DTI-Traktographie der cerebro-cerebellären Bahnen und klinische Evaluation der Ataxie bei Patienten nach Behandlung von Tumoren der hinteren Schädelgrube im Kindes- und Jugendalter

Einleitung: Tumoren des Zentralnervensystems im Kindes- und Jugendalter entstehen häufig in der hinteren Schädelgrube. Die Überlebensrate für diese Tumoren konnte in den letzten Jahrzehnten verbessert werden. Allerdings weisen die Patienten nach zumeist intensiver Therapie Einschränkungen der Lebensqualität auf. Hierzu zählt unter anderem die Ataxie, deren neuroanatomische Substrate, die für das unterschiedliche Ausmaß der Ataxie verantwortlich sind, noch weitgehend unklar sind. Möglicherweise liegen der Entwicklung von ataktischen Langzeitdefiziten cerebro-cerebelläre Verbindungen zugrunde, deren differenzierte Untersuchungen jedoch noch ausstehen. Die vorliegende Arbeit untersucht posttherapeutische Veränderungen in der strukturellen Integrität der afferenten und efferenten Bahnen der reziproken cerebro-cerebellären Verbindungen sowie deren Zusammenhang mit dem Schweregrad der Ataxie bei Patienten mit Hirntumoren der hinteren Schädelgrube im Vergleich zu gesunden Probanden. Methode: Mittels Diffusion Tensor Imaging (DTI)-Traktographie wurden die cerebro-ponto-cerebellären (CPC) und cerebello-thalamo-cerebralen (CTC) Bahnen bei Patienten nach Behandlung von Tumoren der hinteren Schädelgrube im Kindes- und Jugendalter sowie bei gesunden Probanden dargestellt. Die fraktionelle Anisotropie (FA) und die Volumina der rekonstruierten Bahnen wurden bestimmt. Der statistische Zusammenhang zwischen den gemessenen DTI-Traktographiedaten und dem Schweregrad der Ataxie wurde analysiert. Die Evaluation der Ataxie erfolgte mittels „International Cooperative Ataxia Rating Scale (ICARS)“. Ergebnisse: Es wurden 10 Patienten mit pilozytischem Astrozytom (PA) und 9 mit Medulloblastom (MB) sowie 20 gesunde Probanden eingeschlossen. Der ICARS-Score war bei MB-Patienten gegenüber PA-Patienten signifikant erhöht. Bei der Volumenanalyse wurde eine signifikante Abnahme in der bilateralen CTC-Bahn bei MB-Patienten und in der linken CTC-Bahn bei PA-Patienten beobachtet. Die CPC-Bahn bot ausschließlich bei PA-Patienten ein signifikant reduziertes Volumen. Der ICARS-Score wies einen signifikanten Zusammenhang mit der Volumenreduktion der CTC-Bahn auf, wobei sich dies nicht für die CPC-Bahn bestätigte. Patienten mit Cerebellärem-Mutismus-Syndrom (CMS) boten die stärkste Volumenreduktion der CTC-Bahn und höhere ICARS-Scores im Vergleich mit Patienten ohne CMS. Die FA-Analyse für die gesamte CPC- und die gesamte CTC-Bahn zeigte keine signifikanten Unterschiede zwischen den Gruppen. Signifikant reduzierte FA-Werte fanden sich im Pedunculus cerebellaris superior (PCS) beider Patientengruppen, wobei im bilateralen PCS bei MB-Patienten und im linken PCS bei PA-Patienten ein signifikanter Zusammenhang mit dem ICARS-Score vorlag. Schlussfolgerung: Die Ergebnisse dieser Arbeit zeigen, dass insbesondere die Veränderung der CTC-Bahn zum Ausmaß der ataktischen Langzeitdefizite bei Kindern und Jugendlichen nach Behandlung von Tumoren der hinteren Schädelgrube beizutragen scheint. Die DTI-Traktographie kann dazu beitragen, die CTC-Bahn als relevante Struktur besser zu identifizieren und möglicherweise bei der Operation besser zu schonen, so dass assoziierte Spätfolgen reduziert werden können.Introduction: Tumors in the central nervous system of children and adolescents develop frequently in the posterior fossa. The survival rate of patients presenting with these tumors has improved in recent years. However, survivors usually experience restrictions in quality of life especially following intensive therapy. One in particular, Ataxia, of which the neuroanatomical substrates responsible for variations presented in the degree of ataxia remain largely unknown. Cerebrocerebellar connections are possible causes of long-term ataxia, notwithstanding differentiated studies have yet to be undertaken. This study focuses on post-therapeutic alterations in the structural integrity of the afferent and efferent tracts of the reciprocal cerebrocerebellar pathways and their relationship with the severity of ataxia in posterior fossa tumor survivors compared with healthy peers. Methods: Diffusion Tensor Imaging (DTI) tractography was used to visualize the cerebro-ponto-cerebellar (CPC) and cerebello-thalamo-cerebral (CTC) tracts of patients having undergone childhood posterior fossa tumor treatments as also healthy peers. The fractional anisotropy (FA) and volume of the reconstructed tracts were determined. The statistical relationship between these DTI-tractography data and the severity of ataxia was assessed. The degree of ataxia was evaluated using the “International Cooperative Ataxia Rating Scale (ICARS)”. Results: The study included ten patients with pilocytic astrocytoma (PA), nine with medulloblastoma (MB), and twenty healthy peers. ICARS scores were significantly higher in MB-patients compared with the PA-patients. The analysis of tract volume showed a significant decrease in the bilateral CTC-pathway in MB-patients and in the left-hand CTC-pathway in PA-patients. The CPC-pathway presented a significant volume reduction in PA-patients only. The ICARS score exhibited a significant relationship with the volume reduction of the CTC-pathway, but not with the CPC-pathway. Patients with cerebellar mutism syndrome (CMS) presented the most significant reductions in CTC-pathway volume and higher ICARS scores in comparison with patients without CMS. FA analysis for the entire CPC- and CTC-pathway showed no significant differences between the groups. Significantly lower FA values were found within the superior cerebellar peduncle (SCP) of both patient groups, and presented a significant relationship with the ICARS scores in bilateral SCP in MB-patients and in the left SCP in PA-patients. Conclusion: The results of this study suggest that the alteration of the CTC-pathway is of particular significance in contributing to the degree of long-term ataxia after childhood posterior fossa tumor treatments. DTI-tractography could contribute to improving the identification and even intraoperative preserving the important CTC-pathway in order to reduce the associated late effects

