ABSTRACT
PURPOSE: This study aimed to evaluate the substitutive and additive efficacy of multi-peak light-emitting diode (LED) curing units for post-curing of a three-dimensional- (3D-) printed crown and bridge resin. METHODS: A total of 792 disc- and 180 bar-shaped specimens were printed with a crown and bridge resin (NextDent C&B MFH) and post-cured using two LED curing units (VALO Cordless and Bluephase N G4) in fast and standard modes. Conventional post-curing (LC-3D Print Box, Group PC) was compared with LED-only curing (Groups V1, V2, B1, and B2) and LED-combined curing (Groups PV1, PV2, PB1, and PB2) in terms of microhardness, flexural strength, degree of conversion (DC), and CIE L*a*b* color and translucency parameters. Cytotoxicity of the resin eluates was evaluated using the WST-1 assay. Temperature increases on the resin surface were measured with infrared thermography. Data were statistically analyzed using ANOVA and Kruskal-Wallis tests (α=0.05). RESULTS: The microhardness and flexural strength in Groups V1, V2, B1, and DC in all LED-only groups were lower than in other groups (p<0.05). Larger color disparities existed between Group PC and all LED-only groups than between Group PC and the others (p<0.05). There was no significant difference in cytotoxicity among the groups. The temperature increase was lowest in Groups V1 and PV1 during light curing (p<0.05). CONCLUSIONS: Post-curing by multi-peak LED curing units was not as effective as the conventional post-curing device. Additional post-curing by LED curing units did not improve the material properties.
Subject(s)
Crowns , Curing Lights, Dental , Polymerization , Printing, Three-Dimensional , Materials Testing , Composite Resins/therapeutic use , Surface Properties , HardnessABSTRACT
OBJECTIVES: This study aimed to establish an occupational disease surveillance system by identifying high-risk industries for silicosis in Taiwan using a national database linkage approach. METHODS: The study was based on a comprehensive analysis of benefit claims from the National Labor Insurance Research Database and medical records from the National Health Insurance Research Database between 2004 and 2020, providing coverage for more than 88.5% of the workforce and 99.9% of citizens. Silicosis was defined as having received compensation for labor insurance benefits or having received a diagnosis of silicosis (International Classification of Diseases, 10th Revision: J62 or International Classification of Diseases, Ninth Revision: 502). The study used the International Standard Industrial Classification of All Economic Activities for industry-specific classification. Cox proportional hazard models were used to compare the silicosis incidence and risk among each industry and identify high-risk industries for silicosis. RESULTS: This study analyzed 1466 cases of silicosis between 2004 and 2020 and found that 28 industries had incidence rates of over 40 cases per 100,000 workers, indicating more than double the risk of developing silicosis. Of these industries, 14 were considered high risk (relative risk of over four times). Among these, this study identified industries rarely mentioned in the past, such as wholesale of brick, sand, cement, and products, artistic creation, landscape construction, and materials recovery. Stratification by years of work experience reveals those industries such as quarrying of stone, sand, clay, and other mining, construction of buildings, landscape construction, site preparation, foundation and structure construction, building completion and finishing, manufacture of ships, boats, and floating structures, and plumbing, heat, and air conditioning installation display higher hazard ratios for individuals with <10 years of work experience. CONCLUSIONS: The current surveillance system has identified certain industries that are at a higher risk of developing silicosis, which could be used for future occupational epidemiological surveys and targeted preventive measures in these sectors.
