Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

BACKGROUND AND OBJECTIVES: Impaired recovery from left ventricular (LV) dysfunction is a major prognostic factor after myocardial infarction (MI). Because P2Y12 receptor blockade inhibits myocardial injury, ticagrelor with off-target properties may have myocardial protection over clopidogrel. In animal models, ticagrelor vs. clopidogrel protects myocardium against reperfusion injury and improves remodeling after MI. We aimed to investigate the effect of ticagrelor on sequential myocardial remodeling process after MI. METHODS: High platelet inhibition with ticagrelor to improve LV remodeling in patients with ST-segment elevation MI (HEALING-AMI) is an investigator-initiated, randomized, open-label, assessor-blinded, multi-center trial done at 10 sites in Korea. Patients will be enrolled if they have ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention and a planned duration of dual antiplatelet treatment of at least 6 months. Screened patients will be randomly assigned (1:1) using an internet-based randomization with a computer-generated blocking with stratification across study sites to either ticagrelor or clopidogrel treatment. The co-primary primary endpoints are LV remodeling index with three-dimensional echocardiography and the level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) at 6 months representing post-MI remodeling processes. Changes of LV end-systolic/diastolic volume indices and LV ejection fraction between baseline and 6-month follow-up will be also evaluated. Analysis is per protocol. CONCLUSIONS: HEALING-AMI is testing the effect of ticagrelor in reducing adverse LV remodeling following STEMI. Our trial would show the benefit of ticagrelor vs. clopidogrel related to the recovery of post-MI LV dysfunction beyond potent platelet inhibition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02224534
Blood Platelets ; Echocardiography, Three-Dimensional ; Follow-Up Studies ; Humans ; Korea ; Models, Animal ; Myocardial Infarction ; Myocardium ; Natriuretic Peptide, Brain ; Percutaneous Coronary Intervention ; Random Allocation ; Reperfusion Injury ; Ventricular Remodeling

BACKGROUND AND OBJECTIVES: Impaired recovery from left ventricular (LV) dysfunction is a major prognostic factor after myocardial infarction (MI). Because P2Y12 receptor blockade inhibits myocardial injury, ticagrelor with off-target properties may have myocardial protection over clopidogrel. In animal models, ticagrelor vs. clopidogrel protects myocardium against reperfusion injury and improves remodeling after MI. We aimed to investigate the effect of ticagrelor on sequential myocardial remodeling process after MI. METHODS: High platelet inhibition with ticagrelor to improve LV remodeling in patients with ST-segment elevation MI (HEALING-AMI) is an investigator-initiated, randomized, open-label, assessor-blinded, multi-center trial done at 10 sites in Korea. Patients will be enrolled if they have ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention and a planned duration of dual antiplatelet treatment of at least 6 months. Screened patients will be randomly assigned (1:1) using an internet-based randomization with a computer-generated blocking with stratification across study sites to either ticagrelor or clopidogrel treatment. The co-primary primary endpoints are LV remodeling index with three-dimensional echocardiography and the level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) at 6 months representing post-MI remodeling processes. Changes of LV end-systolic/diastolic volume indices and LV ejection fraction between baseline and 6-month follow-up will be also evaluated. Analysis is per protocol. CONCLUSIONS HEALING-AMI is testing the effect of ticagrelor in reducing adverse LV remodeling following STEMI. Our trial would show the benefit of ticagrelor vs. clopidogrel related to the recovery of post-MI LV dysfunction beyond potent platelet inhibition.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02224534

The effects of capsaicin (CAP), a transient receptor potential vanilloid subtype 1 (TRPV1) agonist, were determined on nigrostriatal dopamine (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). The results showed that TRPV1 activation by CAP rescued nigrostriatal DA neurons, enhanced striatal DA functions and improved behavioral recovery in MPTP-treated mice. CAP neuroprotection was associated with reduced expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and reactive oxygen species/reactive nitrogen species from activated microglia-derived NADPH oxidase, inducible nitric oxide synthase or reactive astrocyte-derived myeloidperoxidase. These beneficial effects of CAP were reversed by treatment with the TRPV1 antagonists capsazepine and iodo-resiniferatoxin, indicating TRPV1 involvement. This study demonstrates that TRPV1 activation by CAP protects nigrostriatal DA neurons via inhibition of glial activation-mediated oxidative stress and neuroinflammation in the MPTP mouse model of PD. These results suggest that CAP and its analogs may be beneficial therapeutic agents for the treatment of PD and other neurodegenerative disorders that are associated with neuroinflammation and glial activation-derived oxidative damage.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Animals ; Capsaicin* ; Cytokines ; Dopamine* ; Dopaminergic Neurons* ; Mice ; NADPH Oxidase ; Necrosis ; Neurodegenerative Diseases ; Neurons ; Neuroprotection ; Nitric Oxide Synthase Type II ; Nitrogen ; Oxidative Stress* ; Oxygen ; Parkinson Disease*

