The influence of molecular design on structure-property relationships of a supramolecular polymer prodrug.

Supramolecular self-assemblies of hydrophilic macromolecules functionalized with hydrophobic, structure-directing components have long been used for drug delivery. In these systems, loading of poorly soluble compounds is typically achieved through physical encapsulation during or after formation of the supramolecular assembly, resulting in low encapsulation efficiencies and limited control over release kinetics, which are predominately governed by diffusion and carrier degradation. To overcome these limitations, amphiphilic prodrugs that leverage a hydrophobic drug as both the therapeutic and structure-directing component can be used to create supramolecular materials with higher loading and controlled-release kinetics using biodegradable or enzymatically cleavable linkers. Here, we report the design, synthesis, and characterization of a library of supramolecular polymer prodrugs based on poly(ethylene glycol) (PEG) and the proregenerative drug 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (DPCA). Structure-property relationships were elucidated through experimental characterization of prodrug behavior in both the wet and dry states using scattering techniques and electron microscopy and corroborated by coarse-grained modeling. Molecular architecture and the hydrophobic-to-hydrophilic ratio of PEG-DPCA conjugates strongly influenced their physical state in water, ranging from fully soluble to supramolecular spherical assemblies and nanofibers. Molecular design and supramolecular structure, in turn, were shown to dramatically alter hydrolytic and enzymatic release and cellular transport of DPCA. In addition to potentially expanding therapeutic options for DPCA through control of supramolecular assemblies, the design principles elaborated here may inform the development of other supramolecular prodrugs based on hydrophobic small-molecule compounds.

Accuracy of edentulous full-arch implant impression: An in vitro comparison between conventional impression, intraoral scan with and without splinting, and photogrammetry.

OBJECTIVES: The purpose of this in vitro study was to compare the trueness and precision of complete arch implant impressions using conventional impression, intraoral scanning with and without splinting, and stereophotogrammetry. MATERIALS AND METHODS: An edentulous model with six implants was used in this study. Four implant impression techniques were compared: the conventional impression (CI), intraoral scanning (IOS) without splinting, intraoral scanning with splinting (MIOS), and stereophotogrammetry (SPG). An industrial blue light scanner was used to generate the baseline scan from the model. The CI was captured with a laboratory scanner. The reference best-fit method was then applied in the computer-aided design (CAD) software to compute the three-dimensional, angular, and linear discrepancies among the four impression techniques. The root mean square (RMS) 3D discrepancies in trueness and precision between the four impression groups were analyzed with a Kruskal-Wallis test. Trueness and precision between single analogs were assessed using generalized estimating equations. RESULTS: Significant differences in the overall trueness (p = .017) and precision (p < .001) were observed across four impression groups. The SPG group exhibited significantly smaller RMS 3D deviations than the CI, IOS, and MIOS groups (p < .05), with no significant difference detected among the latter three groups (p > .05). CONCLUSIONS: Stereophotogrammetry showed superior trueness and precision, meeting misfit thresholds for implant-supported complete arch prostheses. Intraoral scanning, while accurate like conventional impressions, exhibited cross-arch angular and linear deviations. Adding a splint to the scan body did not improve intraoral scanning accuracy.

High-Density Polyethylene Custom Focusing Lenses for High-Resolution Transient Terahertz Biomedical Imaging Sensors.

