Determination of Leuprolide-Fatty Acid Conjugate in Rat Plasma Using LC-MS/MS and Its Pharmacokinetics after Subcutaneous Administration in Rats.

Leuprolide is a synthetic nonapeptide drug (pyroGlu-His-Trp-Ser-Tyr-d-Leu-Leu-Arg-Pro-NHEt) that acts as a gonadotropin-releasing hormone agonist. The continuous administration of therapeutic doses of leuprolide inhibits gonadotropin secretion, which is used in androgen-deprivation therapy for the treatment of advanced prostate cancer, central precocious puberty, endometriosis, uterine fibroids, and other sex-hormone-related conditions. To improve the pharmacokinetic properties of peptide drugs, a fatty acid was conjugated with leuprolide for long-term action. In this study, we developed a simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of leuprolide and leuprolide-oleic acid conjugate (LOC) levels. The developed method was validated in terms of linearity, precision, accuracy, recovery, matrix effect, and stability according to the US Food and Drug Administration guidelines, and the parameters were within acceptable limits. Subsequently, the pharmacokinetics of leuprolide and LOCs were evaluated. In vivo rat subcutaneous studies revealed that conjugation with fatty acids significantly altered the pharmacokinetics of leuprolide. After the subcutaneous administration of fatty-acid-conjugated leuprolide, the mean absorption time and half-life were prolonged. To the best of our knowledge, this is the first study showing the effects of fatty acid conjugates on the pharmacokinetics of leuprolide using a newly developed UPLC-MS/MS method for the simultaneous quantification of leuprolide and LOCs.

Global Research Trends on Smart Homes for Older Adults: Bibliometric and Scientometric Analyses.

A growing aging population across the world signifies the importance of smart homes equipped with appropriate technology for the safety and health of older adults. Well-designed smart homes can increase the desire of older adults' aging-in-place and bring economic benefits to the country by reducing budgets for care providers. To obtain a structural overview and provide significant insights into the characteristics of smart homes for older adults, this study conducted bibliometric and scientometric analyses. We used the Web of Science Core Collection database, searching for keywords "smart home*", "home automation", or "domotics" with terms related to older adults, resulting in a total of 1408 documents. VOSviewer software was used to map and visualize the documents. The results showed that research on smart homes for older adults began appearing from 1997 and increased steadily, peaking from 2015. The main research areas were technical engineering fields, such as computer science and engineering, telecommunications with minimal research in humanities, social sciences, and design, indicating the necessity to expand research toward a human-centered perspective, age-friendly technology, and convergence study.

Older Adults' Response to Color Visibility in Indoor Residential Environment Using Eye-Tracking Technology.

Older adults spend relatively more time in indoor residential environments than young people. As their visual and cognitive abilities decline, they experience a high risk of accidents in indoor environments; thus, understanding their gaze behavior while considering cognitive capacity is essential in preventing potential accidents and planning for aging-friendly environments. The purpose of this study was to examine whether the use of color in living environments affects the visual attention of older adults. The following two experiments were conducted using eye-tracking technology: Experiment 1: Older adults' gaze behaviors were measured while viewing four images consisting of nine sets of door-door frames with different color combinations of safety colors, black and white; and Experiment 2: Based on results from Experiment 1, images of simulated living environments were created, and older adults' gaze behaviors were measured while viewing eight images in which two door colors were applied to verify spatial color visibility. Their cognitive state represented by the Mini-Mental State Examination (MMSE) was then compared with their gaze behavior. The results show that: (a) participants paid more attention to doors with color combinations including red (red-black and white-red) and remained longer on the red-black combination; (b) older adults looked at red-black doors faster than white doors in the same position; (c) the dwell time on a red-black door was longer than on that of the corresponding position of a white door; and (d) based on participants' MMSE values, the gaze behaviors of the group with low cognition were less focused and observable than those of the group with normal cognition. The results of this study are significant in that they reveal that indoor color can improve the visibility of elements that can impact safety in the living environments of older adults and enhance their quality of life.

