Racial-ethnic socialization, racial discrimination, and internalization of the model minority myth in East Asian families.

Guided by the integrative model, this study investigated the moderating effect of East Asian American youth-reported (N = 143) racial-ethnic socialization (RES) in the relationship between the youth's experiences of discrimination and internalization of the model minority myth. The results suggest that there was a significant interaction between youth's racial discrimination and youth-reported awareness of discrimination on youth's internalization of the model minority myth (b = 3.52, p < .05). No significant interaction effect emerged between racial discrimination and maintenance of heritage culture on internalization of model minority myth. The findings offer several contributions to inform research, family, and communities in understanding the ways caregivers respond to youth's racialized settings, which also contribute to youth's positive outcomes.

Risk behaviors as correlates of victimization of U.S.-born and foreign-born Asian, Black, and Latinx adolescents in the United States.

The current study examines the association between risk behaviors and victimization and race-based victimization amongst U.S.-born and foreign-born Asian, Black, and Latinx adolescents. Data were derived from the U.S. subset of the 2009-2010 Health Behavior in School-aged Children study. Samples include 662 Asian, 2413 Black, and 3188 Latinx adolescents (M = 12.9, SD = 1.75, 48.6% female) in grades 5-10. Univariate analyses, t-test analyses, and multiple linear regression analyses were conducted. Aggressive behavior was associated with victimization for U.S.-born and foreign-born Asian, Black, and Latinx adolescents. Race-based aggressive behavior was correlated for U.S.-born and foreign-born Black and Latinx adolescents. Smoking was positively associated with victimization amongst foreign-born Asian adolescents. Alcohol use was correlated with victimization and race-based victimization amongst foreign-born Latinx adolescents. Marijuana use was related to victimization amongst U.S.-born Black adolescents. Physical fighting was shown to be positively correlated with race-based victimization for U.S.-born Latinx adolescents. Carrying a weapon was associated with victimization and race-based victimization for U.S.-born and foreign-born Latinx adolescents. It was also associated with victimization amongst U.S.-born Asian adolescents. Befriending deviant peers was negatively associated with U.S.-born and foreign-born Black adolescents and U.S.-born Latinx adolescents, but positively associated with U.S.-born Asian adolescents.

Examining suicidality, bullying, and gun carrying among Latina/o youth over 10 years.

Latino/a youth have reported the highest rates of suicide attempts compared to White and African American youth for over 40 years. The data from the Youth Risk Behavior Surveillance System (YRBSS) cross-sectional subsamples of Latino/a youth (N = 13,378) at every year of data collection between 2005 and 2015 were examined for bullying, gun carrying, and suicidality. Results indicate that Latina girls are significantly more likely than boys to make a suicide attempt and report more bullying and more cyberbullying, but are less likely to carry a gun. Being bullied or carrying a gun were significantly associated with greater likelihood of suicide attempt among both boys and girls. Youth who carried a gun overall had higher rates of suicide attempts whether they were bullied or not, whereas youth who did not carry a gun were significantly more likely to attempt suicide if they were bullied. Over the past 10 years, gun carrying has decreased significantly for Latino boys and suicide attempts have decreased significantly for Latina girls. Findings have important implications of considering intersections of race and gender when developing antibullying and suicide prevention strategies. There are important policy implications for considering the mental well-being of youth who are caught carrying guns at school and considering that victimization varies by ethnicity and gender. (PsycINFO Database Record

Functional and structural properties of ion channels at the nerve terminal depends on compact myelin.

