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This study examined the link between two biological markers of stress vulnerability at 22–26 years of age and telomere length at 30–35 among extremely low birth weight (ELBW; <1000 g) survivors and normal birth weight (NBW; >2500 g) control participants. Sixteen ELBW and 22 NBW participants provided baseline afternoon salivary cortisol samples and resting frontal electroencephalogram (EEG) alpha asymmetry data at 22–26 years. Buccal cells were assayed for telomere length at 30–35 years. Analyses controlled for sex, postnatal steroid exposure, childhood socioeconomic status, time of cortisol sample collection, and body mass index at 22–26 years. Salivary cortisol and frontal asymmetry at age 22–26 independently predicted telomere length at age 30–35, such that relatively higher cortisol and greater relative right frontal asymmetry at rest predicted telomere shortening among NBW controls, but not among ELBW survivors. However, similar associations were not noted in ELBW survivors, suggesting that ELBW survivors may have different mechanisms of stress coping as a result of their early-life exposures. These findings offer preliminary evidence in support of the role of stress in the genesis of cellular senescence at least among those born at NBW, but that these links may differ in those born preterm.
Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.
The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome.
Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission.
Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.
To evaluate the clinical benefit of switching to quetiapine sustained release (SR) in patients with schizophrenia experiencing suboptimal efficacy/tolerability with their current antipsychotic.
This was a 12-week, multicentre, open-label study (D1444C00147). Quetiapine SR (mg/day) was initiated during a 4-day cross titration phase (300 on Day 1; 600 on Day 2; 400, 600 or 800 on Day 3; flexible-dosing [400-800] from Days 4-84). Primary objective was to demonstrate that >50% of patients would achieve clinical benefit (improved CGI-Clinical Benefit [CB] score, based on CGI-I Efficacy index and tolerability burden) at Week 12. Secondary endpoints included CGI-I and PANSS total scores. Tolerability was assessed by adverse events (AEs), SAS and BARS scores. Mean changes in rating scale scores were analysed using ANCOVA.
477 patients were switched to quetiapine SR, 370 (77.6%) completed treatment. 295 of 470 evaluable patients (62.8%) achieved a clinical benefit upon switching to quetiapine SR (95% CI 58.4, 67.1, p<0.0001). Significant improvements were observed in mean [SD] change from baseline in CGI-CB (-2.1 [3.62]) and PANSS total (-13.6 [19.23]) (both p<0.001). Mean [SD] CGI-I score at endpoint was 2.8 [1.49] (p<0.001 for mean CGI-I<4). Common AEs included somnolence (17.8%), sedation (15.1%), dizziness and dry mouth (14.0% each). The incidence of EPS was 8.0%. Mean changes (improvements) from baseline in SAS and BARS scores were -2.1 and -0.4 respectively (both p<0.001).
Switching to quetiapine SR was associated with clinical benefit and was well tolerated in patients with schizophrenia experiencing suboptimal efficacy/tolerability with their previous antipsychotic treatment.
Ghrelin showed antidepressant-like effects in mice. Furthermore, ghrelin influences sleep and the activity of hypothalamic-pituitary-adrenal (HPA) and somatotropic axis in healthy humans as indicated by increased cortisol and growth hormone (GH) plasma levels. Both sleep and the activity of these endocrine axes are disturbed in depression.
To study the effect of ghrelin on psychopathology, sleep and secretion of cortisol and GH in patients with major depression.
Depressive symptoms as assessed by a validated self rating scale (’Befindlichkeits-Skala’, [well-being scale]), secretion profiles of cortisol and GH and sleep-EEGs were determined in 14 unmedicated patients with major depression (7 women) twice, receiving 50 μg ghrelin or placebo at 2200, 2300, 0000, and 0100 hours.
Overall, depressive symptoms did not change significantly after ghrelin administration (placebo: 37 ± 8; ghrelin: 33 ± 10, p = 0.178). However, there was an improvement at trend level in men (placebo: 36 ± 9 to ghrelin: 30 ± 9, p = 0.093) but not in women. In men, ghrelin was associated with less time awake (placebo: 149.0 ± 11.1; ghrelin: 88.0±12.2 min, p = 0.029) and more non-REM sleep (placebo: 263.2 ± 24.1; ghrelin: 304.9 ± 14.1 min, p = 0.027), in women with less REM sleep (placebo: 108.6 ± 15.7; ghrelin: 74.1 ± 13.8 min, p = 0.031) and longer REM latency (placebo: 49.9 ± 6.5; ghrelin: 85.6 ± 14.1 min, p = 0.019). In both sexes, ghrelin caused strong transient increases of GH and cortisol.
Our study may provide an initial indication that ghrelin can exert antidepressant effects in patients with major depression. Ghrelin strongly affected sleep and secretion of GH and cortisol in a partly different way as previously reported in healthy subjects.
To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement.
Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge.
Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC = 0.659) and response (AUC = 0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%).
The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.