Emerging Minimally Invasive Technologies for the Detection of Skin Cancer.

With the increasing incidence of skin cancer, many noninvasive technologies to detect its presence have been developed. This review focuses on reflectance confocal microscopy (RCM), optical coherence tomography (OCT), high-frequency ultrasound (HFUS), electrical impedance spectroscopy (EIS), pigmented lesion assay (PLA), and Raman spectroscopy (RS) and discusses the basic principle, clinical applications, advantages, and disadvantages of each technology. RCM provides high cellular resolution and has high sensitivity and specificity for the diagnosis of skin cancer. OCT provides lower resolution than RCM, although its evaluable depth is deeper than that of RCM. RCM and OCT may be useful in reducing the number of unnecessary biopsies, evaluating the tumor margin, and monitoring treatment response. HFUS can be mainly used to delineate tumor depths or margins and monitor the treatment response. EIS provides high sensitivity but low specificity for the diagnosis of skin malignancies. PLA, which is based on the genetic information of lesions, is applicable for the detection of melanoma with high sensitivity and moderate-to-high specificity. RS showed high accuracy for the diagnosis of skin cancer, although more clinical studies are required. Advances in these technologies for the diagnosis of skin cancer can lead to the realization of optimized and individualized treatments.

Korean Immigrants' Perception of Mental Well-Being and Help-Seeking Behaviors.

This article describes a study that investigated Korean immigrants' perception of mental well-being and help-seeking behaviors with particular focus on those with mental illness. Participants with probable diagnoses of anxiety or depression were more likely to recognize their mental health problems and their impact than those without such diagnoses. However, many of them did not acknowledge experiencing mental health problems and did not show high likelihood of seeking professional mental health services. The cultural beliefs and the lack of culturally competent mental health services appeared to contribute to the low levels of recognition of mental health problems and also the low rates of mental health service utilization. The participants listed mental health professionals' ability to communicate in the language of their preference, confidentiality, and affordability as significant factors in their decision to seek professional help. The study findings emphasize the great need of mental health educational programs within the Korean immigrant community. The findings also suggest that resources and infrastructures be secured for the provision of culturally competent mental health services for this population.

Spatial Color Efficacy in Perceived Luxury and Preference to Stay: An Eye-Tracking Study of Retail Interior Environment.

Color is a significant interior element with the power to influence emotions and behaviors in a particular environment. Numerous studies have investigated the impact of a single color on emotion; however, the collective emotional, cognitive, and behavioral effect created by combinations of colors applied to a space has not been thoroughly investigated. In this study involving both a survey as well as eye-tracking technology, we explored shaping the concept of spatial color efficacy by examining different applications of the same color combination in a space to determine whether they may cause different emotional responses, thereby impacting viewers' perception of luxury and intention to stay. A total of 26 interior design students at a university in Korea participated in the study. An environment simulating a hypothetical retail store was developed using a 3D rendering program, and six variations of spatial applications were created for each high luxury color combination and low luxury color combination to be used as stimuli. While viewing the images, participants were asked to identify which image looked most luxurious and in which space would they most want to stay. Results show the following: (a) the same color combination, if applied differently in a physical environment, can create different emotional responses, thereby affecting perceived luxury and preference to stay; (b) even a low luxury color combination can enhance perceived luxury and preference to stay depending on the spatial application; (c) gaze bias exists when selecting the most luxurious space and stating preference to stay as shown in the high correlation between dwell time and choice; in addition, differences in emotional response across images were also observed in the variations of pupil sizes measured during viewing various applications; (d) dark colors used in large amounts of surface were perceived as more luxurious than light colors when the same color combination was applied; and (e) appropriate contrast among colors was more influential in preference to stay than extreme or minimal contrast. Results expand the understanding of human behavior in relation to spatial color efficacy based on the spatial color combination and potential decision-making process in a retail setting.

