Muscarinic Acetylcholine M2 Receptors Regulate Lateral Habenula Neuron Activity and Control Cocaine Seeking Behavior.

The lateral habenula (LHb) balances reward and aversion by opposing activation of brain reward nuclei and is involved the inhibition of responding for cocaine in a model of impulsive behavior. Previously, we reported that the suppression of cocaine seeking was prevented by LHb inactivation or nonselective antagonism of LHb mAChRs. Here, we investigate mAChR subtypes mediating the effects of endogenous acetylcholine in this model of impulsive drug seeking and define cellular mechanisms in which mAChRs alter LHb neuron activity. Using in vitro electrophysiology, we find that LHb neurons are depolarized or hyperpolarized by the cholinergic agonists oxotremorine-M (Oxo-M) and carbachol (CCh), and that mAChRs inhibit synaptic GABA and glutamatergic inputs to these cells similarly in male and female rats. Synaptic effects of CCh were blocked by the M2-mAChR (M2R) antagonist AFDX-116 and not by pirenzepine, an M1-mAChR (M1R) antagonist. Oxo-M-mediated depolarizing currents were also blocked by AFDX-116. Although M2R activation inhibited excitatory and inhibitory inputs to LHb neurons, the effect on excitation was greater, suggesting a shift in excitatory-inhibitory balance toward net inhibition. Activation of VTA inhibitory inputs to LHb neurons, via channelrhodopsin-2 expression, evoked IPSCs that were inhibited by M2Rs. Finally, we measured LHb-dependent operant response inhibition for cocaine and found it impaired by antagonism of M2Rs, and not M1Rs. In summary, we show that a cholinergic signal to LHb and activation of M2Rs are critical to enable inhibition of responding for cocaine, and we define cellular mechanisms through which this may occur.Significance Statement:The lateral habenula (LHb) is a brain region receiving information from brain areas involved in decision-making, and its output influences motivation, reward, and movement. This interface between thoughts, emotions, and actions is how the LHb permits adaptive behavior, and LHb dysfunction is implicated in psychiatric and drug use disorders. Silencing the LHb impairs control over cocaine seeking in rats, and mAChRs are also implicated. Here, we measured cocaine seeking while blocking different mAChRs and examined mechanisms of mAChR effects on LHb neurons. M2-mAChRs were necessary for control of cocaine seeking, and these receptors altered LHb neuron activity in several ways. Our study reveals that LHb M2-mAChRs represent a potential target for treating substance use disorders.

Development of a FFQ for breast cancer survivors in Korea.

Diet may play an important role in breast cancer recurrence or survival, and therefore assessment of long-term diet among breast cancer survivors is important in breast cancer survivorship research. Given that the diet of breast cancer survivors may differ from that of the general population, the use of a FFQ specific to this group may be needed. The objective of this study was to develop a FFQ for breast cancer survivors, the most commonly used tool to measure long-term dietary patterns in nutritional epidemiological studies. We collected information on the foods and amounts of foods consumed using 3-d dietary records from a total of 192 women who had been diagnosed with stage I-III breast cancers and had undergone breast cancer surgery at least 6 months before the baseline study. A total of 1254 foods and dishes consumed were re-grouped by the similarity of the main ingredients and/or serving units, and several dishes commonly consumed among the Korean population were added. After we performed contribution analyses and variability analyses to detect between-person variation for selected nutrients, we listed a total of 123 foods and dishes for the FFQ specific to breast cancer survivors. Our breast cancer survivor-specific FFQ can be used to estimate long-term dietary intake and to examine its association with breast cancer prognosis in epidemiological studies of breast cancer in Korea.

Retinoic acid-mediated homeostatic plasticity drives cell type-specific CP-AMPAR accumulation in nucleus accumbens core and incubation of cocaine craving.

