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Fine particulate matter (PM2.5) was collected in situ from peat smoke during the 2015 El Niño peat fire episode in Central Kalimantan, Indonesia. Twenty-one PM samples were collected from 18 peat fire plumes that were primarily smoldering with modified combustion efficiency (MCE) values of 0.725–0.833. PM emissions were determined and chemically characterized for elemental carbon (EC), organic carbon (OC), water-soluble OC, water-soluble ions, metals, and organic species. Fuel-based PM2.5 mass emission factors (EFs) ranged from 6.0 to 29.6 g kg−1 with an average of 17.3 ± 6.0 g kg−1. EC was detected only in 15 plumes and comprised  ∼ 1 % of PM mass. Together, OC (72 %), EC (1 %), water-soluble ions (1 %), and metal oxides (0.1 %) comprised 74 ± 11 % of gravimetrically measured PM mass. Assuming that the remaining mass is due to elements that form organic matter (OM; i.e., elements O, H, N) an OM-to-OC conversion factor of 1.26 was estimated by linear regression. Overall, chemical speciation revealed the following characteristics of peat-burning emissions: high OC mass fractions (72 %), primarily water-insoluble OC (84 ± 11 %C), low EC mass fractions (1 %), vanillic to syringic acid ratios of 1.9, and relatively high n-alkane contributions to OC (6.2 %C) with a carbon preference index of 1.2–1.6. Comparison to laboratory studies of peat combustion revealed similarities in the relative composition of PM but greater differences in the absolute EF values. The EFs developed herein, combined with estimates of the mass of peat burned, are used to estimate that 3.2–11 Tg of PM2.5 was emitted to atmosphere during the 2015 El Niño peatland fire event in Indonesia. Combined with gas-phase measurements of CO2, CO, CH4, and volatile organic carbon from Stockwell et al. (2016), it is determined that OC and EC accounted for 2.1 and 0.04 % of total carbon emissions, respectively. These in situ EFs can be used to improve the accuracy of the representation of Indonesian peat burning in emission inventories and receptor-based models.

Clostridioides difficile infection (CDI) is caused by Toxins A and B, secreted from pathogenic strains of C. difficle. This infection can vary greatly in symptom severity and in clinical presentation. Current assays used to diagnose CDI may lack the required sensitivity to detect the exotoxins circulating in blood. The ultrasensitive single molecule array (Simoa) assay was modified to separately detect toxin A and toxin B in serum with a limit of detection at the low picogram level. When applied to a diverse cohort, Simoa was unable to detect toxins A or B in serum from patients with CDI, including many classified as having severe disease. The detection of toxin may be limited by the inference of antitoxin antibodies circulating in serum. This result does not support the hypothesis that toxemia occurs in C. difficile infection, conflicting with the findings of other published reports.

Inflammatory Bowel Disease (IBD) is a chronic condition that affects approximately 1.6 million Americans. While current polyphenols for treating IBD can be expensive and cause unwanted side effects, there is an opportunity regarding a new drug/polymer formulation using silymarin and an electrospray procedure. Silymarin is a naturally occurring polyphenolic flavonoid antioxidant that has shown promising results as a pharmacological agent due to its antioxidant and hepatoprotective characteristics. This study aims to produce a drug–polymer complex named the SILS100-Electrofiber complex, using an electrospray system. The vertical set-up of the electrospray system was optimized at a 1:10 of silymarin and Eudragit® S100 polymer to enhance surface area and microfiber encapsulation. The SILS100-Electrofiber complex was evaluated using drug release kinetics via UV Spectrophotometry, Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Differential Scanning Calorimetry (DSC). Drug loading, apparent solubility, and antioxidant activity were also evaluated. The study was successful in creating fiber-like encapsulation of the silymarin drug with strand diameters ranging from 5–7 μm, with results showing greater silymarin release in Simulated Intestinal Fluid (SIF) compared to Simulated Gastric Fluid (SGF). Moving forward, this study aims to provide future insight into the formulation of drug–polymer complexes for IBD treatment and targeted drug release using electrospray and microencapsulation.