Visible-Light-Promoted Synthesis of Dibenzofuran Derivatives.

Dibenzofurans are naturally occurring molecules that have received considerable attention for a variety of practical applications, such as in pharmaceuticals and electronic materials. Herein, an efficient and eco-friendly method for the synthesis of dibenzofuran derivatives via intramolecular C-O bond formation, which involves the in situ production of a diazonium salt, is described. The transformation requires a diazotizing agent and is promoted by the use of an organic photosensitizer under visible-light irradiation.

Understanding breast cancer screening behaviors of Korean American women in sociocultural contexts.

This study examines the breast cancer screening behaviors of Korean American women focusing on their cultural beliefs and access to health care. A total of 111 Korean American women participated in the cross-sectional survey research. Korean American women who felt embarrassed about breast cancer screenings were less likely to have received clinical breast exams or mammograms. Implications to culturally competent social work practice in promoting their breast cancer screening behaviors are discussed.

Synthesis of Substituted Oxazoles by Visible-Light Photocatalysis.

A simple and practical method for the synthesis of substituted oxazoles has been developed using readily available α-bromoketones and benzylamines by visible-light photocatalysis at room temperature. The process, which requires 1 mol % of [Ru(bpy)3]Cl2 photocatalyst with K3PO4 and CCl3Br, is effective for accessing a variety of valuable oxazole compounds. The synthetic utility of our protocol was also demonstrated by preparing a natural product, texaline.

Effectiveness of an Ongoing, Community-Based Breast Cancer Prevention Program for Korean American Women.

The study evaluates the effectiveness of an ongoing, community-based breast cancer prevention program offered by a local social services agency in the Washington, DC, metropolitan area. Korean American women who participated in this breast cancer prevention program were compared with those who did not participate in their knowledge, attitude, and screening behaviors. The study found that the intervention group was more knowledgeable on breast cancer and related services and reported more positive attitudes toward breast cancer screening services than the comparison group. The participants in the intervention group were also more likely to plan to receive a mammogram than those in the comparison group. However, significant differences were not observed in the two groups in their intention to receive a clinical breast examination. The study findings suggest that an ongoing, community-based breast cancer prevention program can be an effective method of addressing breast cancer prevention disparities observed among Korean American women.

Novel method for setting up 3D navigation system with skin-fixed dynamic reference frame in anterior cervical surgery.

PURPOSE: To introduce easy and useful methods using 3D navigation system with skin-fixed dynamic reference frame (DRF) in anterior cervical surgery and to validate its accuracy. METHODS: From September 2012 to May 2013, 31 patients underwent anterior cervical surgery and a total of 48 caspar distraction pins were inserted into each cervical vertebra. Every operation was performed using O-arm® navigation system with skin-fixed DRF. To validate the accuracy of these methods, a custom-made metal sleeve was used. In surgical field, through the metal sleeve, the tip of a navigation probe promptly contacts to the tip of caspar pin. We measured the vertical and horizontal distances and the angular deviation in sagittal plane between the caspar pin and the navigation probe on the virtual images and evaluated accuracy of navigation system with skin fixed DRF. RESULTS: Total 31 (males 20, females 11) patients and 48 caspar pins were included in this study. The mean horizontal distance between the caspar pin and the navigation probe displayed in navigation monitor was 0.49 ± 0.71 mm. The mean vertical distance between the caspar pin and the navigation probe displayed in navigation monitor was 0.88 ± 0.93 mm. And the mean angular deviation in sagittal plane between the caspar pin and the navigation probe displayed in navigation monitor was 0.59 ± 0.55°. CONCLUSIONS: 3D navigation system with skin-fixed DRF in anterior cervical surgery is a simple and reliable method and it can be a helpful supplement to a spine surgeon's judgement.

Inhibitory effect of hexane fraction from Myagropsis myagroides on pancreatic α-amylase in vitro.