The cannabinoid (CB2) receptor type 2 has been proposed to prevent the degeneration of dopamine neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. However, the mechanisms underlying CB2 receptor-mediated neuroprotection in MPTP mice have not been elucidated. The mechanisms underlying CB2 receptor-mediated neuroprotection of dopamine neurons in the substantia nigra (SN) were evaluated in the MPTP mouse model of Parkinson's disease (PD) by immunohistochemical staining (tyrosine hydroxylase, macrophage Ag complex-1, glial fibrillary acidic protein, myeloperoxidase (MPO), and CD3 and CD68), real-time PCR and a fluorescein isothiocyanate-labeled albumin assay. Treatment with the selective CB2 receptor agonist JWH-133 (10 μg kg⁻¹, intraperitoneal (i.p.)) prevented MPTP-induced degeneration of dopamine neurons in the SN and of their fibers in the striatum. This JWH-133-mediated neuroprotection was associated with the suppression of blood-brain barrier (BBB) damage, astroglial MPO expression, infiltration of peripheral immune cells and production of inducible nitric oxide synthase, proinflammatory cytokines and chemokines by activated microglia. The effects of JWH-133 were mimicked by the non-selective cannabinoid receptor WIN55,212 (10 μg kg⁻¹, i.p.). The observed neuroprotection and inhibition of glial-mediated neurotoxic events were reversed upon treatment with the selective CB2 receptor antagonist AM630, confirming the involvement of the CB2 receptor. Our results suggest that targeting the cannabinoid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with glial activation, BBB disruption and peripheral immune cell infiltration.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Animals ; Blood-Brain Barrier ; Chemokines ; Cytokines ; Dopamine* ; Dopaminergic Neurons* ; Fluorescein ; Glial Fibrillary Acidic Protein ; Macrophages ; Mice ; Microglia ; Neurodegenerative Diseases ; Neuroprotection ; Nitric Oxide Synthase Type II ; Parkinson Disease* ; Peroxidase ; Real-Time Polymerase Chain Reaction ; Receptor, Cannabinoid, CB2* ; Receptors, Cannabinoid ; Substantia Nigra

Canine parvovirus (CPV2) is one of the most virulent virus causing acute hemorrhagic enteritis and myocarditis in dogs. Infection mainly caused by the ingestion of virus through the mucosal route. Therefore, induction of mucosal immunity is essential in prevention of Canine Parvovirus (CPV2) infection. For safe and effective delivery of viral antigens to the mucosal immune system, a novel surface antigen display system for lactic acid bacteria using the poly-gamma-glutamic acid synthetase A protein (pgsA) of Bacillus subtilis as an anchoring matrix was applied in order to display CPV2 antigen on the surface of the recombinant L. casei. Recombinant fusion proteins comprised of pgsA and the capsid protein (VP2-S1) showed stable expression in Lactobacillus casei. Surface localization of the fusion protein was verified by cellular fractionation analyses. Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and mucosal IgA, as demonstrated by ELISA using recombinant VP2-S1 proteins. Mice receiving intranasal immunization mounted higher antibody response than those receiving oral immunization. These results indicate that mucosal immunization with recombinant L. casei expressing CPV2 VP2-S1 protein on its surface provides an effective means for elicitation of strong antibody responses against CPV 2 VP2-S1.
Animals ; Antibody Formation ; Antigens, Surface ; Antigens, Viral ; Bacillus subtilis ; Bacteria ; Capsid Proteins ; Capsid* ; Dogs ; Eating ; Enteritis ; Enzyme-Linked Immunosorbent Assay ; Immune System ; Immunity, Mucosal ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Lactic Acid ; Lactobacillus casei* ; Lactobacillus* ; Ligases ; Mice ; Myocarditis ; Parvovirus, Canine* ; Proteins ; Recombinant Fusion Proteins ; Viruses

