Publications by authors named "Matthew Jackson"

206 Publications

Endocannabinoid system mediates the association between gut-microbial diversity and anhedonia/amotivation in a general population cohort.

Mol Psychiatry 2021 May 17. Epub 2021 May 17.

Department of Psychiatry, University of Oxford, Oxford, UK.

Anhedonia and amotivation are debilitating symptoms and represent unmet therapeutic needs in a range of clinical conditions. The gut-microbiome-endocannabinoid axis might represent a potential modifiable target for interventions. Based on results obtained from animal models, we tested the hypothesis that the endocannabinoid system mediates the association between gut-microbiome diversity and anhedonia/amotivation in a general population cohort. We used longitudinal data collected from 786 volunteer twins recruited as part the TwinsUK register. Our hypothesis was tested with a multilevel mediation model using family structure as random intercept. The model was set using alpha diversity (within-individual gut-microbial diversity) as predictor, serum and faecal levels of the endocannabinoid palmitoylethanolamide (PEA) as mediator, and anhedonia/amotivation as outcome. PEA is considered the endogenous equivalent of cannabidiol, with increased serum levels believed to have anti-depressive effects, while increased stool PEA levels, reflecting increased excretion, are believed to have opposite, detrimental, effects on mental health. We therefore expected that either reduced serum PEA or increased stool PEA would mediate the association between microbial diversity and anhedonia amotivation. Analyses were adjusted for obesity, diet, antidepressant use, sociodemographic and technical covariates. Data were imputed using multiple imputation by chained equations. Mean age was 65.2 ± 7.6; 93% of the sample were females. We found a direct, significant, association between alpha diversity and anhedonia/amotivation (β = -0.37; 95%CI: -0.71 to -0.03; P = 0.03). Faecal, but not serum, levels of the endocannabinoid palmitoylethanolamide (PEA) mediated this association: the indirect effect was significant (β = -0.13; 95%CI: -0.24 to -0.01; P = 0.03), as was the total effect (β = -0.38; 95%CI: -0.72 to -0.04; P = 0.03), whereas the direct effect of alpha diversity on anhedonia/amotivation was attenuated fully (β = -0.25; 95%CI: -0.60 to 0.09; P = 0.16). Our results suggest that gut-microbial diversity might contribute to anhedonia/amotivation via the endocannabinoid system. These findings shed light on the biological underpinnings of anhedonia/amotivation and suggest the gut microbiota-endocannabinoid axis as a promising therapeutic target in an area of unmet clinical need.
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http://dx.doi.org/10.1038/s41380-021-01147-5DOI Listing
May 2021

Belief polarization in a complex world: A learning theory perspective.

Proc Natl Acad Sci U S A 2021 May;118(19)

School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

We present two models of how people form beliefs that are based on machine learning theory. We illustrate how these models give insight into observed human phenomena by showing how polarized beliefs can arise even when people are exposed to almost identical sources of information. In our first model, people form beliefs that are deterministic functions that best fit their past data (training sets). In that model, their inability to form probabilistic beliefs can lead people to have opposing views even if their data are drawn from distributions that only slightly disagree. In the second model, people pay a cost that is increasing in the complexity of the function that represents their beliefs. In this second model, even with large training sets drawn from exactly the same distribution, agents can disagree substantially because they simplify the world along different dimensions. We discuss what these models of belief formation suggest for improving people's accuracy and agreement.
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http://dx.doi.org/10.1073/pnas.2010144118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126847PMC
May 2021

Interacting regional policies in containing a disease.

Proc Natl Acad Sci U S A 2021 May;118(19)

Applied Mathematics, Harvard University, Cambridge, MA 02138.

Regional quarantine policies, in which a portion of a population surrounding infections is locked down, are an important tool to contain disease. However, jurisdictional governments-such as cities, counties, states, and countries-act with minimal coordination across borders. We show that a regional quarantine policy's effectiveness depends on whether 1) the network of interactions satisfies a growth balance condition, 2) infections have a short delay in detection, and 3) the government has control over and knowledge of the necessary parts of the network (no leakage of behaviors). As these conditions generally fail to be satisfied, especially when interactions cross borders, we show that substantial improvements are possible if governments are outward looking and proactive: triggering quarantines in reaction to neighbors' infection rates, in some cases even before infections are detected internally. We also show that even a few lax governments-those that wait for nontrivial internal infection rates before quarantining-impose substantial costs on the whole system. Our results illustrate the importance of understanding contagion across policy borders and offer a starting point in designing proactive policies for decentralized jurisdictions.
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http://dx.doi.org/10.1073/pnas.2021520118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126865PMC
May 2021

Effect of Blood Pressure Variability on Outcomes in Emergency Patients with Intracranial Hemorrhage.

West J Emerg Med 2021 Jan 12;22(2):177-185. Epub 2021 Jan 12.

University of Maryland School of Medicine, Department of Emergency Medicine, Baltimore, Maryland.

Introduction: Patients with spontaneous intracranial hemorrhage (sICH) have high mortality and morbidity, which are associated with blood pressure variability. Additionally, blood pressure variability is associated with acute kidney injury (AKI) in critically ill patients, but its association with sICH patients in emergency departments (ED) is unclear. Our study investigated the association between blood pressure variability in the ED and the risk of developing AKI during sICH patients' hospital stay.

Methods: We retrospectively analyzed patients with sICH, including those with subarachnoid and intraparenchymal hemorrhage, who were admitted from any ED and who received an external ventricular drain at our academic center. Patients were identified by the International Classification of Diseases, Ninth Revision (ICD-9). Outcomes were the development of AKI, mortality, and being discharged home. We performed multivariable logistic regressions to measure the association of clinical factors and interventions with outcomes.

Results: We analyzed the records of 259 patients: 71 (27%) patients developed AKI, and 59 (23%) patients died. Mean age (± standard deviation [SD]) was 58 (14) years, and 150 (58%) were female. Patients with AKI had significantly higher blood pressure variability than patients without AKI. Each millimeter of mercury increment in one component of blood pressure variability, SD in systolic blood pressure (SBP), was significantly associated with 2% increased likelihood of developing AKI (odds ratio [OR] 1.02, 95% confidence interval [CI], 1.005-1.03, p = 0.007). Initiating nicardipine infusion in the ED (OR 0.35, 95% CI, 0.15-0.77, p = 0.01) was associated with lower odds of in-hospital mortality. No ED interventions or blood pressure variability components were associated with patients' likelihood to be discharged home.

