41 research outputs found
Behavioral and Social Influences on Food Choice
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75438/1/j.1753-4887.1998.tb01732.x.pd
Characterization of the dynamics of sitting during a sustained and mentally demanding computer task
Effects of prolonged and acute muscle pain on the force control strategy during isometric contractions
Musculoskeletal pain is associated with multiple adaptions in movement control. This study aimed to determine whether changes in movement control acquired during acute pain are maintained over days of pain exposure. On day 0, the extensor carpi radialis brevis muscle of healthy participants was injected with nerve growth factor (NGF) to induce persistent movement-evoked pain (n\ua0=\ua013) or isotonic saline as a control (n\ua0=\ua013). On day 2, short-lasting pain was induced by injection of hypertonic saline into extensor carpi radialis brevis muscles of all participants. Three-dimensional force components were recorded during submaximal isometric wrist extensions on day 0, day 4, and before, during, and after saline-induced pain on day 2. Standard deviation (variation of task-related force) and total excursion of center of pressure (variation of force direction) were assessed. Maximal movement-evoked pain was 3.3\ua0±\ua0.4 (0â10 numeric scale) in the NGF-group on day 2 whereas maximum saline-induced pain was 6.8\ua0±\ua0.3\ua0cm (10-cm visual analog scale). The difference in centroid position of force direction relative to day 0 was greater in the NGF group than in the control group (P\ua
Glioblastoma extracellular vesicles influence glial cell hyaluronic acid deposition to promote invasiveness
Background.
Infiltration of glioblastoma (GBM) throughout the brain leads to its inevitable recurrence following standard-of-care treatments, such as surgical resection, chemo- and radio-therapy. A deeper understanding of the mechanisms invoked by GMB to infiltrate the brain is needed to develop approaches to contain the disease and reduce recurrence. The aim of this study was to discover mechanisms through which extracellular vesicles (EVs) released by GBM influence the brain microenvironment to facilitate infiltration, and to determine how altered extracellular matrix (ECM) deposition by glial cells might contribute to this.
Methods.
CRISPR was used to delete genes, previously established to drive carcinoma invasiveness and EV production, from patient-derived primary and GBM cell lines. We purified and characterised EVs released by these cells, assessed their capacity to foster pro-migratory microenvironments in mouse brain slices, and evaluated the contribution made by astrocyte-derived extracellular matrix (ECM) to this. Finally, we determined how CRISPR-mediated deletion of genes, which we had found to control EV-mediated communication between GBM cells and astrocytes, influenced GBM infiltration when orthotopically injected into CD1-nude mice.
Results.
GBM cells expressing a p53 mutant (p53 273H) with established pro-invasive gain-of-function release EVs containing a sialomucin, podocalyxin (PODXL), which encourages astrocytes to deposit ECM with increased levels of hyaluronic acid (HA). This HA-rich ECM, in turn, promotes migration of GBM cells. Consistently, CRISPR-mediated deletion of PODXL opposes infiltration of GBM in vivo. Conclusions This work describes several key components of an EV-mediated mechanism though which GBM cells educate astrocytes to support infiltration of the surrounding healthy brain tissue.
Conclusions.
This work describes several key components of an EV-mediated mechanism though which GBM cells educate astrocytes to support infiltration of the surrounding healthy brain tissue
Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data metaâanalysis
Background
Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaaveâs syndrome (BS).
Methods
We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (â€â24 h) and late (>â24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission.
Results
Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8â5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2â7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2â6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, pâ<â0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1â3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1â3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, pâ=â0.001), compared with late TOD.
Conclusions
This individual patient data meta-analysis confirms the general opinion that an early (â€â24 h) compared to a late diagnosis (>â24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.publishedVersio
Medial longitudinal arch development of school children : The College of Podiatry Annual Conference 2015: meeting abstracts
Background Foot structure is often classified into flat foot, neutral and high arch type based on the variability of the Medial Longitudinal Arch (MLA). To date, the literature provided contrasting evidence on the age when MLA development stabilises in children. The influence of footwear on MLA development is also unknown. Aim This study aims to (i) clarify whether the MLA is still changing in children from age 7 to 9 years old and (ii) explore the relationship between footwear usage and MLA development, using a longitudinal approach. Methods We evaluated the MLA of 111 healthy school children [age = 6.9 (0.3) years] using three parameters [arch index (AI), midfoot peak pressure (PP) and maximum force (MF: % of body weight)] extracted from dynamic foot loading measurements at baseline, 10-month and 22-month follow-up. Information on the type of footwear worn was collected using survey question. Linear mixed modelling was used to test for differences in the MLA over time. Results Insignificant changes in all MLA parameters were observed over time [AI: P = .15; PP: P = .84; MF: P = .91]. When gender was considered, the AI of boys decreased with age [P = .02]. Boys also displayed a flatter MLA than girls at age 6.9 years [AI: mean difference = 0.02 (0.01, 0.04); P = .02]. At baseline, subjects who wore close-toe shoes displayed the lowest MLA overall [AI/PP/MF: P < .05]. Subjects who used slippers when commencing footwear use experienced higher PP than those who wore sandals [mean difference = 31.60 (1.44, 61.75) kPa; post-hoc P = .04]. Discussion and conclusion Our findings suggested that the MLA of children remained stable from 7 to 9 years old, while gender and the type of footwear worn during childhood may influence MLA development. Clinicians may choose to commence therapy when a child presents with painful flexible flat foot at age 7 years, and may discourage younger children from wearing slippers when they commence using footwear
Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta-anal
Background: Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaaveâs syndrome (BS). Methods: We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (†24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. Results: Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8â5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2â7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2â6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 nonâcritically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (nâ=â257), ARB (nâ=â248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; nâ=â10), or no RAS inhibitor (control; nâ=â264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ supportâfree days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ supportâfree days among critically ill patients was 10 (â1 to 16) in the ACE inhibitor group (nâ=â231), 8 (â1 to 17) in the ARB group (nâ=â217), and 12 (0 to 17) in the control group (nâ=â231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ supportâfree days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570