Health Behaviors Before and After the Implementation of a Health Community Organization: Gangwon's Health-Plus Community Program.

OBJECTIVES: Community organization is a resident-led movement aimed at creating fundamental social changes in the community by resolving its problems through the organized power of its residents. This study evaluated the effectiveness of health community organization (HCO), Gangwon's Health-Plus community program, implemented from 2013 to 2019 on residents' health behaviors. METHODS: This study had a before-and-after design using 2011-2019 Korea Community Health Survey data. To compare the 3-year periods before and after HCO implementation, the study targeted areas where the HCO had been implemented for 4 years or longer. Therefore, a total of 4512 individuals from 11 areas with HCO start years from 2013 to 2016 were included. Complex sample multi-logistic regression analysis adjusting for demographic characteristics (sex, age, residential area, income level, education level, and HCO start year) was conducted. RESULTS: HCO implementation was associated with decreased current smoking (adjusted odds ratio [aOR], 0.73; 95% confidence interval [CI], 0.57 to 0.95) and subjective stress recognition (aOR, 0.79; 95% CI, 0.64 to 0.97). Additionally, the HCO was associated with increased walking exercise practice (aOR, 1.39; 95% CI, 1.13 to 1.71), and attempts to control weight (aOR, 1.36; 95% CI, 1.12 to 1.64). No significant negative changes were observed in other health behavior variables. CONCLUSIONS: The HCO seems to have contributed to improving community health indicators. In the future, a follow-up study that analyzes only the effectiveness of the HCO through structured quasi-experimental studies will be needed.

Standardization of the Discrimination and Stigma Scale-Korean Version (DISC 12-K) in Patients with Depressive Disorders.

OBJECTIVE: The Discrimination and Stigma Scale (DISC 12), which assesses behavioral and experienced stigma, has not been translated into Korean. We developed and standardized the Korean version of the DISC 12 (DISC 12-K) in patients with depressive disorders. METHODS: The study included 230 patients with depressive disorders who were assessed on the four subscales of the DISC 12-K: Unfair Treatment, Stopping Self, Overcoming Stigma, and Positive Treatment. Additionally, stigma was assessed using the Internalized Stigma of Mental Illness scale, depressive symptoms using the Hamilton Depression Rating Scale and Beck Depression Inventory, level of functioning using the Social and Occupational Functioning Assessment Scale, self-esteem using the Rosenberg Self-Esteem Scale, and quality of life was assessed using the EuroQol-5D. The reliability of DISC 12 was assessed by internal consistency using Cronbach's alpha coefficient and estimating the intercorrelation of items and corrected item-total correlations; interrater reliability and test-retest reliability were assessed using intraclass correlation coefficients at the item and subscale levels; and the concurrent validity of the DISC 12-K relative to the other assessment scales was assessed using Spearman's correlation coefficient. RESULTS: All of the DISC 12-K subscales had high reliability. The validity was good for the Unfair Treatment and Stopping Self subscales, but only fair for the Overcoming Stigma and Positive Treatment subscales. CONCLUSION: The Unfair Treatment and Stopping Self subscales of the new DISC 12-K are reliable and valid measures of stigma in patients with depressive disorders. Future studies are needed to test the validity of this scale in other mental disorders.

Involvement of the Cuneate Nucleus in the Acupuncture Inhibition of Drug-Seeking Behaviors.

Our previous studies have shown that acupuncture suppresses addictive behaviors induced by drugs of abuse, including cocaine, morphine and ethanol, by modulating GABA neurons in the ventral tegmental area (VTA) and dopamine (DA) release in the nucleus accumbens (NAc). The mechanisms by which the peripheral signals generated by acupoint stimulation are transmitted to brain reward systems are largely unexplored. The present study aims to investigate the role of spinal dorsal column (DC) somatosensory pathways in the acupuncture inhibition of drug addictive behaviors. Thus, we tested whether acupuncture at Shenmen (HT7) points reduces drug-seeking behaviors in rats self-administering morphine or ethanol and whether such effects are inhibited by the disruption of the cuneate nucleus (CN). The stimulation of HT7 suppressed morphine and ethanol self-administration, which were completely abolished by surgical lesioning of the CN. In in vivo extracellular recordings, single-unit activity of the CN was evoked during acupuncture stimulation. The results suggest that acupuncture suppresses morphine- and ethanol-seeking behaviors through the modulation of the CN, second-order neurons of the DC somatosensory pathway.

