Design and characterization of colorimetric plasmonic nanostructures for imaging and sensing

Increasing demand for early disease diagnostic techniques has attracted huge interest in plasmon-based optical sensors, which can detect small concentrations of chemical and bio-analytes that are not detectable by the conventional analytic optical tools. Advances in nanofabrication techniques have driven in-depth understanding of plasmons, which result from the interactions between nano-materials and the electromagnetic fields. Precisely designing and controlling unique optical properties of plasmons have shown better sensing limits than the conventional ones by amplifying optical signals as well as detecting sensitive plasmon resonance shift upon dielectric property change on the sensing surface. In this dissertation, a series of experiments are undertaken using a colorimetric plasmonic nanocup array substrate with a single extraordinary optical transmission peak in the visible light range. Sensitive colorimetric sensing is demonstrated by detecting transmission peak shift upon the molecular adsorption or the dielectric property change on the surface. The surface modification of the plasmonic substrate using plasmonic metallic NPs is attempted in order to maximize the plasmonic sensitivity to the refractive index change through heterogeneous plasmon coupling. The plasmon coupling between the plasmons of NPs and nanostructure results in strong localized electric field and denser hot-spot formation; hence, the sensitivity is enhanced. Sensitive detections of specific bioanalytes that undergo antigen-antibody binding as well as bulk refractive index change are detected through a plasmonic dark mode shift, resulted from the heterogeneous plasmon coupling. Optical near-field interactions among plasmons, fluorophores, chromophores, and molecules are studied in order to amplify weak fluorescence, absorbance, and Raman signals from a small number of target molecules. Strong scattering field and large scattering cross-section at the plasmon resonance wavelength are the main factors for amplifying fluorescence, absorbance, and Raman scattering. Tuning plasmon resonance to target molecular optical characteristic wavelengths is critical in each application. The amplification of fluorescence is achieved by matching the plasmon resonance with the fluorescence emission band. The absorbance from chromophores, which are involved in conventional immunoassays, is enhanced by matching the chromophores’ absorbance peak with the plasmon resonance wavelength. The improved surface enhanced Raman scattering is accomplished by tuning the plasmon resonance to be close to the laser excitation wavelength. Understanding the signal amplification mechanisms from these results achieves two orders of magnitude lower limit-of-detection as well as improved sensitivity and signal-to-noise ratio. The colorimetric sensor, which is capable of enhancing fluorescence, absorbance and Raman signals from the nearby molecules, provides a versatile multifunctional sensing platform for chemical, biomedical, and environmental monitoring

Long-term variation of aerosol optical properties associated with aerosol types over East Asia using AERONET and satellite (VIIRS, OMI) data (2012-2019)

We analyzed annual and seasonal frequency in aerosol type over an 8-year period (2012-2019) to identify aerosol parameter trends over four ground sites and country regions in Korea, China, and Japan by using the Aerosol Robotic Network (AERONET), and the satellite-based Visible Infrared Imaging Radiometer Suite (VIIRS) and Ozone Monitoring Instrument (OMI). Decreasing trends are shown for aerosol optical depth (AOD), angstrom ng-stro center dot m exponent (AE), and fine mode fraction (FMF) in all countries. The decreasing trend in these data is considered to be due to a decrease in anthropogenic emissions. For the aerosol type frequency, decreases in the proportions of carbonaceous aerosols (CA) and non-absorbing aerosols (NA) were shown in the ground and satellite data, respectively. At most sites, the fractions of low AOD case (LOW) increased, whereas those of the Black and Brown Carbon (BC + BrC) category decreased. In Seoul, the fraction of LOW increased from 48.9% to 70.0%, and that of BC + BrC decreased continuously from 20.4% to 11.1% during 2012-2019. Beijing, on the other hand, showed decreasing LOW from 83.3% (2012) to 52.0% (2019), and that of BC + BrC increased significantly, from 2.4% to 26.2%. The satellite data showed that the percentage of LOW increased continuously, while that of NA aerosols decreased continuously in East Asia. A noticeable decrease in the fraction of CA was detected in China [21.5% (2013) to 11.2% (2019)]. In all countries, CA and NA aerosols had the greatest effect in winter and summer, respectively. We also detected significant differences between the fractions of NA and BC between the ground and satellite data. Changes in aerosol type and properties were observed concurrently in all ground and satellite data, and changes in aerosol type may explain the increasing and decreasing trends that we recorded for most parameters. Consistent results from both ground and satellite data suggest a steady decreasing in fine aerosol pollution in East Asia