A Myagropsis myagroides (Mm) methanol extract showed α-amylase inhibitory activity of 13% at a concentration of 5 mg/ml. Results showed that the hexane fraction from the Mm methanol extract exhibited α-amylase inhibitory activity with an IC50 value of 4.24 mg/ml. The hexane fraction was separated using silica-gel column chromatography, and six subfractions were obtained. The fraction eluted with CHCl3:MeOH = 50:1 showed the highest α-amylase inhibitory activity with an IC50 value of 0.72 mg/ml. This fraction was purified using Sephadex LH-20 column chromatography and an octadecyl silica (ODS) Sepak cartridge, obtaining seven subfractions. Fraction (Fr.) 4 also showed a strong α-amylase inhibitory activity with an IC50 value of 0.75 mg/ml. Fr. 4 was purified by Sephadex LH-20 column chromatography and ODS Sepak cartridge, obtaining six subfractions. Fr. 4-2 was identified as sargachromanol I with an IC50 value of 0.40 mg/ml, and the inhibition pattern analyzed from Lineweaver-Burk plots revealed it to be an uncompetitive inhibitor. These results suggest that Mm has potential as a natural antidiabetes agent.

The impact of weight changes on nonalcoholic Fatty liver disease in adult men with normal weight.

BACKGROUND: Although it is known that losing weight has an effect on the treatment of non-alcoholic fatty liver disease, the studies that show how losing weight affects the non-alcoholic fatty liver disease for the normal weight male adults are limited so far. In this study, we set body mass index as criteria and investigated how the weight changes for 4 years makes an impact on the risk of non-alcoholic fatty liver disease for the male adults who have the normal body mass index. METHODS: From January to December of 2004, among the normal weight male adults who had general check-up at the Health Promotion Center of Ulsan University Hospital, 180 people (average age, 47.4 ± 4.61 years) who were diagnosed with fatty liver through abdominal ultrasonography were included in this study and were observed according to the variety of data and ultrasonography after 4 years (2008). People who had a history of drinking more than 140 g of alcohol per week or who had a past medical history were excluded from the analysis. The weight change of subjects was calculated using the formula 'weight change = weight of 2008 (kg) - weight of 2004 (kg)' and classified into three groups, loss group (≤-3.0 kg), stable group (-2.9 to 2.9 kg), and gain group (≥3.0 kg). The odds for disappearance of non-alcoholic fatty liver disease in those three different groups were compared. RESULTS: Among 180 subjects, compared with stable group (67.2%, 121 subjects), loss group (11.7%, 21 subjects) showed 18.37-fold increase in the odds of disappearance of non-alcoholic fatty liver disease (95% confidence interval [CI], 4.34 to 77.80) and gain group (21.1%, 38 subjects) showed 0.28-fold decrease in the odds of disappearance of non-alcoholic fatty liver disease (95% CI, 0.10 to 0.83). CONCLUSION: Even for the normal weight people, losing weight has an effect on the improvement of non-alcoholic fatty liver disease.

Comparison of Ecklonia cava, Ecklonia stolonifera and Eisenia bicyclis for phlorotannin extraction.

Phlorotannins are polyphenols of marine algae, particularly brown seaweed, having multiple biological activities. A reverse phase-high performance liquid chromatography method was developed for rapid and routine quantification of two major phlorotannins, dieckol and phlorofucofuroeckol-A (PFE-A), from boiling water- and organic solvent-extracts of brown seaweeds Ecklonia cava, E. stolonifera and Eisenia bicyclis. The regression equations for dieckol and PFE-A were as follows: the concentration (mg ml(-1)) = 16.56 x peak height (cm) + 0.44, and the concentration = 20.60 x peak height (cm) + 0.11, with correlation coefficients of 0.996 and 0.999, respectively. Compared to organic solvent extraction, the recovery yield of dieckol from boiling water extracts of E. cava, E. stolonifera and E. bicyclis was 86%, 93%, and 98%, respectively. The recovery yield of PFE-A was 74%, 86% and 62%, respectively. Antioxidant activity was detected in each E. bicyclis water extract (91%), followed by E. stolonifera (90%) and E. cava (74%). Dieckol and PFE-A showed almost 9- and 7-fold stronger antioxidant activity than the standard butylhydroxytoluene, and 6-and 4-fold greater than L-ascorbic acid in molar concentration, respectively.

