ABSTRACT
Imidazoles are present in Earth's atmosphere in both the gas-phase and in aerosol particles, and have been implicated in the formation of brown carbon aerosols. The gas-phase oxidation of imidazole (C3N2H4) by hydroxyl radicals has been shown to be preferentially initiated via OH-addition to position C5, producing the 5-hydroxyimidazolyl radical adduct. However, the fate of this adduct upon reaction with O2 in the atmospheric gas-phase is currently unknown. We employed an automated approach to investigate the reaction mechanism and kinetics of imidazole's OH-initiated gas-phase oxidation, in the presence of O2 and NOx. The explored mechanism included reactions available to first-generation RO2 radicals, as well as alkoxyl radicals produced from RO2 + NO reactions. Product distributions were obtained by assembling and solving a master equation, under conditions relevant to the Earth's atmosphere. Our calculations show a complex, branched reaction mechanism, which nevertheless converges to yield two major closed-shell products: 4H-imidazol-4-ol (4H-4ol) and N,N'-diformylformamidine (FMF). At 298 K and 1 atm, we estimate the yields of 4H-4ol and FMF from imidazole oxidation initiated via OH-addition to position C5 to be 34 : 66, 12 : 85 and 2 : 95 under 10 ppt, 100 ppt and 1 ppb of NO respectively. This work also revealed O2-migration pathways between the α-N-imino peroxyl radical isomers. This reaction channel is fast for the first-generation RO2 radicals, and may be important during the atmospheric oxidation of other unsaturated organic nitrogen compounds as well.
ABSTRACT
Carbene species play an integral role in high-energy chemistry, transition-metal-carbene chemistry, catalysis, photolytic formation of carbohydrates, and possibly even the formation of interstellar sugars. In 1921, "reactive formaldehyde"ânow known as hydroxymethylene (HCOH)âwas first implicated as an intermediate in photocatalytic processes. However, due to its transient nature, direct observation of HCOH has predominantly been attained using cryogenic isolation methods. As a result, HCOH gas-phase reactivity measurements have been limited. We directly observed HCOH using photoionization spectroscopy following UV photodissociation of methanol. Our measurements show it reacts slowly with O2 at room temperature. This work provides evidence for the formation mechanism of HCOH from CH3OH and its subsequent reactivity under gas-phase reaction conditions.
ABSTRACT
We assess the capability of machine-learned potentials to compute rate coefficients by training a neural network (NN) model and applying it to describe the chemical landscape on the C5H5 potential energy surface, which is relevant to molecular weight growth in combustion and interstellar media. We coupled the resulting NN with an automated kinetics workflow code, KinBot, to perform all necessary calculations to compute the rate coefficients. The NN is benchmarked exhaustively by evaluating its performance at the various stages of the kinetics calculations: from the electronic energy through the computation of zero point energy, barrier heights, entropic contributions, the portion of the PES explored, and finally the overall rate coefficients as formulated by transition state theory.
ABSTRACT
Desde sus inicios, la medicina nuclear se ha enfrentado a cambios tecnológicos que la han obligado a modificar sus modos operativos y a adecuar sus protocolos. En el campo de la cirugía radioguiada (CRG), la incorporación de la imagen gammagráfica preoperatoria y la detección intraoperatoria con la sonda gamma proporcionó un impulso definitivo a la biopsia del ganglio centinela (GC) para convertirse en el procedimiento estándar de aplicación en el melanoma y el cáncer de mama. Las diversas innovaciones tecnológicas y la adaptación consiguiente de protocolos confluyen en lo disruptivo y lo gradual. Como ejemplos evidentes tenemos la introducción de la tomografía por emisión de fotón único/tomografía computarizada (SPECT/TC) en el campo preoperatorio y las sondas Drop-in (Lightpoint Medical Ltd; Crystal photonics, Eurorad) en el intraoperatorio. Otros aspectos innovadores con posible aplicación en la CRG se basan en la utilización de la inteligencia artificial (IA), navegación y teleasistencia (AU)
Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare (AU)
Subject(s)
Humans , Sentinel Lymph Node Biopsy , Surgery, Computer-Assisted , Artificial Intelligence , In Situ Hybridization, FluorescenceABSTRACT
Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare.
