Job analysis of vaccination health workers at public health centers and sub-centers.

OBJECTIVE: To analyze duties, tasks, and task elements of health workers in charge of vaccination at public health centers in South Korea. DESIGN: Descriptive study using a survey. SAMPLE: Health workers in charge of vaccination for more than 1 year at 254 public health centers in South Korea. Of 631 health workers, 401 responded to the questionnaire, and 379 responses were included in the analysis after excluding 22 incomplete responses. MEASUREMENTS: The Developing A Curriculum (DACUM) workshop was conducted to identify the frequency, importance, and difficulty of duties, tasks, and task elements. RESULTS: Four duties (vaccination promotion, vaccination administration and symptom management, execution of vaccination, and vaccination education), 18 tasks, and 81 task elements were identified. "Execution of vaccination" exhibited the highest determinant coefficient. "Implementing the budget" exhibited the highest determinant coefficient among tasks, and "dealing with an emergency in the case of adverse events" exhibited the highest determinant coefficient among task elements. CONCLUSIONS: Duty, task, and task elements with high determinant coefficients have high educational needs. Education demands was higher for administrative work than for direct vaccination. Developing an educational curriculum based on DACUM results could contribute to the professional education of vaccine workers.

Benefits of combination therapy of hydrocortisone, ascorbic acid and thiamine in sepsis and septic shock: A systematic review.

BACKGROUND: Sepsis and septic shock are severe medical conditions that can damage multiple organs with a higher risk of mortality. Recently, the combination of hydrocortisone, ascorbic acid and thiamine (HAT) was hypothesized to work synergistically to reverse septic shock and reduce mortality. AIM: To ascertain the efficacy of HAT therapy and compare whether HAT therapy is more beneficial compared to the standard of care in sepsis and septic shock patients. METHODS: PubMed, Clinicaltrials.gov, Scopus, Web of Science, Cochrane and Embase are databases that were used to identify trials that conducted a study of the combination of HAT in sepsis or septic shock. RESULTS: There were 134 articles identified through a database search and 16 from other sources, which were subsequently reduced to 11 trials (six randomized trials and five non-randomized trials) that were deemed appropriate for inclusion in this review. Most of the outcomes from these studies focused on mortality, the need for renal replacement therapy, duration of vasopressor use, changes in Sequential Organ Failure Assessment score, procalcitonin clearance and lengths of intensive care unit stay. CONCLUSION: Due to inconsistent results from clinical studies, the benefits of HAT therapy cannot be confirmed at this point in sepsis and septic shock. Currently, there are at least 20 randomized controlled trials testing HAT in various combinations and dosages in patients with severe sepsis and septic shock. The results of these studies are required before definitive conclusions can be made regarding the impact of this novel treatment strategy on the morbidity and mortality of patients with sepsis.

Construction of a bivalent vaccine against anthrax and smallpox using the attenuated vaccinia virus KVAC103.

BACKGROUND: Anthrax and smallpox are high-risk infectious diseases, and considered as potential agents for bioterrorism. To develop an effective countermeasure for these diseases, we constructed a bivalent vaccine against both anthrax and smallpox by integrating a gene encoding protective antigen (PA) of Bacillus anthracis to the genome of the attenuated vaccinia virus strain, KVAC103. RESULTS: Immunization with this bivalent vaccine induced antibodies against both PA and vaccinia virus in a mouse model. We also observed that the efficacy of this vaccine can be enhanced by combined immunization with immunoadjuvant-expressing KVAC103. Mouse groups co-immunized with PA-expressing KVAC103 and either interleukin-15 (IL-15) or cholera toxin subunit A (CTA1)-expressing KVAC103 showed increased anti-PA IgG titer and survival rate against B. anthracis spore challenge compared to the group immunized with PA-expressing KVAC103 alone. CONCLUSIONS: We demonstrated that the attenuated smallpox vaccine KVAC103 is an available platform for a multivalent vaccine and co-immunization of immunoadjuvants can improve vaccine performance.

Statin adherence and risk of all-cause, cancer, and cardiovascular mortality among dyslipidemia patients: A time-dependent analysis.

