👤 H Dym

The goal of bone grafting is to replace normal bone volume and structure with healthy, well-vascularized bone that will undergo normal remodeling. The ideal bone will regenerate bone and not repair it. Currently four types of grafting material are available to clinicians for regenerative use in oral and maxillofacial surgery: autologous bone, allogeneic bone, xenogenic bone, and alloplastic bone. Additionally, bioactive agents, growth factors, are now being used to stimulate osteoinductive properties of native bone for bone regeneration. This article reviews the literature and summarizes the benefits and disadvantages of each respective graft and illustrates its use in clinical practice. Show less

Even with the great strides made in the techniques for placement of traditional endosseous dental implants, restoration of the dentition in patients with a severely resorbed or resected maxilla can prove challenging. For many decades, significant bone grafting was the mainstay of treatment for these patients. However, zygomatic implants have been shown to provide a stable and predictable alternative for the restoration of the dentition for patients with severe bone loss of the maxilla. Show less

Burning mouth syndrome/glossodynia and trigeminal neuropathic conditions can have serious negative impact on a patient's overall quality of life. These conditions are often hard to diagnose and even harder to fully treat and manage, but it is important for dentists/oral and maxillofacial surgeons to be aware of these conditions and modalities of their treatment. Often the only method for arriving at the proper diagnosis is for patients to undergo traditional approaches for treatment of presenting signs and symptoms, and it is the unexpected failure of interventional therapies that leads ultimately to a proper diagnosis. Show less

Surgical adjunctive instruments and devices are now available for the up-to-date dental/oral surgical office to help mitigate possible surgical complications. Both the laser and Piezo instruments are unique devices that can offer the clinician certain advantages that may prove beneficial in the treatment of his or her patients. Show less

Excessive gingival display or "gummy smile" is a growing concern to dental patients and often considered detrimental to an esthetic smile. Gingival display of more than 4 mm of gingiva is considered by many to be unattractive. The cause of the gummy smile can be multifactorial and must be accurately diagnosed to render appropriate treatment. Factors that contribute to the gummy smile include altered passive eruption, lip length, lip hypermobility, incisal wear/crown length, and vertical maxillary excess and gingival hyperplasia. The purpose of this article is to review the etiology, diagnosis, and surgical approaches in treating the gummy smile. Show less

Platelet-rich fibrin (PRF) is an autogenous material that is derived from a person's own platelets and is used to enhance wound healing and tissue regeneration. Platelet concentrates have been applied in dermatology, pain management, sports medicine, plastic surgery, cardiac surgery, urology, and also dentistry. PRF has garnered significant interest in the dental community because of its proposed regenerative properties and its ability to aid in wound healing. PRF is proposed to have a direct effect on enhancing a patient's wound healing by suprasaturating the wound with growth factors that promote tissue healing. Clinically, PRF is easily produced chairside from the patient's own blood. The autologous nature of PRF makes it preferred over a variety of allografts used in dentistry today. Therefore, PRF has significant potential in being applicable to all areas of dentistry, including oral and maxillofacial surgeries. Show less

Evolutionary trajectories are deemed largely irreversible. In a newly diverged protein, reversion of mutations that led to the functional switch typically results in loss of both the new and the ancestral functions. Nonetheless, evolutionary transitions where reversions are viable have also been described. The structural and mechanistic causes of reversion compatibility versus incompatibility therefore remain unclear. We examined two laboratory evolution trajectories of mammalian paraoxonase-1, a lactonase with promiscuous organophosphate hydrolase (OPH) activity. Both trajectories began with the same active-site mutant, His115Trp, which lost the native lactonase activity and acquired higher OPH activity. A neo-functionalization trajectory amplified the promiscuous OPH activity, whereas the re-functionalization trajectory restored the native activity, thus generating a new lactonase that lacks His115. The His115 revertants of these trajectories indicated opposite trends. Revertants of the neo-functionalization trajectory lost both the evolved OPH and the original lactonase activity. Revertants of the trajectory that restored the original lactonase function were, however, fully active. Crystal structures and molecular simulations show that in the newly diverged OPH, the reverted His115 and other catalytic residues are displaced, thus causing loss of both the original and the new activity. In contrast, in the re-functionalization trajectory, reversion compatibility of the original lactonase activity derives from mechanistic versatility whereby multiple residues can fulfill the same task. This versatility enables unique sequence-reversible compositions that are inaccessible when the active site was repurposed toward a new function. Show less

