Publications by authors named "Michael Johnson"

1,331 Publications

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Cardiac glycosides cause cytotoxicity in human macrophages and ameliorate white adipose tissue homeostasis.

Br J Pharmacol 2021 Mar 4. Epub 2021 Mar 4.

Centre for Inflammatory Disease, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.

Background And Purpose: Cardiac glycosides (CGs) inhibit the Na ,K -ATPase and are widely prescribed medicines for chronic heart failure and cardiac arrhythmias. Recently, CGs have been described to induce inflammasome activation and pyroptosis in human macrophages, suggesting a cytotoxicity that remains to be elucidated in tissues.

Experimental Approach: To determine the cell type specificity of CG-mediated cytotoxicity, we used human primary monocyte-derived macrophages (hMDMs) and non-adherent peripheral blood cells isolated from healthy donors. Omental white adipose tissue (WAT) and stromal vascular fraction (SVF)-derived pre-adipocytes and adipocytes were isolated from obese patients undergoing bariatric surgery. All these primary cells/tissues were treated with nanomolar concentrations of ouabain (50nM, 100nM and 500nM) to investigate its degree of cytotoxicity and mechanisms leading to cell death. In WAT, we further explored the consequences of ouabain-mediated cytotoxicity by measuring insulin sensitivity, adipose tissue function and extracellular matrix (ECM) deposition ex vivo.

Key Results: The ouabain-induced cell death is through pyroptosis and apoptosis, and more efficient in hMDMs compared to non-adherent PBMC populations. This selective cytotoxicity is dependent on K+ flux, as ouabain causes an intracellular depletion of K , while inducing accumulation of Na and Ca levels. Consistently, the cell-death caused by these ion imbalances can be rescued by addition of potassium chloride in hMDMs. Remarkably, when WAT explants from obese patients are cultured with nanomolar concentrations of ouabain, this causes depletion of macrophages, down-regulation of type VI collagen levels, and amelioration of insulin sensitivity ex vivo.

Conclusions And Implications: These results suggest that the usage of nanomolar concentration of CGs can be an attractive therapeutic avenue in metabolic syndrome characterised by pathogenic infiltration and activation of macrophages.
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http://dx.doi.org/10.1111/bph.15423DOI Listing
March 2021

Modeling approaches and performance for estimating personal exposure to household air pollution: A case study in Kenya.

Indoor Air 2021 Mar 2. Epub 2021 Mar 2.

Department of Public Health and Policy, University of Liverpool, Liverpool, UK.

This study assessed the performance of modeling approaches to estimate personal exposure in Kenyan homes where cooking fuel combustion contributes substantially to household air pollution (HAP). We measured emissions (PM , black carbon, CO); household air pollution (PM , CO); personal exposure (PM , CO); stove use; and behavioral, socioeconomic, and household environmental characteristics (eg, ventilation and kitchen volume). We then applied various modeling approaches: a single-zone model; indirect exposure models, which combine person-location and area-level measurements; and predictive statistical models, including standard linear regression and ensemble machine learning approaches based on a set of predictors such as fuel type, room volume, and others. The single-zone model was reasonably well-correlated with measured kitchen concentrations of PM (R  = 0.45) and CO (R  = 0.45), but lacked precision. The best performing regression model used a combination of survey-based data and physical measurements (R  = 0.76) and a root mean-squared error of 85 µg/m , and the survey-only-based regression model was able to predict PM2.5 exposures with an R of 0.51. Of the machine learning algorithms evaluated, extreme gradient boosting performed best, with an R of 0.57 and RMSE of 98 µg/m .
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http://dx.doi.org/10.1111/ina.12790DOI Listing
March 2021

Learning from the first wave: Lessons about managing patient flow and resource utilization on medical wards at providence health during the COVID-19 pandemic.

Healthc (Amst) 2021 Feb 16;9(2):100530. Epub 2021 Feb 16.

Beedie School of Business, Simon Fraser University, Vancouver, Canada; Luiss, Rome, Italy. Electronic address:

We report the successful implementation of a modified Traffic Control Bundling (TCB) protocol called "Red, Yellow and Green" on the inpatient medical units at St. Paul's Hospital in Vancouver, Canada during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. The modified TCB protocol demonstrates an important example on how hospitals can rapidly reorganize operational and clinical processes to reallocate existing capacity to minimize exposure, improve traffic flow and reduce nosocomial transmissions of COVID-19 to health care workers (HCWs) and other patients. Preliminary evidence demonstrates the benefits on how an existing facility can be redesigned for adjustable ward capacity to provide disease containment under a context of uncertainty of disease transmission and varying patient load. Important lessons in preparation for the evolution of the pandemic fall into categories of risk management, capacity and demand management.
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http://dx.doi.org/10.1016/j.hjdsi.2021.100530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885685PMC
February 2021

Comparative treatment effectiveness of oral fingolimod and conventional injectable disease modifying agents in multiple sclerosis.

Pharmacotherapy 2021 Feb 28. Epub 2021 Feb 28.

Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Texas, USA.

Background: Fingolimod was the first approved oral Disease Modifying Agent (DMA) to reduce relapses in Multiple Sclerosis (MS). Previous observational studies assessed the effectiveness of DMAs only through relapse and did not consider the treatment switch.

Objective: To compare the effectiveness of oral fingolimod and conventional injectable DMAs using the composite endpoint of relapse or treatment switch in patients with MS.

Methods: This retrospective longitudinal study utilized the IBM MarketScan Commercial Claims and Encounters Database from 2010-2012. Adults (≥18 years) with MS diagnosis (ICD-9-CM:340) and newly initiated with a DMA were included. Cox Proportional Hazards (PH) regression model weighted for stabilized Inverse Probability Treatment Weights (IPTW) with robust sandwich estimator was used to evaluate the composite endpoint (time to relapse/treatment switch) between oral fingolimod and injectable DMA users during the one-year follow-up after the treatment initiation. Additional analyses were performed on patients who were adherent (proportion of days covered [PDC]≥0.8) to DMAs during the first three months.

Results: The incident study cohort consisted of 1,997 MS patients who initiated oral fingolimod (15.6%) or injectable (84.4%) DMAs. The proportion of patients who had a composite endpoint (relapse/DMA treatment switch) in oral fingolimod and injectable DMA users was found to be 16.72% and 27.16%, respectively. The Cox PH regression model with stabilized IPTW revealed that fingolimod is equally effective as injectable DMAs in reducing the risk of experiencing the composite endpoint of relapse or DMA switch (adjusted Hazards Ratio [aHR]: 0.67, 95% CI: 0.43-1.03). Additional analysis among patients who were adherent also found no significant difference in the composite endpoint (aHR: 0.70, 95% CI 0.49-1.15) between oral fingolimod and injectable DMA users.

