Genetic association of human Corticotropin-Releasing Hormone Receptor 1 (CRHR1) with Internet gaming addiction in Korean male adolescents.

BACKGROUND: The number of people with Internet gaming addiction (IGA) is increasing around the world. IGA is known to be associated with personal characteristics, psychosocial factors, and physiological factors. However, few studies have examined the genetic factors related to IGA. This study aimed to investigate the association between IGA and stress-related genetic variants. METHODS: This cross-sectional study was conducted with 230 male high school students in a South Korean city. We selected five stress-related candidate genes: DAT1, DRD4, NET8, CHRNA4, and CRHR1. The DAT1 and DRD4 genes were genotyped by polymerase chain reaction, and the NET8, CHRNA4, and CRHR1 genes were genotyped by pyrosequencing analysis. We performed a Chi-square test to examine the relationship of these five candidate genes to IGA. RESULTS: Having the AA genotype and the A allele of the CRHR1 gene (rs28364027) was associated with higher odds of belonging to the IGA participant group (p = .016 and p = .021, respectively) than to the non-IGA group. By contrast, the DAT1, DRD4, NET8, and CHRNA4 gene polymorphisms showed no significant difference between the IGA group and control group. CONCLUSIONS: These results indicate that polymorphism of the CRHR1 gene may play an important role in IGA susceptibility in the Korean adolescent male population. These findings provide a justification and foundation for further investigation of genetic factors related to IGA.

Study on Strain Compensation for Multiple-Quantum Well in Infrared Light-Emitting Diode Using the InxGa1-xP Strain Barrier.

Strain compensation for multiple-quantum wells (MQWs) relative to the efficiency improvement of infrared light-emitting diodes (IR-LEDs) was investigated through the use of an InxGa1-xP strain barrier. The InxGa1-xP barrier, which was inserted between the n-confinement and active regions, developed for the reduction of lattice-mismatched strains in GaAs/AlGaAs and InGaAs/GaAs MQWs. Through photoluminescence, improved intensity was displayed in InGaAs/GaAs MQWs having InxGa1-xP strain barriers, with a significant increase in the intensity observed at the In0.47GaP strain barrier. This result is attributed to strain compensation between the In0.47GaP tensile strain barrier used and the In0.07GaAs compressive strain in MQWs. Through results based on InGaAs/GaAs MQWs, the highest output power of 6 mW was obtained at the In0.47GaP strain barrier, which shows a relative increase of almost 20% as compared to conventional MQWs.

The Melatonin Signaling Pathway in a Long-Term Memory In Vitro Study.

The activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) via phosphorylation in the hippocampus is an important signaling mechanism for enhancing memory processing. Although melatonin is known to increase CREB expression in various animal models, the signaling mechanism between melatonin and CREB has been unknown in vitro. Thus, we confirmed the signaling pathway between the melatonin receptor 1 (MT1) and CREB using melatonin in HT-22 cells. Melatonin increased MT1 and gradually induced signals associated with long-term memory processing through phosphorylation of Raf, ERK, p90RSK, CREB, and BDNF expression. We also confirmed that the calcium, JNK, and AKT pathways were not involved in this signaling pathway by melatonin in HT-22 cells. Furthermore, we investigated whether melatonin regulated the expressions of CREB-BDNF associated with long-term memory processing in aged HT-22 cells. In conclusion, melatonin mediated the MT1-ERK-p90RSK-CREB-BDNF signaling pathway in the in vitro long-term memory processing model and increased the levels of p-CREB and BDNF expression in melatonin-treated cells compared to untreated HT-22 cells in the cellular aged state. Therefore, this paper suggests that melatonin induces CREB signaling pathways associated with long-term memory processing in vitro.

Induction of Inflammation In Vivo by Electrocardiogram Sensor Operation Using Wireless Power Transmission.