Incubation of cocaine craving, a translationally relevant model for the persistence of drug craving during abstinence, ultimately depends on strengthening of nucleus accumbens core (NAcc) synapses through synaptic insertion of homomeric GluA1 Ca 2+ -permeable AMPA receptors (CP-AMPARs). Here we tested the hypothesis that CP-AMPAR upregulation results from a form of homeostatic plasticity, previously characterized in vitro and in other brain regions, that depends on retinoic acid (RA) signaling in dendrites. Under normal conditions, ongoing synaptic transmission maintains intracellular Ca 2+ at levels sufficient to suppress RA synthesis. Prolonged blockade of neuronal activity results in disinhibition of RA synthesis, leading to increased GluA1 translation and synaptic insertion of homomeric GluA1 CP-AMPARs. Using slice recordings, we found that increasing RA signaling in NAcc medium spiny neurons (MSN) from drug-naïve rats rapidly upregulates CP-AMPARs, and that this pathway is operative only in MSN expressing the D1 dopamine receptor. In MSN recorded from rats that have undergone incubation of craving, this effect of RA is occluded; instead, interruption of RA signaling in the slice normalizes the incubation-associated elevation of synaptic CP-AMPARs. Paralleling this in vitro finding, interruption of RA signaling in the NAcc of 'incubated rats' normalizes the incubation-associated elevation of cue-induced cocaine seeking. These results suggest that RA signaling becomes tonically active in the NAcc during cocaine withdrawal and, by maintaining elevated CP-AMPAR levels, contributes to the incubation of cocaine craving.

Basal forebrain-lateral habenula inputs and control of impulsive behavior.

Deficits in impulse control are observed in several neurocognitive disorders, including attention deficit hyperactivity (ADHD), substance use disorders (SUDs), and those following traumatic brain injury (TBI). Understanding brain circuits and mechanisms contributing to impulsive behavior may aid in identifying therapeutic interventions. We previously reported that intact lateral habenula (LHb) function is necessary to limit impulsivity defined by impaired response inhibition in rats. Here, we examine the involvement of a synaptic input to the LHb on response inhibition using cellular, circuit, and behavioral approaches. Retrograde fluorogold tracing identified basal forebrain (BF) inputs to LHb, primarily arising from ventral pallidum and nucleus accumbens shell (VP/NAcs). Glutamic acid decarboxylase and cannabinoid CB1 receptor (CB1R) mRNAs colocalized with fluorogold, suggesting a cannabinoid modulated GABAergic pathway. Optogenetic activation of these axons strongly inhibited LHb neuron action potentials and GABA release was tonically suppressed by an endogenous cannabinoid in vitro. Behavioral experiments showed that response inhibition during signaled reward omission was impaired when VP/NAcs inputs to LHb were optogenetically stimulated, whereas inhibition of this pathway did not alter LHb control of impulsivity. Systemic injection with the psychotropic phytocannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC), also increased impulsivity in male, and not female rats, and this was blocked by LHb CB1R antagonism. However, as optogenetic VP/NAcs pathway inhibition did not alter impulse control, we conclude that the pro-impulsive effects of Δ9-THC likely do not occur via inhibition of this afferent. These results identify an inhibitory LHb afferent that is controlled by CB1Rs that can regulate impulsive behavior.

Retinoic acid-mediated homeostatic plasticity in the nucleus accumbens core contributes to incubation of cocaine craving.

