Risk factors for transmission of Middle East respiratory syndrome coronavirus infection during the 2015 outbreak in South Korea.

Background: Transmission heterogeneity was observed during the 2015 South Korean outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Only 22 of 186 cases transmitted the infection, and 5 super-spreading events caused 150 transmissions. We investigated the risk factors for MERS-CoV transmission. Methods: Epidemiological reports were used to classify patients as non-spreaders, spreaders (1-4 transmission), or those associated with super-spreading event (≥4 transmissions). Logistic regression analyses were used to evaluate the factors that influenced MERS-CoV transmission. Results: Compared to non-spreaders, spreaders exhibited a longer interval from symptom onset to isolation (7 days vs. 3 days) and more frequent pre-isolation pneumonia diagnoses (68.2% vs. 17.1%). Spreaders also exhibited higher values for pre-isolation contacts (149 vs. 17.5), pre-isolation hospitalization (68.2% vs. 16.5%), and emergency room visits (50% vs. 7.3%). Spreaders exhibited lower cycle thresholds for the upE and ORF1a genes (22.7 vs. 27.2 and 23.7 vs. 27.9, respectively). Transmission was independently associated with the cycle threshold (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.75-0.96) and pre-isolation hospitalization or emergency room visits (OR: 6.82, 95% CI: 2.06-22.84). The spreaders with ≥4 transmissions exhibited higher values for pre-isolation contacts (777 vs. 78), pre-isolation emergency room visits (100% vs. 35.3%), and doctor-shopping (100% vs. 47.1%), compared to other spreaders. Conclusions: These findings indicate that transmission is determined by host infectivity and the number of contacts, whereas super-spreading events were determined by the number of contacts and hospital visits. These relationships highlight the importance of rapidly enforcing infection control measures to prevent outbreaks.

Clinical Features of Post-Vaccination Guillain-Barré Syndrome (GBS) in Korea.

Guillain-Barré syndrome (GBS) is the most common immune-mediated polyradiculoneuropathy and it is also the most commonly reported severe adverse event following immunization in adults. To evaluate the results of clinical and laboratory features of GBS after vaccination in Korea, we analyzed the claims-based data from 2002 to 2014 using materials collected for the Advisory Committee Vaccination Injury Compensation (ACVIC) meeting including, clinical features, nerve conduction studies (NCSs), cerebrospinal fluid (CSF) profiles, treatment, and outcomes. Forty-eight compensated GBS cases (median age, 15 years; interquartile range [IQR], 13-51; male:female ratio, 1:1) of 68 suspected GBS were found following immunization and all of them with influenza immunizations with either monovalent (n = 35) or trivalent (n = 13). Among them, 30 cases fulfilled the Brighton criteria level 1-3 (62.5%). The median duration between the onset of symptoms to nadir, duration of the nadir, and total admission period were 3 (IQR, 2-7 days), 2 (IQR, 1-5 days), and 14 (IQR, 6-33 days) days, respectively. The most frequently reported symptom was quadriparesis which was present in 36 cases (75%) at nadir. CSF examination revealed albuminocytologic dissociation in 25.0% and NCS was abnormal in 61.8%. After treatment, most of them showed improvement. Clinical features were similar to typical post-infectious GBS and there were both demyelinating and axonal forms suggesting heterogeneous pathogenic mechanism. In order to improve the diagnostic certainty of post-vaccination GBS, careful documentation of clinical features and timely diagnostic work-up with follow-up studies are needed.

Small deep infarction in patients with atrial fibrillation: evidence of lacunar pathogenesis.