Conclusions: Oral fingolimod has similar effectiveness as injectable DMAs in reducing the risk of experiencing the composite endpoint (relapse or treatment switch). In addition, when assessed independently, oral fingolimod showed no difference in reducing the time to relapse or DMA treatment switch compared to injectable DMA users.
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http://dx.doi.org/10.1002/phar.2517DOI Listing
February 2021

Near SUDEP during bilateral stereo-EEG monitoring characterized by diffuse postictal EEG suppression.

Epilepsia 2021 Feb 22. Epub 2021 Feb 22.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with refractory epilepsy. The pathophysiology of SUDEP is unknown. Postictal phenomena such as postconvulsive immobility (PI), postictal generalized electroencephalography (EEG) suppression (PGES), arousal deficits, cardiac arrhythmias, central apneas, and obstructive apneas due to laryngospasms have been suggested to contribute to SUDEP. We present, to our knowledge, the first case of a near-SUDEP event in a patient undergoing intracranial, stereotactic EEG (sEEG) monitoring. This case spotlights potential mediators of SUDEP, most notably the striking PGES and postictal apnea. The nature of the sEEG investigation illustrates the extent of cortical and subcortical postictal EEG suppression and showcases a transient return of cerebral activity likely to be missed on scalp-EEG recording. Critically, this case emphasizes the importance of continuous cardiorespiratory monitoring and underscores the importance of postictal arousal as a pathophysiological mechanism in SUDEP.
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http://dx.doi.org/10.1111/epi.16852DOI Listing
February 2021

A multi-colour confocal microscopy method for identifying and enumerating macrophage subtypes and adherent cells in the stromal vascular fraction of human adipose.

J Immunol Methods 2021 Feb 12;491:112988. Epub 2021 Feb 12.

School of Life Science, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia. Electronic address:

This study examines leukocytes present in lymphoedema (LE) adipose tissue (AT) by multi-colour confocal microscopy. LE AT, collected by liposuction surgery, was digested with collagenase to separate adipocytes from other tissue cells, comprising blood and lymphatic endothelial cells, fibroblasts, and all vessel- and tissue-resident leukocytes - the stromal vascular fraction (SVF). SVF cells were activated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, adding Brefeldin-A to prevent cytokine secretion during the final 4 hours. Cells were incubated with CD11b-FITC and CD40-APC (M1 MØ)' or CD206-APC (M2 MØ) specific antibodies, fixed, permeabilised, then incubated with either (1) anti-TNF-PE, (2) anti- IL-1β-PE, (3) anti-IL-6-PE, (4) anti-IL-4-PE, (5) anti-TGFβ-PE or (6) isotype-IgG-PE (control), and stained with Hoechst 33342, preserved in permanent mounting media and examined by confocal microscopy. The FITC, PE and APC fluorescence channels were set to achieve minimal cross-channel emission using single-colour controls and voltages set for optimal detection by thresholding on isotype-IgG stained activated cells. Finally, transmission and z-stack images were captured. Cells were analysed as regions of interest (ROI) based on Hoechst-33342 then enumerated as FITC, FITCAPC or FITCAPCPE using an ImageJ script and exported into Excel. This permitted the examination of >9000 SVF cells individually, per LE sample. This method allows for the analysis of a high number of heterogeneous cells defined into any subtype or combination by the investigators' choice of surface and intracellular expression profiles. Fibroblasts, or other cytokine producing cells, can also be analysed by using other antibodies, and the cell count data can be correlated with any clinical or laboratory data.
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http://dx.doi.org/10.1016/j.jim.2021.112988DOI Listing
February 2021

Medicaid Expansion and Racial and Ethnic Disparities in Access to Health Care: Applying the National Academy of Medicine Definition of Health Care Disparities.

Inquiry 2021 Jan-Dec;58:46958021991293

McCormack Graduate School of Policy and Global Studies, University of Massachusetts, Boston, MA, USA.

Since 2014, 32 states implemented Medicaid expansion by removing the categorical criteria for childless adults and by expanding income eligibility to 138% of the federal poverty level (FPL) for all non-elderly adults. Previous studies found that the Affordable Care Act (ACA) Medicaid expansion improved rates of being insured, unmet needs for care due to cost, number of physician visits, and health status among low-income adults. However, a few recent studies focused on the expansion's effect on racial/ethnic disparities and used the National Academy of Medicine (NAM) disparity approach with a limited set of access measures. This quasi-experimental study examined the effect of Medicaid expansion on racial/ethnic disparities in access to health care for U.S. citizens aged 19 to 64 with income below 138% of the federal poverty line. The difference-in-differences model compared changes over time in 2 measures of insurance coverage and 8 measures of access to health care, using National Health Interview Survey (NHIS) data from 2010 to 2016. Analyses used the NAM definition of disparities. Medicaid expansion was associated with significant decreases in uninsured rates and increases in Medicaid coverage among all racial/ethnic groups. There were differences across racial/ethnic groups regarding which specific access measures improved. For delayed care and unmet need for care, decreases in racial/ethnic disparities were observed. After the ACA Medicaid expansion, most access outcomes improved for disadvantaged groups, but also for others, with the result that disparities were not significantly reduced.
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http://dx.doi.org/10.1177/0046958021991293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878957PMC
February 2021

2D Nanomaterial, TiC MXene-Based Sensor to Guide Lung Cancer Therapy and Management.

Biosensors (Basel) 2021 Feb 4;11(2). Epub 2021 Feb 4.

Biomedical Engineering Program, North Dakota State University, Fargo, ND 58108, USA.

