P-Selectin mediates targeting of a self-assembling phototherapeutic nanovehicle enclosing dipyridamole for managing thromboses.

Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.

Customizing Polymers by Controlling Cation Switching Dynamics in Non-Living Polymerization.

Controlling the chain growth process in non-living polymerization reactions is difficult because chain termination typically occurs faster than the time it takes to apply an external trigger. To overcome this limitation, we have developed a strategy to regulate non-living polymerizations by exploiting the chemical equilibria between a metal catalyst and secondary metal cations. We have prepared two nickel phenoxyphosphine-polyethylene glycol variants, one with 2-methoxyphenyl (Ni1) and another with 2,6-dimethoxyphenyl (Ni2) phosphine substituents. Ethylene polymerization studies using these complexes in the presence of alkali salts revealed that chain growth is strongly dependent on electronic effects, whereas chain termination is dependent on both steric and electronic effects. By adjusting the solvent polarity, we can favor polymerizations via non-switching or dynamic switching modes. For example, in a 100:0.2 mixture of toluene/diethyl ether, reactions of Ni1 and both Li+ and Na+ cations in the presence of ethylene yielded bimodal polymers with different relative fractions depending on the Li+/Na+ ratio used. In a 98:2 mixture of toluene/diethyl ether, reactions of Ni2 and Cs+ in the presence of ethylene generated monomodal polyethylene with dispersity <2.0 and increasing molecular weight as the amount of Cs+ added increased. Solution studies by NMR spectroscopy showed that cation exchange between the nickel complexes and alkali cations in 98:2 toluene/diethyl ether is fast on the NMR time scale, which supports our proposed dynamic switching mechanism.

Cone-beam computed tomography and digital model analysis of maxillary buccal alveolar bone thickness for vertical temporary skeletal anchorage device placement.

INTRODUCTION: This study aimed to quantify the buccal alveolar bone thickness (BABT) in the maxillary molar region to provide a practical guideline for vertical temporary skeletal anchorage device (TSAD) placement using cone-beam computed tomography (CBCT). It also aimed to develop a linear regression model for use in digital models to predict available BABT. METHODS: The sample for this retrospective study consisted of 31 sites (24 patients; mean age, 28.75 years; range, 18-44 years) in which vertical TSADs were placed successfully in the maxillary posterior interradicular area during the total arch distalization procedure. BABT was measured at 3 points of the interradicular space using CBCT, and the buccal alveolar region thickness (BART), which included buccal-attached gingival thickness and the buccal alveolar bone, was measured using the digital model. In CBCT, BABT was measured at the most convex point of the lamina dura of the root adjacent to the vertical TSAD mesially, at the most convex point of the lamina dura of the root adjacent to the vertical TSAD distally, and the central point between the mesial and distal points. Three linear measurements were obtained at 2, 4, and 6 mm apical to the alveolar crest: the mesial thickness, the central thickness (centralCBCT), and the distal thickness. In the digital model, the most convex points of the clinical crowns of 2 teeth adjacent to vertical TSAD and their contact point along with the corresponding Will Andrews and Lawrence Andrews ridge were identified. The horizontal distance paralleling the model base was digitally measured and recorded at 3 positions: the mesial, central, and distal points. Then, the following 3 linear measurements were taken directly on each 3-dimensional dental model: the mesial thickness, the central thickness (centralModel), and the distal thickness. RESULTS: Both BABT and BART at the central position (centralCBCT, 3.44 mm; centralModel, 6.28 mm) were thicker than at the 2 exterior positions (mesial thickness, 2.16; distal thickness, 2.59 mm; mesial thickness, 2.74 mm; distal thickness, 2.99 mm). BABT was thinnest at 2 mm from the alveolar crest, and there was no statistically significant difference between 4 mm and 6 mm. There was a strong correlation between centralModel and centralCBCT. CONCLUSIONS: The mean BABT and BART at the central position, in which we suggest placing vertical TSADs, were 3.44 ± 0.69 mm in CBCT and 6.28 ± 1.11 mm in the digital model, respectively. The minimum BABT and BART at the central position in which vertical TSAD was placed successfully were 2.38 mm in CBCT and 4.25 mm in the digital model. There was a strong correlation between centralCBCT and centralModel, and we developed a linear regression model that resulted in a useful formula for estimating the actual available BABT at the central position: centralCBCT = 0.57 × centralModel - 0.15.

