Publications by authors named "Jung-Seok Lee"

242 Publications

Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines.

Vaccines (Basel) 2021 Apr 8;9(4). Epub 2021 Apr 8.

Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil and Onpattro, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.
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http://dx.doi.org/10.3390/vaccines9040359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069344PMC
April 2021

Diverse patterns of bone regeneration in rabbit calvarial defects depending on the type of collagen membrane.

J Periodontal Implant Sci 2021 Feb;51(1):40-52

Department of Periodontology, Research Institute of Periodontal Regeneration, Yonsei University College of Dentistry, Seoul, Korea.

Purpose: Various crosslinking methods have been introduced to increase the longevity of collagen membranes. The aim of this study was to compare and evaluate the degradation and bone regeneration patterns of 3 collagen membranes.

Methods: Four 8-mm-diameter circular bone defects were created in the calvaria of 10 rabbits. In each rabbit, each defect was randomly allocated to 1) the sham control group, 2) the non-crosslinked collagen sponge (NS) group, 3) the chemically crosslinked collagen membrane (CCM) group, or 4) the biphasic calcium phosphate (BCP)-supplemented ultraviolet (UV)-crosslinked collagen membrane (UVM) group. Each defect was covered with the allocated membrane without any graft material. Rabbits were sacrificed at either 2 or 8 weeks post-surgery, and radiographic and histologic analyses were done.

Results: New bone formed underneath the membrane in defects in the CCM and UVM groups, with a distinctive new bone formation pattern, while new bone formed from the base of the defect in the NS and control groups. The CCM maintained its shape until 8 weeks, while the UVM and NS were fully degraded at 8 weeks; simultaneously, sustained inflammatory infiltration was found in the margin of the CCM, while it was absent in the UVM. In conclusion, the CCM showed longer longevity than the UVM, but was accompanied by higher levels of inflammation.

Conclusions: Both the CCM and UVM showed distinctive patterns of enhancement in new bone formation in the early phase. UV crosslinking can be a biocompatible alternative to chemical crosslinking.
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http://dx.doi.org/10.5051/jpis.2004180209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920838PMC
February 2021

Reliability of microarray analysis for studying periodontitis: low consistency in 2 periodontitis cohort data sets from different platforms and an integrative meta-analysis.

J Periodontal Implant Sci 2021 Feb;51(1):18-29

Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry, Seoul, Korea.

Purpose: The aim of this study was to compare the characteristic expression patterns of advanced periodontitis in 2 cohort data sets analyzed using different microarray platforms, and to identify differentially expressed genes (DEGs) through a meta-analysis of both data sets.

Methods: Twenty-two patients for cohort 1 and 40 patients for cohort 2 were recruited with the same inclusion criteria. The 2 cohort groups were analyzed using different platforms: Illumina and Agilent. A meta-analysis was performed to increase reliability by removing statistical differences between platforms. An integrative meta-analysis based on an empirical Bayesian methodology (ComBat) was conducted. DEGs for the integrated data sets were identified using the package to adjust for age, sex, and platform and compared with the results for cohorts 1 and 2. Clustering and pathway analyses were also performed.

Results: This study detected 557 and 246 DEGs in cohorts 1 and 2, respectively, with 146 and 42 significantly enriched gene ontology (GO) terms. Overlapping between cohorts 1 and 2 was present in 59 DEGs and 18 GO terms. However, only 6 genes from the top 30 enriched DEGs overlapped, and there were no overlapping GO terms in the top 30 enriched pathways. The integrative meta-analysis detected 34 DEGs, of which 10 overlapped in all the integrated data sets of cohorts 1 and 2.

Conclusions: The characteristic expression pattern differed between periodontitis and the healthy periodontium, but the consistency between the data sets from different cohorts and metadata was too low to suggest specific biomarkers for identifying periodontitis.
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http://dx.doi.org/10.5051/jpis.2002120106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920837PMC
February 2021

Epidemiology of dengue fever in Gabon: Results from a health facility-based fever surveillance in Lambaréné and its surroundings.

PLoS Negl Trop Dis 2021 Feb 10;15(2):e0008861. Epub 2021 Feb 10.

Centre de Recherches Médicales de Lambaréné, Campus CERMEL, Lambaréné, Gabon.

Background: In Africa, information on dengue is limited to outbreak reports and focused on some countries with continuing transmission in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings in Gabon.

Methods: Non-malarial febrile patients with current fever or history of fever (≤7 days) between 1 and 55 years of age, were enrolled at Albert Schweitzer Hospital (ASH). Acute (visit 1, day of enrollment) and convalescent blood samples were collected between 10 and 21 days after enrollment. Acute/convalescent samples were tested with IgM/IgG ELISA, and a selected subset of acute samples with RT-PCR.

Results: Among 682 non-malarial febrile patients enrolled, 119 (17.4%) were identified as dengue-positive (94 dengue-confirmed and 25 dengue-probable cases). Of these dengue-positive cases, 14 were confirmed with PCR, and based on serotyping, two infections were identified to be DENV-2 and two were DENV-3. The majority of our enrolled patients were <25 years of age and close to 80% of our dengue-positive cases were <15 years of age. In adjusted analyses, retro-orbital pain and abdominal pain were 2.7 and 1.6 times more frequently found among dengue-positive cases, compared to non-dengue cases.

Conclusion: Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Dengue should be considered more frequently in clinicians' diagnosis among non-malarial febrile patients in Lambaréné. Given the lack of data on dengue in Gabon, additional prospective and longitudinal studies would help to further define the burden and patterns of dengue for improved case detection.
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http://dx.doi.org/10.1371/journal.pntd.0008861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875424PMC
February 2021

Passive Immunization with Recombinant Antibody VLRB-PirA/PirB-Enriched Feeds against Infection in Shrimp.

Vaccines (Basel) 2021 Jan 16;9(1). Epub 2021 Jan 16.

Laboratory of Aquatic Animal Diseases, Research Institute of Natural Science, College of Veterinary Medicine, Gyeongsang National University, 501-201, 501, Jinju-daero, Jinju-si, Gyeongsangnam-do 52828, Korea.