Major advances in cancer control can be greatly aided by early diagnosis and effective treatment in its pre-invasive state. Lung cancer (small cell and non-small cell) is a leading cause of cancer-related deaths among both men and women around the world. A lot of research attention has been directed toward diagnosing and treating lung cancer. A common method of lung cancer treatment is based on COX-2 (cyclooxygenase-2) inhibitors. This is because COX-2 is commonly overexpressed in lung cancer and also the abundance of its enzymatic product prostaglandin E2 (PGE). Instead of using traditional COX-2 inhibitors to treat lung cancer, here, we introduce a new anti-cancer strategy recently developed for lung cancer treatment. It adopts more abundant omega-6 (ω-6) fatty acids such as dihomo-γ-linolenic acid (DGLA) in the daily diet and the commonly high levels of COX-2 expressed in lung cancer to promote the formation of 8-hydroxyoctanoic acid (8-HOA) through a new delta-5-desaturase (D5Di) inhibitor. The D5Di does not only limit the metabolic product, PGE but also promote the COX-2 catalyzed DGLA peroxidation to form 8-HOA, a novel anti-cancer free radical byproduct. Therefore, the measurement of the PGE and 8-HOA levels in cancer cells can be an effective method to treat lung cancer by providing in-time guidance. In this paper, we mainly report on a novel sensor, which is based on a newly developed functionalized nanomaterial, 2-dimensional nanosheets, or TiC MXene. The preliminary results have proven to sensitively, selectively, precisely, and effectively detect PGE and 8-HOA in A549 lung cancer cells. The capability of the sensor to detect trace level 8-HOA in A549 has been verified in comparison with the traditional gas chromatography-mass spectrometry (GC-MS) method. The sensing principle could be due to the unique structure and material property of TiC MXene: a multilayered structure and extremely large surface area, metallic conductivity, and ease and versatility in surface modification. All these make the TiC MXene-based sensor selectively adsorb 8-HOA molecules through effective charge transfer and lead to a measurable change in the conductivity of the material with a high signal-to-noise ratio and excellent sensitivity.
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http://dx.doi.org/10.3390/bios11020040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913740PMC
February 2021

Duration of symptomatic stroke and successful reperfusion with endovascular thrombectomy for anterior circulation large vessel occlusive stroke.

J Neurointerv Surg 2021 Feb 1. Epub 2021 Feb 1.

Neuroscience, Mercy Health Saint Vincent Medical Center, Toledo, Ohio, USA

Background: It has been reported that longer time intervals from stroke onset to endovascular therapy are associated with lower rates of successful reperfusion in acute ischemic stroke patients with large vessel occlusion. However, procedural variables and potential mechanisms of this association have not been fully elucidated.

Methods: We performed a secondary analysis of individual patient data from the North American Solitaire Stent Retriever Acute Stroke (NASA) and Trevo Stent-Retriever Acute Stroke (TRACK) registries. We included patients with occlusion of the internal carotid artery or middle cerebral artery (M1 and M2 segments) who were treated by mechanical thrombectomy within 24 hours of last known normal. The primary outcome was reperfusion, defined as a Thrombolysis In Cerebral Infarction (TICI) score ≥2b. The secondary outcome was reperfusion on the first pass. The primary predictor was duration of symptomatic stroke, defined as time from last known normal to time of final pass. Adjusted logistic regression models were utilized to determine associations between variables and outcome.

Results: We included 506 patients, of which 401 (79.3%) achieved successful reperfusion (TICI 2b/3). The mean (SD) duration of symptomatic stroke was 6.8 (3.5) hours and in the adjusted logistic regression model the duration of symptomatic stroke was associated with reperfusion (OR 0.90, 95% CI 0.84 to 0.96) and reperfusion on the first pass (OR 0.89, 95% CI 0.83 to 0.95). In that model, the predicted probability of reperfusion was 88% (95% CI 0.83 to 0.92) at 1 hour, 81% (95% CI 0.78 to 0.84) at 6 hours, 70% (95% CI 0.63 to 0.77) at 12 hours, and 42% (95% CI 0.17 to 0.67) at 24 hours (p=0.001). Reperfused patients were significantly younger, more likely to be male, and to have had a balloon guide catheter used during the procedure.

Conclusion: In a real-world cohort of acute ischemic stroke patients with anterior circulation occlusion treated with endovascular therapy, longer duration of symptomatic stroke is associated with lower rates of successful reperfusion and reperfusion on the first pass.
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http://dx.doi.org/10.1136/neurintsurg-2020-016961DOI Listing
February 2021

Electrochemical Monitoring of Caged Compound Photochemistry: An Internal Actinometer for Substrate Release.

Anal Chem 2021 02 25;93(5):2776-2784. Epub 2021 Jan 25.

Department of Chemistry and R.N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, Kansas 66045, United States.

Caged compounds are molecules that release a protective substrate to free a biologically active substrate upon treatment with light of sufficient energy and duration. A notable limitation of this approach is difficulty in determining the degree of photoactivation in tissues or opaque solutions because light reaching the desired location is obstructed. Here, we have addressed this issue by developing an electrochemical method in which the amount of caged molecule photorelease is determined by fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes. Using -hydroxyphenyl glutamate (HP-Glu) as our model system, we generated a linear calibration curve for oxidation of 4-hydroxyphenylacetic acid (4HPAA), the group from which the glutamate molecule leaves, up to a concentration of 1000 μM. Moreover, we are able to correct for the presence of residual HP-Glu in solution as well as the light artifact that is produced. A corrected calibration curve was constructed by photoactivation of HP-Glu in a 3 μL photoreaction vessel and subsequent analysis by high-performance liquid chromatography. This approach has yielded a linear relationship between 4HPAA concentration and oxidation current, allowing the determination of released glutamate independent of the amount of light reaching the chromophore. Moreover, we have successfully validated the newly developed method by measurement in a whole, intact zebrafish brain. This work demonstrates for the first time the electrochemical monitoring of caged compound photochemistry in brain tissue with FSCV, thus facilitating analyses of neuronal function.
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http://dx.doi.org/10.1021/acs.analchem.0c03452DOI Listing
February 2021

Targeted deletion of HAI-1 increases prostasin proteolysis but decreases matriptase proteolysis in human keratinocytes.

Hum Cell 2021 Jan 24. Epub 2021 Jan 24.

Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, W412 Research Building 3970 Reservoir Road NW, Washington, DC, 20057, USA.

Epidermal differentiation and barrier function require well-controlled matriptase and prostasin proteolysis, in which the Kunitz-type serine protease inhibitor HAI-1 represents the primary enzymatic inhibitor for both proteases. HAI-1, however, also functions as a chaperone-like protein necessary for normal matriptase synthesis and intracellular trafficking. Furthermore, other protease inhibitors, such as antithrombin and HAI-2, can also inhibit matriptase and prostasin in solution or in keratinocytes. It remains unclear, therefore, whether aberrant increases in matriptase and prostasin enzymatic activity would be the consequence of targeted deletion of HAI-1 and so subsequently contribute to the epidermal defects observed in HAI-1 knockout mice. The impact of HAI-1 deficiency on matriptase and prostasin proteolysis was, here, investigated in HaCaT human keratinocytes. Our results show that HAI-1 deficiency causes an increase in prostasin proteolysis via increased protein expression and zymogen activation. It remains unclear, however, whether HAI-1 deficiency increases "net" prostasin enzymatic activity because all of the activated prostasin was detected in complexes with HAI-2, suggesting that prostasin enzymatic activity is still under tight control in HAI-1-deficient keratinocytes. Matriptase proteolysis is, however, unexpectedly suppressed by HAI-1 deficiency, as manifested by decreases in zymogen activation, shedding of active matriptase, and matriptase-dependent prostasin zymogen activation. This suppressed proteolysis results mainly from the reduced ability of HAI-1-deficient HaCaT cells to activate matriptase and the rapid inhibition of nascent active matriptase by HAI-2 and other yet-to-be-identified protease inhibitors. Our study provides novel insights with opposite impacts by HAI-1 deficiency on matriptase versus prostasin proteolysis in keratinocytes.
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http://dx.doi.org/10.1007/s13577-021-00488-1DOI Listing
January 2021

Effects of Prior Voluntary Hyperventilation on the 3-min All-Out Cycling Test in Men.

