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MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood.
We extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness.
The PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing.
Changes in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.
Very few zircon-bearing, kimberlite-hosted mantle eclogite xenoliths have been identified to date; however, the zircon they contain is crucial for our understanding of subcratonic lithospheric mantle evolution and eclogite genesis. In this study, we constrain the characteristics of zircon from mantle eclogite xenoliths based on existing mineralogical and geochemical data from zircons from different geological settings, and on the inferred origin of mantle eclogites. Given the likely origin and subsequent evolution of mantle eclogites, we infer that the xenoliths can contain zircons with magmatic, metamorphic and xenogenic (i.e. kimberlitic zircon) origins. Magmatic zircon can be inherited from low-pressure mafic oceanic crust precursors, or might form during direct crystallization of eclogites from primary mantle-derived melts at mantle pressures. Metamorphic zircon within mantle eclogites has a number of possible origins, ranging from low-pressure hydrothermal alteration of oceanic crustal protoliths to metasomatism related to kimberlite magmatism. This study outlines a possible approach for the identification of inherited magmatic zircon within subduction-related mantle eclogites as well as xenogenic kimberlitic zircon within all types of mantle eclogites. We demonstrate this approach using zircon grains from kimberlite-hosted eclogite xenoliths from the Kasai Craton, which reveals that most, if not all, of these zircons were most likely incorporated as a result of laboratory-based contamination.
One of the primary uses for transmission electron microscopy (TEM) is to measure diffraction pattern images in order to determine a crystal structure and orientation. In nanobeam electron diffraction (NBED), we scan a moderately converged electron probe over the sample to acquire thousands or even millions of sequential diffraction images, a technique that is especially appropriate for polycrystalline samples. However, due to the large Ewald sphere of TEM, excitation of Bragg peaks can be extremely sensitive to sample tilt, varying strongly for even a few degrees of sample tilt for crystalline samples. In this paper, we present multibeam electron diffraction (MBED), where multiple probe-forming apertures are used to create multiple scanning transmission electron microscopy (STEM) probes, all of which interact with the sample simultaneously. We detail designs for MBED experiments, and a method for using a focused ion beam to produce MBED apertures. We show the efficacy of the MBED technique for crystalline orientation mapping using both simulations and proof-of-principle experiments. We also show how the angular information in MBED can be used to perform 3D tomographic reconstruction of samples without needing to tilt or scan the sample multiple times. Finally, we also discuss future opportunities for the MBED method.
With the exception of near-occlusion, CEA is of overall benefit for selected patients with recent symptomatic carotid stenosis =50% (NASCET method), provided surgical stroke/death risk is low. The benefit is greater with greater stenosis, men, the elderly (aged =75y), most recent ischaemic event within 2w, irregular plaque surface, and impaired cerebral perfusion reserve. Patients with recent symptomatic carotid territory ischaemic events should be screened by Doppler ultrasonography, MRA, or CTA, confirming substantial stenosis with a second non-invasive investigation. Catheter angiography may be required to confirm uncertain results. The surgical peri-operative stroke and death rate (7% in RCTs) is higher in women, hypertension, peripheral arterial disease, and occlusion of the contralateral ICA or ipsilateral ECA. The experience of the surgeon and hospital are crucial, and audited peri-operative complication rates should be publically available. Carotid stenting is less invasive than CEA and causes fewer local complications (cranial neuropathy and neck haematoma), but carries a higher procedural risk of stroke. Stenting should be considered in younger patients, or those at increased risk from CEA. While stenting is of high risk for intracranial vertebral artery stenosis, risk is low for extracranial stenosis and should be considered for recurrent symptoms despite optimal medical therapy.
Despite advances in endovascular interventions, including the introduction of drug-eluting stents (DES), high target lesion revascularization (TLR) rates still burden the treatment of symptomatic lower-limb peripheral arterial disease (PAD). EluviaTM, a novel, sustained-release, paclitaxel-eluting DES, was shown to further reduce TLRs when compared with the paclitaxel-coated Zilver® PTX® stent, in the IMPERIAL randomized controlled trial. This evaluation estimated the cost-effectiveness of Eluvia when compared with Zilver PTX in Australia, based on 12-month clinical outcomes from the IMPERIAL trial.
A state-transition, decision-analytic model with a 12-month time horizon was developed from an Australian public healthcare system perspective. Cost parameters were obtained from the Australian National Hospital Cost Data Collection Cost Report (2016–17). All costs were captured in Australian dollars (AUD), where AUD 1 = USD 0.69 (June 2020). Complete sets of clinical parameters (primary patency loss, TLR, amputation, and death) and cost parameters from their respective distributions were bootstrapped in samples of 1,000 patients, for each intervention arm of the model. One-way and probabilistic sensitivity analyses were performed.
