Genetic diversity of ST5 Staphylococcus aureus isolated from swine veterinarians in the USA

The term livestock associated methicillin resistant Staphylococcus aureus (LA-MRSA) has been synonymous with sequence type ST398 since the identification of this lineage of MRSA in Holland. Subsequent research indicates borader genetic diversity of MRSA strains in swine, with MRSA variants belonging to MLST sequence type ST9, and ST5 also being reported in studies of swine in varioust countries

Longitudinal study of Staphylococcus aureus and MRSA colonization of US swine veterinarians

Patterns of detection of S. aureus are being evaluated in a longitudinal study of a cohort of 67 swine veterinarians in the USA. This report presents interim data from the initial period of the study. Overall, approximately 70% of sampling events yielded S. aureus in nasal swabs from veterinarians, and 8% yielded MRSA isolates

Genomic characterization of Staphylococcus aureus at the swine-human interface

The epidemiology of S. aureus in swine held little interest until the ST398 lineage of MRSA was found to be prevalent in pigs and pig farmers in the Netherlands in 2004 (Voss et al. 2005). ST398 MRSA have since been detected in multiple livestock species and in many countries (EFSA, 2009; Smith and Pearson, 2011), while genetically distinct variants of ST398 S. aureus occur in some human populations independent of livestock reservoirs (Carrel et al., 2017). Furthermore, other genotypes of MRSA can occur in pigs, particularly ST9 MRSA in Asia, and ST5 MRSA in North America (Chuang and Huang, 2015; Frana et al. 2013). In the USA, methicillin susceptible variants of the ST398, ST9 and ST5 lineages are widespread in commercial swine, yet MRSA variants appear to occur at relatively low prevalence (Sun, et al., 2015). Despite common exposure to, and colonization of, swine workers by livestock associated S. aureus, significant clinical infections appear to be uncommon in occupationally exposed people. However, invasive and even fatal infections are reported at relatively low incidence in some countries, and medically compromised people appear to be at particular risk, even in the absence of animal contact (Larsen et al., 2017). There is evidence that ST398 MRSA of livestock origin are less transmissible among humans than MRSA of human origin. Also, genomic studies typically have indicated that livestock associated MRSA (both ST398 and ST5) lack most virulence factors that occur in human clinical isolates (Schijffelen et al. 2010; Price et al. 2012; Hau et al, 2015). However, to date there has been little genomic characterization of methicillin susceptible S. aureus (MSSA) that are prevalent in swine populations. The purpose of this study was to describe the occurrence of virulence factors and antibiotic resistance genes in S. aureus isolates from pigs and swine veterinarians in the USA

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration ClinicalTrials.gov Identifier NCT0158936

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This study is being supported by grant no 04-2012-0290 from the SNUH Research fund and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP)(No. 2013005540). Letrozole and metformin are being supplied by the pharmaceutical company, Shin Poong Pharm. Co., Ltd.Background : Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design : Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion : This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration : ClinicalTrials.gov Identifier NCT01589367Peer Reviewe

Low prevalence of methicillin resistant Staphylococcus aureus but high prevalence of multidrug resistant Staphylococcus aureus in pigs in the USA

It has been suggested that the emergence of livestock associated MRSA in swine may be a consequence of feeding antibiotics and/or zinc to control swine diseases or promote growth. However, the dynamics and health implications of interspecies transmission of MRSA from pigs to humans is still incompletely understood. To address these questions, better understanding is required of the broader ecology of S. aureus in pigs, including MRSA. To obtain more representative data on the prevalence and characterization of S. aureus, including MRSA, we collected nasal samples from growing pigs on 36 swine farms across 11 states in the USA. All isolates were spa typed, and MLST typing was conducted on selected isolates of each spa type. Antimicrobial and zinc susceptibility testing was performed on a subset of 130 isolates selected purposively to maximize the diversity of isolates by farm and spa type. S. aureus was detected on 35 of the 36 farms, and from 76% of pigs sampled, but no MRSA were found apart from one farm of known status that was included as a MRSA positive control. A total of 33 spa types were detected, with the most prevalent being t337 (ST9), t034 (ST398) and t002 (ST5). Antimicrobial resistance testing for 18 antibiotics showed that resistance was most common to spectinomycin (100%), tetracycline (94%), clindamycin (75%) and penicillin (72%), and a majority of isolates were resistant to 5 or more antibiotics (multidrug resistant S. aureus, MDRSA). Only ST398 MRSA isolates from the positive control farm were positive for the czrC gene, although phenotypic resistance to zinc was observed in some MSSA isolates. These results support earlier studies indicating a relatively low prevalence of MRSA in pigs in the USA, but a high prevalence of MDRSA. The data also concur with the hypothesis that zinc resistance may be more strongly associated with MRSA in swine reservoirs than is resistance of antibiotics such as tetracyclines.</p

Circuit Optimization Method to Reduce Disturbances in Poly-Si 1T-DRAM

A capacitorless one-transistor dynamic random-access memory device (1T-DRAM) is proposed to resolve the scaling problem in conventional one-transistor one-capacitor random-access memory (1T-1C-DRAM). Most studies on 1T-DRAM focus on device-level operation to replace 1T-1C-DRAM. To utilize 1T-DRAM as a memory device, we must understand its circuit-level operation, in addition to its device-level operation. Therefore, we studied the memory performance depending on device location in an array circuit and the circuit configuration by using the 1T-DRAM structure reported in the literature. The simulation results show various disturbances and their effects on memory performance. These disturbances occurred because the voltages applied to each device during circuit operation are different. We analyzed the voltage that should be applied to each voltage line in the circuit to minimize device disturbance and determine the optimized bias condition and circuit structure to achieve a large sensing margin and realize operation as a memory device. The results indicate that the memory performance improves when the circuit has a source line and the bias conditions of the devices differ depending on the write data at the selected device cell. Therefore, the sensing margin of the 1T-DRAM used herein can expectedly be improved by applying the proposed source line (SL) structure