The autophagy-targeting compound V46 enhances antimicrobial responses to Mycobacteroides abscessus by activating transcription factor EB.

Mycobacteroides abscessus (Mabc) is a rapidly growing nontuberculous mycobacterium that poses a considerable challenge as a multidrug-resistant pathogen causing chronic human infection. Effective therapeutics that enhance protective immune responses to Mabc are urgently needed. This study introduces trans-3,5,4'-trimethoxystilbene (V46), a novel resveratrol analogue with autophagy-activating properties and antimicrobial activity against Mabc infection, including multidrug-resistant strains. Among the resveratrol analogues tested, V46 significantly inhibited the growth of both rough and smooth Mabc strains, including multidrug-resistant strains, in macrophages and in the lungs of mice infected with Mabc. Additionally, V46 substantially reduced Mabc-induced levels of pro-inflammatory cytokines and chemokines in both macrophages and during in vivo infection. Mechanistic analysis showed that V46 suppressed the activation of the protein kinase B/Akt-mammalian target of rapamycin signaling pathway and enhanced adenosine monophosphate-activated protein kinase signaling in Mabc-infected cells. Notably, V46 activated autophagy and the nuclear translocation of transcription factor EB, which is crucial for antimicrobial host defenses against Mabc. Furthermore, V46 upregulated genes associated with autophagy and lysosomal biogenesis in Mabc-infected bone marrow-derived macrophages. The combination of V46 and rifabutin exerted a synergistic antimicrobial effect. These findings identify V46 as a candidate host-directed therapeutic for Mabc infection that activates autophagy and lysosomal function via transcription factor EB.

Composition and variability of core phyllosphere fungal mycobiota on field-grown broccoli.

BACKGROUND: Fresh vegetables harbor an assemblage of different microorganisms on their surfaces. The phyllosphere microbiota is important for maintaining plant health and managing crop quality before and after harvest. However, the diversity and ecology of fungal communities are largely unexplored in fresh vegetables. This study investigated the phyllosphere mycobiota of field-grown broccoli florets (n = 66) collected from 22 farms across four regions in Korea, using culturing, amplicon sequencing of the internal transcribed spacer region, and microbial network analysis. RESULTS: Microbial network analysis identified core genera (Purpureocillium, Filobasidium, Cystofilobasidium, Papiliotrema, Aureobasidium, and unclassified genera of Capnodiales) specific to the broccoli phyllosphere. The composition and network complexity of core and unique populations varied among farming regions, and was associated with local agro-meteorological conditions. The complexity of microbial associations was higher in mature communities than in immature communities, but complexity was lost upon development of plant pathogenic disease. Broccoli mycobiota were classified according to the dominance of Purpurecillium. While Purpurecillium-type microbiota were prevalent in normal samples, Filobasidium-type microbiota were frequently observed in immature, damaged, or postharvest samples. CONCLUSIONS: Together, fungal communities were important components of phyllosphere microbiota on fresh vegetables, and have substantial potential for exploitation to enhance and stabilize plant health and growth.

Effects of anxiety on sedation among pediatric patients undergoing esophagogastroduodenoscopy.

We investigated whether the severity of anxiety among children undergoing endoscopy could affect sedation. We prospectively recruited patients under 18 years of age who were scheduled to undergo esophagogastroduodenoscopy (EGD). Baseline anxiety was evaluated using the Spence Children's Anxiety Scale (SCAS). Our analysis considered the type and dose of sedative drugs, degree of sedation, and complications associated with sedation according to the scale score. The mean total SCAS T-scores and each subscale score were significantly higher in the 6-12-year age group. The mean T-score among patients who exhibited irritability during EGD was higher than that among other patients, with significant differences in the Total, Obsessive Disorder, Panic Agoraphobia and General Anxiety subscales. The midazolam doses of children exhibiting irritability were more likely to need higher (p = 0.006). Other sedation-related complications were not associated with the T-scores in each subscale. Total sleep time was not associated with any T-score subscales. Anxiety levels were significantly higher among 6-12-year-olds and children exhibiting irritability. Anxiety was often associated with irritability, difficulties achieving adequate sedation during EGD, and additional sedative drug administration. We recommend higher doses or more potent drugs to facilitate endoscopy for children with high anxiety levels.