Subject(s)
Occupational Diseases , Occupational Exposure , Silicosis , Humans , Incidence , Sand , Taiwan/epidemiology , Silicosis/epidemiology , Silicosis/diagnosis , Silicosis/prevention & control , Occupational Diseases/epidemiology , Occupational Exposure/adverse effectsABSTRACT
A mixed-valence compound Pb2Cu10O4(SeO3)4Cl7 has a complex structure consisting of one nonmagnetic Cu+ (S = 0) ion and four nonequivalent magnetic Cu2+ (S = 1/2) ions. It exhibits antiferromagnetic ordering at TN = 10.2 K. At a temperature below TN, a sequence of spin-flop transition at Bspin-flop = 1.3 T and 1/3 plateau formation at Bspin-flip = 4.4 K is observed in the magnetization curve M(B). The 1/3 magnetization plateau persists at least up to 53.5 T. The spin exchanges of Pb2Cu10O4(SeO3)4Cl7 evaluated by performing energy-mapping analysis based on DFT+U calculations show that the magnetic properties of Pb2Cu10O4(SeO3)4Cl7 are described by the (Cu2+)7 cluster of corner-sharing (Cu2+)4 tetrahedra, and that each (Cu2+)7 cluster has a S = 3/2 spin arrangement in the ground state. The 1/3 magnetization plateau observed for Pb2Cu10O4(SeO3)4Cl7 is explained by the field-induced flip of every second (Cu2+)7 cluster within a unit cell.
ABSTRACT
METHODS AND MATERIALS: Mesio-occlusal-distal cavities were prepared on 12 extracted mandibular molars. The gingival margin of one proximal box was elevated with resin modified glass ionomer (RMGI) by a height of 2 mm (Group E [elevation]), and the margin of the other side served as a control (Group NE [no elevation]). Lithium disilicate computer-aided design and computer-aided manufacturing (CAD/CAM) inlays were fabricated and bonded with a self-adhesive resin cement. An aging process was simulated on the specimens under thermomechanical cycling by using a chewing simulator. Marginal integration was evaluated under scanning electron miscroscopy (SEM) using epoxy resin replicas before and after cycling. Marginal areas were stained with silver nitrate solution, and the volumetric gap was measured at the bonded interfaces using micro-computed tomography (CT) before and after cycling. Statistical analyses were performed using paired t-tests, the Wilcoxon signed rank test, and the Mann-Whitney test (a<0.05). RESULTS: SEM showed marginal discontinuities in Group NE that increased after thermomechanical cycling. Micro-computed tomography exhibited three-dimensional dye-penetrating patterns at the interfaces before and after cycling. Interfacial disintegration was larger in Group NE before cycling (p<0.05). Thermomechanical cycling increased the gaps in both Groups NE and E (p<0.05). The gap increment from thermomechanical cycling was larger in Group NE (p<0.05). CONCLUSIONS: Thermomechanical cycling induced interfacial disintegration at the lithium disilicate CAD/CAM inlays, with deep proximal margins. Margin elevation with RMGI placement reduced the extent of the interfacial gap formation before and after the aging simulation.
Subject(s)
Ceramics , Inlays , Computer-Aided Design , Dental Marginal Adaptation , Dental Porcelain , Materials Testing , Molar , X-Ray MicrotomographyABSTRACT
The outbreak of the COVID-19 pandemic has drastically disrupted the air cargo industry. This disruption has taken many directions, one of which is the demand imbalance which occurs due to the sudden change in the cargo capacity, as well as demand. Therefore, the random change leads to excessive demand in some routes (hot-selling routes), while some other routes suffer from a big shortage of demand (underutilized routes). Routes are substitutable when there are several adjacent airports in the Origin & Destination (O&D) market. In this market, demand imbalance between substitutable routes occurs because of the above reasons. To tackle the demand imbalance problem, a novel model is introduced to estimate the quantity combinations which maintains the balance between underutilized and hot-selling routes. This model is a variant of the classic Cournot model which captures different quantity scenarios in the form of the best response for each route compared to the other. We then cultivate the model by integrating the Puppet Cournot game with the quantity discount policy. The quantity discount policy is an incentive which motivates the freight forwarders to increase their orders in the underutilized routes. After conducting numerical experiments, the results reveal that the profit can increase up to 25% by using the quantity discount. However, the quantity discount model is only applicable when the profit increase in the hot-selling route is greater than the profit decrease in the underutilized route.
