Background Urban birth, urban living, and ethnic minority status are established risk factors for schizophrenia, but the mechanisms are unclear. Previous evidence suggests a causal role of social ...exposures and adverse experiences, but experimental evidence is scarce. Methods We combine multimodal neuroimaging with ecological momentary assessment, geolocation and geospatial analysis in an epidemiological longitudinal sample in Germany. Results We find that established risk factors converge on the perigenual cingulate-amygdala-ventral striatal pathway as shown by structural and functional imaging, supporting a role for the ventral-striatal system in psychosis risk. Using a combination of PET and fMRI data in migrants, we suggest a mechanistic link to psychosis by increased dopamine release and synthesis in striatum secondary to prefrontal dysregulation. Importantly, the regulatory system identified overlaps with that implicated in racial stereotyping and prejudice. Moreover, an experiment measuring information flow during an exchange between migrants and non-migrants indicates that during a trust interaction, cultural distance governs the exchange. Conclusions This work shows a convergent risk circuit related to minority position and migration that could guide primary prevention of schizophrenia through reduction of manifestation risk by contextual intervention.
Disclosure
No significant relationships.
Genetic variation in catechol-O-methyltransferase (COMT), encoding an enzyme critical for prefrontal dopamine flux, has been studied extensively using both behavioral and neuroimaging methods. In ...behavior, pleiotropic action of a functional Val(158)Met (rs4680) polymorphism on executive cognition and emotional stability has been described and proposed to be of evolutionary significance (the 'warrior/worrier' hypothesis). We conducted a meta-analysis of all available neuroimaging studies of rs4680 to investigate the evidence for a neural substrate of this behavioral pleiotropy. We show significant association between the COMT genotype and prefrontal activation, with large (d=0.73) effect size without evidence for publication bias. Strong and opposing effects were found for executive cognition paradigms (favoring Met allele carriers) and emotional paradigms (favoring Val), providing meta-analytical evidence for a neural substrate for the pleiotropic behavioral effects of COMT genetic variation and validating the use of intermediate phenotypes as a method to bridge between genes and behavior.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives
This study aimed to investigate the recovery of limb function following a single intra‐articular injection of platelet‐rich plasma or hyaluronic acid in dogs with cranial cruciate ligament ...rupture treated with tibial plateau levelling osteotomy compared to dogs receiving no injection intraoperatively.
Materials and Methods
Sixty‐two dogs with cranial cruciate ligament rupture, body weights of 20 to 40 kg, and no other orthopaedic conditions were enrolled in this prospective, randomised, double‐blind, controlled study at the small animal clinic at LMU Munich. All dogs underwent tibial plateau levelling osteotomy. Based on random allocation, they received either a single intra‐articular injection of platelet‐rich plasma, hyaluronic acid or no injection intraoperatively. Gait analysis, clinical examinations, radiography of the stifle joint for osteoarthritis progression and two validated owner questionnaires were compared among groups at three timepoints postoperatively (6 weeks, 3 and 6 months). Limb function was primarily assessed by measuring the ground reaction forces.
Results
At all times postoperatively, no differences were observed among groups regarding clinical examinations, osteoarthritis score values, ground reaction forces or owner questionnaires. All dogs showed significant improvement in limb function clinically, in all ground reaction forces and in the validated questionnaires. Osteoarthritis progressed minimally during rechecks in all dogs regardless of the additional injection or not.
Clinical Significance
All dogs treated with tibial plateau levelling osteotomy for cranial cruciate ligament rupture showed improvements in limb function. No additive effect on faster recovery was demonstrated with the additional intra‐articular injection of platelet‐rich plasma or hyaluronic acid. Addition of platelet‐rich plasma/hyaluronic acid injections during tibial plateau levelling osteotomy is unnecessary considering the lack of benefit observed up to 6 months postoperatively.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
Since the first study published in the Lancet in 1976, structural neuroimaging has been used in psychosis with the promise of imminent clinical utility. The actual impact of structural ...neuroimaging in psychosis is still unclear.
Method
We present here a critical review of studies involving structural magnetic resonance imaging techniques in patients with psychosis published between 1976 and 2015 in selected journals of relevance for the field. For each study, we extracted summary descriptive variables. Additionally, we qualitatively described the main structural findings of each article in summary notes and we employed a biomarker rating system based on quality of evidence (scored 1–4) and effect size (scored 1–4).
Results
Eighty studies meeting the inclusion criteria were retrieved. The number of studies increased over time, reflecting an increased structural imaging research in psychosis. However, quality of evidence was generally impaired by small samples and unclear biomarker definitions. In particular, there was little attempt of replication of previous findings. The effect sizes ranged from small to modest. No diagnostic or prognostic biomarker for clinical use was identified.