The causative agent of acute hepatopancreatic necrosis disease (AHPND) is the bacterium, , which secretes toxins into the gastrointestinal tract of its host. toxins A and B (PirA/PirB) have been implicated in the pathogenesis of this disease, and are, therefore, the focus of studies developing treatments for AHPND. We previously produced recombinant antibodies based on the hagfish variable lymphocyte receptor B (VLRB) capable of neutralizing some viruses, suggesting that this type of antibody may have a potential application for treatment of AHPND. Here, recombinant PirA/PirB, produced using a bacterial expression system, were used as antigens to screen a hagfish VLRB cDNA library to obtain PirA/PirB-specific antibodies. A cell line secreting these antibodies was established by screening and cloning the DNA extracted from hagfish B cells. Supernatants collected from cells secreting the PirA/PirB antibodies were collected and concentrated, and used to passively immunize shrimp to neutralize the toxins PirA or PirB associated with AHPND. Briefly, 10 μg of PirA and PirB antibodies, 7C12 and 9G10, respectively, were mixed with the shrimp feed, and fed to shrimp for three days consecutive days prior to experimentally infecting the shrimp with (containing toxins A and B), and resulting mortalities recorded for six days. Results showed significantly higher level of survival in shrimp fed with the PirB-9G10 antibody (60%) compared to the group fed the PirA-7C12 antibody (3%) and the control group (0%). This suggests that VLRB antibodies may be a suitable alternative to immunoglobulin-based antibodies, as passive immunization treatments for effective management of AHPND outbreaks within shrimp farms.
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http://dx.doi.org/10.3390/vaccines9010055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829966PMC
January 2021

Direct Comparison of B Cell Surface Receptors as Therapeutic Targets for Nanoparticle Delivery of BTK Inhibitors.

Mol Pharm 2021 03 11;18(3):850-861. Epub 2021 Jan 11.

Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, United States.

Targeting different cell surface receptors with nanoparticle (NP)-based platforms can result in differential particle binding properties that may impact their localization, bioavailability, and, ultimately, the therapeutic efficacy of an encapsulated payload. Conventional assays comparing the efficacy of targeted NPs often do not adequately control for these differences in particle-receptor binding, potentially confounding their therapeutic readouts and possibly even limiting their experimental value. In this work, we characterize the conditions under which NPs loaded with Bruton's Tyrosine Kinase (BTK) inhibitor differentially suppress primary B cell activation when targeting either CD19 (internalizing) or B220 (noninternalizing) surface receptors. Surface binding of fluorescently labeled CD19- and B220-targeted NPs was analyzed and quantitatively correlated with the number of bound particles at given treatment concentrations. Using this binding data, suppression of B cell activation was directly compared for differentially targeted (CD19 vs B220) NPs loaded with a BTK inhibitor at a range of particle drug loading concentrations. When NPs were loaded with lower amounts of drug, CD19-mediated internalization demonstrated increased inhibition of B cell proliferation compared with B220 NPs. However, these differences were mitigated when particles were loaded with higher concentrations of BTK inhibitor and B220-mediated "paracrine-like" delivery demonstrated superior suppression of cellular activation when cells were bound to lower overall numbers of NPs. Taken together, these results demonstrate that inhibition of B cell activation can be optimized for NPs targeting either internalizing or noninternalizing surface receptors and that particle internalization is likely not a requisite endpoint when designing particles for delivery of BTK inhibitor to B cells.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00836DOI Listing
March 2021

Hand-ground fullerene-nanodiamond composite for photosensitized water treatment and photodynamic cancer therapy.

J Colloid Interface Sci 2021 Apr 11;587:101-109. Epub 2020 Dec 11.

School of Chemical and Biological Engineering, Institute of Chemical Process (ICP), and Institute of Engineering Research, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:

The unique capability of fullerene (C) to absorb light and generate reactive oxygen species (ROS) has been extensively studied for photosensitized water treatment and cancer therapy. Various material synthesis strategies have been proposed in parallel to overcome its intrinsic hydrophobicity and to enhance availability in water and physiological media. We present here a strikingly simple approach to make C available to these applications by hand-grinding dry C powder with nanodiamond (ND) using a mortar and pestle. The resulting ND-C composite was found to form a stable aqueous colloidal suspension and efficiently drive photosensitized production of ROS under visible light illumination. ND-C rapidly adsorbed and oxidized organic contaminants by photogenerated ROS. In the experiments for photodynamic cancer therapy, ND-C was internalized by cancer cells and induced cell apoptosis without noticeable toxicity. Treatment of tumor-bearing mice with ND-C and light irradiation resulted in tumor shrinkage and prolonged survival time.
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http://dx.doi.org/10.1016/j.jcis.2020.12.020DOI Listing
April 2021

Estimating the Force of Infection for Dengue Virus Using Repeated Serosurveys, Ouagadougou, Burkina Faso.

Emerg Infect Dis 2021 Jan;27(1):130-139

Because of limited data on dengue virus in Burkina Faso, we conducted 4 consecutive age-stratified longitudinal serologic surveys, ≈6 months apart, among persons 1-55 years of age, during June 2015-March 2017, which included a 2016 outbreak. The seroconversion rate before the serosurvey enrollment was estimated by binomial regression, taking age as the duration of exposure, and assuming constant force of infection (FOI) over age and calendar time. We calculated FOI between consecutive surveys and rate ratios for potentially associated characteristics based on seroconversion using the duration of intervals. Among 2,897 persons at enrollment, 66.3% were IgG-positive, and estimated annual FOI was 5.95%. Of 1,269 enrollees participating in all 4 serosurveys, 438 were IgG-negative at enrollment. The annualized FOI ranged from 10% to 20% (during the 2016 outbreak). Overall, we observed high FOI for dengue. These results could support decision-making about control and preventive measures for dengue.
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http://dx.doi.org/10.3201/eid2701.191650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774580PMC
January 2021

Apolipoprotein E ε4 Is Associated With the Development of Incident Dementia in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Patients With p.Arg544Cys Mutation.

Front Aging Neurosci 2020 20;12:591879. Epub 2020 Nov 20.

Department of Neurology, Jeju National University, Jeju, South Korea.

Background And Purpose: To identify clinical, laboratory, and magnetic resonance imaging (MRI) features in predicting incident stroke and dementia in Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Materials And Methods: We enrolled 87 Korean CADASIL patients who had undergone baseline clinical, laboratory, and MRI examinations between March 2012 and February 2015. The primary outcome of this study is the occurrence of stroke and dementia during the study period. The occurrence of incident stroke was confirmed by neuroimaging study, and dementia was defined by the diagnostic and statistical manual of mental disorders, fourth edition, criteria.