A review on revolutionizing ophthalmic therapy: Unveiling the potential of chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer in eye disease treatments.

Ocular disorders, encompassing both common ailments like dry eye syndrome and more severe situations for instance age-related macular degeneration, present significant challenges to effective treatment due to the intricate architecture and physiological barriers of the eye. Polysaccharides are emerging as potential solutions for drug delivery to the eyes due to their compatibility with living organisms, natural biodegradability, and adhesive properties. In this review, we explore not only the recent advancements in polysaccharide-based technologies and their transformative potential in treating ocular illnesses, offering renewed optimism for both patients and professionals but also anatomy of the eye and the significant obstacles hindering drug transportation, followed by an investigation into various drug administration methods and their ability to overcome ocular-specific challenges. Our focus lies on biological adhesive polymers, including chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer, known for their adhesive characteristics enhancing drug retention on ocular surfaces and increasing bioavailability. A detailed analysis of material designs used in ophthalmic formulations, such as gels, lenses, eye drops, nanofibers, microneedles, microspheres, and nanoparticles, their advantages and limitations, the potential of formulations in improving therapeutic outcomes for various eye conditions. Moreover, we underscore the discovery of novel polysaccharides and their potential uses in ocular drug delivery.

Advancing teeth whitening efficacy via dual-phototherapeutic strategy incorporating molybdenum disulfide embedded in carrageenan hydrogel for dental healthcare.

Teeth discoloration poses a widespread challenge in dental health across various regions. Conventional teeth whitening methods often result in enamel deterioration and soft tissue harm due to the utilization of incompatible whitening agents and continuous intense light exposure. Here, we propose an effective phototherapy technique for teeth whitening, employing pathways of energy transition through intersystem crossing. The integration of MoS2 nanosheets into carrageenan gel (MoS2 NSs@Carr) facilitates both photothermal-hyperthermia and the generation of reactive oxygen species (ROS) through photocatalytic processes. The efficacy of ROS generation by the phototherapeutic MoS2 NSs@Carr on teeth whitening in the scenario. This approach ensures comprehensive teeth whitening by eliminating deep-seated stains on the teeth while preserving structural integrity and avoiding any tissue toxicity. This research highlights the efficacy of the phototherapeutic MoS2 NSs@Carr for dental whitening and underscores the potential of exploring nanostructures based on MoS2 NSs for managing dental healthcare issue.

Microbial monomers custom-synthesized to build true bio-derived aromatic polymers.

Aromatic polymers include novel and extant functional materials although none has been produced from biotic building blocks derived from primary biomass glucose. Here we screened microbial aromatic metabolites, engineered bacterial metabolism and fermented the aromatic lactic acid derivative ß-phenyllactic acid (PhLA). We expressed the Wickerhamia fluorescens gene (pprA) encoding a phenylpyruvate reductase in Escherichia coli strains producing high levels of phenylalanine, and fermented optically pure (>99.9 %) D-PhLA. Replacing pprA with bacterial ldhA encoding lactate dehydrogenase generated L-PhLA, indicating that the produced enzymes converted phenylpyruvate, which is an intermediate of phenylalanine synthesis, to these chiral PhLAs. Glucose was converted under optimized fermentation conditions to yield 29 g/l D-PhLA, which was purified from fermentation broth. The product satisfied the laboratory-scale chemical synthesis of poly(D-PhLA) with M w 28,000 and allowed initial physiochemical characterization. Poly(D-PhLA) absorbed near ultraviolet light, and has the same potential as all other biomass-derived aromatic bioplastics of phenylated derivatives of poly(lactic acid). This approach to screening and fermenting aromatic monomers from glucose exploits a new era of bio-based aromatic polymer design and will contribute to petroleum conservation and carbon dioxide fixation.

