A randomized controlled trial using surgical gloves to prevent chemotherapy-induced peripheral neuropathy by paclitaxel in breast cancer patients (AIUR trial).

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxane treatment and can significantly affect patient quality of life. Currently, there are no effective treatments to alleviate symptoms of CIPN; thus, starting with prevention steps in high-risk patients is considered advantageous. However, for these prevention steps to be applicable to all patients, their side effects or accompanying discomforts should be minimal, and the intervention cost-effective. Compression therapy can be considered a prevention intervention, and using surgical gloves is feasible and cost-effective (approximately $0.6 per pair). Although previous studies on compression therapy using surgical gloves have reported decreased incidence of PN, these studies were non-randomized, limited to nab-paclitaxel treatment, and involved the use of small gloves, which may have caused discomfort. Therefore, this study aimed to assess the preventive effects of compression therapy using normal-sized surgical gloves on CIPN in patients treated with paclitaxel. METHODS: This clinical trial is designed to evaluate the preventive effects of compression therapy using surgical gloves on CIPN in women with stage II-III breast cancer who received paclitaxel chemotherapy for at least 12 weeks. This multicenter, randomized-controlled, open-label study will be conducted in six academic hospitals. Patients with medication or a medical history related to neuropathy or hand disease will be excluded. The primary outcome will be the preventive effect of compression therapy using surgical gloves, measured based on changes in the neurotoxicity component of the Functional Assessment of Cancer Therapy-Taxane questionnaire. Furthermore, we will assess the National Cancer Institute's Common Terminology Criteria for Adverse Events grade of CIPN after 6 months. Notably, the estimated sample size, based on a p-value < 0.025 and statistical power of 0.9, will consist of 104 patients (52 per group), accounting for a 10% sample loss. DISCUSSION: This intervention can be easily implemented in clinical practice and may serve as a preventive strategy for CIPNs with strong patient adherence. If successful, this intervention could improve the quality of life and treatment adherence in patients receiving chemotherapy that can induce PN, extending beyond paclitaxel treatment alone. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05771974; Registered on March 16, 2023.

Glycosylation generates an efficacious and immunogenic vaccine against H7N9 influenza virus.

Zoonotic avian influenza viruses pose severe health threats to humans. Of several viral subtypes reported, the low pathogenic avian influenza H7N9 virus has since February 2013 caused more than 1,500 cases of human infection with an almost 40% case-fatality rate. Vaccination of poultry appears to reduce human infections. However, the emergence of highly pathogenic strains has increased concerns about H7N9 pandemics. To develop an efficacious H7N9 human vaccine, we designed vaccine viruses by changing the patterns of N-linked glycosylation (NLG) on the viral hemagglutinin (HA) protein based on evolutionary patterns of H7 HA NLG changes. Notably, a virus in which 2 NLG modifications were added to HA showed higher growth rates in cell culture and elicited more cross-reactive antibodies than did other vaccine viruses with no change in the viral antigenicity. Developed into an inactivated vaccine formulation, the vaccine virus with 2 HA NLG additions exhibited much better protective efficacy against lethal viral challenge in mice than did a vaccine candidate with wild-type (WT) HA by reducing viral replication in the lungs. In a ferret model, the 2 NLG-added vaccine viruses also induced hemagglutination-inhibiting antibodies and significantly suppressed viral replication in the upper and lower respiratory tracts compared with the WT HA vaccines. In a mode of action study, the HA NLG modification appeared to increase HA protein contents incorporated into viral particles, which would be successfully translated to improve vaccine efficacy. These results suggest the strong potential of HA NLG modifications in designing avian influenza vaccines.

Impacts of meteorological variables and machine learning algorithms on rice yield prediction in Korea.

