89 research outputs found

    Predictors of Intraspinal Pressure and Optimal Cord Perfusion Pressure After Traumatic Spinal Cord Injury.

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    BACKGROUND/OBJECTIVES: We recently developed techniques to monitor intraspinal pressure (ISP) and spinal cord perfusion pressure (SCPP) from the injury site to compute the optimum SCPP (SCPPopt) in patients with acute traumatic spinal cord injury (TSCI). We hypothesized that ISP and SCPPopt can be predicted using clinical factors instead of ISP monitoring. METHODS: Sixty-four TSCI patients, grades A-C (American spinal injuries association Impairment Scale, AIS), were analyzed. For 24 h after surgery, we monitored ISP and SCPP and computed SCPPopt (SCPP that optimizes pressure reactivity). We studied how well 28 factors correlate with mean ISP or SCPPopt including 7 patient-related, 3 injury-related, 6 management-related, and 12 preoperative MRI-related factors. RESULTS: All patients underwent surgery to restore normal spinal alignment within 72 h of injury. Fifty-one percentage had U-shaped sPRx versus SCPP curves, thus allowing SCPPopt to be computed. Thirteen percentage, all AIS grade A or B, had no U-shaped sPRx versus SCPP curves. Thirty-six percentage (22/64) had U-shaped sPRx versus SCPP curves, but the SCPP did not reach the minimum of the curve, and thus, an exact SCPPopt could not be calculated. In total 5/28 factors were associated with lower ISP: older age, excess alcohol consumption, nonconus medullaris injury, expansion duroplasty, and less intraoperative bleeding. In a multivariate logistic regression model, these 5 factors predicted ISP as normal or high with 73% accuracy. Only 2/28 factors correlated with lower SCPPopt: higher mean ISP and conus medullaris injury. In an ordinal multivariate logistic regression model, these 2 factors predicted SCPPopt as low, medium-low, medium-high, or high with only 42% accuracy. No MRI factors correlated with ISP or SCPPopt. CONCLUSIONS: Elevated ISP can be predicted by clinical factors. Modifiable factors that may lower ISP are: reducing surgical bleeding and performing expansion duroplasty. No factors accurately predict SCPPopt; thus, invasive monitoring remains the only way to estimate SCPPopt

    Routinely collected data for randomized trials: promises, barriers, and implications

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    This work was supported by Stiftung Institut für klinische Epidemiologie. The Meta-Research Innovation Center at Stanford University is funded by a grant from the Laura and John Arnold Foundation. The funders had no role in design and conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript or its submission for publication.Peer reviewedPublisher PD

    SNCA Triplication Parkinson's Patient's iPSC-derived DA Neurons Accumulate α-Synuclein and Are Susceptible to Oxidative Stress

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    Parkinson's disease (PD) is an incurable age-related neurodegenerative disorder affecting both the central and peripheral nervous systems. Although common, the etiology of PD remains poorly understood. Genetic studies infer that the disease results from a complex interaction between genetics and environment and there is growing evidence that PD may represent a constellation of diseases with overlapping yet distinct underlying mechanisms. Novel clinical approaches will require a better understanding of the mechanisms at work within an individual as well as methods to identify the specific array of mechanisms that have contributed to the disease. Induced pluripotent stem cell (iPSC) strategies provide an opportunity to directly study the affected neuronal subtypes in a given patient. Here we report the generation of iPSC-derived midbrain dopaminergic neurons from a patient with a triplication in the α-synuclein gene (SNCA). We observed that the iPSCs readily differentiated into functional neurons. Importantly, the PD-affected line exhibited disease-related phenotypes in culture: accumulation of α-synuclein, inherent overexpression of markers of oxidative stress, and sensitivity to peroxide induced oxidative stress. These findings show that the dominantly-acting PD mutation is intrinsically capable of perturbing normal cell function in culture and confirm that these features reflect, at least in part, a cell autonomous disease process that is independent of exposure to the entire complexity of the diseased brain

    Exploring the Role of Explicit and Implicit Self-Esteem and Self-Compassion in Anxious and Depressive Symptomatology Following Acquired Brain Injury

