Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Draft genome sequence of two "Candidatus Intestinicoccus colisanans" strains isolated from faeces of healthy humans.

OBJECTIVES: In order to provide a better insight into the functional capacity of the human gut microbiome, we isolated a novel bacterium, "Candidatus Intestinicoccus colisanans" gen. nov. sp. nov., and performed whole genome sequencing. This study will provide new insights into the functional potential of this bacterium and its role in modulating host health and well-being. We expect that this data resource will be useful in providing additional insight into the diversity and functional potential of the human microbiome. DATA DESCRIPTION: Here, we report the first draft genome sequences of "Candidatus Intestinicoccus colisanans" strains MH27-1 and MH27-2, recovered from faeces collected from healthy human donors. The genomes were sequenced using short-read Illumina technology and whole-genome-based comparisons and phylogenomics reconstruction indicate that "Candidatus Intestinicoccus colisanans" represents a novel genus and species within the family Acutalibacteraceae. Both genomes were estimated to be > 98% completed and to range in size from 2.9 to 3.3 Mb with a G + C content of approximately 51%. The gene repertoire of "Candidatus Intestinicoccus colisanans" indicate it is likely a saccharolytic gut bacterium.

Motivational interviewing to improve self-management in youth with type 1 diabetes: A randomized clinical trial.

PURPOSE: Effective interventions are needed to help adolescents with T1D develop independent self-management skills to prevent commonly observed deterioration of disease self-management resulting in poor health outcomes. Using a prospective RCT design, we assessed the impact of a nurse-led education program based on motivational interviewing (MI) in youth with Type 1 diabetes (T1D). DESIGN AND METHODS: After parental consent and youth assent, we prospectively randomized 66 adolescents 13-18 years old with T1D to either usual care (every 3 months visit with pediatric endocrinologist) or usual care supplemented by 2 in-person and 4 follow-up phone calls with a nurse educator in a pediatric endocrinology clinic of the University Hospital Farhat Hached, Sousse, Tunisia. We used MI sessions to support youth general and disease specific self-management skills. Outcomes were change, between baseline and 6 months, in TRAQ (a validated measure of youth self-management) scores and HbA1c values. RESULTS: Mean TRAQ scores (based on a 5-point Likert scale) increased by 1.44 points (s.d. = 0.56) in the Intervention Group versus 0.26 points (s.d. = 0.34) in the control group (p < 0.001). The mean HbA1C value decreased in the intervention group by 0.95 units versus a decrease of 0.12 units in the control group (p = 0.047). CONCLUSION: We found that a brief, nurse-led MI-based educational intervention, integrated into specialty pediatric care, resulted in a significant improvement in both self-reported self-management skills and in HbA1c values. TRIAL REGISTRATION: Registered in ClinicalTrials.gov Identifier: NCT04798937.

Impact of in utero opioid exposure on newborn outcomes: beyond neonatal opioid withdrawal syndrome.

BACKGROUND AND OBJECTIVES: Research on in utero opioid exposure impacts has focused on Neonatal Opioid Withdrawal Syndrome (NOWS). However, possible impacts on fetal growth and newborn wellbeing have emerged, with inconsistencies likely driven by methodological issues. Our goal was to compare birth outcomes between newborns with prenatal opioid exposure and a matched control group. METHODS: Participants were identified via manual review of electronic medical records of all deliveries over five years within a regional health system (6 delivery hospitals across 2 states). From over 18,000 births, 300 with prenatal opioid exposure and 300 control newborns matched on exposure, medical, and background factors were included. Additional factors were statistically controlled. Outcomes included pregnancy/delivery complications, newborn size, and newborn health complications. RESULTS: Compared to biochemically verified controls, exposed newborns had higher rates of fetal growth restriction, weighed less, had decreased length and head circumference, and had higher rates of respiratory distress, sepsis, and jaundice. No significant differences in gestational length, Apgar scores, or neonatal hypoglycemia were found. Adjusted regression analyses revealed that compared to controls, those exposed had an average 150 g decrease in birth weight, a two-fold increased risk for IUGR (OR = 2.09), a nearly three-fold (OR = 2.80) increased risk for jaundice, a more than seven-fold (OR = 7.40) increased risk for respiratory distress, and a thirty-fold (OR = 30.47) increased risk for sepsis. CONCLUSIONS: Results suggest significant pregnancy and newborn outcomes beyond NOWS following pregnancy opioid use, informing clinical screening and treatment decisions to enhance health and wellbeing in pregnancy, during the neonatal period, and beyond.

