Impact of multiple infections on risk of incident dementia according to subjective cognitive decline status: a nationwide population-based cohort study.

Background: The interrelation between infections, subjective cognitive decline (SCD), and dementia development is recognized, but not fully understood. This study explored the combined effect of specific infections and SCD on the risk of dementia. Objectives: To assess the influence of Helicobacter pylori, herpes simplex virus, varicella-zoster virus, and human papillomavirus on dementia risk in individuals with varying cognitive statuses, especially focusing on those with and without SCD. Methods: A cohort of 1,100,540 participants aged 66 years from the Korean National Health Insurance Service was divided into cognitively preserved (CP, n = 825,405) and SCD (n = 275,135) groups. This study analyzed the effects of single, dual, and triple infections on the risk of overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD) using incidence rates and hazard ratios. Results: The SCD group consistently showed a doubled risk of dementia, particularly AD, regardless of the number of infections. In the initial data, both the presence and number of infections, especially in the CP group, were associated with an increased dementia incidence and risk; however, this correlation disappeared after adjusting for covariates, hinting at a possible protective effect. Conclusion: Our findings emphasize that, while SCD is a steadfast risk factor for dementia, the role of infections is layered, subject to various influences, and requires more comprehensive exploration to fully understand their impact on dementia development.

Randomized controlled trial on the efficacy of a custom-made, fully guided implant system for flapless crestal sinus floor elevation: Accuracy and patient-reported outcomes.

OBJECTIVE: To compare fully guided flapless implant surgery using a light-cured surgical guide (FG group) with partially guided open flap surgery (PG group) in the posterior maxilla when performing simultaneous sinus floor elevation in terms of the accuracy, time requirements, and patient/clinician-reported outcomes (PROMs and CROMs). MATERIALS AND METHODS: In this study, 56 tissue-level implants were placed with crestal sinus floor elevation in 56 patients at single-tooth sites, with 28 implants allocated to the PG group and 28 to the FG group. The deviations of the placed implants from the virtually planned positions were measured at the implant platform and apex and for the angular deviation. The presurgical preparation time and the duration of surgery were measured. PROMs and CROMs were made by administering questionnaires at multiple time points. RESULTS: Horizontal deviations at the platform and apex and the angular deviation were significantly smaller in the FG group than the PG group (p < .05). Presurgical preparation and surgery times were significantly shorter in the FG group (p < .001). Patient satisfaction and willingness to receive repeat treatment were significantly better in the FG group than in the PG group (p < .005 and .025, respectively). Clinicians were more satisfied in the FG group than the PG group (p < .05). CONCLUSION: When placing an implant with sinus floor elevation, the flapless approach using a fully guided surgical system can be more accurate, faster, and increase the satisfaction of both the clinician and patient compared to the partially guided surgery.

Impact of Helicobacter pylori eradication on age-specific risk of incident dementia in patients with peptic ulcer disease: a nationwide population-based cohort study.

The impact of peptic ulcer disease (PUD) and Helicobacter pylori (H. pylori) eradication therapy on dementia risk in high H. pylori prevalence populations remains uncertain. This study investigates the relationship between PUD, H. pylori eradication, and dementia risk, including Alzheimer's disease (AD), in an elderly South Korean cohort, considering age and eradication timing. Data from the Korean National Health Insurance Service (2002-2015) for individuals aged 55-79 were analyzed. Participants were divided based on PUD and H. pylori therapy status. Propensity score matching was used to evaluate dementia incidence and hazard ratios over 5 and 10 years, alongside the timing of eradication therapy. PUD is linked to higher dementia risk at 5 and 10 years, more for overall dementia than AD, with eradication status not significantly altering the risk. Age-specific analysis showed increased AD risk in the 60s and 70s age groups. Late eradication therapy is correlated with a higher dementia risk. PUD is a risk factor for dementia in elderly South Koreans, particularly with delayed H. pylori therapy. The findings emphasize timely H. pylori management and its potential role in neurodegenerative disease prevention.

Clinical evaluation of implants placed within or beyond the boundaries of the alveolar ridge preservation: a retrospective case series with 10 weeks of observations in 28 patients.

