Using Nitroxides To Model the Ion Mobility Behavior of Nitroxide-Ended Oligomers: A Bottom-up Approach To Predict Mobility Separation.

Block-truncated poly(phosphodiester)s are digital macromolecules storing binary information that can be decoded by MS/MS sequencing of individual blocks released as primary fragments of the entire polymer. As such, they are ideal species for the serial sequencing methodology enabled by MS-(CID)-IMS-(CID)-MS coupling, where two activation stages are combined in-line with ion mobility spectrometry (IMS) separation. Yet, implementation of this coupling still requires efforts to achieve IMS resolution of inner blocks, that can be considered as small oligomers with α termination composed of one nitroxide decorated with a different tag. As shown by molecular dynamics simulation, these oligomers adopt a conformation where the tag points out of the coil formed by the chain. Accordingly, the sole nitroxide termination was investigated here as a model to reduce the cost of calculation aimed at predicting the shift of collision cross-section (CCS) induced by new tag candidates and extrapolate this effect to nitroxide-terminated oligomers. A library of 10 nitroxides and 7 oligomers was used to validate our calculation methods by comparison with experimental IMS data as well as our working assumption. Based on conformation predicted by theoretical calculation, three new tag candidates could be proposed to achieve the +40 Å2 CCS shift required to ensure IMS separation of oligomers regardless of their coded sequence.

Exchanging and Releasing Information in Synthetic Digital Polymers Using a Strand-Displacement Strategy.

Toehold-mediated strand displacement (TMSD) was tested as a tool to edit information in synthetic digital polymers. Uniform DNA-polymer biohybrid macromolecules were first synthesized by automated phosphoramidite chemistry and characterized by HPLC, mass spectrometry, and polyacrylamide gel electrophoresis (PAGE). These precursors were diblock structures containing a synthetic poly(phosphodiester) (PPDE) segment covalently attached to a single-stranded DNA sequence. Three types of biohybrids were prepared herein: a substrate containing an accessible toehold as well as input and output macromolecules. The substrate and the input macromolecules contained noncoded PPDE homopolymers, whereas the output macromolecule contained a digitally encoded segment. After hybridization of the substrate with the output, incubation in the presence of the input led to efficient TMSD and the release of the digital segment. TMSD can therefore be used to erase or rewrite information in self-assembled biohybrid superstructures. Furthermore, it was found in this work that the conjugation of DNA single strands to synthetic segments of chosen lengths greatly facilitates the characterization and PAGE visualization of the TMSD process.

Conception and Evaluation of a Library of Cleavable Mass Tags for Digital Polymers Sequencing.

A library of phosphoramidite monomers containing a main-chain cleavable alkoxyamine and a side-chain substituent of variable molar mass (i.e. mass tag) was prepared in this work. These monomers can be used in automated solid-phase phosphoramidite chemistry and therefore incorporated periodically as spacers inside digitally-encoded poly(phosphodiester) chains. Consequently, the formed polymers contain tagged cleavable sites that guide their fragmentation in mass spectrometry sequencing and enhance their digital readability. The spacers were all prepared via a seven steps synthetic procedure. They were afterwards tested for the synthesis and sequencing of model digital polymers. Uniform digitally-encoded polymers were obtained as major species in all cases, even though some minor defects were sometimes detected. Furthermore, the polymers were decoded in pseudo-MS3 conditions, thus confirming the reliability and versatility of the spacers library.

Stability of maxillary expansion osteotomy using patient-specific fixation implants without necessitating removable appliances: a retrospective analysis.