As crop productivity is greatly influenced by weather conditions, many attempts have been made to estimate crop yields using meteorological data and have achieved great progress with the development of machine learning. However, most yield prediction models are developed based on observational data, and the utilization of climate model output in yield prediction has been addressed in very few studies. In this study, we estimate rice yields in South Korea using the meteorological variables provided by ERA5 reanalysis data (ERA-O) and its dynamically downscaled data (ERA-DS). After ERA-O and ERA-DS are validated against observations (OBS), two different machine learning models, Support Vector Machine (SVM) and Long Short-Term Memory (LSTM), are trained with different combinations of eight meteorological variables (mean temperature, maximum temperature, minimum temperature, precipitation, diurnal temperature range, solar irradiance, mean wind speed, and relative humidity) obtained from OBS, ERA-O, and ERA-DS at weekly and monthly timescales from May to September. Regardless of the model type and the source of the input data, training a model with weekly datasets leads to better yield estimates compared to monthly datasets. LSTM generally outperforms SVM, especially when the model is trained with ERA-DS data at a weekly timescale. The best yield estimates are produced by the LSTM model trained with all eight variables at a weekly timescale. Altogether this study shows the significance of high spatial and temporal resolution of input meteorological data in yield prediction, which can also serve to substantiate the added value of dynamical downscaling.

Regional Control of Multistimuli-Responsive Structural Color-Switching Surfaces by a Micropatterned DNA-Hydrogel Assembly.

Structural colors have advantages compared with chemical pigments or dyes, such as iridescence, tunability, and unfading. Many studies have focused on developing the ability to switch ON/OFF the structural color; however, they often suffer from a simple and single stimulus, remaining structural colors, and target selectivity. Herein, we present regionally controlled multistimuli-responsive structural color switching surfaces. The key part is the utilization of a micropatterned DNA-hydrogel assembly on a single substrate. Each hydrogel network contains a unique type of stimuli-responsive DNA motifs as an additional cross-linker to exhibit swelling/deswelling via stimuli-responsive DNA interactions. The approach enables overcoming the existing limitations and selectively programming the DNA-hydrogel to a decrypted state (ON) and an encrypted state (OFF) in response to multiple stimuli. Furthermore, the transitions are reversible, providing cyclability. We envision the potential of our method for diverse applications, such as sensors or anticounterfeiting, requiring multistimuli-responsive structural color switching surfaces.

Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society.

BACKGROUND: There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody-drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer. METHODS: Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan-Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups. RESULTS: HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49-0.93; P = 0.019). CONCLUSIONS: These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.

Comamonas fluminis sp. nov., isolated from the Han River, Republic of Korea.

A Gram-stain-negative, aerobic and motile bacterial strain, designated CJ34T, was isolated from Han River water in the Republic of Korea. Strain CJ34T grew optimally on tryptic soy agar at 30 °C and pH 7.0 in the absence of NaCl. Results of phylogenetic analysis based on 16S rRNA gene sequence showed that strain CJ34T belonged to the genus Comamonas within the family Comamonadaceae and was most closely related to Comamonas testosteroni ATCC 11996T and Comamonas thiooxydans DSM 17888T (both 98.63 % similarity). The average nucleotide identity values between strain CJ34T and two closely related type strains C. testosteroni ATCC 11996T and C. thiooxydans DSM 17888T were 82.77 and 82.73 %, respectively. The major isoprenoid quinone of strain CJ34T was ubiquinone Q-8. The major cellular fatty acids of strain CJ34T were C16 : 0, C16 : 1 ω6c and/or C16 : 1 ω7c and C18 : 1 ω6c and/or C18 : 1 ω7c. The predominant polar lipids of strain CJ34T were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unidentified aminophospholipid. Whole genome sequencing revealed that strain CJ34T had a genome of 4.9 Mbp and the G+C content of the genomic DNA was 59.73 mol%. On the basis of the results of this polyphasic taxonomy study, strain CJ34T represents a novel species in the genus Comamonas, for which the name Comamonas fluminis sp. nov. is proposed. The type strain is CJ34T (=KACC 22237T=JCM 34454T).

Pedobacter aquae sp. nov., a multi-drug resistant bacterium isolated from fresh water.