PURPOSE: This study investigated the effect of implant vertical positioning within alveolar ridge preservation (ARP) sites on implant stability quotient (ISQ) values, which were measured 10 weeks post-implantation. METHODS: Patients who underwent ARP using collagenized deproteinized bovine bone mineral, followed by implant placement in the posterior area, were divided into 2 groups: the within-ARP group and the beyond-ARP group. In the within-ARP group, osteotomy and implant placement occurred within the ARP boundary. In contrast, in the beyond-ARP group, these procedures were performed beyond the ARP boundary, incorporating 3 mm of pristine bone at the implant's apex. Bone quality was assessed by tactile sense, and both insertion torque during implant surgery and ISQ values at 10 weeks post-implant surgery were measured. Multiple linear regression analysis and Pearson correlation analysis were used to explore the relationship between insertion torque and ISQ values. RESULTS: In total, 30 ARP sites in 28 patients were analyzed. There was no significant difference in bone quality, as determined by tactile sense, between the within-ARP and beyond-ARP groups. At the time of implant placement, the beyond-ARP group exhibited a higher insertion torque (33.33±13.39 Ncm) compared to the within-ARP group (17.08±11.17 Ncm). However, the ISQ values were similar between the 2 groups 10 weeks after implant placement. A positive correlation between insertion torque and ISQ values was confirmed at 10 weeks post-implant. CONCLUSIONS: The engagement of pristine bone may facilitate high insertion torque during the placement of implants in ARP sites. Nevertheless, by 10 weeks post-implantation, the ISQ values were found to be comparable, irrespective of the implant's position.

A randomized controlled trial of immediate implant placement comparing hydroxyapatite nano-coated and uncoated sandblasted/acid-etched implants using a digital surgical guide.

PURPOSE: This study evaluated the implant stability, volumetric changes, and patient-reported outcome measures (PROMs) of hydroxyapatite (HA) nano-coated sandblasted/acid-etched (SLA) implants compared to uncoated SLA implants. METHODS: Forty patients were recruited and randomly allocated to HA nano-coated SLA group (test, n = 20) and uncoated SLA group (control, n = 20) using single-blinded/block randomization. Implants were immediately placed in maxillary posterior region using a digital surgical guide. Insertion torque and implant stability quotient (ISQ) were measured at implant surgery and 1, 2, 3, and 4 months postoperatively. Intraoral scans, PROMs and soft tissue inflammation data were collected, and multivariable linear regression analysis of ISQ was performed. RESULTS: In total, 48 implants (test; n = 24, control; n = 24) in 37 patients (test; n = 19, control; n = 18) were analyzed. Despite no significant between-group difference at surgery, the test group showed higher ISQ values than the control group at 2 (76.53 ± 4.17 vs. 71.32 ± 4.79, p < 0.01), 3 (77.45 ± 4.41 vs. 73.85 ± 4.69, p < 0.05), and 4 months (79.08 ± 2.96 vs. 73.43 ± 3.52, p < 0.0001) postoperatively. There were no significant differences in linear and volumetric changes, PROMs, and soft tissue inflammation analysis between two groups. The ISQ at implant surgery was influenced by age and diabetes mellitus (DM) at the implant level and DM and predicted total bone-to-implant contact area at the patient level. CONCLUSION: HA nano-coated SLA implants promoted favorable immediate implants stability during early osseointegration phase compared to uncoated SLA implants, but displayed similar dimensional changes, PROMs, and soft tissue inflammation outcomes. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0006364. Registered 21 July 2021, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24221&search_page=L .

Preclinical comparison study of experimental peri-implantitis between alveolar ridge preservation and spontaneous healing sites in infected and noninfected tooth: a randomized blinded in vivo study.

