The natural history of relapsing remitting multiple sclerosis (RRMS) is variable and prediction of individual prognosis challenging. The inability to reliably predict prognosis at diagnosis has ...important implications for informed decision making especially in relation to disease modifying therapies. We conducted a systematic review in order to collate, describe and assess the methodological quality of published prediction models in RRMS. We searched Medline, Embase and Web of Science. Two reviewers independently screened abstracts and full text for eligibility and assessed risk of bias. Studies reporting development or validation of prediction models for RRMS in adults were included. Data collection was guided by the checklist for critical appraisal and data extraction for systematic reviews (CHARMS) and applicability and methodological quality assessment by the prediction model risk of bias assessment tool (PROBAST). 30 studies were included in the review. Applicability was assessed as high risk of concern in 27 studies. Risk of bias was assessed as high for all studies. The single most frequently included predictor was baseline EDSS (n = 11). T2 Lesion volume or number and brain atrophy were each retained in seven studies. Five studies included external validation and none included impact analysis. Although a number of prediction models for RRMS have been reported, most are at high risk of bias and lack external validation and impact analysis, restricting their application to routine clinical practice.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The identification of the trans-acting factors and cis-regulatory modules that are involved in human pluripotent stem cell (hPSC) maintenance and differentiation is necessary to dissect the operating ...regulatory networks in these processes and thereby identify nodes where signal input will direct desired cell fate decisions in vitro or in vivo. To deconvolute these networks, we established a method to influence the differentiation state of hPSCs with a CRISPR-associated catalytically inactive dCas9 fused to an effector domain. In human embryonic stem cells, we find that the dCas9 effectors can exert positive or negative regulation on the expression of developmentally relevant genes, which can influence cell differentiation status when impinging on a key node in the regulatory network that governs the cell state. This system provides a platform for the interrogation of the underlying regulators governing specific differentiation decisions, which can then be employed to direct cellular differentiation down desired pathways.
Ventral spinal cord progenitor cells, which express the basic helix loop helix transcription factor Olig2, sequentially produce motor neurons and oligodendrocyte precursor cells (OPCs). Following ...specification some OPCs differentiate as myelinating oligodendrocytes while others persist as OPCs. Though a considerable amount of work has described the molecular profiles that define motor neurons, OPCs, and oligodendrocytes, less is known about the progenitors that produce them. To identify the developmental origins and transcriptional profiles of motor neurons and OPCs, we performed single-cell RNA sequencing on isolated pMN cells from embryonic zebrafish trunk tissue at stages that encompassed motor neurogenesis, OPC specification, and initiation of oligodendrocyte differentiation. Downstream analyses revealed two distinct pMN progenitor populations: one that appears to produce neurons and one that appears to produce OPCs. This latter population, called Pre-OPCs, is marked by expression of GS Homeobox 2 (gsx2), a gene that encodes a homeobox transcription factor. Using fluorescent in situ hybridizations, we identified gsx2-expressing Pre-OPCs in the spinal cord prior to expression of canonical OPC marker genes. Our data therefore reveal heterogeneous gene expression profiles among pMN progenitors, supporting prior fate mapping evidence.
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•Single-cell RNA sequencing reveals trajectories of neurons and glia produced by pMN progenitor cells in zebrafish embryos.•Distinct pMN progenitors are the apparent sources of neurons or oligodendrocytes, consistent with fate mapping data.•gsx2 expression marks pMN progenitors that produce oligodendrocyte lineage cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Genetically diverse community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) can harbor a bacteriophage encoding Panton-Valentine leukocidin (PVL) lysogenized into its chromosome ...(prophage). Six PVL phages (ΦPVL, Φ108PVL, ΦSLT, ΦSa2MW, ΦSa2USA, and ΦSa2958) are known, and single-nucleotide polymorphisms (SNPs) in the PVL genes have been reported. We sought to determine the distribution of lysogenized PVL phages among MRSA strains with PVL (PVL-MRSA strains), the PVL gene sequences, and the chromosomal phage insertion sites in 114 isolates comprising nine clones of PVL-MRSA that were selected for maximal underlying genetic diversity. The six PVL phages were identified by PCR; ΦSa2USA was present in the highest number of different lineages (multilocus sequence type clonal complex 1 CC1, CC5, CC8, and sequence type 93 ST93) (n = 37 isolates). Analysis of 92 isolates confirmed that PVL phages inserted into the same chromosomal insertion locus in CC22, -30, and -80 but in a different locus in isolates of CC1, -5, -8, -59, and -88 and ST93 (and CC22 in two isolates). Within the two different loci, specific attachment motifs were found in all cases, although some limited inter- and intralineage sequence variation occurred. Overall, lineage-specific relationships between the PVL phage, the genes that encode the toxin, and the position at which the phage inserts into the host chromosome were identified. These analyses provide important insights into the microepidemiology of PVL-MRSA, will prove a valuable adjunct in outbreak investigation, and may help predict the emergence of new strains.