KEY POINTS: In the present study, we document the role of compact myelin in regulating the structural and functional properties of ion channels at the nerve terminals, using electrophysiology, dynamic Na(+) imaging and immunohistochemistry. The subcellular segregation of Na(+) channel expression and intracellular Na(+) dynamics at the heminode and terminal was lost in the dysmyelinated axon from Long-Evans shaker rats, which lack compact myelin. In Long-Evans shaker rats, loss of the Nav ß4 subunit specifically at the heminode reduced resurgent and persistent Na(+) currents, whereas K(+) channel expression and currents were increased. The results of the present study suggest that there is a specific role for compact myelin in dictating protein expression and function at the axon heminode and in regulating excitability of the nerve terminal. ABSTRACT: Axon myelination increases the conduction velocity and precision of action potential propagation. Although the negative effects of demyelination are generally attributed to conduction failure, accumulating evidence suggests that myelination also regulates the structural properties and molecular composition of the axonal membrane. In the present study, we investigated how myelination affects ion channel expression and function, particularly at the last axon heminode before the nerve terminal, which regulates the presynaptic excitability of the nerve terminal. We compared the structure and physiology of normal axons and those of the Long-Evans shaker (LES) rat, which lacks compact myelin. The normal segregation of Na(+) channel expression and dynamics at the heminode and terminal was lost in the LES rat. Specifically, NaV -α subunits were dispersed and NaV ß4 subunit was absent, whereas the density of K(+) channels was increased at the heminode. Correspondingly, resurgent and persistent Na(+) currents were reduced and K(+) current was increased. Taken together, these data suggest a specific role for compact myelin in the orchestration of ion channel expression and function at the axon heminode and in regulating excitability of the nerve terminal.

Developmental profiles of the intrinsic properties and synaptic function of auditory neurons in preterm and term baboon neonates.

The human fetus starts to hear and undergoes major developmental changes in the auditory system during the third trimester of pregnancy. Although there are significant data regarding development of the auditory system in rodents, changes in intrinsic properties and synaptic function of auditory neurons in developing primate brain at hearing onset are poorly understood. We performed whole-cell patch-clamp recordings of principal neurons in the medial nucleus of trapezoid body (MNTB) in preterm and term baboon brainstem slices to study the structural and functional maturation of auditory synapses. Each MNTB principal neuron received an excitatory input from a single calyx of Held terminal, and this one-to-one pattern of innervation was already formed in preterm baboons delivered at 67% of normal gestation. There was no difference in frequency or amplitude of spontaneous excitatory postsynaptic synaptic currents between preterm and term MNTB neurons. In contrast, the frequency of spontaneous GABA(A)/glycine receptor-mediated inhibitory postsynaptic synaptic currents, which were prevalent in preterm MNTB neurons, was significantly reduced in term MNTB neurons. Preterm MNTB neurons had a higher input resistance than term neurons and fired in bursts, whereas term MNTB neurons fired a single action potential in response to suprathreshold current injection. The maturation of intrinsic properties and dominance of excitatory inputs in the primate MNTB allow it to take on its mature role as a fast and reliable relay synapse.

Pharmacokinetic interactions between eperisone hydrochloride and aceclofenac: a randomized, open-label, crossover study of healthy Korean men.

BACKGROUND: Eperisone hydrochloride, a centrally acting muscle relaxant, is a calcium antagonist that causes vasodilation and antispastic actions. Aceclofenac, an anti-inflammatory analgesic and antipyretic drug, has similar efficacy and improved gastrointestinal tolerance compared with other nonsteroidal anti-inflammatory drugs, such as diclofenac. Although eperisone hydrochloride and aceclofenac are frequently coadministered, no published studies have reported on the pharmacokinetic interactions between these 2 drugs. OBJECTIVE: The aim of this study was to investigate any pharmacokinetic interactions between eperisone hydrochloride and aceclofenac in healthy Korean men. METHODS: This was a randomized, open-label, crossover study. Each participant was randomly assigned to 1 of 6 treatment sequences and received eperisone hydrochloride (3 doses of 50 mg each), aceclofenac (2 doses of 100 mg each), or both as a single dose with a 7-day washout period between each dose. Blood samples were collected ≤ 24 hours after dosing, and plasma eperisone hydrochloride and aceclofenac concentrations were determined using validated LC/MS-MS. Pharmacokinetic analyses were conducted using noncompartmental methods. A safety profile was determined using the measurement of vital signs, ECG, and clinical laboratory tests. RESULTS: A total 24 of men were enrolled, and all completed the study. The geometric mean ratios (90% CIs) of the Cmax and AUC0-∞ values for eperisone were 1.18 (0.828-1.673) and 1.12 (0.836-1.507), respectively. The geometric mean ratios (90% CIs) of the Cmax and AUC0-∞ for aceclofenac were 0.93 (0.847-1.022) and 1.01 (0.979-1.036), respectively. A total of 7 adverse events were reported in 7 men. All adverse events were mild, and no significant differences were found between treatment groups. CONCLUSION: No clinically significant pharmacokinetic differences exist between 150 mg eperisone hydrochloride and 200 mg aceclofenac when administrated as a monotherapy or in combination.