Marijuana use in opioid exposed pregnancy increases risk of preterm birth.

BACKGROUND: The prevalence of opioid use disorder has increased across the United States, but the rural population of Appalachia has been disproportionately impacted. Concurrently, the slow, but steady progress in the legalization of marijuana may be affecting perception of marijuana use in pregnancy. However, marijuana use in pregnancy has been associated with adverse perinatal outcomes. Concomitant use of opioids and marijuana in pregnancy has not been evaluated. OBJECTIVE: The primary aim of the study was to evaluate the association between confirmed marijuana use in late pregnancy and preterm birth in opioid-exposed pregnancies. METHODOLOGY: A retrospective chart review was conducted that included all births from July 2011 to June 2016 from 6 delivery hospitals in South-Central Appalachia. Out of 18,732 births, 2368 singleton pregnancies indicated opioid use and met remaining inclusion criteria, with 108 of these mothers testing positive for marijuana at delivery. Independent sample t-test and Chi-Square analyses compared marijuana and non-marijuana exposed groups on maternal and neonatal outcomes. Regression analyses controlled for confounding variables in predicting neonatal abstinence syndrome (NAS), NICU admission, preterm birth, small for gestational age, and low birth weight outcomes as shown in Table 1. RESULTS: Neonates born to marijuana-positive women in opioid-exposed pregnancy were more likely to be born preterm, small for gestational age, have low birth weight, and be admitted to NICU. After statistically controlling for parity, marital status, tobacco and benzodiazepine use, preterm birth and low birth weight remained statistically significant with aOR of 2.35 (1.30-4.24) and 2.01 (1.18-3.44), respectively. CONCLUSIONS: Maternal use of marijuana in any opioid-exposed pregnancy may increase risk of preterm birth and low-birth weight infants. Prospective studies need to examine the dose and timing of marijuana and opioid use in pregnancy to better delineate perinatal effects. Nonetheless, pregnant women using opioids, including recommended medication assisted treatment for opioid use disorder, should be educated about the risks of concurrent marijuana use during pregnancy and may need to be counseled to abstain from marijuana use during pregnancy for an optimal outcome.

Exploring Patterns of the Use of Electronic Nicotine Delivery Systems among Adolescents in High-Risk Appalachian (U.S.A) Communities.

Background: Electronic nicotine delivery systems (ENDS) use among adolescents in the United States (U.S.) has surpassed conventional tobacco products (CTPs), including cigarettes. Increasingly, ENDS are used concurrently with CTPs and substances such as cannabis. However, few studies involve Central Appalachia, a region with historically high rates of tobacco and other substance use. Objective:  To examine prevalence of concurrent use of ENDS and cannabis among school-going adolescents in Appalachian Tennessee and delineate associations between ENDS use and substance-related risk behavior (cannabis use), social relations (peer use), and school-related risk behavior (academic performance). Methods: Data were obtained from a survey conducted with youth aged 13-17 years in 2018 in a county in Appalachian Tennessee (n = 280). A multivariable logistic regression model was fit to evaluate associations between ENDS and cannabis use, and other factors. Results: Overall, lifetime ENDS and cannabis prevalence estimates were 31.1% and 18.6%, respectively. Lifetime ENDS users had increased odds of also being lifetime cannabis users [OR = 9.22, 95% confidence interval (CI): 3.44-24.75]. Lifetime ENDS users had increased odds of reporting ENDS use among peers [OR = 12.11; 95% CI: 5.40-27.12] and lower academic performance (OR associated with mostly C or D vs. A grades was 4.28, 95% CI: 1.68-10.90). Conclusion: This study found an association between ENDS and cannabis use among adolescents in Appalachian Tennessee exists. Additionally, peer use and academic performance were associated with ENDS use. The findings have implications for public health intervention planning to address not only ENDS but also substance use among Appalachian youth.

Probiotic Bifidobacterium longum subsp. longum Protects against Cigarette Smoke-Induced Inflammation in Mice.