A novel bacterial strain designated CJ43T was isolated from fresh water located in Gangwon-do, South Korea, displaying multi-drug resistance. The isolate was Gram-stain-negative, aerobic, orange-pigmented, and rod-shaped. Strain CJ43T grew optimally at 30 °C and pH 7 on R2A agar in the absence of NaCl. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain CJ43T belonged to the genus Pedobacter in the family Sphingobacteriaceae and was most closely related to Pedobacter puniceum HX-22-1 T and P. glucosidilyticus 1-2 T (98.3 and 98.1% sequence similarity). The genome size of strain CJ43T was 3.9 Mb in a single contig with DNA G + C content of 34.9%. The genome included 3144 predicted protein-coding genes, as well as 55 tRNA, 9 rRNA and 3 ncRNA genes. The genome also contained 128 putative antibiotic resistance genes, reflecting its phenotypes. The average nucleotide identity values between strain CJ43T and two closely related strains P. puniceum HX-22-1 T and P. glucosidilyticus 1-2 T were 91.0 and 88.7%, respectively. In silico digital DNA-DNA hybridization results between strain CJ43T and the related strains were 42.8 and 38.6%, respectively. The major fatty acids of strain CJ43T were iso-C15:0, iso-C17:0 3-OH, and summed feature 3 (C16:1 ω6c and/or C16:1 ω7c). Strain CJ43T contained phosphatidylethanolamine as the major polar lipid and menaquinone-7 as the sole respiratory quinone. Based on the polyphasic taxonomy data, strain CJ43T represents a novel species of the genus Pedobacter, for which the name Pedobacter aquae sp. nov. is proposed with the type strain CJ43T (= KACC 21350 T = JCM 33709 T).

Clinical significance of HER2 status in T1bN0 breast cancer: a nationwide study from the Korean Breast Cancer Society.

PURPOSE: The prognosis of patients with node-negative T1b tumors according to human epidermal growth factor receptor 2 (HER2) status is not known. This group of patients has not been studied in the available randomized trials. The objective of this study was to evaluate the survival of patients in a monoethnic group diagnosed with T1b lymph node-negative breast cancer depending on HER2 status. METHODS: We analyzed 3110 patients with T1bN0M0 breast cancer whose data were deposited into the Korean Breast Cancer Society Registry database between 2000 and 2009. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared according to HER2 status. RESULTS: Among all patients, 494 (15.9%) had HER2-positive breast cancer. At a mean follow-up of 93 months, 108 deaths and 86 breast cancer-specific deaths were noted among all patients. There was no significant difference in OS between the HER2-negative and HER2-positive groups (p = 0.103). The same result was observed for BCSS. However, in the subgroup of estrogen receptor (ER)-positive women, HER2-negative patients had a better BCSS prognosis than HER2-positive patients (p = 0.025). Multivariate analysis also indicated a significant difference in BCSS in the ER-positive subgroup (HR 2.60; 95% CI 1.15-5.87; p = 0.021). CONCLUSION: This study analyzed a large nationwide and monoethnic cohort and found a significant difference only in BCSS in the ER-positive subgroup according to HER2 status. Anti-HER2 therapy may be considered in HER2-positive and ER-positive patients with small, node-negative breast cancer.

Myroides fluvii sp. nov., isolated from the Han River, Republic of Korea.

A Gram-stain-negative, aerobic, short rod-shaped, pale yellow-pigmented, non-motile and gentamycin-resistant bacterial strain designated CJ210T was isolated from the Han River, Republic of Korea. Strain CJ210T grew optimally at 30 °C and pH 7.0 in the absence of NaCl on tryptic soy agar. Flexirubin-type pigments were not produced. Phylogenetic analysis based on 16S rRNA gene sequence similarity showed that strain CJ210T belonged to the genus Myroides within the family Flavobacteriaceae and was most closely related to Myroides odoratus KACC 14347T (98.1 % similarity), followed by M. injenensis KCTC 23367T (95.3 % similarity). The average nucleotide identity values between strain CJ210T and two closely related type strains M. odoratus KACC 14347T and M. injenensis KCTC 23367T were 83.7 and 73.8 %, respectively. The digital DNA-DNA hybridization results between strain CJ210T and the related type strains were 27.5 and 20.2 %, respectively. Strain CJ210T contained menaquinone 6 (MK-6) as the predominant menaquinone. The predominant polar lipids were phosphatidylethanolamine, two unidentified aminolipids and two unidentified lipids. The major fatty acids of strain CJ210T were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 9 (comprising iso-C17 : 1 ω9c and/or C16 : 0 10-methyl). Whole genome sequencing revealed that strain CJ210T had a genome of 3.8 Mbp with 36.5 % DNA G+C content. The genome contained several antimicrobial resistance genes including an aminoglycoside-resistant gene. On the basis of the polyphasic taxonomic study, strain CJ210T represents a novel species in the genus Myroides, for which name Myrodies fluvii sp. nov. is proposed. The type strain is CJ210T (=KACC 19954T=JCM 33306T).

