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Objectives: In order to be able to evaluate the speech and language development of hearing impaired children psychometric data of speech-and language and developmental psychology together with audiological evaluation results are necessary Speech-and language development does not depend only on auditory perception, but also on general intelligence, more precisely on neuropsychological components such as auditory memory. Similar to children with normal hearing, hearing impaired children, might have so called neuro- functional weaknesses ("neuropsychologische Teilleistungsstörungen") additional to their hearing loss. These neuro-functional weaknesses will influence their speech and language development. One of the aims of our Follow-Up-Program of hearing impaired children is to give a differential profile of all neuropsychological abilities of a child and to identify underlying neuro-functional weaknesses. Result and Conclusion: The concept of neuropsychological functions relevant for speech and language development will be presented. First results of the long term data analysis of our hearing impaired children, supported with examples demonstrating the effects of specific neuro-functional weaknesses will be discussed. [ABSTRACT FROM AUTHOR]

Microcephaly is often caused by an impairment of the generation of neurons in the brain, a process referred to as neurogenesis. While most neurogenesis in mammals occurs during brain development, it thought to continue to take place through adulthood in selected regions of the mammalian brain, notably the hippocampus. However, the generality of neurogenesis in the adult brain has been controversial. While studies in mice and rats have provided compelling evidence for neurogenesis occurring in the adult rodent hippocampus, the lack of applicability in humans of key methods to demonstrate neurogenesis has led to an intense debate about the existence and, in particular, the magnitude of neurogenesis in the adult human brain. Here, we demonstrate the applicability of a powerful method to address this debate, that is, the in vivo labeling of adult human patients with 15 N-thymidine, a non-hazardous form of thymidine, an approach without any clinical harm or ethical concerns. 15 N-thymidine incorporation into newly synthesized DNA of specific cells was quantified at the single-cell level with subcellular resolution by Multiple-isotype imaging mass spectrometry (MIMS) of brain tissue resected for medical reasons. Two adult human patients, a glioblastoma patient and a patient with drug-refractory right temporal lobe epilepsy, were infused for 24 h with 15 N-thymidine. Detection of 15 N-positive leukocyte nuclei in blood samples from these patients confirmed previous findings by others and demonstrated the appropriateness of this approach to search for the generation of new cells in the adult human brain. 15 N-positive neural cells were easily identified in the glioblastoma tissue sample, and the range of the 15 N signal suggested that cells that underwent S-phase fully or partially during the 24 h in vivo labeling period, as well as cells generated therefrom, were detected. In contrast, within the hippocampus tissue resected from the epilepsy patient, none of the 2,000 dentate gyrus neurons analyzed was positive for 15 N-thymidine uptake, consistent with the notion that the rate of neurogenesis in the adult human hippocampus is rather low. Of note, the likelihood of detecting neurogenesis was reduced because of (i) the low number of cells analyzed, (ii) the fact that hippocampal tissue was explored that may have had reduced neurogenesis due to epilepsy, and (iii) the labeling period of 24 h which may have been too short to capture quiescent neural stem cells. Yet, overall, our approach to enrich NeuN-labeled neuronal nuclei by FACS prior to MIMS analysis provides a promising strategy to quantify even low rates of neurogenesis in the adult human hippocampus after in vivo 15 N-thymidine infusion. From a general point of view and regarding future perspectives, the in vivo labeling of humans with 15 N-thymidine followed by MIMS analysis of brain tissue constitutes a novel approach to study mitotically active cells and their progeny in the brain, and thus allows a broad spectrum of studies of brain physiology and pathology, including microcephaly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Roeder, Bonnin, Wu, Guerquin-Kern, Jabari, Brandner, Eyüpoglu, Gollwitzer, Hamer, Gerner, Döppner, Rummel, Englund, Heimke-Brinck, Borst, Daniel, Amann, Schlötzer-Schrehardt, Tonchev, Roessler, Schwab, Bergmann, Rizzoli and Huttner.)

