3D printing of resilient biogels for omnidirectional and exteroceptive soft actuators.

Soft robotics greatly benefits from nature as a source of inspiration, introducing innate means of safe interaction between robotic appliances and living organisms. In contrast, the materials involved are often nonbiodegradable or stem from nonrenewable resources, contributing to an ever-growing environmental footprint. Furthermore, conventional manufacturing methods, such as mold casting, are not suitable for replicating or imitating the complexity of nature's creations. Consequently, the inclusion of sustainability concepts alongside the development of new fabrication procedures is required. We report a customized 3D-printing process based on fused deposition modeling, printing a fully biodegradable gelatin-based hydrogel (biogel) ink into dimensionally stable, complex objects. This process enables fast and cost-effective prototyping of resilient, soft robotic applications from gels that stretch to six times their original length, as well as an accessible recycling procedure with zero waste. We present printed pneumatic actuators performing omnidirectional movement at fast response times (less than a second), featuring integrated 3D-printed stretchable waveguides, capable of both proprio- and exteroception. These soft devices are endowed with dynamic real-time control capable of automated search-and-wipe routines to detect and remove obstacles. They can be reprinted several times or disposed of hazard-free at the end of their lifetime, potentially unlocking a sustainable future for soft robotics.

Mortality and employment after in-patient opiate detoxification.

AIM: We considered that completed opiate detoxification resulted in increased life expectancy and earning capacity as compared to non-completed detoxification. METHODS: The cohort study sample included pure opioid or poly-substance addicts admitted for voluntary in-patient detoxification between 1997 and 2004. Of 404 patients, 58.7% completed the detoxification program and 41.3% did not. The Austrian Social Security Institution supplied data on survival and employment records for every single day in the individual observation period between discharge and December 2007. Statistical analyses included the calculation of standardized mortality rates for the follow-up period of up to 11 years. RESULTS: The standardized mortality ratios (SMRs) were between 13.5 and 17.9 during the first five years after discharge, thereafter they fell clearly with time. Mortality did not differ statistically significantly between completers and non-completers. The median employment rate was insignificantly higher in completers (12.0%) than in non-completers (5.5%). The odds for being employed were higher in pure opioid addicts than in poly-substance addicts (p=0.003). CONCLUSIONS: The assumption that completers of detoxification treatment have a better outcome than non-completers has not been confirmed. The decrease in mortality with time elapsed since detoxification is interesting. Pure opioid addicts had better employment prospects than poly-substance addicts.

Intensive care in psychiatry.

Psychiatric intensive care is supposed to offer treatment and to hold patients with psychiatric illness, if they pose a threat to themselves or to others. Besides treating the underlying psychiatric diagnoses, it is also necessary to take care of severe somatic comorbidity, which is often impeded by patients' limited ability to cooperate. Treatment often requires the administration of sedative medication and occasionally the use of medical restraints. Involuntary commitment, involuntary treatment and the usage of physical restraints is regulated by national mental health laws. Medical professionals working in the field of psychiatric intensive care must have expert knowledge in the fields of psychopharmacology and intensive care medicine. Treatment concepts should be aimed to provide optimized care for psychiatric inpatients in a potentially life-threatening phase of their illness. This article outlines current clinical practice at the psychiatric intensive care unit of the Medical University of Vienna (Austria). Furthermore, we present diagnoses, diagnostic procedures and specific treatments of a sample of 100 consecutive inpatients treated in the years 2008 and 2009 at this ward.

Ultra-rapid opiate detoxification followed by nine months of naltrexone maintenance therapy in Iran.

INTRODUCTION: The aim of this retrospective study was to assess ultra-rapid opiate detoxification (UROD) and to estimate the retention rate in naltrexone maintenance treatment. METHODS: 45 opiate-addicted male patients (DSM-IV 304.00; opiate per oral or per inhalation n=40, heroin intravenous n=5; concomitant cannabis abuse n=6) were detoxified by 6 h of naloxone infusion under general anesthesia with midazolam, propofol, clonidine and atracurium. Withdrawal signs were evaluated by the objective opiate withdrawal scale (OOWS, range 0-13) up to 24 h after awakening. After UROD, naltrexone 50 mg/day was prescribed for 9 months with assessments in 4-week intervals. RESULTS: Adverse events after UROD were prolonged unconsciousness (n=1), transient confusion (n=8) and depressive mood (n=6). The total sample showed a median OOWS score of 2 (mild withdrawal syndrome). The only two extreme outliers were found only in the subgroups "intravenous" (score 8) and "cannabis" (score 11). 96% (43/45) of the patients could be discharged the day after UROD. Thirty-six patients (80%) continued naltrexone therapy for the entire 9-month observation period. DISCUSSION: UROD and subsequently induction of naltrexone maintenance therapy can be regarded as safe and effective in patients with pure opiate addiction. Owing to cultural and economical factors our Iranian results may not correspond to European and American treatment modalities.