ABSTRACT
Laser microsurgery is a powerful tool for neurobiology, used to ablate cells and sever neurites in-vivo. We compare a relatively new laser source to two well-established designs. Rare-earth-doped mode-locked fibre lasers that produce high power pulses recently gained popularity for industrial uses. Such systems are manufactured to high standards of robustness and low maintenance requirements typical of solid-state lasers. We demonstrate that an Ytterbium-doped fibre femtosecond laser is comparable in precision to a Ti:Sapphire femtosecond laser (1-2 micrometres), but with added operational reliability. Due to the lower pulse energy required to ablate, it is more precise than a solid-state nanosecond laser. Due to reduced scattering of near infrared light, it can lesion deeper (more than 100 micrometres) in tissue. These advantages are not specific to the model system ablated for our demonstration, namely neurites in the nematode C. elegans, but are applicable to other systems and transparent tissue where a precise micron-resolution dissection is required.
Subject(s)
Fiber Optic Technology/instrumentation , Lasers, Solid-State , Microsurgery/methods , Neurons/chemistry , Neurosurgical Procedures/instrumentation , Neurosurgical Procedures/methods , Ytterbium/chemistry , Aluminum Oxide/chemistry , Animals , Caenorhabditis elegans , Titanium/chemistryABSTRACT
Reference intervals (RIs) are one of the essential elements in the procedure of disease diagnosis. This is especially true for feline species in which RI is less available than in canine species. RIs are affected by biological, geographical and instrumental factors, yet published RIs with incomplete background are popularly used. Inappropriate interpretations of RIs may affect classification of disease and subsequent treatment. In this study, we demonstrated the step-by-step establishment of feline RIs following the American Society for Veterinary Clinical Pathology (ASVCP) reference interval guideline. A total of 51 parameters were examined, including 20 hematology and 31 biochemistry parameters, and the results were compared to one local RI and two foreign RIs. Overall, about 29% (10/35) of tested parameters were different form local RIs and 60% (30/50) were different from the two foreign RIs, highlighting geographical variations. A higher upper reference limit (URL) in red blood cell count (RBC), hematocrit (Hct), Hemoglobin (Hgb), albumin, creatinine and lower URL in potassium and white blood cell count (WBC) were identified, which may impact the interpretation. In addition, statistical analysis of age and gender were factored separately and indicated that 10 parameters were significantly higher in the adult group. For the impact of gender, percentage of basophil and total iron-binding capacity (TIBC) were lower in female and male cats, respectively. In conclusion, we have demonstrated that it is desirable to establish in-house RIs or RIs of local sources. An age specific RI for the geriatric feline population is advisable for better diagnosis and monitoring the disease.
Subject(s)
Aging , Cats/blood , Hematologic Tests/veterinary , Animals , Calcium/blood , Cholesterol/blood , Erythrocyte Count/veterinary , Female , Hematocrit/veterinary , Hemoglobins , Leukocyte Count/veterinary , Male , Reference Values , Serum AlbuminABSTRACT
PURPOSE: To compare between deep neuromuscular blockade (NMB) and moderate NMB with respect to endoscopic surgical conditions and recovery profiles in patients with general anesthesia for transurethral resection of bladder (TURB). METHODS: 108 patients undergoing elective TURB were randomized into two groups: the moderate NMB (n = 54) or deep NMB (n = 54) group. After the operation, NMB was reversed with 2 mg/kg sugammadex at a train-of-four (TOF) count of 1 or 2 (moderate NMB group) or with 4 mg/kg sugammadex at post-tetanic count (PTC) of 2 (deep NMB group). Surgeons, who were blinded to the study design, rated the endoscopic surgical condition on a 5-point scale (1 = extremely poor, 2 = poor, 3 = acceptable, 4 = good, 5 = optimal) immediately following the operation. Recovery profiles, including postoperative residual curarization (PORC), respiratory complication, and recovery time, were recorded. RESULTS: No difference was observed between the two groups regarding patients and anesthesia characteristics. There were statistically significant differences in endoscopic surgical conditions between the two groups (P < 0.001). Thirty-eight patients in the deep NMB group (74%) showed optimal surgical conditions, whereas 16 patients in the moderate NMB group (30%) showed optimal endoscopic surgical conditions. No PORC and respiratory complications occurred in both groups, and no difference was found between the two groups in terms of recovery profiles, including recovery time and other adverse events. CONCLUSIONS: Deep NMB and reversal with sugammadex improved the endoscopic surgical condition without complications compared with moderate NMB and reversal with sugammadex in patients undergoing TURB.