OBJECTIVE: This study aimed to evaluate the long-term stability of surgical maxillary expansion using patient-specific fixation implants (PSFIs) without intraoral retention. MATERIALS AND METHODS: Fifteen patients who had undergone segmented Le Fort I osteotomy and PSFIs with available preoperative (t0) early (t1) and 1-year follow-up computed tomography (CT) scans (t2) were evaluated. The early and 1-year 3D models were superimposed to transfer the bony landmarks; the distances between each pair of landmarks at the different time points were then measured. The distances between the canines and second molars were also measured directly on the CT scans. RESULTS: The achieved maxillary expansions ranged from a median of 4.39 (2.00-6.27) mm at the greater palatine foramina to a median of 2.14 (1.56-2 > 83) mm at the canine level of the palatal bone. One year postoperatively, the changes in skeletal diameters ranged from a median of - 0.53 (- 1.65 to 0.41) mm at the greater palatine foramina (p = 0.12) to 0.17 (- 0.09 to 0.32) mm at the canine level of the palatal bone (p = 0.56). Changes in dental arch diameters ranged from a median of - 0.6 (- 2 to 0.00) mm between the second molars to - 1.3 (- 1.8 to - 0.25) mm between the canines (P < 0.05). CONCLUSION: This study showed the stability of maxillary expansion osteotomy using PSFIs, even without postoperative intraoral retention. CLINICAL RELEVANCE: PSFIs are a reliable method for the surgical treatment of transverse maxillary discrepancy. PFSIs are easy-to-use and improve surgical accuracy.

Macromolecular Information Transfer.

Macromolecular information transfer can be defined as the process by which a coded monomer sequence is communicated from one macromolecule to another. In such a transfer process, the information sequence can be kept identical, transformed into a complementary sequence or even translated into a different molecular language. Such mechanisms are crucial in biology and take place in DNA→DNA replication, DNA→RNA transcription and RNA→protein translation. In fact, there would be no life on Earth without macromolecular information transfer. Mimicking such processes with synthetic macromolecules would also be of major scientific relevance because it would open up new avenues for technological applications (e.g. data storage and processing) but also for the creation of artificial life. In this important context, this minireview summarizes recent research about information transfer in synthetic oligomers and polymers. Medium- and long-term perspectives are also discussed.

Receptor for Advanced Glycation End-Products Promotes Activation of Alveolar Macrophages through the NLRP3 Inflammasome/TXNIP Axis in Acute Lung Injury.

The roles of thioredoxin-interacting protein (TXNIP) and receptor for advanced glycation end-products (RAGE)-dependent mechanisms of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-driven macrophage activation during acute lung injury are underinvestigated. Cultured THP-1 macrophages were treated with a RAGE agonist (S100A12), with or without a RAGE antagonist; cytokine release and intracytoplasmic production of reactive oxygen species (ROS) were assessed in response to small interfering RNA knockdowns of TXNIP and NLRP3. Lung expressions of TXNIP and NLRP3 and alveolar levels of IL-1ß and S100A12 were measured in mice after acid-induced lung injury, with or without administration of RAGE inhibitors. Alveolar macrophages from patients with acute respiratory distress syndrome and from mechanically ventilated controls were analyzed using fluorescence-activated cell sorting. In vitro, RAGE promoted cytokine release and ROS production in macrophages and upregulated NLRP3 and TXNIP mRNA expression in response to S100A12. TXNIP inhibition downregulated NLRP3 gene expression and RAGE-mediated release of IL-1ß by macrophages in vitro. In vivo, RAGE, NLRP3 and TXNIP lung expressions were upregulated during experimental acute lung injury, a phenomenon being reversed by RAGE inhibition. The numbers of cells expressing RAGE, NLRP3 and TXNIP among a specific subpopulation of CD16+CD14+CD206- ("pro-inflammatory") alveolar macrophages were higher in patients with lung injury. This study provides a novel proof-of-concept of complex RAGE-TXNIP-NLRP3 interactions during macrophage activation in acute lung injury.

Covalent Attachment and Detachment by Reactive DESI of Sequence-Coded Polymer Taggants.

