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Introduction: In response to growing concerns over negative emotions towards climate change worldwide, it is essential that a validated and reliable scale is available for the generalizability of the constructs being measured, and it is not just applicable to Western context, but also the East. Method: The present study aims to conduct a psychometric investigation of the 13-item Climate Change Anxiety Scale (CCAS) of Clayton and Karazsia in Traditional Chinese using a large sample (N = 1,567) of Chinese individuals in Hong Kong, China. The CCAS was translated, back-translated, cross-culturally adapted and pilot-tested. We performed descriptive, scale reliability, exploratory factor and confirmatory factor analyses. Results: Unlike the two-factor structure of the original scale, our results revealed a three-factor structure of the 13-item CCAS version that captured three dimensions of climate change anxiety: intrusive symptoms, reflections on climate anxiety, and functional impairment. The scale showed good goodness-of-fit indices, internal consistency and reliability. The Chinese CCAS version demonstrated high levels of reliability estimates and significant, albeit weak, correlations with the relevant constructs of well-being, anxiety and depression, environmental orientation, self-efficacy and belief denial. Conclusion: Overall, the Chinese CCAS version has good reliability and validity, and it can be used as a valid assessment tool for climate change anxiety screening with Chinese individuals, thus providing a foundation for better understanding various climate change–related emotions through an anxiety lens in the Chinese context.

Background: Few tools exist for the early identification of patients at risk for chronic lung allograft dysfunction (CLAD). We previously showed hyaluronan (HA), a matrix molecule that regulates lung inflammation and fibrosis, accumulates in bronchoalveolar lavage fluid (BALF) and blood in CLAD. We aimed to determine if early posttransplant HA elevations inform CLAD risk., Methods: HA was quantified in 3,080 BALF and 1,323 blood samples collected over the first posttransplant year in 743 adult lung recipients at 5 centers. The relationship between BALF or blood HA and CLAD was assessed using Cox models with a time-dependent binary covariate for "elevated" HA. Potential thresholds for elevated HA were examined using a grid search between the 50th and 85th percentile. The optimal threshold was identified using fit statistics, and the association between the selected threshold and CLAD was internally validated through iterative resampling. A multivariable Cox model using the selected threshold was performed to evaluate the association of elevated HA with CLAD, considering other factors that may influence CLAD risk., Results: BALF HA levels >19.1 ng/ml (65th percentile) had the largest hazard ratio (HR) for CLAD (HR 1.70, 95% confidence interval [CI] 1.25-1.31; p < 0.001), optimized fit statistics, and demonstrated robust reproducibility. In a multivariable model, the occurrence of BALF HA >19.1 ng/ml in the first posttransplant year conferred a 66% increase in the hazards for CLAD (adjusted HR 1.66, 95% CI 1.19-2.32; p = 0.003). Blood HA was not significantly associated with CLAD., Conclusions: We identified and validated a precise threshold for BALF HA in the first posttransplant year that distinguishes patients at increased CLAD risk., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The Lung Session of the 2022 16th Banff Foundation for Allograft Pathology Conference-held in Banff, Alberta-focused on non-rejection lung allograft pathology and novel technologies for the detection of allograft injury. A multidisciplinary panel reviewed the state-of-the-art of current histopathologic entities, serologic studies, and molecular practices, as well as novel applications of digital pathology with artificial intelligence, gene expression analysis, and quantitative image analysis of chest computerized tomography. Current states of need as well as prospective integration of the aforementioned tools and technologies for complete assessment of allograft injury and its impact on lung transplant outcomes were discussed. Key conclusions from the discussion were: (1) recognition of limitations in current standard of care assessment of lung allograft dysfunction; (2) agreement on the need for a consensus regarding the standardized approach to the collection and assessment of pathologic data, inclusive of all lesions associated with graft outcome (eg, non-rejection pathology); and (3) optimism regarding promising novel diagnostic modalities, especially minimally invasive, which should be integrated into large, prospective multicenter studies to further evaluate their utility in clinical practice for directing personalized therapies to improve graft outcomes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper investigates the full-state constraint event-triggered adaptive control for a class of uncertain strict-feedback systems. The lack of information on the coupling dynamics of virtual variables in backstepping increases the complexity of feedback design. Given this, the requirements of shaping system performance constraints, eliminating initial dependence, and reducing data transfer costs together give rise to an interesting and challenging problem. Constructing the time-receding horizon (TRH) and stitching it with the quadratic Lyapunov function (QLF) is the key to constrained tracking. Specifying TRHs as a set of smooth bounds with fixed-time convergence and forcing the system to stabilize within the constrained region before the prescribed settling time provide a sufficient condition for practical finite-time stability (PFS). For relaxing the initial dependence, a tuning function is designed to match the performance constraints under arbitrary system initial conditions. A dual-channel event-triggered mechanism (ETM) is developed to automatically adjust the controller and estimator data flow updates with less transmission burden. By combining a specific inequality with backstepping, uncertainties are overcome without the "complexity explosion" in recursion steps. Finally, simulations demonstrate the effectiveness of the proposed method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 ISA. Published by Elsevier Ltd. All rights reserved.)

