The Risk of Recurrence in Breast Cancer Patients Treated with Tamoxifen: Polymorphisms of CYP2D6 and ABCB1

CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of Pglycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan–Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57–109.94; P=0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P=0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI=0.79–23.2) compared to those without this combination which was 48 months (95% CI=14.7–81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients

Effects of Shinrin-yoku Retreat on Mental Health: A Pilot Study in Fukushima, Japan

Shinrin-yoku (forest bathing) is a cost-effective healing practice that has recently attracted the interest of social scientists who have attributed it, in part, to mental health benefits. Japanese university students suffer from high rates of mental health problems, and the number of suicides remain high despite the total number of suicides in Japan decreasing. Effective mental health approaches which increase mental wellbeing and self-compassion, and reduce associated deficits, such as loneliness, are sought after for Japanese students, however healthful treatment has not been identified to date. Accordingly, this pre-post pilot study evaluated the levels of mental wellbeing, self-compassion, and loneliness among 25 Japanese undergraduate students who participated in a three-day shinrin-yoku retreat in Fukushima. Measurements were taken prior, straight after, and two weeks-post intervention. One-way ANOVA with Tukey post hoc analysis revealed that the mean scores of self-compassion, common humanity, and mindfulness increased statistically significantly from pre-retreat to follow-up. The mean scores of mental wellbeing and loneliness did not statistically significantly change. The positive effects on self-compassion indicate that shinrin-yoku retreat should be evaluated within a larger sample and in a shorter time frame to establish optimal shinrin-yoku parameters in this arena.N/

Passenger transportation sector gasoline consumption due to friction in Southeast Asian countries

Energy demand in the transportation sector across Southeast Asian (SEA) region is rapidly increasing. This poses a challenge to the sector in mitigating greenhouse gas (GHG) emissions because of its heavy reliance on fossil fuels. Decarbonisation efforts tend to focus on the use of low carbon energy, often neglecting frictional losses in vehicles. Therefore, the study aims to determine the fuel cost savings and the environmental impact from reduction of frictional energy losses in passenger cars and motorcycles for selected SEA countries. An energy analysis framework is proposed; estimating a total of USD 42.6 billion/year is wasted through fuel energy loss in moving these vehicles in the selected SEA countries, emitting 109 Mtonne/year of CO2. By implementing relevant tribological improvement strategies, fuel energy savings of USD 18.3 billion/year could be achieved, leading to 46.6 Mtonne/year of CO2 emissions reduction. This level of CO2 emissions reduction, obtained via friction reduction, can contribute between 0.8% and 1.9% towards the committed GHG reduction targets for the selected SEA countries by 2030. It is emphasised that combined effort, from vehicle manufacturers and end-users, is required in implementing relevant friction reduction strategies to avoid backlash from inappropriate use of these strategies.</p

A study of the tribological impact of biodiesel dilution on engine lubricant properties

The switch from petro-diesel fuel to biodiesel blends for Compression Ignition engines have raised tribological performance concerns among major automobile manufacturers. Biodiesel dilution on engine lubricants could have adverse long-term effects on the engine efficiency, which will reduce the fuel economy, thus, leading to higher greenhouse gas emissions. Therefore, this study investigates the tribological impact of palm methyl ester (PME) diluted in SAE5W40 and SAE10W40 engine lubricants along different lubrication regimes under engine cold start condition. Through lubrication Stribeck curve analysis conducted using a pin-on-disc tribometer, coefficient of friction (CoF) for both engine lubricants showed parabolic maximum behaviour with increasing PME dilution. The CoF reduction beyond these peak values is attributed to the improved friction modifier effect from the now-dominant PME but with reduced load carrying capacity. An effective lubricant should possess both reasonable friction modifier effect and highest load carrying capacity in mitigating boundary friction. Hence, through the study, it could be deduced that the acceptable PME dilution threshold level for SAE5W40 is up to 17.5-vol%, while for SAE10W40 is between 28.0-vol% and 34.5-vol%. PME dilution levels beyond these thresholds could easily cause lubrication film rupture under high load, high shear rate conditions during application along the mixed to boundary lubrication regimes, inducing material wear

Does Debts Have Any Impact on Governance Bundle and Agency Costs? Over-Governance Hypothesis

