Publications by authors named "Ping Du"

207 Publications

Efficacy of a student-led community contact tracing program partnered with an academic medical center during the coronavirus disease 2019 pandemic.

Ann Epidemiol 2021 Apr 22;56:26-33.e1. Epub 2020 Oct 22.

Penn State College of Nursing, State College, PA.

Purpose: Contact tracing has proven successful at controlling coronavirus 2019 (COVID-19) globally, and the Center for Health Security has recommended that the United States add 100,000 contact tracers to the current workforce.

Methods: To address gaps in local contact tracing, health professional students partnered with their academic institution to conduct contact tracing for all COVID-19 cases diagnosed onsite, which included identifying and reaching their contacts, educating participants, and providing social resources to support effective quarantine and isolation.

Results: From March 24 to May 28, 536 laboratory-confirmed COVID-19 cases were contacted and reported an average of 2.6 contacts. Contacts were informed of their exposure, asked to quarantine, and monitored for the onset of symptoms. Callers reached 94% of cases and 84% of contacts. Seventy-four percent of cases reported at least one contact. Household members had higher rates of reporting symptoms (odds ratio, 1.65; 95% confidence interval, 1.19-2.28). The average test turnaround time decreased from 21.8 days for the first patients of this program to 2.3 days on the eleventh week.

Conclusions: This provides evidence for the untapped potential of community contact tracing to respond to regional needs, confront barriers to effective quarantine, and mitigate the spread of COVID-19.
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http://dx.doi.org/10.1016/j.annepidem.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579098PMC
April 2021

Epidemiology and outcomes of COVID-19 in HIV-infected individuals: a systematic review and meta-analysis.

Sci Rep 2021 03 18;11(1):6283. Epub 2021 Mar 18.

Department of Public Health Sciences, Penn State College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, USA.

Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the risk of mortality among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA) is largely unknown. PLWHA are unique due to their altered immune system from their history of chronic HIV infection and their use of antiretroviral therapy, some of which have been used experimentally to treat coronavirus disease 2019 (COVID-19). Therefore, we conducted a systematic review and meta-analysis to assess the epidemiology of SARS-COV-2/HIV coinfection and estimate associated mortality from COVID-19 (Prospero Registration ID: CRD42020187980). PubMed, SCOPUS, OVID and Cochrane Library databases, and medRxiv preprint repositories were searched from January 1, 2020, to December 12, 2020. Data were extracted from studies reporting COVID-19 attack and mortality rates in PLWHA compared to their HIV-negative counterparts. Pooled attack and mortality risks were quantified using random-effects models. We identified 22 studies that included 20,982,498 participants across North America, Africa, Europe, and Asia. The median age was 56 years, and 50% were male. HIV-positive persons had a significantly higher risk of SARS-CoV-2 infection [risk ratio (RR) 1.24, 95% CI 1.05-1.46)] and mortality from COVID-19 (RR 1.78, 95% CI 1.21-2.60) than HIV-negative individuals. The beneficial effects of tenofovir and protease-inhibitors in reducing the risk of SARS-CoV-2 infection and death from COVID-19 in PLWHA remain inconclusive. HIV remains a significant risk factor for acquiring SARS-CoV-2 infection and is associated with a higher risk of mortality from COVID-19. In support of the current Centers for Disease Control and Prevention (CDC) guidelines, persons with HIV need priority consideration for the SARS-CoV-2 vaccine.
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http://dx.doi.org/10.1038/s41598-021-85359-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973415PMC
March 2021

A study on the characteristics of coke in the hearth of a superlarge blast furnace.

PLoS One 2021 3;16(3):e0247051. Epub 2021 Mar 3.

School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, China.

An in-depth study on the characteristics of coke in the hearths of blast furnaces is of great significance for explaining the mechanism of coke deterioration in blast furnaces. In the present work, the changes in macromorphology, degree of graphitization, and microstructure of the coke taken from different hearth locations of a 5,800 m3 superlarge blast furnace during its intermediate repair period were systematically studied. Significant differences were found between cokes obtained from the edge ("edge coke") and from the center ("center coke") of the hearth in terms of properties and degradation mechanisms. Edge coke was severely eroded by liquid metal, and only a small amount of slag was detected in the coke porosity, whereas center coke was basically free from erosion by liquid metal, and a large amount of slag was detected in the coke porosity. The degree of graphitization of edge coke was higher than that of center coke. The carburizing effect of liquid metal was the main cause of the degradation of edge coke and made it smaller or even disappear. Center coke was degraded due to the combination of two factors: slag inserted into micropores on the surface of center coke loosened the surface structure; and graphite-like flakes that appeared on the center coke surface lowered the strength and caused cracks in the surface.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247051PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928459PMC
March 2021

Dual derivatization strategy for the comprehensive quantification and double bond location characterization of fatty acids by ultra-high performance liquid chromatography-tandem mass spectrometry.

J Chromatogr A 2021 Feb 23;1639:461939. Epub 2021 Jan 23.

Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, PR China. Electronic address:

Comprehensive analysis of fatty acids (FAs) has long been challenging due to their poor ionization efficiency, lack of characteristic fragment ions and difficulty of identifying C=C bond locations. In this study, a high coverage ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for the quantification and C=C bond location characterization of FAs using two structural analogues, 2-hydrazinyl-4,6-dimethylpyrimidine (DMP) and 2-hydrazinylpyrimidine (DP), as dual derivatization reagents. DP-labeled FA standards were used as internal standards to reduced matrix effects, which guaranteed the accurate quantification of FAs. The derivatization yields of FAs were larger than 99% and the sensitivities were increased by 400-fold compared with non-derivatized FAs. Pretreatment and instrumental analysis of FAs can be completed in 20 minutes. Only 5 μL rat plasma can satisfy the quantification of 36 FAs with good linearity (r>0.99). Both intra-day and inter-day accuracies were in the range of 85-105%, and the precisions were less than 15%. The extraction recoveries were investigated to be in the range of 88-112%. No obvious matrix effects were observed for the derivatized FAs. In addition, the locations of C=C bonds in DMP-derivatized FAs could be identified by diagnostic fragment ions generated from 1,4-hydrogen elimination and allylic cleavage under low energy collision induced dissociation (CID). The new method was finally employed for FA profiling in plasma from rats with moxifloxacin-induced liver injury. Significant downregulation of butyric acid was observed in moxifloxacin treated model rats, which was believed to be related to the liver injury.
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http://dx.doi.org/10.1016/j.chroma.2021.461939DOI Listing
February 2021

Investigating inpatient rehabilitation outcomes of patients with intensive care unit-acquired weakness, and identifying comorbidities associated with unfavorable outcomes.

PM R 2021 Feb 2. Epub 2021 Feb 2.

Department of Physical Medicine and Rehabilitation, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.

