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Young Gon Kang,1 Eunkyung Suh,2 Jae-woo Lee,3 Dong Wook Kim,4 Kyung Hee Cho,5 Chul-Young Bae1 1Department of R&D, MediAge Research Center, Seongnam, Republic of South Korea; 2Department of Family Medicine, College of Medicine, CHA University, Chaum, Seoul, Republic of South Korea; 3Department of Family Medicine, College of Medicine, Chungbuk National University, Cheongju, Republic of South Korea; 4Department of Policy Research Affairs, National Health Insurance Service Ilsan Hospital, Goyang, Republic of South Korea; 5Department of Family Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of South KoreaPurpose: A comprehensive health index is needed to measure an individual’s overall health and aging status and predict the risk of death and age-related disease incidence, and evaluate the effect of a health management program. The purpose of this study is to demonstrate the validity of estimated biological age (BA) in relation to all-cause mortality and age-related disease incidence based on National Sample Cohort database.Patients and methods: This study was based on National Sample Cohort database of the National Health Insurance Service – Eligibility database and the National Health Insurance Service – Medical and Health Examination database of the year 2002 through 2013. BA model was developed based on the National Health Insurance Service – National Sample Cohort (NHIS – NSC) database and Cox proportional hazard analysis was done for mortality and major age-related disease incidence.Results: For every 1 year increase of the calculated BA and chronological age difference, the hazard ratio for mortality significantly increased by 1.6% (1.5% in men and 2.0% in women) and also for hypertension, diabetes mellitus, heart disease, stroke, and cancer incidence by 2.5%, 4.2%, 1.3%, 1.6%, and 0.4%, respectively (p

Young Gon Kang,1 Eunkyung Suh,2 Hyejin Chun,3 Sun-Hyun Kim,4 Deog Ki Kim,5 Chul-Young Bae1 1MediAge Research Center, Seongnam-si, Gyeonggi-do, 2Department of Family Medicine, College of Medicine, CHA University, Chaum, Seoul, 3Department of Family Medicine, College of Medicine, CHA University, Bundang CHA Medical Center, Seongnam-si, Gyeonggi-do, 4Department of Family Medicine, International St Mary’s Hospital, College of Medicine, Catholic Kwandong University, Incheon, 5Pharmicell Clinical Research Center, Seoul, South Korea Purpose: This study aims to propose a metabolic syndrome (MS) biological age model, through which overall evaluation and management of the health status and aging state in MS can be done easily. Through this model, we hope to provide a novel evaluation and management health index that can be utilized in various health care fields.Patient and methods: MS parameters from American Heart Association/National Heart, Lung, and Blood Institute guidelines in 2005 were used as biomarkers for the estimation of MS biological age. MS biological age model development was done by analyzing data of 263,828 participants and clinical application of the developed MS biological age was assessed by analyzing the data of 188,886 subjects.Results: The principal component accounted for 36.1% in male and 38.9% in female of the total variance in the battery of five variables. The correlation coefficient between corrected biological age and chronological age in males and females were 0.711 and 0.737, respectively. Significant difference for mean MS biological age and chronological age between the three groups, normal, at risk and MS, was seen (P

Chul-Young Bae,1 Young Gon Kang,2 Young-Sung Suh,3 Jee Hye Han,4 Sung-Soo Kim,5 Kyung Won Shim61MediAge Research Center, Seoul, Korea; 2Chaum Power Aging Center, College of Medicine, CHA University, Seoul, Korea; 3Health Promotion Center, Keimyung University Dongsam Medical Center, Daegu, Korea; 4Department of Family Medicine, College of Medicine, Eulji University, Seoul, Korea; 5Department of Family Medicine, College of Medicine, Chungnam National University, Daejeon, Korea; 6Department of Family Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University, Seoul, KoreaBackground: To date, no studies have attempted to estimate body shape biological age using clinical parameters associated with body composition for the purposes of examining a person's body shape based on their age.Objective: We examined the relations between clinical parameters associated with body composition and chronological age, and proposed a model for estimating the body shape biological age.Methods: The study was conducted in 243,778 subjects aged between 20 and 90 years who received a general medical checkup at health promotion centers at university and community hospitals in Korea from 2004 to 2011.Results: In men, the clinical parameters with the highest correlation to age included the waist-to-hip ratio (r = 0.786, P < 0.001), hip circumference (r = −0.448, P < 0.001), and height (r = −0.377, P < 0.001). In women, the clinical parameters with the highest correlation to age include the waist-to-hip ratio (r = 0.859, P < 0.001), waist circumference (r = 0.580, P < 0.001), and hip circumference (r = 0.520, P < 0.001). To estimate the optimal body shape biological age based on clinical parameters associated with body composition, we performed a multiple regression analysis. In a model estimating the body shape biological age, the coefficient of determination (R2) was 0.71 in men and 0.76 in women.Conclusion: Our model for estimating body shape biological age might be a novel approach to variation in body shape that is due to aging. We assume that our estimation model would be used as an adjunctive measure in easily predicting differences in body shape with the use of clinical parameters that are commonly used to assess the status of obesity in a clinical setting.Keywords: chronological age, body shape, biological age

The White Blood Cell (WBC) differential test ranks as the second most frequently performed diagnostic assay. It requires manual confirmation of the peripheral blood smear by experts to identify signs of abnormalities. Automated digital microscopy has emerged as a solution to reduce this labor-intensive process and improve efficiency. Several publicly available datasets provide various WBC subtypes of differing quality and resolution. These datasets have contributed to advancing WBC classification using machine learning techniques. However, digital microscopy of blood cells with high magnification often requires a wider depth of field, posing challenges for automatic digital microscopy that necessitates capturing multiple stacks of focal planes to obtain complete images of specific blood cells. Our dataset provides 25,773 image stacks from 72 patients. The image labels consist of 18 classes encompassing normal and abnormal cells, with two experts reviewing each label. Each image includes 10 z-stacks of cropped 200 by 200 pixel images, captured using a 50X microscope with 400 nm intervals. This study presents a comprehensive multi-focus dataset for WBC classification., (© 2024. The Author(s).)

