Surgical complications in combined rhinoplasty and endoscopic sinus surgery.

KEY POINTS: Complications in combined surgery are equivalent to ESS but are higher than rhinoplasty alone. The most common complications are pneumonia, stroke, and epistaxis. Rhinoplasty surgeries with graft use have a higher risk of complications.

Machine learning-aided engineering of a cytochrome P450 for optimal bioconversion of lignin fragments.

Using machine learning, molecular dynamics simulations, and density functional theory calculations we gain insight into the selectivity patterns of substrate activation by the cytochromes P450. In nature, the reactions catalyzed by the P450s lead to the biodegradation of xenobiotics, but recent work has shown that fungi utilize P450s for the activation of lignin fragments, such as monomer and dimer units. These fragments often are the building blocks of valuable materials, including drug molecules and fragrances, hence a highly selective biocatalyst that can produce these compounds in good yield with high selectivity would be an important step in biotechnology. In this work a detailed computational study is reported on two reaction channels of two P450 isozymes, namely the O-deethylation of guaethol by CYP255A and the O-demethylation versus aromatic hydroxylation of p-anisic acid by CYP199A4. The studies show that the second-coordination sphere plays a major role in substrate binding and positioning, heme access, and in the selectivity patterns. Moreover, the local environment affects the kinetics of the reaction through lowering or raising barrier heights. Furthermore, we predict a site-selective mutation for highly specific reaction channels for CYP199A4.

Preservation Rhinoplasty by the Ones Who Do It: A Worldwide Survey.

Dorsal preservation (DP) rhinoplasty techniques, including surface techniques (STs) and foundation techniques (FTs) have garnered significant attention internationally over the past few years. The practice patterns and opinions from 117 of these surgeons were surveyed from a cohort of these surgeons who participate in an online Evidence-Based Rhinoplasty Research Group. The findings of the survey are merely a snapshot of the international rhinoplasty community's practices, yet did capture data from surgeons from a diverse geographic, years of experience, and training background. STs were most used for the bone changes, and the high-strip technique was preferred for the cartilaginous septal surgery. STs are mostly performed by younger surgeons (<10 years of experience), whereas FTs were more common in older surgeons (10-30 years of experience). STs were considered more stable (p < 0.001), more predictable (p < 0.001), and associate with a shorter learning curve (p = 0.015). Revision surgery rates were not different. Regarding why many surgeons using DP still perform structural rhinoplasty, the most cited concern was hump persistence/recurrence. In summary, among surgeons using DP rhinoplasty techniques, the majority perform DP in over half of their primary rhinoplasty surgeries, highlighting the importance of updating educational programs in medical training, conferences, and courses.

Craspase Orthologs Cleave a Nonconserved Site in Target Protein Csx30.

The Craspase CRISPR-Cas effector consists of the RNA-guided ribonuclease gRAMP and the protease TPR-CHAT, coupling target RNA recognition to protease activation. The natural substrate of Craspase is Csx30, a protein cleaved in two fragments that subsequently activates downstream antiviral pathways. Here, we determined the protease substrate specificity of Craspase from Candidatus "Jettenia caeni" (Jc-Craspase). We find that Jc-Craspase cleaves Jc-Csx30 in a target RNA-dependent fashion in A|S, which is different from the sites found in two other studied Craspases (L|D and M|K for Candidatus "Scalindua brodae" and Desulfonema ishimotonii, respectively). The fact that Craspase cleaves a nonconserved site across orthologs indicates the evolution of specific protein interactions between Craspase and its respective Csx30 target protein. The Craspase family thus represents a panel of proteases with different substrate specificities, which we exploited for the development of a readout for multiplexed RNA detection.

The impact of phage and phage resistance on microbial community dynamics.

