Tag: nevin manimala

J Patient Saf. 2022 Jul 11. doi: 10.1097/PTS.0000000000001066. Online ahead of print.

ABSTRACT

OBJECTIVE: The COVID-19 pandemic prompted labor and delivery units to establish ways to decrease viral exposure to healthcare workers while continuing to deliver optimal patient care. A laborist model was implemented to improve safety at our tertiary care hospital in Long Island. The aim of the study is to determine whether implementation of a laborist model during the COVID-19 pandemic is associated with a change in the frequency of cesarean birth.

METHODS: The retrospective cohort study included patients who delivered at a single tertiary center during March 2019 to May 2019 and March 2020 to May 2020 when our laborist model was initiated. The primary outcome compared the frequency of a cesarean delivery between both models. Secondary outcomes were the frequency of adverse obstetrical complications, which included intensive care unit admission, shoulder dystocia, intra-amniotic infection, hemorrhage, and need for blood transfusion. Statistical analysis included multivariable regression to adjust for potential confounders.

RESULTS: A total of 1506 patients were included. Baseline characteristics were similar between the 2 groups. After adjusting for potential confounders, there was no significant difference in the frequency of cesarean births between both models (37% versus 35%; adjusted odds ratio, 1.003; 95% confidence interval, 0.46-2.89). Similarly, there were no significant differences in adverse outcomes between the study populations (adjusted odds ratio, 1.064; 95% confidence interval, 0.68-1.59).

CONCLUSIONS: A change in practice behavior during a pandemic was not associated with an increase in frequency of cesarean births or adverse obstetrical outcomes.

PMID:35858475 | DOI:10.1097/PTS.0000000000001066

Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2201208119. doi: 10.1073/pnas.2201208119. Epub 2022 Jul 18.

ABSTRACT

Completion of the Lassa virus (LASV) life cycle critically depends on the activities of the virally encoded, RNA-dependent RNA polymerase in replication and transcription of the viral RNA genome in the cytoplasm of infected cells. The contribution of cellular proteins to these processes remains unclear. Here, we applied proximity proteomics to define the interactome of LASV polymerase in cells under conditions that recreate LASV RNA synthesis. We engineered a LASV polymerase-biotin ligase (TurboID) fusion protein that retained polymerase activity and successfully biotinylated the proximal proteome, which allowed the identification of 42 high-confidence LASV polymerase interactors. We subsequently performed a small interfering RNA (siRNA) screen to identify those interactors that have functional roles in authentic LASV infection. As proof of principle, we characterized eukaryotic peptide chain release factor subunit 3a (eRF3a/GSPT1), which we found to be a proviral factor that physically associates with LASV polymerase. Targeted degradation of GSPT1 by a small-molecule drug candidate, CC-90009, resulted in strong inhibition of LASV infection in cultured cells. Our work demonstrates the feasibility of using proximity proteomics to illuminate and characterize yet-to-be-defined host-pathogen interactome, which can reveal new biology and uncover novel targets for the development of antivirals against highly pathogenic RNA viruses.

PMID:35858434 | DOI:10.1073/pnas.2201208119

Proc Natl Acad Sci U S A. 2022 Aug 2;119(31):e2200732119. doi: 10.1073/pnas.2200732119. Epub 2022 Jul 19.

NO ABSTRACT

PMID:35858388 | DOI:10.1073/pnas.2200732119

Proc Natl Acad Sci U S A. 2022 Jul 19;119(29):e2114365119. doi: 10.1073/pnas.2114365119. Epub 2022 Jul 11.

ABSTRACT

Molecular analysis on the single-cell level represents a rapidly growing field in the life sciences. While bulk analysis from a pool of cells provides a general molecular profile, it is blind to heterogeneities between individual cells. This heterogeneity, however, is an inherent property of every cell population. Its analysis is fundamental to understanding the development, function, and role of specific cells of the same genotype that display different phenotypical properties. Single-cell mass spectrometry (MS) aims to provide broad molecular information for a significantly large number of cells to help decipher cellular heterogeneity using statistical analysis. Here, we present a sensitive approach to single-cell MS based on high-resolution MALDI-2-MS imaging in combination with MALDI-compatible staining and use of optical microscopy. Our approach allowed analyzing large amounts of unperturbed cells directly from the growth chamber. Confident coregistration of both modalities enabled a reliable compilation of single-cell mass spectra and a straightforward inclusion of optical as well as mass spectrometric features in the interpretation of data. The resulting multimodal datasets permit the use of various statistical methods like machine learning-driven classification and multivariate analysis based on molecular profile and establish a direct connection of MS data with microscopy information of individual cells. Displaying data in the form of histograms for individual signal intensities helps to investigate heterogeneous expression of specific lipids within the cell culture and to identify subpopulations intuitively. Ultimately, t-MALDI-2-MSI measurements at 2-µm pixel sizes deliver a glimpse of intracellular lipid distributions and reveal molecular profiles for subcellular domains.

