Publications by authors named "Tri Le"

55 Publications

The complete mitochondrial genome of the Indian leafwing butterfly (insecta: Lepidoptera: Nymphalidae).

Mitochondrial DNA B Resour 2021 Jan 27;6(1):274-277. Epub 2021 Jan 27.

Department of Biological Sciences, University of Manitoba, Winnipeg, Canada.

The Indian leafwing butterfly (Horsfield, 1829) (Nymphalidae) is an Asian forest-dwelling, leaf-mimic. Genome skimming by Illumina sequencing permitted assembly of a complete circular mitogenome of 15,200 bp from consisting of 79.5% AT nucleotides, 22 tRNAs, 13 protein-coding genes, two rRNAs and a control region in the typical butterfly gene order. features an atypical CGA start codon, while , , and exhibit incomplete stop codons completed by 3' A residues added to the mRNA. Phylogenetic reconstruction places within the monophyletic genus , sister to in the subfamily Nymphalinae. These data support the monophyly of tribe Kallimini and contribute to the evolutionary systematics of the Nymphalidae.
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http://dx.doi.org/10.1080/23802359.2020.1862000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850329PMC
January 2021

Feasibility of ecological momentary assessment to study depressive symptoms among cancer caregivers.

Psychooncology 2021 Jan 11. Epub 2021 Jan 11.

Department of Psychiatry and Neurobehavioral Sciences, Center for Behavioral Health and Technology, University of Virginia, Charlottesville, Virginia, USA.

Objective: Ecological momentary assessment (EMA) may help with the development of more targeted interventions for caregivers' depression, yet the use of this method has been limited among cancer caregivers. This study aimed to demonstrate the feasibility of EMA among cancer caregivers and the use of EMA data to understand affective correlates of caregiver depressive symptoms.

Methods: Caregivers (N = 25) completed a depressive symptom assessment (Patient Health Questionnaire-8) and then received eight EMA survey prompts per day for 7 days. EMA surveys assessed affect on the orthogonal dimensions of valence and arousal. Participants completed feedback surveys regarding the EMA protocol at the conclusion of the week-long study.

Results: Of 32 caregivers approached, 25 enrolled and participated (78%), which exceeded the a priori feasibility cutoff of 55%. The prompt completion rate (59%, or 762 of 1,286 issued) did not exceed the a priori cutoff of 65%, although completion was not related to caregivers' age, employment status, physical health quality of life, caregiving stress, or depressive symptoms or the patients' care needs (ps > 0.22). Caregivers' feedback about their study experience was generally positive. Mixed-effects location scale modeling showed caregivers' higher depressive symptoms were related to overall higher reported negative affect and lower positive affect, but not to affective variability.

Conclusions: Findings from this feasibility study refute potential concerns that an EMA design is too burdensome for distressed caregivers. Clinically, findings suggest the potential importance of not only strategies to reduce overall levels of negative affect, but also to increase opportunities for positive affect.
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http://dx.doi.org/10.1002/pon.5627DOI Listing
January 2021

Prevalence and Significance of Potential Pharmacokinetic Drug-Drug Interactions Among Patients with Lung Cancer: Implications for Clinical Trials.

Clin Drug Investig 2021 Feb 8;41(2):161-167. Epub 2021 Jan 8.

Pharmacy Practice, Texas Tech University Health Sciences Center, 5920 Forest Park Rd, Suite 400, Dallas, TX, 75235, USA.

Background: The overall prevalence of potential drug-drug interactions (DDIs) among patients with lung cancer is unknown.

Objective: The objective of this study was to determine the prevalence of potential DDIs and major DDIs among individuals newly diagnosed with lung cancer in a national cohort.

Patients And Methods: We performed a retrospective cross-sectional study of adult patients in the United States Veterans' Affairs (VA) medical system diagnosed with lung cancer between 2003 and 2016. The primary endpoint was the prevalence of prescriptions for medications associated with any potential DDIs during the 3 months leading up to and including the date of lung cancer diagnosis. The secondary endpoint was the prevalence of prescriptions associated with major DDIs during the same time period.

Results: Overall, 280,068 patients were included in the study; 55.9% of patients were prescribed medications associated with potential DDIs, while 5.3% received prescriptions for medications associated with major DDIs. Among the 20 most commonly prescribed drugs associated with potential DDIs, only two were associated with major DDIs.

Conclusion: Medications with potential DDIs are prescribed to the majority of patients with lung cancer; however, only about 5% of patients are prescribed medications with major DDIs that might be prohibited in certain clinical trials.
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http://dx.doi.org/10.1007/s40261-020-00994-4DOI Listing
February 2021

Primary sludge fermentate as carbon source for mainstream partial denitrification-anammox (PdNA).

Water Environ Res 2020 Dec 4. Epub 2020 Dec 4.

DC Water and Sewer Authority, Washington, DC, USA.