Transient terahertz time-domain spectroscopy (THz-TDS) imaging has emerged as a novel non-ionizing and noninvasive biomedical imaging modality, designed for the detection and characterization of a variety of tissue malignancies due to their high signal-to-noise ratio and submillimeter resolution. We report our design of a pair of aspheric focusing lenses using a commercially available lens-design software that resulted in about 200 × 200-µm2 focal spot size corresponding to the 1-THz frequency. The lenses are made of high-density polyethylene (HDPE) obtained using a lathe fabrication and are integrated into a THz-TDS system that includes low-temperature GaAs photoconductive antennae as both a THz emitter and detector. The system is used to generate high-resolution, two-dimensional (2D) images of formalin-fixed, paraffin-embedded murine pancreas tissue blocks. The performance of these focusing lenses is compared to the older system based on a pair of short-focal-length, hemispherical polytetrafluoroethylene (TeflonTM) lenses and is characterized using THz-domain measurements, resulting in 2D maps of the tissue refractive index and absorption coefficient as imaging markers. For a quantitative evaluation of the lens effect on the image resolution, we formulated a lateral resolution parameter, R2080, defined as the distance required for a 20-80% transition of the imaging marker from the bare paraffin region to the tissue region in the same image frame. The R2080 parameter clearly demonstrates the advantage of the HDPE lenses over TeflonTM lenses. The lens-design approach presented here can be successfully implemented in other THz-TDS setups with known THz emitter and detector specifications.

Treatment outcomes of permanent teeth with uncomplicated and complicated crown fractures and factors associated with pulp survival: A retrospective study.

BACKGROUND: Crown fracture is the most common injury in permanent teeth. This study aimed to evaluate the treatment outcomes of permanent teeth with uncomplicated and complicated crown fractures and to investigate potential factors. MATERIALS AND METHODS: This retrospective study included patients who experienced crown fractures in permanent teeth from 2018 to 2021 with at least 12 months of follow-up. All complicated crown fractured teeth were treated with pulpotomy, while for teeth with uncomplicated crown fractures, three treatments (restoration, indirect pulp capping, or pulpotomy) were employed. The chi-square test was used to compare the prognosis of teeth with uncomplicated and complicated crown fractures. Potential factors associated with pulp survival including gender, interval, root development, enamel infraction, mobility, concomitant luxation injury, treatment, and coronal restoration were identified via Cox regression analysis. RESULTS: A total of 307 teeth from 220 children (average age = 9.3 ± 1.4 years; age range, 6-14 years) with a median follow-up of 23 months were included, and 82.1% of all teeth had immature roots. Complicated crown fractured teeth (93.6%, 102/109) had a significantly higher success rate compared with uncomplicated crown fractured teeth (85.4%, 169/198) (p < .05). Pulpotomy (96.9%) had the highest success rate of all treatments for uncomplicated crown fractures, followed by only restoration (85.0%) and indirect pulp capping (76.9%). The success rate of teeth that received pulpotomy was significantly higher than those treated by indirect pulp capping (p < .05). In uncomplicated crown fractures, teeth with Class II mobility were more vulnerable to failure than teeth without abnormal mobility (HR = 34.83; 95% CI, 9.59-126.56; p < .05); teeth that received pulpotomy were less prone to failure than teeth that received indirect pulp capping (HR = 13.53; 95% CI, 1.58-115.72; p < .05). CONCLUSION: Crown fractures treated with conservative pulp treatments had a relatively highly favorable prognosis. The prognosis of uncomplicated crown fractured teeth was impacted by the severity of periodontal injury and treatment strategies. Accurate diagnosis and identification of micro-exposures are important. Dentists should take multiple risk factors into account and select optimal treatment strategies.

Treatment outcomes of immature permanent necrotic evaginated teeth: A retrospective study comparing regenerative endodontic procedures with apexification.