RATIONALE: Incubation of cocaine craving refers to the progressive intensification of cue-induced craving during abstinence from cocaine self-administration. We showed previously that homomeric GluA1 Ca2+-permeable AMPARs (CP-AMPAR) accumulate in excitatory synapses of nucleus accumbens core (NAcc) medium spiny neurons (MSN) after ∼1 month of abstinence and thereafter their activation is required for expression of incubation. Therefore, it is important to understand mechanisms underlying CP-AMPAR plasticity. OBJECTIVES: We hypothesize that CP-AMPAR upregulation represents a retinoic acid (RA)-dependent form of homeostatic plasticity, previously described in other brain regions, in which a reduction in neuronal activity disinhibits RA synthesis, leading to GluA1 translation and CP-AMPAR synaptic insertion. We tested this using viral vectors to bidirectionally manipulate RA signaling in NAcc during abstinence following extended-access cocaine self-administration. RESULTS: We used shRNA targeted to the RA degradative enzyme Cyp26b1 to increase RA signaling. This treatment accelerated incubation; rats expressed incubation on abstinence day (AD) 15, when it is not yet detected in control rats. It also accelerated CP-AMPAR synaptic insertion measured with slice physiology. CP-AMPARs were detected in Cyp26b1 shRNA-expressing MSN, but not control MSN, on AD15-18. Next, we used shRNA targeted to the major RA synthetic enzyme Aldh1a1 to reduce RA signaling. In MSN expressing Aldh1a1 shRNA, synaptic CP-AMPARs were reduced in late withdrawal (AD42-60) compared to controls. However, we did not detect an effect of this manipulation on incubated cocaine seeking (AD40). CONCLUSIONS: These findings support the hypothesis that increased RA signaling during abstinence contributes to CP-AMPAR accumulation and incubation of cocaine craving.

Persistent Neuroadaptations in the Nucleus Accumbens Core Accompany Incubation of Methamphetamine Craving in Male and Female Rats.

Relapse is a major problem in treating methamphetamine use disorder. "Incubation of craving" during abstinence is a rat model for persistence of vulnerability to craving and relapse. While methamphetamine incubation has previously been demonstrated in male and female rats, it has not been demonstrated after withdrawal periods greater than 51 d and most mechanistic work used males. Here, we address both gaps. First, although methamphetamine intake was higher in males during self-administration training (6 h/d × 10 d), incubation was similar in males and females, with "incubated" craving persisting through withdrawal day (WD)100. Second, using whole-cell patch-clamp recordings in medium spiny neurons (MSNs) of the nucleus accumbens (NAc) core, we assessed synaptic levels of calcium-permeable AMPA receptors (CP-AMPARs), as their elevation is required for expression of incubation in males. In both sexes, compared with saline-self-administering controls, CP-AMPAR levels were significantly higher in methamphetamine rats across withdrawal, although this was less pronounced in WD100-135 rats than WD15-35 or WD40-75 methamphetamine rats. We also examined membrane properties and NMDA receptor (NMDAR) transmission. In saline controls, MSNs from males exhibited lower excitability than females. This difference was eliminated after incubation because of increased excitability of MSNs from males. NMDAR transmission did not differ between sexes and was not altered after incubation. In conclusion, incubation persists for longer than previously described and equally persistent CP-AMPAR plasticity in NAc core occurs in both sexes. Thus, abstinence-related synaptic plasticity in NAc is similar in males and females although other methamphetamine-related behaviors and neuroadaptations show differences.

Positive Allosteric Modulation of mGlu1 Reverses Cocaine-Induced Behavioral and Synaptic Plasticity Through the Integrated Stress Response and Oligophrenin-1.

BACKGROUND: Cue-induced cocaine craving progressively intensifies (incubates) during abstinence from cocaine self-administration. Expression of incubated cocaine craving depends on elevated calcium-permeable AMPA receptors (CP-AMPARs) on medium spiny neurons in the nucleus accumbens (NAc) core. After incubation has occurred, stimulation of NAc metabotropic glutamate 1 (mGlu1) receptors or systemic administration of mGlu1 positive allosteric modulators removes CP-AMPARs from NAc synapses via dynamin-dependent internalization (mGlu1 long-term depression [LTD]) and thereby reduces incubated cocaine craving. Because mGlu1 positive allosteric modulators are potential therapeutics for cocaine craving, it is important to further define the mechanism triggering this mGlu1-LTD. METHODS: Male and female rats self-administered saline or cocaine (10 days) using a long access regimen (6 h/day). Following ≥40 days of abstinence, we assessed the ability of an mGlu1 positive allosteric modulator to inhibit expression of incubated craving and remove CP-AMPARs from NAc synapses under control conditions, after blocking the integrated stress response (ISR), or after knocking down oligophrenin-1, a mediator of the ISR that can promote AMPAR endocytosis. AMPAR transmission in NAc medium spiny neurons was assessed with ex vivo slice recordings. RESULTS: mGlu1 stimulation reduced cue-induced craving and removed synaptic CP-AMPARs. When the ISR was blocked prior to mGlu1 stimulation, there was no reduction in cue-induced craving, nor were CP-AMPARs removed from the synapse. Further, selective knockdown of oligophrenin-1 blocked mGlu1-LTD. CONCLUSIONS: Our results indicate that mGlu1-LTD in the NAc and consequently the reduction of cue-induced seeking occur through activation of the ISR, which induces translation of oligophrenin-1. We also demonstrate CP-AMPAR accumulation and mGlu1 reversal in female rats, as previously shown in male rats.