Itaconate, Arginine, and Gamma-Aminobutyric Acid: A Host Metabolite Triad Protective Against Mycobacterial Infection.

Immune metabolic regulation shapes the host-pathogen interaction during infection with Mycobacterium tuberculosis (Mtb), the pathogen of human tuberculosis (TB). Several immunometabolites generated by metabolic remodeling in macrophages are implicated in innate immune protection against Mtb infection by fine-tuning defensive pathways. Itaconate, produced by the mitochondrial enzyme immunoresponsive gene 1 (IRG1), has antimicrobial and anti-inflammatory effects, restricting intracellular mycobacterial growth. L-arginine, a component of the urea cycle, is critical for the synthesis of nitric oxide (NO) and is implicated in M1-mediated antimycobacterial responses in myeloid cells. L-citrulline, a by-product of NO production, contributes to host defense and generates L-arginine in myeloid cells. In arginase 1-expressing cells, L-arginine can be converted into ornithine, a polyamine precursor that enhances autophagy and antimicrobial protection against Mtb in Kupffer cells. Gamma-aminobutyric acid (GABA), a metabolite and neurotransmitter, activate autophagy to induce antimycobacterial host defenses. This review discusses the recent updates of the functions of the three metabolites in host protection against mycobacterial infection. Understanding the mechanisms by which these metabolites promote host defense will facilitate the development of novel host-directed therapeutics against Mtb and drug-resistant bacteria.

A Smartphone App (AnSim) With Various Types and Forms of Messages Using the Transtheoretical Model for Cardiac Rehabilitation in Patients With Coronary Artery Disease: Development and Usability Study.

BACKGROUND: Despite strong evidence of clinical benefit, cardiac rehabilitation (CR) programs are currently underutilized and smartphone-based CR strategies are thought to address this unmet need. However, data regarding the detailed process of development are scarce. OBJECTIVE: This study focused on the development of a smartphone-based, patient-specific, messaging app for patients who have undergone percutaneous coronary intervention (PCI). METHODS: The AnSim app was developed in collaboration with a multidisciplinary team that included cardiologists, psychiatrists, nurses, pharmacists, nutritionists, and rehabilitation doctors and therapists. First, a focus group interview was conducted, and the narratives of the patients were analyzed to identify their needs and preferences. Based on the results, health care experts and clinicians drafted messages into 5 categories: (1) general information regarding cardiovascular health and medications, (2) nutrition, (3) physical activity, (4) destressing, and (5) smoking cessation. In each category, 90 messages were developed according to 3 simplified steps of the transtheoretical model of behavioral change: (1) precontemplation, (2) contemplation and preparation, and (3) action and maintenance. After an internal review and feedback from potential users, a bank of 450 messages was developed. RESULTS: The focus interview was conducted with 8 patients with PCI within 1 year, and 450 messages, including various forms of multimedia, were developed based on the transtheoretical model of behavioral change in each category. Positive feedback was obtained from the potential users (n=458). The mean Likert scale score was 3.95 (SD 0.39) and 3.91 (SD 0.39) for readability and usefulness, respectively, and several messages were refined based on the feedback. Finally, the patient-specific message delivery system was developed according to the baseline characteristics and stages of behavioral change in each participant. CONCLUSIONS: We developed an app (AnSim), which includes a bank of 450 patient-specific messages, that provides various medical information and CR programs regarding coronary heart disease. The detailed process of multidisciplinary collaboration over the course of the study provides a scientific basis for various medical professionals planning smartphone-based clinical research.

Clomiphene Citrate Shows Effective and Sustained Antimicrobial Activity against Mycobacterium abscessus.