BACKGROUND: Few studies have compared the outcomes of regenerative endodontic procedures (REPs) and calcium hydroxide apexification focusing on necrotic teeth with dens evaginatus. AIM: To qualitatively and quantitatively compare the treatment outcomes of REPs and calcium hydroxide apexification in teeth with dens evaginatus. DESIGN: Immature permanent necrotic evaginated teeth treated with REPs or calcium hydroxide apexification for a follow-up period of at least 12 months were included. Tooth success and survival rates were analyzed. Changes in radiographic root length, apical diameter, and radiographic root area (RRA) were quantified. Prognostic factors that might influence RRA were identified via multivariate linear regression analysis. RESULTS: A total of 112 teeth (50 REP cases and 62 apexification cases) with a median follow-up period of 26.5 months were included. Regenerative endodontic procedures and calcium hydroxide apexification exhibited similar satisfactory success and survival rates (p > .05). Additionally, 88 teeth were quantitatively analyzed. The REP group presented a significantly greater percentage increase in RRA and less decrease in apical diameter than the calcium hydroxide apexification group (p < .05). Teeth treated with REPs and with Stages 7 and 8 of root development showed a better gain in RRA (p < .05). CONCLUSION: While REP and calcium hydroxide apexification had similar success and survival rates, teeth with REPs showed an increase in RRA, indicating that REP is the preferred choice.

Efficacy of concentrated growth factor (CGF) in the surgical treatment of oral diseases: a systematic review and meta-analysis.

BACKGROUND: Concentrated growth factor (CGF), a new autologous platelet concentrate, has been widely investigated to the adjunctive treatment of oral diseases. This study aims to evaluate the efficacy of CGF in the surgical treatment of oral diseases. METHODS: MEDLINE, Web of Science, Scopus, Cochrane, and EMBASE databases were searched up to July 2023. Only randomized clinical trials were included. The methodologic quality was evaluated by the Cochrane Risk of Bias Tool. RevMan 5.4 software was used for data analysis. RESULTS: In the treatment of periodontal intrabony defects, bone graft combined with CGF was significantly superior to bone graft (P < 0.01), with mean intrabony defect depth reduction of 1.41 mm and mean clinical attachment level gain of 0.55 mm. In the regenerative surgery of furcation defects, the effect of CGF group was significantly better than control group (P < 0.0001), with mean probing depth reduction of 0.99 mm, vertical bone gain of 0.25 mm, and horizontal bone gain of 0.34 mm. CGF combined with coronally advanced flap (CAF) was more effective than CAF alone (mean keratinized tissue width increase of 0.41 mm, mean gingival thickness increase of 0.26 mm, P < 0.00001), but less effective than connective tissue graft (CTG) combined with CAF (mean root coverage difference of -15.1%, mean gingival thickness difference of -0.5 mm, P < 0.0001). In the alveolar ridge preservation, additional use of CGF reduced horizontal bone resorption by 1.41 mm and buccal vertical bone resorption by 1.01 mm compared to control group (P < 0.0001). The VAS score of CGF group was significantly lower than that of the control group at the 1st and 7th day after oral surgery (P < 0.0001). CONCLUSIONS: CGF can exert a positive adjunctive effect for the regenerative surgery of periodontal intrabony defects, furcation defects, and alveolar ridge preservation procedure. CGF combined with CAF has a better therapeutic effect on gingival recession compared to CAF alone, although it is not as effective as CTG combined with CAF. CGF could promote postoperative healing and pain relief in oral surgery within a week. There is currently not enough evidence to support the clinical benefits of CGF in other oral surgeries.

Efficacy of surgical methods for peri-implantitis: a systematic review and network meta-analysis.

BACKGROUND: Peri-implantitis is the most difficult biological complication associated with dental implants, often requiring surgical treatments in advanced stages. This study compares the effectiveness of different surgical methods for peri-implantitis. METHODS: Randomized controlled trials (RCTs) of different surgical treatments for peri-implantitis were extracted from EMBASE, Web of Science, Cochrane Library databases, and PubMed systematically. Pairwise comparisons and network meta-analyses (NMA) were conducted to analyze the effect of surgical treatments on probing depth (PD), radiographic bone fill (RBF), mucosal recession (MR), bleeding on probing (BOP), and clinical attachment level (CAL). In addition, risk of bias, quality of evidence, and statistical heterogeneity of the selected studies were evaluated. A total of 13 articles were included in this study, involving open flap debridement (OFD), resective therapy (RT), and augmentative therapy (AT) with and without adjunctive treatments (laser therapy, photodynamic therapy, local antibiotics, phosphoric acid, and ozone therapy). RESULTS: AT improved RBF and CAL more than OFD, but does not outperform OFD in reducing peri-implant soft-tissue inflammation. AT, OFD and RT did not significantly alter the levels of MR. Addition of ozone therapy improved the effect of AT, but addition of photodynamic therapy did not affect PD reduction and CAL gain significantly. Similarly, adjuvant treatment with phosphoric acid during RT did not significantly change the outcome of BOP. CONCLUSIONS: Within the limitation of this systematic review and NMA, AT was superior to OFD in improving peri-implantitis outcomes. While adjunct use of ozone therapy may further improve the efficacy of AT, the limited evidence supporting this combination therapy argues for cautionary interpretation of these results.