Results: Of the 87 patients, 57.5% were men, and the mean age was 63 ± 13 years (range 34-90 years), and 82 patients (94.3%) had p.Arg544Cys mutation. During an average follow-up of 67 months (interquartile range: 53-69 months), incident stroke occurred in 14 of 87 patients (16.1%) and incident dementia in 7 of 70 non-demented patients (10.0%). In adjusted analysis, increased systolic blood pressure was associated with increased risk of incident stroke [for every 10-mmHg increase; hazard ratio, 1.44 (1.02-2.03)]. Apolipoprotein E ε4 genotype was associated with an increased risk of incident dementia [hazard ratio, 10.70 (1.27-89.88)].

Conclusion: In this study, apolipoprotein E ε4 genotype was associated with the development of incident dementia, and higher blood pressure was associated with increased risk of incident stroke in CADASIL patients with predominant p.Arg544Cys mutation.
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http://dx.doi.org/10.3389/fnagi.2020.591879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714778PMC
November 2020

Significant increase in the secretion of extracellular vesicles and antibiotics resistance from methicillin-resistant Staphylococcus aureus induced by ampicillin stress.

Sci Rep 2020 12 3;10(1):21066. Epub 2020 Dec 3.

Laboratory of Aquatic Animal Diseases, College of Veterinary Medicine, Research Institute of Natural Science, Gyeongsang National University, Jinju, 52828, Republic of Korea.

Extracellular vesicles (EVs) containing specific cargo molecules from the cell of origin are naturally secreted from bacteria. EVs play significant roles in protecting the bacterium, which can contribute to their survival in the presence of antibiotics. Herein, we isolated EVs from methicillin-resistant Staphylococcus aureus (MRSA) in an environment with or without stressor by adding ampicillin at a lower concentration than the minimum inhibitory concentration (MIC). We investigated whether EVs from MRSA under stress condition or normal condition could defend susceptible bacteria in the presence of several β-lactam antibiotics, and directly degrade the antibiotics. A comparative proteomic approach was carried out in both types of EVs to investigate β-lactam resistant determinants. The secretion of EVs from MRSA under antibiotic stressed conditions was increased by 22.4-fold compared with that of EVs without stress. Proteins related to the degradation of β-lactam antibiotics were abundant in EVs released from the stressed condition. Taken together, the present data reveal that EVs from MRSA play a crucial role in the survival of β-lactam susceptible bacteria by acting as the first line of defense against β-lactam antibiotics, and antibiotic stress leads to release EVs with high defense activity.
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http://dx.doi.org/10.1038/s41598-020-78121-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713300PMC
December 2020

Proteomic Analysis of Porcine-Derived Collagen Membrane and Matrix.

Materials (Basel) 2020 Nov 17;13(22). Epub 2020 Nov 17.

Department of Oral Biology, School of Dentistry, Medical University of Vienna, 1090 Vienna, Austria.

Collagen membranes and matrices being widely used in guided bone regeneration and soft tissue augmentation have characteristic properties based on their composition. The respective proteomic signatures have not been identified. Here, we performed a high-resolution shotgun proteomic analysis on two porcine collagen-based biomaterials designed for guided bone regeneration and soft tissue augmentation. Three lots each of a porcine-derived collagen membrane and a matrix derived from peritoneum and/or skin were digested and separated by nano-reverse-phase high-performance liquid chromatography. The peptides were subjected to mass spectrometric detection and analysis. A total of 37 proteins identified by two peptides were present in all collagen membranes and matrices, with 11 and 16 proteins being exclusively present in the membrane and matrix, respectively. The common extracellular matrix proteins include fibrillar collagens (COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL5A3, COL11A2), non-fibrillar collagens (COL4A2, COL6A1, COL6A2, COL6A3, COL7A1, COL16A1, COL22A1), and leucine-rich repeat proteoglycans (DCN, LUM, BGN, PRELP, OGN). The structural proteins vimentin, actin-based microfilaments (ACTB), annexins (ANXA1, ANXA5), tubulins (TUBA1B, TUBB), and histones (H2A, H2B, H4) were also identified. Examples of membrane-only proteins are COL12A1 and COL14A1, and, of matrix only proteins, elastin (ELN). The proteomic signature thus revealed the similarities between but also some individual proteins of collagen membrane and matrix.
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http://dx.doi.org/10.3390/ma13225187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698422PMC
November 2020

Do periodontal defects affect periodontal inflammation and destruction? -Histological/microbiological changes and gene expression profiles of a pilot study in beagle dogs.

J Periodontol 2020 Oct 30. Epub 2020 Oct 30.

Department of Periodontology, College of Dentistry, Research Institute for Periodontal Regeneration, Yonsei University, Seoul, Republic of Korea.

Background: The present study focused on the inflammatory disease progress after periodontal defect induction and aimed to specifically determine periodontal tissue responses following dental plaque accumulation by ligatures on a site with/without standardized periodontal defect induction.

Methods: After 1 month from extraction of the adjacent teeth, semi-circumferential defects were surgically created in the unilateral second and fourth premolars (test group), whereas no defects were being induced at the contralateral sites (control group). One week later, silk was used to ligate the tooth cervix at both sites to encourage the accumulation of dental plaque. Four weeks later, the tissue samples were collected for histological/histomorphometric and microarray analysis. Microbiological analysis was performed before defect induction and at ligatures, and after 4 weeks of dental plaque accumulation.

Results: Remarkable inflammation was clinically and histologically observed in both groups after plaque accumulation, and the intrabony type of periodontal defect exaggerated inflammatory cell infiltration into the connective tissue layer. Expression of genes related to inflammation such as IL-1 was highly up-regulated in test sites. However, these inflammatory infiltrations did not invade to a boundary of periodontal ligament and connective tissue attachment in both groups, and histomorphometric results corresponds to these observational results. Bacterial findings also showed no significant differences in detected microbiome compositions between control and test groups at three-time points.