Med Sci Sports Exerc 2021 Jan 21. Epub 2021 Jan 21.

Exercise and Health Research Group, Sport, Health and Performance Enhancement (SHAPE) Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.

Introduction: The ergogenic effects of respiratory alkalosis induced by prior voluntary hyperventilation (VH) are controversial. This study examined the effects of prior VH on derived parameters from the 3-min all-out cycling test (3MT).

Methods: Eleven men ([Combining Dot Above]V˙O2max = 46 ± 8 mL⋅kg-1⋅min-1) performed a 3MT preceded by 15-min of rest (CONT) or voluntary hyperventilation (V˙E = 38 ± 5 L⋅min-1) with PETCO2 reduced to 21 ± 1 mmHg (HYP). End-test power (EP; synonymous with critical power) was calculated as the mean power output over the last 30-s of the 3MT, and the work done above EP (WEP; synonymous with W') was calculated as the power-time integral above EP.

Results: At the start of the 3MT, capillary blood PCO2 and [H+] were lower in HYP (25.2 ± 3.0 mmHg, 27.1 ± 2.6 nmol⋅L-1) than CONT (43.2 ± 2.0 mmHg, 40.0 ± 1.5 nmol⋅L-1) (P < 0.001). At the end of the 3MT, blood PCO2 was still lower in HYP (35.7 ± 5.4 mmHg) than CONT (40.6 ± 5.0 mmHg) (P < 0.001). WEP was 10% higher in HYP (19.4 ± 7.0 kJ) than CONT (17.6 ± 6.4 kJ) (P = 0.006), whereas EP was 5% lower in HYP (246 ± 69 W) than CONT (260 ± 74 W) (P = 0.007). The ΔWEP (J·kg-1) between CONT and HYP correlated positively with the PCO2 immediately before the 3MT in HYP (r = 0.77, P = 0.006).

Conclusion: These findings suggest that acid-base changes elicited by prior voluntary hyperventilation increase WEP but decrease EP during the all-out 3MT.
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http://dx.doi.org/10.1249/MSS.0000000000002608DOI Listing
January 2021

Use of Machine Learning to Screen for Acute Respiratory Distress Syndrome Using Raw Ventilator Waveform Data.

Crit Care Explor 2021 Jan 8;3(1):e0313. Epub 2021 Jan 8.

Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of California Davis, Sacramento, CA.

To develop and characterize a machine learning algorithm to discriminate acute respiratory distress syndrome from other causes of respiratory failure using only ventilator waveform data.

Design: Retrospective, observational cohort study.

Setting: Academic medical center ICU.

Patients: Adults admitted to the ICU requiring invasive mechanical ventilation, including 50 patients with acute respiratory distress syndrome and 50 patients with primary indications for mechanical ventilation other than hypoxemic respiratory failure.

Interventions: None.

Measurements And Main Results: Pressure and flow time series data from mechanical ventilation during the first 24-hours after meeting acute respiratory distress syndrome criteria (or first 24-hr of mechanical ventilation for non-acute respiratory distress syndrome patients) were processed to extract nine physiologic features. A random forest machine learning algorithm was trained to discriminate between the patients with and without acute respiratory distress syndrome. Model performance was assessed using the area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value. Analyses examined performance when the model was trained using data from the first 24 hours and tested using withheld data from either the first 24 hours (24/24 model) or 6 hours (24/6 model). Area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value were 0.88, 0.90, 0.71, 0.77, and 0.90 (24/24); and 0.89, 0.90, 0.75, 0.83, and 0.83 (24/6).

Conclusions: Use of machine learning and physiologic information derived from raw ventilator waveform data may enable acute respiratory distress syndrome screening at early time points after intubation. This approach, combined with traditional diagnostic criteria, could improve timely acute respiratory distress syndrome recognition and enable automated clinical decision support, especially in settings with limited availability of conventional diagnostic tests and electronic health records.
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http://dx.doi.org/10.1097/CCE.0000000000000313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803688PMC
January 2021

Alkaline-Encrusted Pyelitis Causing Renal Failure in a Transplant Kidney: Treatment with Percutaneous Nephrolithotomy and Urinary Acidification.

J Endourol Case Rep 2020 29;6(4):435-437. Epub 2020 Dec 29.

Vattikuti Urology Institute, Henry Ford Health System, Detroit Michigan, USA.

Alkaline-encrusted pyelitis (AEP) is rare and most often stems from a triad of immunodeficiency, urogenital tract trauma, and alkaline urinary infection. Corynebacterium Group D2 is the most common organism. It results in encrusting calcifications that adhere to most of the urothelial lining of the pelvicaliceal system and ureter. Left unchecked, or unrecognized, the disease process can progress to renal compromise. Studies suggest that management is based on elimination of the bacterium, acidification of the urine, and elimination of calcified plaques and encrustations. Herein, we report a case of a 56-year-old woman who developed AEP in her second transplanted kidney, and detail the diagnosis and treatment of the uncommon, yet potentially devastating, disease. A 56-year-old woman with a history of lupus, end-stage renal disease, who was on her second renal transplant presented with symptoms of urinary tract infection. Urine was consistently alkaline with cultures repeatedly growing urease-splitting Corynebacterium. Subsequent imaging showed large obstructing ureteral and renal stones concerning for AEP. She was treated with transplant kidney percutaneous nephrolithotomy, culture-specific antibiotics, and urinary acidification. Clinical presentation, urinalysis, culture, and renal imaging, often with CT, are the mainstays for diagnosing AEP. If not addressed, AEP can advance to renal failure. Management often includes a multimodal approach involving treatment and prevention of the underlying infection, urinary acidification, and percutaneous or endoscopic removal of obstructing and large burden stones and encrustation.
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http://dx.doi.org/10.1089/cren.2020.0183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803248PMC
December 2020

Adult polyglucosan body disease: an acute presentation leading to unmasking of this rare disorder.

Hosp Pract (1995) 2021 Jan 27:1-7. Epub 2021 Jan 27.

