Red Fluorescence from Organic Microdots: Leveraging Foldamer-Linked Azobenzene for Enhanced Stability and Intensity in Bioimaging Applications.

Azobenzene, while relevant, has faced constraints in biological system applications due to its suboptimal quantum yield and short-wavelength emission. This study presents a pioneering strategy for fabricating organic microdots by coupling foldamer-linked azobenzene, resulting in robust fluorescence intensity and stability, especially in aggregated states, thereby showing promise for bioimaging applications. Comprehensive experimental and computational examinations elucidate the mechanisms underpinning enhanced photostability and fluorescence efficacy. In vitro and in vivo evaluations disclose that the external layer of cis-azo-foldamer microdots performs a self-sacrificial function during photo-bleaching. Consequently, these red-fluorescent microdots demonstrate extraordinary structural and photochemical stabilities over extended periods. The conjugation of a ß-peptide foldamer to the azobenzene chromophore through a glycine linker instigates a blue-shifted and amplified π*-n transition. Molecular dynamics simulations reveal that the aggregated state of cis-azo-foldamers fortifies the stability of cis isomers, thereby augmenting fluorescence efficiency. This investigation furnishes crucial insights into conceptualizing novel, biologically inspired materials, promising stable and enduring imaging applications, and carries implications for diverse arenas such as medical diagnostics, drug delivery, and sensing technologies.

State transitions across the Strep A disease spectrum: scoping review and evidence gaps.

The spectrum of diseases caused by Streptococcus pyogenes (Strep A) ranges from superficial to serious life-threatening invasive infections. We conducted a scoping review of published articles between 1980 and 2021 to synthesize evidence of state transitions across the Strep A disease spectrum. We identified 175 articles reporting 262 distinct observations of Strep A disease state transitions. Among the included articles, the transition from an invasive or toxin-mediated disease state to another disease state (i.e., to recurrent ARF, RHD or death) was described 115 times (43.9% of all included transition pairs) while the transition to and from locally invasive category was the lowest (n = 7; 0.02%). Transitions from well to any other state was most frequently reported (49%) whereas a relatively higher number of studies (n = 71) reported transition from invasive disease to death. Transitions from any disease state to locally invasive, Strep A pharyngitis to invasive disease, and chronic kidney disease to death were lacking. Transitions related to severe invasive diseases were more frequently reported than superficial ones. Most evidence originated from high-income countries and there is a critical need for new studies in low- and middle-income countries to infer the state transitions across the Strep A disease spectrum in these high-burden settings.

The distance of insertion points from wound margins in interrupted and vertical mattress sutures influences the tensile load capacity: An in vitro experimental study.

AIM: To determine the tensile load capacity (TLC) and the tearing characteristics for interrupted and vertical mattress sutures with different insertion points from the wound margin, and the effect of the bite size when using vertical mattress sutures. MATERIALS AND METHODS: A total of 120 gingiva and lining mucosa samples obtained from pig jaws were divided into groups according to the suturing technique (interrupted and vertical mattress sutures), distance of the insertion points from the wound margin (margin, 1, 3, and 5 mm) and bite size (1, 3, and 5 mm). The TLC of the suture and the tearing characteristics were evaluated using a tensile tester device. RESULTS: The TLC was significantly higher for vertical mattress sutures than for interrupted sutures regardless of the distance of the insertion points from the wound margin (intergroup p < .001). This distance significantly influenced the TLC for vertical mattress sutures (p < .05) but not for interrupted sutures (p > .05). Testing the tearing characteristics revealed that no tissue tearing occurred in groups when the insertion points were more than 3 mm from the wound margin. CONCLUSION: The TLC is higher for vertical mattress sutures than for interrupted sutures, and it increases when the insertion points are farther from the wound margin.

Enhancing guided bone regeneration with cross-linked collagen-conjugated xenogeneic bone blocks and membrane fixation: A preclinical in vivo study.