BACKGROUND AND AIM: Results have been mixed and uncertainty still remains regarding the impact of statin adherence on premature deaths. Thus, we investigated the association between statin adherence and risks of all-cause, cancer, and cardiovascular mortality among dyslipidemia patients in South Korea. METHODS AND RESULTS: We used data from the National Health Insurance Service (NHIS) National Sample Cohort for the years 2003-2013, which included data on 107,954 middle-aged and elderly dyslipidemia patients. Among these patients, a time-dependent Cox proportional hazards model was used to estimate the hazard ratios (HRs) of all-cause, cancer, and cardiovascular mortality depending on proportion of days covered (PDC) by statin medication. A total of 3073 (2.85%) individuals died within the study period. Of these individuals, 1143 (1.06%) died from cancer, and 687 (0.64%) died from cardiovascular diseases. Relative to good medication adherence (>80%), moderate (50-80%) (hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.14-1.43) and poor (<50%) (HR: 1.58, 95% CI: 1.41-1.78) adherence were associated with increased risk of all-cause mortality. Poor adherence was also associated with increased risk of cancer (HR: 1.33, 95% CI: 1.16-1.52) and cardiovascular (HR: 1.27, 95% CI: 1.06-1.51) mortality. CONCLUSION: Such findings reveal that relative to good statin adherence, moderate and/poor adherence is associated with increased risks of all-cause, cancer, and cardiovascular mortality. Clinicians should assess for dyslipidemia, link statin adherence problems to potential mortality risk, and monitor outcomes in both medication adherence and disease complications.

Eravacycline, a newly approved fluorocycline.

Complicated intra-abdominal infections (cIAIs) are commonly associated with multimicroorganisms and treatment choices are becoming narrower due to developing resistance, especially in the gram-negative Enterobacteriaceae species. Eravacycline is a newly developed, fully synthetic tetracycline derivative that has shown potent broad-spectrum activity against a wide variety of microorganisms, including those such as extended spectrum ß-lactamase producing Enterobacteriaceae and Acinetobacter. Eravacycline has shown activity against many gram-positive organisms such as methicillin-resistant S. aureus and vancomycin resistant Enterococcus faecalis and Enterococcus faecium (VRE), gram-negative organisms such as Escherichia coli, and anaerobic species of microorganisms such as Bacteroides. This fluorocycline has been compared to ertapenem and meropenem for the treatment of complicated intra-abdominal infections and levofloxacin for the treatment of complicated urinary tract infections. Eravacycline was shown to be noninferior to ertapenem but did not meet noninferiority criteria in comparison to levofloxacin. Oral and IV formulations on eravacycline were tested in clinical trials, but at this time, only the IV formulation is FDA approved. Eravacycline has been noted to have a half-life of 20 h with protein binding around 80%; AUC over minimum inhibitory concentration (MIC) has also been shown to be eravacycline's best predictor of efficacy. Of note, eravacycline does not require any renal dose adjustments, as the majority of its clearance is by nonrenal pathways.

Delafloxacin for the Treatment of Acute Bacterial Skin and Skin Structure Infections.

Objective: To review the microbiological activity, safety, and efficacy of the new fluoroquinolone delafloxacin for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Data Sources: A PubMed search from 1945 to September 2018 was done using the terms delafloxacin, acute bacterial skin and skin structure infections, skin and soft tissue infections, and fluoroquinolone. Additional sources include the Food and Drug Administration website, ClinicalTrials.gov, and the Melinta Therapeutics website. Study Selection and Data Extraction: The literature search was limited to those published in the English language and included in vitro and human studies that evaluated microbiological coverage, pharmacokinetics, pharmacodynamics, safety, and/or efficacy. Data Synthesis: Delafloxacin is a new fluoroquinolone with a unique structure for its class that covers both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. This new antibiotic has demonstrated noninferiority to vancomycin plus aztreonam for the treatment of ABSSSIs in both an intravenous-only regimen and an intravenous to an oral regimen. Relevance to Patient Care and Clinical Practice: ABSSSIs are infections that are most often caused by Staphylococcus and represent one of the most common types of hospital infections. MRSA represents about half of all staphylococcal skin infections, and along with gram-negative infections, increase the rates of patient morbidity and health care costs. Delafloxacin is an additional treatment option that covers both of these types of microorganisms. Conclusions: Delafloxacin is a safe and effective treatment option for ABSSSIs, particularly in those with polymicrobial infections and those with MRSA.

Red ginseng powder fermented with probiotics exerts antidiabetic effects in the streptozotocin-induced mouse diabetes model.