Subject(s)
Cystectomy/methods , Neuromuscular Blockade/methods , Urinary Bladder Neoplasms/surgery , Aged , Aged, 80 and over , Anesthesia, General , Cystoscopy , Double-Blind Method , Elective Surgical Procedures , Humans , Male , Middle Aged , Prospective Studies , Recovery of FunctionABSTRACT
OBJECTIVE: The aim was to investigate prevalence and degree of ocular and oral involvement in patients with primary Sjögren's syndrome (PSS). METHOD: We analysed 134 participants from the Korean Initiative of PSS cohort who completed a 2 year follow-up oral and ocular sign test. The severity of keratoconjunctivitis sicca (KCS) was determined with the Schirmer I test value (STV) [abnormal (AB) ≤ 5 mm/5 min; normal (N) > 5 mm/5 min]. Salivary gland dysfunction (SGD) was determined by unstimulated whole salivary (UWS) flow rate [moderate to severe (MS) < 0.1 mL/min; mild (Mi) ≥ 0.1 mL/min]. Subgroups were divided into three groups according to STV and severity of SGD: AB-STV/MS-SGD, AB-STV/Mi-SGD, and N-STV/MS-SGD groups. We analysed the changes in STV and SGD during the follow-up period. RESULTS: Among the 134 participants enrolled in this study, 105 (78%) were placed in the AB-STV/MS-SGD group, 16 (12%) in the AB-STV/Mi-SGD, and 13 (10%) in the N-STV/MS-SGD at the 2 year follow-up. The AB-STV/Mi-SGD group was younger than the other two groups, and had a lower Xerostomia Inventory score and lower level of ß2-microglobulin. Participants in the N-STV/MS-SGD group had less hyperimmunoglobulinaemia, rheumatoid factor (RF), and antinuclear antibodies (ANAs). Patients and those with positive RF or ANA ≥ 1:320 at baseline were more likely to have abnormal STV at the 2 year follow-up. CONCLUSIONS: Patients with PSS and positive RF or ANA ≥ 1:320 at baseline may benefit from regular ophthalmology examinations, even if they do not have KCS at baseline or dry eye symptoms.
Subject(s)
Keratoconjunctivitis Sicca , Sjogren's Syndrome/complications , Xerostomia , Adult , Age Factors , Antibodies, Antinuclear/blood , Cohort Studies , Female , Humans , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/etiology , Keratoconjunctivitis Sicca/immunology , Male , Middle Aged , Prevalence , Republic of Korea/epidemiology , Rheumatoid Factor/blood , Severity of Illness Index , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/epidemiology , Symptom Assessment , Xerostomia/diagnosis , Xerostomia/etiology , Xerostomia/immunologyABSTRACT
While immune checkpoint inhibitors (ICIs) are improving outcomes for many cancers, they can have severe adverse effects. Though cardiac immune-related adverse effects (irAEs) are rare, they have considerable morbidity and mortality. Prior case studies have demonstrated successful treatment of ICI induced autoimmune myocarditis with a variety of immunosuppressive regimens. This case describes steroid-refractory autoimmune myocarditis after treatment with pembrolizumab. Treatment with equine anti-thymocyte globulin, a regimen previously documented to reverse ICI induced autoimmune myocarditis, temporarily improved clinical status and cardiac biomarkers, however eventually failed to prevent progression to heart failure and cardiovascular death. This case highlights the importance of early stress-dose steroids, identifies troponin as a potential marker of treatment response, and underscores the value of collaboration between oncology and cardiology for optimal management.
