Mirror neuron activity during contagious yawning—an fMRI study

Yawning is contagious. However, little research has been done to elucidate the neuronal representation of this phenomenon. Our study objective was to test the hypothesis that the human mirror neuron system (MNS) is activated by visually perceived yawning. We used functional magnetic resonance imaging to assess brain activity during contagious yawning (CY). Signal-dependent changes in blood oxygen levels were compared when subjects viewed videotapes of yawning faces as opposed to faces with a neutral expression. In response to yawning, subjects showed unilateral activation of their Brodmann's area 9 (BA 9) portion of the right inferior frontal gyrus, a region of the MNS. In this way, two individuals could share physiological and associated emotional states based on perceived motor patterns. This is one component of empathy (motor empathy) that underlies the development of cognitive empathy. The BA 9 is reportedly active in tasks requiring mentalizing abilities. Our results emphasize the connection between the MNS and higher cognitive empathic functions, including mentalizing. We conclude that CY is based on a functional substrate of empath

Mirror neuron activity during contagious yawning-an fMRI study

Yawning is contagious. However, little research has been done to elucidate the neuronal representation of this phenomenon. Our study objective was to test the hypothesis that the human mirror neuron system (MNS) is activated by visually perceived yawning. We used functional magnetic resonance imaging to assess brain activity during contagious yawning (CY). Signal-dependent changes in blood oxygen levels were compared when subjects viewed videotapes of yawning faces as opposed to faces with a neutral expression. In response to yawning, subjects showed unilateral activation of their Brodmann's area 9 (BA 9) portion of the right inferior frontal gyrus, a region of the MNS. In this way, two individuals could share physiological and associated emotional states based on perceived motor patterns. This is one component of empathy (motor empathy) that underlies the development of cognitive empathy. The BA 9 is reportedly active in tasks requiring mentalizing abilities. Our results emphasize the connection between the MNS and higher cognitive empathic functions, including mentalizing. We conclude that CY is based on a functional substrate of empathy

Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation

Osteosclerotic metaphyseal dysplasia (OSMD) is a rare autosomal recessive sclerosing skeletal dysplasia. We report on a 34-year-old patient with sandwich vertebrae, platyspondyly, osteosclerosis of the tubular bones, pathologic fractures, and anemia. In the third decade, he developed osteonecrosis of the jaws, which was progressive in spite of repeated surgical treatment over a period of 11 years. An iliac crest bone biopsy revealed the presence of hypermineralized cartilage remnants, large multinucleated osteoclasts with abnormal morphology, and inadequate bone resorption typical for osteoclast-rich osteopetrosis. After exclusion of mutations in TCIRG1 and CLCN7 we performed trio-based exome sequencing. The novel homozygous splice-site mutation c.261G>A in the gene LRRK1 was found and co-segregated with the phenotype in the family. cDNA sequencing showed nearly complete skipping of exon 3 leading to a frameshift (p.Ala34Profs*33). Osteoclasts differentiated from the patient's peripheral blood monocytes were extremely large. Instead of resorption pits these cells were only capable of superficial erosion. Phosphorylation of L-plastin at position Ser5 was strongly reduced in patient-derived osteoclasts showing a loss of function of the mutated LRRK1 kinase protein. Our analysis indicates a strong overlap of LRRK1-related OSMD with other forms of intermediate osteopetrosis, but an exceptional abnormality of osteoclast resorption. Like in other osteoclast pathologies an increased risk for progressive osteonecrosis of the jaws should be considered in OSMD, an intermediate form of osteopetrosis

Agomelatine for depression in schizophrenia: A case-series

OBJECTIVES: Agomelatine, a melatonin (MT1/MT2) receptor agonist and 5-HT2C receptor antagonist, is a new antidepressant and a potential therapeutic option for major depressive episodes and negative symptoms in persons with schizophrenia. We investigated such treatment outcomes with respect to antidepressant efficacy, safety, and tolerability. METHODS: We report a consecutive case series of seven patients with schizophrenia and comorbid major depressive symptoms who received agomelatine for a period of at least six weeks in addition to stable doses of antipsychotic agents. General psychopathology, positive, negative and depressive symptoms were assessed with standardized interviews. Relevant blood parameters were assessed. RESULTS: Depressive symptoms improved significantly. Positive symptoms remained stable, while negative symptoms and global psychopathology improved significantly. Agomelatine was well tolerated in most patients. CONCLUSIONS: Our findings provide initial evidence that agomelatine is safe and efficacious in treating depressive symptoms in patients with schizophrenia. Furthermore, agomelatine seems to be effective for the treatment of negative symptoms. Randomized controlled trials are necessary to confirm these first observations

Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7‐related osteopetrosis

Human induced pluripotent stem cells (hiPSCs) hold great potential for modeling human diseases and the development of innovative therapeutic approaches. Here, we report on a novel, simplified differentiation method for forming functional osteoclasts from hiPSCs. The three-step protocol starts with embryoid body formation, followed by hematopoietic specification, and finally osteoclast differentiation. We observed continuous production of monocyte-like cells over a period of up to 9 weeks, generating sufficient material for several osteoclast differentiations. The analysis of stage-specific gene and surface marker expression proved mesodermal priming, the presence of monocyte-like cells, and of terminally differentiated multinucleated osteoclasts, able to form resorption pits and trenches on bone and dentine in vitro. In comparison to peripheral blood mononuclear cell (PBMC)-derived osteoclasts hiPSC-derived osteoclasts were larger and contained a higher number of nuclei. Detailed functional studies on the resorption behavior of hiPSC-osteoclasts indicated a trend towards forming more trenches than pits and an increase in pseudoresorption. We used hiPSCs from an autosomal recessive osteopetrosis (ARO) patient (BIHi002-A, ARO hiPSCs) with compound heterozygous missense mutations p.(G292E) and p.(R403Q) in CLCN7, coding for the Cl-/H+-exchanger ClC-7, for functional investigations. The patient's leading clinical feature was a brain malformation due to defective neuronal migration. Mutant ClC-7 displayed residual expression and retained lysosomal co-localization with OSTM1, the gene coding for the osteopetrosis-associated transmembrane protein 1, but only ClC-7 harboring the mutation p.(R403Q) gave strongly reduced ion currents. An increased autophagic flux in spite of unchanged lysosomal pH was evident in undifferentiated ARO hiPSCs. ARO hiPSC-derived osteoclasts showed an increased size compared to hiPSCs of healthy donors. They were not able to resorb bone, underlining a loss-of-function effect of the mutations. In summary, we developed a highly reproducible, straightforward hiPSC-osteoclast differentiation protocol. We demonstrated that osteoclasts differentiated from ARO hiPSCs can be used as a disease model for ARO and potentially also other osteoclast-related diseases. (c) 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Does psychopathology at admission predict the length of inpatient stay in psychiatry? Implications for financing psychiatric services

Background: The debate on appropriate financing systems in inpatient psychiatry is ongoing. In this context, it is important to control resource use in terms of length of stay (LOS), which is the most costly factor in inpatient care and the one that can be influenced most easily. Previous studies have shown that psychiatric diagnoses provide only limited justification for explaining variation in LOS, and it has been suggested that measures such as psychopathology might be more appropriate to predict resource use. Therefore, we investigated the relationship between LOS and psychopathological syndromes or symptoms at admission as well as other characteristics such as sociodemographic and clinical variables. Methods: We considered routine medical data of patients admitted to the Psychiatric University Hospital Zurich in the years 2008 and 2009. Complete data on psychopathology at hospital admission were available in 3,220 inpatient episodes. A subsample of 2,939 inpatient episodes was considered in final statistical models, including psychopathology as well as complete datasets of further measures (e.g. sociodemographic, clinical, treatment-related and psychosocial variables). We used multivariate linear as well as logistic regression analysis with forward selection procedure to determine the predictors of LOS. Results: All but two syndrome scores (mania, hostility) were positively related to the length of stay. Final statistical models showed that syndromes or symptoms explained about 5% of the variation in length of stay. The inclusion of syndromes or symptoms as well as basic treatment variables and other factors led to an explained variation of up to 25%. Conclusions: Psychopathological syndromes and symptoms at admission and further characteristics only explained a small proportion of the length of inpatient stay. Thus, according to our sample, psychopathology might not be suitable as a primary indicator for estimating LOS and contingent costs. This might be considered in the development of future costing systems in psychiatry

Assessing a financial incentive for reducing length of stay of psychiatric inpatients: Implications for financing psychiatric services

