Predicting seasonal influenza outbreaks with regime shift-informed dynamics for improved public health preparedness.

In this study, we propose a novel approach that integrates regime-shift detection with a mechanistic model to forecast the peak times of seasonal influenza. The key benefit of this approach is its ability to detect regime shifts from non-epidemic to epidemic states, which is particularly beneficial with the year-round presence of non-zero Influenza-Like Illness (ILI) data. This integration allows for the incorporation of external factors that trigger the onset of the influenza season-factors that mechanistic models alone might not adequately capture. Applied to ILI data collected in Korea from 2005 to 2020, our method demonstrated stable peak time predictions for seasonal influenza outbreaks, particularly in years characterized by unusual onset times or epidemic magnitudes.

A novel indicator in epidemic monitoring through a case study of Ebola in West Africa (2014-2016).

The E/S (exposed/susceptible) ratio is analyzed in the SEIR model. The ratio plays a key role in understanding epidemic dynamics during the 2014-2016 Ebola outbreak in Sierra Leone and Guinea. The maximum value of the ratio occurs immediately before or after the time-dependent reproduction number (Rt) equals 1, depending on the initial susceptible population (S(0)). It is demonstrated that transmission rate curves corresponding to various incubation periods intersect at a single point referred to as the Cross Point (CP). At this point, the E/S ratio reaches an extremum, signifying a critical shift in transmission dynamics and aligning with the time when Rt approaches 1. By plotting transmission rate curves, ß(t), for any two arbitrary incubation periods and tracking their intersections, we can trace CP over time. CP serves as an indicator of epidemic status, especially when Rt is close to 1. It provides a practical means of monitoring epidemics without prior knowledge of the incubation period. Through a case study, we estimate the transmission rate and reproduction number, identifying CP and Rt = 1 while examining the E/S ratio across various values of S(0).

Human magnetic sense is mediated by a light and magnetic field resonance-dependent mechanism.

Numerous organisms use the Earth's magnetic field as a sensory cue for migration, body alignment, or food search. Despite some contradictory reports, yet it is generally accepted that humans do not sense the geomagnetic field. Here, we demonstrate that a magnetic field resonance mechanism mediates light-dependent magnetic orientation in men, using a rotary chair experiment combined with a two-alternative forced choice paradigm. Two groups of subjects were classified with different magnetic orientation tendencies depending on the food context. Magnetic orientation of the subjects was sensitive to the wavelength of incident light and was critically dependent on blue light reaching the eyes. Importantly, it appears that a magnetic field resonance-dependent mechanism mediates these responses, as evidenced by disruption or augmentation of the ability to orient by radiofrequency magnetic fields at the Larmor frequency and the dependence of these effects on the angle between the radiofrequency and geomagnetic fields. Furthermore, inversion of the vertical component of the geomagnetic field revealed a non-canonical inclination compass effect on the magnetic orientation. These results establish the existence of a human magnetic sense and suggest an underlying quantum mechanical magnetoreception mechanism.

Optimal control problems of mosquito-borne disease subject to changes in feeding behavior of Aedes mosquitoes.

Dengue viruses (DENV) are transmitted to humans by the bite of Aedes mosquitoes. It is known that dengue virus infection in Aedes aegypti female mosquitoes makes a change in the feeding behavior of the infected mosquitoes. In this study, using the forces of infection, we incorporated the effect of changes in the feeding behavior of mosquitoes into the standard vector-borne SIR-SI model. It has been proved that both a single-strain model and a two-strain model exhibit forward bifurcations. Moreover, optimal implementations of control with specific prevention measures for dengue transmission are analyzed. As a result we found that more implementation of controls on the secondary infection of humans should be considered for the behavioral changes in feeding of the infected mosquitoes.

Effects of Timely Control Intervention on the Spread of Middle East Respiratory Syndrome Coronavirus Infection.

