Publications by authors named "Matthew Miller"

800 Publications

Gut microbiota-based vaccination engages innate immunity to improve blood glucose control in obese mice.

Mol Metab 2021 Nov 25:101404. Epub 2021 Nov 25.

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada; Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Canada.

Objective: Obesity and diabetes increase circulating levels of microbial components derived from the gut microbiota. Individual bacterial factors (i.e., postbiotics) can have opposing effects on blood glucose.

Methods: We tested the net effect of gut bacterial extracts on blood glucose using a microbiota-based vaccination strategy in mice.

Results: Male and female mice had improved glucose and insulin tolerance five weeks after a single subcutaneous injection of a specific dose of a bacterial extract obtained from the luminal contents of the upper small intestine (SI), lower SI or cecum. Injection of mice with intestinal extracts from germ-free mice revealed that bacteria were required for a microbiota-based vaccination to improve blood glucose control. Vaccination of Nod1, Nod2, and Ripk2 mice showed that each of these innate immune proteins was required for bacterial extract injection to improve blood glucose control. A microbiota-based vaccination promoted an immunoglobulin-G (IgG) response directed against bacterial extract antigens, where subcutaneous injection of mice with the luminal contents of the lower SI elicited a bacterial extract-specific IgG response that is compartmentalized to the lower SI of vaccinated mice. A microbiota-based vaccination was associated with an altered microbiota composition in the lower SI and colon of mice. Lean mice only required a single injection of small intestinal-derived bacterial extract, but high fat diet (HFD)-fed, obese mice required prime-boost bacterial extract injections for improvements in blood glucose control.

Conclusions: Subversion of the gut barrier by vaccination with a microbiota-based extract engages innate immunity to promote long-lasting improvements in blood glucose control in a dose-dependent manner.
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http://dx.doi.org/10.1016/j.molmet.2021.101404DOI Listing
November 2021

Lasting Changes to Circulating Leukocytes in People with Mild SARS-CoV-2 Infections.

Viruses 2021 11 8;13(11). Epub 2021 Nov 8.

McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.

Survivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections ( = 22), compared to those that had recovered from other mild respiratory infections ( = 11). Individuals who had experienced mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1-3 months after symptom onset, and changes in phenotype and function of circulating T-cells that were not apparent in individuals 6-9 months post-symptom onset. Markers of monocyte activation, and expression of adherence and chemokine receptors indicative of altered migratory capacity, were also higher at 1-3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6-9 months post-infection. Perhaps most surprisingly, significantly more T-cells could be activated by polyclonal stimulation in individuals who had recently experienced a mild SARS-CoV-2, infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for at least three months after mild or asymptomatic SARS-CoV-2 infections.
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http://dx.doi.org/10.3390/v13112239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622816PMC
November 2021

Mass Spectrometry-Based Metabolomic and Lipidomic Analysis of the Effect of High Fat/High Sugar Diet and Greenshell Mussel Feeding on Plasma of Ovariectomized Rats.

Metabolites 2021 Oct 31;11(11). Epub 2021 Oct 31.

School of Health Sciences, College of Health, Massey University, Palmerston North 4442, New Zealand.

This study aimed to examine the changes in lipid and metabolite profiles of ovariectomized (OVX) rats with diet-induced metabolic syndrome-associated osteoarthritis (MetOA) after supplementation with greenshell mussel (GSM) using an untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach. Ninety-six rats were fed with one of four diets: control, control supplemented with GSM + GSM, high fat/high sugar (HFHS), or high fat/high sugar enriched with GSM (HFHS + GSM). After 8 weeks on experimental diets, half of the rats in each group underwent OVX and the other half were sham operated. After being fed for an additional 28 weeks, blood samples were collected for the metabolomics analysis. Lipid and polar metabolites were extracted from plasma and analysed by LC-MS. We identified 29 lipid species from four lipid subclasses (phosphatidylcholine, lysophosphatidylcholine, diacylglycerol, and triacylglycerol) and a set of eight metabolites involved in amino acid metabolism (serine, threonine, lysine, valine, histidine, pipecolic acid, 3-methylcytidine, and cholic acid) as potential biomarkers for the effect of HFHS diet and GSM supplementation. GSM incorporation more specifically in the control diet generated significant alterations in the levels of several lipids and metabolites. Further studies are required to validate these findings that identify potential biomarkers to follow OA progression and to monitor the impact of GSM supplementation.
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http://dx.doi.org/10.3390/metabo11110754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622240PMC
October 2021

A multicenter evaluation of the accuracy of prehospital eFAST by a physician-staffed helicopter emergency medical service.

Emerg Radiol 2021 Nov 24. Epub 2021 Nov 24.

Aeromedical Operations, NSW Ambulance, 33 Nancy Ellis Leebold Drive, Bankstown Airport, Sydney, NSW, 2200, Australia.

Purpose: The purpose of this study is to report the relative accuracy of prehospital extended focused assessment with sonography in trauma (eFAST) examinations performed by HEMS physicians.

Methods: Trauma patients who received prehospital eFAST by HEMS clinicians between January 2013 and December 2017 were reviewed. The clinician's interpretations of these ultrasounds were compared to gold standard references of CT imaging or operating room findings. The outcomes measured include the calculated accuracy of eFAST for detecting intraperitoneal free fluid (IPFF), pneumothorax, hemothorax, and pericardial fluid compared to available gold standard results.

Results: Of the 411 patients with adequate data for comparison, the median age was 39.5 years with 73% male and 98% sustaining blunt force trauma. For the detection of IPFF, eFAST had a sensitivity of 25% (95% CI 16-36%) and specificity of 96% (95% CI 93-98%). Sensitivities and specificities were calculated for pneumothorax (38% and 96% respectively), hemothorax (17% and 97% respectively), and pericardial effusion (17% and 100% respectively). These results did not change significantly when reassessed with several sensitivity analyses.

Conclusion: Prehospital eFAST is reliable for detecting the presence of intraperitoneal free fluid. This finding should inform receiving trauma teams to prepare for early definitive care in these patients. The low sensitivities across all components of the eFAST highlight the importance of cautiously interpreting negative studies while prompting the need for further studies.

