Robotic thyroidectomy using gas-insufflation one-step single-port transaxillary (GOSTA) approach.

BACKGROUND: We conducted this study to report our novel robotic thyroidectomy using gas-insufflation one-step single-port transaxillary (GOSTA) approach and compare it with a conventional transaxillary (CTA) approach using a retraction method for intraoperative and postoperative outcomes. METHODS: We retrospectively analyzed 354 patients who underwent robotic thyroidectomy between January 2019 and April 2023. Of these patients, 143 underwent the procedure through the GOSTA approach, which involves a small incision of 3 cm along the axillary folds with both arms down and a gas-insufflation, from skin flap creation to the completion of thyroidectomy as a one-step single-port procedure without the need for a retractor. The remaining 211 patients underwent the CTA approach. We analyzed the GOSTA approach and compared the surgical outcomes of the GOSTA (n = 100) and CTA (n = 167) approaches in patients with differentiated thyroid cancer who underwent thyroid lobectomy. RESULTS: Out of the 143 patients who underwent the GOSTA approach, 12 underwent total thyroidectomy and 9 underwent lateral neck lymph node dissection with total thyroidectomy. GOSTA-thyroid lobectomy was performed on 122 patients; of these, 100 were diagnosed with differentiated thyroid carcinoma. A comparative study with the CTA approach was only conducted in patients who underwent thyroid lobectomy. No significant differences were found in operative time, hospital stay, or complications between the two groups. CONCLUSIONS: Despite proceeding in one-step with a single smaller incision, from skin flap creation to the completion of thyroidectomy, the GOSTA approach is as feasible and safe as the CTA approach. Additionally, the GOSTA approach allows for thyroidectomy without using a retractor and reduces the workload for the surgeon and assistants.

Comparison of robotic and laparoscopic lateral transperitoneal adrenalectomies.

Purpose: This study aimed to compare the intraoperative and postoperative outcomes between robotic and laparoscopic transperitoneal adrenalectomies. Methods: In this retrospective study, 93 patients underwent adrenalectomy using 2 surgical modalities: 45 patients underwent adrenalectomy using the da Vinci Xi system (robotic group), and 48 patients using laparoscopic devices (laparoscopic group). We compared the operation time, intraoperative bleeding, and hospital stay according to the surgical modality and tumor characteristics. Results: There were no significant differences in the operative time (P = 0.827), hospital stay (P = 0.177), and intraoperative bleeding (P = 0.174) between the groups. However, the robotic group showed a lower coefficient of variation in total operative time than that of the laparoscopic group (100.6 ± 23.3 minutes vs. 101.9±32.7 minutes, 0.230 vs. 0.321). When divided into 2 subgroups based on the tumor size (<3 cm and ≥3 cm), the robotic group with a tumor sized >3 cm had a shorter operative time than that of the laparoscopic group (P = 0.032). The robotic group also had fewer cases of intraoperative bleeding (P = 0.034). Conclusions: Compared to the laparoscopic transperitoneal adrenalectomy, the robotic one achieved a lower deviation in total operative time and showed less bleeding and a shorter operative time, especially for tumors sized >3 cm.

PIK3CA Mutation as Potential Poor Prognostic Marker in Asian Female Breast Cancer Patients Who Received Adjuvant Chemotherapy.

Background: The prognostic relevance of the PIK3CA mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy. Methods: We analyzed PIK3CA mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the PIK3CA mutation with PD-L1/c-Met/MMR was explored. Results: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-wildtype within the c-Met-positive, MSS, triple-negative, or age onset <50 years subgroups, which showed a similar trend of association in TCGA data. Conclusions: PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.

Autistic-like social deficits in hippocampal MeCP2 knockdown rat models are rescued by ketamine.