Conclusion: Intrabony defect might exaggerate the plaque-induced inflammation in the aspect of inflammatory cell infiltration and the related gene expression, but both dental plaque and the pre-existing periodontal defect negligibly disrupt periodontal attachment and the underlying alveolar bone.
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http://dx.doi.org/10.1002/JPER.20-0508DOI Listing
October 2020

Transcriptomic profiles and their correlations in saliva and gingival tissue biopsy samples from periodontitis and healthy patients.

J Periodontal Implant Sci 2020 Oct;50(5):313-326

Department of Periodontology, Research Institute of Periodontal Regeneration, Yonsei University College of Dentistry, Seoul, Korea.

Purpose: This study was conducted to analyze specific RNA expression profiles in gingival tissue and saliva samples in periodontitis patients and healthy individuals, and to determine their correlations in light of the potential use of microarray-based analyses of saliva samples as a periodontal monitoring tool.

Methods: Gingival tissue biopsies and saliva samples from 22 patients (12 with severe periodontitis and 10 with a healthy periodontium) were analyzed using transcriptomic microarray analysis. Differential gene expression was assessed, and pathway and clustering analyses were conducted for the samples. The correlations between the results for the gingival tissue and saliva samples were analyzed at both the gene and pathway levels.

Results: There were 621 differentially expressed genes (DEGs; 320 upregulated and 301 downregulated) in the gingival tissue samples of the periodontitis group, and 154 DEGs (44 upregulated and 110 downregulated) in the saliva samples. Nine of these genes overlapped between the sample types. The periodontitis patients formed a distinct cluster group based on gene expression profiles for both the tissue and saliva samples. Database for Annotation, Visualization and Integrated Discovery analysis revealed 159 enriched pathways from the tissue samples of the periodontitis patients, as well as 110 enriched pathways In the saliva samples. Thirty-four pathways overlapped between the sample types.

Conclusions: The present results indicate the possibility of using the salivary transcriptome to distinguish periodontitis patients from healthy individuals. Further work is required to enhance the extraction of available RNA from saliva samples.
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http://dx.doi.org/10.5051/jpis.1905460273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606893PMC
October 2020

TGF-β Activity Related to the Use of Collagen Membranes: In Vitro Bioassays.

Int J Mol Sci 2020 Sep 10;21(18). Epub 2020 Sep 10.

Department of Oral Biology, School of Dentistry, Medical University of Vienna, 1090 Vienna, Austria.

Collagen membranes commonly used in guided bone regeneration are supposed to actively influence tissue regeneration and are not exclusively serving as passive barriers shielding away the soft tissue. The molecular mechanisms by which collagen membranes might affect tissue regeneration might involve the activation of transforming growth factor beta (TGF-β) signaling pathways. Here, we determined the TGF-β activity of supernatants and proteolytic lysates of five commercially available collagen membranes. The expression of TGF-β target genes interleukin 11 (IL11), NADPH oxidase 4 (NOX4), and proteoglycan 4 (PRG4) was evaluated by reverse transcriptase polymerase chain reaction and IL11 immunoassay in gingival fibroblasts. TGF-β signaling activation was further assessed by blocking the TGF-β receptor I kinase, a TGF-β neutralizing antibody, and showing the nuclear localization of phosphorylated Smad3 and total Smad2/3. We could identify two collagen membranes whose supernatants and lysates caused a robust increase of TGF-β receptor I kinase-dependent expression of IL11 in gingival fibroblasts. Moreover, the supernatant of a particular one membrane caused the nuclear localization of phosphorylated Smad3 and Smad2/3 in the fibroblasts. These results strengthen the evidence that some collagen membranes possess an intrinsic TGF-β activity that might actively influence the process of guided bone regeneration.
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http://dx.doi.org/10.3390/ijms21186636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555929PMC
September 2020

Changes in mucogingival junction after an apically positioned flap with collagen matrix at sites with or without previous guided bone regeneration: A prospective comparative cohort study.

Clin Oral Implants Res 2020 Dec 22;31(12):1199-1206. Epub 2020 Sep 22.

Clinic of Reconstructive Dentistry, University of Zurich, Zurich, Switzerland.

Aim: To assess changes in the position of the mucogingival junction (MGJ) after an apically positioned flap (APF) with collagen matrix performed at sites with or without previous guided bone regeneration (GBR).

Materials And Methods: Dental implants were placed with or without GBR (group GBR or non-GBR) depending on the available ridge width in 30 patients with a limited width of keratinized mucosa (MGJ placed more coronally than the expected prosthetic margin). An apically positioned flap with collagen matrix was performed in both groups. Changes in the position of the MGJ from the day of an apically positioned flap up to 1, 3, and 12 months thereafter were assessed on digital scans (primary endpoint). Secondary endpoints were the width and thickness of the keratinized mucosa, and the position of the mucosal margin.

Results: The position of the MGJ changed significantly from baseline to the first month, by 5.25 ± 2.10 and 4.40 ± 1.41 mm in groups GBR and non-GBR, respectively. Thereafter, the position remained stable in both groups up to 1 year (changes from baseline of 5.46 ± 2.28 and 4.58 ± 1.92 mm, respectively; p = .34). The position of the mucosal margin did not differ between groups GBR and non-GBR (-1.57 ± 2.04 and -1.75 ± 2.08 mm, respectively; p = .84), nor did the width of the keratinized mucosa (1.20 ± 1.03 and 0.99 ± 0.66 mm, p = .91) or its thickness (1.28 ± 0.44 and 1.40 ± 0.78 mm, p = .87).

Conclusion: Apically positioned flap combined with a collagen matrix results in a more apical position of the MGJ at sites with or without GBR. Following a coronal shift during the first month after the apical positioning of the flap, the level of the MGJ remained stable.
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http://dx.doi.org/10.1111/clr.13665DOI Listing
December 2020

Clinical factors influencing implant positioning by guided surgery using a nonmetal sleeve template in the partially edentulous ridge: Multiple regression analysis of a prospective cohort.

Clin Oral Implants Res 2020 Dec 22;31(12):1187-1198. Epub 2020 Sep 22.

Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry, Seoul, Korea.

Objective: To determine the positional accuracy of implants placed with a three-dimensionally printed template having nonmetal sleeves and to determine the contributing factors to observed deviations.

Materials And Methods: One hundred and eighty-seven implants placed in 72 patients were analyzed. Presurgical intraoral scans and cone-beam computed tomography images obtained before and after surgery were superimposed, and vertical, angular, platform, and apex deviations were measured between the virtually planned and actually placed positions. A multiple linear regression model was designed for identifying the contributing factors. Statistical significance was set at p < .05, with Bonferroni correction if necessary (p < .0167).