Primary sludge fermentate, a concentrated hydrolyzed wastewater carbon, was evaluated for use as an alternative carbon source for mainstream partial denitrification-anammox (PdNA) in a suspended growth activated sludge process in terms of partial denitrification (PdN) efficiency, PdNA nitrogen removal contributions, and final effluent quality. Fermenter operation at a 2-day sludge retention time (SRT) resulted in the maximum achievable yield of 0.14 ± 0.05 g sCOD/g VSS without release of excessive ammonia and phosphorus to the system. Based on the results of batch experiments, fermentate addition led to PdN efficiency of 93 ± 14%, which was similar to acetate at a nitrate residual of 2-3 mg N/L. In the pilot-scale mainstream deammonification reactor, PdN efficiency using fermentate was 49 ± 24%, which was lower than acetate (66 ± 24% during acetate period I and 70 ± 21% during acetate period II), most probably due to lower nitrate and ammonium kinetics in the PdN zone. Methanol cost-saving potential for the application of PdNA as the main short-cut nitrogen pathway was estimated to be 30% to 55% depending on the PdN efficiency achieved. PRACTITIONER POINTS: Primary sludge fermentate was evaluated as an alternative carbon source for mainstream partial denitrification-anammox (PdNA). Fermenter operated at a 1 to 2 day SRT resulted in the maximum achievable yield without the release of excessive ammonia and phosphorus to the system. Although 93% partial denitrification efficiency was achieved with fermentate in batch experiments, around 49% PdN efficiency was achieved in pilot studies. Application of PdNA with fermentate can result in significant methanol cost savings.
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http://dx.doi.org/10.1002/wer.1492DOI Listing
December 2020

Blood extracellular vesicles from healthy individuals regulate hematopoietic stem cells as humans age.

Aging Cell 2020 11 7;19(11):e13245. Epub 2020 Oct 7.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

Hematopoietic stem cells (HSCs) maintain balanced blood cell production in a process called hematopoiesis. As humans age, their HSCs acquire mutations that allow some HSCs to disproportionately contribute to normal blood production. This process, known as age-related clonal hematopoiesis, predisposes certain individuals to cancer, cardiovascular and pulmonary pathologies. There is a growing body of evidence suggesting that factors outside cells, such as extracellular vesicles (EVs), contribute to the disruption of stem cell homeostasis during aging. We have characterized blood EVs from humans and determined that they are remarkably consistent with respect to size, concentration, and total protein content, across healthy subjects aged 20-85 years. When analyzing EV protein composition from mass spectroscopy data, our machine-learning-based algorithms are able to distinguish EV proteins based on age and suggest that different cell types dominantly produce EVs released into the blood, which change over time. Importantly, our data show blood EVs from middle and older age groups (>40 years) significantly stimulate HSCs in contrast to untreated and EVs sourced from young subjects. Our study establishes for the first time that although EV particle size, concentration, and total protein content remain relatively consistent over an adult lifespan in humans, EV content evolves during aging and potentially influences HSC regulation.
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http://dx.doi.org/10.1111/acel.13245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681054PMC
November 2020

Antimicrobial and Efflux Pump Inhibitory Activity of Carvotacetones from Against Mycobacteria.

Antibiotics (Basel) 2020 Jul 8;9(7). Epub 2020 Jul 8.

Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria.

Carvotacetones () isolated from were screened for their antimycobacterial and efflux pump (EP) inhibitory potential against the mycobacterial model strains mc 155, ATCC 23366, and BCG ATCC 35734. The minimum inhibitory concentrations (MICs) of the carvotacetones were detected through high-throughput spot culture growth inhibition (HT-SPOTi) and microbroth dilution assays. In order to assess the potential of the compounds and to accumulate ethidium bromide (EtBr) in and , a microtiter plate-based fluorometric assay was used to determine efflux activity. Compounds and were analyzed for their modulating effects on the MIC of EtBr and the antibiotic rifampicin (RIF) against . Carvotacetones and had potent antibacterial effects on and BCG (MIC ≤ 31.25 mg/L) and could successfully enhance EtBr activity against . Compound appeared as the most efficient agent for impairing the efflux mechanism in . Both compounds and were highly effective against and BCG. In particular, compound was identified as a valuable candidate for inhibiting mycobacterial efflux mechanisms and as a promising adjuvant in the therapy of tuberculosis or other non-tubercular mycobacterial infections.
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http://dx.doi.org/10.3390/antibiotics9070390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400215PMC
July 2020

Lemon Grass Essential Oil Does not Modulate Cancer Cells Multidrug Resistance by Citral-Its Dominant and Strongly Antimicrobial Compound.

Foods 2020 May 5;9(5). Epub 2020 May 5.

Department of Biochemistry and Microbiology UCT Prague, Faculty of Food and Biochemical Technology, Technicka 3, 166 28 Prague, Czech Republic.

With strong antimicrobial properties, citral has been repeatedly reported to be the dominant component of lemongrass essential oil. Here, we report on a comparison of the antimicrobial and anticancer activity of citral and lemongrass essential oil. The lemongrass essential oil was prepared by the vacuum distillation of fresh leaves, with a yield of 0.5% (). Citral content was measured by gas chromatography/high-resolution mass spectrometry (GC-HRMS) and determined to be 63%. Antimicrobial activity was tested by the broth dilution method, showing strong activity against all tested bacteria and fungi. Citral was up to 100 times more active than the lemongrass essential oil. Similarly, both citral and essential oils inhibited bacterial communication and adhesion during and biofilm formation; however, the biofilm prevention activity of citral was significantly higher. Both the essential oil and citral disrupted the maturated biofilm with the IC 7.3 ± 0.4 and 0.1 ± 0.01 mL/L, respectively. Although it may seem that the citral is the main biologically active compound of lemongrass essential oil and the accompanying components have instead antagonistic effects, we determined that the lemongrass essential oil-sensitized methicillin-resistant (MRSA) and doxorubicin-resistant ovarian carcinoma cells and that this activity was not caused by citral. A 1 mL/L dose of oil-sensitized MRSA to methicillin up to 9.6 times and a dose of 10 µL/L-sensitized ovarian carcinoma to doxorubicin up to 1.8 times. The mode of multidrug resistance modulation could be due to P-glycoprotein efflux pump inhibition. Therefore, the natural mixture of compounds present in the lemongrass essential oil provides beneficial effects and its direct use may be preferred to its use as a template for citral isolation.
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http://dx.doi.org/10.3390/foods9050585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278871PMC
May 2020

Rates of appropriate laxative prophylaxis for opioid-induced constipation in veterans with lung cancer: a retrospective cohort study.