Sustained Exosome-Guided Macrophage Polarization Using Hydrolytically Degradable PEG Hydrogels for Cutaneous Wound Healing: Identification of Key Proteins and MiRNAs, and Sustained Release Formulation.

Macrophages (Mφs) are characterized by remarkable plasticity, an essential component of chronic inflammation. Thus, an appropriate and timely transition from proinflammatory (M1) to anti-inflammatory (M2) Mφs during wound healing is vital to promoting resolution of acute inflammation and enhancing tissue repair. Herein, exosomes derived from M2-Mφs (M2-Exos), which contain putative key regulators driving Mφ polarization, are used as local microenvironmental cues to induce reprogramming of M1-Mφs toward M2-Mφs for effective wound management. As an injectable controlled release depot for exosomes, hydrolytically degradable poly(ethylene glycol) (PEG) hydrogels (Exogels) are designed and employed for encapsulating M2-Exos to maximize their therapeutic effects in cutaneous wound healing. The degradation time of the hydrogels is adjustable from 6 days or up to 27 days by controlling the crosslinking density and tightness. The localization of M2-Exos leads to a successful local transition from M1-Mφs to M2-Mφs within the lesion for more than 6 days, followed by enhanced therapeutic effects including rapid wound closure and increased healing quality in an animal model for cutaneous wound healing. Collectively, the hydrolytically degradable PEG hydrogel-based exosome delivery system may serve as a potential tool in regulating local polarization state of Mφs, which is crucial for tissue homeostasis and wound repair.

Electrochemical aptasensor based on electrodeposited poly(3,4-ethylenedioxythiophene)-graphene oxide coupled with Au@Pt nanocrystals for the detection of 17ß-estradiol.

An electrochemical aptasensor is reported for the sensitive and specific monitoring of 17ß-estradiol (E2) based on the modification of electrodeposited poly(3,4-ethylenedioxythiophene) (PEDOT)-graphene oxide (GO) coupled with Au@Pt nanocrystals (Au@Pt). With excellent conductivity, chemical stability and active sites, the PEDOT-GO nanocomposite film was firstly in situ polymerized on the glassy carbon electrode by cyclic voltammetry. Subsequently, one-step synthesized Au@Pt were decorated on the conductive polymer, providing a platform for immobilizing the aptamer and enhancing the detecting sensitivity. With the addition of E2, since the interfacial electron transfer process was retarded by the E2-aptamer complex, the differential pulse voltammetry signal decreased gradually. Under optimum conditions, the calibration curve of E2 exhibited a linear range between 0.1 pM and 1 nM, with a low detection limit (S/N = 3) of 0.08 pM. The developed aptasensor showed admiring selectivity, stability, and reproducibility. It was tested in human serum, lake water and tap water samples after low-cost and simple pretreatment. Consequently, the developed platform could provide a new design thought for ultrasensitive detection of E2 in clinical and environmental samples.

An injectable hydrogel-formulated inhibitor of prolyl-4-hydroxylase promotes T regulatory cell recruitment and enhances alveolar bone regeneration during resolution of experimental periodontitis.