Background: Chronic lung allograft dysfunction (CLAD) increases morbidity and mortality for lung transplant recipients. Club cell secretory protein (CCSP), produced by airway club cells, is reduced in the bronchoalveolar lavage fluid (BALF) of lung recipients with CLAD. We sought to understand the relationship between BALF CCSP and early posttransplant allograft injury and determine if early posttransplant BALF CCSP reductions indicate later CLAD risk., Methods: We quantified CCSP and total protein in 1606 BALF samples collected over the first posttransplant year from 392 adult lung recipients at 5 centers. Generalized estimating equation models were used to examine the correlation of allograft histology or infection events with protein-normalized BALF CCSP. We performed multivariable Cox regression to determine the association between a time-dependent binary indicator of normalized BALF CCSP level below the median in the first posttransplant year and development of probable CLAD., Results: Normalized BALF CCSP concentrations were 19% to 48% lower among samples corresponding to histological allograft injury as compared with healthy samples. Patients who experienced any occurrence of a normalized BALF CCSP level below the median over the first posttransplant year had a significant increase in probable CLAD risk independent of other factors previously linked to CLAD (adjusted hazard ratio 1.95; p = 0.035)., Conclusions: We discovered a threshold for reduced BALF CCSP to discriminate future CLAD risk; supporting the utility of BALF CCSP as a tool for early posttransplant risk stratification. Additionally, our finding that low CCSP associates with future CLAD underscores a role for club cell injury in CLAD pathobiology., Competing Interests: Disclosure statement None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Emission source microscopy (ESM) technique can be utilized for localization of electromagnetic interference sources in the electronic systems, but its accuracy is limited by the typical planar scanning mode. In order to increase the accuracy, this paper presents a novel cylinder-aperture ESM measurement system driven by 6-DOF manipulator, and investigated the control strategy to generate the maximum-area aperture and optimized scanning trajectory. Based on the multiple constraints of the cylinder-aperture ESM measurement, we proposes analyzing the impact of the constraints by steps. This can obtain the analytical solution of the manipulator workspace and support solving the maximum aperture area. Besides, a modified RRT*(Rapidly-exploring Random Trees) algorithm is addressed to optimize the manipulator trajectory. The simulation and tests have proven that this algorithm could obviously reduce the joint mutation and cumulative tracking error. In the experimental section, the near-field scanning (NFS) tests, planar-aperture ESM measurement and proposed cylinder-aperture ESM measurement were conducted to measure one benchmark emission source. The results have demonstrated that the cylinder-aperture ESM measurement has the best convergences on the radiation pattern of the emission source., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 ISA. Published by Elsevier Ltd. All rights reserved.)

Macrophage activation and hypercytokinemia are notable presentations in certain viral infections leading to severe disease and poor prognosis. Viral infections can cause macrophage polarization into the pro-inflammatory M1 or anti-inflammatory M2 phenotype. Activated M1 macrophages usually restrict viral replication whereas activated M2 macrophages suppress inflammation and promote tissue repair. In response to inflammatory stimuli, macrophages polarize to the M2 phenotype expressing hemoglobin scavenger CD163 surface receptor. The CD163 receptor is shed as the soluble form, sCD163, into plasma or tissue fluids. sCD163 causes detoxification of pro-oxidative hemoglobin which produces anti-inflammatory metabolites that promote the resolution of inflammation. Hence, increased CD163 expression in tissues and elevated circulatory levels of sCD163 have been associated with acute and chronic inflammatory diseases. CD163 and other macrophage activation markers have been commonly included in the investigation of disease pathogenesis and progression. This review provides an overview of the involvement of CD163 in viral diseases. The clinical utility of CD163 in viral disease diagnosis, progression, prognosis and treatment evaluation is discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (>90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Histopathologic lung allograft injuries are putative harbingers for chronic lung allograft dysfunction (CLAD). However, the mechanisms responsible are not well understood. CXCL9 and CXCL10 are potent chemoattractants of mononuclear cells and potential propagators of allograft injury. We hypothesized that these chemokines would be quantifiable in plasma, and would associate with subsequent CLAD development. In this prospective multicenter study, we evaluated 721 plasma samples for CXCL9/CXCL10 levels from 184 participants at the time of transbronchial biopsies during their first-year post-transplantation. We determined the association between plasma chemokines, histopathologic injury, and CLAD risk using Cox proportional hazards models. We also evaluated CXCL9/CXCL10 levels in bronchoalveolar lavage (BAL) fluid and compared plasma to BAL with respect to CLAD risk. Plasma CXCL9/CXCL10 levels were elevated during the injury patterns associated with CLAD, acute rejection, and acute lung injury, with a dose-response relationship between chemokine levels and CLAD risk. Importantly, there were strong interactions between injury and plasma CXCL9/CXCL10, where histopathologic injury associated with CLAD only in the presence of elevated plasma chemokines. We observed similar associations and interactions with BAL CXCL9/CXCL10 levels. Elevated plasma CXCL9/CXCL10 during allograft injury may contribute to CLAD pathogenesis and has potential as a minimally invasive immune monitoring biomarker., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: Transbronchial lung cryobiopsy (TBLC) has emerged as a promising alternative to surgical lung biopsy for the diagnosis of interstitial lung disease. However, uncertainty remains regarding its overall complications due to a lack of procedural standardization including the size of cryoprobe utilized., Methods: This is a prospective cohort study of a protocolized transbronchial cryobiopsy program utilizing a 2.4 mm cryoprobe. 201 consecutive subjects were enrolled at a single academic center., Results: The average biopsy size was 106.2 ± 39.3 mm 2 . Complications included a total pneumothorax rate of 4.9% with 3.5% undergoing chest tube placement. Severe bleeding defined by the Nashville Working Group occurred in 0.5% of cases. There were no deaths at 30-days., Discussion: A protocolized transbronchial cryobiopsy program utilizing a 2.4 mm cryoprobe in can achieve a high diagnostic yield with a favorable safety profile., Competing Interests: Declaration of competing interest The authors have no conflict of interest with regards to this paper., (Published by Elsevier Ltd.)