Background: Timing of surgery remains controversial in patients with infective endocarditis and stroke. Guidelines on infective endocarditis suggest delaying surgery for up to 4 weeks. However, with early heart failure due to progression of the infection or recurrent septic embolism, urgent surgery becomes imperative., Methods: Out of 688 patients who were surgically treated for left-sided infective endocarditis, 187 presented with preoperative neurological events. The date of cerebral stroke onset was documented in 147 patients. The patients were stratified according to timing of surgery: 61 in the early group (0-7 days) vs. 86 in the delayed group (>7 days). Postoperative neurological outcome was assessed by the modified Rankin Scale., Results: Preoperative sepsis was more prevalent in patients with preoperative neurological complications (46.0% vs. 29.5%, p < 0.001). Patients with haemorrhagic stroke were operated on later (19.8% vs. 3.3%, p = 0.003). Postoperative cerebrovascular accidents were comparable between both groups ( p = 0.13). Overall, we observed good neurological outcomes ( p = 0.80) and a high recovery rate, with only 5% of cases showing neurological deterioration after surgery ( p = 0.29). In-hospital mortality and long-term survival were not significantly different in the early and delayed surgery groups (log-rank, p = 0.22)., Conclusions: Early valve surgery in high-risk patients with infective endocarditis and stroke can be performed safely and is not associated with worse outcomes.

BACKGROUND A retrospective analysis was conducted of the early and long-term outcomes after surgery for infective endocarditis (IE). MATERIAL AND METHODS We included 360 patients with IE operated upon between 1993 and 2012. The primary endpoint was overall cumulative postoperative survival at 30 days. Secondary endpoints were early postoperative outcomes and complication rates. Factors associated with 30-day mortality were analyzed. RESULTS Mean age was 58.7±14.7 years and 26.9% (n=97) were female. The mean follow-up was 4.41±4.53 years. Postoperative survival was 81.7% at 30 days, 69.4% at 1 year, 63.3% at 5 years, and 63.3% at 10 years. Non-survivors were significantly older (p=0.014), with higher NYHA Class (p=0.002), had higher rates of preoperative diabetes mellitus (p=0.005), renal failure (p=0.001), and hepatic disease (p=0.002). Furthermore, non-survivors had higher baseline alanine aminotransferase (ALT, p=0.048), aspartate transaminase (AST, p=0.027), bilirubin (p=0.013), white cell count (WCC, p=0.034), and CRP (p=0.049). Factors associated with 30-day mortality were longer duration of surgery, CPB, and aortic cross-clamping times (p<0.001, p<0.001, and p=0.003, respectively), as well as higher RBC, FFP, and platelet transfusion requirements (p<0.001, p=0.005, and p<0.001, respectively). Multivariate logistic regression analysis revealed liver cirrhosis (OR 4.583, 95-CI: 1.096-19.170, p=0.037) and longer CPB time (OR 1.025, 95-CI 1.008-1.042, p=0.004) as independent predictors of 30-day mortality. CONCLUSIONS Surgical treatment of IE shows satisfactory early, midterm, and long-term results. Multivariate logistic regression analysis revealed cirrhosis and longer CPB time as independent predictors of 30-day mortality.

