Influence of human chorionic gonadotropin (hCG) on in vitro growth of Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>During pregnancy, women are more susceptible to <it>Plasmodium falciparum </it>infections and frequently have a higher parasitaemia than non-pregnant women. Several mechanisms are responsible for their increased susceptibility, including down-modulation of immune responses that aid in parasite clearance and sequestration of infected erythrocytes in the placenta. Early in pregnancy, a third mechanism may contribute to higher parasitaemia, since it has been reported that addition of human chorionic gonadotropin (hCG) to <it>in vitro </it>cultures of the NF54-strain of <it>P. falciparum </it>results in increased parasite growth rates. The goal of this study was to further examine the effect of hCG on <it>P. falciparum </it>growth.</p> <p>Methods</p> <p>The NF54-3D7, FVO and 7G8 strains of <it>P. falciparum </it>were cultured <it>in vitro </it>with various physiological concentrations of hCG purchased from three sources. Infected erythrocytes were also co-cultured with a human cell line that naturally secretes hCG.</p> <p>Results</p> <p>Results from 14 experiments using different combinations of parasite strains and concentrations of hCG from different sources, as well as the co-culture studies, failed to provide convincing evidence that hCG enhances parasite growth <it>in vitro</it>.</p> <p>Conclusion</p> <p>Based on these data, it seems unlikely that hCG has a direct effect on the rate of parasite growth early in pregnancy.</p

Regular Dimpled Nickel Surfaces for Improved Efficiency of the Oxygen Evolution Reaction

Persistent bubble accumulation during the oxygen evolution reaction (OER) can effectively block catalytically active surface sites and reduce overall system performance. The OER is an essential half-reaction with relevance to metal–air batteries, fuel cells, and water electrolysis for power to gas applications. The renewable energy sector could benefit from the identification of surface morphologies that can effectively reduce the accumulation of bubbles on electrocatalytic surfaces. In this work, regular dimpled nickel (Ni) features were prepared to investigate how electrode morphology and therefore its roughness and wetting properties may affect the efficiency of the OER. The dimpled Ni features were prepared using spherical poly(styrene) (PS) templates with a diameter of 1 μm. The electrodeposition against regular, self-assembled arrays of PS templates was tuned to produce four types of dimpled features each with a different depth. Enhancements to the OER efficiency were observed for some types of dimpled Ni features when compared to a planar electrodeposited Ni electrode, while the dimpled features that were the most recessed demonstrated reduced efficiencies for the OER. The findings from this study emphasize the influences of electrode surface morphology on processes involving electrocatalytic gas evolution

The Influence of Electrochemical Aging on Bead-Blasted Nickel Electrodes for the Oxygen Evolution Reaction

The oxygen evolution reaction (OER) is of importance to both electrochemical energy conversion and energy storage. Low-cost, non-precious metal electrocatalysts that can withstand high operational current densities will likely be the best candidates for meeting the commercial needs for a range of OER applications. In addition to electrode composition, the surface morphology of gas evolving electrodes can affect their efficiency and performance. In this work, we demonstrate the influence of electrochemical aging on the performance of micro- and nanoscale textures for the OER. A series of textured Ni electrodes were prepared by rapid, scalable techniques, which included the use of bead-blasting. Two distinct approaches to induce the formation of the active Ni (oxy)hydroxide phase were conducted by electrochemical aging using cyclic voltammetry (CV) methods. The influence of the aging technique was assessed and correlated to the performance of these surface textures. Differences in the morphology of these textures and their resulting surface areas were estimated using three-dimensional (3D) reconstructions obtained from electron microscopy analyses. Focused ion beam (FIB) milling was also performed on the bead-blasted electrodes to visualize buried cracks and voids. The potential required for the OER at an applied current density of 500 mA/cm2 exhibited a reduction of 0.7 V for the electrodes aged by the steady-state treatment. The OER performance of the textured electrodes were found to correlate to both the electrode surface morphology and the type of electrochemical aging applied to the electrodes

Derivation and Characterization of Induced Pluripotent Stem Cells from Equine Fibroblasts