The purpose of this article is to extend the bundles of corporate governance theory and propose the role of corporate debt in determining the governance structure of a company. This research intended to answer some questions have been put forward by scholars to explain the inter-relationship between debt, corporate governance, and agency costs: (i) what exactly is the disciplinary role of debts? (ii) how is governance structure influenced by the debt level? and (iii) are extremely high debt ratios required? Previous works have looked at interrelations between debt, corporate governance, and agency costs in isolation result in inclusive findings. However, we argue that debt level is a key determinant of the effective governance structure that maintains agency costs at the optimal level. Based on the governance bundle theory, we contribute to the literature by introducing a new model (over-governance model) that suggests financial leverage as a critical contingency linking governance bundle and agency costs. Also, it provides a clear picture on the different type of agency costs. Our paper provides a theoretical framework to guide further studies and provide important implications for the board, corporate management, and regulators

Steady-state, transient and WLTC drive-cycle experimental performance comparison between single-scroll and twin-scroll turbocharger turbine

The use of twin-scroll turbocharger turbine in automotive powertrain has been known for providing better transient performance over conventional single-scroll turbine. This has been accredited to the preservation of exhaust flow energy in the twin-scroll volute. In the current study, the performance comparison between a single and twin-scroll turbine has been made experimentally on a 1.5L passenger car gasoline engine. The uniqueness of the current study is that nearly identical engine hardware has been used for both the single and twin-scroll turbine volutes. This includes the intake and exhaust manifold geometry, turbocharger compressor, turbine rotor and volute scroll A/R variation trend over circumferential location. On top of that, the steady-state engine performance with both the volutes, has also been tuned to have matching brake torque. Such highly comparable setup enabled a more precise evaluation on the effect of pulse-isolation in the twin-scroll turbine volute during transient process. The steady-state performance comparison shows the amplitude of exhaust pulse in the twin-scroll volute is substantially higher than in the single-scroll volute, hence confirming the preservation of pulse exhaust energy. As a result, twin-scroll volute is found to be able to accelerate the engine boost pressure at a faster rate, therefore results in better transient response. The ultimate advantage of the twin-scroll turbine is further exemplified via engine Worldwide harmonized Light vehicles Test Cycle (WLTC) testing, where approximately 2.7% of averaged reduction in fuel consumption has been recorded. Majority of this improvement has been contributed by low to medium speed driving condition

High occurrence of CYP3A5 variants among breast cancer and organ transplant patients

Abstract CYP3A5 is one of the important drug metabolising enzyme and its polymorphism shows marked differences in protein expression and catalytic activities between different geographical ethnic groups. Both tamoxifen and tacrolimus are substrates of CYP3A5 and thus the polymorphism may cause pharmacokinetics variation which explains the wide variaton in the dose requirement and patients’s responses. CYP3A5*3 (A22893G) allele resulted in a truncated protein with loss of CYP3A5 expression whilst the CYP3A5*6 (G 30597A) allele caused deletion of exon 6 from the splice variant and was associated with lower CYP3A5 catalytic activity. Both of these polymorphisms lead to the inability of an individual to express full functional CYP3A5. Aim This study aims to investigate the frequency of CYP3A5 haplotypes among healthy volunteers, breast cancer and kidney transplant patients in selected hospitals. Methods This study was approved by the Medical Research Ethic Committee and local institution. Subjects were screened for inclusion and exclusion criteria and recruited after informed consent. Five ml of blood was obtained from subjected and DNA was extracted and subjected to genotyping of CYP3A5 variants. Multiplex PCR were designed with novel primers specific to 3’ end that amplify the variants of A6986G and G14690A. The optimized method was validated by direct sequencing. Result Twelve breast cancer patients (tamoxifen therapy), 6 organ transplant patients (tacrolimus therapy) and 264 healthy blood donors (98 Malay and Chinese; 74 Indian) were successfully recruited. CYP3A5 is highly polymorphic in the Malaysian populations with the *3 allele having a frequency of more than 60% among the healthy volunteers. The frequency of *3 allele was lower (54.17%) in breast cancer patients. All the 6 patients treated with tacrolimus carry at least one mutated variant (1 patient was heterozygous and 5 were homozygous CYP3A5*3). CYP3A5 *6 allele was absent all patients. Conclusion High percentage of patients and volunteers carry at least one CYP3A5*3 allele and this may be an important genetic contributor to interindividual as well as interethnic differences in the clearance of CYP3A5 substrates. However, we are conducting an on-going study with a larger sample size of the patients to understand the impact of pharmacodiagnostics of drug metabolizing enzyme and drug receptors in local clinical settings