Support Care Cancer 2020 Nov 2;28(11):5315-5321. Epub 2020 Mar 2.

School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, TX, USA.

Purpose: Opioid-induced constipation (OIC) is the most common side effect in patient-prescribed opioids for cancer pain treatment. Current guidelines recommend routine prescription of a laxative for preventing OIC in all patients prescribed an opioid unless a contraindication exists. We determined patterns of prescription of laxative agents in patients with lung cancer initiating opioids.

Methods: We performed a retrospective cohort study evaluating the prescription of laxatives for OIC to adult patients with incident lung cancer seen in the Veteran's Affairs (VA) system, between January 1, 2003, and December 31, 2016. Exposure to laxative agents was categorized as follows: none, docusate monotherapy, docusate plus another laxative, and other laxatives only. Prevalence of OIC prophylaxis was analyzed using descriptive statistics. Linear regression was performed to identify time trends in the prescription of OIC prophylaxis.

Results: Overall, 130,990 individuals were included in the analysis. Of these, 87% of patients received inadequate prophylaxis (75% no prophylaxis and 12% docusate alone), while 5% received OIC prophylaxis with the unnecessary addition of docusate to another laxative. Through the study period, laxative prescription significantly decreased, while all other categories of OIC prophylaxis were unchanged. We noted an inverse relationship with OIC prophylaxis and likelihood of a diagnosis of constipation at 3 and 6 months.

Conclusions: In this study of veterans with lung cancer, almost 90% received inadequate or inappropriate OIC prophylaxis. Efforts to educate physicians and patients to promote appropriate OIC prophylaxis in combination with systems-level changes are warranted.
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http://dx.doi.org/10.1007/s00520-020-05364-6DOI Listing
November 2020

Superiority of high sensitivity cardiac troponin T vs. I for long-term prognostic value in patients with chest pain; data from the Akershus cardiac Examination (ACE) 3 study.

Clin Biochem 2020 Apr 31;78:10-17. Epub 2019 Dec 31.

Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway; Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address:

Background: Cardiac troponins (cTn) are essential in the diagnostic assessment of non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Elevated concentrations of cTnT and cTnI predict cardiovascular events in non-acute settings, but the individual troponin isotype association with long-term mortality in patients with suspected unstable angina pectoris (UAP) is less clear.

Methods: Patients hospitalized with chest pain between June 2009 and December 2010 were included in the Akershus Cardiac Examination 3 Study and followed for median 6.6 (IQR 6.2-7.1) years. The index diagnosis was adjudicated by an independent committee as NSTE-myocardial infarction (NSTEMI), UAP or non-ACS. Blood samples were collected within 24 h of admission and analyzed with high sensitivity assays for cTnT (hs-cTnT, Roche) and cTnI (hs-cTnI, Singulex).

Results: Of 402 patients included, 74 (18%) were classified as NSTEMI, 88 (22%) UAP and 240 (60%) non-ACS. hs-cTnI concentrations were detectable in all patients (median 3 [IQR 1-11] ng/L), while hs-cTnT concentrations were above the level of blank in 205 (51%) (median 3 [IQR 3-16] ng/L). In patients with UAP, both log-transformed hs-cTnT and hs-cTnI were associated with all-cause mortality in analyses that adjusted for other risk factors: HR 2.40 [95% CI 1.75-3.30], p < 0.001 and HR 1.44 [1.14-1.81], p = 0.002. There were no significant sex-dependent differences in the association between hs-cTnT or hs-cTnI and outcome. Time dependent receiver-operating characteristics area under the curve was 0.85 (95% CI 0.79-0.92) for hs-cTnT and 0.74 (0.64-0.84) for hs-cTnI, p = 0.008 for difference between values.

Conclusions: Higher concentrations of hs-cTnT and hs-cTnI were both associated with all-cause mortality in patients with UAP, but the association with outcome was stronger for hs-cTnT than for hs-cTnI.
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http://dx.doi.org/10.1016/j.clinbiochem.2019.12.016DOI Listing
April 2020

QTc Interval-Prolonging Medications Among Patients With Lung Cancer: Implications for Clinical Trial Eligibility and Clinical Care.

Clin Lung Cancer 2020 01 25;21(1):21-27.e5. Epub 2019 Nov 25.

Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX; Division of Hematology-Oncology, UT Southwestern Medical Center, Dallas, TX; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX; Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX. Electronic address:

Background: Concomitant medication use, including agents that prolong the corrected QT (QTc) interval, can result in the exclusion of patients with cancer from clinical trials. To estimate the potential effects on accrual, we determined the prevalence of QTc-prolonging medication prescriptions in a national patient cohort.

Patients And Methods: We identified adult patients in the Veterans Affairs system with a diagnosis of lung cancer from 2003 to 2016. The use of QTc interval-prolonging medications and risk category were obtained from CredibleMeds. We calculated the prevalence of prescriptions for QTc-prolonging medications with a known or possible risk of torsade de pointes in the 3 months up to and including the date of cancer diagnosis. The rates across patient groups were compared using χ test.

Results: A total of 280,068 patients were included in the present study. The mean age was 70 years, 98% were male, and 72% were white. Overall, 28.4% had been prescribed a QTc-prolonging medication, and 7.3% had been prescribed ≥2 in the 3 months before the cancer diagnosis. The most commonly prescribed QTc-prolonging medications were antimicrobial agents (14.0%), psychiatric agents (10.2%), antiemetic agents (2.6%), and cardiac medications (1.7%). Excluding the antimicrobial agents, 18.4% of the patients had been prescribed a QTc-prolonging medication.

