A 3D <i>in vitro</i> model reveals differences in the astrocyte response elicited by potential stem cell therapies for CNS injury.

Aim: This study aimed to develop a 3D culture model to test the extent to which transplanted stem cells modulate astrocyte reactivity, where exacerbated glial cell activation could be detrimental to CNS repair success. Materials & methods: The reactivity of rat astrocytes to bone marrow mesenchymal stem cells, neural crest stem cells (NCSCs) and differentiated adipose-derived stem cells was assessed after 5 days. Schwann cells were used as a positive control. Results: NCSCs and differentiated Schwann cell-like adipose-derived stem cells did not increase astrocyte reactivity. Highly reactive responses to bone marrow mesenchymal stem cells and Schwann cells were equivalent. Conclusion: This approach can screen therapeutic cells prior to in vivo testing, allowing cells likely to trigger a substantial astrocyte response to be identified at an early stage. NCSCs and differentiated Schwann cell-like adipose-derived stem cells may be useful in treating CNS damage without increasing astrogliosis

Vibroacoustic stimulation for fetal assessment in labour in the presence of a nonreassuring fetal heart rate trace (Review)

Background: Fetal vibroacoustic stimulation (VAS) is a simple, non-invasive technique where a device is placed on the maternal abdomen over the region of the fetal head and sound is emitted at a predetermined level for several seconds. It is hypothesised that the resultant startle reflex in the fetus and subsequent fetal heart rate (FHR) acceleration or transient tachycardia following VAS provide reassurance of fetal well-being. This technique has been proposed as a tool to assess fetal well-being in the presence of a nonreassuring cardiotocographic (CTG) trace during the first and second stages of labour. Objectives: To evaluate the clinical effectiveness and safety of VAS in the assessment of fetal well-being during labour, compared with mock or no stimulation for women with a singleton pregnancy exhibiting a nonreassuring FHR pattern. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 September 2012) and reference lists of all retrieved articles. We sought unpublished trials and abstracts submitted to major international congresses and contacted expert informants. Selection criteria: All published and unpublished randomised trials that compared maternal and fetal/neonatal/infant outcomes when VAS was used to evaluate fetal status in the presence of a nonreassuring CTG trace during labour, compared with mock or no stimulation. Data collection and analysis: Two review authors independently sought to assess for inclusion all the potential studies we identified as a result of the search strategy. We planned to resolve any disagreement through discussion or, if required, to consult a third person. Where there was uncertainty about a particular study, we attempted to contact study authors for additional information. However, these attempts were unsuccessful. Main results: The search strategies yielded six studies for consideration of inclusion. However, none of these studies fulfilled the requirements for inclusion in this review. Authors' conclusions: There are currently no randomised controlled trials that address the safety and efficacy of VAS used to assess fetal well-being in labour in the presence of a nonreassuring CTG trace. Although VAS has been proposed as a simple, non-invasive tool for assessment of fetal well-being, there is insufficient evidence from randomised trials on which to base recommendations for use of VAS in the evaluation of fetal well-being in labour in the presence of a nonreassuring CTG trace

Resveratrol Inhibits KSHV Reactivation by Lowering the Levels of Cellular EGR-1

In the field of herpesvirus research, the exact molecular mechanism by which such viruses reactivate from latency remains elusive. Kaposi's sarcoma-associated herpesvirus (KSHV) primarily exists in a latent state, while only 1–3% of cells support lytic infection at any specific time. KSHV reactivation from latency is an exceedingly intricate process mediated by the integration of viral and cellular factors. Previously, our lab has described early growth response-1 (Egr-1) as an essential component for the KSHV reactivation process via its ability to mediate transcription of KSHV ORF50, the gene encoding for replication and transcription activator (RTA), a viral component known to control the switch from latent to lytic infection. In here, electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) experiments revealed that Egr-1 binds KSHV ORF50 promoter (ORF50P) in at least two different GC-rich binding domains. Expression profiles of cellular egr-1 and KSHV-encoded ORF50 follow a similar pattern during de novo KSHV infection. Over-expressing Egr-1, a signaling component downstream of Raf>MEK>ERK1/2, in KSHV-infected cells activates KSHV lytic replication. Through performing more physiologically relevant experiments, we analyzed the effect of a dietary supplement containing resveratrol on KSHV-infected cells. Our results, for the first time, demonstrate resveratrol to act in lowering ERK1/2 activity and expression of Egr-1 in KSHV-infected cells, resulting in the suppression of virus reactivation from latency. Taken together, these findings will undoubtedly contribute to future studies on not only combating KSHV related disease conditions, but also on other herpesviruses-induced pathogenesis