Ameloblastic fibro-odontoma (AFO) is a rare benign mixed odontogenic tumor that affects children and young adults. AFO occurs mainly intraosseous. Extraosseous AFO is extremely rare. We report 2 cases of rare peripheral ameloblastic fibro-odontoma in 2- and 12-year-old female patients. Microscopic examination revealed a benign proliferation of odontogenic epithelium associated with a dentinoid material distributed within a cell-rich mesenchymal stroma resembling dental papilla. Simple surgical excision of the lesion is usually curative. There was no recurrence after a short period of follow-up. Clinicians should be cognizant of this rare entity, which can be considered in a differential diagnosis of gingival growths that are noted in early childhood., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Endobronchial ultrasound (EBUS)-guided transbronchial needle aspirate (TBNA) is a widely used method of minimally invasive lymph node sampling. The benefit of processing samples by cytologic methods versus "core biopsy" is unclear. It is unknown if safety or diagnostic yield varies by needle gauge., Materials and Methods: Between June 2018 and July 2019, 40 patients (56 lesions) undergoing EBUS TBNA lymph node evaluation were enrolled in this single-center prospective trial. Patients were chosen by permuted block randomization to undergo EBUS TBNA starting with 22-gauge (22g) or 19-gauge (19g) needles. Separate samples were sent for processing by cytologic methods and histopathology. Surgical pathologists and cytopathologists were blinded to needle size. The primary endpoint was diagnostic yield. Secondary endpoints compared specimen adequacy by rapid onsite evaluation (ROSE), sample adequacy for molecular testing, sample quality, and safety., Results: Diagnostic yield for histopathologic examination was 87.5% and 83.9% for 19g and 22g respectively (P = 0.625). There was no significant difference in diagnostic yield by cytologic examination based on needle size. There was no significant difference in slide quality. Molecular adequacy for core-biopsy was 77% and 80% for 22g and 19g needles, respectively. Molecular adequacy for cytology cell block was 77% and 80% for 22g and 19g needles, respectively. There were no significant procedural complications., Conclusion: Both the 22g and 19g EBUS TBNA needles provided a similar diagnostic yield and clinical utility for ancillary testing. Processing techniques by cytologic methods or "core biopsy" showed no significant impact in diagnostic yield or utility of molecular testing., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Despite the common detection of non-donor specific anti-HLA antibodies (non-DSAs) after lung transplantation, their clinical significance remains unclear. In this retrospective single-center cohort study of 325 lung transplant recipients, we evaluated the association between donor-specific HLA antibodies (DSAs) and non-DSAs with subsequent CLAD development. DSAs were detected in 30% of recipients and were associated with increased CLAD risk, with higher HRs for both de novo and high MFI (>5000) DSAs. Non-DSAs were detected in 56% of recipients, and 85% of DSA positive tests had concurrent non-DSAs. In general, non-DSAs did not increase CLAD risk in multivariable models accounting for DSAs. However, non-DSAs in conjunction with high BAL CXCL9 levels were associated with increased CLAD risk. Multivariable proportional hazards models demonstrate the importance of the HLA antibody-CXCL9 interaction: CLAD risk increases when HLA antibodies (both DSAs and non-DSAs) are detected in conjunction with high CXCL9. Conversely, CLAD risk is not increased when HLA antibodies are detected with low CXCL9. This study supports the potential utility of BAL CXCL9 measurement as a biomarker to risk stratify HLA antibodies for future CLAD. The ability to discriminate between high versus low-risk HLA antibodies may improve management by allowing for guided treatment decisions., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Sweet's Syndrome (SS), also known as acute febrile neutrophilic dermatosis, is one of several cutaneous inflammatory disorders classified as neutrophilic dermatoses. Respiratory complications are described in <50 cases in the literature, 1 without prior report of lung transplantation (LT). This article explains the clinical course of the first patient to receive LT for pulmonary SS and presents evidence suggesting recurrence of the primary lung disease in the allograft., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Depression is a common comorbidity among Black women with systemic lupus erythematosus (SLE), an understudied autoimmune disease characterized by major racial and gender inequities. Research is needed that examines how area-level factors influence risk of depression in this population. Latent profile analysis revealed four neighborhood typologies among metropolitan Atlanta, Georgia census tracts that participants (n=438) in the Black Women's Experiences Living with Lupus (BeWELL) Study were living in: Integrated/High-SES, Moderately Segregated/Mid-SES, Highly Segregated/Mid-SES, and Highly Segregated/Low-SES. Structural equation models indicated that highly segregated census tracts were associated with the greatest levels of depression via increased subjective assessments of neighborhood disorder. Policies that invest in segregated areas and address physical and social aspects of the environment that contribute to neighborhood disorder may promote mental health among Black women with SLE., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Viral infections are major causes of morbidity and mortality in solid-organ and hematopoietic stem cell transplant recipients. This study evaluated the performance of the Galileo Pathogen Solution metagenomics Next-Generation sequencing assay to detect and quantify 11 DNA viruses (cytomegalovirus, Epstein-Barr virus, BK virus, human adenovirus, JC virus, herpes simplex virus 1 and 2, varicella zoster virus, human herpesvirus 6A and 6B, and parvovirus B19) and to qualitatively detect torque teno virus. DNA extracted from 47 plasma samples of viremic transplant recipients were subjected to DNA library preparation with pathogen enrichment/human background depletion, sequencing, and automated data analysis. The viral loads were determined with the Galileo assay using a standard curve generated from a calibration panel. All of the samples tested had a 100% agreement with the real-time quantitative PCR (qPCR) assays in detecting the primary virus targets and the majority of the quantified samples had a viral load difference within 0.46 log 10 IU/mL or copies/mL. The mean difference for cytomegalovirus between the Galileo and qPCR assays was 0.21 log 10 IU/mL (SD, ±0.43 log 10 IU/mL). The mean difference for BK virus between the Galileo and qPCR assays was 0.17 log 10 cp/mL (SD, ±0.67 log 10 cp/mL). Additionally, 75 co-infections were detected in 31 samples by the Galileo assay. The study findings show that the Galileo assay can simultaneously detect and quantify multiple viruses in transplant recipients with results that are comparable with standard-of-care qPCR assays., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Surface Enhanced Raman Scattering (SERS) is a field of research that has shown promising application in the analysis of various substrate molecules by means of rough metallic surfaces. In directing the enhancement of substrate molecules in micro and nano-molar concentrations, plasmonic coupling of metal nanoparticles (NPs), morphology of metal NPs and