Estimating eGFR using serum creatinine or cystatin C in healthy Vietnamese population.

Very few studies worldwide have assessed the estimated glomerular filtration rate (eGFR) using serum cystatin C (ScysC) in comparison to the gold standard measured glomerular filtration rate (mGFR) with a gamma camera technique using 99m-Technetium-Diethylene Triaminepentoacetic Acid (99mTc-DTPA). To determine the eGFR formula with the most accurate estimate of glomerular filtration rate when compared with mGFR in a healthy population in Vietnam. We conducted a cross-sectional descriptive study of more than 100 adults without hypertension. The study subjects were examined for general characteristics and blood biochemistry tests to assess eGFR, and the glomerular filtration rate was measured using 99mTc-DTPA with the Gates technique to record mGFR. The estimated values of the eGFR formula were evaluated and compared with the actual mGFR using 99mTechnetium-DTPA. Serum creatinine (Scr) concentration showed a significant difference between males and females: 0.9 ±â€…0.1 versus 0.8 ±â€…0.1 (P < .001), while ScysC concentration did not show this difference. The mGFR in the age groups < 40, 40 to 59, and ≥ 60: 105.0 ±â€…9.9, 94.8 ±â€…8.6, and 93.4 ±â€…10.6, respectively (P < .001). The eGFR-CKD-EPI-cystatin C 2012 formula showed the highest positive correlation with mGFR (ΔGFR = -1.6, R = 0.68, P < .001). eGFR calculated using cystatin C does not require sex adjustment, whereas, for creatinine, sex adjustment is necessary. The eGFR-CKD-Epi-CysC formula showed the lowest difference and a strong correlation with mGFR.

Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling.

Three quarters of all breast cancers express the estrogen receptor (ER, ESR1 gene), which promotes tumor growth and constitutes a direct target for endocrine therapies. ESR1 mutations have been implicated in therapy resistance in metastatic breast cancer, in particular to aromatase inhibitors. ESR1 mutations promote constitutive ER activity and affect other signaling pathways, allowing cancer cells to proliferate by employing mechanisms within and without direct regulation by the ER. Although subjected to extensive genetic and transcriptomic analyses, understanding of protein alterations remains poorly investigated. Towards this, we employed an integrated mass spectrometry based proteomic approach to profile the protein and phosphoprotein differences in breast cancer cell lines expressing the frequent Y537N and Y537S ER mutations. Global proteome analysis revealed enrichment of mitotic and immune signaling pathways in ER mutant cells, while phosphoprotein analysis evidenced enriched activity of proliferation associated kinases, in particular CDKs and mTOR. Integration of protein expression and phosphorylation data revealed pathway-dependent discrepancies (motility vs proliferation) that were observed at varying degrees across mutant and wt ER cells. Additionally, protein expression and phosphorylation patterns, while under different regulation, still recapitulated the estrogen-independent phenotype of ER mutant cells. Our study is the first proteome-centric characterization of ESR1 mutant models, out of which we confirm estrogen independence of ER mutants and reveal the enrichment of immune signaling pathways at the proteomic level.

Efficacy of Dyslipidemia Control by Combination Therapy with Rosuvastatin 10 Mg and Ezetimibe 10 Mg Compared with Rosuvastatin 20 Mg Monotherapy in Patients with Chronic Coronary Syndromes: A Randomized, Single-blind Controlled Trial.

BACKGROUND: Studies have shown the combination treatment effectiveness of using rosuvastatin and ezetimibe in patients with chronic coronary artery disease. Our study aim to evaluate the effectiveness of dyslipidemia treatment with the combination of rosuvastatin and ezetimibe 10mg in patients with chronic coronary artery disease compared with 20 mg rosuvastatin. OBJECTIVES: To evaluate the effectiveness of dyslipidemia treatment with the target of LDL-c < 1.4 mmol/L between combination therapy with rosuvastatin 10 mg and ezetimibe 10 mg in patients with chronic coronary artery disease compared with monotherapy increasing the dose of rosuvastatin 20 mg in Vietnam. METHODS: A randomized controlled clinical trial, single-blind, parallel-group with a 1:1 randomized ratio in 103 outpatients with chronic coronary syndromes treated with rosuvastatin 10mg daily. Group A received the combination therapy with rosuvastatin 10 mg plus ezetimibe 10 mg daily, and group B received rosuvastatin 20 mg daily. The primary outcome was to assess the efficacy of low-density lipoprotein - cholesterol (LDL-c) control between rosuvastatin 10 mg plus ezetimibe 10 mg versus rosuvastatin 20 mg after 4 weeks and 8 weeks. RESULTS: After 8 weeks of intervention, the proportion of archived treatment target patients with LDL-c < 1.4 mmol/L in groups A and B was 69.2% and 44.2%, respectively (Risk ratio (RR) = 1.57, p < 0.01), 50% LDL reduction was 27.9% and 55.8%, respectively (RR = 2.00, p < 0.01), and archived both targets were 51.9% and 25.6% (RR = 2.03, p < 0.01). CONCLUSION: Group A's LDL-c reduction effect and target achievement proportion (Rosuvastatin 10mg + Ezetimibe 10 mg) were significantly higher than Group B's (Rosuvastatin 20 mg). Both medication therapies were safe in patients, and the increased dose of monotherapy showed more side effects than the combination therapy.