Pluripotent stem cells offer unprecedented potential not only for human medicine but also for veterinary medicine, particularly in relation to the horse. Induced pluripotent stem cells (iPSCs) are particularly promising, as they are functionally similar to embryonic stem cells and can be generated in vitro in a patient-specific manner. In this study, we report the generation of equine iPSCs from skin fibroblasts obtained from a foal and reprogrammed using viral vectors coding for murine Oct4, Sox2, c-Myc, and Klf4 sequences. The reprogrammed cell lines were morphologically similar to iPSCs reported from other species and could be stably maintained over more than 30 passages. Immunostaining and polymerase chain reaction analyses revealed that these cell lines expressed an array of endogenous markers associated with pluripotency, including OCT4, SOX2, NANOG, REX1, LIN28, SSEA1, SSEA4, and TRA1-60. Furthermore, under the appropriate conditions, the equine iPSCs readily formed embryoid bodies and differentiated in vitro into cells expressing markers of ectoderm, mesoderm, and endoderm, and when injected into immunodeficient mice, gave raise to tumors containing differentiated derivatives of the 3 germ layers. Finally, we also reprogrammed fibroblasts from a 2-year-old horse. The reprogrammed cells were similar to iPSCs derived from neonatal fibroblasts in terms of morphology, expression of pluripotency markers, and differentiation ability. The generation of these novel cell lines constitutes an important step toward the understanding of pluripotency in the horse, and paves the way for iPSC technology to potentially become a powerful research and clinical tool in veterinary biomedicine

Very Low-Mass Objects in the Coronet Cluster: The Realm of the Transition Disks

We present optical and IR spectra of a set of low-mass stars and brown dwarfs in the Coronet cluster (aged ~1Myr), obtained with the multifiber spectrograph FLAMES/VLT and IRS/Spitzer. The optical spectra reveal spectral types between M1 and M7.5, confirm the youth of the objects (via Li 6708 A absorption), and show the presence of accretion (via Halpha) and shocks (via forbidden line emission). The IRS spectra, together with IR photometry from the IRAC/MIPS instruments on Spitzer and 2MASS, confirm the presence of IR excesses characteristic of disks around ~70% of the objects. Half of the disks do not exhibit any silicate emission, or present flat features characteristic of large grains. The rest of the disks show silicate emission typical of amorphous and crystalline silicate grains a few microns in size. About 50% of the objects with disks do not show near-IR excess emission, having "transitional" disks, according to their classical definition. This is a very high fraction for such a young cluster. The large number of "transitional" disks suggests lifetimes comparable to the lifetimes of typical optically thick disks. Therefore, these disks may not be in a short-lived phase, intermediate between Class II and Class III objects. The median spectral energy distribution of the disks in the Coronet cluster is also closer to a flat disk than observed for the disks around solar-type stars in regions with similar age. The differences in the disk morphology and evolution in the Coronet cluster could be related to fact that these objects have very late spectral types compared to the solar-type stars in other cluster studies. Finally, the optical spectroscopy reveals that one of the X-ray sources is produced by a Herbig Haro object in the cloud.Comment: 51 pages, 13 figures, 10 table

