Septic shock caused by Slackia exigua in a patient with diabetes.

We report a case of septic shock caused by Slackia exigua, an obligatory anaerobic gram-positive rod, in an 82-year-old woman with diabetes. Dental assessment revealed a palatal lesion and untreated periodontitis. Although a resident species in the oral cavity and associated with localized disorders, S. exigua can cause extra-oral diseases, which can be fatal in individuals with risk factors, such as diabetes. Thus, control of oral lesions caused by S. exigua is important to prevent systemic infection.

Clinical Implications of Poloxamer 407 as Packing Material in an Animal Model.

BACKGROUND: Endoscopic ear surgery has recently increased, but it is still inconvenient and time-consuming to place packing material in the middle ear with one hand. Poloxamer 407 (P407) is a thermo-reversible gel that can be easily administered with one hand into the middle ear cavity in liquid form. Upon warming to body temperature, the gel form of P407 can support the graft in the target position and is known to prevent postsurgical tissue adhesion. OBJECTIVES: We aim to investigate the feasibility of P407 as packing material in an animal model. Male Hartley guinea pigs (350 and 400 g) were utilized in this study. METHOD: The animals were randomly divided into 3 groups according to the packing material: the control group, the P407 group, and the gelatin group. To assess the role of packing material on bacterial colonization, left ears were inoculated with Streptococcus pneumoniae through the tympanic membrane using a 0° endoscope. Five days after inoculation, the middle ear cavity was packed through a transbullar approach using 18% P407 or gelatin in both ears. In the control group, no ear pack was inserted. The tympanic membrane was examined every week using a 0° 1.9-mm endoscope until 6 weeks. Half of the animals in each group were sacrificed 6 weeks after placement of the packing materials. RESULTS: Compared with the absorbable gelatin sponge, the P407 group showed little inflammation or fibrosis in the tympanic membrane and middle ear mucosa regardless of bacterial inoculation. The gelatin group showed severe otorrhea or perforation until 2 weeks in the right ear (2 of 4) and the left ear (1 of 4). Even though the endoscopic findings were similar between both packing groups at 6 weeks, histological analysis showed persistent packing material, inflammatory cells, and fibrosis in the gelatin group compared to the P407 group. CONCLUSIONS: This study suggested that P407 is feasible as a packing material to handle with one hand and to prevent adhesion, especially in infected middle ear mucosa. Although there is a lack of data on how well P407 supports grafts, we suggest that P407 could be a candidate for packing material in endoscopic ear surgery.

Cell-selectivity of tryptophan and tyrosine in amphiphilic α-helical antimicrobial peptides against drug-resistant bacteria.

The increasing emergence of drug-resistant bacteria creates a requirement for new antibiotics and various types of antibiotic materials such as proteins, peptides, polymers, and chemical compounds. Among these, antimicrobial peptides (AMPs) are considered to be promising antibiotic candidates for clinical treatments. In this study, we have designed a novel series of peptides with repeated sequences of minimum membrane-active motif, 'XWZX' basic sequence (X: lysine or arginine, Z: leucine, tyrosine, valine, or glycine), and an α-helical secondary structure. Some peptides displayed a potent antibacterial activity via membranolytic action and high therapeutic index (toxic dose/minimum inhibitory concentration) in vitro. Furthermore, in vivo experiments using bacterial ear-skin infection models verified that these peptides have the potential to be powerful and safe antibiotics. The present study provides a lead sequence for designing peptide antibiotics against bacterial membranes and information for cell-selectivity of hydrophobic amino acids with aromatic side chains such as Trp and Tyr.

Biocompatible and Biodegradable Fe3+-Melanoidin Chelate as a Potentially Safe Contrast Agent for Liver MRI.

Currently, most MRI probes available for clinical use contain gadolinium, which is a high-risk paramagnetic metal that can cause severe side effects (e.g., nephrogenic systemic fibrosis). To limit such side effects and improve diagnostic efficacy, we developed a novel biocompatible MRI contrast agent using glucose, glycine, and paramagnetic iron ion. Glucose and glycine were polymerized into melanoidin by the nonenzymatic Maillard reaction, and Fe3+ was chelated stably with the melanoidin during polymerization. The Fe3+-melanoidin chelate had biocompatibility, biodegradability, and unique contrast effects on both T1- and T2-weighted MRI, depending on the pH and oxidative environments. The administration of the Fe3+-melanoidin chelate to a mouse model of liver cancer showed highly enhanced liver-to-tumor contrasts on both T1- and T2-weighted MRI.