CONTEXT: Red ginseng (heat-processed Panax ginseng) is a well-known alternative medicine with pharmacological antidiabetic activity. It exerts pharmacological effects through the transformation of saponin into metabolites by the intestinal microbiota. Given that intestinal conditions and intestinal microflora vary among individuals, the pharmacological effects of orally administered red ginseng likely may vary among individuals. OBJECTIVE: To overcome this variation and produce homogeneously effective red ginseng, we evaluated the antidiabetic effects of probiotic-fermented red ginseng in a mouse model. MATERIALS AND METHODS: The antidiabetic efficacy of orally administered probiotic-fermented red ginseng was assessed in ICR mice after induction of diabetes using streptozotocin (170 mg/kg body weight). Samples were given orally for 8 weeks, and indicators involved in diabetic disorders such as body weight change, water intake, blood glucose, glucose tolerance and various biochemical parameters were determined. RESULTS: Oral administration of probiotic-fermented red ginseng significantly decreased the level of blood glucose of about 62.5% in the fasting state and induced a significant increase in glucose tolerance of about 10.2% compared to the control diabetic mice. Additionally, various indicators of diabetes and biochemical data (e.g., blood glycosylated haemoglobin level, serum concentrations of insulin, and α-amylase activity) showed a significant improvement in the diabetic conditions of the mice treated with probiotic-fermented red ginseng in comparison with those of control diabetic mice. DISCUSSION AND CONCLUSION: Our results demonstrate the antidiabetic effects of probiotic-fermented red ginseng in the streptozotocin-induced mouse diabetes model and suggest that probiotic-fermented red ginseng may be a uniformly effective red ginseng product.

Guidelines on Hair Restoration for East Asian Patients.

BACKGROUND: In East Asian countries, hair transplantation is a quite common procedure for treating pattern hair loss, cosmetically correcting the hairline, and correcting eyebrow and pubic hair defects. Although there are general guidelines concerning hair transplantation, certain factors need to be addressed to make the guidelines more specific and suitable to East Asian requirements. OBJECTIVE: To provide guidelines for hairline design, donor harvesting, graft preparation and placement, and medical treatment that are appropriate for hair transplantation in East Asian patients. METHODS: Recommendations are based on the experience of the authors, surgeons who perform hair transplantation, and a comprehensive review of the available literature on hair transplantation in East Asians. RESULTS: Data on hair thickness and graft density, hairline design, and graft creation and placement techniques have been collaboratively evaluated and used to establish overall guidelines. CONCLUSION: The use of the proposed guidelines by surgeons will hopefully enhance outcomes and bring greater consistency to hair transplantation procedures for East Asian patients.

Influenza Virus-Derived CD8 T Cell Epitopes: Implications for the Development of Universal Influenza Vaccines.

The influenza virus poses a global health burden. Currently, an annual vaccine is used to reduce influenza virus-associated morbidity and mortality. Most influenza vaccines have been developed to elicit neutralizing Abs against influenza virus. These Abs primarily target immunodominant epitopes derived from hemagglutinin (HA) or neuraminidase (NA) of the influenza virus incorporated in vaccines. However, HA and NA are highly variable proteins that are prone to antigenic changes, which can reduce vaccine efficacy. Therefore, it is essential to develop universal vaccines that target immunodominant epitopes derived from conserved regions of the influenza virus, enabling cross-protection among different virus variants. The internal proteins of the influenza virus serve as ideal targets for universal vaccines. These internal proteins are presented by MHC class I molecules on Ag-presenting cells, such as dendritic cells, and recognized by CD8 T cells, which elicit CD8 T cell responses, reducing the likelihood of disease and influenza viral spread by inducing virus-infected cell apoptosis. In this review, we highlight the importance of CD8 T cell-mediated immunity against influenza viruses and that of viral epitopes for developing CD8 T cell-based influenza vaccines.

BiVax: a peptide/poly-IC subunit vaccine that mimics an acute infection elicits vast and effective anti-tumor CD8 T-cell responses.