Where there are bacteria, there will be bacteriophages. These viruses are known to be important players in shaping the wider microbial community in which they are embedded, with potential implications for human health. On the other hand, bacteria possess a range of distinct immune mechanisms that provide protection against bacteriophages, including the mutation or complete loss of the phage receptor, and CRISPR-Cas adaptive immunity. While our previous work showed how a microbial community may impact phage resistance evolution, little is known about the inverse, namely how interactions between phages and these different phage resistance mechanisms affect the wider microbial community in which they are embedded. Here, we conducted a 10-day, fully factorial evolution experiment to examine how phage impact the structure and dynamics of an artificial four-species bacterial community that includes either Pseudomonas aeruginosa wild-type or an isogenic mutant unable to evolve phage resistance through CRISPR-Cas. Additionally, we used mathematical modelling to explore the ecological interactions underlying full community behaviour, as well as to identify general principles governing the impacts of phage on community dynamics. Our results show that the microbial community structure is drastically altered by the addition of phage, with Acinetobacter baumannii becoming the dominant species and P. aeruginosa being driven nearly extinct, whereas P. aeruginosa outcompetes the other species in the absence of phage. Moreover, we find that a P. aeruginosa strain with the ability to evolve CRISPR-based resistance generally does better when in the presence of A. baumannii, but that this benefit is largely lost over time as phage is driven extinct. Finally, we show that pairwise data alone is insufficient when modelling our microbial community, both with and without phage, highlighting the importance of higher order interactions in governing multispecies dynamics in complex communities. Combined, our data clearly illustrate how phage targeting a dominant species allows for the competitive release of the strongest competitor while also contributing to community diversity maintenance and potentially preventing the reinvasion of the target species, and underline the importance of mapping community composition before therapeutically applying phage.

An Active Site Tyr Residue Guides the Regioselectivity of Lysine Hydroxylation by Nonheme Iron Lysine-4-hydroxylase Enzymes through Proton-Coupled Electron Transfer.

Lysine dioxygenase (KDO) is an important enzyme in human physiology involved in bioprocesses that trigger collagen cross-linking and blood pressure control. There are several KDOs in nature; however, little is known about the factors that govern the regio- and stereoselectivity of these enzymes. To understand how KDOs can selectively hydroxylate their substrate, we did a comprehensive computational study into the mechanisms and features of 4-lysine dioxygenase. In particular, we selected a snapshot from the MD simulation on KDO5 and created large QM cluster models (A, B, and C) containing 297, 312, and 407 atoms, respectively. The largest model predicts regioselectivity that matches experimental observation with rate-determining hydrogen atom abstraction from the C4-H position, followed by fast OH rebound to form 4-hydroxylysine products. The calculations show that in model C, the dipole moment is positioned along the C4-H bond of the substrate and, therefore, the electrostatic and electric field perturbations of the protein assist the enzyme in creating C4-H hydroxylation selectivity. Furthermore, an active site Tyr233 residue is identified that reacts through proton-coupled electron transfer akin to the axial Trp residue in cytochrome c peroxidase. Thus, upon formation of the iron(IV)-oxo species in the catalytic cycle, the Tyr233 phenol loses a proton to the nearby Asp179 residue, while at the same time, an electron is transferred to the iron to create an iron(III)-oxo active species. This charged tyrosyl residue directs the dipole moment along the C4-H bond of the substrate and guides the selectivity to the C4-hydroxylation of the substrate.

Axial Ligation Impedes Proton-Coupled Electron-Transfer Reactivity of a Synthetic Compound-I Analogue.

The nature of the axial ligand in high-valent iron-oxo heme enzyme intermediates and related synthetic catalysts is a critical structural element for controlling proton-coupled electron-transfer (PCET) reactivity of these species. Herein, we describe the generation and characterization of three new 6-coordinate, iron(IV)-oxo porphyrinoid-π-cation-radical complexes and report their PCET reactivity together with a previously published 5-coordinate analogue, FeIV(O)(TBP8Cz+•) (TBP8Cz = octakis(p-tert-butylphenyl)corrolazinato3-) (2) (Cho, K. A high-valent iron-oxo corrolazine activates C-H bonds via hydrogen-atom transfer. J. Am. Chem. Soc. 2012, 134, 7392-7399). The new complexes FeIV(O)(TBP8Cz+•)(L) (L = 1-methyl imidazole (1-MeIm) (4a), 4-dimethylaminopyridine (DMAP) (4b), cyanide (CN-)(4c)) can be generated from either oxidation of the ferric precursors or by addition of L to the Compound-I (Cpd-I) analogue at low temperatures. These complexes were characterized by UV-vis, electron paramagnetic resonance (EPR), and Mössbauer spectroscopies, and cryospray ionization mass spectrometry (CSI-MS). Kinetic studies using 4-OMe-TEMPOH as a test substrate indicate that coordination of a sixth axial ligand dramatically lowers the PCET reactivity of the Cpd-I analogue (rates up to 7000 times slower). Extensive density functional theory (DFT) calculations together with the experimental data show that the trend in reactivity with the axial ligands does not correlate with the thermodynamic driving force for these reactions or the calculated strengths of the O-H bonds being formed in the FeIV(O-H) products, pointing to non-Bell-Evans-Polanyi behavior. However, the PCET reactivity does follow a trend with the bracketed reduction potential of Cpd-I analogues and calculated electron affinities. The combined data suggest a concerted mechanism (a concerted proton electron transfer (CPET)) and an asynchronous movement of the electron/proton pair in the transition state.