BACKGROUND: This study compared the progression of experimental peri-implantitis between alveolar ridge preservation (ARP) and spontaneous healing (SH) sites in infected (IT) and noninfected tooth (NIT). METHODS: Bilateral mandibular third or fourth premolars of six beagle dogs were randomly assigned to IT and NIT groups. Before extraction, chronic dehiscence defects were created at the mesial root of mid-buccal area in IT group. Four weeks later, the mesial roots of the third and fourth premolars were extracted in all groups.ARP procedure was randomly conducted on one side of the extraction sockets using collagenated bovine bone substitutes and resorbable collagen membrane, and contralateral side was allowded spontaneous healing. After 12 weeks of healing, bone-level implants (ϕ 3.6 × 8.0 mm) were placed at the extraction sockets. Three months of ligature induced peri-implantitis and three months of spontaneous progression were allowed, with radiographs taken at each phase. Biopsies were retrieved at the implant site for histomorphometric, immunohistochemical, and polarized light-microscopic analyses. RESULTS: Radiography demonstrated that the changes in the marginal bone level during the spontaneous progression period showed no significant differences between ARP and SH sites. Only small and/or nonsignificant differences in the progression of peri-implantitis were observed between ARP and SH sites in histomorphometric, immunohistochemical, and polarized light microscopic analyses. Additionally, the IT and NIT groups exhibited similar outcomes for most parameters. CONCLUSION: ARP with xenogenic bone substitutes might provide similarly robust results as SH sites regarding the progression of experimental peri-implantitis, irrespective of the infected or noninfected nature of the site before tooth extraction.

Lactate Levels as a Predictor of Emergency Department Revisits in Infants With Acute Bronchiolitis.

OBJECTIVE: This study aimed to identify predictive biomarkers for unscheduled emergency department (ED) revisits within 24 hours of discharge in infants diagnosed with acute bronchiolitis (AB). METHODS: A retrospective observational study was conducted on infants diagnosed with AB who visited 3 emergency medical centers between January 2020 and December 2022. The study excluded infants with comorbidities, congenital diseases, and prematurity and infants who revisited the ED after 24 hours of discharge. Demographic data, vital signs, and laboratory results were collected from the medical records. Univariable and multivariable logistic regression analyses were performed on factors with P of less than 0.1 in univariable analysis. Receiver operator curve analysis was used to assess the accuracy of lactate measurements in predicting ED revisits within 24 hours of discharge. RESULTS: Out of 172 participants, 100 were in the revisit group and 72 in the discharge group. The revisit group was significantly younger and exhibited higher lactate levels, lower pH values, and higher pCO 2 levels compared to the discharge group. Univariable logistic regression identified several factors associated with revisits. Multivariable analysis found that only lactate was a variable correlated with predicting ED revisits (odds ratio, 18.020; 95% confidence interval [CI], 5.764-56.334). The receiver operator curve analysis showed an area under the curve of 0.856, with an optimal lactate cutoff value of 2.15. CONCLUSION: Lactate value in infants diagnosed with AB were identified as a potential indicator of predicting unscheduled ED revisits within 24 hours of discharge. The predictive potential of lactate levels holds promise for enhancing prognosis prediction, reducing health care costs, and alleviating ED overcrowding. However, given the study's limitations, a more comprehensive prospective investigation is recommended to validate these findings.

Correlation of two different devices for the evaluation of primary implant stability depending on dental implant length and bone density: An in vitro study.

Non-invasive objective implant stability measurements are needed to determine the appropriate timing of prosthetic fitting after implant placement. We compared the early implant stability results obtained using resonance frequency analysis (RFA) and damping capacity analysis (DCA) depending on the implant length and bone density. Total 60, 4.0 mm diameter implants of various lengths (7.3 mm, 10 mm, and 13 mm) were used. In Group I, low-density bone was described using 15 PCF (0.24 g/cm3) polyurethane bone blocks, and in Group II, 30 PCF (0.48 g/cm3) polyurethane bone blocks were used to describe medium density bone. RFA was performed using an Osstell® Beacon+; DCA was performed using Anycheck®. Measurements were repeated five times for each implant. Statistical significance was set at P <0.05. In Group I, bone density and primary implant stability were positively correlated, while implant length and primary implant stability were positively correlated. In Group II, the implant stability quotient (ISQ) and implant stability test (IST) values in did not change significantly above a certain length. Primary implant stability was positively correlated with bone density and improved with increasing implant length at low bone densities. Compared with the Osstell® Beacon+, the simplicity of Anycheck® was easy to use and accessible.