Therapeutic vaccines for the treatment of cancer are an attractive alternative to some of the conventional therapies that are currently used. More importantly, vaccines could be very useful to prevent recurrences when applied after primary therapy. Unfortunately, most therapeutic vaccines for cancer have performed poorly due to the low level of immune responses that they induce. Previous work done in our laboratory in cancer mouse models demonstrated that vaccines consisting of synthetic peptides representing minimal CD8 T-cell epitopes administered i.v. mixed with poly-IC and anti-CD40 antibodies (TriVax) were capable of inducing massive T cell responses similar to those found during acute infections. We now report that some peptides are capable of inducing similarly large T cell responses after vaccination with poly-IC alone (BiVax). The results show that amphiphilic peptides are more likely to function as strong immunogens in BiVax and that systemic immunizations (i.v. or i.m.) were more effective than local (s.c.) vaccine administration. The immune responses induced by BiVax were found to be effective against established tumors in two mouse cancer models. The roles of various immune-related pathways such as type-I IFN, CD40 costimulation, CD4 T cells, TLRs and the MDA5 RNA helicase were examined. The present findings could facilitate the development of simple and effective subunit vaccines for diseases where CD8 T cells provide a therapeutic benefit.

Interferon γ limits the effectiveness of melanoma peptide vaccines.

The development of effective therapeutic vaccines to generate tumor-reactive cytotoxic T lymphocytes (CTLs) continues to be a top research priority. However, in spite of some promising results, there are no clear examples of vaccines that eradicate established tumors. Most vaccines are ineffective because they generate low numbers of CTLs and because numerous immunosuppressive factors abound in tumor-bearing hosts. We designed a peptide vaccine that produces large numbers of tumor-reactive CTLs in a mouse model of melanoma. Surprisingly, CTL tumor recognition and antitumor effects decreased in the presence of interferon γ (IFNγ), a cytokine that can provide therapeutic benefit. Tumors exposed to IFNγ evade CTLs by inducing large amounts of noncognate major histocompatibility complex class I molecules, which limit T-cell activation and effector function. Our results demonstrate that peptide vaccines can eradicate large, established tumors in circumstances under which the inhibitory activities of IFNγ are curtailed.

Influencing factors of early childhood teachers' disaster preparedness.

Background: The risk of disasters and infectious diseases continues to persist in modern times. Children are a vulnerable group in disaster prevention and management due to their limited ability to cope on their own. Hence, the role and disaster preparedness capacity of early childhood teachers (ECTs) is vital for children's protection. Objectives: This study aims to explore how ECTs can improve their personal resilience to adapt to and overcome disasters as part of early childhood education and care (ECEC). To this end, this study examined the effects of ECTs' self-efficacy, resilience, disaster awareness, COVID-19 stress, and work-related stress on their disaster preparedness. Results: According to the outcomes of disaster preparedness of ECTs based on their general and job characteristics, full-time employees and principals scored significantly higher in work-related disaster preparedness (WrDP) compared to part-time workers and general and assistant teachers, respectively. Resilience and WrDP were identified as influencing factors of general disaster preparedness (GdP), with an explanatory power of 26.4%. GdP and self-efficacy were identified as influencing factors of WrDP, with an explanatory power of 25.7%. Discussion: According to the findings, ECTs' self-efficacy and GdP must be improved, followed by developing strategies to strengthen their resilience and WrDP. Doing so would ensure the safety and disaster preparedness of ECTs and infants who have low self-care capacity.

Complete Genome Sequence of Bacillus sp. Strain KICET-1, Isolated from Soybean Paste (Doenjang).

Bacillus sp. strain KICET-1, a bacterium isolated from traditional Korean soybean paste (Doenjang) at Osong, has one 4,099,652-bp DNA chromosome. The G+C content is 46.1%, and KICET-1 shares 99.64% similarity with Bacillus velezensis CR-502T (AY603658), according to phylogenetic classification based on 16S rRNA gene sequences.

Facile Solvent-Free Preparation of Antioxidant Idebenone-Loaded Nanoparticles for Efficient Wound Healing.

The excessive production of reactive oxygen species (ROS) causes harmful effects, including biomolecular damage and inflammation. ROS due to ultraviolet rays, blue light, and fine dust harm the skin, causing urban-related aging. Therefore, a strong antioxidant that relieves oxidative stress in the skin and removes ROS is required. Idebenone (IB) is a powerful antioxidant but is poorly soluble and thus has low solubility in water, resulting in low bioavailability. In this study, IB-loaded nanoparticles (IB@NPs) were synthesized by loading IB without an organic solvent into nanoparticles that can provide high loading efficiency and stability for solubilization. Indeed, the synthesized IB@NPs exhibited long-term stability through dynamic light scattering, methylene blue staining, and redispersion assays, and IB@NPs prepared with a 5 wt% IB loading content were found to be optimal. The antioxidant activity of IB@NPs evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was significantly higher than that of unloaded IB. In addition, IB@NPs showed excellent biocompatibility, inhibited oxidative damage to mouse NIH-3T3 fibroblasts, and reduced intracellular ROS generation according to an in vitro DPPH antioxidant assay. Most notably, IB@NPs significantly promoted wound healing in vitro, as demonstrated by scratch assays. Therefore, as carriers with excellent stability, IB@NPs have potential cosmetic and pharmaceutical applications.