The US Surgeon General's report Oral Health in America highlighted ways in which oral health and systemic conditions are associated with each other. An oral examination can reveal signs and symptoms associated with systemic diseases. In this article, multiple systemic diseases including but not limited to viral and immune modulated conditions and associated oral symptoms are discussed. Show less

Interpreting findings seen at CT of the neck is challenging owing to the complex and nuanced anatomy of the neck, which contains multiple organ systems in a relatively small area. In the emergency department setting, CT is performed to investigate acute infectious or inflammatory symptoms and chronic processes. With few exceptions, neck CT should be performed with intravenous contrast material, which accentuates abnormally enhancing phlegmonous and neoplastic tissues and can be used to delineate any abscesses or necrotic areas. As part of the evaluation, the vascular structures and aerodigestive tract must be scrutinized, particularly for patency. Furthermore, although the patient may present because of symptoms that suggest non-life-threatening conditions involving structures such as the teeth or salivary glands, there may be serious implications for other areas, such as the orbits, brain, and spinal cord, that also may be revealed at the examination. With a focus on the emergency setting, the authors propose using an approach to interpreting neck CT findings whereby 12 areas are systematically evaluated and reported on: the cutaneous and subcutaneous soft tissues, aerodigestive tract and adjacent soft tissues, teeth and periodontal tissues, thyroid gland, salivary glands, lymph nodes, vascular structures, bony airspaces, cervical spine, orbits and imaged brain, lung apices, and superior mediastinum. The use of a systematic approach to interpreting neck CT findings is essential for identifying all salient findings, recognizing and synthesizing the implications of these findings to formulate the correct diagnosis, and reporting the findings and impressions in a complete, clear, and logical manner. Show less

Antibodies developed for research and clinical applications may exhibit suboptimal stability, expressibility, or affinity. Existing optimization strategies focus on surface mutations, whereas natural affinity maturation also introduces mutations in the antibody core, simultaneously improving stability and affinity. To systematically map the mutational tolerance of an antibody variable fragment (Fv), we performed yeast display and applied deep mutational scanning to an anti-lysozyme antibody and found that many of the affinity-enhancing mutations clustered at the variable light-heavy chain interface, within the antibody core. Rosetta design combined enhancing mutations, yielding a variant with tenfold higher affinity and substantially improved stability. To make this approach broadly accessible, we developed AbLIFT, an automated web server that designs multipoint core mutations to improve contacts between specific Fv light and heavy chains (http://AbLIFT.weizmann.ac.il). We applied AbLIFT to two unrelated antibodies targeting the human antigens VEGF and QSOX1. Strikingly, the designs improved stability, affinity, and expression yields. The results provide proof-of-principle for bypassing laborious cycles of antibody engineering through automated computational affinity and stability design. Show less

Pacemakers and implantable cardioverter defibrillators are commonly encountered in clinical practice, and entails special consideration when magnetic resonance imaging (MRI) is required. It is estimated that 50-75% of patients with cardiac implantable electronic devices (CIED) will have an indication for MRI during their lifetime. Radiologists may want to recommend MRI or may be consulted about the need to perform MRI in a patient with a CIED, at which point they may need to approve or at least provide guidance as to whether MRI may be performed safely. Even in situations where final clearance will not be provided by the radiologist, he or she can provide valuable information by reviewing radiographs and determining (a) whether a device is MRI-conditional and MRI may ultimately be permitted, (b) is not MRI-conditional and MRI using the standard workflow will therefore not be approved, or (c) when additional information will clearly be required. CIED identification and verification of leads can be accomplished through review of the medical record and/or evaluation of a chest radiograph. In patients with MRI-conditional CIEDs (as well as with legacy CIEDs in those institutions that perform MRI of these patients), specific imaging protocols must be adhered to in order to prevent death or injury to the patient or damage to the device. In this update, we provide details regarding the above topics and provide an algorithm for integrating this information into a clinical workflow to efficiently triage patients with CIEDs who are being considered for MRI. Show less