OBJECTIVES: The 2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak in Korea caused major economic and social problems. The control intervention was conducted during the MERS-CoV outbreak in Korea immediately after the confirmation of the index case. This study investigates whether the early risk communication with the general public and mass media is an effective preventive strategy. METHODS: The SEIR (Susceptible, Exposed, Infectious, Recovered) model with estimated parameters for the time series data of the daily MERS-CoV incidence in Korea was considered from May to December 2015. For 10,000 stochastic simulations, the SEIR model was computed using the Gillespie algorithm. Depending on the time of control intervention on the 20th, 40th, and 60th days after the identification of the index case, the box plots of MERS-CoV incidences in Korea were computed, and the results were analyzed via ANOVA. RESULTS: The box plots showed that there was a significant difference between the non-intervention and intervention groups (the 20th day, 40th day, and 60th day groups) and seemed to show no significant difference based on the time of intervention. However, the ANOVA revealed that early intervention was a good strategy to control the disease. CONCLUSION: Appropriate risk communication can secure the confidence of the general public in the public health authorities.

Optimal implementation of intervention strategies for elderly people with ludomania.

OBJECTIVES: Now-a-days gambling is growing especially fast among older adults. To control the gratuitous growth of gambling, well-analyzed scientific strategies are necessary. We tried to analyze the adequacy of the health of society mathematically through immediate treatment of patients with early prevention. METHODS: The model from Lee and Do was modified and control parameters were introduced. Pontryagin's Maximum Principle was used to obtain an optimal control strategy. RESULTS: Optimal control can be achieved through simultaneous use of the control parameters, though it varies from society to society. The control corresponding to prevention needed to be implemented in full almost all the time for all types of societies. In the case of the other two controls, the scenario was greatly affected depending on the types of societies. CONCLUSION: Prevention and treatment for elderly people with ludomania are the main intervention strategies. We found that optimal timely implementation of the intervention strategies was more effective. The optimal control strategy varied with the initial number of gamblers. However, three intervention strategies were considered, among which, preventing people from engaging in all types of gambling proved to be the most crucial.

Optimal Implementation of Intervention to Control the Self-harm Epidemic.

OBJECTIVES: Deliberate self-harm (DSH) of a young person has been a matter of growing concern to parents and policymakers. Prevention and early eradication are the main interventional techniques among which prevention through reducing peer pressure has a major role in reducing the DSH epidemic. Our aim is to develop an optimal control strategy for minimizing the DSH epidemic and to assess the efficacy of the controls. METHODS: We considered a deterministic compartmental model of the DSH epidemic and two interventional techniques as the control measures. Pontryagin's Maximum Principle was used to mathematically derive the optimal controls. We also simulated the model using the forward-backward sweep method. RESULTS: Simulation results showed that the controls needed to be used simultaneously to reduce DSH successfully. An optimal control strategy should be adopted, depending on implementation costs for the controls. CONCLUSION: The long-term success of the optimum control depends on the implementation cost. If the cost is very high, the control could be used for a short term, even though it fails in the long run. The control strategy, most importantly, should be implemented as early as possible to attack a comparatively fewer number of addicted individuals.

The effect of public health interventions on the spread of influenza among cities.

Infectious disease is no longer a local problem. Modern populations are more mobile than ever before, and with this mobility comes active global mixing of infectious disease. To understand the spread of diseases such as influenza, we use a multi-city epidemic model. We extend the SEIR (susceptible-exposed-infectious-recovered) model to incorporate population migration between cities, and use this model to analyze the geographic spread of influenza. We investigate the effectiveness of travel restrictions as a control against the spread of influenza. First we obtain the basic reproduction number for the single city case, and observe two other control strategies suggested by this case: increasing the number of clinically ill individuals that are treated, and reducing the interval between infection and treatment of such individuals. We evaluate the effectiveness of the three control strategies with numerical simulations. It is shown that travel restrictions are less effective than the other two strategies. In general, travel restriction tends to delay the spread of the disease into new cities. However, it can increase the peak height of infected populations in all cities. An understanding of the epidemiological structures of related cities is strongly recommended in order to effectively apply the travel restriction strategy.

Optimal Control Strategy of Plasmodium vivax Malaria Transmission in Korea.

OBJECTIVE: To investigate the optimal control strategy for Plasmodium vivax malaria transmission in Korea. METHODS: A Plasmodium vivax malaria transmission model with optimal control terms using a deterministic system of differential equations is presented, and analyzed mathematically and numerically. RESULTS: If the cost of reducing the reproduction rate of the mosquito population is more than that of prevention measures to minimize mosquito-human contacts, the control of mosquito-human contacts needs to be taken for a longer time, comparing the other situations. More knowledge about the actual effectiveness and costs of control intervention measures would give more realistic control strategies. CONCLUSION: Mathematical model and numerical simulations suggest that the use of mosquito-reduction strategies is more effective than personal protection in some cases but not always.