Department of Neurology, Lehigh Valley Health Network , Allentown, PA, USA.

: Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy caused by abnormal intracellular accumulation of glycogen byproducts. This disorder is linked to a deficiency in glycogen branching enzyme-1 (GBE-1). Neurologic manifestations include upper and lower motor neuron signs, dementia, and peripheral neuropathy. APBD is typically a progressive disease. In this report, we discuss a novel case of APBD in a patient who had a sudden onset of spastic quadriparesis preceded by gradual difficulty with gait. Genetic and postmortem analysis confirmed the diagnosis of APBD. : A 65-year-old man was evaluated for a new-onset of spastic quadriparesis, right-gaze preference, and left-sided beat nystagmus. Magnetic resonance imaging (MRI) of the brain revealed areas of white matter hyperintensities most prominent in the brainstem and periventricular regions. MRI of the cervical spine showed marked cord atrophy. Laboratory workup and cerebrospinal fluid analysis were unremarkable. Genetic testing supported the diagnosis of APBD due to GBE-1 deficiency. Postmortem analysis showed multiple white matter abnormalities suggestive of a leukodystrophy syndrome, and histopathologic testing revealed abnormal accumulation of polyglucosan bodies in samples from the patient's central nervous system supporting the diagnosis of APBD. : APBD is a rare disorder that can affect the nervous system. The diagnosis can be confirmed with a combination of genetic testing and pathologic analysis of affected brain tissue.
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http://dx.doi.org/10.1080/21548331.2021.1874182DOI Listing
January 2021

Back Dominant Pain Has Equal Outcomes to Radicular Dominant Pain Following Posterior Lumbar Fusion in Adult Isthmic Spondylolisthesis: A CSORN Study.

Global Spine J 2021 Jan 7:2192568220985471. Epub 2021 Jan 7.

Division of Orthopaedics, Department of Surgery, Western University /London Health Sciences Centre, London, Ontario, Canada.

Study Design: Retrospective Cohort Study.

Objectives: This study aimed to determine how the surgeon-determined and patient-rated location of predominant pain influences patient-rated outcomes at 1-year after posterior lumbar fusion in adult isthmic spondylolisthesis.

Methods: We retrospectively reviewed consecutive patients prospectively enrolled in the Canadian Spine Outcomes and Research Network national registry between 2009 and 2017 that underwent posterior lumbar fusion for isthmic spondylolisthesis. Using longitudinal mixed-model repeated-measures analysis the change from baseline in patient-reported outcome measures (PROMs) at 1 year after surgery was compared between surgeon-determined groups (back vs. radicular) and between patient-rated pain groups (back, leg, and equal) derived from preoperative pain scores on the numerical rating scale (NRS).

Results: 83/252 (33%) patients had a surgeon-determined chief complaint of back pain, while 103 (41%) patients rated their back pain as the predominant pain location, and 78 (31%) rated their back and leg pain to be equal. At baseline patients in the surgeon-determined radicular group had worse NRS-leg pain than those in the back-pain group but equal NRS-back pain. At baseline patients in the patient-rated equal pain group had similar back pain compared to the patient-rated back pain group and similar leg pain compared to the patient-rated leg pain group. All PROMs improved post-operatively and were not different between the 2 groups at 1 year.

Conclusions: Our study found no difference in outcome, irrespective of whether a surgeon determines the patient's primary pain complaint back or radicular dominant, or the patient rates pain in one location greater than another.
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http://dx.doi.org/10.1177/2192568220985471DOI Listing
January 2021

Lumbar Fusion Surgery for Patients With Back Pain and Degenerative Disc Disease: An Observational Study From the Canadian Spine Outcomes and Research Network.

Global Spine J 2021 Jan 7:2192568220985470. Epub 2021 Jan 7.

University of Calgary Spine Program, University of Calgary, Alberta, Canada.

Study Design: Uncontrolled retrospective observational study.

Objectives: Surgery for patients with back pain and degenerative disc disease is controversial, and studies to date have yielded conflicting results. We evaluated the effects of lumbar fusion surgery for patients with this indication in the Canadian Spine Outcomes and Research Network (CSORN).

Methods: We analyzed data that were prospectively collected from consecutive patients at 11 centers between 2015 and 2019. Our primary outcome was change in patient-reported back pain at 12 months of follow-up, and our secondary outcomes were satisfaction, disability, health-related quality of life, and rates of adverse events.

Results: Among 84 patients, we observed a statistically significant improvement of back pain at 12 months that exceeded the threshold of Minimum Clinically Important Difference (MCID) (mean change -3.7 points, SD 2.6, p < 0.001, MCID = 1.2; 77% achieved MCID), and 81% reported being "somewhat" or "extremely" satisfied. We also observed improvements of Oswestry Disability Index (-17.3, SD 16.6), Short Form-12 Physical Component Summary (10.3, SD 9.6) and Short Form-12 Mental Component Summary (3.1, SD 8.3); all p < 0.001). The overall rate of adverse events was 19%.

Conclusions: Among a highly selective group of patients undergoing lumbar fusion surgery for degenerative disc disease, most experienced a clinically significant improvement of back pain as well as significant improvements of disability and health-related quality of life, with high satisfaction at 1 year of follow-up. These findings suggest that surgery for this indication may provide some benefit, and that further research is warranted.
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http://dx.doi.org/10.1177/2192568220985470DOI Listing
January 2021

Automatically Explaining Machine Learning Prediction Results on Asthma Hospital Visits in Patients With Asthma: Secondary Analysis.

JMIR Med Inform 2020 Dec 31;8(12):e21965. Epub 2020 Dec 31.

Department of Pediatrics, University of Utah, Salt Lake City, UT, United States.

Background: Asthma is a major chronic disease that poses a heavy burden on health care. To facilitate the allocation of care management resources aimed at improving outcomes for high-risk patients with asthma, we recently built a machine learning model to predict asthma hospital visits in the subsequent year in patients with asthma. Our model is more accurate than previous models. However, like most machine learning models, it offers no explanation of its prediction results. This creates a barrier for use in care management, where interpretability is desired.

Objective: This study aims to develop a method to automatically explain the prediction results of the model and recommend tailored interventions without lowering the performance measures of the model.

Methods: Our data were imbalanced, with only a small portion of data instances linking to future asthma hospital visits. To handle imbalanced data, we extended our previous method of automatically offering rule-formed explanations for the prediction results of any machine learning model on tabular data without lowering the model's performance measures. In a secondary analysis of the 334,564 data instances from Intermountain Healthcare between 2005 and 2018 used to form our model, we employed the extended method to automatically explain the prediction results of our model and recommend tailored interventions. The patient cohort consisted of all patients with asthma who received care at Intermountain Healthcare between 2005 and 2018, and resided in Utah or Idaho as recorded at the visit.