Rhinoplasty Outcomes in Patients With Symptoms of Body Dysmorphia.

BACKGROUND: Patients with symptoms of body dysmorphia often seek consultation for aesthetic rhinoplasty. While body dysmorphic disorder is a formal psychiatric diagnosis, recent evidence indicates that patients with symptoms of this condition who seek rhinoplasty may experience increased satisfaction with their appearance following surgery. OBJECTIVES: To determine the psychological impact of rhinoplasty in patients screened preoperatively and postoperatively with a body dysmorphia screening questionnaire. METHODS: Retrospective chart review was performed of patients who underwent aesthetic and/or functional rhinoplasty by a single surgeon from June 2021 to April 2023. Adult patients with a complete preoperative and postoperative Body Dysmorphic Disorder-Aesthetic Surgery questionnaire (BDDQ-AS), Standardized Cosmesis and Health Nasal Outcomes Survey-Obstruction and Cosmesis (SCHNOS), and visual analog scale (VAS) were included. Patient characteristics and outcomes were analyzed, stratifying by BDDQ-AS screen. RESULTS: One-hundred fifteen patients (88% female) met criteria for inclusion. There was an 83% resolution rate of BDDQ-AS positive screening following rhinoplasty. Positive BDDQ-AS screening status preoperatively and postoperatively correlated with worse aesthetic satisfaction (all P < .002). No patient-reported outcome measures were indicative of which patients with a BDDQ-AS positive screen preoperatively would experience "resolution" postoperatively. CONCLUSIONS: Body dysmorphia screening resolution following surgical intervention correlated with improved patient aesthetic satisfaction, pointing to a potential positive psychological impact of undergoing rhinoplasty.

Does Size Really Matter? Incidence of Periprosthetic Fractures After Femoral Osteotomy in Patients With Cerebral Palsy.

OBJECTIVE: Of children, 30% to 35% with cerebral palsy (CP) develop hip subluxation or dislocation and often require reconstructive hip surgery, including varus derotation osteotomy (VDRO). A recent literature review identified postoperative fractures as the most common complication (9.4%) of VDROs. This study aimed to assess risk factors for periprosthetic fracture after VDRO in children with CP. METHODS: A total of 347 patients (644 hips, 526 bilateral hips) with CP and hip subluxation or dislocation (129 females; mean age at index VDRO: 8.6 y, SD 3.4, range: 1.5 to 17.7; 2 Gross Motor Function Classification System (GMFCS) I, 35 GMFCS II, 39 GMFCS III, 119 GMFCS IV, 133 GMFCS V, 21 unavailable) were included in this retrospective, single-group intervention (VDRO) study at a tertiary referral center. Imaging and clinical documentation for patients age 18 years or younger at index surgery, treated with VDRO were reviewed to determine demographic data, GMFCS level, surgeon, type of hardware implanted, use of anticonvulsants and steroids, type of postoperative immobilization, presence of periprosthetic fractures, fracture location and mechanism, and time from surgery to fracture. Potential determinants of periprosthetic fractures were assessed using mixed effects logistic regression. RESULTS: Of 644 hips, 14 (2.2%, 95% CI: 1.3%, 3.6%) sustained a periprosthetic fracture, at a median of 2.1 years postoperatively (interquartile range: 4.6 y, range: 1.2 mo to 7.8 y). Patients with a fracture had a median age at index surgery of 7.3 years (interquartile range: 4.3, range: 2.8 to 17.8; 1 GMFCS II, 6 GMFCS IV, 7 GMFCS V). Periprosthetic fractures were not significantly related to age at index surgery ( P = 0.18), sex ( P = 0.30), body mass index percentile ( P = 0.87), surgery side ( P = 0.16), anticonvulsant use ( P = 0.35), type of postoperative immobilization ( P = 0.40), GMFCS level ( P = 0.31), or blade plate size ( P = 0.17). Only surgeon volume significantly related to periprosthetic fracture (odds ratio = 5.03, 95% CI: 1.53, 16.56, P = 0.008), with the highest-volume surgeon also using smaller blade plates ( P < 0.01). CONCLUSIONS: Periprosthetic fractures after VDRO surgery in children with CP are uncommon, and routine hardware removal appears unnecessary. The data suggest that the common dogma of putting in the largest blade plate possible to maximize fixation may increase the risk of periprosthetic fracture. Due to the overall low fracture rate, especially when contextualized relative to the risk of hardware removal, a reactive approach to hardware removal appears warranted. LEVEL OF EVIDENCE: Level III-retrospective study (targeting varus derotational osteotomies in children with cerebral palsy).