The hypoxia-inducible factor 1α (HIF-1α) is critically involved in tissue regeneration. Hence, the pharmacological prevention of HIF-1α degradation by prolyl hydroxylase (PHD) under normoxic conditions is emerging as a promising option in regenerative medicine. Using a mouse model of ligature-induced periodontitis and resolution, we tested the ability of an injectable hydrogel-formulated PHD inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA/hydrogel), to promote regeneration of alveolar bone lost owing to experimental periodontitis. Mice injected subcutaneously with 1,4-DPCA/hydrogel at the onset of periodontitis resolution displayed significantly increased gingival HIF-1α protein levels and bone regeneration, as compared to mice treated with vehicle control. The 1,4-DPCA/hydrogel-induced increase in bone regeneration was associated with elevated expression of osteogenic genes, decreased expression of pro-inflammatory cytokine genes, and increased abundance of FOXP3+ T regulatory (Treg) cells in the periodontal tissue. The enhancing effect of 1,4-DPCA/hydrogel on Treg cell accumulation and bone regeneration was reversed by AMD3100, an antagonist of the chemokine receptor CXCR4 that mediates Treg cell recruitment. In conclusion, the administration of 1,4-DPCA/hydrogel at the onset of periodontitis resolution promotes CXCR4-dependent accumulation of Treg cells and alveolar bone regeneration, suggesting a novel approach for regaining bone lost due to periodontitis.

Simply Mixing Poly Protein G with Detection Antibodies Enhances the Detection Limit and Sensitivity of Immunoassays.

An insufficient amount of detection antibodies bound to their antigens usually limits the sensitivity of immunoassays. Here, we describe a simple method to improve the detection limit and sensitivity of various immunoassays by mixing detection antibodies with a soluble poly protein G (named 8pG). 8pG was developed by fusing eight repeated fragment crystallizable (Fc) binding domains of streptococcal protein G to a linear polymer. Simply mixing detection antibodies with 8pG to form an antibody/8pG complex largely increased the accumulation of detection antibody to target molecules, which dramatically enhanced the sensitivity in direct ELISA, sandwich ELISA, Western blot, and flow cytometry systems, separately. The detection limit of Western blot for low-abundance PEGylated interferon (Pegasys) and recombinant human CTLA4 (rhCTLA4) improved by at least 13-fold and 31-fold, respectively, upon mixing detection antibodies with 8pG. Moreover, the nanoscale size of the antibody/8pG complex did not influence the granularity and dimension of target cells in the flow cytometry system. Collectively, we provide a quick and easy-to-operate method to make various immunoassays to sensitively detect low-abundance target molecules by just mixing their detection antibodies with 8pG.

Nanoparticles Based on Poly (ß-Amino Ester) and HPV16-Targeting CRISPR/shRNA as Potential Drugs for HPV16-Related Cervical Malignancy.

Persistent high-risk HPV infection is the main cause of cervical cancer. The HPV oncogene E7 plays an important role in HPV carcinogenesis. Currently, HPV vaccines do not offer an effective treatment for women who already present with cervical disease, and recommended periodical cervical screenings are difficult to perform in countries and areas lacking medical resources. Our aim was to develop nanoparticles (NPs) based on poly (ß-amino ester) (PBAE) and HPV16 E7-targeting CRISPR/short hairpin RNA (shRNA) to reduce the levels of HPV16 E7 as a preliminary form of a drug to treat HPV infection and its related cervical malignancy. Our NPs showed low toxicity in cells and mouse organs. By reducing the expression of HPV16 E7, our NPs could inhibit the growth of cervical cancer cells and xenograft tumors in nude mice, and they could reverse the malignant cervical epithelium phenotype in HPV16 transgenic mice. The performance of NPs containing shRNA is better than that of NPs containing CRISPR. HPV-targeting NPs consisting of PBAE and CRISPR/shRNA could potentially be developed as drugs to treat HPV infection and HPV-related cervical malignancy.