Silicon membrane filter designed by fluid dynamics simulation and near-field stress analysis for selective cell enrichment.

Selective cell enrichment technologies can play an important role in both diagnostic and therapeutic areas. However, currently used cell sorting techniques have difficulties in rapidly isolating only the desired target cells from a large volume of body fluids. In this work, we developed a filtering system that can quickly separate and highly concentrate cells from a large volume of solution, depending on their size, using a silicon membrane filter. To overcome the problems caused by material limitations of the brittle silicon, we designed a novel membrane filter with various pore designs. From these designs, the most optimal design with high pore density, while preventing crack formation was derived by applying fluid dynamics simulation and near-field stress analysis. The membrane filter system using the selected design was fabricated, and cell filtration performance was evaluated. The LNCaP cell in horse blood was recovered up to 86% and enriched to 187-fold compared to initial cell populations after filtration at a flow rate of 5 mL/min. The results demonstrate that the filter presented in this study can rapidly and selectively isolate target cells from a large volume of body fluid sample.

Hydrophilic and positively charged polyethylenimine-functionalized mesoporous magnetic clusters for highly efficient removal of Pb(II) and Cr(VI) from wastewater.

We develop mesoporous magnetic clusters (MMCs) functionalized with hydrophilic branched polyethylenimine (b-PEI), later called b-MG, and MMCs functionalized with positively charged b-PEI (p-MG). These materials efficiently remove Pb(II) and Cr(VI) from wastewater. Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, and nitrogen adsorption-desorption analysis results clearly indicate that hydrophilic b-PEI and positively charged b-PEI are successfully attached to the MMC surfaces. Wide-angle X-ray diffraction, high-resolution transmission electron microscopy, and field-emission scanning electron microscopy analyses confirm that the crystal structures and morphologies of the MMCs are maintained well even when wet chemical modification processes are used to introduce hydrophilic b-PEI and positively charged b-PEI to the MMC surfaces. Langmuir and Sips isotherm models are applied to describe Pb(II) adsorption behavior of the b-MG and Cr(VI) adsorption behavior of the p-MG. The isotherm models indicate that the maximum adsorption capacities of b-MG and p-MG, respectively, are 216.3 and 334.1 mg g-1, respectively. These are higher than have previously been found for other adsorbents. In reusability tests, using magnetic separation and controlling the pH, the Pb(II) recovery efficiency of the b-MG is 95.6% and the Cr(VI) recovery efficiency of the p-MG is 68.0% even after the third cycle.

Effect of an oral healthcare program on gingival health status in rural areas of South Korea.

INTRODUCTION: The purpose of this study was to analyze the effects of an oral health care program administered at rural public health subcenters on oral hygiene status and bleeding on probing (BOP) scores among Korean rural residents older than 40 years. METHODS: Residents older than 40 years living in two rural areas were allocated randomly by order of visit into an intervention group (n=23) and control group (n=23). Changes in plaque and BOP score were analyzed between the groups using repeated-measures ANOVA. Hierarchical multiple regression analysis was conducted to identify factors affecting changes in BOP score. RESULTS: The BoP score decreased by 22.87 in the intervention group and 0.27 in the control group between baseline and the eighth week (p<0.001). Multiple regression analysis showed that the change in BoP score (ΔBoP score) increased significantly with an increase in the reduction of the plaque (PHP) index (ΔPHP index) (t=-2.174, p<0.05) and increased significantly more in the intervention group than in the control group (t=2.143, p<0.05). CONCLUSIONS: Professional care and continuous oral health education for 8 weeks prior to scaling among adults older than 40 years living in rural environments resulted in a change in oral health behaviors and a substantial reduction in gingival bleeding.

A case of bacteremia caused by Dialister pneumosintes and Slackia exigua in a patient with periapical abscess.