Spatiotemporally Controlled Plasticity and Elasticity in 3D Multi-Shape Memory Structures Enabled by Elemental Sulfur-Derived Polysulfide Networks with Intrinsic NIR Responsiveness.

Thermadapt shape memory polymers (SMPs), utilizing a variety of dynamic covalent bond exchange mechanisms, have been extensively studied in recent years but it is still challenging to address several constraints in terms of limited accuracy and complexity for constructing 3D shape memory structures. Here, an effective and facile preparation of thermadapt SMPs based on elemental sulfur-derived poly(phenylene polysulfide) networks (PSNs) is presented. These SMPs possess intrinsic near-infrared (NIR)-induced photothermal conversion properties for spatiotemporal control of their plasticity and elasticity. The NIR-controllable plasticity and elasticity of the PSNs enable versatile shape manipulation of 3D multi-shape memory structures, including building block assembly, reconfiguration, shape fixing/recovery, and repair.

Selection of priority management of rivers by assessing heavy metal pollution and ecological risk of surface sediments.

This study aimed to select rivers of priority management through the assessment of heavy metal pollution of sediments. We investigated the distribution characteristics of heavy metals in surface sediments of the Nakdong River in South Korea and used various pollution indices to assess pollution risk and identify factors influencing pollution. The kriging method was used to determine heavy metal distribution. The pollution load index, potential ecological risk index, mean PEL quotient, and the Canada Council of Ministers of the Environment sediment quality index were used as sediment pollution assessment methods. The toxicity evaluation was performed on sites that appeared to be contaminated, by applying existing methods for assessing sediment pollution level and the national standards for evaluating the pollution level. The toxicity test was performed on Hyalella azteca, and a methodology for assessing sediment pollution level was proposed. Ecotoxicity was assessed at seven sites that were found to have heavy metal contaminants. The results showed that sites N1, N8, T28, and T29 were not toxic, while T8, T19, and T21 were. Thus, this study shows that high heavy metal pollution does not necessarily lead to a toxic environment. To assess sediment pollution, an additional assessment of toxicity should be made, along with assessments of existing sediment pollution. Our results demonstrate that streams showing high sediment pollution levels should be granted priority in management. The efforts should particularly focus on Cu at T8, Cr at T19, and Hg at T21.

Distribution of metal contamination and grain size in the sediments of Nakdong River, Korea.

To assess distribution of metal contamination and grain size in the sediments of Nakdong River (South Korea), surface sediments were collected from 21 sites and analyzed. Within the study area, sand was typically the dominant grain size. However, because of the reduced flow rate and flow velocity, sites adjacent to weirs were composed of relatively fine sediments. A comparison of sediment metal concentrations with sediment quality guidelines proposed by the USA, Canada, and South Korea revealed that sites adjacent to weirs had concentrations that exceeded the standard values. The enrichment factor, index of geo-accumulation, and pollution load index calculation results that the sites adjacent to weirs showed high contamination, with Cd accounting for the highest contamination levels. The metals in the study area varies due to the effect of fine sediments; therefore, high concentrations of metals accumulated adjacent to weirs where fine sediments were distributed in greater proportions. Furthermore, Cd exhibited the greatest contribution to metal contamination in the study area and the highest contamination levels were found at NS19 (adjacent to the Haman weir). Thus, the accumulation of fine sediment increased due to the influence of the weirs, thereby increasing the overall amount of metal contamination.

Optimal treatment of breast cancer in women older than 75 years: a Korea Breast Cancer Registry analysis.