The adjunctive effect of polydeoxyribonucleotide on bone formation in alveolar ridge preservation: A pre-clinical in vivo study.

AIM: This study investigated the adjunctive effect of polydeoxyribonucleotide (PDRN) on bone formation in alveolar ridge preservation (ARP) sockets. MATERIALS AND METHODS: Both mandibular second, third and fourth premolars of eight beagle dogs were randomly divided into ARP and ARP/PDRN groups. Following tooth extraction, ARP procedures were conducted using collagenized alloplastic graft material and bilayer collagen membrane soaked with normal saline (ARP group) or PDRN (ARP/PDRN group) for 10 min before application. Both groups were also randomly allocated to 2-, 4- or 12-week healing subgroups. The primary endpoint of this study was to compare histomorphometric differences between ARP and ARP/PDRN. The secondary endpoints of this study were to compare micro-CT analysis and three-dimensional volumetric measurement between the two groups. RESULTS: In the histomorphometric analysis, the ARP/PDRN group exhibited greater new bone formation at coronal, middle and total position compared with the ARP group at 2-week healing. The number of newly formed blood vessels was higher in the ARP/PDRN group than in the ARP group at 2- and 4-week healing. In micro-CT analysis, the mean new bone volume/total bone volume between ARP and ARP/PDRN was statistically significant at 2-week healing. Ridge volume alterations were significantly decreased in the ARP/PDRN group during entire healing time compared with the ARP group, especially on the buccal side. CONCLUSIONS: The application of PDRN in ARP might provide additional benefits for early bone regeneration and maintenance of buccal ridge volume.

Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial.

PURPOSE: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR-tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer carrying EGFR mutations. PATIENTS AND METHODS: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth. Subsequently, 110 consecutive patients with stage IV lung cancer who had EGFR mutations were recruited: 70 females (63.6%) and 84 never-smokers (76.4%). The patients were randomly assigned to receive either nicotinamide (1 g/day, n = 55) or placebo (n = 55). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. RESULTS: After a median follow-up of 54.3 months, the nicotinamide group exhibited a median PFS of 12.7 months [95% confidence interval (CI), 10.4-18.3], while the placebo group had a PFS of 10.9 months (9.0-13.2; P = 0.2). The median OS was similar in the two groups (31.0 months with nicotinamide vs. 29.4 months with placebo; P = 0.2). Notably, subgroup analyses revealed a significant reduction in mortality risk for females (P = 0.01) and never-smokers (P = 0.03) treated with nicotinamide. CONCLUSIONS: The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked (ClinicalTrials.gov Identifier: NCT02416739).

A One-Year Randomized Controlled Clinical Trial of Three Types of Narrow-Diameter Implants for Fixed Partial Implant-Supported Prosthesis in the Mandibular Incisor Area.

Narrow-diameter implants (NDI) serve as a solution for treating limited bone volume in the anterior mandible. This study aimed to evaluate the one-year clinical outcomes of various NDIs in the mandibular incisor area after immediate loading in partially edentulous patients. This single-center, prospective, single-blinded, randomized controlled trial study included 21 patients, with 7 patients in each of the following groups: control (BLT NC SLActive®; Straumann), experimental group 1 (CMI IS-III Active® S-Narrow; Neobiotech), and experimental group 2 (CMI IS-III Active® Narrow; Neobiotech). Using full digital flow, two fixtures were placed in each patient and immediately provisionalized on the day of surgery. Evaluations encompassed periapical radiographs, implant stability quotient (ISQ), implant stability test (IST) readings, per-implant soft tissue health, patient satisfaction surveys, and esthetic score assessments. Definitive prostheses were delivered twelve weeks post-surgery (CRiS, number: KCT0007300). Following exclusions due to low stability values (n = 2), fixture failure (n = 5), and voluntary withdrawal (n = 1), the implant success rate for patients completing all clinical protocols stood at 100%. The resulting patient failure rates in the control, experimental group 1, and experimental group 2 were 50.0%, 42.9%, and 14.3%, respectively. There were no significant differences between the groups in terms of marginal bone loss, soft tissue health, patient satisfaction, and esthetic scores. Narrow implants showed superior clinical outcomes, followed by S-Narrow and Straumann implants. Calculated one-year survival rates at the implant level were 66.7% for the control group, 85.7% for experimental group 1, and 100% for experimental group 2. All three types of NDIs showed acceptable clinical and radiographic results during the year-long observation period.