PMID:35858333 | DOI:10.1073/pnas.2114365119

Chem Res Toxicol. 2022 Jul 20. doi: 10.1021/acs.chemrestox.2c00145. Online ahead of print.

ABSTRACT

Carcinogen and toxicant uptake by e-cigarette users have not been fully evaluated. In the study reported here, we recruited 30 e-cigarette users, 63 nonsmokers, and 33 cigarette smokers who gave monthly urine samples over a period of 4-6 months. Their product use status was confirmed by measurements of exhaled CO, urinary total nicotine equivalents, cyanoethyl mercapturic acid (CEMA), and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Urinary biomarkers of exposure to the carcinogens acrolein (3-hydroxypropyl mercapturic acid, 3-HPMA), benzene (S-phenyl mercapturic acid, SPMA), acrylonitrile (CEMA), and a combination of crotonaldehyde, methyl vinyl ketone, and methacrolein (3-hydroxy-1-methylpropyl mercapturic acid, HMPMA) were quantified at each visit. Data from subject visits with CEMA > 27 pmol/mL were excluded from the statistical analysis of the results because of possible unreported exposures to volatile combustion products such as secondhand cigarette smoke or marijuana smoke exposure; this left 22 e-cigarette users with 4 or more monthly visits and all 63 nonsmokers. Geometric mean levels of 3-HPMA (1249 versus 679.3 pmol/mL urine) were significantly higher (P = 0.003) in e-cigarette users than in nonsmokers, whereas levels of SPMA, CEMA, and HMPMA did not differ between these two groups. All analytes were significantly higher in cigarette smokers than in either e-cigarette users or nonsmokers. The results of this unique multimonth longitudinal study demonstrate consistent significantly higher uptake of the carcinogen acrolein in e-cigarette users versus nonsmokers, presenting a warning signal regarding e-cigarette use.

PMID:35858275 | DOI:10.1021/acs.chemrestox.2c00145

J Speech Lang Hear Res. 2022 Jul 19:1-12. doi: 10.1044/2022_JSLHR-20-00722. Online ahead of print.

ABSTRACT

PURPOSE: Core lexicon measures have received growing attention in research. They are intended to provide clinicians with a clinician-friendly means to quantify word retrieval ability in discourse based on normal expectations of discourse production for specific discourse elicitation tasks. To date, different criteria have been used to develop core lexicon measures by groups of researchers. The need for statistical guidance in pursuit of the psychologically robust measure has been recognized.

AIMS: This study was to investigate the best criterion for accurate measurement. Specifically, we focused on two criteria (frequency vs. percentage) that have previously been used for the development of core lexicon measures.

METHOD: Core lexicon measures consisting of five different checklists by word class (verbs, nouns, adjectives, adverbs, and function words) and developed by the two criteria were applied to language samples produced by 470 cognitively healthy adults. Performance in word retrieval ability at the discourse level was modeled as a latent variable based on the observed proportions of the production of core lexicon items in two different sets of core lexicon measures using structural equation modeling.

RESULTS: Results indicated that both criterion for core lexicon measures capture word retrieval ability in discourse. Greater residual variances were found in the core lexicon measure established by the percentage criterion compared to the one established by the frequency criterion. This indicates that the measure based on the percentage criterion is more affected by measurement errors.

CONCLUSIONS: The findings provide evidence that the frequency criterion is better to use for the development of core lexicon measures for core nouns, verbs, adjectives, and adverbs, but not for function words. However, our findings are limited to core lexicon measures based on language samples elicited by wordless picture books. This may not be easily applied to other core lexicon measures that use different discourse elicitation tasks due to the difference in quality and quantity of language samples. Ideally, the same approach should be replicated to evaluate the appropriateness of respective criteria in the development of core lexicon measures.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20304144.

PMID:35858271 | DOI:10.1044/2022_JSLHR-20-00722

Am J Speech Lang Pathol. 2022 Jul 12;31(4):1845-1853. doi: 10.1044/2022_AJSLP-21-00385. Epub 2022 Jul 7.

ABSTRACT

PURPOSE: The tongue plays a key role in bolus propulsion during swallowing, with reduced lingual pressure generation representing a risk factor for impaired swallowing safety and efficiency. We compared lingual pressure generation capacity in people with Parkinson disease (PwPD), people with amyotrophic lateral sclerosis (PwALS), and healthy older adults. We hypothesized that both patient cohorts would demonstrate reduced maximum anterior isometric pressure (MAIP) and regular effort saliva swallow (RESS) pressures compared with healthy controls, with the greatest reductions expected in the ALS cohort.