Prolonged monitoring by cardiac electrocardiogram (ECG) sensors is useful for patients with emergency heart conditions. However, implant monitoring systems are limited by lack of tissue biocompatibility. Here, we developed an implantable ECG sensor for real-time monitoring of ventricular fibrillation and evaluated its biocompatibility using an animal model. The implantable sensor comprised transplant sensors with two electrodes, a wireless power transmission system, and a monitoring system. The sensor was inserted into the subcutaneous tissue of the abdominal area and operated for 1 h/day for 5 days using a wireless power system. Importantly, the sensor was encapsulated by subcutaneous tissue and induced angiogenesis, inflammation, and phagocytosis. In addition, we observed that the levels of inflammation-related markers increased with wireless-powered transmission via the ECG sensor; in particular, levels of the Th-1 cytokine interleukin-12 were significantly increased. The results showed that induced tissue damage was associated with the use of wireless-powered sensors. We also investigated research strategies for the prevention of adverse effects caused by lack of tissue biocompatibility of a wireless-powered ECG monitoring system and provided information on the clinical applications of inflammatory reactions in implant treatment using the wireless-powered transmission system.

In vitro and in vivo effects of melatonin on sister chromatid exchange in human blood lymphocytes exposed to hypoxia.

OBJECTIVE: Many studies have shown that melatonin (MLT) has an anti-genotoxic effect in various tissues and cell lines. The aim of this study was to investigate the anti-genotoxic effect of MLT on normal human peripheral lymphocytes by assessing sister chromatid exchange (SCE) in vitro and in vivo. MATERIALS AND METHODS: Cells were treated with 50 and 200 µM of MLT. The human volunteers (n = 20) for the in vivo study were administered a single dose of 3 mg MLT daily for 2 weeks. After sufficient time for its clearance, 1.5 mg of MLT daily was then administered to the same volunteers at same the period. RESULTS: Our results demonstrated the anti-genotoxic effect of MLT in human blood lymphocyte in vitro and in vivo. In vitro, hypoxia increased the SCE frequency compared to the control and both doses of MLT significantly decreased the SCE frequency in the hypoxic cells (p < 0.001). In vivo, oral administration of 3 mg MLT significantly increased the frequency of SCE, yet a small increase of SCE by hypoxia was found. Oral administration of 1.5 mg MLT showed no DNA damage but it had an anti-genotoxic effect. DISCUSSION AND CONCLUSION: MLT may prove useful for reducing the genotoxic effects of hypoxia in peripheral lymphocytes and suggest its possible role for ischemic diseases.

PIK3CA Amplification Is Common in Left Side-Tubular Adenomas but Uncommon Sessile Serrated Adenomas Exclusively with KRAS Mutation.

Colorectal cancer is a heterogeneous disorder than arises via multiple distinct pathways, from tubular adenomas (TAs) and sessile serrated adenomas (SSAs), which are clinically, morphologically, and molecularly different. We examined PIK3CA amplification in colorectal precancerous legions, including TAs and SSAs. DNA was isolated from paired normal and tumoral tissues in 64 TAs and 32 SSAs. PIK3CA amplification, KRAS mutation, and BRAF mutation were analyzed by real-time PCR and pyrosequencing. PIK3CA amplification was found in 25% of TAs and 9.4% of SSAs, respectively. KRAS and BRAF mutations were mutually exclusive in both TAs and SSAs. In TAs, PIK3CA amplification was associated with left side and it was mutually exclusive with KRAS mutation. These results suggest that PIK3CA amplification may be early and important event in colorectal carcinogenesis and may drive the development of left-side TAs independently with KRAS mutation.

A SNP in the ABCC11 gene is the determinant of human earwax type.

Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. Here we show that a SNP, 538G --> A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type. The AA genotype corresponds to dry earwax, and GA and GG to wet type. A 27-bp deletion in ABCC11 exon 29 was also found in a few individuals of Asian ancestry. A functional assay demonstrated that cells with allele A show a lower excretory activity for cGMP than those with allele G. The allele A frequency shows a north-south and east-west downward geographical gradient; worldwide, it is highest in Chinese and Koreans, and a common dry-type haplotype is retained among various ethnic populations. These suggest that the allele A arose in northeast Asia and thereafter spread through the world. The 538G --> A SNP is the first example of DNA polymorphism determining a visible genetic trait.

Association of sleep quality and mitochondrial DNA copy number in healthy middle-aged adults.