Enhanced Reactivity through Equatorial Sulfur Coordination in Nonheme Iron(IV)-Oxo Complexes: Insights from Experiment and Theory.

Sulfur ligation in metalloenzymes often gives the active site unique properties, whether it is the axial cysteinate ligand in the cytochrome P450s or the equatorial sulfur/thiol ligation in nonheme iron enzymes. To understand sulfur ligation to iron complexes and how it affects the structural, spectroscopic, and intrinsic properties of the active species and the catalysis of substrates, we pursued a systematic study and compared sulfur with amine-ligated iron(IV)-oxo complexes. We synthesized and characterized a biomimetic N4S-ligated iron(IV)-oxo complex and compared the obtained results with an analogous N5-ligated iron(IV)-oxo complex. Our work shows that the amine for sulfur replacement in the equatorial ligand framework leads to a rate enhancement for oxygen atom and hydrogen atom transfer reactions. Moreover, the sulfur-ligated iron(IV)-oxo complex reacts through a different reaction mechanism as compared to the N5-ligated iron(IV)-oxo complex, where the former reacts through hydride transfer with the latter reacting via radical pathways. We show that the reactivity differences are caused by a dramatic change in redox potential between the two complexes. Our studies highlight the importance of implementing a sulfur ligand into the equatorial ligand framework of nonheme iron(IV)-oxo complexes and how it affects the physicochemical properties of the oxidant and its reactivity.

Computational Study Into the Oxidative Ring-Closure Mechanism During the Biosynthesis of Deoxypodophyllotoxin.

The nonheme iron dioxygenase deoxypodophyllotoxin synthase performs an oxidative ring-closure reaction as part of natural product synthesis in plants. How the enzyme enables the oxidative ring-closure reaction of (-)-yatein and avoids substrate hydroxylation remains unknown. To gain insight into the reaction mechanism and understand the details of the pathways leading to products and by-products we performed a comprehensive computational study. The work shows that substrate is bound tightly into the substrate binding pocket with the C7'-H bond closest to the iron(IV)-oxo species. The reaction proceeds through a radical mechanism starting with hydrogen atom abstraction from the C7'-H position followed by ring-closure and a final hydrogen transfer to form iron(II)-water and deoxypodophyllotoxin. Alternative mechanisms including substrate hydroxylation and an electron transfer pathway were explored but found to be higher in energy. The mechanism is guided by electrostatic perturbations of charged residues in the second-coordination sphere that prevent alternative pathways.

Gaze Patterns of Normal and Microtia Ears Pre- and Post-Reconstruction.

OBJECTIVES: To understand attentional preferences for normal and microtia ears. METHODS: Eye-tracking technology was used to characterize gaze preferences. A total of 71 participants viewed images of 5 patients with unilateral microtia. Profile images of patient faces and isolated ears including normal, microtia, and post-reconstruction microtia ears were shown. Total time of fixation in predefined areas of interest (AOI) was measured. Inferential statistics were used to assess significance of fixation differences between AOIs within and between facial or auricular features. RESULTS: The ear received most visual attention in lateral view of the face (1.91 s, 1.66-2.16 s) [mean, 95% CI], followed by features of the "central triangle"-the eyes (1.26 s, 1.06-1.46), nose (0.48 s, 0.38-0.58), and mouth (0.15 s, 0.15-0.20). In frontal view, microtia ears received less attention following surgical reconstruction (0.74 s vs. 0.4 s, p < 0.001). The concha was the most attended feature for both normal (2.97 s, 2.7-3.23) and reconstructed microtia ears (1.87 s, 1.61-2.13). Scars on reconstructed ears altered the typical visual scanpath. CONCLUSION: The ear is an attentional gaze landmark of the face. Attention to microtia ears, both pre- and post-reconstruction, differs from gaze patterns of normal ears. The concha was the most attended to subunit of the ear. Attentional gaze may provide an unbiased method to determine what is important in reconstructive surgery. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3136-3142, 2024.

