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1.
J Dent ; : 105070, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740251

RESUMO

OBJECTIVES: The objective of this study was to assess whether zinc-doped fluorapatite (ZnFA) could serve as an effective antimicrobial dental bone filler for bone regeneration compared to autografts. METHODS: FA and 2% zinc-doped FA (2ZnFA) were synthesized and characterized in-house. Compressed and sintered FA and 2ZnFA disks were incubated with bacteria to assess antimicrobial properties. Adipose-derived stem cells were cultured on these discs to evaluate the surfaces' ability to support cell growth and promote osteogenic differentiation. Surfaces exhibiting the highest expressions of the bone markers osteopontin and osteocalcin were selected for an in vivo study in a rat mandibular defect model. Twenty rats were divided into 5 groups, equally, and a 5mm surgical defect of the jaw was left untreated or filled with 2ZnFA, FA, autograft, or demineralized bone matrix (DBM). At 12 weeks, the defects and surrounding tissues were harvested and subjected to microCT and histological evaluations. RESULTS: Standard techniques such as FTIR, ICP-MS, fluoride probe, and XRD revealed the sintered FA and ZnFA's chemical compositions and structures. Bacterial studies revealed no significant differences in surface bacterial adhesion properties between FA and 2ZnFA, but significantly fewer bacterial loads than control titanium discs (p<0.05). Cell culture data confirmed that both surfaces could support cell growth and promote the osteogenic differentiation of stem cells. MicroCT analysis confirmed statistical similarities in bone regeneration within FA, 2ZnFA, and autograft groups. CONCLUSION: The data suggests that both FA and 2ZnFA could serve as alternatives to autograft materials, which are the current gold standard. Moreover, these bone fillers outperformed DBM, an allograft material commonly used as a dental bone void filler. CLINICAL SIGNIFICANCE: The use of FA or 2ZnFA for treating mandibular defects led to bone regeneration statistically similar to autograft repair and significantly outperformed the widely used dental bone filler, DBM. Additional translational research may confirm FA-based materials as superior substitutes for existing synthetic bone fillers, ultimately enhancing patient outcomes.

2.
Plast Reconstr Surg ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652817

RESUMO

BACKGROUND: Partial-thickness skin wounds are some of the most painful injuries due to large areas of exposed nerve endings. These injuries often require systemic opioid treatments to manage pain adequately. However, in 2021 alone, the CDC reported nearly 17,000 prescription opioid-related deaths in the USA, highlighting the ongoing need for non-opioid treatment strategies. In this manuscript, we developed a novel single-application ropivacaine-eluting primary wound dressing that could provide sustained ropivacaine delivery to partial-thickness wounds and assessed its in vivo feasibility for prolonged non-opioid analgesia. METHODS: Sustained release of ropivacaine from a poly(lactide-co-e-caprolactone) matrix was first optimized in vitro using dissolution testing and a Box Behnken design of experiments. The optimized dressing was then tested against a clinical control silicone dressing in a porcine partial-thickness wound study to assess analgesic effect, pharmacokinetics, and wound healing. RESULTS: The ropivacaine-eluting dressing showed a moderate analgesic effect in vivo, where normalized single pinprick scores significantly improved pain over the testing period (4-168h) (control vs treatment: 232±25% vs 145±16%, p<0.0003). Ropivacaine blood plasma levels peaked at 8 hours post-treatment, with a maximum concentration of 246 ± 74 ng/mL. No significant differences in wound healing were found when compared to control. CONCLUSION: The ropivacaine-loaded poly(lactide-co-e-caprolactone)-based wound dressing provided sustained delivery of ropivacaine to partial-thickness skin wounds and enhanced analgesic effect compared to a clinical standard control dressing.