Introduction: Data are consistent on the benefits of inpatient rehabilitation for intensive care unit-acquired weaknesses (ICUAW), including critical illness myopathy, critical illness polyneuropathy, critical illness polyneuromyopathy, and disuse atrophy. This study focuses on the effects of inpatient rehabilitation on patients with ICUAW, specifically those with a clinical pattern of proximal muscle weakness and sensory sparing.

Objectives: To evaluate the impact of inpatient rehabilitation on patients with ICUAW versus other medically complex patients, and to identify comorbidities associated with poor rehabilitation outcomes.

Design: Retrospective cohort study.

Setting: Institutional, inpatient rehabilitation hospital.

Patients: Two hundred seventy adult patients (≥18 years) divided into two groups: diagnosis of ICUAW (N = 55) or otherwise medically complex (N = 215), and admitted under the care of one physiatrist.

Interventions: Not applicable.

Main Outcome Measures: For all patients we compared functional independence measure (FIM) gain, FIM efficiency, rehabilitation length of stay (RLOS), discharge disposition, and major medical comorbidities.

Results: Patients with ICUAW had significantly greater FIM gain (P = .015) and RLOS (P = .02). There was no significant difference in FIM efficiency (P = .15). Patients with ICUAW had a significantly lower odds of acute hospital transfer (odds ratio [OR] = 0.52, with 95% confidence interval [CI] 0.47, 0.58) and skilled nursing facility discharge (OR = 0.19, with 95% CI 0.038, 0.95). However, patients with ICUAW did have a higher percent of acute hospital transfers than other medically complex patients (P = .017). In addition, patients with ICUAW were more medically complex, as evidenced by a significantly higher Charlson Comorbidity Index (P < .001), prevalence of anemia (P < .001), atrial fibrillation (P = .009), obstructive sleep apnea (P = .018), and bacteremia (P = .041).

Conclusions: Patients with ICUAW with a clinical pattern of proximal muscle weakness and sensory sparing benefit from inpatient rehabilitation as evidenced by FIM gain and high home discharge rate. However, they have multiple medical comorbidities, which require judicious medical management and may contribute to a longer RLOS.
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http://dx.doi.org/10.1002/pmrj.12565DOI Listing
February 2021

Desilylation Induced by Metal Fluoride Nanocrystals Enables Cleavage Chemistry In Vivo.

J Am Chem Soc 2021 Feb 31;143(5):2250-2255. Epub 2021 Jan 31.

Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Metal fluoride nanocrystals are widely used in biomedical studies owing to their unique physicochemical properties. The release of metal ions and fluorides from nanocrystals is intrinsic due to the solubility equilibrium. It used to be considered as a drawback because it is related to the decomposition and defunction of metal fluoride nanocrystals. Many strategies have been developed to stabilize the nanocrystals, and the equilibrium concentrations of fluoride are often <1 mM. Here we make good use of this minimum amount of fluoride and unveil that metal fluoride nanocrystals could effectively induce desilylation cleavage chemistry, enabling controlled release of fluorophores and drug molecules in test tubes, living cells, and tumor-bearing mice. Biocompatible PEG (polyethylene glycol)-coated CaF nanocrystals have been prepared to assay the efficiency of desilylation-induced controlled release of functional molecules. We apply the strategy to a prodrug activation of monomethyl auristatin E (MMAE), showing a remarkable anticancer effect, while side effects are almost negligible. In conclusion, this desilylation-induced cleavage chemistry avails the drawback on empowering metal fluoride nanocrystals with a new function of perturbing or activating for further biological applications.
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http://dx.doi.org/10.1021/jacs.0c10399DOI Listing
February 2021

Bi-functional gold nanocages enhance specific immunological responses of foot-and-mouth disease virus-like particles vaccine as a carrier and adjuvant.

Nanomedicine 2021 Jan 20;33:102358. Epub 2021 Jan 20.

State Key Laboratory of Veterinary Etiological Biology and Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China; School of Animal Science, Yangtze University, Jingzhou, PR China.. Electronic address:

Virus-like particle (VLP) vaccines have become one of the dominant vaccine candidates for foot-and-mouth disease (FMD). To further enhance the immunogenicity of VLP vaccines, gold nanocages (AuNCs) were selected as an adjuvant for the vaccine. Our experiments demonstrated that AuNCs had little biotoxicity in vivo and in vitro and improved the uptake of VLP in BHK-21 and RAW264.7 cell lines. The VLP-AuNCs activated DCs mainly through toll-like receptor 4 (TLR4) and promoted the secretion of IL-6, IL-1β, and TNF-α. The conjugation of VLP and AuNCs triggered a strong immune response against FMD virus (FMDV) in mice and guinea pigs. The VLP-AuNCs significantly enhanced the proliferation of CD8 T cells (P < 0.05) and the secretion of cellular immune-related cytokines (IFN-γ, P < 0.05; IL-12p70, P < 0.01) compared with VLP. The present study demonstrated that AuNCs, as a great potential adjuvant for FMDV VLP vaccines, significantly enhance the immune response.
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http://dx.doi.org/10.1016/j.nano.2021.102358DOI Listing
January 2021

Novel ECM Patch Combines Poly(vinyl alcohol), Human Fibroblast-Derived Matrix, and Mesenchymal Stem Cells for Advanced Wound Healing.

ACS Biomater Sci Eng 2020 07 22;6(7):4266-4275. Epub 2020 Jun 22.

Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.

Decellularized extracellular matrix (ECM)-based scaffold has been a very useful resource for effective tissue regeneration. In this study, we report a novel ECM patch that physically combines human fibroblast-derived matrix (hFDM) and poly(vinyl alcohol) (PVA) hydrogel. hFDM was obtained after decellularization of cultured human fibroblasts. We investigated the basic characteristics of hFDM alone using immunofluorescence (fibronectin, collagen type I) and angiogenesis-related factor analysis. Successful incorporation of hFDM with PVA produced an hFDM/PVA patch, which showed excellent cytocompatibility with human mesenchymal stem cells (hMSCs), as assessed via cell adhesion, viability, and proliferation. Moreover, scratch assay using human dermal fibroblasts showed a significant improvement of cell migration when treated with the paracrine factors originated from the hMSC-incorporated hFDM. To evaluate the therapeutic effect on wound healing, hMSCs were seeded on the hFDM/PVA patch and they were then transplanted into a mouse full-thickness wound model. Among four experimental groups (control, PVA, hFDM/PVA, hMSC/hFDM/PVA), we found that hMSC/hFDM/PVA patch accelerated the wound closure with time. More notably, histology and immunofluorescence demonstrated that compared to the other interventions tested, hMSC/hFDM/PVA patch could lead to significantly advanced tissue regeneration, as confirmed via nearly normal epidermis thickness, skin adnexa regeneration (hair follicle), mature collagen deposition, and neovascularization. Additionally, cell tracking of prelabeled hMSCs suggests the retention of transplanted cells in the wound region after the transplantation of hMSC/hFDM/PVA patch. Taken together, our engineered ECM patch supports a strong regenerative potential toward advanced wound healing.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00657DOI Listing
July 2020

Cultivation and Medicinal Value of the Red Belt Conk Mushroom Fomitopsis pinicola (Agaricomycetes).