the closely arrangement of rough metal surfaces that produces 'hot spots' can effectively increase the so-called enhancement factor (EF) that will be applicable in various fields. As the mechanistic aspects are still not clear, research has been triggered all over the world for the past two decades to have a clear understanding in chemical and electromagnetic effects. As the reproducibility of intensity of signals at low concentrations of probe molecules is of a big concern, metal NPs with various scaffolds were prepared and recently bio-molecule, DNA has been studied and showed promising advantages. This review first time highlights metal NPs with DNA interface as an effective rough metallic surface for SERS with high intensity and also with better reproducibility. Based on this review, similar kinds of scaffolds like DNA can be used to further analyze SERS activities of various metal NPs with different morphologies to have high intense signals at low concentrations of probe molecules., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Transduodenal ampullectiomy (TDA) is a surgical local excision method that can be performed in patients with ampullary tumors, but it has not been widely used clinically. Recently, TDA is considered as a good alternative surgical technique in patients who are unable to perform the endoscopic ampullectomy (EA) or pancreaticoduodenectomy (PD) for various reasons. The purpose of this study is to evaluate the surgical outcomes of TDA and the clinicopathological significance of pathologic findings in TDA., Methods: We reviewed the medical records of 31 patients diagnosed as ampullary tumor and underwent TDA from March 2004 to December 2019 in a single center., Results: All 31 patients were planned to perform TDA, and 4 of them were converted to PPPD due to the marginal status results of frozen biopsy. Of the 31 patients, 19 were diagnosed with malignancy and 12 were diagnosed with benign. Of the 18 patients who were diagnosed as malignancy in final biopsy, only 9 patients (50%) were diagnosed with malignancy on the preoperative endoscopic biopsy. In 15 patients who underwent only TDA for malignancy, there was no recurrence during the follow-up period (mean: 51.1 months, range: 19-137)., Conclusions: In benign ampullary tumor, TDA is a choice of treatment for patients who are unsuitable for endoscopic ampullectomy. TDA may be considered as an alternative operation in highly selective patients with early ampullary cancer (Tis and T1). Further studies on consensus of TDA indication for ampullary tumor will be needed in the future., Competing Interests: Declaration of competing interest Yun Kyung Jung, Seung Sam Paik, Dongho Choi and Kyeong Geun Lee have no conflicts of interest or financial ties to disclose., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Limitations in the ability to assemble large cohorts of patients with lupus from previously underrepresented groups have inhibited better understanding of many unanswered questions. The Georgians Organized Against Lupus (GOAL) Research Cohort is designed to overcome many of these limitations and is a rich and diverse repository of clinical, biological, sociodemographic, psychosocial, and health services data, and biologic material. Studies with the GOAL cohort will improve the understanding of how various factors interact and may lead to interventions on an individual and systems and societal level and help to mitigate the significant disparities that continue to exist in lupus., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The biomolecule DNA with the presence of different functionalities found to interact with different kinds of metal ions and show relatively higher stability over a long period of time when optimized appropriately. With the presence of A-T and G-C pairs, sugar moieties, phosphate functional groups and the double-helical structure, it can assemble both cationic and anionic species and forms a perfect metal-DNA self-assembly. Depending upon the aspect ratio of metal-DNA self-assemblies, metal content and their morphological outcomes, they could deliver variance in the catalytic activities. Such differences can be brought out by varying the synthesis reaction parameters focusing on a specific electrocatalytic application. In this review, recent developments in DNA metallization is elaborated first highlighting the underlying interactions between DNA and cationic/anionic species of various metals following which application of metal-DNA assemblies in electrocatalytic water oxidation and reduction are discussed critically. Knowledge provided in this review thus acts as the guide to various DNA metallization strategies and their subsequent application to water electrolysis for hydrogen generation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Chronic lung allograft dysfunction (CLAD), a condition of excess matrix deposition and airways fibrosis, limits survival after lung transplantation. Amphiregulin (Areg) is an epidermal growth factor receptor (EGFR) ligand suggested to regulate airway injury and repair. We sought to determine whether Areg expression increases in CLAD, localize the cellular source of Areg induction in CLAD, and assess its effects on airway matrix deposition. Lung fluid Areg protein was quantified in patients with or without CLAD. In situ hybridization was performed to localize Areg and EGFR transcript in CLAD and normal lung tissue. Expression of hyaluronan, a matrix constituent that accumulates in CLAD, was measured in Areg-exposed bronchial epithelial cells in the presence or absence of an EGFR inhibitor. We demonstrated that lung fluid Areg protein was significantly increased in CLAD in a discovery and replication cohort. Areg and EGFR transcripts were abundantly expressed within CLAD tissue, localized to basally distributed airway epithelial cells overlying fibrotic regions. Areg-exposed bronchial epithelial cells increased hyaluronan and hyaluronan synthase expression in an EGFR-dependent manner. Collectively, these novel observations suggest that Areg contributes to airway remodeling and CLAD. Moreover these data implicate a role for EGFR signaling in CLAD pathogenesis, suggesting novel therapeutic targets., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Tracking the fate of individual cells and their progeny through lineage tracing has been widely used to investigate various biological processes including embryonic development, homeostatic tissue turnover, and stem cell function in regeneration and disease. Conventional lineage tracing involves the marking of cells either with dyes or nucleoside analogues or genetic marking with fluorescent and/or colorimetric protein reporters. Both are imaging-based approaches that have played a crucial role in the field of developmental biology as well as adult stem cell biology. However, imaging-based lineage tracing approaches are limited by their scalability and the lack of molecular information underlying fate transitions. Recently, computational biology approaches have been combined with diverse tracing methods to overcome these limitations and so provide high-order scalability and a wealth of molecular information. In this review, we will introduce such novel computational methods, starting from single-cell RNA sequencing-based lineage analysis to DNA barcoding or genetic scar analysis. These novel approaches are complementary to conventional imaging-based approaches and enable us to study the lineage relationships of numerous cell types during vertebrate, and in particular human, development and disease.

