Kidney-specific biomarkers for predicting acute kidney injury following cardiac arrest.

AIM: To evaluate the performance of kidney-specific biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C) in early detection of acute kidney injury (AKI) following cardiac arrest (CA) when compared to serum creatinine. METHODS: Adult CA patients who had kidney-specific biomarkers of AKI collected within 12 h of return of spontaneous circulation (ROSC) were included. The association between renal biomarker levels post-ROSC and the development of KDIGO stage III AKI within 7 days of enrollment were assessed as well as their predictive value of future AKI development, neurological outcomes, and survival to discharge. RESULTS: Of 153 patients, 54 (35%) developed stage III AKI within 7 days, and 98 (64%) died prior to hospital discharge. Patients who developed stage III AKI, compared to those who did not, had higher median levels of creatinine, NGAL, and cystatin-C (p < 0.001 for all). There was no statistically significant difference in KIM-1 between groups. No biomarker outperformed creatinine in the ability to predict stage III AKI, neurological outcomes, or survival outcomes (p > 0.05 for all). However, NGAL, cystatin-C, and creatinine all performed better than KIM-1 in their ability to predict AKI development (p < 0.01 for all). CONCLUSION: In post-CA patients, creatinine, NGAL, and cystatin-C (but not KIM-1) measured shortly after ROSC were higher in patients who subsequently developed AKI. No biomarker was statistically superior to creatinine on its own for predicting the development of post-arrest AKI.

Removable versus fixed myo-functional appliances in class II malocclusion among Indians.

It is of interest to compare two myofunctional appliances (frankal appliance and twin bloc) and two fixed orthodontic appliances (PowerScope and Forsus) in management of class II div 1 malocclusion. A total of 56 Class II division 1 malocclusion patients indicated for treatment with myofunctional appliances and fixed functional appliances were randomized. They were equally divided among frankal appliance (n=14), twin block appliance (n=14), PowerScope (American Orthodontics) (n=14), Forsus (3M Unitek Corp) groups (n=14). Skeletal and dentoalveolar effects of all appliances were compared. SNB increased remarkably by 4.2° in the Twin block group and it was high among all treatment groups. There was a significant decrease in vertical dimensions (SN-GoGn) in the Twin block (p = 0.002). Early treatment of Class II due to mandibular retrusion with Twin block functional appliance is recommended due to its favorable skeletal effect.

Distinct environmental parameters influence the abundance of living benthic foraminifera morphogroups in the southeastern Arabian Sea.

The ambient environmental parameters have a great bearing on the morphology of living flora and fauna. In this study, we tested this hypothesis on one of the most dominant groups of living unicellular marine microorganism, benthic foraminifera, in the dynamic region of the southeastern Arabian Sea. The living benthic foraminifera from 43 surface samples collected between 25 and 2980 m of water depth were segregated into eight morphogroups (tapered/cylindrical, flattened-ovoid, biconvex, planoconvex, flattened-tapered, spherical, rounded-trochospiral, and rounded-planispiral). We report that the high organic carbon availability is combined with deficiency of oxygen results in benthic foraminifera with low surface area to volume ratio and mostly consists of tapered/cylindrical, flattened-ovoid forms, with a preference for infaunal habitat. However, the tests of the living benthic foraminifera thriving in the oxygen-rich bottom waters have a high surface area to volume ratio, commonly reported as epifaunal, consisting of biconvex and planoconvex forms. Additionally, we also report that the abundance of other morphogroups, namely flattened-tapered, spherical, rounded-trochospiral, and rounded-planispiral, is also controlled by the distinct environmental parameters. We suggest that the living benthic foraminifera are an excellent indicator of the ambient environmental parameters and can be used to reconstruct paleoenvironments.

Resuscitation Quality in the ICU: A Retrospective Analysis.