PURPOSE: To evaluate the combined role of mescenchymal stem cells (MSCs) infected with recombinant adenoviruses expressing human BDNF (rAd/hBDNF) on the erectile dysfunction in rat with cavernous nerve injury. MATERIALS AND METHODS: Rats divided into 4 groups: control group, bilateral cavernous nerve crushing group (BCNC group), BCNC with MSCs group and BCNC with MSCs infected with rAd/hBDNF group. After 4-week, functional assessment was done. PKH26 and BDNF staining of major pelvic ganglion and masson's trichrome staining of corpus cavernosum were performed. Western blot analysis of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) was done in corpus cavernosum. RESULTS: After 4 weeks, BCNC with MSCs and MSCs infected with rAd/hBDNF groups showed significantly well-preserved erectile function compared with BCNC group. Moreover, the erectile function of MSCs infected with rAd/hBDNF group was significantly well-preserved than BCNC with MSCs group. The smooth muscle of corpus cavernosum was significantly preserved in BCNC with MSCs and MSCs infected with rAd/hBDNF groups compared with BCNC group. More preservation of smooth muscle was observed in rats with MSCs infected with rAd/hBDNF than with MSCs alone. Significant increase expression of eNOS and nNOS was noted in rats with MSCs infected with rAd/hBDNF than with MSCs alone. CONCLUSIONS: The erectile function was more preserved after injection with MSCs infected with rAd/hBDNF in rat with ED caused by cavernous nerve injury. Therefore, the use of MSC infected with rAd/hBDNF may have a better treatment effect on ED cause by cavernous nerve injury.
Adenoviridae ; Animals ; Blotting, Western ; Brain-Derived Neurotrophic Factor ; Caves ; Erectile Dysfunction ; Ganglion Cysts ; Humans ; Male ; Mesenchymal Stromal Cells ; Muscle, Smooth ; Nerve Crush ; Nitric Oxide Synthase Type I ; Nitric Oxide Synthase Type III ; Organic Chemicals ; Rats ; Stem Cells

INTRODUCTIONIntellectual disabilities are as prevalent in East Asian countries as in the West (0.06%-1.3%). Widespread discrimination against intellectual disabilities in Asia may initiate stigma that places unfair restrictions on the social life of these individuals and their caregivers. We utilised established stigma frameworks to assess the extent to which a child's intellectual disability contributes to the social exclusion of caregivers in Vietnam.

METHODSA mixed quantitative and qualitative approach was employed to examine the experience of social life restriction among parents of children with intellectual disabilities. The child's disability level and restrictions on caregivers' social experiences were assessed among 70 mothers and fathers recruited from schools in Hue City, Vietnam. Qualitative responses describing social exclusion were also recorded.

RESULTSCaregivers reported elevated levels of social exclusion. As hypothesised, parents of children with greater intellectual disability experienced more restrictions on their social life (Beta = 0.79, 95% confidence interval 0.27-1.30, standard error = 0.26, p < 0.01). Qualitative analyses indicated that the threatening of core cultural norms (inability to be employed or married upsets community harmony) initiated labelling, social exclusion and efforts to keep the condition secret or withdraw from others.

CONCLUSIONThis study is among the first to demonstrate the impacts of intellectual disabilities on caregivers' social functioning in Asia. The findings illustrate how traditional Asian norms initiate stigma, which in turn restricts key social interactions among caregivers. Psycho-educational interventions may address the social domains in which caregivers are impacted and encourage sustained help-seeking among caregivers for their children.

Attitude to Health ; Caregivers ; Child ; Child, Preschool ; Disabled Children ; Female ; Humans ; Intellectual Disability ; psychology ; therapy ; Male ; Parents ; Social Adjustment ; Social Behavior ; Social Stigma ; Social Support ; Stress, Psychological ; Surveys and Questionnaires ; Vietnam

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (beta1) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and P(corr)=0.05). The minor allele frequency (MAF) of ITGB1 haplotype-2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.
Carcinoma, Hepatocellular ; Gene Frequency ; Haplotypes ; Humans ; Integrins ; Linkage Disequilibrium ; Liver ; Logistic Models ; Neoplasm Metastasis ; Proportional Hazards Models ; Proteins ; Sequence Analysis, DNA