Results: A total of 187 implants demonstrated deviations of 0.65 [0.56, 0.75] mm (mean [95% confidence interval]) vertically, 3.59° [3.30°, 3.89°] angularly, 1.16 [1.04, 1.28] mm at platform, and 1.50 [1.36, 1.65] mm at apex. Implants placed in the mandible showed larger angular, platform, and apex deviations compared with those in the maxilla (p = .049, p = .014 and p = .003, respectively). Implants placed at the third or fourth nearest sites from the most-distal tooth had larger deviations than those placed at the first or second nearest sites, in vertical, platform, and apical aspects (p = .015, p = .011 andp = .018, respectively). This was only applicable to free-ending-supported templates (p < .0167), and anchor pin-supported free-ending templates (p < .0167).

Conclusion: Using a three-dimensionally printed surgical template with a nonmetal sleeve in the partial edentulous ridge resulted in larger deviations in implants placed in the mandible or distal free-end third or fourth nearest site.
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http://dx.doi.org/10.1111/clr.13664DOI Listing
December 2020

Clinical and epidemiologic characteristics associated with dengue fever in Mombasa, Kenya.

Int J Infect Dis 2020 Nov 3;100:207-215. Epub 2020 Sep 3.

Eastern and Southern Africa Centre of International Parasite Control (ESACIPAC), Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.

Objectives: Information on dengue in Africa is limited. To estimate the proportion of dengue-positive cases among febrile patients and describe clinical indicators of dengue, we conducted passive health facility-based fever surveillance in Mombasa, Kenya.

Methods: Non-malarial febrile patients between one and 55 years were enrolled at three health facilities between March 2016 and May 2017. Acute and convalescent blood samples were collected with an interval of 10-21 days. Acute samples were tested with dengue RDT and a selected subset with RT-PCR, and acute/convalescent samples with IgM/IgG ELISA.

Results: Among 482 enrollees, 295 (61.2%) were dengue-positive based on laboratory results. The surveillance covered the beginning of a dengue outbreak in April-May 2017, during which 73.9% of enrollees were dengue-positive. By contrast, during the non-outbreak period, 54.6% were dengue-positive. Dengue case status was positively associated with rash, fatigue, headache, retro-orbital pain, nausea/vomiting, nose bleeding, gum bleeding, loss of appetite, myalgia, and arthralgia. Dengue-positive cases in our study had mostly mild disease, with only two requiring observation, and no DHF.

Conclusions: The clinical response was generally mild relative to what was observed in SE Asia and the Americas. Given the high level of DENV transmission in Mombasa, more data would be needed to further understand the disease burden and improve case detection for surveillance/monitoring of outbreaks.
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http://dx.doi.org/10.1016/j.ijid.2020.08.074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670221PMC
November 2020

Characterization of CD4-Positive Lymphocytes in the Antiviral Response of Olive Flounder () to Nervous Necrosis Virus.

Int J Mol Sci 2020 Jun 11;21(11). Epub 2020 Jun 11.

Laboratory of Aquatic Animal Diseases, Research Institute of Natural Science, College of Veterinary Medicine, Gyeongsang National University, 501 Jinju, Gyeongnam 52828, Korea.

The presence of CD4 T lymphocytes has been described for several teleost species, while many of the main T cell subsets have not been characterized at a cellular level, because of a lack of suitable tools for their identification, e.g., monoclonal antibodies (mAbs) against cell markers. We previously described the tissue distribution and immune response related to CD3ε and CD4-1 T cells in olive flounder () in response to a viral infection. In the present study, we successfully produce an mAb against CD4-2 T lymphocytes from olive flounder and confirmed its specificity using immuno-blotting, immunofluorescence staining, flow cytometry analysis and reverse transcription polymerase chain reaction (RT-PCR). Using these mAbs, we were able to demonstrate that the CD3ε T cell populations contain both types of CD4 cells, with the majority of the CD4 T cell subpopulations being CD4-1/CD4-2 cells, determined using two-color flow cytometry analysis. We also examined the functional activity of the CD4-1 and CD4-2 cells in vivo in response to a viral infection, with the numbers of both types of CD4 T cells increasing significantly during the virus infection. Collectively, these findings suggest that the CD4 T lymphocytes in olive flounder are equivalent to the helper T cells in mammals in terms of their properties and function, and it is the CD4-2 T lymphocytes rather than the CD4-1 T cells that play an important role in the Th1 immune response against viral infections in olive flounder.
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http://dx.doi.org/10.3390/ijms21114180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312829PMC
June 2020

Continuous Label-Free Electronic Discrimination of T Cells by Activation State.

ACS Nano 2020 07 25;14(7):8646-8657. Epub 2020 Jun 25.

Department of Electrical Engineering, School of Engineering and Applied Sciences, Yale University, New Haven, Connecticut 06511, United States.

The sensitivity and speed with which the immune system reacts to host disruption is unrivaled by any detection method for pathogenic biomarkers or infectious signatures. Engagement of cellular immunity in response to infections or cancer is contingent upon activation and subsequent cytotoxic activity by T cells. Thus, monitoring T cell activation can reliably serve as a metric for disease diagnosis as well as therapeutic prognosis. Rapid and direct quantification of T cell activation states, however, has been hindered by challenges associated with antigen target identification, labeling requirements, and assay duration. Here we present an electronic, label-free method for simultaneous separation and evaluation of T cell activation states. Our device utilizes a microfluidic design integrated with nanolayered electrode structures for dielectrophoresis (DEP)-driven discrimination of activated naïve T cells at single-cell resolution and demonstrates rapid (<2 min) separation of T cells at high single-pass efficiency as quantified by an on-chip Coulter counter module. Our device represents a microfluidic tool for electronic assessment of immune activation states and, hence, a portable diagnostic for quantitative evaluation of immunity and disease state. Further, its ability to achieve label-free enrichment of activated immune cells promises clinical utility in cell-based immunotherapies.
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http://dx.doi.org/10.1021/acsnano.0c03018DOI Listing
July 2020

Oral Fluid Biomarkers for Diagnosing Gingivitis in Human: A Cross-Sectional Study.