OBJECTIVES: Mitochondria contribute to various compromised health, yet the association between sleep and mitochondria remains unclear. This study investigated the association between sleep quality and mitochondrial function in healthy middle-aged adults in the Republic of Korea. METHOD: This cross-sectional study recruited 238 middle-aged adults using convenience sampling. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Mitochondrial function, represented by mitochondrial DNA copy number (mtDNAcn), was measured using real-time quantitative polymerase chain reaction on peripheral blood leukocytes. Multivariate linear regression analyses were performed to determine the association between sleep quality and mtDNAcn. RESULTS: Sleep quality was negatively associated with mtDNAcn (r = -.15, p = .025); the poor sleep quality group had a notably lower mtDNAcn compared to the good sleep quality group (t = 2.40, p = .017). Among the PSQI components, sleep latency was significantly associated with reduced mtDNAcn (r = -.18, p = .005). Univariate regression analysis revealed that mtDNAcn was significantly associated with education level (ß = 0.15, p = .017), shift work (ß = -0.17, p = .010), global PSQI score (ß = -0.15, p = .025), and sleep latency (ß = -0.18, p = .005). After adjusting for educational level and shift work in the final model, longer sleep latency was independently associated with reduced mtDNAcn (ß = -.16, p = .011). CONCLUSIONS: Poor sleep quality is associated with reduced mtDNAcn, suggesting a potential biological mechanism whereby poor sleep quality, specifically long sleep latency, accelerates cellular aging and impairs health through mitochondrial dysfunction. These findings enhance our understanding of the health effects of sleep quality and highlight the importance of screening and intervention strategies for mitochondrial dysfunction.

The lateral thoracic artery passing through duplicated axillary vein: a case report.

The axillary vein is a large-blood vessel that lies on the medial side to the axillary artery. The veins of the axilla are more abundant than the arteries and their variations were extremely common. During educational dissection, a rare form of the axillary vein accompanying arterial variation was founded in left arm of 70-year-old female cadaver. The axillary vein was divided into two large veins, anterior and posterior axillary veins according to their anatomical position. The lateral-thoracic artery arose from the second part of the axillary artery and passed through the gap of duplicated axillary vein. Before the lateral-thoracic artery passed through the gap of duplicated axillary vein, the lateral-thoracic artery gave-off an additional branch, which descended superficial to the anterior axillary vein. It surrounded the anterior axillary vein as annular form and the diameter of surrounded part of the anterior axillary vein became narrow. This novel case was reported and its clinical implications of such a variant were discussed.

Enhanced Light Output Power on Near-Infrared Light-Emitting Diodes with TITO/Ag Multilayer Reflector.

A titanium-indium tin oxide (TITO) multilayer reflector was investigated to improve the light efficiency of high-power, near-infrared, light-emitting diodes (NIR-LEDs). The TITO/Ag was fabricated by combining a patterned TITO and an omnidirectional reflector (ODR). For fabricating a high-power NIR-LED, the wafer bond process required the TITO reflective structure, which has patterns filled by AlAu contact metal, bonded directly to the Ag reflector deposited on the silicon wafer. Among Ag-based single- and multilayer reflectors, the TITO/Ag showed the highest reflectance (R = 96%), which was favorable for wafer-bonded high-power NIR-LEDs. Therefore, the TITO/Ag reflector enabled the production of wafer-bonded NIR-LED chips that exhibit superior output performance (190 mW) compared with conventional cases using a single Ag reflector.

Analysis of microsatellite instability in Korean patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a dangerous malignancy with a high mortality rate. Diagnosing PC at an early stage is difficult, and approximately 5% of the patients survive for 5 years. Microsatellite instability (MSI) plays an important role in colorectal cancer (CRC) for prognosis and immunotherapy. Evaluation of MSI status is important as it is recognized biomarker for the positive response of immune checkpoint blockade therapy in cancer. To our knowledge, there is no report yet on the prevalence of MSI in Korean PC patients. Studies have reported conflicting prevalence of MSI in PC. METHODS: Therefore, to improve the likelihood of MSI identification in PC, we included 133 patients with PC; paired tumor and normal tissue DNA were isolated and MSI was analyzed using Promega panel and immunohistochemistry (IHC) was also performed. RESULTS: Our results from the Promega panel indicated that one (0.7%) tumor was MSI-high (MSI-H), 13 (9.8%) were MSI-low (MSI-L), and 119 (89.5%) were microsatellite stable (MSS). IHC result also confirmed dMMR in only one sample. CONCLUSIONS: The finding of low incidence of MSI-H observed by the Promega panel also matched IHC results, so this study suggested that in Korean PC patients, MSI prevalence is infrequent.