Autism or autism spectrum disorder (ASD) is a behavioral syndrome characterized by persistent deficits in social interaction, and repetitive patterns of behavior, interests, or activities. The gene encoding Methyl-CpG binding protein 2 (MeCP2) is one of a few exceptional genes of established causal effect in ASD. Although genetically engineered mice studies may shed light on how MeCP2 loss affects synaptic activity patterns across the whole brain, such studies are not considered practical in ASD patients due to the overall level of impairment, and are technically challenging in mice. For the first time, we show that hippocampal MeCP2 knockdown produces behavioral abnormalities associated with autism-like traits in rats, providing a new strategy to investigate the efficacy of therapeutics in ASD. Ketamine, an N-Methyl-D-aspartate (NMDA) blocker, has been proposed as a possible treatment for autism. Using the MeCP2 knockdown rats in conjunction with a rat model of valproic acid (VPA)-induced ASD, we examined gene expression and ASD behaviors upon ketamine treatment. We report that the core symptoms of autism in MeCP2 knockdown rats with social impairment recovered dramatically following a single treatment with ketamine. [BMB Reports 2022; 55(5): 238-243].

LGI1 governs neuritin-mediated resilience to chronic stress.

Depression is accompanied by neuronal atrophy and decreased neuroplasticity. Leucine-rich glioma-inactivated protein 1 (LGI1), a metastasis suppressor, plays an important role in the development of CNS synapses. We found that LGI1 expression was reduced in the hippocampi of mice that underwent chronic unpredictable stress (CUS), and could be rescued by the antidepressant, fluoxetine. Recombinant soluble neuritin, an endogenous protein previously implicated in antidepressant-like behaviors, elevated hippocampal LGI1 expression in a manner dependent on histone deacetylase 5 (HDAC5) phosphorylation. Accordingly, Nrn1 flox/flox ;Pomc-cre (Nrn1 cOE) mice, which conditionally overexpress neuritin, displayed increases in hippocampal LGI1 level under CUS and exhibited resilience to CUS that were blocked by hippocampal depletion of LGI1. Interestingly, neuritin-mediated LGI1 expression was inhibited by HNMPA-(AM)3, an insulin receptor inhibitor, as was neuritin-mediated HDAC5 phosphorylation. We thus establish hippocampal LGI1 as an effector of neurite outgrowth and stress resilience, and suggest that HDAC5-LGI1 plays a critical role in ameliorating pathological depression.

SGK1 inhibition in glia ameliorates pathologies and symptoms in Parkinson disease animal models.

Astrocytes and microglia are brain-resident glia that can establish harmful inflammatory environments in disease contexts and thereby contribute to the progression of neuronal loss in neurodegenerative disorders. Correcting the diseased properties of glia is therefore an appealing strategy for treating brain diseases. Previous studies have shown that serum/ glucocorticoid related kinase 1 (SGK1) is upregulated in the brains of patients with various neurodegenerative disorders, suggesting its involvement in the pathogenesis of those diseases. In this study, we show that inhibiting glial SGK1 corrects the pro-inflammatory properties of glia by suppressing the intracellular NFκB-, NLRP3-inflammasome-, and CGAS-STING-mediated inflammatory pathways. Furthermore, SGK1 inhibition potentiated glial activity to scavenge glutamate toxicity and prevented glial cell senescence and mitochondrial damage, which have recently been reported as critical pathologic features of and therapeutic targets in Parkinson disease (PD) and Alzheimer disease (AD). Along with those anti-inflammatory/neurotrophic functions, silencing and pharmacological inhibition of SGK1 protected midbrain dopamine neurons from degeneration and cured pathologic synuclein alpha (SNCA) aggregation and PD-associated behavioral deficits in multiple in vitro and in vivo PD models. Collectively, these findings suggest that SGK1 inhibition could be a useful strategy for treating PD and other neurodegenerative disorders that share the common pathology of glia-mediated neuroinflammation.

Downregulation of SIRT2 by Chronic Stress Reduces Expression of Synaptic Plasticity-related Genes through the Upregulation of Ehmt2.