Conclusions: A substantial proportion of individuals with lung cancer will be prescribed QTc-prolonging medications. These prescriptions can limit patients' eligibility for clinical trials and complicate the administration of standard cancer therapies. Further research into the actual clinical risks and optimal management of QTc-prolonging medications in cancer populations is warranted.
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http://dx.doi.org/10.1016/j.cllc.2019.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937372PMC
January 2020

Minimally Invasive Mitral Valve Surgery for Rheumatic Valve Disease.

Heart Surg Forum 2019 Sep 24;22(5):E390-E395. Epub 2019 Sep 24.

Department of Cardiovascular Surgery, University Medical Center, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam.

Background: The development of minimally invasive mitral valve surgery has created the motivation for using this approach in young patients with chronic rheumatic valve disease. We report our recent experience with patients undergoing minimally mitral valve surgery in this group of patients.

Methods: Between July 2014 and June 2018, 142 patients with rheumatic mitral valve dysfunction underwent minimally invasive surgery through a right thoracotomy approach at the University Medical Center of Ho Chi Minh City in Vietnam. Diagnosis was confirmed with transthoracic and transesophageal echocardiography (TTE and TEE). We analyzed the in-hospital and midterm follow-up outcomes of this group.

Results: The mean age was 42.6 ± 9.6 years. Sixty patients (42.3%) were male. Sixty-three patients were diagnosed with functional severe tricuspid regurgitation, 29 patients were identified with moderate tricuspid regurgitation, and tricuspid annulus was more than 21 mm/m²). Mitral valve repair was performed in 16 patients (11.3%), and 126 patients underwent mitral valve replacement. Mitral valve repair techniques included annuloplasty, leaflet peeling, and commissurotomy. Thirty-day mortality was 0.7%. Two patients had to be converted to conventional sternotomy, due to left atrial appendage laceration and mitral annular rupture. The overall survival rate was 98.6%. Freedom from reoperation was 97.1%.

Conclusions: In patients with rheumatic valve disease, minimally invasive mitral surgery safely and effectively can be performed with few perioperative complications and good midterm results.
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http://dx.doi.org/10.1532/hsf.2529DOI Listing
September 2019

Comparative Effectiveness of Lymphadenectomy Strategies During Curative Resection for Gastric Adenocarcinoma.

J Gastrointest Surg 2020 10 12;24(10):2212-2218. Epub 2019 Sep 12.

Department of Surgery, Division of Surgical Oncology, University of Virginia School of Medicine, PO Box 800709, Charlottesville, VA, 22908-0679, USA.

Background: The purpose of this study was to compare the long-term effectiveness of three lymphadenectomy strategies in patients with gastric cancer. We hypothesized that, compared with the traditional standard (D2) lymph node dissection strategy, the less aggressive modified standard (mD2) lymphadenectomy may offer superior effectiveness due to reduced operative morbidity and comparable long-term recurrence-free survival.

Methods: A Markov decision analysis model was created to simulate 5-year outcomes across three lymphadenectomy approaches for gastric cancer: limited regional (D1), traditional standard (D2), and modified standard (mD2). The primary outcome was discounted quality-adjusted life-years (dQALY). Model variable estimates were derived from outcomes data and quality of life estimates published in Europe and America within the last 15 years. One-way and probabilistic sensitivity analyses were performed for clinically relevant variables.

Results: The mD2 lymphadenectomy offered 3.03 dQALY over 5 years, outperforming D2 (2.62 dQALY) and D1 (2.37 dQALY). Monte Carlo simulations indicated that both mD2 and D2 lymph node dissection strategies outperformed D1 in 94.9% of simulations. Sensitivity analyses demonstrated that the mD2 approach would be less effective than D2 if the perioperative mortality rate of mD2 was greater than 6.9% (3.2% baseline).

Conclusions: Across modern series, the modified standard mD2 lymphadenectomy is an effective alternative to the traditional D2 lymphadenectomy for patients with gastric cancer. A D1-limited regional lymphadenectomy is not recommended during gastric cancer resection.
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http://dx.doi.org/10.1007/s11605-019-04393-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065947PMC
October 2020

Nitrate residual as a key parameter to efficiently control partial denitrification coupling with anammox.

Water Environ Res 2019 Nov 4;91(11):1455-1465. Epub 2019 Jun 4.

DC Water and Sewer Authority, Washington, District of Columbia.

Despite the increased research efforts, full-scale implementation of shortcut nitrogen removal strategies has been challenged by the lack of consistent nitrite-oxidizing bacteria out-selection. This paper proposes an alternative path using partial denitrification (PdN) selection coupled with anaerobic ammonium-oxidizing bacteria (AnAOB). A nitrate residual concentration (>2 mg N/L) was identified as the crucial factor for metabolic PdN selection using acetate as a carbon source, unlike the COD/N ratio which was often suggested. Therefore, a novel and simple acetate dosing control strategy based on maintaining a nitrate concentration was tested in the absence and presence of AnAOB, achieving PdN efficiencies above 80%. The metabolic-based PdN selection allowed for flexibility to move between PdN and full denitrification when required to meet effluent nitrate levels. Due to the independence of this strategy on species selection and management of nitrite competition, this novel approach will guarantee nitrite availability for AnAOB under mainstream conditions unlike shortcut nitrogen removal approaches based on NOB out-selection. Overall, a COD addition of only 2.2 g COD/g TIN removed was needed for the PdN-AnAOB concept showing its potential for significant savings in external carbon source needs to meet low TIN effluent concentrations making this concept a competitive alternative. PRACTITIONER POINTS: Nitrate residual is the key control parameter for partial denitrification selection. Metabolic selection allowed for flexibility of moving from partial to full denitrification. 2.2 g COD/g TIN removed was needed for partial denitrification-anammox process.
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http://dx.doi.org/10.1002/wer.1140DOI Listing
November 2019

Newer-Generation EGFR Inhibitors in Lung Cancer: How Are They Best Used?