Trial Registration: ACTRN12618001973202 (Registered on 06/12/2018).
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http://dx.doi.org/10.1007/s10140-021-02002-4DOI Listing
November 2021

Knowledge of State Gun Laws Among US Adults in Gun-Owning Households.

JAMA Netw Open 2021 Nov 1;4(11):e2135141. Epub 2021 Nov 1.

Harvard Injury Control Research Center, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.35141DOI Listing
November 2021

The RabGAPs EPI64A and EPI64B regulate the apical structure of epithelial cells.

Mol Biol Cell 2021 Nov 10:mbcE21050268. Epub 2021 Nov 10.

Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca NY 14850.

Here we report on the related TBC/RabGAPs EPI64A and EPI64B and show that they function to organize the apical aspect of epithelial cells. EPI64A binds the scaffolding protein EBP50/NHERF1, which itself binds active ezrin in epithelial cell microvilli. Epithelial cells additionally express EPI64B that also localizes to microvilli. However, EPI64B does not bind EBP50 and both proteins are shown to have a microvillar localization domain that spans the RabGAP domains. CRISPR/Cas9 was used to inactivate expression of each protein individually or both in Jeg-3 and Caco2 cells. In Jeg-3 cells, loss of EPI64B resulted in a reduction of apical microvilli, and a further reduction was seen in the double knockout, mostly likely due to misregulation of Rab8 and Rab35. In addition, apical junctions were partially disrupted in cells lacking EPI64A, and accentuated in the double knock out. In Caco2 loss of EPI64B resulted in wavy junctions, whereas loss of both EPI64A and EPI64B had a severe phenotype often resulting in cells with a stellate apical morphology. In the knockout cells, the basal region of the cell remained unchanged, so EPI64A and EPI64B specifically localize to and regulate the morphology of the apical domain of polarized epithelial cells.
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http://dx.doi.org/10.1091/mbc.E21-05-0268DOI Listing
November 2021

Effect of inactivated influenza vaccination on human coronavirus infection: Secondary analysis of a randomized trial in Hutterite colonies.

Vaccine 2021 11 18;39(48):7058-7065. Epub 2021 Oct 18.

Department of Medicine, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; Department of Mathematics and Statistics, McMaster University, Hamilton, ON, Canada. Electronic address:

Background: Although influenza vaccines provide protection against influenza viruses, concern has been raised that they may increase susceptibility to non-influenza respiratory viruses. As pandemic lockdowns end, temporal overlap of circulation of seasonal influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expected. Understanding the impact of influenza vaccination on risk of coronavirus infection is therefore of considerable public health importance.

Methods: We performed a secondary analysis of a randomized trial where children and adolescents in Canadian Hutterite colonies were randomly assigned by colony to receive the 2008-2009 seasonal inactivated trivalent influenza vaccine (TIV) or a control hepatitis A (HepA) vaccine. All 3273 colony members (vaccinated children and nonvaccine recipients) were followed for the primary outcome of RT-PCR confirmed seasonal coronavirus infection. Serum collected pre- and post-vaccination was analyzed for titers of IgG antibodies towards human coronaviruses (HCoV).

Results: The incidence of coronavirus infection was 0·18/1000 person-days in the colonies that received TIV vs 0.36/1000 person-days in the control group, hazard ratio (HR) 0.49 [0.21-1.17]. The risk reduction among non-vaccine recipients in the TIV group compared to the control group was HR 0.55 [0.24-1.23]. There was an increase in the geometric mean fold change of HCoV-OC43 antibody titers following TIV compared to HepA vaccine (mean difference 1.2 [0.38-2.06], p = 0.007), and an increase in geometric mean HCoV-NL63 antibody titers post-TIV (262.9 vs 342.9, p = 0.03).

Conclusion: The influenza vaccine does not increase the risk of a coronavirus infection. Instead, the influenza vaccine may reduce the rate of coronavirus infections by inducing cross-reactive anti-coronavirus IgG antibodies.
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http://dx.doi.org/10.1016/j.vaccine.2021.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520850PMC
November 2021

Effects of fasting and temperature on the biological parameters, proximal composition, and fatty acid profile of Chinook salmon (Oncorhynchus tshawytscha) at different life stages.

Comp Biochem Physiol A Mol Integr Physiol 2021 Nov 6;264:111113. Epub 2021 Nov 6.

Cawthron Institute, Nelson 7010, New Zealand. Electronic address:

We investigated the effects of temperature and fasting on chinook salmon (Oncorhynchus tshawytscha) at different life stages. In the first stage, fish were reared at 13 °C (198.5 ± 34.6 g) or 17 °C (218.3 ± 47.6 g) and fasted for 27 and 26 days, respectively. In the second stage, fish reared at 13 °C (481.8 ± 54.3 g) and 17 °C (597.3 ± 64.3 g) were fasted for 42 and 41 days respectively. At the third stage, fish were reared only at 17 °C (1065.7 ± 190.9 g) and fasted for 42 days. At the end of each fasting period performance, fillet and whole-body proximal composition, and whole-body fatty acid profile were compared among fish before and after fasting. Additionally, fillet fatty acid daily loss was compared in fasted fish from different treatments. The results showed that body weight was not significantly impacted by fasting. However, at 17 °C fasting at all three stages had a negative impact on fillet weight and total fatty acid daily loss. With few exceptions, saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids from n-6 series (n-6 PUFA) were preserved in fillet of fish at 17 °C, while higher daily losses of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and consequently polyunsaturated from n-3 series (n-3 PUFA) were observed in these same fish and in smaller fish at 13 °C. The results presented in this study provide important information regarding the influence of fasting and temperature on chinook salmon performance and metabolism, providing basis for future nutritional and compositional studies for this important commercial species.
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http://dx.doi.org/10.1016/j.cbpa.2021.111113DOI Listing
November 2021

Antibody Responses 3-5 Months Post-Vaccination with mRNA-1273 or BNT163b2 in Nursing Home Residents.

J Am Med Dir Assoc 2021 Dec 1;22(12):2512-2514. Epub 2021 Nov 1.

Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; Centre for Integrated Care, St. Joseph's Health System, Hamilton, ON, Canada.

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http://dx.doi.org/10.1016/j.jamda.2021.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558841PMC
December 2021

iSDAsoil: The first continent-scale soil property map at 30 m resolution provides a soil information revolution for Africa.

PLoS Biol 2021 Nov 1;19(11):e3001441. Epub 2021 Nov 1.

Innovative Solutions for Decision Agriculture Ltd (iSDA), Harpenden, United Kingdom.

Open access, high-resolution soil property maps have been created for Africa at 30 m resolution, using machine learning trained on over 100,000 analysed soil samples. Combined with other field-level information, iSDAsoil enables the possibility of site-specific agronomy advisory for smallholder farmers.
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http://dx.doi.org/10.1371/journal.pbio.3001441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584968PMC
November 2021

Firearm Background Checks in States With and Without Background Check Laws.

Am J Prev Med 2021 Oct 24. Epub 2021 Oct 24.

Department of Health Science, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts.

Introduction: A total of 21 states have enacted laws that extend the types of firearm transfers that require the prospective purchaser to undergo a background check, often referred to as comprehensive background check laws. Utilizing a national representative survey of gun owners, this study estimates the proportion of firearm transfers that occur without background checks in states with and without these laws.

Methods: Data came from the 2019 National Firearms Survey, a nationally representative survey of 2,950 firearm owners in the U.S.

Results: A smaller proportion of gun owners in states with comprehensive background check laws did not undergo a background check when they acquired their most recent firearm compared with gun owners in states without comprehensive background check laws (12%, 95% CI=9, 16 vs 24%, 95% CI=21, 28). In states with comprehensive background check laws, 40% (95% CI=23, 60) of purchasers who bought their firearm from a friend, family member, or acquaintance did not undergo a background check compared with 74% (95% CI=58, 85) in states without comprehensive background check laws. Differences in background check frequency by comprehensive background check law status was largely due to differences for 2 types of transactions: (1) private sales between friends/family members/acquaintances and (2) nonpurchase transfers.

Conclusions: Fewer gun owners acquired their most recent firearm without a background check when the transfer occurred in a state with, relative to without, comprehensive background check laws. Private firearm sales that do not occur at traditional retail locations continue to be the type of sale least likely to have a background check.
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http://dx.doi.org/10.1016/j.amepre.2021.08.013DOI Listing
October 2021

Increased left and right atrial volume indices are associated with decreased survival times post-cardiac arrest.

Resuscitation 2021 Oct 22. Epub 2021 Oct 22.

Division of Cardiovascular Medicine, University of Virginia Health System, Charlottesville, VA, United States. Electronic address:

Background: Left and right atrial volume indices (LAVI and RAVI) are markers of cardiac remodeling. LAVI and RAVI are associated with worse outcomes in other cardiac conditions. This study aimed to determine the associations of these atrial volume indices with survival time post-cardiac arrest.

Methods: This was a single center, retrospective study of patients with a sudden cardiac arrest event during index hospitalization from 2014-2018 based on pre-arrest parameters. The analysis was stratified based on whether a pulseless ventricular tachycardia/ventricular fibrillation (pVT/VF) event or a pulseless electrical activity (PEA)/asystole event occurred. Cox proportional hazards regression and model selection with best subsets approach evaluated the association of atrial volume parameters with survival times in the context of other covariates.

Results: Of 305 patients studied (64 ± 14 years, 37% female), the mean LAVI was 34.0 ± 15.8 mL/m (based on 162 reliable measurements), and mean RAVI was 25.0 ± 15.6 mL/m (based on 163 measurements). Increased atrial volume indices were most strongly associated with survival in patients who had sustained pVT/VF (LAVI HR 0.47, 95% CI 0.25-0.90, p = 0.020; RAVI HR 0.57, 95% CI 0.30-1.05, p = 0.074). In multivariable best subsets Cox regression with LAVI, RAVI, and 13 other scaled covariates, LAVI < 34 ml/m was by far the best single predictor of survival (p < 0.0001), and the next best predictor was the absence of pulmonary hypertension.

Conclusion: Among patients with cardiac arrest from ventricular arrhythmias, those with no more than mild left atrial enlargement pre-arrest by LAVI measurement had the best prognosis. Additional studies are indicated to validate the importance of this finding for clinical management decisions.

Condensed Abstract: In patients with sudden cardiac arrest associated with ventricular arrhythmias, a left atrial volume index (LAVI) < 34 mL/m prior to the arrest had the strongest association with survival among fifteen candidate predictors. Pulmonary hypertension was more common in patients with an elevated right atrial volume index (RAVI), and the absence of pulmonary hypertension was the next best pre-arrest parameter predictive of survival. Larger studies are indicated to validate the use of LAVI for clinical management decisions in this condition.
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http://dx.doi.org/10.1016/j.resuscitation.2021.10.023DOI Listing
October 2021

Physical inactivity in older adults with cognitive impairment without dementia: room for improvement.

Aging Clin Exp Res 2021 Oct 21. Epub 2021 Oct 21.

Division of Geriatrics, University of California, San Francisco, San Francisco, CA, USA.

Background: Persons with cognitive impairment without dementia are at high risk of adverse health outcomes. Tailored intervention targeting moderate-vigorous physical activity (MVPA) may reduce these risks.

Aims: To identify the prevalence and predictors of physical inactivity among older adults with cognitive impairment, no dementia (CIND); and estimate the proportion of inactive people with CIND who are capable of greater MVPA.

Methods: We studied 1875 community dwelling participants (over age 65) with CIND in the Health and Retirement Study. Physical inactivity was defined as MVPA ≤ 1x/week. Associations of physical inactivity with sociodemographic, health, and physical function were examined using chi-square and modified Poisson regression. We considered physically inactive participants capable of greater MVPA if they reported MVPA at least 1-3x/month, no difficulty walking several blocks, or no difficulty climbing several flights of stairs.

