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Aim To compare the 1-year outcomes of immediate loading (IL) and delayed loading (DL) protocols for implants placed by fully guided surgery in partially edentulous jaws. Materials and methods This study included 72 patients who received implant surgery with either IL (93 implants, 36 patients) or DL (94 implants, 26 patients). A prefabricated provisional prosthesis was delivered immediately for the IL group (86 implants, 32 patients) with the exception of 4 subjects in whom an initial torque of >20 Ncm and an implant stability quotient of >65 were not achieved, while all DL-group implants were loaded after 3 months. The 1-year implant survival rate estimated by intention-to-treat (ITT) and per-protocol (PP) analyses, and the marginal bone loss (MBL) estimated by cone-beam computed tomography were statistically evaluated (p Results The survival rate in the DL group was 100% at both patient and implant levels. With only 26 subjects with 78 implants surviving in the IL group, the survival rates were 69.4% and 83.4% at the patient and implant levels, respectively, in the ITT analysis, and 78.1% and 90.2% in the PP analysis. All intergroup differences in survival rates were statistically significant (p 0.05). Conclusions IL for implants placed by fully guided surgery in the partially edentulous jaws increased the probability of failure compared to 3-month DL. Regardless of when loading occurred, marginal bone levels remained stable.

Aim To identify invasive dental procedures as a risk factor for postoperative spinal infection (PSI) and evaluate the effectiveness of antibiotic prophylaxis. Materials and Methods We analysed 229,335 patients who underwent spinal surgery with instrumentation from 2010 to 2017, using the nationwide database. The incidence of spinal infection 2 years after surgery was determined. Invasive dental procedures as a risk factor for PSI and the effects of antibiotic prophylaxis during this period were also analysed. Results A total of 15,346 patients (6.69%) were diagnosed with PSI. It was found that advanced age, male sex, and a high Charlson Comorbidity Index were risk factors for PSI. The risk of PSI did not increase following dental procedures (adjusted hazard ratio [HR] 0.850; 95% confidence interval [CI], 0.793–0.912) and was not affected by antibiotics (adjusted HR 1.097; 95% CI, 0.987–1.218). Patients who received dental treatment as early as 3 months after spinal surgery had the lowest risk of postoperative infection (adjusted HR 0.869; 95% CI, 0.795–0.950). Conclusions Invasive dental procedure does not increase the risk of PSI, and antibiotic prophylaxis before dental procedure was not effective in preventing spinal infection.

Background Clinical benefits of local antibiotics as an adjunct to nonsurgical treatment of peri-implantitis have been widely reported, but most studies evaluated incipient peri-implantitis lesions, and showed incomplete treatment success rates. Purpose To assess the clinical and microbiological outcomes of administering metronidazole in combination with minocycline as a local adjunct to the nonsurgical treatment of peri-implantitis. Materials and methods One hundred and eighteen subjects with peri-implantitis were recruited in a four-center, three-arm, and 12-week randomized controlled trial. Subjects were randomly assigned to receive one of the following treatments: (a) MM-mechanical debridement + metronidazole-minocycline ointment, (b) MC-mechanical debridement + minocycline ointment, (c) NST-mechanical debridement only. Results Except for four subjects who was excluded during the trial, a total of 114 patients with 114 implants (one implant per each patient) finally completed the trial and were included in the analyses. Multivariate logistic regression analysis revealed that the treatment success rates (absence of bleeding or suppuration on probing, and sites showing pocket probing depth [PPD] ≥5 mm) on at 12 weeks were higher in MM-group patients (31.6%) and MC-group patients (20.5%) compared to NST-group patients (2.7%; p = 0.011 and 0.040, respectively). Subjects with deepest PPD ≥8 mm showed a significant difference in the PPD reduction between MM and MC groups at week 4 (p = 0.025) and week 12 (p = 0.047). Detection ratio of Tannerella forsythia was significantly lower for MM group than MC group (p = 0.038). Conclusions Additive use of either MM or MC results in significantly higher treatment success rates compared to sole mechanical debridement in nonsurgical treatment of peri-implantitis. Moreover, MM contributes to a significantly greater reduction in the PPD compared to MC in deep pockets (cris.nih.go.kr KCT0004557).

Exosomes have been widely demonstrated as an effective anticancer therapeutic moiety. However, their clinical translation has been limited by the requirement of prohibitively high therapeutic doses due to their lack of specificity in delivery and, consequently, short systemic half-life. To overcome these challenges, we engineered a platform for modifying exosomes with an active targeting modality composed of membrane Anchor (BODIPY)-Spacer (PEG)-targeting Ligands (cyclic RGD peptide) (ASL). Herein, we show that the intramembrane incorporation of a trackable, targeting system renders ASL exosomes (AExs) a modular platform. AExs significantly overcome challenges associated with exosome modification, including potential damage for functionalization, or destabilizing interactions between dyes and drugs. ASL-modification not only enhanced stability in imparting active targeting but also introduced a built-in bioimaging modality. Our studies show that AExs target B16F10 melanoma tumor sites by the specific interaction of cyclic RGD and integrin. Doxorubicin encapsulated AExs (dAExs) significantly inhibited the growth of melanoma in vitro and in vivo. Thus, we conclude that ASL-modification allows exosomes to be transformed into a novel therapeutic vehicle uniquely integrating in vivo tracking and robust targeting with drug delivery. We anticipate that the therapeutic, targeting, and diagnostic modularity provided by ASL will potentiate translational applications of exosome-based vehicles beyond anticancer therapy.

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

The aim of this study was to investigate the association between the changes in masticatory function and cognitive impairment by analyzing longitudinal data of older Korean patients.Patients aged over 60 years with dental records between 2005 to 2010 (baseline; T1) and 2014 to 2020 (follow-up; T2) were selected in a single medical center. Based on the dementia diagnosis after T2, the cohort was classified into two groups, the dementia group (n=122) and the control group (n=366). Changes in masticatory function were calculated using the total functional tooth unit (T-FTU) in both groups. The incidence of tooth extraction (%) and the subsequent rehabilitation during the observation period were also evaluated.In the dementia group, T-FTU significantly decreased from T1 to T2 (9.81±2.78 to 9.11±3.16, respectively,There might be a causative relationship between the neglected missing dentition and the onset of dementia.

To determine whether vertical ridge augmentation (VRA) can be obtained through guided bone regeneration (GBR) using exclusively resorbable collagen membranes and particulate bone substitutes without additional stabilization.This study retrospectively examined 22 participants who underwent VRA with staged or simultaneous implant placement. The vertical defects of all participants were filled with particulate bone substitutes and covered with resorbable collagen membranes. The augmented sites were stabilized with unfixed collagen membranes and the flap without any additional fixation. The augmented tissue height was assessed using cone-beam computed tomography at baseline, immediately after surgery, and at annual follow-ups.The vertical bone gain of the 22 augmented sites amounted to 6.48 ± 2.19 mm (mean ± SD) immediately after surgery and 5.78 ± 1.72 mm at 1- to 7-year follow-up. Of the 22 augmented sites, 18 exhibited changes of less than 1 mm, while the other 4 showed changes of greater than 1 mm. Histological observation of three representative cases revealed new bone apposition on the remaining material.The present findings indicate that GBR procedures using exclusively collagen membranes and particulate biomaterials without any additional fixation are feasible options for VRA.

Highlights • Data are lacking on dengue in Africa. • This surveillance covered the beginning of a dengue outbreak in April-May 2017. • 61% of 482 patients with non-malarial fever in Mombasa were dengue-positive. • Dengue cases presented with rash, retro-orbital pain, myalgia, arthralgia, etc. • Dengue cases were mostly mild with only two cases requiring observation, and no DHF., 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.

