Arctic. Comparisons against coincident Airborne Topographic Mapper (ATM) elevation anomalies are used to demonstrate the methodology and evaluate DMS-derived sail heights. Sail heights and elevation anomalies were correlated at 0.81 or above. On average mean and maximum sail height agreed with ATM elevation to within 0.11 and 0.49 m, respectively. Of the ridges mapped, mean sail height ranged from 0.99 to 2.16 m, while maximum sail height ranged from 2.1 to 4.8 m. DMS also delivered higher sampling along ridge crests than coincident ATM data.
Plasticity in as-grown gold nanowires deformed in three-point bending configuration was studied by Laue microdiffraction. One-dimensional orientation maps of the Au crystal along the nanowire were generated from which the deformation profile was inferred. The crystal lattice was found to rotate continuously around the Au
direction, which is transverse to the wire axis evidencing the storage of geometrically necessary dislocations (GNDs). The analysis of the diffraction peak shape points to the activation of multiple slip systems in contrast to the formation of wedge shaped twins predicted by MD simulations.
Depression and anxiety in the antenatal period are of public health concern given potential adverse effects for both mother and infant. Both are under-researched in the first trimester of pregnancy, especially in Africa. We examine the prevalence of first trimester antenatal depression and anxiety in a cohort of South African women and investigate associated risk factors. Data were collected from 946 women (2014–2016) in the Soweto First 1000 Days Cohort, a prospective pregnancy cohort in Soweto, South Africa. Antenatal depression was assessed using the Edinburgh Postnatal Depression Scale with a score of ⩾13 indicating probable depression. Anxiety was assessed using the short form of the State-Trait Anxiety Index with a score ⩾12 indicating probable anxiety. Prevalence of antenatal depression was 27% [95% confidence interval (CI) 24.2–29.8] and anxiety 15.2% (95% CI 12.9–17.5). Factors associated with antenatal depression and anxiety were predominantly relationship- and family-centred. Women who perceived that their partner made life harder for them had three-fold increased odds for depression [(odds ratio (OR) 3.33 [2.28–4.85] P<0.001], whereas those with family stressors had almost double the odds for depression (OR 1.78 [1.22–2.59] P=0.003) and anxiety (OR 1.75 [1.44–2.69] P=0.0011). Antenatal depression and anxiety are common in the first trimester of pregnancy, and partner and family relationship stressors are central. Longitudinal analysis is needed to determine if this is a phase of adjustment to pregnancy or onset of persistent symptomology. Early intervention may have secondary preventative effects and should involve the partner and family.
Older people have a higher risk of drug-related problems (DRPs). However, little is known about the prevalence of DRPs in community-dwelling people who screened positive for dementia. Our study aimed to determine (1) the prevalence and types of DRPs and (2) the socio-demographic and clinical variables associated with DRPs in people screened positive for dementia in primary care.
The Dementia: life- and person-centered help in Mecklenburg-Western Pomerania (DelpHi-MV) study is a general practitioner (GP)-based cluster-randomized controlled intervention study to implement and evaluate an innovative concept of collaborative dementia care management in the primary care setting in Germany. Medication reviews of 446 study participants were conducted by pharmacists based on a comprehensive baseline assessment that included a computer-based home medication assessment. ClinicalTrials.gov Identifier: NCT01401582.
A total of 1,077 DRPs were documented. In 414 study participants (93%), at least one DRP was detected by a pharmacist. The most frequent DRPs were administration and compliance problems (60%), drug interactions (17%), and problems with inappropriate drug choice (15%). The number of DRPs was significantly associated with the total number of drugs taken and with a formal diagnosis of a mental or behavioral disorder.
Degree of cognitive impairment (MMSE defined) and formal diagnosis of dementia were not risk factors for an increased number of DRPs. However, the total number of drug taken and the presence of a diagnosis of mental and behavioral disorders were associated with an increased total number of DRPs.
Emerging CVD risk factors (e.g. HDL function and central haemodynamics) may account for residual CVD risk experienced by individuals who meet LDL-cholesterol and blood pressure (BP) targets. Recent evidence suggests that these emerging risk factors can be modified by polyphenol-rich interventions such as soya, but additional research is needed. This study was designed to investigate the effects of an isoflavone-containing soya protein isolate (delivering 25 and 50 g/d soya protein) on HDL function (i.e. ex vivo cholesterol efflux), macrovascular function and blood markers of CVD risk. Middle-aged adults (n 20; mean age=51·6 (sem 6·6) years) with moderately elevated brachial BP (mean systolic BP=129 (sem 9) mmHg; mean diastolic BP=82·5 (sem 8·4) mmHg) consumed 0 (control), 25 and 50 g/d soya protein in a randomised cross-over design. Soya and control powders were consumed for 6 weeks each with a 2-week compliance break between treatment periods. Blood samples and vascular function measures were obtained at baseline and following each supplementation period. Supplementation with 50 g/d soya protein significantly reduced brachial diastolic BP (−2·3 mmHg) compared with 25 g/d soya protein (Tukey-adjusted P=0·03) but not the control. Soya supplementation did not improve ex vivo cholesterol efflux, macrovascular function or other blood markers of CVD risk compared with the carbohydrate-matched control. Additional research is needed to clarify whether effects on these CVD risk factors depend on the relative health of participants and/or equol producing capacity.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
We present the preliminary results from observing the nearby radio galaxy M 87 for 156 hours (between the years 2012 and 2015) with the MAGIC telescopes, which lead to a significant very high energy (VHE, E > 100 GeV) detection of the source in quiescent states each year. Our VHE analysis combined with quasi-simultaneous data at other energies (from gamma-rays, X-rays, optical and radio) provides a unique opportunity to study the source variability and its broadband spectral energy distribution, which is found to disfavour a one-zone synchrotron/synchrotron self-Compton model. Therefore, other alternative scenarios for the photon emission are explored. We also find that the VHE emission is compatible with being produced close to the source radio core as previous data already indicated. A detailed paper presenting full results of the observing campaign is in preparation.