High inductance magnetic-core coils have enhanced efficiency in inducing suprathreshold motor response in rats.

Objective. Transcranial magnetic stimulation (TMS) coil design involves a tradeoff among multiple parameters, including magnetic flux density (B), inductance (L), induced electric (E) field, focality, penetration depth, coil heating, etc. Magnetic materials with high permeability have been suggested to enhance coil efficiency. However, the introduction of magnetic core invariably increases coil inductance compared to its air-core counterpart, which in turn weakens theEfield. Our lab previously reported a rodent-specific TMS coil with silicon steel magnetic core, achieving 2 mm focality. This study aims to better understand the tradeoffs amongB,L,andEin the presence of magnetic core.Approach. The magnetic core initially operates within the linear range, transitioning to the nonlinear range when it begins to saturate at high current levels and reverts to the linear range as coil current approaches zero; both linear and nonlinear analyses were performed. Linear analysis assumes a weak current condition when magnetic core is not saturated; a monophasic TMS circuit was employed for this purpose. Nonlinear analysis assumes a strong current condition with varying degrees of core saturation.Main results. Results reveal that, the secondaryEfield generated by the silicon steel core substantially changed the dynamics during TMS pulse. Linear and nonlinear analyses revealed that higher inductance coils produced stronger peakEfields and longerEfield waveforms. On a macroscopic scale, the effects of these two factors on neuronal activation could be conceptually explained through a one-time-constant linear membrane model. Four coils with differentB,L,andEcharacteristics were designed and constructed. BothEfield mapping and experiments on awake rats confirmed that inductance could be much higher than previously anticipated, provided that magnetic material possesses a high saturation threshold.Significance. Our results highlight the novel potentials of magnetic core in TMS coil designs, especially for small animals.

Oral health in patients scheduled for hematopoietic stem cell transplantation in the Orastem study.

Despite advances in transplant medicine, prevalence of complications after hematopoietic stem cell transplantation (HSCT) remains high. The impact of pre-HSCT oral health factors on the incidence and severity of complications post-HSCT is poorly understood. The aim of this prospective, observational study was to analyze oral health in patients planned for HSCT. Patients ≥18 years requiring HSCT were included from five sites between 2011-2018. General health, oral findings and patient-reported symptoms were registered in 272 patients. Oral symptoms around disease onset were reported by 43 patients (15.9%) and 153 patients (58.8%) reported oral complications during previous chemotherapy. One third of patients experienced oral symptoms at the oral examination before conditioning regimen and HSCT. In total, 124 (46.1%) patients had dental caries, 63 (29.0%) had ≥one tooth with deep periodontal pockets, 147 (75.0%) had ≥one tooth with bleeding on probing. Apical periodontitis was observed in almost 1/4 and partially impacted teeth in 17 (6.3%) patients. Oral mucosal lesions were observed in 84 patients (30.9%). A total of 45 (17.4%) of 259 patients had at least one acute issue to be managed prior to HSCT. In conclusion, oral symptoms and manifestations of oral disease were prevalent in patients planned for HSCT. The extent of oral and acute dental diseases calls for general oral screening of patients pre-HSCT.

Photothermal-Irradiated Polyethyleneimine-Polypyrrole Nanopigment Film-Coated Polyethylene Fabrics for Infrared-Inspired with Pathogenic Evaluation.

