Search

Hung-Chen Chen,1,2 Yung-Che Chen,1 Tsu-Nai Wang,3 Wen-Feng Fang,1 Ya-Chun Chang,1 Yu-Mu Chen,1 I-Ya Chen,2 Meng-Chih Lin,1 Ming-Yu Yang2,4 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; 3Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanCorrespondence: Ming-Yu YangGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan Dist., Taoyuan City, 33302, TaiwanEmail yangmy@mail.cgu.edu.twMeng-Chih LinDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Road Niaosong Dist., Kaohsiung City, 83301, TaiwanEmail mengchih@cgmh.org.twPurpose: Circadian clock is synchronized to the 24-hour day by the daily light–dark cycle and proper function of circadian rhythm is essential for many physiological processes. Disruption of circadian rhythm can affect disease processes and influence disease severity, treatment responses, and even survivorship. In this retrospective case-controlled study, we tried to explore whether expression of circadian clock genes was disturbed in patients with bronchial asthma.Patients and Methods: We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes (BMAL1, CK1ϵ, CLOCK, CRY1, CRY2, PER1, PER2, PER3, and TIM) in total leukocytes of peripheral blood collected at chest clinics from 120 patients with asthma and 60 health individuals.Results: Expression levels of the nine circadian clock genes were significantly different between patients and healthy individuals, but not associated with the asthma control status. We also noted the difference of PER3 expression in asthmatic patients with and without nocturnal symptoms. In well-controlled asthmatics, expression of BMAL1, CK1ϵ, CLOCK, CRY1, CRY2, and PER1 was significantly lower in patients with nocturnal symptoms than those without nocturnal symptoms. However, in not well-controlled asthmatics, expression of only BMAL1, CK1ϵ, PER1, and PER2 was significantly different between patients with and without nocturnal symptoms. Binary logistic regression analysis selected BMAL1, CKIϵ, PER3, and TIM as independent factors for bronchial asthma and ROC curves showed the combined expression of these four genes enhanced the capability of predicting asthma (AUC=0.924; 95% CI=0.875– 0.958; P< 0.001).Conclusion: Our results showed altered expression of circadian clock genes in patients with bronchial asthma and down-regulated PER3 in patients with nocturnal symptoms. Altered expression of circadian clock genes was also observed in asthmatics with or without nocturnal symptoms in well- or not well-controlled subgroups. Combined expression of BMAL1, CKIϵ, PER3, and TIM could be a potential predictor for bronchial asthma.Keywords: bronchial asthma, nocturnal symptom, circadian clock genes, PER3

Dan-Li Hao, Ran Xie, Ge-Jing De, Hong Yi, Chen Zang, Mi-Yi Yang, Li Liu, Hai Ma, Wei-Yan Cai, Qing-He Zhao, Feng Sui, Yan-Jun Chen Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of ChinaCorrespondence: Qing-He Zhao; Yan-Jun Chen Tel/ Fax +86-10-84036059Email qhzhao@icmm.ac.cn; yjchen@icmm.ac.cnPurpose: In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(β-amino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model.Methods: The as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core.Results: The pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37°C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%± 1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor.Conclusion: The pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.Keywords: artesunate, micelles, pH responsive, polymer prodrug, poly(2-ethyl-2-oxazoline), poly(β-amino ester)

Li Cheng,1 Doris Yin-ping Leung,1 Janet Wing-hung Sit,1 Xiao-mei Li,2 Yu-ning Wu,3 Miao-yan Yang,4 Cui-xia Gao,5 Rong Hui6 1The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Ma Liu Shui, Shatin, New Territories, Hong Kong; 2The Department of Nursing, Faculty of Medicine, The Xi’an Jiaotong University, 3The Department of Endocrinology, The Ninth Affiliated Hospital of Xi’an Jiaotong University, 4The Department of Endocrinology, The Second Affiliated Hospital of Xi’an Jiaotong University, 5The Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, 6The Department of Endocrinology, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China Background: The study was conducted to investigate the diet barriers perceived by patients with poorly controlled type 2 diabetes and examine the associations between diet barriers and sociodemographic characteristics, medical condition, and patient-centered variables. Methods: Secondary subgroup analyses were conducted based on the responses of 246 adults with poorly controlled type 2 diabetes from a multicenter, cross-sectional study. Diet barriers were captured by the Diet Barriers subscale of the Personal Diabetes Questionnaire. Participants also completed validated measures of diet knowledge, empowerment level, and appraisal of diabetes. Multiple regression techniques were used for model building, with a hierarchical block design to determine the separate contribution of sociodemographic characteristics, medical condition, and patient-centered variables to diet barriers. Results: Diet barriers were moderately evident (2.23±0.86) among Chinese patients with poorly controlled type 2 diabetes. The feeling of deprivation as a result of complying with a diet was the most recognized diet barrier (3.24±1.98), followed by “eating away from home” (2.79±1.82). Significantly higher levels of diet barriers were observed among those with lower levels of diet knowledge (β=-0.282, P

To the Editor: In 1998, a new lineage of triple reassortant influenza A (H3N2) virus (TR-H3N2) with genes from humans (hemmaglutinin [HA], neuraminidase [NA], and polymerase basic 1 [PB1]), swine [...]