Cancers (Basel) 2019 Mar 15;11(3). Epub 2019 Mar 15.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8852, USA.

The FLAURA trial established osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), as a viable first-line therapy in non-small cell lung cancer (NSCLC) with sensitizing mutations, namely exon 19 deletion and L858R. In this phase 3 randomized, controlled, double-blind trial of treatment-naïve patients with mutant NSCLC, osimertinib was compared to standard-of-care EGFR TKIs (i.e., erlotinib or gefinitib) in the first-line setting. Osimertinib demonstrated improvement in median progression-free survival (18.9 months vs. 10.2 months; hazard ratio 0.46; 95% CI, 0.37 to 0.57; < 0.001) and a more favorable toxicity profile due to its lower affinity for wild-type EGFR. Furthermore, similar to later-generation anaplastic lymphoma kinase (ALK) inhibitors, osimertinib has improved efficacy against brain metastases. Despite this impressive effect, the optimal sequencing of osimertinib, whether in the first line or as subsequent therapy after the failure of earlier-generation EGFR TKIs, is not clear. Because up-front use of later-generation TKIs may result in the inability to use earlier-generation TKIs, this treatment paradigm must be evaluated carefully. For mutant NSCLC, considerations include the incidence of T790M resistance mutations, quality of life, whether there is a potential role for earlier-generation TKIs after osimertinib failure, and overall survival. This review explores these issues for EGFR inhibitors and other molecularly targeted therapies.
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http://dx.doi.org/10.3390/cancers11030366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468595PMC
March 2019

Checkpoint Inhibitor Pneumonitis: Too Clinically Serious For Benefit?

J Thorac Oncol 2019 03;14(3):332-335

Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2018.12.017DOI Listing
March 2019

Impact of carbon source and COD/N on the concurrent operation of partial denitrification and anammox.

Water Environ Res 2019 Mar 30;91(3):185-197. Epub 2019 Jan 30.

DC Water and Sewer Authority, Washington, District of Columbia.

In this study, concurrent operation of anammox and partial denitrification within a nonacclimated mixed culture system was proposed. The impact of carbon sources (acetate, glycerol, methanol, and ethanol) and COD/NO3 -N ratio on partial denitrification selection under both short- and long-term operations was investigated. Results from short-term testing showed that all carbon sources supported partial denitrification. However, acetate and glycerol were preferred due to their display of efficient partial denitrification selection, which may be related to their different electron transport pathways in comparison with methanol. Long-term operation confirmed results of batch tests by showing the contribution of partial denitrification to nitrate removal above 90% after acclimation in both acetate and glycerol reactors. In contrast, methanol showed challenges of maintaining efficient partial denitrification. COD/NO3 -N ratio mainly controlled the rate of nitrate reduction and not directly partial denitrification selection; thus, it should be used to balance between denitrification rate and anammox rate. PRACTITIONER POINTS: The authors aimed to investigate the impact of carbon sources and COD/NO3-N ratio on partial denitrification selection. All the carbon sources supported partial denitrification as long as the nitrite sink was available. 90% partial denitrification could be achieved with both acetate and glycerol in long-term operations. COD/NO3-N ratio did not directly control partial denitrification but can be used to balance between denitrification rate and anammox rate.
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http://dx.doi.org/10.1002/wer.1016DOI Listing
March 2019

Implementing a Chronic Wound Care Workshop for Internal Medicine Residents.

Adv Skin Wound Care 2019 Feb;32(2):85-87

Elizabeth Foy White-Chu, MD, CWSP, AGSF, is Assistant Professor of Medicine, Oregon Health and Science University; Tri Le, MD, is Geriatrician, Adena Medical Group; and Renee Cordrey, PhD(c), MSPT, MPH, PT, CWS, is Rehabilitation Director, HealthPRO Heritage at Home. Acknowledgments: The authors thank the Scholarship and Innovation Petal of the Educational Consortium at Oregon Health and Science University for providing support for this article. The authors have disclosed no financial relationships related to this article. Submitted May 8, 2018; accepted July 11, 2018.

Objective: To determine the feasibility of a piloted wound care curriculum within a busy internal medicine (IM) curriculum.

Methods: This prospective pilot study was conducted with 89 IM residents at an academic teaching hospital. The residents were provided a 90-minute workshop in chronic wound care. They anonymously completed a clinical vignette to target practice behavior prior to the workshop. The workshop was mixture of didactic and hands-on practice of sharp debridement and wound dressing selection. Three months later, the residents completed the same clinical vignette along with questions on changes and barriers to change in their practice.

Main Outcome Measures: Change in behavior of chronic wound care management, measurements of barriers to change in participant continuity clinics.

Main Results: Of the participants, 57 residents (64%) and 25 residents (28%) completed a pre- and postvignette, respectively. Ten (40%) of the postvignette respondents stated that they had made changes in their care. Barriers to change included having a supervising attending physician who is not comfortable with wound care, a lack of wound care resources available in clinic, and a lack of confidence even after the session.

Conclusions: It is feasible to insert a chronic wound care education into a busy IM curriculum. Future efforts will be aimed at assessing the wound care needs/resources of the IM outpatient clinics, addressing the comfort of the supervising attending physicians and residents with wound care, and focusing the curriculum on high-yield interventions.
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http://dx.doi.org/10.1097/01.ASW.0000549609.21974.6fDOI Listing
February 2019

Improved Survival Outcomes for Kidney Cancer Patients With Brain Metastases.