OBJECTIVE: To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can enhance guided bone regeneration (GBR) in the overaugmented calvarial defect model. MATERIALS AND METHODS: Four circular defects with a diameter of 8 mm were prepared in the calvarium of 13 rabbits. Defects were randomly assigned to receive one of the following treatments: (i) non-cross-linked (NCL) porcine-derived collagen-embedded bone block covered by a CM without fixation (NCL + unfix group); (ii) NCL bone block covered by CM with fixation using bone-tack (NCL + fix group); (iii) cross-linked (CL) porcine-derived collagen-embedded bone block covered by CM without fixation (CL + unfix group); and (iv) CL bone block covered by CM with fixation using bone-tack fixation (CL + fix group). The efficacy of GBR was assessed through histological and molecular analyses after 2 and 8 weeks. RESULTS: At 2 weeks, there were no significant differences in histologically measured areas of newly formed bone among the groups. At 8 weeks, however, the CL + fix group exhibited a larger area of new bone (5.08 ± 1.09 mm2, mean ± standard deviation) compared to the NCL + unfix (1.62 ± 0.42 mm2; p < .0083), NCL + fix (3.97 ± 1.39 mm2) and CL + unfix (2.55 ± 1.04 mm2) groups. Additionally, the expression levels of tumour necrosis factor-alpha, fibroblast growth factor-2, vascular endothelial growth factor, osteocalcin and calcitonin receptor were significantly higher in the CL + fix group compared to the other three groups (p < .0083). CONCLUSION: Cross-linked bone blocks stabilized with collagen membrane fixation can significantly enhance GBR.

Changes in dementia treatment patterns associated with changes in the National Policy in South Korea among patients with newly diagnosed Alzheimer's disease between 2011 and 2017: results from the multicenter, retrospective CAPTAIN study.

BACKGROUND: The South Korean government has been actively involved in plans to combat dementia, implementing a series of national strategies and plans since 2008. In July 2014, eligibility for mandatory long-term care insurance (LTCI) was extended to people with dementia enabling access to appropriate long-term care including the cognitive function training program and home nursing service. This study aimed to investigate changes in treatment patterns for Alzheimer's disease (AD) between July 2011 and June 2017 which spanned the 2014 revision. METHODS: This multicenter, retrospective, observational study of patients with newly diagnosed AD analyzed electronic medical records from 17 general hospitals across South Korea. Based on their time of AD diagnosis, subjects were categorized into Cohort 1 (1 July 2011 to 30 June 2014) and Cohort 2 (1 July 2014 to 30 June 2017). RESULTS: Subjects (N=3,997) divided into Cohorts 1 (n=1,998) and 2 (n=1,999), were mostly female (66.4%) with a mean age of 84.4 years. Cohort 1 subjects were significantly older (P<0.0001) and had a lower number of comorbidities (P=0.002) compared with Cohort 2. Mean Mini-Mental State Examination (MMSE) scores in Cohorts 1 and 2 at the time of AD diagnosis or start of initial treatment were 16.9 and 17.1, respectively (P=0.2790). At 1 year, mean MMSE scores in Cohorts 1 and 2 increased to 17.9 and 17.4, respectively (P=0.1524). Donepezil was the most frequently administered medication overall (75.0%), with comparable rates between cohorts. Rates of medication persistence were ≥98% for acetylcholinesterase inhibitor or memantine therapy. Discontinuation and switch treatment rates were significantly lower (49.7% vs. 58.0%; P<0.0001), and mean duration of initial treatment significantly longer, in Cohort 2 vs. 1 (349.3 vs. 300.2 days; P<0.0001). CONCLUSIONS: Comparison of cohorts before and after revision of the national LTCI system for dementia patients found no significant difference in mean MMSE scores at the time of AD diagnosis or start of initial treatment. The reduction in the proportion of patients who discontinued or changed their initial treatment, and the significant increase in mean duration of treatment, were observed following revision of the LTCI policy which enabled increased patient access to long-term care.

Ultra-Wideband Vertical Transition in Coplanar Stripline for Ultra-High-Speed Digital Interfaces.

A design method for an ultra-wideband coplanar-stripline-based vertical transition that can be used for ultra-high-speed digital interfaces is proposed. A conventional via structure, based on a differential line (DL), inherently possesses performance limitations (<10 GHz) due to difficulties in maintaining constant line impedance and smooth electric field transformation, in addition to the effects of signal skews, FR4 fiber weave, and unbalanced EM interferences. DL-based digital interfaces may not meet the demands of ultra-high-speed digital data transmission required for the upcoming 6G communications. The use of a coplanar stripline (CPS), a type of planar balanced line (BL), for the vertical transition, along with the ultra-wideband DL-to-CPS transition, mostly removes the inherent and unfavorable issues of the DL and enables ultra-high-speed digital data transmission. The design process of the transition is simplified using the analytical design formulas, derived using the conformal mapping method, of the transition. The characteristic line impedances of the transition are calculated and found to be in close agreement with the results obtained from EM simulations. Utilizing these results, the CPS-based vertical transition, maintaining the characteristic line impedance of 100 Ω, is designed and fabricated. The measured results confirm its ultra-wideband characteristics, with a maximum of 1.6 dB insertion loss and more than 10 dB return loss in the frequency range of DC to 30 GHz. Therefore, the proposed CPS-based vertical transition offers a significantly wider frequency bandwidth, i.e., more than three times that of conventional DL-based via structures.