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    [EN] Objectives Acquired brain injury (ABI) can lead to the emergence of several disabilities and is commonly associated with high rates of anxiety and depression symptoms. Self-related constructs, such as self-esteem and self-compassion, might play a key role in this distressing symptomatology. Low explicit (i.e., deliberate) self-esteem is associated with anxiety and depression after ABI. However, implicit (i.e., automatic) self-esteem, explicit-implicit self-discrepancies, and self-compassion could also significantly contribute to this symptomatology. The purpose of the present study was to examine whether implicit self-esteem, explicit-implicit self-discrepancy (size and direction), and self-compassion are related to anxious and depressive symptoms after ABI in adults, beyond the contribution of explicit self-esteem. Methods The sample consisted 38 individuals with ABI who were enrolled in a long-term rehabilitation program. All participants completed the measures of explicit self-esteem, implicit self-esteem, self-compassion, anxiety, and depression. Pearson's correlations and hierarchical regression models were calculated. Results Findings showed that both self-compassion and implicit self-esteem negatively accounted for unique variance in anxiety and depression when controlling for explicit self-esteem. Neither the size nor direction of explicit-implicit self-discrepancy was significantly associated with anxious or depressive symptomatology. Conclusions The findings suggest that the consideration of self-compassion and implicit self-esteem, in addition to explicit self-esteem, contributes to understanding anxiety and depression following ABI.Lorena Desdentado is supported by a FPU doctoral scholarship (FPU18/01690) from the Spanish Ministry of Universities. 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    Oksidacijski stres u lakirera izloženih niskim razinama olova

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    Lead toxicity is a public health problem particularly to the children and to occupationally exposed adults. Evidence is mounting successively regarding the adverse health effects of lead at low levels. This study was undertaken to assess the antioxidant status of lead-exposed residential and commercial painters of Lucknow city in Uttar Pradesh, India. Thirty-five painters aged 20 to 50 years who had blood lead levels ≤400 µg L-1 were selected for the study from a population of 56 male painters initially screened for blood lead. The control group included an equal number of subjects of the same age group without any occupational exposure to lead. We studied the association between low lead level exposure and antioxidant status and found that blood lead levels in painters were approximately seven times as high as in controls [(219.2 ± 61.9) µg L-1 vs. (30.6±10.1) µg L-1, respectively]. Among the biomarkers of lead toxicity a significant decrease in the level of delta-aminolevulinic acid dehydratase [(9.13±4.62) UL-1 vs. (39.38±5.05) UL-1] and an increase in the level of zinc protoporphyrin [(187.9±49.8) µg L-1 vs. (26.4±5.5) µg L-1] were observed in painters compared to controls. Among antioxidant enzymes, painters showed a significant decrease in catalase [(56.77±11.11) UL-1 vs. (230.30±42.55) UL-1] and superoxide dismutase [(0.64±0.19) UL-1 vs. (2.68±0.62) UL-1] compared to controls. Lipid peroxidation was monitored by measuring thiobarbituric acid reactive substances (TBARS) that were expressed in terms of malondialdehyde (MDA) equivalents. Concentration of MDA in plasma was higher in painters than in controls [(7.48±1.31) nmol mL-1 vs. (3.08±0.56) nmol mL-1]. Significant changes were also observed in reduced and oxidised glutathione levels. The strong association between blood lead levels and oxidative stress markers in this population suggests that oxidative stress should be considered in the pathogenesis of lead-related diseases among people with low level environmental exposure to lead.Toksičnost olova javnozdravstveni je problem, napose u djece i odraslih osoba koje su im izložene profesionalno. Sve je više dokaza o štetnom djelovanju olova pri niskim razinama. Svrha je ovog ispitivanja bila procijeniti antioksidacijski status u lakirera iz grada Lucknowa u indijskoj pokrajini Uttar Pradesh. Iz skupine od 56 muškaraca lakirera u dobi od 20 do 50 godina s pozitivnim početnim nalazima olova u krvi, za ispitivanje su izabrana 35-orica čije su razine iznosile ≤400 µg L-1. Izabran je i jednaki broj kontrolnih ispitanika iz iste dobne skupine, koji nisu bili profesionalno izloženi olovu. Ispitana je povezanost izme|u izloženosti niskim razinama olova i antioksidacijskoga stanja te je utvrđeno da su razine olova u krvi lakirera [(219,2±61,9) µg L-1] bile oko sedam puta više negoli u kontrolnih ispitanika [(30,6±10,1) µg L-1]. Od biopokazatelja toksičnosti olova u lakirera je zamijećen značajan pad razina delta- ALAD [(9,13±4,62) UL-1 prema (39,38±5,05) UL-1] te rast razina cinkova protoporfirina [(187,9±49,8) µg L-1 prema (26,4±5,5) µg L-1] u odnosu na kontrolne ispitanike. Od antioksidacijskih enzima u lakirera je značajno pala aktivnost katalaze [(56,77±11,11) UL-1 prema (230,30±42,55) UL-1] i superoksid dismutaze [(0,64±0.19) UL-1 prema (2,68±0,62) UL-1] u odnosu na kontrolu, dok je produkt lipidne peroksidacije u plazmi (izv. thiobarbituric acid reactive substances, TBARS) izražen kao koncentracija malondialdehida (MDA) porastao [(7,48±1,31) nmol mL-1 prema (3,08±0,56) nmol mL-1]. Značajne su promjene također zamijećene u smanjenim razinama glutationa i njihovoj oksidaciji. Snažna povezanost razina olova u krvi s pokazateljima oksidacijskoga stresa upućuje na to da u osoba s niskom razinom izloženosti olovu iz okoliša kod razmatranja patogeneze bolesti povezane s olovom u obzir valja uzeti oksidacijski stres

