Effects of Herbal Medicine (Gan Mai Da Zao Decoction) on Several Types of Neuropsychiatric Disorders in an Animal Model: A Systematic Review: Herbal medicine for animal studies of neuropsychiatric diseases.

OBJECTIVES: Gan Mai Da Zao (GMDZ) decoction is widely used for the treatment of various diseases of the internal organ and of the central nervous system. The aim of this study is to investigate the effects of GMDZ decoction on neuropsychiatric disorders in an animal model. METHODS: We searched seven databases for randomized animal studies published until April 2015: Pubmed, four Korean databases (DBpia, Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, and Research Information Sharing Service), and one Chinese database (China National Knowledge Infrastructure). The randomized animal studies were included if the effects of GMDZ decoction were tested on neuropsychiatric disorders. All articles were read in full and extracted predefined criteria by two independent reviewers. RESULTS: From a total of 258 hits, six randomized controlled animal studies were included. Five studies used a Sprague Dawley rat model for acute psychological stress, post-traumatic stress disorders, and unpredictable mild stress depression whereas one study used a Kunming mouse model for prenatal depression. The results of the studies showed that GMDZ decoction improved the related outcomes. CONCLUSION: Regardless of the dose and concentration used, GMDZ decoction significantly improved neuropsychiatric disease-related outcomes in animal models. However, additional systematic and extensive studies should be conducted to establish a strong conclusion.

Detection of novel oxazolidinone and phenicol resistance gene optrA in enterococcal isolates from food animals and animal carcasses.

Altogether 7720 Enterococcus faecalis and 3939 E. faecium isolated from food animals and animal carcasses during 2003-2014 in Korea were investigated to determine if linezolid-resistant (LR) enterococci (≥8µg/ml) are present. Overall, 12 E. faecalis and 27 E. faecium recovered from chickens (n=32), pigs (n=6), and cattle (n=1) were resistant to linezolid and were further characterized using molecular methods Most LR isolates were also resistant to chloramphenicol (97.44%) and florfenicol (92.31%). Molecular analysis showed no mutations in the 23S ribosomal RNA and in the ribosomal protein L3. The optrA gene was found in 89.74% of the LR enterococci, including 12 E. faecalis and 23 E. faecium isolates. Among them, 30 optrA-positive isolates co-carried phenicol exporter gene fexA. Seven LR E. faecium isolates had Asn130Lys mutations in the ribosomal protein L4, of which six also carried optrA gene. None of the isolates carried the mutliresistance gene cfr. Transfer of optrA gene was observed in 16 of the 35 optrA-positive isolates by conjugation. Pulsed-field gel electrophoresis demonstrated that the vast majority of Enterococcus strains carrying optrA gene were genetically heterogeneous. Multi-locus sequence typing revealed eight novel Sequence types among E. faecalis and E. faecium strains. To our knowledge, this is the first report of optrA gene in isolates from cattle and animal carcasses. This is also the first report of optrA gene in Korea. Active surveillance of optrA in enterococci is urgently warranted.

Antimicrobial susceptibility and characterization of extended-spectrum ß-lactamases in Escherichia coli isolated from bovine mastitic milk in South Korea from 2012 to 2015.

In this study, we aimed to assess trends in antimicrobial resistance and to investigate the characteristics of extended-spectrum ß-lactamase (ESBL)-producing isolates from bovine mastitic milk from 2012 to 2015. A total of 374 Escherichia coli isolates were analyzed (154 in 2012, 113 in 2013, 76 in 2014, and 31 in 2015). No consistent trends in antimicrobial resistance of E. coli isolates occurred during the 4-yr period. The most frequently observed resistance was tetracycline (23.3%), followed by streptomycin (17.1%), ampicillin (16.6%), neomycin (11.8%), and trimethoprim/sulfamethoxazole (11.2%). Multidrug resistance was observed in 15.5% of isolates. Among these isolates, 15 (4.0%) carried one or more blaCTX-M and AmpC ESBL genes from 11 different farms, including blaCTX-M-15 at 4 farms, blaCTX-M-3 at 2 farms, blaCTX-M-1 at 3 farms, and blaCMY-2 at 3 farms. This study is the first report of blaCTX-M-3-producing E. coli in dairy milk. Transfer of ESBL was observed in 3 blaCTX-M-3-producing isolates, 1 blaCTX-M-1-producing isolate, and all 3 blaCMY-2-producing isolates. Almost all blaCTX-M-15 and blaCTX-M-1 genes possessed an insertion sequence, ISECP1, upstream of the blaCTX-M gene. Identical pulsed-field gel electrophoresis profiles were also observed in blaCTX-M-producing E. coli from the same farm. These results suggested that ESBL might spread by both clonal and horizontal spread in dairy farms in South Korea. Although no significant changes occurred in the antimicrobial resistance of E. coli during the 4-yr study period, the resistance rates and presence of ESBL were high compared with those in other countries. Thus, these findings suggest the importance of control measures for E. coli, particularly ESBL-producing bacteria, on dairy farms to reduce treatment failure and transmission to humans.