3.
PLoS One ; 18(3): e0281911, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36881592

RESUMO

The objective of this study was to determine if locally delivered FK506 could prevent allogeneic nerve graft rejection long enough to allow axon regeneration to pass through the nerve graft. An 8mm mouse sciatic nerve gap injury repaired with a nerve allograft was used to assess the effectiveness of local FK506 immunosuppressive therapy. FK506-loaded poly(lactide-co-caprolactone) nerve conduits were used to provide sustained local FK506 delivery to nerve allografts. Continuous and temporary systemic FK506 therapy to nerve allografts, and autograft repair were used as control groups. Serial assessment of inflammatory cell and CD4+ cell infiltration into the nerve graft tissue was performed to characterize the immune response over time. Nerve regeneration and functional recovery was serially assessed by nerve histomorphometry, gastrocnemius muscle mass recovery, and the ladder rung skilled locomotion assay. At the end of the study, week 16, all the groups had similar levels of inflammatory cell infiltration. The local FK506 and continuous systemic FK506 groups had similar levels of CD4+ cell infiltration, however, it was significantly greater than the autograft control. In terms of nerve histmorphometry, the local FK506 and continunous systemic FK506 groups had similar amounts of myelinated axons, although they were significantly lower than the autograft and temporary systemic FK506 group. The autograft had significantly greater muscle mass recovery than all the other groups. In the ladder rung assay, the autograft, local FK506, and continuous systemic FK506 had similar levels of skilled locomotion performance, whereas the temporary systemic FK506 group had significanty better performance than all the other groups. The results of this study suggest that local delivery of FK506 can provide comparable immunosuppression and nerve regeneration outcomes as systemically delivered FK506.


Assuntos
Axônios , Rejeição de Enxerto , Regeneração Nervosa , Tacrolimo , Animais , Camundongos , Aloenxertos , Tacrolimo/farmacologia , Sistemas de Liberação de Medicamentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle
4.
Head Neck ; 44(7): 1690-1701, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35535730

RESUMO

BACKGROUND: Patients with head and neck cancer were treated with either 70 Gy in 35 fractions (Arm A) or 66 Gy in 30 fractions (Arm B). MATERIALS AND METHODS: Total 168 patients of carcinoma oropharynx, larynx, and hypopharynx treated with radical chemoradiation in two Arm A versus B (65 vs. 103 patients). RESULTS: With a median follow-up of 16 months (0-67), 2 year disease-free survival (DFS) and overall survival (OS) was 56.3% versus 62.1% (p = 0.64) and 44.5% versus 53.0% (p = 0.51) in Arm A versus B. Total 22 (33.8%) versus 28 (27.2%) failed locoregionally. Majority of failures were infield for both primary (17 vs. 23 cases) and nodes (13 vs. 12) in Arm A versus B. Ten (71.4%) vs. 10 (76.9%) had nodal failure in index nodal level only. CONCLUSION: Commonly seen failure in head-neck radical chemoradiation is within infield high-risk volume, nodal failure being most common in index nodal level.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Radioterapia de Intensidade Modulada , Quimiorradioterapia/métodos , Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Pescoço , Radioterapia de Intensidade Modulada/métodos
5.
PLoS One ; 17(5): e0268977, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35617338

RESUMO

AIMS: While the benefits of direct skeletal attachment of artificial limbs are well recognized, device failure due to infection and insufficient osseointegration remain obstacles to obtaining consistently successful outcomes. Currently, the potential for device failure is assessed by subjective pain, clinical function scores, radiographic evidence of bone atrophy, and the presence of radiolucent lines at the bone-implant interface, and subjective pain and function scores. Our hypothesis is that measurable biological indices might add another objective means to assess trends toward bone and stomal healing. This longitudinal cohort study was undertaken to identify potential serological biomarkers suggestive of bone remodeling and the presence of stomal tissue inflammation. METHODS: Ten unilateral transfemoral amputee veterans, who were implanted with a percutaneous osseointegrated (OI) skeletal limb docking system, were recruited to participate in this IRB-approved study. Venous blood samples were obtained from before the Stage 1 Surgery up to 1 year following the Stage 2 Surgery. Whole-blood RNA was extracted, sequenced, mapped, and analyzed. Of the significant differentially expressed (DEGs) genes (p<0.05) identified, four genes of interest (IL12B, IL33, COL2A1, and SOST) were validated using qPCR. Enrichment analysis was performed to identify significant (p<0.01) Gene Ontology (GO) terms. RESULTS: Most differentially expressed genes were only detected at PoS1 immediately after the first surgery. Of the significant genes identified, IL12B and IL33 were related to inflammation, and COL2A1 and SOST were associated with bone remodeling. These four genes were identified with greater than 20 log fold-change. CONCLUSION: Whole-blood RNA-seq data from 10 patients who previously underwent percutaneous osseointegrated lower limb implantation revealed four genes of interest that are known to be involved in inflammation or bone remodeling. If verified in future studies, these genes may serve as markers for predicting optimal bone remodeling and stomal tissue healing following OI device implantation.