At 12 months, modeled TLR rates were 4.5 percent for Eluvia and 8.9 percent for Zilver PTX, and mean total direct costs were AUD 6,537 [USD 4,511] and AUD 6,908 [USD 4,767], respectively (Eluvia average per patient savings; overall cohort=AUD 371 [USD 256]; diabetic cohort=AUD 625 [USD 431]). In probabilistic sensitivity analyses, Eluvia was cost-effective relative to Zilver PTX in 92.0 percent of all simulations at a threshold of $10,000 per TLR avoided. Eluvia was more effective and less costly (dominant) than Zilver PTX in 76.0 percent of simulations.
In the first year after the intervention, Eluvia was more effective and less costly than Zilver PTX, making Eluvia the dominant treatment strategy for treatment of symptomatic lower-limb PAD, from an Australian public healthcare system perspective. These findings should be considered when formulating policy and practice guidelines in the context of priority setting and making evidence-based resource allocation decisions for treatment of PAD in Australia.
In Brazil, the buffalo milk market has been growing. However, identity and quality standards have not been established for this raw material, nor have proper distinctions between buffalo milk and bovine milk been defined. Currently, the State of Rio Grande do Sul (RS) has only three producers that supply raw material for officially marketed derivatives. The aim of this study was to determine the identity and quality standards of raw buffalo milk in this region. Samples were obtained biweekly from three farm cooling tanks between June 2017 and August 2018, to reach a total of 69 samples. The averages for the results of the physicochemical parameters fat, protein, lactose, total solids, SNF (solids-not-fat), calcium, density, FP, acidity and SCC were 5.5 g/100 g, 4.06 g/100 g, 5.07 g/100 g, 15.5 g/100 g, 9.96 g/100 g, 0.161 g/100 g, 1.034 g/ml, −0.527°C, 16°D and 95 × 103 cells/ml, respectively. With reference to the microbiological parameters, the mean of the Standard Plate Count (SPC) and thermotolerant coliforms were 9,0 × 104 CFU/ml and 1.6 × 102 MPN/ml, respectively. Regarding coagulase-positive staphylococci, 36 samples tested positive (52% of total). Neither Salmonella spp. nor Listeria monocytogenes, nor antibiotic or antiparasitic residues were detected in any sample. In conclusion, the buffalo milk used as raw material for dairy products in southern Brazil demonstrated satisfactory physicochemical and microbiological characteristics, in accordance with recent scientific literature.
Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.
We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.
We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.
This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).
Although well researched and praised in academic publications, function modelling (FM) does not have gained much traction in industrial application. To investigate into possible reasons for this, this publication researches literature of nine different projects where enhanced function-means modelling has been applied. The projects are analysed for their purpose of FM-use, applied benefits and discovered challenges of the FM approach. From this, the main challenges for FM application are the abstraction level of the modelling language as well as the lack of an interface to CAD modelling.
Fluoroquinolones (FQs) and extended-spectrum cephalosporins (ESCs) are associated with higher risk of Clostridioides difficile infection (CDI). Decreasing the unnecessary use of FQs and ESCs is a goal of antimicrobial stewardship. Understanding how prescribers perceive the risks and benefits of FQs and ESCs is needed.
We conducted interviews with clinicians from 4 hospitals. Interviews elicited respondent perceptions about the risk of ESCs, FQs, and CDI. Interviews were audio recorded, transcribed, and analyzed using a flexible coding approach.
Interviews were conducted with 64 respondents (38 physicians, 7 nurses, 6 advance practice providers, and 13 pharmacists). ESCs and FQs were perceived to have many benefits, including infrequent dosing, breadth of coverage, and greater patient adherence after hospital discharge. Prescribers stated that it was easy to make decisions about these drugs, so they were especially appealing to use in the context of time pressures. They described having difficulty discontinuing these drugs when prescribed by others due to inertia and fear. Prescribers were skeptical about targeting specific drugs as a stewardship approach and felt that the risk of a negative outcome from under treatment of a suspected bacterial infection was a higher priority than the prevention of CDI.
Prescribers in this study perceived many advantages to using ESCs and FQs, especially under conditions of time pressure and uncertainty. In making decisions about these drugs, prescribers balance risk and benefit, and they believed that the risk of CDI was acceptable in compared with the risk of undertreatment.