BACKGROUND: American Heart Association quality metrics of resuscitation include time to epinephrine ≤ 5 min, time to defibrillation ≤ 2 min, and confirmation of airway device placement in trachea. This study examined trends in adherence to these quality metrics in the ICU and identified predictors of failure to adhere to these metrics. RESEARCH QUESTION: What is the registered adherence to time to epinephrine ≤ 5 min, time to defibrillation ≤ 2 min, and confirmation of airway device placement in trachea in the ICU setting? STUDY DESIGN AND METHODS: This was a retrospective analysis. Using the Get With The Guidelines-Resuscitation registry, adult patients with an index cardiac arrest in adult ICUs between 2006 and 2018 in the United States were identified. Modified Poisson regression with generalized estimation equations were used for the analyses. RESULTS: A total of 97,009 adult ICU patients from 538 hospitals were identified using the Get With The Guidelines-Resuscitation registry, and 75,668 patients were included in the final analysis. From 2006 to 2018, adherence to time to epinephrine ≤ 5 min increased from 93% (95% CI, 93-94) to 98% (95% CI, 97-98), time to defibrillation ≤ 2 min increased from 72% (95% CI, 69-75) to 75% (95% CI, 72-78), and confirmation of airway device placement in trachea increased from 93% (95% CI, 91-94) to 97% (95% CI, 96-98). Nonwitnessed status (P < .001), nonmonitored status (P = .003), and nighttime arrest (P = .002) were associated with adherence failure for time to epinephrine ≤ 5 min, whereas a noncardiac (P < .001) or traumatic (P < .001) illness category, renal insufficiency (P = .001), and nighttime arrest (P = .03) were associated with adherence failure for time to defibrillation ≤ 2 min. INTERPRETATION: Overall, quality metric adherence was high in the ICU, with the exception of time to defibrillation ≤ 2 min.

Viral load and disease severity in COVID-19.

The relationship between COVID-19 severity and viral load is unknown. Our objective was to assess the association between viral load and disease severity in COVID-19. In this single center observational study of adults with laboratory confirmed SARS-CoV-2, the first positive in-hospital nasopharyngeal swab was used to calculate the log10 copies/ml [log10 copy number (CN)] of SARS-CoV-2. Four categories based on level of care and modified sequential organ failure assessment score (mSOFA) at time of swab were determined. Median log10CN was compared between different levels of care and mSOFA quartiles. Median log10CN was compared in patients who did and did not receive influenza vaccine, and the correlation between log10CN and D-dimer was examined. We found that of 396 patients, 54.3% were male, and 25% had no major comorbidity. Hospital mortality was 15.7%. Median mSOFA was 2 (IQR 0-3). Median log10CN was 5.5 (IQR 3.3-8.0). Median log10CN was highest in non-intubated ICU patients [6.4 (IQR 4.4-8.1)] and lowest in intubated ICU patients [3.6 (IQR 2.6-6.9)] (p value < 0.01). In adjusted analyses, this difference remained significant [mean difference 1.16 (95% CI 0.18-2.14)]. There was no significant difference in log10CN between other groups in the remaining pairwise comparisons. There was no association between median log10CN and mSOFA in either unadjusted or adjusted analyses or between median log10CN in patients with and without influenza immunization. There was no correlation between log10CN and D-dimer. We conclude, in our cohort, we did not find a clear association between viral load and disease severity in COVID-19 patients. Though viral load was higher in non-intubated ICU patients than in intubated ICU patients there were no other significant differences in viral load by disease severity.

Determination of thyroid hormones in dietary supplements using liquid chromatography-tandem mass spectrometry.

More than 27 million Americans have some kind of thyroid disease. Numerous dietary supplements claiming to support healthy thyroid function and healthy metabolism and balance or promote weight loss are available for purchase in retail stores and on the internet. In the literature, there have been reports of adverse events associated with the consumption of thyroid hormone-containing products. In this study, an LC-MS/MS method was developed and validated for the analysis of thyroxine (T4), 3,3',5-triiodo-l-thyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,5-diiodothyronine (3,5-T2) and 3,3'-diiodothyronine (3,3'-T2) in dietary supplements. Sonication with methanol was used for the extraction of free hormones from nonglandular products. The tissue-bound hormones from glandular thyroid products were extracted using a modified enzymatic digestion, in which the matrix was first extracted by sonication with methanol and then by enzymatic digestion with proteases. Both extraction methods provided acceptable recovery values between 78% and 116%. Fifty-eight products making claims related to thyroid management were purchased over the internet from 2017-2018 and quantitatively analyzed for five hormones using the validated methods. Eleven out of 19 glandular products were found to contain quantifiable amounts of hormones. Maximum daily servings were also calculated for each product based on label information. The maximum amount of T4, T3, and rT3 per daily serving in the glandular products were up to 210, 32, and 7.6 µg/day, respectively. In the case of nonglandular products, which were labeled to contain plant extracts, vitamins, minerals, diiodo compounds, and so forth, the amounts of 3,5-T2 and 3,3'-T2 were up to 740 and 2700 µg/day, respectively.