Improvements in digital microscopy are critical for the development of a malaria diagnosis method that is accurate at the cellular level and exhibits satisfactory clinical performance. Digital microscopy can be enhanced by improving deep learning algorithms and achieving consistent staining results. In this study, a novel miLab™ device incorporating the solid hydrogel staining method was proposed for consistent blood film preparation, eliminating the use of complex equipment and liquid reagent maintenance. The miLab™ ensures consistent, high-quality, and reproducible blood films across various hematocrits by leveraging deformable staining patches. Embedded-deep-learning-enabled miLab™ was utilized to detect and classify malarial parasites from autofocused images of stained blood cells using an internal optical system. The results of this method were consistent with manual microscopy images. This method not only minimizes human error but also facilitates remote assistance and review by experts through digital image transmission. This method can set a new paradigm for on-site malaria diagnosis. The miLab™ algorithm for malaria detection achieved a total accuracy of 98.86% for infected red blood cell (RBC) classification. Clinical validation performed in Malawi demonstrated an overall percent agreement of 92.21%. Based on these results, miLab™ can become a reliable and efficient tool for decentralized malaria diagnosis., Competing Interests: Authors CYB, YMS, MK, YS, HJL, KWK, HWL, YJK, B-IK, SH, S-HC, BMW, CYL, K-HC were employed by Noul Co. Ltd. H-PB, DKL were a member of Scientific Advisory Board (Technical Consultant) in Noul Co., Ltd. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bae, Shin, Kim, Song, Lee, Kim, Lee, Kim, Kanyemba, Lungu, Kang, Han, Beck, Cho, Woo, Lim and Choi.)

The imaging and quantification of stained red blood cells (RBCs) are important for identifying RBCs in hematology and for diagnosing diseased RBCs or parasites in cytopathology. Romanowsky staining has been used traditionally to produce hues in blood cells using a mixture of anionic eosin Y and cationic methylene blue and azure B. While Romanowsky stains have been widely used in cytopathology, end-users have experienced problems with varying results in staining due to the premature precipitation or evaporation of methanol, leading to the inherent inconsistency of solution-based Romanowsky staining. Herein, we demonstrate that the staining and destaining of blood smears are controllable by the contact time of agarose gel stamps. While the extent of staining and destaining is discernable by the hue values of stamped red blood cells in micrographs, the quantification of adsorbed and desorbed Romanowsky dye molecules (in particular, eosin Y, methylene blue and azure B) from and to the agarose gel stamps needs a model that can explain the sorption process. We found predictable sorption of the Romanowsky dye molecules from the pseudo-second-order kinetic model for adsorption and the one phase decay model for desorption. Thus, the method of agarose gel stamping demonstrated here could be an alternative to solution-based Romanowsky staining with the predictable quantity of sorption and timing of contact.

Background: Cancer is one of the main global health threats. Early personalized prediction of cancer incidence is crucial for the population at risk. This study introduces a novel cancer prediction model based on modern recurrent survival deep learning algorithms. Methods: The study includes 160,407 participants from the blood-based cohort of the Korea Cancer Prevention Research-II Biobank, which has been ongoing since 2004. Data linkages were designed to ensure anonymity, and data collection was carried out through nationwide medical examinations. Predictive performance on ten cancer sites, evaluated using the concordance index (c-index), was compared among nDeep and its multitask variation, Cox proportional hazard (PH) regression, DeepSurv, and DeepHit. Results: Our models consistently achieved a c-index of over 0.8 for all ten cancers, with a peak of 0.8922 for lung cancer. They outperformed Cox PH regression and other survival deep neural networks. Conclusion: This study presents a survival deep learning model that demonstrates the highest predictive performance on censored health dataset, to the best of our knowledge. In the future, we plan to investigate the causal relationship between explanatory variables and cancer to reduce cancer incidence and mortality.

Bacterial two-component signal transduction systems provide sensory inputs for appropriately adapting gene expression. These systems rely on a histidine kinase that phosphorylates a response regulator which alters gene expression. Several two-component systems include additional sensory components that can activate the histidine kinase. In Escherichia coli, the lipoprotein NlpE was identified as a sensor for the Cpx cell envelope stress response. It has remained unclear how NlpE signals to Cpx in the periplasm. In this study, we used a combination of genetics, biochemistry, and AlphaFold2 complex modeling to uncover the molecular details of how NlpE triggers the Cpx response through an interaction with the CpxA histidine kinase. Remarkably, only a short loop of NlpE is required to activate the Cpx response. A single substitution in this loop inactivates NlpE signaling to Cpx and abolishes an in vivo biochemical NlpE:CpxA interaction. An independent AlphaFold multimer prediction supported a role for the loop and predicted an interaction interface at CpxA. Mutations in this CpxA region specifically blind the histidine kinase to NlpE activation but preserve the ability to respond to other cell envelope stressors. Hence, our work additionally reveals a previously unrecognized complexity in signal integration by the CpxA periplasmic sensor domain., (© 2023 John Wiley & Sons Ltd.)

Objectives: The world is witnessing a sharp increase in its elderly population, accelerated by longer life expectancy and lower birth rates, which in turn imposes enormous medical burden on society. Although numerous studies have predicted medical expenses based on region, gender, and chronological age (CA), any attempt has rarely been made to utilize biological age (BA)-an indicator of health and aging-to ascertain and predict factors related to medical expenses and medical care use. Thus, this study employs BA to predict factors that affect medical expenses and medical care use., Materials and Methods: Referring to the health screening cohort database of the National Health Insurance Service (NHIS), this study targeted 276,723 adults who underwent health check-ups in 2009-2010 and kept track of the data on their medical expenses and medical care use up to 2019. The average follow-up period is 9.12 years. Twelve clinical indicators were used to measure BA, while the total annual medical expenses, total annual number of outpatient days, total annual number of days in hospital, and average annual increases in medical expenses were used as the variables for medical expenses and medical care use. For statistical analysis, this study employed Pearson correlation analysis and multiple regression analysis., Results: Regression analysis of the differences between corrected biological age (cBA) and CA exhibited statistically significant increases (p<0.05) in all the variables of the total annual medical expenses, total annual number of outpatient days, total annual number of days in hospital, and average annual increases in medical expenses., Conclusions: This study quantified decreases in the variables for medical expenses and medical care use based on improved BA, thereby motivating people to become more health-conscious. In particular, this study is significant in that it is the first of its kind to predict medical expenses and medical care use through BA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bae et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: As the population ages rapidly, the incidence of age-related diseases (ARDs) is also increasing fast. Predicting the incidence of ARDs is a challenge since the rates of individual aging vary, and objective assessments of the stages of aging based on chronological age (CA) may be inaccurate. Thus, in this study, we developed a biological age (BA) model based on the National Health Examination (NHE) data and analyzed the model prediction results for the incidence of 16 ARDs., Methods: This study was based on the 2002-2019 National Health Information Databases of the National Health Insurance Service (NHIS-NHID). The data from a total of 10,002,494 subjects were selected between 2009 and 2010, and the principal component analysis (PCA) was performed to develop the BA model. The Cox-proportional hazard model was used to perform predictive analysis of the ARD incidence., Results: For the unit increase in the difference between corrected biological age (cBA) and chronological age (CA), the hazard ratios (HRs) of ARDs increased significantly for both sexes (p < 0.001). In descending order, the corresponding ARDs' HRs were obesity (1.655), chronic renal failure (1.362), hypertension (1.301), hyperlipidemia (1.264), diabetes mellitus (1.261), fracture (1.119), dementia (1.163), cataract (1.116), myocardial infarction (1.097), stroke (1.169), macular degeneration (1.075), osteoarthritis (1.059), osteoporosis (1.124), Parkinson's disease (1.048), and chronic obstructive pulmonary disease (1.026)., Conclusions: In this study, the incidence of 16 ARDs were analyzed based on BA. Therefore, conducting the NHIS health examination can facilitate the prevention of ARDs by estimating HRs for at least 16 diseases., Competing Interests: Declaration of Competing Interest Declarations of interest: none., (Copyright © 2022. Published by Elsevier B.V.)