Silent information regulator 2 (Sirtuin2 / SIRT2) is a NAD+-dependent deacetylase that regulates the cellular oxidative stress response. It modulates transcriptional silencing and protein stability through deacetylation of target proteins including histones. Previous studies have shown that SIRT2 plays a role in mood disorders and hippocampus-dependent cognitive function, but the underlying neurobiological mechanism is poorly understood. Here, we report that chronic stress suppresses SIRT2 expression in the hippocampus. Molecular and biochemical analyses indicate that the stress-induced decrease in the SIRT2 expression downregulates synaptic plasticity-related genes in the hippocampus through the increase of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2) (also known as G9a). shRNA-mediated knockdown of SIRT2 in the dentate gyrus alters the expression of synaptic plasticity- related genes in a way similar to those induced by chronic stress, and produces depression-like behaviors. Our results indicate that SIRT2 plays an important role in the response to stress, thereby modulating depression-like behaviors.

Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors.

Major depressive disorder (MDD) is a devastating disease that arises in a background of environmental risk factors, such as chronic stress, that produce reactive oxygen species (ROS) in the brain. The chronic stress-induced ROS production involves Ca2+ signals; however, the mechanism is poorly understood. Transient receptor potential melastatin type 2 (TRPM2) is a Ca2+-permeable cation channel that is highly expressed in the brain. Here we show that in animal models of chronic unpredictable stress (CUS), deletion of TRPM2 (Trpm2-/- ) produces antidepressant-like behaviors in mice. This phenotype correlates with reduced ROS, ROS-induced calpain activation, and enhanced phosphorylation of two Cdk5 targets including synapsin 1 and histone deacetylase 5 that are linked to synaptic function and gene expression, respectively. Moreover, TRPM2 mRNA expression is increased in hippocampal tissue samples from patients with MDD. Our findings suggest that TRPM2 is a key agent in stress-induced depression and a possible target for treating depression.

Obesity increases the risk of erosive esophagitis but metabolic unhealthiness alone does not: a large-scale cross-sectional study.

BACKGROUND: Obesity is a known risk factor for erosive esophagitis (EE) and metabolic unhealthiness has been implicated in EE pathogenesis. However, obesity and metabolic unhealthiness are not synonymous and the associations between obesity, metabolic health, and EE are unclear. Therefore, our aim was to investigate the relationship between EE, obesity, and metabolic health. METHODS: We performed a retrospective cross-sectional study of subjects undergoing health screening at a university hospital. Subjects were classified into 4 groups based on metabolic and obesity criteria: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese (MUO). Multivariable analysis was used to identify EE risk factors with MHNO subjects as reference. To determine if there were synergistic interactions between metabolic health and obesity status, the Rothman's synergy index and attributable proportion of risk were also calculated. RESULTS: We included 10,338 subjects (5448 MHNO, 1605 MHO, 1600 MUNO, 1685 MUO). The prevalence of EE was 6.5% in MHNO, 12.6% in MHO, 9.3% in MUNO, and 14.3% in MUO. EE risk was increased significantly by obesity (MHO: OR, 1.589, 95% CI, 1.314-1.921, P < 0.001; MUO: OR, 1.734, 95% CI, 1.441-2.085, P < 0.001), but not in MUNO subjects (OR, 1.224, 95% CI, 0.991-1.511, P = 0.060). Male sex, blood leukocyte count, alcohol, and smoking significantly increased EE risk, but H. pylori infection was protective. Replacement of obesity with abdominal obesity gave similar results. The Rothman's synergy index was 0.920 (95% CI, 0.143-5.899) and the attributable proportion of risk was - 0.051 (95% CI, - 1.206-1.105), indicating no interaction between metabolic and obesity status on EE risk. CONCLUSIONS: We demonstrated that obesity increased the risk of EE, regardless of metabolic health status. However, EE risk was not significantly increased in MUNO subjects, suggesting that metabolic unhealthiness may not be involved in EE pathogenesis. As observational cross-sectional studies cannot prove causality, prospective longitudinal studies involving obesity and metabolic treatment should be performed to further investigate the association between obesity, metabolic health, and EE risk.

Capsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice.

Transient receptor potential vanilloid 1 (TRPV1) affects mood and neuroplasticity in the brain, where its role is poorly understood. In the present study we investigated whether capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide), an agonist of TRPV1, induced chromatin remodeling and thereby altered gene expression related to synaptic plasticity. We found that capsaicin treatment resulted in upregulation of histone deacetylase 2 (HDAC2) in the mouse hippocampus and HDAC2 was enriched at Psd95, synaptophysin, GLUR1, GLUR2 promoters. Viral-mediated hippocampal knockdown of HDAC2 induced expression of Synapsin I and prevented the detrimental effects of capsaicin on Synapsin I expression in mice, supporting the role of HDAC2 in regulation of capsaicin-induced Synapsin I expression. Taken together, our findings implicate HDAC2 in capsaicin-induced transcriptional regulation of synaptic molecules and support the view that HDAC2 is a molecular link between TRPV1 activity and synaptic plasticity.

Obesity and Metabolic Unhealthiness Have Different Effects on Colorectal Neoplasms.

Context: Obesity and insulin resistance are risk factors for colorectal neoplasms (CRN), but data regarding metabolic status, obesity, and CRN are lacking. Objective: To investigate the relationship between metabolic status, obesity, and CRN in Koreans who underwent colonoscopy. Design: Retrospective, cross-sectional. Participants: Subjects were divided based on metabolic and obesity criteria, as follows: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese (MUO). Main Outcome Measures: Multiple regression was used to identify CRN and advanced CRN risk factors, with the MHNO group as reference. Results: A total of 10,235 subjects was included, as follows: 5096 MHNO, 1538 MHO, 1746 MUNO, and 1855 MUO. Of these, 3297 had CRN (32.2%), and 434 (4.2%) had advanced CRN. Number of subjects with CRN in each group were: MHNO 25.8%, MHO 33.9%, MUNO 38.9%, and MUO 42.0% (P for trend < 0.001). Risk of CRN was increased in the MHO [odds ratio (OR) 1.239, 95% confidence interval (CI) 1.082 to 1.418, P = 0.002], the MUNO (OR 1.233, 95% CI 1.086 to 1.400, P = 0.001), and the MUO groups (OR 1.510, 95% CI 1.338 to 1.706, P < 0.001), whereas risk of advanced CRN was increased in the MUNO (OR 1.587, 95% CI 1.222 to 2.062, P = 0.001) and the MUO groups (OR 1.456, 95% CI 1.116 to 1.900, P = 0.006). Conclusions: Obesity increased CRN risk with metabolically unhealthy status adding risk. For advanced CRN, metabolically unhealthy status increased the risk but obesity did not.

TRPV1 Regulates Stress Responses through HDAC2.

Stress causes changes in neurotransmission in the brain, thereby influencing stress-induced behaviors. However, it is unclear how neurotransmission systems orchestrate stress responses at the molecular and cellular levels. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel involved mainly in pain sensation, affects mood and neuroplasticity in the brain, where its role is poorly understood. Here, we show that Trpv1-deficient (Trpv1-/-) mice are more stress resilient than control mice after chronic unpredictable stress. We also found that glucocorticoid receptor (GR)-mediated histone deacetylase 2 (HDAC) 2 expression and activity are reduced in the Trpv1-/- mice and that HDAC2-regulated, cell-cycle- and neuroplasticity-related molecules are altered. Hippocampal knockdown of TRPV1 had similar effects, and its behavioral effects were blocked by HDAC2 overexpression. Collectively, our findings indicate that HDAC2 is a molecular link between TRPV1 activity and stress responses.