ABSTRACT
High-risk human papillomavirus (HPV) is a major risk factor for oral and pharyngeal cancers (OPCs), yet the detailed mechanisms by which HPV promotes OPCs are not understood. Forkhead box M1B (FoxM1B) is an oncogene essential for cell cycle progression and tumorigenesis, and it is aberrantly overexpressed in many tumors. We previously showed that FoxM1B was the putative target of an epithelial-specific transcription factor, Grainyhead-like 2 (GRHL2). In the current study, we demonstrate that HPV type 16 (HPV-16) E6 induces FoxM1B in human oral keratinocytes (HOKs) and tonsillar epithelial cells (TECs) in part through GRHL2. FoxM1B was barely detectable in cultured normal human oral keratinocytes (NHOKs) and progressively increased in immortalized HOKs harboring HPV-16 genome (HOK-16B) and tumorigenic HOK-16B/BaP-T cells. Retroviral expression of HPV-16 E6 and/or E7 in NHOKs, TECs, and hypopharyngeal carcinoma cells (FaDu) revealed induction of FoxM1B and GRHL2 by the E6 protein but not E7. Both GRHL2 and FoxM1B were strongly induced in the epidermis of HPV-16 E6 transgenic mice and HPV+ oral squamous cell carcinomas. Ectopic expression of FoxM1B led to acquisition of transformed phenotype in HOK-16B cells. Loss of FoxM1B by lentiviral short hairpin RNA vector or chemical inhibitor led to elimination of tumorigenic characteristics of HOK-16B/BaP-T cells. Luciferase reporter assay revealed that GRHL2 directly bound and regulated the FoxM1B gene promoter activity. Using epithelial-specific Grhl2 conditional knockout mice, we exposed wild-type (WT) and Grhl2 KO mice to 4-nitroquinolin 1-oxide (4-NQO), which led to induction of FoxM1B in the tongue tissues and rampant oral tumor development in the WT mice. However, 4-NQO exposure failed to induce tongue tumors or induction of FoxM1B expression in Grhl2 KO mice. Collectively, these results indicate that HPV-16 induces FoxM1B in part through GRHL2 transcriptional activity and that elevated FoxM1B level is required for oropharyngeal cancer development.
Subject(s)
DNA-Binding Proteins/physiology , Epithelial Cells/metabolism , Forkhead Box Protein M1/metabolism , Keratinocytes/metabolism , Oncogene Proteins, Viral/physiology , Oropharyngeal Neoplasms/virology , Repressor Proteins/physiology , Transcription Factors/physiology , Animals , Blotting, Western , Carcinogenesis/metabolism , Cell Line, Tumor , Disease Models, Animal , Gene Knockout Techniques , Humans , Immunohistochemistry , Palatine Tonsil/cytology , Papillomavirus Infections/virology , Polymerase Chain Reaction , Tumor Cells, CulturedABSTRACT
We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n = 4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.