Actin disruption agents induce phosphorylation of histone H2AX in human breast adenocarcinoma MCF-7 cells.

Modified actin dynamics are a unique feature of transformed cancer cells and thereby promising targets for cancer chemotherapy. While latrunculin B (LB) and pectenotoxin-2 (PTX-2), both derived from natural sources, inhibit actin polymerization, jasplakinolide (JSP) prevents actin depolymerization. The purpose of this study was to examine the detailed molecular action of actin disruption inducing apoptosis via double strand breaks (DSBs). Actin disruption induced phosphorylation of H2AX, a well known DSB marker leading to G2 arrest and consequently resulted in apoptosis on MCF-7 cancer cells. Cells impaired by actin disruption activated Erk (extracellular signal-related kinase) and p53 protein was involved in DNA damage responses, but did not change the levels of p21Cip1/WAF1 protein in MCF-7 cells. To overcome the DSBs by actin disruption, MCF-7 cells set the repair system through the homologous recombination (HR) pathway. These results indicate that actin is involved in the signaling inducing DSBs and HR repair as well as G2 cell cycle arrest in human cancer. Therefore, the results suggest that actin disruption might be a potential candidate for developing anti-cancer therapies in human breast cancer.

Mathematical Modeling of Vibrio vulnificus Infection in Korea and the Influence of Global Warming.

OBJECTIVES: To investigate the possible link between Vibrio vulnificus population size in seawater and water temperature. METHODS: We collected incidence and water temperature data in coastal regions of Korea and constructed a mathematical model that consisted of three classes; susceptible fish, infected fish available to humans, and infected humans. RESULTS: We developed a mathematical model to connect V. vulnificus incidence with water temperature using estimated bacterial population sizes and actual coastal water temperatures. CONCLUSION: Increased V. vulnificus population sizes in marine environments may increase the risk of infection in people who eat at coastal restaurants in Korea. Furthermore, we estimated the near-future number of infected patients using our model, which will help to establish a public-health policy to reduce the disease burden.

A note on obesity as epidemic in Korea.

OBJECTIVE: To analyze the incidence of obesity in adults aged 19-59 years in Korea and predict its trend in the future. METHODS: We considered a two-compartmental deterministic mathematical model Susceptible-Infected-Susceptible (SIS), a system of difference equations, to predict the evolution of obesity in the population and to propose strategies to reduce its incidence. RESULTS: The prevention strategy on normal-weight individuals produced a greater improvement than that produced by treatment strategies. CONCLUSIONS: Mathematical model sensitivity analysis suggests that obesity prevention strategies are more effective than obesity treatment strategies in controlling the increase of adult obesity in Korea.

Rodent-specific hypoxia response elements enhance PAI-1 expression through HIF-1 or HIF-2 in mouse hepatoma cells.

Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of numerous pathophysiological processes such as inflammation, thrombosis, angiogenesis and tumor metastasis. Its expression is induced by hypoxia at the transcriptional level, via the hypoxia inducible factor-1 (HIF-1) or -2 (HIF-2). In this study, we elucidated the mechanism of transcriptional regulation of mouse PAI-1 gene by hypoxia in mouse hepatoma cells. We searched for hypoxia response elements (HREs) of murine PAI-1 promoter using several molecular biological assays. DNAse I hypersensitivity assay first suggested that PAI-1 gene expression is up-regulated by protein-DNA interactions at the -3.6- and -3-kb upstream regions of the PAI-1 gene transcription start site. An approximately 6.4-kb region of DNA containing the 5'-flanking promoter region of the PAI-1 gene was isolated, mapped, and cloned into reporter gene assay vectors and sequenced. Luciferase reporter gene assay subsequently identified two functional HREs, located around -3.6 kb of the 5'-flanking promoter region of PAI-1 gene that were responsible for the enhancement of luciferase reporter gene activity. Mutation of the HREs in this fragment abolished luciferase reporter gene activity. Finally, in vitro and in vivo protein-DNA interaction assays confirmed binding of the two HREs to HIF-1 or HIF-2 protein. Our results show that two HREs located around -3.6 kb of the 5'-flanking promoter region of the mouse PAI-1 gene function as hypoxia enhancers, which, alongside other regulatory regions, control PAI-1 gene transcription by HIF-1 or HIF-2 under hypoxic environments in mouse hepatoma cells.

