Cerebral [18 F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F]T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr⩾1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTE-related tauopathy in living subjects.

Deep sequencing analysis of defective genomes of parainfluenza virus 5 and their role in interferon induction.

Preparations of parainfluenza virus 5 (PIV5) that are potent activators of the interferon (IFN) induction cascade were generated by high-multiplicity passage in order to accumulate defective interfering virus genomes (DIs). Nucleocapsid RNA from these virus preparations was extracted and subjected to deep sequencing. Sequencing data were analyzed using methods designed to detect internal deletion and "copyback" DIs in order to identify and characterize the different DIs present and to approximately quantify the ratio of defective to nondefective genomes. Trailer copybacks dominated the DI populations in IFN-inducing preparations of both the PIV5 wild type (wt) and PIV5-VΔC (a recombinant virus that does not encode a functional V protein). Although the PIV5 V protein is an efficient inhibitor of the IFN induction cascade, we show that nondefective PIV5 wt is unable to prevent activation of the IFN response by coinfecting copyback DIs due to the interfering effects of copyback DIs on nondefective virus protein expression. As a result, copyback DIs are able to very rapidly activate the IFN induction cascade prior to the expression of detectable levels of V protein by coinfecting nondefective virus.

Heterocellular induction of interferon by negative-sense RNA viruses.

The infection of cells by RNA viruses is associated with the recognition of virus PAMPs (pathogen-associated molecular patterns) and the production of type I interferon (IFN). To counter this, most, if not all, RNA viruses encode antagonists of the IFN system. Here we present data on the dynamics of IFN production and response during developing infections by paramyxoviruses, influenza A virus and bunyamwera virus. We show that only a limited number of infected cells are responsible for the production of IFN, and that this heterocellular production is a feature of the infecting virus as opposed to an intrinsic property of the cells.

The representation of anaesthesia in children's literature.

Hospital admission for an operation can be a frightening and bewildering experience for a child. Effective communication is a prerequisite for all those who anaesthetise children, and good pre-operative preparation reduces anxiety and improves the child's ability to cope. Books are familiar to children and their use in providing information is an established practice in paediatric nursing. By searching web-based bookshops, we identified 19 books whose subject was admission to hospital for an operation. These books were analysed according to the accuracy of their description of the anaesthetic element of the surgical experience. Seven of these books can be recommended as useful descriptions of the key elements involved in general anaesthesia. These books provide a simple, effective and cheap resource to help children and their parents prepare for anaesthesia. They may also provide a useful tool for trainee anaesthetists by giving an insight into the child's level of understanding.

Arterial to end-tidal carbon dioxide tension difference in children with congenital heart disease.

In children with congenital cyanotic heart disease, right-to-left intracardiac shunting causes an obligatory difference between arterial and end-tidal carbon dioxide tension (PaCO2-PE'CO2) as venous blood, rich in carbon dioxide, is added to the arterial circulation. This obligatory PaCO2-PE'CO2 difference, which can be predicted from knowledge of oxygen saturation, haemoglobin concentration and PaCO2, increases as oxygen saturation decreases, most markedly when the haemoglobin concentration is high. A second possible cause of the PaCO2-PE'CO2 difference is the effect of pulmonary hypoperfusion caused by the shunt. We studied 60 children undergoing cardiac surgery and compared the predicted the PaCO2-PE'CO2 difference with measured values to investigate the extent to which additional factors influence the clinically observed PaCO2-PE'CO2. In many children, observed values were much greater than predicted, which is compatible with some degree of pulmonary hypoperfusion. However, this was not felt to represent the complete picture in all patients. Another cause of ventilation-perfusion mismatch was suspected in those children who showed a considerable improvement in oxygen saturation during ventilation with an increased FIO2. We believe that pulmonary congestion caused by large left-to-right shunts may further increase the PaCO2-PE'CO2 difference.

Noninvasive blood pressure measurement in the upper and lower limbs of anaesthetized children.

A group of 50 children, aged 5 months to 15 years, and who were undergoing routine surgery under general anaesthesia, were studied to investigate the difference in noninvasive blood pressure readings obtained from inflatable cuffs placed on the upper arm and the lower leg. In contrast to adult data, it was found that the blood pressure measured from the leg in children aged 8 years and under, was significantly lower than that measured from the arm. The leg cuff measurements could not, however, be reliably used to predict arm blood pressure.

Use of diclofenac in children with asthma.