To evaluate final-year pharmacy students' perceptions toward pharmacogenomics education, their attitudes on its clinical relevance, and their readiness to use such knowledge in practice. A 19-question survey was developed and modified from prior studies and was pretested on a small group of pharmacogenomics faculty and pharmacy students. The final survey was administered to 978 final-year pharmacy students in 8 school/colleges of pharmacy in New York and New Jersey between January and May 2017. The survey targeted 3 main themes: perceptions toward pharmacogenomics education, attitudes toward the clinical relevance of this education, and the students' readiness to use knowledge of pharmacogenomics in practice. With a 35% response rate, the majority (81%) of the 339 student participants believed that pharmacogenomics was a useful clinical tool for pharmacists, yet only 40% felt that it had been a relevant part of their training. Almost half (46%) received only 1-3 lectures on pharmacogenomics and the majority were not ready to use it in practice. Survey results pointed toward practice-based trainings such as pharmacogenomics rotations as the most helpful in preparing students for practice. Final-year student pharmacists reported varying exposure to pharmacogenomics content in their pharmacy training and had positive attitudes toward the clinical relevance of the discipline, yet they expressed low confidence in their readiness to use this information in practice. Show less

Dysgerminomas are aggressive germ cell tumors that typically have a favorable prognosis, especially in patients diagnosed with early stage disease. We recount the history of a 23-year-old woman who was treated for a stage IA ovarian dysgerminoma in November 2017. Postoperatively, the patient was noncompliant insofar as obtaining routine lab evaluations; ten months later, she was diagnosed with a cranial metastasis that extended into the meninges. The patient subsequently underwent a posterior fossa craniotomy and adjuvant etoposide, bleomycin and cisplatin chemotherapy to which she initially responded; however, during cycle 4, she developed pancytopenia whereupon the chemotherapy was summarily discontinued. Thereafter, the patient was surveilled and currently, she remains in clinical remission. Early stage ovarian dysgerminoma, albeit rarely, has the capacity to metastasize to the cranium or brain, further underscoring the significance of employing active follow-up with these patients. Show less

Electronic stimulation devices are implanted in various locations in the body to decrease pain, modulate nerve function, or stimulate various end organs. The authors describe these devices using a craniocaudal approach, first describing deep brain stimulation (DBS) devices and ending with sacral nerve stimulation (SNS) devices. The radiology-relevant background information for each device and its imaging appearance are also described. These devices have a common design theme and include the following components: Show less

The crystal structures of truncated forms of cholinesterases provide good models for assessing the role of non-covalent interactions in dimer assembly in the absence of cross-linking disulfide bonds. These structures identify the four-helix bundle that serves as the interface for formation of acetylcholinesterase and butyrylcholinesterase dimers. Here we performed a theoretical comparison of the structural and energetic factors governing dimerization. This included identification of inter-subunit and intra-subunit hydrogen bonds and hydrophobic interactions, evaluation of solvent-accessible surfaces, and estimation of electrostatic contributions to dimerization. To reveal the contribution to dimerization of individual amino acids within the contact area, free energy perturbation alanine screening was performed. Markov state modelling shows that the loop between the α13 and α14 helices in BChE is unstable, and occupies 4 macro-states. The order of magnitude of mean first passage times between these macrostates is ~10 Show less

Silent sinus syndrome (SSS) describes enophthalmos and hypoglobus in association with disease of the maxillary sinus. This syndrome has rarely been presented in the dental literature. Many dentists are not familiar with the syndrome and its associated clinical and radiologic features. A 57-year-old female patient presented to the Oral and Maxillofacial Surgery Outpatient Clinic at The Brooklyn Hospital Center for a routine dental examination. During this examination, she indicated that she felt her right eye had been sinking. Routine dental panoramic radiography showed opacification on the right maxillary sinus. Maxillofacial computed tomography showed a small maxillary sinus with retraction of the sinus walls. The floor of the orbit was thinned, causing hypoglobus. Obstruction of the right ostiomeatal complex was noted, with complete opacification of the right maxillary sinus. A diagnosis of SSS was made. SSS usually occurs in individuals in the third to fifth decade of life. It presents with enopthalmos and hypoglobus. On imaging, a small and opacified maxillary sinus is visualized with retraction of the orbital floor and a blocked ostiomeatal complex. Management includes functional endoscopic sinus surgery. The orbital floor can be reconstructed during the same operation, at a later date, or not at all. Knowledge about SSS can lead to prompt diagnosis and treatment recommendations while avoiding unnecessary diagnostic tests. Show less