Purpose To investigate clinical factors and cellular responses of in situ human alveolar bone-derived mesenchymal stromal cells involved in early periimplant marginal bone loss. Materials and methods Thirty-seven completely or partially edentulous patients were enrolled in this study. Periapical radiographs were taken at the time of implant surgery, at 3-month follow-up, and at 1-year follow-up. Univariate analysis and multiple logistic regression were performed to investigate the associations between marginal bone loss and study variables. The mRNA expression levels of 21 bone-remodeling- and tissue-healing-associated genes were analyzed by subgroup. Results Thirty-one patients with 98 implants were followed. The incidence and mean amount of bone loss were higher for overdentures than for other prosthesis and higher for the maxilla than for the mandible. The bone loss group showed lower mRNA expression levels of runt-related transcription factor-2, bone morphogenetic protein-2, and peroxisome proliferator-activated receptor gamma-2 and higher receptor activator of NKκB ligand/osteoprotegerin (RANKL/OPG) ratio. Conclusion Within the limitations of the study, certain genes involved in bone remodeling (runt-related transcription factor-2 [Runx-2], bone morphogenetic protein-2 [BMP-2], and peroxisome proliferator-activated receptor gamma-2 [PPARγ-2]) and RANKL/OPG are correlated with early periimplant bone loss, with the type of suprastructure and the involved jaw being significant clinical factors.

Background To evaluate gingival inflammation from fixed-dose combinations of vitamin C, vitamin E, lysozyme and carbazochrome (CELC) in the treatment of chronic periodontitis following scaling and root planing. Methods One hundred patients were randomly assigned to receive CELC (test) or placebo (control) for the first 4 weeks at a 1:1 ratio, and both groups received CELC for the remaining 4 weeks. Primary outcome was the mean change in the gingival index (GI) after 4 weeks. Secondary outcomes included mean change in GI after 8 weeks and plaque index, probing depth, clinical attachment level, and VAS at 4 weeks and 8 weeks. Results Ninety-three patients completed the study. The GI in the test group significantly decreased after 4 weeks (p

Background Invasive non-typhoidal Salmonella (iNTS) is a growing health-concern in many parts of sub-Saharan Africa. iNTS is associated with fatal diseases such as HIV and malaria. Despite high case fatality rates, the disease has not been given much attention. The limited number of population-based surveillance studies hampers accurate estimation of global disease burden. Given the lack of available evidence on the disease, it is critical to identify high risk areas for future surveillance and to improve our understanding of iNTS endemicity. Methods Considering that population-based surveillance data were sparse, a composite index called the iNTS risk factor (iNRF) index was constructed based on risk factors that commonly exist across countries. Four risk factors associated with the prevalence of iNTS were considered: malaria, HIV, malnutrition, and safe water. The iNRF index was first generated based on the four risk factors which were collected within a 50 km radius of existing surveillance sites. Pearson product-moment correlation was used to test statistical associations between the iNRF index and the prevalence of iNTS observed in the surveillance sites. The index was then further estimated at the subnational boundary level across selected countries and used to identify high risk areas for iNTS. Results While the iNRF index in some countries was generally low (i.e. Rwanda) or high (i.e. Cote d’Ivoire), the risk-level of iNTS was variable not only by country but also within a country. At the provincial-level, the highest risk area was identified in Maniema, the Democratic Republic of Congo, whereas Dakar in Senegal was at the lowest risk. Conclusions The iNRF index can be a useful tool to understand the geographically varying risk-level of iNTS. Given that conducting a population-based surveillance study requires extensive human and financial resources, identifying high risk areas for iNTS prior to a study implementation can facilitate an appropriate site-selection process in the future.

Magnetic resonance is a key imaging tool for the detection of prostate cancer; however, better tools focusing on cancer specificity are required to distinguish benign from cancerous regions. We found higher expression of claudin-3 (CLDN-3) and -4 (CLDN-4) in higher grade than lower-grade human prostate cancer biopsies (n = 174), leading to the design of functionalized nanoparticles (NPs) with a non-toxic truncated version of the natural ligand Clostridium perfringens enterotoxin (C-CPE) that has a strong binding affinity to Cldn-3 and Cldn-4 receptors. We developed a first-of-its-type, C-CPE-NP-based MRI detection tool in a prostate tumor-bearing mouse model. NPs with an average diameter of 152.9 ± 15.7 nm (RS1) had a 2-fold enhancement of tumor specificity compared to larger (421.2 ± 33.8 nm) NPs (RS4). There was a 1.8-fold (P 0.01) and 1.6-fold (P 0.01) upregulation of the tumor-to-liver signal intensities of C-RS1 and C-RS4 (functionalized NPs) compared to controls, respectively. Also, tumor specificity was 3.1-fold higher (P 0.001) when comparing C-RS1 to C-RS4. This detection tool improved tumor localization of contrast-enhanced MRI, supporting potential clinical applicability.

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

To use resonance frequency analysis to evaluate tapered implants placed at maxillary posterior sites after lateral sinus augmentation.Patients who had missing teeth in the maxillary posterior area and required lateral sinus augmentation before implant placement were enrolled in this study. After a 6-month healing period, a tapered implant (Osstem TSIV) was placed. Implant success rate, survival rate, and marginal bone loss of the implants were measured. For resonance frequency analysis, implant stability quotient (ISQ) values were measured at each visit during a 1.5-year follow-up period.Twenty-four patients completed the study procedure. The residual bone height was 2.57 ± 1.10 mm (mean ± SD). Healing of the grafted area was uneventful in all cases, and 55 tapered implants were installed. The implant success rate was 95.56%, and the survival rate was 100% throughout the observation period. The marginal bone loss was limited to 0.22 ± 0.44 mm. ISQ increased gradually from 68.40 ± 11.14 to 82.24 ± 4.75 during the 1.5-year follow-up period.The tapered implants showed good initial and final stability after placement in the soft bone of the maxillary posterior area after lateral sinus augmentation.

Lamprey, one of the living representatives of jawless vertebrates, uses variable lymphocyte receptors B (VLRB) for antigen recognition, rather than immunoglobulin (Ig) based receptors as used by higher vertebrates. The C-terminus of lamprey VLRB (LC) possess a glycosylphosphatidylinositol (GPI) signal sequence and seven cysteine residues providing dual functionality of the VLRB antibody in the form of a humoral agglutinin and cell membrane receptors. Here, we show that the LC can be either secreted or be membrane anchored as a heterologous fused protein in a multimeric form comprising of eight or ten monomeric units. Using serially truncated LC variants, we showed that the LC, in which the last three amino acid "RKR" were deleted, referred to as LC7, was the most suitable domain for multimeric construction, whereas, the intact LC is more tailored for applications involving membrane anchorage. We show that an antibody specific for viral hemorrhagic septicemia virus (VHSV) (VLR43), displayed on HEK-293F cells using a PiggyBac (PB) transposase system, exhibited a dose-dependent reaction with its antigen, verifying that the LC can be applied in antibody display technology. Therefore, the present report provides valuable insight into the structure of the lamprey VLRB and highlights its potential use as a novel fusion partner for multimerization and membrane anchorage of chimeric proteins.

The variable lymphocyte receptor (VLR) B of jawless vertebrates functions as a secreted Ab of jawed vertebrates and has emerged as an alternative Ab with a single polypeptide chain. After observing an upregulated VLRB response in hagfish immunized with avian influenza virus (AIV) subtype H9N2, we screened AIV H9N2–specific VLRB using a mammalian expression system. To improve the binding avidity of the Ag-specific VLRB to the Ag, we enabled multimerization of the VLRB by conjugating it with C-terminal domain of human C4b-binding protein. To dramatically enhance the expression and secretion of the Ag-specific VLRB, we introduced a glycine–serine linker and the murine Ig κ leader sequence. The practical use of the Ag-specific VLRB was also demonstrated through various immunoassays, detected by anti-VLRB Ab (11G5). Finally, we found that the Ag-specific VLRB decreased the infectivity of AIV H9N2. Together, our findings suggest that the generated Ag-specific VLRB could be used for various immunoapplications.

