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.

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.

An electron-microscope study of naturally occurring and cultured cells of Neisseria Gonorrhoeae.

Electron-microscope studies are reported in which gonococci grown in cultures are compared with those present in urethral exudates. Whereas naturally occurring cells presented a smooth appearance with parallel cell layers, cultured cells were rough and their surface layers appeared to be disorganised. Three different types of pili were observed in cultures; the most common type seemed to be a product of unfavourable growth conditions. The number of piliate cells in pus was variable but always much lower than the number of non-piliate cells found. A study of free endotoxin present in cultures was made and its fine structure is described. Further observations suggest that although the majority of gonococci are killed after phagocytosis, others survive and multiply--giving rise to clusters of gonococci within remnants of phagocytes. It is suggested that these coated clusters are infectious units.

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.

Efficacy of a combined paste formulation of praziquantel/febantel against immature Echinococcus granulosus and immature Echinococcus multilocularis.

A combined paste formulation of praziquantel (1 mg/kg of body wt)/febantel (10 mg/kg) given for 3 consecutive days gave 100% clearance of immature Echinococcus granulosus and E multilocularis in experimentally infected dogs. The formulation was extremely convenient to administer. Adverse reactions were not noted in the treated animals.

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.

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.

The location of bacterial antigens on sections of Bacillus cereus by use of the soluble peroxidase--anti-peroxidase complex and unlabelled antibody.

The location of antigens on sections of bacteria using the soluble peroxidase-anti-peroxidase complex in conjunction with unlabelled antibody is described. Using this technique, spore antigens have been detected in the cytoplasm of vegetative cells during forespore septum formation and subsequent stages of sporulation. Antigenic sites were first associated with poly-beta-hydroxybutyric acid granules and subsequently were found in increasing quantities in the cytoplasm of the sporangium. Vegetative cell antigens were located on the cell wall and in the cortical region during sporulation. During germination antigens were located in the cortical region, and during outgrowth on the cell wall. These findings are discussed in the light of existing biochemical data.

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.

Standardization and validation of the Multidimensional Observation Scale for Elderly Subjects (MOSES).

Objective, reliable and valid means of assessing the cognitive and psychosocial functionings of elderly persons are in demand for several reasons. Clinical needs for initial assessment, placement, and treatment monitoring are supplemented by the need for research tools for program evaluation and clinical trials. The set of behavior rating scales called the Multidimensional Observation Scale for Elderly Subjects (MOSES) was developed with these needs in mind. This paper describes the development of the MOSES scale and its rationale and norming on 2,391 residents of hospitals and residential settings. Internal consistency reliabilities in the .8 range and interrater reliabilities from .58 to .97 are reported. Validity correlations with the Zung Depression, Robertson Short Mental Status, Kingston Dementia, and the Physical and Mental Impairment-of-function Evaluation (PAMIE) scales were all satisfactory. The applications and advantages of the use of MOSES are discussed.

Eimeria chihuahuaensis sp.n. and other coccidia from Dipodomys spp. in El Paso County, Texas.

Dipodomys merriami Mearns and Dipodomys ordi Woodhouse were surveyed for coccidia in El Paso County, Texas. Infections with Eimeria chobotari, Eimeria dipodomysis and Eimeria balphae were 24.8%, 4.4%, and 11%, respectively, for D. ordi. Dipodomys merriami had an infection level of 23.8% with E. chobotari. Four animals concurrently harbored E. chobotari and E. balphae or E. dipodomysis or a new species Eimeria chihuahuaensis. Male and female host infection levels were not significantly different. The new species is described and photographs of 3 previously described Eimeria from Dipodomys are presented.

A reliable cross-circulation model: its use in studying humoral agents.