We consider Riemann mappings from bounded Lipschitz domains in the plane to a triangle. We show that in this case the Riemann mapping has a linear variational principle: It is the minimizer of the Dirichlet energy over an appropriate affine space. By discretizing the variational principle in a natural way we obtain discrete conformal maps which can be computed by solving a sparse linear system. We show that these discrete conformal maps converge to the Riemann mapping in [Formula: see text], even for non-Delaunay triangulations. Additionally, for Delaunay triangulations the discrete conformal maps converge uniformly and are known to be bijective. As a consequence we show that the Riemann mapping between two bounded Lipschitz domains can be uniformly approximated by composing the discrete Riemann mappings between each Lipschitz domain and the triangle. Show less

The purpose of this article is to describe a case of an accidental turbinectomy during nasal intubation for an elective oral and maxillofacial surgical case that was confirmed after extubation. While there are several reported cases, this still tends to be an overall rare complication in the field of anesthesia. This article highlights the complications encountered due to turbinectomy while also identifying causes, signs, and methods to prevent it. Show less

Protein networks in all organisms comprise homologous interacting pairs. In these networks, some proteins are specific, interacting with one or a few binding partners, whereas others are multispecific and bind a range of targets. We describe an algorithm that starts from an interacting pair and designs dozens of new pairs with diverse backbone conformations at the binding site as well as new binding orientations and sequences. Applied to a high-affinity bacterial pair, the algorithm results in 18 new ones, with cognate affinities from pico- to micromolar. Three pairs exhibit 3-5 orders of magnitude switch in specificity relative to the wild type, whereas others are multispecific, collectively forming a protein-interaction network. Crystallographic analysis confirms design accuracy, including in new backbones and polar interactions. Preorganized polar interaction networks are responsible for high specificity, thus defining design principles that can be applied to program synthetic cellular interaction networks of desired affinity and specificity. Show less

Substantial improvements in enzyme activity demand multiple mutations at spatially proximal positions in the active site. Such mutations, however, often exhibit unpredictable epistatic (non-additive) effects on activity. Here we describe FuncLib, an automated method for designing multipoint mutations at enzyme active sites using phylogenetic analysis and Rosetta design calculations. We applied FuncLib to two unrelated enzymes, a phosphotriesterase and an acetyl-CoA synthetase. All designs were active, and most showed activity profiles that significantly differed from the wild-type and from one another. Several dozen designs with only 3-6 active-site mutations exhibited 10- to 4,000-fold higher efficiencies with a range of alternative substrates, including hydrolysis of the toxic organophosphate nerve agents soman and cyclosarin and synthesis of butyryl-CoA. FuncLib is implemented as a web server (http://FuncLib.weizmann.ac.il); it circumvents iterative, high-throughput experimental screens and opens the way to designing highly efficient and diverse catalytic repertoires. Show less

Folding of proteins to their functional conformation is paramount to life. Though 75% of the proteome consists of multidomain proteins, our knowledge of folding has been based primarily on studies conducted on single-domain and fast-folding proteins. Nonetheless, the complexity of folding landscapes exhibited by multidomain proteins has received increased scrutiny in recent years. We study the three-domain protein adenylate kinase from E. coli (AK), which has been shown to fold through a series of pathways involving several intermediate states. We use a protein design method to manipulate the folding landscape of AK, and single-molecule FRET spectroscopy to study the effects on the folding process. Mutations introduced in the NMP binding (NMPbind) domain of the protein are found to have unexpected effects on the folding landscape. Thus, while stabilizing mutations in the core of the NMPbind domain retain the main folding pathways of wild-type AK, a destabilizing mutation at the interface between the NMPbind and the CORE domains causes a significant repartition of the flux between the folding pathways. Our results demonstrate the outstanding plasticity of the folding landscape of AK and reveal how specific mutations in the primary structure are translated into changes in folding dynamics. The combination of methodologies introduced in this work should prove useful for deepening our understanding of the folding process of multidomain proteins. Show less