Haddad syndrome with PHOX2B gene mutation in a Korean infant.

Congenital central hypoventilation syndrome with Hirschsprung's disease, also known as Haddad syndrome, is an extremely rare disorder with variable symptoms. Recent studies described that congenital central hypoventilation syndrome had deep relation to the mutation of the PHOX2B gene in its diagnosis and phenotype. We report a newborn male infant with clinical manifestations of recurrent hypoventilation with hypercapnea and bowel obstruction. These clinical manifestations were compatible with congenital central hypoventilation syndrome and Hirschsprung's disease, and polyalanine 26 repeats in the PHOX2B gene supported the diagnosis of congenital central hypoventilation. We described a first case of Haddad syndrome in Korean and its clinical and genetic characteristics were discussed.

Insertional anatomy and clinical relevance of the distal biceps tendon.

PURPOSE: This study was undertaken to evaluate the incidence of bifurcated distal biceps tendons and the tendon's insertional footprint on the radial tuberosity. METHODS: Twenty-five embalmed cadaveric specimens were dissected. The relationships and orientation of the muscle bellies and distal biceps tendon were examined. The insertional length, width, and footprint area of the distal biceps tendon on the radial tuberosity were evaluated. RESULTS: In 12 specimens (48%), the distal biceps tendon was in 2 distinct, easily separated parts. The average footprint length, width, and area of the tendon's insertion on the radial tuberosity were 20.5 mm ± 2.0 mm, 9.7 mm ± 1.3 mm, and 156.3 mm(2) ± 29.4 mm(2), respectively. We calculated that the tendon's insertion occupied approximately 35.9% of the area of the radial tuberosity. In the specimens with a bifurcated distal biceps tendon, the long head of the tendon inserted at the posterosuperior portion of the radial tuberosity, and the average area was 71.4 mm(2) ± 11.3 mm(2). The short head of the distal biceps tendon inserted at the anteroinferior portion, and the average area was 88.3 mm(2) ± 24.1 mm(2). CONCLUSION: This study confirmed that bifurcated distal biceps tendon insertion is not a rare anatomical variation, showed by recent investigations, and found that the short head of the distal biceps tendon was inserted more anteriorly than the long head on the radial tuberosity. These findings may allow functional independence and isolated rupture of each portion. It can make correct diagnosis possible and allow for a more anatomical orientation of the tendon during surgical repair.

Differences in the mitochondrial microsatellite instability of Keratoacanthoma and cutaneous squamous cell carcinoma.

Keratoacanthoma (KA) is a common cutaneous neoplasm which often resembles typical squamous cell carcinoma (SCC) in both its clinical and historical presentation. Several studies have attempted to identify methods for distinguishing between KA and SCC, however, none of these have proven to play any obvious roles in these tumors. Given this we went on to evaluate mitochondrial microsatellite instability (mtMSI) in KA and SCC in an effort to understand these tumors better. DNA was isolated from paired normal and tumoral tissues donated by 57 KA patients and 43 SCC patients. MtMSI was then analyzed using eight microsatellite markers and was observed in 2 (3.5%) of the 57 KA patients and 8 (18.6%) of the 43 SCC patients, respectively. MtMSI was also shown to affect different locations depending on tumor type. In KA patients, mtMSI was detected at mitochondrial D514 D-loop and presented with (CA) n repeats, in contrast, all of the SCC patient experienced mtMSI at the D310 with (C)n repeats of the D-loop region. These differences in location were found to be significant, which may support the hypothesis that KA and SCC have different pathogenetic pathways. Our results also suggest that mtMSI may be a candidate for developing novel differential diagnostic methods for KA and SCC.

Alterations in telomere length and mitochondrial DNA copy number in human lymphocytes on short-term exposure to moderate hypoxia.