Objectives To evaluate dimensional ridge alterations and sequential healing processes following ridge augmentation after tooth extraction in damaged extraction sockets with buccal-bone-deficiency. Material and methods Bilateral dental roots of three mandibular premolars were extracted with entire removal of the buccal-bone plate in eight beagle dogs. Unilateral sites were grafted with biomaterials (test group) and contralateral sites were healed without grafting (control group). Observations were made after 1, 2, 4, and 8 weeks, and all sites were distributed evenly (n = 6 for each group and period). Radiographic/histomorphometric analyses were performed. Results In spontaneous healing of damaged extraction sockets, the dimension of regenerated alveolar ridge gradually increased until 4 weeks and then remained stable, but radiographic/histomorphometric analyses revealed evident dimensional shrinkage compared to the pristine tissue at 8 weeks in the coronal and middle areas. Bone grafting retained the pristine dimension of alveolar ridge, and newly formed bone area within the augmented space continuously expanded during the observational period to the outermost border of the space. Conclusions Spontaneous healing of damaged extraction sockets caused substantial dimensional shrinkage. However, ridge augmentation can provide space into which new bone may grow continuously, resulting in the final dimensions comparable to those of the pristine alveolar ridge.

Backgrounds Clinical benefits in bone grafting of intact extraction socket have been widely known, but limited evidence is available for the procedure in damaged extraction sockets due to periodontal disease. Purpose This study aimed to determine the dimensional alteration of alveolar ridge following bone grafting of damaged extraction sockets, and compare the outcomes of using deproteinized bovine (DBBM) versus porcine bone mineral (DPBM) in the damaged sockets. Materials and Methods One hundred patients (n = 50 for each group) with periodontitis‐induced damaged extraction socket were included in this randomized, single‐blind trial. After removal of tooth and granulation tissue, sites were grafted with either DBBM (DBBM group) or DPBM (DPBM group), and covered with collagen membrane. Linear/volumetric analyses of hard and soft‐tissue dimensions were performed on reconstructed/superimposed computed tomography and scanned cast images, taken immediately and 4 months after surgery. Results The two groups showed comparable hard tissue augmentation with minimal reductions in the grafted volume, as well as in vertical (1.22 ± 2.16 and 1.45 ± 1.92 mm for DPBM and DBBM group, respectively) and horizontal (1.43 ± 3.40 and 1.83 ± 2.85 mm on the central section, respectively) dimensions at 4 months after surgery. However, several cases showed large variations in maintenance of the grafted volume. None of the measured parameters in hard and soft tissue dimensions differed significantly between DBBM and DPBM sites. Conclusions DBBM and DPBM can comparably augment damaged extraction sockets with minimal postoperative reduction of the grafted volume. However, the large variations in the results should be further evaluated for application in routine dental clinics.

Variable lymphocyte receptors B (VLRBs) are non-immunoglobulin components of the humoral immune system in jawless vertebrates including hagfish (Eptatretus burgeri) and lamprey (Petromyzon marinus). Hagfish VLRBs consist of leucine rich repeat (LRR) modules with a superhydrophobic C-terminal tail, the latter of which leads to extremely low expression levels in recombinant protein technology. Here, we present an artificially oligomerized VLRB (arVLRB) that conjugates via the C4bp oligomerization domain derived from human C4b-binding protein (hC4bp) rather than the superhydrophobic tail. The resulting arVLRB had a tightly multimerized form with seven monomeric VLRB arms and showed high expression and secretion levels in a mammalian expression system. To isolate antigen-specific arVLRB, we constructed large VLRB libraries from hagfish immunized with the fish pathogen, viral hemorrhagic septicemia virus (VHSV). The selected arVLRBs were found to recognize various types of antigens, including the recombinant target protein, purified viruses, and progeny viruses, with high antigen binding abilities and specificities. We also performed in vitro affinity maturation of the arVLRBs through LRRCT mutagenesis, and found that this enhanced their antigen-binding properties by at least 125-fold. Our epitope mapping analysis revealed that 37DWDTPL42, which is located in a region conserved among the glycoproteins of all VHSV isolates, is the recognition epitope of the arVLRBs. Thus, our newly developed arVLRB could prove useful in the development of universal diagnostic tools and/or therapeutic agents for the virus. Together, our novel findings provide valuable insights into hagfish VLRB and its potential use as a novel alternative to conventional antibodies for biotechnological applications.

This study is designed to determine the effect of collagen membrane (CM) soaked with bone morphogenetic protein-2 (rhBMP-2) for the treatment of peri-implant dehiscence defects. Material and Methods. Three treatment groups were allocated at each defect in 5 dogs: (i) collagenated synthetic bone (OC) and CM soaked with rhBMP-2 (BMP group), (ii) OC and CM soaked with saline (nonBMP group), and (iii) no further treatment (control group). Titanium pins were used to stabilize the membranes in two dogs. Radiographic and histomorphometric analyses were performed 4 weeks later. Results. The median augmented volumes were 4.27 mm3, 6.24 mm3, and 2.75 mm3 in the BMP, nonBMP, and control groups, respectively; the corresponding median first bone-to-implant contact (fBIC) distances were 3.25 mm, 3.08 mm, and 2.56 mm (P>0.05). The placement of pins (with the BMP and nonBMP groups pooled) significantly improved bone regeneration: the augmented volumes were 17.60 mm3 with pins and 3.68 mm3 without pins (P=0.024), with corresponding fBIC distances of 2.25 mm and 3.31 mm, respectively (P<0.001). Conclusions. The addition of rhBMP-2 to CM failed to improve bone regeneration of peri-implant dehiscence defects compared to using an unsoaked CM after 4 weeks. However, the stabilization of CMs using pins positively influenced the outcomes.

This study aimed to determine the cellular characteristics and behaviors of human bone marrow stromal cells (hBMSCs) expanded in media in a hypoxic or normoxic condition and with or without fibroblast growth factor-2 (FGF-2) treatment. hBMSCs isolated from the vertebral body and expanded in these four groups were evaluated for cellular proliferation/migration, colony-forming units, cell-surface characterization, in vitro differentiation, in vivo transplantation, and gene expression. Culturing hBMSCs using a particular environmental factor (hypoxia) and with the addition of FGF-2 increased the cellular proliferation rate while enhancing the regenerative potential, modulated the multipotency-related processes (enhanced chondrogenesis-related processes/osteogenesis, but reduced adipogenesis), and increased cellular migration and collagen formation. The gene expression levels in the experimental samples showed activation of the hypoxia-inducible factor-1 pathway and glycolysis in the hypoxic condition, with this not being affected by the addition of FGF-2. The concurrent application of hypoxia and FGF-2 could provide a favorable condition for culturing hBMSCs to be used in clinical applications associated with bone tissue engineering, due to the enhancement of cellular proliferation and regenerative potential. Keywords: Bone marrow stromal cells, Hypoxia, Fibroblast growth factor, Tissue regeneration, Microenvironment interactions

Background To determine the seroprevalence and transmission dynamics of dengue virus (DENV), age-stratified longitudinal serological surveys were conducted in Bangphae district, Ratchaburi province, Thailand, for 3 years between April 2012 and April 2015. Methodology The surveys enrolled 2012 healthy children and adults between 1 and 55 years-of-age, and a longitudinal serosurvey of six repeated bleeds of the same cohort of individuals was conducted every 8 months for the first 2 years (M0, M8, M16) and every half a year (M24, M30, M36) for the rest of the study period. All samples were tested using in-house indirect sandwich dengue IgG ELISA to determine DENV antibody titer, and 640 paired samples which showed rising of DENV IgG titers in paired serum were further tested using in-house neutralization assay, Plaque Reduction Neutralization Test (PRNT50). Principal findings When compared against the gold standard based on the results of PRNT50, sensitivity and specificity of indirect ELISA were found to be both about 85%. The overall DENV IgG positivity determined by ELISA was 74.3% in 2012 and increased to 79.4% by the final sample collection in 2015. In our study sample, more than 98% of subjects older than 25 years were found to be seropositive. Among 518 IgG negative subjects at enrollment, the seroconversion rates were measured in paired bleeds; the rates (between successive visits, approximately 6 months) ranged between 4.8% (between M16 and M24) and 14.7% (between M0 and M8). The dominant serotype of primary DENV infection cases based on seroconversion was identified from the PRNT results and it was DENV-2. Conclusions Our study documented high levels of seroprevalence and rate of transmission. Given the importance of the serostatus and disease burden in consideration for dengue vaccine introduction, our data could be used in decision-making on implementation of various dengue control and preventive measures., Author summary To estimate the proportion of individuals with past exposure to dengue virus (DENV), we conducted repeated serological surveys in Bangphae district, Ratchaburi province, Thailand, between April 2012 and April 2015. About 45% of the subjects were under 15 years-of-age. The surveys enrolled 2012 healthy individuals between 1 and 55 years-of-age, and a longitudinal serosurvey of six repeated bleeds of the same cohort of individuals was conducted approximately every 6 months. All samples were tested using an indirect dengue IgG ELISA and a subset of paired samples which showed rising of IgG values in pairs were tested using neutralization assay, used as the gold standard. When compared against the gold standard, sensitivity and specificity of indirect ELISA were found to be both 85%. The proportion of the study population with past DENV infection measured by IgG ELISA was 74.3% in 2012 and increased to 79.4% by 2015. More than 98% of subjects older than 25 years showed to have past exposure to dengue. Among 518 subjects without past exposure, the rate of getting infection was between 4.8–14.7% (between successive visits, approximately 6 months). The dominant serotype was DENV-2. The level of proportion of individuals with past DENV infection is an important consideration, and our data could be used in decision-making for dengue vaccine introduction.