J Clin Med 2020 Jun 3;9(6). Epub 2020 Jun 3.

Department of Periodontology, Research Institute of Periodontal Regeneration, Yonsei University College of Dentistry, Seoul 120-749, Korea.

Diagnoses based on oral fluid biomarkers have been introduced to overcome limitations of periodontal probe-based diagnoses. Diagnostic ability of certain biomarkers for periodontitis have been identified and widely studied, however, such studies targeting gingivitis is scarce. The aims of this study were to determine and compare the efficacies and accuracies of eight biomarkers in diagnosing gingivitis with the aid of receiver operating characteristic (ROC) curves. The probing depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP), gingival index (GI), and plaque index (PI) were examined in 100 participants. Gingival crevicular fluid was collected using paper points, and whole-saliva samples were collected using cotton roll. Samples were analyzed using enzyme-linked immunosorbent assay kits for the different biomarkers. The levels of matrix metalloproteinase (MMP)-8, MMP-9, lactoferrin, cystatin C, myeloperoxidase (MPO), platelet-activating factor, cathepsin B, and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen were analyzed. MPO and MMP-8 levels in saliva were strongly correlated with gingivitis, with Pearson's correlation coefficients of 0.399 and 0.217, respectively. The area under the curve (AUC) was largest for MMP-8, at 0.814, followed by values of 0.793 and 0.777 for MPO and MMP-9, respectively. The clinical parameters of GI and PI showed strong correlations and large AUC values, whereas PD and CAL did not. MMP-8 and MPO were found to be effective for diagnosing gingivitis. Further investigations based on the results of this study may identify clinically useful biomarkers for the accurate and early detection of gingivitis.
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http://dx.doi.org/10.3390/jcm9061720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356847PMC
June 2020

The Importance of Porins and β-Lactamase in Outer Membrane Vesicles on the Hydrolysis of β-Lactam Antibiotics.

Int J Mol Sci 2020 Apr 17;21(8). Epub 2020 Apr 17.

Laboratory of Aquatic Animal Diseases, Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea.

Gram-negative bacteria have an outer membrane inhibiting the entry of antibiotics. Porins, found within the outer membrane, are involved in regulating the permeability of β-lactam antibiotics. β-lactamases are enzymes that are able to inactivate the antibacterial properties of β-lactam antibiotics. Interestingly, porins and β-lactamase are found in outer membrane vesicles (OMVs) of β-lactam-resistant and may be involved in the survival of susceptible strains of in the presence of antibiotics, through the hydrolysis of the β-lactam antibiotic. In this study, OMVs isolated from β-lactam-resistant and from mutants, lacking porin or β-lactamase, were evaluated to establish if the porins or β-lactamase in OMVs were involved in the degradation of β-lactam antibiotics. OMVs isolated from deficient in β-lactamase did not show any degradation ability against β-lactam antibiotics, while OMVs lacking OmpC or OmpF showed significantly lower levels of hydrolyzing activity than OMVs from parent . These data reveal an important role of OMVs in bacterial defense mechanisms demonstrating that the OmpC and OmpF proteins allow permeation of β-lactam antibiotics into the lumen of OMVs, and antibiotics that enter the OMVs can be degraded by β-lactamase.
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http://dx.doi.org/10.3390/ijms21082822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215730PMC
April 2020

Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes.

Sci Adv 2020 03 11;6(11):eaaz1580. Epub 2020 Mar 11.

Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06511, USA.

Dendritic cells (DCs) are adept at cross-presentation and initiation of antigen-specific immunity. Clinically, however, DCs produced by in vitro differentiation of monocytes in the presence of exogenous cytokines have been met with limited success. We hypothesized that DCs produced in a physiological manner may be more effective and found that platelets activate a cross-presentation program in peripheral blood monocytes with rapid (18 hours) maturation into physiological DCs (phDCs). Differentiation of monocytes into phDCs was concomitant with the formation of an "adhesion synapse," a biophysical junction enriched with platelet P-selectin and monocyte P-selectin glycoprotein ligand 1, followed by intracellular calcium fluxing and nuclear localization of nuclear factor κB. phDCs were more efficient than cytokine-derived DCs in generating tumor-specific T cell immunity. Our findings demonstrate that platelets mediate a cytokine-independent, physiologic maturation of DC and suggest a novel strategy for DC-based immunotherapies.
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http://dx.doi.org/10.1126/sciadv.aaz1580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065880PMC
March 2020

Green Silver Nanoparticles Formed by and Leaf Extracts and the Antifungal Activity.

Nanomaterials (Basel) 2020 Mar 17;10(3). Epub 2020 Mar 17.

Biomaterials and Nanotechnology Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, 700000 Vietnam.

Phytoconstituents presenting in herbal plant broths are the biocompatible, regenerative, and cost-effective sources that can be utilized for green synthesis of silver nanoparticles. Different plant extracts can form nanoparticles with specific sizes, shapes, and properties. In the study, we prepared silver nanoparticles (P.uri.AgNPs, P.zey.AgNPs, and S.dul.AgNPs) based on three kinds of leaf extracts ( and , respectively) and demonstrated the antifungal capacity. The silver nanoparticles were simply formed by adding silver nitrate to leaf extracts without using any reducing agents or stabilizers. Formation and physicochemical properties of these silver nanoparticles were characterized by UV-vis, Fourier transforms infrared spectroscopy, scanning electron microscope, transmission electron microscope, and energy dispersive X-ray spectroscopy. P.uri.AgNPs were 28.3 nm and spherical. P.zey.AgNPs were 26.7 nm with hexagon or triangle morphologies. Spherical S.dul.AgNPs were formed and they were relatively smaller than others. P.uri.AgNPs, P.zey.AgNPs and S.dul.AgNPs exhibited the antifungal ability effective against and demonstrating their potentials as fungicides in the biomedical and agricultural applications.
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http://dx.doi.org/10.3390/nano10030542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153602PMC
March 2020

Distinctive bone regeneration of calvarial defects using biphasic calcium phosphate supplemented ultraviolet-crosslinked collagen membrane.

J Periodontal Implant Sci 2020 Feb 19;50(1):14-27. Epub 2019 Dec 19.

Department of Periodontology, Research Institute of Periodontal Regeneration, Yonsei University College of Dentistry, Seoul, Korea.