Neutropenia in Barth syndrome:characteristics, risks, and management

PURPOSE OF REVIEW: Barth syndrome (BTHS) is an X-linked disease characterized by defective remodeling of phospholipid side chains in mitochondrial membranes. Major features include neutropenia, dilated cardiomyopathy, motor delay and proximal myopathy, feeding problems, and constitutional growth delay. We conducted this review of neutropenia in BTHS to aid in the diagnosis of this disease, and to improve understanding of both the consequences of neutropenia and the benefits of treatment with granulocyte colony-stimulating factor (G-CSF). RECENT FINDINGS: In 88 patients with BTHS, neutropenia, that is, at least one count below 1.5 × 10/l, was detected in 74 (84%) and 44% had severe chronic neutropenia, with multiple counts below 0.5 × 10/l. The pattern of neutropenia varied between intermittent and unpredictable, chronic and severe, or cyclical with mathematically regular oscillations. Monocytosis, that is, monocytes more than 1.0 × 10/l, was observed at least once in 64 of 85 (75%) patients. G-CSF was administered to 39 of 88 patients (44%). Weekly average G-CSF doses ranged from 0.12 to 10.92 μg/kg/day (mean 1.16 μg/kg/day, median 1.16 μg/kg/day). Antibiotic prophylaxis was additionally employed in 21 of 26 neutropenic patients. Pretreatment bone marrow evaluations predominantly showed reduced myeloid maturation which normalized on G-CSF therapy in seven of 13 examined. Consistent clinical improvement, with reduced signs and symptoms of infections, was observed in response to prophylactic G-CSF ± prophylactic antibiotics. However, despite G-CSF and antibiotics, one adult patient died with multiple infections related to indwelling medical devices and gastrostomy site infection after 15.5 years on G-CSF and a pediatric patient required gastrostomy removal for recurrent abdominal wall cellulitis. SUMMARY: BTHS should be considered in any men with neutropenia accompanied by any of the characteristic features of this syndrome. Prophylaxis with G-CSF ± antibiotics prevents serious bacterial infections in the more severe neutropenic patients although infections remain a threat even in patients who are very compliant with therapy, especially in those with indwelling devices

Teaching Seasoned Doctors New Technology: An Intervention to Reduce Barriers and Improve Comfort With Clinical Ultrasound

Introduction: Although clinical ultrasound (CUS) is a core skill that is a requirement for emergency medicine (EM) residency graduation, only a fraction of EM practitioners who trained prior to this requirement are certified in CUS. The objective of the study was to implement a CUS workshop for practicing EM physicians, identify barriers to utilization, and assess comfort with the machine, obtaining and interpreting images, and incorporating CUS into clinical practice. Methods: This was a prospective descriptive cohort study of EM physician faculty who participated in an interactive 5-hour CUS workshop intervention that introduced four core CUS modalities via didactics and hands-on scanning stations. Pre- and post-surveys were administered to identify barriers to utilization and assess perceived comfort with CUS using a 5-point Likert scale. Results were analyzed using Fisher's exact and paired t-tests. Results: Thirty-five EM physicians participated with a 100% survey response rate. Only five of the physicians were ultrasound certified at the time of the workshop. On average, physicians were 16 years post-residency. Prior to the workshop, 29% had minimal ultrasound experience and 43% had not performed more than 50 ultrasounds. In the pre-course survey, every physician expressed at least one barrier to CUS utilization. Post-workshop, physicians felt significantly more comfortable using the ultrasound machine (p=0.0008), obtaining and interpreting images (p=0.0009 and p=0.0004), and incorporating CUS into clinical practice (p=0.002). Conclusion: This workshop is an effective tool to expose practicing physicians to core concepts of CUS, improve their comfort level, and reduce barriers to ultrasound utilization

cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

Creating 'good' self-managers?: Facilitating and governing an online self care skills training course

<p>Abstract</p> <p>Background</p> <p>In chronic disease management, patients are increasingly called upon to undertake a new role as lay tutors within self-management training programmes. The internet constitutes an increasingly significant healthcare setting and a key arena for self-management support and communication. This study evaluates how a new quasi-professional health workforce – volunteer tutors – engage, guide and attempt to manage people with long-term conditions in the ways of 'good' self-management within the context of an online self-management course.</p> <p>Methods</p> <p>A qualitative analysis of postings to the discussion centre of 11 online classes (purposively selected from 27) run as part of the Expert Patients Programme. Facilitators (term for tutors online) and participants posted questions, comments and solutions related to self-management of long-term conditions; these were subjected to a textual and discursive analysis to explore:</p> <p>a) how facilitators, through the internet, engaged participants in issues related to self-management;</p> <p>b) how participants responded to and interacted with facilitators.</p> <p>Results</p> <p>Emergent themes included: techniques and mechanisms used to engage people with self-management; the process facilitators followed – 'sharing', 'modelling' and 'confirming'; and the emergence of a policing role regarding online disclosure. Whilst exchanging medical advice was discouraged, facilitators often professed to understand and give advice on psychological aspects of behaviour.</p> <p>Conclusion</p> <p>The study gave an insight into the roles tutors adopt – one being their ability to 'police' subjective management of long-term conditions and another being to attempt to enhance the psychological capabilities of participants.</p