Cyclopropavir inhibits the normal function of the human cytomegalovirus UL97 kinase

Cyclopropavir (CPV) is active against human cytomegalovirus (CMV), as well as both variants of human herpesvirus 6 and human herpesvirus 8. The mechanism of action of CPV against CMV is similar to that of ganciclovir (GCV) in that it is phosphorylated initially by the CMV UL97 kinase, resulting in inhibition of viral DNA synthesis. Resistance to CPV maps to the UL97 kinase but is associated primarily with H520Q mutations and thus retains good antiviral activity against most GCV-resistant isolates. An examination of CMV-infected cultures treated with CPV revealed unusual cell morphology typically associated with the absence of UL97 kinase activity. A surrogate assay for UL97 kinase activity confirmed that CPV inhibited the activity of this enzyme and that its action was similar to the inhibition seen with maribavir (MBV) in this assay. Combination studies using real-time PCR indicated that, like MBV, CPV also antagonized the efficacy of GCV and were consistent with the observed inhibition of the UL97 kinase. Deep sequencing of CPV-resistant laboratory isolates identified a frameshift mutation in UL27, presumably to compensate for a loss of UL97 enzymatic activity. We conclude that the mechanism of action of CPV against CMV is complex and involves both the inhibition of DNA synthesis and the inhibition of the normal activity of the UL97 kinase.     

Whole-Genome Analysis of Exserohilum rostratum from an Outbreak of Fungal Meningitis and Other Infections

Exserohilum rostratum was the cause of most cases of fungal meningitis and other infections associated with the injection of contaminated methylprednisolone acetate produced by the New England Compounding Center (NECC). Until this outbreak, very few human cases of Exserohilum infection had been reported, and very little was known about this dematiaceous fungus, which usually infects plants. Here, we report using whole-genome sequencing (WGS) for the detection of single nucleotide polymorphisms (SNPs) and phylogenetic analysis to investigate the molecular origin of the outbreak using 22 isolates of E. rostratum retrieved from 19 case patients with meningitis or epidural/spinal abscesses, 6 isolates from contaminated NECC vials, and 7 isolates unrelated to the outbreak. Our analysis indicates that all 28 isolates associated with the outbreak had nearly identical genomes of 33.8 Mb. A total of 8 SNPs were detected among the outbreak genomes, with no more than 2 SNPs separating any 2 of the 28 genomes. The outbreak genomes were separated from the next most closely related control strain by ∼136,000 SNPs. We also observed significant genomic variability among strains unrelated to the outbreak, which may suggest the possibility of cryptic speciation in E. rostratum.     

Isometric grip strength and social gerontological research: results and analytic potentials of SHARE and SOEP

This paper shows that the measurement of hand grip strength provides a non-invasive and reliable objective health indicator for social science research and is easy to collect in general population surveys. Grip strength is not only a useful complement of self-reported indicators of health, but it also exhibits a considerable predictive power with regard to a number of further relevant variables for social gerontological research, such as mortality risks. New data from the 2004 Survey of Health, Ageing and Retirement in Europe (SHARE) and the 2006 wave of the German Socio-Economic Panel Study (SOEP) allow insightful methodological and very first substantive cross-sectional analyses of grip strength in Germany. The focus of the present study is on the analysis of individuals aged 50 or older. The experience of both surveys when measuring grip strength is consistently positive, particularly with regard to the respondents' feedback. Major determinants of isometric grip strength are - beyond the individual's gender - age, body size and weight. A multivariate analysis also provides evidence for a clear positive association between various health indicators and grip strength.     

Chronic kidney disease impairs prognosis in electrical storm

Journal of Interventional Cardiac Electrophysiology - The study sought to assess the prognostic impact of chronic kidney disease (CKD) in patients with electrical storm (ES). ES represents a...     

Interdisziplinäre Zusammenarbeit zwischen Zahnheilkunde und manueller Medizin

Patients with diseases of the musculoskeletal system often have concatenation problems with the craniomandibular system (CMS). Peripheral manual tests allow conclusions to be made as to whether a descendant disorder originating from the CMS is present or whether this originates from the periphery (ascendant). If this is an exclusively ascendant problem the patient is treated by manual medicine. Only patients with a descendant or mixed problematic will be treated by dental and/or dentofacial orthopedic methods. Manual therapy and physiotherapy can also be necessary. Successful therapy is often only possible in an interdisciplinary cooperation. An appropriate form interdisciplinary cooperation between dentistry and manual medicine will be demonstrated using a flow chart.     

Inspiratory stridor and dysphagia in two newborn infants caused by ectopic thymus tissue

We report two cases of ectopic cervical thymus, a solid thymic lesion, and a thymus cyst causing inspiratory stridor and mild dysphagia in the neonatal period. Because of the rarity of thymic dystopia, the two masses were initially misdiagnosed as more common entities, namely, lymph node enlargement and lymphangioma, respectively. The correct diagnosis was made only after surgical excision and histopathological examination. This case report is completed by a short review of embryogenic development, diagnostic procedures with differential diagnoses, and therapeutic outcome of ectopic thymus.     

Brief Report: Theatre as Therapy for Children with Autism Spectrum Disorder

The pilot investigation evaluated a theatrical intervention program, Social Emotional NeuroScience Endocrinology (SENSE) Theatre, designed to improve socioemotional functioning and reduce stress in children with autism spectrum disorder (ASD). Eight children with ASD were paired with typically developing peers that served as expert models. Neuropsychological, biological (cortisol and oxytocin), and behavioral measures were assessed in a pretest–posttest design. The intervention was embedded in a full musical theatrical production. Participants showed some improvement in face identification and theory of mind skills. The intervention shows potential promise in improving the socioemotional functioning in children with ASD through the utilization of peers, video and behavioral modeling, and a community-based theatrical setting.     

Affective picture processing: Alpha‐ and lower beta‐band desynchronization reflects emotional arousal

EEG power analysis is firmly established in the cognitive domain. This contrasts with emotional stimulus processing, which thus far has yielded a complex and ambiguous pattern of findings. To further advance understanding, the present study examined emotional stimulus processing in the context of task variations and baseline activity, which included several manipulation checks as well as internal replication of findings across conditions. Participants (N = 16) viewed erotic and romantic pictures, differing in stimulus arousal. Pictures were presented briefly (120 ms), and intertrial interval was systematically varied (~1 vs. ~8 s). In one condition, participants passively viewed the pictures, in the other, they performed an active picture categorization task. The processing of erotic compared to romantic images was associated with a decrease in power in the alpha and lower beta band in posterior and anterior sensor clusters between 600–1,000 ms poststimulus. The finding was robust and confirmed across conditions, different quantifications, and independent from baseline activity. Furthermore, key findings regarding explicit task effects as well as ERPs sensitive to emotional arousal were replicated. Results are discussed with respect to the hypothesis that alpha‐ and lower beta‐band activity may reflect cortical activation associated with emotional stimulus significance.