Subject(s)
Breast Neoplasms/blood supply , Breast Neoplasms/drug therapy , Neoadjuvant Therapy , Optical Imaging , Adult , Aged , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/metabolism , Female , Humans , Longitudinal Studies , Middle Aged , Oxygen/metabolism , Spectrum AnalysisABSTRACT
The anaphylatoxin C5a constitutes a powerful fragment generated by complement system activation. Interestingly, this complement active fragment is also an important mediator of tissue regeneration. Recent findings suggest that C5a could be an initial signal orchestrating pulp nerve sprouting beneath carious injury, a critical step in dentin-pulp regeneration. Indeed, the expression and activation of the C5a active receptor (C5aR/CD88) by injured pulp fibroblasts controls the direction of neurite outgrowth toward carious injuries by modulating the secretion of brain-derived neurotrophic factor (BDNF) by pulp fibroblasts. A second C5a receptor, C5L2, has also been cloned but has received much less attention because its interaction with the ligand induces no signaling. This work aims to investigate the role of C5L2 in pulp nerve regeneration in the secretion of BDNF by pulp fibroblasts under sites of carious injury. Using fluorescence immunostaining on human tooth sections in vivo and on primary human pulp fibroblasts in vitro, the authors reveal that C5L2 and C5aR are co-expressed by pulp fibroblasts under lipoteichoic acid (LTA) stimulation. Moreover, silencing C5L2 significantly increases BDNF secretion by LTA-stimulated pulp fibroblasts. Finally, an analysis of the subcellular distribution of C5aR and C5L2 indicates that the negative regulation of BDNF secretion by C5L2 correlates with C5aR activation and its subsequent intracellular co-localization with C5L2. Overall, the current study sheds light on the mechanism of pulp nerve regeneration by identifying C5L2 as a negative regulator of BDNF secretion by pulp fibroblasts under carious teeth. This knowledge significantly increases the understanding of the functional mechanism linking C5aR and C5L2 in pulp nerve regeneration, which may be useful in future dentin-pulp engineering strategies that target fibroblast C5L2 to induce pulp innervation.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Dental Pulp/cytology , Fibroblasts/physiology , Lipopolysaccharides/pharmacology , Receptors, Chemokine/physiology , Teichoic Acids/pharmacology , Cells, Cultured , Dental Caries/metabolism , Dental Caries/physiopathology , Dental Pulp/drug effects , Dental Pulp/innervation , Dental Pulp/metabolism , Fibroblasts/drug effects , Humans , In Vitro Techniques , Nerve Regeneration/drug effects , Nerve Regeneration/physiology , Receptor, Anaphylatoxin C5a/physiologyABSTRACT
PURPOSE: The authors introduce a state-of-the-art all-optical clinical diffuse optical tomography (DOT) imaging instrument which collects spatially dense, multispectral, frequency-domain breast data in the parallel-plate geometry. METHODS: The instrument utilizes a CCD-based heterodyne detection scheme that permits massively parallel detection of diffuse photon density wave amplitude and phase for a large number of source-detector pairs (10(6)). The stand-alone clinical DOT instrument thus offers high spatial resolution with reduced crosstalk between absorption and scattering. Other novel features include a fringe profilometry system for breast boundary segmentation, real-time data normalization, and a patient bed design which permits both axial and sagittal breast measurements. RESULTS: The authors validated the instrument using tissue simulating phantoms with two different chromophore-containing targets and one scattering target. The authors also demonstrated the instrument in a case study breast cancer patient; the reconstructed 3D image of endogenous chromophores and scattering gave tumor localization in agreement with MRI. CONCLUSIONS: Imaging with a novel parallel-plate DOT breast imager that employs highly parallel, high-resolution CCD detection in the frequency-domain was demonstrated.
Subject(s)
Breast Neoplasms/diagnostic imaging , Imaging, Three-Dimensional/methods , Mammography/methods , Tomography, Optical/methods , Aged , Equipment Design , Female , Humans , Mammography/instrumentation , Models, Anatomic , Phantoms, Imaging , Tomography, Optical/instrumentationABSTRACT
With the booming economy and increasing population, the accumulation of waste has become an increasingly arduous issue and has aroused the attention from all sectors of society. Hong Kong which has a relative high daily per capita domestic waste generation rate in Asia has not yet established a comprehensive waste management system. This paper conducts a review of waste management approaches and models. Researchers highlight that mathematical models provide useful information for decision-makers to select appropriate choices and save cost. It is suggested to consider municipal solid waste management in a holistic view and improve the utilization of waste management infrastructures. A mathematical model which adopts integer linear programming and mixed integer programming has been developed for Hong Kong municipal solid waste management. A sensitivity analysis was carried out to simulate different scenarios which provide decision-makers important information for establishing Hong Kong waste management system.