Int J Med Mushrooms 2020 ;22(10):1021-1031

College of Modern Agriculture and Bioengineering, Yangtze Normal University, Chongqing, P.R. China.

This study examined biological characteristics, liquid fermentation, and cultivation of Fomitopsis pinicola. A single-factor test concluded that the optimal carbon and nitrogen sources for mycelial growth were soluble starch and yeast paste; the optimal culture temperature was 31°C, and the optimal pH was 6.0. The orthogonal experiment indicated that the optimal formula for mycelial culture was 25 g soluble starch, 2 g yeast extract, 1 g KH2PO4, and 1.5 g MgSO4 added to 1 L water. The optimal conditions for liquid fermentation culture consisted of the following: a loading volume 90 mL, inoculation volume 30 mL, and rotation speed 160 rpm. The optimal substrate formula for domestic culture was 20% corn cob, 30% sawdust, 20% wheat bran, 25% cotton seed shell, 3% corn meal, 1% gypsum, and 1% lime, which produced the highest yield of fruiting bodies. The results provided basic data for deep liquid fermentation culture and recommendations for the further development and utilization of F. pinicola.
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http://dx.doi.org/10.1615/IntJMedMushrooms.2020035811DOI Listing
January 2020

DGT methodology is more sensitive than conventional extraction strategies in assessing amendment-induced soil cadmium availability to rice.

Sci Total Environ 2021 Mar 8;760:143949. Epub 2020 Dec 8.

College of Water Science, Beijing Normal University, Beijing 100875, China; State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

Using diffusive gradients in thin films (DGT) is a recently developed alternative method of rapidly evaluating the bioavailability of metals in soil. However, the method has found only limited application in systematic assessment of the bioavailability of cadmium (Cd) in red limestone paddy soils treated with different soil amendments. Of the four methods compared for estimating Cd content of rice grains from plants grown in such soils of central China treated with eleven different soil amendments in pot culture, Cd content of DGT-labile soil was significantly correlated to Cd concentrations in brown rice (R = 0.447, p < 0.01). The other three methods involved CaCl, diethylenetriaminepentaacetic acid (DTPA), or NHNO. Some other properties of soil, such as pH, redox potential, content of dissolved organic matter, and cation exchange capacity were also determined. A simple algorithm developed to evaluate the sensitivity of the four methods also confirmed DGT as the most efficient method to predict the bioavailability of Cd in red limestone paddy soils.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143949DOI Listing
March 2021

Longitudinal Pharmacometabonomics for Predicting Malignant Tumor Patient Responses to Anlotinib Therapy: Phenotype, Efficacy, and Toxicity.

Front Oncol 2020 12;10:548300. Epub 2020 Nov 12.

Pharmaceutical Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Anlotinib is an oral small molecule inhibitor of multiple receptor tyrosine kinases (RTKs), which was approved by the National Medical Products Administration (NMPA) of China in 2018 for the third-line treatment of non-small cell lung cancer (NSCLC). Here, for the first time, the longitudinal pharmacometabonomics was explored for predicting malignant tumor patient responses to anlotinib, including the metabolic phenotype variation, drug efficacy, and toxicity. A total of 393 plasma samples from 16 subjects collected from a phase I additional study of anlotinib (NCT02752516) were submitted to targeted metabolomics analysis. The orthogonal partial least-squares discriminant analysis (OPLS-DA) models were constructed for the predication of anlotinib efficacy and toxicity based on the longitudinal pharmacometabonomics data. Statistical results showed that 38 metabolites, mainly involved in aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and steroid hormone biosynthesis, were all significantly upregulated attributing to anlotinib treatment. The anti-tumor efficacy and occurrence of proteinuria after anlotinib administration can be predicted with 100% accuracy using the established OPLS-DA models. Glycodeoxycholic acid and glycocholic acid possessed the most excellent sensitivity and specificity in predicting the efficacy of anlotinib, with area under the receiver operating characteristic curve (AUC of ROC curve) 0.847 and 0.828, respectively. NG, NG-dimethylarginine was the most promising biomarker for the prediction of proteinuria occurrence after anlotinib administration, with AUC of ROC curve 0.814. In conclusion, this work developed efficient and convenient discriminant models that can accurately predict the efficacy and toxicity of anlotinib based on longitudinal pharmacometabonomics study.
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http://dx.doi.org/10.3389/fonc.2020.548300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689013PMC
November 2020

Engineering Bacillus subtilis Isoleucine Dioxygenase for Efficient Synthesis of (2,3,4)-4-Hydroxyisoleucine.

J Agric Food Chem 2020 Dec 28;68(49):14555-14563. Epub 2020 Nov 28.

State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, School of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.

Isoleucine dioxygenase (IDO)-catalyzed hydroxylation of isoleucine is a promising method for the synthesis of the diabetic drug (2,3,4)-4-hydroxyisoleucine [(2,3,4)-4-HIL]. However, the low activity of IDO significantly limits its practical application. In this work, a high-throughput screening method was developed and directed evolution was performed on the IDO from , resulting in a double mutant with improvements in specific activity, protein expression level, and fermentation titer of 3.2-, 2.8-, and 9.4-fold, respectively. l-Isoleucine (228 mM) was completely converted to (2,3,4)-4-HIL by the best variant with a space-time yield of up to 80.8 g L d, which is the highest record reported so far. With a further increase of the substrate loading to 1 M, a high conversion of 91% could also be achieved. At last, enzymatic synthesis of (2,3,4)-4-HIL was successfully carried out on a 3 L scale, indicating tremendous potential of the IDO variant I162T/T182N for green and efficient production of (2,3,4)-4-HIL.
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http://dx.doi.org/10.1021/acs.jafc.0c06544DOI Listing
December 2020

Changing Urban-Rural Disparities in the Utilization of Direct-Acting Antiviral Agents for Hepatitis C in U.S. Medicare Patients, 2014-2017.

Am J Prev Med 2021 02 19;60(2):285-293. Epub 2020 Nov 19.

Department of Health Policy and Administration, College of Health and Human Development, Pennsylvania State University, University Park, Pennsylvania.

Introduction: The advent of direct-acting antiviral agents for treating hepatitis C virus infection has made hepatitis C virus elimination possible. Rural patients with hepatitis C virus infection may be less likely to access direct-acting antiviral agents, but the real-world evidence is scarce on urban-rural disparities in direct-acting antiviral agent utilization.