Mycobacterium abscessus (M. abscessus) causes chronic pulmonary infections and is the most difficult non-tuberculous mycobacteria (NTM) to treat due to its resistance to current antimicrobial drugs, with a treatment success rate of 45.6%. Thus, novel treatment drugs are needed, of which we identified the drug clomiphene citrate (CC), known to treat infertility in women, to exhibit inhibitory activity against M. abscessus. To assess the potential of CC as a treatment for M. abscessus pulmonary diseases, we measured its efficacy in vitro and established the intracellular activity of CC against M. abscessus in human macrophages. CC significantly inhibited the growth of not only wild-type M. abscessus strains but also clinical isolate strains and clarithromycin (CLR)-resistant strains of M. abscessus. CC's drug efficacy did not have cytotoxicity in the infected macrophages. Furthermore, CC worked in anaerobic non-replicating conditions as well as in the presence of biofilm. The results of this in vitro study on M. abscessus activity suggest the possibility of using CC to develop new drug hypotheses for the treatment of M. abscessus infections.

Stress-associated neurobiological activity is linked with acute plaque instability via enhanced macrophage activity: a prospective serial 18F-FDG-PET/CT imaging assessment.

AIMS: Emotional stress is associated with future cardiovascular events. However, the mechanistic linkage of brain emotional neural activity with acute plaque instability is not fully elucidated. We aimed to prospectively estimate the relationship between brain amygdalar activity (AmygA), arterial inflammation (AI), and macrophage haematopoiesis (HEMA) in acute myocardial infarction (AMI) as compared with controls. METHODS AND RESULTS: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging was performed within 45 days of the index episode in 62 patients (45 with AMI, mean 60.0 years, 84.4% male; 17 controls, mean 59.6 years, 76.4% male). In 10 patients of the AMI group, serial 18F-FDG-PET/CT imaging was performed after 6 months to estimate the temporal changes. The signals were compared using a customized 3D-rendered PET reconstruction. AmygA [target-to-background ratio (TBR), mean ± standard deviation: 0.65 ± 0.05 vs. 0.60 ± 0.05; P = 0.004], carotid AI (TBR: 2.04 ± 0.39 vs. 1.81 ± 0.25; P = 0.026), and HEMA (TBR: 2.60 ± 0.38 vs. 2.22 ± 0.28; P < 0.001) were significantly higher in AMI patients compared with controls. AmygA correlated significantly with those of the carotid artery (r = 0.350; P = 0.005), aorta (r = 0.471; P < 0.001), and bone marrow (r = 0.356; P = 0.005). Psychological stress scales (PHQ-9 and PSS-10) and AmygA assessed by PET/CT imaging correlated well (P < 0.001). Six-month after AMI, AmygA, carotid AI, and HEMA decreased to a level comparable with the controls. CONCLUSION: AmygA, AI, and HEMA were concordantly enhanced in patients with AMI, showing concurrent dynamic changes over time. These results raise the possibility that stress-associated neurobiological activity is linked with acute plaque instability via augmented macrophage activity and could be a potential therapeutic target for plaque inflammation in AMI.

Development and validation study of Game Overuse Screening Questionnaire.

The aim of this study was to develop a screening questionnaire to distinguish high-risk individuals associated with game overuse from casual internet users. Reliability, validity, and diagnostic ability were evaluated for the newly developed Game Overuse Screening Questionnaire (GOS-Q). Preliminary items were assessed by 50 addiction experts online and 30 questions were selected. A total of 158 subjects recruited from six community centers for internet addiction participated in this study. Finally, 150 people were used in the analysis after excluding eight non-respondents. GOS-Q, Young's internet addiction scale, and Korean scale for internet addiction were used to assess concurrent validity. Internal consistency and item-total correlations were favorable (α= 0.96, r= 0.47-0.82). Test-retest reliability was moderate in size (r= 0.74). GOS-Q showed superior concurrent validity, and the highest correlation with Y-Scale (r= 0.77). The construct validity was marginally supported by a six-factor model using exploratory factor analysis. The area under the Receiver Operating Characteristic curve was 0.945. The high-risk addiction group was effectively characterized by a cut-off point of 38.5, with a sensitivity of 0.87 and a specificity of 0.88. Overall, the current study supports the use of GOS-Q as a reliable screening tool in a variety of settings.