Adjunctive effect of 470-nm and 630-nm light-emitting diode irradiation in experimental periodontitis treatment: a preclinical study.

PURPOSE: This study investigated the adjunctive effect of light-emitting diodes (LEDs) in the treatment of experimental periodontitis. METHODS: Experimental periodontitis was induced by placing ligatures around the mandibular second, third, and fourth premolars of 6 beagles for 3 months. After ligature removal, periodontitis progressed spontaneously for 2 months. The animals' hemimandibles were allocated among the following 3 groups: 1) no treatment (control), 2) scaling and root planing (SRP), and 3) SRP with LED irradiation at 470-nm and 630-nm wavelengths (SRP/LED). The probing pocket depth (PPD) and gingival recession (GR) were measured at baseline, 6 weeks, and 12 weeks. The clinical attachment level (CAL) was calculated. After 12 weeks, histological and histomorphometric assessments were performed. The distances from the gingival margin to the apical extent of the junctional epithelium (E) and to the connective tissue (CT) attachment were measured, as was the total length of soft tissue (ST). RESULTS: PPD and CAL increased at 12 weeks compared with baseline in the control group (6.31±0.43 mm to 6.93±0.50 mm, and 6.46±0.60 mm to 7.61±0.78 mm, respectively). PPD and CAL decreased at 12 weeks compared with baseline in the SRP group (6.01±0.59 to 4.81±0.65 mm, and 6.51±0.98 to 5.39±0.93 mm, respectively). PPD and CAL decreased at 12 weeks compared with baseline in the SRP/LED group (6.03±0.39 to 4.46±0.47 mm, and 6.11±0.47 to 4.78±0.57 mm, respectively). The E/ST and CT/ST ratios significantly differed among the 3 groups (P<0.05). The clinical parameters and histologic findings demonstrated that 470-nm and 630-nm wavelength LED irradiation accompanying SRP could improve treatment results. CONCLUSIONS: Within the study limitations, 470 nm and 630 nm wavelength LED irradiation might provide additional benefits for periodontitis treatment.

Diagnostic performance of a point-of-care test device for periodontitis using human saliva: a single-center, single-blinded, confirmatory study.

OBJECTIVE: Recently, matrix metalloproteinase-8 (MMP-8) has been used to diagnose periodontal disease in a point-of-care (POC) test in order to save time and cost relative to the traditional diagnostic workflow. This study aimed to investigate the diagnostic performance of INCLIX TRF MMP-8, a POC testing device for periodontitis using the area under the receiver operating characteristic curve, sensitivity, specificity, and predictive values. MATERIALS AND METHODS: Full-mouth periodontal examination and radiographic analysis were used for evaluating periodontal condition based on the 2018 classification of periodontal disease. A dichotomous diagnosis of clinical periodontal condition was performed using the POC device. The relationships among periodontal condition and the concentration of MMP-8, tooth loss (TL), gingival index (GI), plaque index (PI), and alveolar bone loss (ABL) were assessed by the Spearman rank correlations (rs). RESULTS: In all, 108 cases of non-periodontitis (NP) and 191 cases of periodontitis (P), including 38 cases of periodontitis stage I, 42 cases of periodontitis stage II, 99 cases of periodontitis stage III, and 11 cases of periodontitis stage IV, were enrolled in this study. Diagnostic accuracy in assessing periodontal condition with the POC device improved when it was used with participants aged ≥ 40 years. There were weak positive correlations between periodontal condition and MMP-8 and between periodontal condition and GI (rs2 = 0.1124 and rs2 = 0.0906, respectively), whereas a strong positive correlation between periodontal condition and alveolar bone loss (rs2 = 0.6877) was observed. CONCLUSION: The POC device investigated in this study is a potential tool to distinguish between NP and P in individuals ≥ 40 years of age.

Comparative evaluation of 3D-printed and conventional implants in vivo: a quantitative microcomputed tomographic and histomorphometric analysis.