Analysis on bilateral hindlimb mapping in motor cortex of the rat by an intracortical microstimulation method.

Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the right cerebral hemisphere at 0.3 mm intervals vertically and horizontally from the bregma, and any movement of the hindlimbs was noted. The majority (80%± 11%) of responses were not restricted to a single joint, which occurred simultaneously at two or three hindlimb joints. The size and shape of hindlimb motor cortex was variable among rats, but existed on the convex side of the cerebral hemisphere in all rats. The results did not show symmetry according to specific joints in each rats. Conclusively, the hindlimb representation in the rat motor cortex was conveniently mapped using ICMS, but the characteristics and inter-individual variability suggest that precise individual mapping is needed to clarify motor distribution in rats.

Inhibitory effects of brown algae extracts on histamine production in mackerel muscle via inhibition of growth and histidine decarboxylase activity of Morganella morganii.

This study was performed to investigate the inhibitory effects of brown algae extracts on histamine production in mackerel muscle. First, antimicrobial activities of brown algae extracts against Morganella morganii were investigated using a disk diffusion method. An ethanol extract of Ecklonia cava (ECEE) exhibited strong antimicrobial activity. The minimum inhibitory concentration (MIC) of ECEE was 2 mg/ml. Furthermore, the brown algae extracts were examined for their ability to inhibit crude histidine decarboxylase (HDC) of M. morganii. The ethanol extract of Eisenia bicyclis (EBEE) and ECEE exhibited significant inhibitory activities (19.82% and 33.79%, respectively) at a concentration of 1 mg/ml. To obtain the phlorotannin dieckol, ECEE and EBEE were subjected to liquid-liquid extraction, silica gel column chromatography, and HPLC. Dieckol exhibited substantial inhibitory activity with an IC50 value of 0.61 mg/ml, and exhibited competitive inhibition. These extracts were also tested on mackerel muscle. The viable cell counts and histamine production in mackerel muscle inoculated with M. morganii treated with ≥2.5 MIC of ECEE (weight basis) were highly inhibited compared with the untreated sample. Furthermore, treatment of crude HDC-inoculated mackerel muscle with 0.5% ECEE and 0.5% EBEE (weight basis), which exhibited excellent inhibitory activities against crude HDC, reduced the overall histamine production by 46.29% and 56.89%, respectively, compared with the untreated sample. Thus, these inhibitory effects of ECEE and EBEE should be helpful in enhancing the safety of mackerel by suppressing histamine production in this fish species.

The efficacy of hydroxyapatite for screw augmentation in osteoporotic patients.

The stability of screw constructs is of considerable importance in determining the outcome, especially in spinal osteoporosis. Polymethylmethacrylate (PMMA) has been proven as an effective material for increasing the pullout strength of pedicle screws inserted into the osteoporotic bones. However, PMMA has several disadvantages, such as its exothermic properties, the risk of neural injury in the event of extravasation, and difficulties in performing revision surgery. In the current study, we used hydroxyapatite (HA) cement for screw augmentation in spinal osteoporosis. We conclude that HA cement is a useful tool for screw augmentation and recommend it as a promising option for spinal instrumentation in osteoporotic patients.

Solid fusion after lumbosacral arthroplasty.