Assessment of the trueness and tissue surface adaptation of CAD-CAM maxillary denture bases manufactured using digital light processing.

STATEMENT OF PROBLEM: Limited information is available evaluating the trueness and tissue surface adaptation of computer-aided design and computer-aided manufacturing (CAD-CAM) maxillary denture bases fabricated using digital light processing (DLP). PURPOSE: The purpose of this in vitro study was to evaluate the trueness of DLP-fabricated denture bases and to compare the tissue surface adaptation of DLP with milling (MIL) and pack and press (PAP). MATERIAL AND METHODS: The maxillary denture bases were virtually designed on the reference cast and were fabricated using DLP and MIL. Their intaglio surfaces were scanned and superimposed on the reference computer-aided design denture base to evaluate the trueness. A total of 20 denture bases (10 per technique) were also fabricated on the duplicated master casts using DLP and MIL. Ten denture bases were additionally made using PAP. The intaglio surfaces of the dentures were scanned and superimposed on the corresponding casts to compare the degree of tissue surface adaptation among the 3 techniques. The Mann-Whitney test and Kruskal-Wallis ANOVA were used for statistical analyses (α=.05). RESULTS: The trueness of the DLP denture base was significantly better than that of the MIL denture base (P<.001). Statistically significant differences were detected with respect to tissue surface adaptation of the denture base among the groups (P<.001). The DLP denture base showed the best denture base fit among the 3 techniques with a small interquartile range. CONCLUSIONS: Within the limitations of this in vitro study, the DLP maxillary denture base showed better trueness and tissue surface adaptation of ≤100 µm of the 3-dimensional surface deviation than the MIL and PAP denture bases.

Impact of left ventricular hypertrophy on long-term clinical outcomes in hypertensive patients who underwent successful percutaneous coronary intervention with drug-eluting stents.

Left ventricular hypertrophy (LVH) is associated with increased risk for vascular events and mortality. This study investigated 8-year clinical outcomes of hypertensive patients with LVH who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES) compared with hypertensive patients without LVH.A total of 1704 consecutive hypertensive patients who underwent PCI from 2004 to 2014 were enrolled. We classified them into either the LVH group (n = 406) or the control group (without LVH, n = 1298). LVH was defined by LV mass index > 115 g/m in men and > 95 g/m in women. After propensity score matched (PSM) analysis, 2 PSM groups (366 pairs, n = 732, c-statistic = 0.629) were generated.For up to 8 years, the LVH group showed a higher incidence of cardiac death (4.4% vs 1.2%, log-rank P = .023, hazard ratio: 3.371, 95% confidence interval: 1.109-10.25; P = .032) compared with the control group. However, there were no significant differences between the 2 groups in the incidence of total death, myocardial infarction, revascularization, and major adverse cardiac events up to 8 years.LVH in hypertensive patients who underwent successful PCI with DES was associated with higher incidence of cardiac death up to 8 years of follow-up. More careful managements and clinical follow-up are needed and treatment strategies should specifically focus to target prevention and reversal of LVH in hypertensive patients.

Three-Year Major Clinical Outcomes of Angiography-Guided Single Stenting Technique in Non-Complex Left Main Coronary Artery Diseases.