Antidepressant effects of augmentative transcranial magnetic stimulation: randomised multicentre trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a new treatment option for depression. Previous studies were performed with low sample sizes in single centres and reported heterogeneous results. AIMS: To investigate the efficacy of rTMS as augmentative treatment in depression. METHOD: In a randomised, double-blind, sham-controlled multicentre trial 127 patients with moderate to severe depressive episodes were randomly assigned to real or sham stimulation for 3 weeks in addition to simultaneously initiated antidepressant medication. RESULTS: We found no difference in the responder rates of the real and the sham treatment groups (31% in each) or in the decrease of the scores on the depression rating scales. CONCLUSIONS: The data do not support previous reports from smaller samples indicating an augmenting or accelerating antidepressant effect of rTMS. Further exploration of the possible efficacy of other stimulation protocols or within selected sub-populations of patients is necessary.

Determination of stale-flavor carbonyl compounds in beer by stir bar sorptive extraction with in-situ derivatization and thermal desorption-gas chromatography-mass spectrometry.

A method for the determination of stale-flavor carbonyl compounds including E-2-octenal, E-2-nonenal, E,Z-2,6-nonadienal and E,E-2,4-decadienal in beer was developed using stir bar sorptive extraction (SBSE) with in-situ derivatization followed by thermal desorption-GC-MS analysis. The derivatization conditions with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine and the SBSE conditions--sampling mode, salt addition, sample volume, polydimethylsiloxane volume (sample/polydimethylsiloxane phase ratio) and extraction time--were examined. The method showed good linearity over the concentration range from 0.1 to 10 ng ml(-1) for all analytes and the correlation coefficients were higher than 0.9993. The limits of detection ranged from 0.021 to 0.032 ng ml(-1) for all analytes. The recoveries (98-101%) and precision (RSD 2.4-7.3%) of the method were examined by analyzing beer samples fortified at the 0.5-ng ml(-1) level. The method was successfully applied to low-level concentration samples.

Determination of trace amounts of off-flavor compounds in drinking water by stir bar sorptive extraction and thermal desorption GC-MS.

A method for the determination of trace amounts of off-flavor compounds including 2-methylisoborneol, geosmin and 2,4,6-trichloroanisole in drinking water was developed using the stir bar sorptive extraction technique followed by thermal desorption-GC-MS analysis. The extraction conditions such as extraction mode, salt addition, extraction temperature, sample volume and extraction time were examined. Water samples (20, 40 and 60 ml) were extracted for 60-240 min at room temperature (25 degrees C) using stir bars with a length of 10 mm and coated with a 500 microm layer of polydimethylsiloxane. The extract was analyzed by thermal desorption-GC-MS in the selected ion monitoring mode. The method showed good linearity over the concentration range from 0.1 or 0.2 or 0.5 to 100 ng l(-1) for all the target analytes, and the correlation coefficients were greater than 0.9987. The detection limits ranged from 0.022 to 0.16 ng l(-1). The recoveries (89-109%) and precision (RSD: 0.80-3.7%) of the method were examined by analyzing raw water and tap water samples fortified at the 1 ng l(-1) level. The method was successfully applied to low-level samples (raw water and tap water).

Quetiapine: efficacy and tolerability in schizophrenia.

Quetiapine, in common with clozapine, has a greater affinity for 5-HT(2) receptors than D(2) receptors and preclinical studies have consistently predicted efficacy against schizophrenia, with a low potential for causing extrapyramidal symptoms (EPS). In clinical trials, the efficacy of quetiapine was consistently superior to placebo and it was effective against both positive and negative symptoms. Quetiapine was also at least as effective as chlorpromazine or haloperidol in improving the symptoms of acute schizophrenia and moreover was associated with higher response rates. The consistent, placebo-level incidence of EPS associated with quetiapine in clinical trials was not seen with haloperidol. Thus, the combination of efficacy comparable to other antipsychotic agents, with an acceptable side effect and tolerability profile, provides support for the use of quetiapine as a first-line antipsychotic agent in the long-term treatment of schizophrenia.