Assuntos
Membros Artificiais , Amputação Cirúrgica , Humanos , Inflamação/genética , Interleucina-33 , Estudos Longitudinais , Osseointegração/genética , Dor , Análise de Sequência de RNA
6.
Plast Reconstr Surg ; 149(2): 306-313, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34898525

RESUMO

BACKGROUND: Decreasing length of stay benefits patients and hospital systems alike. This should be accomplished safely without negatively impacting patient outcomes. The authors hypothesize that in the United States, the average length of stay for patients undergoing microsurgical breast reconstruction has decreased since 2012 without a concurrent increase in complication and readmission rates. METHODS: The authors identified female patients who underwent microvascular breast reconstruction (CPT 19364) from the 2012 to 2018 National Surgical Quality Improvement Program database. Trends in complication and readmission rates and length of stay were examined over 7 years. Multivariable logistic regression models and Mann-Kendall trend tests were used to evaluate associations between length of stay and complication and readmission rates. RESULTS: A total of 10,465 cases were identified. The number of autologous microvascular breast reconstruction procedures performed increased annually between 2012 and 2018. Length of stay decreased significantly from 2012 to 2018 (from 4.47 days to 3.90 days) (p < 0.01). Minor and major complication rates remained constant, although major complications showed a decreasing trend (from 27 percent to 21 percent) (p = 0.07). Thirty-day readmission, surgical-site infection, and wound dehiscence rates remained consistent over the study period, whereas rates of blood transfusion or bleeding decreased (p = 0.02). CONCLUSIONS: Using a national sample from 2012 to 2018, the authors observed a significant decrease in length of stay for patients undergoing microvascular breast reconstruction without a concurrent increase in complication and readmission rates. Current efforts to reduce length of stay have been successful without increasing complication or readmission rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.


Assuntos
Tempo de Internação/tendências , Mamoplastia/métodos , Microvasos/cirurgia , Adulto , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Melhoria de Qualidade , Estados Unidos , Procedimentos Cirúrgicos Vasculares/métodos
7.
J Mech Behav Biomed Mater ; 123: 104681, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34362677

RESUMO

A previously reported microvascular coupler was shown to effectively create vascular anastomoses, but was too large for practical clinical use. To safely reduce coupler size, certain failure modes needed to be better understood. The coupler functions, in part, by compressing the vessel wall between two concentric rings, creating a friction fit that anchors the device to the vessel. This work investigates the relationship between vessel wall compression and resulting friction fit strength to ensure reducing coupler size will not unduly increase the risk that this friction fit might fail. Vascular walls were compressed to a specified strain and the tensile force required to overcome the resulting friction was measured. Experiments were conducted with various vessel types (Porcine common carotid artery, splenic artery, and jugular vein), across a range of compressive strains (55-95%), and by using either PEEK or HDPE to compress the vessel. Tensile force was increased at a rate of 5 g/min or held constant for 24 h. For experiments with incrementally increasing force, the force at failure varied with compressive strain via a power function. At 70% compression, PEEK produced 4.6 times stronger friction fits than HDPE, and common carotid arteries and splenic arteries produced 1.8 and 1.3 times stronger fits than jugular veins respectively. For experiments where tensile force was applied for 24 h, much lower forces were required to overcome friction. These results were compared to friction fit failure in a coupler prototype and it was found that the prototypes failed at just 30% of the force required to cause vessel slip under the other test conditions. These results were used to develop a model that predicts the probability of device failure via vessel slipping (one design, smaller than previously reported, was estimated to fail at maximum in vivo axial stress once in 500 anastomoses, a potentially safe level of risk).