Peroxiredoxin-2 (Prx-2) is a critical antioxidant protein in red blood cells (RBC). Prx-2 is oxidized to a disulfide covalently-bound dimer by H 2 O 2 , and then reduced back by the NADPH-dependent thioredoxin-thioredoxin reductase system. The reduction of oxidized Prx-2 is relatively slow in RBCs. Since Prx-2 is highly abundant, Prx-2s' peroxidase catalytic cycle is not considered to be limiting under normal conditions. However, whether Prx-2 recycling becomes limiting when RBCs are exposed to stress is not known. Using three different model systems characterized by increased oxidative damage to RBCs spanning the physiologic (endogenous RBCs of different ages), therapeutic (cold-stored RBCs in blood banks) and pathologic (RBCs from sickle cell disease (SCD) patients and humanized SCD mice) spectrum, basal levels of Prx-2 oxidation and Prx-2 recycling kinetics after addition of H 2 O 2 were determined. The reduction of oxidized Prx-2 was significantly slower in older versuin older versus younger RBCs, in RBCs stored for 4-5 weeks compared to 1 week, and in RBC from pediatric SCD patients compared to RBCs from control non-SCD patients. Similarly, the rate of Prx-2 recycling was slower in humanized SCD mice compared to WT mice. Treatment of RBC with carbon monoxide (CO) to limit heme-peroxidase activity had no effect on Prx-2 recycling kinetics. Treatment with glucose attenuated slowed Prx-2 recycling in older RBCs and SCD RBCs, but not stored RBCs. In conclusion, the reduction of oxidized Prx-2 can be further slowed in RBCs, which may limit the protection afforded by this antioxidant protein in settings associated with erythrocyte stress., (© 2022 Federation of American Societies for Experimental Biology.)

Metabolic syndrome (MS) is diagnosed using absolute criteria that do not consider age and sex, but most studies have shown that the prevalence of MS increases with age in both sexes. Thus, the evaluation of MS should consider sex and age. We aimed to develop a new index that considers the age and sex for evaluating an individual's relative overall MS status. Data of 16,518,532 subjects (8,671,838 males and 7,846,694 females) who completed a validated health survey of the National Health Insurance Service of the Republic of Korea (2014‒2015) were analyzed to develop an MS-biological age model. Principal component score analysis using waist circumference, pulse pressure, fasting blood sugar, triglyceride levels, and high-density lipoprotein level, but not age, as independent variables were performed to derive an index of health status and biological age. In both sexes, the age according to the MS-biological age model increased with rising smoking and alcohol consumption habits and decreased with rising physical activity. Particularly, smoking and drinking affected females, whereas physical activity affected males. The MS-biological age model can be a supplementary tool for evaluating and managing MS, quantitatively measuring the effect of lifestyle changes on MS, and motivating patients to maintain a healthy lifestyle.

Hydrogel sheets have emerged as a promising biomaterial scaffold for the encapsulation and transfer of multicellular structures. Although the improvement of the chemical interactions and the design of micro-scaled geometry have contributed to the development of multipurpose hydrogel scaffolds, the application of hydrogel sheets to assess multicellular structures is still challenging. To expand the technical applicability of hydrogel sheets, we here demonstrate that a single layer of the hydrogel sheet can be integrated as an interposed module in a microfluidic device for multicellular analysis. As a cell culture unit, encapsulated pancreatic insulinoma (MIN6) cells in the hydrogel sheet were labeled and examined via multiple microchannels. After obtaining simultaneously multi-labeled cells in the hydrogel sheet that had been incorporated into the microfluidic device, each modular hydrogel sheet was also recoverable and re-cultured without any distortion. The modular hydrogel sheet can be simply manipulated and conserved as a multicellular module in a three-dimensional (3D) in vitro culture platform. Using the modular concept of hydrogel sheets capable of cell culture and/or assay, an integrated multicellular analysis in the microfluidic device is expected to improve accessibility, scalability, and practicality for end users.

Background: Chronic rhinosinusitis (CRS) is often associated with persistent bacterial infection despite the use of systemic antibiotics. Topically administered antibiotics are an alternative strategy, but require effective local concentrations, prolonged mucosal contact time, minor systemic absorption, and minimal depletion. The objectives of the current study were to analyze the in vitro release rate and in vivo drug delivery tolerance and pharmacokinetics of a ciprofloxacin-coated sinus stent (CSS)., Methods: The CSS (2 mg) was created from biodegradable poly-D/L-lactic acid. After analyzing in vitro release profile, CSSs were placed unilaterally in maxillary sinuses of 16 rabbits via dorsal sinusotomy. Animals were euthanized between 1 and 3 weeks postoperatively. Ciprofloxacin concentrations in the sinus tissue and plasmas were assessed using high-performance liquid chromatography. Radiological and histological evaluations were performed., Results: In the in vitro release profile, an initial burst release was observed over the first 24 hours, followed by sustained release through the 14-day time point. In the rabbit model, ciprofloxacin was continuously released from the stent up to 3 weeks at doses >50 ng/mL. Histologic examination found no evidence of inflammation, epithelial ulceration, or bony reaction upon euthanization of the animals at 21 days. Computed tomography also demonstrated no signs of mucosal edema or opacification in the sinus., Conclusion: The CSS was safe in this preclinical model and sustained release was observed in both the in vitro and in vivo analyses. The innovative stent design coated with ciprofloxacin may provide a unique therapeutic strategy for chronic rhinosinusitis (CRS)., (© 2016 ARS-AAOA, LLC.)