Influenza A virus (IAV) active surveillance in pigs prior to weaning is commonly conducted by collecting individual samples, mostly nasal swabs. Recently, the use of udder skin wipes collected from lactating sows was identified as an effective sampling method to indicate IAV status of suckling piglets prior to weaning. However, there is limited information on the effect of pooling multiple udder wipes on the ability to detect IAV. We evaluated the effect of pooling 3, 5, or 10 udder wipes on the sensitivity of detecting IAV and compared the results with testing the wipes individually. The likelihood of detecting positive udder wipes decreased with pooling when the initial positive cycle threshold value was ≥31.5; pooling of up to 3 samples could be performed without affecting sensitivity significantly. Our results support pooling of udder skin wipes to conduct surveillance of IAV in pigs prior to weaning. [ABSTRACT FROM AUTHOR]

There has been little surveillance of influenza A viruses (IAVs) circulating in swine at live animal markets, particularly in the United States. To address this gap, we conducted active surveillance of IAVs in pigs, the air, and the environment during a summer and winter season in a live animal market in St. Paul, Minnesota, that had been epidemiologically associated with swine‐origin influenza cases in humans previously. High rates of IAV were detected by PCR in swine lungs and oral fluids during both summer and winter seasons. Rates of IAV detection by PCR in the air were similar during summer and winter, although rates of successful virus isolation in the air were lower during summer than in winter (26% and 67%, respectively). H3N2 was the most prevalent subtype in both seasons, followed by H1N2. Genetically diverse viruses with multiple gene constellations were isolated from both winter and summer, with a total of 19 distinct genotypes identified. Comparative phylogenetic analysis of all eight segments of 40 virus isolates from summer and 122 isolates from winter revealed that the summer and winter isolates were genetically distinct, indicating IAVs are not maintained in the market, but rather are re‐introduced, likely from commercial swine. These findings highlight the extent of IAV genetic diversity circulating in swine in live animal markets, even during summer months, and the ongoing risk to humans. [ABSTRACT FROM AUTHOR]

Background: People working with pigs are at elevated risk of harboring methicillin resistant S. aureus (MRSA) in their nose, which is attributable to occupational exposure to animals harboring livestock adapted S. aureus. To obtain insight into the biological nature of occupationally related nasal culture positivity, we conducted a longitudinal study of 66 swine veterinarians in the USA.Methods: The study cohort resided in 15 US states and worked predominantly with swine. Monthly for 18 months, participants self-collected nasal swabs and completed a survey to report recent exposure to pigs and other animals; the occurrence of work related injuries; and any relevant health events such as skin and soft tissue infections or confirmed staphylococcal infections. Nasal swabs were cultured using selective methods to determine the presence of MRSA and methicillin susceptible S. aureus (MSSA), and isolates were characterized by spa typing and MLST.Results: Prevalences of S. aureus (64%, monthly range from 58 to 82%) and MRSA (9.5%; monthly range from 6 to15%) were higher than reported for the US population (30% and 1.5% respectively). Predominant spa types were t034 (ST398, 37%), t002 (ST5, 17%) and t337 (ST9/ST398 13%), a distribution similar to that found in a concurrent study in pigs in the USA. Veterinarians were classified into three groups: Persistent carriers (PC, 52%), Intermittent carriers (IC, 47%) and Non-carriers (NC, 1%). Persistent carriage of a single spa type was observed in 14 (21%) of participants, and paired (first and last) isolates from PC subjects had minor genetic differences. Swabs from PC veterinarians carried higher numbers of S. aureus. Among IC veterinarians, culture positivity was significantly associated with recent contact with pigs.Conclusions: Exposure to pigs did not lead to prolonged colonization in most subjects, and the higher numbers of S. aureus in PC subjects suggests that unknown host factors may determine the likelihood of prolonged colonization by S. aureus of livestock origin. Exposure to S. aureus and persistent colonization of swine veterinarians was common but rarely associated with S. aureus disease. [ABSTRACT FROM AUTHOR]

Despite active research into methicillin-resistant Staphylococcus aureus (MRSA) in pigs since 2004, the ecology of the susceptible ancestral organism has been neglected. A longitudinal study of pigs in 2 intensive production systems was conducted to investigate the effects of age and anatomical site on detection of S. aureus. Sampling was replicated in 2 cohorts per farm, with swabs collected from the nares, tonsils, skin (axilla), and rectum in lactating sows, suckling, weaned, and market-age pigs, plus the vagina of sows. No MRSA were isolated, but S. aureus was detected in a least 1 site in 175 (91.1%) out of 192 pigs. Pig-level prevalence did not differ among the age groups, but the proportion of positive samples (all sites) was higher in market-age pigs (75.2%) and nursery-age pigs (63.2%) than in sows (40.7%) and suckling piglets (38%). Prevalence did not differ among nasal (67.9%), skin (62.3%), and tonsil (61.7%) swabs, but was lower in rectal (42%) and vaginal swabs (39.6%). Multiple multilocus sequence typing (MLST) and spa types were found in both production systems, but all isolates were of ST398, ST9, or ST5. These MLST lineages have been variably predominant among reports of MRSA in pigs on 3 continents, and the presence of methicillin-sensitive variants in several countries raises the likelihood that MRSA in pigs has likely resulted from independent acquisition of the mecA gene by multiple S. aureus lineages that have been adapted to swine over the long term, rather than recent introduction of novel clones into swine populations. [ABSTRACT FROM PUBLISHER]