Dialister pneumosintes and Slackia exigua are both obligatory anaerobe and known to be associated with periodontal diseases and other oral infection. We report a case of blood stream infection caused by D. pneumosintes and S. exigua. This occurred in a 78-year-old female patient that presented with general weakness and fever. We revealed that she had a periapical abscess. The blood culture was positive for D. pneumosintes and S. exigua; however, identifying them was challenging. Ultimately, 16S rRNA sequencing was used to identify the organisms. The patient recovered after being treated with ceftriaxone and clindamycin. To the best of our knowledge, this is the first report of bacteremia caused by mixed infection of D. pneumosintes and S. exigua.

Gamma analysis dependence on specified low-dose thresholds for VMAT QA.

The American Association of Physicists in Medicine Task Group 119 instructed institutions to use a low-dose threshold of 10% or a region of interest determined by the jaw setting when they collected gamma analysis quality assurance (QA) data for the planar dose distribution. However, there are no clinical data to quantitatively demonstrate the impact of the low-dose threshold on the gamma index. Therefore, we performed a gamma analysis with various low-dose thresholds in the range of 0% to 15% according to both global and local normalization and different acceptance criteria (3%/3 mm, 2%/2 mm, and 1%/1 mm). A total of 30 treatment plans--10 head and neck, 10 brain, and 10 prostate cancer cases--were randomly selected from the Varian Eclipse treatment planning system (TPS). For the gamma analysis, a calculated portal image was acquired through a portal dose calculation algorithm in the Eclipse TPS, and a measured portal image was obtained using an electronic portal-imaging device. Then, the gamma analysis was performed using the Portal Dosimetry software (Varian Medical Systems, Palo Alto, CA). The gamma passing rate (%GP) for the global normalization decreased as the low-dose threshold increased, and all low-dose thresholds led to %GP values above 95% for both the 3%/3 mm and 2%/2 mm criteria. However, for the local normalization, %GP for a low-dose threshold of 10% was 7.47%, 10.23%, and 6.71% greater than the low-dose threshold of 0% for head and neck, brain, and prostate for the 3%/3 mm criteria, respectively. The results indicate that applying the low-dose threshold to global normalization does not have a critical impact on patient-specific QA results. However, in the local normalization, the low-dose threshold level should be carefully selected because the excluded low-dose points could cause the average %GP to increase rapidly.

Human Fibroblast Growth Factor-Treated Adipose-Derived Stem Cells Facilitate Wound Healing and Revascularization in Rats with Streptozotocin-Induced Diabetes Mellitus.

Diabetes mellitus contributes to 15-25% of all chronic foot ulcers. Peripheral vascular disease is a cause of ischemic ulcers and exacerbates diabetic foot disease. Cell-based therapies are viable options to restore damaged vessels and induce the formation of new vessels. Adipose-derived stem cells (ADSCs) have the potential for angiogenesis and regeneration because of their greater paracrine effect. Preclinical studies are currently using other forced enhancement techniques (e.g., genetic modification or biomaterials) to increase the efficacy of human ADSC (hADSC) autotransplantation. Unlike genetic modifications and biomaterials, many growth factors have been approved by the equivalent regulatory authorities. This study confirmed the effect of enhanced human ADSC (ehADSC)s with a cocktail of FGF and other pharmacological agents to promote wound healing in diabetic foot disease. In vitro, ehADSCs exhibited a long and slender spindle-shaped morphology and showed significantly increased proliferation. In addition, it was shown that ehADSCs have more functionalities in oxidative stress toleration, stem cell stemness, and mobility. In vivo, the local transplantation of 1.2 × 106 hADSCs or ehADSCs was performed in animals with diabetes induced by STZ. The ehADSC group showed a statistically decreased wound size and increased blood flow compared with the hADSC group and the sham group. Human Nucleus Antigen (HNA) positive cells were observed in some ADSC-transplanted animals. The ehADSC group showed a relatively higher portion of HNA-positive animals than the hADSC group. The blood glucose levels showed no significant difference among the groups. In conclusion, the ehADSCs showed a better performance in vitro, compared with conventional hADSCs. Additionally, a topical injection of ehADSCs into diabetic wounds enhanced wound healing and blood flow, while improving histological markers suggesting revascularization.