Fetal pulse oximetry for fetal assessment in labour (Review)

Backgroun

Generic Medications and Blood Pressure Control in Diabetic Hypertensive Subjects

OBJECTIVE To investigate temporal improvements in blood pressure (BP) control in subjects with diabetes and policy changes regarding generic antihypertensives. RESEARCH DESIGN AND METHODS In a cross-sectional study we used logistic regression models to investigate the temporal relationship between access to generic antihypertensive medications and BP control (<130/80 mmHg) in 5,375 subjects (mean age, 66 ± 9 years; 61% African American) with diabetes and hypertension (HTN) enrolled in the national Results from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study between 2003 and 2007. At enrollment, BP was measured and medications in the home determined by medication label review by a trained professional. Generic antihypertensive medication status was ascertained from the U.S. Food and Drug Administration. RESULTS The percentage of subjects accessing generically available antihypertensive medications increased significantly from 66% in 2003 to 81% in 2007 (P < 0.0001), and the odds of achieving a BP <130/80 mmHg in 2007 was 66% higher (odds ratio 1.66 [95% CI 1.30–2.10]) than in 2003. Nevertheless, <50% of participants achieved this goal. African American race, male sex, limited income, and medication nonadherence were significant predictors of inadequate BP control. There was no significant relationship between access to generic antihypertensives and BP control when other demographic factors were included in the model (0.98 [0.96–1.00]). CONCLUSIONS Among African American and white subjects with HTN and diabetes, BP control remained inadequate relative to published guidelines, and racial disparities persisted. Although access to generic antihypertensives increased, this was not independently associated with improved BP control, suggesting that poor BP control is multifactorial

Evidence of Resilience in Reef Islands in Response to Rising Sea Level on Huvadhoo Atoll, Maldives

Reef islands are at the forefront of concern for future accelerating sea-level rise since their low-lying and isolated nature puts them at higher risk of marine inundation compared to continental coastlines. However, the perceived threat of complete submersion as implied by projected future sea-level rise and current island elevations do not consider the morphologically resilient nature of reef island systems. In particular, the role of sediment supply in the resilience of these islands is still relatively poorly studied. This study presents detailed descriptions of the sedimentary characteristics and stratigraphy of two lagoonal platform islands in Huvadhoo Atoll, Maldives, that formed during periods of Holocene sea-level rise. Island subsurface stratigraphy was reconstructed by analysing the skeletal composition and textural properties of 306 sediment samples from 37 cores extracted across the islands. Island sediments were dominated by coral sands with varied proportions of secondary constituents (molluscs, Halimeda, foraminifera, and crustose coralline algae). Downcore variations in composition show that the proportion of coral sands decrease with depth and the proportion of molluscs and Halimeda increase with depth (with the exception of cores that terminated on lagoon infill). The increased proportion of Halimeda and molluscs in these early island deposits may have resulted from the catch-up growth strategy of the reef during the mid-Holocene highstand as both organisms have high turnover rates and directly contribute to sediment production after death. The sedimentological response of increased Halimeda and molluscs highlights the resilient and dynamic nature of reef islands and the ability of reefs to adjust ecologically to changing sea levels

Lagoonal reef island formation in Huvadhoo atoll, Maldives, highlights marked temporal variations in island building across the archipelago