There is limited long-term comparative clinical outcome data concerning angiography- versus intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in non-complex left main coronary artery (LMCA) disease treated with the single stenting technique in the drug-eluting stent (DES) era.The aim of this study was to investigate whether angiography-guided stenting is comparable to IVUS-guided stenting during 3-year clinical follow-up periods in patients with non-complex LM disease treated with the single stenting technique.A total of 196 patients treated with either angiography-guided (n = 74) or IVUS-guided (n = 122) PCI were included. The primary outcome was the occurrence of major adverse cardiac events (MACE) defined as total death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and non-target vessel revascularization (Non-TVR). To adjust for any potential confounders, propensity score (PS) adjusted analysis was performed.During 3-year follow-up, the PS adjusted Cox-proportional hazard ratio (HR) was not significantly different between the two groups for total death, cardiac death, and MI. Also, TLR and the combined rates of TVR and non-TVR were not significantly different. Finally, MACE was not significantly different between the two groups (HR: 0.63, 95% Confidence interval (CI): 0.33-1.17; P = 0.149).Angiography-guided PCI for non-complex LMCA diseases treated with the single stenting technique showed comparable results compared with IVUS-guided PCI in reducing clinical events during 3-year clinical follow-up in the DES era. Although IVUS guided PCI is the ideal strategy, angiography-guided PCI can be an option for LMCA PCI in some selected cases.

Anti-inflammatory activity of Ternstroemia gymnanthera stem bark extracts in bacterial lipopolysaccharide-stimulated RAW264.7 murine macrophage cells.

CONTEXT: Ternstroemia gymnanthera Sprague (Theaceae) possesses various known pharmacological properties. However, its anti-inflammatory activity has not been reported. OBJECTIVE: The anti-inflammatory activity of Ternstroemia gymnanthera stem bark aqueous extract (TGSBE) was evaluated using LPS-stimulated RAW264.7 macrophages. MATERIALS AND METHODS: Cytotoxicity was assessed by MTT assay after 24 h with TGSBE (25-200 µg/mL). Further testing used TGSBE at 100 and 200 µg/mL. Griess and ELISA methods after 24 h with TGSBE determined NO and cytokine levels, respectively; then, mRNA levels (iNOS & cytokines) were analyzed by Quantitative-PCR after 12 h. NF-κB and MAPK were assessed by immunoblotting after TGSBE treatment for 12 h, followed by LPS for 30 min. Immunofluorescence assay was also performed for NF-κB. ROS and MMP, after 12 h with TGSBE, were determined by flow cytometry. The antioxidant potential of TGSBE was analyzed by ABTS assay. The Folin-Ciocalteu method determined the total phenolic content of TGSBE. LPS concentration was 0.5 µg/mL. RESULTS: TGSBE at 200 µg/mL showed about 96.2% viability while suppressing the production of NO (88.99%), TNFα (24.38%), IL-6 (61.70%) and IL-1ß (55.12%) and gene expression by 67.88, 45.24, 65.84, and 70.48%, respectively. TGSBE decreased ROS (79.26%) and improved MMP (48.01%); it inhibited translocation of NF-κB and MAPK activation. Radical scavenging activity was 50% at 402.17 µg/mL (ascorbic acid standard: 88.8 µg/mL). Total phenolic content was 240.9 mg GAE/g. DISCUSSION AND CONCLUSION: TGSBE suppresses the inflammatory response by inhibiting the NF-κB and MAPK cascades exhibiting therapeutic potential to treat inflammatory diseases associated with increased activation of macrophages.

Deoxyrhapontigenin, a Natural Stilbene Derivative Isolated From Rheum undulatum L. Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Human Breast Cancer Cells.

Although current chemotherapeutic agents are active at the beginning of therapy, the most common risk is the development of resistance during later stages in almost all cancer types including breast cancer. Hence, investigation of novel drugs is still a priority goal for cancer treatment. The objective of the present study is to investigate the anticancer effect of a derivative of stilbene, deoxyrhapontigenin (DR) isolated from Rheum undulatum L. root extracts against the chemoresistant MCF-7/adr and its parental MCF-7 human breast cancer cells. The morphological images indicate that DR induces an extensive cytoplasmic vacuolation in breast cancer cells. Mechanistic investigations revealed that DR treatment causes endoplasmic reticulum (ER) dilation and upregulated the expression of ER stress markers GRP78, IRE1α, eIF2α, CHOP, JNK, and p38. Subsequently, we also identified that DR increases the levels of apoptotic fragment of PARP (89 kDa) in breast cancer cells. Blocking the expression of one of the components of the ER stress-mediated apoptosis pathway, CHOP using siRNA significantly decreased DR-induced apoptotic cleavage of PARP. In summary, the present study suggests that the induction of ER stress-mediated apoptosis by DR may account for its cytotoxic effects in human breast cancer cells.