The use of sequence-defined polymers is an interesting emerging solution for materials identification and traceability. Indeed, a very large amount of identification sequences can be created using a limited alphabet of coded monomers. However, in all reported studies, sequence-defined taggants are usually included in a host material by noncovalent adsorption or entrapment, which may lead to leakage, aggregation, or degradation. To avoid these problems, sequence-defined polymers are covalently attached in the present work to the mesh of model materials, namely acrylamide hydrogels. To do so, sequence-coded polyurethanes containing a disulfide linker and a terminal methacrylamide moiety are synthesized by stepwise solid-phase synthesis. These methacrylamide macromonomers are afterward copolymerized with acrylamide and bisacrylamide in order to achieve cross-linked hydrogels containing covalently-bound polyurethane taggants. It is shown herein that these taggants can be selectively detached from the hydrogel mesh by reactive desorption electrospray ionization. Using dithiothreitol the disulfide linker that links the taggant to the gel can be selectively cleaved. Ultimately, the released taggants can be decoded by tandem mass spectrometry.

In-house 3D printing: Why, when, and how? Overview of the national French good practice guidelines for in-house 3D-printing in maxillo-facial surgery, stomatology, and oral surgery.

3D-printing is part of the daily practice of maxillo-facial surgeons, stomatologists and oral surgeons. To date, no French health center is producing in-house medical devices according to the new European standards. Based on all the evidence-based data available, a group of experts from the French Society of Stomatology, Maxillo-Facial Surgery and Oral Surgery (Société Française de Chirurgie Maxillofaciale, Stomatologie et Chirurgie Orale, SFSCMFCO), provide good practice guidelines for in-house 3D-printing in maxillo-facial surgery, stomatology, and oral surgery. Briefly, technical considerations related to printers and CAD software, which were the main challenges in the last ten years, are now nearly trivial questions. The central current issues when planning the implementation of an in-house 3D-printing platform are economic and regulatory. Successful in-house 3D platforms rely on close collaborations between health professionals and engineers, backed by regulatory and logistic specialists. Several large-scale academic projects across France will soon provide definitive answers to governance and economical questions related to the use of in-house 3D printing.

Do mandibular miniplates increase the risk of complex fracture in facial trauma recurrence? Case series.

Whether to conserve or remove miniplates, widely used in oral and maxillofacial surgery, has not been agreed on in the literature. Complications such as pain, infection, and screw exposure or loosening have already been largely described. We present the consequences of a trauma recurrence on a mandible with miniplates. The data of 13 patients who had a mandibular fracture previously surgically treated with miniplates (ten mandibular fractures and three mandibular osteotomies) were analysed. All the patients were male; the average age was 32 years (range, 20-64 years). The mechanism of the second trauma was assault in most of the cases. The average time between the first osteosynthesis and the new fracture was 35 months (range, 6-128 months). The fractures occurred at a distance from the miniplates in all the cases except two. No plate fracture was reported. We hypothesised that miniplates reinforced the underlying bone, protecting it from fractures, and transmitted the forces to areas anterior or posterior to the miniplates or to the condyle. Thus, the risk of mandible trauma recurrence should be taken into account in the indication of plate removal, and the biomechanical consequences of the conservation of the miniplates should be studied.

Design of Abiological Digital Poly(phosphodiester)s.