Conclusion: Our study suggests that greater SBP during patients' ED stay is associated with higher likelihood of AKI, while starting nicardipine infusion is associated with lower odds of in-hospital mortality. Further studies about interventions and outcomes of patients with sICH in the ED are needed to confirm our observations.
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http://dx.doi.org/10.5811/westjem.2020.9.48072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972364PMC
January 2021

Analysis of 14 endocannabinoids and endocannabinoid congeners in human plasma using column switching high-performance atmospheric pressure chemical ionization liquid chromatography-mass spectrometry.

Anal Bioanal Chem 2021 May 5;413(12):3381-3392. Epub 2021 Apr 5.

Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.

The endocannabinoid system (ECS) is a complex cell-signaling system. To address the growing need of analytics capturing endocannabinoid levels to investigate the ECS, we developed and validated an assay for the quantitative analysis of 14 endocannabinoids and congeners. A simple extraction using protein precipitation with acetonitrile followed by online-trapping high-performance liquid chromatography-tandem mass spectrometry (LC/LC-MS/MS) was used to monitor the levels of 14 endocannabinoids in plasma. The assay was validated and intra-run and inter-run accuracies and imprecisions as well as matrix effects, recoveries, and sample stabilities were determined. As a proof of concept, a subset of study samples after naturalistic administration of Cannabis flower and concentrate was analyzed. With the exception of N-oleoyl dopamine and oleamide, all endocannabinoids fulfilled the predefined acceptance criteria. Reproducible recoveries and no significant matrix effects were observed. Sample stability was an issue. Analysis of the proof-of-concept study samples revealed a significantly (p = 0.006) higher concentration of docosatetraenoyl ethanolamide in concentrate users (300 ± 13 pg/mL) compared to flower users (252 ± 11 pg/mL). A robust, sensitive high-throughput assay for the quantitation of 14 endocannabinoids and congeners was successfully validated. Our study showed that it is mandatory to (A) appropriately stabilize samples and (B) separate and separately quantify 1-AG and 2-AG; otherwise, study results are unreliable. The analysis of study samples from Cannabis flower users versus Cannabis concentrate users revealed higher levels of docosatetraenoyl ethanolamide and anandamide (n.s.) in high THC concentrate users in accordance with the existing literature, supporting the validity of the assay measurements. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-021-03280-0DOI Listing
May 2021

NIH funding for vaccine readiness before the COVID-19 pandemic.

Vaccine 2021 04 8;39(17):2458-2466. Epub 2021 Mar 8.

Department of Natural & Applied Sciences, Bentley University, Waltham, MA 02452, United States; Center for Integration of Science and Industry, Bentley University, Waltham, MA 02452, United States; Department of Management, Bentley University, Waltham, MA 02452, United States. Electronic address:

Rapid development of vaccines for COVID-19 has relied on the application of existing vaccine technologies. This work examines the maturity of ten technologies employed in candidate vaccines (as of July 2020) and NIH funding for published research on these technologies from 2000-2019. These technologies vary from established platforms, which have been used successfully in approved products, to emerging technologies with no prior clinical validation. A robust body of published research on vaccine technologies was supported by 16,358 fiscal years of NIH funding totaling $17.2 billion from 2000-2019. During this period, NIH funding for published vaccine research against specific pandemic threats such as coronavirus, Zika, Ebola, and dengue was not sustained. NIH funding contributed substantially to the advance of technologies available for rapid development of COVID-19 vaccines, suggesting the importance of sustained public sector funding for foundational technologies in the rapid response to emerging public health threats.
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http://dx.doi.org/10.1016/j.vaccine.2021.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938738PMC
April 2021

Simultaneous Quantification of 17 Cannabinoids bY LC-MS-MS in Human Plasma.

J Anal Toxicol 2021 Mar 23. Epub 2021 Mar 23.

Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.

Background: In recent years, the surge in use and of clinical trials involving tetrahydrocannabinol (THC) and cannabidiol (CBD) has increased the need for sensitive and specific analytical assays to measure said compounds in patients, to establish dose-effect relationships and to gain knowledge of their pharmacokinetics and metabolism. We developed and validated an online extraction high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of 17 cannabinoids and metabolites including THC and its metabolites, CBD and its metabolites and other minor cannabinoids in human plasma.

Methods: CBD-glucuronide (CBD-gluc) standard was produced in-house by isolation of CBD-gluc from urine of patients using pure CBD oil. For calibration standards and quality control samples, human plasma was spiked with cannabinoids at varying concentrations within the working range of the respective compound and 200 µL was extracted using a simple one-step protein precipitation procedure. The extracts were analyzed using online trapping LC/LC-atmospheric pressure chemical ionization (APCI)-MS/MS running in the positive multiple reaction monitoring (MRM) mode.

Results: The lower limit of quantification ranged from 0.78 ng/mL to 7.8 ng/mL and the upper limits of quantification were between 100 ng/mL and 2000 ng/mL. Inter-day analytical accuracy and imprecision ranged from 90.4 to 111% and from 3.1 to 17.4%, respectively. The analysis of plasma samples collected during clinical studies showed that (3R-trans)-Cannabidiol-7-oic Acid (7-CBD-COOH) was the major human metabolite with 5960% of CBD followed by 7-hydroxy-CBD (177%), CBD-gluc (157%) and 6α-hydroxy-CBD (39.8%); 6β-hydroxy-CBD was not detected in any of the samples.

Conclusions: In the present study, we developed and validated a robust LC-MS/MS assay for the simultaneous quantification of cannabinoids and their metabolites, which has been used to measure >5,000 samples in clinical studies. Moreover, we were able to quantify CBD-gluc and showed that 7-CBD-COOH, 7-hydroxy-CBD and CBD-gluc are the major CBD metabolites in human plasma.
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http://dx.doi.org/10.1093/jat/bkab030DOI Listing
March 2021

Extreme isotopic heterogeneity in Samoan clinopyroxenes constrains sediment recycling.

Nat Commun 2021 Feb 23;12(1):1234. Epub 2021 Feb 23.

Department of Earth Science, University of California Santa Barbara, Santa Barbara, CA, USA.