To compare rates of clinical response in children with infection (CDI) treated with metronidazole vs vancomycin. Retrospective cohort study was performed as a secondary analysis of a previously established prospective cohort of hospitalized children with CDI. For 187 participants 2-17 years of age who were treated with metronidazole and/or vancomycin, the primary outcome of clinical response (defined as resolution of diarrhea within 5 days of treatment initiation) was identified retrospectively. Baseline variables associated with the primary outcome were included in a logistic regression propensity score model estimating the likelihood of receiving metronidazole vs vancomycin. Logistic regression using inverse probability of treatment weighting (IPTW) was used to estimate the effect of treatment on clinical response. One hundred seven subjects received metronidazole and 80 subjects received vancomycin as primary treatment. There was no univariable association between treatment group and clinical response; 78.30% (N = 83) of the metronidazole treatment group and 78.75% (N = 63) of the vancomycin group achieved clinical response ( = 0.941). After adjustment using propensity scores with IPTW, the odds of a clinical response for participants who received metronidazole was 0.554 (95% CI: 0.272, 1.131) times the odds of those who received vancomycin ( = 0.105). In this observational cohort study of pediatric inpatients with CDI, the rate of resolution of diarrhea after 5 days of treatment did not differ among children who received metronidazole vs vancomycin.

Abstract Background Recent data indicate that Clostridioides difficile toxin concentrations in stool do not differentiate between C. difficile infection (CDI) and asymptomatic carriage. Thus, we lack a method to distinguish a symptomatic patient with CDI from a colonized patient with diarrhea from another cause. To address this, we evaluated markers of innate and adaptive immunity in adult inpatients with CDI (diagnosed per US guidelines), asymptomatic carriage, or non-CDI diarrhea. Methods CDI-NAAT patients had clinically significant diarrhea and positive nucleic acid amplification testing (NAAT) and received CDI treatment. Carrier-NAAT patients had positive stool NAAT but no diarrhea. NAAT-negative patients (with and without diarrhea) were also enrolled. A panel of cytokines and anti–toxin A and B immunoglobulin (Ig) were measured in serum; calprotectin and anti–toxin B Ig A/G were measured in stool. NAAT-positive stool samples were tested by an ultrasensitive toxin assay (clinical cutoff, 20 pg/mL). Results Median values for interleukin (IL)-4, IL-6, IL-8, IL-10, IL-15, granulocyte colony-stimulating factor (GCSF), MCP-1, tumor necrosis factor α (TNF-α), and IgG anti–toxin A in blood and IgA/G anti–toxin B in stool were significantly higher in CDI patients compared with all other groups (P < .05). Concentration distributions for IL-6, GCSF, TNF-α, and IgG anti–toxin A in blood, as well as IgA and IgG anti–toxin B in stool, separated CDI patients from all other groups. Conclusions Specific markers of innate and adaptive immunity distinguish CDI from all other groups, suggesting potential clinical utility for identifying which NAAT- and toxin-positive patients with diarrhea truly have CDI. We compared markers of innate and acquired immunity in adults with symptomatic Clostridioides difficile infection (CDI), asymptomatic carriage, or non-CDI diarrhea. We found markers that distinguish CDI from all other groups, suggesting utility for identifying patients with true clinical CDI.

In adults with infection (CDI), higher stool concentrations of toxins A and B are associated with severe baseline disease, CDI-attributable severe outcomes, and recurrence. We evaluated whether toxin concentration predicts these presentations in children with CDI. We conducted a prospective cohort study of inpatients aged 2-17 years with CDI who received treatment. Patients were followed for 40 days after diagnosis for severe outcomes (intensive care unit admission, colectomy, or death, categorized as CDI primarily attributable, CDI contributed, or CDI not contributing) and recurrence. Baseline stool toxin A and B concentrations were measured using ultrasensitive single-molecule array assay, and 12 plasma cytokines were measured when blood was available. We enrolled 187 pediatric patients (median age, 9.6 years). Patients with severe baseline disease by IDSA-SHEA criteria (n = 34) had nonsignificantly higher median stool toxin A+B concentration than those without severe disease (n = 122; 3,217.2 vs 473.3 pg/mL; = .08). Median toxin A+B concentration was nonsignificantly higher in children with a primarily attributed severe outcome (n = 4) versus no severe outcome (n = 148; 19,472.6 vs 429.1 pg/mL; = .301). Recurrence occurred in 17 (9.4%) of 180 patients. Baseline toxin A+B concentration was significantly higher in patients with versus without recurrence: 4,398.8 versus 280.8 pg/mL ( = .024). Plasma granulocyte colony-stimulating factor concentration was significantly higher in CDI patients versus non-CDI diarrhea controls: 165.5 versus 28.5 pg/mL ( < .001). Higher baseline stool toxin concentrations are present in children with CDI recurrence. Toxin quantification should be included in CDI treatment trials to evaluate its use in severity assessment and outcome prediction.