Frowning expresses negative emotions like anger, fear, and sadness. According to the facial feedback hypothesis, suppression of frowning will also diminish the corresponding negative emotions. Hence, mood improvement has been observed in patients who underwent treatment of glabellar frown lines with botulinum neurotoxin. This observation suggests the possibility that the intervention may be employed for the management of psychiatric disorders associated with negative emotions. Preliminary data from an open case series indicate that the intervention might improve the symptoms of depression.
Aims & objectives
To test whether an onabotulinumtoxinA injection into the glabellar region is benefical as an adjunctive treatment of major depression within a clinical trial.
We used a randomized, double-blinded, placebo-controlled study design (n = 30; ClinicalTrials.gov, number, NCT00934687).
We show that a single onabotulinumtoxinA treatment shortly leads to a strong and sustained improvement in partly chronic major depression that did not respond sufficiently to previous treatment. As for the primary end-point, Hamilton Depression Rating Scale (HAM-D17) six weeks after treatment compared to baseline, scores of onabotulinumtoxinA recipients showed 37.9% (8.34 points) more improvement than those of placebo-treated participants (F = 12.30, p = 0.002, η2 = 0.31, d = 1.28).
Our findings support the concept that the facial musculature not only expresses, but also regulates, mood states. As it stands, treatment of glabellar frown lines with botulinum neurotoxin can be considered for depressed patients with the objective of inducing mood-lifting effects.
Attachment and companionship are fundamental basic needs of human beings and contribute the feeling of security and social affiliation. It is assumed that dysfunctional attachment behaviour in people with Borderline Personality Disorder leads to difficulties in the interpersonal contact. Unsecure and especially disorganized manners of attachment seem to be frequently represented by mentally ill people. In this study the release of oxytocin according to attachment relevant situations was investigated and attachment representations of people with BPD have been analysed.
In order to determine attachment representations of healthy people and of people with BPD we used the validated ‘Adult Attachment Projective’/ ‘AAP’ by George, West and Pettem (1999). The projective contains eight contour drawings of attachment relevant situations. The participant should make up a story of each picture, which was evaluated by its coherence, its content and the used defence mechanisms. Attachment representations of 30 patients with BPD were surveyed. Furthermore we measured the release of oxytocin evoked by an activation of the attachment system via the ‘AAP’ in 10 healthy people. Therefor blood drawings were performed at four different points of time.
Here, we present pilot data on oxytocin measures induced via the ‘AAP’. We could detect a decrease of oxytocin in healthy people caused by an activation of the attachment system. Moreover attachment representations of patients with BPD will be presented and discussed. These preliminary data could lead to further studies on a possible dysregulation of the attachment- and the oxytocin system of people with BPD.
Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms.
Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient’s symptoms.
The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of > 6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors.
The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms.
Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.
The South Fork of Wright Valley contains one of the largest rock glaciers in the McMurdo Dry Valleys, Antarctica, stretching 7 km from the eastern boundary of the Labyrinth and terminating at Don Juan Pond (DJP). Here, we use results from ground-penetrating radar (GPR), qualitative field observations, soil leaching analyses and X-ray diffraction analyses to investigate rock glacier development. The absence of significant clean ice in GPR data, paired with observations of talus and interstitial ice influx from the valley walls, support rock glacier formation via talus accumulation. A quartz-dominated subsurface composition and discontinuous, well-developed desert pavements suggest initial rock glacier formation occurred before the late Quaternary. Major ion data from soil leaching analyses show higher salt concentrations in the rock glacier and talus samples that are close to hypersaline DJP. These observations suggest that DJP acts as a local salt source to the rock glacier, as well as the surrounding talus slopes that host water track systems that deliver solutes back into the lake, suggesting a local feedback system. Finally, the lack of lacustrine sedimentation on the rock glacier is inconsistent with the advance of a glacially dammed lake into South Fork during the Last Glacial Maximum.
We discuss the process of estimating the ecosystem service value (ESV) for provisioning of non-timber forest products (NTFPs) to market, with a focus on the United States. NTFPs are harvested throughout the U.S. for numerous purposes, and those sold in market contribute significantly to household and local economies. While estimates of ESV can aid decision-making related to conservation and management, NTFPs have been generally neglected. We discuss challenges and approaches for prioritizing valuation, quantifying production, measuring costs and benefits, and finding data sources. Many NTFP markets are informal, and market players may have an interest in withholding information. Data about geographic and temporal distribution, production cost, quantity harvested, and price may therefore be limited. In two case studies, we explore the nuances of estimating ESV of forests for medicinal products.
Outpatient interventions for adult anorexia nervosa typically have a modest impact on weight and eating disorder symptomatology. This study examined whether adding a brief online intervention focused on enhancing motivation to change and the development of a recovery identity (RecoveryMANTRA) would improve outcomes in adults with anorexia nervosa.
Participants with anorexia nervosa (n = 187) were recruited from 22 eating disorder outpatient services throughout the UK. They were randomised to receiving RecoveryMANTRA in addition to treatment as usual (TAU) (n = 99; experimental group) or TAU only (n = 88; control group). Outcomes were measured at end-of-intervention (6 weeks), 6 and 12 months.