Thiamine Supplementation in Patients With Alcohol Use Disorder Presenting With Acute Critical Illness : A Nationwide Retrospective Observational Study.

BACKGROUND: Thiamine supplementation is recommended for patients with alcohol use disorder (AUD). The authors hypothesize that critically ill patients with AUD are commonly not given thiamine supplementation. OBJECTIVE: To describe thiamine supplementation incidence in patients with AUD and various critical illnesses (alcohol withdrawal, septic shock, traumatic brain injury [TBI], and diabetic ketoacidosis [DKA]) in the United States. DESIGN: Retrospective observational study. SETTING: Cerner Health Facts database. PATIENTS: Adult patients with a diagnosis of AUD who were admitted to the intensive care unit with alcohol withdrawal, septic shock, TBI, or DKA between 2010 and 2017. MEASUREMENTS: Incidence and predicted probability of thiamine supplementation in alcohol withdrawal and other critical illnesses. RESULTS: The study included 14 998 patients with AUD. Mean age was 52.2 years, 77% of participants were male, and in-hospital mortality was 9%. Overall, 7689 patients (51%) received thiamine supplementation. The incidence of thiamine supplementation was 59% for alcohol withdrawal, 26% for septic shock, 41% for TBI, and 24% for DKA. Most of those receiving thiamine (n = 3957 [52%]) received it within 12 hours of presentation in the emergency department. The predominant route of thiamine administration was enteral (n = 3119 [41%]). LIMITATION: Specific dosing and duration were not completely captured. CONCLUSION: Thiamine supplementation was not provided to almost half of all patients with AUD, raising a quality-of-care issue for this cohort. Supplementation was numerically less frequent in patients with septic shock, DKA, or TBI than in those with alcohol withdrawal. These data will be important for the design of quality improvement studies in critically ill patients with AUD. PRIMARY FUNDING SOURCE: National Institutes of Health.

Cardiopulmonary resuscitation and defibrillation for cardiac arrest when patients are in the prone position: A systematic review.

AIM: To perform a systematic review of cardiopulmonary resuscitation (CPR) and/or defibrillation in the prone position compared to turning the patient supine prior to starting CPR and/or defibrillation. METHODS: The search included PubMed, Embase, Web of Science, Cochrane, CINAHL Plus, and medRxiv on December 9, 2020. The population included adults and children in any setting with cardiac arrest while in the prone position. The outcomes included arterial blood pressure and end-tidal capnography during CPR, time to start CPR and defibrillation, return of spontaneous circulation, survival and survival with favorable neurologic outcome to discharge, 30 days or longer. ROBINS-I was performed to assess risk of bias for observational studies. RESULTS: The systematic review identified 29 case reports (32 individual cases), two prospective observational studies, and two simulation studies. The observational studies enrolled 17 patients who were declared dead in the supine position and reported higher mean systolic blood pressure from CPR in prone position (72 mmHg vs 48 mmHg, p < 0.005; 79 ± 20 mmHg vs 55 ± 20 mmHg, p = 0.028). One simulation study reported a faster time to defibrillation in the prone position. Return of spontaneous circulation, survival to discharge or 30 days were reported in adult and paediatric case reports. Critical risk of bias limited our ability to perform pooled analyses. CONCLUSIONS: We identified a limited number of observational studies and case reports comparing prone versus supine CPR and/or defibrillation. Prone CPR may be a reasonable option if immediate supination is difficult or poses unacceptable risks to the patient.

Identification of Two Subsets of Murine DC1 Dendritic Cells That Differ by Surface Phenotype, Gene Expression, and Function.