Subject(s)
Melanoma , Surgery, Computer-Assisted , Humans , Artificial Intelligence , Sentinel Lymph Node Biopsy/methods , Single Photon Emission Computed Tomography Computed Tomography , Surgery, Computer-Assisted/methodsABSTRACT
BACKGROUND: Infection is one of the challenging complications after open reduction and internal fixation for ankle fractures. Previously published case series conclude that Staphylococcus aureus is the most frequent causative microorganism. An unexpected increase in Enterobacter cloacae infections after this surgery was observed in a preliminary analysis of data at the promoting center of the study. In traumatology, its incidence has been reported in chronic osteomyelitis, prosthetic infections, septic osteoarthritis, open fractures in children and adults, and fractures other than the ankle. Because of this unexpected finding, we decided to perform this study to analyze the demographic and microbiological variables of acute osteosynthesis infection after ankle fracture and determine the distinctive features of the patients with E cloacae infection. METHODS: We performed a retrospective multicenter study including 4 university hospitals. All patients diagnosed with acute osteosynthesis infection after ankle fracture fixation between January 2015 and December 2018 were included. We analyzed demographic data, type of fracture, surgical technique, and microorganisms responsible for the infection. We performed a descriptive statistical analysis of the variables. Univariate and multivariate regression analysis were performed to compare patients with E cloacae infection to patients with infection caused by other microorganisms. RESULTS: A total of 65 patients were included. A predominance of polymicrobial infections (24.62%), followed by infections caused by S aureus (23.07%) and E cloacae (23.07%) was observed. When E cloacae isolated in polymicrobial infections were added, the incidence of E cloacae as a causative microorganism increased to 32.3%. Patients with E cloacae infection were older (64/53, P = .008) and had a higher requirement of negative-pressure therapy after surgical debridement (71%/40%, P = .017). CONCLUSION: A high incidence of E cloacae infections was observed. Patients with E cloacae infection were generally older and required a higher use of negative-pressure therapy after debridement. LEVEL OF EVIDENCE: Level V, mechanism-based reasoning.
Subject(s)
Ankle Fractures , Coinfection , Adult , Child , Humans , Ankle Fractures/surgery , Enterobacter cloacae , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/methods , Open Fracture Reduction/methods , Retrospective Studies , Treatment OutcomeABSTRACT
We used aerosol mass spectrometry coupled with tunable synchrotron photoionization to measure radical and closed-shell species associated with particle formation in premixed flames and during pyrolysis of butane, ethylene, and methane. We analyzed photoionization (PI) spectra for the C7H7 radical to identify the isomers present during particle formation. For the combustion and pyrolysis of all three fuels, the PI spectra can be fit reasonably well with contributions from four radical isomers: benzyl, tropyl, vinylcyclopentadienyl, and o-tolyl. Although there are significant experimental uncertainties in the isomeric speciation of C7H7, the results clearly demonstrate that the isomeric composition of C7H7 strongly depends on the combustion or pyrolysis conditions and the fuel or precursors. Fits to the PI spectra using reference curves for these isomers suggest that all of these isomers may contribute to m/z 91 in butane and methane flames, but only benzyl and vinylcyclopentadienyl contribute to the C7H7 isomer signal in the ethylene flame. Only tropyl and benzyl appear to play a role during pyrolytic particle formation from ethylene, and only tropyl, vinylcyclopentadienyl, and o-tolyl appear to participate during particle formation from butane pyrolysis. There also seems to be a contribution from an isomer with an ionization energy below 7.5 eV for the flames but not for the pyrolysis conditions. Kinetic models with updated and new reactions and rate coefficients for the C7H7 reaction network predict benzyl, tropyl, vinylcyclopentadienyl, and o-tolyl to be the primary C7H7 isomers and predict negligible contributions from other C7H7 isomers. These updated models provide better agreement with the measurements than the original versions of the models but, nonetheless, underpredict the relative concentrations of tropyl, vinylcyclopentadienyl, and o-tolyl in both flames and pyrolysis and overpredict benzyl in pyrolysis. Our results suggest that there are additional important formation pathways for the vinylcyclopentadienyl, tropyl, and o-tolyl radicals and/or loss pathways for the benzyl radical that are currently unaccounted for in the present models.