Results: Fifty-six percent of participants with CIND were physically inactive. Variables with the highest age, sex, and race/ethnicity adjusted risk ratio (ARR) for physical inactivity were self-rated health (poor [76.9%]vs. excellent [34.2%]; ARR [95% CI] 2.27 [1.56-3.30]), difficulty walking (across the room [86.5%] vs. none [40.5%]; ARR [95% CI] 2.09 [1.87-2.35]), total assets (lowest quartile [62.6%] vs. highest quartile [43.1%]; ARR [95% CI] 1.54 [1.29-1.83]), and lower education attainment (less than high school [59.6%] vs college graduate [42.8%]; ARR [95% CI] 1.46 [1.17-1.83]). Among physically inactive older adults with CIND, 61% were estimated to be capable of greater MVPA.

Conclusions: Although physical inactivity is prevalent among older adults with CIND, many are capable of greater MVPA. Developing tailored physical activity interventions for this vulnerable population may improve cognitive, health, and quality of life outcomes.
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http://dx.doi.org/10.1007/s40520-021-01999-5DOI Listing
October 2021

Potentiation of long-acting β-agonist and glucocorticoid responses in human airway epithelial cells by modulation of intracellular cAMP.

Respir Res 2021 Oct 19;22(1):266. Epub 2021 Oct 19.

Firestone Institute for Respiratory Health-Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON, L8N 4A6, Canada.

Introduction: Over 300 million people in the world live with asthma, resulting in 500,000 annual global deaths with future increases expected. It is estimated that around 50-80% of asthma exacerbations are due to viral infections. Currently, a combination of long-acting beta agonists (LABA) for bronchodilation and glucocorticoids (GCS) to control lung inflammation represent the dominant strategy for the management of asthma, however, it is still sub-optimal in 35-50% of moderate-severe asthmatics resulting in persistent lung inflammation, impairment of lung function, and risk of mortality. Mechanistically, LABA/GCS combination therapy results in synergistic efficacy mediated by intracellular cyclic adenosine monophosphate (cAMP).

Hypothesis: Increasing intracellular cAMP during LABA/GCS combination therapy via inhibiting phosphodiesterase 4 (PDE4) and/or blocking the export of cAMP by ATP Binding Cassette Transporter C4 (ABCC4), will potentiate anti-inflammatory responses of mainstay LABA/GCS therapy.

Methods: Expression and localization experiments were performed using in situ hybridization and immunohistochemistry in human lung tissue from healthy subjects, while confirmatory transcript and protein expression analyses were performed in primary human airway epithelial cells and cell lines. Intervention experiments were performed on the human airway epithelial cell line, HBEC-6KT, by pre-treatment with combinations of LABA/GCS with PDE4 and/or ABCC4 inhibitors followed by Poly I:C or imiquimod challenge as a model for viral stimuli. Cytokine readouts for IL-6, IL-8, CXCL10/IP-10, and CCL5/RANTES were quantified by ELISA.

Results: Using archived human lung and human airway epithelial cells, ABCC4 gene and protein expression were confirmed in vitro and in situ. LABA/GCS attenuation of Poly I:C or imiquimod-induced IL-6 and IL-8 were potentiated with ABCC4 and PDE4 inhibition, which was greater when ABCC4 and PDE4 inhibition was combined. Modulation of cAMP levels had no impact on LABA/GCS modulation of Poly I:C-induced CXCL10/IP-10 or CCL5/RANTES.

Conclusion: Modulation of intracellular cAMP levels by PDE4 or ABCC4 inhibition potentiates LABA/GCS efficacy in human airway epithelial cells challenged with viral stimuli. The data suggest further exploration of the value of adding cAMP modulators to mainstay LABA/GCS therapy in asthma for potentiated anti-inflammatory efficacy.
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http://dx.doi.org/10.1186/s12931-021-01862-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527633PMC
October 2021

Real-World Comparison of Bezlotoxumab to Standard of Care Therapy for Prevention of Recurrent Clostridioides difficile Infection in Patients at High Risk for Recurrence.

Clin Infect Dis 2021 Aug 4. Epub 2021 Aug 4.

Department of Pharmacy, University of Colorado Hospital, Aurora, Colorado, USA.

Background: Bezlotoxumab (BEZ) is a monoclonal antibody used to prevent recurrent Clostridioides difficile infection (rCDI). This study investigates BEZ effectiveness in relation to rCDI and patient-specific risk factors in a real-world setting.

Methods: A matched, retrospective cohort study was conducted from 2015 to 2019 to compare BEZ to historical standard of care (SoC) therapy with vancomycin or fidaxomicin. The primary outcome was incidence of 90-day rCDI. Secondary outcomes were incidence of all-cause hospital readmission and all-cause mortality at 90 days, infusion-related reactions, and incidence of heart failure exacerbation. Baseline confounding was addressed using inverse probability of treatment weighting (IPTW).

Results: Overall, 107 participants were included (54 BEZ and 53 SoC). Mean number of prior CDI episodes was 2, median number of risk factors for rCDI was 4, and 28% of participants had severe CDI. Incidence of 90-day rCDI was 11% BEZ vs 43% SoC (P = < .001) and 90-day all-cause readmission was 40% BEZ vs 64% SoC (P = .011). In IPTW-adjusted analyses, BEZ was associated with significantly reduced odds of rCDI (odds ratio [OR], 0.14 [95% confidence interval {CI}: .05-.41]) and all-cause readmission (OR, 0.36 [95% CI: .16-.81]). No safety signals were detected with BEZ use.

Conclusions: BEZ is effective for the prevention of rCDI and reduction in all-cause hospital readmission for patients at high risk for recurrence, supporting current guideline recommendations.
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http://dx.doi.org/10.1093/cid/ciab674DOI Listing
August 2021

Anisocoria and Poor Pupil Reactivity by Quantitative Pupillometry in Patients With Intracranial Pathology.

Crit Care Med 2021 Sep 22. Epub 2021 Sep 22.

Department of Neurology, Boston Medical Center, Boston, MA. Department of Neurology, Boston University School of Medicine, Boston, MA. Department of Neurology, Brigham & Women's Hospital, Boston, MA. Harvard Medical School, Boston, MA. Department of Neurology, Massachusetts General Hospital, Boston, MA. Boston University School of Public Health, Boston, MA.