[Use of electroconvulsive therapy in psychiatry]. / Einsatz der Elektrokrampftherapie in der Psychiatrie.

Electroconvulsive therapy (ECT) has antidepressive and antipsychotic effects. Since being introduced in Italy in 1938, its mode of action has still not been clarified. Treatment modalities have changed in many ways. ECT, in which a generalized epileptic seizure is provoked by electrical stimulation of the brain, is performed under short intravenous anesthesia and muscle relaxation. Considering careful previous clinical examination and anesthesiological and internal counterindications, ECT is a very safe form of treatment. Single cases of persisting memory impairment were described after the formerly common bilateral sinus wave stimulation. However, recent developments such as brief pulse stimulation, unilateral electrode placement, and individual stimulus titration (on the basis of EEG monitoring) make memory impairment as a consequence of ECT a rare event which mostly remits completely in 4-8 weeks. Today, ECT is performed mainly in patients suffering from severe, therapy-resistant affective or schizophrenic disorders. Pernicious catatonia and the neuroleptic malignant syndrome are emergency indications. Adequate ECT treatment requires a series of 6-12 individual sessions (every second or third day). In therapy-resistant depression, for which the greatest number of data are available, the response rate lies between 50 and 60%. This has been confirmed by a descriptive analysis of all ECT treatments at the Department of Psychiatry, University of Vienna, between 1994 and 2000. There is a need for controlled studies on continuation therapy subsequent to successful ECT.

Inverse relation between stimulus intensity and seizure duration: implications for ECT procedure.

A retrospective analysis of the effects of electroconvulsive therapy (ECT) was performed for two groups of 11 patients matched according to age (mean age, 52 years), sex, and diagnosis. Group 1 received ECT according to the age-dose protocol; group 2 was treated according to the titration method. A higher dose relative to the seizure threshold appeared to shorten the seizure duration. At the first treatment, the correlation between stimulus intensity and seizure duration was negative. In the titration group, the initial mean charge of 91 mC resulted in a seizure duration of 51 s, whereas in the age-dose group the seizure duration of 31 s was significantly shorter despite a higher mean charge of 312 mC. Seizure duration decreased during the ECT course in the group treated first at low dose (titrated) and then at 2.5 times the initial threshold. High stimulus intensity represented adequate treatment, although it produced short seizures. Thus, seizure duration proved to be an unreliable guideline for effective treatment. Furthermore, focus on seizure duration led to frequent high-dose restimulation in the elderly. The titration method obviates inadequate or excessive charges because the seizure threshold must first be determined.

Neurodevelopmental schizophrenia: obstetric complications, birth weight, premorbid social withdrawal and learning disabilities.

Neurodevelopmental schizophrenia seems to be caused by impaired cerebral development and is supposed to be associated with obstetric complications (OCs), poor premorbid adjustment, schizotypal or schizoid personality traits and negative symptoms. In the present study, 36 schizophrenic and schizoaffective patients and their same-sex, healthy siblings were recruited. They were diagnosed according to DSM-III-R, using structured psychiatric interviews and a consensus of 2 psychiatrists. Information on OCs, birth weight, premorbid social and learning functioning was obtained from their mothers. The main results show significant differences in OCs, birth weight, premorbid social and learning functioning between patients and their same-sex, healthy siblings. Using multivariate analyses, both premorbid variables were again identified to discriminate well between affected and unaffected siblings. Our findings seem to confirm the concept of schizophrenia as a neurodevelopmental process.

Association study of schizophrenia spectrum disorders and dopamine D3 receptor gene: is schizoaffective disorder special?

Alterations in dopamine neurotransmission have been hypothesized to play a role in the etiology of schizophrenia. We considered the dopamine D3 receptor gene on chromosome 3 as a candidate gene for an association analysis. We compared PCR-based genotype markers for healthy controls (n=120) and patients (n=95) with schizophrenia and schizophrenia spectrum disorders as diagnosed by consensus according to DSM-III-R. Our results possibly indicate an association of schizoaffective disorder with DRD3 homozygosity (P=0.056).

Association studies of candidate genes in bipolar disorders.

