Molecular Mechanisms Associated with Aging Kidneys and Future Perspectives.

The rapid growth of the elderly population is making the need for extensive and advanced information about age-related organ dysfunction a crucial research area. The kidney is one of the organs most affected by aging. Aged kidneys undergo functional decline, characterized by a reduction in kidney size, decreased glomerular filtration rate, alterations in renal blood flow, and increased inflammation and fibrosis. This review offers a foundation for understanding the functional and molecular mechanisms of aging kidneys and for selecting identifying appropriate targets for future treatments of age-related kidney issues.

Nonatheroscleotic Isolated Middle Cerebral Artery Disease May Be Early Manifestation of Moyamoya Disease.

BACKGROUND AND PURPOSE: Middle cerebral artery steno-occlusive disease (MCAD) is not an uncommon cause of ischemic stroke in young Asians. Aside from atherosclerosis, the pathogenesis of MCAD include various nonatherosclerotic vasculopathies, most of which are yet to be defined. This study investigated the pathogenesis of symptomatic isolated MCAD in young Asian patients using high-resolution magnetic resonance imaging (HR-MRI) and mutation analysis of RNF213. METHODS: Patients aged <60 years with stroke or transient ischemic attack caused by MCAD were prospectively enrolled. Patients with a confirmed diagnosis of moyamoya disease, dissection, and vasculitis; with significant steno-occlusion in cerebral arteries other than the MCA; or with high-risk cardioembolic source were excluded. Using high-resolution MRI, patients were classified into an atherosclerosis group and a nonatherosclerosis group. RESULTS: Eighty-one patients were enrolled, 45 (56.6%) in the atherosclerosis and 36 (44.4%) in the nonatherosclerosis group. The nonatherosclerosis group was significantly younger (P=0.013), had a smaller number of vascular risk factors (P=0.001), showed a lower homocysteine level (P<0.001), thinner intima-media thickness (P=0.006), and had more frequent heterozygotes at RNF213 (P=0.045) than the atherosclerosis group. Diffusion-weighted image lesion pattern showed no significant differences in assumed stroke mechanisms between the 2 groups. CONCLUSIONS: Nonatherosclerotic pathogenesis are common in young Asians with symptomatic isolated MCAD. Clinical findings, high-resolution MRI features, and results of RNF213 mutation analysis suggest that moyamoya disease is responsible etiologically for a significant portion of nonatherosclerotic lesions. Symptomatic isolated MCAD may be an early manifestation of moyamoya disease in young Asian adults.

Phospholipase-catalyzed hydrolysis in an artificial cell membrane in the presence of melittin.

Biomimicry involves the use of the structure and function of biological systems as models for the design and engineering of materials and machines. An artificial cell membrane was developed using biomembrane components, and the membrane, formed by a lipid bilayer, was analyzed using surface plasmon resonance (SPR) to monitor hydrolysis by phospholipase (PL). The simultaneous atomic force microscope (AFM) images show that PL catalyzed the nanometer-scale hydrolysis of the artificial lipid biomembranes through enzymatic hydrolysis. In addition, it was confirmed that the combination of PL and melittin allowed the control of enzyme hydrolysis for the degradation of the lipid bilayer. Regarding the expected activating effect of melittin on hydrolysis, no difference with respect to the non-treated lipid membrane was observed in the AFM images. It is assumed that the partitioning of melittin into the membrane might prevent the binding or hydrolysis of Phospholipase A2 (PLA2). This study provides basic knowledge on a new approach for patterning biomimicking lipid membranes on a nano-scale.

Detection of single nucleotide polymorphisms using a biosensor-containing titanium-well array.

The rapid identification and verification of single nucleotide polymorphisms (SNPs) were demonstrated using a well array sensor containing anti-biofouling titanium (Ti). Probe single-stranded DNA (ssDNA) was immobilized inside a titanium-well array on amine-modified glass surfaces with anti-biofouling behavior via a streptavidin-biotin interaction. Fluorescence intensity changes originating from the hybridization of nucleic acids to protein-bound nucleic acids linked to Alexa Fluor (FL) 647 were observed. The protocol was highly sensitive and reproducible for the detection of DNA hybridization. Significant changes in fluorescence signals were observed when using target DNA with a single base mismatch, indicating that this method is applicable to SNP detection. The microarray technology for the detection of SNPs using anti-biofouling Ti and other methods can be used as a highly sensitive in vitro medical sensor, as highlighted by an increase in genotyping accuracy.

Blood pressure and mortality after percutaneous coronary intervention: a population-based cohort study.