Lavas erupted at hotspot volcanoes provide evidence of mantle heterogeneity. Samoan Island lavas with high Sr/Sr (>0.706) typify a mantle source incorporating ancient subducted sediments. To further characterize this source, we target a single high Sr/Sr lava from Savai'i Island, Samoa for detailed analyses of Sr/Sr and Nd/Nd isotopes and major and trace elements on individual magmatic clinopyroxenes. We show the clinopyroxenes exhibit a remarkable range of Sr/Sr-including the highest observed in an oceanic hotspot lava-encompassing ~30% of the oceanic mantle's total variability. These new isotopic data, data from other Samoan lavas, and magma mixing calculations are consistent with clinopyroxene Sr/Sr variability resulting from magma mixing between a high silica, high Sr/Sr (up to 0.7316) magma, and a low silica, low Sr/Sr magma. Results provide insight into the composition of magmas derived from a sediment-infiltrated mantle source and document the fate of sediment recycled into Earth's mantle.
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http://dx.doi.org/10.1038/s41467-021-21416-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902626PMC
February 2021

Accurate identification and quantification of commensal microbiota bound by host immunoglobulins.

Microbiome 2021 01 30;9(1):33. Epub 2021 Jan 30.

Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.

Background: Identifying which taxa are targeted by immunoglobulins can uncover important host-microbe interactions. Immunoglobulin binding of commensal taxa can be assayed by sorting bound bacteria from samples and using amplicon sequencing to determine their taxonomy, a technique most widely applied to study Immunoglobulin A (IgA-Seq). Previous experiments have scored taxon binding in IgA-Seq datasets by comparing abundances in the IgA bound and unbound sorted fractions. However, as these are relative abundances, such scores are influenced by the levels of the other taxa present and represent an abstract combination of these effects. Diversity in the practical approaches of prior studies also warrants benchmarking of the individual stages involved. Here, we provide a detailed description of the design strategy for an optimised IgA-Seq protocol. Combined with a novel scoring method for IgA-Seq datasets that accounts for the aforementioned effects, this platform enables accurate identification and quantification of commensal gut microbiota targeted by host immunoglobulins.

Results: Using germ-free and Rag1 mice as negative controls, and a strain-specific IgA antibody as a positive control, we determine optimal reagents and fluorescence-activated cell sorting (FACS) parameters for IgA-Seq. Using simulated IgA-Seq data, we show that existing IgA-Seq scoring methods are influenced by pre-sort relative abundances. This has consequences for the interpretation of case-control studies where there are inherent differences in microbiota composition between groups. We show that these effects can be addressed using a novel scoring approach based on posterior probabilities. Finally, we demonstrate the utility of both the IgA-Seq protocol and probability-based scores by examining both novel and published data from in vivo disease models.

Conclusions: We provide a detailed IgA-Seq protocol to accurately isolate IgA-bound taxa from intestinal samples. Using simulated and experimental data, we demonstrate novel probability-based scores that adjust for the compositional nature of relative abundance data to accurately quantify taxon-level IgA binding. All scoring approaches are made available in the IgAScores R package. These methods should improve the generation and interpretation of IgA-Seq datasets and could be applied to study other immunoglobulins and sample types. Video abstract.
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http://dx.doi.org/10.1186/s40168-020-00992-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847592PMC
January 2021

Large-scale association analyses identify host factors influencing human gut microbiome composition.

Nat Genet 2021 02 18;53(2):156-165. Epub 2021 Jan 18.

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10 < P < 5 × 10) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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http://dx.doi.org/10.1038/s41588-020-00763-1DOI Listing
February 2021

Remnants of early Earth differentiation in the deepest mantle-derived lavas.

Proc Natl Acad Sci U S A 2021 01 21;118(1). Epub 2020 Dec 21.

Kimberlites and Diamonds, School of Earth Sciences, The University of Melbourne, Parkville, VIC 3010, Australia.

The noble gas isotope systematics of ocean island basalts suggest the existence of primordial mantle signatures in the deep mantle. Yet, the isotopic compositions of lithophile elements (Sr, Nd, Hf) in these lavas require derivation from a mantle source that is geochemically depleted by melt extraction rather than primitive. Here, this apparent contradiction is resolved by employing a compilation of the Sr, Nd, and Hf isotope composition of kimberlites-volcanic rocks that originate at great depth beneath continents. This compilation includes kimberlites as old as 2.06 billion years and shows that kimberlites do not derive from a primitive mantle source but sample the same geochemically depleted component (where geochemical depletion refers to ancient melt extraction) common to most oceanic island basalts, previously called PREMA (prevalent mantle) or FOZO (focal zone). Extrapolation of the Nd and Hf isotopic compositions of the kimberlite source to the age of Earth formation yields a Nd/Nd-Hf/Hf composition within error of chondrite meteorites, which include the likely parent bodies of Earth. This supports a hypothesis where the source of kimberlites and ocean island basalts contains a long-lived component that formed by melt extraction from a domain with chondritic Nd/Nd and Hf/Hf shortly after Earth accretion. The geographic distribution of kimberlites containing the PREMA component suggests that these remnants of early Earth differentiation are located in large seismically anomalous regions corresponding to thermochemical piles above the core-mantle boundary. PREMA could have been stored in these structures for most of Earth's history, partially shielded from convective homogenization.
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http://dx.doi.org/10.1073/pnas.2015211118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817169PMC
January 2021

Making hidden resources visible in a minority serving college context.

Cultur Divers Ethnic Minor Psychol 2021 Apr 28;27(2):256-268. Epub 2020 Dec 28.

Department of Psychology, California State University, Los Angeles.

Objectives: Navigating pathways of higher education means uncovering hidden "rules" about how to be successful in university systems that privilege dominant ways of knowing. To unpack these rules, universities have attempted a range of approaches from enrolling students in semester-long courses focused on the transition to college to more cost-effective psychological interventions that use stories to highlight pathways for navigating the transition. These cost-effective approaches are of increased interest to universities and effective in promoting student outcomes. Yet, their effects have mostly been examined in predominantly White institutions leaving open the question of how to tailor these interventions in less-resourced institutions serving a more diverse student body. We examined the effect of making these hidden resources known in concrete ways and of contextualizing these resources with student stories through a scalable online video-based assignment.

Method: Across 2 large-scale experiments at a minority serving institution, participants watched either resource videos only or resource videos coupled with students' stories.

Results: Compared to a no-treatment control group, we found that first-generation-to-college students benefited from receiving both types of resource information. Continuing-generation-to-college students benefited the most when resources were coupled with student stories.