A 55-year-old female was diagnosed with L5-S1 degenerative disc disease (DDD). Initial scores by the visual analogue scale (VAS) were 5 (back) and 9 (leg) and the Oswestry disability index (ODI) was 32. Arthroplasty was performed. Clinical and radiographic monitoring took place thereafter at one month, three months, six months and annually. At one month, VAS scores were 2 (back) and 3 (leg), ODI was 12 and ROM was 2.1° by radiographs. At two years, VAS scores were 1 (back) and 2 (leg), ODI was 6 and ROM was approaching 0. Five years after surgery, the entire operated segment (L5-S1) was solidly fused. A malpositioned disc implant may impair normal spinal movement, culminating in heterotopic ossification or complete fusion of the operated segment.

Induction of antifouling diterpene production by Streptomyces cinnabarinus PK209 in co-culture with marine-derived Alteromonas sp. KNS-16.

An active antifouling diterpene was isolated from marine actinomycete strain PK209 and productivity was induced in a co-culture experiment. The active constituent was identified as the diterpene lobocompactol by interpretion of nuclear magnetic resonance and mass spectroscopy data. A PK209 co-culture was designed and a lobocompactol-resistant bacterium, KNS-16, was selected as co-culture competitor to induce lobocompactol production. Adding a small volume of 16-h-old KNS-16 culture to the 96-h-old PK209 culture caused rapid induction of lobocompactol production. The final yield was 2.7 mg/L, 10.4-fold higher than that collected from a single PK209 culture. The two bacteria, strains PK209 and KNS-16, were identified as Streptomyces cinnabarinus and Alteromonas sp. based on 16S rDNA sequencing. Lobocompactol showed significant antifouling activity, of 0.18 and 0.43 µg/mL, for EC50 against the macroalga Ulva pertusa and the diatom Navicula annexa respectively. It showed activity with MIC of 61-112 µg/mL against fouling bacteria.

The accuracy of 3D image navigation with a cutaneously fixed dynamic reference frame in minimally invasive transforaminal lumbar interbody fusion.

OBJECTIVE: In contrast to preoperative image-based 3D navigation systems, which require surgeon-dependent registration, an intraoperative cone-beam computed tomography (cb-CT) image-based 3D navigation system allows automatic registration during the acquisition of 3D images intraoperatively. Thus, the need for spinal exposure for point matching is obviated, making a cb-CT image-based navigation system ideal for use in minimally invasive spinal procedures. Conventionally, the dynamic reference frame (DRF) is mounted to an adjacent spinous process or iliac bone through a separate incision. However, the close proximity of the DRF to the surgical area may result in its interfering with the surgical procedure or causing streak artifacts on the navigation images. Cutaneous placement of the DRF overlying the sacral hiatus is one possible solution to these problems, but such a placement does not provide a solid bony fixation point and is distant from the surgical area, both of which factors may hinder the accuracy of the navigation. The purpose of this study was to evaluate the accuracy of a novel idea for DRF placement in a series of mini-open transforaminal lumbar interbody fusion (TLIF) procedures performed with intraoperative cb-CT image-based 3D navigation. METHODS: From June 2009 to December 2009, 20 patients underwent mini-open TLIF for a total 82 pedicle screws placed in the lumbar spine with cutaneous placement of the DRF overlying the sacral hiatus. The pedicle screws were inserted under navigational guidance using cb-CT data acquired intraoperatively with a Medtronic O-arm. Screw positions were subsequently checked with a final intraoperative cb-CT scan. Nineteen patients underwent single-level fusion (8 at L4-5, 6 at L5-S1, 4 at L3-4, and 1 at L2-3) and one patient underwent two-level fusion (from L3-5). RESULTS: There were 4 (4.9%) pedicle perforations greater than 2 mm out of the 82 pedicle screw insertions in the 20 patients. Two of these breached screws were repositioned and confirmed to be in place with a final intraoperative cb-CT. There were no complications of neural injury associated with these perforations. CONCLUSION: A cutaneously mounted DRF overlying the sacral hiatus provides accuracy in intraoperative 3D image guided navigation for mini-open TLIF that is comparable to that obtained in other reported series using a fixed bony attachment point for the DRF.