Revascularization procedures, including percutaneous coronary intervention (PCI), for coronary artery disease (CAD) are increasingly performed in Korea. However, studies on blood pressure control targets in these patients remain insufficient. To assess the relationship between baseline blood pressure and all-cause mortality in CAD patients who underwent PCI. A population-based retrospective cohort study based on the national claims database of the Korean National Health Insurance System, which represents the entire Korean population. A total 38,330 patients with a history of PCI for CAD between 2005 and 2008 were recruited and followed up for all-cause mortality until December 31, 2017. Baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and they were classified into eight SBP and DBP groups each. The hazard ratios (HRs) for all-cause mortality were measured for each group. The pattern of SBP and DBP in this population followed a J-curve relationship for all-cause mortality, with the nadir point at 119 and 74 mmHg, respectively. In subjects aged > 60 years, high SBP (≥ 160 mmHg) and high DBP (≥ 90 mmHg) were significantly related to death. Moreover, in subjects aged > 60 years, low DBP (< 70 mmHg) was significantly related to mortality. There is a J-curve relationship between baseline blood pressure and all-cause mortality in patients who underwent PCI, and intensive lowering of blood pressure may be beneficial for these patients. However, the elderly population needs more attention as excessive BP lowering, particularly DBP, could instead increase the risk of death.

Effect of pyroligneous acid on soil urease, amidase, and nitrogen use efficiency by Chinese cabbage (Brassica campestris var. Pekinensis).

Urea is one of the most commonly used nitrogen fertilizers in agricultural soil and is easily decomposed by soil urease resulting in ammonium release. The produced ammonium can be volatilized or converted to nitrate, which is susceptible to leaching, leading to groundwater contamination unless used by plants. Hence, it is important to control the release of nitrogen from the urea. Pyroligneous acid inhibited the urease activity and decreased ammonium release up to 80% compared to the control. Amidase including asparaginase and glutaminase is an enzyme that catalyzes hydrolysis of amide group, similar to urease. Therefore, the effect of pyroligneous acid on the inhibition of soil amidase was also tested and the results showed that pyroligneous acid competitively inhibited asparaginase while glutaminase was not inhibited. However, inhibitory effect of pyroligneous acid on asparaginase was negligible compared to the urease. The application of pyroligneous acid with a smaller amount of urea for controlled nitrogen release during Chinese cabbage growth showed that dry biomass and nutrient contents of Chinese cabbage were similar to the case of the conventional urea application. The nitrogen utilization efficiency (NUE) was highest for 33% less amount of urea supply with pyroligneous acid (2.21) compared to conventional treatment (1.81). Consequently, the use of pyroligneous acid with urea enhances nitrogen use efficiency while also protecting environments from non-point source contamination.

A Mobile-Based Comprehensive Weight Reduction Program for the Workplace (Health-On): Development and Pilot Study.

BACKGROUND: There is a growing interest in mobile technology for obesity management. Despite the known effectiveness of workplace-based weight loss programs, there are few studies on mobile phone-delivered interventions. OBJECTIVE: This study aimed to develop and verify an integrated and personalized mobile technology-based weight control program, named Health-On, optimized for workplaces. METHODS: A weight reduction algorithm was developed for calorie prescription, continuous monitoring, periodic feedback and reevaluation, goal resetting, and offline intervention with behavior-changing strategies. A total of 30 obese volunteers (body mass index ≥25 kg/m2) participated in the 12-week Health-On pilot program. The primary outcome was weight reduction, and secondary outcomes were improved anthropometric measures, metabolic profiles, and fat computed tomography measures, all assessed pre- and postintervention. RESULTS: Health-On incorporated proprietary algorithms and several strategies intended to maximize adherence, using compatible online and offline interventions. The mean weight of 30 participants decreased by 5.8%, and median weight also decreased from 81.3 kg (interquartile range [IQR] 77.1-87.8) before intervention to 76.6 kg (IQR 70.8-79.5) after the 12-week intervention period (P<.001). The metabolic profiles and fat measures (blood pressure, glycosylated hemoglobin, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, alanine aminotransferase, and visceral and subcutaneous adipose tissue; P<.05) also improved significantly. CONCLUSIONS: In this single-group evaluation of 30 participants before and after the Health-On program, body weight decreased and metabolic profiles and fat measures improved. Follow-up studies are needed to assess effectiveness and long-term adherence.

Factors associated with quality of life in patients with depression: A nationwide population-based study.