Coral reef islands provide the only pedestals of human habitation in mid-ocean atoll archipelagoes. Understanding the environmental controls on island formation is critical for evaluating the future response of islands to environmental change and sea-level rise. This study examines the evolution of lagoonal reef islands in Huvadhoo atoll, southern Maldives. Using extensive ground penetrating radar (GPR) imaging of island sediment structure, combined with comprehensive analysis of island morphology, sedimentology, and 49 radiometric dates, detailed reconstructions of the evolution of two lagoonal islands is presented. A four-stage model shows a complex history of island formation across various stages of sea-level change during the late-Holocene: 1) lagoon infill occurring from ~3000–2000 years ago during a period of sea-level fall from the mid-Holocene highstand; 2) emergence of the island core through vertical aggradation during the latter stages of sea-level fall between ~2000 and 1500 yBP; 3) rapid lateral expansion of the islands between 1500 and 500 yBP coincident with the availability of sandsize sediments and during a period of sea-level oscillation; and, 4) subsequent minor expansion and modification of island shorelines through alongshore reworking of island sediments over the past 500 years. Results provide evidence of marked differences in the timing and mode of island formation within Huvadhoo atoll. Significantly, the formation of the lagoonal islands post-dates the formation of islands on the atoll rim by 1000–2000 years. Furthermore, the formation of sand islands over infilled shallow lagoons contrasts the formation of most atoll rim islands through the sequential deposition of storm-generated rubble deposited directly across reef surfaces that have reached their vertical growth limit. Results of lagoonal island formation in the southern Maldives provide comparative data for the northern Maldives. While the sequence of island formation follows the faro infill model identified in the northern archipelago, lagoonal islands in the south appear to have formed 2000 years after those in the north. This difference is likely to reflect lagged reef growth response from deeper foundations in the southern archipelago

Membrane-protein interactions in mechanosensitive channels

In this paper, we examine the mechanical role of the lipid bilayer in ion channel conformation and function with specific reference to the case of the mechanosensitive channel of large conductance (MscL). In a recent paper (Wiggins and Phillips, 2004), we argued that mechanotransduction very naturally arises from lipid-protein interactions by invoking a simple analytic model of the MscL channel and the surrounding lipid bilayer. In this paper, we focus on improving and expanding this analytic framework for studying lipid-protein interactions with special attention to MscL. Our goal is to generate simple scaling relations which can be used to provide qualitative understanding of the role of membrane mechanics in protein function and to quantitatively interpret experimental results. For the MscL channel, we find that the free energies induced by lipid-protein interaction are of the same order as the free energy differences between conductance states measured by Sukharev et al. (1999). We therefore conclude that the mechanics of the bilayer plays an essential role in determining the conformation and function of the channel. Finally, we compare the predictions of our model to experimental results from the recent investigations of the MscL channel by Perozo et al. (2002), Powl et al. (2003), Yoshimura et al. (2004), and others and suggest a suite of new experiments

Modeling of Non-Small Cell Lung Cancer Volume Changes during CT-Based Image Guided Radiotherapy: Patterns Observed and Clinical Implications

Background. To characterize the lung tumor volume response during conventional and hypofractionated radiotherapy (RT) based on diagnostic quality CT images prior to each treatment fraction. Methods. Out of 26 consecutive patients who had received CT-on-rails IGRT to the lung from 2004 to 2008, 18 were selected because they had lung lesions that could be easily distinguished. The time course of the tumor volume for each patient was individually analyzed using a computer program. Results. The model fits of group L (conventional fractionation) patients were very close to experimental data, with a median Δ% (average percent difference between data and fit) of 5.1% (range 3.5–10.2%). The fits obtained in group S (hypofractionation) patients were generally good, with a median Δ% of 7.2% (range 3.7–23.9%) for the best fitting model. Four types of tumor responses were observed—Type A: “high� kill and “slow� dying rate; Type B: “high� kill and “fast� dying rate; Type C: “low� kill and “slow� dying rate; and Type D: “low� kill and “fast� dying rate. Conclusions. The models used in this study performed well in fitting the available dataset. The models provided useful insights into the possible underlying mechanisms responsible for the RT tumor volume response

Higher harmonic anisotropic flow measurements of charged particles at 2.76 TeV with the ALICE detector

We report the measurements of elliptic flow $v_{2}$, as well as higher harmonics triangular flow $v_{3}$ and quadrangular flow $v_{4}$, in $\sqrt{s_{_{NN}}} =$ 2.76 TeV Pb--Pb collisions, measured with the ALICE detector. We show that the measured elliptic and triangular flow can be understood from the initial spatial anisotropy and its event--by--event fluctuations. The resulting fluctuations of $v_{2}$ and $v_{3}$ are also discussed.Comment: 6 pages, 4 figures, proceeding of Strangeness in Quark Matter 2011, Cracow, Polan