Classical dendritic cells (cDCs) in mice have been divided into 2 major subsets based on the expression of nuclear transcription factors: a CD8+Irf8+Batf3 dependent (DC1) subset, and a CD8-Irf4+ (DC2) subset. We found that the CD8+DC1 subset can be further divided into CD8+DC1a and CD8+DC1b subsets by differences in surface receptors, gene expression, and function. Whereas all 3 DC subsets can act alone to induce potent Th1 cytokine responses to class I and II MHC restricted peptides derived from ovalbumin (OVA) by OT-I and OT-II transgenic T cells, only the DC1b subset could effectively present glycolipid antigens to natural killer T (NKT) cells. Vaccination with OVA protein pulsed DC1b and DC2 cells were more effective in reducing the growth of the B16-OVA melanoma as compared to pulsed DC1a cells in wild type mice. In conclusion, the Batf3-/- dependent DC1 cells can be further divided into two subsets with different immune functional profiles in vitro and in vivo.

Development of immunosuppressive myeloid cells to induce tolerance in solid organ and hematopoietic cell transplant recipients.

Replacement of failed organs followed by safe withdrawal of immunosuppressive drugs has long been the goal of organ transplantation. We studied changes in the balance of T cells and myeloid cells in the blood of HLA-matched and -mismatched patients given living donor kidney transplants followed by total lymphoid irradiation, anti-thymocyte globulin conditioning, and donor hematopoietic cell transplant to induce mixed chimerism and immune tolerance. The clinical trials were based on a conditioning regimen used to establish mixed chimerism and tolerance in mice. In preclinical murine studies, there was a profound depletion of T cells and an increase in immunosuppressive polymorphonuclear (pmn) myeloid-derived suppressor cells (MDSCs) in the spleen and blood following transplant. Selective depletion of pmn MDSCs in mice abrogated mixed chimerism and tolerance. In our clinical trials, patients given an analogous tolerance conditioning regimen developed similar changes, including profound depletion of T cells and a marked increase in MDSCs in blood posttransplant. Posttransplant pmn MDSCs transiently increased expression of lectin-type oxidized LDL receptor-1, a marker of immunosuppression, and production of the T-cell inhibitor arginase-1. These posttransplant pmn MDSCs suppressed the activation, proliferation, and inflammatory cytokine secretion of autologous T-cell receptor microbead-stimulated pretransplant T cells when cocultured in vitro. In conclusion, we elucidated changes in receptors and function of immunosuppressive myeloid cells in patients enrolled in the tolerance protocol that were nearly identical to those of MDSCs required for tolerance in mice. These trials were registered at www.clinicaltrials.gov as #NCT00319657 and #NCT01165762.

Comparison between Patients Hospitalized with Influenza and COVID-19 at a Tertiary Care Center.

BACKGROUND: Widespread reports suggest the characteristics and disease course of coronavirus disease 2019 (COVID-19) and influenza differ, yet detailed comparisons of their clinical manifestations are lacking. OBJECTIVE: Comparison of the epidemiology and clinical characteristics of COVID-19 patients during the pandemic with those of influenza patients in previous influenza seasons at the same hospital DESIGN: Admission rates, clinical measurements, and clinical outcomes from confirmed COVID-19 cases between March 1 and April 30, 2020, were compared with those from confirmed influenza cases in the previous five influenza seasons (8 months each) beginning September 1, 2014. SETTING: Large tertiary care teaching hospital in Boston, MA PARTICIPANTS: Laboratory-confirmed COVID-19 and influenza inpatients MEASUREMENTS: Patient demographics and medical history, mortality, incidence and duration of mechanical ventilation, incidences of vasopressor support and renal replacement therapy, and hospital and intensive care admissions. RESULTS: Data was abstracted from medical records of 1052 influenza patients and 582 COVID-19 patients. An average of 210 hospital admissions for influenza occurred per 8-month season compared to 582 COVID-19 admissions over 2 months. The median weekly number of COVID-19 patients requiring mechanical ventilation was 17 (IQR: 4, 34) compared to a weekly median of 1 (IQR: 0, 2) influenza patient (p=0.001). COVID-19 patients were significantly more likely to require mechanical ventilation (31% vs 8%) and had significantly higher mortality (20% vs. 3%; p<0.001 for all). Relatively more COVID-19 patients on mechanical ventilation lacked pre-existing conditions compared with mechanically ventilated influenza patients (25% vs 4%, p<0.001). Pneumonia/ARDS secondary to the virus was the predominant cause of mechanical ventilation in COVID-19 patients (94%) as opposed to influenza (56%). LIMITATION: This is a single-center study which could limit generalization. CONCLUSION: COVID-19 resulted in more weekly hospitalizations, higher morbidity, and higher mortality than influenza at the same hospital.

