Effect of Iron Therapy on Platelet Counts in Patients with Inflammatory Bowel Disease-Associated Anemia

Secondary thrombocytosis is a clinical feature of unknown significance. In inflammatory bowel disease (IBD), thrombocytosis is considered a marker of active disease; however, iron deficiency itself may trigger platelet generation. In this study we tested the effect of iron therapy on platelet counts in patients with IBD-associated anemia.Platelet counts were analyzed before and after iron therapy from four prospective clinical trials. Further, changes in hemoglobin, transferrin saturation, ferritin, C-reactive protein, and leukocyte counts, before and after iron therapy were compared. In a subgroup the effect of erythropoietin treatment was tested. The results were confirmed in a large independent cohort (FERGIcor).A total of 308 patient records were available for the initial analysis. A dose-depended drop in platelet counts (mean 425 G/L to 320 G/L; p<0.001) was found regardless of the type of iron preparation (iron sulphate, iron sucrose, or ferric carboxymaltose). Concomitant erythropoietin therapy as well as parameters of inflammation (leukocyte counts, C-reactive protein) had no effect on the change in platelet counts. This effect of iron therapy on platelets was confirmed in the FERGIcor study cohort (n=448, mean platelet counts before iron therapy: 383 G/L, after: 310 G/L, p<0.001).Iron therapy normalizes elevated platelet counts in patients with IBD-associated anemia. Thus, iron deficiency is an important pathogenetic mechanism of secondary thrombocytosis in IBD

Structural and Functional Insights into the Pilotin-Secretin Complex of the Type II Secretion System

Gram-negative bacteria secrete virulence factors and assemble fibre structures on their cell surface using specialized secretion systems. Three of these, T2SS, T3SS and T4PS, are characterized by large outer membrane channels formed by proteins called secretins. Usually, a cognate lipoprotein pilot is essential for the assembly of the secretin in the outer membrane. The structures of the pilotins of the T3SS and T4PS have been described. However in the T2SS, the molecular mechanism of this process is poorly understood and its structural basis is unknown. Here we report the crystal structure of the pilotin of the T2SS that comprises an arrangement of four α-helices profoundly different from previously solved pilotins from the T3SS and T4P and known four α-helix bundles. The architecture can be described as the insertion of one α-helical hairpin into a second open α-helical hairpin with bent final helix. NMR, CD and fluorescence spectroscopy show that the pilotin binds tightly to 18 residues close to the C-terminus of the secretin. These residues, unstructured before binding to the pilotin, become helical on binding. Data collected from crystals of the complex suggests how the secretin peptide binds to the pilotin and further experiments confirm the importance of these C-terminal residues in vivo

Analgesic management of an eight-year-old Springer Spaniel after amputation of a thoracic limb

Analgesic agents were administered perioperatively to an eight-year-old Springer Spaniel undergoing amputation of its right thoracic limb. The amputation was carried out due to a painful, infiltrative and poorly differentiated sarcoma involving the nerves of the brachial plexus. A combination of pre-emptive and multimodal perioperative analgesic strategies was used; including intravenous (IV) infusions of fentanyl, morphine, lidocaine and ketamine

Sex dependency of inhibitory control functions

BACKGROUND: Inhibition of irrelevant responses is an important aspect of cognitive control of a goal-directed behavior. Females and males show different levels of susceptibility to neuropsychological disorders such as impulsive behavior and addiction, which might be related to differences in inhibitory brain functions. METHODS: We examined the effects of ‘practice to inhibit’, as a model of rehabilitation approach, and ‘music’, as a salient contextual factor in influencing cognition, on the ability of females and males to perform a stop-signal task that required inhibition of initiated or planned responses. In go trials, the participants had to rapidly respond to a directional go cue within a limited time window. In stop trials, which were presented less frequently, a stop signal appeared immediately after the go-direction cue and the participants had to stop their responses. RESULTS: We found a significant difference between females and males in benefiting from practice in the stop-signal task: the percentage of correct responses in the go trials increased, and the ability to inhibit responses significantly improved, after practice in females. While listening to music, females became faster but males became slower in responding to the go trials. Both females and males became slower in performing the go trials following an error in the stop trials; however, music significantly affected this post-error slowing depending on the sex. Listening to music decreased post-error slowing in females but had an opposite effect in males. CONCLUSIONC: Here, we show a significant difference in executive control functions and their modulation by contextual factors between females and males that might have implications for the differences in their propensity for particular neuropsychological disorders and related rehabilitation approaches

Estudo biológico e comportamental de lagartas de Spodoptera frugiperda visando à produção de Baculovírus spodoptera