BACKGROUND: It is difficult to clarify whether small deep infarction is caused by cardioembolism or intrinsic small vessel disease in patients with atrial fibrillation (AF). The purpose of this study was to determine whether preexisting small vessel disease would differ according to the presenting infarct pattern and to determine the factors associated with acute single small deep infarction in stroke patients with AF. METHODS: Between January 2008 and August 2012, 1,592 consecutive patients with acute ischemic stroke presenting within 7 days of symptom onset were entered in a prospectively maintained stroke registry. For the present study, 231 stroke patients with AF were enrolled irrespective of the stroke subtype. We divided these patients into 2 groups (lacunar infarct pattern, n = 20, vs. nonlacunar infarct pattern, n = 211) according to the acute infarct pattern on diffusion-weighted imaging. Patients with acute single small deep infarction on diffusion-weighted imaging were assigned to the lacunar infarct pattern group. We assessed the severity of preexisting small vessel disease by grading white matter lesions (WMLs) according to the Fazekas scale (periventricular WML score ranging from 0 to 3 and deep WML score ranging from 0 to 3 were added to give a total WML score ranging from 0 to 6), multilacunar state (number of chronic lacunes ≥2) and the presence of microbleeds. Demographic characteristics, vascular risk factors and neuroimaging data were compared between the two groups. RESULTS: Patients with a lacunar infarct pattern showed more severe WMLs than those with a nonlacunar pattern [median total WML score 2.5 (range 2-4) vs. 1.0 (0-2); p < 0.001]. A multilacunar state was more prevalent in the lacunar infarct pattern group compared with the nonlacunar pattern group (65 vs. 28.9%; p = 0.001). However, the presence of microbleeds did not differ between the groups. Multiple logistic regression analyses revealed periventricular WMLs [odds ratio (OR) 4.12, 95% confidence interval (CI) 2.14-7.92], deep WMLs (OR 3.42, 95% CI 1.75-6.66) and multilacunar state (OR 7.85, 95% CI 2.45-25.6) as the predictors of a lacunar infarct pattern. CONCLUSIONS: The severity of WMLs and chronic lacunes were independent predictors of the incident infarct pattern, which suggested that acute single small deep infarction might be caused by intrinsic small vessel disease despite the presence of concomitant AF.

IL-1ß induction and IL-6 suppression are associated with aggravated neuronal damage in a lipopolysaccharide-pretreated kainic acid-induced rat pup seizure model.

OBJECTIVES: Reportedly, hippocampal neuronal degeneration by kainic acid (KA)-induced seizures in rats <14 days old was enhanced by lipopolysaccharide (LPS). This study was to test the hypothesis that cytokines such as interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α are associated with aggravated neuronal damage. MATERIALS AND METHODS: Sixty male Sprague-Dawley, 14-day-old rats were used. Experiments were conducted in saline, LPS + saline, saline + KA and LPS + KA groups. Intraperitoneal LPS injections (0.04 mg/kg) were administered 3 h prior to KA injection (3 mg/kg). RESULTS: The LPS + KA group showed a tendency toward shorter latency to seizure onset (p = 0.086) and significantly longer seizure duration (p < 0.05) compared with the KA group. Induction of the proconvulsant cytokine IL-1ß in rat pup brains was significantly greater in the LPS + KA group compared to the KA group (38.8 ± 5.5 vs. 9.2 ± 1.0 pg/µg; p < 0.05); however, IL-6 levels were higher in the KA group than in the LPS + KA group (108.7 ± 6.8 vs. 60.9 ± 4.7 pg/µg; p < 0.05). The difference in tumor necrosis factor-α between the LPS + KA group and the KA group was insignificant (12.1 ± 0.6 vs. 10.9 ± 2.3 pg/µg; p = 0.64). CONCLUSIONS: Our results showed an increase in the proconvulsant cytokine IL-1ß and a decrease in a potentially neuroprotective cytokine, IL-6, in rat pups treated with LPS + KA. These results warrant further investigation into the possible role of IL-1ß induction and IL-6 suppression in LPS-promoted neuronal damage.

Fluorescence enhancement by a two-dimensional dielectric annular Bragg resonant cavity.

We show that photons can be efficiently extracted from fluorescent molecules, utilizing the strongly enhanced local field of a two-dimensional dielectric annular Bragg resonant cavity. Due to the diffraction and constructive interference together with the annular focusing, the periodic ring structure converts the normal incident light into planar guided modes and forms a hot spot at the center of the structure. Theoretically, the field can be enhanced more than 40 times, which leads to the averaged 20-fold enhancement of the fluorescence signal observed in experiments. Compared with fluorescence enhancement by plasmonic structures, this dielectric approach does not suffer from pronounced quenching that often occurs near metallic structures. These results not only can be applied as ultrasensitive sensors for various biological systems, but also have broad potential applications, such as optical trapping and fluorescent microscopy.