In biological systems, the storage and transfer of genetic information rely on sequence-controlled nucleic acids such as DNA and RNA. It has been realized for quite some time that this property is not only crucial for life but could also be very useful in human applications. For instance, DNA has been actively investigated as a digital storage medium over the past decade. Indeed, the "hard-disk of life" is an obvious choice and a highly optimized material for storing data. Through decades of nucleic acids research, technological tools for parallel synthesis and sequencing of DNA have been readily available. Consequently, it has already been demonstrated that different types of documents (e.g., texts, images, videos, and industrial data) can be stored in chemically synthesized DNA libraries. However, DNA is subject to biological constraints, and its molecular structure cannot be easily varied to match technological needs. In fact, DNA is not the only macromolecule that enables data storage. In recent years, it has been demonstrated that a wide variety of synthetic polymers can also be used for such a purpose. Indeed, modern polymer synthesis allows the preparation of synthetic macromolecules with precisely controlled monomer sequences. Altogether, about a dozens of synthetic digital polymers have already been described, and many more can be foreseen. Among them, sequence-defined poly(phosphodiester)s are one of the most promising options. These polymers are prepared by stepwise phosphoramidite chemistry like chemically synthesized oligonucleotides. However, they are constructed with non-natural building blocks and therefore share almost no structural characteristics with nucleic acids, except phosphate repeat units. Still, they contain readable digital messages that can be deciphered by nanopore sequencing or mass spectrometry sequencing. In this Account, we describe our recent research efforts in synthesizing and sequencing optimal abiological digital poly(phosphodiester)s. A major advantage of these polymers over DNA is that their molecular structure can easily be varied to tune their properties. During the last 5 years, we have engineered the molecular structure of these polymers to adjust crucial parameters such as the storage density, storage capacity, erasability, and readability. Consequently, high-capacity PPDE chains, containing hundreds of bits per chains, can now be synthesized and efficiently sequenced using a routine mass spectrometer. Furthermore, sequencing data can be automatically decrypted with the help of decoding software. This new type of coded matter can also be edited using practical physical triggers such as light and organized in space by programmed self-assembly. All of these recent improvements are summarized and discussed herein.

Chain Entropy Beats Hydrogen Bonds to Unfold and Thread Dialcohol Phosphates inside Cyanostar Macrocycles To Form [3]Pseudorotaxanes.

The recognition of substituted phosphates underpins many processes including DNA binding, enantioselective catalysis, and recently template-directed rotaxane synthesis. Beyond ATP and a few commercial substrates, however, little is known about how substituents effect organophosphate recognition. Here, we examined alcohol substituents and their impact on recognition by cyanostar macrocycles. The organophosphates were disubstituted by alcohols of various chain lengths, dipropanol, dihexanol, and didecanol phosphate, each accessed using modular solid-phases syntheses. Based on the known size-selective binding of phosphates by π-stacked dimers of cyanostars, threaded [3]pseudorotaxanes were anticipated. While seen with butyl substituents, pseudorotaxane formation was disrupted by competitive OH···O- hydrogen bonding between both terminal hydroxyls and the anionic phosphate unit. Crystallography also showed formation of a backfolded propanol conformation resulting in an 8-membered ring and a perched cyanostar assembly. Motivated by established entropic penalties accompanying ring formation, we reinstated [3]pseudorotaxanes by extending the size of the substituent to hexanol and decanol. Chain entropy overcomes the enthalpically favored OH···O- contacts to favor random-coil conformations required for seamless, high-fidelity threading of dihexanol and didecanol phosphates inside cyanostars. These studies highlight how chain length and functional groups on phosphate's substituents can be powerful design tools to regulate binding and control assembly formation during phosphate recognition.

Precisely Defined Aptamer-b-Poly(phosphodiester) Conjugates Prepared by Phosphoramidite Polymer Chemistry.

Uniform conjugates combining a DNA aptamer (either anti-MUC1 or ATP aptamer) and a synthetic polymer segment were synthesized by automated phosphoramidite chemistry. This multistep growth polymer chemistry enables the use of both natural (i.e., nucleoside phosphoramidites) and non-natural monomers (e.g., alkyl- and oligo(ethylene glycol)-phosphoramidites). Thus, in the present work, six different aptamer-polymer conjugates were synthesized and characterized by ion-exchange HPLC, circular dichroism spectroscopy, and electrospray mass spectrometry. All these methods evidenced the formation of uniform molecules with precisely controlled chain-length and monomer sequences. Furthermore, aptamer folding was not affected by polymer bioconjugation. The method described herein is straightforward and allows covalent attachment of homopolymers and copolymers to biofunctional DNA aptamers.

Precise Alkoxyamine Design to Enable Automated Tandem Mass Spectrometry Sequencing of Digital Poly(phosphodiester)s.