Hydrogel-based bottom-up tissue engineering depends on assembly of cell-laden modules for complex three-dimensional tissue reconstruction. Though sheet-like hydrogel modules enable rapid and controllable assembly, they have limitations in generating spatial microenvironments and mass transport. Here, we describe a simple method for forming large-scale cell-hydrogel assemblies via stacking cell-embedded mesh-like hydrogel sheets to create complex macroscale cellular scaffolds. Freestanding stacked hydrogel sheets were fabricated for long-term cell culturing applications using a facile stacking process where the micropatterned hydrogel sheets (8.0 mm × 8.7 mm) were aligned using a polydimethylsiloxane drainage well. The stacked hydrogel sheets were precisely aligned so that the openings could facilitate mass transport through the stacked sheets. Despite the relatively large height of the stacked structure (400-700 μm), which is larger than the diffusion limit thickness of 150-200 μm, the freestanding cell-ydrogel assemblies maintained cell viability and exhibited enhanced cellular function compared with single hydrogel sheets. Furthermore, a three-dimensional co-culture system was constructed simply by stacking different cell-containing hydrogel sheets. These results show that stacked hydrogel sheets have significant potential as a macroscale cell-culture and assay platform with complex microenvironments for biologically relevant in vitro tissue-level drug assays and physiological studies., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hydrogels can be patterned at the micro-scale using microfluidic or micropatterning technologies to provide an in vivo-like three-dimensional (3D) tissue geometry. The resulting 3D hydrogel-based cellular constructs have been introduced as an alternative to animal experiments for advanced biological studies, pharmacological assays and organ transplant applications. Although hydrogel-based particles and fibers can be easily fabricated, it is difficult to manipulate them for tissue reconstruction. In this video, we describe a fabrication method for micropatterned alginate hydrogel sheets, together with their assembly to form a macro-scale 3D cell culture system with a controlled cellular microenvironment. Using a mist form of the calcium gelling agent, thin hydrogel sheets are easily generated with a thickness in the range of 100 - 200 µm, and with precise micropatterns. Cells can then be cultured with the geometric guidance of the hydrogel sheets in freestanding conditions. Furthermore, the hydrogel sheets can be readily manipulated using a micropipette with an end-cut tip, and can be assembled into multi-layered structures by stacking them using a patterned polydimethylsiloxane (PDMS) frame. These modular hydrogel sheets, which can be fabricated using a facile process, have potential applications of in vitro drug assays and biological studies, including functional studies of micro- and macrostructure and tissue reconstruction.

Pancreatic islet transplantation has been validated as a treatment for type 1 diabetes since it maintains consistent and sustained type 1 diabetes reversal. However, one of the major challenges in pancreatic islet transplantation is the body's natural immune response to the implanted islets. Immunosuppressive drug treatment is the most popular immunomodulatory approach for islet graft survival. However, administration of immunosuppressive drugs gives rise to negative side effects, and long-term effects are not clearly understood. A bioartificial pancreas is a therapeutic approach to enable pancreatic islet transplantation without or with minimal immune suppression. The bioartificial pancreas encapsulates the pancreatic islets in a semi-permeable environment which protects islets from the body's immune responses, while allowing the permeation of insulin, oxygen, nutrients, and waste. Many groups have developed various types of the bioartificial pancreas and tested their efficacy in animal models. However, the clinical application of the bioartificial pancreas still requires further investigation. In this review, we discuss several types of bioartificial pancreases and address their advantages and limitations. We also discuss recent advances in bioartificial pancreas applications with microfluidic or micropatterning technology.

Cell-containing hydrogel modules as cell-hydrogel microunits for creating a physiologically relevant 3D in vivo-like microenvironment with multiple cell types and unique extracellular matrix (ECM) compositions facilitate long-term cell maintenance and bioassays. To date, there have been many important advances in microfluidic bioassays, which incorporate hydrogel scaffolds into surface-accessible microchambers, driven by the strong demand for the application of spatiotemporally defined biochemical stimuli to construct in vivo-like conditions and perform real-time imaging of cell-matrix interactions. In keeping with the trend of fostering collaborations among biologists, clinicians, and microfluidic engineers, it is essential to create a simpler approach for coupling cell-containing hydrogel modules and an automated bioassay platform in a user-friendly format. In this article, we review recent progress in hydrogel-incorporated microfluidics for long-term cell maintenance and discuss some of the simpler and user-friendly 3D bioassay techniques combined with cell-containing hydrogel modules that can be applied to mutually beneficial collaborations with non-engineers. We anticipate that this modular and user-friendly format interfaced with existing laboratory infrastructure will help address several clinical questions in ways that extend well beyond the current 2D cell-culture systems.

Neonatal hypoxic-ischemic brain injury and its related illness hypoxic-ischemic encephalopathy (HIE) are major causes of nervous system damage and neurological morbidity in children. Hypoxic preconditioning (HPC) is known to be neuroprotective in cerebral ischemic brain injury. K(ATP) channels are involved in ischemic preconditioning in the heart; however the involvement of neuronal K(ATP) channels in HPC in the brain has not been fully investigated. In this study, we investigated the role of HPC in hypoxia-ischemia (HI)-induced brain injury in postnatal seven-day-old (P7) CD1 mouse pups. Specifically, TTC (2,3,5-triphenyltetrazolium chloride) staining was used to assess the infarct volume, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling) to detect apoptotic cells, Western blots to evaluate protein level, and patch-clamp recordings to measure K(ATP) channel current activities. Behavioral tests were performed to assess the functional recovery after hypoxic-ischemic insults. We found that hypoxic preconditioning reduced infarct volume, decreased the number of TUNEL-positive cells, and improved neurobehavioral functional recovery in neonatal mice following hypoxic-ischemic insults. Pre-treatment with a K(ATP) channel blocker, tolbutamide, inhibited hypoxic preconditioning-induced neuroprotection and augmented neurodegeneration following hypoxic-ischemic injury. Pre-treatment with a K(ATP) channel opener, diazoxide, reduced infarct volume and mimicked hypoxic preconditioning-induced neuroprotection. Hypoxic preconditioning induced upregulation of the protein level of the Kir6.2 isoform and enhanced current activities of K(ATP) channels. Hypoxic preconditioning restored the HI-reduced PKC and pAkt levels, and reduced caspase-3 level, while tolbutamide inhibited the effects of hypoxic preconditioning. We conclude that K(ATP) channels are involved in hypoxic preconditioning-induced neuroprotection in neonatal hypoxic-ischemic brain injury. K(ATP) channel openers may therefore have therapeutic effects in neonatal hypoxic-ischemic brain injury., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A microstructure-based hydrogel was employed to study the relationship between spatial specificity and cellular behavior, including cell fate, proliferation, morphology, and insulin secretion in pancreatic β-cells. To effectively form homogeneous cell clusters in vitro, we made cell-containing hydrogel membrane constructs with an adapted grid structure based on a hexagonal micropattern. Homogeneous cell clusters (average diameter: 83.6 ± 14.2 μm) of pancreatic insulinoma (MIN6) cells were spontaneously generated in the floating hydrogel membrane constructs, including a hexagonal grid structure (size of cavity: 100 μm, interval between cavities: 30 μm). Interestingly, 3D clustering of MIN6 cells mimicking the structure of pancreatic islets was coalesced into a merged aggregate attaching to each hexagonal cavity of the hydrogel grid structure. The fate and insulin secretion of homogeneous cell clusters in the hydrogel grid structure were also assessed. The results of these designable hydrogel-cell membrane constructs suggest that facultative in vitro β-cell proliferation and maintenance can be applied to biofunctional assessments.