Spatiotemporal organization, regulation and function of traction during neutrophil chemotaxis

Despite recent advances in our understanding of biochemical regulation of neutrophil chemotaxis, little is known about how mechanical factors control neutrophils’ persistent polarity and rapid motility. Here, by using a human neutrophil-like cell line and human primary neutrophils, we describe a dynamic spatiotemporal pattern of tractions in neutrophils during chemotaxis. Tractions are located at both the leading and the trailing edge of neutrophils, where they oscillate with a defined periodicity. Interestingly, traction oscillations at the leading and the trailing edge are out of phase with the tractions at the front leading those at the back, suggesting a temporal mechanism that coordinates leading edge and trailing edge activities. The magnitude and periodicity of tractions depend upon the activity of non-muscle myosin IIA. Specifically, traction development at the leading edge requires myosin light chain kinase (MLCK)-mediated myosin II contractility and is necessary for α5β1-integrin activation and leading edge adhesion. Localized myosin II activation induced by spatially activated small GTPase Rho and its downstream kinase p160-ROCK, as previously reported, leads to contraction of actin-myosin II complexes at the trailing edge, causing it to de-adhere. Our data identify a key biomechanical mechanism for persistent cell polarity and motility

Thermogenic effect and substrate oxidation of protein from animal and plant sources in adults

Background: Changing nutrient source is one of the efforts to increase thermogenic effect (TEF) which may be significant for body weight reduction.Objective: The aim of this study was to investigate the effects of high protein diets using animal (chicken) and plant (tofu) sources on the thermogenic effect (TEF) and substrate oxidation.Method: Ten female adults (mean age 20.8+1.2 y) participated in two isocaloric diet ingestions. Each meal provided 30% of the daily basal energy need (32/26/42% as protein/fat/carbohydrates, respectively). Postprandial energy expenditure was measured by indirect calorimetry.Results: There were no significant differences in TEF and substrate oxidation. The postprandial fat oxidation rate was higher than that at the preprandial state, while carbohydrate and protein oxidation rates were lower.Conclusion: No differences were observed in TEF and substrate oxidation in animal- and plant-based diets. A high protein diet could be beneficial for weight loss, but animal protein does not appear to offer superior benefits compared to plant protein