Macrolide resistance mechanisms and virulence factors in erythromycin-resistant Campylobacter species isolated from chicken and swine feces and carcasses.

Resistance to antimicrobials was measured in 73 isolates of Campylobacter jejuni (C. jejuni) and 121 isolates of Campylobacter coli (C. coli) from chicken and swine feces and carcasses in Korea. Both bacterial species showed the highest resistance to (fluoro) quinolones (ciprofloxacin and nalidixic acid) out of the nine antimicrobials tested. Erythromycin resistance was much higher in C. coli (19.0%, 23/121) than in C. jejuni (6.8%, 5/73). The mutation in the 23S rRNA gene was primarily responsible for macrolide resistance in Campylobacter isolates. Several amino acid substitutions in the L4 and L22 ribosomal proteins may play a role in the mechanism of resistance, but the role requires further evaluation. A total of eight virulence genes were detected in 28 erythromycin-resistant Campylobacter isolates. All C. jejuni isolates carried more than four such genes, while C. coli isolates carried fewer than three such genes. The high rate of resistance highlights the need to employ more prudent use of critically important antimicrobials, such as fluoroquinolones and macrolides, in swine and poultry production, and to more carefully monitor antimicrobial resistance in Campylobacter isolates in food animals.

Prevalence and characterization of Salmonella in pigs from conventional and organic farms and first report of S. serovar 1,4,[5],12:i:- from Korea.

This study compared the prevalence of Salmonella spp. and their antimicrobial susceptibilities in pigs from conventional and organic farms during 2012-2013 in Korea and characterized them by molecular methods. Altogether, 100 nontyphoid Salmonella were isolated: 47 from 1324 pigs (3.5%) from conventional farms and 53 from 641 pigs (8.3%) from organic farms. The most frequent serovar was Typhimurium (49%) followed by Panama (24%), 1,4,[5],12:i:- (5%), and Virchow (5%). Overall, the isolates were most often resistant to tetracycline (75%) followed by ampicillin (66%), streptomycin (57%), and gentamicin (44%). The prevalence of antimicrobial resistance, multi-drug resistance phenotype, and resistance to tetracycline, ampicillin, and gentamicin were significantly higher in swine Salmonella from conventional farms than those from organic farms. The most common resistance pattern was ampicillin-gentamicin-tetracycline (n=16). All eight ceftiofur-resistant Salmonella identified produced CTX-M-15. Overall, decreased susceptibility to ciprofloxacin was observed in 39 isolates. Among them, a single isolate was positive for qnrS1 gene. An insertion sequence ISEcp1 was detected upstream of blaCTX-M gene in all isolates. The spread of blaCTX-M-15 gene was attributed to combination of clonal expansion and horizontal dissemination mediated by IncHI2 plasmid. Multilocus variable number of tandem repeats analysis demonstrated clonal dissemination of S. Typhimurium and S. 1,4,[5],12:i:- strains in pigs. To our knowledge, this is the first report of blaCTX-M-15 gene in S. Virchow from pigs and qnrS1 gene in S. Rissen from animals. This study also reports the first occurrence of Salmonella serovar 1,4,[5],12:i:- from Korea and CTX-M-15 producing Salmonella from pigs in Korea.