Objectives: To describe the prevalence and associated risk factors of new onset anisocoria (new pupil size difference of at least 1 mm) and its subtypes: new onset anisocoria accompanied by abnormal and normal pupil reactivities in patients with acute neurologic injuries.

Design: We tested the association of patients who experienced new onset anisocoria subtypes with degree of midline shift using linear regression. We further explored differences between quantitative pupil characteristics associated with first-time new onset anisocoria and nonnew onset anisocoria at preceding observations using mixed effects logistic regression, adjusting for possible confounders.

Setting: All quantitative pupil observations were collected at two neuro-ICUs by nursing staff as standard of care.

Patients: We conducted a retrospective two-center study of adult patients with intracranial pathology in the ICU with at least a 24-hour stay and three or more quantitative pupil measurements between 2016 and 2018.

Measurements And Main Results: We studied 221 patients (mean age 58, 41% women). Sixty-three percent experienced new onset anisocoria. New onset anisocoria accompanied by objective evidence of abnormal pupil reactivity occurring at any point during hospitalization was significantly associated with maximum midline shift (β = 2.27 per mm; p = 0.01). The occurrence of new onset anisocoria accompanied by objective evidence of normal pupil reactivity was inversely associated with death (odds ratio, 0.34; 95% CI, 0.16-0.71; p = 0.01) in adjusted analyses. Subclinical continuous pupil size difference distinguished first-time new onset anisocoria from nonnew onset anisocoria in up to four preceding pupil observations (or up to 8 hr prior). Minimum pupil reactivity between eyes also distinguished new onset anisocoria accompanied by objective evidence of abnormal pupil reactivity from new onset anisocoria accompanied by objective evidence of normal pupil reactivity prior to first-time new onset anisocoria occurrence.

Conclusions: New onset anisocoria occurs in over 60% of patients with neurologic emergencies. Pupil reactivity may be an important distinguishing characteristic of clinically relevant new onset anisocoria phenotypes. New onset anisocoria accompanied by objective evidence of abnormal pupil reactivity was associated with midline shift, and new onset anisocoria accompanied by objective evidence of normal pupil reactivity had an inverse relationship with death. Distinct quantitative pupil characteristics precede new onset anisocoria occurrence and may allow for earlier prediction of neurologic decline. Further work is needed to determine whether quantitative pupillometry sensitively/specifically predicts clinically relevant anisocoria, enabling possible earlier treatments.
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http://dx.doi.org/10.1097/CCM.0000000000005272DOI Listing
September 2021

Non-polar lipid from greenshell mussel (Perna canaliculus) inhibits osteoclast differentiation.

Bone Rep 2021 Dec 24;15:101132. Epub 2021 Sep 24.

School of Food and Advanced Technology, Massey University, Palmerston North 4442, New Zealand.

The osteoclast-dependent bone resorption process is a crucial part of the bone regulatory system. The excessive function of osteoclasts can cause diseases of bone, joint, and other tissues such as osteoporosis and osteoarthritis. Greenshell mussel oil (GSM), a good source of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs), was fractionated into total lipid, polar lipid, and non-polar lipid components and their anti-osteoclastogenic activity tested in RAW 264.7 cell cultures. Osteoclast differentiation process was achieved after 5 days of incubation with RANKL in 24-well culture plates. Introducing the non-polar lipid fraction into the culture caused a lack of cell differentiation, and a reduction in tartrate-resistant acid phosphatase (TRAP) activity and TRAP cell numbers in a dose-dependent manner (50% reduction at the concentration of 20 μg/mL, p < 0.001). Moreover, actin ring formation was significantly diminished by non-polar lipids at 10-20 μg/mL. The bone digestive enzymes released by osteoclasts into the pit formation were also compromised by downregulating gene expression of cathepsin K, carbonic anhydrase II (CA II), matrix metalloproteinase 9 (MMP-9), and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). This study revealed that the non-polar lipid fraction of GSM oil contains bioactive substances which possess potent anti-osteoclastogenic activity.
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http://dx.doi.org/10.1016/j.bonr.2021.101132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493498PMC
December 2021

Influence of redox gradients on nitrate transport from the landscape to groundwater and streams.

Sci Total Environ 2021 Dec 9;800:150200. Epub 2021 Sep 9.

U.S. Geological Survey, 3215 Marine St., Boulder, CO 80303, United States of America.

Increases in nitrogen applications to the land surface since the 1950s have led to a cascade of negative environmental impacts, including degradation of drinking water supplies, nutrient enrichment of aquatic ecosystems and contributions to global climate change. In this study, groundwater, streambed porewater, and stream sampling were used to establish trends in nitrate concentrations and how redox gradients influence nitrate transport across diverse glacial terranes. Decadal sampling has found that elevated nitrate concentrations in shallow groundwater beneath cropland have been sustained for decades. Redox gradients established in the saturated zone using dissolved O, iron, nitrate and excess N from denitrification suggest that nitrate-bearing zones are thin in glacial terranes dominated by fine materials. These thin nitrate-bearing zones lead to suboxic, low nitrate streambed porewater and limit the contributions of nitrate to streams from slow-flow groundwater. In contrast, thick oxic zones in more coarse-grained glacial terranes allow nitrate to reach deeper groundwater, resulting in streambed porewater with elevated nitrate concentrations and causing a large portion of stream nitrate to be derived from slow-flow groundwater. Groundwater age tracer data indicate that denitrification occurs more quickly in the terrane dominated by fine material than in the more coarse-grained terrane. The quicker depletion of nitrate in the more fine-grained terrane suggests that the thinner oxic zone in this terrane is due, in part, to the greater availability and reactivity of electron donors in this terrane than in the more coarse-grained terrane. Groundwater age tracer data and hydrograph separation analysis suggest that saturated zone lag times between when changes in land use practices occur and when changes in stream water are fully observed may vary widely across hydrogeologic settings.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150200DOI Listing
December 2021

Activity density at a continental scale: What drives invertebrate biomass moving across the soil surface?

Ecology 2021 Oct 6:e03542. Epub 2021 Oct 6.

Department of Geography and Environmental Sustainability, University of Oklahoma, Norman, Oklahoma, 73019, USA.