A major step towards reliable reading of information coded in the sequence of long poly(phosphodiester)s was previously achieved by introducing an alkoxyamine spacer between information sub-segments. However, MS/MS decoding had to be performed manually to safely identify useful fragments of low abundance compared to side-products from the amide-based alkoxyamine used. Here, alternative alkoxyamines were designed to prevent side-reactions and enable automated MS/MS sequencing. Different styryl-TEMPO spacers were prepared to increase radical delocalization and stiffness of the structure. Their dissociation behavior was investigated by EPR and best results were obtained with spacers containing in-chain benzyl ring, with no side-reaction during synthesis or sequencing. Automated decoding of these polymers was performed using the MS-DECODER software, which interprets fragmentation data recorded for each sub-segment and re-align them in their original order based on location tags.

Impact of intraoperative cone beam computed tomography in the management of zygomatic fractures.

AIM: To evaluate the impact of intraoperative cone beam computed tomography (CBCT) assessment for the surgical management of zygomatic bone fracture (ZF). METHODS: A prospective study was conducted on patients operated on for unilateral ZF during a two-year period. Repositioning of the fractured zygoma was assessed intraoperatively by measuring the position of malar eminences in three dimensions on CBCT. A difference of more than 2 mm between both sides was considered significant and the reduction was judged inadequate. Surgical procedure was adapted to intraoperative imaging findings. RESULTS: The surgical procedures of 47 patients treated for ZF were analyzed. In 15% of the cases (7 patients), the intraoperative CBCT showed an inadequate reduction while the morphological results seemed correct. Those patients benefited from an immediate correction of the reduction. From these 7 patients, reduction was optimized further without the need of osteosynthesis in one case, additional osteosynthesis was performed in 4 cases and 2 patients required both reduction and osteosynthesis revision. CONCLUSION: Intraoperative CBCT control helps to achieve anatomic repositioning in case of ZF. It may reduce the risk of under-treatment and possible reoperation, and of over-treatment meaning systematic ORIF in all fractures.

Aerolysin nanopores decode digital information stored in tailored macromolecular analytes.

Digital data storage is a growing need for our society and finding alternative solutions than those based on silicon or magnetic tapes is a challenge in the era of "big data." The recent development of polymers that can store information at the molecular level has opened up new opportunities for ultrahigh density data storage, long-term archival, anticounterfeiting systems, and molecular cryptography. However, synthetic informational polymers are so far only deciphered by tandem mass spectrometry. In comparison, nanopore technology can be faster, cheaper, nondestructive and provide detection at the single-molecule level; moreover, it can be massively parallelized and miniaturized in portable devices. Here, we demonstrate the ability of engineered aerolysin nanopores to accurately read, with single-bit resolution, the digital information encoded in tailored informational polymers alone and in mixed samples, without compromising information density. These findings open promising possibilities to develop writing-reading technologies to process digital data using a biological-inspired platform.

Damage and Repair in Informational Poly(N-substituted urethane)s.

The degradation and repair of uniform sequence-defined poly(N-substituted urethane)s was studied. Polymers containing an ω-OH end-group and only ethyl carbamate main-chain repeat units rapidly degrade in NaOH solution through an ω→α depolymerization mechanism with no apparent sign of random chain cleavage. The degradation mechanism is not notably affected by the nature of the side-chain N-substituents and took place for all studied sequences. On the other hand, depolymerization is significantly influenced by the molecular structure of the main-chain repeat units. For instance, hexyl carbamate main-chain motifs block unzipping and can therefore be used to control the degradation of specific sequence sections. Interestingly, the partially degraded polymers can also be repaired; for example by using a combination of N,N'-disuccinimidyl carbonate with a secondary amine building-block. Overall, these findings open up interesting new avenues for chain-healing and sequence editing.

Prediction of Post-Traumatic Enophthalmos Based on Orbital Volume Measurements: A Systematic Review.