Hypoxia is related to a variety of diseases, such as cardiovascular and inflammatory diseases and various cancers. Telomere length (TL) may vary according to the hypoxia level and cell types. To the best of our knowledge, no study has investigated the effect of moderate hypoxia on TL and mitochondrial DNA copy number (mtDNAcn) in human lymphocytes. Therefore, in this study, we analyzed the effect of moderate hypoxia on TL in correlation with mtDNAcn. This study included 32 healthy male nonsmoker's subjects; in this cohort, we had previously studied sister chromatid exchange and microsatellite instability. Blood samples from each subject were divided into three groups: a control group and two experimental groups exposed to moderate hypoxia for 12 or 24 h. Relative TL and mtDNAcn were measured by a quantitative real-time polymerase chain reaction. The TL in the control group did not significantly differ from that in the experimental group subjected to hypoxia for 12 h; however, the TL in the 24 h hypoxia-treated experimental group was significantly higher than that in the control group. The correlation between TL and mtDNAcn was not statistically significant in the two hypoxic states. The increase in TL was observed on exposure to hypoxia for 24 h and not for 12 h; thus, the findings suggest that telomere elongation is related to hypoxia exposure duration. The mtDNAcn in the two experimental groups did not significantly differ from that in the control group. These observations suggest that mtDNAcn alterations show more genetic stability than TL alterations. To the best of our knowledge, this is the first in vitro study on human lymphocytes reporting an increase in TL and no alteration in mtDNAcn after short-time exposure to moderate hypoxia.

Alzheimer's Disease: An Overview of Major Hypotheses and Therapeutic Options in Nanotechnology.

Alzheimer's disease (AD), a progressively fatal neurodegenerative disorder, is the most prominent form of dementia found today. Patients suffering from Alzheimer's begin to show the signs and symptoms, like decline in memory and cognition, long after the cellular damage has been initiated in their brain. There are several hypothesis for the neurodegeneration process; however, the lack of availability of in vivo models makes the recapitulation of AD in humans impossible. Moreover, the drugs currently available in the market serve to alleviate the symptoms and there is no cure for the disease. There have been two major hurdles in the process of finding the same-the inefficiency in cracking the complexity of the disease pathogenesis and the inefficiency in delivery of drugs targeted for AD. This review discusses the different drugs that have been designed over the recent years and the drug delivery options in the field of nanotechnology that have been found most feasible in surpassing the blood-brain barrier (BBB) and reaching the brain.

No Association between Merkel Cell Polymavirus Infection and Keratoacanthoma in Korean Patients

Objectives: Keratoacanthoma (KA) is a relatively common benign tumor and resembles squamous cell carcinoma (SCC). The definitive cause of KA remains unclear, but trauma, ultraviolet light, chemical carcinogens, human papillomavirus, genetic factors, and immunocompromised status have been implicated as etiologic or triggering factors. Merkel cell polyomavirus (MCPyV) is suspected to cause the majority of cases of Merkel cell carcinoma (MCC). MCPyV-DNA was found significantly more frequently in MCC and only found in about one fourth of KAs. In a recent study, MCPyV was found in Korean patients with MCC. The aim of this study was to determine the presence of MCPyV in Korean patients with KA. Methods: Paraffin-embedded tissue samples were analyzed for the presence of MCPyV-DNA by polymerase chain reaction (PCR). A total of 105 KA samples were analyzed. Results: A study of MCPyV has not been reported about KA in Korean cases. In the present study the MCPyV was not detected with KA in the Korean patients. Conclusions: This supports that KA and MCPyV are not related to each other and MCVyP is not a major factor in the pathogenesis of KA.

Photobiomodulation (660 nm) therapy reduces oxidative stress and induces BDNF expression in the hippocampus.