Results: Our method explained the prediction results for 89.7% (391/436) of the patients with asthma who, per our model's correct prediction, were likely to incur asthma hospital visits in the subsequent year.

Conclusions: This study is the first to demonstrate the feasibility of automatically offering rule-formed explanations for the prediction results of any machine learning model on imbalanced tabular data without lowering the performance measures of the model. After further improvement, our asthma outcome prediction model coupled with the automatic explanation function could be used by clinicians to guide the allocation of limited asthma care management resources and the identification of appropriate interventions.
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http://dx.doi.org/10.2196/21965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808890PMC
December 2020

Tissue Modification in Nonsurgical Facelift Options.

Facial Plast Surg 2020 Dec 24;36(6):688-695. Epub 2020 Dec 24.

Department of Plastic Surgery, Wright State University, Dayton, Ohio.

Nonsurgical facelifts are a term for a heterogeneous group of procedures used by physicians to improve facial rejuvenation without the use of operative techniques. Patients demand these services due to the reduced recovery time and generally lower risk. However, nonsurgical techniques, to be effective, must induce conformational change in the cells and tissues of the face. Therefore, these techniques are significant procedures that have associated risks. Understanding the tissue modifications and mechanisms of action of these techniques is vital to their safe and effective use. The purpose of this article is to provide a background of tissue modification in nonsurgical facelift options.
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http://dx.doi.org/10.1055/s-0040-1721115DOI Listing
December 2020

Agreement Between the OptoGait and Instrumented Treadmill System for the Quantification of Spatiotemporal Treadmill Running Parameters.

Front Sports Act Living 2020 23;2:571385. Epub 2020 Oct 23.

Department of Physical Therapy, High Point University, High Point, NC, United States.

The measurement of spatiotemporal gait parameters is commonly utilized to assess gait in healthy and injured individuals. The OptoGait system is a portable system and can be mounted to a treadmill to collect data in a clinical, training, or research setting. The purpose of this method comparison study was to examine the agreement of spatiotemporal gait parameters calculated by the OptoGait compared to an instrumented treadmill system during running. Thirty healthy runners ran on an instrumented treadmill with the OptoGait 1-m system mounted along the treadmill platform. Spatiotemporal running variables of step rate, step length, and contact time were calculated during the final minute of treadmill running. The level of agreement between the OptoGait and treadmill was analyzed using intraclass correlation coefficients [ICC (2,3)] for step rate, step length, and contact time. Step rate and step length demonstrated excellent agreement. Contact time demonstrated good agreement. Intraclass correlation coefficients for spatiotemporal parameters ranged from 0.83 to 0.99. The OptoGait demonstrated good to excellent agreement in the evaluation of running step rate, step length, and contact time and should be considered for use in clinical, training, or research settings.
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http://dx.doi.org/10.3389/fspor.2020.571385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739620PMC
October 2020

CC16 Binding to α4β1 Integrin (VLA-4) Protects Against Infection.

Am J Respir Crit Care Med 2020 Dec 16. Epub 2020 Dec 16.

University of Arizona, Cellular & Molecular Medicine, Tucson, Arizona, United States;

Club cell secretory protein (CC16) is a pneumoprotein produced predominantly by pulmonary club cells. Circulating CC16 is associated with protection from the inception and progression of the two most common obstructive lung diseases: asthma and COPD. While exact mechanisms remain elusive, studies consistently suggest a causal role of CC16 in mediating anti-inflammatory and antioxidant functions in the lung. We sought to determine any novel receptor systems that could participate in CC16's role in obstructive lung diseases. Protein alignment of CC16 across species led to the discovery of a highly conserved sequence of amino acids, Leucine-Valine-Aspartic Acid (LVD), a known integrin binding motif. Recombinant CC16 was generated with and without the putative integrin binding site. A Mycoplasma pneumoniae mouse model and a flourescent cellular adhesion assay were used to determine the impact of the LVD site in regards to CC16 function during live infection and on cellular adhesion during inflammatory conditions. CC16 bound to integrin alpha 4 and beta 1 (α4β1), also known as the adhesion molecule very late antigen-4 (VLA-4), dependent on the presence of the LVD integrin binding motif. During infection, rCC16 rescued lung function parameters both when administered to the lung and intravenously, but only when the LVD integrin binding site is intact; likewise, neutrophil recruitment during infection and leukocyte adhesion were both impacted by the loss of the LVD site. We discovered a novel receptor for CC16, VLA-4, which has important mechanistic implications for the role of CC16 in circulation as well as in the lung compartment.
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http://dx.doi.org/10.1164/rccm.202006-2576OCDOI Listing
December 2020

Inhibits Growth and Migration of Lung Cancer Cells through Regulating p53-Bcl2 and MMPs Pathways.

Am J Chin Med 2020 9;48(8):1941-1953. Epub 2020 Dec 9.

School of Life Sciences, University of Technology Sydney, NSW 2007, Australia.

has been shown to possess antitumor activity. This study investigated the effects and mechanisms of extract (ACE) on growth and migration of human non-small cell lung cancer A549 cells. The effect of ACE on cell viability was determined by MTT assay and fluorescent live-cell imaging. The apoptotic effect of ACE was determined by cell cycle distribution using flow cytometry. A P53-mediated apoptosis pathway was identified by measuring protein expression of p53 and Bcl-2 with Western blotting. Additionally, mRNA expression of p53 and -2 and was detected by qRT-PCR. The effect of ACE on cancer cell migration was confirmed by a wound-healing assay. Expression of MMP-2 and MMP-9 at the protein and gene levels was determined by western blot and qRT-PCR analysis. This study demonstrates the inhibitory effect of ACE on A549 cell proliferation in a dose-response manner with an [Formula: see text]. It was determined that ACE concentration at [Formula: see text] induced cell cycle arrest at S phase in A549 cells. The apoptosis-regulating protein p53 expression was enhanced and also associated with the downregulation of Bcl-2 in ACE treatment cells. The mRNA expression of and associated with was consistent with protein expression. The inhibition of migration of cancer cells treated with ACE was clearly evident. At the same time, suppression of expression of MMP-2 and MMP-9 at protein and mRNA levels was observed. The findings of this study highlight ACE as a potential agent of adjuvant therapy for lung cancer.
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http://dx.doi.org/10.1142/S0192415X20500974DOI Listing
December 2020

The Arabidopsis Mitochondrial Glutaredoxin GRXS15 Provides [2Fe-2S] Clusters for ISCA-Mediated [4Fe-4S] Cluster Maturation.