Impairment of Synaptic Plasticity by Cannabis, Δ9-THC, and Synthetic Cannabinoids.

The ability of neurons to dynamically and flexibly encode synaptic inputs via short- and long-term plasticity is critical to an organism's ability to learn and adapt to the environment. Whereas synaptic plasticity may be encoded by pre- or postsynaptic mechanisms, current evidence suggests that optimization of learning requires both forms of plasticity. Endogenous cannabinoids (eCBs) play critical roles in modulating synaptic transmission via activation of cannabinoid CB1 receptors (CB1Rs) in many central nervous system (CNS) regions, and the eCB system has been implicated, either directly or indirectly, in several forms of synaptic plasticity. Because of this, perturbations within the eCB signaling system can lead to impairments in a variety of learned behaviors. One agent of altered eCB signaling is exposure to "exogenous cannabinoids" such as the primary psychoactive constituent of cannabis, Δ9-THC, or illicit synthetic cannabinoids that in many cases have higher potency and efficacy than Δ9-THC. Thus, by targeting the eCB system, these agonists can produce widespread impairment of synaptic plasticity by disrupting ongoing eCB function. Here, we review studies in which Δ9-THC and synthetic cannabinoids impair synaptic plasticity in a variety of neuronal circuits and examine evidence that this contributes to their well-documented ability to disrupt cognition and behavior.

mGlu5 function in the nucleus accumbens core during the incubation of methamphetamine craving.

Many studies have demonstrated that negative allosteric modulators (NAM) of metabotropic glutamate receptor 5 (mGlu5) reduce cocaine and methamphetamine seeking in extinction-reinstatement animal models of addiction. Less is known about effects of mGlu5 NAMs in abstinence models, particularly for methamphetamine. We used the incubation of drug craving model, in which cue-induced craving progressively intensifies after withdrawal from drug self-administration, to conduct the first studies of the following aspects of mGlu5 function in the rat nucleus accumbens (NAc) core during abstinence from methamphetamine self-administration: 1) functionality of the major form of synaptic depression in NAc medium spiny neurons, which is induced postsynaptically via mGlu5 and expressed presynaptically via cannabinoid type 1 receptors (CB1Rs), 2) mGlu5 surface expression and physical associations between mGlu5, Homer proteins, and diacylglycerol lipase-α, and 3) the effect of systemic and intra-NAc core administration of the mGlu5 NAM 3-((2-methyl-4-)ethynyl)pyridine (MTEP) on expression of incubated methamphetamine craving. We found that mGlu5/CB1R-dependent synaptic depression was lost during the rising phase of methamphetamine incubation but then recovered, in contrast to its persistent impairment during the plateau phase of incubation of cocaine craving. Furthermore, whereas the cocaine-induced impairment was accompanied by reduced mGlu5 levels and mGlu5-Homer associations, this was not the case for methamphetamine. Systemic MTEP reduced incubated methamphetamine seeking, but also reduced inactive hole nose-pokes and locomotion, while intra-NAc core MTEP had no significant effects. These findings provide the first insight into the role of mGlu5 in the incubation of methamphetamine craving and reveal differences from incubation of cocaine craving.

Altered Corticolimbic Control of the Nucleus Accumbens by Long-term Δ9-Tetrahydrocannabinol Exposure.