Conclusions
Structural neuroimaging in psychosis research has not yet delivered on the clinical applications that were envisioned.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Structure and function in the human brain are closely related. At the onset of psychosis, brain imaging studies have identified robust changes in brain function and structure, but no data are ...available relating these two domains. After systematic literature searches, we included all available studies reporting whole-brain structural or cognitive functional imaging findings in first-episode (FEP) subjects in multimodal Signed Differential Mapping (SDM). Forty-three studies met the inclusion criteria. The structural database comprised 965 FEP subjects matched with 1040 controls whilst the functional cohort included 362 FEP subjects matched with 403 controls. The analysis identified conjoint structural and functional differences in the insula/superior temporal gyrus and the medial frontal/anterior cingulate cortex bilaterally. In these regions, large and robust decreases in grey matter volume were found with either reduced or enhanced activation. Meta-regression analyses indicated that grey matter volume in the anterior cingulate and left insular clusters was influenced by exposure to antipsychotics: patients receiving medication were more likely to show structural abnormalities in these regions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
There is a surge of interest in developing environmentally friendly solid-state-based cooling technology. Here, we point out that a fast cooling rate (≈10^{11} K/s) can be achieved by driving solid ...crystals to a high-temperature phase with a properly designed electric field pulse. Specifically, we predict that an ultrafast electric field pulse can cause a giant temperature decrease up to 32 K in PbTiO_{3} occurring on few picosecond time scales. We explain the underlying physics of this giant electric field pulse-induced temperature change with the concept of internal energy redistribution: the electric field does work on a ferroelectric crystal and redistributes its internal energy, and the way the kinetic energy is redistributed determines the temperature change and strongly depends on the electric field temporal profile. This concept is supported by our all-atom molecular dynamics simulations of PbTiO_{3} and BaTiO_{3}. Moreover, this internal energy redistribution concept can also be applied to understand electrocaloric effect. We further propose new strategies for inducing giant cooling effect with ultrafast electric field pulse. This Letter offers a general framework to understand electric-field-induced temperature change and highlights the opportunities of electric field engineering for controlled design of fast and efficient cooling technology.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily ...focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum. Results showed that total cerebellar grey matter volume was robustly reduced in SZ relative to HCs (Cohens's d=-0.35), with the strongest effects in cerebellar regions showing functional connectivity with frontoparietal cortices (d=-0.40). Effect sizes for cerebellar volumes were similar to the most consistently reported cerebral structural changes in SZ (e.g., hippocampus volume and frontotemporal cortical thickness), and were highly consistent across samples. Within groups, we further observed positive correlations between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in SZ). This cerebellocerebral structural covariance was strongest in SZ, suggesting common underlying disease processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar volume reduction in SZ was highly consistent across the included age span (16-66 years) and present already in the youngest patients, a finding that is more consistent with neurodevelopmental than neurodegenerative etiology. Taken together, these novel findings establish the cerebellum as a key node in the distributed brain networks underlying SZ.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Degrading metal alloys are a new class of implant materials suitable for bone surgery. The aim of this study was to investigate the degradation mechanism at the bone–implant interface of different ...degrading magnesium alloys in bone and to determine their effect on the surrounding bone. Sample rods of four different magnesium alloys and a degradable polymer as a control were implanted intramedullary into the femora of guinea pigs. After 6 and 18 weeks, uncalcified sections were generated for histomorphologic analysis. The bone–implant interface was characterized in uncalcified sections by scanning electron microscopy (SEM), element mapping and X-ray diffraction. Results showed that metallic implants made of magnesium alloys degrade in vivo depending on the composition of the alloying elements. While the corrosion layer of all magnesium alloys accumulated with biological calcium phosphates, the corrosion layer was in direct contact with the surrounding bone. The results further showed high mineral apposition rates and an increased bone mass around the magnesium rods, while no bone was induced in the surrounding soft tissue. From the results of this study, there is a strong rationale that in this research model, high magnesium ion concentration could lead to bone cell activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective
The aim of the study was to assess lameness in dogs with advanced osteoarthritis of the hip and knee joints after a single autologous point‐of‐care transplantation of the Stromal Vascular ...Fraction (SVF) into the affected joint.
Materials and methods
During a minilaparotomy, 10 g of falciform fat was removed from each patient for each joint to be treated. A modern and time‐saving procedure (ARC TM System, InGeneron GmbH, Houston, USA) was used for the in‐house preparation of the SVF, so that the isolated cells could be applied to the respective joint within 2 h after fat removal. In total, five knee joints of five patients and seven hip joints of four patients were treated.
Results
Improvement in lameness according to owner questionnaires was seen in 3 of 5 patients with knee joint arthritis and 2 of 4 patients with hip joint arthritis. Based on gait analysis, only one dog with gonarthrosis and one dog with coxarthrosis showed improvement up to a maximum of 3 months after surgery.
Conclusion
This is the first case series on the treatment of osteoarthrosis of the knee or hip joint using point‐of‐care transplantation of the SVF. In individual cases, this method may represent a therapeutic approach for the treatment in dogs with advanced cox‐ or gonarthrosis, although only a short‐term effect can be expected, which calls into question the effort and costs involved.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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