Time to diagnosis of nontuberculous mycobacterial pulmonary disease and longitudinal changes on CT before diagnosis.

Background: The healthcare burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, but the diagnosis remains challenging and sometimes requires considerable time. This nested case-control study aims to clarify the time to diagnosis of NTM-PD, the factors that affect diagnosis and diagnostic delay, and changes in CT findings before diagnosis. Patients and methods: We retrospectively analyzed 187 patients suspected of having NTM-PD based on computed tomography (CT) findings at our institution between January 2019 and September 2020. We investigated the time to diagnosis of NTM-PD for all suspected and diagnosed patients. Multivariate analyses identified the factors affecting diagnosis and diagnostic delay over 6 months. We also evaluated longitudinal changes in CT findings during the observation period using CT scoring system. Results: The median times to diagnosis of NTM-PD were 71.8 months in all suspected patients and 3.2 months in only the diagnosed patients. Multivariable analysis showed that severity of the cavity domain of the CT score and anti-glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody positivity were significantly associated with establishing the diagnosis. A low CT score in the cavity domain was a risk factor for delayed diagnosis. In patients with delayed diagnosis, the total CT score was less severe than that in the early diagnosis patients at their first visits; however, it had deteriorated prior to the diagnosis. Conclusion: The diagnosis of NTM-PD sometimes required several years, and the absence or mild cavitation predicted a diagnostic delay. Of concern, a delay in diagnosis can result in a delay in treatment.

Er:YAG laser-induced cavitation can activate irrigation for the removal of intraradicular biofilm.

We investigated the biofilm removal effects of laser activated irrigation (LAI) using a pig model, focusing on the impact of the fiber tip position, and used a high-speed camera to observe the occurrence and positioning of the cavitation associated with laser irradiation. A total of 16 roots of deciduous mandibular second premolars from 4 pigs were used. After a pulpectomy, the canals were left open for 2 weeks and sealed for 4 weeks to induce intraradicular biofilm. Root canal irrigation was then performed with Er:YAG laser activation. The fiber tip was inserted at two different positions, i.e., into the root canal in the intracanal LAI group and into the pulp chamber in the coronal LAI group. Intracanal needle irrigation with saline or 5% NaOCl was utilized in the positive control and conventional needle irrigation (CNI) groups. SEM and qPCR were carried out to evaluate treatment efficacy. Statistical analysis was performed using ANOVA and a Tukey-Kramer post-hoc test for qPCR and with a Steel-Dwass test to compare the SEM scores, with α = 0.05. A high-speed camera was used to observe the generation of cavitation bubbles and the movement of the induced bubbles after laser irradiation. The intracanal and coronal LAI groups showed significantly lower amounts of bacteria than either the positive control or CNI groups. There was no significant difference found between the intracanal and coronal LAI groups. SEM images revealed opened dentinal tubules with the destruction of biofilm in both LAI groups. High-speed camera images demonstrated cavitation bubble production inside the root canal after a single pulse irradiation pulse. The generated bubbles moved throughout the entire internal multi-rooted tooth space. Coronal LAI can generate cavitation in the root canal with a simply placed fiber inside the pulp chamber, leading to effective biofilm removal. This method could thus contribute to the future development of endodontic treatments for refractory apical periodontitis caused by intraradicular biofilm.

Correction of large jawbone defect in the mouse using immature osteoblast-like cells and a 3D polylactic acid scaffold.

Bone tissue engineering has been developed using a combination of mesenchymal stem cells (MSCs) and calcium phosphate-based scaffolds. However, these complexes cannot regenerate large jawbone defects. To overcome this limitation of MSCs and ceramic scaffolds, a novel bone regeneration technology must be developed using cells possessing high bone forming ability and a scaffold that provides space for vertical bone augmentation. To approach this problem in our study, we developed alveolar bone-derived immature osteoblast-like cells (HAOBs), which have the bone regenerative capacity to correct a large bone defect when used as a grafting material in combination with polylactic acid fibers that organize the 3D structure and increase the strength of the scaffold material (3DPL). HAOB-3DPL constructs could not regenerate bone via xenogeneic transplantation in a micromini pig alveolar bone defect model. However, the autogenic transplantation of mouse calvaria-derived immature osteoblast-like cells (MCOBs) isolated using the identical protocol for HAOBs and mixed with 3DPL scaffolds successfully regenerated the bone in a large jawbone defect mouse model, compared to the 3DPL scaffold alone. Nanoindentation analysis indicated that the regenerated bone had a similar micromechanical strength to native bone. In addition, this MCOB-3DPL regenerated bone possesses osseointegration ability wherein a direct structural connection is established with the titanium implant surface. Hence, a complex formed between a 3DPL scaffold and immature osteoblast-like cells such as MCOBs represents a novel bone tissue engineering approach that enables the formation of vertical bone with the micromechanical properties required to treat large bone defects.

Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy.

Bone tissue engineering (BTE) is a process of combining live osteoblast progenitors with a biocompatible scaffold to produce a biological substitute that can integrate into host bone tissue and recover its function. Mesenchymal stem cells (MSCs) are the most researched post-natal stem cells because they have self-renewal properties and a multi-differentiation capacity that can give rise to various cell lineages, including osteoblasts. BTE technology utilizes a combination of MSCs and biodegradable scaffold material, which provides a suitable environment for functional bone recovery and has been developed as a therapeutic approach to bone regeneration. Although prior clinical trials of BTE approaches have shown promising results, the regeneration of large bone defects is still an unmet medical need in patients that have suffered a significant loss of bone function. In this present review, we discuss the osteogenic potential of MSCs in bone tissue engineering and propose the use of immature osteoblasts, which can differentiate into osteoblasts upon transplantation, as an alternative cell source for regeneration in large bone defects.