Molecular Basis of Resistance to Selected Antimicrobial Agents in the Emerging Zoonotic Pathogen Streptococcus suis.

Characterization of 227 Streptococcus suis strains isolated from pigs during 2010 to 2013 showed high levels of resistance to clindamycin (95.6%), tilmicosin (94.7%), tylosin (93.8%), oxytetracycline (89.4%), chlortetracycline (86.8%), tiamulin (72.7%), neomycin (70.0%), enrofloxacin (56.4%), penicillin (56.4%), ceftiofur (55.9%), and gentamicin (55.1%). Resistance to tetracyclines, macrolides, aminoglycosides, and fluoroquinolone was attributed to the tet gene, erm(B), erm(C), mph(C), and mef(A) and/or mef(E) genes, aph(3')-IIIa and aac(6')-Ie-aph(2″)-Ia genes, and single point mutations in the quinolone resistance-determining region of ParC and GyrA, respectively.

Indeterminate pulmonary nodules in colorectal cancer.

AIM: To investigate the clinicopathologic parameters of pulmonary metastasis in colorectal cancer (CRC) patients after lung operation of indeterminate pulmonary nodules (IPNs). METHODS: From a prospective database of CRC patients, 40 cases that underwent lung operation between November 2008 and December 2012 for suspicious metastatic pulmonary nodules on chest computed tomography (CT) were enrolled. The decision to perform a lung operation was made if the patient met the following criteria: (1) completely resected or resectable primary CRC; (2) completely resectable IPNs; (3) controlled or controllable extrapulmonary metastasis; and (4) adequate general condition and pulmonary function to tolerate pulmonary operation. Lung operation was performed by a thoracic surgeon without CT-guided biopsy for pathologic confirmation. RESULTS: A total of 40 cases of lung resection was performed in 29 patients. Five patients underwent repeated lung resection. The final pathology result showed metastasis from the CRC in 30 cases (75%) and benign pathology in 10 cases (25%). The primary tumor site was the rectum in 26/30 (86.6%) cases with pulmonary metastasis, but only 3/10 (30%) cases in the benign group had a primary rectal cancer (P = 0.001). Positron emission tomography (PET)-CT was performed for 22/30 (73.4%) patients in the lung metastasis group and for 6/10 (60.0%) patients in the benign group. PET-CT revealed hot uptake of (18)fluorine 2-fluoro-2-deoxy-D-glucose with all IPNs in both groups. The group with pulmonary metastasis had a higher incidence of primary rectal cancer (P = 0.001), a more advanced tumor stage (P = 0.011), and more frequent lymphatic invasion of tumor cells (P = 0.005). Six cases with previous liver metastasectomy were present in the lung metastasis group. Serum carcinoembryonic antigen levels before lung operation were not elevated in any of the patients. CONCLUSION: The stage and location of the primary tumor and tumor cell infiltration of lymphatics provide useful indicators for deciding on lung resection of IPNs in CRC.

Multiscale, hierarchically patterned topography for directing human neural stem cells into functional neurons.

Various biophysical and biochemical factors are important for determining the fate of neural stem cells (NSCs). Among biophysical signals, topographical stimulation by micro/nanopatterns has been applied to control NSC differentiation. In this study, we developed a hierarchically patterned substrate (HPS) platform that can synergistically enhance the differentiation of human NSCs (hNSCs) by simultaneously providing microscale and nanoscale spatial controls to facilitate the alignment of the cytoskeleton and the formation of focal adhesions. The multiscale HPS was fabricated by combining microgroove patterns (groove size: 1.5 µm), prepared by a conventional photolithographic process, and nanopore patterns (pore diameter: 10 nm), prepared from cylinder-forming block copolymer thin films. The hNSCs grown on the HPS exhibited not only a highly aligned, elongated morphology, but also a greatly enhanced differentiation into neuronal and astrocyte lineages, compared to hNSCs on a flat substrate (FS) or single-type patterned substrates [microgroove patterned substrate (MPS) and nanopore patterned substrate (NPS)]. Interestingly, the application of the HPS directed hNSC differentiation toward neurons rather than astrocytes. The expression of focal adhesion proteins in hNSCs was also significantly increased on the HPS compared to the FS, MPS, and NPS, likely a result of the presence of more focal contact points provided by nanopore structures. Inhibition of both ß1 integrin-mediated binding and the intracellular Rho-associated protein kinase pathway of hNSCs eliminated the beneficial effects of the HPS on focal adhesion formation and actin filament alignment, which subsequently reduced hNSC differentiation. More importantly, hNSCs on the HPS differentiated into functional neurons exhibiting sodium currents and action potentials. The multiscale, hierarchically patterned topography would be useful for the design of functional biomaterial scaffolds to potentiate NSC therapeutic efficacy.