    Protocol for the development of a CONSORT extension for RCTs using cohorts and routinely collected health data.

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    Background: Randomized controlled trials (RCTs) are often complex and expensive to perform. Less than one third achieve planned recruitment targets, follow-up can be labor-intensive, and many have limited real-world generalizability. Designs for RCTs conducted using cohorts and routinely collected health data, including registries, electronic health records, and administrative databases, have been proposed to address these challenges and are being rapidly adopted. These designs, however, are relatively recent innovations, and published RCT reports often do not describe important aspects of their methodology in a standardized way. Our objective is to extend the Consolidated Standards of Reporting Trials (CONSORT) statement with a consensus-driven reporting guideline for RCTs using cohorts and routinely collected health data. Methods: The development of this CONSORT extension will consist of five phases. Phase 1 (completed) consisted of the project launch, including fundraising, the establishment of a research team, and development of a conceptual framework. In phase 2, a systematic review will be performed to identify publications (1) that describe methods or reporting considerations for RCTs conducted using cohorts and routinely collected health data or (2) that are protocols or report results from such RCTs. An initial "long list" of possible modifications to CONSORT checklist items and possible new items for the reporting guideline will be generated based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statements. Additional possible modifications and new items will be identified based on the results of the systematic review. Phase 3 will consist of a three-round Delphi exercise with methods and content experts to evaluate the "long list" and generate a "short list" of key items. In phase 4, these items will serve as the basis for an in-person consensus meeting to finalize a core set of items to be included in the reporting guideline and checklist. Phase 5 will involve drafting the checklist and elaboration-explanation documents, and dissemination and implementation of the guideline. Discussion: Development of this CONSORT extension will contribute to more transparent reporting of RCTs conducted using cohorts and routinely collected health data

    Ceres Evolution and current state

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    International audienc

    Ceres, Vesta and Pallas : protoplanets not just asteroids,

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    Nonrandomized studies using causal-modeling may give different answers than RCTs: a meta-epidemiological study

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    To evaluate how estimated treatment effects agree between nonrandomized studies using causal modeling with marginal structural models (MSM-studies) and randomized trials (RCTs).; Meta-epidemiological study.; MSM-studies providing effect estimates on any healthcare outcome of any treatment were eligible. We systematically sought RCTs on the same clinical question and compared the direction of treatment effects, effect sizes, and confidence intervals.; The main analysis included 19 MSM-studies (1,039,570 patients) and 141 RCTs (120,669 patients). MSM-studies indicated effect estimates in the opposite direction from RCTs for eight clinical questions (42%), and their 95% CI (confidence interval) did not include the RCT estimate in nine clinical questions (47%). The effect estimates deviated 1.58-fold between the study designs (median absolute deviation OR [odds ratio] 1.58; IQR [interquartile range] 1.37 to 2.16). Overall, we found no systematic disagreement regarding benefit or harm but confidence intervals were wide (summary ratio of odds ratios [sROR] 1.04; 95% CI 0.88 to 1.23). The subset of MSM-studies focusing on healthcare decision-making tended to overestimate experimental treatment benefits (sROR 1.44; 95% CI 0.99 to 2.09).; Nonrandomized studies using causal modeling with MSM may give different answers than RCTs. Caution is still required when nonrandomized "real world" evidence is used for healthcare decisions
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