ABSTRACT
The automated kinetics workflow code, KinBot, was used to explore and characterize the regions of the C7H7 potential energy surface that are relevant to combustion environments and especially soot inception. We first explored the lowest-energy region, which includes the benzyl, fulvenallene + H, and cyclopentadienyl + acetylene entry points. We then expanded the model to include two higher-energy entry points, vinylpropargyl + acetylene and vinylacetylene + propargyl. The automated search was able to uncover the pathways from the literature. In addition, three important new routes were discovered: a lower-energy pathway connecting benzyl with vinylcyclopentadienyl, a decomposition mechanism from benzyl that results in side-chain hydrogen atom loss to produce fulvenallene + H, and shorter and lower energy routes to the dimethylene-cyclopentenyl intermediates. We systematically reduced the extended model to a chemically relevant domain composed of 63 wells, 10 bimolecular products, 87 barriers, and 1 barrierless channel and constructed a master equation using the CCSD(T)-F12a/cc-pVTZ//ωB97X-D/6-311++G(d,p) level of theory to provide rate coefficients for chemical modeling. Our calculated rate coefficients show excellent agreement with measured ones. We also simulated concentration profiles and calculated branching fractions from the important entry points to provide an interpretation of this important chemical landscape.
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Automation of rate-coefficient calculations for gas-phase organic species became possible in recent years and has transformed how we explore these complicated systems computationally. Kinetics workflow tools bring rigor and speed and eliminate a large fraction of manual labor and related error sources. In this paper we give an overview of this quickly evolving field and illustrate, through five detailed examples, the capabilities of our own automated tool, KinBot. We bring examples from combustion and atmospheric chemistry of C-, H-, O-, and N-atom-containing species that are relevant to molecular weight growth and autoxidation processes. The examples shed light on the capabilities of automation and also highlight particular challenges associated with the various chemical systems that need to be addressed in future work.
ABSTRACT
Following surgery, healing within the oral cavity occurs in a hostile environment, and proper oral care and hygiene are required to accelerate recovery. The aim of the current study is to investigate and compare the bioreactivity characteristics of mouthwashes based on either chlorhexidine (CHX) or a novel bone bioactive liquid (BBL) in terms of oral healing within seven days application post-surgery. A randomized, double blind clinical trial was conducted in 81 patients, wherein the mouthwashes were applied twice a day for a period of 7 days. The visual analog scale (VAS) protocol was applied to determine pain index scores. Early wound healing index (EHI) score was determined for evaluating oral cavity healing progress. No adverse effects were observed using the mouthwashes, but CHX application resulted in stained teeth. Applications of both CHX and BBL were sufficient to reduce pain over a period of 7 days. However, the BBL group demonstrated a statistically significant reduction in VAS scores starting on day 4. The EHI scores were significantly higher in the BBL group compared with the CHX group, independent of tooth location. No differences in either VAS or EHI scores due to gender were observed. Compared with the commercially available CHX mouthwash, application of the BBL mouthwash reduced pain and accelerated oral cavity healing to a greater extent, suggesting it effectively improves the oral cavity microenvironment at the wound site in mediating soft tissue regeneration.