Immediate loading on two adjacent single dental implants with definitive nonsplinted restorations: A proof of concept in the posterior zone.

OBJECTIVES: To evaluate clinical, clinician- and patient-reported outcomes (PROs) of two adjacent single posterior implants immediately loaded with definitive single crowns up to 1 year. Ten patients in need of two adjacent posterior single implants were included. All implants were placed applying a fully digital workflow. Definitive screw-retained single zirconia crowns were delivered within 72 h after implant placement. Clinical parameters, patient- and clinician-reported outcomes were assessed up to 1 year of follow-up. CLINICAL CONSIDERATIONS: Clinical outcomes remained stable, with no implant failures or technical and biological complications throughout the observation period. Patient satisfaction was very high at baseline (crown delivery) and remained consistently high at 6 and 12 months of follow-up. Crown insertion 3 days after implant placement was rated as an easy procedure by clinicians. CONCLUSIONS: Two adjacent single implants with immediate definitive restorations (<72 h) in the posterior region appear to be a viable and easy treatment option to shorten the overall treatment time and potentially enhancing patient satisfaction. However, randomized controlled trials are needed to confirm the advantages of this treatment protocol over a delayed loading approach. CLINICAL SIGNIFICANCE: In selected cases, immediate implant loading with definitive restorations in the posterior region appears a valuable and straightforward option to shorten the overall treatment time.

The Threat of Climate Change on Tick-Borne Infections: Rising Trend of Infections and Geographic Distribution of Climate Risk Factors Associated With Ticks.

Ticks transmit a wide range of pathogens. The spread of tick-borne infections is an emerging, yet often overlooked, threat in the context of climate change. The infections have rapidly increased over the past few years in South Korea despite no significant changes in socioeconomic circumstances. We investigated the impact of climate change on the surge of tick-borne infections and identified potential disease hot spots at a resolution of 5 km by 5 km. A composite index was constructed based on multiple climate and environmental indicators and compared with the observed tick-borne infections. The surge of tick-borne episodes corresponded to the rising trend of the index over time. High-risk areas identified by the index can be used to prioritize locations for disease prevention activities. Monitoring climate risk factors may provide an opportunity to predict the spread of the infections in advance.

Vaccination to Reduce Antimicrobial Resistance Burden-Data Gaps and Future Research.

Antimicrobial resistance (AMR) poses an immediate danger to global health. If unaddressed, the current upsurge in AMR threatens to reverse the achievements in reducing the infectious disease-associated mortality and morbidity associated with antimicrobial treatment. Consequently, there is an urgent need for strategies to prevent or slow the progress of AMR. Vaccines potentially contribute both directly and indirectly to combating AMR. Modeling studies have indicated significant gains from vaccination in reducing AMR burdens for specific pathogens, reducing mortality/morbidity, and economic loss. However, quantifying the real impact of vaccines in these reductions is challenging because many of the study designs used to evaluate the contribution of vaccination programs are affected by significant background confounding, and potential selection and information bias. Here, we discuss challenges in assessing vaccine impact to reduce AMR burdens and suggest potential approaches for vaccine impact evaluation nested in vaccine trials.

AXL+SIGLEC6+ dendritic cells in cerebrospinal fluid and brain tissues of patients with autoimmune inflammatory demyelinating disease of CNS.