Assuntos
Veias Jugulares , Fenômenos Mecânicos , Anastomose Cirúrgica , Animais , Fricção , Pressão , Suínos
9.
Am J Otolaryngol ; 41(6): 102726, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32979668

RESUMO

PURPOSE: To evaluate the impact of surgeon volume on total thyroidectomy complications and outcomes among otolaryngologists. MATERIALS AND METHODS: This state-wide, multi-hospital retrospective review identified patients who underwent total thyroidectomy (TT) (ICD9-06.4) through the Statewide Planning and Research Cooperative System (SPARCS) between 1995 and 2015. Surgeons were categorized into high (>100), medium (10-99), and low (<10) volume groups and differences in complication rates were analyzed. Statistical analysis employed Spearman's rank correlation, Kruskal-Wallis testing, and chi-squared testing. RESULTS: 32,133 TT performed by 1032 otolaryngologists were identified. Overall complication rate in our cohort was 9.83% (CI: 9.48-10.18). The most common complication identified overall was hypocalcemia occurring in 3.85% of cases. Surgeons in the high volume group had a complication rate of 9.6%, compared to 10.0% and 11.6% in the medium and low volume groups. This represents a moderate, but statistically significant difference (rho: -0.4, p < 0.0001; KW p ≤0.0001). When looking at individual complications, temporary tracheostomy rate was higher in the low volume group (5.1%, p = 0.001). Other variables such as advanced age, sex, non-white race, or thyroid malignancy were not predictors of increased complication rates for TT. CONCLUSIONS: Otolaryngologists who perform a high volume of total thyroidectomy were found to have overall less perioperative complications than those with less volume. In particular, the risk of temporary tracheostomy is higher among low volume surgeons. These findings are consistent with previous studies of the effect of thyroidectomy volume on surgical complications.


Assuntos
Otorrinolaringologistas/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Tireoidectomia/efeitos adversos , Tireoidectomia/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hipocalcemia/epidemiologia , Hipocalcemia/etiologia , Lactente , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Muscle Nerve ; 60(5): 613-620, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31397908

RESUMO

INTRODUCTION: The objective of this study is to assess the efficacy of local tacrolimus (FK506) delivery to improve outcomes in the setting of nerve transection injury. METHODS: FK506 embedded poly(lactide-co-caprolactone) films capable of extended, localized release of FK506 were developed. FK506 rate of release testing and bioactivity assay was performed. Mouse sciatic nerve transection and direct repair model was used to evaluate the effect extended, local delivery of FK506 had on nerve regeneration outcomes. RESULTS: Linear release of FK506 was observed for 30 days and released FK506 matched control levels of neurite extension in the dorsal root ganglion assay. Groups treated with local FK506 had greater gastrocnemius muscle weight, foot electromyogram, and number of axons distal of the repair site than non-FK506 groups. DISCUSSION: Results of this study indicate that extended, localized delivery of FK506 to nerve injuries can improve nerve regeneration outcomes in a mouse sciatic nerve transection and repair.