Surface-facilitated formation of polydopamine and its implications in melanogenesis.

This manuscript examines influences of differently functionalized surfaces on the formation of solution-dispersed polydopamine (pDA). Glass vials functionalized with different functional groups provided a set of conditions with which the relationship between the area of active surface and the rate of pDA formation could be systematically studied. The results suggest that charged and polar surfaces accelerate pDA formation in solution, with the effect of -NH2 surfaces being exceptionally strong. In the vials, pDA formed as both forms of dispersions in solution and films at solid-liquid interface. Further analyses confirmed that both forms of pDA formed with -NH2 surfaces were chemically similar to conventional pDA synthesized without help of functional surfaces. Among short peptide-based amyloid fibers with defined surface functional groups, and those displaying lysines (-NH2) greatly accelerated the formation of pDA, consistent with the results of -NH2-functionalized vials. The results suggest that pDA formation may be facilitated by surface functional groups of solid-liquid interfaces, and have implications for the overlooked roles of amyloid fibers in biological melanogenesis.

Round-window delivery of lithium chloride regenerates cochlear synapses damaged by noise-induced excitotoxic trauma via inhibition of the NMDA receptor in the rat.

Noise exposure can destroy the synaptic connections between hair cells and auditory nerve fibers without damaging the hair cells, and this synaptic loss could contribute to difficult hearing in noisy environments. In this study, we investigated whether delivering lithium chloride to the round-window can regenerate synaptic loss of cochlea after acoustic overexposure. Our rat animal model of noise-induced cochlear synaptopathy caused about 50% loss of synapses in the cochlear basal region without damaging hair cells. We locally delivered a single treatment of poloxamer 407 (vehicle) containing lithium chloride (either 1 mM or 2 mM) to the round-window niche 24 hours after noise exposure. Controls included animals exposed to noise who received only the vehicle. Auditory brainstem responses were measured 3 days, 1 week, and 2 weeks post-exposure treatment, and cochleas were harvested 1 week and 2 weeks post-exposure treatment for histological analysis. As documented by confocal microscopy of immunostained ribbon synapses, local delivery of 2 mM lithium chloride produced synaptic regeneration coupled with corresponding functional recovery, as seen in the suprathreshold amplitude of auditory brainstem response wave 1. Western blot analyses revealed that 2 mM lithium chloride suppressed N-methyl-D-aspartate (NMDA) receptor expression 7 days after noise-exposure. Thus, round-window delivery of lithium chloride using poloxamer 407 reduces cochlear synaptic loss after acoustic overexposure by inhibiting NMDA receptor activity in rat model.

Role of Transient Receptor Potential Vanilloid 1 in Sonic Hedgehog-Dependent Taste Bud Differentiation.

Taste bud cell differentiation is extremely important for taste sensation. Immature taste bud cells cannot function during taste perception transmission to the nerve. In this study, we investigated whether hedgehog signaling affected taste bud cell differentiation and whether transient receptor potential vanilloid 1 (TRPV1) played a key role in dry mouth. The induction of dry mouth due to salivary gland resection (SGR) was confirmed on the basis of reduced salivation and disrupted fungiform papillae. The expression of keratin 8 (K8) of taste bud cells, neurofilament (NF), sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (Gli1) around taste bud cells was downregulated; however, the expression of TRPV1, P2X purinoceptor 3 (P2X3), and hematopoietic stem cell factor (c-Kit) was upregulated at the NF ends in the dry mouth group. To investigate the effect of TRPV1 defect on dry mouth, we induced dry mouth in the TRPV-/- group. The K8, NF, and P2X3 expression patterns were the same in the TRPV1 wild-type and TRPV1-/- dry mouth groups. However, Shh and c-Kit expression decreased regardless of dry mouth in the case of TRPV1 deficiency. These results indicated that TRPV1 positively regulated proliferation during taste bud cell injury by blocking the Shh/Gli1 pathway. In addition, not only cell proliferation but also differentiation of taste bud cells could not be regulated under TRPV1-deficiency conditions. Thus, TRPV1 positively regulates taste bud cell innervation and differentiation; this finding could be valuable in the clinical treatment of dry mouth-related taste dysfunction.