Purpose: To overcome several drawbacks of chemically-crosslinked collagen membranes, modification processes such as ultraviolet (UV) crosslinking and the addition of biphasic calcium phosphate (BCP) to collagen membranes have been introduced. This study evaluated the efficacy and biocompatibility of BCP-supplemented UV-crosslinked collagen membrane for guided bone regeneration (GBR) in a rabbit calvarial model.

Methods: Four circular bone defects (diameter, 8 mm) were created in the calvarium of 10 rabbits. Each defect was randomly allocated to one of the following groups: 1) the sham control group (spontaneous healing); 2) the M group (defect coverage with a BCP-supplemented UV-crosslinked collagen membrane and no graft material); 3) the BG (defects filled with BCP particles without membrane coverage); and 4) the BG+M group (defects filled with BCP particles and covered with a BCP-supplemented UV-crosslinked collagen membrane in a conventional GBR procedure). At 2 and 8 weeks, rabbits were sacrificed, and experimental defects were investigated histologically and by micro-computed tomography (micro-CT).

Results: In both micro-CT and histometric analyses, the BG and BG+M groups at both 2 and 8 weeks showed significantly higher new bone formation than the control group. On micro-CT, the new bone volume of the BG+M group (48.39±5.47 mm) was larger than that of the BG group (38.71±2.24 mm, =0.032) at 8 weeks. Histologically, greater new bone area was observed in the BG+M group than in the BG or M groups. BCP-supplemented UV-crosslinked collagen membrane did not cause an abnormal cellular reaction and was stable until 8 weeks.

Conclusions: Enhanced new bone formation in GBR can be achieved by simultaneously using bone graft material and a BCP-supplemented UV-crosslinked collagen membrane, which showed high biocompatibility and resistance to degradation, making it a biocompatible alternative to chemically-crosslinked collagen membranes.
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http://dx.doi.org/10.5051/jpis.2020.50.1.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040443PMC
February 2020

Digital scanning is more accurate than using a periodontal probe to measure the keratinized tissue width.

Sci Rep 2020 02 28;10(1):3665. Epub 2020 Feb 28.

Department of Oral Biology, School of Dentistry, Medical University of Vienna, Vienna, Austria.

This study aimed to compare the accuracy and reliability of digital versus conventional clinical measurements of the width of keratinized tissue. To this end, the keratinized tissue width was measured at 110 tooth sites in 5 pig jaws. The measurements were made at each site using three-dimensional (3D) scanned images and a periodontal probe. The actual keratinized tissue width was subsequently measured on histologic slides prepared from the same sites, and differences between the histologic slides and the digital and clinical measurements were analyzed to determine their accuracy in two measurement rounds. Furthermore, intrarater and interrater reliabilities were evaluated using the intraclass correlation coefficient (ICC). Here we show that the mean differences (and lower/upper limits of agreement) between the histologic and the digital/clinical measurements were 0.10 mm (-1.34/1.54 mm) and 1.11 mm (-0.69/2.92 mm), respectively, in the first round of measurements (p < 0.01), and 0.04 mm (-1.52/1.59 mm) and 1.05 mm (-0.37/2.48 mm) in the second round of measurements (p < 0.01). Moreover, we found that the intrarater reliability was higher for the digital measurements (ICC = 0.97, confidence interval [CI] = 0.96-0.97) than for the clinical measurements (ICC = 0.87, CI = 0.86-0.89; p < 0.01). Taken together, our results demonstrate that digital measurements of the keratinized tissue width using 3D scanned images can replace conventional clinical measurements using a periodontal probe since they are more accurate and reliable.
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http://dx.doi.org/10.1038/s41598-020-60291-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048786PMC
February 2020

The Importance of Poly(ethylene glycol) Alternatives for Overcoming PEG Immunogenicity in Drug Delivery and Bioconjugation.

Polymers (Basel) 2020 Feb 2;12(2). Epub 2020 Feb 2.

Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.

Poly(ethylene glycol) (PEG) is widely used as a gold standard in bioconjugation and nanomedicine to prolong blood circulation time and improve drug efficacy. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles is a well-established technique known as PEGylation, with PEGylated products have been using in clinics for the last few decades. However, it is increasingly recognized that treating patients with PEGylated drugs can lead to the formation of antibodies that specifically recognize and bind to PEG (i.e., anti-PEG antibodies). Anti-PEG antibodies are also found in patients who have never been treated with PEGylated drugs but have consumed products containing PEG. Consequently, treating patients who have acquired anti-PEG antibodies with PEGylated drugs results in accelerated blood clearance, low drug efficacy, hypersensitivity, and, in some cases, life-threatening side effects. In this succinct review, we collate recent literature to draw the attention of polymer chemists to the issue of PEG immunogenicity in drug delivery and bioconjugation, thereby highlighting the importance of developing alternative polymers to replace PEG. Several promising yet imperfect alternatives to PEG are also discussed. To achieve asatisfactory alternative, further joint efforts of polymer chemists and scientists in related fields are urgently needed to design, synthesize and evaluate new alternatives to PEG.
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http://dx.doi.org/10.3390/polym12020298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077443PMC
February 2020

Characterization of Hagfish () Variable Lymphocyte Receptor-Based Antibody and Its Potential Role in the Neutralization of Nervous Necrosis Virus.

J Immunol 2020 02 13;204(3):718-725. Epub 2019 Dec 13.

Laboratory of Aquatic Animal Diseases, Research Institute of Natural Science, College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 52828, South Korea;

The variable lymphocyte receptor (VLR) mediates the humoral immune response in jawless vertebrates, including lamprey () and hagfish (). Hagfish VLRBs are composed of leucine-rich repeat (LRR) modules, conjugated with a superhydrophobic C-terminal tail, which contributes to low levels of expression in recombinant protein technology. In this study, we screened Ag-specific VLRBs from hagfish immunized with nervous necrosis virus (NNV). The artificially multimerized form of VLRB was constructed using a mammalian expression system. To enhance the level of expression of the Ag-specific VLRB, mutagenesis of the VLRB was achieved in vitro through domain swapping of the LRR C-terminal cap and variable LRR module. The mutant VLRB obtained, with high expression and secretion levels, was able to specifically recognize purified and progeny NNV, and the Ag binding ability of this mutant was increased by at least 250-fold to that of the nonmutant VLRB. Furthermore, preincubation of the Ag-specific VLRB with NNV reduced the infectivity of NNV in E11 cells in vitro, and in vivo experiment. Our results suggest that the newly developed Ag-specific VLRB has the potential to be used as diagnostic and therapeutic reagents for NNV infections in fish.
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http://dx.doi.org/10.4049/jimmunol.1900675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971507PMC
February 2020

Clinical benefits of ridge preservation for implant placement compared to natural healing in maxillary teeth: A retrospective study.