Photobiomodulation therapy (PBMT) effects an important role in neural regeneration and function enhancement, such as expression of nerve growth factor and nerve regeneration, in neuronal tissues, and inhibition of cell death by amyloid beta in neurons is inhibited by PBMT. However, there no studies evaluated the effects of PBMT on oxidative stress in the hippocampus. The aim of this study is to evaluate the effects of PBMT on oxidative stress in the hippocampus. This study assessed the anti-oxidative effect, the expression of BDNF and antioxidant enzymes, as well as the activation of cAMP response element binding (CREB) and extracellular signal-regulated kinase (ERK) signal transduction pathways assess using a hippocampal cell line (HT-22) and mouse organotypic hippocampal tissues by PBMT (LED, 660 nm, 20 mW/cm2). PBMT inhibited HT-22 cell death by oxidative stress and increased BDNF expression via ERK and CREB signaling pathway activation. In addition, PBMT increased BDNF expression in hippocampal organotypic slices and the levels of phosphorylated ERK and CREB, which were reduced by oxidative stress, as well as the expression of the antioxidant enzyme superoxide dismutase. These data demonstrate that PBMT inhibits hippocampal damage induced by oxidative stress and increases the expression of BDNF, which can be used as an alternative to treat a variety of related disorders that lead to nerve damage. Activation and redox homeostasis in neuronal cells may be a notable mechanism of the 660-nm PBMT-mediated photobioreactivity.

Thymol exposure mediates pro-oxidant shift by regulating Nrf2 and apoptotic events in zebrafish (Danio rerio) embryos.

The biochemical process of oxidative stress is an integral mechanism of chemical toxicity, contributing to complex pathological disorders. Thymol (THY) has a wide range of therapeutic applications for several ailments, although a better understanding of signaling cues regulated by this compound is needed to address the mechanism of its action. To better perceive the mode of action, we investigated the potential impact of THY on zebrafish embryos, with special emphasis on ROS biogenesis. In this study, we exposed the zebrafish embryos to 25, 50 and 100µM of THY for 96 hours post fertilization (hpf). Noticeable teratogenic effects were observed upon assessing the survival rate (LC50 = 42.35µM), hatching process, morphological exam and cardiac functions, thereby verifying the toxicity of THY on zebrafish embryos. Furthermore, we analyzed the effect of THY on the levels of ROS, mitochondrial membrane potential (ΔΨm) and immunofluorescence by DCFH-DA, JC-1, Casp-3-FITIC staining, respectively. Furthermore, we preformed the expressional analysis of Nrf2, superoxide dismutase-1 (SOD-1), catalase (CAT), Cytochrome P450 (CYP450) and apoptotic marker proteins (AIF, p53, Bax, Bcl-2, Casp-3 and Casp-9) in zebrafish embryos. As expected, we noticed a significant modulatory effect on the above-mentioned activities by THY. Collectively, our findings suggest that ROS might be the prime mediator responsible for THY-induced oxidative damage, thereby affecting the cellular defense mechanism and apoptotic events in zebrafish embryos.

Association between internet gaming addiction and leukocyte telomere length in Korean male adolescents.

Internet gaming addiction (IGA) has been associated with many negative health outcomes, especially for youth. In particular, the potential association between IGA and leukocyte telomere length (LTL) has yet to be examined. In this study we compared LTL in Korean male adolescents with and without IGA and examined the association between LTL and autonomic functions. Specifically, plasma catecholamine, serum cortisol, and psychological stress levels were measured as autonomic functions. Data were collected using participant blood samples analyzed for LTL, catecholamine, and cortisol levels and a set of questionnaires to assess IGA and psychological stress levels of the participants. The LTL measurements were made using a qPCR-based technique, and the relative LTL was calculated as the telomere/single copy (T/S) ratio. T/S ratio was significantly shorter in the IGA group than in the non-IGA group (150.43 ±â€¯6.20 and 187.23 ±â€¯6.42, respectively; p < .001) after adjusting for age. In a univariate regression analysis, age, daily Internet gaming time, IGA score, and catecholamine level (epinephrine and norepinephrine) were significantly associated with T/S ratio. However, duration of Internet gaming exposure, dopamine, cortisol, and psychological stress levels were not found to be associated with T/S ratio. In the final multiple linear regression model, age, daily Internet gaming time, and epinephrine level showed statistically significant relationships with T/S ratio. Our results indicate that in addition to age, involvement in excessive Internet gaming may induce LTL shortening in male adolescents, which may be partially attributable to changes in autonomic function such as catecholamine level. These findings further understanding of the health effects of IGA and highlight the need for screening and intervention strategies for male adolescents with IGA.