Automated design of enzymes with wild-type-like catalytic properties has been a long-standing but elusive goal. Here, we present a general, automated method for enzyme design through combinatorial backbone assembly. Starting from a set of homologous yet structurally diverse enzyme structures, the method assembles new backbone combinations and uses Rosetta to optimize the amino acid sequence, while conserving key catalytic residues. We apply this method to two unrelated enzyme families with TIM-barrel folds, glycoside hydrolase 10 (GH10) xylanases and phosphotriesterase-like lactonases (PLLs), designing 43 and 34 proteins, respectively. Twenty-one GH10 and seven PLL designs are active, including designs derived from templates with <25% sequence identity. Moreover, four designs are as active as natural enzymes in these families. Atomic accuracy in a high-activity GH10 design is further confirmed by crystallographic analysis. Thus, combinatorial-backbone assembly and design may be used to generate stable, active, and structurally diverse enzymes with altered selectivity or activity. Show less

Much of our knowledge on the function of proteins is deduced from their mature, folded states. However, it is unknown whether partially synthesized nascent protein segments can execute biological functions during translation and whether their premature folding states matter. A recent observation that a nascent chain performs a distinct function, co-translational targeting in vivo, has been made with the Escherichia coli signal recognition particle receptor FtsY, a major player in the conserved pathway of membrane protein biogenesis. FtsY functions as a membrane-associated entity, but very little is known about the mode of its targeting to the membrane. Here we investigated the underlying structural mechanism of the co-translational FtsY targeting to the membrane. Our results show that helices N Show less

Proteins have evolved to balance efficient binding of desired partners with rejection of unwanted interactions. To investigate the evolution of protein-protein interactions, we selected a random library of pre-stabilized TEM1 β-lactamase against wild-type TEM1 using yeast surface display. Three mutations were sufficient to achieve micromolar affinity binding between the two. The X-ray structure emphasized that the main contribution of the selected mutations was to modify the protein fold, specifically removing the N'-terminal helix, which consequently allowed protein coupling via a β-sheet-mediated interaction resembling amyloid interaction mode. The only selected mutation located at the interaction interface (E58V) is reminiscent of the single mutation commonly causing sickle-cell anemia. Interestingly, the evolved mutations cannot be inserted into the wild-type protein due to reduced thermal stability of the resulting mutant protein. These results reveal a simple mechanism by which undesirable binding is purged by loss of thermal stability. Show less

Indwelling Foley catheter is a rare cause of urinary bladder perforation, a serious injury with high mortality that demands accurate and prompt diagnosis. While the gold standard for diagnosis of bladder injury is computed tomography (CT) cystography, few bladder ruptures associated with Foley catheter have been reported to be diagnosed in the emergency department (ED). An 83-year-old man with indwelling Foley catheter presented to the ED for hematuria and altered mental status. He was diagnosed to have intraperitoneal rupture of the urinary bladder in the ED using abdominal and pelvic CT without contrast, which demonstrated bladder wall discontinuity, intraperitoneal free fluid, and pneumoperitoneum. The patient was treated successfully with medical management and bladder drainage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To our knowledge, this is the first report of intraperitoneal urinary bladder perforation associated with Foley catheter diagnosed in the ED by CT without contrast. Pneumoperitoneum found in this case was a clue to the diagnosis and is a benign finding that does not necessitate urgent surgical intervention. The early and accurate diagnosis in this case allowed for effective management with good clinical outcome. The use of indwelling Foley catheter has a high prevalence, especially in long-term care facility residents, who are frequent visitors in the ED. Therefore, emergency physicians and radiologists should be familiar with the presentation and imaging findings of this potential injury associated with Foley catheters. Show less

Natural proteins must both fold into a stable conformation and exert their molecular function. To date, computational design has successfully produced stable and atomically accurate proteins by using so-called "ideal" folds rich in regular secondary structures and almost devoid of loops and destabilizing elements, such as cavities. Molecular function, such as binding and catalysis, however, often demands nonideal features, including large and irregular loops and buried polar interaction networks, which have remained challenging for fold design. Through five design/experiment cycles, we learned principles for designing stable and functional antibody variable fragments (Fvs). Specifically, we ( Show less