Inflammatory demyelinating disease of the CNS (IDD) is a heterogeneous group of autoimmune diseases, and multiple sclerosis is the most common type. Dendritic cells (DCs), major antigen-presenting cells, have been proposed to play a central role in the pathogenesis of IDD. The AXL+SIGLEC6+ DC (ASDC) has been only recently identified in humans and has a high capability of T cell activation. Nevertheless, its contribution to CNS autoimmunity remains still obscure. Here, we aimed to identify the ASDC in diverse sample types from IDD patients and experimental autoimmune encephalomyelitis (EAE). A detailed analysis of DC subpopulations using single-cell transcriptomics for the paired cerebrospinal fluid (CSF) and blood samples of IDD patients (total n = 9) revealed that three subtypes of DCs (ASDCs, ACY3+ DCs, and LAMP3+ DCs) were overrepresented in CSF compared with their paired blood. Among these DCs, ASDCs were also more abundant in CSF of IDD patients than in controls, manifesting poly-adhesional and stimulatory characteristics. In the brain biopsied tissues of IDD patients, obtained at the acute attack of disease, ASDC were also frequently found in close contact with T cells. Lastly, the frequency of ASDC was found to be temporally more abundant in acute attack of disease both in CSF samples of IDD patients and in tissues of EAE, an animal model for CNS autoimmunity. Our analysis suggests that the ASDC might be involved in the pathogenesis of CNS autoimmunity.

Endothelial Cell TGF-ß (Transforming Growth Factor-Beta) Signaling Regulates Venous Adaptive Remodeling to Improve Arteriovenous Fistula Patency.

BACKGROUND: Arteriovenous fistulae (AVF) are the gold standard for vascular access for hemodialysis. Although the vein must thicken and dilate for successful hemodialysis, excessive wall thickness leads to stenosis causing AVF failure. Since TGF-ß (transforming growth factor-beta) regulates ECM (extracellular matrix) deposition and smooth muscle cell (SMC) proliferation-critical components of wall thickness-we hypothesized that disruption of TGF-ß signaling prevents excessive wall thickening during venous remodeling. METHODS: A mouse aortocaval fistula model was used. SB431542-an inhibitor of TGF-ß receptor I-was encapsulated in nanoparticles and applied to the AVF adventitia in C57BL/6J mice. Alternatively, AVFs were created in mice with conditional disruption of TGF-ß receptors in either SMCs or endothelial cells. Doppler ultrasound was performed serially to confirm patency and to measure vessel diameters. AVFs were harvested at predetermined time points for histological and immunofluorescence analyses. RESULTS: Inhibition of TGF-ß signaling with SB431542-containing nanoparticles significantly reduced p-Smad2-positive cells in the AVF wall during the early maturation phase (days 7-21) and was associated with decreased AVF wall thickness that showed both decreased collagen density and decreased SMC proliferation. SMC-specific TGF-ß signaling disruption decreased collagen density but not SMC proliferation or wall thickness. Endothelial cell-specific TGF-ß signaling disruption decreased both collagen density and SMC proliferation in the AVF wall and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency. CONCLUSIONS: Endothelial cell-targeted TGF-ß inhibition may be a translational strategy to improve AVF patency.

Platelet-rich fibrin combined with a particulate bone substitute versus guided bone regeneration in the damaged extraction socket: An in vivo study.

AIM: It has been proposed that platelet-rich fibrin (PRF) can be used to support bone regeneration during alveolar ridge augmentation. The aim of this study was to determine whether an approach utilizing PRF provides similar performance to the established guided bone regeneration (GBR) procedure. MATERIALS AND METHODS: Two-wall defects were surgically created in beagle dogs and treated in three experimental groups: (i) a sticky bone (SB) substitute prepared using liquid PRF and deproteinized porcine bone mineral (DPBM); (ii) SB covered with solid PRF compressed into a membrane; and (iii) GBR performed using DPBM covered by a collagen membrane. Quantitative reverse-transcription polymerase chain reaction was applied to the specimen after 1 week of healing, and microcomputed tomography (micro-CT) and histological outcomes were analysed after 8 weeks of healing. RESULTS: Compared with GBR, PRF resulted in a moderate increase in the expression levels of osteoblast and osteoclast markers, osteocalcin, and calcitonin receptor. Moreover, PRF modestly increased angiogenesis and the inflammation markers vascular endothelial growth factor (VEGF) and IL-6. Micro-CT and histological analyses confirmed the expected increased alveolar ridge area, with no significant differences between the three groups. Consistently, graft consolidation, as indicated by new bone formation at the defect site, did not differ significantly between groups. CONCLUSIONS: The present results demonstrate that PRF-based approaches perform comparably to the established GBR procedure in terms of the consolidation of DPBM in two-wall alveolar defects.

FasL is a catabolic factor in alveolar bone homeostasis.

AIM: Fas ligand (FasL) belongs to the tumour necrosis factor superfamily regulating bone turnover, inflammation, and apoptosis. The appendicular and axial skeleton phenotype of mature Faslgld mice has been reported. The impact of FasL on the alveolar bone providing support for the teeth at mature stages under healthy and induced inflammatory conditions remains unknown. MATERIALS AND METHODS: We performed a phenotypical analysis of mice carrying the homozygous Faslgld mutation and wild-type (WT) mice (C57BL/6) under healthy conditions and upon ligature-induced periodontitis. After 12 days, micro-computed tomography analysis revealed the distance between the cement enamel junction and the alveolar bone crest. Additional structural parameters, such as the bone volume fraction (BV/TV) and the periodontal ligament space volume, were measured. Histological analyses were performed to visualize the catabolic changes at the defect site. RESULTS: Healthy Faslgld mice were found to have more periodontal bone than their WT littermates. Faslgld had no significant effect on inflammatory osteolysis compared to WT controls with ligatures. Histology revealed eroded surfaces at the root and in the inter-proximal bone in both strains. CONCLUSIONS: Our findings suggest that FasL is a catabolic factor in alveolar bone homeostasis but it does not affect the inflammatory osteolysis.

Oral Porphyromonas gingivalis infection affects intestinal microbiota and promotes atherosclerosis.

AIM: The link between periodontitis and intestinal dysbiosis, two factors that contribute to atherosclerosis, has not been clearly defined. We investigated the integrative effects of oral infection with Porphyromonas gingivalis (PG), the major pathogen for periodontitis, on intestinal microbiota and atherosclerosis. MATERIALS AND METHODS: ApoE-/- mice were fed a normal chow diet (NC), a Western diet (WD) or a WD with oral PG infection (PG). The PG infection was investigated by placing a total of 109 CFUs of live PG into the oral cavity of each mouse using a feeding needle five times a week for 3 weeks. Atherosclerotic lesions of the aortae were measured, and blood lipoproteins and the expression of molecules related to lipid metabolism in the liver were analysed. We also performed 16S RNA sequencing and a microbiome analysis using faeces. RESULTS: En face bloc preparation of the aortae showed that the PG group had a 1.7-fold increase in atherosclerotic lesions compared with the WD group (p < .01). Serum analyses showed that oral PG infection induced a significant decrease in high-density lipoprotein (HDL) and triglyceride. Western blots of hepatic tissue lysates revealed that PG infection reduced the expression of scavenger receptor class B type 1 (SR-B1) in the liver by 50%. Faecal microbiota analysis revealed that species richness estimates (Chao1, ACE) decreased immediately after PG infection. PG infection also induced a significant decrease in Shannon diversity and an increase in Simpson's indices in the WD-fed mice. PG infection significantly increased the phyla Actinobacteria and Deferribacteres, along with the species Mucispirillum schaedleri and Lactobacillus gasseri, in the mice. The functional study showed that PG infection increased the expression of proteins that function in carbohydrate and glucose metabolism, including phosphotransferase system (PTS) proteins and the GntR family transcriptional regulator. CONCLUSIONS: Oral PG infection promotes atherosclerosis and induces significant metabolic changes, including reduced serum HDL and reduced hepatic SR-B1 and ABCA1 expression, as well as changes in intestinal microbiota. Our study suggests that intestinal dysbiosis accompanies periodontitis and could play a role in atherosclerosis.

Does the fixture thread depth affect the accuracy of implant placement during fully guided immediate implant placement?: A human cadaver study.

BACKGROUND: The fixture thread depth reportedly influences the primary stability of dental implant, but its effect on the positional accuracy in immediate implant placement has not been reported previously. MATERIALS AND METHODS: Fifty-six single-rooted, anterior and premolar teeth were extracted from six human cadavers, followed by installing either regular-threaded implants (RT group, N = 30) or deep-threaded implants (DT group, N = 26) completely relying on the surgical guide. Optical impressions taken after osteotomy and fixture installation were superimposed with the preoperative virtual planning data to measure the vertical, angular, platform and apex deviations that occurred during osteotomy and installation. RESULTS: While the osteotomy deviations were similar between the two groups, the angular and apex deviation of the DT group (2.67 ± 2.56°; 1.04 ± 0.49 mm, respectively) were significantly larger than those of the RT group (1.61 ± 1.04°; 0.67 ± 0.41 mm, respectively) during installation (p < .05). When the installation deviations were analysed in the anterior and premolar areas separately, the angular, platform and apex deviations of the DT group (3.05 ± 3.26°; 0.75 ± 0.32 mm; 1.08 ± 0.56 mm, respectively) were significantly larger than those of the RT group (1.56 ± 0.73°, 0.59 ± 0.28 mm; 0.62 ± 0.38 mm, respectively) in the anterior site (p < .05), whereas there was no significant intergroup difference in the premolar site. CONCLUSION: In immediate-implant surgery, using an implant with a deeper thread might increase the deviations during installation, especially in the anterior area.