The combination of CYP2C19 polymorphism and inflammatory cell ratios in prognosis cardiac adverse events after acute coronary syndrome.

Background: CYP2C19 gene polymorphism combination with inflammatory cell ratios was significant in the prognosis of coronary heart disease. Materials and methods: A cross-sectional analysis study, with 6 months follow-up on 142 patients with acute coronary syndrome. Patients were analyzed for CYP2C19 gene polymorphisms by real-time polymerase chain reaction (PCR) and complete blood count to determine inflammatory cell ratios and recorded cardiovascular events (CEs) after following up to 6 months. Results: For 90-day CEs, CYP2C19 gene polymorphism (Hazard Ratio (HR): 1.965, 95 % Confidence Interval (CI): 1.012-3.814), the combination of a neutrophil and lymphocyte ratio (NLR) ≥ 2.982 (HR: 13.001, 95 % CI: 1.37-97.304) or a platelet to lymphocyte ratio (PLR) ≥ 162.42 (HR: 2.878, 95 % CI: 1.212-6.835) was independent predictors of CEs. For 180-day CEs, CYP2C19 gene polymorphism combination with NLR ≥3.02 (HR: 13.946, 95 % CI: 1.833-106.121) or PLR ≥160.38 (HR: 5.349, 95 % CI: 1.379-20.745) or monocyte to lymphocyte ratio (MLR) ≥ 0.3 (HR: 4.699, 95 % CI: 1.032-31.393) were independent predictors of CEs. Conclusion: NLR, PLR or MLR combined with CYP2C19 gene polymorphism were stronger independent predictors of cardiovascular events in patients with acute coronary syndromes compared to CYP2C19 gene polymorphism and inflammatory cell ratios separately. CYP2C19 polymorphism and high NLR was the strongest predictor of both CEs at 90 days and 180 days.

Discovery of benzimidazole-indazole derivatives as potent FLT3-tyrosine kinase domain mutant kinase inhibitors for acute myeloid leukemia.

The FMS-like tyrosine kinase 3 (FLT3) gene encodes a class III receptor tyrosine kinase that is expressed in hematopoietic stem cells. The mutations of FLT3 gene found in 30% of acute myeloid leukemia (AML), leads to an abnormal constitutive activation of FLT3 kinase of the receptor and results in immature myeloblast cell proliferation. Although small molecule drugs targeting the FLT3 kinase have been approved, new FLT3 inhibitors are needed owing to the side effects and drug resistances arising from kinase domain mutations, such as D835Y and F691L. In this study, we have developed benzimidazole-indazole based novel inhibitors targeting mutant FLT3 kinases through the optimization of diverse chemical moieties substituted around the core skeleton. The most optimized compound 22f exhibited potent inhibitory activities against FLT3 and FLT3/D835Y, with IC50 values of 0.941 and 0.199 nM, respectively. Furthermore, 22f exhibited strong antiproliferative activity against an AML cell line, MV4-11 cells with a GI50 of 0.26 nM. More importantly, 22f showed single-digit nanomolar GI50 values in the mutant FLT kinase expressed Ba/F3 cell lines including FLT-D835Y (GI50 = 0.29 nM) and FLT3-F691L (GI50 = 2.87 nM). Molecular docking studies indicated that the compound exhibits a well-fitted binding mode as a type 1 inhibitor in the homology model of active conformation of FLT3 kinase.

Diagnostic performance of 128-slice computed tomography angiography in patients with suspected coronary artery disease.