Methods: This retrospective cohort study was conducted in 2019-2020 using Medicare data to examine urban-rural disparities in direct-acting antiviral agent utilization among newly diagnosed patients with hepatitis C virus infection in 2014-2016. Direct-acting antiviral agent use was defined as filling ≥1 prescription for direct-acting antiviral agents during 2014-2017, and patient's urban-rural status was classified on the basis of their ZIP code of residence. This study evaluated the associations between multilevel factors and direct-acting antiviral agent use with a focus on urban-rural disparities. It also assessed changes over time in urban-rural disparities in direct-acting antiviral agent utilization using multivariable cause-specific Cox regression analyses with time-varying hazard ratios.

Results: Among 204,018 new patients with hepatitis C virus infection, about 30% received direct-acting antiviral agents during 2014-2017. Cumulative direct-acting antiviral agent use gradually increased over time in both urban and rural patients. However, the increase was greater in urban patients than in rural patients. In the first year of follow-up, rural patients had a similar rate of receiving direct-acting antiviral agents (adjusted hazard ratio=1.03, 95% CI=1.00, 1.07), but they were less likely to use direct-acting antiviral agents in later years than urban patients (adjusted hazard ratio=0.85, 95% CI=0.81, 0.90 in the second year, adjusted hazard ratio=0.82, 95% CI=0.76, 0.89 in the third year, and adjusted hazard ratio=0.76, 95% CI=0.64, 0.90 in the fourth year of follow-up).

Conclusions: This study reveals important gaps in hepatitis C virus treatment and suggests increasing urban-rural disparities in direct-acting antiviral agent utilization. Enhancing direct-acting antiviral agent uptake in rural populations with hepatitis C virus infection will help reduce hepatitis C virus‒related health disparities and reach the national goal of eliminating hepatitis C virus infection.
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http://dx.doi.org/10.1016/j.amepre.2020.08.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855597PMC
February 2021

Using Persuasion science to improve COVID-19 contact tracing.

Am J Infect Control 2021 04 5;49(4):528-529. Epub 2020 Nov 5.

Department of Psychology, Arizona State University, Tempe, AZ.

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http://dx.doi.org/10.1016/j.ajic.2020.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642730PMC
April 2021

Renin-angiotensin-aldosterone system inhibitors and the risk of mortality in patients with hypertension hospitalised for COVID-19: systematic review and meta-analysis.

Open Heart 2020 11;7(2)

Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania, USA.

Objective: The association between the use of renin-angiotensin-aldosterone (RAAS) inhibitors and the risk of mortality from COVID-19 is unclear. We aimed to estimate the association of RAAS inhibitors, including ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality risk in patients with hypertension.

Methods: PubMed (MEDLINE) SCOPUS, OVID, Cochrane Library databases and medrxiv.org were searched from 1 January 2020 to 1 September 2020. Studies reporting the association of RAAS inhibitors (ACEi or ARBs) and mortality in patients with hypertension, hospitalised for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio (RR) estimates, and heterogeneity was quantified.

Results: Fourteen studies were included in the systematic review (n=73,073 patients with COVID-19; mean age 61 years; 53% male). Overall, the between-study heterogeneity was high (I=80%, p<0.01). Patients with hypertension with prior use of RAAS inhibitors were 35% less likely to die from COVID-19 compared with patients with hypertension not taking RAAS inhibitors (pooled RR 0.65, 95% CI 0.45 to 0.94). The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations was graded as 'moderate' quality.

Conclusions: In this meta-analysis, with prior use of RAAS inhibitors was associated with lower risk mortality from COVID-19 in patients with hypertension. Our findings suggest a potential protective effect of RAAS-inhibitors in COVID-19 patients with hypertension.

Prospero Registration Number: The present study has been registered with PROSPERO (registration ID: CRD 42020187963).
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http://dx.doi.org/10.1136/openhrt-2020-001353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646321PMC
November 2020

Extracellular matrices derived from different cell sources and their effect on macrophage behavior and wound healing.

J Mater Chem B 2020 11;8(42):9744-9755

Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea. and Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology (UST), Seoul 02792, Republic of Korea.

A decellularized extracellular matrix (dECM) is an excellent biomaterial in regenerative medicine, due to its biomimetic nature in targeting tissues and organs. In this study, we prepared cell-derived ECMs (CDM) derived from four different cell sources, characterized them individually, and found that intrinsic properties of each CDM were substantially different in terms of the fibrous matrix, total protein, and biochemical factors. Based on such information, we selected two ECM candidates, the human lung fibroblast derived matrix (hFDM) and the umbilical cord-blood mesenchymal stem cell derived matrix (UMDM) for the study of ECM-macrophage interactions in vitro and in vivo. In fact, UMDM was the richer in both total protein and angiogenic-related cytokines than any other CDM. When THP-1 cell-derived macrophages (M0) were seeded onto the UMDM or the hFDM, it showed a mixed cell morphology of macrophage phenotype and the macrophages (M0) preconditioned on UMDM presented more diverse cytokine release profiles. The treatment of conditioned medium obtained from CDM-seeded macrophages showed that UMDM could yield significantly advanced wound closure in 24 h via the human dermal fibroblast scratch model. To investigate the role of ECM on macrophage polarization in vivo, we prepared an ECM hydrogel, a mixture of each CDM and Pluronic F127/hyaluronan, and applied them onto a full-thickness mouse skin wound model for 2 weeks. The therapeutic efficacy as assessed via histology and immunofluorescence staining (α-SMA and CD206) revealed that the UMDM-treated group showed more effective wound healing compared to the other groups, as proven via the thinner epidermal layer, significant recovery of skin appendage, better neovascularization, and higher recruitment of myofibroblasts and larger number of macrophages (M2) at 7 days. The difference between UMDM and hFDM was marginal. Taken together, among the CDMs, UMDM and hFDM are promising resources of ECM, showing a great potential for wound healing. Although the mechanism is not fully understood, bioactive innate factors in UMDM may contribute individually and/or collectively to advance wound healing.
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http://dx.doi.org/10.1039/d0tb01885fDOI Listing
November 2020

Can Telementoring Reduce Urban-Rural Disparities in Utilization of Direct-Acting Antiviral Agents?

Telemed J E Health 2020 Sep 2. Epub 2020 Sep 2.

Department of Health Policy and Administration, College of Health and Human Development, The Pennsylvania State University, University Park, Pennsylvania, USA.