Central dysmyelination reduces the temporal fidelity of synaptic transmission and the reliability of postsynaptic firing during high-frequency stimulation.

Auditory brain stem circuits rely on fast, precise, and reliable neurotransmission to process auditory information. To determine the fundamental role of myelination in auditory brain stem function, we examined the evoked auditory brain stem response (ABR) from the Long Evans shaker (LES) rat, which lacks myelin due to a genetic deletion of myelin basic protein. In control rats, the ABR evoked by a click consisted of five well-defined waves (denoted waves I-V). In LES rats, waves I, IV, and V were present, but waves II and III were undetectable, indicating disrupted function in the earliest stages of central nervous system auditory processing. In addition, the developmental shortening of the interval between waves I and IV that normally occurs in control rats was arrested and resulted in a significant increase in the central conduction time in LES rats. In brain stem slices, action potential transmission between the calyx of Held terminals and the medial nucleus of the trapezoid body (MNTB) neurons was delayed and less reliable in LES rats, although the resting potential, threshold, input resistance, and length of the axon initial segment of the postsynaptic MNTB neurons were normal. The amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) and the degree of synaptic depression during high-frequency stimulation were not different between LES rats and controls, but LES rats exhibited a marked slow component to the EPSC decay and a much higher rate of presynaptic failures. Together, these results indicate that loss of myelin disrupts brain stem auditory processing, increasing central conduction time and reducing the reliability of neurotransmission.

Pharmacokinetic and pharmacodynamic properties of a new long-acting granulocyte colony-stimulating factor (HM10460A) in healthy volunteers.

BACKGROUND: HM10460A is a newly developed recombinant human granulocyte colony-stimulating factor with long-lasting characteristics. This factor is expected to be used for chemotherapy-related neutropenic conditions. OBJECTIVE: The aim of the present study was to evaluate the pharmacokinetics and pharmacodynamics of HM10460A following subcutaneous administration to healthy Korean subjects. METHODS: A randomized, double-blind, placebo-controlled, escalating single-dose study was conducted in 40 healthy Korean subjects. The subjects were allocated to single-dose groups of 5, 15, 45, 135 or 350 µg/kg, or placebo. Serial blood samples for pharmacokinetic/pharmacodynamic analyses were collected up to 22 days, and urine samples for pharmacokinetic analysis were collected up to 3 days after subcutaneous administration of HM10460A. The serum and urine concentrations were analyzed by enzyme-linked immunosorbent assay. RESULTS: Most of the serum concentrations in the 5 and 15 µg/kg dosing groups were below the lower limit of quantification (LLOQ). The median times to the peak concentration (T(max)) of HM10460A in the 45, 135, and 350 µg/kg dosing groups were 8.0, 14.0, and 24.0 h, respectively. The mean ± standard deviation values of the dose-normalized maximum concentration (C(max)) and dose-normalized area under the concentration-time curve (AUC(last)) for the 45, 135, and 350 µg/kg dosing groups were 14.13 ± 6.37, 66.19 ± 38.71, and 34.65 ± 19.69 µg/L/mg, respectively, and 265.0 ± 124.1, 2144 ± 1232, and 1386 ± 701.2 µg h/L/mg, respectively. The concentrations of HM10460A in the urine were below the LLOQ in all of the subjects. In all of the dosing groups, the area under the effect-time curve (AUEC(last)) of both the absolute neutrophil count (ANC) and the CD34(+) cell count increased as the dose increased. CONCLUSION: HM10460A showed dose-dependent pharmacokinetic characteristics, and the systemic exposure of HM10460A was positively correlated with the ANC and CD34(+) cell counts.

Prenatal diagnosis of congenital heart disease: trends in pregnancy termination rate, and perinatal and 1-year infant mortalities in Korea between 1994 and 2005.