BACKGROUND: Depression, one of the most costly and common mental disorders, is reported to be associated with lower quality of life (QoL) in several studies. Improved understanding of the associated factors with QoL is necessary to optimize long-term outcomes and reduce disability in patients with depression. Therefore, the aim of this study was to identify factors that are associated with lower QoL among patients with depression. METHODS: The study was based on the Korea National Health and Nutrition Examination Survey, a cross-sectional health examination, years 2008 to 2014. The final analyzed sample consisted of a total of 1,502 study subjects who had been diagnosed by clinicians as having depression. A multivariate logistic regression model was performed to exam the association between the clinical characteristics (age, sex, demographic and health-related characteristics) and QoL. Analysis of covariance was also used to analyze EQ-5D according to mental health. RESULTS: Older age, lower level of education, lower income, worse subjective perception of health, unemployment, obesity and mental health struggles were found to be significantly associated with low QoL in depressive individuals after adjustment for multiple covariates. CONCLUSIONS: This study has outlined grounding data in identifying patients who are at risk of QoL impairment. Policy makers should direct their interests to these individuals and provide appropriate management.

Role of fatty acid composites in the toxicity of titanium dioxide nanoparticles used in cosmetic products.

It has been recognized that the use of nanoparticles (NPs) in the cosmetic industry results in products with better efficacy and functionality. However, recent advances in molecular toxicology have revealed that NP exposure can promote cytotoxicity and oxidative damage, which has raised health concerns in the use of NPs in personal care products. Nevertheless, the mechanistic basis for the toxicity and safety of cosmetic NPs is poorly understood. The goal of the study was to determine the cytotoxicity and intracellular distribution of titanium dioxide (TiO2) NPs containing fatty acid composites (palmitoleic acid, palmitic acid, stearic acid and oleic acid) commonly used in cosmetic products. Two types of cells, human fibroblast skin cells and adenocarcinoma lung cells, were exposed to either bare TiO2 NPs or TiO2 NPs mixed with fatty acids for up to 48 hr. NMR analysis confirmed that the fatty acid composites remained in the NPs after wash. The cytotoxicity of TiO2 NPs was determined by cell viability measurement using quantitative confocal microscopy, and the localization of two different forms of TiO2 NPs were assessed using electron spectroscopic imaging with transmission electron microscopy. TiO2 NPs containing fatty acids posed significantly reduced cytotoxicity (80-88% decreases) than bare NPs in both cell types. Furthermore, there was less intracellular penetration of the NPs containing fatty acid composites compared with bare NPs. These results provide important insights into the role of fatty acids in protecting the cells from possible toxicity caused by NPs used in the production of cosmetic products.

Glomerular Filtration Rate and Urine Albumin to Creatinine Ratio Associated With Hearing Impairment Among Korean Adults With Diabetes: A Nationwide Population-Based Study.

The objective of this study was to examine the association of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) with hearing impairment among diabetic adults in Korea. The study was based on data from Korea National Health and Nutrition Examination Survey 2011 to 2012. Participants were 1206 diabetic adults, aged over 19 years, who completed audiometric testing supervised by nationally certified clinicians. Hearing impairment was defined in three grades: no hearing impairment (pure-tone average 0-25 dB), slight hearing impairment (26-40 dB), and disabling hearing impairment (>40 dB) in the better ear at frequencies 0.5, 1, 2, 3, 4 and 6 kHz. Using logistic regression, risk of hearing impairment was assessed after having controlled for confounding factors. Higher levels of ACR and lower levels of eGFR correlated with an increase in percentage of disabling hearing impairment both unilaterally and bilaterally (P < 0.001). Controlling for possible confounding covariates, odds ratios for hearing impairment showed tendency to increase in higher ACR groups (P for trend = 0.029). Similar pattern was examined between eGFR and hearing impairment (P for trend = 0.006). Odds ratios were 1.981 (1.146, 3.424) for ACR Q4 and 2.773 (1.286, 5.983) for eGFR < 60 mL/min. Fall in eGFR and rise in ACR correlated with severity of hearing impairment. The association existed independently of age, sex, body mass index (BMI), smoking, drinking, exercise, new onset of diabetes, education, income, mental stress, noise exposure, and metabolic syndrome.

The role of androgen in the adipose tissue of males.

Adipose tissue, where various metabolic hormones are secreted, plays a role in metabolizing different substances including androgen. Within fat tissue, enzymes such as aromatase and aldo-keto reductase 1C are responsible for metabolizing testosterone into estrogen and 5-dihydrotestosterone into inactive metabolites. Adipose tissue can also affect the secretion of gonadotropin, which influences the formation of androgen in the testes. At the same time, androgen has an impact on the distribution and proliferation of adipose tissue. The adrenoreceptors for catecholamines, which have been proven to play an essential role in controlling lipolysis, function by being up-regulated by androgens. Furthermore, androgens regulate the activity of lipoprotein lipase, a key enzyme involved in intracellular esterification of adipose tissue.