Expanding access to direct-acting antiviral agents (DAAs) for treating hepatitis C virus (HCV) infection is the national goal for HCV elimination, but important urban-rural disparities exist in DAA use. Evidence is needed to evaluate intervention efforts to reduce urban-rural disparities in DAA utilization. We used Medicare data to compare DAA use between urban HCV patients and rural HCV patients in two states: State A with a telementoring approach to train rural providers to treat HCV patients and State B without such an intervention. We focused on DAA utilization among newly diagnosed HCV patients in 2014-2016 and defined DAA use as filling at least one prescription of DAAs during 2014-2017. We classified patient's urban-rural status based on their ZIP code of residence. We assessed overtime changes in urban-rural disparities in DAA utilization for each state using multivariable cause-specific Cox regression analyses with time-varying hazard ratios. Among 1,872 new HCV patients in State A, 135 (17.00%) rural patients and 243 (22.54%) urban patients received DAAs in 2014-2017. Although there was noticeable urban-rural disparities in DAA use during the first 24 months of follow-up (hazard ratios [HRs] = 0.73 [0.51 to 1.03] for 0-12 months and 0.61 [0.39 to 0.95] for 13-24 months), the disparities became nonsignificant afterward (HR = 1.06 [0.58 to 1.93] after 24 months). Most DAA users in rural areas (94, 70%) in State A received DAAs prescribed by primary care providers (PCPs). In State B, among 8,928 new HCV patients, 227 (18.22%) rural patients and 1,600 (20.83%) urban patients received DAAs in 2014-2017. Rural patients were less likely to receive DAAs over time (HR = 1.12 [0.93 to 1.36] in the first 12 months and HR = 0.62 [0.40 to 0.96] after 24 months). Only 81 (36%) DAA users in rural areas in State B were treated by PCPs. Our study suggests that the telementoring approach may help reduce urban-rural disparities in DAA utilization.
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http://dx.doi.org/10.1089/tmj.2020.0090DOI Listing
September 2020

Three new species of (Polyporales, Basidiomycota) from China.

MycoKeys 2020 14;72:1-16. Epub 2020 Aug 14.

Shandong Provincial Key Laboratory of Applied Mycology, Qingdao Agricultural University, Qingdao 266109, China Qingdao Agricultural University Qingdao China.

In this study, taxonomic and phylogenetic analyses of were performed. Three new species were characterised according to morphological characteristics and molecular phylogenetic analysis using ITS and nLSU sequences. They are , and is characterised by resupinate, thin basidiomata with white to buff-yellow hymenophore, small pores (9-11 per mm), clamped generative hyphae possessing hymenial cystidia, ellipsoid basidiospores (2.5-3 × 1.7-2 µm) and growth on fallen bamboo or angiosperm branch. is characterised by resupinate basidiomata with pink to salmon pores and a distinct white margin, clamp generative hyphae, interwoven tramal hyphae, ellipsoid basidiospores measuring 2.6-3.2 × 1.8-2 µm and growth on . is characterised by resupinate basidiomata with pale salmon to brownish vinaceous hymenophore, small pores (10-12 per mm), generative hyphae with simple septa and clamp connections, interwoven tramal hyphae, lunate basidiospores measuring 2.9-3.4 × 1.6-1.8 µm and thriving on rotten wood of angiosperms.
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http://dx.doi.org/10.3897/mycokeys.72.51872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442768PMC
August 2020

Implementation and Process of a COVID-19 Contact Tracing Initiative: Leveraging Health Professional Students to Extend the Workforce During a Pandemic.

Am J Infect Control 2020 12 13;48(12):1451-1456. Epub 2020 Aug 13.

Penn State College of Medicine, Penn State Hershey Medical Center, Hershey, PA.

Background: The Centers for Disease Control and Prevention recommends aggressive contact tracing to control the COVID-19 pandemic. In this work, we (1) describe the development of a COVID-19 contact tracing initiative that includes medical, nursing, and public health students, and is led by clinicians and infectious disease epidemiologists within our health system, and, (2) articulate process steps for contact tracing including workflows and telephone scripts, and, (3) highlight the key challenges and strategies to overcome these challenges.

Methods: A single academic institution-based contact tracing initiative was rapidly scaled to 110 health professional students, four physicians, two epidemiologists, and a research team. Following training, students called patients who were COVID-19 positive and the individuals they were in contact with to ensure proper isolation and quarantine measures. Students also assisted those who faced barriers to quarantine.

Implications: In total, between March 24 and May 28 - this initiative completed contact tracing for 536 confirmed cases, which resulted in the identification of 953 contacts. We aim to disseminate this process, including telephone scripts and workflow, to other health systems for use in their initiatives to respond to the COVID-19 pandemic and future public health emergencies.
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http://dx.doi.org/10.1016/j.ajic.2020.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425552PMC
December 2020

OPT-In For Life: A Mobile Technology-Based Intervention to Improve HIV Care Continuum for Young Adults Living With HIV.

Health Promot Pract 2020 09 6;21(5):727-737. Epub 2020 Aug 6.

Pennsylvania State University, Hershey, PA, USA.

Young adults living with HIV (YALH) have lower rates of retention in care and HIV viral suppression. Multiple barriers exist to engage YALH in care. We developed and implemented a multifaceted, mobile application-based intervention, "OPT-In for Life," by targeting YALH to encourage retention in care and eventually viral suppression. The app integrated multiple user-friendly features for YALH to manage their HIV care, including a two-way secure messaging function, HIV-related laboratory results, and appointment or medication reminders. We recruited 92 YALH who were 18 to 34 years old and were newly diagnosed with HIV, had a history of falling out of care, or had a detectable HIV viral load into this intervention. Study participants used the app to manage their HIV care and to communicate and interact with their HIV care team. During the intervention period, the retention rate among our study participants increased from 41.3% at baseline to 78.6% at 6-month follow-up, maintained at 12-month follow-up (79.8%), and slightly decreased to 73.4% at 18-month follow-up but it was still significantly higher than the baseline retention rate ( < .0001). The viral suppression rate (HIV RNA <200 copies/ml) increased from 64.1% at baseline to about 85% at 6-month and at 12-month follow-up and reached 91.4% at 18-month ( = .0002) among participants who were retained in care. Our study demonstrated using a HIPAA-compliant mobile application as an effective intervention to engage YALH in care. This mobile technology-based intervention can be incorporated into routine clinical practice to improve HIV care continuum.
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http://dx.doi.org/10.1177/1524839920936247DOI Listing
September 2020

[Construction, expression and identification of chimeric foot-and-mouth disease virus-like particles].

Sheng Wu Gong Cheng Xue Bao 2020 Jul;36(7):1305-1313

State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, Gansu, China.

