Effect of pulsed methylprednisolone on pain, in patients with HTLV-1-associated myelopathy

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immune mediated myelopathy caused by the human T-lymphotropic virus type 1 (HTLV-1). The efficacy of treatments used for patients with HAM/TSP is uncertain. The aim of this study is to document the efficacy of pulsed methylprednisolone in patients with HAM/TSP. Data from an open cohort of 26 patients with HAM/TSP was retrospectively analysed. 1g IV methylprednisolone was infused on three consecutive days. The outcomes were pain, gait, urinary frequency and nocturia, a range of inflammatory markers and HTLV-1 proviral load. Treatment was well tolerated in all but one patient. Significant improvements in pain were: observed immediately, unrelated to duration of disease and maintained for three months. Improvement in gait was only seen on Day 3 of treatment. Baseline cytokine concentrations did not correlate to baseline pain or gait impairment but a decrease in tumour necrosis factor-alpha (TNF-α) concentration after pulsed methylprednisolone was associated with improvements in both. Until compared with placebo, treatment with pulsed methylprednisolone should be offered to patients with HAM/TSP for the treatment of pain present despite regular analgesia

Duration of ruptured membranes and mother-to-child HIV transmission: a prospective population-based surveillance study

OBJECTIVE: To investigate the association between duration of rupture of membranes (ROM) and mother-to-child HIV transmission (MTCT) rates in the era of combination antiretroviral therapy (cART). DESIGN: The National Study of HIV in Pregnancy and Childhood (NSHPC) undertakes comprehensive population-based surveillance of HIV in pregnant women and children. SETTING: UK and Ireland. POPULATION: A cohort of 2398 singleton pregnancies delivered vaginally, or by emergency caesarean section, in women on cART in pregnancy during the period 2007-2012 with information on duration of ROM; HIV infection status was available for 1898 infants. METHODS: Descriptive analysis of NSHPC data. MAIN OUTCOME MEASURES: Rates of MTCT. RESULTS: In 2116 pregnancies delivered at term, the median duration of ROM was 3 hours 30 minutes (interquartile range, IQR 1-8 hours). The overall MTCT rate for women delivering at term with duration of ROM ≥4 hours was 0.64% compared with 0.34% for ROM <4 hours, with no significant difference between the groups (OR 1.90, 95% CI 0.45-7.97). In women delivering at term with a viral load of <50 copies/ml, there was no evidence of a difference in MTCT rates with duration of ROM ≥4 hours, compared with <4 hours (0.14% for ≥4 hours versus 0.12% for <4 hour; OR 1.14, 95% CI 0.07-18.27). Among infants born preterm with infection status available, there were no transmissions in 163 deliveries where the maternal viral load was <50 copies/ml. CONCLUSIONS: No association was found between duration of ROM and MTCT in women taking cART. TWEETABLE ABSTRACT: Rupture of membranes of more than 4 hours is not associated with MTCT of HIV in women on effective ART delivering at term

Accelerometer use in young people with Down syndrome: A preliminary cross-validation and reliability study

Background Inadequate physical activity is a problem for people with Down syndrome and objective monitoring using accelerometers may be inaccurate in this population. Method This was a cross-validation and reliability study comparing two triaxial accelerometers (the SenseWear and RT3) to a criterion measure (the OxyCon Mobile) in 10 young people (M age = 20 ± 2) with Down syndrome. A ROC curve analysis was conducted to determine intensity thresholds from RT3 activity counts. Results During self-selected pace walking, the accelerometers overestimated energy expenditure and had large limits of agreement (SenseWear: −0.5–3.6 METs; RT3: −0.2–2.7 METs). At this pace, SenseWear armband step counts were highly correlated with observed steps (r = .98) but underestimated steps by up to 12%. We developed RT3 thresholds that demonstrated good to excellent sensitivity and specificity in classifying physical activity intensity. Conclusions SenseWear steps and RT3 activity count thresholds can be used to monitor physical activity in young people with Down syndrome, although energy expenditure estimates should be used with caution in this population

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Effect of Dietary Components on Larval Life History Characteristics in the Medfly (Ceratitis capitata: Diptera, Tephritidae)