Subject(s)
Models, Theoretical , Refuse Disposal/methods , Hong Kong , Incineration , Linear Models , Solid WasteABSTRACT
Dentin-pulp regeneration is closely linked to the presence of nerve fibers in the pulp and to the healing mechanism by sprouting of the nerve fiber's terminal branches beneath the carious injury site. However, little is known about the initial mechanisms regulating this process in carious teeth. It has been recently demonstrated that the complement system activation, which is one of the first immune responses, contributes to tissue regeneration through the local production of anaphylatoxins such as C5a. While few pulp fibroblasts in intact teeth and in untreated fibroblast cultures express the C5a receptor (C5aR), here we show that all dental pulp fibroblasts, localized beneath the carious injury site, do express this receptor. This observation is consistent with our in vitro results, which showed expression of C5aR in lipoteichoic acid-stimulated pulp fibroblasts. The interaction of C5a, produced after complement synthesis and activation from pulp fibroblasts, with the C5aR of these cells mediated the local brain-derived neurotropic factor (BDNF) secretion. Overall, this activation guided the neuronal growth toward the lipoteichoic acid-stimulated fibroblasts. Thus, our findings highlight a new mechanism in one of the initial steps of the dentin-pulp regeneration process, linking pulp fibroblasts to the nerve sprouting through the complement system activation. This may provide a useful future therapeutic tool in targeting the fibroblasts in the dentin-pulp regeneration process.
Subject(s)
Complement Activation/physiology , Dental Pulp/physiology , Fibroblasts/physiology , Nerve Regeneration/physiology , Brain-Derived Neurotrophic Factor/physiology , Cells, Cultured , Dental Pulp/cytology , Dental Pulp/innervation , Dentin/physiology , Fluorescent Antibody Technique , Humans , Nerve Fibers/physiology , Receptor, Anaphylatoxin C5a/metabolismABSTRACT
The p38α mitogen-activated protein kinase (MAPK) is one of the serine/threonine kinases regulating a variety of biological processes, including cell-type specification, differentiation and migration. Previous in vitro studies using pharmacological inhibitors suggested that p38 MAPK is essential for oligodendrocyte (OL) differentiation and myelination. To investigate the specific roles of p38α MAPK in OL development and myelination in vivo, we generated p38α conditional knockout (CKO) mice under the PLP and nerve/glial antigen 2 (NG2) gene promoters, as these genes are specifically expressed in OL progenitor cells (OPCs). Our data revealed that myelin synthesis was completely inhibited in OLs differentiated from primary OPC cultures derived from the NG2 Cre-p38α CKO mouse brains. Although an in vivo myelination defect was not obvious after gross examination of these mice, electron microscopic analysis showed that the ultrastructure of myelin bundles was severely impaired. Moreover, the onset of myelination in the corpus callosum was delayed in the knockout mice compared with p38α fl/fl control mice. A delay in OL differentiation in the central nervous system was observed with concomitant downregulation in the expression of OPC- and OL-specific genes such as Olig1 and Zfp488 during early postnatal development. OPC proliferation was not affected during this time. These data indicate that p38α is a positive regulator of OL differentiation and myelination. Unexpectedly, we observed an opposite effect of p38α on remyelination in the cuprizone-induced demyelination model. The p38α CKO mice exhibited better remyelination capability compared with p38α fl/fl mice following demyelination. The opposing roles of p38α in myelination and remyelination could be due to a strong anti-inflammatory effect of p38α or a dual reciprocal regulatory action of p38α on myelin formation during development and on remyelination after demyelination.