Exploration of rare earth metals for the Surface Enhanced Raman Scattering (SERS) is greatly preferred to identify probe molecules even at nano molar level. Highly stable Rh nanoparticles (NPs) which are ultra-small size have been prepared within 20 min of reaction time as a colloidal solution using a bio-molecular scaffold DNA and NaBH 4 as a reducing agent under room temperature. While keeping metal ion concentration fixed and by making difference in DNA concentration, three different sets of Rh@DNA such as 0.08, 0.085 and 0.09 M were formed as nanochains like structure with varying diameters. The average chain length of Rh NPs for varying concentrations of DNA is ∼98 nm and the Rh particles size is below 5 nm in all the cases. These ultra-small Rh NPs have been utilized for two distinct potential applications such as in catalysis and SERS studies. From the catalysis reaction, reduction of 4-Nitro benzaldehyde to 4-amino benzaldehyde, Rh@DNA (0.08 M) has shown rate constant value of 0.26 min -1 which is highest among other concentrations studied. SERS study revealed that the calculated Enhancement Factor (EF) value was 1.19 × 10 5 for Rh@DNA (0.08 M) which is highest while compared with other concentrations. Apart from catalysis and SERS, the as-synthesized Rh NPs can find applications in other interdisciplinary fields such as organic catalysis, electro-catalysis and so on in near future., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This paper investigates the impulsive stabilization problem of fractional differential systems (FDSs in short). Both the global exponential stability and ultimate boundedness criteria are established using Lyapunov functions, algebraic inequality techniques and boundedness of Mittag-Leffler functions. It is shown that unstable and unbounded FDSs can be stable and bounded respectively under impulsive control. Examples and simulations are also provided to demonstrate the effectiveness of the derived theoretical results., (Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the reproducibility of three-dimensional (3D) ultrasound (US) over two-dimensional (2D) US in characterizing atherosclerotic carotid plaques using inter- and intra-observer agreement metrics., Methods: A Total of 51 patients with 105 carotid artery plaques were screened using 3D and 2D US probes attached to the same US scanner. Two independent observers characterized the plaques based on the morphological features namely echotexture, echogenicity and surface characteristics. The scores assigned to each morphological feature were used to determine intra- and inter-observer performance. The level of agreement was measured using Kappa coefficient., Results: The first observer with 2D US showed fair (k=0.4-0.59) and very strong (k>0.8) with 3D US intra-observer agreements using three morphological features. The second observer indicated moderate strong (k=0.6-0.79) with 2D US and very strong with 3D US (k>0.8) intra-observer performances. Moderate strong (k=0.6-0.79) and very strong (k>0.8) inter-observer agreements were reported with 2D US and 3D US respectively. The results with 2D and 3D US were correlated 62% using only echotexture and 56% using surface morphology coupled with echogenicity. 3D US gave a lower score than 2D 71% of the time (p=0.005) in disagreement cases., Conclusion: High reproducibility in carotid plaque characterization was obtained using 3D US rather than 2D US. Hence, it can be a preferred imaging modality in routine or follow up plaque screening of patients with carotid artery disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Idiopathic pulmonary fibrosis is a fatal lung disease with a median survival of 2 to 5 years. A decade of studies has downplayed inflammation contributing to its pathogenesis. However, these studies preceded the discovery of regulatory T cells (Tregs) and all of their functions. On the basis of human studies demonstrating Tregs can decrease graft-versus-host disease and vasculitides, there is consideration of their use to treat idiopathic pulmonary fibrosis. We hypothesized that Treg therapy would attenuate the fibroplasia involved in a preclinical murine model of pulmonary fibrosis. IL-2 complex was used in vivo to expand CD4(+)CD25(hi)Foxp3(+) cells in the lung during intratracheal bleomycin challenge; however, this unexpectedly led to an increase in lung fibrosis. More important, this increase in fibrosis was a lymphocyte-dependent process. We corroborated these results using a CD4(+)CD25(hi)Foxp3(+) cellular-based therapy. Mechanistically, we demonstrated that CD4(+)CD25(hi)Foxp3(+) cells undergo alterations during bleomycin challenge and the IL-2 complex had no effect on profibrotic (eg, transforming growth factor-β) or type 17 immune response cytokines; however, there was a marked down-regulation of the type 1 and augmentation of the type 2 immune response cytokines from the lungs. Collectively, our animal studies show that a specific lung injury can induce Treg alterations, which can augment pulmonary fibrosis., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: The diagnosis of antibody-mediated rejection (AMR) in the lung transplant is still an area under investigation. We performed a blinded multicenter study to determine if any statistically significant histologic findings in transbronchial biopsy specimens from lung transplant patients correlate with the presence of donor-specific antibodies (DSAs)., Methods: We asked 9 pathologists with experience in lung transplantation to evaluate 161 lung transplant biopsy specimens for various histologic parameters. The findings were correlated with antibody status positive for DSAs, positive for non-DSAs, and no antibodies (NABs) present. The significance of each histologic variable was reviewed., Results: We found no statistically significant association with acute cellular rejection, airway inflammation, or bronchiolitis obliterans and the presence or absence of antibodies. However, biopsy specimens with DSAs had a statistically significant difference vs NABs in the setting of acute lung injury, with or without diffuse alveolar damage (p = 0.0008), in the presence of capillary neutrophilic inflammation (p = 0.0014), and in samples with endotheliitis (p = 0.0155). In samples with complement 4d staining, there was a trend but no statistically significant difference between specimens associated with DSAs and specimens with NABs., Conclusions: Capillary inflammation, acute lung injury, and endotheliitis significantly correlated with DSAs. The infrequently observed diffuse staining for complement 4d limits the usefulness of this stain., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to model the growth kinetics of Listeria monocytogenes on ready-to-eat ham and sausage at different temperatures (4 to 35°C). The observed data fitted well with four primary models (Baranyi, modified Gompertz, logistic, and Huang) with high coefficients of determination (R(2) > 0.98) at all measured temperatures. After the mean square error (0.009 to 0.051), bias factors (0.99 to1.06), and accuracy factors (1.01 to 1.09) were obtained in all models, the square root and the natural logarithm model were employed to describe the relation between temperature and specific growth rate (SGR) and lag time (LT) derived from the primary models. These models were validated against the independent data observed from additional experiments using the acceptable prediction zone method and the proportion of the standard error of prediction. All secondary models based on each of the four primary models were acceptable to describe the growth of the pathogen in the two samples. The validation results indicate that the optimal primary model for estimating the SGR was the Baranyi model, and the optimal primary model for estimating LT was the logistic model in ready-to-eat (RTE) ham. The Baranyi model was also the optimal model to estimate the SGR and LT in RTE sausage. These results could be used to standardize predictive models, which are commonly used to identify critical control points in hazard analysis and critical control point systems or for the quantitative microbial risk assessment to improve the food safety of RTE meat products.