Demineralized deciduous tooth as a source of bone graft material: its biological and physicochemical characteristics.

OBJECTIVE: To examine structural and physicochemical characteristics of demineralized deciduous tooth powder (DDTP) in relation to demineralization time and to present potential of using DDTP as a bone graft material. STUDY DESIGN: For structural and physicochemical analysis, scanning electron microscopy, inductively coupled plasma spectrometry, energy-dispersive X-ray analysis, X-ray diffraction analysis, differential scanning calorimetry, and Brunauer-Emmett-Teller surface area analysis were performed. In in vivo experiments, DDTP was grafted in 20 Sprague-Dawley rats' calvarial defects, and radiographic and histologic examination and histomorphometric analysis were performed. RESULTS: In vitro studies confirmed physicochemical demands for collagen-based bone graft material, such as lowered calcium content, lowered crystallinity of hydroxyapatite, and exposed organic structures to demineralization. In vivo experiment indicated new bone formation in DDTP-grafted sites and gradual resorption of the grafted particles. Defect closure rate was significantly higher in the 8-week DDTP-grafted group compared with control (P < .05). CONCLUSIONS: Deciduous teeth had structural and physicochemical characteristics suitable for grafting with appropriate demineralization. Bone healing was observed to have successfully occurred in DDTP-grafted sites.

An alternative treatment option for a bony defect from large odontoma using recycled demineralization at chairside.

Odontoma is the most common odontogenic benign tumor, and the treatment of choice is generally surgical removal. After excision, bone grafts may be necessary depending on the need for further treatment, or the size and location of the odontoma. Although the osteogenic capacity of a demineralized tooth was verified as early as 1967 by Urist and many other investigators, the cumbersome procedure, including a long demineralization time, may be less than comfortable for clinicians. A modified ultrasonic technology, with periodic negative pressure and temperature control, facilitated rapid and aseptic preparation of demineralized teeth for bone grafts. This approach reduces the demineralization time dramatically (≤80 minutes), so that the graft material can be prepared chairside on the same day as the extraction. The purpose of this article is to describe two cases of large compound odonotomas used as graft material prepared chairside for enucleation-induced bony defects. These two clinical cases showed favorable wound healing without complications, and good bony support for future dental implants or orthodontic treatment. Finally, this report will suggest the possibility of recycling the benign pathologic hard tissue as an alternative treatment option for conventional bone grafts in clinics.

A typical case of L-transposition of the great arteries initially presented as complete atrioventricular block in middle-aged man.

L-transposition of the great arteries (L-TGA) is a rare congenital anomaly and could cause complete atrioventricular (AV) block at relatively younger age. We present a case of 43-year-old male who complained of dizziness due to complete AV block. We confirmed L-TGA using transthoracic echocardiography and cardiac computed tomography. Permanent pacemaker was inserted without complications. No invasive treatment including corrective surgery was performed because patient's cardiac function was almost normal and the symptom was completely resolved after pacemaker insertion.

A survey of the satisfaction of patients who have undergone implant surgery with and without employing a computer-guided implant surgical template.