Conclusions: We speculate that first-generation students at minority serving institutions have concrete concerns that need to be addressed alongside identity and social belonging needs. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/cdp0000423DOI Listing
April 2021

Clustered cardiometabolic risk and arterial stiffness of recreational adult tennis players.

J Sports Med Phys Fitness 2020 Dec 14. Epub 2020 Dec 14.

School of Health Sciences, Faculty of Science, Liverpool Hope University, Liverpool, UK.

Background: Recent evidence highlights racquet sports as being associated with a substantially reduced risk of CVD mortality. The purpose of this investigation was to evaluate clustered cardiometabolic risk (CMR) and arterial stiffness in recreational adult tennis players.

Methods: Forty-three recreational tennis players (T) and a matched group of 45 healthy, active non-tennis (NT) players, mean age (± SEM) 41.6 ± 1.8 years participated in this cross-sectional comparative study. Measurements included emerging and traditional CMR factors with pulse wave analysis/velocity utilised to assess indexes of arterial stiffness. Clustered cardiometabolic risk was calculated using two composites: CMR1 (central aortic systolic blood pressure, carotid-femoral pulse wave velocity, percentage body fat, HDL-C and maximal oxygen uptake) and CMR2 (brachial systolic blood pressure, triglycerides, TC:HDL-C, percentage body fat, HbA1c and maximal oxygen uptake).

Results: Analysis of covariance, controlling for age, revealed T had significantly lower (healthier) CMR1 scores than NT (EMM ± SEM, T: -0.48 ± 0.3 vs NT: 0.50 ± 0.3, P = 0.03). Similarly, T also demonstrated lower clustered CMR2 scores (EMM, T: -0.66 ± 0.4 vs NT: 0.59 ± 0.4, P = 0.04). Augmentation index of the pulse pressure wave, normalised to heart rate 75 bpm (AIx75), was lower in T vs NT (EMM, T: 10.7 ± 1.7% vs NT: 12.7 ± 1.6%; P = 0.03), when controlling for age and gender.

Conclusions: Tennis appears to be a suitable and effective physical activity modality for targeting cardiometabolic and vascular health and should be more frequently advocated in physical activity promotion strategies.
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http://dx.doi.org/10.23736/S0022-4707.20.11674-8DOI Listing
December 2020

Dietary Fatty Acids Change Circulating Fatty Acids, Microbial Putrefactive Postbiotics and Betaine Status in the Cat.

Animals (Basel) 2020 Dec 6;10(12). Epub 2020 Dec 6.

Hill's Pet Nutrition, Topeka, KS 66601, USA.

There is a normal variation of polyunsaturated fatty acids (PUFA) in the foods consumed both by the domestic cat and wild felines. This variation may lead to specific changes in metabolites and circulating fatty acids that influence health and response to disease. Therefore, in order to evaluate the response to these changes in dietary PUFA three foods were formulated: a complete and balanced control food (COF) with no enhanced source of added PUFA (ARA = 0.08%, EPA & DHA = 0.01%), Test food 1 (E&DF) like the COF with added eicosapentaenoic acid EPA and docosahexaenoic acid DHA (E&D = 0.36%)) from menhaden fish oil, and Test Food 2 (ARAF) like the COF with added arachidonic acid (ARA = 0.16%) from liver. All test foods had similar protein concentrations and similar vitamin and mineral concentrations while the PUFA supplemented foods had slightly higher fat concentrations. Cats ( = 36) were fed a pre-trial food for 28 days and then assigned to a group fed either the control, E&DF or ARAF for 56 days (12 cats per group). Blood samples were drawn and serum analyzed for fatty acids, albumin, urea, creatinine, cholesterol and triglycerides at the beginning of the study and after consuming the test foods for 28 and 56 days. Plasma was similarly analyzed for metabolomics. Increasing dietary E&D resulted in reduced cholesterol, betaine, dimethyl glycine, sarcosine and 4-ethylphenylsulfate. Increasing dietary ARA resulted in reduced betaine, dimethyl glycine and sarcosine and an increased concentration of indoleacetate, indolepropionate and indoleacetylglutamine. These data suggest a benefit of dietary single carbon metabolism support for cats supplemented with ARA or E&D. Moreover, the reduction in circulating cholesterol and triglycerides through dietary E&D supplementation could benefit cats with hyperlipidemia. Further research into the interrelationship between dietary PUFA and the gut microbe will benefit from the data showing that ARA increased specific positive postbiotics (i.e., indoleacetate, indolepropionate) while E&D supplementation showed the benefit of reducing some postbiotics which have been associated with reduced health (4-ethylphenylsulfate, 3-methyl catechol sulfate and 4-vinylphenol sulfate).
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http://dx.doi.org/10.3390/ani10122310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762147PMC
December 2020

Ancient helium and tungsten isotopic signatures preserved in mantle domains least modified by crustal recycling.

Proc Natl Acad Sci U S A 2020 12 23;117(49):30993-31001. Epub 2020 Nov 23.

Department of Earth & Planetary Sciences, Harvard University, Cambridge, MA 02138.

Rare high-He/He signatures in ocean island basalts (OIB) erupted at volcanic hotspots derive from deep-seated domains preserved in Earth's interior. Only high-He/He OIB exhibit anomalous W-an isotopic signature inherited during the earliest history of Earth-supporting an ancient origin of high He/He. However, it is not understood why some OIB host anomalous W while others do not. We provide geochemical data for the highest-He/He lavas from Iceland (up to 42.9 times atmospheric) with anomalous W and examine how Sr-Nd-Hf-Pb isotopic variations-useful for tracing subducted, recycled crust-relate to high He/He and anomalous W. These data, together with data on global OIB, show that the highest-He/He and the largest-magnitude W anomalies are found only in geochemically depleted mantle domains-with high Nd/Nd and low Pb/Pb-lacking strong signatures of recycled materials. In contrast, OIB with the strongest signatures associated with recycled materials have low He/He and lack anomalous W. These observations provide important clues regarding the survival of the ancient He and W signatures in Earth's mantle. We show that high-He/He mantle domains with anomalous W have low W and He concentrations compared to recycled materials and are therefore highly susceptible to being overprinted with low He/He and normal (not anomalous) W characteristic of subducted crust. Thus, high He/He and anomalous W are preserved exclusively in mantle domains least modified by recycled crust. This model places the long-term preservation of ancient high He/He and anomalous W in the geodynamic context of crustal subduction and recycling and informs on survival of other early-formed heterogeneities in Earth's interior.
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http://dx.doi.org/10.1073/pnas.2009663117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733831PMC
December 2020

Correlation of history and physical examination with imaging in traumatic near-shore aquatic head and spinal injury.