To retrospectively determine the profile of the sinus membrane (SM), potential factors affecting SM thickening (SMT), and the correlation between SMT and sinus augmentation (SA) complications.In the patients who received lateral SA, SMT was classified in sagittal sections of cone-beam computed tomography according to its thickness and morphology. The correlation between SMT and the following factors was analyzed: age, sex, endodontic and periodontic statuses of neighboring teeth, and shape of the sinus inferior border. The association between SMT and SA complications was investigated.SMT of ≤2 mm was prevalent (60%). Irregular SM was mostly observed for SMT of2 mm. There was no statistically significant association between SMT and the included factors. SMT did not significantly correlate with either perforation or postoperative complications. There was a statistically significant increase in implant failure when SMT was2 mm, but it was hard to determine that the failure was solely affected by SMT.SMT was not influenced by the factors included in this study, and it might not be a risk factor for SA and implant failure.

The objective of this study was to determine the validity of a graft-free sinus floor elevation (SFE) procedure with simultaneous placement of recombinant morphogenetic protein-2 (rhBMP-2)-coated implants compared to uncoated control implants. In 10 rabbits, SFE was performed on both sides. Dental implants were randomly placed in the sinus filled with a blood clot. Test implants were coated with rhBMP-2, whereas in the control group, implants were uncoated. Micro-computed tomographic and histomophometric analyses were performed at 4 and 8 weeks, including measurement for newly formed bone height (NBHm). Bone formation was evident along the implant surfaces up to the apex in test, but limited in control implants at 4 weeks. NBHm amounted to 5.1 mm (Q1 = 4.1; Q3 = 5.3) for test implants and to 3.4 mm (2.6; 3.7) for control implants at 4 weeks. NBHm then decreased to 8 weeks (3.4 mm (3.3; 3.7)) for test implants, whereas in control sites, NBHm increased slightly to 4.4 mm (4.1; 4.5) (p = 0.1250; p = 0.6250). Implants coated with rhBMP-2 presented a strong osteogenic reaction at 4 weeks with more favorable outcomes in terms of bone formation along the implant surface up to the apex compared to uncoated control implants. Remodeling and resorption process between 4 and 8 weeks did not further improve the outcomes in the test, but in the control group. The use of rhBMP-2-coated implants in a graft-free SFE might show an advantage in early implant stability to prevent collapse of membrane. However, a potential clinical benefit still needs to be proven.

A Typhoid Conjugate Vaccine (TCV) is expected to acquire WHO prequalification soon, which will pave the way for its use in many low- and middle-income countries where typhoid fever is endemic. Thus it is critical to forecast future vaccine demand to ensure supply meets demand, and to facilitate vaccine policy and introduction planning. We forecasted introduction dates for countries based on specific criteria and estimated vaccine demand by year for defined vaccination strategies in 2 scenarios: rapid vaccine introduction and slow vaccine introduction. In the rapid introduction scenario, we forecasted 17 countries and India introducing TCV in the first 5 y of the vaccine's availability while in the slow introduction scenario we forecasted 4 countries and India introducing TCV in the same time period. If the vaccine is targeting infants in high-risk populations as a routine single dose, the vaccine demand peaks around 40 million doses per year under the rapid introduction scenario. Similarly, if the vaccine is targeting infants in the general population as a routine single dose, the vaccine demand increases to 160 million doses per year under the rapid introduction scenario. The demand forecast projected here is an upper bound estimate of vaccine demand, where actual demand depends on various factors such as country priorities, actual vaccine introduction, vaccination strategies, Gavi financing, costs, and overall product profile. Considering the potential role of TCV in typhoid control globally; manufacturers, policymakers, donors and financing bodies should work together to ensure vaccine access through sufficient production capacity, early WHO prequalification of the vaccine, continued Gavi financing and supportive policy.

Background Various biomaterials have been introduced for vertical ridge augmentation to replace autogenous block bone grafting. Purpose This retrospective study radiographically evaluated dimensional alterations of the vertically augmented alveolar ridge using collagen membrane and 3 types of materials: autogenous bone block, allogenous bone block, and particulated bone substitute. Materials and methods The electronic medical records of 32 patients who received vertical ridge augmentation using 3 types of materials were searched: 9 for autogenous bone block, 12 for allogenous bone block, and 11 for particulated bone substitutes. The vertical bone gain, progression of bone resorption, and peri-implant marginal bone loss after prosthetic loading were measured on follow-up radiographs. Results The alveolar ridge was vertically augmented by 5.13 ± 1.61, 4.54 ± 2.48, and 3.90 ± 0.85 mm (mean ± standard deviation) after grafting with autogenous bone block, allogenous bone block, and particulated bone substitute, respectively. The radiographic vertical height of the augmented ridge that received autogenous bone block reduced continuously during the first year but was stable thereafter. Sites that received allogenous bone block or particulated bone substitute exhibited dimensional shrinkage for up to 1.5 years postsurgery. However, the peri-implant marginal bone loss did not exceed 1 mm throughout the observational periods in all groups. Conclusions The clinical findings of this study suggest that the alveolar ridge can be vertically augmented using either allogenous bone block or particulated bone substitute. However, they require a longer healing period to ensure dimensional stability compared to the autogenous bone block.

Purpose The aim of this study was to radiographically compare horizontal and vertical alterations of the alveolar ridge after ridge preservation using different combinations of biomaterials. Materials and methods The patients were randomly assigned into two groups: (a) the test group, which received collagenated porcine bone plus cross-linked collagen membrane (n = 15), and (b) the control group, which received collagenated bovine bone plus non-cross-linked collagen membrane (n = 15). Cone beam computed tomography (CBCT) was performed immediately after ridge preservation and 4 months thereafter to compare the horizontal and vertical alterations of the ridge. Intention-to-treat (ITT) and per protocol (PP) analyses were performed. Results In both analyses, there was no statistically significant difference in the horizontal alteration of the alveolar ridge between the test and control groups: −1.3 ± 0.6 (ITT)/1.2 ± 0.5 (PP) vs. −1.5 ± 0.9 mm at the 1-mm level; −1.2 ± 0.7 (ITT and PP) vs. −1.2 ± 0.7 mm at the 3-mm level; and −0.9 ± 0.7 (ITT)/ −0.9 ± 0.7 (PP) vs. −0.9 ± 0.9 mm at the 5-mm level, whereas the vertical height in the midfacial area was significantly reduced in the test group compared with the control group: −-1.1 ± 2.8 (ITT)/1.5 ± 3.0 (PP) vs. −0.7 ± 1.8 mm. Conclusions The horizontal ridge alteration in ridge preservation did not differ significantly between using the test the control groups, but the vertical ridge alteration was more pronounced when using the test group (KCT0001709).