This study was conducted to develop a predictive model to estimate the growth of Listeria monocytogenes on fresh pork during storage at constant temperatures (5, 10, 15, 20, 25, 30, and 35°C). The Baranyi model was fitted to growth data (log CFU per gram) to calculate the specific growth rate (SGR) and lag time (LT) with a high coefficient of determination (R(2) > 0.98). As expected, SGR increased with a decline in LT with rising temperatures in all samples. Secondary models were then developed to describe the variation of SGR and LT as a function of temperature. Subsequently, the developed models were validated with additional independent growth data collected at 7, 17, 27, and 37°C and from published reports using proportion of relative errors and proportion of standard error of prediction. The proportion of relative errors of the SGR and LT models developed herein were 0.79 and 0.18, respectively. In addition, the standard error of prediction values of the SGR and LT of L. monocytogenes ranged from 25.7 to 33.1% and from 44.92 to 58.44%, respectively. These results suggest that the model developed in this study was capable of predicting the growth of L. monocytogenes under various isothermal conditions.

Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n=38), early gastric cancer (EGC) (n=38), and advanced gastric cancer (AGC) (n=38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways., (Copyright © 2014 Elsevier Inc. All rights reserved.)

MicroRNAs (miRNAs) are 19∼22 nucleotide-long, noncoding, small RNAs, involved in post-transcriptional regulation of many target genes. The miRNA-200 family has been shown to play a crucial role in the epithelial to mesenchymal transition in human cancers. In situ hybridization (ISH) was used to investigate the expression level of miRNA-200a in breast cancers. Formalin-fixed, paraffin embedded (FFPE) tissues from normal breast, ductal carcinoma in situ (DCIS), primary cancers, and metastatic lymph nodes were achieved and constructed to tissue microarrays. MiRNA-200a expression was demonstrated in 95.2% of normal breast tissue samples and 80.4% of DCIS, whereas 178 (58.0%) of 307 breast cancers and 83.3% of metastatic lymph node samples lacked miRNA-200a expression (P < 0.001). Moreover, loss of MiRNA-200a expression correlated with high histologic grade (P = 0.017) and perinodal tumor extension (P = 0.026). However, miRNA-200a expression did not predict tumor recurrence or patient survival. In conclusion, loss of miRNA-200a is frequently observed in breast cancers, especially tumors with high grade histology. These findings suggest that miRNA-200a may play an important role in breast cancer initiation and progression. ISH can be used to detect miRNAs in FFPE sections, and should permit the validation of miRNAs as biomarkers in large clinical samples., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Hepatitis C viral infection is a major cause of progressive liver disease. HCV genotype is one of the most significant baseline predictors of response to HCV antiviral therapy. The objective was to evaluate an HCV genotyping method that targets the 5'-untranslated region (UTR) to detect genotypes/subtypes using the GenMark eSensor® XT-8 system. The HCV amplicon of major genotypes/subtypes from the Roche TaqMan® HCV assay served as a template for the nested PCR followed by a direct analysis on the XT-8 detection system. The assay was validated for limit of detection (LOD), specificity, accuracy and precision. The LOD determined was below 175 IU/ml for all the subtypes except 6ab. The genotypes detected using this assay were in concordance with the LiPA assay. The high performance characteristics (LOD, specificity, intra- and inter-assay precision, and accuracy), make this assay particularly well suited for clinical HCV genotyping in order to guide antiviral therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Osteochondroma is a cartilage-capped osseous protrusion that arises from the surface of a bone. Osteochondroma occurs mostly in the metaphysis of long tubular bones such as the femur, tibia, and humerus. Osteochondroma is rare in the diaphysis and in the epiphysis. There was only one case in which a patient had a limited range of motion in the shoulder joint due to an intraarticular osteochondroma of the proximal humerus. We present a rare case of intraarticular osteochondroma involving the proximal humerus with pathologic findings and imaging features on computed tomography and magnetic resonance imaging., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: We evaluated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis of lipids may distinguish intrahepatic cholangiocarcinomas from adjacent normal tissue and from other adenocarcinomas that frequently metastasize to liver., Methods: Four pairs of frozen surgical specimens of cholangiocarcinomas and adjacent normal tissue were analyzed using histology-directed, MALDI MS analysis. 2,5-dihydroxybenzoic acid / α-cyano-4-hydroxycinnamic acid were manually deposited on tumor-rich areas, and mass spectra were acquired using a MALDI-time of flight instrument., Results: Cholangiocarcinomas and adjacent normal tissue samples demonstrated different lipid profiles, as evidenced by permutation P value<0.05 for the cross-validated misclassification rate. Cancer-associated lipid alteration was similar between cholangiocarcinomas and pancreatic cancers, but not between cholangiocarcinomas and colorectal cancers. Baseline lipid profiles were different between cholangiocarcinoma and colorectal cancers., Conclusions: MALDI MS analysis of lipid distinguishes cancerous epithelium of cholangiocarcinoma from adjacent normal tissue, and between cholangiocarcinomas and colorectal cancers., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The activating transcription factor 3 (ATF3) is expressed by various types of cellular insults. It has been suggested to serve diverse functions in both cellular survival and death signal cascades, but the exact role of ATF3 in brain