Background: The ability to respond to heterogenous nutritional resources is an important factor in the adaptive radiation of insects such as the highly polyphagous Medfly. Here we examined the breadth of the Medfly’s capacity to respond to different developmental conditions, by experimentally altering diet components as a proxy for host quality and novelty. Methodology/Principal Findings: We tested responses of larval life history to diets containing protein and carbohydrate components found in and outside the natural host range of this species. A 40% reduction in the quantity of protein caused a significant increase in egg to adult mortality by 26.5%±6% in comparison to the standard baseline diet. Proteins and carbohydrates had differential effects on larval versus pupal development and survival. Addition of a novel protein source, casein (i.e. milk protein), to the diet increased larval mortality by 19.4%±3% and also lengthened the duration of larval development by 1.93±0.5 days in comparison to the standard diet. Alteration of dietary carbohydrate, by replacing the baseline starch with simple sugars, increased mortality specifically within the pupal stage (by 28.2%±8% and 26.2%±9% for glucose and maltose diets, respectively). Development in the presence of the novel carbohydrate lactose (milk sugar) was successful, though on this diet there was a decrease of 29.8±1.6 µg in mean pupal weight in comparison to pupae reared on the baseline diet. Conclusions: The results confirm that laboratory reared Medfly retain the ability to survive development through a wide range of fluctuations in the nutritional environment. We highlight new facets of the responses of different stages of holometabolous life histories to key dietary components. The results are relevant to colonisation scenarios and key to the biology of this highly invasive species

Composite-pulse magnetometry with a solid-state quantum sensor

The sensitivity of quantum magnetometers is challenged by control errors and, especially in the solid-state, by their short coherence times. Refocusing techniques can overcome these limitations and improve the sensitivity to periodic fields, but they come at the cost of reduced bandwidth and cannot be applied to sense static (DC) or aperiodic fields. Here we experimentally demonstrate that continuous driving of the sensor spin by a composite pulse known as rotary-echo (RE) yields a flexible magnetometry scheme, mitigating both driving power imperfections and decoherence. A suitable choice of RE parameters compensates for different scenarios of noise strength and origin. The method can be applied to nanoscale sensing in variable environments or to realize noise spectroscopy. In a room-temperature implementation based on a single electronic spin in diamond, composite-pulse magnetometry provides a tunable trade-off between sensitivities in the microT/sqrt(Hz) range, comparable to those obtained with Ramsey spectroscopy, and coherence times approaching T1

The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs

The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised

Safety evaluation of substituted thiophenes used as flavoring ingredients.

This publication is the second in a series by the Expert Panel of the Flavor and Extract Manufacturers Association summarizing the conclusions of its third systematic re-evaluation of the safety of flavorings previously considered to be generally recognized as safe (GRAS) under conditions of intended use. Re-evaluation of GRAS status for flavorings is based on updated considerations of exposure, structural analogy, metabolism, pharmacokinetics and toxicology and includes a comprehensive review of the scientific information on the flavorings and structurally related substances. Of the 12 substituted thiophenes reviewed here, 11 were reaffirmed as GRAS based on their rapid absorption, metabolism and excretion in humans and animals; the low estimated dietary exposure from flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels; and the lack of significant genotoxic and mutagenic potential. For one of the substituted thiophenes, 3-acetyl-2,5-dimethylthiophene, it was concluded that more detailed exposure information, comparative metabolism studies and comprehensive toxicity data, including an in-depth evaluation of the mechanism of action for any adverse effects observed, are required for continuation of its FEMA GRAS™ status. In the absence of these data, the compound was removed from the FEMA GRAS list

A qualitative exploration of the effect of visual field loss on daily life in home-dwelling stroke survivors

Objective: To explore the effect of visual field loss on the daily life of community-dwelling stroke survivors. Design: A qualitative interview study. Participants: Adult stroke survivors with visual field loss of at least six months’ duration. Methods: Semi-structured interviews were conducted with a non-purposive sample of 12 stroke survivors in their own homes. These were recorded, transcribed verbatim and analyzed with the framework method, using an inductive approach. Results: Two key analytical themes emerged. ‘Perception, experience and knowledge’ describes participant’s conflicted experience of having knowledge of their impaired vision but lacking perception of that visual field loss and operating under the assumption that they were viewing an intact visual scene when engaged in activities. Inability to recognize and deal with visual difficulties, and experiencing the consequences, contributed to their fear and loss of self-confidence. ‘Avoidance and adaptation’ were two typologies of participant response to visual field loss. Initially, all participants consciously avoided activities. Some later adapted to vision loss using self-directed head and eye scanning techniques. Conclusions: Visual field loss has a marked impact on stroke survivors. Stroke survivors lack perception of their visual loss in everyday life, resulting in fear and loss of confidence. Activity avoidance is a common response, but in some, it is replaced by self-initiated adaptive techniques