Exogenous schwann cells migrate, remyelinate and promote clinical recovery in experimental auto-immune encephalomyelitis

Schwann cell (SC) transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). However this assumes they will not only survive but also remyelinate demyelinated axons in the chronically inflamed CNS. To address this question we investigated the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in the Dark Agouti rat; an animal model that reproduces the complex inflammatory demyelinating immunopathology of MS. We now report that SCs expressing green fluorescent protein (GFP-SCs) allografted after disease onset not only survive but also migrate to remyelinate lesions in the inflamed CNS. GFP-SCs were detected more frequently in the parenchyma after direct injection into the spinal cord, than via intra-thecal delivery into the cerebrospinal fluid. In both cases the transplanted cells intermingled with astrocytes in demyelinated lesions, aligned with axons and by twenty one days post transplantation had formed Pzero protein immunoreactive internodes. Strikingly, GFP-SCs transplantation was associated with marked decrease in clinical disease severity in terms of mortality; all GFP-SCs transplanted animals survived whilst 80% of controls died within 40 days of disease

The valanginian weissert oceanic anoxic event recorded in central-Eastern Sardinia (Italy)

Investigations on the S\u2019Ozzastru section from the northern part of the Mt Albo area (central-eastern Sardinia, Italy) for integrated litho- bio- and chemostratigraphy allowed the identification of the Valanginian Weissert Oceanic Anoxic Event (OAE), testified by a positive carbon isotope excursion (CIE). The section, which represents the deepest-water succession of the Valanginian in Sardinia, is composed of the Schiridd\ue8 Limestone followed by the Siniscola Marl, both proposed as new lithostratigraphic units. The presence among the ammonites of Busnardoites campylotoxus allows the attribution of the Schiridd\ue8 Limestone to the upper Lower Valanginian Inostranzewi Zone of Reboulet et al. 2014. Further characterization of this unit was not possible since it is barren/almost barren of nannofossils. The Siniscola Marl can be ascribed to the lower Upper Valanginian on the basis of the ammonite fauna indicating the Verrucosum Zone, and of the nannofossil content suggesting the Zone NK3. The carbon isotope record in the Siniscola Marl is characterized by a positive excursion with values up to 2.98 \u2030. In the nannofossil assemblages, nannoconids are not particularly abundant and are found, among others, together with C. oblongata, D. lehmanii, and pentaliths. The scarcity of nannoconids is regarded as a biostratigraphic support for the identification of the Weissert OAE, as it possibly reflects the \u201cnannoconid decline\u201d interval which characterizes this event. The end of the Weissert OAE CIE is not recorded probably because of suppression of the upper part of the succession for tectonic causes

Managed Care for Elderly People: A Compendium of Findings

Although managed care seems to serve well the in terests of non-elderly enrollees and their payers, elderly people face more risks. Chronic conditions, multiple prob lems, and more limited resources make them more vul nerable, whereas multiple payer sources make them more complicated to cover. This synthesis of managed care de livered in Medicare and Medicaid demonstration projects serving elderly beneficiaries shows that managed care plans either select or attract enrollees who suffer fewer frailties than those served in fee-for-service settings, ex hibit reluctance to enter rural markets, provide a broad range of elderly-specific services, offer more compre hensive coverage and services, and result in greater per ceived access problems, particularly for vulnerable subgroups. Plans operate more cheaply by using fewer resources, even after adjusting for case mix differences. Managed care enrollees tend to be more satisfied with financial and coverage aspects, whereas fee-for-service enrollees report higher satisfaction on other dimensions. In acute care settings, process of care findings were mixed, whereas clinical and self-reported outcome indi cators were no better and in some instances worse in managed care. Long-term care enrollees, in the few stud ies reported, consistently faired worse in both the processes and outcomes of care. These findings suggest that further research on the effects of managed care in its rapidly changing incarnations is needed, particularly with respect to how to improve the quality of acute and long-term care delivered to elderly people and the proper role of government and other key actors in the health care system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66514/2/10.1177_106286069801300304.pd

The Method for Assigning Priority Levels (MAPLe): A new decision-support system for allocating home care resources