To improve the specific recognition and presentation of virus-like particle (VLPs), and to develop immune-targeted VLPs vaccine, the gene fragment encoding OVA₂₅₇₋₂₆₄ peptide was inserted into the VP3 gene of foot-and-mouth disease virus (FMDV) between the 171th and 172th amino acids (aa) or 173th and 174th aa by reverse PCR. The recombinant proteins were expressed by using Escherichia coli and assembled into chimeric VLP (VLP(OVA)) in vitro after purification. The VLP(OVA) was measured by dynamic light scattering and transmission electron microscopy. The recombinant protein and the assembled VLPs were evaluated by Western blotting, enzyme-linked immunosorbent assay and laser scanning confocal microscopy to confirm the insertion of OVA₂₅₇₋₂₆₄ peptide into VP3 and its location. The results show that insertion of OVA₂₅₇₋₂₆₄ into the 173th and 174th aa of FMDV VP3 did not affect the assembly of VLPs. The VLP(OVA) in size was larger than VLPs, and the OVA₂₅₇₋₂₆₄ peptide was located on the surface of VLP(OVA).
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http://dx.doi.org/10.13345/j.cjb.190520DOI Listing
July 2020

Simultaneous quantitative determination of arachidonic acid and cascade metabolites in rat serum by UPLC-MS/MS: application for longitudinal metabolomics of anlotinib.

Analyst 2020 Jul 9;145(14):4972-4981. Epub 2020 Jun 9.

Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Arachidonic acid (AA) and cascade metabolites have been shown to be involved in cancer pathologic states. Anlotinib, a novel oral small molecule inhibitor of multiple receptor tyrosine kinases, has brought significant improvement to the survival of patients with advanced lung cancer. Here, a robust and reproducible ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed, optimized and validated for quantitating AA and cascade metabolites for the first time. Through careful optimization of the analytical conditions, a total of 69 analytes can be efficiently separated and quantitated in a single run of 17 min. A simple and labor-saving protein precipitation procedure was utilized for serum sample pretreatment. The validation parameters and quality control chart of all analytes satisfy the acceptance criteria of bioanalytical method guidelines. The limit of detection (LOD) ranged from 0.005 ng mL to 1 ng mL, and the volume of serum was only 20 μL. This rapid and sensitive UPLC-MS/MS method was successfully applied to a longitudinal metabolomics study in rat serum after a single administration of anlotinib (6 mg kg). Finally, a total of 41 metabolites can be calculated under the present conditions. Serum samples from the same rat were segregated into a tight cluster in both unsupervised principal component analysis (PCA) and supervised orthogonal partial least-squares discriminant analysis (OPLS-DA) at different sampling time points after anlotinib treatment. Moreover, the number of analytes whose variable importance (VIP) values were larger than 1.0 was 17. The present study not only offers a UPLC-MS/MS analytical reference for AA but also brings out insights for future mechanistic studies or biomarkers to predict the efficacy, toxicity and clinical outcomes in patients with cancer.
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http://dx.doi.org/10.1039/d0an00867bDOI Listing
July 2020

An injectable, self-assembled multicellular microsphere with the incorporation of fibroblast-derived extracellular matrix for therapeutic angiogenesis.

Mater Sci Eng C Mater Biol Appl 2020 Aug 19;113:110961. Epub 2020 Apr 19.

Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology (UST), Seoul 02792, Republic of Korea. Electronic address:

Decellularized human lung fibroblast-derived matrix (hFDM) has demonstrated its excellent proangiogenic capability. In this study, we propose a self-assembled, injectable multicellular microspheres containing human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cell (MSCs), collagen hydrogel (Col), and hFDM toward therapeutic angiogenesis. Those multicellular microspheres are spontaneously formed by the mixtures of cell and hydrogel after being dropped on the parafilm for several hours. The size of microspheres can be manipulated via adjusting the initial volume of droplets and the culture period. The cells in the microspheres are highly viable. Multicellular microspheres show good capability of cell migration on 2D culture plate and also exhibit active cell sprouting in 3D environment (Col) forming capillary-like structures. We also find that multiple angiogenic-related factors are significantly upregulated with the multicellular microspheres prepared via Col and hFDM (Col/hFDM) than those prepared using Col alone or single cells (harvested from cocultured HUVECs/MSCs in monolayer). For therapeutic efficacy evaluation, three different groups of single cells, Col and Col/hFDM microspheres are injected to a hindlimb ischemic model, respectively, along with PBS injection as a control group. It is notable that Col/hFDM microspheres significantly improve the blood reperfusion and greatly attenuate the fibrosis level of the ischemic regions. In addition, Col/hFDM microspheres show higher cell engraftment level than that of the other groups. The incorporation of transplanted cells with host vasculature is detectable only with the treatment of Col/hFDM. Current results suggest that hFDM plays an important role in the multicellular microspheres for angiogenic cellular functions in vitro as well as in vivo. Taken together, our injectable multicellular microspheres (Col/hFDM) offer a very promising platform for cell delivery and tissue regenerative applications.
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http://dx.doi.org/10.1016/j.msec.2020.110961DOI Listing
August 2020

Blocking the LncRNA MALAT1/miR-224-5p/NLRP3 Axis Inhibits the Hippocampal Inflammatory Response in T2DM With OSA.

Front Cell Neurosci 2020 12;14:97. Epub 2020 May 12.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.

Studies have shown that diabetes can cause cognitive dysfunction, and cognitive dysfunction in patients with diabetes combined with obstructive sleep apnea (OSA) is more severe. LncRNAs are known to be associated with type 2 diabetes mellitus (T2DM) with OSA. This study aimed to investigate the role and underlying mechanism of the lncRNA MALAT1/miR-224-5p/NLRP3 axis in T2DM with OSA. qRT-PCR was used to quantify the expression of MALAT1, miR-224-5p, and NLRP3 in brain tissues. NLRP3 expression was assessed by immunohistochemistry (IHC) and immunofluorescent labeling. The interaction involving MALAT1, miR-224-5p, and NLRP3 was evaluated by transfection. Western blotting was utilized to evaluate the expression levels of the pathway-related proteins NLRP3, caspase 1, tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) both and . qRT-PCR was used to assess the mRNA expression levels of NLRP3, caspase 1, TNF-α and IL-1β both and . In brain tissues of T2DM with OSA, MALAT1 and NLRP3 were overexpressed, while miR-224-5p was downregulated, which was consistent with subsequent cell experiments. We screened the miRNAs that could bind to MALAT1 and NLRP3 by the StarBase database and the TargetScanMouse7.2 website. Our research showed that among these miRNAs, the level of miR-224-5p was most significantly negatively correlated with the levels of MALAT1 and NLRP3. Also, a firefly luciferase assay showed that miR-224-5p, which is a target of MALAT1, directly reduced the expression of the downstream protein NLRP3. Overexpression of miR-224-5p significantly inhibited the expression levels of NLRP3, caspase 1, TNF-α and IL-1β . MALAT1 promoted NLRP3 expression by acting as a competing endogenous RNA and sponging miR-224-5p. MiR-224-5p reduces microglial inflammation activation through the regulation of NLRP3 expression, which ultimately affected the NLRP3/IL-1β pathway in the hippocampus. This suggests that miR-224-5p may serve as a potential target for T2DM and OSA therapy.
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http://dx.doi.org/10.3389/fncel.2020.00097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235443PMC
May 2020

Factors Associated with Urinary Iodine Concentration among Women of Reproductive Age, 20-49 Years Old, in Tanzania: A Population-Based Cross-Sectional Study.