Background Dengue is a major public health problem in the tropics and sub-tropics, but the disease is less known to non-dengue-endemic countries including in Northeast Asia. However, an unexpected dengue outbreak occurred in 2014 in Japan. Given that autochthonous (domestic) dengue cases had not been reported for the past 70 years in Japan, this outbreak was highly unusual and suggests that several environmental factors might have changed in a way that favors vector mosquitoes in the Northeast Asian region. Methods A Climate Risk Factor (CRF) index, as validated in previous work, was constructed using climate and non-climate factors. This CRF index was compared to the number of reported dengue cases in Tokyo, Japan where the outbreak was observed in 2014. In order to identify high-risk areas, the CRF index was further estimated at the 5 km by 5 km resolution and mapped for Japan and South Korea. Results The high-risk areas determined by the CRF index corresponded well to the provinces where a high number of autochthonous cases were reported during the outbreak in Japan. At the provincial-level, high-risk areas for dengue fever were the Eastern part of Tokyo and Kanakawa, the South-Eastern part of Saitama, and the North-Western part of Chiba. While a relatively small number of high-risk areas were identified in South Korea compared with Japan, the high-risk areas in South Korea include popular tourist destinations where international visitors have been increasing. Conclusion The recent dengue outbreak in Japan may signal that the two adjacent non-dengue-endemic countries are also exposed to the risk of temporal and sporadic behavior of dengue fever. It is critical to understand potential high-risk areas for future outbreaks and to set up appropriate prevention activities at the governmental-level.

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.

Background Calcium phosphate (CaP)-coated surface showed enhanced contact osteogenesis around dental implant and finally accelerate osseointegration in early healing phase. Purpose The aim of this randomized controlled trial was to compare the peri-implant marginal bone level around uncoated and CaP-coated sandblasted, large-grit, acid-etched (SLA) surface implants during the first year after placement. Materials and methods This study was performed upon 34 patients with randomized and double-blinded design. Clinical and radiographic examinations were performed immediately after implant placement, at re-entry after 3 months, and after 12 months to evaluate the initial stability and change in the marginal bone level. The distance from the implant shoulder to the top of the bone-to-implant contact was defined as the marginal bone level, and its alteration was measured at 1 year after implant installation. Results None of the implants failed, and most of them showed a marginal bone loss of less than 1 mm. Small changes in the bone level were noted at all sites in the control and test groups, and there were no clinically significant differences in the changes in the marginal bone. Conclusion Both CaP-coated and uncoated SLA surface implants showed comparably successful marginal bone stability without any complications during the first year after placement.

Background Dengue is a major public health problem in Thailand, but data are often focused on certain dengue-endemic areas. Methods: To better understand dengue epidemiology and clinical characteristics in Thailand, a fever surveillance study was conducted among patients aged 1–55 years, who presented with non-localized febrile illness at Bang Phae Community Hospital in Ratchaburi province, Thailand from October 2011 to September 2016. Results Among 951 febrile episodes, 130 were dengue-confirmed. Individuals aged 10–14 years were mostly affected, followed by those 15–19 years-of-age, with about 15% of dengue-confirmed cases from adults 25 years and older. There were annual peaks of dengue occurrence between June-November. Most prevalent serotype in circulation was DENV-2 in 2012, DENV-3 in 2014, and DENV-4 & -3 in 2015. Among dengue cases, 65% were accurately detected using the dengue NS1 RDT. Detection rate was similar between secondary and primary dengue cases where 66% of secondary vs. 60% of primary dengue cases had positive results on the NS1 RDT. Among dengue cases, 66% were clinically diagnosed with suspected dengue or DHF, prior to lab confirmation. Dengue was positively associated with rash, headache, hematemesis and alterations to consciousness, when compared to non-dengue. Dengue patients were 10.6 times more likely to be hospitalized, compared to non-dengue cases. Among dengue cases, 95 were secondary and 35 were primary infections. There were 8 suspected DHF cases and all were identified to be secondary dengue. Secondary dengue cases were 3.5 times more likely to be hospitalized compared to primary dengue cases. Although the majority of our dengue-positive patients were secondary dengue cases, with few patients showing manifestations of DHF, our dengue cases were mostly mild disease. Even among children < 10 years-of-age, 61% had secondary infection and the rate of secondary infection increased with age. Conclusion While the majority of dengue-confirmed cases were children, almost three-quarters of dengue-confirmed cases in this study were secondary dengue. Our study results consistent with previous data from the country confirm the hyperendemic transmission of DENV in Thailand, even in the non-epidemic years. With various interventions becoming available for dengue prevention and control, including dengue vaccines, decision-making on future implementation strategies should be based on such burden of disease data., Author summary Dengue is a well-known public health problem in Thailand. To identify epidemiologic and clinical patterns of dengue in Thailand, we studied 951 febrile patients with fever, aged 1–55 years, who attended Bang Phae district hospital in Ratchaburi province, Thailand. Patients were tested with a rapid test for dengue, and further tests were carried out on paired blood samples taken 10–21 days apart. Overall, 14% of the febrile episodes identified between October 2011 and September 2016 were dengue-confirmed. Teenagers were mostly affected with only few adults. Dengue peaks occurred between June-November, but there was no large epidemic during the study period. DENV type 2 was the main serotype in circulation in 2012, DENV type 3 in 2014, and DENV types 4 and 3 in 2015. Dengue cases were 11 times more likely to be hospitalized than non-dengue cases. Dengue patients were more likely to present with rash, headache, hematemesis and alterations to consciousness, compared to non-dengue. Two thirds of the dengue cases were clinically diagnosed with suspected dengue or DHF, even without lab confirmation. Secondary dengue cases were about three times more common than primary cases. Even among children < 10 years-of-age, 61% of the patients were of secondary infection. Among dengue cases, 65% were accurately detected using the dengue RDT. This was not different between secondary and primary dengue cases. All 8 patients clinically diagnosed with DHF were secondary dengue cases. Although most of our dengue-positive patients were secondary dengue cases, we only observed few patients showing DHF. Thus, we concluded that our dengue cases were mostly of mild dengue illness. Our study results support the previous data confirming the high burden of dengue in Thailand and such information would help to make decisions on future implementation of various tools for dengue prevention and control.

Subluxation of the extensor tendon results from a disruption to the sagittal band at the metacarpophalangeal joint. When conservative treatment fails to correct the subluxation, surgical treatment may be necessary. Surgical techniques for chronic cases vary in graft source and graft pathway. We present a surgical technique to recentralize and stabilize the extensor tendon using a residual ruptured sagittal band. This technique is simple and effective without donor site morbidity and seems to provide potential biomechanical advantages by restoring nearly normal anatomy.

Centrifugation based on density gradients is a general methodology for isolating human bone marrow (hBM)-derived mesenchymal stem cells (hBMSCs). The mononuclear cell (MNC) layer can be obtained using a density gradient solution in the conventional protocol, but it is not suitable for direct transplantation due to the possible toxicity of this solution. The results obtained are also influenced by the skill level when applying the technique, which involves time-consuming processes. We have developed a novel protocol for isolating hBMSCs using hyaluronic acid (HA), which is the most widely used injectable biomaterial in clinical settings and a major component of the extracellular matrix. Laying hBM over the HA and then applying centrifugation yielded three separate layers, with the HA layer, including MNCs being the most superficial one. Increasing the volume of HA and/or its crosslinking rate enhanced the yield of MNCs from hBM, and the cell yield was also significantly higher for a lower centrifugal acceleration (530 g) than for a higher one (1500 g). Isolated hBMSCs by HA exhibited similar biological characteristics such as in terms of their proliferation rate, fibroblast-like morphology, cell-cycle status, immunophenotype, and multipotency. The use of either type of hBMSC confirmed the regenerative potential of bone and bone marrow-like tissue in ectopic transplantation models. This is the first report of a novel protocol for isolating hBMSCs that utilize HA. We suggest that this novel isolation technique can be used for the direct application of autogenous MSCs with advantages of being less time-consuming and involving steps that are easier to perform.

