Body Composition and Performance Associations with Common Carotid Artery Hemodynamics and Stiffness Indices in Males and Females

Sex differences in physiological parameters are being increasingly recognized as a robust prognostic factor in individuals at risk or suffering from cardiovascular disease. Body composition and physical performance measures of cardiorespiratory fitness and muscular strength are strongly associated with overall vascular health. PURPOSE: This study aimed to determine if body composition and physical performance measures were related to common carotid artery (CCA) hemodynamics and stiffness in males and females. METHODS: College-aged males and females who were free from cardiovascular risk factors performed a maximal oxygen consumption test (VO2max) via indirect calorimetry and a maximal leg strength test (1RM) by seated leg press. CCA peak systolic velocity (PS), end-diastolic velocity (ED), time-averaged maximal velocity (TAMAX), time-averaged mean velocity (TAMEAN), pulsatility index (PI), and average diameter (DIAM) were captured in the supine position by Doppler ultrasound. Carotid stiffness index (β), Peterson’s Elastic Modulus (Ep), distensibility, compliance, and average diameter were calculated. RESULTS: Significant associations were observed between VO2max and β (r=-0.724, p=0.008) within the male sample. Within the female group, associations were evident between 1RM and CCA distensibility (r=-0.537, p=0.039). Total mass (kg) was associated with peak systolic velocity (PSV) (r=-0.524, p=0.037), end diastolic velocity (EDV) (r=-0.516, p=0.041), and CCA diameter (r=0.618, p=0.011). Fat free mass (kg) was associated with ED (r=-0.565, p=0.023) and diameter (r=0.533, p=0.033), in addition to FFM (%) presenting associations with pulsatility index (r=0.531, p=0.034). CONCLUSION: Associations between performance and body composition measures with CCA hemodynamic and stiffness parameters vary between males and females

Hemodynamic changes in progressive cerebral infarction: An observational study based on blood pressure monitoring.

Progressive cerebral infarction (PCI) is a common complication in patients with ischemic stroke that leads to poor prognosis. Blood pressure (BP) can indicate post-stroke hemodynamic changes which play a key role in the development of PCI. The authors aim to investigate the association between BP-derived hemodynamic parameters and PCI. Clinical data and BP recordings were collected from 80 patients with cerebral infarction, including 40 patients with PCI and 40 patients with non-progressive cerebral infarction (NPCI). Hemodynamic parameters were calculated from the BP recordings of the first 7 days after admission, including systolic and diastolic BP, mean arterial pressure, and pulse pressure (PP), with the mean values of each group calculated and compared between daytime and nighttime, and between different days. Hemodynamic parameters and circadian BP rhythm patterns were compared between PCI and NPCI groups using t-test or non-parametric equivalent for continuous variables, Chi-squared test or Fisher's exact test for categorical variables, Cox proportional hazards regression analysis and binary logistic regression analysis for potential risk factors. In PCI and NPCI groups, significant decrease of daytime systolic BP appeared on the second and sixth days, respectively. Systolic BP and fibrinogen at admission, daytime systolic BP of the first day, nighttime systolic BP of the third day, PP, and the ratio of abnormal BP circadian rhythms were all higher in the PCI group. PCI and NPCI groups were significantly different in BP circadian rhythm pattern. PCI is associated with higher systolic BP, PP and more abnormal circadian rhythms of BP

Effects of egg and vitamin A supplementation on hemoglobin, retinol status and physical growth levels of primary and middle school students in