Am J Emerg Med 2020 10 15;38(10):2049-2054. Epub 2020 Jul 15.

Department of Emergency Medicine, University of Maryland School of Medicine, 110 South Paca Street; 6th Floor, Suite 200, Baltimore, MD 21201, USA; The Research Associate Program in Emergency Medicine & Critical Care, University of Maryland School of Medicine, Baltimore, MD; 22 South Greene Street, suite P1G01, Baltimore, MD 21201, USA; Program in Trauma, The R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD; 22 South Greene Street, Baltimore, MD 21201, USA. Electronic address:

Objective: It remains unclear whether clinicians can rely on specific symptoms and signs to detect or exclude serious head and spinal injury sustained during near-shore aquatic activities. Our study investigated patients' history of present illness (HPI) and physical examination (PE) for their utility in detecting serious head and spinal injury.

Methods: We conducted a multicenter retrospective comparative analysis of adult patients who were transported from the beach in Ocean City, Maryland, to three nearby emergency departments for possible spinal injury from 2006 through 2017. Patients suspected to have any spinal injury from beach activities were eligible. We excluded patients who could not verbalize their symptoms or with insufficient emergency department records. We compared components of each patient's HPI and PE with radiologic evidence of spinal injury. We calculated sensitivity, specificity, and negative and positive likelihood ratios (LRs).

Results: We analyzed 278 patients with suspected spinal injury. Midline spinal tenderness was associated with increased likelihood of thoracic (LR+ 2.6) and lumbar spinal fractures (LR+ 3.5). HPI complaints of paralysis (LR+ 13.9) and sensory loss (LR+ 5.8) had strong associations with spinal cord injuries. Weakness found through PE was also associated with spinal cord injury (LR+ 5.3).

Conclusions: We identified several components of the clinical evaluation that had clinically significant association with spinal injuries from beach-related trauma. While prospective studies are needed to confirm our observations, clinicians may consider these high-risk features in patients with beach-related trauma and adjust testing and level of care appropriately.
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http://dx.doi.org/10.1016/j.ajem.2020.06.091DOI Listing
October 2020

Dietary resistant starch preserved through mild extrusion of grain alters fecal microbiome metabolism of dietary macronutrients while increasing immunoglobulin A in the cat.

PLoS One 2020 3;15(11):e0241037. Epub 2020 Nov 3.

Pet Nutrition Center, Hill's Pet Nutrition, Inc., Topeka, KS, United States of America.

Dietary digestion-resistant starch (RS) provides health benefits to the host via gut microbiome-mediated metabolism. The degree to which cats manifest beneficial changes in response to RS intake was examined. Healthy cats (N = 36) were fed identically formulated foods processed under high (n = 17) or low (n = 19) shear extrusion conditions (low and high RS levels [LRS and HRS], respectively). Fecal samples collected after 3 and 6 weeks' feeding were assayed for stool firmness score, short-chain fatty acids, ammonia, and changes to the global metabolome and microbiome; fecal immunoglobulin A (IgA) was analyzed at week 6. Few differences were seen in proximate analyses of the foods; stool firmness scores did not differ. In cats consuming HRS food, concentrations of fecal butyrate and the straight chain:branched chain fatty acid ratio were significantly greater in feces at both weeks 3 and 6, while fecal ammonia was reduced at week 6 relative to feces from LRS-fed cats. Fecal IgA concentrations were significantly higher at week 6 with HRS food. RS consumption altered 47% of the fecal metabolome; RS-derived sugars and metabolites associated with greater gut health, including indoles and polyamines, increased in the cats consuming HRS food relative to those fed the LS food, while endocannabinoid N-acylethanolamines decreased. Consumption of HRS food increased concentrations of the ketone body 3-hydroxybutyrate in feces and elevated concentrations of reduced members of NADH-coupled redox congeners and NADH precursors. At the microbiome genus-level, 21% of operational taxonomic units were significantly different between food types; many involved taxa with known saccharolytic or proteolytic proclivities. Microbiome taxa richness and Shannon and Simpson alpha diversity were significantly higher in the HRS group at both weeks. These data show that feline consumption of grain-derived RS produces potentially beneficial shifts in microbiota-mediated metabolism and increases IgA production.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241037PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608938PMC
December 2020

Genomic and transcriptomic analysis unveils population evolution and development of pesticide resistance in fall armyworm Spodoptera frugiperda.

Protein Cell 2020 Oct 27. Epub 2020 Oct 27.

Department of Biochemistry, Genetics and Microbiology, Forestry and Agricultural Biotechnology Institute, University of Pretoria, Pretoria, South Africa.

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
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http://dx.doi.org/10.1007/s13238-020-00795-7DOI Listing
October 2020

Early Predictors of Near-Shore Spinal Injuries Among Emergency Department Patients.

J Emerg Med 2021 Jan 4;60(1):17-24. Epub 2020 Sep 4.

Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Program in Trauma, The R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland.

Background: Spinal injuries (SIs) can pose a significant burden to patients and family; delayed surgical intervention, associated with interhospital transfer, results in worse outcomes.

Objective: This study aimed to identify early patient-centered factors associated with risk for near-shore SIs to assist clinicians with expeditious medical decision-making.

Methods: We performed a multicenter retrospective study of all adults transported from Ocean City, Maryland to two emergency departments (EDs) and one regional trauma center for evaluation of suspected SIs from 2006 to 2017. Outcomes were any SI and any spinal cord injury (SCI). Multivariable logistic regression was performed for association of environmental and clinical factors with outcomes.

Results: We analyzed 278 records, 102 patients (37%) were diagnosed with any SI and 41 (15%) were diagnosed with SCIs. Compared with patients without SI, patients with SI were more likely to be older (48 vs. 39 years), male (90% vs. 70%), with pre-existing spinal condition (62% vs. 33%), and injury caused by diving (11% vs. 2%). Multivariable logistic regression showed age (odd ratio [OR] 1.07; 95% confidence interval [CI] 1.04-1.11), diving (OR 3.5; 95% CI 3-100+), and wave height (OR 4.5; 95% CI 1.35-15.2) were associated with any SI, and a chief complaint of extremity numbness or tingling (OR 5.73; 95% CI 1.2-27.9) was associated with SCI.