Subject(s)
Central Nervous System/enzymology , Demyelinating Diseases/enzymology , Mitogen-Activated Protein Kinase 14/metabolism , Alleles , Animals , Cell Differentiation/physiology , Cells, Cultured , Central Nervous System/pathology , Demyelinating Diseases/genetics , Demyelinating Diseases/pathology , Mice , Mice, Knockout , Mice, Transgenic , Mitogen-Activated Protein Kinase 14/genetics , Neuroglia/enzymology , Neuroglia/pathologyABSTRACT
BACKGROUND: Recently, the pulsed radiofrequency (PRF, pulsed fashion) procedure was introduced for neuropathic pain management. Since PRF-induced lesions do not need high temperature compared with conventional continuous RF (CRF)-induced lesions, there is no significant loss of sensory fibres after application. METHODS: The progressive changes in the expression of eight representative inflammatory cytokines - glial fibrillary acidic protein, tumour necrosis factor alpha, interleukin-6, cyclooxygenase-II, inducible nitric oxide synthase, nuclear factor-κB, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α - as well as the morphological changes in extracellular matrices by Masson's trichrome and Verhoeff-van Gieson staining and atomic force microscopy were assessed for normal (control), sham (no RF current), PRF and CRF (positive control) rats. The RF procedure used in this study was similar to the methods used in human clinical trials. RESULTS: All proposed inflammatory proteins showed up-regulation after RF thermal treatments. Specifically, PRF-treated rats showed recovery of up-regulated inflammatory cytokines on day 30 after application, while CRF rats showed significant up-regulation that persisted until day 30. The control and sham groups showed normal unmyelinated axon and collagen structures. PRF-induced lesions showed less fibre destruction than CRF-induced lesions. PRF-induced lesions also showed mild axonal damage and little swelling of the mitochondria. CRF-induced lesions showed ultrastructural changes of sciatic nerve fibres that were irreversible. CONCLUSIONS: PRF-induced pain relief may be due to temporary blockage of nerve signals through the nerve pathway responsible for reversible neuronal depression. However, CRF-induced pain relief may be due to permanent blockage of nerve signals through other nerve pathways. Therefore, CRF could be applied to chronic inflammatory models used to study the mechanism of neuropathic pain.
Subject(s)
Cytokines/metabolism , Neuralgia/pathology , Neuralgia/therapy , Sciatic Nerve/pathology , Animals , Axons/pathology , Disease Models, Animal , Male , Neuralgia/metabolism , Radio Waves , Rats , Rats, Sprague-Dawley , Sciatic Nerve/metabolism , Up-RegulationABSTRACT
BACKGROUND: While common in cardiac surgery, median sternotomy (MS) is rarely required in general paediatric surgery. In the era of advancing endoscopic techniques, sternotomy is perceived as an extremely invasive incision, associated with prolonged postoperative recovery and significant morbidity. METHODS: We conducted a retrospective chart review of all children undergoing MS for non-cardiac indications between January 2007 and September 2012 and describe the pathology, number of ventilated days, duration of intensive care unit stay and analgesic requirements. RESULTS: Our experience over the past 6 years includes 14 children, aged between 8 months and 13 years. Indications for surgery included penetrating mediastinal trauma (1), anterior and posterior mediastinal masses (4), acquired tracheo-oesophageal fistulas secondary to button battery impaction (2), bronchial foreign bodies (2) and bilateral pulmonary metastases secondary to malignancy (5). The range of postoperative ventilation required was 0 - 34 days (median 1 day) and the range of duration of stay in the paediatric intensive care unit 1 - 39 days (median 4 days). Postoperative analgesia was provided with intravenous or oral paracetamol with or without the addition of morphine. All the children tolerated the procedure well with no sternotomy-related complications on follow-up. CONCLUSION: This review highlights the variety of conditions in which MS provides unrivalled access to the mediastinum and how well the procedure is tolerated by the paediatric patient, and emphasises the importance of sternotomy being within the armamentarium of access techniques of the general paediatric surgeon.