Objectives: To determine the diagnostic performance and influencing factors of 128-slice coronary computed tomography angiography (CCTA) compared with invasive coronary angiography (ICA) in patients with suspected coronary artery disease (CAD). Methods: A cross-sectional analysis study enrolled 139 patients suspected of having CAD, who underwent and received a 128-slice CCTA and ICA. Results: The patient-based model showed high sensitivity and a positive predictive value of 93.2% and 95.3%, respectively (for stenosis ≥50%). However, these values were lower when analyzed using vessel-based (85.6% and 81.1%) and segment-based (73.9% and 66.6%) models. Specificity and negative predictive value were highest in the segment-based model, decreasing in vessel- and patient-based models at 96.4% and 95.4%, 90.5% and 90.0%, and 36.4% and 42.1%, respectively (for stenosis ≥70%). All diagnostic values were reduced when the calcium score was ≥400 Agatston units. Conclusion: 128-slice CCTA is an optimal, minimally invasive, and high-performance method to diagnose the stenosis and morphology of coronary artery lesions. The diagnostic performance of 128-slice CCTA is very high. Heart rate and body mass index do not affect diagnostic accuracy, whereas a calcium score ≥400 Agatston units is a factor that causes a decrease in diagnostic performance.

Effect of Pharmacist-Led Interventions on Medication Adherence among Vietnamese Patients with Asthma: A Randomized Controlled Trial.

BACKGROUND: Medication adherence in asthmatic patients enhances the effectiveness of treatments, but some studies in low and middle-income countries still show some limitations. Our study aimed to determine if pharmacist-led interventions could increase medication adherence, improve treatment effectiveness, and relieve symptom severity in outpatients with asthma. METHODS: We conducted a randomized, controlled trial on 247 asthmatic outpatients (aged ≥ 16) with a 1:1 ratio randomization at the hospitalization time and repeated after 1-month discharge. The primary outcome was to detect the difference in medication adherence between groups. Adherence was assessed by the general medication adherence scale (GMAS). Data collected by questionnaire was coded and entered into SPSS_20 for statistical analysis; Results: 247 patients (123 intervention, 124 control) were enrolled (61.1% male). After intervention, the adherence rate was higher among the intervention group than the control group (94.3% vs. 82.8%, p = 0.001). Patient behavior and knowledge were enhanced in the intervention group (p < 0.05). Asthma symptoms were relieved in the intervention group (p = 0.014). Pharmacist-led interventions on adherence rate were higher with OR: 3.550, 95% CI: 1.378-9.143, p = 0.009. CONCLUSIONS: pharmaceutical intervention could improve medication adherence, treatment efficacy, and the outcome should not be taken for granted; further research should be carried out in this regard.

Early detection of reduced left ventricular systolic function by 2D speckle tracking echocardiography in patients with primary mitral regurgitation in a Vietnamese cohort.

Background: Mitral regurgitation (MR) is a common heart valve disease, causing many serious complications in several organ systems, especially the cardiovascular system. The 2D speckle tracking echocardiography (STE) is a new technique for detecting potential cardiac dysfunction when only tissue function abnormalities are present. The study aimed to assess left ventricular (LV) systolic function early by STE in patients with primary MR through global LV deformity along the global longitudinal strain (GLS). Methods: An analytical cross-sectional study was performed on 46 patients with moderate to severe primary MR as recommended by the American Society of Echocardiography (ASE) 2017. Results: The prevalence of patients with GLS reduction with ejection fraction (EF) >60%, New York Heart Association (NYHA) I, and left ventricular internal diameter systolic (LVIDs) <40 mm was 38.1%, 35.7%, and 39.5%, respectively. 100% of patients with EF<60% and LVIDs ≥40 mm had reduced GLS (<16%). The GLS index strongly correlates with the NYHA classification, degree of MR, EF, and echocardiographic parameters. Conclusion: GLS index gives a significant sign in the early detection of cardiac function abnormalities before symptoms or other echocardiographic parameters in patients with MR.

Relationship between plumage color and eggshell patterns with egg production and egg quality traits of Japanese quails.

AIM: This study was conducted to identify the diversity of feather color and to determine the relationship between plumage color and egg yield as well as eggshell patterns and internal egg quality traits of Japanese quails. MATERIALS AND METHODS: For investigating phenotypic diversity, a total of 600 quails from five breeding farms were evaluated to record head feather, shank, and plumage color. An on-station experiment was also conducted on 360 laying quails to examine the relationship between plumage color and egg production and egg weight during 24 weeks of laying. Eggs collected during this period were also used for identifying eggshell patterns and examining their relationship with internal egg quality characteristics. RESULTS: Plumage color was primarily wild-type, with the highest proportion being 56.3% (p<0.001). Brown color was also found at a relatively high proportion in the population (16.7%), followed by black color (11.3%). The egg production and laying rate of quails with wild-type and brown plumage colors also significantly (p=0.001) differed from those of quails with other plumage types. Egg weight was also higher in these quail groups, especially than that of quails with yellow plumage color. Four patterns of eggshell were identified, among which spotted and dark eggshells were predominant (45.2% and 43.1%, respectively); however, patterns did not affect internal egg quality characteristics. CONCLUSION: Plumage color was primarily wild-type in both male and female quails. Egg yield over a 24-week laying period was superior in quails with wild-type and brown plumage colors, whereas a relationship between eggshell patterns and egg quality traits could not be established.