A PDE1 inhibitor reduces adipogenesis in mice via regulation of lipolysis and adipogenic cell signaling.

Vinpocetine, a phosphodiesterase (PDE) type-1 inhibitor, increases cAMP and cGMP levels and is currently used for the management of cerebrovascular disorders, such as stroke, cerebral hemorrhage, and cognitive dysfunctions. In this study, we first determined that vinpocetine effectively suppressed adipogenesis and lipid accumulation. However, we questioned which molecular mechanism is involved because the role of PDE in adipogenesis is still controversial. Vinpocetine decreased adipogenic cell signaling, including the phosphorylation of ERK, AKT, JAK2, and STAT3, and adipokine secretion, including IL-6, IL-10, and IFN-α. Interestingly, vinpocetine increased the phosphorylation of HSL, suggesting the induction of the lipolysis pathway. Moreover, vinpocetine increased UCP1 expression via increasing cAMP and PKA phosphorylation. The administration of vinpocetine with a normal-chow diet (NFD) or a high-fat diet (HFD) in mice attenuated body weight gain in mice fed both the NFD and HFD. These effects were larger in the HFD-fed mice, without a difference in food intake. Vinpocetine drastically decreased fat weight and adipocyte cell sizes in gonadal and inguinal white adipose tissues and in the liver in both diet groups. Serum triacylglycerol levels and fasting blood glucose levels were reduced by vinpocetine treatment. This study suggested that vinpocetine prevents adipocyte differentiation through the inhibition of adipogenesis-associated cell signaling in the early stages of adipogenesis. Moreover, upregulating cAMP levels leads to an increase in lipolysis and UCP1 expression and then inhibits lipid accumulation. Therefore, we suggest that vinpocetine could be an effective agent for treating obesity, as well as improving cognition and cardiovascular function in older individuals.

Acupuncture inhibition of methamphetamine-induced behaviors, dopamine release and hyperthermia in the nucleus accumbens: mediation of group II mGluR.

Methamphetamine (METH) increases metabolic neuronal activity in the mesolimbic dopamine (DA) system and mediates the reinforcing effect. To explore the underlying mechanism of acupuncture intervention in reducing METH-induced behaviors, we investigated the effect of acupuncture on locomotor activity, ultrasonic vocalizations, extracellular DA release in the nucleus accumbens (NAcs) using fast-scan cyclic voltammetry and alterations of brain temperature (an indicator of local brain metabolic activity) produced by METH administration. When acupuncture was applied to HT7, but not TE4, both locomotor activity and 50-kHz ultrasonic vocalizations were suppressed in METH-treated rats. Acupuncture at HT7 attenuated the enhancement of electrically stimulated DA release in the NAc of METH-treated rats. Systemic injection of METH produced a sustained increase in NAc temperature, which was reversed by the DA D1 receptor antagonist SCH 23390 or acupuncture at HT7. Acupuncture inhibition of METH-induced NAc temperature was prevented by pre-treatment with a group II metabotropic glutamate receptors (mGluR2/3) antagonist EGLU into the NAc or mimicked by injection of an mGluR2/3 agonist DCG-IV into the NAc. These results suggest that acupuncture reduces extracellular DA release and metabolic neuronal activity in the NAc through activation of mGluR2/3 and suppresses METH-induced affective states and locomotor behavior.

Effects of acupuncture on the anxiety-like behavior induced by withdrawal from chronic morphine use.