Inpatients with blood cultures positive for Staphylococcus aureus, Enterococcus faecalis, E. faecium, Streptococcus pneumoniae, S. pyogenes, S. agalactiae, S. anginosus, Streptococcus spp., and Listeria monocytogenes during the 6 months before and after implementation of Verigene Gram-positive blood culture microarray (BC-GP) with an antimicrobial stewardship intervention.
Before the intervention, no rapid diagnostic technology was used or antimicrobial stewardship intervention was undertaken, except for the use of peptide nucleic acid fluorescent in situ hybridization and MRSA agar to identify staphylococcal isolates. After the intervention, all Gram-positive blood cultures underwent BC-GP microarray and the antimicrobial stewardship intervention consisting of real-time notification and pharmacist review.
In total, 513 patients with bacteremia were included in this study: 280 patients with S. aureus, 150 patients with enterococci, 82 patients with stretococci, and 1 patient with L. monocytogenes. The number of antimicrobial switches was similar in the pre–BC-GP (52%; 155 of 300) and post–BC-GP (50%; 107 of 213) periods. The time to antimicrobial switch was significantly shorter in the post–BC-GP group than in the pre–BC-GP group: 48±41 hours versus 75±46 hours, respectively (P<.001). The most common antimicrobial switch was de-escalation and time to de-escalation, was significantly shorter in the post-BC-GP group than in the pre–BC-GP group: 53±41 hours versus 82±48 hours, respectively (P<.001). There was no difference in mortality or hospital length of stay as a result of the intervention.
The combination of a rapid microarray diagnostic test with an antimicrobial stewardship intervention improved time to antimicrobial switch, especially time to de-escalation to optimal therapy, in patients with Gram-positive blood cultures.
Various transmission routes contribute to spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospitalized patients. Patients with readmissions during which CRKP is again isolated (“CRKP readmission”) potentially contribute to transmission of CRKP.
To evaluate CRKP readmissions in the Consortium on Resistance against Carbapenems in K. pneumoniae (CRaCKLe).
Cohort study from December 24, 2011, through July 1, 2013.
Multicenter consortium of acute care hospitals in the Great Lakes region.
All patients who were discharged alive during the study period were included. Each patient was included only once at the time of the first CRKP-positive culture.
All readmissions within 90 days of discharge from the index hospitalization during which CRKP was again found were analyzed. Risk factors for CRKP readmission were evaluated in multivariable models.
Fifty-six (20%) of 287 patients who were discharged alive had a CRKP readmission. History of malignancy was associated with CRKP readmission (adjusted odds ratio [adjusted OR], 3.00 [95% CI, 1.32–6.65], P<.01). During the index hospitalization, 160 patients (56%) received antibiotic treatment against CRKP; the choice of regimen was associated with CRKP readmission (P=.02). Receipt of tigecycline-based therapy (adjusted OR, 5.13 [95% CI, 1.72–17.44], using aminoglycoside-based therapy as a reference in those treated with anti-CRKP antibiotics) was associated with CRKP readmission.
Hospitalized patients with CRKP—specifically those with a history of malignancy—are at high risk of readmission with recurrent CRKP infection or colonization. Treatment during the index hospitalization with a tigecycline-based regimen increases this risk.
Infect. Control Hosp. Epidemiol. 2016;37(3):281–288
To determine the rates of and risk factors for tigecycline nonsusceptibility among carbapenem-resistant Klebsiella pneumoniae (CRKPs) isolated from hospitalized patients
Multicenter prospective observational study
Acute care hospitals participating in the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRaCKle)
A cohort of 287 patients who had CRKPs isolated from clinical cultures during hospitalization
For the period from December 24, 2011 to October 1, 2013, the first hospitalization of each patient with a CRKP during which tigecycline susceptibility for the CRKP isolate was determined was included. Clinical data were entered into a centralized database, including data regarding pre-hospital origin. Breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were used to interpret tigecycline susceptibility testing.
Of 287 patients included in the final cohort, 155 (54%) had tigecycline-susceptible CRKPs. Of all index isolates, 81 (28%) were tigecycline-intermediate and 51 (18%) were tigecycline resistant. In multivariate modeling, independent risk factors for tigecycline nonsusceptibility were (1) admission from a skilled nursing facility (OR, 2.51; 95% CI, 1.51–4.21; P=.0004), (2) positive culture within 2 days of admission (OR, 1.82; 95% CI, 1.06–3.15; P=.03), and (3) receipt of tigecycline within 14 days (OR, 4.38, 95% CI, 1.37–17.01, P=.02).
In hospitalized patients with CRKPs, tigecycline nonsusceptibility was more frequently observed in those admitted from skilled nursing facilities and occurred earlier during hospitalization. Skilled nursing facilities are an important target for interventions to decrease antibacterial resistance to antibiotics of last resort for treatment of CRKPs.
From a behavioural biologist's point of view, we argue: (1) The study of resilience in animals should not be restricted to neuronal mechanisms. Rather, questions of ontogeny, function, and evolution also should be addressed to achieve a comprehensive understanding. (2) Implementing new paradigms from animal welfare research in studies of resilience would allow an assessment of appraisal styles in animals.