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OBJECTIVES: This study aims to evaluate the usefulness of liquid-based brush cytology for malignancy diagnosis and HPV detection in patients with suspected oropharyngeal and oral carcinomas, as well as for the diagnosis of tumoral persistence after treatment. MATERIAL AND METHODS: Seventy-five patients with suspicion of squamous cell carcinoma of the oropharynx or oral cavity were included. Two different study groups were analyzed according to the date of the sample collection: (1) during the first endoscopy exploration and (2) in the first control endoscopy after treatment for squamous cell carcinoma. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for malignancy diagnosis as well as for HPV-DNA detection on brush cytologies were assessed. RESULTS: Before treatment, the brush cytology showed a sensitivity of 88%, specificity of 100%, and accuracy of 88%. After treatment, it showed a sensitivity of 71%, specificity of 77%, and accuracy of 75%. HPV-DNA detection in cytology samples showed a sensitivity of 85%, specificity of 100%, and accuracy of 91% before treatment and an accuracy of 100% after treatment. CONCLUSIONS: Liquid-based brush cytology showed good accuracy for diagnosis of oropharyngeal and oral squamous cell carcinoma before treatment, but its value decreases after treatment. Nevertheless, it is useful for HPV-DNA detection, as well as to monitor the patients after treatment. CLINICAL RELEVANCE: Brush cytology samples are reliable for the detection of HPV-DNA before and after treatment and may be a useful method to incorporate in the HPV testing guidelines.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Humans , Mouth Neoplasms/diagnosis , Mouth Neoplasms/pathology , Mouth Neoplasms/therapy , Oropharyngeal Neoplasms/diagnosis , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/therapy , Oropharynx , Papillomavirus Infections/diagnosis , Sensitivity and SpecificityABSTRACT
Liver diseases are major causes of morbidity and mortality. Dental pulp pluripotent-like stem cells (DPPSCs) are of a considerable promise in tissue engineering and regenerative medicine as a new source of tissue-specific cells; therefore, this study is aimed at demonstrating their ability to generate functional hepatocyte-like cells in vitro. Cells were differentiated on a collagen scaffold in serum-free media supplemented with growth factors and cytokines to recapitulate liver development. At day 5, the differentiated DPPSC cells expressed the endodermal markers FOXA1 and FOXA2. Then, the cells were derived into the hepatic lineage generating hepatocyte-like cells. In addition to the associated morphological changes, the cells expressed the hepatic genes HNF6 and AFP. The terminally differentiated hepatocyte-like cells expressed the liver functional proteins albumin and CYP3A4. In this study, we report an efficient serum-free protocol to differentiate DPPSCs into functional hepatocyte-like cells. Our approach promotes the use of DPPSCs as a new source of adult stem cells for prospective use in liver regenerative medicine.
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BACKGROUND: Bioactive chemical surface modifications improve the wettability and osseointegration properties of titanium implants in both animals and humans. The objective of this animal study was to investigate and compare the bioreactivity characteristics of titanium implants (BLT) pre-treated with a novel bone bioactive liquid (BBL) and the commercially available BLT-SLA active. METHODS: Forty BLT-SLA titanium implants were placed in in four foxhound dogs. Animals were divided into two groups (n = 20): test (BLT-SLA pre-treated with BBL) and control (BLT-SLA active) implants. The implants were inserted in the post extraction sockets. After 8 and 12 weeks, the animals were sacrificed, and mandibles were extracted, containing the implants and the surrounding soft and hard tissues. Bone-to-implant contact (BIC), inter-thread bone area percentage (ITBA), soft tissue, and crestal bone loss were evaluated by histology and histomorphometry. RESULTS: All animals were healthy with no implant loss or inflammation symptoms. All implants were clinically and histologically osseo-integrated. Relative to control groups, test implants demonstrated a significant 1.5- and 1.7-fold increase in BIC and ITBA values, respectively, at both assessment intervals. Crestal bone loss was also significantly reduced in the test group, as compared with controls, at week 8 in both the buccal crests (0.47 ± 0.32 vs 0.98 ± 0.51 mm, p < 0.05) and lingual crests (0.39* ± 0.3 vs. 0.89 ± 0.41 mm, p < 0.05). At week 12, a pronounced crestal bone loss improvement was observed in the test group (buccal, 0.41 ± 0.29 mm and lingual, 0.54 ± 0.23 mm). Tissue thickness showed comparable values at both the buccal and lingual regions and was significantly improved in the studied groups (0.82-0.92 mm vs. 33-48 mm in the control group). CONCLUSIONS: Relative to the commercially available BLT-SLA active implants, BLT-SLA pre-treated with BBL showed improved histological and histomorphometric characteristics indicating a reduced titanium surface roughness and improved wettability, promoting healing and soft and hard tissue regeneration at the implant site.