Curr Dev Nutr 2020 May 29;4(5):nzaa079. Epub 2020 Apr 29.

Department of Nutritional Sciences, Penn State University, State College, PA, USA.

Background: Universal salt iodization (USI) is the most feasible and cost-effective, and equitable, approach to prevent iodine deficiency. Severe maternal iodine deficiency during pregnancy is associated with serious adverse gestational and birth outcomes.

Objectives: The aim was to assess iodine status and identify independent factors associated with urinary iodine concentration (UIC) among women of reproductive age in Tanzania.

Methods: This was a weighted, population-based, cross-sectional study in 2985 women of reproductive age (20-49 y) in Tanzania who participated in the Demographic and Health Surveys in 2015-2016 (DHS 2015-2016) and had measured UIC. Multivariable generalized linear regression was used to identify potential factors that were associated with UIC.

Results: The median UICs among women consuming inadequately iodized salt (93.6 μg/L; 25th and 75th percentiles: 43.1, 197.9 μg/L) and women in the lowest socioeconomic status (92.3 μg/L; 45.6, 194.4 μg/L) were below the WHO-recommended ranges (≥150 μg/L for pregnant women and ≥100 μg/L for nonpregnant women). The results of multivariable models indicated that pregnant women had 1.21 μg/L lower UIC than nonpregnant women (β = -1.21; 95% CI: -3.42, -0.12), breastfeeding women had 1.02 μg/L lower UIC than nonbreastfeeding women (β = -1.02; 95% CI: -2.25, -0.27), and women with no education had a 1.88 μg/L lower UIC compared with those with secondary/highest education (β = -1.88; 95% CI: -4.58, -0.36). Women consuming inadequately iodized salt had 6.55 μg/L lower UIC than those consuming adequately iodized salt (β = -6.55; 95% CI: -9.24, -4.33). The median UIC varied substantially across geographic zones, ranging from 83.2 μg/L (45.9, 165.3) in the Western region to 347.8 μg/L (185.0, 479.8) in the Eastern region.

Conclusions: Our findings indicated a great heterogeneity in median UIC across regions of Tanzania among women of reproductive age. Poverty, consuming inadequately iodized salt, and lack of education appeared to be the driving factors for lower UIC in Tanzania.
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http://dx.doi.org/10.1093/cdn/nzaa079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236838PMC
May 2020

High-Score US-Suspicious Subcentimeter Thyroid Nodules: What Factors Affect Adequate Sampling of US-Guided Fine-Needle Aspiration Biopsy?

Int J Endocrinol 2020 21;2020:8464623. Epub 2020 Apr 21.

Department of Radiology, The Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong 637000, Sichuan, China.

Background: Fine-needle aspiration biopsy (FNAB) is diagnostic standard for thyroid nodules. However, the influence of adequate sample rate of US-guided FNAB for subcentimeter thyroid nodules is not known well.

Objectives: To assess the factors affecting adequate sample rate of US-guided FNAB for subcentimeter thyroid nodules.

Methods: Three hundred and forty-nine consecutive US-guided FNAB procedures were performed in 344 patients with subcentimeter thyroid nodules. The adequate sample rate was analyzed for all nodules on the basis of nodule-related and technical factors. The factors affecting adequate sample rate of US-guided FNAB for subcentimeter thyroid nodules were determined by multivariate logistic regression.

Results: The adequate sample rate increased with larger nodules (72.7% for 3-6 mm nodules and 84.9% for 7-10 mm nodules (=0.007)). The adequate sample rate was 63.9%, 81.3%, and 90.6% in nodules with macrocalcifcation, microcalcification, and no calcification, respectively ( < 0.001). The adequate sample rate was 71.8% for biopsies performed with a perpendicular needle path and 85.0% with a parallel needle path (=0.004). The significant factors affecting adequate sample rate of US-guided FNAB for subcentimeter thyroid nodules were nodule size ( < 0.001; odds ratio (OR) for 7-10 mm nodules was approximately 3.0 times higher than that for 3-6 mm nodules), calcification ( < 0.001; OR for nodules without calcification was approximately 5.3 times higher than that for the nodules with macrocalcification), and needle path (=0.044; OR for the use of the parallel needle path was about 1.8 times higher than that for the perpendicular needle path).

Conclusion: Nodule size, calcification, and needle path were the determinants of sample adequacy. The adequate sample rate was higher in larger nodules, in nodules without calcification, and upon using a parallel needle path for biopsy.
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http://dx.doi.org/10.1155/2020/8464623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191365PMC
April 2020

In vitro and in vivo synergistic efficacy of ceritinib combined with programmed cell death ligand-1 inhibitor in anaplastic lymphoma kinase-rearranged non-small-cell lung cancer.

Cancer Sci 2020 Jun 22;111(6):1887-1898. Epub 2020 May 22.

Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Both ceritinib (CER) and programmed cell death (PD)-1/PD ligand-1 (PD-L1) have brought significant breakthroughs for anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). However, the overall clinical efficacy of either CER or PD-1/PD-L1 inhibitor monotherapy has been limited to a large extent. In addition, the antitumor effect of combined CER and PD-L1 inhibitor in ALK-rearranged NSCLC is not fully understood. In H2228 cells, we examined the tumor killing effect of CER plus PD-L1 inhibitor in vitro by quantitative RT-PCR, flow cytometry, ELISA, western blot analysis, PBMC coculture system, and plasmid and transfection experiments. A Ba/F3 (EML4-ALK-WT) xenograft mouse model was also utilized to further evaluate the synergistic anticancer effects of CER and PD-L1 inhibitor in vivo. The coculture system of PBMCs with H2228 cells promotes the expression of PD-L1 and phospho-ERK, and combined treatments facilitate lymphocyte proliferation and activation, inhibit PD-L1 expression, and enhance lymphocyte cytotoxicity and cell death. In the in vivo NSCLC xenograft model, the volumes of tumors treated with CER and PD-L1 inhibitor in combination were significantly smaller than those treated with CER or PD-L1 alone. The relative tumor growth inhibitions were 84.9%, 20.0%, and 91.9% for CER, PD-L1 inhibitor, and CER plus PD-L1 groups, respectively. Ceritinib could synergize with PD-1/PD-L1 blockade to yield enhanced antitumor responses along with favorable tolerability of adverse effects. Ceritinib and PD-L1 inhibitor combined produced a synergistic antineoplastic efficacy in vitro and in vivo, which provides a key insight and proof of principle for evaluating CER plus PD-L1 blockade as combination therapy in clinical therapeutic practice.
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http://dx.doi.org/10.1111/cas.14397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293083PMC
June 2020

Discontinuation of new hepatitis C drugs among Medicare patients.