Bifidobacterium are prominent gut commensals that produce the short-chain fatty acid (SCFA) acetate, and they are often used as probiotics. Connections between the gut and the lung, termed the gut-lung axis, are regulated by the microbiome. The gut-lung axis is increasingly implicated in cigarette smoke-induced diseases, and cigarette smoke exposure has been associated with depletion of Bifidobacterium species. In this study, we assessed the impact of acetate-producing Bifidobacterium longum subsp. longum (WT) and a mutant strain with an impaired acetate production capacity (MUT) on cigarette smoke-induced inflammation. The mice were treated with WT or MUT B. longum subsp. longum and exposed to cigarette smoke for 8 weeks before assessments of lung inflammation, lung tissue gene expression and cecal SCFAs were performed. Both strains of B. longum subsp. longum reduced lung inflammation, inflammatory cytokine expression and adhesion factor expression and alleviated cigarette smoke-induced depletion in caecum butyrate. Thus, the probiotic administration of B. longum subsp. longum, irrespective of its acetate-producing capacity, alleviated cigarette smoke-induced inflammation and the depletion of cecal butyrate levels.

Autism-related dietary preferences mediate autism-gut microbiome associations.

There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.

Evaluation of the Microba Community Profiler for Taxonomic Profiling of Metagenomic Datasets From the Human Gut Microbiome.

A fundamental goal of microbial ecology is to accurately determine the species composition in a given microbial ecosystem. In the context of the human microbiome, this is important for establishing links between microbial species and disease states. Here we benchmark the Microba Community Profiler (MCP) against other metagenomic classifiers using 140 moderate to complex in silico microbial communities and a standardized reference genome database. MCP generated accurate relative abundance estimates and made substantially fewer false positive predictions than other classifiers while retaining a high recall rate. We further demonstrated that the accuracy of species classification was substantially increased using the Microba Genome Database, which is more comprehensive than reference datasets used by other classifiers and illustrates the importance of including genomes of uncultured taxa in reference databases. Consequently, MCP classifies appreciably more reads than other classifiers when using their recommended reference databases. These results establish MCP as best-in-class with the ability to produce comprehensive and accurate species profiles of human gastrointestinal samples.

Critical evaluation of faecal microbiome preservation using metagenomic analysis.

The ability to preserve microbial communities in faecal samples is essential as increasing numbers of studies seek to use the gut microbiome to identify biomarkers of disease. Here we use shotgun metagenomics to rigorously evaluate the technical and compositional reproducibility of five room temperature (RT) microbial stabilisation methods compared to the best practice of flash-freezing. These methods included RNALater, OMNIGene-GUT, a dry BBL swab, LifeGuard, and a novel method for preserving faecal samples, a Copan FLOQSwab in an active drying tube (FLOQSwab-ADT). Each method was assessed using six replicate faecal samples from five participants, totalling 180 samples. The FLOQSwab-ADT performed best for both technical and compositional reproducibility, followed by RNAlater and OMNIgene-GUT. LifeGuard and the BBL swab had unpredictable outgrowth of Escherichia species in at least one replicate from each participant. We further evaluated the FLOQSwab-ADT in an additional 239 samples across 10 individuals after storage at -20 °C, RT, and 50 °C for four weeks compared to fresh controls. The FLOQSwab-ADT maintained its performance across all temperatures, indicating this method is an excellent alternative to existing RT stabilisation methods.

Aqueous Ni-rich-cathode dispersions processed with phosphoric acid for lithium-ion batteries with ultra-thick electrodes.

Lithium-ion battery (LIB) production can benefit both economically and environmentally from aqueous processing. Although these electrodes have the potential to surpass electrodes conventionally processed with N-methyl-2-pyrrolidone (NMP) in terms of performance, significant issues still exist with respect to ultra-thick cathodes (≫4 mAh/cm2 areal capacities). A major concern for these types of electrodes with high-nickel active material stems from lithium leaching from active material, which drives the pH of the dispersion in excess of 12 and subsequently corrodes the current collector interface. As this corrosion reaction proceeds, hydrogen generation at the interface creates bubbles which cause severe cracking in the dried electrode surface. When areal loadings are increased, this effect becomes more pronounced and is detrimental to both mechanical and electrochemical properties of these electrodes. Herein, a technique for mitigating corrosion at the current collector by adjusting the pH of the dispersion with the addition of phosphoric acid is investigated. Phosphoric acid was added in 0.5 wt% increments between 0.0 and 1.5 wt%, and effects on rheology, adhesion, corrosion, and electrochemical performance were investigated. A technique is reported for producing aqueous processed cathodes with areal loadings of 6-8 mAh/cm2 with reduced surface cracking and superior high-rate discharge capacity (i.e. high-power performance) for this class of cathode loadings.

Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the third commonest cause of death globally, and manifests as a progressive inflammatory lung disease with no curative treatment. The lung microbiome contributes to COPD progression, but the function of the gut microbiome remains unclear. Here we examine the faecal microbiome and metabolome of COPD patients and healthy controls, finding 146 bacterial species differing between the two groups. Several species, including Streptococcus sp000187445, Streptococcus vestibularis and multiple members of the family Lachnospiraceae, also correlate with reduced lung function. Untargeted metabolomics identifies a COPD signature comprising 46% lipid, 20% xenobiotic and 20% amino acid related metabolites. Furthermore, we describe a disease-associated network connecting Streptococcus parasanguinis_B with COPD-associated metabolites, including N-acetylglutamate and its analogue N-carbamoylglutamate. While correlative, our results suggest that the faecal microbiome and metabolome of COPD patients are distinct from those of healthy individuals, and may thus aid in the search for biomarkers for COPD.

Styrene-Based Elastomer Composites with Functionalized Graphene Oxide and Silica Nanofiber Fillers: Mechanical and Thermal Conductivity Properties.

The mechanical and thermal conductivity properties of two composite elastomers were studied. Styrene-butadiene rubber (SBR) filled with functionalized graphene oxide (GO) and silica nanofibers, and styrene-butadiene-styrene (SBS) block copolymers filled with graphene oxide. For the SBR composites, GO fillers with two different surface functionalities were synthesized (cysteamine and dodecylamine) and dispersed in the SBR using mechanical and liquid mixing techniques. The hydrophilic cysteamine-based GO fillers were dispersed in the SBR by mechanical mixing, whereas the hydrophobic dodecylamine-based GO fillers were dispersed in the SBR by liquid mixing. Silica nanofibers (SnFs) were fabricated by electrospinning a sol-gel precursor solution. The surface chemistry of the functionalized fillers was studied in detail. The properties of the composites and the synergistic improvements between the GO and SnFs are presented. For the SBS composites, GO fillers were dispersed in the SBS elastomer at several weight percent loadings using liquid mixing. Characterization of the filler material and the composite elastomers was performed using x-ray photoelectron spectroscopy, x-ray diffraction, transmission electron microscopy, scanning electron microscopy, thermogravimetric analysis, dynamic mechanical analysis, tensile testing, nanoindentation, thermal conductivity and abrasion testing.

Exploring Associations between Susceptibility to the Use of Electronic Nicotine Delivery Systems and E-Cigarette Use among School-Going Adolescents in Rural Appalachia.

Electronic nicotine delivery systems (ENDS) use, including e-cigarettes, has surpassed the use of conventional tobacco products. Emerging research suggests that susceptibility to e-cigarette use is associated with actual use among adolescents. However, few studies exist involving adolescents in high-risk, rural, socioeconomically distressed environments. This study examines susceptibility to and subsequent usage in school-going adolescents in a rural distressed county in Appalachian Tennessee using data from an online survey (N = 399). Relying on bivariate analyses and logistic regression, this study finds that while 30.6% of adolescents are ever e-cigarette users, 15.5% are current users. Approximately one in three adolescents are susceptible to e-cigarettes use, and susceptibility is associated with lower odds of being a current e-cigarette user (OR = 0.03; CI: 0.01-0.12; p < 0.00). The age of tobacco use initiation was significantly associated with decreased current use of e-cigarettes (OR = 0.89; CI: 0.83-0.0.97; p < 0.01). Overall, the results of this exploratory study suggest the need for larger studies to identify unique and generalizable factors that predispose adolescents in this high-risk rural, socioeconomically disadvantaged region to ENDS use. Nevertheless, this study offers insight into e-cigarette usage among U.S adolescents in rural, socioeconomically disadvantaged environments and provides a foundation for a closer examination of this vulnerable population.

Eutectic Synthesis of the P2-Type NaxFe1/2Mn1/2O2 Cathode with Improved Cell Design for Sodium-Ion Batteries.