Far-field measurement of ultra-small plasmonic mode volume.

Light-matter interaction can be greatly enhanced in nano-scale plasmonic cavities with tightly confined optical mode, where the mode volume determines the interaction strength. The experimental determination of the mode volume of plasmonic elements is therefore of fundamental importance. Mapping the electric field distribution using near-field scanning optical microscopy (NSOM) may disturb the field distribution hence prevent a reliable measurement of the mode volume. Here, we develop a non-pertubative technique to experimentally determine the mode volume of plasmonic resonators in the far field through a unique optical force method.

Bone health in neuromyelitis optica: Bone mineral density and fractures.

BACKGROUND: The bone health in neuromyelitis optica spectrum disorder with aquaporin-4 immunoglobulin G antibodies (NMOSD-AQP4) have not been fully evaluated. To evaluate the prevalence of fractures and bone loss in patients with NMOSD-AQP4 compared to healthy controls and patients with multiple sclerosis (MS) and to identify the risk factors associated with fractures and low bone mineral density (BMD) in patients with NMOSD-AQP4. METHODS: Seventy-one patients with NMOSD-AQP4 were included. The two control groups consisted of 213 age-, sex-, menopause-, and body mass index (BMI)-matched healthy participants from the Korean National Health and Nutrition Examination Survey (healthy controls) and 41 patients with multiple sclerosis (disease controls). We collected demographic and clinical data related to bone health including BMD and FRAX score. RESULTS: Patients with NMOSD-AQP4 had a higher prevalence of fractures than the healthy control group (OR = 5.40, CI = 2.004-14.524, p = 0.001), with falling, but not steroid use, being associated with an increased risk of fractures after diagnosis with NMOSD-AQP4 (OR = 24.902, CI = 3.086-200.947, p = 0.003). They also had significantly lower BMD than controls (femur neck, p = 0.044; total hip, p < 0.001), which was more prominent in young participants. The BMD in the NMOSD-AQP4 group was associated with cumulative dose of oral steroids, age, sex, BMI, and partly with the prophylactic calcium supplements. Though the patients with NMOSD-AQP4 did not differ significantly from patients with MS in terms of fracture rate and BMD, they had higher risk of fractures as measured by the Fracture Risk Assessment Tool (for major osteoporotic fractures, (p = 0.001; for hip fractures, p = 0.018). CONCLUSION: Patients with NMOSD-AQP4 had a significantly higher risk of fractures that could mostly be attributed to falling. Additionally, low BMD was observed in these patients; it was more prominent among young patients, associated with steroid use, and may partially prevented by the use of prophylactic calcium supplements.

The first case of the 2015 Korean Middle East Respiratory Syndrome outbreak.

OBJECTIVES: This study reviewed problems in the prevention of outbreak and spread of Middle East Respiratory Syndrome (MERS) and aimed to provide assistance in establishing policies to prevent and manage future outbreaks of novel infectious diseases of foreign origin via in-depth epidemiological investigation of the patient who initiated the MERS outbreak in Korea, 2015. METHODS: Personal and phone interviews were conducted with the patient and his guardians, and his activities in Saudi Arabia were investigated with the help of the Saudi Arabian Ministry of Health. Clinical courses and test results were confirmed from the medical records. RESULTS: The patient visited 4 medical facilities and contacted 742 people between May 11, 2015, at symptom onset, and May 20, at admission to the National Medical Center; 28 people were infected and diagnosed with MERS thereafter. CONCLUSIONS: Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments.

Epidemiologic features of the first MERS outbreak in Korea: focus on Pyeongtaek St. Mary's Hospital.