The aim of the investigation was to test genes for predisposition to bipolar affective disorder. Therefore, we studied candidate genes in a sample of unrelated patients (n = 102) and healthy controls (n = 79) of Austrian origin, searching for a possible association between polymorphic DNA markers of 5 candidate genes (serotonin transporter, 5-HTT; serotonin 2a receptor, 5-HT2a; dopamine D2 receptor, DRD2; dopamine D3 receptor, DRD3; dopamine transporter, DAT1) and bipolar disorder. There was an association between allelic and genotypic frequencies of 5-HTT and affection status (p = 0.014 and p = 0.017, respectively). However, after correction for multiple comparisons (Bonferroni), these results did not remain significant. Nevertheless, the findings might suggest that alterations in the structure of 5-HTT are involved in the pathogenesis of bipolar disorder, which could have major implications in treatment. No association between 5-HT2a, DRD2, DRD3, DAT1 and bipolar disorder was found.

Linkage of mood disorders with D2, D3 and TH genes: a multicenter study.

BACKGROUND: It has been suggested that the dopaminergic system is involved in the pathophysiology of mood disorders. We conducted a multicenter study of families with mood disorders, to investigate a possible linkage with genes coding for dopamine receptor D2, dopamine receptor D3 and tyrosine hydroxylase (TH). METHODS: Twenty three mood disorder pedigrees collected within the framework of the European Collaborative Project on Affective Disorders were analyzed with parametric and non-parametric linkage methods. Various potential phenotypes were considered, from a narrow (only bipolar as affected) to a broad (bipolar+major depressive+schizoaffective disorders) definition of affection status. RESULTS: Parametric analyses excluded linkage for all the candidate genes, even though small positive LOD (Limit of Detection) scores were observed for TH in three families. Non-parametric analyses yielded negative results for all markers. CONCLUSION: The D2 and D3 dopamine receptors were, therefore, not a major liability factor for mood disorders in our sample, whereas TH may play a role in a subgroup of patients.

TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling.

Bone resorption and remodeling is an intricately controlled, physiological process that requires the function of osteoclasts. The processes governing both the differentiation and activation of osteoclasts involve signals induced by osteoprotegerin ligand (OPGL), a member of tumor necrosis factor (TNF) superfamily, and its cognate receptor RANK. The molecular mechanisms of the intracellular signal transduction remain to be elucidated. Here we report that mice deficient in TNF receptor-associated factor 6 (TRAF6) are osteopetrotic with defects in bone remodeling and tooth eruption due to impaired osteoclast function. Using in vitro assays, we demonstrate that TRAF6 is crucial not only in IL-1 and CD40 signaling but also, surprisingly, in LPS signaling. Furthermore, like TRAF2 and TRAF3, TRAF6 is essential for perinatal and postnatal survival. These findings establish unexpectedly diverse and critical roles for TRAF6 in perinatal and postnatal survival, bone metabolism, LPS, and cytokine signaling.

Anticipation in schizophrenia.

In various genetic disorders it has been observed that the severity of illness increases and the age at onset decreases in successive generations. This phenomenon is termed anticipation. We sampled 15 families, totalling 123 individuals with at least one person affected by a disease of the schizophrenia spectrum in the index generation in each family (IG; n = 33 affected out of a total of 67 individuals) and in the parental generation (PG; n = 16 affected out of a total of 56 individuals). The pedigrees had originally been identified for linkage studies in schizophrenia. We found a significant difference between IG and PG regarding severity of illness as defined by Kendler et al's hierarchical model of categories of the schizophrenia spectrum (p = 0.001). Age at onset was significantly earlier in the IG (21.6 +/- 6.6 years) than in the PG (40.2 +/- 9.2 years) (p = 0.0001). We excluded a potential birth cohort effect by investigating a control sample consisting of two non-overlapping birth cohorts of patients with schizophrenia. Age at onset between the two groups of the control sample did not differ. Anticipation is an important aspect in the investigation of a possible genetic basis, at least for the familial form of schizophrenia. Active research on a molecular level with special emphasis on trinucleotide repeats might be able to shed further light on this phenomenon.

Long-term measurements of energy expenditure in severe burn injury.