Conclusions: We identified older age, diving, and higher wave height as risk factors for any SI and symptoms of numbness and tingling were associated with SCIs. Clinicians should consider expediting these patients' transfers to a trauma center with neurosurgical capability.
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http://dx.doi.org/10.1016/j.jemermed.2020.07.037DOI Listing
January 2021

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

JAMA 2020 10;324(13):1317-1329

School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.

Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).

Main Outcomes And Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).

Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.

Conclusions And Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.
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http://dx.doi.org/10.1001/jama.2020.17022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489418PMC
October 2020

Monitoring alpha-synuclein oligomerization and aggregation using bimolecular fluorescence complementation assays: What you see is not always what you get.

J Neurochem 2021 05 27;157(4):872-888. Epub 2020 Oct 27.

Laboratory of Molecular and Chemical Biology of Neurodegeneration, Faculty of Life Sciences, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Bimolecular fluorescence complementation (BiFC) was introduced a decade ago as a method to monitor alpha-synuclein (α-syn) oligomerization in intact cells. Since then, several α-syn BiFC cellular assays and animal models have been developed based on the assumption that an increase in the fluorescent signal correlates with increased α-syn oligomerization or aggregation. Despite the increasing use of these assays and models in mechanistic studies, target validation and drug screening, there have been no reports that (1) validate the extent to which the BiFC fluorescent signal correlates with α-syn oligomerization at the biochemical level; (2) provide a structural characterization of the oligomers and aggregates formed by the BiFC. To address this knowledge gap, we first analysed the expression level and oligomerization properties of the individual constituents of α-syn-Venus, one of the most commonly used BiFC systems, in HEK-293 & SH-SY5Y cells from three different laboratories using multiple biochemical approaches and techniques. Next, we investigated the biochemical and aggregation properties of α-syn upon co-expression of both BiFC fragments. Our results show that (1) the C-terminal-Venus fused to α-syn (α-syn-Vc) is present in much lower abundance than its counterpart with N-terminal-Venus fused to α-syn (Vn-α-syn); (2) Vn-α-syn exhibits a high propensity to form oligomers and higher-order aggregates; and (3) the expression of either or both fragments does not result in the formation of α-syn fibrils or cellular inclusions. Furthermore, our results suggest that only a small fraction of Vn-α-syn is involved in the formation of the fluorescent BiFC complex and that some of the fluorescent signal may arise from the association or entrapment of α-syn-Vc in Vn-α-syn aggregates. The fact that the N-terminal fragment exists predominantly in an aggregated state also indicates that one must exercise caution when using this system to investigate α-syn oligomerization in cells or in vivo. Altogether, our results suggest that cellular and animal models of oligomerization, aggregation and cell-to-cell transmission based on the α-syn BiFC systems should be thoroughly characterized at the biochemical level to ensure that they reproduce the process of interest and measure what they are intended to measure.
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http://dx.doi.org/10.1111/jnc.15147DOI Listing
May 2021

Associations between UK tap water and gut microbiota composition suggest the gut microbiome as a potential mediator of health differences linked to water quality.

Sci Total Environ 2020 Oct 26;739:139697. Epub 2020 May 26.

Department of Twin Research and Genetic Epidemiology, King's College London, 3-4th Floor South Wing Block D, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK; Department of Ageing and Health, St Thomas' Hospital, 9th floor, North Wing, Westminster Bridge Road, London SE1 7EH, UK. Electronic address:

Tap water composition has been widely linked to differences in human health, however the biological pathways underlying this association are less clearly defined. We provide the first investigation of the potential for the gut microbiota to mediate this association. Tap water samples and drinking habits from 85 Mono-zygotic twins with existing faecal microbiota profiles from around the UK were used to assess associations of water composition with the gut microbiome. Water composition was captured using the first 3 principle components (PCs) from multiple factor analysis of ion concentrations, additionally estimating average daily dose (ADD) of the primary three solutes contributing to its variance: chloride, sulphate and sodium. Geographic differences in water composition were assessed. We used measures of faecal microbial diversity, between-individual differences in composition and differences in taxa abundance estimated from 16S rRNA sequencing data. Differences between twin pairs were also considered. We observed significant associations of sodium ADD with microbiota diversity (Chao1), chloride, sodium and sulphate ADD with dissimilarity between samples, and significant associations for all PCs and ADD-adjusted solutes with abundances of individual microbial taxa. These results support the hypothesis that the gut microbiota could mediate the effects of tap water composition on host health, warranting further investigation into tap-water as an influencer of microbiota composition.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139697DOI Listing
October 2020

Functional assessment of bioprosthetic mitral valves by cardiovascular magnetic resonance: An in vitro validation and comparison to Doppler echocardiography.

J Cardiovasc Magn Reson 2020 07 30;22(1):55. Epub 2020 Jul 30.

Department of Cardiology, Houston Methodist Hospital, Houston, TX, USA.

Background: A comprehensive non-invasive evaluation of bioprosthetic mitral valve (BMV) function can be challenging. We describe a novel method to assess BMV effective orifice area (EOA) based on phase contrast (PC) cardiovascular magnetic resonance (CMR) data. We compare the performance of this new method to Doppler and in vitro reference standards.

Methods: Four sizes of normal BMVs (27, 29, 31, 33 mm) and 4 stenotic BMVs (27 mm and 29 mm, with mild or severe leaflet obstruction) were evaluated using a CMR- compatible flow loop. BMVs were evaluated with PC-CMR and Doppler methods under flow conditions of; 70 mL, 90 mL and 110 mL/beat (n = 24). PC-EOA was calculated as PC-CMR flow volume divided by the PC- time velocity integral (TVI).

Results: PC-CMR measurements of the diastolic peak velocity and TVI correlated strongly with Doppler values (r = 0.99, P < 0.001 and r = 0.99, P < 0.001, respectively). Across all conditions tested, the Doppler and PC-CMR measurement of EOA (1.4 ± 0.5 vs 1.5 ± 0.7 cm, respectively) correlated highly (r = 0.99, P < 0.001), with a minimum bias of 0.13 cm, and narrow limits of agreement (- 0.2 to 0.5 cm).