A utilização de bioinseticida a base de Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) possui potencial para o controle de Spodoptera frugiperda (Lepidoptera: Noctuidae), porém sua obtenção em larga escala depende da maximização da produção in vivo. Assim, alguns fatores biológicos e comportamentais devem ser estudados para aperfeiçoar a produção de SfMNPV com intuito de disponibilizar um bioinseticida eficiente, economicamente viável e que possa ser usado no manejo de S. frugiperda nos mais diversos sistemas agrícolas. Entre os fatores relacionados ao hospedeiro, a temperatura e a idade para inoculação do vírus são de extrema importância, pois interferem diretamente no ciclo de vida e na replicação viral. O comportamento também deve ser avaliado, para evitar condições de criação do hospedeiro que favoreçam o canibalismo e causa prejuízo na multiplicação in vivo do SfMNPV. Assim, objetivou-se determinar a melhor condição térmica para criar as lagartas e a idade ideal, para inocular e multiplicar o vírus no hospedeiro, bem como, verificar a ocorrência do comportamento canibal em lagartas de S. frugiperda. Os experimentos foram conduzidos no Laboratório de Controle Microbiano de Insetos do Núcleo de Desenvolvimento Científico e Tecnológico em Manejo Fitossanitário de Pragas e Doenças (NUDEMAFI), localizado no Centro de Ciências Agrárias da UFES, em Alegre, Espírito Santo, Brasil. A pesquisa foi desenvolvida em duas etapas, a primeira para determinar a condição térmica e a idade ideais para criar e inocular, respectivamente, o hospedeiro com o vírus, para multiplicação in vivo de SfMNPV. A segunda etapa foi para avaliar o comportamento canibal de lagartas da espécie S. frugiperda criadas a 22, 25 e 31°C, inoculadas com SfMNPV quando com idades de 10, 8 e 4 dias, respectivamente, e mantidas em diferentes densidades populacionais (5, 10, 25 e 50 lagartas por recipiente). A mortalidade diminuiu com o aumento da temperatura e da idade do hospedeiro nas temperaturas de 25, 28 e 31 °C. O aumento na taxa de canibalismo foi 12 diretamente proporcional à densidade populacional quando as lagartas foram criadas a 22 °C, inoculadas aos 10 dias de idade e 25 ºC, inoculadas aos 8 dias e atingiram 63,5 e 62,5%, respectivamente na densidade populacional de 50 lagartas. Mas, quando as lagartas foram criadas a 31ºC e inoculadas com idade de 4 dias, a densidade populacional não afetou o comportamento canibal, taxa média de 24%, inferior aos outros tratamentos com 50 lagartas por recipiente. Demonstrando que é viável para a multiplicação viral, criar lagartas a 31 °C e aos 4 dias de idade inocular o vírus, podendo a partir de então colocar até 50 lagartas por recipiente, o que reduz a mão-de-obra necessária para individualizar as lagartas e otimiza o espaço físico em uma biofábrica. Portanto, se para otimizar o processo produção viral e o serviço em uma biofábrica, é preciso maximizar a produção viral, reduzir o tempo de multiplicação do vírus e o canibalismo entre as lagartas, com ausência de contaminação da criação, a temperatura e idade ideais para criação massal de S. frugiperda e inoculação do vírus nas lagartas, respectivamente, visando produção de baculovírus em larga escala são de 31 ºC e 4 dias

Meta-analysis of pre-clinical studies of early decompression in acute spinal cord injury:a battle of time and pressure

The use of early decompression in the management of acute spinal cord injury (SCI) remains contentious despite many pre-clinical studies demonstrating benefits and a small number of supportive clinical studies. Although the pre-clinical literature favours the concept of early decompression, translation is hindered by uncertainties regarding overall treatment efficacy and timing of decompression.We performed meta-analysis to examine the pre-clinical literature on acute decompression of the injured spinal cord. Three databases were utilised; PubMed, ISI Web of Science and Embase. Our inclusion criteria consisted of (i) the reporting of efficacy of decompression at various time intervals (ii) number of animals and (iii) the mean outcome and variance in each group. Random effects meta-analysis was used and the impact of study design characteristics assessed with meta-regression.Overall, decompression improved behavioural outcome by 35.1% (95%CI 27.4-42.8; I(2)=94%, p<0.001). Measures to minimise bias were not routinely reported with blinding associated with a smaller but still significant benefit. Publication bias likely also contributed to an overestimation of efficacy. Meta-regression demonstrated a number of factors affecting outcome, notably compressive pressure and duration (adjusted r(2)=0.204, p<0.002), with increased pressure and longer durations of compression associated with smaller treatment effects. Plotting the compressive pressure against the duration of compression resulting in paraplegia in individual studies revealed a power law relationship; high compressive forces quickly resulted in paraplegia, while low compressive forces accompanying canal narrowing resulted in paresis over many hours.These data suggest early decompression improves neurobehavioural deficits in animal models of SCI. Although much of the literature had limited internal validity, benefit was maintained across high quality studies. The close relationship of compressive pressure to the rate of development of severe neurological injury suggests that pressure local to the site of injury might be a useful parameter determining the urgency of decompression

Benefits of Objective Collapse Models for Cosmology and Quantum Gravity

We display a number of advantages of objective collapse theories for the resolution of long-standing problems in cosmology and quantum gravity. In particular, we examine applications of objective reduction models to three important issues: the origin of the seeds of cosmic structure, the problem of time in quantum gravity and the information loss paradox; we show how reduction models contain the necessary tools to provide solutions for these issues. We wrap up with an adventurous proposal to relate the spontaneous collapse events of objective collapse models to microscopic virtual black holes