The 'Individualized Therapy for Relapsed Malignancies in Childhood' (INFORM) precision medicine study is a nationwide German program for children with high-risk relapsed/refractory malignancies, which aims to identify therapeutic targets on an individualised basis. In a pilot phase, reported here, we developed the logistical and analytical pipelines necessary for rapid and comprehensive molecular profiling in a clinical setting. Fifty-seven patients from 20 centers were prospectively recruited. Malignancies investigated included sarcomas (n = 25), brain tumours (n = 23), and others (n = 9). Whole-exome, low-coverage whole-genome, and RNA sequencing were complemented with methylation and expression microarray analyses. Alterations were assessed for potential targetability according to a customised prioritisation algorithm and subsequently discussed in an interdisciplinary molecular tumour board. Next-generation sequencing data were generated for 52 patients, with the full analysis possible in 46 of 52. Turnaround time from sample receipt until first report averaged 28 d. Twenty-six patients (50%) harbored a potentially druggable alteration with a prioritisation score of 'intermediate' or higher (level 4 of 7). Common targets included receptor tyrosine kinases, phosphoinositide 3-kinase-mammalian target of rapamycin pathway, mitogen-activated protein kinase pathway, and cell cycle control. Ten patients received a targeted therapy based on these findings, with responses observed in some previously treatment-refractory tumours. Comparative primary relapse analysis revealed substantial tumour evolution as well as one case of unsuspected secondary malignancy, highlighting the importance of re-biopsy at relapse. This study demonstrates the feasibility of comprehensive, real-time molecular profiling for high-risk paediatric cancer patients. This extended proof-of-concept, with examples of treatment consequences, expands upon previous personalised oncology endeavors, and presents a model with considerable interest and practical relevance in the burgeoning era of personalised medicine., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Infective endocarditis is a life threatening complication of intravenous drug abuse, which continues to be a major burden with inadequately characterised long-term outcomes. We reviewed our institutional experience of surgical treatment of infective endocarditis in active intravenous drug abusers with the aim of identifying the determinants long-term outcome of this distinct subgroup of infective endocarditis patients., Methods: A total of 451 patients underwent surgery for infective endocarditis between January 1993 and July 2013 at the University Hospital of Heidelberg. Of these patients, 20 (7 female, mean age 35 ± 7.7 years) underwent surgery for infective endocarditis with a history of active intravenous drug abuse. Mean follow-up was 2504 ± 1842 days., Results: Staphylococcus aureus was the most common pathogen detected in preoperative blood cultures. Two patients (10%) died before postoperative day 30. Survival at 1, 5 and 10 years was 90%, 85% and 85%, respectively. Freedom from reoperation was 100%. Higher NYHA functional class, higher EuroSCORE II, HIV infection, longer operating time, postoperative fever and higher requirement for red blood cell transfusion were associated with 90-day mortality., Conclusions: In active intravenous drug abusers, surgical treatment for infective endocarditis should be performed as extensively as possible and be followed by an aggressive postoperative antibiotic therapy to avoid high mortality. Early surgical intervention is advisable in patients with precipitous cardiac deterioration and under conditions of staphylococcal endocarditis. However, larger studies are necessary to confirm our preliminary results.

ABSTRACT The Fort St. Vrain Nuclear Generating Station was a one-of-its-kind High Temperature Gas Cooled Reactor located near Denver, CO. Due to operational difficulties, the reactor was permanently shut down in August 1989. Plans to ship the spent reactor fuel to Idaho were thwarted by the Governor of Idaho. The inability to ship the spent reactor fuel offsite necessitated the construction of an Independent Spent Fuel Storage Installation (ISFSI) in order to proceed with the decommissioning of the reactor. After loading the ISFSI, decommissioning of the reactor was initiated and successfully completed. At the same time, the site was repowered using natural gas. As part of a settlement with the owner of the reactor, the U.S. Department of Energy agreed to take title to the spent fuel in the ISFSI and obtain an NRC license for the facility. The license for the ISFSI was transferred to the DOE in June 1999. Day-to-day operations of the ISFSI are accomplished by the DOE's Maintenance and Operations contractor, Bechtel Babcock Wilcox Idaho (BBWI). BBWI also operates the Three Mile Island Unit 2 ISFSI in Idaho for the DOE. This paradigm for ISFSI operations has been highly successful and is expandable to additional ISFSIs that may come under the jurisdiction of the DOE.

The purpose of the present study was to investigate attachment and fear of intimacy among rape survivors. As previous research has documented that several domains of functioning are affected by the experience of rape, it was hypothesized that the survivors may have difficulties with attachment and intimacy. Subjects were selected from an undergraduate general psychology class on the basis of responses to a questionnaire on sexual experiences. All of the subjects were female and included 44 rape survivors and 57 controls. As predicted, rape survivors reported greater fear surrounding intimacy. Survivors also differed from the controls on all of the attachment dimensions. They reported less confidence in others' dependability, less comfort with closeness, and more fear of abandonment. Trait anxiety was also controlled in the analyses, and except for fear of abandonment, it attenuated the differences between the groups such that they were no longer significantly different.