Clinical characteristics, risk factors and outcomes of asymptomatic rectal neuroendocrine tumors.

BACKGROUND: Rectal neuroendocrine tumors (NET) are often asymptomatic and frequently discovered during health examinations. However, data on the risk factors of asymptomatic rectal NETs are lacking. We investigated the risk factors, clinical characteristics and outcomes of asymptomatic rectal NETs discovered during health screening. MATERIALS AND METHODS: Asymptomatic subjects who underwent colonoscopy during routine health screening at a tertiary hospital from March 2009 to July 2014 were reviewed. Subjects with histologically confirmed rectal NETs were compared with healthy controls from the same population. Risk factors for rectal NETs were analyzed by multivariable analysis. Clinical outcomes of the resected NETs were also analyzed. RESULTS: A total of 21,706 Subjects underwent screening colonoscopy during the study period. 3417 were excluded from the study, and 180 rectal NET subjects were compared with 18,109 controls. Multivariable analysis showed that a previous history of malignancy (OR 2.960, 95% CI 1.673-5.237, p < 0.001), hypertriglyceridemia (OR 1.482, 95% CI 1.046-2.100, p = 0.027), higher fasting plasma glucose levels (OR 1.008, 95% CI 1.003-1.014, p = 0.001) and higher carcinoembryonic antigen levels (OR 1.019, 95% CI 1.003-1.035, p = 0.021) were significant risk factors while older age (OR 0.964, 95% CI 0.951-0.977, p < 0.001) was a preventive factor. One hundred and sixty nine subjects had endoscopic resection, five were treated by local surgery and six by radical surgery. Complete resection was achieved in 152 subjects. There were three cases of positive lymph nodes and one metastasis. Histology revealed four lymphatic, five vascular and two cases of perineural invasion. One hundred and fifty seven subjects were followed up for at least 1 year (median 38.6 months, 12-84 months). There were no recurrences during the follow-up period. CONCLUSIONS: Younger age, previous history of malignancy, higher fasting plasma glucose levels and hypertriglyceridemia are significantly associated with rectal NET risk.

Association between gamma-glutamyltransferase and albuminuria in nondiabetic adults with normal renal function.

BACKGROUND: Serum gamma-glutamyltransferase (GGT) has been associated with albuminuria in diabetes patients, but it has not been investigated in the general population. We aimed to investigate the association between serum GGT and albuminuria in the nondiabetic Korean population with normal kidney function. METHODS: Study participants (3948; 1549 men and 2399 women) with an estimated glomerular filtration rate ≥60 mL/min/1.73 m2 were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2011). Albuminuria was defined as an albumin-creatinine ratio >30 mg/g. Serum GGT was analyzed by dividing into quartiles. Multiple logistic models were used to analyze the associations between GGT and albuminuria. RESULTS: The prevalence of albuminuria was 5.1% and increased linearly according to increasing GGT quartiles (P for trend = 0.005). A linear regression analysis revealed that GGT was positively related with albuminuria (P = 0.008). After adjusting for confounding factors, the odds ratio for albuminuria was 1.80 (95% CI 1.079-3.010, P for trend = 0.029) for the highest quartile group compared with those observed in the lowest quartile of GGT. In addition, this independent relationship did not change when the cut-off value of GGT (30 IU/L) was applied to this analysis. Compared with GGT value ≤30 IU/L, the adjusted odds ratio of albuminuria in participants with GGT >30 IU/L was 1.96 (95% CI 1.319-2.906, P < 0.001). CONCLUSION: Higher serum GGT levels within the reference range were significantly associated with albuminuria in nondiabetic Koreans with preserved kidney function, independently of traditional cardio-renal risk factors.

Women Who Sleep More Have Reduced Risk of Peptic Ulcer Disease; Korean National Health and Nutrition Examination Survey (2008-2009).