Circumferential phased array of shear-horizontal wave magnetostrictive patch transducers for pipe inspection.

Several investigations report effective uses of magnetostrictive patch transducers to generate and measure longitudinal and torsional guided waves in a pipe. They can be used to form a phased array for the circumferential inspection of pipes. Although there are circumferential phased arrays employing piezoelectric transducers or EMAT's, no magnetostrictive patch transducer based array system has been attempted. In this investigation, we aim to develop a circumferential phased magnetostrictive patch transducer (PMPT) array that can focus shear-horizontal waves at any target point on a cylindrical surface of a pipe. For the development, a specific configuration of a PMPT array employing six magnetostrictive patch transducers is proposed. A wave simulation model is also developed to determine time delays and amplitudes of signals generated by the transducers of the array. This model should be able to predict accurately the angular profiles of shear-horizontal waves generated by the transducers. For wave focusing, the time reversal idea will be utilized. The wave focusing ability of the developed PMPT array is tested with multiple-crack detection experiments. Imaging of localized surface inspection regions is also attempted by using wave signals measured by the developed PMPT array system.

Omnidirectional Lamb waves by axisymmetrically-configured magnetostrictive patch transducer.

This work presents the generation of omnidirectional Lamb waves by a new magnetostrictive patch transducer (MPT) and investigates its generation mechanism. Although MPTs have been widely used for wave transduction in plates and pipes, no investigation reports the generation of omnidirectional Lamb waves in a plate by an MPT. For the generation, we propose an axisymmetrically-configured MPT that installs multiple axisymmetric turns of coil outside of a permanent cylindrical magnet located above the center of a circular magnetostrictive patch. After confirming the omnidirectivity of the proposed MPT experimentally, the mechanism of the Lamb wave generation and its frequency characteristics are investigated. It is also shown that the Lamb wave is most efficiently generated in a test plate when its wavelength is equal to two-thirds of the magnetostrictive patch diameter. If this wavelength¿patch diameter relation holds, the second radial extensional vibration mode of the patch of the proposed MPT is shown to be the mode responsible for generating the Lamb wave in a plate.

Higher torsional mode suppression in a pipe for enhancing the first torsional mode by using magnetostrictive patch transducers.

Small-sized defects in pipes can be better detected if the first nondispersive torsional mode is used in a higher frequency range. However, dispersive higher torsional modes accompany the first mode if the actuation frequency is above the first cutoff frequency, thereby making the detection difficult. This study proposes a new technique that is particularly useful for guided torsional waves in a pipe; it enhances the desired first nondispersive mode and suppresses the undesired second mode. The technique uses two transmitting transducers separated by an optimized distance and actuated with an optimized delay time. Unlike previous methods, such as a method tuning the delay time for desired mode enhancement and tuning the distance for undesired mode suppression, the proposed approach determines both the distance and delay time mainly to suppress the undesired second mode. With the selected values, the desired first mode is substantially enhanced. This phenomenon is unique in torsional waves, not longitudinal waves, for which delay time and distance controlling methods have been developed. After wave simulations were carried out to show why the proposed method is more effective for the case of torsional waves, several experiments using magnetostrictive transducers were performed to demonstrate the effectiveness of the proposed method.

A case of multiple system atrophy-cerebellar type preceded by dementia.

Multiple system atrophy (MSA) is a sporadic, adult-onset disease characterized by progressive degeneration of nervous systems including cerebellar, pyramidal, extrapyramidal, and autonomic system. Although a few recent studies reported that cognitive impairments could occur in patients with MSA, prominent dementia with progressive decline is not a typical clinical manifestation of MSA. In particular, dementia with MSA-cerebellar type is very rare. We have experienced a patient with 2-year history of severe cognitive impairment, who was finally diagnosed as MSA-cerebellar type.

Bioconversion of compactin into pravastatin by Streptomyces sp.

Streptomyces sp. Y-110, isolated from soil, modified compactin to pravastatin, a therapeutic agent for hypercholesterolemia. In a batch culture, the highest production of pravastatin was 340 mg l(-1) from 750 mg compactin l(-1) in 24 h. By intermittent feeding of compactin into the culture medium, both the compactin concentration and its conversion increased to 2000 mg l(-1) and 1000 mg pravastatin l(-1), respectively, with the conversion rate of 10 mg l(-1) h(-1). Continuous feeding of compactin increased production of pravastatin to 15 mg l(-1) h(-1).