Efficient Anti-Tumor Immunotherapy Using Tumor Epitope-Coated Biodegradable Nanoparticles Combined With Polyinosinic-Polycytidylic Acid and an Anti-PD1 Monoclonal Antibody.

Vaccination with tumor peptide epitopes associated with MHC class I molecules is an attractive approach directed at inducing tumor-specific CTLs. However, challenges remain in improving the therapeutic efficacy of peptide epitope vaccines, including the low immunogenicity of peptide epitopes and insufficient stimulation of innate immune components in vivo. To overcome this, we aimed to develop and test an innovative strategy that elicits potent CTL responses against tumor epitopes. The essential feature of this strategy is vaccination using tumor epitope-loaded nanoparticles (NPs) in combination with polyinosinic-polycytidylic acid (poly-IC) and anti-PD1 mAb. Carboxylated NPs were prepared using poly(lactic-co-glycolic acid) and poly(ethylene/maleic anhydride), covalently conjugated with anti-H-2Kb mAbs, and then attached to H-2Kb molecules isolated from the tumor mass (H-2b). Native peptides associated with the H-2Kb molecules of H-2Kb-attached NPs were exchanged with tumor peptide epitopes. Tumor peptide epitope-loaded NPs efficiently induced tumor-specific CTLs when used to immunize tumor-bearing mice as well as normal mice. This activity of the NPs significantly was increased when co-administered with poly-IC. Accordingly, the NPs exerted significant anti-tumor effects in mice implanted with EG7-OVA thymoma or B16-F10 melanoma, and the anti-tumor activity of the NPs was significantly increased when applied in combination with poly-IC. The most potent anti-tumor activity was observed when the NPs were co-administered with both poly-IC and anti-PD1 mAb. Immunization with tumor epitope-loaded NPs in combination with poly-IC and anti-PD1 mAb in tumor-bearing mice can be a powerful means to induce tumor-specific CTLs with therapeutic anti-tumor activity.

Cut Flower Characteristics and Growth Traits under Salt Stress in Lily Cultivars.

Salt stress is a major constraint of crop productivity because it reduces yield and limits the expansion of agriculture. This study investigated salt tolerance in 26 cultivars of cut lilies (Lilium hybrids) by examining the effect of salt stress on the growth and morphological characteristics of flowers and leaves and their physiological properties (chlorophyll a fluorescence). Salt stress significantly affected the growth and development of cut lilies. Canonical discriminant analysis indicates that the middle leaf width, number of flowers, first flower diameter, petal width, and chlorophyll a fluorescence were correlated with salt stress, whereas plant height, the middle leaf length, days to flowering, and sepal width were less affected by the stress. The cultivars examined were divided into three groups: Group 1 included the salt-sensitive cultivars, which failed to develop normal flowers; Group 2 included cultivars sensitive to salt stress but tolerant to osmotic stress; and Group 3 was the salt-tolerant group, which developed commercially valuable flowers. In conclusion, the cultivars contained a variable range of cut flower characteristics and growth traits that can be employed for lily breeding programs and as material for molecular mechanisms and signaling networks under salt stress.

Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes.

Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide half-life in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2Kb molecules, and then the natural peptide epitopes associated with the H-2Kb molecules were exchanged with a model tumor peptide, SIINFEKL (OVA257-268). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H-2Kb complex-specific CD8+ T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKL-specific CD8+ T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.

Cefiderocol, a New Siderophore Cephalosporin for the Treatment of Complicated Urinary Tract Infections Caused by Multidrug-Resistant Pathogens: Preclinical and Clinical Pharmacokinetics, Pharmacodynamics, Efficacy and Safety.