Int J Mol Sci 2020 Dec 3;21(23). Epub 2020 Dec 3.

Department of Chemistry and Center for Metalloenzyme Studies, University of Georgia, Athens, GA 30602, USA.

Iron-sulfur (Fe-S) proteins are crucial for many cellular functions, particularly those involving electron transfer and metabolic reactions. An essential monothiol glutaredoxin GRXS15 plays a key role in the maturation of plant mitochondrial Fe-S proteins. However, its specific molecular function is not clear, and may be different from that of the better characterized yeast and human orthologs, based on known properties. Hence, we report here a detailed characterization of the interactions between GRXS15 and ISCA proteins using both in vivo and in vitro approaches. Yeast two-hybrid and bimolecular fluorescence complementation experiments demonstrated that GRXS15 interacts with each of the three plant mitochondrial ISCA1a/1b/2 proteins. UV-visible absorption/CD and resonance Raman spectroscopy demonstrated that coexpression of ISCA1a and ISCA2 resulted in samples with one [2Fe-2S] cluster per ISCA1a/2 heterodimer, but cluster reconstitution using as-purified [2Fe-2S]-ISCA1a/2 resulted in a [4Fe-4S] cluster-bound ISCA1a/2 heterodimer. Cluster transfer reactions monitored by UV-visible absorption and CD spectroscopy demonstrated that [2Fe-2S]-GRXS15 mediates [2Fe-2S] cluster assembly on mitochondrial ferredoxin and [4Fe-4S] cluster assembly on the ISCA1a/2 heterodimer in the presence of excess glutathione. This suggests that ISCA1a/2 is an assembler of [4Fe-4S] clusters, via two-electron reductive coupling of two [2Fe-2S] clusters. Overall, the results provide new insights into the roles of GRXS15 and ISCA1a/2 in effecting [2Fe-2S] to [4Fe-4S] cluster conversions for the maturation of client [4Fe-4S] cluster-containing proteins in plants.
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http://dx.doi.org/10.3390/ijms21239237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730481PMC
December 2020

Fragment Binding to the Nsp3 Macrodomain of SARS-CoV-2 Identified Through Crystallographic Screening and Computational Docking.

bioRxiv 2020 Nov 24. Epub 2020 Nov 24.

The SARS-CoV-2 macrodomain (Mac1) within the non-structural protein 3 (Nsp3) counteracts host-mediated antiviral ADP-ribosylation signalling. This enzyme is a promising antiviral target because catalytic mutations render viruses non-pathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of diverse fragment libraries resulted in 214 unique macrodomain-binding fragments, out of 2,683 screened. An additional 60 molecules were selected from docking over 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several crystallographic and docking fragment hits were validated for solution binding using three biophysical techniques (DSF, HTRF, ITC). Overall, the 234 fragment structures presented explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.
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http://dx.doi.org/10.1101/2020.11.24.393405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709169PMC
November 2020

Ideas for supporting student-centered stem learning through remote labs: a response.

Educ Technol Res Dev 2020 Nov 25:1-6. Epub 2020 Nov 25.

Brigham Young University, Provo, UT USA.

This paper is in response to the article entitled "Identifying potential types of guidance for supporting student inquiry when using virtual and remote labs in science: a literature review" by Zacharia et al. (2015). In their review, Zacharia et al. (2015) adopted de Jong and Lazondo's (2014) framework of five inquiry phases for online labs: orientation, conceptualization, investigation, conclusion, and discussion. Zacharia et al. reviewed the literature on Computer-supported Inquiry Learning (CoSIL), and identified best practices for each phase. They concluded, for example, that the orientation/conclusion/discussion phases received the least amount of guidance, while there were many more tools and strategies for providing guidance in the conceptualization/investigation phases. In this paper, we adopt the same inquiry framework as Zacharia et al. (2015) and report strategies that we learned from STEM faculty about how they supported and guided virtual student lab-based learning in these five phases during the recent COVID-19 shutdown. While Zacharia et al. identified tools and processes for enabling all five inquiry phases, add additional practical examples of faculty implementing these phases online as part of COVID-19 emergency remote teaching, and we provide insights for extending the 5-phase framework for future research.
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http://dx.doi.org/10.1007/s11423-020-09905-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687981PMC
November 2020

IgG Seroconversion and Pathophysiology in Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Emerg Infect Dis 2021 01 30;27(1). Epub 2020 Nov 30.

We investigated the dynamics of seroconversion in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During March 29-May 22, 2020, we collected serum samples and associated clinical data from 177 persons in London, UK, who had SARS-CoV-2 infection. We measured IgG against SARS-CoV-2 and compared antibody levels with patient outcomes, demographic information, and laboratory characteristics. We found that 2.0%-8.5% of persons did not seroconvert 3-6 weeks after infection. Persons who seroconverted were older, were more likely to have concurrent conditions, and had higher levels of inflammatory markers. Non-White persons had higher antibody concentrations than those who identified as White; these concentrations did not decline during follow-up. Serologic assay results correlated with disease outcome, race, and other risk factors for severe SARS-CoV-2 infection. Serologic assays can be used in surveillance to clarify the duration and protective nature of humoral responses to SARS-CoV-2 infection.
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http://dx.doi.org/10.3201/eid2701.203074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774532PMC
January 2021

Types of Partner Violence in Couples Affected by Incarceration: Applying Johnson's Typology to Understand the Couple-level Context for Violence.

J Interpers Violence 2020 Nov 27:886260520971266. Epub 2020 Nov 27.

Penn State University, State College, PA, USA.

In prior research, samples of incarcerated and reentering men and their partners report partner violence at roughly 10 times the frequency found in the general population. The relationship dynamics underlying these experiences remain poorly understood. Addressing this gap and expanding prior applications of Johnson's typology in other populations-which typically rely on survey data alone and include reports from just one member of a couple-we applied latent class analysis with dyadic survey data from 1,112 couples to identify types of partner violence in couples affected by incarceration. We assessed congruence between quantitative types and couples' qualitative accounts and compared the two major types using two-sample -tests.In some couples, one partner used various tactics to systematically dominate and control the other, as in Johnson's coercive controlling violence. In others, physical violence arose in the context of jealousy but no other controlling behavior. This type resembled Johnson's situational couple violence. Qualitative data suggested that jealousy represented a common, situational response to periods of prolonged separation, relationship instability, status insecurity, and partnership concurrence and not a tactic of control per se. Victims of coercive controlling violence experienced more PTSD symptoms and felt less safe in their relationships than victims of jealous-only violence. Perpetrators of coercive controlling violence were more likely to use severe physical violence against their partners than perpetrators of jealous-only violence. Findings indicate that broader context is critical for interpreting the presence of jealousy (and whether it constitutes a control tactic). They indicate that prevention and response strategies tailored to these types could help couples cope safely with the extreme relationship stressors of incarceration and reentry. Finally, they suggest a need to move from an exclusive focus on individual accountability and services toward a model that also incorporates institutional accountability and change.
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http://dx.doi.org/10.1177/0886260520971266DOI Listing
November 2020

Exposure contrasts associated with a liquefied petroleum gas (LPG) intervention at potential field sites for the multi-country household air pollution intervention network (HAPIN) trial in India: results from pilot phase activities in rural Tamil Nadu.

