Diffusion magnetic resonance imaging assessment of regional white matter maturation in preterm neonates.

PURPOSE: Diffusion magnetic resonance imaging (dMRI) studies report altered white matter (WM) development in preterm infants. Neurite orientation dispersion and density imaging (NODDI) metrics provide more realistic estimations of neurite architecture in vivo compared with standard diffusion tensor imaging (DTI) metrics. This study investigated microstructural maturation of WM in preterm neonates scanned between 25 and 45 weeks postmenstrual age (PMA) with normal neurodevelopmental outcomes at 2 years using DTI and NODDI metrics. METHODS: Thirty-one neonates (n = 17 male) with median (range) gestational age (GA) 32+1 weeks (24+2-36+4) underwent 3 T brain MRI at median (range) post menstrual age (PMA) 35+2 weeks (25+3-43+1). WM tracts (cingulum, fornix, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), optic radiations) were delineated using constrained spherical deconvolution and probabilistic tractography in MRtrix3. DTI and NODDI metrics were extracted for the whole tract and cross-sections along each tract to assess regional development. RESULTS: PMA at scan positively correlated with fractional anisotropy (FA) in the CST, fornix and optic radiations and neurite density index (NDI) in the cingulum, CST and fornix and negatively correlated with mean diffusivity (MD) in all tracts. A multilinear regression model demonstrated PMA at scan influenced all diffusion measures, GA and GAxPMA at scan influenced FA, MD and NDI and gender affected NDI. Cross-sectional analyses revealed asynchronous WM maturation within and between WM tracts.). CONCLUSION: We describe normal WM maturation in preterm neonates with normal neurodevelopmental outcomes. NODDI can enhance our understanding of WM maturation compared with standard DTI metrics alone.

Testing three-body quantum electrodynamics with trapped Ti20+ ions: evidence for a Z-dependent divergence between experiment and calculation.

We report a new test of quantum electrodynamics (QED) for the w (1s2p(1)P(1)→1s(2)(1)S(0)) x-ray resonance line transition energy in heliumlike titanium. This measurement is one of few sensitive to two-electron QED contributions. Systematic errors such as Doppler shifts are minimized in our experiment by trapping and stripping Ti atoms in an electron beam ion trap and by applying absolute wavelength standards to calibrate the dispersion function of a curved-crystal spectrometer. We also report a more general systematic discrepancy between QED theory and experiment for the w transition energy in heliumlike ions for Z>20. When all of the data available in the literature for Z=16-92 are taken into account, the divergence is seen to grow as approximately Z(3) with a statistical significance on the coefficient that rises to the level of 5 standard deviations. Our result for titanium alone, 4749.85(7) eV for the w line, deviates from the most recent ab initio prediction by 3 times our experimental uncertainty and by more than 10 times the currently estimated uncertainty in the theoretical prediction.

Paediatric angiodysplasia of the jejunum: a case report and review of the literature.

Gastrointestinal angiodysplasia (GIAD) of the jejunum is a rare cause of acute upper and lower gastrointestinal bleeding in the paediatric population. This is the case of a previously well 10-year-old girl who presented with acute rectal haemorrhage, haematemesis and syncope. Despite an exploratory laparotomy, the cause of bleeding remained unknown. A computerized tomography angiogram was performed once she was haemodynamically stable. It indicated bleeding in the jejunum. Repeat laparotomy was performed including enterotomy, copious small bowel washout and visualization of the whole small bowel. The lesion was identified at approximately 100 cm from the duodenojejunal flexure and confirmed by isolating the lesion and testing for bleeding. A 30 cm length of jejunum was resected and primary anastomosis performed. She recovered well and was discharged three days postoperatively. She remained well at six-month follow-up. This case highlights the importance of considering upper GIAD in an acute paediatric gastrointestinal bleed and the way in which surgical management can prevent a potentially fatal outcome.

Clavicle fracture nonunion in the paediatric population: a systematic review of the literature.