An engaging area of research in sodium-ion batteries (SIBs) has been focusing on discovery, design, and synthesis of high-capacity cathode materials in order to boost energy density to levels close enough to that of state-of-the-art lithium-ion batteries. Of particular interest, P2-type layered oxide, Na2/3Fe1/2Mn1/2O2, has been researched as a potential cathode in SIBs based on its high theoretical capacity of 260 mA h/g and use of noncritical materials. However, the reported synthesis methods are not only complex and energy-demanding but also often yield inhomogeneous and impure materials with capacities less than 200 mA h/g under impractical test conditions. Here, we report a novel synthesis route using low-temperature eutectic reaction to produce highly homogeneous, crystalline, and impurity-free P2-NaxFe1/2Mn1/2O2 with enhanced Na-ion diffusivity and kinetics. The overall electrochemical performances of the Na-ion cells have been improved by pairing the P2-cathode with presodiated hard carbon anodes, leading to reversible capacities in the range of 180 mA h/g. This new approach is a contribution toward the simplification of synthesis and scalability of sodium-based cathodes with high crystallinity and fine-tuned morphology and the realization of a sodium-ion battery system with lower cost and improved electrochemical performance.

Bulk and surface structural changes in high nickel cathodes subjected to fast charging conditions.

A layered oxide cathode, LiNi0.6Mn0.2Co0.2O2, undergoes noticeable crystal expansion by losing significantly higher amounts of Li+ at the end of fast charging cycles. However, the bulk structure of the cycled NMC622 is restored back to its pristine discharged state when intercalated with enough lithium ions during an electrochemical process.

Water-Based Electrode Manufacturing and Direct Recycling of Lithium-Ion Battery Electrodes-A Green and Sustainable Manufacturing System.

It is critical to develop a low-cost and environmentally friendly system to manufacture and recycle lithium-ion batteries (LIBs) as the demand on LIBs keeps increasing dramatically. Conventional LIB cathodes are manufactured using N-methyl-2-pyrrolidone as the solvent, which is expensive, highly toxic, flammable, and energy intensive to produce and recover. Ideally, a close-loop industrial supply chain should be built, in which the batteries are manufactured, market harvested, and recycled with minimal external toxic solvent through the whole system. This work demonstrates a green and more sustainable manufacturing method for LIBs where no hazardous organic solvent is used during electrode manufacturing and recycling. The electrodes fabricated via water-based processing demonstrate comparable rate performance and cycle life to the ones from conventional solvent-based processing. Utilization of a water-soluble binder enables recovering the cathode compound from spent electrodes using water, which is successfully regenerated to deliver comparable electrochemical performance to the pristine one.

Impact of pregnancy marijuana use on birth outcomes: results from two matched population-based cohorts.

OBJECTIVE: To examine associations between in utero marijuana exposure and birth outcomes. STUDY DESIGN: In two separate cohorts (Appalachian, Rocky Mountain), data were collected from medical records. Marijuana exposure was positive based on urine drug screening at delivery, with nonexposed controls matched on multiple factors including other substance exposure. RESULT: Marijuana-exposed newborns (n = 531) had significantly worse birth outcomes than controls (n = 531), weighing 218 g less, 82%, 79%, and 43% more likely to be low birth weight, preterm, or admitted to the NICU, respectively, and significantly lower Apgar scores. CONCLUSION: Marijuana exposure in utero predicted newborn factors linked to longer-term health and development issues. Effects were not attributable to other comorbidities in this study due to rigorous matching and biochemical verification of marijuana and other drug use. Findings add to growing evidence linking marijuana exposure to adverse birth and longer-term outcomes. Women should be encouraged to avoid marijuana use during pregnancy.

The systems medicine of neonatal abstinence syndrome.

This review will focus on a systems medicine approach to neonatal abstinence syndrome (NAS). Systems medicine utilizes information gained from the application of "omics" technology and bioinformatics (1). The omic approaches we will emphasize include genomics, epigenomics, proteomics, and metabolomics. The goals of systems medicine are to provide clinically relevant and objective insights into disease diagnosis, prognosis, and stratification as well as pharmacological strategies and evidence-based individualized clinical guidance. Despite the increasing incidence of NAS and its societal and economic costs, there has been only a very modest emphasis on utilizing a systems medicine approach, and this has been primarily in the areas of genomics and epigenomics. As detailed below, proteomics and metabolomics hold great promise in advancing our knowledge of NAS and its treatment. Metabolomics, in particular, can provide a quantitative assessment of the exposome, which is a comprehensive picture of both internal and external environmental factors affecting health.