Novel Diketopyrrolopyrrole-Based π-Conjugated Molecules Synthesized Via One-Pot Direct Arylation Reaction.

Diketopyrrolopyrrole (DPP) is an important type of π-conjugated building block for high-performance organic electronic materials. DPP-based conjugated materials are usually synthesized via Suzuki, Stille, or Negishi cross-coupling reactions, which require organometallic precursors. In this paper, a series of novel phenyl-cored DPP molecules, including five meta-phenyl-cored molecules and four para-phenyl-cored molecules, have been synthesized in moderate to good yields, in a facile manner, through the Pd-catalyzed direct arylation of C-H bonds, and their optoelectrical properties have been investigated in detail. All new molecules have been fully characterized by NMR, MALDI-TOF MS, elemental analysis, UV-visible spectroscopy, and cyclic voltammetry. This synthetic strategy has evident advantages of atom- and step-economy and low cost, compared with traditional cross-coupling reactions.

Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

Improvement of sulfamethoxazole (SMX) elimination and inhibition of formations of hydroxylamine-SMX and N4-acetyl-SMX by membrane bioreactor systems.

Sulfamethoxazole (SMX) has frequently been detected in aquatic environments. In natural environment, not only individual microorganism but also microbial consortia are involved in some biotransformation of pollutants. The competition for space under consortia causing cell-cell contact inhibition changes the cellular behaviors. Herein, the membrane bioreactor system (MBRS) was applied to improve SMX elimination thorough exchanging the cell-free broths (CFB). The removal efficiency of SMX was increased by more than 24% whether under the pure culture of A. faecalis or under the co-culture of A. faecalis and P. denitrificans with MBRS. Meanwhile, MBRS significantly inhibited the formation of HA-SMX, and Ac-SMX from parent compound. Additionally, the cellular growth under MBRS was obviously enhanced, indicating that the increases in the cellular growth under MBRS are possibly related to the decreases in the levels of HA-SMX and Ac-SMX compared to that without MBRS. The intracellular NADH/NAD+ ratios of A. faecalis under MBRS were increased whether thorough itself-recycle of CFB or exchanging CFB between the pure cultures of A. faecalis and P. denitrificans, suggesting that the enhancement in the bioremoval efficiencies of SMX under MBRS by A. faecalis is likely related to the increases in the NADH/NAD+ ratio. Taken together, the regulation of cell-to-cell communication is preferable strategy to improve the bioremoval efficiency of SMX.

Mutation in SSUH2 Causes Autosomal-Dominant Dentin Dysplasia Type I.

Dentin dysplasia type I (DDI) is an autosomal-dominant genetic disorder resulting from dentin defects. The molecular basis of DDI remains unclear. DDI exhibits unique characteristics with phenotypes featuring obliteration of pulp chambers and diminutive root, thus providing a useful model for understanding the genetics of tooth formation. Using a large Chinese family with 14 DDI patients, we mapped the gene locus responsible for DDI to 3p26.1-3p24.3 and further identified a missense mutation, c.353C>A (p.P118Q) in the SSUH2 gene on 3p26.1, which co-segregated with DDI. We showed that SSUH2 (p.P118Q) perturbed the structure and significantly reduced levels of mutant (MT) protein and mRNA compared with wild-type SSUH2. Furthermore, MT P141Q knock-in mice (+/- and -/-) had a unique partial obliteration of the pulp cavity and upregulation or downregulation of six major genes involved in odontogenesis: Dspp, Dmp1, Runx2, Pax9, Bmp2, and Dlx2. The phenotype of missing teeth was determined in zebrafish with morpholino gene knockdowns and rescued by injection of normal human mRNA. Taken together, our observations demonstrate that SSUH2 disrupts dental formation and that this novel gene, together with other odontogenesis genes, is involved in tooth development.

Control of hierarchical polymer mechanics with bioinspired metal-coordination dynamics.