Clin Genitourin Cancer 2019 04 5;17(2):e263-e272. Epub 2018 Dec 5.

Kidney Cancer Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX; Division of Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX. Electronic address:

Background: Brain metastases (BM) occur frequently in patients with metastatic kidney cancer and are a significant source of morbidity and mortality. Although historically associated with a poor prognosis, survival outcomes for patients in the modern era are incompletely characterized. In particular, outcomes after adjusting for systemic therapy administration and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors are not well-known.

Patients And Methods: A retrospective database of patients with metastatic renal cell carcinoma (RCC) treated at University of Texas Southwestern Medical Center between 2006 and 2015 was created. Data relevant to their diagnosis, treatment course, and outcomes were systematically collected. Survival was analyzed by the Kaplan-Meier method. Patients with BM were compared with patients without BM after adjusting for the timing of BM diagnosis, either prior to or during first-line systemic therapy. The impact of stratification according to IMDC risk group was assessed.

Results: A total of 56 (28.4%) of 268 patients with metastatic RCC were diagnosed with BM prior to or during first-line systemic therapy. Median overall survival (OS) for systemic therapy-naive patients with BM compared with matched patients without BM was 19.5 versus 28.7 months (P = .0117). When analyzed according to IMDC risk group, the median OS for patients with BM was similar for favorable- and intermediate-risk patients (not reached vs. not reached; and 29.0 vs. 36.7 months; P = .5254), and inferior for poor-risk patients (3.5 vs. 9.4 months; P = .0462). For patients developing BM while on first-line systemic therapy, survival from the time of progression did not significantly differ by presence or absence of BM (11.8 vs. 17.8 months; P = .6658).

Conclusions: Survival rates for patients with BM are significantly better than historical reports. After adjusting for systemic therapy, the survival rates of patients with BM in favorable- and intermediate-risk groups were remarkably better than expected and not statistically different from patients without BM, though this represents a single institution experience, and numbers are modest.
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http://dx.doi.org/10.1016/j.clgc.2018.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534272PMC
April 2019

VIETHERB: A Database for Vietnamese Herbal Species.

J Chem Inf Model 2019 01 3;59(1):1-9. Epub 2018 Dec 3.

Computational Biology Center , International University-VNU , Ho Chi Minh City 700000 , Vietnam.

Vietnam carries a highly diverse practice of traditional medicine in which various combinations of herbs have been widely used as remedies for many types of diseases. Poor hand-written records and current text-based databases, however, perplex the process of conventionalizing and evaluating canonical therapeutic effects. In efforts to reorganize the valuable information, we provide the VIETHERB database ( http://vietherb.com.vn/ ) for herbs documented in Vietnamese traditional medicines. This database is constructed with confidence to provide users with information on herbs and other side information including metabolites, diseases, morphologies, and geographical locations for each individual species. Our data in this release consist of 2,881 species, 10,887 metabolites, 458 geographical locations, and 8,046 therapeutic effects. The numbers of species-metabolite, species-therapeutic effect, species-morphology, and species-distribution binary relationships are 17,602, 2,718, 11,943, and 16,089, respectively. The information on Vietnamese herbal species can be easily accessed or queried using their scientific names. Searching for species sharing side information can be simply done by clicking on the data. The database primarily serves as an open source facilitating users in studies of modernizing traditional medicine, computer-aided drug design, conservation of endangered plants, and other relevant experimental sciences.
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http://dx.doi.org/10.1021/acs.jcim.8b00399DOI Listing
January 2019

Safety and effectiveness of apixaban compared to warfarin in dialysis patients.

Res Pract Thromb Haemost 2018 Apr 26;2(2):291-298. Epub 2018 Mar 26.

Division of Hematology & Oncology University of Virginia Charlottesville VA USA.

The use of apixaban for stroke prophylaxis or for the treatment of venous thromboembolism in end stage renal disease (ESRD) patients maintained on dialysis is based on one single-dose pharmacokinetic study. There is a deficiency of clinical evidence supporting safety in this population. The purpose of this study was to determine the safety and efficacy of apixaban compared with warfarin in dialysis patients. This is a retrospective cohort study conducted at the University of Virginia Medical Center. A total of 124 ESRD patients maintained on dialysis who either received apixaban (n = 74) or warfarin (n = 50) between January 1, 2014 and October 31, 2016 were included in the study. We used multivariable logistic regression to compare the likelihood of patients experiencing a bleeding event based on anticoagulant therapy. The apixaban group experienced fewer overall bleeding events than the warfarin group (18.9% vs 42.0%; =.01); this significant difference persisted in adjusted analysis (OR = 0.15; 95% CI = 0.05-0.46; =.001). Major bleeding events were less frequent in the apixaban group compared with patients on warfarin (5.4% vs 22.0%; =.01). There were no recurrent ischemic strokes in either groups. A lower, non-significant, incidence of recurrent VTE was found in patients on apixaban compared with warfarin (4.4% vs 28.6%; =.99). Compared to warfarin, our findings suggest that apixaban is a safe and effective alternative in patients with ESRD maintained on dialysis, with apixaban patients experiencing fewer bleeding events than warfarin patients.
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http://dx.doi.org/10.1002/rth2.12083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055495PMC
April 2018

Variation in mortality rates after admission to long-term acute care hospitals for ventilator weaning.

J Crit Care 2018 08 23;46:6-12. Epub 2018 Mar 23.

CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Department of Health Policy & Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, United States.