The purpose of this study was to develop an expeditious and reliable system to examine early alterations in proliferating liver tissue in vivo, uncomplicated by the haemodynamic changes associated with partial hepatectomy. We describe an improved, dependable, massive blood-exchange system, involving aortic blood transposition between two rats, which meets these criteria. The use of heparinized, silicone-rubber tubing and postoperative recirculation obviate the need for supplemental anticoagulants and minimizes haemorrhage. The procedure is rapid, and survival is > 95% for up to 48 h. We cite both the advantages of using this model generally to study humoral agents, and specific advantages associated with studies relating to a humoral hepatic mitogen. As an example in this regard, we present results obtained using this system to examine chromatin protein methylation in the intact liver of rats coupled to partially hepatectomized partners. Labelling with a mixture of 3H-methyl-L-methionine and 2-14C-DL-methionine, we demonstrate an enhancement of methylation in crude chromatin protein fractions obtained from intact liver tissue responding to humoral agents provided by blood exchanged from partially hepatectomized rats. This substituent enhancement appears to correlate with the degree of stimulation of DNA replication in this organ.

Saline infusion and amiloride in the management of lithium toxicity.

This paper describes the case of a 74 year old patient who became lithium toxic after 15 years of lithium therapy. We discuss the clinical presentation of the case and some of the possible causes of the sudden development of his toxicity. Although haemodialysis is the treatment of choice for severe lithium toxicity it is not always available. In this paper we propose that the combination of saline diuresis and Amiloride may provide a suitable alternative in the management of lithium toxicity.

VDJ genes in VHa2 allotype-suppressed rabbits. Limited germline VH gene usage and accumulation of somatic mutations in D regions.

In this study we investigate the molecular genetic basis for VHa- Ig. Knowing that the expression of VHa allotype Ig is suppressed by neonatal injection of rabbits with anti-VHa allotype antibody, and that the decreased level of VHa allotype Ig, VHa+, in the suppressed rabbits is compensated for by an increase in VHa- Ig, we determined the nucleotide sequences of 41 VDJ genes from a2/a2 rabbits neonatally suppressed for the expression of a2 Ig. We compared these nucleotide sequences to each other and identified two groups of VH sequences. We predict that the molecules of each group are encoded by one germline VH gene. Inasmuch as VHa+ Ig is encoded predominantly by one germline VH gene, VH1, it appears that more than 95% of the VDJ repertoire of rabbits may be encoded by as few as three germline VH genes. A genomic VDJ gene whose VH sequence was similar to those of group I molecules was expressed in vitro and was shown by ELISA to encode molecules of the VHa- allotype, y33. Analysis of the D regions in the VDJ gene indicated that germline D2b and D3 gene segments were preferentially used in the VDJ gene rearrangement. A comparison of sequences of D regions of the 41 VDJ gene rearrangements in 3-, 6-, and 9-wk-old rabbits to sequences of germline D gene segments showed an accumulation of mutations in the D region. Inasmuch as we have previously shown that V regions of rabbit VDJ genes are diversified, in part, by somatic gene conversion, it appears now that rabbit VDJ genes diversify by a combination of somatic mutation and somatic gene conversion.

IgG4 in human colostrum and human milk: continued local production or selective transport from serum.

Colostrum, mature milk, and paired plasma samples were obtained from 10 postpartum women who had not been previously studied. The geometric mean concentration of IgG4 in colostrum (3.3 micrograms/ml) was similar to the mean concentration in mature milk (3.0 micrograms/ml). The arithmetic mean for the percent of IgG = IgG4 was 10.3 +/- 3.3% for colostrum, 10.3 +/- 3.1% for mature milk, 2.6 +/- 0.3% for early plasma, and 1.7 +/- 0.3% for later plasma. Local mammary production of immunoglobulin was determined by subtracting the estimated serum contribution from the measured concentration in colostrum or milk. Evidence for local mammary production of IgG4 was found in 5 of 10 colostrum samples and 8 of 10 mature milk samples. These observations indicate that the previously observed selective enrichment of IgG4 in colostrum is also true for mature milk. These are the first studies suggesting continued local production of any immunoglobulin other than IgA in mature human breast milk.