BMC Public Health 2020 Nov 26;20(1):1799. Epub 2020 Nov 26.

Department of Environmental Health Engineering, ICMR Center for Advanced Research on Air Quality, Climate and Health, Faculty of Public Health, Sri Ramachandra Institute of Higher Education and Research (Deemed University), Porur, Chennai, 600116, India.

Background: The Household Air Pollution Intervention Network (HAPIN) trial aims to assess health benefits of a liquefied petroleum gas (LPG) cookfuel and stove intervention among women and children across four low- and middle-income countries (LMICs). We measured exposure contrasts for women, achievable under alternative conditions of biomass or LPG cookfuel use, at potential HAPIN field sites in India, to aid in site selection for the main trial.

Methods: We recruited participants from potential field sites within Villupuram and Nagapattinam districts in Tamil Nadu, India, that were identified during a feasibility assessment. We performed. (i) cross-sectional measurements on women (N = 79) using either biomass or LPG as their primary cookfuel and (ii) before-and-after measurements on pregnant women (N = 41), once at baseline while using biomass fuel and twice - at 1 and 2 months - after installation of an LPG stove and free fuel intervention. We involved participants to co-design clothing and instrument stands for personal and area sampling. We measured 24 or 48-h personal exposures and kitchen and ambient concentrations of fine particulate matter (PM2.5) using gravimetric samplers.

Results: In the cross-sectional analysis, median (interquartile range, IQR) kitchen PM2.5 concentrations in biomass and LPG using homes were 134 μg/m3 [IQR:71-258] and 27 μg/m3 [IQR:20-47], while corresponding personal exposures were 75 μg/m3 [IQR:55-104] and 36 μg/m3 [IQR:26-46], respectively. In before-and-after analysis, median 48-h personal exposures for pregnant women were 72 μg/m3 [IQR:49-127] at baseline and 25 μg/m3 [IQR:18-35] after the LPG intervention, with a sustained reduction of 93% in mean kitchen PM2.5 concentrations and 78% in mean personal PM2.5 exposures over the 2 month intervention period. Median ambient concentrations were 23 μg/m3 [IQR:19-27). Participant feedback was critical in designing clothing and instrument stands that ensured high compliance.

Conclusions: An LPG stove and fuel intervention in the candidate HAPIN trial field sites in India was deemed suitable for achieving health-relevant exposure reductions. Ambient concentrations indicated limited contributions from other sources. Study results provide critical inputs for the HAPIN trial site selection in India, while also contributing new information on HAP exposures in relation to LPG interventions and among pregnant women in LMICs.

Trial Registration: ClinicalTrials.Gov. NCT02944682 ; Prospectively registered on October 17, 2016.
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http://dx.doi.org/10.1186/s12889-020-09865-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690197PMC
November 2020

3D printed gradient index glass optics.

Sci Adv 2020 Nov 18;6(47). Epub 2020 Nov 18.

Lawrence Livermore National Laboratory, Livermore, CA, USA.

We demonstrate an additive manufacturing approach to produce gradient refractive index glass optics. Using direct ink writing with an active inline micromixer, we three-dimensionally print multimaterial green bodies with compositional gradients, consisting primarily of silica nanoparticles and varying concentrations of titania as the index-modifying dopant. The green bodies are then consolidated into glass and polished, resulting in optics with tailored spatial profiles of the refractive index. We show that this approach can be used to achieve a variety of conventional and unconventional optical functions in a flat glass component with no surface curvature.
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http://dx.doi.org/10.1126/sciadv.abc7429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673801PMC
November 2020

Comparative Adherence Trajectories of Oral Fingolimod and Injectable Disease Modifying Agents in Multiple Sclerosis.

Patient Prefer Adherence 2020 4;14:2187-2199. Epub 2020 Nov 4.

Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Houston, TX, USA.

Background: Oral fingolimod is convenient to use than injectable disease modifying agents (DMAs) in patients with multiple sclerosis (MS). However, the existing literature regarding the comparative adherence trajectories between oral fingolimod and injectable DMAs is limited.

Objective: To compare the adherence trajectories between oral DMA, fingolimod, and injectable DMAs in patients with MS.

Methods: A retrospective longitudinal study was conducted using adults (≥18 years) with MS (ICD-9-CM: 340 and a DMA prescription) from the IBM MarketScan Commercial Claims and Encounters Database between 2010 and 2012. Patients were grouped into oral fingolimod or injectable DMA users based on the index DMA among patients with MS. The annual DMA adherence trajectories, based on the proportion of days covered (PDC), were examined using group-based trajectory modeling (GBTM) during the one-year follow-up period after treatment initiation. Multivariable multinomial logistic regression using stabilized inverse probability treatment weights (IPTW) was performed to assess the association between the DMA route of administration (Oral vs Injectable) and the adherence trajectory groups. The balance of covariates between oral and injectable DMAs before and after IPTW was checked against a standardized difference threshold of 0.25.

Results: The study cohort consisted of 1,700 MS patients who were initiated with oral (15.8%) or injectable (84.2%) DMAs between 2010 and 2012. The adherence rates (PDC≥0.8) in oral fingolimod and injectable DMA users were found to be 64.7% and 50.8%, respectively. The GBTM grouped individuals in the study cohort into three adherence trajectories - rapid discontinuers (23.5%), complete adherers (49.9%), and slow decliners (26.6%). The multinomial logistic regression model with stabilized IPTW revealed that oral fingolimod users had higher odds to be a complete adherer (adjusted odds ratio [AOR]: 2.78, 95% CI: 1.85-4.16) or a slow discontinuer (AOR: 2.62, 95% CI: 1.70-4.05) than injectable DMA users.

Conclusions: Oral DMA fingolimod was associated with better adherence than injectable DMAs across group-based trajectories. Further research is warranted to evaluate the adherence trajectories with newer oral DMAs introduced in the last decade for MS.
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http://dx.doi.org/10.2147/PPA.S270557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649232PMC
November 2020