Microalgae, a group of microorganisms that grow using sunlight as the sole energy source and carbon dioxide as an only carbon source, have been considered as a feedstock of choice for the production of biofuels such as biodiesel. To explore the economic feasibility of such application, however, many technical hurdles must first be overcome; the selection and/or screening of competent species are some of the most important and yet challenging tasks. To greatly accelerate this rather slow and laborious step, we developed a droplet-based microfluidic system that uses alginate hydrogel microcapsules with a mean diameter of 26 μm, each of which is able to encapsulate a single microalgal cell. This novel device was successfully demonstrated using three microalgae species, namely, Chlorella vulgaris , Chlamydomonas sp., and Botryococcus braunii . In situ analysis of the lipid content of individual microalgal cells by nondestructive fluorescence staining using BODIPY (4,4-difluoro-1,3,5,7,-tetramethyl-4-bora-3a,4a-diaza-s-indacene) was possible. In all cases, we confirmed that the lipid content of microalgal species in alginate hydrogel microcapsules was comparable to that of free-living cells. Stochastic heterogeneity in the lipid content was verified under a highly viable physiological condition, implying that other analyses were possible after the determination of lipid content. Furthermore, the designed microwell arrays enabled us to distinguish the BODIPY fluorescence response of a single live alga within the microcapsules.

We report a contraction-expansion array (CEA) microchannel device that performs label-free high-throughput separation of cancer cells from whole blood at low Reynolds number (Re). The CEA microfluidic device utilizes hydrodynamic field effect for cancer cell separation, two kinds of inertial effects: (1) inertial lift force and (2) Dean flow, which results in label-free size-based separation with high throughput. To avoid cell damages potentially caused by high shear stress in conventional inertial separation techniques, the CEA microfluidic device isolates the cells with low operational Re, maintaining high-throughput separation, using nondiluted whole blood samples (hematocrit ~45%). We characterized inertial particle migration and investigated the migration of blood cells and various cancer cells (MCF-7, SK-BR-3, and HCC70) in the CEA microchannel. The separation of cancer cells from whole blood was demonstrated with a cancer cell recovery rate of 99.1%, a blood cell rejection ratio of 88.9%, and a throughput of 1.1 × 10(8) cells/min. In addition, the blood cell rejection ratio was further improved to 97.3% by a two-step filtration process with two devices connected in series.

Objectives: To date, no worldwide studies have been conducted to estimate the biological age of five organs using clinical biomarkers that are associated with the aging status. Therefore, we conducted this study to develop the models for estimating the biological age of five organs (heart, lung, liver, pancreas, and kidney) using clinical biomarkers which are commonly measured in clinical practice., Design: A cross sectional study., Methods: Subjects were recruited from the routine health check-up centers in Korea from 2004 through 2010. Data obtained from 121,189 subjects (66,168 men and 55,021 women) were used for clinical evaluation and statistical analysis. We examined the relations between clinical biomarkers associated with five organs and the chronological age and proposed a model for estimating the biological age of five organs., Results: In the models for predicting the biological ages of the heart, lung, liver, pancreas and kidney in men, 12, 2, 8, 3, and 5 parameters were respectively included (R(2)=0.652, 0.427, 0.107, 0.245, and 0.651). In contrast to men, 10, 2, 8, 3, and 5 parameters in women were respectively included (R(2)=0.780, 0.435, 0.140, 0.384, and 0.501)., Conclusion: We first proposed the models for predicting the biological age of five organs in the current study. We developed those using clinical parameters that can be easily obtained in clinical practice settings. Our biological age prediction models may be used as supplementary tools to assess the aging status of five organs in clinical practice settings., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aim: To evaluate the role of swelling-induced activation of volume-regulated anion channels (VRACs) in a neonatal hypoxic-ischemic injury model using the selective VRAC blocker 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on5-yl) oxobutyric acid (DCPIB)., Methods: Cerebral hypoxic-ischemic injury was induced in 7-day-old mouse pups with Rice-Vannucci method. Prior to the onset of ischemia, the animals were ip administered DCPIB (10 mg/kg). The animals were sacrificed 24 h afterwards, coronal sections of the brains were cut and the areas of infarct were examined using TTC staining and an image-analysis system. Cultured PC12 cells were subjected to oxygen-glucose deprivation (OGD) for 4 h. The cellular viability was assessed using Cell Counting Kit 8. Intracellular chloride concentration [Cl(-)](i) was measured using 6-methoxy-N-ethylquinolinium iodide., Results: DCPIB-treated mice showed a significant reduction in hemispheric corrected infarct volume (26.65%±2.23%) compared to that in vehicle-treated mice (45.52%±1.45%, P<0.001). DCPIB-treated mice also showed better functional recovery as they were more active than vehicle-treated mice at 4 and 24 h post injury. In cultured PC12 cells, DCPIB (10 μmol/L) significantly reduced OGD-induced cell death. Moreover, DCPIB (20 μmol/L) blocked hypotonic-induced decrease in [Cl(-)](i) in PC12 cells of both control and OGD groups., Conclusion: The results further support the pathophysiological role of VRACs in ischemic brain injury, and suggest DCPIB as a potential, easily administrable agent targeting VRACs in the context of perinatal and neonatal hypoxic-ischemic brain injury.