Assuntos
Imunossupressores/farmacologia , Denervação Muscular , Músculo Esquelético/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Nervo Isquiático/lesões , Tacrolimo/farmacologia , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Preparações de Ação Retardada , Eletromiografia , Gânglios Espinais/efeitos dos fármacos , Imunossupressores/administração & dosagem , Camundongos , Músculo Esquelético/patologia , Neuritos/efeitos dos fármacos , Neuritos/patologia , Procedimentos Neurocirúrgicos , Tamanho do Órgão , Traumatismos dos Nervos Periféricos , Poliésteres , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/cirurgia , Tacrolimo/administração & dosagem
11.
J Orthop Res ; 37(12): 2645-2654, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31317568

RESUMO

Percutaneous osseointegrated (OI) prostheses (POPs) are used to skeletally attach artificial limbs in amputees. While any permanent percutaneous interface is at risk of becoming infected by the resident microbiota colonizing the stoma, most of these patients remain infection-free. Avoidance of infection likely depends upon a mechanically and/or biologically stable skin-to-implant interface. The ultimate question remains, "why do some stomata become infected while others do not?" The answer might be found in the dynamic bacterial communities of the patient and within the stomal site itself. This study is an appendix to the first Food and Drug Administration approved prospective early feasibility study of OI prosthetic docking, in which, 10 transfemoral amputees were implanted with a unique POP device. In this analytical, longitudinal cohort study, each patient's skin and stomal microbiota were analyzed from the initial surgery to 1 year following the second-stage surgery. During each follow-up visit, three swab samples-stomal, device thigh skin and contralateral thigh skin-were obtained. DNA was extracted, and bacterial 16S ribosomal RNA (rRNA) genes were amplified and sequenced to profile microbial communities. The stomal microbiota were distinct from the microbiota on the adjacent thigh skin and the skin of the contralateral thigh, with a significantly increased abundance of Staphylococcus aureus within the stoma. Early on stomal microbiota were characterized by high diversity and high relative abundance of obligate anaerobes. Over time, the stomal microbiota shifted and stabilized in communities of lower diversity dominated by Streptococcus, Corynebacterium, and/or Staphylococcus spp. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2645-2654, 2019.


Assuntos
Microbioma Gastrointestinal , Osseointegração , Implantação de Prótese , Pele/microbiologia , Estômago/microbiologia , Humanos , Estudos Longitudinais , Estudos Prospectivos , Estomas Cirúrgicos/microbiologia
12.
Laryngoscope ; 129(5): 1067-1070, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30604483

RESUMO

OBJECTIVES/HYPOTHESIS: Optimal treatment for patients with vocal fold polyps (VFPs) remains controversial. We compared the short-term outcomes of treatment with voice therapy alone (VT), surgery alone (SUR)m or voice therapy and surgery (VTS). STUDY DESIGN: Retrospective case series. METHODS: A retrospective study was performed for patients diagnosed with VFP (International Classification of Diseases, Ninth Revision code 478.4 and Tenth Revision code J38.1) between January 2010 and April 2016. Inclusion criteria were age greater than 18 years and charted evidence of treatment with voice therapy, surgery, or both. Exclusion criteria were history of laryngeal cancer or radiation above the clavicles. Outcomes measured included chart records of lesion absence, persistence or recurrence, and differences between pretreatment and post-treatment Voice Handicap Index-10 and GRBAS (G/grade, R/roughness, B/breathiness, A/asthenia, S/strain) scores. RESULTS: One hundred twenty patients with VFPs were identified (SUR = 23, 19.2%, VT = 29, 24.2%, VTS = 68, 56.7%). Mean follow-up was 5.5 months. There were no recurrences in 115 patients (95.8%). There was significant improvement from pre- to post-treatment VHI-10 scores in the SUR (mean improvement = 12.5, standard deviation [SD] = 12.7) and VTS (mean improvement = 12.3, SD = 10.3) groups compared to the VT (mean improvement = 2.84, SD = 11.9) group (P = .009). Pre- and post-treatment GRBAS scores did not significantly change in any group. CONCLUSIONS: When using patient-reported outcomes measures, patients with VFPs receive the greatest short-term gains from treatment paradigms involving surgery or a combination of surgery and voice therapy. Voice therapy alone did not result in significant short-term changes. Perceptual voice characteristics did not change significantly for any group. Further research on long-term treatment outcomes for patients with VFPs is needed. LEVEL OF EVIDENCE: 3 Laryngoscope, 129:1067-1070, 2019.