OBJECTIVES: In the previous studies, it has been demonstrated that acupuncture treatment was effective on the suppression of withdrawal signs as well as self-administration behavior induced by morphine. Based on, the present study has investigated whether acupuncture could attenuate the anxiety-like behavior induced by withdrawal from chronic morphine treatment. MATERIALS & METHODS: Male Sprague-Dawley rats weighing 270-300g were treated saline or morphine hydrochloride (10mg/kg, s.c.) for 2 weeks. Following abstinence of 5days in home cage, rats were subjected to the measurement of anxiety-like behavior in the elevated plus maze. Bicuculline (1mg/kg, i.p.) and SCH 50911 (2mg/kg, i.p.) were used to investigate the possible mechanism of acupuncture effects focusing on the GABA receptors system. RESULTS: Acupuncture at HT7 increased the time spent in open arms significantly. Also, these effects of acupuncture at HT7 were blocked by GABAA receptor antagonist. CONCLUSION: Results of the present study suggest that acupuncture at HT7 can attenuate anxiety-like behavior induced by withdrawal from chronic morphine treatment through the mediation of GABAA receptor system.

Acupuncture suppresses intravenous methamphetamine self-administration through GABA receptor's mediation.

OBJECTIVES: Methamphetamine is one of the widely abused drugs. In spite of a number of studies, there is still little successful therapy to suppress the methamphetamine abuse. Acupuncture has shown to attenuate the reinforcing effects of psychostimulant. Based on, the present study investigated if acupuncture could suppress intravenous methamphetamine self-administration behavior. In addition, a possible neuronal mechanism was investigated. MATERIALS & METHODS: Male Sprague-Dawley rats weighing 270-300g were trained to intake food pellet. After catheter implantation, animal was trained to self-administer methamphetamine (0.05mg/kg) intravenously using fixed ratio 1 schedule in daily 2h session during 3 weeks. After training, rats who established baseline (infusion variation less than 20% of the mean for 3 consecutive days) received acupuncture treatment on the next day. Acupuncture was performed at each acupoint manually. In the second experiment, the selective antagonists of GABAA or GABAB receptor were given before acupuncture to investigate the possible neuronal involvement of GABA receptor pathway in the acupuncture effects. C-Fos expression was examined in the nucleus accumbens to support behavioral data. RESULTS: Acupuncture at HT7, but not at control acupoint LI5, reduced the self-administration behavior significantly. Also, the effects of acupuncture were blocked by the GABA receptor antagonists. C-Fos expression was shown to be parallel with the behavioral data. CONCLUSIONS: Results of this study have shown that acupuncture at HT7 suppressed methamphetamine self-administration through GABA receptor system, suggesting that acupuncture at HT7 can be a useful therapy for the treatment of methamphetamine abuse.

Enhanced Therapeutic Treatment of Colorectal Cancer Using Surface-Modified Nanoporous Acupuncture Needles.

Acupuncture originated within the auspices of Oriental medicine, and today is used as an alternative method for treating various diseases and symptoms. The physiological mechanisms of acupuncture appear to involve the release of endogenous opiates and neurotransmitters, with the signals mediating through electrical stimulation of the central nervous system (CNS). Earlier we reported a nanoporous stainless steel acupuncture needle with enhanced therapeutic properties, evaluated by electrophysiological and behavioral responses in Sprague-Dawley (SD) rats. Herein, we investigate molecular changes in colorectal cancer (CRC) rats by acupuncture treatment using the nanoporous needles. Treatment at acupoint HT7 is found most effective at reducing average tumor size, ß-catenin expression levels, and the number of aberrant crypt foci in the colon endothelium. Surface modification of acupuncture needles further enhances the therapeutic effects of acupuncture treatment in CRC rats.

Spinal pathways involved in somatosensory inhibition of the psychomotor actions of cocaine.