Development of a standardized mucositis and osteoradionecrosis animal model using external radiation.

OBJECTIVES: Although the side effects of radiation therapy vary from mucositis to osteomyelitis depending on the dose of radiation therapy, to date, an experimental animal model has not yet been proposed. The aim of this study was to develop an animal model for assessing complications of irradiated bone, especially to quantify the dose of radiation needed to develop a rat model. MATERIALS AND METHODS: Sixteen Sprague-Dawley rats aged seven weeks with a mean weight of 267.59 g were used. Atraumatic extraction of a right mandibular first molar was performed. At one week after the extraction, the rats were randomized into four groups and received a single dose of external radiation administered to the right lower jaw at a level of 14, 16, 18, or 20 Gy, respectively. Clinical alopecia with body weight changes were compared and bony volumetric analysis with micro-computed tomography (CT), histologic analysis with H&E were performed. RESULTS: The progression of the skin alopecia was different depending on the irradiation dose. Micro-CT parameters including bone volume, bone volume/tissue volume, bone mineral density, and trabecular spaces, showed no significant differences. The progression of osteoradionecrosis (ORN) along with that of inflammation, fibrosis, and bone resorption, was found with increased osteoclast or fibrosis in the radiated group. As the radiation dose increases, osteoclast numbers begin to decrease and osteoclast tends to increase. Osteoclasts respond more sensitively to the radiation dose, and osteoblasts are degraded at doses above 18 Gy. CONCLUSION: A standardized animal model clinically comparable to ORN of the jaw is a valuable tool that can be used to examine the pathophysiology of the disease and trial any potential treatment modalities. We present a methodology for the use of an experimental rat model that incorporates a guideline regarding radiation dose.

Development of a DNA isolation device using poly(3,4-dihydroxy-L-phenylalanine)-coated swab for on-site molecular diagnostics.

For on-site molecular diagnostics, a pre-treatment step for isolation of nucleic acid from clinical samples on site is desired. However, conventional commercialized silica-based nucleic acid isolation kits require repetitive pipetting and a centrifugation or permanent magnet for buffer exchange. In this study, we developed a poly(3,4-dihydroxy-L-phenylalanine) (L-DOPA)-coated swab that can absorb and desorb DNA depending on pH of buffers and a portable integrated DNA isolation device that comprises integrated chambers containing DNA isolation buffers. The poly(L-DOPA)-coated swab interacts with each buffer by passing through the membrane between the integrated chambers. Our device involves a simple operation and does not require any large equipment or skilled experts. By connecting the device with an automated polymerase chain reaction system, an isothermal amplification system, or a non-amplified DNA detection method, on-site molecular diagnosis of various diseases can be quickly realized.

Metal artifacts with dental implants: Evaluation using a dedicated CT/MR oral phantom with registration of the CT and MR images.

The aims of this study were to develop a computed tomography/magnetic resonance (CT/MR) oral phantom with insertable dental implants and to register CT/MR images to generate artifact-free MR images for patients undergoing teeth restorations. All measurements were done using a human MR scanner with spin echo (SE) and gradient echo (GRE) sequences image scan together with CT image. The metal regions and normal teeth parts are extracted with a suitable threshold from an initial image reconstructed with artifact from the CT images. Corrected metal projection regions of MR images and CT images are fused to produce artifact-free MR image that include dental restorations. After CT/MR registration, artifact size presented differences on the x- (SE, 12.0 mm; GRE, 18.0 mm) and y- (SE, 24.0 mm; GRE, 36.6 mm). When comparing the dental restoration with normal teeth, the structural similarity index metric (SSIM) of GRE 50 was lower than for the GRE 8 sequence and the SSIM of SE 145 shown higher than for the SE 490 sequence. The dedicated phantom provides a useful tool in head and neck research for multi-modality images. Therefore, CT/MR image-based approach for ground truth and registration offers visualization in diagnostic system and radiation treatment planning system.

Provision of oral hygiene services as a potential method for preventing periodontal disease and control hypertension and diabetes in a community health centre in Korea.