Sleep is integral to life and sleep duration is important in sleep quality, physical, and psychological health. Disturbances in sleep duration have been associated with increased risk of metabolic disorders, hypertension, and overall mortality. Sleep disturbance has also been linked with various gastrointestinal disorders. However, the association between sleep and peptic ulcer disease (PUD) has not been evaluated. We investigated the association between sleep duration and PUD. Subjects were included from the fifth Korean National Health and Nutrition Examination Survey conducted from 2008-2009. Individuals with PUD were defined as those with a physician diagnosis of PUD. Daily sleep duration was established by asking participants the amount of time that they slept per day. Multiple logistic regression models were used to evaluate the association of PUD and sleep duration. This study included 14,290 participants (8,209 women). The prevalence of PUD was 5.7% and was higher in men (6.8%) than in women (4.9%). Women who slept ≥9 hours were significantly less likely to have PUD compared to women who slept 7 hours. In men, longer sleep duration (≥9 hours) had a tendency toward PUD prevention. Our results suggest that longer sleep duration may play a protective role for PUD development.

Balloon-assisted maturation for arteriovenous fistula maturation failure: an early period experience.

PURPOSE: Balloon-assisted maturation (BAM) is emerging as a salvage management for arteriovenous fistula maturation failure (AVF MF). However, BAM is a relatively new, yet controversial technique for AVF maturation. Therefore, we evaluated the effectiveness of BAM for AVF MF. METHODS: Between January 2012 and December 2014, 249 AVFs were created. The total MF rate was 24.8%. But, only 110 AVFs were enrolled, including 74 brachiocephalic (BC) AVFs and 36 radiocephalic (RC) AVFs. The follow-up period was 12 months. Among those, there were 42 MFs (22 BC AVFs and 20 RC AVFs) and 68 maturation successes (MS) (52 BC AVFs and 16 RC AVFs). BAM was involved in MF group. We compared the clinical characteristics, AVF flows, and AVF flow ratios of MF and MS groups. Also, we evaluated the etiology, management, and result of MF. RESULTS: There was no difference in clinical characteristics between MF and MS groups. In MF group, 39 balloon angioplasties (BAs) for 42 AVF MFs were performed. Number of BA was 1.45 ± 0.57 and duration of BA was 21.30 ± 21.24 weeks. BAM rate was 46.2%. For 1 year after AVF creation, AVF flows of MS group were significantly larger than those of MF group (P < 0.05) but there was no difference in AVF flow ratio between MF and MS groups (P > 0.05). CONCLUSION: BA for AVF MF is a relatively applicable and effective modality. Although a large volume study is necessary, we suggest BAM is an effective salvage management for AVF MF.

Spontaneous fracture and migration of catheter of a totally implantable venous access port via internal jugular vein--a case report.

BACKGROUND: The totally implantable venous access ports (TIVAPs) are indicated for patients undergoing chemotherapy, total parenteral nutrition and long-term antibiotic treatment. But, among their complications, the fracture and migration of the catheter of a TIVAP via internal jugular vein represents a very rare but potentially severe condition. CASE PRESENTATION: A 50-year-old woman indentified with a spontaneous fracture and migration of catheter of a TIVAP via right internal jugular vein after adjuvant chemotherapy for ovary cancer. She had been not evaluated and not managed with the heparin lock flush solution during three months after adjuvant chemotherapy. And then, she complained right neck bulging during saline infusion via a TIVAP and a chest radiography showed the fractured and migrated catheter of a TIVAP in right atrium. So, we emergently removed the catheter fragment by a goose neck snare via right femoral vein. After then, there was no problem. CONCLUSIONS: If the fractured catheter of a TIVAP is detected, it is desirable to remove a fragment by an endovascular approach if it is possible.

Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats.