BACKGROUND: The decriminalization and legalization of cannabis and the expansion of availability of medical cannabis in North America have led to an increase in cannabis use and the availability of high-potency strains. Cannabis potency is determined by the concentration of Δ9-tetrahydrocannabinol (Δ9-THC), a psychoactive constituent that activates cannabinoid CB1 and CB2 receptors. The use of high-potency cannabis is associated with cannabis use disorder and increased susceptibility to psychiatric illness. The nucleus accumbens (NAc) is part of a brain reward circuit affected by Δ9-THC through modulation of glutamate afferents arising from corticolimbic brain areas implicated in drug addiction and psychiatric disorders. Moreover, brain imaging studies show alterations in corticolimbic and NAc properties in human cannabis users. METHODS: Using in vitro electrophysiology and optogenetics, we examined how Δ9-THC alters corticolimbic input to the NAc in rats. RESULTS: We found that long-term exposure to Δ9-THC weakens prefrontal cortex glutamate input to the NAc shell and strengthens input from basolateral amygdala and ventral hippocampus. Further, whereas long-term exposure to Δ9-THC had no effect on net strength of glutamatergic input to NAc shell arising from midbrain dopamine neurons, it alters fundamental properties of these synapses. CONCLUSIONS: Long-term exposure to Δ9-THC shifts control of the NAc shell from cortical to limbic input, likely contributing to cognitive and psychiatric dysfunction that is associated with cannabis use.

Pain and Menopause Symptoms of Breast Cancer Patients with Adjuvant Hormonal Therapy in Korea: Secondary Analysis.

OBJECTIVE: The purpose of this study was to describe the prevalence and levels of pain and menopause symptoms of breast cancer patients with adjuvant hormonal therapy (HT). METHODS: A cross-sectional survey design was used. Secondary analysis was used from the primary data collected in 2013 from a total of 110 breast cancer patients receiving HT for more than 3 months, using questionnaires of the Korean version of brief pain inventory and the menopause rating scale. RESULTS: Mean age of the participants was 53.56. Most (88.2%) of the participants reported to have pain and almost (95.5%) of them reported to have menopause symptoms. More pain was reported in participants with aromatase inhibitor (AI) than those with tamoxifen. Adherence to HT showed a significant difference according to the rate of feeling increased pain (P = 0.001). Among the menopause symptoms, fatigue was the most common symptom (97.3%). Sweating/flush was significantly higher in tamoxifen group (P < 0.005), and joint and muscle complaints were higher in AI group (P < 005). CONCLUSIONS: The results of the study show that the prevalence and levels of pain and menopause symptoms among breast cancer patients receiving HT were high. Thus, oncology professionals need to provide appropriate interventions to relieve pain and menopause symptom to improve adherence to HT.

Lateral Habenula Involvement in Impulsive Cocaine Seeking.

The lateral habenula (LHb) is a brain structure receiving inputs from limbic forebrain areas and innervating major midbrain monoaminergic nuclei. Evidence indicates LHb involvement in sleep control, reward-based decision making, avoidance of punishment, and responses to stress. Additional work has established that the LHb mediates negative feedback in response to aversive events. As a hallmark of drug addiction is the inability to limit drug use despite negative consequences, we hypothesize that LHb dysfunction may have a role in the lack of control over drug seeking. Here we examine the effects of LHb inactivation in control over drug seeking in several cocaine self-administration (SA) paradigms in rats. We find that inhibition of the LHb with GABAergic agonists did not alter cocaine SA under progressive ratio or seeking/taking chained reinforcement schedules, or during punishment-induced suppression of cocaine-reinforced responding. In contrast, LHb inhibition increased cocaine seeking when the drug was not available in rats trained to discriminate its presence using an environmental cue. This effect of LHb inhibition was selective for cocaine, as it did not impair responding for sucrose reinforcement. The effect of LHb injection of GABA agonists was mimicked by intra-LHb muscarinic cholinergic (mACh) antagonist injection, and activation of mACh receptors excited a majority of LHb neurons in in vitro electrophysiology experiments. These results indicate that the LHb participates in the suppression of impulsive responding for cocaine through the activation of a cholinergic circuit, and they suggest that LHb dysfunction may contribute to impaired impulse control associated with drug addiction.