Influenza, pneumonia, and pathogenic infection of the respiratory system are boosted in cold environments. Low temperatures also result in vasoconstriction, restraint of blood flow, and decreased oxygen to the heart, and the risk of a heart attack would increase accordingly. The present face mask fabric fails to preserve its air-filtering function as its electrostatic function vanishes once exposed to water. Therefore, its filtering efficacy would be decreased meaningfully, making it nearly impracticable to reuse the disposable face masks. The urgent requirement for photothermal fabrics is also rising. Nanobased polyethyleneimine-polypyrrole nanopigments (NPP NPs) have been developed and have strong near-infrared spectrum absorption and exceptional photothermal convertible performance. Herein, the mask fabric used PE-fiber-constructed membrane (PEFM) was coated by the binding affinity of the cationic polyethyleneimine component of NPP NPs forming NPP NPs-PEFM. To the best of our knowledge, no study has investigated NPP NP-coated mask fabric to perform infrared red (solar or body) photothermal conversion efficacy to provide biocompatible warming, remotely photothermally captured antipathogen, and antivasoconstriction in vivo. This pioneering study showed that the developed NPP NPs-PEFM could be washable, reusable, breathable, biocompatible, and photothermal conversable for active eradication of pathogenic bacteria. Further, it possesses warming preservation and antivasoconstriction.

Electric field stimulation through a biodegradable polypyrrole-co-polycaprolactone substrate enhances neural cell growth.

Nerve guidance conduits (NGCs) are FDA-approved devices used to bridge gaps across severed nerve cables and help direct axons sprouting from the proximal end toward the distal stump. In this article, we present the development of a novel electrically conductive, biodegradable NGC made from a polypyrrole-block-polycaprolactone (PPy-PCL) copolymer material laminated with poly(lactic-co-glycolic acid) (PLGA). The PPy-PCL has a bulk conductivity ranging 10-20 S/cm and loses 40 wt % after 7 months under physiologic conditions. Dorsal root ganglia (DRG) grown on flat PPy-PCL/PLGA material exposed to direct current electric fields (EF) of 100 mV/cm for 2 h increased axon growth by 13% (± 2%) toward either electrode of a 2-electrode setup, compared with control grown on identical substrates without EF exposure. Alternating current increased axon growth by 21% (±3%) without an observable directional preference, compared with the same control group. The results from this study demonstrate PLGA-coated PPy-PCL is a unique biodegradable material that can deliver substrate EF stimulation to improve axon growth for peripheral nerve repair.

Microbial sampling process can change results of microbiological analysis in periodontitis diagnosis. A minireview.

This minireview aims to verify the supposition that the microbial sampling process can change results of microbiological analysis in periodontitis diagnosis. The literature search via Pubmed yielded 52 appropriate articles for analysis. Of which 38% (20/52) described that the sampling sites were isolated from saliva, whereas 62% (32/52) did not. Also, 29% (15/52) declared that the microbial sampling was performed before probing pocket depth (PPD), whereas 71% (37/52) did not. Comparison of the results of microbiological analysis in these studies showed that the bacteria most frequently detected in periodontal pockets was variable. Therefore, a sampling process that includes both the microbial sample being taken before PPD and saliva isolation of the sampling sites is needed to ensure the accuracy of microbiological analysis in periodontitis diagnosis.

Methanogenic archaea in subgingival sites: a review.

Archaea are non-bacterial prokaryotes associated with oral microbiota in humans, but their roles in oral pathologies remain controversial. Several studies reported the molecular detection of methanogenic archaea from periodontitis, but the significance of this association has not been confirmed yet. An electronic search was therefore conducted in MEDLINE-Pubmed to identify all papers published in English connecting archaea and periodontal infections. Data analysis of the selected studies showed that five genera of methanogenic archaea have been detected in the subgingival microbiota, Methanobrevibacter oralis being the most frequently detected species in 41% of periodontitis patients and 55% of periodontal pockets compared to 6% of healthy subjects and 5% of periodontally-healthy sites (p < 10(-5) , Chi-squared test). Based on the five determination-criteria proposed by Socransky (association with disease, elimination of the organism, host response, animal pathogenicity and mechanisms of pathogenicity), M. oralis is a periodontal pathogen. The methanogenic archaea load correlating with periodontitis severity further supports the pathogenic role of methanogenic archaea in periodontitis. Therefore, detection and quantification of M. oralis in periodontal pockets could help the laboratory diagnosis and follow-up of periodontitis. Determining the origin, diversity and pathogenesis of archaea in periodontal infections warrants further investigations.