This study investigated the effect of diclofenac on the lung function of 70 children aged 6-15 years with a diagnosis of asthma, recruited from a hospital respiratory clinic. Peak flow and a forced expiratory flow-volume loop were measured and the patients were then given 1-1.5 mg.kg-1 effervescent diclofenac orally. Spirometry was repeated at 10, 20 and 30 min, a 15% decrease in results being considered a significant reduction in lung function. No patient demonstrated a consistent reduction in lung function of > 15% during the study and there were no reports of wheezing or increased bronchodilator use after completion of the spirometry. In conclusion, we studied a group of genuine asthmatics and found no clinically significant incidence of bronchospasm with the use of a single therapeutic dose of diclofenac.

Suspected recurrence of malignant hyperthermia after post-extubation shivering in the intensive care unit, 18 h after tonsillectomy.

A 25-yr-old man, subsequently shown to be malignant hyperthermia (MH) susceptible by in vitro contracture testing, developed MH during anaesthesia for tonsillectomy. Prompt treatment, including dantrolene, led to rapid resolution of the metabolic crisis. Eighteen hours later the patient's trachea was extubated in the ICU, when he had been stable and apyrexial overnight. Twenty minutes after extubation, an episode of shivering was followed by the onset of tachycardia, hypertension, tachypnoea and a rapid increase in temperature. Recurrence of MH was suspected and the patient was given another dose of dantrolene with good clinical effect. Shivering in this patient may have been an indicator or a causative factor of recurrence of MH.

Human cytomegalovirus UL144 open reading frame: sequence hypervariability in low-passage clinical isolates.

Human cytomegalovirus (HCMV) infects a number of organs and cell types in vivo, leading to the hypothesis that HCMV disease and tissue tropism may be related to specific sequence variants. A potential component of HCMV variant strains is the UL144 open reading frame (ORF), which encodes a homologue of the herpesvirus entry mediator, HveA, a member of the tumor necrosis factor receptor superfamily. Sequence analysis of the UL144 ORF in 45 low-passage clinical isolates demonstrated significant strain-specific variability. In individual isolates, nucleotide substitutions occur at up to 21% of the 531 positions, resulting in approximately the same percentage of substitutions in the predicted 176-amino-acid sequence. Phylogenetic analysis indicated that the nucleotide and amino acid sequences diverge into three major groups. For genotypic comparison, the known hypervariable region encompassing the proteolytic cleavage site of the glycoprotein B (gB) gene was also sequenced. All of the isolates could be typed according to the four known gB groups; however, the gB and UL144 sequence groups appeared to be phylogenetically unlinked. The predicted UL144 product homology with tumor necrosis factor receptor family members, along with the unexpectedly high level of sequence variability of the UL144 ORF, suggests that the predicted product may play a role in HCMV infectivity and subsequent host disease.

A comparison of canal centering ability of four instrumentation techniques.

The purpose of this study was to compare three engine driven (nickel-titanium) NiTi instrument systems with hand files for their effect on canal transportation. Mesial roots of mature lower first molars with separate canals were paired on the basis of curvature and morphology. Canal lengths were standardized to 11 mm from orifice to apical foramen. Profile, Lightspeed, McXIM, and Flex-R hand filing techniques respectively were randomly assigned to one of the four canals of each tooth pair. The roots were mounted and sectioned at 1 mm, 3 mm, and 5 mm from working length using a modified Bramante technique. All sections were video imaged preoperatively after instrumentation to size #30 and after final instrumentation to size #40. The images were computer analyzed for changes in canal area and centering at each stage of instrumentation. Preparation time was also recorded. Data were analyzed using ANOVA. The NiTi systems remained better centered in the canal than stainless steel hand files. There were no significant differences among the NiTi systems at any level. The difference between hand filing and the NiTi techniques was more pronounced at size #40 than at size #30. The NiTi systems were all significantly faster than hand filing. No significant differences in preparation were found between the NiTi systems when canals were instrumented to the size nearest #40.

The role of the automation development group in analytical research and development at Dupont Merck.

Laboratory robotics has been firmly established in many non-QC laboratories as a valuable tool for automating pharmaceutical dosage form analysis. Often a single project or product line is used to justify an initial robot purchase thus introducing robotics to the laboratory for the first time. However, to gain widespread acceptance within the laboratory and to justify further investment in robotics, existing robots must be used to develop analyses for existing manual methods as well as new projects beyond the scope off the original purchase justification. The Automation Development Group in Analytical Research and Development is a team of analysts primarily devoted to developing new methods and adapting existing methods for the robot. This team approach developed the expertise and synergy necessary to significantly expand the contribution of robotics to automation in the authors' laboratory.