HPLC-UV, Metabarcoding and Genome Skims of Botanical Dietary Supplements: A Case Study in Echinacea.

The use of DNA-based methods to authenticate botanical dietary supplements has been vigorously debated for a variety of reasons. More comparisons of DNA-based and chemical methods are needed, and concordant evaluation of orthogonal approaches on the same products will provide data to better understand the strengths and weaknesses of both approaches. The overall application of DNA-based methods is already firmly integrated into a wide array of continually modernizing stand alone and complementary authentication protocols. Recently, the use of full-length chloroplast genome sequences provided enhanced discriminatory capacity for closely related species of Echinacea compared to traditional DNA barcoding approaches (matK and rbcL). Here, two next-generation sequencing approaches were used: (1) genome skimming and (2) PCR amplicon (metabarcoding). The two genetic approaches were then combined with HPLC-UV to evaluate 20 commercially available dietary supplements of Echinacea representing "finished" products. The trade-offs involved in different DNA approaches were discussed, with a focus on how DNA methods support existing, accepted chemical methods. In most of the products (19/20), HPLC-UV suggested the presence of Echinacea spp. While metabarcoding was not useful with this genus and instead only resolved 7 products to the family level, genome skimming was able to resolve to species (9) or genus (1) with the 10/20 products where it was successful. Additional ingredients that HPLC-UV was unable to identify were also found in four products along with the relative sequence proportion of the constituents. Additionally, genome skimming was able to identify one product that was a different Echinacea species entirely.

A survey of cannabinoids and toxic elements in hemp-derived products from the United States marketplace.

The 2018 Agricultural Improvement Act removed hemp from Schedule I control, creating a market for hemp products, including cannabidiol-containing products. Due to the market's rapid growth, little is known about the presence and concentration of cannabinoids in commercial products. Herein, 11 cannabinoids were quantified using liquid chromatography with diode-array detection in a non-representative sampling of 147 products labeled as containing hemp or cannabidiol. A subset of 133 products were analyzed for toxic elements using inductively coupled plasma-mass spectrometry. Cannabinoid content ranged from < LOD - 143 mg/serving, with a median of 16.7 mg/serving. Fewer than half of products surveyed contained cannabidiol concentrations within 20 % of their label declarations. The estimated exposure to lead was below the Interim Reference Level of 12.5 µg/day Pb for women of childbearing age, and most products presented concentrations of Δ9-tetrahydrocannabinol below LOQ. These findings emphasize the need for further testing and representative investigation of the cannabidiol marketplace.

Variation in SOFA (Sequential Organ Failure Assessment) Score Performance in Different Infectious States.

INTRODUCTION: In this study, we investigated whether the Sequential Organ Failure Assessment (SOFA) score performance differs based on the type of infection among patients admitted to the intensive care unit (ICU) with infection. MATERIALS AND METHODS: Single-center, retrospective study of adult ICU patients admitted with infection between January 2008 and April 2018 at an urban tertiary care center. Patients were uniquely classified into different infection types based on International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes. Infection types included were pneumonia, meningitis, bacteremia, cellulitis, cholangitis/cholecystitis, intestinal and diarrheal disease, endocarditis, urinary tract infection (UTI), and peritonitis. The SOFA score performance and mortality in relation to SOFA score were compared across infection types. RESULTS: A total of 12 283 patients were included. Of these, 50.6% were female and the median age was 70 years (interquartile range: 57-82). The most common infection types were pneumonia (32.2%) and UTI (31.0%). Overall, 1703 (13.9%) patients died prior to hospital discharge. The median baseline SOFA score (within 24 hours of ICU admission) for the cohort was 5 (3-8). Patients with peritonitis had the highest median SOFA score, 7 (4-9), and patients with cellulitis and UTI had the lowest median SOFA score, 4 (2-7). The SOFA score discrimination to predict mortality was highest among patients with endocarditis (area under the receiver operating characteristic [AUC]: 0.79, 95% CI: 0.69-0.90) and lowest for patients with isolated bacteremia (AUC: 0.59, 95% CI: 0.49-0.70). Observed mortality by quartile of SOFA score differed substantially across infection types. CONCLUSIONS: Type of infection is an important consideration when interpreting the SOFA score. This is relevant as SOFA emerges as an important tool in the definition and prognostication of sepsis.

Analysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC-MS/MS.

Citrus aurantium, commonly known as bitter orange, is a popular dietary supplement ingredient sold worldwide. Bitter orange supplements are sold primarily as weight management and sports performance products and have gained popularity after Ephedra products were banned from the US market. Supplements containing synephrine are reported to exhibit adverse cardiovascular effects especially in the presence of caffeine. In this study, an LC-MS/MS method was established to quantify five natural amines (synephrine, octopamine, tyramine, N-methyltyramine, and hordenine) and four synthetic phenethylamines (phenylephrine, methylsynephrine, etilefrine, and isopropyloctopamine) in dietary supplements sold in the US. The method was validated and found to have acceptable performance to accurately measure analytes in complex botanical products. The average recoveries from a blank matrix were 88-125% with an RSD of 0.5-7.0%. Fifty-nine products labeled to contain bitter orange peel, extract, or its amines were purchased and their amine content was measured. Several products were found to contain higher amounts of amines than that expected from a typical bitter orange extract. Of the 23 products that made label claims for synephrine, only 5 products (22%) were within 80-120% of labeled synephrine content. The presence of synthetic amines, methylsynephrine (up to 240 mg/daily serving), and isopropyloctopamine (up to 76 mg/daily serving), whose effects in humans are not known, were detected in six products and one product, respectively. While the use of methylsynephrine and isopropyloctopamine are not permitted in dietary supplements, hordenine, N-methyltyramine, and octopamine are currently listed on the FDA's Dietary Supplement Ingredient Advisory List.

RNAseq Reveals the Contribution of Interferon Stimulated Genes to the Increased Host Defense and Decreased PPR Viral Replication in Cattle.

Peste des petits ruminants virus (PPRV) is known to replicate in a wide variety of ruminants causing very species-specific clinical symptoms. Small ruminants (goats and sheep) are susceptible to disease while domesticated cattle and buffalo are dead-end hosts and do not display clinical symptoms. Understanding the host factors that influence differential pathogenesis and disease susceptibility could help the development of better diagnostics and control measures. To study this, we generated transcriptome data from goat and cattle peripheral blood mononuclear cells (PBMC) experimentally infected with PPRV in-vitro. After identifying differentially expressed genes, we further analyzed these immune related pathway genes using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and selected candidate genes were validated using in-vitro experiments. Upon PPRV infection, we identified 12 and 22 immune related genes that were differentially expressed in goat and cattle respectively. In both species, this included the interferon stimulated genes (ISGs) IFI44, IFI6, IFIT1, IFIT2, IFIT3, ISG15, Mx1, Mx2, OAS1X, RSAD2, IRF7, DDX58 and DHX58 that were transcribed significantly higher in cattle. PPRV replication in goat PBMCs significantly increased the expression of phosphodiesterase 12 (PDE12), a 2',5'-oligoadenylate degrading enzyme that contributes to the reduced modulation of interferon-regulated gene targets. Finally, a model is proposed for the differential susceptibility between large and small ruminants based on the expression levels of type-I interferons, ISGs and effector molecules.

How effective is LENA in detecting speech vocalizations and language produced by children and adolescents with ASD in different contexts?