Arsenic decreases rice yield, and inorganic grain As threatens human health; thus, strategies to decrease rice As are critically needed. Increased plant-available silica (Si) can decrease rice As, ...yet the source of Si matters. Rice husk, an underutilized and Si-rich byproduct of rice production that contains less labile C and an order of magnitude less As than rice straw, may be an economically viable Si resource to decrease rice As, yet the impact of rice husk incorporation on As in the rice–soil nexus has not been reported. This proof-of-concept study shows that rice husk incorporation to soil (1% w/w) decreases inorganic grain As by 25–50% without negatively affecting grain Cd, yield, or dissolved CH4 levels. Rice husk is a critical yet perhaps overlooked resource to improve soil quality through enhanced nutrient availability and attenuate human health risks through consumption of As-laden grain.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Prevention of multiple sclerosis requires intervention on modifiable causes of the condition making it necessary to establish what those causes are. MS is often stated to be a polygenic disease, with ...causal contributions from environmental factors and gene-environment interactions, implying an additive and independent relationship of these factors. Mechanistically there are no independent contributions of genes or environmental factors to traits. This model is unrealistic but still useful and underlies the concept of heritability, a foundational parameter in population genetics. However, it perpetuates a debate on an irreconcilable dichotomy about whether MS is primarily genetic or environmental. In particular, epidemiological evidence now exists for a causal, possibly even necessary, role for Epstein Barr Virus in MS. The additive model makes it unintuitive to reconcile MS as a genetic disease but also independently a viral illness. In this perspective it is argued that starting from a realistic interaction only model, based on broadly accepted biological premises, and working forward to explain why the classical additive model gives useful results, there is actually no paradox. An integrated approach using population genetic studies, immunology and molecular virology offers a particularly promising route to establish the elusive role of EBV in MS pathology, as EBV is a large and complex virus and its latency, dysregulated in most EBV-related pathologies, is hard to study
. This approach may offer a route to prevention of MS altogether.
Geographies of mental health in the era of deinstitutionalisation have examined a range of places, policy processes and people's experiences associated with community care. However, such assessments ...have tended, given their community focus, to necessarily be silent on the character of inpatient spaces of care. There is silence too on the potential of such spaces to assist in the healing journey. While there have been a few investigations of hospital design, there has been little consideration of users' experiences of hospital spaces as critical sites and spaces of transition on the illness journey. In this paper, we critically reflect on a project that seeks, two decades after the closure of the last major institution in New Zealand, to investigate the acute care environment with an emphasis on its capacity for healing. The vehicle facilitating this investigation is a novel approach to understanding the inpatient journey: autoethnography. This methodology allows the first author (JL) to critically reflect on her multiple roles as compassionate observer, service-user and mental health professional, and developing transdisciplinary insights that, in conversation with the other authors' geographical (RK) and psychological (PA) vantage points, assist in the reconsideration of the place of the inpatient unit as a place of healing. The paper reveals how voice, experience and theory become mutually entwined concerns in an investigation which potentially stretches the therapeutic landscape idea through critical attention to the redemptive qualities of place by means of attentiveness to both the world within and the world without.
► Autoethnography is proposed for an investigation of the healing capacity of psychiatric acute care environments. ► Autoethnography places the service-user within the research process as key collaborator if not sole investigator. ► The authors critically draw on their multiple roles including service-user, health professional, geographer, and psychologist. ► Voice, experience and theory become mutually entwined concerns potentially stretching the therapeutic landscape concept.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We successfully demonstrated an electrically injected blue(202¯1¯)semipolar vertical-cavity surface-emitting laser with a 5λ cavity length, an ion implanted aperture, and a dual dielectric DBR ...design. The peak power under pulsed operation was 1.85 mW, the threshold current was 4.6 kA/cm
and the differential efficiency was 2.4% for the mode at 445 nm of a device with a 12 µm aperture. Lasing was achieved up to a 50% duty cycle and the thermal impedance was estimated to be 1800 K/W. The lasing emission was found to be 100% plane polarized along the a-direction.
Staphylococcus argenteus and Staphylococcus schweitzeri, previously known as divergent Staphylococcus aureus clonal lineages, have been recently established as novel, difficult-to-delimit, ...coagulase-positive species within the S. aureus complex. Methicillin-resistant strains of S. argenteus are known from Australia and the UK. Knowledge of their epidemiology, medical significance and transmission risk is limited and partly contradictory, hampering definitive recommendations. There is mounting evidence that the pathogenicity of S. argenteus is similar to that of ‘classical’ S. aureus, while as yet no S. schweitzeri infections have been reported.
To provide decision support on whether and how to distinguish and report both species.
PubMed, searched for S. argenteus and S. schweitzeri.
This position paper reviews the main characteristics of both species and draws conclusions for microbiological diagnostics and surveillance as well as infection prevention and control measures.
We propose not distinguishing within the S. aureus complex for routine reporting purposes until there is evidence that pathogenicity or clinical outcome differ markedly between the different species. Primarily for research purposes, suitably equipped laboratories are encouraged to differentiate between S. argenteus and S. schweitzeri. Caution is urged if these novel species are explicitly reported. In such cases, a specific comment should be added (i.e. ‘member of the S.aureus complex’) to prevent confusion with less- or non-pathogenic staphylococci. Prioritizing aspects of patient safety, methicillin-resistant isolates should be handled as recommended for methicillin-resistant Staphylococcus aureus (MRSA). In these cases, the clinician responsible should be directly contacted and informed by the diagnosing microbiological laboratory, as they would be for MRSA. Research is warranted to clarify the epidemiology, clinical impact and implications for infection control of such isolates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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