The initial excitement and countless efforts to find a pharmacological agent that disrupts the excitotoxic pathway of ischemic neuronal death have only led to disappointing clinical trials. Currently, a thrombolytic agent called recombinant tissue plasminogen activator (rt-PA) is the only pharmacological treatment available for patients with acute ischemic stroke in most countries. Even though its efficacy has been confirmed repeatedly, rt-PA is considerably underused due to reasons including a short therapeutic window and repeated complications associated with its use. A search for alternative mechanisms that may operate dependently or independently with the well-established excitotoxic mechanism has led researchers to the discovery of newly described non-glutamate mechanisms. Among the latter, transient receptor potential melastatin 7 (TRPM7) is one of the important nonglutamate mechanisms in stroke, which has been evaluated in both in-vitro and in-vivo. In this review, we will discuss the current state of pharmacological treatments of ischemic stroke and provide evidence that TRPM7 is a promising therapeutic target of stroke.

Background: To date, no studies have attempted to estimate body shape biological age using clinical parameters associated with body composition for the purposes of examining a person's body shape based on their age., Objective: We examined the relations between clinical parameters associated with body composition and chronological age, and proposed a model for estimating the body shape biological age., Methods: The study was conducted in 243,778 subjects aged between 20 and 90 years who received a general medical checkup at health promotion centers at university and community hospitals in Korea from 2004 to 2011., Results: In men, the clinical parameters with the highest correlation to age included the waist- to-hip ratio (r = 0.786, P < 0.001), hip circumference (r = -0.448, P < 0.001), and height (r = -0.377, P < 0.001). In women, the clinical parameters with the highest correlation to age include the waist-to-hip ratio (r = 0.859, P < 0.001), waist circumference (r = 0.580, P < 0.001), and hip circumference (r = 0.520, P < 0.001). To estimate the optimal body shape biological age based on clinical parameters associated with body composition, we performed a multiple regression analysis. In a model estimating the body shape biological age, the coefficient of determination (R(2)) was 0.71 in men and 0.76 in women., Conclusion: Our model for estimating body shape biological age might be a novel approach to variation in body shape that is due to aging. We assume that our estimation model would be used as an adjunctive measure in easily predicting differences in body shape with the use of clinical parameters that are commonly used to assess the status of obesity in a clinical setting.

Microarchitectured freestanding cellular hydrogel biopaper as a novel 3D cell culture or tissue reconstruction module is reported. New harvesting, transfer, and assembly techniques are used to construct laminated tissue composites of the biopaper, such as hepatic hydrogel sheet modules with augmented liver function for stratified 3D hepatic tissue reconstruction., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Searching for effective pharmacological agents for stroke treatment has largely been unsuccessful. Despite initial excitement, antagonists for glutamate receptors, the most studied receptor channels in ischemic stroke, have shown insufficient neuroprotective effects in clinical trials. Outside the traditional glutamate-mediated excitotoxicity, recent evidence suggests few non-glutamate mechanisms, which may also cause ionic imbalance and cell death in cerebral ischemia. Transient receptor potential melastatin 7 (TRPM7) is a Ca(2+) permeable, non-selective cation channel that has recently gained attention as a potential cation influx pathway involved in ischemic events. Compelling new evidence from an in vivo study demonstrated that suppression of TRPM7 channels in adult rat brain in vivo using virally mediated gene silencing approach reduced delayed neuronal cell death and preserved neuronal functions in global cerebral ischemia. In this review, we will discuss the current understanding of the role of TRPM7 channels in physiology and pathophysiology as well as its therapeutic potential in stroke.

Background: Biomarkers play a key role in risk assessment, assessing treatment response, and detecting recurrence and the investigation of multiple biomarkers may also prove useful in accurate prediction and prognosis of cancers. Immunohistochemistry (IHC) has been a major diagnostic tool to identify therapeutic biomarkers and to subclassify breast cancer patients. However, there is no suitable IHC platform for multiplex assay toward personalized cancer therapy. Here, we report a microfluidics-based multiplexed IHC (MMIHC) platform that significantly improves IHC performance in reduction of time and tissue consumption, quantification, consistency, sensitivity, specificity and cost-effectiveness., Methodology/principal Findings: By creating a simple and robust interface between the device and human breast tissue samples, we not only applied conventional thin-section tissues into on-chip without any additional modification process, but also attained perfect fluid control for various solutions, without any leakage, bubble formation, or cross-contamination. Four biomarkers, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR) and Ki-67, were examined simultaneously on breast cancer cells and human breast cancer tissues. The MMIHC method improved immunoreaction, reducing time and reagent consumption. Moreover, it showed the availability of semi-quantitative analysis by comparing Western blot. Concordance study proved strong consensus between conventional whole-section analysis and MMIHC (n = 105, lowest Kendall's coefficient of concordance, 0.90). To demonstrate the suitability of MMIHC for scarce samples, it was also applied successfully to tissues from needle biopsies., Conclusions/significance: The microfluidic system, for the first time, was successfully applied to human clinical tissue samples and histopathological diagnosis was realized for breast cancers. Our results showing substantial agreement indicate that several cancer-related proteins can be simultaneously investigated on a single tumor section, giving clear advantages and technical advances over standard immunohistochemical method. This novel concept will enable histopathological diagnosis using numerous specific biomarkers at a time even for small-sized specimens, thus facilitating the individualization of cancer therapy.

This Letter describes a quantitative phase microscopy for microfluidic devices using a simple self-referencing interferometry. Compared with the gross dimensions of the microfluidic device, the microchannel occupies only a small area of the device. Hence, the reference field can be generated by inverting the relative position of the specimen and background. Our system is realized using an extended depth-of-field optics in the form of Michelson interferometry, which allows quantitative phase measurement for an increased depth-of-field without moving objective lens or specimen. Furthermore, the system can be readily converted to a higher signal-to-noise ratio Hilbert phase microscopy thanks to the simultaneous acquisition of double interferograms. The performance of our system is verified using polymer beads, micropatterning poly(dimethylsiloxane) (PDMS), and embryo cells in the microchannels.

This work demonstrates a novel microfluidic in vitro cultivation system for embryos that improves their development using a partially constricted channel that mimics peristaltic muscle contraction. Conventional photolithography and a PDMS replica molding process were used to make straight or constricted microchannels. To investigate the effects of constriction geometry on embryonic development, different constriction widths of the channel were designed. Bovine embryos were loaded and incubated by simply placing them on a tilting machine to provide embryo movement via gravity. The fertilized embryos were cultivated on the microfluidic in vitro cultivation system until the blastocyst, hatching, or hatched blastocyst stages. To confirm the quality of blastocysts in the microfluidic channel, double staining was performed and compared with bovine embryos cultivated by the conventional droplet method. The proportion of eight-cell development among total embryos in the constricted channel (56.7+/-13.7%; mean+/-SD) was superior to that in the straight channel (23.9+/-11.0%). This suggests that the effect of constriction is vital for the early development of bovine embryos in assisted-reproduction research.