Objectives The aim of this study was to evaluate the hybrid technique, which was modified from the lateral approach in sinus elevation by combining transalveolar access. Materials and methods Sixty patients (mean age of 53.3 ± 11.6 years) with 105 implants placed in the posterior maxilla with the average remaining bone height (RBH) of 4.3 ± 1.8 mm (range of 1.2–9.2 mm) were enrolled in the hybrid group and followed up for 96 months. The control group included 36 patients with 44 implants placed in the corresponding site with sufficient RBH. Cumulative survival rate (CSR), radiographic measurements in RBH, augmented bone height (ABH), and marginal bone loss (MBL) were analyzed during the follow-up period. Results Cumulative survival rate in the hybrid group was 98.1%, which was comparable to the control group (97.7%). MBL of the mesial and distal aspects in the hybrid group (0.28 ± 0.66 mm and 0.41 ± 0.93 mm, respectively) was comparable to the control group (0.84 ± 1.11 mm and 0.76 ± 0.88 mm, respectively). In the hybrid group, the membrane perforation rate during the surgery was 4.5%. ABH was 8.3 ± 1.8 mm after the surgery and maintained consistently during the follow-up period (7.4 ± 1.9 mm after 4 years). Conclusion The hybrid technique is a simple and predictable surgical method for simultaneous placement of a dental implant with sinus floor elevation regardless of the RBH.

Nanoparticle-based imaging and therapy are of interest for theranostic nanomedicine. In particular, superparamagnetic iron oxide (SPIO) nanoparticles (NPs) have attracted much attention in cancer imaging, diagnostics, and treatment because of their superior imagability and biocompatibility (approved by the Food and Drug Administration). Here, we developed SPIO nanoparticles (NPs) that self-assembled into magnetic nanoclusters (SAMNs) in aqueous environments as a theranostic nano-system. To generate multi-functional SPIO NPs, we covalently conjugated β-cyclodextrin (β-CD) to SPIO NPs using metal-adhesive dopamine groups. Polyethylene glycol (PEG) and paclitaxel (PTX) were hosted in the β-CD cavity through high affinity complexation. The core-shell structure of the magnetic nanoclusters was elucidated based on the condensed SPIO core and a PEG shell using electron microscopy and the composition was analyzed by thermogravimetric analysis (TGA). Our results indicate that nanocluster size could be readily controlled by changing the SPIO/PEG ratio in the assemblies. Interestingly, we observed a significant enhancement in magnetic resonance contrast due to the large cluster size and dense iron oxide core. In addition, tethering a tumor-targeting peptide to the SAMNs enhanced their uptake into tumor cells. PTX was efficiently loaded into β-CDs and released in a controlled manner when exposed to competitive guest molecules. These results strongly indicate that the SAMNs developed in this study possess great potential for application in image-guided cancer chemotherapy. Statement of Significance In this study, we developed multi-functional SPIO NPs that self-assembled into magnetic nanoclusters (SAMNs) in aqueous conditions as a theranostic nano-system. The beta-cyclodextrin (β-CD) was immobilized on the surfaces of SPIO NPs and RGD-conjugated polyethylene glycol (PEG) and paclitaxel (PTX) were hosted in the β-CD cavity through high affinity complexation. We found that nanocluster size could be readily controlled by varying the SPIO/PEG ratio in the assemblies, and also demonstrated significant improvement of the functional nanoparticles for theranostic systems; enhanced magnetic resonance, improved cellular uptake, and efficient PTX loading and sustained release at the desired time point. These results strongly indicate that the SAMNs developed in this study possess great potential for application in image-guided cancer chemotherapy.

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, Author summary In Africa, information on dengue is limited to outbreak reports focused on some countries 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 health facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings, Gabon. Among the patients with negative malaria RDT results, those with current fever or history of fever (≤7 days) between 1 and 55 years of age were enrolled at Albert Schweitzer Hospital (ASH). Two samples were collected with an interval of 10 to 21 days after enrollment. Samples underwent different testing for dengue confirmation. Among 682 febrile patients enrolled, 17.4% were identified as dengue-positive. Of these dengue-positive cases, we found DENV-2 and DENV-3 serotypes. Close to 80% of our dengue-positive cases were < 15 years old. Retro-orbital pain and abdominal pain were more commonly found among dengue-positive cases, compared to non-dengue cases. Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Clinicians should consider dengue more frequently among non-malarial febrile patients. Given the lack of data on dengue in Gabon, more data should be generated to understand the burden and patterns of dengue for improved case detection.

The purpose of this study was to determine the clinical, microbial, and radiographic effects of local minocycline combined with surgical treatment of peri-implantitis. Fifty patients with peri-implantitis were recruited, and surgical treatment with the local application of either minocycline or placebo ointment was performed. The application of minocycline was repeated with supragingival debridement at 1, 3, and 6 mo postoperatively. Plaque index, gingival index (GI), probing pocket depth (PPD), and bleeding/suppuration on probing were measured at baseline and 1-, 3-, and 6-mo evaluations. The change in supporting bone level (SBL) measured with cone beam computed tomography was analyzed between baseline and 6 mo. Microbial analysis was performed with real-time polymerase chain reaction. Both groups exhibited improvements in clinical and radiographic measurements after surgical treatment. There was a significant difference in the changes of mean PPD between the test and control groups (2.68 ± 1.73 and 1.55 ± 1.86 mm, respectively, P = 0.039). The changes of mean GI and SBL differed significantly between the groups (ΔGI: 0.83 ± 0.60 and 0.40 ± 0.68; ΔSBL: 0.72 ± 0.56 and 0.31 ± 0.49 mm, respectively, P = 0.026 and 0.014). Treatment success rates (defined as PPD

Invasive non-typhoidal Salmonella (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the breadth of blood culture-based surveillance systems that are able to accurately diagnose the etiology of bacteremia. The accessibility of whole genome sequencing has allowed for genetic characterization of pathogens, shedding light on its evolutionary history and sounding alerts for its future progression. iNTS disease is observed to be a particular threat in sub-Saharan Africa, with a case fatality rate greatly exceeding that of typhoid fever, and commonly affecting infants, young children and immunocompromised adults. While iNTS disease might also be a threat in Asia and Latin America, its burden is not well characterized, primarily owing to the lack of comprehensive reporting in these regions. Drug-resistant Salmonella enterica (S. enterica) serovars (e.g. Typhimurium sequence type 313 (ST313)) have emerged as a potential consequence of sustained antibiotic pressure. Genetic analyses have identified distinguished iNTS disease-causing strains that are particularly virulent in certain human host populations. Effective treatment strategies, including vaccination, are necessary; iNTS vaccines targeting the most common S. enterica serovars, Typhimurium, Enteritidis and Dublin, are currently in early developmental stages. Funding and political support is needed to promote vaccine development and implementation programs to ultimately reduce the threat of iNTS disease in high risk areas.

Background The dengue vaccination era began when Dengvaxia (CYD-TDV) became available in 2016. In addition, several second-generation vaccine candidates are currently in phase 3 trials, suggesting that a broader availability of dengue vaccines may be possible in the near future. Advancing on the recent WHO-SAGE recommendations for the safe and effective use of CYD-TDV at the regional level on average, this study investigates the vaccination impacts and cost-effectiveness of CYD-TDV and of a hypothetical new vaccine candidate (NVC) in a country-specific manner for three endemic countries: Vietnam, Thailand, and Colombia. Methods The vaccination impacts of CYD-TDV and NVC were derived by fitting the empirical seroprevalence rates of 9 year olds into an individual-based meta-population transmission model, previously used for the WHO-SAGE working group. The disability-adjusted life years were estimated by applying country-specific parametric values. The cost-effectiveness analyses of four intervention strategies in combination with routine and catch-up campaigns were compared for both vaccines to inform decision makers regarding the most suitable immunization program in each of the three countries. Results and conclusion Both CYD-TDV and NVC could be cost-effective at the DALY threshold cost of $2000 depending upon vaccination costs. With CYD-TDV, targeting 9 year olds in routine vaccination programs and 10–29 year olds as a one-off catch-up campaign was the most cost-effective strategy in all three countries. With NVC, while the most cost-effective strategy was to vaccinate 9–29 and 9–18 year olds in Vietnam and Thailand respectively, vaccinating younger age cohorts between 1 and 5 years old in Colombia was more cost-effective than other strategies. Given that three countries will soon face decisions regarding whether and how to incorporate CYD-TDV or future dengue vaccines into their budget-constrained national immunization programs, the current study outcomes can be used to help decision makers understand the expected impacts and cost-effectiveness of such vaccines.