ischemia is little known so far. Thus, the authors examined the expression pattern of ATF3 following middle cerebral artery occlusion (MCAO) and reperfusion injury. At 1-2 days after MCAO and reperfusion injury, numerous number of ATF3-immunoreacitive (-ir) nuclei was observed in the ipsilateral peri-infarct cortex, but declined rapidly at 3 days. Almost all ATF3-ir nuclei were co-localized with NeuN-ir neurons. Neither GFAP- nor OX42-ir neuroglia were co-localized with ATF3. Double labeling of Fluoro-Jade B with ATF3 showed that ATF3-ir nuclei mismatched with Fluoro-Jade B-ir neurons. To further examine the role of ATF3 in ischemic peri-infarct regions, double immunofluorescent labeling of ATF3/caspase 3, ATF3/Bcl-xl, and ATF3/HSP27 was conducted. Semiquantitive estimation showed that about 15% of ATF3-ir neurons also expressed caspase 3. However, about only 0.4% and 2.6% of ATF3-ir neurons were double-stained with Bcl-xl and Hsp27, respectively. Consequently, it would be suggested that ATF3 seem to play an important role in caspase-dependent neuronal apoptotic signal transduction pathways caused by focal cerebral ischemia and reperfusion injury., (Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Background: The combined genetic effects of single nucleotide polymorphisms may additively or synergistically contribute to the increased cancer risk. The interactions associated with xenobiotic metabolizing enzymes and transporter protein involved in the biotransformation and transport of xenobiotics could determine the functional outcomes over the independent effects of a single susceptibility gene in the risk of upper aerodigestive tract cancers., Methods: The hospital-based case-control study evaluated CYP1A1 (*2A and *2C), CYP2E1 (*1B, *5B, and *6), GST (M1, T1, and P1) and ABCB1 3435C>T polymorphisms among 408 histopathologically confirmed cases and 220 controls using polymerase chain reaction based methods in an Indian population., Results: The multivariate logistic regression analyses demonstrated potentially high risk gene-gene interactions with the concurrent deletions of the GSTT1 and GSTM1 genes and GSTP1 variant genotypes (OR 5.81; 95% CI 1.01-40.28), the deletions of GSTT1 and GSTM1 genotypes with variant genotypes of CYP1A1*2A (OR 8.21; 95% CI 1.91-49.48), GSTT1 and GSTM1 deficient genotypes along with CYP2E1*1B variant genotypes (OR 6.73; 95% CI 1.32-22.81), the polymorphic genotypes of ABCB1 and deficient GSTT1 (OR 6.08; 95% CI 2.21-16.76) and an enhanced risk with the combined variant genotypes of CYP1A1*2A, GSTT1 and ABCB1 (OR 11.14; 95% CI 2.70-46.02)., Conclusion: The findings indicate that the interactions associated with various drug metabolizing enzymes and transporter protein exhibit high risk for UADT cancers than that ascribed to a single susceptible gene. This was particularly established among the polymorphic carriers of CYP1A1*2A, GSTT1 and ABCB1 genes in the population investigated., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: The single-nucleotide polymorphism (SNP) 3435C > T in exon 26 of the MDR1 gene has been shown to correlate with the functioning of P-glycoprotein. We studied the frequency of SNP in exon 26 of the MDR1 gene in breast cancer and its role in predicting response to neoadjuvant chemotherapy in breast cancer., Patients and Methods: Ninety-six patients with locally advanced breast carcinoma were enrolled. Genotyping of exon 26 of the MDR1 gene was performed, and computed tomography scans were performed before and after neoadjuvant chemotherapy. Response to 3 cycles of the 5-fluorouracil/doxorubicin/ cyclophosphamide (FAC) regimen was assessed. The prevalence of SNP was compared with that of historical controls. Association of the response was compared with the genotypes., Results: The frequency of genotypes was different from that of healthy sex-matched historical controls. Prevalence of TT genotype was significantly increased in breast cancer patients (P = .025). The patients with TT genotype had 2.26 times the chance of responding to neoadjuvant chemotherapy when compared with patients with the CC genotype (P = .44)., Conclusion: Significantly higher prevalence of 3435TT genotype in exon 26 of the MDR1 gene in patients with breast cancer might suggest the possibility of increased breast cancer susceptibility. The genotypes did not show any significant association to response to chemotherapy in the population studied.

Parosteal lipoma is a rare benign tumor that is composed mainly of benign mature lipocytes, and it has an intimate association with the underlying periosteum of affected bone. Parosteal lipoma involving the rib is quite rare. We believe that only four cases have been previously reported in the English literature. Here we describe an exceedingly rare case of parosteal lipoma that developed in the right seventh rib, which presented in a 50-year-old man having a previous history of trauma at this site.

Due to its ability to emit light, the luciferase from Renilla reniformis (RLuc) is widely employed in molecular biology as a reporter gene in cell culture experiments and small animal imaging. To accomplish this bioluminescence, the 37-kDa enzyme catalyzes the degradation of its substrate coelenterazine in the presence of molecular oxygen, resulting in the product coelenteramide, carbon dioxide, and the desired photon of light. We successfully crystallized a stabilized variant of this important protein (RLuc8) and herein present the first structures for any coelenterazine-using luciferase. These structures are based on high-resolution data measured to 1.4 A and demonstrate a classic alpha/beta-hydrolase fold. We also present data of a coelenteramide-bound luciferase and reason that this structure represents a secondary conformational form following shift of the product out of the primary active site. During the course of this work, the structure of the luciferase's accessory green fluorescent protein (RrGFP) was also determined and shown to be highly similar to that of Aequorea victoria GFP.

