BackgroundThe Middle East respiratory syndrome (MERS) coronavirus has caused recurrent outbreaks in the Arabian Peninsula since 2012. Although MERS has low overall human-to-human transmission potential, there is occasional amplification in the healthcare setting, a pattern reminiscent of the dynamics of the severe acute respiratory syndrome (SARS) outbreaks in 2003. Here we provide a head-to-head comparison of exposure patterns and transmission dynamics of large hospital clusters of MERS and SARS, including the most recent South Korean outbreak of MERS in 2015.MethodsTo assess the unexpected nature of the recent South Korean nosocomial outbreak of MERS and estimate the probability of future large hospital clusters, we compared exposure and transmission patterns for previously reported hospital clusters of MERS and SARS, based on individual-level data and transmission tree information. We carried out simulations of nosocomial outbreaks of MERS and SARS using branching process models rooted in transmission tree data, and inferred the probability and characteristics of large outbreaks.ResultsA significant fraction of MERS cases were linked to the healthcare setting, ranging from 43.5 % for the nosocomial outbreak in Jeddah, Saudi Arabia, in 2014 to 100 % for both the outbreak in Al-Hasa, Saudi Arabia, in 2013 and the outbreak in South Korea in 2015. Both MERS and SARS nosocomial outbreaks are characterized by early nosocomial super-spreading events, with the reproduction number dropping below 1 within three to five disease generations. There was a systematic difference in the exposure patterns of MERS and SARS: a majority of MERS cases occurred among patients who sought care in the same facilities as the index case, whereas there was a greater concentration of SARS cases among healthcare workers throughout the outbreak. Exposure patterns differed slightly by disease generation, however, especially for SARS. Moreover, the distributions of secondary cases per single primary case varied highly across individual hospital outbreaks (Kruskal–Wallis test; P < 0.0001), with significantly higher transmission heterogeneity in the distribution of secondary cases for MERS than SARS. Simulations indicate a 2-fold higher probability of occurrence of large outbreaks (>100 cases) for SARS than MERS (2 % versus 1 %); however, owing to higher transmission heterogeneity, the largest outbreaks of MERS are characterized by sharper incidence peaks. The probability of occurrence of MERS outbreaks larger than the South Korean cluster (n = 186) is of the order of 1 %.ConclusionsOur study suggests that the South Korean outbreak followed a similar progression to previously described hospital clusters involving coronaviruses, with early super-spreading events generating a disproportionately large number of secondary infections, and the transmission potential diminishing greatly in subsequent generations. Differences in relative exposure patterns and transmission heterogeneity of MERS and SARS could point to changes in hospital practices since ...

No abstract

ObjectivesThe outbreak of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) was one of the major events in South Korea in 2015. In particular, this study pays attention to formulating a mathematical model for MERS transmission dynamics and estimating transmission rates.MethodsIncidence data of MERS-CoV from the government authority was analyzed for the first aim and a mathematical model was built and analyzed for the second aim of the study. A mathematical model for MERS-CoV transmission dynamics is used to estimate the transmission rates in two periods due to the implementation of intensive interventions.ResultsUsing the estimates of the transmission rates, the basic reproduction number was estimated in two periods. Due to the superspreader, the basic reproduction number was very large in the first period; however, the basic reproduction number of the second period has reduced significantly after intensive interventions.ConclusionIt turned out to be the intensive isolation and quarantine interventions that were the most critical factors that prevented the spread of the MERS outbreak. The results are expected to be useful to devise more efficient intervention strategies in the future.

In normal cells, the cellular reactive oxygen species (ROS) level is proportional to the activity of mitochondrial electron transport and tightly controlled by endogenous antioxidant system. However, energy metabolism and ROS homeostasis in cancer cells are much different from those in normal cells. For example, a majority of cellular glucose is metabolized through aerobic glycolysis ("Warburg effect") and the pentose phosphate pathway. Cancer cells harbor functional mitochondria, but many mutations in nuclear DNA-encoded mitochondrial genes and mitochondrial genome result in the mitochondrial metabolic reprogramming. The other characteristic of cancer cells is to maintain much higher ROS level than normal cells. Ironically, cancer cells overexpress the ROS-producing NADPH oxidase and the ROS-eliminating antioxidant enzymes, both of which enzyme systems share NADPH as a reducing power source. In this article, we review the complex connection between ROS and energy metabolisms in cancer cells.

Although obesity is a risk factor for colorectal cancer, the underlying mechanism is not clear. Adiponectin is an adipokine that binds to 2 types of receptors, AdipoR1 and AdipoR2. The plasma concentrations of adiponectin are reduced in obese individuals and adiponectin has been reported to have anticarcinogenic properties. Furthermore, AdipoR1 and AdipoR2 have been reported to be expressed in several malignancies. However, little is known about the expression of AdipoR1 and AdipoR2 in colorectal cancer and its clinicopathological implications. In addition, the relationship between adiponectin and colorectal cancer has not yet been determined. Here, we sought to investigate adiponectin and adiponectin receptors in relation to colorectal cancer. AdipoR1 and AdipoR2 immunostaining was detected in 72 and 68% of human colorectal cancer tissue, respectively. AdipoR1 and AdipoR2 expression levels were inversely related to T stage. The lowest AdipoR1 and AdipoR2 expression were detected in poorly differentiated adenocarcinoma. RT-PCR also showed the expression of AdipoR1 and AdipoR2 in HCT116 and SW620. MTT assay and TUNEL assay demonstrated the tendency of growth inhibition and apoptosis induction in both cell lines after full-length adiponectin treatment although statistically insignificant. Microarray analysis revealed several gene responses to full-length adiponectin, including upregulation of ENDOGL1 and MT1G.In conclusion, AdipoR1 and AdipoR2 may be intimately related to the progression of colorectal cancer. Further studies may be warranted to assess adiponectin and its receptors as a novel target for inhibition of colorectal cancer growth.Colorectal cancer has long been prevalent in Western populations and was estimated to comprise 10.4% of new cancer cases and be the second leading cause of cancer death in the United States in 2008. 1 Over the past few decades, the incidence of colorectal cancer has increased in Asia and it is now one of the most common malignancies worldwide. 2 Obesity is one of the risk factors for colorectal cancer. Several case-control studies assessing body mass index and colorectal cancer incidence have reported an increased risk of colorectal cancer in obese individuals compared with normal weight individuals. [3][4][5] In addition, prospective cohort investigations have reported a positive association between body mass index and colorectal cancer, with relative risks of 1.2-3.4. 6-9 Indices such as waist-to-hip ratio or waist circumference, which indicate abdominal or visceral adiposity, have also been suggested to be independent risk factors for colorectal cancer. [9][10][11] Together with other researchers, we have further demonstrated the importance of visceral adiposity to colorectal cancer risk by the direct measurement of visceral fat by computed tomography (CT) analysis. 12,13 Although the pathophysiological mechanism by which obesity is linked to colorectal cancer is not completely understood, several mechanisms have been proposed. Obesityinduced insulin resistance increases the...