Lack of protein and vitamin A influences the growth of student in impoverished mountain areas. The aim of the study was to assess the effects of egg and vitamin A supplementation on hemoglobin, serum retinol and anthropometric indices of 10-18 years old students of a low socioeconomic status. A total number of 288 students from four boarding schools were randomly selected by using cluster sampling method in Chongqing, and they were assigned into supplement group and control group non-randomly. Students in supplement group received a single 200,000 international units vitamin A and 1 egg/day (including weekends) for 6 months. The control group did not receive any supplementation. We measured hemoglobin, serum retinol and height and weight at baseline and after supplementation. The supplementation increased the mean hemoglobin concentration by 7.13 g/L compared with 1.38 g/L in control group (p<0.001), the mean serum retinol concentration by 0.31 μmol/L compared with 0.09 μmol/L in the control group (p=0.005), the mean height-for-age z score by 0.05 compared with 0.03 in the control group (p=0.319), the mean weight-for-age z score by 0.05 compared with -0.12 in the control group (p<0.001). Our results revealed that egg and vitamin A supplementation is an effective, convenient, and practical method to improve the levels of hemoglobin, serum retinol and prevent the deterioration of growth in terms of weight for primary and middle school students from outlying poverty-stricken areas. Our intervention did not have a beneficial effect on linear growth

The EGFR C797S Mutation Confers Resistance to a Novel EGFR Inhibitor CLN-081 to EGFR Exon 20 Insertion Mutations

Introduction: EGFR exon 20 insertion mutations account for 5% to 10% of EGFR-mutated NSCLC. CLN-081 (formerly known as TAS6417), a novel covalent EGFR tyrosine kinase inhibitor, exhibits pan-mutation selective efficacy, including exon 20 insertions, in the clinical setting. Nevertheless, some patients may not respond to CLN-081 and resistance to CLN-081 may emerge over time in others. Methods: We exposed Ba/F3 cells transduced with EGFR exon 20 insertions (Y764_V765 insHH or A767_S768insSVD) to increasing concentrations of CLN-081 to generate resistant cells and then subjected their complementary DNA to sequencing to identify acquired mutations. We then evaluated effects of small molecules on engineered Ba/F3 cells on the basis of proliferation assays, Western blotting, and xenograft models. Results: All CLN-081 resistant clones harbored the EGFR C797S mutation. Ba/F3 cells with C797S (Ba/F3-C797S) were resistant to EGFR tyrosine kinase inhibitors targeting EGFR exon 20 insertion mutations, including CLN-081. Pimitespib, a selective heat shock protein 90 inhibitor, induced apoptosis in Ba/F3-C797S cells in vitro and inhibited growth of Ba/F3-C797S tumors in vivo. Ba/F3 cells with A763_Y764insFQEA-C797S remained sensitive to erlotinib. Conclusions: We conclude that the EGFR C797S mutation confers resistance to CLN-081. Our preclinical data suggest a potential small molecule to overcome CLN-081 resistance, which may benefit patients with lung cancer with EGFR exon 20 insertions

Association of adverse birth outcomes with prenatal exposure to vanadium: a population-based cohort study

Background: Vanadium, an important pollutant produced from anthropogenic activities, has been suggested to be embryotoxic and fetotoxic in animal studies. However, little is known about its effects on humans. We aimed to assess the association of prenatal exposure to vanadium with the risk of adverse birth outcomes in babies born to women in China. Methods: For this population-based cohort study, the Healthy Baby Cohort, women were recruited from three cities in Hubei Province, China. Women included in this analysis were recruited from Wuhan Women and Children Medical Care Center, Wuhan. We measured urinary concentrations of vanadium and other metals simultaneously using inductively coupled plasma mass spectrometry. We used multivariable logistic regressions, with adjustment for potential confounders, to estimate the associations of natural logarithm transformed creatinine-corrected urinary vanadium (Ln-vanadium) concentrations as continuous variables and categorised into quartiles (Q; Q1: ≤0·84 μg/g creatinine, Q2: 0·84–1·40 μg/g creatinine, Q3: 1·40–2·96 μg/g creatinine, Q4: >2·96 μg/g creatinine, with the lowest quartile set as reference) with preterm delivery, early-term delivery, low birthweight, and being small for gestational age. We applied restricted cubic spline models to evaluate the dose-response relationships. Findings: Data from 7297 women recruited between Sept 22, 2012, and Oct 22, 2014, were included in this study. Urinary Ln-vanadium concentrations showed non-linear dose-response relationships with risk of preterm delivery (S-shaped, p<0·0001) and low birthweight (J-shaped, p=0·0001); the adjusted odds ratios (ORs) for increasing quartiles of urinary vanadium were 1·76 (95% CI 1·05–2·95) for Q2, 3·17 (1·96–5·14) for Q3, and 8·86 (5·66–13·86) for Q4 for preterm delivery, and 2·29 (95% CI 1·08–4·84) for Q2, 3·22 (1·58–6·58) for Q3, and 3·56 (1·79–7·10) for Q4 for low birthweight. Ln-vanadium concentrations were linearly associated with the risk of early-term delivery (linear, p<0·0001) and being small for gestational age (linear, p=0·0027), with adjusted ORs of 1·15 (95% CI 1·10–1·21) for early-term delivery and 1·12 (1·04–1·21) for being small for gestational age per unit increase in Ln-vanadium concentrations. Interpretation: Our findings reveal a relationship between prenatal exposure to higher levels of vanadium and increased risk of adverse birth outcomes, suggesting that vanadium might be a potential toxic metal for human beings. Further studies are needed to replicate the observed associations and investigate the interaction effects of prenatal exposure to different metals on adverse birth outcomes. Funding: National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Key Laboratory of Environment and Health