This study explored the feasibility of applying the electrokinetic-Fenton process (EK-Fenton process) for the remediation of contaminant sorbed onto soil possessing low-permeability. The relationship of H2O2 stability and phenanthrene treatment, and the variation in the monitoring values were also investigated during the EK-Fenton process when catalyzed by heterogeneous minerals. Phenanthrene was chosen to represent hydrophobic organic contaminants (HOCs), which are widespread in the environment, and kaolinite was used as the low-permeability soil. In these experiments, the H2O2 concentrations in pore water, the electrical potential distributions and the electrical currents were measured or monitored to assess the electrochemical effect in relation to injections of H2O2 from the anode. The results suggested that intermediate anions (HO2-, O2-) with Fenton-like reaction affected significantly the variations in the electrical current during the EK-Fenton process. The addition of 0.01 N H2SO4 to the anode reservoir improved the H2O2 stability and the treatment of phenanthrene in the entire soil specimen. Therefore, use of H2O2 and dilute acid, as an anode purging solution is a possible method for treating HOCs in low-permeability subsurface environments.

Calcifying fibrous pseudotumor is an uncommon benign lesion that has unique histologic features. We report a case of calcifying fibrous pseudotumor of the pleura occurring in a 31-year-old woman. A computed tomographic scan revealed a pleural mass in the right anterior costophrenic angle. The excised mass was well circumscribed, nonencapsulated, solid, and firm. The tumor showed dense hyalinized collagenous tissue interspersed with spindle cells, psammomatous calcifications, and a predominantly lymphoplasmocytic infiltrate. Most spindle cells were diffusely positive for vimentin, focally positive for CD34, and negative for desmins, smooth muscle actin, S-100 protein, and anaplastic lymphoma kinase-1.

[18F]fluorodeoxyglucose positron emission tomography (FDG-PET) is a metabolic imaging modality that has increasing applications in oncology, neurology, and cardiology. Among the oncology applications, breast cancer is one of the most extensively studied diseases. FDG-PET has been performed for diagnosis, staging, and restaging of invasive breast cancer and for monitoring responsiveness to therapies. At the present time, the results of FDG-PET in detection of primary breast cancer and axillary staging are mixed and inconclusive. However, results demonstrating the superiority of FDG-PET over anatomic imaging modalities in detection of distant metastasis, recurrence, and monitoring therapies are relatively well documented. These applications have been accepted by medical professionals and the public, as evidenced by a recent decision by the Centers for Medicare and Medicaid Services (formerly Health Care Financing Agency) to provide coverage for the procedure. Future trends in this exciting area include development of novel breast cancer-specific PET radiopharmaceuticals and use of dedicated breast PET technologies for scans of breast/axillary lesions. PET/computed tomography technology, which combines anatomic and molecular/biochemical information, is also rapidly proliferating and should help to further improve the management of patients with breast cancer. The role of FDG-PET in breast cancer is increasing and evolving, and this metabolic imaging modality, in conjunction with newer tracers and other anatomic imaging methods, should improve diagnosis and management of patients with breast cancer

This study was undertaken to investigate the capacity of polymorphonuclear neutrophils (PMNs) to secrete Macrophage Inflammatory Protein (MIP)-1alpha and MIP-1beta after stimulation with Porphyromonas endodontalis lipopolysaccharide (LPS). Escherichia coli LPS was used as a positive control. Venous blood was collected and PMNs were isolated from healthy volunteers. Cells were cultured with various concentrations of LPS for different periods of time. Cell supernatants were assayed by enzyme-linked immunosorbent assay. The levels of chemokine secretion in PMNs stimulated with each LPS were found to be significantly higher than in the unstimulated control cells (p < 0.05), and this expression occurred in a time- and dose-dependent manner. E. coli LPS induced higher levels of cytokines than P. endodontalis LPS. These findings demonstrated that P. endodontalis LPS is capable of stimulating PMNs to produce chemotactic cytokines and suggested that PMNs stimulated with P. endodontalis LPS may play a crucial role in the inflammatory and immunopathological reactions of pulpal and periapical diseases.

The purpose of this study was to evaluate the tissue levels of matrix metalloproteinase (MMP)-1, -2, -3 and their distributions in inflamed human dental pulps and periapical lesions. Samples were subjected to enzyme-linked immunosorbent assay and/or immunohistochemistry by using specific antibodies to MMP-1, -2, and -3. Results from enzyme-linked immunosorbent assay were analyzed by using the Mann-Whitney U test and presented as p values. The concentrations of MMP-1 in all experimental groups were significantly higher than in the control (p < 0.05). The acute pulpitis and control groups were significant different in terms of their MMP-2 levels (p < 0.05). The concentration of MMP-3 in acute pulpitis was significantly higher than the control and chronic pulpitis groups (p < 0.05). Immunohistochemically, MMP-1 and MMP-3 were localized in the infiltrating neutrophils, macrophages, and extracellular matrix of the acute pulpitis group. These results suggest that MMPs play an important role in the pulp tissue destruction of acute, inflamed pulp.

The objective of this study was to investigate the expression of surface markers on T lymphocytes and the Th1/Th2 immune response in pulpal inflammation associated with specific bacteria. Pulpal inflammation was experimentally induced in rat mandibular incisors by drilling, without coolant, to open pulp chambers. Streptococcus mutans (S. mutans group), Porphyromonas endodontalis (P. endodontalis group), and a sterile cotton pellet only (control group) were inoculated in the canal. The expression of CD25 and CD54 on CD4+, and CD8+ lymphocytes in pulp tissues was determined by using a flow cytometer. The levels of interleukin (IL)-2, interferon (IFN)-gamma, and IL-4 were measured by ELISA. Flow-cytometric analysis showed that the mean ratio of CD4+:CD8+ was 0.96 in the control group, 0.99 in the S. mutans group, and 0.52 in the P. endodontalis group. An increase in CD25 and CD54 expression on CD4+ T lymphocytes was related to the bacterial infection (p < 0.05) and accompanied an increase in IL-2 concentration. The higher concentration of IFN-gamma than IL-4 in the P. endodontalis group suggested a Th1 reaction in the early stage of pulpal inflammation induced by P. endodontalis.