PURPOSE: The aim of this study was to investigate the therapeutic efficacy of adjuvant modalities for elderly Asian breast cancer patients using population-based data from the Korean Breast Cancer Registry database. METHODS: We identified 53,582 patients who underwent curative surgery between January 2005 and December 2010. The primary end point was the comparison of overall survival between the administration or omission of adjuvant treatment modalities, including endocrine treatment, radiation therapy, and chemotherapy, in the elderly group (older than 75 years) compared with the control group (younger than 75 years). RESULTS: Of the 53,582 patients analyzed, the total number of elderly patients was 901 (1.7%), and the number of control patients was 52,681 (98.3%). Although elderly patients were found to have larger tumor sizes (p = 0.024) and higher pathological stages (p < 0.001) than the control group, elderly patients were less likely to undergo adjuvant treatment compared to the control group. However, use of endocrine treatment in elderly patients with HR-positive breast cancer is associated with improved overall survival (OS) (adjusted OR 0.417; 95% confidence interval [CI] 0.240-0.726; p = 0.002). Furthermore, chemotherapy was associated with a significant improvement in OS in patients with stage II and III breast cancer (adjusted OR 0.657; 95% CI 0.462-0.934; p = 0.019). CONCLUSION: Endocrine treatment and chemotherapy for elderly patients are associated with improved OS. Therefore, personalized decision-making based on the potential survival benefit of adjuvant treatment modalities should be made with the careful counseling of all elderly patients with breast cancer.

Evaluation of tissue computed tomography number changes and dosimetric shifts after conventional whole-breast irradiation in patients undergoing breast-conserving surgery.

The aim of this study was to assess tissue computed tomography (CT) number changes and corresponding dosimetric shifts in repeatedly performed simulation CT (re-sim CT) scans after conventionally fractionated irradiation in breast cancer patients. A total of 28 breast cancer patients who underwent breast-conserving surgery were enrolled in this study. All the patients had received 50.4 Gy of conventional whole-breast irradiation (WBI) and underwent re-sim CT scans for tumor bed boost. For evaluation of dosimetric shifts between initial and re-sim CT scans, electron boost plans in the same field size with the same monitor unit with source-to-skin distance of 100 cm were conducted. Dosimetric parameters (V105%, V103%, V100%, V98%, V95%, V90%: Vx% indicates volumes which receive X% of prescribed doses) between initial and re-sim CT scans were compared. The CT number data (CTmean, CTmax, CTmin) of the original and irradiated CT (re-sim CT) scans from each representative structure (lung, rib bone, soft tissue, muscle, etc.) were examined and recruited. CT numbers showed highly variable changes. Soft tissue CTmean and muscle CTmax/CTmin showed statistically and significantly increased values in the CT (re-sim CT) compared to the original CT scans. Rib bone CTmean/CTmin showed statistically and significantly decreased values in the re-sim CT compared to the original CT scans. Other CT number values showed no statistically significant changes. Among the dosimetric parameters, only V105% (p = 0.015, mean = 3.07 cc versus 1.63 cc) and V103% (p = 0.017, mean = 13.8 cc versus 11.9 cc) exhibited statistically increased values in the re-sim CT compared to the original CT scans. CT number changes after conventional WBI were different according to tissue component. For electron boost plans, the implementation of a re-sim CT might be helpfully considered because significant dosimetric factor changes were observed especially in the high-dose areas (hot spots: V105% and V103%).

Paenibacillus translucens sp. nov., isolated from tidal flat sediment.

A Gram-stain-variable, aerobic, rod-shaped, motile and spore-forming bacterial strain, designated CJ11T, was isolated from a tidal flat sediment sample from Ganghwa-do, Republic of Korea. Strain CJ11T grew optimally on R2A at 30 °C and pH 7.0. Sequencing results of the 16S rRNA gene revealed that strain CJ11T possesses two copies of the 16S rRNA gene varying at five nucleotide positions. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CJ11T belonged to the genus Paenibacillus within the family Paenibacillaceae and was most closely related to Paenibacillus lacus KCTC 33691T (99.36-99.15 % similarity). DNA-DNA relatedness levels of strain CJ11T was 41.7 % (reciprocal, 57.8 %) to P. lacus KCTC 33691T. The G+C content of the genomic DNA was 51.0 mol%. Strain CJ11Tcontained meso-diaminopimelic acid in the cell-wall peptidoglycan. The major isoprenoid quinone was menaquinone-7. The major cellular fatty acids were anteiso-C15 : 0, C16 : 0 and iso-C16 : 0. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, an unidentified glycolipid and several unidentified lipids. On the basis of the polyphasic taxonomic study, strain CJ11T represents a novel species in the genus Paenibacillus, for which the name Paenibacillustranslucens sp. nov. is proposed. The type strain is CJ11T (=KACC 19304T=JCM 32080T).