Ketamine produces rapid antidepressant-like effects in animal assays for depression, although the molecular mechanisms underlying these behavioral actions remain incomplete. Here, we demonstrate that ketamine rapidly stimulates histone deacetylase 5 (HDAC5) phosphorylation and nuclear export in rat hippocampal neurons through calcium/calmodulin kinase II- and protein kinase D-dependent pathways. Consequently, ketamine enhanced the transcriptional activity of myocyte enhancer factor 2 (MEF2), which leads to regulation of MEF2 target genes. Transfection of a HDAC5 phosphorylation-defective mutant (Ser259/Ser498 replaced by Ala259/Ala498, HDAC5-S/A), resulted in resistance to ketamine-induced nuclear export, suppression of ketamine-mediated MEF2 transcriptional activity, and decreased expression of MEF2 target genes. Behaviorally, viral-mediated hippocampal knockdown of HDAC5 blocked or occluded the antidepressant effects of ketamine both in unstressed and stressed animals. Taken together, our results reveal a novel role of HDAC5 in the actions of ketamine and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of ketamine.

Overexpression of human GATA-1 and GATA-2 interferes with spine formation and produces depressive behavior in rats.

Functional consequences to which vertebrate GATA transcription factors contribute in the adult brain remain largely an open question. The present study examines how human GATA-1 and GATA-2 (hGATA-1 and hGATA-2) are linked to neuronal differentiation and depressive behaviors in rats. We investigated the effects of adeno-associated viral expression of hGATA-1 and hGATA-2 (AAV-hGATA1 and AAV-hGATA2) in the dentate gyrus (DG) of the dorsal hippocampus on dendrite branching and spine number. We also examined the influence of AAV-hGATA1 and AAV-hGATA2 infusions into the dorsal hippocampus on rodent behavior in models of depression. Viral expression of hGATA-1 and hGATA-2 cDNA in rat hippocampal neurons impaired dendritic outgrowth and spine formation. Moreover, viral-mediated expression of hGATA-1 and hGATA-2 in the dorsal hippocampus caused depressive-like deficits in the forced swim test and learned helplessness models of depression, and decreased the expression of several synapse-related genes as well as spine number in hippocampal neurons. Conversely, shRNA knockdown of GATA-2 increased synapse-related gene expression, spine number, and dendrite branching. The results demonstrate that hGATA-1 and hGATA-2 expression in hippocampus is sufficient to cause depressive like behaviors that are associated with reduction in spine synapse density and expression of synapse-related genes.

Higher incidence of gastroesophageal reflux disease after gastric wedge resections of gastric submucosal tumors located close to the gastroesophageal junction.

PURPOSE: We hypothesized that gastroesophageal reflux disease (GERD) would be more prevalent after a gastric wedge resection of a submucosal tumor (SMT) located close to the gastroesophageal junction (GEJ) than after a gastric wedge resection of an SMT at other locations because of the damage to the lower esophageal sphincter during surgery. METHODS: Fifty-eight patients with gastric SMT who underwent open or laparoscopic gastric wedge resection between January 2000 and August 2012 at the Department of Surgery, Incheon St. Mary's Hospital were enrolled into this study. The patients were divided into 2 groups according to the location of the tumor, upper or lateral border of the tumor within 5 cm of the GEJ (GEJ ≤ 5 cm group) and upper or lateral border of the tumor greater than 5 cm distal to the GEJ (GEJ > 5 cm group). The surgical records, clinicopathologic findings, postoperative GERD symptoms, postoperative use of acid suppressive medications and preoperative and postoperative endoscopic findings were retrospectively reviewed and compared between the 2 groups. RESULTS: There was no difference in the frequency of the preoperative GERD symptoms between the 2 groups, whereas postoperative GERD symptoms and postoperative use of acid suppressive medications were more frequent in the GEJ ≤ 5 cm group (P = 0.045 and P = 0.031). However, there were no differences in the follow-up endoscopic findings in terms of reflux esophagitis and Hill's grade between the 2 groups. CONCLUSION: The incidence of GERD was higher after gastric wedge resection of SMTs located close to the GEJ. Hence, adequate care should be taken during the follow-up of these patients.