Background Despite accumulating evidence for the longitudinal stability of the marginal bone level around an implant, there is limited evidence of predisposing risk factors for marginal bone loss based on some implants in a relatively large patient population. Purpose The aim of this study was to retrospectively determine the marginal bone loss around Straumann tissue-level dental implants during follow-up periods among which the maximum lasts up to 10 years, as well as the predisposing risk factors for peri-implant marginal bone loss. Materials and methods This study analyzed 1692 Straumann tissue-level dental implants in 881 patients, and relevant data were collected. The peri-implant marginal bone level was measured on periodic radiographs, and the changes in bone level were analyzed cumulatively from surgery until up to 10 years later. The log-rank test was used to select candidate critical risk factors for marginal bone loss, and multivariate analysis using Cox regression with the shared frailty model was performed. Results The overall peri-implant bone loss was 0.07 ± 0.21mm, 0.09 ± 0.26mm, 0.14 ± 0.41mm, and 0.17 ± 0.45mm at 3, 5, 7, and 9 years, respectively. Only 14 implants showed pathologic marginal bone loss exceeding 2mm during the follow-up period. While 2 implants were removed with continuous progressive marginal bone loss, 5 of the 14 implants showed early bone loss exceeding 1mm within the first year but then subsequently tended to show a stable marginal bone level. In the other seven implants, bone loss started after the first year and progressed continuously. Multivariate analysis revealed that diameter of the implant affected the peri-implant marginal bone loss. Conclusions Straumann tissue-level dental implants showed only slight peri-implant marginal bone loss, with a very low incidence of pathologic marginal bone loss exceeding 2mm.

Background Implant dentistry is progressing based on extensive scientific results including preclinical and clinical studies. Researchers and clinicians have focused on implant designs and surface characteristics, which has resulted in various features being developed and introduced for enhancing osseointegration and reducing complications. Purpose The purpose of this study was to determine the cumulative survival rates of Straumann tissue-level dental implants over a 10-year period and identify the patterns of implant loss at a single research institution. Materials and methods In total, 1692 implants were installed in 881 patients who visited the Department of Periodontology, Dental Hospital, Yonsei University, Seoul from January 2003 to December 2009. Cases in which the implant was completely removed were defined as implant failures. Electronic or paper charts and radiographs were used to determine whether the implants failed. The survival rate of implants was analyzed using lifetime tables and Kaplan-Meier survival estimates. Log-rank test and Cox regression with shared frailty were used to analyze the risk factors and the types of implant failure. Results The 10-year cumulative survival rates were 98.23% and 95.70% at the implant and patient levels, respectively. Before installing a prosthesis (defined as the early stage), 13 implants in 10 patients were removed, while eight implants in seven patients were removed after completing a prosthesis (defined as the late stage). The cumulative survival rate was related to the implant diameter, length, site, and insertion torque. Most implant failures within 1 year were attributable to osseointegration failure. There were several cases of failure in the late stage without apparent marginal bone loss. Conclusion Straumann tissue-level dental implants showed low failure rates and can be considered a useful long-term treatment option. The length, placement site, and insertion torque might affect implant survival.

Human bone marrow mesenchymal stem cells (hBMSCs) were isolated from bone marrow of the vertebral body. The hBMSCs were cultured under either hypoxic (1% O2) or normoxic (21% O2; control) conditions and the characteristics as mesenchymal stem cells were compared. Results revealed that hypoxia reduced proliferative potential and colony-forming efficiency of hBMSCs, and significantly enhanced osteogenic and chondrogenic differentiation. The hBMSCs enhanced the regenerative potential of bone in vivo. In vitro synthesis of soluble and insoluble collagen was significantly increased in the hypoxic condition. In vivo collagen tissue regeneration was also enhanced under the hypoxic condition, with concomitant increased expressions of various subtypes of collagen and lysyl-oxidase family mRNA. MicroRNA assays revealed that miR-155-5p, which negatively regulates HIF-1α, was significantly highly expressed. These observations demonstrate that hBMSCs obtained from human vertebrae exhibit altered characteristics under hypoxic conditions, and each factor contributing to hBMSC-mediated tissue healing should be evaluated with the goal of allowing their clinical application.

Myasthenia gravis (MG) is an autoimmune disease associated with antibodies directed to the postsynaptic muscle components of the neuromuscular junction. The heterogeneous nature of the acetylcholine receptor (AChR) antibody response had led to the categorization of AChR antibodies into 3 types: binding, blocking, and modulating antibodies. The purpose of this study is to compare the AChR antibodies' type with the clinical severity of MG patients. The patients enrolled in the study had been tested for both binding and blocking antibodies and had disease duration exceeding 2 years since diagnosis. The patients were divided into five main classes by the Myasthenia Gravis Foundation of America clinical classification. Again, the enrolled patients were divided into ocular and generalized group. We compared the type and titer of antibodies and the thymus status between the ocular and generalized group. Thirty-five patients met the inclusion criteria. Of these, 16 patients (47 %) had both blocking and binding AChR antibodies, 11 patients (31 %) had only binding antibodies, and 8 patients (22 %) had only blocking antibodies. By defined clinical classification, the ocular and generalized groups included 10 and 25 patients, respectively. Sixteen patients in the generalized group possessed both AChR antibodies, with the remaining patients displaying only the binding antibody. All the patients with only blocking antibody were classified into ocular group. Use of binding and blocking antibodies' tests may, therefore, be more helpful in predicting the prognosis and diagnoses of MG patient.

The effects of fibroblast growth factor-2 (FGF-2) on collagen tissue regeneration by human bone marrow stem cells (hBMSCs) were investigated. hBMSCs were isolated from human vertebral body bone marrow during vertebral surgery and a population of hBMSCs with the characteristics of mesenchymal stem cells was observed. The FGF-2 treatment (5 ng/mL) affected on the colony-forming efficiency, proliferation, and in vitro differentiation of hBMSCs. Insoluble/soluble collagen and hydroxyproline synthesis was significantly enhanced in hBMSCs expanded with FGF-2 and the treatment of FGF-2 caused a reduction in the mRNA expression of collagen type I, but an increase of collagen types II and III along with lysyl oxidase family genes. Collagen formation was also examined using an in vivo assay model by transplanting hBMSCs into immunocompromised mice (n=4) and the histologic and immunohistochemical results revealed that significantly more collagen with a well-organized structure was formed by FGF-2-treated hBMSCs at 8 weeks posttransplantation (P

The insertion of a stent in diseased arteries is a common endovascular procedure that can be compromised by the development of short- and long-term inflammatory responses leading to restenosis and thrombosis, respectively. While treatment with drugs, either systemic or localized, has decreased the incidence of restenosis and thrombosis these complications persist and are associated with a high mortality in those that present with stent thrombosis. We reasoned that if stents could be made to undergo accelerated endothelialization in the deployed region, then such an approach would further decrease the occurrence of stent thrombosis and restenosis thereby improving clinical outcomes. Toward that objective, the first step necessitated efficient capture of progenitor stem cells, which eventually would become the new endothelium. To achieve this objective, we engineered intrinsic ferromagnetism within nonmagnetizable, biodegradable magnesium (Mg) bare metal stents. Mg stents were coated with biodegradable polylactide (PLA) polymer embedding magnetizable iron-platinum (FePt) alloy nanoparticles, nanomagnetic particles