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.

The antidepressant action of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid is mediated by phosphorylation of histone deacetylase 5.

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant-like effects in animal models of depression. However, the molecular mechanisms underlying these behavioral actions remain unknown. Here, we demonstrate that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. These effects are accompanied by calcium/calmodulin kinase II (CaMKII) and protein kinase D (PKD) phosphorylation. Behavioral experiments revealed that viral-mediated hippocampal knockdown of HDAC5 blocked the antidepressant effects of CPP in stressed animals. Taken together, our results imply that CPP acts via HDAC5 and suggest that HDAC5 is a common regulator contributing to the antidepressant actions of NMDA receptor antagonists such as CPP.

The potential theragnostic (diagnostic+therapeutic) application of exosomes in diverse biomedical fields.

Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells. Theragnosis is a concept in next-generation medicine that simultaneously combines accurate diagnostics with therapeutic effects. Molecular components in exosomes have been found to be related to certain diseases and treatment responses, indicating that they may have applications in diagnosis via molecular imaging and biomarker detection. In addition, recent studies have reported that exosomes have immunotherapeutic applications or can act as a drug delivery system for targeted therapies with drugs and biomolecules. In this review, we describe the formation, structure, and physiological roles of exosomes. We also discuss their roles in the pathogenesis and progression of diseases including neurodegenerative diseases, cardiovascular diseases, and cancer. The potential applications of exosomes for theragnostic purposes in various diseases are also discussed. This review summarizes the current knowledge about the physiological and pathological roles of exosomes as well as their diagnostic and therapeutic uses, including emerging exosome-based therapies that could not be applied until now.

Ketamine induces brain-derived neurotrophic factor expression via phosphorylation of histone deacetylase 5 in rats.

Ketamine shows promise as a therapeutic agent for the treatment of depression. The increased expression of brain-derived neurotrophic factor (BDNF) has been associated with the antidepressant-like effects of ketamine, but the mechanism of BDNF induction is not well understood. In the current study, we demonstrate that the treatment of rats with ketamine results in the dose-dependent rapid upregulation of Bdnf promoter IV activity and expression of Bdnf exon IV mRNAs in rat hippocampal neurons. Transfection of histone deacetylase 5 (HDAC5) into rat hippocampal neurons similarly induces Bdnf mRNA expression in response to ketamine, whereas transfection of a HDAC5 phosphorylation-defective mutant (Ser259 and Ser498 replaced by Ala259 and Ala498), results in the suppression of ketamine-mediated BDNF promoter IV transcriptional activity. Viral-mediated hippocampal knockdown of HDAC5 induces Bdnf mRNA and protein expression, and blocks the enhancing effects of ketamine on BDNF expression in both unstressed and stressed rats, and thereby providing evidence for the role of HDAC5 in the regulation of Bdnf expression. Taken together, our findings implicate HDAC5 in the ketamine-induced transcriptional regulation of Bdnf, and suggest that the phosphorylation of HDAC5 regulates the therapeutic actions of ketamine.

Impact of a Delayed Laparoscopic Appendectomy on the Risk of Complications in Acute Appendicitis: A Retrospective Study of 4,065 Patients.

BACKGROUND: Urgent surgery performed for appendicitis is hypothesized to avoid complications such as perforation or abscess. This study aimed to evaluate the effect of the timing of surgery on the complications of laparoscopic appendectomy. METHODS: A retrospective review of 4,065 patients who underwent a laparoscopic appendectomy was conducted. The demographic data, time of presentation, physical findings, diagnostic data and complications were recorded. The patients were divided into 4 groups (Group A, 0-6 h; Group B, 6-12 h; Group C, 12-18 h; Group D, over 18 h) based on the time elapsed from the evaluation at the emergency room to the appendectomy. RESULTS: Group A consisted of 2,084 (51.3%) patients, Group B consisted of 1,553 (38.2%) patients, Group C consisted of 388 (9.5%) patients and Group D consisted of 40 (1.8%) patients. A perforated appendicitis was observed in 560 (13.8%) patients. Postoperative complications developed in 293 (7.2%) patients. No significant differences in perforation and postoperative complications were observed between the 4 groups. CONCLUSION: The timing of surgery did not affect the incidence of complications or perforated appendicitis.