The objective of this study was to evaluate resting energy expenditure (REE) in spontaneously breathing and artificially ventilated burn patients during the entire intensive care period. In 27 patients with 51 +/- 20% body surface area burned (BSAB) the REE was determined via indirect calorimetry. Three groups were formed according to the mortality prognosis index of Zawacki et al. In groups A, B, and C the predicted mortality rates were <20%, 20% to 80%, and >80%, respectively. The frequency of acute respiratory distress syndrome (ARDS), sepsis, renal failure, and mortality increased from group A toward group C. The REE test revealed wide individual variation and was usually overestimated by all tested formulas. The mean REE was comparable in groups A, B, and C during the first 20 days (49 +/- 16% vs. 59 +/- 21% vs. 57 +/- 18% above the REE calculated by the Harris-Benedict equation, or HBEE). The REE of patients in groups A and B declined after this period, whereas the long-term ventilated patients in the prognostically unfavorable group C showed a high REE up to the 45th day, usually accompanied by severe organ dysfunction and major metabolic disorders. During this time a nutritional regimen meeting the actual REE could not be achieved. In the clinical situation when indirect calorimetry is not available, REE can be stated to be 50% to 60% above HBEE in patients with >20% BSAB for at least 20 days. Expecting a stable clinical course in patients with a predicted mortality of <20% (group A), oral nutrition usually seems sufficient after a short period of artificial nutritional support (1 week). Patients with a predicted mortality of more than 20% have a complication-burdened clinical course and a prolonged period of ventilation (groups B and C). These patients need parenteral and enteral nutrition for at least 20 days after trauma to prevent severe malnutrition.

Treatment of severe mania with intravenous magnesium sulphate as a supplementary therapy.

Ten patients with severe, therapy-resistant manic agitation received magnesium sulphate infusions with a continuous magnesium (Mg) flow of approximately 200 mg/h (4353+/-836 mg/day; daily monitored Mg plasma level: 2.44+/-0.34 mmol/l) for periods ranging from 7 to 23 days. Concomitant psychotropic treatment consisted of lithium (n = 10), haloperidol (n = 5) and clonazepam (n = 10). During i.v. Mg treatment the mean values of the maximum dosages of neuroleptics (in chlorpromazine equivalents) and benzodiazepines (in diazepam equivalents) were significantly lower than during the last day of pretreatment (= baseline). Seven patients showed a marked improvement in the Clinical Global Impression scale. In case of bradycardia detected by the ECG monitor (n = 5), Mg flow was reduced and bradycardia disappeared promptly. Mg i.v. may be a useful supplementary therapy for the clinical management of severe manic agitation. This open study needs double-blind confirmation.

Myo-inositol in depressive and healthy subjects determined by frontal 1H-magnetic resonance spectroscopy at 1.5 tesla.

Myo-inositol (mI) as a precursor in the phosphatidylinositol second messenger system has been reported to be reduced in depression. By means of proton-magnetic resonance spectroscopy (1H-MRS) the mI levels in the frontal brain were investigated in vivo in the present study. Twenty-two patients (mean age: 42.8 +/- 10.7 years) with depressive episodes according to ICD 10 (HAMD score > 17) were compared to 22 healthy subjects (28.0 +/- 5.3 years). Two voxels (30 x 20 x 20 mm3) in the frontal lobes were examined in a Siemens Magnetom SP 4000 at 1.5 T (STEAM sequence: TR = 3500 ms, TE = 55 ms). With the total creatine (Cr) as an internal standard, mI/Cr ratios were calculated to follow the mI levels. In the left frontal lobe, mI/Cr was 0.43 +/- 0.06 in depressive patients and 0.46 +/- 0.07 in healthy subjects; concerning the right frontal lobe, mI/Cr was 0.46 +/- 0.08 and 0.48 +/- 0.06, respectively. There were neither significant differences between the two groups nor between the hemispheres. Since there was a significant positive correlation (R = 0.6) between the age and the mI/Cr in the right frontal lobe of depressed patients, age matched pairs analysis was performed (n = 2 x 10, in each group: nine females, one male, < 40 years). In the right frontal lobe, the patients' mI/Cr of 0.40 +/- 0.05 was now significantly lower than the controls' mI/Cr of 0.45 +/- 0.06. However, most of the patients were on antidepressive medication. Interestingly, it was exactly this group of patients which showed significantly lower mI levels. We regard our investigation as a pilot study which suggests an influence of age and antidepressants on mI levels and should be taken into consideration in further investigations in depressive patients.