Activity density (AD), the rate that an individual taxon or its biomass moves through the environment, is used both to monitor communities and quantify the potential for ecosystem work. The Abundance Velocity Hypothesis posited that AD increases with aboveground net primary productivity (ANPP) and is a unimodal function of temperature. Here we show that, at continental extents, increasing ANPP may have nonlinear effects on AD: increasing abundance, but decreasing velocity as accumulating vegetation interferes with movement. We use 5 yr of data from the NEON invertebrate pitfall trap arrays including 43 locations and four habitat types for a total of 77 habitat-site combinations to evaluate continental drivers of invertebrate AD. ANPP and temperature accounted for one-third to 92% of variation in AD. As predicted, AD was a unimodal function of temperature in forests and grasslands but increased linearly in open scrublands. ANPP yielded further nonlinear effects, generating unimodal AD curves in wetlands, and bimodal curves in forests. While all four habitats showed no AD trends over 5 yr of sampling, these nonlinearities suggest that trends in AD, often used to infer changes in insect abundance, will vary qualitatively across ecoregions.
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http://dx.doi.org/10.1002/ecy.3542DOI Listing
October 2021

In Vitro Human Skin Absorption of Solvent-deposited Solids: Niacinamide and Methyl Nicotinate.

J Pharm Sci 2021 Sep 30. Epub 2021 Sep 30.

The Procter & Gamble Company, Data and Modeling Sciences, Brussels Innovation Center, Belgium.

A quantitative understanding of the dose dependence of topical delivery is important to cosmetic and dermatological product development and to risk assessment for hazardous chemicals contacting the skin. Despite considerable research, predictive capability in this area remains limited. To this end we conducted an experimental skin absorption study of two closely related skin care agents, niacinamide (nicotinamide, NA) and methyl nicotinate (MN), and analyzed the results quantitatively using a transient diffusion model described separately (Yu et al. submitted for publication). Radiolabeled test compounds were solvent-deposited onto ex vivo human skin mounted in Franz diffusion cells over a dose range exceeding 4.5 orders of magnitude, and permeation was measured over a 1-4 day period. At low doses, the permeation rate of NA was approximately 60-fold lower than that of its lower melting, more lipophilic analog, MN; at high doses an even greater difference was observed. The difference can be qualitatively explained based on higher lipid solubility and lower crystallinity of MN relative to NA. Dissolution-limited mass transfer through a lipid layer at the SC surface is suggested. Relevance of the results to practical skin care formulations was confirmed by a parallel study of NA in an o/w emulsion.
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http://dx.doi.org/10.1016/j.xphs.2021.09.040DOI Listing
September 2021

Selective Breeding for Disease-Resistant Variants to Manage Chronic Wasting Disease in Farmed Whitetail Deer.

Genes (Basel) 2021 Sep 10;12(9). Epub 2021 Sep 10.

Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Glendale, AZ 85331, USA.

Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy (TSE) of cervids caused by a misfolded variant of the normal cellular prion protein, and it is closely related to sheep scrapie. Variations in a host's prion gene, , and its primary protein structure dramatically affect susceptibility to specific prion disorders, and breeding for variants that prevent scrapie infection has led to steep declines in the disease in North American and European sheep. While resistant alleles have been identified in cervids, a variant that completely prevents CWD has not yet been identified. Thus, control of the disease in farmed herds traditionally relies on quarantine and depopulation. In CWD-endemic areas, depopulation of private herds becomes challenging to justify, leading to opportunities to manage the disease in situ. We developed a selective breeding program for farmed white-tailed deer in a high-prevalence CWD-endemic area which focused on reducing frequencies of highly susceptible variants and introducing animals with less susceptible variants. With the use of newly developed primers, we found that breeding followed predictable Mendelian inheritance, and early data support our project's utility in reducing CWD prevalence. This project represents a novel approach to CWD management, with future efforts building on these findings.
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http://dx.doi.org/10.3390/genes12091396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471411PMC
September 2021

Two-photon excitation fluorescent spectral and decay properties of retrograde neuronal tracer Fluoro-Gold.

Sci Rep 2021 09 10;11(1):18053. Epub 2021 Sep 10.

Surgical Photonics and Engineering Laboratory, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles Street, Boston, MA, 02114, USA.

Fluoro-Gold is a fluorescent neuronal tracer suitable for targeted deep imaging of the nervous system. Widefield fluorescence microscopy enables visualization of Fluoro-Gold, but lacks depth discrimination. Though scanning laser confocal microscopy yields volumetric data, imaging depth is limited, and optimal single-photon excitation of Fluoro-Gold requires an unconventional ultraviolet excitation line. Two-photon excitation microscopy employs ultrafast pulsed infrared lasers to image fluorophores at high-resolution at unparalleled depths in opaque tissue. Deep imaging of Fluoro-Gold-labeled neurons carries potential to advance understanding of the central and peripheral nervous systems, yet its two-photon spectral and temporal properties remain uncharacterized. Herein, we report the two-photon excitation spectrum of Fluoro-Gold between 720 and 990 nm, and its fluorescence decay rate in aqueous solution and murine brainstem tissue. We demonstrate unprecedented imaging depth of whole-mounted murine brainstem via two-photon excitation microscopy of Fluoro-Gold labeled facial motor nuclei. Optimal two-photon excitation of Fluoro-Gold within microscope tuning range occurred at 720 nm, while maximum lifetime contrast was observed at 760 nm with mean fluorescence lifetime of 1.4 ns. Whole-mount brainstem explants were readily imaged to depths in excess of 450 µm via immersion in refractive-index matching solution.
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http://dx.doi.org/10.1038/s41598-021-97562-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433443PMC
September 2021

Use of the PROMIS-10 global health in patients with chronic low back pain in outpatient physical therapy: a retrospective cohort study.

J Patient Rep Outcomes 2021 Sep 6;5(1):81. Epub 2021 Sep 6.

Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, 1500 Owens St., Suite 400, San Francisco, CA, 94158, USA.