OBJECTIVES: This study investigated the epidemiologic features of the confirmed cases of Middle East Respiratory Syndrome (MERS) in Pyeongtaek St. Mary's Hospital, where the outbreak first began, in order to identify lessons relevant for the prevention and control of future outbreaks. METHODS: The patients' clinical symptoms and test results were collected from their medical records. The caregivers of patients were identified by phone calls. RESULTS: After patient zero (case #1) was admitted to Pyeongtaek St. Mary's Hospital (May 15-May 17), an outbreak occurred, with 36 cases between May 18 and June 4, 2015. Six patients died (fatality rate, 16.7%). Twenty-six cases occurred in the first-generation, and 10 in the second-generation. The median incubation period was five days, while the median period from symptom onset to death was 12.5 days. While the total attack rate was 3.9%, the attack rate among inpatients was 7.6%, and the inpatients on the eighth floor, where patient zero was hospitalized, had an 18.6% attack rate. In contrast, caregivers and medical staff showed attack rates of 3.3% and 1.1%, respectively. CONCLUSIONS: The attack rates were higher than those of the previous outbreaks in other countries. The outbreak spread beyond Pyeongtaek St. Mary's Hospital when four of the patients were moved to other hospitals without appropriate quarantine. The best method of preventing future outbreaks is to overcome the vulnerabilities observed in this outbreak, such as ward crowding, patient migration without appropriate data sharing, and the lack of an initial broad quarantine.

Public health crisis preparedness and response in Korea.

Since the 2006 Pandemic Influenza Preparedness and Response Plan according to the World Health Organization's recommendation, the Republic of Korea has prepared and periodically evaluated the plan to respond to various public health crises including pandemic influenza. Korea has stockpiled 13,000,000 doses of antiviral drugs covering 26% of the Korean population and runs 519 isolated beds in 16 medical institutions. The division of public health crisis response in Korea Centers for Disease Control and Prevention are in charge of responding to public health crises caused by emerging infectious diseases including severe acute respiratory syndrome, avian influenza human infection, and pandemic influenza. Its job description includes preparing for emerging infectious diseases, securing medical resources during a crisis, activating the emergency response during the crisis, and fortification of capabilities of public health personnel. It could evolve into a comprehensive national agency to deal with public health crisis based on the experience of previous national emerging infectious diseases.

Symmetry breaking and optical negative index of closed nanorings.

Metamaterials have extraordinary abilities, such as imaging beyond the diffraction limit and invisibility. Many metamaterials are based on split-ring structures, however, like atomic orbital currents, it has long been believed that closed rings cannot produce negative refractive index. Here we report a low-loss and polarization-independent negative-index metamaterial made solely of closed metallic nanorings. Using symmetry breaking that negatively couples the discrete nanorings, we measured negative phase delay in our composite 'chess metamaterial'. The formation of an ultra-broad Fano-resonance-induced optical negative-index band, spanning wavelengths from 1.3 to 2.3 µm, is experimentally observed in this structure. This discrete and mono-particle negative-index approach opens exciting avenues towards symmetry-controlled topological nanophotonics with on-demand linear and nonlinear responses.

Photoinduced handedness switching in terahertz chiral metamolecules.

Switching the handedness, or the chirality, of a molecule is of great importance in chemistry and biology, as molecules of different handedness exhibit dramatically different physiological properties and pharmacological effects. Here we experimentally demonstrate handedness switching in metamaterials, a new class of custom-designed composites with deep subwavelength building blocks, in response to external optical stimuli. The metamolecule monolayer flips the ellipticity and rotates the polarization angle of light in excess of 10° under optical excitation, a much stronger electromagnetic effect than that of naturally available molecules. Furthermore, the experimentally demonstrated optical switching effect does not require a structural reconfiguration, which is typically involved in molecular chirality switching and is inherently slow. The handedness switching in chiral metamolecules allows electromagnetic control of the polarization of light and will find important applications in manipulation of terahertz waves, such as dynamically tunable terahertz circular polarizers and polarization modulators for terahertz radiations.

Negative refractive index in chiral metamaterials.

We experimentally demonstrate a chiral metamaterial exhibiting negative refractive index at terahertz frequencies. The presence of strong chirality in the terahertz metamaterial lifts the degeneracy for the two circularly polarized waves and allows for the achievement of negative refractive index without requiring simultaneously negative permittivity and negative permeability. The realization of terahertz chiral negative index metamaterials offers opportunities for investigation of their novel electromagnetic properties, such as negative refraction and negative reflection, as well as important terahertz device applications.