In conventional polymer materials, mechanical performance is traditionally engineered via material structure, using motifs such as polymer molecular weight, polymer branching, or block copolymer design. Here, by means of a model system of 4-arm poly(ethylene glycol) hydrogels crosslinked with multiple, kinetically distinct dynamic metal-ligand coordinate complexes, we show that polymer materials with decoupled spatial structure and mechanical performance can be designed. By tuning the relative concentration of two types of metal-ligand crosslinks, we demonstrate control over the material's mechanical hierarchy of energy-dissipating modes under dynamic mechanical loading, and therefore the ability to engineer a priori the viscoelastic properties of these materials by controlling the types of crosslinks rather than by modifying the polymer itself. This strategy to decouple material mechanics from structure is general and may inform the design of soft materials for use in complex mechanical environments. Three examples that demonstrate this are provided.

Intensity-modulated radiotherapy for localized nasopharyngeal amyloidosis : Case report and literature review.

BACKGROUND: Primary localized amyloidosis is characterized by the deposition of amyloid proteins restricted to one organ, without systemic involvement. Primary nasopharyngeal amyloidosis is an exceedingly rare condition, for which the standard treatment remains unknown. Because of its challenging anatomical position, surgery alone hardly results in complete resection of the localized amyloidosis. Therefore, an interdisciplinary planning board to design optimal treatment is of particular importance. PATIENT AND METHODS: A 39-year-old man presented with a several-week history of nasal obstruction and epistaxis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a retro-odontoid nonenhancing soft tissue mass. RESULTS: The endoscopic biopsy demonstrated that the mass was amyloid in nature. An extensive systemic workup revealed an absence of inflammatory process, systemic amyloidosis, or plasma cell dyscrasia. The patient was treated with a combination of surgery and radiotherapy, showing no evidence of recurrence or progression at his 1­year follow-up. CONCLUSION: Primary solitary amyloidosis is a rare form of amyloidosis. To the best of our knowledge, this is the first report of a nasopharyngeal amyloidosis case treated with excision and radiation leading to complete remission. Because of the difficulty for surgeons to achieve radical resection with such lesions, radiotherapy proved to be an excellent adjuvant treatment in this case.

Non-operative anti-caries agents and dental caries increment among adults at high caries risk: a retrospective cohort study.

BACKGROUND: Consensus guidelines support non-operative preventives for dental caries management; yet, their use in practice is far from universal. The purpose of this study was to evaluate the effectiveness of non-operative anti-caries agents in caries prevention among high caries risk adults at a university clinic where risk-based caries management is emphasized. METHODS: This retrospective observational study drew data from the electronic patient records of non-edentulous adult patients deemed to be at high risk for dental caries during baseline oral evaluations that were completed between July 1, 2007 and December 31, 2012 at a dental university in the United States. We calculated and compared adjusted mean estimates for the number of new decayed or restored teeth (DFT increment) from baseline to the next completed oral evaluation (N = 2,724 patients with follow-up) across three categories of delivery of non-operative anti-caries agents (e.g., high-concentration fluoride toothpaste, chlorhexidine rinse, xylitol products): never, at a single appointment, or at ≥2 appointments ≥4 weeks apart. Estimates were adjusted for patient and provider characteristics, baseline dental status, losses-to-follow-up, and follow-up time. RESULTS: Approximately half the patients did not receive any form of non-operative anti-caries agent. Most that received anti-caries agents were given more than one type of product in combination. One-time delivery of anti-caries agents was associated with a similar DFT increment as receiving no such therapy (difference in increment: -0.04; 95% CI: -0.28, 0.21). However, repeated, spaced delivery of anti-caries agents was associated with approximately one decayed or restored tooth prevented over 18 months for every three patients treated (difference in increment: -0.35; 95% CI: -0.65, -0.08). CONCLUSIONS: These results lend evidence that repeatedly receiving anti-caries agents can reduce tooth decay among high-risk patients engaged in regular dental care.