Excessive Consumption of Green Tea as a Risk Factor for Periodontal Disease among Korean Adults.

This study was performed to assess the relationship between the amount of green tea that is consumed and periodontitis. It is based on data obtained from the Korea National Health and Nutrition Examination Survey, conducted between 2008 and 2010. A community periodontal index equal to code 3 was defined as moderate periodontitis, and code 4 was defined as severe periodontitis (n = 16,726). Consumption of green tea less than one cup per day was associated with a decreased prevalence of periodontal disease among Korean adults. The association between the consumption of green tea and periodontal disease was independent of various potential confounding factors, such as age, sex, body mass index, smoking, drinking, exercise, metabolic syndrome, frequency of tooth brushing per day, use of secondary oral products, the number of dental examination per year, diabetes, hypertension, and white blood cell count. Adjusted odds ratio and 95% confidence interval of no consumption was 1.360 (1.156, 1.601) when participants with consumption of two times per week ≤ x < 7 times per week was considered as a reference. However, consumption of one or more cups per day increased the prevalence of moderate and severe periodontitis. In conclusion, excessive consumption of green tea may be considered as a risk factor for periodontal disease among Korean adults.

Association between Consumption of Coffee and the Prevalence of Periodontitis: The 2008-2010 Korea National Health and Nutrition Examination Survey.

BACKGROUND: This study was performed to assess the relationship between the consumption of coffee and periodontitis using nationally representative data. METHODS: The data from the Korea National Health and Nutrition Examination Survey were used; the analysis in this study was confined to a total of 16,730 respondents over 19 years old who had no missing values for the consumption of coffee or outcome variables. A community periodontal index greater than or equal to code 3 was defined as periodontal disease. RESULTS: Consumption of coffee was significantly higher in the individuals with periodontitis in males. The odds ratios of the percentage of individuals with periodontitis tended to increase with the consumption of coffee. Adjusted odds ratios and their 95% confidence intervals of the male participants were 1, 1.131(0.792-1.617), 1.161(0.857-1.573), 1.053(0.805-1.379), 1.299(1.007-1.676), and 1.458(1.141-1.862) for once per month or less, once per month

Adherence to Guidelines for Cancer Survivors and Health-Related Quality of Life among Korean Breast Cancer Survivors.

There is limited evidence on the association between adherence to guidelines for cancer survivors and health-related quality of life (HRQoL). In a cross-sectional study of Korean breast cancer survivors, we examined whether adherence to the guidelines of the American Cancer Society (ACS) and World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) for cancer survivors was related to levels of HRQoL, assessed by the Korean version of Core 30 (C30) and Breast cancer module 23 (BR23) of the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ). We included a total of 160 women aged 21 to 79 years who had been diagnosed with breast cancer according to American Joint Committee on Cancer (AJCC) stages I to III and had breast cancer surgery at least six months before the interview. Increasing adherence to ACS guidelines was associated with higher scores of social functioning (p for trend = 0.05), whereas increasing adherence to WCRF/AICR recommendations was associated with higher scores of arm symptoms (p for trend = 0.01). These associations were limited to those with stage II or III cancer. Diet may be an important factor in relation to quality of life among Korean breast cancer survivors, however our findings warrant further prospective studies to evaluate whether healthy diet improves survivors' quality of life.

[Factors influencing quality of life in patients with breast cancer on hormone therapy].