The LENA system was designed and validated to provide information about the language environment in children 0 to 4 years of age and its use has been expanded to populations with a number of communication profiles. Its utility in children 5 years of age and older is not yet known. The present study used acoustic data from two samples of children with autism spectrum disorders (ASD) to evaluate the reliability of LENA automated analyses for detecting speech utterances in older, school age children, and adolescents with ASD, in clinic and home environments. Participants between 5 and 18 years old who were minimally verbal (study 1) or had a range of verbal abilities (study 2) completed standardized assessments in the clinic (study 1 and 2) and in the home (study 2) while speech was recorded from a LENA device. We compared LENA segment labels with manual ground truth coding by human transcribers using two different methods. We found that the automated LENA algorithms were not successful (<50% reliable) in detecting vocalizations from older children and adolescents with ASD, and that the proportion of speaker misclassifications by the automated system increased significantly with the target-child's age. The findings in children and adolescents with ASD suggest possibly misleading results when expanding the use of LENA beyond the age ranges for which it was developed and highlight the need to develop novel automated methods that are more appropriate for older children. Autism Research 2019, 12: 628-635. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Current commercially available speech detection algorithms (LENA system) were previously validated in toddlers and children up to 48 months of age, and it is not known whether they are reliable in older children and adolescents. Our data suggest that LENA does not adequately capture speech in school age children and adolescents with autism and highlights the need to develop new automated methods for older children.

Silicosis and Silica-Induced Autoimmunity in the Diversity Outbred Mouse.

Epidemiological studies have confidently linked occupational crystalline silica exposure to autoimmunity, but pathogenic mechanisms and role of genetic predisposition remain poorly defined. Although studies of single inbred strains have yielded insights, understanding the relationships between lung pathology, silica-induced autoimmunity, and genetic predisposition will require examination of a broad spectrum of responses and susceptibilities. We defined the characteristics of silicosis and autoimmunity and their relationships using the genetically heterogeneous diversity outbred (DO) mouse population and determined the suitability of this model for investigating silica-induced autoimmunity. Clinically relevant lung and autoimmune phenotypes were assessed 12 weeks after a transoral dose of 0, 5, or 10 mg crystalline silica in large cohorts of DO mice. Data were further analyzed for correlations, hierarchical clustering, and sex effects. DO mice exhibited a wide range of responses to silica, including mild to severe silicosis and importantly silica-induced systemic autoimmunity. Strikingly, about half of PBS controls were anti-nuclear antibodies (ANA) positive, however, few had disease-associated specificities, whereas most ANAs in silica-exposed mice showed anti-ENA5 reactivity. Correlation and hierarchical clustering showed close association of silicosis, lung biomarkers, and anti-ENA5, while other autoimmune characteristics, such as ANA and glomerulonephritis, clustered separately. Silica-exposed males had more lung inflammation, bronchoalveolar lavage fluid cells, IL-6, and autoantibodies. DO mice are susceptible to both silicosis and silica-induced autoimmunity and show substantial individual variations reflecting their genetic diverseness and the importance of predisposition particularly for autoimmunity. This model provides a new tool for deciphering the relationship between silica exposure, genes, and disease.

Validation of an LC-MS/MS method for analysis of anti-diabetic drugs in botanical dietary supplements labeled for blood sugar management.

We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect and quantitate 14 anti-diabetic, 2 anti-obesity, and 3 cholesterol-lowering drugs in botanical dietary supplements marketed for blood sugar management. Many botanical dietary supplements which carry label statements related to blood sugar management are available over the Internet. Potential adulteration of such dietary supplements with anti-diabetic and other prescription drugs, some of which have been removed from the market due to adverse events, is of concern. No significant matrix effects were observed and mean recoveries of all 19 analytes from a single product matrix were 88 to 113% at spiking concentrations from 500 to 2000 µg/g. Mean recoveries of metformin, phenformin, and sibutramine from matrices prepared from multiple product composites ranged from 93 to 115% at a spiking concentration of 100 µg/g. The relative standard deviations (RSD) (%) of intra-day analyses ranged from 0.2 to 13 for all recovery studies. Eighty dietary supplements obtained in the USA and carrying label statements related to blood sugar management were analyzed using this method and none were found to be adulterated with the above 19 drugs. Two products obtained outside of the USA and known to be adulterated were also analyzed by this method and found to contain phenformin, glibenclamide, and sibutramine. This method provided satisfactory selectivity, linearity, accuracy, precision, and sensitivity for rapid determination of 19 drugs and has broad applicability for the analysis of dietary supplements for possible adulteration with these compounds.