<p>Abstract</p> <p>Background</p> <p>Home care plays a vital role in many health care systems, but there is evidence that appropriate targeting strategies must be used to allocate limited home care resources effectively. The aim of the present study was to develop and validate a methodology for prioritizing access to community and facility-based services for home care clients.</p> <p>Methods</p> <p>Canadian and international data based on the Resident Assessment Instrument – Home Care (RAI-HC) were analyzed to identify predictors for nursing home placement, caregiver distress and for being rated as requiring alternative placement to improve outlook.</p> <p>Results</p> <p>The Method for Assigning Priority Levels (MAPLe) algorithm was a strong predictor of all three outcomes in the derivation sample. The algorithm was validated with additional data from five other countries, three other provinces, and an Ontario sample obtained after the use of the RAI-HC was mandated.</p> <p>Conclusion</p> <p>The MAPLe algorithm provides a psychometrically sound decision-support tool that may be used to inform choices related to allocation of home care resources and prioritization of clients needing community or facility-based services.</p

Environmental consequences of Ontong Java Plateau and Kerguelen Plateau Volcanism

The mid-Cretaceous was marked by emplacement of large igneous provinces (LIPs) that formed gigantic oceanic plateaus, affecting ecosystems on a global scale, with biota forced to face excess CO2 resulting in climate and ocean perturbations. Volcanic phases of the Ontong Java Plateau (OJP) and the southern Kerguelen Plateau (SKP) are radiometrically dated and correlate with paleoenvironmental changes, suggesting causal links between LIPs and ecosystem responses. Aptian biocalcifi cation crises and recoveries are broadly coeval with C, Pb, and Os isotopic anomalies, trace metal infl uxes, global anoxia, and climate changes. Early Aptian greenhouse or supergreenhouse conditions were followed by prolonged cooling during the late Aptian, when OJP and SKP developed, respectively. Massive volcanism occurring at equatorial versus high paleolatitudes and submarine versus subaerial settings triggered very different climate responses but similar disruptions in the marine carbonate system. Excess CO2 arguably induced episodic ocean acidifi cation that was detrimental to marine calcifi ers, regardless of hot or cool conditions. Global anoxia was reached only under extreme warming, whereas cold conditions kept the oceans well oxygenated even at times of intensifi ed fertility. The environmental disruptions attributed to the OJP did not trigger a mass extinction: rock-forming nannoconids and benthic communities underwent a signifi cant decline during Oceanic Anoxic Event (OAE) 1a, but recovered when paroxysmal volcanism fi nished. Extinction of many planktonic foraminiferal and nannoplankton taxa, including most nannoconids, and most aragonitic rudists in latest Aptian time was likely triggered by severe ocean acidifi cation. Upgraded dating of paleoceanographic events, improved radiometric ages of the OJP and SKP, and time-scale revision are needed to substantiate the links between magmatism and paleoenvironmental perturbations

Sleepiness and fatigue in multiple sclerosis - same same but different? A systematic review on the Epworth Sleepiness Scale as an assessment tool

Objectives: Fatigue is a frequent and distressing symptom in patients with multiple sclerosis (MS). In contrast, sleepiness, characterized by difficulties to stay awake and alert during the day, seems to be less prevalent in MS; however exact studies are lacking. In addition, there is a semantic confusion of the concepts of “fatigue” and “sleepiness”, which are often used interchangeably. Methods: We conducted a systematic review of studies using the Epworth Sleepiness Scale (ESS) for the assessment of daytime sleepiness in patients with MS. Results: The summarized results of 48 studies demonstrate that sleepiness, as indicated by elevated ESS scores, is less prevalent and less severe than fatigue but is present in a significant proportion of patients with MS. In most cross-sectional and longitudinal studies, there was a moderate association between ESS scores and various fatigue rating scales. Longitudinal studies on the effect of wakefulness- promoting agents failed to show a consistent improvement of sleepiness or fatigue as compared to placebo. It has also been shown that daytime sleepiness is frequently associated with comorbid sleep disorders that are often underrecognized and undertreated in MS. Conclusions: Sleepiness and potential sleep disorders may also precipitate and perpetuate fatigue in patients with MS and should be part of the differential diagnostic assessment. To support an appropriate decision-making process, we propose an algorithm for the evaluation of sleepiness as compared to fatigue in patients with MS. Disclosure: Nothing to disclose

Lithium-isotope evidence for enhanced silicate weathering during OAE 1a (Early Aptian Selli event)