CO2 Reduction by an Iron(I) Porphyrinate System: Effect of Hydrogen Bonding on the Second Coordination Sphere.

Transforming CO2 into valuable materials is an important reaction in catalysis, especially because CO2 concentrations in the atmosphere have been growing steadily due to extensive fossil fuel usage. From an environmental perspective, reduction of CO2 to valuable materials should be catalyzed by an environmentally benign catalyst and avoid the use of heavy transition-metal ions. In this work, we present a computational study into a novel iron(I) porphyrin catalyst for CO2 reduction, namely, with a tetraphenylporphyrin ligand and analogues. In particular, we investigated iron(I) tetraphenylporphyrin with one of the meso-phenyl groups substituted with o-urea, p-urea, or o-2-amide groups. These substituents can provide hydrogen-bonding interactions in the second coordination sphere with bound ligands and assist with proton relay. Furthermore, our studies investigated bicarbonate and phenol as stabilizers and proton donors in the reaction mechanism. Potential energy landscapes for double protonation of iron(I) porphyrinate with bound CO2 are reported. The work shows that the bicarbonate bridges the urea/amide groups to the CO2 and iron center and provides a tight bonding pattern with strong hydrogen-bonding interactions that facilitates easy proton delivery and reduction of CO2. Specifically, bicarbonate provides a low-energy proton shuttle mechanism to form CO and water efficiently. Furthermore, the o-urea group locks bicarbonate and CO2 in a tight orientation and helps with ideal proton transfer, while there is more mobility and lesser stability with an o-amide group in that position instead. Our calculations show that the o-urea group leads to reduction in proton-transfer barriers, in line with experimental observation. We then applied electric-field-effect calculations to estimate the environmental effects on the two proton-transfer steps in the reaction. These calculations describe the perturbations that enhance the driving forces for the proton-transfer steps and have been used to make predictions about how the catalysts can be further engineered for more enhanced CO2 reduction processes.

QM/MM Study Into the Mechanism of Oxidative C=C Double Bond Cleavage by Lignostilbene-α,ß-Dioxygenase.

The enzymatic biosynthesis of fragrance molecules from lignin fragments is an important reaction in biotechnology for the sustainable production of fine chemicals. In this work we investigated the biosynthesis of vanillin from lignostilbene by a nonheme iron dioxygenase using QM/MM and tested several suggested proposals via either an epoxide or dioxetane intermediate. Binding of dioxygen to the active site of the protein results in the formation of an iron(II)-superoxo species with lignostilbene cation radical. The dioxygenase mechanism starts with electrophilic attack of the terminal oxygen atom of the superoxo group on the central C=C bond of lignostilbene, and the second-coordination sphere effects in the substrate binding pocket guide the reaction towards dioxetane formation. The computed mechanism is rationalized with thermochemical cycles and valence bond schemes that explain the electron transfer processes during the reaction mechanism. Particularly, the polarity of the protein and the local electric field and dipole moments enable a facile electron transfer and an exergonic dioxetane formation pathway.

Comparison of Functional and Cosmetic Outcomes Between Dorsal Preservation and Spreader Flap Rhinoplasty: A Randomized Trial.

BACKGROUND: Preservation rhinoplasty is a novel and increasingly utilized method in nasal plastic surgery. OBJECTIVES: The study aimed to compare the functional and aesthetic outcomes of dorsal preservation rhinoplasty, a new and interesting method, with conventional hump resection. METHODS: A total of 84 rhinoplasty applicants were randomly assigned to 2 groups. The first group underwent convention dorsal hump resection with spreader flap midvault reconstruction and the second group underwent dorsal preservation rhinoplasty with the modified subdorsal strip method. Aesthetic and functional outcomes, including residual hump, nasal width, projection, and rotation, were evaluated after 1 year with the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS), visual analog scale (VAS), and image analysis. RESULTS: Eighty-four patients with a mean age of 30.96 ± 6.75 years were recruited, of whom 15 (17.6%) were male. There were no significant differences in confounding variables between the 2 groups. There were no significant differences in residual hump (P = .11), nasal width (P = .37), projection (P = .70), rotation (P = .79), VAS (P = .81), or SCHNOS (P = .90) between the 2 groups. CONCLUSIONS: Dorsal preservation rhinoplasty with the modified subdorsal strip method may have comparable aesthetic and functional outcomes to spreader flaps midvault reconstruction.

Sliding Spine Relocation Surgery with Anterior Septal Reconstruction.