PURPOSE: The purpose of the study was to identify degrees of pain, menopause symptoms, and quality of life, and to identify factors influencing quality of life of patients with breast cancer who were on hormone therapy. METHODS: A cross-sectional survey design was utilized. Data were collected using questionnaires from 110 patients with breast cancer who had been on hormone therapy for 3 months or more and were being treated at a university hospital in Seoul. Data were analyzed using χ²-test, t-test, ANOVA, Pearson correlation coefficient and multiple linear regression. RESULTS: Mean age of the participants was 53.56 (SD=6.67) and 54 (51.4%) had stage 0 or I at the time of diagnosis. Most of the participants reported having pain and menopause symptoms (88.2% and 95.5% respectively). The mean score for quality of life was 87.84±21.17. Pain, menopause symptoms and quality of life had strong correlations with each other (p<.005). Quality of life was explained by menopause symptoms (ß=-.71), economic status (ß=.20) and occupation (ß=.16). CONCLUSION: The results of the study suggest that menopause symptoms should be incorporated into oncologic nursing care to improve quality of life of patients with breast cancer on hormone therapy.

5HT(1B) receptor-mediated pre-synaptic depression of excitatory inputs to the rat lateral habenula.

Accumulating lines of evidence indicate that the lateral habenula (LHb), which reciprocally interacts with raphe nuclei (RN), displays hyperactivity including synaptic potentiation of excitatory inputs to the LHb during a depressed state. Despite the potential importance of glutamatergic excitatory synapses in depression-like behavior, modulation of these LHb synapses by monoamines such as serotonin (5HT) is not fully understood at the cellular and molecular level. Therefore, we used whole cell voltage-clamp recording to examine the molecular mechanisms by which 5HT modulates glutamatergic transmission in the LHb. The present study provides the first evidence that glutamatergic transmission of LHb synapses is inhibited by activation of the 5HT(1B) receptor at the pre-synapse in both acute depression (5HT-AD) and long-term depression (5HT-LTD). We further show that 5HT-AD results from the activation of Shaker-type K(+) channels whereas 5HT-LTD depends on inhibition of the adenylyl cyclase-cAMP (AC-cAMP) pathway with an increase in pre-synaptic Ca(2+) release from ryanodine-sensitive internal stores in an NO-dependent manner.

Couples' experiences of breast cancer in Korea: a descriptive qualitative study.

BACKGROUND: Breast cancer is not a disease merely experienced by the diagnosed woman. Despite the increased prevalence of breast cancer in Korea, the impact of the illness on married couples has not previously been studied. OBJECTIVE: This study aimed to explore the experiences of women with breast cancer and their spouses in South Korea. METHODS: A descriptive, single-occasion study design was used. Fourteen participants, comprising 7 dyads, were recruited from a university-affiliated hospital breast clinic in Seoul. Inclusion criteria were that the women were married and with a diagnosis of primary breast cancer without metastasis or recurrence. Using a semistructured interview schedule, interviews were conducted in a private room. Audio-recorded data in the Korean language were translated into English and coded using an inductive content analysis method. RESULTS: The core constructs found in the experiences of women, husbands, and couples were "Coming Into My Own Voice," "Doing What It Takes to Keep Her Alive," and "Learning Through Struggling," respectively. CONCLUSIONS: The diagnosis of breast cancer caused substantial distress for the couples and was transformative for the women and their husbands. The couples were still experiencing some unresolved hardships that required open communication and mutual effort for coping. IMPLICATIONS FOR PRACTICE: Health care practitioners should be sensitive to the cultural traditions and values that couples with breast cancer hold. After training nurse interventionists, educational counseling interventions should be launched, so as to empower the dyads.

Chiral attachment of styrene mediated by surface dimers on Ge100.

We have investigated the chiral adsorption configurations of styrene on Ge(100) using scanning tunneling microscopy at 300 K. The chemisorbed styrene on a single Ge dimer reduces the symmetry of the molecule, which produces a chiral center, and leads to the (S) or (R) chiral on-top configuration. We have found that the dimeric adsorption of styrene induced by the Ge surface dimer structure forms the enantiomeric and diastereomeric paired end-bridge configurations. We determine the absolute chirality of adsorbed styrene on Ge(100) and demonstrate a novel method for the achiral molecule to produce dimeric enantiomers and diastereomers attached to the semiconductor surface.