J Clin Periodontol 2020 03 7;47(3):382-391. Epub 2020 Jan 7.

Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry, Seoul, South Korea.

Aim: The purpose of this retrospective study was to determine clinical benefits of ridge preservation in terms of surgical invasiveness of implant placement compared to natural healing in the maxilla.

Materials & Methods: This study included 178 patients with 206 implants placed at ridge-preserved sites and 493 patients with 656 implants placed at naturally healed sites in maxillary anterior and posterior regions. Patient- and implant-related data were collected from electronic dental records including additional augmentation procedures performed before or during implant placement and surgical complications. Cumulative survival rate was assessed using Kaplan-Meier method. The annual peri-implant marginal bone loss between the two groups was compared using the Mann-Whitney U test.

Results: The follow-up period was 24.4 ± 18.1 months (mean ± standard deviation) for ridge-preserved sites and 45.7 ± 29.6 months for naturally healed sites. Sinus augmentation was performed at similar frequencies in the two groups, but lateral approach was applied significantly more at naturally healed sites (37.2%) than ridge-preserved sites (8.3%, p ≤ .001). There was no intergroup difference in the cumulative survival rate or annual peri-implant marginal bone loss.

Conclusion: Ridge preservation can be clinically beneficial for minimizing the invasiveness of implant surgery by simplifying the procedure when sinus augmentation is expected in the maxilla.
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http://dx.doi.org/10.1111/jcpe.13231DOI Listing
March 2020

Clinical and epidemiologic characteristics associated with dengue during and outside the 2016 outbreak identified in health facility-based surveillance in Ouagadougou, Burkina Faso.

PLoS Negl Trop Dis 2019 12 6;13(12):e0007882. Epub 2019 Dec 6.

Institute for Research on Sustainable Development (IRD), CEPED, Université de Paris, ERL INSERM SAGESUD, Paris, France.

Background: In Africa, the magnitude of dengue virus (DENV) transmission is largely unknown. In Burkina Faso, several outbreaks have been reported and data are often based on findings from outbreak investigations.

Methods: To better understand dengue epidemiology and clinical characteristics in Burkina Faso, a fever surveillance study was conducted among patients aged 1-55 years, who presented with non-malarial febrile illness at five primary healthcare facilities in Ouagadougou, Burkina Faso from December 2014 to February 2017, encompassing a 3-month dengue outbreak in September-November 2016. Acute and convalescent blood samples were collected within an interval of 10-21 days between visits. Acute samples were tested with dengue rapid diagnostic tests (RDT) and a selected subset with RT-PCR, and all acute/convalescent samples with IgM/IgG ELISA.

Results: Among 2929 non-malarial febrile patients, 740 (25%) were dengue-positive based on RT-PCR and/or IgM/IgG ELISA; 428 out of 777 patients (55%) and 312 out of 2152 (14%) were dengue-positive during outbreak and non-outbreak periods, respectively. There were 11% (316/2929) and 4% (129/2929) patients showing positive for NS1 and IgM, on the RDT, respectively. DENV 2 predominated during the outbreak, whereas DENV 3 predominated before the outbreak. Only 25% of dengue-positive cases were clinically diagnosed with suspected dengue. The odds of requiring observation for ≤3 days (versus routine outpatient care) were 11 times higher among dengue-positive cases than non-dengue cases. In adjusted analyses, dengue-positivity was associated with rash and retro-orbital pain (OR = 2.6 and 7.4, respectively) during the outbreak and with rash and nausea/vomiting (OR = 1.5 and 1.4, respectively) during the non-outbreak period.

Conclusion: Dengue virus is an important pathogen in Burkina Faso, accounting for a substantial proportion of non-malarial fevers both during and outside outbreak, but is only infrequently suspected by clinicians. Additional longitudinal data would help to further define characteristics of dengue for improved case detection and surveillance.
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http://dx.doi.org/10.1371/journal.pntd.0007882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897397PMC
December 2019

Histologic analysis following grafting of damaged extraction sockets using deproteinized bovine or porcine bone mineral: A randomized clinical trial.

Clin Oral Implants Res 2020 Jan 27;31(1):93-102. Epub 2019 Nov 27.

Department of Periodontology, Research Institute for Periodontal regeneration, Yonsei University College of Dentistry, Seoul, Korea.

Objectives: This study histologically analyzed biopsy samples obtained from sites of damaged extraction socket grafting using deproteinized bovine bone mineral (DBBM) or deproteinized porcine bone mineral (DPBM) with coverage by a collagen membrane.

Material And Methods: One hundred patients participated in this randomized controlled clinical trial of extraction socket grafts performed in cases of periodontally compromised teeth. All participants were blinded to their group allocations, and each material was grafted with coverage by collagen membranes after extraction of the tooth and removal of granulation tissue. At implant placement at 4 months, a biopsy was harvested at the implant site using a trephine was analyzed histologically.

Results: Eighty-five biopsy samples were acquired, of which 81 were finally included in the histologic analysis (42 in DBBM and 39 in DPBM group). Both DBBM and DPBM groups showed comparable proportions of residual biomaterial (12.37 ± 5.67% and 12.21 ± 5.75%, respectively), newly formed bone (15.07 ± 10.52% and 18.47 ± 11.47%, respectively), and nonmineralized tissue (72.56 ± 10.07% and 71.55 ± 15.47%, respectively). There were no significant differences in these histologic parameters between the two groups with different biomaterials.

Conclusion: Comparable histologic bone formation was found in both socket grafted groups with DBBM or DPBM covered by collagen membranes in periodontally damaged extraction sockets. However, a wide variation in new bone formation was found after 4 months of postsurgical healing and a tendency of higher new bone formation was shown at damaged sockets that had an intact unilateral residual wall regardless of buccal or lingual side.
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http://dx.doi.org/10.1111/clr.13557DOI Listing
January 2020