Medication-related osteonecrosis of the jaw using periodontitis-induced rat before tooth extraction.

OBJECTIVE: This study aimed to investigate the occurrence of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction due to periodontitis in ovariectomized rats. METHODS: Twenty-four osteoporosis-induced rats were administered with zoledronic acid (ZA; ZA group) or saline (CONT group). In both groups, tooth extraction was performed after inducing periodontitis, and all animals were sacrificed 8-week after tooth extraction. RESULTS: Micro-CT of the tibia showed that the bone volume fraction, bone surface density, trabecular number, and bone mineral density were significantly higher in the ZA group than in the CONT group. Histologically, the proliferative zone on the growth plate was thicker in the ZA group than in the CONT group. Micro-CT of the extraction sites revealed that the bone volume fraction was significantly higher in the ZA group than in the CONT group. Radiologically, the ZA group showed partial healing and delayed healing. Histological analysis revealed normal bone healing status with completely healed epithelium in the extraction sites of the CONT group, whereas abnormal empty osteocytes in the necrotic bone and inflammatory infiltration were observed in the ZA group. CONCLUSION: The incidence of MRONJ increased in the rats administered with ZA.

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

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

Effect of collagen membrane fixation on ridge volume stability and new bone formation following guided bone regeneration.

AIM: To test the effect of membrane fixation on ridge volume stability and new bone formation using guided bone regeneration. MATERIALS AND METHODS: In eight beagle dogs, after bilateral extraction of the maxillary pre-molars, a box-shaped defect was created on each side. All defect sites were augmented with a particulate bone substitute material, covered with either one of two non-cross-linked collagen membranes (CM1 or CM2) with or without fixation (-F or -UF). Samples were collected after 8 weeks. Histomorphometric and micro-computed tomography analyses were performed. RESULTS: Membrane fixation made no significant difference to the total augmented volume for both membranes (p > .05). Histological data indicated that at the ridge crest the augmented tissue width amounted to 2.4 ± 0.4 mm in the group CM1-F and 2.4 ± 0.5 mm in the group CM1-UF, with no significant difference between the groups. Conversely, in CM2-F the augmented tissue width was significantly larger than in CM2-UF (2.3 ± 0.1 vs. 1.57 ± 0.27, p < .05). CONCLUSIONS: Membrane fixation in contained defects failed to improve ridge volume stability regardless of the membrane type. However, it may enhance the width of the augmented ridge at the coronal portion depending on the type of membrane.

Membrane fixation enhances guided bone regeneration in standardized calvarial defects: A pre-clinical study.

AIM: To determine whether collagen membrane (CM) fixation enhances guided bone regeneration in standardized defects. MATERIALS AND METHODS: Four 8-mm-diameter defects were surgically made in eight rabbit calvaria, and randomly allocated into four groups: control (empty), unfixed-CM, fixed-CM, and unfixed-CM with bone graft (BG + CM) (positive control). After 1- and 4-week healing periods, the animals were sacrificed and quantitative reverse transcription polymerase chain reaction, micro-computed tomography, and histological outcomes were assessed. RESULTS: At week 1, the expression levels of BMP-2, FGF-2, VEGF, and osteocalcin were significantly higher in the fixed-CM group than in the unfixed-CM and control groups (p < .05). Conversely, cathepsin-K was significantly expressed in the unfixed-CM group. No significant differences in expression markers were observed between the fixed-CM and BG + CM groups (p > .05). At week 4, new bone formation was significantly higher in the fixed-CM group than the unfixed-CM and control groups (p < .05), but similar to the BG + CM group (p > .05). CONCLUSIONS: CM fixation enhances the expression of osteogenic factors similar to BG + CM, leading to significantly more new bone formation. This suggests that the osteogenic potential is greater when membranes are fixed, thereby limiting the necessity of membrane-supporting materials to enhance bone formation.

Targeting prostate cancer with Clostridium perfringens enterotoxin functionalized nanoparticles co-encapsulating imaging cargo enhances magnetic resonance imaging specificity.

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 ±â€¯15.7 nm (RS1) had a 2-fold enhancement of tumor specificity compared to larger (421.2 ±â€¯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.