Assuntos
Doenças da Laringe/reabilitação , Doenças da Laringe/cirurgia , Pólipos/cirurgia , Prega Vocal , Treinamento da Voz , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
13.
Am J Otolaryngol ; 40(2): 143-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30661890

RESUMO

OBJECTIVE: Syphilis is a sexually transmitted infection with various presentations. Although, oropharyngeal manifestations are known to occur, the purpose of this study is to present the first case series in which the lesions were initially mistaken for human-papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). METHODS: A multi-institutional retrospective review. RESULTS: Six cases of oropharyngeal syphilis were initially thought to be secondary to OPSCC due to presentation. Symptoms were vague and exam findings consisted of either a tonsillar or base of tongue mass, or lymphadenopathy. Biopsies were negative for OPSCC. Further workup diagnosed syphilis, with resolution of symptoms and lesions after antibiotic treatment. CONCLUSIONS: Head and neck manifestations of syphilis have been reported in the literature. However, this is the first series reporting on oropharyngeal syphilis masquerading as HPV-related OPSCC. Ultimately, otolaryngologists must maintain a high suspicion for syphilis in order to ensure prompt diagnosis and treatment.


Assuntos
Orofaringe , Sífilis/diagnóstico , Adulto , Idoso , Carcinoma de Células Escamosas , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Penicilinas/administração & dosagem , Estudos Retrospectivos , Sífilis/tratamento farmacológico , Sífilis/microbiologia , Sífilis/patologia , Sorodiagnóstico da Sífilis , Tomografia Computadorizada por Raios X , Treponema pallidum/isolamento & purificação
14.
Chemphyschem ; 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30270472

RESUMO

In this work we provide high level ab initio treatments of the structures, vibrational frequencies, and electronic energies of the HCN monomer and dimer systems along with several isotopologues. The plethora of information related to this system within the literature is summarized and serves as a basis for comparison with the results of this paper. The geometry of the dimer and monomer are reported at the all electroncoupled-cluster singles, doubles, and perturbative triples level of theory [AE-CCSD(T)] with the correlation consistent quadruple-zeta quality basis sets with extra core functions (cc-pCVQZ) from Dunning. The theoretical geometries and electronic structures are further analyzed through the use of the Natural Bond Orbital (NBO) method and Natural Resonance Theory (NRT). At the AE-CCSD(T)/cc-pCVQZ level of theory, the full cubic with semi-diagonal quartic force field for nine dimer and four monomer isotopologues (the parent isotopologue along with 15 N, 13 C, and D derivatives) were obtained to treat the anharmonicity of the vibrations via second order vibrational perturbation theory (VPT2). Lastly, the enthalpy change associated with the formation of the dimer from two monomer units was determined using the focal point analysis. Computations including coupled-cluster through perturbative quadruples as well as basis sets up to six-zeta quality, including core functions (cc-pCVXZ, X=D,T,Q,5,6) were used to extrapolate to the AE-CCSDT(Q)/CBS energy associated with this hydrogen-bond forming process. After appending anharmonic zero-point vibrational, relativistic, and diagonal Born-Oppenheimer corrections, we report a value of -3.93 kcal mol-1 for the enthalpy of formation. To our knowledge, each set of results (geometries, vibrational frequencies, and energetics) reported in this study represents the highest-level and most reliable theoretical predictions reported for this system.

15.
J Chem Phys ; 149(6): 064108, 2018 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30111157

RESUMO

We use a direct product basis, basis vectors computed by evaluating matrix-vector products, and rank reduction to calculate vibrational energy levels of uracil and naphthalene, with 12 and 18 atoms, respectively. A matrix representing the Hamiltonian in the direct product basis and vectors with as many components as there are direct product basis functions are neither calculated nor stored. We also introduce an improvement of the Hierarchical Intertwined Reduced-Rank Block Power Method (HI-RRBPM), proposed previously in Thomas and Carrington, Jr. [J. Chem. Phys. 146, 204110 (2017)]. It decreases the memory cost of the HI-RRBPM and enables one to compute vibrational spectra of molecules with over a dozen atoms with a typical desktop computer.