Adherence rates to RecoveryMANTRA were 83% for the online guidance sessions and 77% for the use of self-help materials (workbook and/or short video clips). Group differences in body mass index at 6 weeks (primary outcome) were not significant. Group differences in eating disorder symptoms, psychological wellbeing and work and social adjustment (at 6 weeks and at follow-up) were not significant, except for a trend-level greater reduction in anxiety at 6 weeks in the RecoveryMANTRA group (p = 0.06). However, the RecoveryMANTRA group had significantly higher levels of confidence in own ability to change (p = 0.02) and alliance with the therapist at the outpatient service (p = 0.005) compared to the control group at 6 weeks.
Augmenting outpatient treatment for adult anorexia nervosa with a focus on recovery and motivation produced short-term reductions in anxiety and increased confidence to change and therapeutic alliance.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
Excavations at several locations in Verteba Cave have uncovered a large amount of human skeletal remains in association with faunal bones and Tripolye material culture. We aim to establish radiocarbon (14C) dates for eight sites and to evaluate whether these deposits are singular events, or slow accumulations over time. 14C measurements, along with stable carbon and nitrogen isotope data from human and faunal remains, were collected from 18 specimens. Stable isotope values were used to evaluate human and animal diet, and whether freshwater reservoir effects offset measured dates. We found diets of the sampled species had limited to no influence from freshwater resources. Human diet appears to be dominated by terrestrial plants and herbivores. Four new sites were identified as Eneolithic. Comparisons of dates from top and bottom strata for two sites (7 and 20) reveal coeval dates, and we suggest that these deposits represent discrete events rather than slow continuous use. Lastly, we identified dates from the Mesolithic (8490±45 BP, 8765±30 BP), Iron Age (2505±20 BP), Slavic state era (1315±25 BP), and Medieval Period (585±15 BP), demonstrating periodic use of the cave by humans prior to and after the Eneolithic.
The analysis of stable isotopes of carbon and nitrogen has been used as a fingerprint for understanding the trophic interactions of organisms. Most of these studies have been applied to free-living organisms, while parasites have largely been neglected. Studies dealing with parasites so far have assessed the carbon and nitrogen signatures in endoparasites or ectoparasites of different hosts, without showing general trends concerning the nutritional relationships within host–parasite associations. Moreover, in most cases such systems involved a single host and parasite species. The present study is therefore the first to detail the trophic interactions of a freshwater monogenean–host model using δ13C and δ15N, where a single monogenean species infects two distinctly different hosts. Host fishes, Labeobarbus aeneus and Labeobarbus kimberleyensis from the Vaal Dam, South Africa, were assessed for the monogenean parasite Paradiplozoon ichthyoxanthon, individuals of which were removed from the gills of the hosts. The parasites and host muscle samples were analysed for signatures of δ13C and δ15N using an elemental analyser connected to an isotope ratio mass spectrometer. Host fish appear to use partly different food sources, with L. aeneus having slightly elevated δ13C signatures compared to L. kimberleyensis, and showed only small differences with regard to their nitrogen signatures, suggesting that both species range on the same trophic level. Carbon and nitrogen signatures in P. ichthyoxanthon showed that the parasites mirrored the small differences in dietary carbon sources of the host but, according to δ15N signatures, the parasite ranged on a higher trophic level than the hosts. This relationship resembles predator–prey relationships and therefore suggests that P. ichthyoxanthon might act as a micropredator, similar to blood-sucking arthropods such as mites and fleas.
To reduce inappropriate antimicrobial prescribing across ambulatory care, understanding the patient-, provider-, and practice-level characteristics associated with antibiotic prescribing is essential. In this study, we aimed to elucidate factors associated with inappropriate antimicrobial prescribing across urgent care, family medicine, and pediatric and internal medicine ambulatory practices.
DESIGN, SETTING, AND PARTICIPANTS
Data for this retrospective cohort study were collected from outpatient visits for common upper respiratory conditions that should not require antibiotics. The cohort included 448,990 visits between January 2014 and May 2016. Carolinas HealthCare System urgent care, family medicine, internal medicine and pediatric practices were included across 898 providers and 246 practices.
Prescribing rates were reported per 1,000 visits. Indications were defined using the International Classification of Disease, Ninth and Tenth Revisions, Clinical Modification (ICD-9/10-CM) criteria. In multivariable models, the risk of receiving an antibiotic prescription was reported with adjustment for practice, provider, and patient characteristics.
The overall prescribing rate in the study cohort was 407 per 1,000 visits (95% confidence interval [CI], 405–408). After adjustment, adult patients seen by an advanced practice practitioner were 15% more likely to receive an antimicrobial than those seen by a physician provider (incident risk ratio [IRR], 1.15; 95% CI, 1.03–1.29). In the pediatric sample, older providers were 4 times more likely to prescribe an antimicrobial than providers aged ≤30 years (IRR, 4.21; 95% CI, 2.96–5.97).
Our results suggest that patient, practice, and provider characteristics are associated with inappropriate antimicrobial prescribing. Future research should target antibiotic stewardship programs to specific patient and provider populations to reduce inappropriate prescribing compared to a “one size fits all” approach.