QUESTIONS UNDER STUDY: Restricted government budgets are forcing countries to implement more efficient health measures. Unlike in somatic medicine, the process of evaluating payment systems in psychiatry in Switzerland is ongoing. A pilot approach in one psychiatric hospital, here called “new remuneration system (NRS)”, was introduced to better control length of stay (LOS) by combining a lump sum with degressive daily rates. This is a first evaluation of the NRS in terms of a reduction of the LOS, and the prevention of early readmissions by analysing meaningful outcome categories. METHODS: The total sample consisted of N = 66,626 psychiatric inpatient episodes and a subsample of N = 60,847. Data were collected from the hospital using the NRS and three comparison hospitals in the Canton of Zurich. The observation period covered 2005 to 2011, the years before and after the implementation of the NRS in 2009. To examine the outcome categories, general logistic models were used. RESULTS: The median LOS at all four hospitals was 21 days (IQR: 46–8). In the NRS-hospital, there was a significantly higher proportion of 6 to10-day stays after 2009, indicating an influence of the lumpsum measure. At the same time, data revealed a somewhat lower proportion of readmissions within 30 days in the NRS-hospital. In general, effect sizes were small. CONCLUSIONS: Within the observation period of three years since 2009, the NRS had a small influence on LOS and early readmissions. The stability of effects needs to be monitored. More sophisticated modellings of the NRS might lead to further insights.ISSN:1424-7860ISSN:1424-399

Anomie

Sander U. Anomie. In: Gosepath S, Hinsch W, Rössler B, eds. Handbuch der politischen Philosophie und Sozialphilosophie. Vol 1. Berlin: De Gruyter; 2008: 33-36

Microglomerular Synaptic Complexes in the Sky-Compass Network of the Honeybee Connect Parallel Pathways from the Anterior Optic Tubercle to the Central Complex

While the ability of honeybees to navigate relying on sky-compass information has been investigated in a large number of behavioral studies, the underlying neuronal system has so far received less attention. The sky-compass pathway has recently been described from its input region, the dorsal rim area (DRA) of the compound eye, to the anterior optic tubercle (AOTU). The aim of this study is to reveal the connection from the AOTU to the central complex (CX). For this purpose, we investigated the anatomy of large microglomerular synaptic complexes in the medial and lateral bulbs (MBUs/LBUs) of the lateral complex (LX). The synaptic complexes are formed by tubercle-lateral accessory lobe neuron 1 (TuLAL1) neurons of the AOTU and GABAergic tangential neurons of the central body’s (CB) lower division (TL neurons). Both TuLAL1 and TL neurons strongly resemble neurons forming these complexes in other insect species. We further investigated the ultrastructure of these synaptic complexes using transmission electron microscopy. We found that single large presynaptic terminals of TuLAL1 neurons enclose many small profiles (SPs) of TL neurons. The synaptic connections between these neurons are established by two types of synapses: divergent dyads and divergent tetrads. Our data support the assumption that these complexes are a highly conserved feature in the insect brain and play an important role in reliable signal transmission within the sky-compass pathway

Natural Orifice Transluminal Endoscopic Surgery: Long-Term Experience with Hybrid Transvaginal Cholecystectomies

Objective. To assess outcome and safety of 571 hybrid natural orifice transluminal endoscopic surgery (NOTES) cholecystectomies. Methods. We retrospectively analyzed all consecutive NOTES cholecystectomies performed at our center between June 2009 and January 2018. All procedures were performed using a hybrid transvaginal technique, including an umbilical small-size trocar. End points, calculated at discharge, 30 and up to 90 days postoperatively, included intra- and postoperative morbidity assessed by the validated Clavien–Dindo classification and the Comprehensive Complication Index (CCI). Special focus was held on outcome and necessity of pre- and postoperative gynecological examinations. Results. We performed 571 hybrid NOTES cholecystectomies within 9 years. The vast majority were elective, 9.6% were emergency cholecystectomies. 6.7% of patients developed at least one complication until discharge, most of them minor (≤grade II). 30- and 90-day complication rates were 10.7% and 11%, respectively. Mean CCI at discharge and postoperative days 30 and 90 was 1.45 (±6.4), 2.3 (±7.7), and 2.4 (±7.8), respectively. Major complications (≥grade IIIa) occurred in 1.6% of patients, and 4 patients required emergency reoperation. No mortality was observed. In 9.8%, an additional abdominal trocar was placed. All patients underwent routine gynecological examination, whereof only 5 were rejected for transvaginal access preoperatively. In no case transvaginal access was discontinued intraoperatively due to gynecological disease. Conclusion. Hybrid NOTES transvaginal cholecystectomy represents a safe and feasible alternative to standard laparoscopic cholecystectomy. Preoperative gynecological examination is no longer routinely necessary, as intraoperative assessment is adequate