In recent years, 3D-printing technology to fabricate dental implants has garnered widespread attention due to its patient-specific customizability and cost-effectiveness. This preclinical animal study analyzed the radiographic and histomorphometric outcomes of 3D-printed implants (3DIs) placed immediately after extraction and compared them to conventional implants (CIs). 3DIs and CIs of the same dimensions placed immediately were analyzed at 2, 6, and 12 weeks. The micro-computed tomography (micro-CT) analysis revealed statistically significant differences at 2 weeks in favor of 3DIs over the CIs in terms of bone volume/tissue volume (BV/TV), bone surface/bone volume (BS/BV), trabecular bone pattern factor (Tb.Pf), and structure model index (SMI). At 2 weeks, the mean bone-to-implant contact (BIC) of the 3DIs was greater than that of the CIs; the mean bone area fraction occupancy (BAFO) and the number of Haversian canals of the 3DIs showed no statistically significant differences compared to CIs at 2 weeks. At 6 and 12 weeks, there were no statistically significant differences between the 3DIs and CIs in any parameters. Within limitations, in the early stage of extraction socket healing, the 3DIs demonstrated a higher BIC than the CIs, presenting that 3DIs may be a potential option for immediate placement to enhance osseointegration.

Runx3 Restoration Regresses K-Ras-Activated Mouse Lung Cancers and Inhibits Recurrence.

Oncogenic K-RAS mutations occur in approximately 25% of human lung cancers and are most frequently found in codon 12 (G12C, G12V, and G12D). Mutated K-RAS inhibitors have shown beneficial results in many patients; however, the inhibitors specifically target K-RASG12C and acquired resistance is a common occurrence. Therefore, new treatments targeting all kinds of oncogenic K-RAS mutations with a durable response are needed. RUNX3 acts as a pioneer factor of the restriction (R)-point, which is critical for the life and death of cells. RUNX3 is inactivated in most K-RAS-activated mouse and human lung cancers. Deletion of mouse lung Runx3 induces adenomas (ADs) and facilitates the development of K-Ras-activated adenocarcinomas (ADCs). In this study, conditional restoration of Runx3 in an established K-Ras-activated mouse lung cancer model regressed both ADs and ADCs and suppressed cancer recurrence, markedly increasing mouse survival. Runx3 restoration suppressed K-Ras-activated lung cancer mainly through Arf-p53 pathway-mediated apoptosis and partly through p53-independent inhibition of proliferation. This study provides in vivo evidence supporting RUNX3 as a therapeutic tool for the treatment of K-RAS-activated lung cancers with a durable response.

Effect of polydeoxyribonucleotide on early bone formation in lateral bone augmentation with immediate implant placement: an experimental in vivo study.

This study investigated early bone formation using collagenated biphasic calcium phosphate (CBCP) with or without polynucleotide (PDRN). Third (P3) or fourth (P4) premolars of six male beagle dogs were extracted and 5-mm-high dehiscence defects were created, followed by 3D-printed implant placement. The buccal bone defects were grafted with (i) CBCP and collagen membrane or (ii) CBCP soaked in polydeoxyribonucleotide (CBCP/PDRN) and collagen membrane. Samples of the experimental sites were harvested at 2- and 6-weeks post-surgery. The specimens were evaluated with radiologic and histomorphometric analysis. No significant differences were found between the CBCP and CBCP/PDRN groups in the micro-CT analysis at 2 or 6 weeks. No significant differences were observed in bone-to-implant contact (BIC) or bone area fraction occupancy (BAFO) in buccal augmented and lingual non-augmented areas. In the qualitative analysis, the new bone (NB) area and NB proportion in buccal augmented areas showed significantly higher values in the CBCP/PDRN group than in the CBCP group at 2 and 6 weeks. Peri-implant buccal dehiscence defects with immediate 3D-printed implant placement were corrected using a collagen membrane and CBCP or CBCP/PDRN. PDRN might have the potential to facilitate early bone formation with sufficient stability over time in dehiscence defects.

The TGFß→TAK1→LATS→YAP1 Pathway Regulates the Spatiotemporal Dynamics of YAP1.