A model for the transmission dynamics of Orientia tsutsugamushi among its natural reservoirs.

The bacteria Orientia tsutsugamushi is the causative agent of scrub typhus, a prevalent disease in Asian countries that can affect humans and which shows an alarming increase of cases during the last years, especially in rural areas. Unfortunately, there is no vaccine for scrub typhus, and antibiotic treatments successfully used in the past appear to be inefficient to treat some strains of O. tsutsugamushi. We introduce a mathematical model that approximates the dynamics of the bacteria among its natural reservoirs. After computing the basic reproductive number from the proposed model, we explore its sensitivity to the parameter values that may be affected by application of control measures. This theoretical model may be of interest to pest managers as well as health authorities interested in gaining insight into the public management of the disease, through a better understanding of its qualitative dynamics.

The dilution effect of the domestic animal population on the transmission of P. vivax malaria.

The diversion of disease carrying insect from humans to animals may reduce transmission of diseases such as malaria. The use of animals to mitigate mosquito bites on human is called 'zooprophylaxis'. We introduce a mathematical model for Plasmodium vivax malaria transmission with two bloodmeal hosts (humans and domestic animals) to study the effect of zooprophylaxis. After computing the basic reproduction number from the proposed model, we explore how perturbations in the parameters, sensitive to the effects of control measures, affect its value. Zooprophylaxis is shown to determine whether a basic reproduction becomes bigger than an outbreak threshold value or not. Sensitivity analysis shows that increasing the relative animal population size works better in P. vivax malaria control than decreasing the mosquito population when the relative animal population size is larger than a threshold value.

The trajectory of iliac screw in the axial plane in 200 korean patients.

STUDY DESIGN: A retrospective radiographic analysis. PURPOSE: To estimate the accurate trajectory in the axial plane for iliac screw insertion in 200 Korean patients using radiographic images. OVERVIEW OF LITERATURE: Several complications have been encountered after fusion to the lumbosacral junction, including pseudarthrosis, S1 screw loosening, and sacral fractures. Iliac screw fixation is considered an efficient method for augmenting sacral screw fixation but there are few reports on the trajectory of iliac screw insertion. The trajectory in the sagittal plane can be visualized by intraoperative fluoroscopy. However, there is no method to check the accuracy of the trajectory in the axial plane during surgery. METHODS: Between January 2007 and February 2009, 200 patients (107 men and 93 women) who underwent L-spine computed tomography were enrolled in this study. The mean age of the patients was 55.6 +/- 18.3 years (range, 13 to 92 years). The spino-iliac angle (SIA) was measured on the axial image at the S1 level, which was defined as the angle between a vertical line through the center of the spinous process and an oblique line that passed through the center of the outer and inner cortices of the ilium. RESULTS: The group mean SIA was 30.1 degrees +/- 7.8 degrees ; 30.1 degrees +/- 7.7 degrees for men and 29.9 degrees +/- 81.1 degrees for women. There was no significant difference according to gender or age (p > 0.05). CONCLUSIONS: The SIA for the axial trajectory of iliac screws is approximately 30 degrees in Korean patients.

Actin disruption inhibits hypoxia inducible factor-1α expression via inactivity of Mdm2-mediated p70S6K.

The intracellular actin cytoskeleton is a central player in tumor cell migration and adhesion, and interacts with the extracellular matrix during the progression to metastasis. Although recent reports on motility events have revealed that the destabilization of actin affects cancer progression and hypoxia inducible factor-1α (HIF-1α) activity, little is known about the responsive activity of HIF-1α following actin disruption. Here, we demonstrate that the inhibition of actin polymerization or depolymerization attenuates HIF-1α expression independently of proteasomal degradation. The disruption of actin dynamics inactivates HIF-1α translational expression through p70S6K translational signaling; this is independent of p53 activation, suggesting that actin dysfunction-mediated HIF-1α destabilization may lead to the development of novel anticancer chemotherapeutic targets.