AIMS: Clavicle fracture nonunions are extremely rare in children. The aim of this systematic review was to assess what factors may predispose children to form clavicle fracture nonunions and evaluate the treatment methods and outcomes. METHODS: We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, aiming to find papers reporting clavicle fracture nonunion in children under the age of 18 years. Data was collected on patient demographics, fracture type, mechanism of injury (MOI), surgical intervention and reported outcome. Two independent reviewers evaluated all the data. RESULTS: A total of 13 articles reporting 21 cases of clavicle fracture nonunion were identified. The mean age at time of injury was 11.4 years (4 to 17). Falls were the most common MOI. The majority of nonunions occurred after displaced fractures on the right side. Six were refractures. Mean time of presentation following injury was 13.5 months (4 to 60). In all, 16 were treated surgically. Radiographic union was eventually achieved in 12 cases, with functional outcome satisfactory in all cases. CONCLUSION: Clavicle nonunion is an extremely rare but possible complication in children. The majority occur after displaced right-sided fractures or refractures and present around one year after injury. Surgical fixation provides good radiographic healing and functional outcomes. LEVEL OF EVIDENCE: IV.

Neuromuscular characterisation in Cerebral Palsy using hybrid Hill-type models on isometric contractions.

BACKGROUND: Muscles of individuals with Cerebral Palsy (CP) undergo structural changes over their lifespan including an increase in muscle stiffness, decreased strength and coordination. Being able to identify these changes non-invasively would be beneficial to improve understanding of CP and assess therapy effectiveness over time. This study aims to adapt an existing EMG-driven Hill-type muscle model for neuromuscular characterisation during isometric contractions of the elbow joint. METHODS: Participants with (n = 2) and without CP (n = 8) performed isometric force ramps with contraction levels ranging between 15 and 70% of their maximum torque. During these contractions, high-density EMG data were collected from the M. Biceps and Triceps brachii with 64 electrodes on each muscle. The EMG-driven Hill-type muscle model was used to predict torques around the elbow joint, and muscle characterisation was performed by applying a genetic algorithm that tuned individuals' parameters to reduce the RMS error between observed and predicted torque data. RESULTS: Observed torques could be predicted accurately with an overall mean error of 1.24Nm ± 0.53Nm when modelling individual force ramps. The first four parameters of the model could be identified relatively reliably across different experimental protocols with a full-scale variation of below 20%. CONCLUSION: An HD-EMG muscle modelling approach to evaluating neuromuscular properties in participants with and without CP has been presented. This pilot study confirms the feasibility of the experimental protocol and demonstrates some parameters can be identified robustly using the isometric contraction force ramps.

Ophthalmic outcomes of fractured zygomas.

In patients with fractures of the zygomatic complex, computed tomography (CT) often identifies extensive defects in the orbital floor. Some surgeons recommend routine exploration and repair of these defects during repair of the zygoma, while others advocate a more selective approach, but there is a paucity of evidence either way. We report a retrospective case series of 50 patients who had open reduction and internal fixation of zygomatic fractures by a single surgeon in the maxillofacial department at the John Radcliffe Hospital, Oxford, between 2011and 2014. The orbit was repaired only in those with severe diplopia, or restriction or malpositioning of the globe. Patients were evaluated by age, sex, aetiology, preoperative findings including diplopia and ocular malpositioning, fracture pattern, and morbidity. A total of 14 had preoperative ophthalmic signs. In five these were minimal so treatment was conservative. Nine (eight with diplopia and one with a malpositioned globe) had exploration and seven of them had the orbit repaired at the same time as the zygoma. This was not possible in the remaining two because of the complexity of the defect. There were no postoperative ophthalmic signs in the 41 who did not have orbit explored, or in the seven who had it repaired, and residual signs resolved after planned secondary reconstruction in the remaining two. We recommend that the orbit is explored only in patients with severe diplopia, or restriction or malpositioning of the globe.

Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene.

We have constructed a HeLa cell line that both expresses high levels of CD4 and contains a single integrated copy of a beta-galactosidase gene that is under the control of a truncated human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). This cell line, called CD4-LTR/beta-gal, can be used to determine quantitatively the titer of laboratory-adapted HIV strains, and the method used to do so is as sensitive as the determination of viral titers in a T-cell line by end point dilution. Using this cell line as a titer system, we calculated that HIV-1 stocks contain only one infectious particle per 3,500 to 12,000 virions. Virus derived from a molecular clone of a macrophagetropic provirus will not infect this cell line. We have also cocultivated peripheral blood lymphocyte cultures from HIV-infected individuals with the CD4-LTR/beta-gal indicator cells. In a majority of primary isolates (five of eight), including isolates from asymptomatic patients, rare virus-infected cells that can activate the beta-galactosidase gene are present.