Because of the complexity of cancer, an ideal anticancer strategy is better to target both cancer cells and the tumor microenvironment. In this study, for the first time, we demonstrated that zinc oxide nanoparticles (ZnO NPs) were able to target multiple cell types of cancer, including cancer cells, cancer stem cells (CSCs), and macrophages, and simultaneously perform several key functions, including inhibition of cancer proliferation, sensitization of drug-resistant cancer, prevention of cancer recurrence and metastasis, and resuscitation of cancer immunosurveillance. As a nanocarrier, the chemotherapy drug, doxorubicin (Dox), could be loaded to ZnO NPs and the Dox-loaded ZnO NPs (ZnO/Dox) possessed excellent physicochemical and pH-responsive drug release properties. ZnO/Dox could be effectively internalized by both drug-sensitive and multidrug resistant (MDR) cancer cells and penetrate more efficiently through three-dimensional (3D) cancer cell spheroids compared with free Dox. As a cytotoxic agent, ZnO NPs were more efficient to kill MDR cancer cells. Interestingly, neither ZnO nor Dox showed high cytotoxicity in the 3D cancer cell spheroids, whereas ZnO/Dox showed remarkable synergistic anticancer effects. More importantly, we demonstrated that ZnO NPs could effectively downregulate CD44, a key CSC surface marker, and decrease the stemness of CSCs, leading to the sensitization of the Dox treatment, inhibition of the cancer cell adhesion and migration, and prevention of the tumor (3D cancer cell spheroid) formation. As an immunomodulator, ZnO NPs could protect macrophages from the Dox-induced toxicity and boost the Dox-induced macrophage polarization toward an M1-like phenotype. The macrophage-conditioned medium could promote the cancer cell apoptosis in both cancer cell monolayers and 3D spheroids. The findings in this study indicated that ZnO NPs were a multifunctional and multitarget nanocarrier and nanomedicine that would have more profound effects on cancer treatment.

This study aimed to quantify the healing following vertical augmentation of allogenic bone blocks with/without recombinant human bone morphogenetic protein-2 (rhBMP-2) on rabbit calvaria. Experiments were performed using allogenic bone blocks which were grafted bilaterally with or without rhBMP-2 on 20 rabbit calvaria, and these animals were divided to four groups according to the use of rhBMP-2 and healing periods (2 and 8 weeks; n = 10 in each group). Onlay-type bone blocks (8 mm in diameter and 5 mm high) were fixed with a self-tapping screw after removing the cortex in the control group, and the same protocol was applied with the addition of soaking the bone blocks with rhBMP-2 for 15 min in the test group. Radiographic and histologic analyses were performed after 2 or 8 weeks to evaluate the volumetric stability and bone regeneration within the grafted area. The radiographic analysis revealed that the height of the allogenic bone block decreased but its volume was maintained from 2 to 8 weeks in both the control and test groups. The histologic results demonstrated a statistically significant increase in new bone area in the test group, especially in the lower region adjacent to the preexisting calvarial floor. The amount of newly formed bone in all regions of the augmented bone blocks in both the control and test groups was greater at 8 weeks than at 2 weeks. In conclusion, the vertically grafted allogenic bone block maintained its volume with new bone formation, and this was accelerated by the addition of rhBMP-2. These findings indicate that allogenic bone block soaked with rhBMP-2 could be a useful candidate biomaterial for vertical augmentation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2700-2707, 2018.

Background Dengue fever has been a major public health concern in Colombia, Thailand, and Vietnam. Unlike other infectious diseases, dengue vaccines had not been available for a long time, causing difficulties to control the disease. However, the first live attenuated, tetravalent dengue vaccine (CYD-TDV) became available in 2016 and has been already licensed in some dengue-endemic countries. Because several second-generation dengue vaccines are also in the pipeline, it is critical to understand the efficient allocation of dengue vaccines considering the geographical variation of the disease. Methods The Climate Risk Factor (CRF) index was created using the climate and non-climate factors in the three countries. A random-coefficient negative binomial model was chosen to validate the relationship between the CRF index and dengue incidence proxy. Given the statistical significance of the CRF index, high risk areas for dengue fever were identified at the 5 km by 5 km resolution and used to estimate vaccination coverage rates and the number of doses required for various types of vaccination scenarios by country. Results and conclusions Based upon a three-dose scheme, the estimated number of vaccines required for routine vaccination targeting 9 years old ranged from 1 to 2.6 million doses across the countries during the first year of introduction. A one-off catch-up campaign targeting the age group of 10–17 year olds would require 8 to 18 million additional doses. Routine vaccination (with or without a catch-up campaign) covered 63%, 90%, and 91% of the targeted age group populations in Colombia, Thailand, and Vietnam respectively. Given that many dengue-endemic countries face limited resources and that the costs for mass vaccination campaigns may not be trivial, the findings of this study can guide the decision makers in the three countries regarding the efficient distribution of vaccines by identifying populations at high risk at 5 km by 5 km resolution.

Background Dengue fever is a major public health concern in many parts of the tropics and subtropics. The first dengue vaccine has already been licensed in six countries. Given the growing interests in the effective use of the vaccine, it is critical to understand the economic burden of dengue fever to guide decision-makers in setting health policy priorities. Methods/Principal findings A standardized cost-of-illness study was conducted in three dengue endemic countries: Vietnam, Thailand, and Colombia. In order to capture all costs during the entire period of illness, patients were tested with rapid diagnostic tests on the first day of their clinical visits, and multiple interviews were scheduled until the patients recovered from the current illness. Various cost items were collected such as direct medical and non-medical costs, indirect costs, and non-out-of-pocket costs. In addition, socio-economic factors affecting disease severity were also identified by adopting a logit model. We found that total cost per episode ranges from $141 to $385 for inpatient and from $40 to $158 outpatient, with Colombia having the highest and Thailand having the lowest. The percentage of the private economic burden of dengue fever was highest in the low-income group and lowest in the high-income group. The logit analyses showed that early treatment, higher education, and better knowledge of dengue disease would reduce the probability of developing more severe illness. Conclusions/Significance The cost of dengue fever is substantial in the three dengue endemic countries. Our study findings can be used to consider accelerated introduction of vaccines into the public and private sector programs and prioritize alternative health interventions among competing health problems. In addition, a community would be better off by propagating the socio-economic factors identified in this study, which may prevent its members from developing severe illness in the long run., Author summary Dengue fever has been prevalent in South-East Asia and South America. Despite the increase of dengue fever cases, there continues to be a lack of economic assessment partly due to the absence of vaccines until recent times. Many of the previous economic burden studies for dengue fever were not standardized, making them difficult to compare. We implemented the standardized economic burden survey for dengue fever in a multi-country setting: Vietnam, Thailand, and Colombia. We found that the economic burden of dengue fever is substantial in all three dengue endemic countries. Our study also identified socio-economic factors which are related to the probability of experiencing severe illness. The first live attenuated, tetravalent dengue vaccine (CYD-TDV) has been already licensed in some dengue-endemic countries. As three countries will soon face decisions on whether and how to incorporate current and future vaccine candidates within their budget constraints, the updated economic burden estimates can be used to develop sustainable financing plans.

Summary Background No access to safe water is an important risk factor for typhoid fever, yet risk-level heterogeneity is unaccounted for in previous global burden estimates. Since WHO has recommended risk-based use of typhoid polysaccharide vaccine, we revisited the burden of typhoid fever in low-income and middle-income countries (LMICs) after adjusting for water-related risk. Methods We estimated the typhoid disease burden from studies done in LMICs based on blood-culture-confirmed incidence rates applied to the 2010 population, after correcting for operational issues related to surveillance, limitations of diagnostic tests, and water-related risk. We derived incidence estimates, correction factors, and mortality estimates from systematic literature reviews. We did scenario analyses for risk factors, diagnostic sensitivity, and case fatality rates, accounting for the uncertainty in these estimates and we compared them with previous disease burden estimates. Findings The estimated number of typhoid fever cases in LMICs in 2010 after adjusting for water-related risk was 11·9 million (95% CI 9·9–14·7) cases with 129 000 (75 000–208 000) deaths. By comparison, the estimated risk-unadjusted burden was 20·6 million (17·5–24·2) cases and 223 000 (131 000–344 000) deaths. Scenario analyses indicated that the risk-factor adjustment and updated diagnostic test correction factor derived from systematic literature reviews were the drivers of differences between the current estimate and past estimates. Interpretation The risk-adjusted typhoid fever burden estimate was more conservative than previous estimates. However, by distinguishing the risk differences, it will allow assessment of the effect at the population level and will facilitate cost-effectiveness calculations for risk-based vaccination strategies for future typhoid conjugate vaccine. Funding Bill and Melinda Gates Foundation.