Purpose: We sought to examine variation in long-term acute care hospital (LTACH) quality based on 90-day in-hospital mortality for patients admitted for weaning from mechanical ventilation.

Methods: We developed an administrative risk-adjustment model using data from Medicare claims. We validated the administrative model against a clinical model using data from LTACHs participating in a 2002 to 2003 clinical registry. We then used our validated administrative model to assess national variation in 90-day in-hospital mortality rates in LTACHs from 2013.

Results: The administrative risk-adjustment model was derived using data from 9447 patients admitted to 221 LTACHs in 2003. The model had good discrimination (C statistic=0.72) and calibration. Compared to a clinically derived model using data from 1163 patients admitted to 14 LTACHs, the administrative model generated similar performance estimates. National variation in risk-adjusted mortality was assessed using data from 20,453 patients admitted to 380 LTACHs in 2013. LTACH-specific risk-adjusted mortality rates varied from 8.4% to 48.1% (median: 24.2%, interquartile range: 19.7%-30.7%).

Conclusions: LTACHs vary widely in mortality rates, underscoring the need to better understand the sources of this variation and improve the quality of care for patients requiring long-term ventilator weaning.
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http://dx.doi.org/10.1016/j.jcrc.2018.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014911PMC
August 2018

Kinetics of CO and CO with N and O atoms.

J Chem Phys 2018 Feb;148(8):084305

University of North Florida, Jacksonville, Florida 32224, USA.

We have measured reaction rate constants for CO and CO reacting with N and O atoms using a selected ion flow tube apparatus equipped with a microwave discharge atom source. Experimental work was supplemented by molecular structure calculations. Calculated pathways show the sensitivity of kinetic barriers to theoretical methods and imply that high-level ab initio methods are required for accurate energetics. We report room-temperature rate constants of 1.0 ± 0.4 × 10 cm s and 4.0 ± 1.6 × 10 cm s for the reactions of CO with N and O atoms, respectively, and 8.0 ± 3.0 × 10 cm s and 2.0 ± 0.8 × 10 cm s for the reactions of CO with N and O atoms, respectively. The reaction of CO + O is observed to yield O exclusively. These values help resolve discrepancies in the literature and are important for modeling of the Martian atmosphere.
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http://dx.doi.org/10.1063/1.5011195DOI Listing
February 2018

Long-term peritoneal port-catheter in a patient with cardiac ascites.

BMJ Case Rep 2017 Jul 19;2017. Epub 2017 Jul 19.

Department of Cardiology, Akershus Universitetssykehus HF, Lorenskog, Norway.

A peritoneal port-catheter was inserted in a 70-year-old man because of repeated paracentesis due to cardiac ascites. Instead of frequent hospital admissions, the patient could drain his ascites at home, which dramatically improved his quality of life and enabled him to perform his daily activities.
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http://dx.doi.org/10.1136/bcr-2017-219258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534896PMC
July 2017

Implementing a Chronic Wound Care Curriculum for Internal Medicine Residents.

Wounds 2017 Jun;29(6):E36-E37

Oregon Health & Science University, Portland, OR.

Objective: The objective of this study was to determine if participation in a practice-based learning session would change the residents' reported wound care practice.

Methods: A 90-minute didactic and skills workshop in chronic wound care was provided to 89 internal medicine (IM) residents divided into 4 groups, who were asked to complete an anonymous clinical vignette survey prior to the session and again 3 months after the practice-based learning session.

Results: Comparisons of the pretest and posttest scores (Mann-Whitney U Test) showed only ordering moisture-retentive dressing changed significantly. Residents reported likelihood of preventing/managing wounds in their future career on a 10-point Likert scale (mean 4.92).

Conclusion: Future directions aimed at assessing the wound care needs/resources of the IM outpatient clinics, the comfort of the supervising clinicians and residents, and targeting the curriculum to those most likely to benefit should be addressed before further refining the curriculum.
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June 2017

dbVar structural variant cluster set for data analysis and variant comparison.

F1000Res 2016 13;5:673. Epub 2016 Apr 13.

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.

dbVar houses over 3 million submitted structural variants (SSV) from 120 human studies including copy number variations (CNV), insertions, deletions, inversions, translocations, and complex chromosomal rearrangements. Users can submit multiple SSVs to dbVAR  that are presumably identical, but were ascertained by different platforms and samples,  to calculate whether the variant is rare or common in the population and allow for cross validation. However, because SSV genomic location reporting can vary - including fuzzy locations where the start and/or end points are not precisely known - analysis, comparison, annotation, and reporting of SSVs across studies can be difficult. This project was initiated by the Structural Variant Comparison Group for the purpose of generating a non-redundant set of genomic regions defined by counts of concordance for all human SSVs placed on RefSeq assembly GRCh38 (RefSeq accession GCF_000001405.26). We intend that the availability of these regions, called structural variant clusters (SVCs), will facilitate the analysis, annotation, and exchange of SV data and allow for simplified display in genomic sequence viewers for improved variant interpretation. Sets of SVCs were generated by variant type for each of the 120 studies as well as for a combined set across all studies. Starting from 3.64 million SSVs, 2.5 million and 3.4 million non-redundant SVCs with count >=1 were generated by variant type for each study and across all studies, respectively. In addition, we have developed utilities for annotating, searching, and filtering SVC data in GVF format for computing summary statistics, exporting data for genomic viewers, and annotating the SVC using external data sources.
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http://dx.doi.org/10.12688/f1000research.8290.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345777PMC
April 2016

Histologic transformation of EGFR mutant lung adenocarcinoma without exposure to EGFR inhibition.