Pharmacogenetics in schizophrenia comprises pharmacokinetical and pharmacodynamical aspects as well as an approach to identify candidate genes associated with therapy response or side effects. Firstly focussing on classical drug targets like dopaminergic or serotonergic receptors, currently also developmental and regulatory genes presumably associated with effects of antipsychotic therapy are identified. The aim of this study was to investigate associations between therapy response in schizophrenic patients and different polymorphisms previously been identified within a genome wide array in rodents treated with MK-801 and/or haloperidol combined with some well-known schizophrenia candidate genes. We genotyped for 200 different polymorphisms in 285 schizophrenic patients, who were treated with different antipsychotics within randomized controlled trials. Psychopathology was measured weekly using the PANSS scale. Correlations between psychopathology and genotypes were calculated by using a linear model (ANCOVA).
We found significant associations between some well-known candidate genes (e.g. D2-, 5HT1A-, and α1A-receptors) and different PANSS subscales at baseline and after four weeks of antipsychotic treatment considered as therapy response. Furthermore we also identified several significant associations between some genes introduced from the animal model and psychopathology at baseline and towards therapy response. Some of them were formerly described in the literature (e.g. Homer1, Phospholipase C and Transthyretin), but most of them have not been related to schizophrenia or antipsychotic treatment by now (e.g. PLEKHA6, CLIC6 and SOSTDC1).
This indicates an involvement of genes in the pathophysiology of schizophrenia apart from yet known candidate genes and might further help in detecting differential therapy response in individuals with schizophrenia.
Until now, no studies have been published about the prevalence and needs of children with a mentally ill parent nor about interventions for this vulnerable group in the federal state of Saxony, Germany.
Therefore, the multi-centre study HELP-S for Children was initiated by the University of Leipzig in cooperation with the Technical University of Dresden. The aim of HELP-S for Children is to identifiy the prevalence and specific needs of children with a mentally ill parent.
All psychiatric outpatients of Leipzig and Dresden at an appointed date will be asked to participate in the study. Patients with minor children will be asked to fill out a detailed questionnaire about the perceived needs of their children and the existing and lacking support possibilities. Because there is no adequate instrument to assess the needs of the children with a mentally ill parent, we will develop a standardized questionnaire by using expert interviews and a pre-test with mentally ill parents.
The standardized questionnaire, which we will develop for this study, will be useable in other studies about needs of children with a mentally ill parent. Furthermore, we will gather information about the prevalence of children of mentally ill parents who are outpatients and about the specific needs of these children in the age of 0 to 18. These results will be presented and discussed during an expert workshop at the end of the project to explore ways to improve the situation of children with a mentally ill parent.
At present, limited quantitative data about computer addiction of young people are available. The study was designed to obtain the prevalence rate of computer addiction of children. A further objective was to increase the know-how about cyber-related addictions and their comorbidity of mental disorders.
Survey among children/young people and their parents using questionnaires CBCL, YSR, CSVK, OSV and View. The children answered the questions of CSVK and OSV, adolescents over the age of 11 further filled in YSR. The parents were interviewed using CBCL and View.
Data collection was in the paediatric psychiatry in Munich, data analysis in the University of Mainz.
100 patients between 8 and 18 years of age, who asked for an outpatient or inpatient treatment of various mental disorders, filled in the questionnaires from July to November 2009 (63% male and 37% female).
The prevalence of computer addiction was 3%. The prevalence of computer abuse was 7%.
The study exhibited a significant difference in gender: boys showed to be mainly addicted, girls mainly improper users.
It was further observed that the young cyber junkies use games, chats, emails and communities more frequently than average users.
In accordance with other studies it was determined that possible comorbidities are depression, anxiety disorders and aggressive behaviour.
In addition to other mental disorders, 3-6% of the patients in a German psychiatry were found to be computer addicted. It is important to do research for a better diagnostic and therapeutic treatment or implementation of preventive interventions.
Since the introduction of second generation antipsychotics (SGA) extrapyramidal-motor symptoms (EPS) have become a lesser problem in the treatment of schizophrenic patients. Yet, some SGAs display these adverse events and first generation antipsychotics are still widely used. Several genetic polymorphisms have been found to be associated with the occurance of EPS.
In this study we tried to identify genes related to EPS from an animal model and then replicated the findings in schizophrenic patients.
To identify new genes and show their relevance in the treatment of schizophrenic patients.
Rats were treated with haloperidol or saline and differential gene expression was assessed by using microarrays. We genotyped 285 schizophrenic patients for candidate genes and differentially expressed genes derived from the animal model. All patients were treated monotherapeutically with different antipsychotics within randomized controlled trials. EPS were assessed weekly using the ESRS and BAS. We used a linear model (ANCOVA) with PANSS total at baseline, type of medication and premedication as covariates for all investigated SNP's.