Cefiderocol (Fetroja®) is a siderophore cephalosporin and has demonstrated potent activity against extended-spectrum beta-lactamases producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and nonfermenting Gram-negative bacilli, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii, Burkholderia cepacia, and Klebsiella pneumoniae. However, cefiderocol has limited activity against Gram-positive bacteria and anaerobes like Bacterodies fragilis. In the APEKS-cUTI study, 183 (73%) of 252 patients in the cefiderocol group versus 65 (55%) of 119 patients in the imipenem-cilastatin group achieved the composite outcome of clinical and microbiological eradication of Gram-negative bacteria (treatment difference of 18.58%; 95% CI 8.23-28.92, p = 0.0004) in complicated urinary tract infections (cUTIs). Cefiderocol was non-inferior to imipenem-cilastatin in cUTIs caused by Gram-negative bacteria such as E. coli, K. pneumoniae, P. aeruginosa, Proteus mirabilis, Enterobacter cloacae, Morganella morganii, and Citrobacter freundii. Cefiderocol required dose adjustment in patients with renal impairment and percentage of time that free drug concentrations above the minimum inhibitory concentration (%fT > MIC) best correlated with clinical outcomes. The most common adverse events with cefiderocol were gastrointestinal symptoms such as diarrhea, constipation, nausea, vomiting, or upper abdominal pain. Two phase III clinical trials, the CREDIBLE-CR study and the APEKS-NP study, investigated the efficacy and safety of cefiderocol for the treatment of pneumonia or cUTI, and both studies showed higher all-cause mortality associated with cefiderocol. Therefore, the use of cefiderocol should be limited only to the treatment of cUTIs from Gram-negative bacteria, especially in patients who have limited or no alternative treatment options.

Analysis of Relative Scent Intensity, Volatile Compounds and Gene Expression in Freesia "Shiny Gold".

Scent is one of the most important economic traits in Freesia hybrida. "Shiny Gold", a popular cultivar in South Korea, is widely cultivated for its scent. The relative scent intensity of "Shiny Gold" was approximately 16% higher in full-bloomed flower when compared to the yellow bud stage, while tissue-specifically, tepals showed higher intensity in electronic-nose (e-nose) analysis. E-nose analysis also showed that the scent intensity of "Shiny Gold" was higher and lower than "10C3-424" and "10C3-894", respectively, and was similar to "Yvonne". These results correlated to those of the olfactory tests. In total, 19 volatile compounds, including linalool, ß-ocimene, D-limonene, trans-ß-ionone were detected in gas chromatography-mass spectrometry analysis. Among these, linalool was the major volatile compound, accounting for 38.7% in "Shiny Gold". Linalool synthase and TPS gene expression corresponded to the scent intensity of the four cultivars, with the lowest expression in the "10C3-424". TPS 2, TPS 3, TPS 5, TPS 6 and TPS 8 were highly expressed in both bud and flower in "Shiny Gold", while the expression of TPS 4 was lower, relative to other TPS genes in both the flowering stages. These results may aid in enhancing scent composition in Freesia cultivars using marker-assisted selection.

Selection and identification of a novel bone-targeting peptide for biomedical imaging of bone.

The global burden of bone-related diseases is increasing in the aging society; thus, improved bone targeted imaging for their early identification and treatment are needed. In this study, we screened novel peptide ligands for hydroxyapatite, a major inorganic component of teeth and bones, and identified a peptide enabling in vivo bone targeting and real-time fluorescence bone detection. To isolate peptides highly specific for hydroxyapatite, we used negative and positive selection from a randomized 8-mer peptide phage library and identified hydroxyapatite-specific peptides (HA-pep2, HA-pep3, and HA-pep7). Among these three peptides, HA-pep3 showed the highest binding capacity and superior dissociation constant towards hydroxyapatite surfaces over time (~ 88.3% retained on hydroxyapatite after two weeks). Furthermore, HA-pep3 was highly specific for hydroxyapatite compared to other calcium salt-based materials. Using this superior specificity, HA-pep3 showed higher accumulation in skull, spine, and joints in comparison with scrambled control peptide during real-time whole-body imaging. Ex vivo analysis of the major organs and bone from mice demonstrated that the fluorescence intensity in bone was about 3.32 folds higher in the case of HA-pep3 than the one exhibited by the scrambled control peptide. Our study identified a novel approach for targeting ligands for bone specific imaging and can be useful for drug delivery applications.