Peri-implantitis: from diagnosis to therapeutics.

Peri-implantitis is an infection of the tissue around an implant, resulting in the loss of supporting bone. Risk factors for peri-implantitis consist of a history of periodontitis, dental plaque, poor oral hygiene, smoking, alcohol consumption and diabetes. A clinical diagnosis indicates inflammatory signs including bleeding on probing with or without suppuration and a peri-implant pocket depth ≥5 mm. A radiograph shows images of marginal bone loss ≥2 mm. A differential diagnosis of peri-implant mucositis, occlusal overload, retrograde peri-implantitis and inflammatory implant periapical lesions suggests the appropriate treatment in each case. The non-surgical treatment of peri-implantitis, including a mechanical treatment alone or combined with antiseptics or antibiotics can improve clinical parameters in the short term but residual defects may still persist. Surgical treatment such as guided bone regeneration results in a gain of clinical attachment level and bone reconstruction in the long term. The limited effect of laser-assisted therapy needs to be further evaluated. The concept of prevention based on early detection and regular maintenance plays a principal role in reducing the occurrence of peri-implantitis.

Gingival recession associated with predisposing factors in young vietnamese: a pilot study.

AIMS: Several studies have shown a large diversity in the prevalence, extent and severity of gingival recession as well as controversial conclusions of its associated factors. Therefore, the aim of this pilot study was to evaluate gingival recession with predisposing factors in young Vietnamese. METHODS: A cross-sectional study using clinical examination was performed in 120 dental students. Oral hygiene status, tooth malposition and fraenal attachment were recorded. The width of keratinised gingiva was measured after mucosa staining with Lugol's iodine solution. Measurements of gingival recession were performed on labial tooth surfaces. Chisquare test, t-test and Pearsonâs correlation were used for data analysis. RESULTS: The prevalence of gingival recession was 72.5% of the studied population. The extent of affected teeth was 11.1% of the examined teeth. The proportion of root-surface exposure was statistically higher (P<0.05) in the maxilla (12.5%) than in the mandible (9.6%). Premolars and right canines were the teeth most frequently and most seriously associated with gingival recession, respectively. There was a strong negative correlation between narrow width of keratinised gingiva and gingival recession (P<0.001). The recession was statistically associated with tooth malposition (P<0.001) but it was not related to high fraenal attachment and gender. CONCLUSIONS: A high prevalence of gingival recession was found in Vietnamese dental students. Gingival recession was associated with narrow width of keratinised gingiva, tooth malposition and maxillary teeth. Further studies performed in larger populations with more extended age groups are needed to confirm these findings.

The seroprevalence and seroincidence of enterovirus71 infection in infants and children in Ho Chi Minh City, Viet Nam.

Enterovirus 71 (EV71)-associated hand, foot and mouth disease has emerged as a serious public health problem in South East Asia over the last decade. To better understand the prevalence of EV71 infection, we determined EV71 seroprevalence and seroincidence amongst healthy infants and children in Ho Chi Minh City, Viet Nam. In a cohort of 200 newborns, 55% of cord blood samples contained EV71 neutralizing antibodies and these decayed to undetectable levels by 6 months of age in 98% of infants. The EV71 neutralizing antibody seroconversion rate was 5.6% in the first year and 14% in the second year of life. In children 5-15 yrs of age, seroprevalence of EV71 neutralizing antibodies was 84% and in cord blood it was 55%. Taken together, these data suggest EV71 force of infection is high and highlights the need for more research into its epidemiology and pathogenesis in high disease burden countries.

Evidence of a louse-borne outbreak involving typhus in Douai, 1710-1712 during the war of Spanish succession.