Conclusion: We describe a novel method to assess BMV function based on PC measures of transvalvular flow volume and velocity integration. PC-CMR methods can be used to accurately measure EOA for both normal and stenotic BMV's and may provide an important new parameter of BMV function when Doppler methods are unobtainable or unreliable.
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http://dx.doi.org/10.1186/s12968-020-00635-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392719PMC
July 2020

Consumption of identically formulated foods extruded under low and high shear force reveals that microbiome redox ratios accompany canine immunoglobulin A production.

J Anim Physiol Anim Nutr (Berl) 2020 Sep 23;104(5):1551-1567. Epub 2020 Jul 23.

Department of Grain Science and Industry, Kansas State University, Manhattan, KS, USA.

Digestion-resistant starch (RS) can provide health benefits to the host via gut microbiome-mediated metabolism. This study tested the physiological effects on healthy dogs of identically formulated foods processed under high (n = 16) or low (n = 16) shear extrusion conditions resulting in respective lower and higher levels of RS. Faecal samples collected at weeks 3 and 6 were assayed for stool score, proximate analysis, short-chain fatty acids (SCFA), immunoglobulin A (IgA) and microbiome; faecal metabolome was characterized at week 6. Proximate and digestibility analyses of the foods and stool scores and stool proximate analysis showed few differences between the two shear methods except for increased apparent fibre digestibility in the low shear food. In contrast, levels of butyrate (p = .030) and total SCFA (p = .043) were significantly greater in faeces at week 6 from dogs who consumed the low versus high shear food. Faecal IgA levels were significantly higher at week 3 (p = .001) but not week 6 (p = .110) in the low shear food. Significant differences in 166 metabolites between consumption of the two foods were identified via faecal metabolomic analysis, with changes in sugars, bile acids, advanced glycation end products and few amino acids. Strikingly, consumption of the low shear food resulted in elevated levels of the reduced members of redox couples derived from metabolized sugars and branched-chain and phenyl amino acids. Alpha diversity of the microbiome showed significantly higher species richness in faeces from the low shear group at week 6, though other measures of diversity were similar for both foods. Twelve genus-level operational taxonomic units (OTU; half Firmicutes) significantly differed between the food types. Six OTU significantly correlated with RS-derived sugars and ratios of the redox couples. Taken together, these data show that RS impacts microbiome-mediated metabolism in the gut, resulting in changes in the reducing state.
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http://dx.doi.org/10.1111/jpn.13419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540571PMC
September 2020

The Effects of Nutrition on the Gastrointestinal Microbiome of Cats and Dogs: Impact on Health and Disease.

Front Microbiol 2020 25;11:1266. Epub 2020 Jun 25.

Texas A&M College of Veterinary Medicine & Biomedical Sciences, College Station, TX, United States.

The gastrointestinal (GI) microbiome of cats and dogs is increasingly recognized as a metabolically active organ inextricably linked to pet health. Food serves as a substrate for the GI microbiome of cats and dogs and plays a significant role in defining the composition and metabolism of the GI microbiome. The microbiome, in turn, facilitates the host's nutrient digestion and the production of postbiotics, which are bacterially derived compounds that can influence pet health. Consequently, pet owners have a role in shaping the microbiome of cats and dogs through the food they choose to provide. Yet, a clear understanding of the impact these food choices have on the microbiome, and thus on the overall health of the pet, is lacking. Pet foods are formulated to contain the typical nutritional building blocks of carbohydrates, proteins, and fats, but increasingly include microbiome-targeted ingredients, such as prebiotics and probiotics. Each of these categories, as well as their relative proportions in food, can affect the composition and/or function of the microbiome. Accumulating evidence suggests that dietary components may impact not only GI disease, but also allergies, oral health, weight management, diabetes, and kidney disease through changes in the GI microbiome. Until recently, the focus of microbiome research was to characterize alterations in microbiome composition in disease states, while less research effort has been devoted to understanding how changes in nutrition can influence pet health by modifying the microbiome function. This review summarizes the impact of pet food nutritional components on the composition and function of the microbiome and examines evidence for the role of nutrition in impacting host health through the microbiome in a variety of disease states. Understanding how nutrition can modulate GI microbiome composition and function may reveal new avenues for enhancing the health and resilience of cats and dogs.
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http://dx.doi.org/10.3389/fmicb.2020.01266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329990PMC
June 2020

Chronic kidney disease in cats alters response of the plasma metabolome and fecal microbiome to dietary fiber.

PLoS One 2020 2;15(7):e0235480. Epub 2020 Jul 2.

Pet Nutrition Center, Hill's Pet Nutrition, Topeka, Kansas, United States of America.

Methods: A cross-over study within a split-plot design was performed using healthy (n = 10) and CKD cats [IRIS Stage 1 and 2; n = 10]. Cats were fed dry Prescription Diet® k/d® Feline with chicken, during a pre-trial period and then randomly assigned to two fiber treatments for 4 weeks each. Treatment foods were formulated similar to pre-trial food, with the exception that they contained 0.500% betaine, 0.586% oat beta glucan, and either 0.407% short chain fructooligosaccharides (scFOS) fiber or 3.44% apple pomace. Both foods had similar crude fiber percent (2.0 and 2.1% for scFOS and apple pomace, respectively) whereas soluble fiber was 0.8 and 1.6%, respectively.

Results: Plasma metabolites separated cats based on health status. At baseline, cats with CKD had significantly higher circulating concentrations of creatinine, urea, and some microbial and host tryptophan metabolites including several indole sulfates and kynurenate. Healthy cats had higher concentrations of the antioxidant α-tocopherol after consuming apple pomace; alternatively, they had higher concentrations of inflammatory sphingolipid metabolites after consuming scFOS, but not after consuming apple pomace. The CKD cats had higher concentrations of the more oxidized glutathione metabolites after consuming apple pomace compared with scFOS, as well as higher concentrations of inflammatory sphingolipid metabolites after consuming apple pomace, but not scFOS. After consuming scFOS, CKD cats had lower concentrations of the phenolic uremic toxins guaiacol sulfate and 4-vinylphenol sulfate compared with after consuming apple pomace. At baseline, there were five significant microbiota OTU differences in CKD cats compared with healthy cats. Overall, the OTUs in CKD cats were more resistant to change after feeding either fiber source. Counts of an unclassified genus in the family S24-7 in the order Bacteroidales (OTU 100296), were lower in CKD cats compared with healthy cats at baseline (P = 0.001), but increased after consumption of food containing scFOS (P = 0.006). Linear regression analysis showed that this genus had significant negative correlations with several microbial uremic toxins. None of the baseline differences in OTUs between healthy and CKD cats changed after CKD cats consumed food containing apple pomace.