Previous studies have demonstrated that somatosensory stimuli influence dopamine transmission in the mesolimbic reward system and can reduce drug-induced motor behaviors, craving and dependence. Until now, the central links between somatosensory and brain reward systems are not known. Here, we show that the dorsal column (DC) somatosensory pathway contains projections that convey an inhibitory input from the periphery to mesolimbic reward circuits. Stimulation of the ulnar nerve under HT7 acupoint suppressed psychomotor response to cocaine, which was abolished by disruption of the DC pathway, but not the spinothalamic tract (STT). Low-threshold or wide-dynamic range neurons in the cuneate nucleus (CN) were excited by peripheral stimulation. Lesions of dorsal column or lateral habenula (LHb) prevented the inhibitory effects of peripheral stimulation on cocaine-induced neuronal activation in the nucleus accumbens (NAc). LHb neurons projecting to the ventral tegmental area (VTA)/rostromedial tegmental nucleus (RMTg) regions were activated by peripheral stimulation and LHb lesions reversed the inhibitory effects on cocaine locomotion produced by peripheral stimulation. These findings suggest that there exists a pathway in spinal cord that ascends from periphery to mesolimbic reward circuits (spino-mesolimbic pathway) and the activation of somatosensory input transmitted via the DC pathway can inhibit the psychomotor response to cocaine.

Kahweol inhibits lipid accumulation and induces Glucose-uptake through activation of AMP-activated protein kinase (AMPK).

Weight loss ≥ 5 percent is sufficient to significantly reduce health risks for obese people; therefore, development of novel weight loss compounds with reduced toxicity is urgently required. After screening of natural compounds with antiadipogenesis properties in 3T3-L1 cells, we determined that kahweol, a coffee-specific diterpene, inhibited adipogenesis. Kahweol reduced lipid accumulation and expression levels of adipogenesis and lipid accumulation-related factors. Levels of phosphorylated AKT and phosphorylated JAK2, that induce lipid accumulation, decreased in kahweol-treated cells. Particularly, kahweol treatment significantly increased AMP-activated protein kinase (AMPK) activation. We revealed that depletion of AMPK alleviated reduction in lipid accumulation from kahweol treatment, suggesting that inhibition of lipid accumulation by kahweol is dependent on AMPK activation. We detected more rapid reduction in blood glucose levels in mice administrated kahweol than in control mice. We suggest that kahweol has anti-obesity effects and should be studied further for possible therapeutic applications. [BMB Reports 2017; 50(11): 566-571].

The role of reactive oxygen species in methamphetamine self-administration and dopamine release in the nucleus accumbens.

Methamphetamine (METH) markedly increases dopamine (DA) release in the mesolimbic DA system, which plays an important role in mediating the reinforcing effects of METH. METH-induced DA release results in the formation of reactive oxygen species (ROS), leading to oxidative damage. We have recently reported that ROS are implicated in behavior changes and DA release in the nucleus accumbens (NAc) following cocaine administration. The aim of this study was to evaluate the involvement of ROS in METH-induced locomotor activity, self-administration and enhancement of DA release in the NAc. Systemic administration of a non-specific ROS scavenger, N-tert-butyl-α-phenylnitrone (PBN; 0, 50 and 75 mg/kg, IP) or a superoxide-selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL; 0, 50 and 100 mg/kg, IP), attenuated METH-induced locomotor activity without affecting generalized behavior in METH-naïve rats. PBN and TEMPOL significantly attenuated METH self-administration without affecting food intake. Increased oxidative stress was found in neurons, but not astrocytes, microglia or oligodendrocytes, in the NAc of METH self-administering rats. In addition, TEMPOL significantly decreased METH enhancement of DA release in the NAc. Taken together, these results suggest that enhancement of ROS in the NAc contributes to the reinforcing effect of METH.

Acupuncture Suppresses Morphine Craving in Progressive Ratio Through the GABA System.

Previous studies revealed that acupuncture suppressed both morphine self-administration and morphine-seeking behavior after abstinence. Based on these results, this study examined whether acupuncture attenuated morphine-craving under a progressive ratio (PR) schedule and investigated the possible neuronal mechanism. Male Sprague-Dawley rats were trained to self-administer morphine (0.5 mg/kg) at a fixed ratio for 9 days, and rats who achieved stable infusion were switched to a PR schedule. When animals had taken no more morphine for 1 hour, the number of infusions was defined as the break point (BP). After PR training, animals that had established a stable BP received acupuncture the next day. Acupuncture was applied for 1 minute immediately before the test session. Bicuculline (1.0 mg/kg) and SCH 50911 (2.0 mg/kg) were given 30 minutes prior to acupuncture. The c-Fos levels in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) were examined. Acupuncture at SI5 reduced the BP significantly. Moreover, the effects of acupuncture were blocked by either bicuculline or SCH 50911. Immunofluorescence revealed that acupuncture at SI5 decreased c-Fos expressions in the VTA and the NAc. This study demonstrates that acupuncture at SI5 is effective for the treatment of morphine-craving and that this effect is mediated via the GABA pathway.