Individual differences are the hallmark of aging. Chronological age (CHA) is known that fails to provide an accurate indicator of the aging but biological age (BA) estimates the functional status of an individual in reference to his or her chronological peers on the basis of how well he or she functions in comparison with others of the same CHA. Therefore, we developed models for predicting BA that can be applicable in clinical practice settings. This was a community-based cross-sectional study. Subjects were recruited from the health promotion center in Korea from 2001 to 2005. Among these, data obtained from the 3575 participants (1302 men and 2273 women) was used for clinical evaluation and statistical analysis. For our test battery we selected 25 parameters among the routine tests. For males, the best models were developed using 15, 7, 5, and 4 of the 25 chosen parameters for total, physical, biochemical and hormonal characteristics, respectively (R(2)=0.62, 0.38, 0.33, and 0.36, respectively). Similar to males, for the females, 14, 6, 8, and 3 parameters were developed as the models (R(2)=0.66, 0.40, 0.42, and 0.37, respectively). Our BA prediction models may be used as supplementary tools adding knowledge in the evaluation of aging status.

Conidial adhesion and appressorium formation of Magnaporthe oryzae on the rice surface are important early events in the infection process. As an initiative step to understand the mechanisms underlying these cellular processes at a biochemical level, the effect of a human fibronectin antibody (HFA) and RGD peptides on conidial adhesion and appressorium formation was evaluated. HFA inhibited conidial adhesion and appressorium formation in a dosage-dependent manner. RGD peptides also inhibited these cellular events. Conidial adhesion and appressorium formation inhibited by RGD peptides were restored by chemicals involved in the cyclic AMP-dependent signaling pathway. These results suggest that extracellular matrix proteins might be involved in conidial adhesion and appressorium formation through integrin-like receptor mediation and modulation of cAMP-dependent signaling in the cells.

Two novel spore-forming bacteria with broad antimicrobial activity were isolated from roots of Perilla frutescens. The isolates, SD17(T) and SD18, were facultatively anaerobic and showed variable Gram reaction. Growth was observed between 20 and 45 degrees C. DNA G+C content of SD17(T) was 51.7 mol%, and the major fatty acid was anteiso-C(15 : 0) (54.1 %). 16S rRNA gene sequence similarity of SD17(T) ranged from 98.6 to 91.3 % with other Paenibacillus species. The phylogenetic tree showed that isolate SD17(T) formed a significant monophyletic clade with Paenibacillus koreensis KCTC 2393(T) and Paenibacillus ehimensis IFO 15659(T). DNA-DNA relatedness values for strain SD17(T) with Paenibacillus koreensis KCTC 2393(T) and Paenibacillus ehimensis IFO 15659(T) were 17.4 and 19.8 %, respectively. These isolates thus merit species status within Paenibacillus, for which the name Paenibacillus elgii sp. nov. is proposed. The type strain is SD17(T) (=KCTC 10016BP(T)=NBRC 100335(T)).

This study was undertaken to observe the effects of the blend of partially purified Yucca schidigera and Quillaja saponaria extracts on cholesterol levels in the human's blood and gastrointestinal functions, and to determine if a new cholesterol-lowering drug can be developed by the further purification of the extracts. Ultrafiltration and sequential diafiltration increased the amounts of steroidal saponin in aqueous yucca extract and terpenoid saponin in aqueous quillaja extract from 9.3% and 21.4% to 17.2% and 61.8%, respectively. Taking 0.9 mg of the blend (6:4, v:v) of the resulting filtrates a day for 4 weeks resulted in the decreases in total and LDL cholesterol levels in blood plasma of hyper-cholesterolemic patients with enhancement in gastrointestinal symptoms of patients.

The objective of this study was to determine whether testosterone and sex hormone binding globulin (SHBG) levels are different between healthy men and men with chronic illness, and to evaluate the age-related changes of testosterone and SHBG in healthy men in Korea. enrollment took place between January 2000 and December 2001 at Pundang CHA General Hospital in Korea. All men who came for male climacteric and geriatric health screening examinations were eligible. Of the 762 men recruited, 136 men had at least one present or previous medical illness and 626 men were healthy. Higher serum concentrations of total testosterone (5.31 +/- 1.88 ng/ml vs. 4.96 +/- 1.43 ng/ml; p < 0.05), free androgen index (16.60 +/- 7.36 vs. 14.57 +/- 5.55; p < 0.01) and calculated bioavailable testosterone (8.88 +/- 3.52 nmol/l vs. 7.91 +/- 2.52 nmol/l; p < 0.01) were demonstrated in the healthy compared with the disease group. Total testosterone declined at a rate of 0.2% per year, SHBG increased by 1.74% per year, calculated bioavailable testosterone declined by 0.8% per year, and free androgen index declined by 1.15% per year in healthy subjects aged between 40 and 70. The above results seem to be consistent with previous Western studies, showing higher concentrations of testosterone in healthy men, that decline with increasing age.

A pepper esterase gene (PepEST) that is highly expressed during an incompatible interaction between pepper (Capsicum annuum) and the anthracnose fungus Colletotrichum gloeosporioides has been previously cloned. Glutathione-S-transferase-tagged recombinant PepEST protein expressed in Escherichia coli showed substrate specificity for p-nitrophenyl esters. Inoculation of compatible unripe pepper fruits with C. gloeosporioides spores amended with the recombinant protein did not cause anthracnose symptoms on the fruit. The recombinant protein has no fungicidal activity, but it significantly inhibits appressorium formation of the anthracnose fungus in a dose-dependent manner. An esterase from porcine liver also inhibited appressorium formation, and the recombinant protein inhibited appressorium formation in the rice blast fungus, Magnaporthe grisea. Inhibition of appressorium formation in M. grisea by the recombinant protein was reversible by treatment with cyclic AMP (cAMP) or 1,16-hexadecanediol. The results suggest that the recombinant protein regulates appressorium formation by modulating the cAMP-dependent signaling pathway in this fungus. Taken together, the PepEST esterase activity can inhibit appressorium formation of C. gloeosporioides, which may result in protection of the unripe fruit against the fungus.