We found several SNPs to be associated with the occurance of EPS. The best results were obtained for SNPs within the genes of Phospholipase C epsilon 1 (PLCe1), Methionine Sulfoxide Reductase B3 (MSRB3), Chloride Intracellular Channel 6 (CLIC6), Prolactin Receptor (PRLR) and Dopamine Receptor D4 (DRD4). Effect sizes were between 1.7 and 4.9.
We could replicate some findings of the literature and identified four new genes possibly related to EPS. Some of these genes were recently related to schizophrenia.
Demographical and clinical characteristics have been reported to modulate the risk for suicide. This study analysed demographical and clinical characteristics with respect to lifetime suicide attempts in 500 individuals affected with schizophrenic or affective disorders. Suicide attempts were associated with poor premorbid social adjustment, low age at onset, low scores on the “Global Assessment Scale” and childlessness in females.
Cognitive behavioural therapy (CBT) is an important treatment in conjunction with psychopharmacotherapy in schizophrenia. However, there is only very little research on the effects of such interventions on brain function.
Recent studies have suggested that jumping to conclusions and a specific attributional bias is a predominant cognitive style in patients which might lead to the development of delusions. In this multi-centre fMRI trial, we investigated the effect of nine months of CBT on neural correlates of “jumping to conclusions” and the “attributional style” in patients with psychosis. Eighty patients and 80 control subjects were recruited in six centres and measured with 3-Tesla functional magnetic imaging (fMRI) before and after CBT.
It could be shown that CBT ameliorates differences in brain activations between patients and controls after nine months.
These results support the feasibility of fMRI multicenter trials and sheds further light into the mechanisms relating psychotherapy to brain function in Schizophrenia.
At present there is a paucity of standardised group behaviour therapy approaches targeting different kinds of personality disorders. On this background, our research group developed a new manualised treatment approach ("Schema-focused Emotive Behavioral Therapy"; SET), which integrates schematherapeutic, emotion-focused, cognitive and behavioural therapy methods. A multi-centre RCT-study evaluated SET based on a sample of 93 patients with personality disorders of clusters B and C. This study compared SET (n=47) with a classical Social Skills Training (SST, n=46) over 30 sessions. Patients were assessed before and after treatment and one year after study intake (follow-up). SET showed significantly higher improvements in several domains such as interpersonal behaviour, emotional coping, and symptomatic impairments. Clinically relevant effects on the SET occurred both in a reduction of the suffering from the disorder, severeness of the disorder, and hope for improvement. Furthermore, SET obtained a highly significant reduction of the dropout rate and a significantly increased use of therapy. Similar results for both comparison groups were found regarding behavioural coping and self-effectiveness. Results indicate that SET both entails a high acceptance of treatment and offers an adequate and effective group therapy for patients with personality disorders. From a clinical and economic point of view, SET promises to significantly contribute to mental health care.
Structural and functional deviations in schizophrenic patients with formal thought disorder (FTD) point towards a dysfunction within left sided language network.
Independent component analysis (ICA), a new approach to fMRI analysis, enables to target the question of a network dysfunction directly. Using this method in healthy controls it was possible to identify the language networks separately for the left and the right hemispheres In the present study we use ICA analysis to examine changes of the language network separate for each hemisphere in relation to the severity of FTD.
We hypothesize increasing disintegration with increasing severity of FTD only in the left sided language network while the right language network should remain unaffected.
We investigated 16 schizophrenic patients with different severity of FTD and matched healthy controls using ICA decomposition of the BOLD signal. The spatial similarity of the individual language networks was correlated to the severity of FTD.
The integrity of the left language network decrease with increasing severity of FTD (r = -0.79, p < 0.01), while the integrity of the right language network show no significant correlation to the severity of FTD.
For the first time the isolated breakdown of the left sided language network was linked specifically to schizophrenic FTD. This result unites older manly left hemispheric findings of structural and functional abnormalities in schizophrenic FTD.
In neuroleptic long-term medication, only part of the patients accept regular intake of neuroleptic drugs. The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication. In a 2-year prospective study, 122 patients were randomised to an interval and 164 to a continuous neuroleptic medication regimen. The drop out rates were 62.5% in the interval and 53.7% in the continuous medication group. Drop outs generally show more negative attitudes towards treatment. Patients with negative attitudes do not do better under interval medication. Moreover, this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen. Interval medication therefore is a strategy which can only be successful in highly cooperative, but not in treatment-reluctant patients.