Improving disclosure of medical error through educational program as a first step toward patient safety

Participant’s Response to medical errors. Description of data: Raw data of participant’s response to medical errors (3 clinical cases with different severity of error outcome), satisfaction and change after the education program. (XLSX 18 kb

Microhomology-mediated end joining induces hypermutagenesis at breakpoint junctions

Microhomology (MH) flanking a DNA double-strand break (DSB) drives chromosomal rearrangements but its role in mutagenesis has not yet been analyzed. Here we determined the mutation frequency of a URA3 reporter gene placed at multiple locations distal to a DSB, which is flanked by different sizes (15-, 18-, or 203-bp) of direct repeat sequences for efficient repair in budding yeast. Induction of a DSB accumulates mutations in the reporter gene situated up to 14-kb distal to the 15-bp MH, but more modestly to those carrying 18- and 203-bp or no homology. Increased mutagenesis in MH-mediated end joining (MMEJ) appears coupled to its slower repair kinetics and the extensive resection occurring at flanking DNA. Chromosomal translocations via MMEJ also elevate mutagenesis of the flanking DNA sequences 7.1 kb distal to the breakpoint junction as compared to those without MH. The results suggest that MMEJ could destabilize genomes by triggering structural alterations and increasing mutation burden

Sleep Quality, Fatigue, and Postpartum Depression of Mother at Six Months after Delivery

PURPOSE: This study was correlation study to identify the factors influencing sleep quality, fatigue, and postnatal depression in mothers who have given birth during the past 6 months. METHODS: The study was conducted using a survey with questionnaires to 329 mothers who visited E University Medical Center, or three local clinics located in D city, between August and October 2013. Collected data were analyzed using the SPSS/WIN 20.0 program. RESULTS: Out of 329 subjects, 18.2% showed that they had mild postnatal depression whereas 24.3% had severe postnatal depression. Accordingly, 42.5% reported having postnatal depression. Postnatal depression had a significant correlation with sleep hours after childbirth (r=-.16, p=.003), spousal support (r=-.28, p<.001), sleep quality (r=-.35, p<.001), physical fatigue (r=.66, p<.001), psychological fatigue (r=.69, p<.001), and neurosensory fatigue (r=.56, p<.001). Factors influencing postnatal depression include psychological fatigue, sleep quality, number of child births, and neurosensory fatigue, and these accounted for 53% of postnatal depression. CONCLUSION: Results indicate that factors influencing postnatal depression involve psychological fatigue, sleep quality, number of child births, and neurosensory fatigue. Therefore for nursing intervention for postpartum mothers, it is necessary to assess the level of depression, fatigue, and sleep quality, and to provide interventions to relieve depression

Effects of Maxillary Sinus Graft on the Survival of Endosseous Implants: A 10-Year Retrospective Study

Purpose: The aim of this study was to determine the survival rates of implants placed in grafted maxillary sinuses and compare the results obtained with graft materials, implant surfaces and timing of implant placement. Materials and Methods: Between January 1996 and December 2005, 391 implants are placed in 161 patients who underwent sinus grafting treatment simultaneously or separately at Ewha Womans University Hospital. According to inclusion critieria, 272 impants were placed in 102 patients with 112 sinus grafts (30 females, 72 males), aged 26 to 88 years (mean age 49.0±9.7). The follow-up period ranged from 12 to 134 months (mean F/U 47±32). Survival rates were evaluated according to graft material, implant surface and timing of implant placement, The Kaplan-Meier procedure and the log rank (Mantel-Cox) test were used to estimate survival rates and test for equality of survival rates between different groups of patients. Results: Ten-year cumultative survival rate for implants placed in the grafted sinuses was 90.1%. The survival rates for autogenous bone, combination and bone substitutes were 94.6%, 85.9% and 100% respectively (p\u3e0.05). According to implant surface, survival rates were 84.8% in machined group and 97.5% in rough group (p0.05). Conclusion: Ten-year cumultative survival rate for implants placed in the grafter sinuses was 90.1% Rough-shaped implants have a higher survival rate than machined-surface implants when placed in grafted sinuses. (p\u3c0.05)