AIM: To determine the pregnancy termination rate, and perinatal and 1-year infant mortality rates following prenatally-detected congenital heart disease (CHD) and trends over an 11-year period. METHODS: Between 1994 and 2005, 1603 gravidas underwent fetal echocardiography in our institution, in which 378 fetuses were diagnosed with CHD. The study period was divided into the following three groups for time-trend analysis: 1994-1997, 1998-2001, and 2002-2005. Data regarding gestational age at diagnosis and delivery, the presence of extracardiac or chromosomal abnormalities, pregnancy termination rate, and perinatal and 1-year mortalities were collected by review of medical records and telephone interviews. RESULTS: Among 378 fetuses with a prenatally-detected CHD, complete perinatal and infant outcomes were available for 336 fetuses (88.9%). There was a gradual increase in prenatally-detected CHD by fetal echocardiography during the study period (1994-1997, 10.3%; 1998-2001, 17.3%; and 2002-2005, 24.3%). The mean gestational ages at diagnosis and delivery were 27.2 +/- 5.6 and 37.8 +/- 2.9 weeks, respectively. Overall, the pregnancy termination rate in this study population was 20.2% and the perinatal and 1-year infant mortality rates were 6.3% and 9.7%, respectively. Among the fetuses who underwent cardiac surgery, surgical mortality occurred in two (3.8%); both died more than 1 month after surgery. Although the pregnancy termination rates remained unchanged, there was a significant decrease in perinatal and 1-year infant mortality rates over the study period. CONCLUSION: Although the perinatal and 1-year infant mortalities following prenatally-detected CHD have continued to decrease significantly during the past 11 years, pregnancy termination rates have remained unchanged.

The role of cytoreductive surgery for non-genital tract metastatic tumors to the ovaries.

OBJECTIVE: The aim of this study was to investigate prognostic factors of patients with metastases to the ovaries from non-genital organs. STUDY DESIGN: From September 1994 to December 2006, 158 patients with pathologically confirmed metastatic tumors to the ovaries at Samsung Medical Center (SMC) were included in this study. The data were obtained from the patients' medical records and pathology reports. RESULTS: The primary tumor origin was mostly stomach (73 cases) and colon (61 cases). Krukenberg tumor (pathologically proven signet ring cell carcinoma) was found in 34 cases: stomach (25), colon (2), appendix (1), and unknown (6). Residual disease after surgery was >2 cm in 65 (41.1%) cases and <2 cm in 93 (58.9%) cases. The overall 5-year survival was 7.2% and the median survival time was 15 months. The median survival times according to the primary tumor site showed significant differences (p=0.002) and were as follows: stomach 12 months, colon 17 months. The median survival in cases with residual disease <2 cm vs. >2 cm was 26 months vs. 15 months (p=0.017) and the median survival with vs. without adjuvant chemotherapy was 16 months vs. 10 months (p=0.001). However, age, bilateral tumors, chronology of diagnosis and mass size did not affect survival. CONCLUSION: Cytoreductive surgery and post-operative adjuvant chemotherapy had a beneficial effect on survival in selected patients.

Nuclear inhibitor of protein phosphatase-1 (NIPP1) directs protein phosphatase-1 (PP1) to dephosphorylate the U2 small nuclear ribonucleoprotein particle (snRNP) component, spliceosome-associated protein 155 (Sap155).

Pre-mRNA splicing entails reversible phosphorylation of spliceosomal proteins. Recent work has revealed essential roles for Ser/Thr phosphatases, such as protein phosphatase-1 (PP1), in splicing, but how these phosphatases are regulated is largely unknown. We show that nuclear inhibitor of PP1 (NIPP1), a major PP1 interactor in the vertebrate nucleus, recruits PP1 to Sap155 (spliceosome-associated protein 155), an essential component of U2 small nuclear ribonucleoprotein particles, and promotes Sap155 dephosphorylation. C-terminally truncated NIPP1 (NIPP1-DeltaC) formed a hyper-active holoenzyme with PP1, rendering PP1 minimally phosphorylated on an inhibitory site. Forced expression of NIPP1-WT and -DeltaC resulted in slight and severe decreases in Sap155 hyperphosphorylation, respectively, and the latter was accompanied with inhibition of splicing. PP1 overexpression produced similar effects, whereas small interfering RNA-mediated NIPP1 knockdown enhanced Sap155 hyperphosphorylation upon okadaic acid treatment. NIPP1 did not inhibit but rather stimulated Sap155 dephosphorylation by PP1 in vitro through facilitating Sap155/PP1 interaction. Further analysis revealed that NIPP1 specifically recognizes hyperphosphorylated Sap155 thorough its Forkhead-associated domain and dissociates from Sap155 after dephosphorylation by associated PP1. Thus NIPP1 works as a molecular sensor for PP1 to recognize phosphorylated Sap155.