16.
J Chem Theory Comput ; 14(3): 1333-1350, 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29474074

RESUMO

Geometric energy derivatives which rely on core-corrected focal-point energies extrapolated to the complete basis set (CBS) limit of coupled cluster theory with iterative and noniterative quadruple excitations, CCSDTQ and CCSDT(Q), are used as elements of molecular gradients and, in the case of CCSDT(Q), expansion coefficients of an anharmonic force field. These gradients are used to determine the CCSDTQ/CBS and CCSDT(Q)/CBS equilibrium structure of the S0 ground state of H2CO where excellent agreement is observed with previous work and experimentally derived results. A fourth-order expansion about this CCSDT(Q)/CBS reference geometry using the same level of theory produces an exceptional level of agreement to spectroscopically observed vibrational band origins with a MAE of 0.57 cm-1. Second-order vibrational perturbation theory (VPT2) and variational discrete variable representation (DVR) results are contrasted and discussed. Vibration-rotation, anharmonicity, and centrifugal distortion constants from the VPT2 analysis are reported and compared to previous work. Additionally, an initial application of a sum-over-states fourth-order vibrational perturbation theory (VPT4) formalism is employed herein, utilizing quintic and sextic derivatives obtained with a recursive algorithmic approach for response theory.

17.
J Chem Phys ; 148(1): 014305, 2018 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-29306279

RESUMO

The methylene amidogen radical (H2CN) plays a role in high-energy material combustion and extraterresterial atmospheres. Recent theoretical work has struggled to match experimental assignments for its CN and antisymmetric CH2 stretching frequencies (ν2 and ν5), which were reported to occur at 1725 and 3103 cm-1. Herein, we compute the vibrational energy levels of this molecule by extrapolating quadruples-level coupled-cluster theory to the complete basis limit and adding corrections for vibrational anharmonicity. This level of theory predicts that ν2 and ν5 should occur at 1646 and 2892 cm-1, at odds with the experimental assignments. To investigate the possibility of defects in our theoretical treatment, we analyze the sensitivity of our approach to each of its contributing approximations. Our analysis suggests that the observed deviation from experiment is too large to be explained as an accumulation of errors, leading us to conclude that these transitions were misassigned. To help resolve this discrepancy, we investigate possible byproducts of the H + HCN reaction, which was the source of H2CN in the original experiment. In particular, we predict vibrational spectra for cis-HCNH, trans-HCNH, and H2CNH using high-level coupled-cluster computations. Based on these results, we reassign the transition at 1725 cm-1 to ν3 of trans-HCNH, yielding excellent agreement. Supporting this identification, we assign a known contaminant peak at 886 cm-1 to ν5 of the same conformer. Our computations suggest that the peak observed at 3103 cm-1, however, does not belong to any of the aforementioned species. To facilitate further investigation, we use structure and bonding arguments to narrow the range of possible candidates. These arguments lead us to tentatively put forth formaldazine [(H2CN)2] as a suggestion for further study, which we support with additional computations.