Objective: To assess the efficacy and safety of Cerebrolysin over 4 weeks in patients with probable Alzheimer's disease (AD)., Design: A 4-week randomized, double-blind, placebo-controlled, multicenter clinical trial. An unequal (Cerebrolysin:placebo = 2:1) randomization was used to assign more patients to the treatment group., Settings: University medical centers and community geriatric hospitals in Korea., Participants: Fifty-three men and women at least 50 years of age admitted to hospitals with mild to moderate AD and otherwise in good health., Intervention: The treatment group (n = 34) received Cerebrolysin (30 mL Cerebrolysin in 100 mL physiologic saline IV) once a day from Monday to Friday for 4 weeks. The control group (n = 19) received placebo., Measurements: Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Clinical Global Impression of Severity/ Change (CGIS/C). Secondary outcome measures included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Katz Index of Activities of Daily Living (ADL), and Lawton Instrumental Activities of Daily Living (IADL) Scale., Results: After 4 weeks of treatment, Cerebrolysin-treated patients demonstrated significant improvements in the ADAS-Cog (P = .02), CGIS/C (P = .01), and MMSE (P = .04) compared with placebo-treated patients. Among Cerebrolysin-treated patients, 82%, 62%, and 44% were rated improved on ADAS-Cog, CGIS/C, and MMSE, respectively, compared with 31.6%, 22%, and 17% of placebo-treated patients, respectively. However, there were no significant improvements in the Cerebrolysin group compared with the placebo group on the GDS, ADL, and IADL. There were no dropouts in either groups, with 100% compliance to Cerebrolysin and placebo. Only one patient reported a febrile sensation, which was transient and mild in severity., Conclusions: This study indicates that Cerebrolysin is a safe drug that improves the cognitive deficits and global function in patients with mild to moderate AD. Long-term efficacy and safety of Cerebrolysin in Alzheimer's patients should be evaluated in the future.

Objectives: To determine the efficacy of the American Heart Association Step-One Diet for lowering blood lipid levels and to assess its nutritional adequacy in younger (< 50 years old) and older (> or = 50 years old) subgroups., Study Design: A prospective cohort study; 383 subjects were instructed in the American Heart Association Step-One Diet. Adherence to the diet was assessed at 6 weeks. Eighty-seven subjects continued the diet for an additional 12 weeks., Setting: General community participants: volunteers from community cholesterol screening programs and chart reviews at family practice clinics., Study Participants: Men and women, aged 20 to 70 years, with baseline low-density lipoprotein cholesterol levels between the 50th and 95th percentile, and excluded if receiving any medications that affect blood lipid levels or if there was a history of diabetes, gout, peptic ulcer, or liver disease., Intervention: Instruction by a registered dietitian and adherence to the American Heart Association Step-One Diet for 6 (n = 383) and 18 weeks (n = 87). This diet involves an intake of total fat not to exceed 30% of calories, saturated fatty acids not to exceed 10% of calories, and dietary cholesterol limited to 300 mg/d., Results: Subjects aged 50 to 70 years averaged a reduction in total cholesterol level and low-density lipoprotein cholesterol level of 4% after 6 weeks. At the end of 18 weeks, mean total cholesterol and low-density lipoprotein cholesterol levels in subjects younger than 50 years exceeded their baseline levels, and in those older than 50 years returned to baseline lipid levels. Inadequate intake of several micronutrients were reported, notably, zinc, calcium, and vitamins A, D, and E., Conclusions: When recommending the American Heart Association Step-One Diet to persons with hyperlipidemia, baseline dietary behavior should be assessed to determine whether that diet offers therapeutic advantage over the persons's self-selected diet. Follow-up should include monitoring of lipid response and nutritional adequacy. Special emphasis should be placed on selection of foods with appropriate micronutrient content.

Objective: Compare lipid response, side effect profile and toxicity of younger (less than 50 years) versus older (50 to 70 years) hypercholesterolemic subjects taking wax-matrix sustained-release niacin (Endur-acin)., Study Design: An 8-week randomized double-blind placebo controlled trial., Setting: General community., Participants: Volunteers from community cholesterol screening programs and chart review of patients at family practice clinics. Male and female subjects, age 20 to 70, with baseline low density lipoprotein cholesterol level within the 75th to 95th percentile, excluded if on medications that affect lipids or if a history of diabetes, gout, peptic disease, or liver disease is present., Intervention: Nicotinic acid dosage schedules were 1,000 mg/day, 1,250 mg/day, 1,500 mg/day, or 2,000 mg/day for 8 weeks., Main Outcome Measures: Change in blood lipids and blood chemistries, side effects, and pill compliance., Results: 158 subjects (79%) completed the study. Higher dose groups (1,500 mg and 2,000 mg) demonstrated improvements in total cholesterol, LDL-cholesterol, HDL cholesterol, and total-to-HDL-cholesterol ratio (P less than 0.05) compared to baseline and controls. Higher-dose older subjects demonstrated significantly greater improvements than younger subjects on comparable doses for total cholesterol, HDL cholesterol, total-to-HDL-cholesterol ratio, and triglycerides, P less than 0.02). Adherence to medication schedules was better and incidence of side effects and toxicity no greater in older subjects compared to younger., Conclusion: Wax-matrix niacin (Endur-acin) was shown to be effective and well tolerated for the pharmacological treatment of hypercholesterolemia. Older persons, ages 50 to 70, appear to experience greater benefits with no greater side effects when compared to younger subjects on similar doses.

Background: Although diet therapy is the primary treatment for hypercholesterolemia, a trial to determine the effectiveness of the new American Heart Association Step One Diet (AHA diet) in lowering cholesterol has to our knowledge never been carried out., Methods: A clinical trial was conducted to assess the plasma lipids response and adherence to the AHA diet in 120 men and women with hypercholesterolemia. All subjects were advised to follow the AHA diet for 18 weeks., Results: After 6 weeks of the AHA diet intervention, there were modest but significant reductions in plasma total cholesterol (-2.6%) and low-density lipoprotein (LDL) cholesterol (-3.5%), but no further significant reductions were observed thereafter. Rather, there was a tendency to return to and even exceed baseline levels of total cholesterol and LDL cholesterol over the subsequent 12 weeks, in spite of the subjects' reported continued adherence to the AHA diet and maintenance of weight loss throughout the entire study period. Nevertheless, 51% of the subjects had experienced improvement (-0.2% to -26.3%) in their plasma LDL cholesterol levels by the end of the study., Conclusions: A probable reason for the limited response of the diet was low baseline levels in intake of saturated fat and cholesterol by participants. The subjects who were older and had higher levels of plasma LDL cholesterol and total fat intake at baseline experienced better plasma LDL cholesterol response to the AHA diet. Thus, practicing physicians should consider assessing the baseline dietary fat and cholesterol intake of patients with hypercholesterolemia before starting the AHA diet, since patients may already be following a relatively prudent self-selected diet. Additional dietary gains in lipid management might well require a more severe restriction of dietary fats and cholesterol. Long-term efficacy of the AHA diet should also be evaluated clinically with periodic lipid profiles.