The Hippo kinase cascade functions as a central hub that relays input from the "outside world" of the cell and translates it into specific cellular responses by regulating the activity of Yes-associated protein 1 (YAP1). How Hippo translates input from the extracellular signals into specific intracellular responses remains unclear. Here, we show that transforming growth factor ß (TGFß)-activated TAK1 activates LATS1/2, which then phosphorylates YAP1. Phosphorylated YAP1 (p-YAP1) associates with RUNX3, but not with TEAD4, to form a TGFß-stimulated restriction (R)-point-associated complex which activates target chromatin loci in the nucleus. Soon after, p-YAP1 is exported to the cytoplasm. Attenuation of TGFß signaling results in re-localization of unphosphorylated YAP1 to the nucleus, where it forms a YAP1/TEAD4/SMAD3/AP1/p300 complex. The TGFß-stimulated spatiotemporal dynamics of YAP1 are abrogated in many cancer cells. These results identify a new pathway that integrates TGFß signals and the Hippo pathway (TGFß→TAK1→LATS1/2→YAP1 cascade) with a novel dynamic nuclear role for p-YAP1.

Precise Filtration of Chronic Myeloid Leukemia Cells by an Ultrathin Microporous Membrane with Backflushing to Minimize Fouling.

A cell filtration platform that affords accurate size separation and minimizes fouling was developed. The platform features an ultra-thin porous membrane (UTM) filter, a pumping head filtration with backflush (PHF), and cell size measurement (CSM) software. The UTM chip is an ultrathin free-standing membrane with a large window area of 0.68 mm2, a pore diameter of 5 to 9 µm, and a thickness of less than 0.9 µm. The PHF prevents filter fouling. The CSM software analyzes the size distributions of the supernatants and subnatants of isolated cells and presents the data visually. The D99 particle size of cells of the chronic myeloid leukemia (CML) line K562 decreased from 22.2 to 17.5 µm after passage through a 5-µm filter. K562 cells could be separated by careful selection of the pore size; the recovery rate attained 91.3%. The method was compared to conventional blocking models by evaluating the mean square errors (MSEs) between the measured and calculated filtering volumes. The filtering rate was fitted by a linear regression model with a significance that exceeded 0.99 based on the R2 value. The platform can be used to separate various soft biomaterials and afford excellent stability during filtration.

Comparison of osteogenesis and osseointegration following implant placement with simultaneous maxillary sinus augmentation using particulate and collagenated block types of deproteinized porcine bone mineral: a radiographic and histomorphometric analysis.

OBJECTIVES: This study aimed to compare osseointegration and osteogenesis after single-stage maxillary sinus augmentation with the lateral window using particulate deproteinized porcine bone mineral (PDPBM) and collagenated block deproteinized porcine bone mineral (BDPBM). MATERIALS AND METHODS: Bi-maxillary premolars of six beagle dogs were extracted. Eight weeks later, an implant was placed into each augmented sinus with PDPBM or BDPBM according to a split-mouth design. Eight weeks later, all specimens were harvested. Each specimen was separated into the region of interest with the implant (ROI-I) and region of interest with sinus augmented area (ROI-S) 5 mm away from ROI-I. ROI-I and ROI-S were evaluated through micro-computed tomography and histomorphometry. RESULTS: Bone substitute insertion took longer for the PDPBM group than for the BDPBM group (P = 0.002). In ROI-I, three-dimensional bone-to-implant contact (BIC) did not show statistically significant differences between the groups. Two-dimensional BIC also showed comparable values for both groups. In ROI-S, the graft material volume/tissue volume, trabecular bone pattern factor, and structural model index were higher in the BDPBM group than in the PDPBM group (P < 0.05). The proportions of new bone, graft material, and connective tissue were not significantly statistically different between groups. Less new bone was found in the apical area than in the coronal or middle areas in the BCPBM group (P < 0.05). CONCLUSIONS: BDPBM may save time in inserting bone substitutes and provide comparable osteogenesis and osseointegration to PDPBM. CLINICAL RELEVANCE: When performing sinus augmentation, BDPBM might improve operator's convenience with comparable biological results compared to PDPBM.