Comparative studies on use of fresh and frozen peripheral blood lymphocyte specimens for isolation of human immunodeficiency virus and effects of cell lysis on isolation efficiency.

Heparinized blood specimens (n = 44) and frozen peripheral blood lymphocyte (PBL) specimens (n = 42) were used to evaluate the effects of lysis on human immunodeficiency virus (HIV) isolation. In the two respective groups, 17 and 27 specimens were HIV antibody positive. In the first group there were 8 and in the second group there were 25 that were symptomatic and were classified as indicating an acquired immunodeficiency syndrome-related condition or a pre-acquired immunodeficiency syndrome-related condition by the Centers for Disease Control definition. One-half of the cells from each specimen were frozen and thawed three times before cocultivation with uninfected lymphocytes, and the isolation rates from whole and lysed cells were compared. HIV was isolated from 15 (88%) of 17 fresh specimens and from 24 (89%) of 27 frozen PBLs from HIV antibody-positive patients, and lysis had no overall effect on the isolation rate, which suggested that frozen PBLs were as suitable as fresh blood for HIV isolation attempts and that it was not necessary to maintain cell integrity when submitting PBL samples. Of 21 asymptomatic patients, 20 were culture positive, and of 23 symptomatic patients, 19 were culture positive. Specimens from the 42 antibody-negative individuals were culture negative.

Isolation of human immunodeficiency virus from peripheral blood lymphocytes stored in various transport media and frozen at -60 degrees C.

The peripheral blood lymphocytes from 48 heparinized blood specimens from human immunodeficiency virus (HIV) antibody-positive individuals were divided into two aliquots. One aliquot was reconstituted in one of the following five media. Medium 1 consisted of tryptose broth with 0.5% gelatin; medium 2 consisted of RPMI 1640 containing 10% fetal bovine serum (FBS); medium 3 consisted of RPMI 1640 containing 20% FBS, Polybrene, interleukin 2, and anti-alpha interferon; medium 4 consisted of medium 2 plus 10% dimethyl sulfoxide (DMSO); and medium 5 consisted of medium 3 plus 10% DMSO. Lymphocytes were stored in these five media at -60 degrees C. The other aliquot of cells was stored at -190 degrees C in RPMI 1640 containing 50% FBS and 10% DMSO. After 1 week, both aliquots were cocultivated with phytohemagglutinin-stimulated uninfected peripheral blood lymphocytes, and presence of HIV was detected by the reverse transcriptase test. Storage in medium 1, 2, or 3 did not result in satisfactory isolation rates, but storage at -60 degrees C in medium 4 or 5 gave equal or better isolation rates than did storage at -190 degrees C. Inactivation of HIV by freezing of the cells without DMSO correlated with high antibody titers to core and polymerase proteins as measured by Western (immuno-) blotting.

Cellular latency in human immunodeficiency virus-infected individuals with high CD4 levels can be detected by the presence of promoter-proximal transcripts.

We have investigated the molecular basis of human immunodeficiency virus type 1 (HIV-1) latency in a tissue culture model and in HIV-infected people. We show that increased levels of Tat, but not Rev, can release the proviruses from latency in U1 cells. The absence of Tat in these cells is manifested by the accumulation of promoter-proximal viral transcripts, whereas the presence of Tat correlates with increased expression of viral proteins and an increase in promoter-distal transcripts. The presence of promoter-proximal transcripts also serves as a marker for latency in humans. We observed the exclusive presence of promoter-proximal viral transcripts in peripheral mononuclear cells from the majority (10/11) of asymptomatic HIV-infected individuals examined. Activation of these cells in vitro, and viremia in vivo, correlated with a switch from promoter-proximal transcription to promoter-distal transcription. These results suggest that the control between latency and replication of HIV in vivo is at the level of transcription elongation.