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The objective of our study was to evaluate the association between acute periprosthetic joint infection (APJI) and radiographic measurement of soft-tissue thickness in elective total hip replacement surgery. A case-control study was conducted to compare the soft-tissue thickness radiographic measurement (SRM) at the hip in patients diagnosed with APJI based on Tsukayama et al. (2003) criteria after total hip replacement with patients that were not infected, at a single institution from 2013 to 2019. To minimize selection bias, each case was matched with two controls using the following methodology: patients of the same sex, with an age variation of ± 5 years, and nearest in surgery date to the cases were selected. All postoperative radiographs were performed in the first 24â¯h after total hip arthroplasty (THA) surgery as it is protocolized in our institution. Soft-tissue thickness radiographic measurement was defined as the distance from the tip of the greater trochanter to the skin following a perpendicular line to the femoral diaphysis in postoperative anteroposterior hip radiographs. In total, 78 patients were included (26 cases and 52 controls). The SRM median of the cases was 76.19â¯mm (SD: 26.518) and 53.5â¯mm (SD: 20.47) in controls. A multivariate logistic regression model showed an independent association between APJI and SRM (odds ratio (OR)⯠= â¯1.033, 95â¯% confidence interval (CI) 1.007-1.059, p = 0 .012). Patients with an SRM greater than 60â¯mm had a 7-fold increase in the odds of APJI (OR⯠= â¯7.295, 95â¯% CI⯠= â¯2.364-22.511, p < 0 .001). The results of our study suggest an association between large SRM at the hip and the risk of APJI in patients with primary total hip arthroplasty. SRM may be a helpful and easy tool for evaluating the risk of APJI before elective primary total hip replacement surgery.
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We present the open-source python package DockOnSurf which automates the generation and optimization of low-energy adsorption configurations of molecules on extended surfaces and nanoparticles. DockOnSurf is especially geared toward handling polyfunctional flexible adsorbates. The use of this high-throughput workflow allows us to carry out the screening of adsorbate-surface configurations in a systematic, customizable, and traceable way, while keeping the focus on the chemically relevant structures. The screening strategy consists in splitting the exploration of the adsorbate-surface configurational space into chemically meaningful domains, that is, by choosing among different conformers to adsorb, surface adsorption sites, adsorbate anchoring points, and orientations and allowing dissociation of (acidic) protons. We demonstrate the performance of the main features based on varying examples, ranging from CO adsorption on a gold nanoparticle to sorbitol adsorption on hematite. Through the use of the presented program, we aim to foster efficiency, traceability, and ease of use in research within tribology, catalysis, nanoscience, and surface science in general.
Subject(s)
Gold , Metal Nanoparticles , Adsorption , High-Throughput Screening Assays , Surface PropertiesABSTRACT
To accelerate the conversion to more sustainable lubricants, there is a need for an improved understanding of the adsorption at the solid/liquid interface. As a first step, the density functional theory computed adsorption energies can be used to screen the ability of additives to cover a surface. Analogously to what has been found in catalysis with the universal scaling relations, we investigate here if a general universal ranking of additives can be found, independently of the surface considered. We divided our set of 25 diverse representative molecules into aprotic and protic molecules. We compared their adsorption over alumina and hematite, which are models of surface oxidized aluminum and steel, respectively. The adsorption energy ranking of our set is not strongly affected by alumina hydration. In contrast, adsorption on hematite is more strongly affected by hydration since all exposed Fe Lewis acid sites are converted into hydroxylated Brønsted basic sites. However, the ranking obtained on hydrated hematite is close to the one obtained on dry alumina, paving the road to a fast screening of additives. In our library, protic molecules are more strongly adsorbed than non-protic molecules. In particular, methyl and dimethyl phosphates are the most strongly adsorbed ones, followed by N-methyldiethanolamine, succinimide, and ethanoic acid. Additives combining these functional groups are expected to strongly adsorb at the solid/liquid interface and, therefore, likely to be relevant components of lubricant formulations.