Stopping Preemptive Antiviral Therapy for Hepatitis B Virus Can Be Considered for Patients with Favorable Predictors.

BACKGROUND: Preemptive antiviral therapy is recommended for chronic hepatitis B virus (HBV)-infected patients receiving cytotoxic chemotherapy. However, little data are available for the stopping therapy. AIMS: We evaluated clinical outcome and predictors of off-treatment virological response of patients who discontinued therapy. METHODS: Ninety-five adult patients who discontinued therapy were enrolled. They were analyzed for sustained off-treatment virological response, defined as HBV DNA levels below 2000 IU/ml for at least 12 months after the end of therapy. RESULTS: Sustained off-treatment virological response was seen in 52 patients (54.7%). The baseline HBV DNA level was an independent factor associated with sustained off-treatment virological response, and the rate was 72.1 and 23.5% for those with HBV DNA < 2000 IU/ml and ≥ 2000 IU/ml, respectively (P < 0.001). The duration of consolidation treatment showed marginal association with sustained off-treatment virological response [odd ratio (95% confidence interval) 1.20 (0.98-1.47), P = 0.069] for those with baseline HBV DNA < 2000 IU/ml, but not for those with ≥ 2000 IU/ml. The sustained off-treatment virological response rate was 54.5, 71.4, 73.9, and 100% for consolidation treatment duration of <3, 3-6, 6-12, and ≥ 12 months, respectively, among those with baseline HBV DNA < 2000 IU/ml. CONCLUSIONS: The baseline HBV DNA level was indicator for sustained off-treatment virological response after stopping preemptive antiviral therapy. Consolidation treatment duration showed association with sustained off-treatment virological response only for those with low baseline HBV DNA levels.

Acupuncture at HT7 suppresses morphine self-administration at high dose through GABA system.

In the previous study, acupuncture at HT7 has shown to attenuate the self-administration of morphine at a low dose (0.1mg/kg). In this study, it was further investigated whether acupuncture at HT7 could attenuate the morphine self-administration at a high dose (0.5mg/kg). Male Sprague-Dawley rats weighing 270-300g were used. After surgery of catheterization, animals were trained to self-administer morphine solution (0.5mg/kg) using daily 1h session under fixed ratio 1 schedule for 3 weeks. Animals that had shown stable morphine-taking (establish baseline: variation less than 20% of the mean of three consecutive days) were subjected to the acupuncture treatment. Bicuculline and SCH 50911 were used to investigate the possible relation between the effect of acupuncture and the GABA receptor system. Acupuncture at HT7, but not at control acupoint, LI5, suppressed spontaneous morphine-taking behavior significantly. In addition, the effect of acupuncture was blocked by both GABA receptor antagonists. The results of this study suggest that acupuncture at HT7 suppresses morphine-taking behavior through the mediation of GABA receptor system.

A case report of paraneoplastic pemphigus associated with esophageal squamous cell carcinoma.

Paraneoplastic pemphigus is an autoimmune blistering and erosive mucocutaneous syndrome associated with underlying neoplasm. It is primarily associated with lymphoproliferative disorders, and uncommonly with malignancies of epithelial origin. We report on a case of a 68-year-old male who presented with whole body bullous and erosive skin lesions. Findings on upper gastrointestinal endoscopy and skin biopsy revealed esophageal squamous cell carcinoma and paraneoplastic pemphigus. Palliative chemotherapy and systemic glucocorticoid were started, however, the patient died of overwhelming sepsis on the ninth day of chemotherapy. This case demonstrates that paraneoplastic pemphigus can occur in esophageal squamous cell carcinoma and could be a cause of morbidity.