Evaluation of MDP and NaF in Two-step Self-etch Adhesives on Enamel Microshear Bond Strength and Morphology of the Adhesive-Enamel Interface.

PURPOSE: To evaluate the roles of MDP and NaF in the bonding resin of a two-step self-etch adhesive (2-SEA) on enamel bonding performance. MATERIALS AND METHODS: The experimental 2-SEAs were composed of an MDP-containing self-etching primer and four different bonding resins which were MDP- and NaF-free (00), MDP-containing and NaF-free (M0), MDP-free and NaF-containing (0F), and MDP- and NaF-containing (MF) adhesives. Microshear bond strength (µSBS) to enamel and ultimate tensile strength (UTS) of the adhesive resin were determined. The morphological characteristics of the adhesive-enamel interface after acid-base challenge were observed using SEM to evaluate the acid-base resistant zone (ABRZ). RESULTS: No decrease in µSBS was observed even after thermocycling (TC) in 00, 0F and MF. However, the µSBS of M0 significantly decreased after TC. The UTS of M0 significantly decreased after 1- and 180-day storage in water. SEM observations indicated that ABRZ was present in all groups. However, formation of erosion beneath the ABRZ was observed in M0 and 00, whereas formation of a slope without erosion was observed at the bottom of the ABRZ in MF. CONCLUSION: In the experimental 2-SEAs, the addition of MDP alone to the adhesive resin did not contribute to an improvement in enamel bonding durability and interfacial morphology, whereas the addition of NaF in the adhesive resin demonstrated an enhancement of the bonding durability and improvement of acid resistance at the bonded interface.

[PROBLEMS ASSOCIATED WITH THE DIAGNOSIS OF PROLONGED/CHRONIC COUGH IN CLINICAL SETTINGS].

BACKGROUND: Many patients visit primary care clinics or local hospitals with a complaint of prolonged/chronic cough. Among the different types of chronic cough, cough variant asthma (CVA) and postinfectious cough may be the most common types, and their differential diagnosis is difficult. Some physicians tend to prescribe inhaled corticosteroids before establishing a definitive diagnosis. METHODS: We retrospectively investigated useful findings for diagnosis in 77 patients with a complaint of prolonged/ chronic cough to detect meaningful findings for differential diagnosis and to identify problems associated with diagnosis in clinical practice. RESULTS: CVA was diagnosed in 39 patients, and postinfectious cough was diagnosed in 19. Compared with postinfectious cough, CVA was associated with significant characteristics such as "diurnal variation of symptoms," "response to inhalation of short acting ß2 agonist (SABA)," and "recurrent episodes of symptoms." CVA was associated with high FeNO levels as well, and high FeNO levels were specific to CVA. However, these useful characteristics were not significant in the patients who had been prescribed ICS before visiting our hospital. CONCLUSIONS: Medical examination and determination of FeNO levels are useful for the differential diagnosis of prolonged/chronic cough, before treatment with ICS.

Hemoptysis following Talc Pleurodesis in a Pneumothorax Patient.

The purpose of this article is to report a case of hemoptysis occurring in combination with secondary spontaneous pneumothorax following chemical pleurodesis by talc. A Japanese male with cancer of renal pelvis was found with the left pneumothorax and multiple lung metastases. A computed-tomography scan revealed severe emphysema throughout the lungs. Talc pleurodesis was employed to arrest air leakage. The patient developed hemoptysis 45 minutes after talc injection into the thorax. This is the first report of hemoptysis following talc pleurodesis. The agent could induce severe inflammation in capillary vessels of the lung following visceral pleura infiltration.

Overexpression of microRNA-155 suppresses chemokine expression induced by Interleukin-13 in BEAS-2B human bronchial epithelial cells.

BACKGROUND: MicroRNAs are non-coding small RNAs that regulate expression of target genes by binding to 3' untranslated regions. In this study, we used bronchial epithelial cells to investigate in vitro the role of the microRNA miR-155 in the expression of chemokines associated with airway inflammation. miR-155 has previously been reported to regulate allergic inflammation. METHODS: BEAS-2B bronchial epithelial cells were cultured and transfected with mimic or inhibitor oligonucleotides to overexpress or downregulate miR-155, as confirmed by real-time PCR. Cells were then stimulated with tumor necrosis factor-alpha, interleukin-13 (IL-13), and a double stranded RNA that binds Toll-like receptor 3. Expression and secretion of the chemokines CCL5, CCL11, CCL26, CXCL8, and CXCL10 were then quantified by real-time PCR and ELISA, respectively. Phosphorylation of signal transducer and activator of transcription 6 (STAT6), a target of the IL-13 receptor, was analyzed by ELISA. RESULTS: miR-155 overexpression significantly suppressed IL-13-induced secretion of CCL11 and CCL26. These effects were specific, and were not observed for other chemokines, nor in cells with downregulated miR-155. miR-155 overexpression also suppressed CCL11 and CCL26 mRNA, but did not affect expression of the IL-13 receptor or phosphorylation of STAT6. CONCLUSIONS: miR-155 specifically inhibits IL-13-induced expression of eosinophilic chemokines CCL11 and CCL26 in bronchial epithelial cells, even though the 3'-untranslated region of these genes do not contain a consensus binding site for miR-155.