ABSTRACT
BACKGROUND: Oral premalignant lesions (OPML) are frequently extensive and multifocal leading high morbidity for patients. Although oral squamous carcinoma (OSCC) in non-smoker patients is increasing, little is known about OPML and the carcinogenesis process in these patients. The aims of the study were to insight and compare the clinicopathological and molecular characteristics of OPML of non-smoker and smoker patients from which one or multiple OSCC have developed. METHODS: Eighty-one patients showing extensive and/or multifocal OPML were included in the survey. HPV and EBV were investigated by PCR and in situ hybridization respectively. Cytogenetic studies were performed by microarray in sequential progressive 30 lesions; p53 expression was investigated by immunohistochemistry. RESULTS: The patients were 41 males and 40 females, ages ranging from 32 to 93 years (median 64); 43 (53%) were smokers. Non-smokers were more frequently female with a median age of 68, whereas smokers were men with a median age of 60 (P = 0.005). HPV and EBV were negative in all cases. The most consistent and earliest cytogenetic alterations in both non-smokers and smokers were loss of heterozygosity (LOH) and losses of locus harboring tumor suppressor genes. Progression to high-grade dysplasia and OSCC showed progressive addition of LOH, tumor suppressor losses, and oncogenic gains. CONCLUSION: Non-smoker patients are mostly elderly female and show oral carcinogenic pathways and outcomes similar to smoker patients.
Subject(s)
Mouth Neoplasms , Precancerous Conditions , Adult , Aged , Aged, 80 and over , Carcinogenesis/genetics , Female , Humans , Male , Middle Aged , Mouth Neoplasms/genetics , Non-Smokers , Precancerous Conditions/genetics , SmokersABSTRACT
The scope of this article is to present an overview of the Density Functional based Tight Binding (DFTB) method and its applications. The paper introduces the basics of DFTB and its standard formulation up to second order. It also addresses methodological developments such as third order expansion, inclusion of non-covalent interactions, schemes to solve the self-interaction error, implementation of long-range short-range separation, treatment of excited states via the time-dependent DFTB scheme, inclusion of DFTB in hybrid high-level/low level schemes (DFT/DFTB or DFTB/MM), fragment decomposition of large systems, large scale potential energy landscape exploration with molecular dynamics in ground or excited states, non-adiabatic dynamics. A number of applications are reviewed, focusing on -(i)- the variety of systems that have been studied such as small molecules, large molecules and biomolecules, bare orfunctionalized clusters, supported or embedded systems, and -(ii)- properties and processes, such as vibrational spectroscopy, collisions, fragmentation, thermodynamics or non-adiabatic dynamics. Finally outlines and perspectives are given.
ABSTRACT
Nasal amputation and nasomaxillary defects, need to reconstruct the internal lining, osteochondral structure, and external coating of the nose. Authors report a 70-year-old male and a 65-year-old female treated for nasomaxillary defects (Brown JS, Shaw RJ. The Lancet Oncology 2010;11:1001-1008) due to squamous cell carcinoma (SCC) where the tip of the nose was preserved. A new custom design of the radial forearm free flap (RFFF) consisting on a subcutaneous tissue (SCT) component, a skin paddle for the internal nasal vault lining, and a skin paddle for the external nasal skin coating was raised to treat both total thickness nasal defects. The dimension of each skin paddle corresponds to the defect measurements. The skin incisions of the custom design correspond to those of a conventional RFFF. The SCT component was harvested in a subcutaneous plane continuously with the skin island for the internal nasal lining which is drawn on the ulnar skin of the forearm. The component for the external nasal coating was drawn on the radial skin area of the flap. No postoperative complications and a satisfactory outcome was reported after 1 year of follow-up. This new custom design of the RFFF is described for reconstruction of nasomaxillary defects when the tip of the nose is preserved.