Background: Although evidence-based guidelines for physical therapy for patients with chronic low back pain (cLBP) are available, selecting patient-reported outcome measures to capture complexity of health status and quality of life remains a challenge. PROMIS-10 Global Health (GH) may be used to screen for impactful health risks and enable patient-centered care. The purpose of this study was to investigate the interrelationships between PROMIS-10 GH scores and patient demographics, health status, and healthcare utilization in patients with cLBP who received physical therapy.

Methods: A retrospective review of de-identified electronic health records of patients with cLBP was performed. Data were collected for 328 patients seen from 2017 to 2020 in three physical therapy clinics. Patients were grouped into HIGH and LOW initial assessment scores on the PROMIS-10 Global Physical Health (PH) and Global Mental Health (MH) measures. Outcomes of interest were patient demographics, health status, and healthcare utilization. Mann-Whitney U and chi-square tests were used to determine differences between groups, and binary logistic regression was used to calculate odds ratios (OR) to determine predictors of PH-LOW and MH-LOW group assignments.

Results: The PH-LOW and MH-LOW groups contained larger proportions of patients who were African American, non-Hispanic, and non-commercially insured compared to PH-HIGH and MH-HIGH groups (p < .05). The PH-LOW and MH-LOW groups also had a higher Charlson comorbidity index (CCI), higher rates of diabetes and depression, and more appointment cancellations or no-shows (p < .05). African American race (OR 2.54), other race (2.01), having Medi-Cal insurance (OR 3.37), and higher CCI scores (OR 1.55) increased the likelihood of being in the PH-LOW group. African American race (OR 3.54), having Medi-Cal insurance (OR 2.19), depression (OR 3.15), kidney disease (OR 2.66), and chronic obstructive pulmonary disease (OR 1.92) all increased the likeihood of being in the MH-LOW group.

Conclusions: Our study identified groups of patients with cLBP who are more likely to have lower PH and MH scores. PROMIS-10 GH provides an opportunity to capture and identify quality of life and global health risks in patients with cLBP. Using PROMIS-10 in physical therapy practice could help identify psychosocial factors and quality of life in the population with cLBP.
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http://dx.doi.org/10.1186/s41687-021-00360-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421489PMC
September 2021

High-Affinity Dimeric Aptamers Enable the Rapid Electrochemical Detection of Wild-Type and B.1.1.7 SARS-CoV-2 in Unprocessed Saliva.

Angew Chem Int Ed Engl 2021 11 4;60(45):24266-24274. Epub 2021 Oct 4.

Department of Biochemistry and Biomedical Sciences, McMaster University, Canada.

We report a simple and rapid saliva-based SARS-CoV-2 antigen test that utilizes a newly developed dimeric DNA aptamer, denoted as DSA1N5, that specifically recognizes the spike proteins of the wildtype virus and its Alpha and Delta variants with dissociation constants of 120, 290 and 480 pM, respectively, and binds pseudotyped lentiviruses expressing the wildtype and alpha trimeric spike proteins with affinity constants of 2.1 pM and 2.3 pM, respectively. To develop a highly sensitive test, DSA1N5 was immobilized onto gold electrodes to produce an electrochemical impedance sensor, which was capable of detecting 1000 viral particles per mL in 1:1 diluted saliva in under 10 min without any further sample processing. Evaluation of 36 positive and 37 negative patient saliva samples produced a clinical sensitivity of 80.5 % and specificity of 100 % and the sensor could detect the wildtype virus as well as the Alpha and Delta variants in the patient samples, which is the first reported rapid test that can detect any emerging variant of SARS-CoV-2.
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http://dx.doi.org/10.1002/anie.202110819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596624PMC
November 2021

Possible Predictive Factor of Acute Respiratory Distress Syndrome Development After Mild Traumatic Brain Injury: A Single Rural Trauma Center Preliminary Study.

Cureus 2021 Jul 20;13(7):e16508. Epub 2021 Jul 20.

Trauma/Surgical Critical Care, Guthrie Robert Packer Hospital, Sayre, USA.

Introduction Acute respiratory distress syndrome (ARDS) after mild traumatic brain injury (TBI) can be associated with significant morbidity and mortality. This study aimed to evaluate the potential predictive factors of ARDS development following mild TBI in trauma patients. Methods A retrospective chart review was done for adult trauma patients with mild TBI (GCS 13-15) requiring admission at our center from 2012 to 2020. Linear regression analysis and chi-square test were utilized to identify independent predictors of the association with ARDS in adults with mild TBI.  Results A total of 784 mild TBI patients were admitted during the time of interest; 34 patients developed ARDS during their index hospitalization. Patients who had ARDS were more likely to have acute kidney injury (AKI; p < 0.0001), sepsis (p < 0.01), rib fractures (p < 0.05), use of anticoagulants (p < 0.001), deep vein thrombosis (p < 0.001), transfusion during the first 4four hours upon admission (p = 0.01), intravenous fluid (IVF) resuscitation during the first four hours (p <0.05), the first eight hours (p = 0.01), the first 12 hours (p = 0.03), and intubation upon the admission (p < 0.0001). ARDS associated with mild TBI demonstrated a statistically significant increase in mortality during the index hospitalization (p < 0.0001). Conclusion ARDS after mild TBI can be associated with significant morbidity and mortality. Key risk factors identified include AKI, sepsis, anticoagulant use, deep vein thrombosis (DVT), transfusion in the first four hours, IVF resuscitation in the first four, eight, and 12 hours, and intubation upon admission.
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http://dx.doi.org/10.7759/cureus.16508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374992PMC
July 2021

Supraspinatus Rotator Cuff Repair: A Mouse Model and Technique.

Arthrosc Tech 2021 Aug 13;10(8):e1949-e1954. Epub 2021 Jul 13.

Department of Orthopaedics, University of Utah, Salt Lake City, Utah, U.S.A.

To improve understanding of the pathophysiology of rotator cuff repair and develop therapeutic treatments an animal model is essential. This Technical Note describes a comprehensive step-by-step description of rotator cuff repair in the mouse. This technique is particularly beneficial because the murine rotator cuff is anatomically similar to that of humans. The mouse model can also be used to test the biological role of candidate genes during repair and be used to identify drugs that accelerate the healing process.
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http://dx.doi.org/10.1016/j.eats.2021.04.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355505PMC
August 2021

Impact of Perioperative Complications on Living Kidney Donor Health-Related Quality of Life and Mental Health: Results From a Prospective Cohort Study.