Abstract Background Clostridioides difficile infection (CDI) immune response is influenced by the innate and adaptive (humoral) immune systems. Our prior research found attenuated humoral responses to C difficile in immunocompromised hosts (ICHs) with CDI. We sought to evaluate whether the innate immune response to CDI was influenced by ICH status. Methods We conducted a prospective study of hospitalized adults with CDI (acute diarrhea, positive C difficile stool nucleic acid amplification testing [NAAT], and decision to treat), with and without immunosuppression and measured a panel of cytokines (granulocyte colony-stimulating factor [G-CSF], interleukin [IL]–10, IL-15, IL-1β, IL-4, IL-6, IL-8, and tumor necrosis factor–α) in blood and stool at CDI diagnosis. Results were compared with measurements from a cohort of asymptomatic carrier patients (ASCs) (NAAT positive, without diarrhea) with and without immunocompromise. Results One hundred twenty-three subjects (42 ICHs, 50 non-ICHs, 31 ASCs) were included. Median values for blood and stool cytokines were similar in ICH versus non-ICH CDI subjects. In blood, G-CSF, IL-10, IL-15, IL-6, and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). In stool, IL-1β and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). Median stool concentrations of IL-1β demonstrated significant differences between the groups (ICHs, 10.97 pg/mL; non-ICHs, 9.71 pg/mL; and ASCs, 0.56 pg/mL) (P < .0001). Conclusions In this small exploratory analysis, ICH status did not significantly impact blood and fecal patterns of cytokines in humans at the diagnosis of CDI, suggesting that the innate immune response to C difficile may be conserved in immunocompromised patients. Blood and fecal cytokine patterns were similar in immunocompromised and nonimmunocompromised patients with Clostridioides difficile infection (CDI) at time of CDI diagnosis. These data suggest the innate immune response to C difficile infection may be conserved in immunocompromised hosts.

Abstract Background The humoral immune response to Clostridioides difficile toxins in C difficile infection (CDI) is incompletely characterized in immunocompromised hosts (ICHs). Methods We conducted a prospective study of hospitalized adults with CDI, with and without immunosuppression (hematologic malignancy, active solid tumor, solid organ or stem cell transplant, inflammatory bowel disease, autoimmune disease, congenital or acquired immunodeficiency, asplenia, chronic receipt of high-dose steroids, or receipt of immunosuppressing medications within 12 months). Serum and stool antibody concentrations of immunoglobulin (Ig)M, IgG, and IgA to C difficile toxins A and B at treatment days 0, 3, and 10–14 were compared. Results Ninety-eight subjects (47 ICH; 51 non-ICH) were enrolled. Baseline serum antitoxin A and B antibody levels were similar. At day 3, ICHs demonstrated lower serum levels of antitoxin A IgG, antitoxin A IgA, and antitoxin B IgA (all P < .05). At day 10–14, lower antitoxin A IgG concentrations were observed in ICHs (ICH, 21 enzyme-linked immunosorbent assay [ELISA] units; interquartile range [IQR], 16.4–44.6) compared with non-ICH subjects (49.0 ELISA units; IQR, 21.5–103; P = .045). In stool, we observed lower concentrations of antitoxin B IgA antibodies at baseline and at day 3 for ICH subjects, with a notable difference in concentrations of antitoxin B IgA at day 3 (ICH, 6.7 ELISA units [IQR, 1.9–13.9] compared with non-ICH, 18.1 ELISA units [IQR, 4.9–31.7]; P = .003). Conclusions The ICHs with CDI demonstrated lower levels of C difficile antitoxin antibodies in serum and stool during early CDI therapy compared with non-ICHs. These data provide insight into the humoral response to CDI in ICHs. Immunocompromised patients with CDI demonstrated lower levels of Clostridioides difficile toxin-specific antibodies in the serum and stool at treatment day 3 compared with non-immunocompromised subjects. These data provide insight into the natural history of CDI humoral response in immunocompromised subjects.