BACKGROUND: The new field of paleomicrobiology allows past outbreaks to be identified by testing dental pulp of human remains with PCR. METHODS: We identified a mass grave in Douai, France dating from the early XVIII(th) century. This city was besieged during the European war of Spanish succession. We tested dental pulp from 1192 teeth (including 40 from Douai) by quantitative PCR (qPCR) for R. prowazekii and B. quintana. We also used ultra-sensitive suicide PCR to detect R. prowazekii and genotyped positive samples. RESULTS AND DISCUSSION: In the Douai remains, we identified one case of B. quintana infection (by qPCR) and R. prowazekii (by suicide PCR) in 6/21 individuals (29%). The R. prowazekii was genotype B, a genotype previously found in a Spanish isolate obtained in the first part of the XX(th) century. CONCLUSION: Louse-borne outbreaks were raging during the XVIII(th) century; our results support the hypothesis that typhus was imported into Europe by Spanish soldiers from America.

Biocompatibility implications of polypyrrole synthesis techniques.

Polypyrrole (PPy) is an inherently conducting polymer that has shown great promise for biomedical applications within the nervous system. However, to effectively use PPy as a biomaterial implant, it is important to understand and reproducibly control the electrical properties, physical topography and surface chemistry of the polymer. Although there is much research published on the use of PPy in various applications, there is no systematic study linking the methodologies used for PPy synthesis to PPy's basic polymeric properties (e.g., hydrophilicity, surface roughness), and to the biological effects these properties have on cells. Electrochemically synthesized PPy films differ greatly in their characteristics depending on synthesis parameters such as dopant, substrate and thickness, among other parameters. In these studies, we have used three dopants (chloride (Cl), tosylate (ToS), polystyrene sulfonate (PSS)), two substrates (gold and indium tin oxide-coated glass), and a range of thicknesses, to measure and compare the biomedically important characteristics of surface roughness, contact angle, conductivity, dopant stability and cell adhesion (using PC-12 cells and Schwann cells). As predicted, we discovered large differences in roughness depending on the dopant used and the thickness of the film, while substrate choice had little effect. From contact angle measurements, PSS was found to yield the most hydrophilic material, most likely because of free charges from the long PSS chains exposed on the surface of the PPy. ToS-doped PPy films were tenfold more conductive than Cl- or PSS-doped films. X-ray photoelectron spectroscopy studies were used to evaluate dopant concentrations of PPy films stored in water and phosphate buffered saline over 14 days, and conductance studies over the same timeframe measured electrical stability. PSS proved to be the most stable dopant, though all films experienced significant decay in conductivity and dopant concentration. Cell adhesion studies demonstrated the dependence of cell outcome on film thickness and dopant choice. The strengths and weaknesses of different synthesis parameters, as demonstrated by these experiments, are critical design factors that must be leveraged when designing biomedical implants. The results of these studies should provide practical insight to researchers working with conducting polymers, and particularly PPy, on the relationships between synthesis parameters, polymeric properties and biological compatibility.

Enhanced cell attachment and osteoblastic activity by P-15 peptide-coated matrix in hydrogels.

The cells in bone grow on a composite matrix made up of mineral and organic (mainly type-I collagen) components. In this study, anorganic bone mineral (ABM) particles were coated with a cell-binding domain of type-I collagen (P-15 peptide) to mimic the bone matrix components and suspended in injectable hyaluronate (Hy) hydrogels. The ABM/P-15/Hy was compared to ABM/Hy-the same matrix without P-15 peptide. Osteoblast-like HOS cells migrated through the hydrogels around ABM/P-15 or ABM particles; however, more cells adhered to ABM/P-15/Hy particles, and the cells formed better surface coverage and had more stress fibers on ABM/P-15/Hy. HOS cells cultured on ABM/P-15/Hy had increased osteogenic gene expression for alkaline phosphatase and bone morphogenetic proteins, and deposited more mineralized matrix. Studies with two different hydrogels (carboxymethylcellulose and sodium alginate) showed similar enhanced cell attachment and mineralization. The studies suggest that the ABM/P-15 in hydrogels can be used as an injectable biomimetic matrix to facilitate bone repair.