Can J Kidney Health Dis 2021 11;8:20543581211037429. Epub 2021 Aug 11.

Department of Epidemiology & Biostatistics, Western University, London, ON, Canada.

Background: Although living kidney donation is safe, some donors experience perioperative complications.

Objective: This study explored how perioperative complications affected donor-reported health-related quality of life, depression, and anxiety.

Design: This research was a conducted as a prospective cohort study.

Setting: Twelve transplant centers across Canada.

Patients: A total of 912 living kidney donors were included in this study.

Measurements: Short Form 36 health survey, Beck Depression Inventory and Beck Anxiety Inventory.

Methods: Living kidney donors were prospectively enrolled predonation between 2009 to 2014. Donor perioperative complications were graded using the Clavien-Dindo classification system. Mental and physical health-related quality of life was assessed with the 3 measurements; measurements were taken predonation and at 3- and 12-months postdonation.

Results: Seventy-four donors (8%) experienced a perioperative complication; most were minor (n = 67 [91%]), and all minor complications resolved before hospital discharge. The presence (versus absence) of a perioperative complication was associated with lower mental health-related quality of life and higher depression symptoms 3-month postdonation; neither of these differences persisted at 12-month. Perioperative complications were not associated with any changes in physical health-related quality of life or anxiety 3-month postdonation.

Limitations: Minor complications may have been missed and information on complications postdischarge were not collected. No minimal clinically significant change has been defined for kidney donors across the 3 measurements.

Conclusions: These findings highlight a potential opportunity to better support the psychosocial needs of donors who experience perioperative complications in the months following donation.

Trial Registration: NCT00319579 and NCT00936078.
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http://dx.doi.org/10.1177/20543581211037429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361543PMC
August 2021

Using error-estimation to probe the psychological processes underlying contextual interference effects.

Hum Mov Sci 2021 Oct 7;79:102854. Epub 2021 Aug 7.

Program in Physical Therapy, Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA. Electronic address:

Although the learning benefits of interleaved practice schedules relative to blocked schedules are well-reported, the mechanisms underlying these effects are not fully understood. Researchers have generally suggested that random schedules of practice increase task-related information processing which arises due to switching between variations of the same task (or switching between different tasks). Thus, one potentially useful way to both probe and manipulate contextual interference is to pair it with error estimation during practice. Forced error estimation increases task-related information processing and recording these estimates provides insight into learners' self-awareness of their errors. In the present study, 84 participants were randomly allocated to four groups. Participants practiced a timing task under blocked or random schedules, with and without error estimations prior to feedback. During the acquisition phase, three target times were trained (1500, 1700, 1900 ms), with feedback delivered after every trial. We used delayed post-tests (24 hrs later) to evaluate the retention of these target times and their transfer to two new target times (1600, 1800 ms). Participants who practiced with a random schedule performed worse (i.e., greater absolute error) than those with a blocked schedule during acquisition (p = .006); however, randomly scheduled participants also showed reduced error (p = .004) on the retention and transfer tests. Although prompting error estimations led to greater self-reported mental effort being invested on the task (p = .001), error estimation was not reliably associated with superior learning (p = .133). The accuracy of error estimations did not differ as a function of practice structure (p = .070), although the accuracy of error estimations improved during acquisition (p = .006). Findings highlight the robustness of the contextual interference effect, but we did not find evidence that error estimations moderated the effect on this task. It is in some ways surprising that we found an effect of contextual interference, as past-work suggests that interference effects are attenuated (or eliminated) when participants switch between different parameters of the same task. We speculate that this might be due to the difficulty of the task; even though participants switched between parametric variations of the same task, the distinction between parameters was subtle (i.e., tenths of a second).
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http://dx.doi.org/10.1016/j.humov.2021.102854DOI Listing
October 2021

Effect of Greenshell mussel on osteoarthritis biomarkers and inflammation in healthy postmenopausal women: a study protocol for a randomized double-blind placebo-controlled trial.

Trials 2021 Jul 28;22(1):498. Epub 2021 Jul 28.

School of Health Sciences, College of Health, Massey University, Private Bag 11222, Palmerston North, 4442, New Zealand.

Background: New Zealand Greenshell™ mussels (GSM; Perna canaliculus) have recently been shown to decrease cartilage degradation in a rat model of induced metabolic osteoarthritis (MetOA). However, this effect has not been investigated in human subjects. This study aims to determine the effect of GSM powder on biomarkers of cartilage metabolism, bone resorption, and inflammation in New Zealand healthy overweight/obese postmenopausal women who are at early stage or at high risk of OA.

Method: Fifty overweight or obese (BMI 25-35 kg/m) postmenopausal women (aged 55-75 years) will be recruited by advertisement. Participants will be randomized based on a double-blind randomization schedule and stratified randomization based on BMI and age distribution. The participant will be assigned with a 1:1 allocation ratio to receive 3 g/d whole meat GSM powder or placebo (sunflower seed protein) for 12 weeks. Data on socio-demographics, physical activity, and dietary intake will be collected for each subject. Cartilage turnover biomarkers [(C-telopeptide of type II collagen (CTX-II), C-propeptide of type II procollagen (CPII), Cartilage oligomeric matrix protein (COMP)], and bone resorption marker (CTX-I) will be measured in blood and urine samples. Inflammatory status (hs-CRP and cytokine panel) will be assessed and iron status will be measured. Body composition including fat mass (FM), lean mass (LM), and fat percentage will be measured using dual-energy X-ray absorptiometry (DXA). Joint pain and knee function will be assessed using a 100-mm visual analog scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, respectively.

Discussion: This trial will be the first to explore the effects of whole meat GSM powder on cartilage turnover, bone resorption, and inflammation biomarkers in overweight/obese postmenopausal women. The results from this trial will provide evidence on the efficacy of GSM in the prevention of OA.

Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000413921p . Registration on 27 March 2020.
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http://dx.doi.org/10.1186/s13063-021-05473-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317363PMC
July 2021
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