Study Design: Technical note. Objective: The lower nasal architecture is dependent on caudal septal integrity. Deviations of the caudal septum can compromise nasal airflow. The presence of anterior nasal spine deviations contributes to septal and medial crural shifting with ipsilateral encroachment. It is essential to identify nasal spine deviation during surgery in order to reconstruct the septum in a midline position at its base. This allows an appropriate management plan that creates a better functional and aesthetically pleasing outcome. A stable midline anterior nasal spine is warranted to support the newly reconstructed straight caudal strut, which can be effectively corrected by anterior septal reconstruction. Methods: The proposed method intends to combine anterior nasal spine centralization with correcting caudal septal deviation and nasal obstruction through a modified extracorporeal septoplasty technique. We describe a novel technique to centralize the deviated anterior nasal spine using the piezoelectric device by performing a contralateral adjacent ostectomy and en-bloc relocation and fixation of the anterior nasal spine with microplates and screws. Results: This surgical approach creates a stable caudal septum and a centrally positioned anterior nasal spine, which improves nasal airflow and ensures a stable repair. Conclusion: Sliding spine relocation surgery with anterior septal reconstruction repositions a deviated anterior nasal spine and corrects caudal septum deviation, that can impair the nasal airway.

Translation, cultural adaptation, and validation of the Standardized Cosmesis and Health Nasal Outcomes Survey in Japanese (J-SCHNOS).

BACKGROUND: Rhinoplasty is one of the most popular plastic surgery techniques. The evaluation of both functional and cosmetic aspects of rhinoplasty is essential for planning and assessing surgery results. The Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) is a validated questionnaire used to assess both functional and aesthetic symptoms in patients with nasal problems, and it has been translated into several languages. The purpose of this study was to translate, culturally adapt, and validate the SCHNOS in Japanese among patients undergoing rhinoplasty. METHODS: This was a prospective validation study of the Japanese version of the SCHNOS (J-SCHNOS). The first phase involved translation and cross-cultural adaptation of the SCHNOS. The second phase included validation of the J-SCHNOS among native Japanese speakers. RESULTS: In total, 357 participants completed the final version of the J-SCHNOS (219 males and 138 females; mean age 43.4 years). The J-SCHNOS showed high internal consistency with excellent Cronbach's alpha values for both obstruction (SCHNOS-O) (0.96) and cosmetic (SCHNOS-C) (0.93) domains. The reproducibility was high, with an excellent intraclass correlation coefficient (ICC) >0.9 for all items. Exploratory factor analysis showed unidimensional structures in both the SCHNOS-O and the SCHNOS-C. CONCLUSION: The J-SCHNOS is a reliable and valid tool to assess the severity of nasal problems in patients undergoing rhinoplasty.

Catalytic divergencies in the mechanism of L-arginine hydroxylating nonheme iron enzymes.

Many enzymes in nature utilize a free arginine (L-Arg) amino acid to initiate the biosynthesis of natural products. Examples include nitric oxide synthases, which generate NO from L-Arg for blood pressure control, and various arginine hydroxylases involved in antibiotic biosynthesis. Among the groups of arginine hydroxylases, several enzymes utilize a nonheme iron(II) active site and let L-Arg react with dioxygen and α-ketoglutarate to perform either C3-hydroxylation, C4-hydroxylation, C5-hydroxylation, or C4-C5-desaturation. How these seemingly similar enzymes can react with high specificity and selectivity to form different products remains unknown. Over the past few years, our groups have investigated the mechanisms of L-Arg-activating nonheme iron dioxygenases, including the viomycin biosynthesis enzyme VioC, the naphthyridinomycin biosynthesis enzyme NapI, and the streptothricin biosynthesis enzyme OrfP, using computational approaches and applied molecular dynamics, quantum mechanics on cluster models, and quantum mechanics/molecular mechanics (QM/MM) approaches. These studies not only highlight the differences in substrate and oxidant binding and positioning but also emphasize on electronic and electrostatic differences in the substrate-binding pockets of the enzymes. In particular, due to charge differences in the active site structures, there are changes in the local electric field and electric dipole moment orientations that either strengthen or weaken specific substrate C-H bonds. The local field effects, therefore, influence and guide reaction selectivity and specificity and give the enzymes their unique reactivity patterns. Computational work using either QM/MM or density functional theory (DFT) on cluster models can provide valuable insights into catalytic reaction mechanisms and produce accurate and reliable data that can be used to engineer proteins and synthetic catalysts to perform novel reaction pathways.