18.
J Neural Eng ; 14(6): 066011, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28829045

RESUMO

OBJECTIVE: This paper describes the design of a novel drug delivery apparatus integrated with a poly lactic-co-glycolic acid (PLGA) based nerve guide conduit for controlled local delivery of nerve growth factor (NGF) and application in peripheral nerve gap injury. APPROACH: An NGF dosage curve was acquired to determine the minimum in vitro concentration for optimal neurite outgrowth of dorsal root ganglion (DRG) cells; PLGA based drug delivery devices were then designed and tested in vitro and in vivo across 15 mm rat sciatic nerve gap injury model. MAIN RESULTS: The drug delivery nerve guide was able to release NGF for 28 d at concentrations (0.1-10 ng ml-1) that were shown to enhance DRG neurite growth. Furthermore, the released NGF was bioactive and able to enhance DRG neurite growth. Following these tests, optimized NGF-releasing nerve conduits were implanted across 15 mm sciatic nerve gaps in a rat model, where they demonstrated significant myelination and muscle innervation in vivo as compared to empty nerve conduits (p < 0.05). This drug delivery nerve guide can release NGF for extended periods of time and enhance axon growth in vitro and in vivo and has the potential to improve nerve regeneration following a peripheral nerve injury. SIGNIFICANCE: This integrated drug delivering nerve guide simplifies the design process and provides increased versatility for releasing a variety of different growth factors. This innovative device has the potential for broad applicability and allows for easier customization to change the type of drugs and dosage of individual drugs without devising a completely new biomaterial-drug conjugate each time.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Ácido Láctico/administração & dosagem , Fator de Crescimento Neural/administração & dosagem , Regeneração Nervosa/fisiologia , Ácido Poliglicólico/administração & dosagem , Neuropatia Ciática/tratamento farmacológico , Animais , Embrião de Galinha , Relação Dose-Resposta a Droga , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/fisiologia , Bombas de Infusão Implantáveis , Masculino , Regeneração Nervosa/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley , Neuropatia Ciática/patologia
19.
Phys Chem Chem Phys ; 19(24): 15715-15723, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28590466

RESUMO

Interest in peroxy radicals derives from their central role in tropospheric and low-temperature combustion processes; however, their transient nature limits the scope of possible experimental characterization. As a result, theoretical methods (notably, coupled-cluster theory) have become indispensable in the reliable prediction of properties of such ephemeral open-shell systems. Herein, the X[combining tilde] and à state conformers of ethylperoxy radical (C2H5O2) have been structurally optimized at the CCSD(T)/ANO2 level of theory. Relative enthalpies at 0 K [including à ← X[combining tilde] transition origins (T0)] are reported, incorporating CCSD(T) electronic energies extrapolated to the complete basis set limit via the focal point approach. Higher-level computations, employing basis sets as large as cc-pV5Z and post-HF methods up to CCSDT(Q), prove essential in achieving predictions to within 10 cm-1 for experimental T0; we predict 7363 and 7583 cm-1 for the trans and gauche conformers, respectively. Furthermore, predictions of X[combining tilde] state fundamental transitions incorporating CCSD(T)/ANO0 anharmonic contributions are given. For each conformer, all 21 modes were characterized, improving upon the 16 modes reported in the experimental literature, and providing predictions for the 5 remaining modes.

20.
Am J Otolaryngol ; 38(4): 505-507, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28528729

RESUMO

BACKGROUND: Pleomorphic liposarcoma (PL) is an exceedingly rare tumor of the head and neck. This aggressive liposarcoma variant portends a poorer prognosis compared to more typical sarcomatous tumors. METHODS: Multi-institutional study including two cases of PL, the first case occurring in the post-auricular region and the second in the cheek with later recurrence within the parotid bed. RESULTS: Both patients were treated surgically with wide local excision. One patient required reoperation to obtain negative margins. The other patient underwent a total parotidectomy with neck dissection for recurrent intraparotid nodal disease. Both patients underwent adjuvant radiotherapy. No patient had evidence of recurrent disease with minimum one year follow-up. CONCLUSION: Although the literature is sparse on this disease, wide surgical extirpation with negative margins and adjuvant radiation is recommended. Increased reports of this pathology can be helpful in providing practitioners with experienced-based information that can aid in early detection and treatment. We present the first case series of PL of the head and neck in the literature.


Assuntos
Lipossarcoma/diagnóstico , Lipossarcoma/terapia , Neoplasias Parotídeas/diagnóstico , Neoplasias Parotídeas/terapia , Humanos , Masculino , Pessoa de Meia-Idade
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