METHOD: We enrolled 20 PwPD, 18 PwALS, and 20 healthy adults over 60 years of age. The Iowa Oral Performance Instrument was used to measure MAIP, RESS, and lingual functional reserve (LFR, i.e., MAIP – RESS). Descriptive statistics were calculated; between-groups differences were explored using univariate analyses of variance and post hoc Sidak tests with alpha set at .05.

RESULTS: Mean MAIPs for the PD, ALS, and heathy cohorts were 54.7, 33.5, and 47.4 kPa, respectively. Significantly lower MAIP was found in PwALS compared with PwPD and healthy controls. RESS values did not differ significantly across groups. LFR was significantly higher in PwPD versus PwALS and healthy controls.

CONCLUSIONS: Lingual pressure generation capacity and functional reserve were reduced in PwALS, but not in PwPD, beyond changes seen with healthy aging. Both patient cohorts displayed preserved lingual pressure during saliva swallows. Future studies exploring longitudinal changes in tongue pressure generation on isometric and saliva swallowing tasks will be needed to confirm whether tongue pressure measures serve as noninvasive clinical biomarkers of swallowing impairment.

PMID:35858265 | DOI:10.1044/2022_AJSLP-21-00385

J Speech Lang Hear Res. 2022 Jul 18;65(7):2594-2607. doi: 10.1044/2022_JSLHR-22-00141. Epub 2022 Jul 5.

ABSTRACT

PURPOSE: The purpose of this meta-analysis was to assess the frequency of sex, race, and ethnicity reporting and proportional representation in funded, noncancerous voice clinical trials to determine the state of compliance with National Institutes of Health (NIH) guidelines for inclusivity in clinical research.

METHOD: Clinical trials registered with the NIH/U.S. National Library of Medicine between January 1988 and September 2021 were analyzed. Primary reports of the trials were obtained from clinicaltrials.gov and PubMed. Outcomes included the proportion of trials reporting sex, race, and ethnicity and the proportion of participants by sex, race, and ethnicity in the trials. Descriptive statistics and chi-square tests were used to analyze the data with 95% confidence intervals (CIs) reported.

RESULTS: The search yielded 46 research studies. After inclusion and exclusion criteria were applied and attempts to locate studies were conducted, 11 total articles were ultimately evaluated. Descriptively, there were more female subjects, yet overall, no significant difference in sex distribution (χ² = 0.07, p = .75, 95% CI [-0.25, -0.19]). Race and ethnicity were only reported in two clinical trials. Black participants were underrepresented in one clinical trial (χ² = 4.93, p = .02, 95% CI [-0.11, -0.02]), whereas Hispanic participants were underrepresented in a second trial (χ² = 11.27, p < .00, 95% CI [-0.20, – 0.13]).

CONCLUSIONS: This preliminary analysis highlights the disparities in race and ethnicity recruitment and reporting in noncancerous voice clinical trials. There is a need for strategic recruitment strategies and improved reporting practices to adhere to the NIH inclusivity directives.

PMID:35858261 | DOI:10.1044/2022_JSLHR-22-00141

J Speech Lang Hear Res. 2022 Jul 18;65(7):2586-2593. doi: 10.1044/2022_JSLHR-21-00632. Epub 2022 Jul 5.

ABSTRACT

PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects bulbar functions including speech and voice. Voice onset time (VOT) was examined in speakers with ALS in early and late stages to explore the coordination of the articulatory and phonatory systems during speech production.

METHOD: VOT was measured in nonword /bap/ produced by speakers with early-stage ALS (n = 11), late-stage ALS (n = 6), and healthy controls (n = 13), and compared with speech performance decline (a marker of disease progression) in ALS.

RESULTS: Overall comparison of the VOT values among the three groups showed a significant difference, F(2,27) = 11.71, p < .01. Speakers in late-stage ALS displayed longer voicing lead (negative VOT) than both healthy speakers and speakers in early-stage ALS. VOT was also significantly negatively correlated with speech performance (i.e., Intelligible Speaking Rate), r(15) = .74, p < .01.

CONCLUSIONS: Speakers with more severe ALS showed greater occurrence of voicing lead and longer voicing lead. Findings show voicing precedes articulatory onset with disease progression in the production of bilabial stops, which suggests that the relative timing of coordination between the supralaryngeal structures and the phonatory system is affected in the late stage of ALS.

PMID:35858258 | DOI:10.1044/2022_JSLHR-21-00632