Seroprevalence of Toxoplasma gondii among School Children in Pyin Oo Lwin and Naung Cho, Upper Myanmar

Toxoplasma gondii is an apicomplexan parasite that can cause toxoplasmosis in a wide range of warm-blooded animals including humans. In this study, we analyzed seroprevalence of T. gondii among 467 school children living in the rural areas of Pyin Oo Lwin and Naung Cho, Myanmar. The overall seroprevalence of T. gondii among school children was 23.5%; 22.5% of children were positive for T. gondii IgG, 0.4% of children were positive for T. gondii IgM, and 0.6% of children were positive for both T. gondii IgG and IgM. Geographical factors did not significantly affect the seroprevalence frequency between Pyin Oo Lwin and Naung Cho, Myanmar. No significant difference was found between males (22.2%) and females (25.0%). The overall seroprevalence among school children differed by ages (10 years old [13.6%], 11–12 years old [19.8%], 13–14 years old [24.6%], and 15–16 years old [28.0%]), however, the result was not significant. Polymerase chain reaction analysis for T. gondii B1 gene for IgG-positive and IgM-positive blood samples were negative, indicating no direct evidence of active infection. These results collectively suggest that T. gondii infection among school children in Myanmar was relatively high. Integrated and improved strategies including reinforced education on toxoplasmosis should be implemented to prevent and control T. gondii infection among school children in Myanmar.

Partial Characterization of Two Cathepsin D Family Aspartic Peptidases of Clonorchis sinensis

Cathepsin D (CatD, EC 3.4.23.5) is a member belonging to the subfamily of aspartic endopeptidases, which are classified into the MEROPS clan AA, family A1. Helminth parasites express a large set of different peptidases that play pivotal roles in parasite biology and pathophysiology. However, CatD is less well known than the other classes of peptidases in terms of biochemical properties and biological functions. In this study, we identified 2 novel CatDs (CsCatD1 and CsCatD2) of Clonorchis sinensis and partially characterized their properties. Both CsCatDs represent typical enzymes sharing amino acid residues and motifs that are tightly conserved in the CatD superfamily of proteins. Both CsCatDs showed similar patterns of expression in different developmental stages of C. sinensis, but CsCatD2 was also expressed in metacercariae. CsCatD2 was mainly expressed in the intestines and eggs of C. sinensis. Sera obtained from rats experimentally infected with C. sinensis reacted with recombinant CsCatD2 beginning 2 weeks after infection and the antibody titers were gradually increased by maturation of the parasite. Structural analysis of CsCatD2 revealed a bilobed enzyme structure consisting of 2 antiparallel β-sheet domains packed against each other forming a homodimeric structure. These results suggested a plausible biological role of CsCatD2 in the nutrition and reproduction of parasite and its potential utility as a serodiagnostic antigen in clonorchiasis.

Molecular and Biochemical Properties of a Cysteine Protease of Acanthamoeba castellanii

Acanthamoeba spp. are free-living protozoa that are opportunistic pathogens for humans. Cysteine proteases of Acanthamoeba have been partially characterized, but their biochemical and functional properties are not clearly understood yet. In this study, we isolated a gene encoding cysteine protease of A. castellanii (AcCP) and its biochemical and functional properties were analyzed. Sequence analysis of AcCP suggests that this enzyme is a typical cathepsin L family cysteine protease, which shares similar structural characteristics with other cathepsin L-like enzymes. The recombinant AcCP showed enzymatic activity in acidic conditions with an optimum at pH 4.0. The recombinant enzyme effectively hydrolyzed human proteins including hemoglobin, albumin, immunoglobuins A and G, and fibronectin at acidic pH. AcCP mainly localized in lysosomal compartment and its expression was observed in both trophozoites and cysts. AcCP was also identified in cultured medium of A. castellanii. Considering to lysosomal localization, secretion or release by trophozoites and continuous expression in trophozoites and cysts, the enzyme could be a multifunctional enzyme that plays important biological functions for nutrition, development and pathogenicity of A. castellanii. These results also imply that AcCP can be a promising target for development of chemotherapeutic drug for Acanthamoeba infections.