Am J Manag Care 2020 02;26(2):84-88

Department of Health Policy and Administration, College of Health and Human Development, The Pennsylvania State University, 601E Ford Bldg, University Park, PA 16801. Email:

Objectives: To examine factors associated with discontinuation of new hepatitis C drugs-second-generation direct-acting antivirals (DAAs)-among Medicare beneficiaries with chronic hepatitis C.

Study Design: A retrospective analysis using 2014-2016 Medicare claims.

Methods: The study population was patients with chronic hepatitis C in fee-for-service Medicare with Part D who initiated a DAA therapy between January 1, 2014, and September 1, 2016. We defined discontinuation of DAA therapy as filling prescriptions for fewer weeks than the expected duration of the DAA identified. We estimated adjusted odds ratios (aORs) of DAA discontinuation by patient characteristics using multivariable logistic regression. We estimated the model separately for patients with a Part D low-income subsidy (LIS) and those without an LIS.

Results: Of 82,056 patients who initiated a DAA therapy during the study period, 5171 (6.3%) did not complete the therapy. Discontinuation rates varied across DAAs, ranging from 4.7% (elbasvir/grazoprevir) to 11.8% (ombitasvir/paritaprevir/ritonavir/dasabuvir). Women with an LIS were more likely to discontinue DAA therapy than men with an LIS (aOR, 1.16; 95% CI, 1.08-1.25; P <.01). Non-LIS black and Hispanic patients had higher odds of discontinuation than non-LIS white patients (black: aOR, 1.49; 95% CI, 1.28-1.73; P <.01; Hispanic: aOR, 1.56; 95% CI, 1.01-2.44; P <.05). High comorbidity index score increased the odds of DAA discontinuation among patients with an LIS.

Conclusions: Real-world discontinuation of DAA therapy was low, but it was 3 times more likely than in clinical trials and varied by patient characteristics. Efforts to increase DAA adherence would help lower patients' risk of developing resistance to future treatments and reduce potential waste of resources.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027667PMC
http://dx.doi.org/10.37765/ajmc.2020.42397DOI Listing
February 2020

Low Utilization of Direct-Acting Antiviral Agents in a Large National Cohort of HIV and HCV Coinfected Medicare Patients in the United States: Implications for HCV Elimination.

J Public Health Manag Pract 2020 Jan 30. Epub 2020 Jan 30.

Department of Medicine (Drs Du, Riley, and Whitener) Department of Public Health Sciences (Dr Du), and Department of Pharmacy (Dr Farrow), College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania; and Department of Health Policy and Administration, College of Health and Human Development, The Pennsylvania State University, University Park, Pennsylvania (Dr Jung and Ms Kalidindi).

Hepatitis C virus (HCV) infection is common in people living with HIV/AIDS (PLWHA). The advent of direct-acting antiviral agents (DAAs) has made HCV elimination a realistic goal. We conducted a retrospective cohort study using the US Medicare Fee-For-Service claims data and outpatient prescription drug data to assess the HCV DAA initiation and completion among newly diagnosed HIV-HCV-coinfected Medicare patients enrolled in 2014-2016. DAA initiation was defined as filling at least 1 prescription of DAAs during 2014-2016. DAA completion was defined as taking an 8-week or longer DAA treatment course for patients without cirrhosis and a 12-week or longer treatment duration for those with cirrhosis. Among 12 152 HIV-HCV-coinfected Medicare patients, 20.9% received the DAA treatment in 2014-2016. The average time from HCV diagnosis to DAA initiation was 277 days. The overall DAA completion rate was 92% among 2537 patients who used DAAs. Interventions are needed to improve DAA uptake in PLWHA.
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http://dx.doi.org/10.1097/PHH.0000000000001147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391052PMC
January 2020

Changes in Flavor Preference in a Cohort of Long-Term Electronic Cigarette Users.

Ann Am Thorac Soc 2020 05;17(5):573-581

Department of Public Health Sciences.

The use of electronic cigarettes (e-cigarettes) has rapidly increased in the United States, and thousands of e-cigarette flavors are available. However, there remains a dearth of evidence on e-cigarette flavor use patterns among older e-cigarette users. This longitudinal study examined changes in flavor use patterns in long-term e-cigarette users, assessed self-reported adverse reactions, and evaluated users' anticipated reactions to possible U.S. Food and Drug Administration e-cigarette flavor regulatory scenarios. The study population was 383 adult participants who completed two online e-cigarette surveys in 2012-2014 (baseline survey) and in 2017-2019 (follow-up survey). In both surveys, participants were asked, "Thinking about your preferred liquid, what is the name of this liquid flavor?" and to list all flavors used in the past 30 days. Flavor preference was classified using the Penn State Three-Step Flavor Classification method. Participants reported adverse events (open-ended description) with the associated flavor. Regulatory scenarios were presented, and participants selected perceived actions from among a list of 15 options. Participants' age averaged 44 ± 12 years; 86% were exclusive e-cigarette users, and 13% reported "poly-use" (i.e., e-cigarette and other tobacco product use). E-cigarette flavor preference migration occurred in all demographic groups: only 36-44% maintained a preference for their original flavor. Preference for tobacco and menthol or mint decreased over time (40% baseline vs. 22% follow-up); preference for fruit remained stable (23% baseline and follow-up), but chocolate/candy or other sweets preference significantly increased (16% baseline vs. 29% follow-up), and other flavors increased slightly. Migration to sweet flavors was more noticeable in younger adults (18-45 yr); exclusive e-cigarette users preferred sweet flavors more commonly than poly-users did (31% vs. 19%). Flavor-associated adverse reactions, mainly respiratory irritations, were reported by 26 (6.9%) participants. Nearly 50% of the participants reported that they would "find a way" to buy their preferred flavor or add flavoring agents themselves if nontobacco flavors were banned. Flavor migration toward sweet flavors occurred in long-term e-cigarette users, a trend most pronounced in younger and exclusive e-cigarette users. The anticipated maintenance of access to flavors despite regulation suggests an element of e-cigarette-related dependence that requires further evaluation. This information could help clinicians understand the health impacts of e-cigarette flavors, develop appropriate strategies for smoking cessation, and inform the U.S. Food and Drug Administration to plan future regulation of e-cigarette flavors.
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http://dx.doi.org/10.1513/AnnalsATS.201906-472OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193816PMC
May 2020