Conclusions: Health status impacts the influence of dietary fermentable fibers on the feline plasma metabolome and fecal microbiome. A more readily fermented fiber such as scFOS is preferable to apple pomace as a fiber source for cats with CKD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235480PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331996PMC
September 2020

Why understanding multiplex social network structuring processes will help us better understand the evolution of human behavior.

Evol Anthropol 2020 May;29(3):102-107

External Faculty, Santa Fe Institute, Santa Fe, New Mexico, USA.

Social scientists have long appreciated that relationships between individuals cannot be described from observing a single domain, and that the structure across domains of interaction can have important effects on outcomes of interest (e.g., cooperation; Durkheim, 1893). One debate explicitly about this surrounds food sharing. Some argue that failing to find reciprocal food sharing means that some process other than reciprocity must be occurring, whereas others argue for models that allow reciprocity to span domains in the form of trade (Kaplan and Hill, 1985.). Multilayer networks, high-dimensional networks that allow us to consider multiple sets of relationships at the same time, are ubiquitous and have consequences, so processes giving rise to them are important social phenomena. The analysis of multi-dimensional social networks has recently garnered the attention of the network science community (Kivelä et al., 2014). Recent models of these processes show how ignoring layer interdependencies can lead one to miss why a layer formed the way it did, and/or draw erroneous conclusions (Górski et al., 2018). Understanding the structuring processes that underlie multiplex networks will help understand increasingly rich data sets, giving more accurate and complete pictures of social interactions.
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http://dx.doi.org/10.1002/evan.21850DOI Listing
May 2020

Transportation Management Affecting Outcomes of Patients With Spontaneous Intracranial Hemorrhage.

Air Med J 2020 May - Jun;39(3):189-195. Epub 2020 Jan 14.

Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD; Program in Trauma, The R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD. Electronic address:

Objective: Patients with spontaneous intracranial hemorrhage (sICH) have poor outcomes, in part because of blood pressure variability (BPV). Patients with sICH causing elevated intracranial pressure (ICP) are frequently transferred to tertiary centers for neurosurgical interventions. We hypothesized that BPV and care intensity during transport would correlate with outcomes in patients with sICH and elevated ICP.

Methods: We analyzed charts from adult sICH patients who were transferred from emergency departments to a quaternary academic center from January 1, 2011, to September 30, 2015, and received external ventricular drainage. Outcomes were in-hospital mortality and the Glasgow Coma Scale on day 5 (HD5GCS). Multivariable and ordinal logistic regressions were used for associations between clinical factors and outcomes.

Results: We analyzed 154 patients, 103 (67%) had subarachnoid hemorrhage and 51 (33%) intraparenchymal hemorrhage; 38 (25%) died. BPV components were similar between survivors and nonsurvivors and not associated with mortality. Each additional intervention during transport was associated with a 5-fold increase in likelihood to achieve a higher HD5GCS (odds ratio = 5.4; 95% confidence interval, 1.7-16; P = .004).

Conclusion: BPV during transport was not associated with mortality. However, high standard deviation in systolic blood pressure during transport was associated with lower HD5GCS in patients with intraparenchymal hemorrhage. Further studies are needed to confirm our observations.
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http://dx.doi.org/10.1016/j.amj.2019.12.001DOI Listing
June 2021

Uncrossable and undilatable lesions-A practical approach to optimizing outcomes in PCI.

Catheter Cardiovasc Interv 2021 01 26;97(1):121-126. Epub 2020 May 26.

Cardiac Department, Freeman Hospital, Newcastle upon Tyne, UK.

Uncrossable lesions are those that cannot be crossed with a balloon after successful guidewire crossing. These lesions are challenging and are commonly encountered in tortuous and calcified arteries as well as chronic total occlusions. They are the second most common barrier to successful PCI in CTO intervention after inability to cross the CTO segment with a guidewire. Procedures involving balloon uncrossable lesions during routine and CTO PCI utilise longer procedural times, radiation dose and contrast volumes with a lower likelihood of procedural success. In this article, we describe a pragmatic approach of managing balloon uncrossable lesions utilising the most contemporary equipment available in an algorithmic fashion beginning with simple, cost effective techniques right up to complex strategies for advanced operators. In addition, some of these lesions, even when crossed by any technique, they may remain difficult to dilate and prepare for stent insertion. We describe an approach of how to manage these undilatable lesions.
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http://dx.doi.org/10.1002/ccd.29001DOI Listing
January 2021

Docosahexaenoate-enriched fish oil and medium chain triglycerides shape the feline plasma lipidome and synergistically decrease circulating gut microbiome-derived putrefactive postbiotics.

PLoS One 2020 12;15(3):e0229868. Epub 2020 Mar 12.

Pet Nutrition Center, Hill's Pet Nutrition, Inc., Topeka, Kansas, United States of America.

The purpose of this study was to examine the influence of medium-chain fatty acid-containing triglycerides (MCT), long-chain polyunsaturated fatty acid-containing triglycerides, and their combination on the plasma metabolome of cats (Felis catus), including circulating microbiome-derived postbiotics. After a 14-day lead-in on the control food, cats were randomized to one of four foods (control, with 6.9% MCT, with fish oil [FO; 0.14% eicosapentaenoate, 1.0% docosahexaenoate], or with FO+MCT; n = 16 per group) for 28 days. Analysis of plasma metabolites showed that the addition of FO and MCT led to synergistic effects not seen with either alone across a number of lipid classes, including fatty acids, acylcarnitines, and acylated amines including endocannabinoids. Notably, the FO+MCT group had an increase in ketone body production relative to baseline and beyond that seen with MCT alone. N-acyl taurines, the accumulation of which has been implicated in the onset of type 2 diabetes, were significantly decreased in the FO+MCT group. Significant decreases in the gut microbiome-derived postbiotic classes of indoles/indolic sulfates and phenols/phenolic sulfates were observed only the FO+MCT group. Overall, the combination of MCT and FO led to number of changes in plasma metabolites that were not observed with either oil alone, particularly in postbiotics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229868PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067441PMC
June 2020