Preliminary and Comparative Experiment Study Between F-Flurpiridaz and N-NHHO Myocardial Perfusion Imaging With PET/CT in Miniature Pigs

Objectves: To comparatively explore the differences between 18 F-Flurpiridaz and 13 N-NH 3 ·H 2 O PET/CT myocardial perfusion imaging in miniature pigs. Methods: Ten Bama minipigs were divided into normal group and myocardial infarction group. The changes of the ratio of left ventricular myocardium to main organs with time were calculated and the best imaging time was confirmed for 18 F-Flurpiridaz imaging in normal group. The image quality score, summed rest score(SRS), Extend, total perfusion deficit(TPD) and left ventricle ejection fraction(LVEF) were respectively compared for 18 F-Flurpiridaz and 13 N-NH 3 ·H 2 O in infarction group. Results: 18 F-Flurpiridaz was rapid distributed in myocardium, and the background counts of cardiac cavity were very low, and no obvious interference extracardiac radioactivity was observed. The radioactive ratio of the left ventricular myocardium to cardiac blood pool and adjacent liver were high. Compared with 13 N-NH 3 ·H 2 O, there were no significant differences in functional parameters, including SRS, Extend, TPD and LVEF. Conclusion: The results preliminaryly show that 18 F-FIurpiridaz is a promising positron MPI agent with good image quality, ability of accurately evaluating cardiac function, and also convenience for application

Adjuvant Osimertinib in Patients With Stage IB to IIIA EGFR Mutation-Positive NSCLC After Complete Tumor Resection: ADAURA China Subgroup Analysis

Introduction: In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People’s Republic of China from ADAURA. Methods: In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety. Results: Of 682 patients enrolled globally, 159 patients in the People’s Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13–0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17–0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21–1.20). HRQoL was maintained from baseline, and safety was consistent with the global population. Conclusions: In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population

Optimizing Respondent-Driven Sampling Survey to Identify Factors Associated With HIV Risk Behaviors Among Student MSM Aged 15 to 19

Male homosexual behavior dominates the mode of HIV infection among students in China. This study aims to identify factors associated with HIV risk behaviors among male students who have sex with men (student MSM) aged 15 to 19 in China. The online sampling used the standard respondent-driven sampling (RDS) method, with recruitment support from community-based organizations (CBOs) in Tianjin and Guangzhou. Multivariate logistic regression models were performed to identify factors associated with multiple HIV risk behaviors. A total of 449 subjects were recruited in this study, including 206 in Tianjin and 243 in Guangzhou. The presence of multiple HIV risk behaviors among student MSM, in many cases, was found to positively correlate with parental or friends’ awareness of their same-sex sexual behavior or sexual orientation, with some geographical differences. The prevalence of HIV risk behaviors among student MSM aged 15 to 19 was high and associated with the disclosure of their sexual orientation or their sex with males to parents and friends. These findings highlight the importance of addressing social support in HIV prevention among student MSM when delivering HIV-related education or services