This study aimed to evaluate the effects of a community-based oral hygiene service on general and periodontal health indicators of patients with hypertension and type 2 diabetes mellitus visiting a community health centre in Korea. The study used a one-group pretest-posttest and interrupted time-series design. A total of 151 participants (45% male), with a mean age of 63 ± 8.4 years, were included in the study; these included patients with hypertension (62%), diabetes (12%) and both hypertension and diabetes (26%). Two dental hygienists dedicated 2 days per week to this project, providing oral hygiene services to 10-13 participants per day. Four oral hygiene service sessions were provided per patient. The objective oral hygiene status and subjective self-reported periodontal status were compared before and after the service. The changes in blood pressure and glycosylated haemoglobin levels were also assessed. A lower frequency of subjective swelling was reported at the fourth session (37.9%) compared to the first (55.6%) session. Further, significantly fewer cases of calculus and bleeding were observed (p < .05), and significantly more patients reported having no gum problems at the fourth session (43.1% vs. 27.2%; p < .05) than at the first session. Finally, the participants maintained stable blood pressures at each of the four sessions, and their glycosylated haemoglobin levels were significantly lower at the fourth session. In conclusion, the findings of this study suggest that community oral hygiene services provided by dental hygienists can promote objective oral hygiene and subjective periodontal status in the local community, and may help in the control of hypertension and diabetes.

Targeting and synergistic action of an antifungal peptide in an antibiotic drug-delivery system.

Amphotericin B (AmB) has been widely used against fungal infections throughout almost the entire body, including the skin, nails, oral cavity, respiratory tract, and urinary tract. However, the development of AmB-loaded nanoparticles demands a novel technique that reduces its toxicity and other associated problems. Here, we developed a pH-responsive and redox-sensitive polymer-based AmB-delivery carrier system. In particular, this system was functionalized by conjugation with the antifungal peptide histatin 5, which acts both as a targeting ligand and a synergistic antifungal molecule against Candida albicans, a major systemic fungal pathogen of humans. Our results in vitro and in vivo suggest that this drug-delivery system may serve as a novel tool to facilitate the use of antimicrobial peptides as targeting ligands to pathogenic microbes, which would open new avenues of investigation in the field of drug delivery.

Biodegradable Photonic Melanoidin for Theranostic Applications.

Light-absorbing nanoparticles for localized heat generation in tissues have various biomedical applications in diagnostic imaging, surgery, and therapies. Although numerous plasmonic and carbon-based nanoparticles with strong optical absorption have been developed, their clearance, potential cytotoxicity, and long-term safety issues remain unresolved. Here, we show that "generally regarded as safe (GRAS)" melanoidins prepared from glucose and amino acid offer a high light-to-heat conversion efficiency, biocompatibility, biodegradability, nonmutagenicity, and efficient renal clearance, as well as a low cost for synthesis. We exhibit a wide range of biomedical photonic applications of melanoidins, including in vivo photoacoustic mapping of sentinel lymph nodes, photoacoustic tracking of gastrointestinal tracts, photothermal cancer therapy, and photothermal lipolysis. The biodegradation rate and renal clearance of melanoidins are controllable by design. Our results confirm the feasibility of biodegradable melanoidins for various photonic applications to theranostic nanomedicines.

Polyacetylenes from a marine sponge Petrosia sp. inhibit DNA replication at the level of initiation.

In the course of our search for bioactive metabolites from the marine sponges collected from Korean water, we found that the polyacetylenes of marine sponge, genus Petrosia, deliver significant selective cytotoxicity against several human tumor cell lines. The effects of polyacetylene on DNA replication were examined using simian virus 40 DNA replication system in vitro. We found that polyacetylenes inhibited DNA replication, and predominantly inhibited the initiation stage of DNA replication. Polyacetylenes inhibited the DNA cleavage by topoisomerase I, and also significantly reduced polymerase alpha-primase activity. The ssDNA binding activity of replication protein A was little affected by polyacetylenes. We suggest that polyacetylenes might inhibit proteins required to establish replication forks during the initiation reaction, and their cytotoxicities might be related to the inhibitory effect they have on this fundamental cellular process.