Lung Cancer 2017 03 11;105:14-16. Epub 2017 Jan 11.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States; The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address:

Resistance to EGFR kinase inhibitors appears to be invariable in the treatment of non-small cell lung cancer. Several mechanisms have been described. Here, we report the first case of histologic transformation of EGFR mutant lung adenocarcinoma without prior exposure to EGFR inhibition.
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http://dx.doi.org/10.1016/j.lungcan.2017.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330183PMC
March 2017

Upper lip metastasis of sarcomatoid carcinoma of the lung - an unusual site of disease: a case report.

J Med Case Rep 2017 Jan 19;11(1):18. Epub 2017 Jan 19.

Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, 2201 Inwood Road, 3rd Floor, Suite 500, Dallas, TX, 75390-9125, USA.

Background: Lip metastases are rare clinical events that are frequently mistaken for other diagnoses. For sarcomatoid lung carcinoma, a rare histologic variant of non-small cell lung cancer, the incidence and pattern of cutaneous spread is poorly understood.

Case Presentation: We present a case of a 79-year-old African American man with a rapidly progressive upper lip cutaneous lesion that provided the first evidence of distant metastatic spread of sarcomatoid lung carcinoma.

Conclusions: This is the first reported case of lip metastasis in sarcomatoid lung carcinoma. It highlights the importance of maintaining a high level of suspicion for metastatic disease in the presence of new cutaneous findings as they may be the first evidence of advanced disease.
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http://dx.doi.org/10.1186/s13256-016-1178-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244539PMC
January 2017

Determining Rate Constants and Mechanisms for Sequential Reactions of Fe with Ozone at 500 K.

J Phys Chem A 2017 Jan 20;121(1):24-30. Epub 2016 Dec 20.

Space Vehicles Directorate, Air Force Research Laboratory , Kirtland AFB, New Mexico 87117-5776, United States.

We present rate constants and product branching ratios for the reactions of FeO (x = 0-4) with ozone at 500 K. Fe is observed to react with ozone at the collision rate to produce FeO + O. The FeO in turn reacts with ozone at the collision rate to yield both Fe and FeO product channels. Ions up to FeO display similar reactivity patterns. Three-body clustering reactions with O prevent us from measuring accurate rate constants at 300 K although the data do suggest that the efficiency is also high. Therefore, it is probable that little to no temperature dependence exists over this range. Implications of our measurements to the regulation of atmospheric iron and ozone are discussed. Density functional calculations on the reaction of Fe with ozone show no substantial kinetic barriers to make the FeO + O product channel, which is consistent with the reaction's efficiency. While a pathway to make FeO + O is also found to be barrierless, our experiments indicate no primary FeO formation for this reaction.
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http://dx.doi.org/10.1021/acs.jpca.6b08971DOI Listing
January 2017

ALK alterations and inhibition in lung cancer.

Semin Cancer Biol 2017 02 13;42:81-88. Epub 2016 Sep 13.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address:

The advent of precision medicine in non-small cell lung cancer has remarkably altered the direction of research and improved clinical outcomes. The identification of molecular subsets with differential response to targeted therapies began with the identification of epidermal growth factor receptor mutated tumors in subsets of non-small cell lung cancer (NSCLC). Emboldened by unprecedented response rates to kinase inhibitors seen in that subset, the oncologic community searched for other molecular subsets featuring oncogene addiction. An early result of this search was the discovery of NSCLC driven by activating rearrangements of the anaplastic lymphoma kinase (ALK) gene. In an astoundingly brief period following the recognition of ALK-positive NSCLC, details of the biology, clinicopathologic features, development of targeted inhibitors, mechanisms of therapeutic resistance, and new generations of treatment were elucidated. This review summarizes the current understanding of the pathologic features, diagnostic approach, treatment options, resistance mechanisms, and future research areas for ALK-positive NSCLC.
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http://dx.doi.org/10.1016/j.semcancer.2016.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316306PMC
February 2017

α-Glucosidase inhibitors from the bark of Mangifera mekongensis.

Chem Cent J 2016 21;10:45. Epub 2016 Jul 21.

Faculty of Chemistry, University of Science, Vietnam National University Hochiminh City, 227 Nguyen Van Cu, District 5, Hochiminh City, Vietnam ; Cancer Research Laboratory, Vietnam National University Hochiminh City, 227 Nguyen Van Cu, District 5, Hochiminh City, Vietnam.

Background: Mangifera mekongensis (Anacardiaceae) is cultivated for its edible fruit and has been used in traditional Vietnamese medicine for its anti-aging properties and for treating diabetes, vermifuge, and dysentery. As part of a search for biologically active compounds with reduction of the rate of glucose absorption, a screening has been initiated to evaluate natural product extracts for the inhibition of enzyme α-glucosidase. A n-hexane extract of the bark of M. mekongensis showed strong α-glucosidase inhibitory activity with IC50 value of 1.71 µg/mL. Thus, the constituents of this plant were examined.

Results: Two new steroids named mekongsterol A (1) and mekongsterol B (2), were isolated from the n-hexane extract of the bark of M. mekongensis (Anacardiaceae), together with seven known compounds (3-9). Their chemical structures were elucidated on the basis of spectroscopic data. All compounds possessed significant α-glucosidase inhibitory activity in a concentration-dependent manner, except for 3 and 4. Compounds 1, 2, 5-9 showed more potent inhibitory activity, with IC50 values ranging from 1.2 to 112.0 µM, than that of a positive control acarbose (IC50, 214.5 µM).

Conclusions: These results suggested that the traditional use of the bark of M. mekongensis for the treatment of diabetes diseases in Vietnam may be attributable to the α-glucosidase inhibitory activity of its steroid and cycloartane constituents.
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http://dx.doi.org/10.1186/s13065-016-0193-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955201PMC
July 2016