An abrupt rise in temperature, forced by a massive input of CO2 into the atmosphere, is commonly invoked as the main trigger for Oceanic Anoxic Events (OAEs). Global warming initiated a cascade of palaeoenvironmental perturbations starting with increased continental weathering and an accelerated hydrological cycle that delivered higher loads of nutrients to coastal areas, stimulating biological productivity. The end-result was widespread anoxia and deposition of black shales: the hallmarks of OAEs. In order to assess the role of weathering as both an OAE initiator and terminator (via CO2 sequestration) during the Early Aptian OAE 1a (Selli Event, ∼120 Ma) the isotopic ratio of lithium isotopes was analysed in three sections of shallow-marine carbonates from the Pacific and Tethyan realms and one basinal pelagic section from the Tethyan domain. Because the isotopic composition of lithium in seawater is largely controlled by continental silicate weathering and high- and low-temperature alteration of basaltic material, a shift to lighter δ7Li values is expected to characterize OAEs. The studied sections illustrate this phenomenon: δ7Li values decrease to a minimum coincident with the negative carbon-isotope excursion that effectively records the onset of OAE 1a. A second negative δ7Li excursion occurs coeval with the minimum in strontium isotopes after the event. The striking similarity to the strontium-isotope record argues for a common driver. The formation and destruction (weathering) of an oceanic LIP could account for the parallel trend in both isotope systems. The double-spike in lithium isotopes is probably related to a change in weathering congruencies. Such a chemostratigraphy is consistent with the hypothesis that an increase in silicate weathering, in conjunction with organic-carbon burial, led to drawdown of atmospheric CO2 during the early Aptian OAE 1a

Impact of tobacco industry and other corporations in the defeat of the 1994 Clinton health care plan

Abstract Background: The primary reason cited by many scholars for the defeat of the Clinton Administration’s 1994 health care reform bill has long been identified as Health Insurance Association of America and National Federation of Independent Businesses opposition to the bill. Given this predominant consensus combined with sizeable proposed funding for the bill by a large tobacco product tax, this manuscript examined what the tobacco industry’s role was in whole or part in defeating the Clinton health care bill. Methods: This research occurred through crosschecking internal tobacco industry documents and Clinton White House documents. Results: Prior to the passage of the bill, the tobacco industry accepted a compromise of 45 cents per pack increase phased in over five years. Due to this compromise, the industry or third party allies had no role in the ultimate defeat in the bill. Conclusions: The primary reason for the bill’s ultimate defeat was general business (but not tobacco industry and third party ally) opposition, the bill running out of time, and conflicting bills. Secondary reasons for the bill’s defeat included issues with: employer mandates, high taxes on insurance plans, impacts on medical research and education, Congressional attention to other issues, election year politics, and possible future excise tax possibilities.Ye

BurkDiff: A Real-Time PCR Allelic Discrimination Assay for Burkholderia Pseudomallei and B. mallei

A real-time PCR assay, BurkDiff, was designed to target a unique conserved region in the B. pseudomallei and B. mallei genomes containing a SNP that differentiates the two species. Sensitivity and specificity were assessed by screening BurkDiff across 469 isolates of B. pseudomallei, 49 isolates of B. mallei, and 390 isolates of clinically relevant non-target species. Concordance of results with traditional speciation methods and no cross-reactivity to non-target species show BurkDiff is a robust, highly validated assay for the detection and differentiation of B. pseudomallei and B. mallei

An extraterrestrial trigger for the Early Cretaceous massive volcanism? Evidence from the paleo-Tethys Ocean

The Early Cretaceous Greater Ontong Java Event in the Pacific Ocean may have covered ca. 1% of the Earth's surface with volcanism. It has puzzled scientists trying to explain its origin by several mechanisms possible on Earth, leading others to propose an extraterrestrial trigger to explain this event. A large oceanic extraterrestrial impact causing such voluminous volcanism may have traces of its distal ejecta in sedimentary rocks around the basin, including the paleo-Tethys Ocean which was then contiguous with the Pacific Ocean. The contemporaneous marine sequence at central Italy, containing the sedimentary expression of a global oceanic anoxic event (OAE1a), may have recorded such ocurrence as indicated by two stratigraphic intervals with 187Os/188Os indicative of meteoritic influence. Here we show, for the first time, that platinum group element abundances and inter-element ratios in this paleo-Tethyan marine sequence provide no evidence for an extraterrestrial trigger for the Early Cretaceous massive volcanism