PURPOSE: Enophthalmos greater than 2 mm should be considered clinically relevant and can be responsible for esthetic and functional morbidity. The difficulty has always been the best method to use to accurately determine when the orbital wall displacement will lead to clinically relevant enophthalmos. None of the currently used techniques is able to accurately predict for post-traumatic enophthalmos (PE). The aim of the present study was to systematically review the use of orbital volumetric tools in the prediction of PE after orbital fracture. MATERIALS AND METHODS: The terms searched in each database were "(orbital volumetry) and enophthalmos," "volumetry and enophthalmos," "volume and enophthalmos," and "volumetric and enophthalmos." The relationship between PE and the orbital volume (OV) was assessed. RESULTS: The initial search yielded 346 results. Of the 346 studies, 14 were included and analyzed. Every study reported a different numerical relationship between the OV and PE, with a mean enophthalmos of 0.80 mm after a 1-cm3 increase in the OV. CONCLUSIONS: The present review found that most studies concluded that a direct relationship exists between the OV and PE and defined the degree of PE in relation to the OV expansion. Enophthalmos assessment using radiologic evaluation provides increased accuracy and reproducibility compared with clinical measurement using an exophthalmometer. It has been notoriously difficult to determine when orbital wall displacement will lead to clinically relevant enophthalmos. Measurement of the OV could have a role in the decision for surgical or conservative treatment.

Standard and Customized Alloplastic Facial Implants Refining Orthognathic Surgery: Outcome Evaluation.

PURPOSE: Conventional orthognathic osteotomies provide appropriate functional outcomes but might be unable to correct midface deficiency, achieve a satisfactory outcome in asymmetrical cases, or allow sufficient chin advancement. We evaluated the outcome of both standard and customized facial high-density porous polyethylene implants used to refine the cosmetic outcome of orthognathic surgery. PATIENTS AND METHODS: We implemented a retrospective study. The sample was composed of all patients who underwent facial alloplastic augmentation between June 2011 and October 2018 in our department. The complication rate was recorded after a mean follow-up period of 41 months postoperatively, and patient satisfaction was assessed through a qualitative evaluation based on an 11-item questionnaire. RESULTS: The sample was composed of 24 implants placed in 14 patients: 13 mandibular angle implants, among which 4 were customized; 8 malar implants; and 3 chin implants. No physical complications such as hematoma, infection, migration, or hypoesthesia were observed. Two implants had to be removed because of early unsatisfactory esthetic outcomes. Of 14 patients, 11 answered our questionnaire. Eighty-two percent strongly agreed that the overall outcome was satisfactory. CONCLUSIONS: The results of this study confirm the low physical complication rate described in the literature, and the esthetic complication rate remains lower than the rates observed in previous reports. A high satisfaction rate was found among patients. The lowest mean satisfaction score was noted for appropriate implant symmetry (3.5), whereas the highest mean satisfaction score (3.8) was achieved when using customized implants. If standard high-density porous polyethylene implants appear to be relevant adjuncts to orthognathic surgery, customized implants seem to achieve higher satisfaction, although their prohibitive cost should be considered.

Selective Bond Cleavage in Informational Poly(Alkoxyamine Phosphodiester)s.

The collision-induced dissociation (CID) of sequence-defined poly(alkoxyamine phosphodiester)s is studied by electrospray ionization mass spectrometry. These informational polymers are synthesized using three different nitroxide building blocks, namely proxyl-, SG1-, and TEMPO-derivatives. For a polymer containing TEMPO- and SG1-based main chain alkoxyamines, it is found that both types of alkoxyamines break in CID tandem mass spectrometry (MS/MS). However, SG1-sites are preferentially cleaved and this predominance can be increased by reducing collision energy, even though selective bond fragmentation is not observed. On the other hand, for a polymer containing proxyl- and SG1-alkoxyamines, selective bond cleavage is observed at all studied collision energies. The SG1-alkoxyamines can be first cleaved in MS/MS conditions and secondly the proxyl-alkoxyamines in pseudo-MS3 conditions. These results open up interesting new avenues for the design of readable, erasable or programmable informational polymers.