Short-term Outcomes of Hand-Assisted Laparoscopic Surgery vs. Open Surgery on Right Colon Cancer: A Case-Controlled Study.

PURPOSE: This study was designed to evaluate short-term clinical outcomes by comparing hand-assisted laparoscopic surgery with open surgery for right colon cancer. METHODS: Sixteen patients who underwent a hand-assisted laparoscopic right hemicolectomy (HAL-RHC group) and 33 patients who underwent a conventional open right hemicolectomy (open group) during the same period were enrolled in this study with a case-controlled design. RESULTS: The operation time was 217 minutes in the HAL-RHC group and 213 minutes in the open group (P = 0.389). The numbers of retrieved lymph nodes were similar between the two groups (31 in the HAL-RHC group and 36 in the open group, P = 0.737). Also, there were no significant difference in the incidence of immediate postoperative leukocytosis, the administration of additional pain killers, and the postoperative recovery parameters. First flatus was shown on postoperative days 3.5 in the HAL-RHC group and 3.4 in the open group (P = 0.486). Drinking water and soft diet were started on postoperative days 4.8 and 5.9, respectively, in the HAL-RHC group and similarly 4.6 and 5.6 in the open group (P = 0.402 and P = 0.551). The duration of hospital stay was shorter in the HAL-RHC group than in the open group (10.3 days vs. 13.5 days, P = 0.048). No significant difference in the complication rates was shown between the two groups, and no postoperative mortality was encountered in either group. CONCLUSION: The patients with right colon cancer in the HAL-RHC group had similar pathologic and postoperative recovery parameters to those of the patients in the open group. The patients in the HAL-RHC group had shorter hospital stays than those in the open group. Therefore, hand-assisted laparoscopic right hemicolectomy for right-sided colon cancer is feasible.

Molecular characterization of CTX-M ß-lactamase and associated addiction systems in Escherichia coli circulating among cattle, farm workers, and the farm environment.

A total of 84 extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli isolates from cattle, farm workers, and the farm environment isolated from February to September 2008 in the Republic of Korea were investigated. All 84 ESBL-producing isolates carried blaCTX-M genes that belonged to the CTX-M-1 (n = 35) or CTX-M-9 (n = 49) family. The most predominant CTX-M type identified was CTX-M-14 (n = 49), followed by CTX-M-32 (n = 26). The blaCTX-M genes were identified most commonly in E. coli isolates from feces (n = 29), teats (n = 25), and milk (n = 14). A blaCTX-M-14 gene was also detected in an E. coli isolate from a farmer's hand. Transfer of the blaCTX-M gene from 60 blaCTX-M-positive E. coli isolates to the recipient E. coli J53 strain by conjugation was demonstrated. Plasmid isolation from blaCTX-M-positive transconjugants revealed a large (95- to 140-kb) conjugative plasmid. Almost all (82/84) blaCTX-M genes possessed an insertion sequence, ISEcp1, upstream of the blaCTX-M gene. Only in the case of the CTX-M-14 genes was IS903 downstream of the gene. The blaCTX-M genes were associated with seven kinds of addiction systems. Among them, pndAC, hok-sok, and srnBC were the most frequently identified addiction systems in both wild strains and transconjugants. The spread of blaCTX-M genes was attributed to both clonal expansion and horizontal dissemination. Our data suggest that a combination of multiple addiction systems in plasmids carrying blaCTX-M genes could contribute to their maintenance in the host cells. To our knowledge, the blaCTX-M-32 gene has not previously been reported in animal isolates from the Republic of Korea.