PURPOSE: This study aims to investigate the degree of subjective pain and the satisfaction of patients who have undergone an implant treatment using a computer-guided template. MATERIALS AND METHODS: A survey was conducted for 135 patients who have undergone implant surgery with and without the use of the computer-guided template during the period of 2012 and 2013 in university hospitals, dental hospitals and dental clinics that practiced implant surgery using the computer-guided template. Likert scale and VAS score were used in the survey questions, and the independent t-test and One-Way ANOVA were performed (α=.05). RESULTS: The route that the subjects were introduced to the computer-guided implant surgery using a surgical template was mostly advices by dentists, and the most common reason for which they chose to undergo such surgery was that it was accurate and safe. Most of them gave an answer that they were willing to recommend it to others. The patients who have undergone the computer-guided implant surgery felt less pain during the operation and showed higher satisfaction than those who have undergone conventional implant surgery. Among the patients who have undergone computer-guided implant surgery, those who also had prior experience of surgery without a computer-guided template expressed higher satisfaction with the former (P<.05). CONCLUSION: In this study, it could be seen that the patients who have undergone computer-guided implant surgery employing a surgical template felt less pain and had higher satisfaction than those with the conventional one, and the dentist's description could provide the confidence about the safety of surgery.

Pulmonary toxocariasis mimicking invasive aspergillosis in a patient with ulcerative colitis.

A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia.

Comparison of five-axis milling and rapid prototyping for implant surgical templates.

PURPOSE: This study aims to compare and evaluate the accuracy of surgical templates fabricated using coordinate synchronization processing with five-axis milling and design-related processing with rapid prototyping (RP). MATERIALS AND METHODS: Master phantoms with 10 embedded gutta-percha cylinders hidden under artificial gingiva were fabricated and imaged using cone beam computed tomography. Vectors of the hidden cylinders were extracted and transferred to those of the planned implants through reverse engineering using virtual planning software. An RP-produced template was fabricated by stereolithography in photopolymer at the RP center according to planned data. Metal sleeves were bonded after holes were bored (group RP). For the milled template, milling coordinates were synchronized using the conversion process for the coordinate synchronization platform located on the model's bottom. Metal bushings were set on holes milled on the five-axis milling machine, on which the model was fixed through the coordinate synchronization plate, and the framework was constructed on the model using orthodontic resin (group CS). A computed tomography image was taken with templates firmly fixed on models using anchor pins (RP) or anchor screws (CS). The accuracy was analyzed via reverse engineering. Differences between the two groups were compared by repeated measures two-factor analysis. RESULTS: From the reverse-engineered image of the template on the experimental model, RP-produced templates showed significantly larger deviations than did milled surgical guides. Maximum deviations of the group RP were 1.58 mm (horizontal), 1.68 mm (vertical), and 8.51 degrees (angular); those of the group CS were 0.68 mm (horizontal), 0.41 mm (vertical), and 3.23 degrees (angular). CONCLUSIONS: A comparison of milling and RP template production methods showed that a vector-milled surgical guide had significantly smaller deviations than did an RP-produced template. The accuracy of computer-guided milled surgical templates was within the safety margin of previous studies.

Reusable floating-electrode sensor for the quantitative electrophysiological monitoring of a nonadherent cell.

We report a reusable floating-electrode sensor based on aligned semiconducting single-walled carbon nanotubes for the quantitative monitoring of the electrophysiological responses from a nonadherent cell. This method allowed us to monitor and distinguish the real-time responses from normal and small-cell lung cancer (SCLC) cells to the addition of nicotine. The difference was attributed to the overexpressed nicotinic acetylcholine receptors (nAChRs) in the SCLC cells. The sensor was also utilized to monitor the effect of various drugs on the cells. The treatment with inhibitors such as genistin or daidzein was found to reduce Ca(2+) influx in SCLC cells. Moreover, tamoxifen, though known as the antiestrogen compound, was found to only partly block the binding of daidzein to nAChRs. Significantly, the activities of multiple individual cells could be measured repeatedly using a single sensor device, enabling statistically meaningful measurements without errors from the device-to-device variations of the sensor characteristics. This capability of the quantitative monitoring of nonadherent cells should be a major breakthrough for electrophysiology research and various biomedical applications such as drug screening and therapeutic monitoring.