Sedative and analgesic effects of intravenous xylazine and tramadol on horses

This study was performed to evaluate the sedative and analgesic effects of xylazine (X) and tramadol (T) intravenously (IV) administered to horses. Six thoroughbred saddle horses each received X (1.0 mg/kg), T (2.0 mg/kg), and a combination of XT (1.0 and 2.0 mg/kg, respectively) IV. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), indirect arterial pressure (IAP), capillary refill time (CRT), sedation, and analgesia (using electrical stimulation and pinprick) were measured before and after drug administration. HR and RR significantly decreased from basal values with X and XT treatments, and significantly increased with T treatment (p < 0.05). RT and IAP also significantly increased with T treatment (p < 0.05). CRT did not change significantly with any treatments. The onset of sedation and analgesia were approximately 5 min after both X and XT treatments; however, the XT combination produced a longer duration of sedation and analgesia than X alone. Two horses in the XT treatment group displayed excited transient behavior within 5 min of drug administration. The results suggest that the XT combination is useful for sedation and analgesia in horses. However, careful monitoring for excited behavior shortly after administration is recommended

Protective Role of Colitis in Inflammatory Arthritis via Propionate-Producing Bacteroides in the Gut

OBJECTIVES: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events. METHODS: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated propionate-deficient mutant bacteria. Short-chain fatty acids were measured in the bacterial culture supernatant, serum, feces, and cecum contents using gas chromatography-mass spectrometry. Mice fed with candidate and mutant bacteria were subjected to inflammatory arthritis. RESULTS: Contrary to expectations, the mice treated with DSS exhibited fewer symptoms of inflammatory arthritis. Intriguingly, the gut microbiota contributes, at least in part, to the improvement of colitis-mediated arthritis. Among the altered microorganisms, CONCLUSIONS: We suggest a novel relationship between the gut and joints and an important role of the gut microbiota as communicators. Moreover, the propionate-producin

Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea

BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited. OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea. METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. RESULTS: Of the 1,163 patients, 695 (59.8%) were men (mean age [years]±standard deviation: 31.6±12.1). Overall, 52.9% (n=615) patients had moderate-to-severe disease (EASI\u3e7). The QoL of 72.3% (n=840) patients was affected moderately-to-severely (DLQI score: 6~30). Systemic immunosuppressants were used ≥1 over past 12 months in 51.9% (n=603) patients, and the most commonly used were cyclosporines (45.7%, n=531) and systemic corticosteroids (40.5%, n=471). Approximately, 10.8% (n=126) patients consulted or received treatment for AD-related eye problem. Of these, 40% (n=50) patients reported poor, very poor, or completely blind status; approximately, 16.7% patients (n=192) reported having depression or anxiety; and 35.5% (n=410) reported suicidal ideation or suicidal attempt. CONCLUSION: A large proportion of patients had moderate-to-severe AD, a compromised QoL, and ocular or mental health comorbidities, indicating a high disease burden despite systemic treatment. These findings highlight the importance of a holistic approach for the evaluation and treatment of patients with AD

APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer's Disease Risk in a Multiracial Sample

Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes

SEALONE (Safety and Efficacy of Coronary Computed Tomography Angiography with Low Dose in Patients Visiting Emergency Room) trial: study protocol for a randomized controlled trial

Objective Chest pain is one of the most common complaints in the emergency department (ED). Cardiac computed tomography angiography (CCTA) is a frequently used tool for the early triage of patients with low- to intermediate-risk acute chest pain. We present a study protocol for a multicenter prospective randomized controlled clinical trial testing the hypothesis that a low-dose CCTA protocol using prospective electrocardiogram (ECG)-triggering and limited-scan range can provide sufficient diagnostic safety for early triage of patients with acute chest pain. Methods The trial will include 681 younger adult (aged 20 to 55) patients visiting EDs of three academic hospitals for acute chest pain or equivalent symptoms who require further evaluation to rule out acute coronary syndrome. Participants will be randomly allocated to either low-dose or conventional CCTA protocol at a 2:1 ratio. The low-dose group will undergo CCTA with prospective ECG-triggering and restricted scan range from sub-carina to heart base. The conventional protocol group will undergo CCTA with retrospective ECG-gating covering the entire chest. Patient disposition is determined based on computed tomography findings and clinical progression and all patients are followed for a month. The primary objective is to prove that the chance of experiencing any hard event within 30 days after a negative low-dose CCTA is less than 1%. The secondary objectives are comparisons of the amount of radiation exposure, ED length of stay and overall cost. Results and Conclusion Our low-dose protocol is readily applicable to current multi-detector computed tomography devices. If this study proves its safety and efficacy, dose-reduction without purchasing of expensive newer devices would be possible

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis