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1.
Nature ; 574(7776): 108-111, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31534223

RESUMO

Light discrimination according to colour can confer survival advantages by guiding animals towards food and shelter and away from potentially harmful situations1,2. Such colour-dependent behaviour can be learned or innate. Data on innate colour preference in mammals remain controversial3 and there are limited data for simpler organisms4-7. Here we show that, when given a choice among blue, green and dim light, fruit flies exhibit an unexpectedly complex pattern of colour preference that changes according to the time of day. Flies show a strong preference for green in the early morning and late afternoon, a reduced green preference at midday and a robust avoidance of blue throughout the day. Genetic manipulations reveal that the peaks in green preference require rhodopsin-based visual photoreceptors and are controlled by the circadian clock. The midday reduction in green preference in favour of dim light depends on the transient receptor potential (TRP) channels dTRPA1 and Pyrexia, and is also timed by the clock. By contrast, avoidance of blue light is primarily mediated by multidendritic neurons, requires rhodopsin 7 and the TRP channel Painless, and is independent of the clock. Our findings show that several TRP channels are involved in colour-driven behaviour in Drosophila, and reveal distinct pathways of innate colour preference that coordinate the behavioural dynamics of flies in ambient light.


Assuntos
Relógios Circadianos/fisiologia , Relógios Circadianos/efeitos da radiação , Cor , Drosophila melanogaster/fisiologia , Drosophila melanogaster/efeitos da radiação , Luz , Canais de Potencial de Receptor Transitório/metabolismo , Animais , Antenas de Artrópodes/fisiologia , Antenas de Artrópodes/efeitos da radiação , Dendritos/fisiologia , Dendritos/efeitos da radiação , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Larva/fisiologia , Larva/efeitos da radiação , Luz/efeitos adversos , Masculino , Neurônios/fisiologia , Neurônios/efeitos da radiação , Rodopsinas Sensoriais/metabolismo , Fatores de Tempo , Visão Ocular/efeitos da radiação
2.
J Am Chem Soc ; 144(11): 4759-4763, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35262338

RESUMO

A water-soluble thermochromic molecular switch with spectrally resolved fluorescence in its two interconvertible states can be assembled in three synthetic steps by integrating a fluorescent coumarin chromophore, a hydrophilic oligo(ethylene glycol) chain, and a switchable oxazole heterocycle in the same covalent skeleton. Measurements of its two emissions in separate detection channels of a fluorescence microscope permit the noninvasive and ratiometric sensing of temperature at the micrometer level with millisecond response in aqueous solutions and within hydrogel matrices. The ratiometric optical output of this fluorescent molecular switch overcomes the limitations of single-wavelength fluorescent probes and enables noninvasive temperature mapping at length scales that are not accessible to conventional thermometers based on physical contact.


Assuntos
Corantes Fluorescentes , Água , Fluorescência , Espectrometria de Fluorescência , Temperatura , Termômetros
3.
Bioconjug Chem ; 31(5): 1497-1509, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32337973

RESUMO

We detail the preparation of highly fluorescent quantum dots (QDs), surface-engineered with multifunctional polymer ligands that are compact and readily compatible with strain-promoted click conjugation, and the use of these nanocrystals in immunofluorescence and in vivo imaging. The ligand design combines the benefits of mixed coordination (i.e., thiol and imidazole) with zwitterion motifs, yielding sterically-stabilized QDs that present a controllable number of azide groups, for easy conjugation to biomolecules via the selective click chemistry. The polymer coating was characterized using NMR spectroscopy to extract estimates of the diffusion coefficient, hydrodynamic size, and ligand density. The azide-functionalized QDs were conjugated to anti-tropomyosin receptor kinase B antibody (α-TrkB) or to the brain-derived neurotrophic factor (BDNF). These conjugates were highly effective for labeling the tropomyosin receptor kinase B (TrkB) in pyramidal neurons within cortical tissue and for monitoring the BDNF induced activation of TrkB signaling in live neuronal cells. Finally, the polymer-coated QDs were applied for in vivo imaging of Drosophila melanogaster embryos, where the QDs remained highly fluorescent and colloidally stable, with no measurable cytotoxicity. These materials would be of great use in various imaging applications, where a small size, ease of conjugation, and great colloidal stability for in vivo studies are needed.


Assuntos
Imunofluorescência , Corantes Fluorescentes/química , Imagem Óptica/métodos , Polímeros/química , Pontos Quânticos/química , Animais , Azidas/química , Linhagem Celular , Química Click , Drosophila melanogaster/embriologia , Imidazóis/química , Ligantes , Neurônios/citologia , Tamanho da Partícula , Transdução de Sinais , Compostos de Sulfidrila/química
4.
J Shoulder Elbow Surg ; 29(6): 1214-1222, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32113866

RESUMO

HYPOTHESIS: The purpose of this study was to correlate the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing (CAT) domains with commonly used legacy patient-reported outcome measures (PROMs) preoperatively in a population of patients presenting to a tertiary care orthopedic center for biceps and labral pathology. METHODS: Prospective data were collected on 175 patients scheduled to undergo isolated biceps tenodesis at a tertiary center. Enrollees completed legacy scores (Veterans RAND 12-Item Health Survey, Short Form 12, American Shoulder and Elbow Surgeons [ASES] Assessment Form, Single Assessment Numeric Evaluation, and Constant-Murley score) and PROMIS CAT questionnaires (Upper Extremity [UE], Pain Interference [PIF], and Depression). In addition, patients were asked to provide an assessment of the strength, function, and pain of the affected shoulder using a custom visual analog scale (VAS) questionnaire. Spearman rank correlations of the PROMIS CAT with legacy measures and the custom VAS were calculated. Floor and ceiling effects were assessed. RESULTS: The UE CAT yielded moderate correlations with the ASES score (r = 0.57) and the custom VAS strength score (r = 0.50-0.57). The PIF CAT demonstrated moderate correlations with the VAS pain score (r = 0.45) and high-moderate correlations with the ASES score, VR6D score, and UE CAT (r = 0.61-0.66). The Depression CAT demonstrated high-moderate correlations with the mental health legacy measures (r = -0.64 to -0.61). There was a significant relative floor effect for the Depression CAT at a score of 34.2 (19%). CONCLUSION: The PIF CAT was comparable to the ASES score, the current gold standard. Compared with legacy measures, both the UE CAT and PIF CAT are less burdensome and have few floor or ceiling effects. The PIF CAT may be a viable alternative to describe the physical and psychosocial impact of pain in biceps tenodesis patients.


Assuntos
Diagnóstico por Computador , Medidas de Resultados Relatados pelo Paciente , Tendinopatia/cirurgia , Tenodese , Extremidade Superior , Adulto , Artroscopia , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético , Medição da Dor , Estudos Prospectivos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Tendinopatia/etiologia , Resultado do Tratamento
5.
J Shoulder Elbow Surg ; 29(1): 50-57, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31439428

RESUMO

HYPOTHESIS: We hypothesized that players in the National Basketball Association (NBA) who sustained a shoulder destabilizing injury could return to play (RTP) successfully at a high rate regardless of treatment type. METHODS: We used publicly available data to identify and evaluate 50 players who sustained an in-season shoulder instability event (subluxation/dislocation) while playing in the NBA. Demographic variables, return to NBA gameplay, incidence of surgery, time to RTP, recurrent instability events, and player efficiency rating (PER) were collected. Overall RTP was determined, and players were compared by type of injury and mode of treatment. RESULTS: All players (50/50) returned to game play after sustaining a shoulder instability event. In those treated nonoperatively, athletes who sustained shoulder subluxations returned after an average of 3.6 weeks, compared with 7.6 weeks in those who sustained a shoulder dislocation (P = .037). Players who underwent operative management returned after an average of 19 weeks. Athletes treated operatively were found to have a longer time interval between a recurrent instability event (70 weeks vs. 28.5 weeks, P = .001). CONCLUSION: We found 100% rate of RTP after a shoulder instability event in an NBA athlete. Players who experience shoulder dislocations were found to miss more time before RTP and were more likely to undergo surgical intervention compared with those who experienced a subluxation. Surgical repair maintained a longer interval between recurrent instability. Future investigations should aim to evaluate outcomes based on surgical procedures and identify possible risk factors predictive of recurrent instability or failure to RTP.


Assuntos
Basquetebol/lesões , Tratamento Conservador , Instabilidade Articular/cirurgia , Volta ao Esporte , Luxação do Ombro/cirurgia , Lesões do Ombro/cirurgia , Adulto , Desempenho Atlético , Humanos , Instabilidade Articular/terapia , Masculino , Recidiva , Luxação do Ombro/terapia , Lesões do Ombro/terapia , Fatores de Tempo , Adulto Jovem
6.
Hum Mol Genet ; 24(14): 4006-23, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25882707

RESUMO

Despite significant progress in the genetics of autism spectrum disorder (ASD), how genetic mutations translate to the behavioral changes characteristic of ASD remains largely unknown. ASD affects 1-2% of children and adults, and is characterized by deficits in verbal and non-verbal communication, and social interactions, as well as the presence of repetitive behaviors and/or stereotyped interests. ASD is clinically and etiologically heterogeneous, with a strong genetic component. Here, we present functional data from syngap1 and shank3 zebrafish loss-of-function models of ASD. SYNGAP1, a synaptic Ras GTPase activating protein, and SHANK3, a synaptic scaffolding protein, were chosen because of mounting evidence that haploinsufficiency in these genes is highly penetrant for ASD and intellectual disability (ID). Orthologs of both SYNGAP1 and SHANK3 are duplicated in the zebrafish genome and we find that all four transcripts (syngap1a, syngap1b, shank3a and shank3b) are expressed at the earliest stages of nervous system development with pronounced expression in the larval brain. Consistent with early expression of these genes, knockdown of syngap1b or shank3a cause common embryonic phenotypes including delayed mid- and hindbrain development, disruptions in motor behaviors that manifest as unproductive swim attempts, and spontaneous, seizure-like behaviors. Our findings indicate that both syngap1b and shank3a play novel roles in morphogenesis resulting in common brain and behavioral phenotypes.


Assuntos
Transtorno do Espectro Autista/genética , Encéfalo/embriologia , Proteínas Ativadoras de GTPase/genética , Proteínas do Tecido Nervoso/genética , Organogênese/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Proteínas Ativadoras de ras GTPase/genética , Animais , Bases de Dados Genéticas , Desenvolvimento Embrionário , Proteínas Ativadoras de GTPase/metabolismo , Duplicação Gênica , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Haploinsuficiência , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/metabolismo , Proteínas Ativadoras de ras GTPase/metabolismo
7.
Proc Natl Acad Sci U S A ; 111(1): 320-5, 2014 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-24367072

RESUMO

Endosymbiotic associations have played a major role in evolution. However, the molecular basis for the biochemical interdependence of these associations remains poorly understood. The aphid-Buchnera endosymbiosis provides a powerful system to elucidate how these symbioses are regulated. In aphids, the supply of essential amino acids depends on an ancient nutritional symbiotic association with the gamma-proteobacterium Buchnera aphidicola. Buchnera cells are densely packed in specialized aphid bacteriocyte cells. Here we confirm that five putative amino acid transporters are highly expressed and/or highly enriched in Acyrthosiphon pisum bacteriocyte tissues. When expressed in Xenopus laevis oocytes, two bacteriocyte amino acid transporters displayed significant levels of glutamine uptake, with transporter ACYPI001018, LOC100159667 (named here as Acyrthosiphon pisum glutamine transporter 1, ApGLNT1) functioning as the most active glutamine transporter. Transporter ApGLNT1 has narrow substrate selectivity, with high glutamine and low arginine transport capacity. Notably, ApGLNT1 has high binding affinity for arginine, and arginine acts as a competitive inhibitor for glutamine transport. Using immunocytochemistry, we show that ApGLNT1 is localized predominantly to the bacteriocyte plasma membrane, a location consistent with the transport of glutamine from A. pisum hemolymph to the bacteriocyte cytoplasm. On the basis of functional transport data and localization, we propose a substrate feedback inhibition model in which the accumulation of the essential amino acid arginine in A. pisum hemolymph reduces the transport of the precursor glutamine into bacteriocytes, thereby regulating amino acid biosynthesis in the bacteriocyte. Structural similarities in the arrangement of hosts and symbionts across endosymbiotic systems suggest that substrate feedback inhibition may be mechanistically important in other endosymbioses.


Assuntos
Sistemas de Transporte de Aminoácidos/metabolismo , Afídeos/metabolismo , Buchnera/metabolismo , Glutamina/metabolismo , Proteínas de Insetos/metabolismo , Simbiose/genética , Animais , Transporte Biológico , Membrana Celular/metabolismo , Clonagem Molecular , Citoplasma/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hemolinfa/metabolismo , Interações Hospedeiro-Parasita , Oócitos/metabolismo , Simbiose/fisiologia , Xenopus laevis
8.
Development ; 140(7): 1605-13, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23482495

RESUMO

We describe LOLLIbow, a Brainbow-based live imaging system with applications in developmental biology and neurobiology. The development of an animal, including the environmentally sensitive adaptation of its brain, is thought to proceed through continual orchestration among diverse cell types as they divide, migrate, transform and interact with one another within the body. To facilitate direct visualization of such dynamic morphogenesis by individual cells in vivo, we have modified the original Brainbow for Drosophila in which live imaging is practical during much of its development. Our system offers permanent fluorescent labels that reveal fine morphological details of individual cells without requiring dissection or fixation of the samples. It also features a non-invasive means to control the timing of stochastic tricolor cell labeling with a light pulse. We demonstrate applicability of the new system in a variety of settings that could benefit from direct imaging of the developing multicellular organism with single-cell resolution.


Assuntos
Rastreamento de Células/métodos , Drosophila/citologia , Coloração e Rotulagem , Animais , Animais Geneticamente Modificados , Cor , Criptocromos/genética , Criptocromos/metabolismo , Diagnóstico por Imagem , Drosophila/embriologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Embrião não Mamífero , Integrases/genética , Integrases/metabolismo , Microscopia de Vídeo , Modelos Biológicos , Morfogênese/fisiologia , Coloração e Rotulagem/métodos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
9.
Chemistry ; 22(42): 15027-15034, 2016 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-27571689

RESUMO

This study reports the synthesis of a photoactivatable fluorophore with optimal photochemical and photophysical properties for the real-time tracking of motion in vivo. The photoactivation mechanism designed into this particular compound permits the conversion of an emissive reactant into an emissive product with resolved fluorescence, under mild illumination conditions that are impossible to replicate with conventional switching schemes based on bleaching. Indeed, the supramolecular delivery of these photoswitchable probes into the cellular blastoderm of Drosophila melanogaster embryos allows the real-time visualization of translocating molecules with no detrimental effects on the developing organisms. Thus, this innovative mechanism for fluorescence photoactivation can evolve into a general chemical tool to monitor dynamic processes in living biological specimens.


Assuntos
Corantes Fluorescentes/química , Animais , Drosophila melanogaster , Processos Fotoquímicos
10.
J Am Chem Soc ; 137(14): 4709-19, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25794143

RESUMO

Self-assembling nanoparticles of amphiphilic polymers can transport hydrophobic molecules across hydrophilic media and, as a result, can be valuable delivery vehicles for a diversity of biomedical applications. Strategies to monitor their dynamics noninvasively and in real time are, therefore, essential to investigate their translocation within soft matrices and, possibly, rationalize the mechanisms responsible for their diffusion in biological media. In this context, we designed molecular guests with photoactivatable fluorescence for these supramolecular hosts and demonstrated that the activation of the fluorescent cargo, under optical control, permits the tracking of the nanocarrier translocation across hydrogel matrices with the sequential acquisition of fluorescence images. In addition, the mild illumination conditions sufficient to implement these operating principles permit fluorescence activation within developing Drosophila melanogaster embryos and enable the monitoring of the loaded nanocarriers for long periods of time with no cytotoxic effects and no noticeable influence on embryogenesis. These photoresponsive compounds combine a borondipyrromethene (BODIPY) chromophore and a photocleavable oxazine within their covalent skeleton. Under illumination at an appropriate activation wavelength, the oxazine ring cleaves irreversibly to bring the adjacent BODIPY fragment in conjugation with an indole heterocycle. This structural transformation shifts bathochromically the BODIPY absorption and permits the selective excitation of the photochemical product with concomitant fluorescence. In fact, these operating principles allow the photoactivation of BODIPY fluorescence with large brightness and infinite contrast. Thus, our innovative structural design translates into activatable fluorophores with excellent photochemical and photophysical properties as well as provides access to a general mechanism for the real-time tracking of supramolecular nanocarriers in hydrophilic matrices.


Assuntos
Compostos de Boro/química , Portadores de Fármacos/química , Corantes Fluorescentes/química , Nanopartículas/química , Processos Fotoquímicos , Animais , Drosophila melanogaster/embriologia , Portadores de Fármacos/metabolismo , Desenho de Fármacos , Indóis/química , Imagem Óptica , Oxazinas/química
11.
Org Biomol Chem ; 13(36): 9477-84, 2015 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-26257246

RESUMO

Several new DNA-targeting probes that exhibit binding-induced 'turn on' fluorescence are presented. Two of the dyes, orange emissive 1, (E)-4-(4(-4-methylpiperazin-1-yl)phenyl)6-(4-(4-methylpi-perazin-1-yl)styryl)pyrimidin-2-ol), and red emissive 2, (E)-4-(4(-4-methyl-piperazin-1-yl)-phenyl)6-(4-(4-methylpiperazin-1-yl)styryl)-1,3-propanedionato-κO,κO']difluoroborane), are brightly fluorescent when bound to DNA, but are virtually non-fluorescent in aqueous solutions. Confocal fluorescence microscopy of live BT474, MCF7 and HEK293 cells demonstrates that both probes are cell permeable and rapidly accumulated intracellularly into cell nuclei and the cytosol. Taking advantage of their environmental sensitivity, these two pools of fluorophores are readily resolved into separate channels, and thus, a single dye allows two-color imaging of the nuclear and cytosolic compartments.


Assuntos
Núcleo Celular/química , Citosol/química , Sondas de DNA/química , DNA de Neoplasias/química , Corantes Fluorescentes/química , Linhagem Celular Tumoral , Fluorescência , Células HEK293 , Humanos , Células MCF-7 , Microscopia Confocal , Estrutura Molecular
12.
J Orthop Trauma ; 38(4): 210-214, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38163916

RESUMO

OBJECTIVES: Tibiotalocalcaneal (TTC) nailing in the setting of acute ankle trauma has become increasingly popular. No consensus exists as to whether formal joint preparation is necessary, although there is some concern that residual motion at unprepared joints may lead to implant loosening and/or breakage. The objective of this study was to quantify the proportion of tibiotalar and subtalar articular surface destruction that occurs during reaming for TTC nail fixation. METHODS: Twelve cadaver lower extremities were procured. The specimens were pinned into neutral ankle and hindfoot alignment. A guidewire was inserted under fluoroscopy, followed by a 12-mm opening reamer. The specimens were then dissected, exposing the tibial plafond, talar dome, posterior facet of the talus, and posterior facet of the calcaneus. Images of each joint were obtained, and ImageJ software was used to calculate the total joint surface area and the area of articular destruction. RESULTS: The mean proportion of articular cartilage destruction was 9.3%, 10.3%, 8.9%, and 10.3% for the tibial plafond, talar dome, posterior facets of the talus, and posterior facets of the calcaneus, respectively. No joint destruction was observed in the middle facets of the subtalar joint. CONCLUSIONS: Reaming for TTC nail placement violates approximately 10% of each articular surface of the tibiotalar and subtalar joints. Retention of 90% of the articular surface may allow for residual motion at the joints and therefore potentially substantial stress on the implant. Formal joint preparation for the purposes of achieving fusion during TTC nail placement may be beneficial to prevent implant loosening or breakage.


Assuntos
Calcâneo , Fixação Intramedular de Fraturas , Artropatias , Articulação Talocalcânea , Humanos , Tornozelo , Articulação Talocalcânea/cirurgia , Artrodese/métodos , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Extremidade Inferior , Pinos Ortopédicos , Calcâneo/cirurgia
13.
J Neurosurg Spine ; 40(2): 169-174, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37922555

RESUMO

OBJECTIVE: Herniated nucleus pulposus (HNP) is one of the most common lumbar spine conditions treated surgically, often through a minimally invasive surgery (MIS) microdiscectomy approach. This technique attempts to reduce damage to the paraspinal muscular-ligamentous envelope. However, there are currently limited data regarding comparative outcomes using patient-reported outcome measures (PROMs) for one- and two-level MIS discectomies. The aim of this study was to quantify comparative clinical outcomes in patients undergoing one-level and two-level MIS lumbar microdiscectomy for HNP using PROMs. METHODS: The authors performed a retrospective review of patients undergoing MIS lumbar microdiscectomy between 2004 and 2019 for the primary diagnosis of HNP at a single academic institution. All patients had a minimum 1-year follow-up. Patient demographics and comorbidities were collected to establish baselines between cohorts. PROMs and minimal clinically important differences (MCIDs) were used to examine the patient's perception of operative success. Bivariate and multivariate linear/logistic regression analyses were used to compare one- and two-level discectomies. The bivariate analysis included the t-test and chi-square test, which were used to assess continuous and categorical variables, respectively. Statistical significance was established at p < 0.05. RESULTS: A total of 293 patients underwent one-level (n = 250) or two-level (n = 43) MIS discectomies. The mean follow-ups for the one- and two-level cohorts were 50.4 (SD 35.5) months and 61.6 (SD 39.8) months, respectively. Fewer female patients underwent two-level discectomies, and BMI and operative duration were higher in the two-level group (p < 0.001). Recurrent herniation requiring reoperation was recorded at rates of 6.80% and 11.6% in the one- and two-level groups, respectively (p = 0.270). Pre- and postoperative PROMs were largely similar between the cohorts; however, patients undergoing one-level discectomy had greater improvement in leg pain, and a significantly greater proportion of these patients achieved MCID for the leg pain visual analog scale score (p < 0.001). CONCLUSIONS: At the 1-year clinical follow-up, patients who underwent two-level discectomy had significantly less improvement in leg pain scores with lower achievement of MCID for leg pain improvement than patients undergoing one-level procedures. At the 1-year follow-up, there were no other significant differences in PROMs between the two cohorts. Given these findings, patients should be counseled regarding the anticipated outcomes to better manage expectations. Further studies are warranted to examine the long-term clinical outcomes associated with single- and multilevel MIS discectomy.


Assuntos
Discotomia , Deslocamento do Disco Intervertebral , Humanos , Feminino , Resultado do Tratamento , Discotomia/métodos , Deslocamento do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/etiologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Dor/cirurgia , Vértebras Lombares/cirurgia , Estudos Retrospectivos
14.
Phys Chem Chem Phys ; 15(36): 14851-5, 2013 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-23694991

RESUMO

The photoinduced cleavage of a 2-nitrobenzyl group from a pyridinium quencher covalently attached to the meso position of a BODIPY fluorophore activates the emission of the latter. This photochemical transformation prevents the transfer of one electron from the BODIPY platform to its heterocyclic appendage upon excitation and, as a result, permits the radiative deactivation of the excited fluorophore. This versatile mechanism for fluorescence switching can translate into the realization of an entire family of photoactivatable fluorophores based on the outstanding photophysical properties of BODIPY chromophores.


Assuntos
Compostos de Boro/química , Fluorescência , Compostos de Piridínio/síntese química , Alquilação , Estrutura Molecular , Processos Fotoquímicos , Compostos de Piridínio/química
15.
JBJS Rev ; 11(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722839

RESUMO

INTRODUCTION: Resorption after lumbar disk herniation is a common yet unpredictable finding. It is hypothesized that nearly 70% of lumbar herniated nucleus pulposus (HNP) undergo the resorption to a significant degree after acute herniation, which has led to nonoperative management before surgical planning. METHODS: This narrative review on the literature from 4 databases (MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Cochrane) examines historical and recent advancements related to disk resorption. Studies were appraised for their description of the predictive factor (e.g., imaging or morphologic factors), pathophysiology, and treatment recommendations. OBSERVATIONS: We reviewed 68 articles considering the possibility of resorption of lumbar HNP. Recent literature has proposed various mechanisms (inflammation and neovascularization, dehydration, and mechanical traction) of lumbar disk resorption; however, consensus has yet to be established. Current factors that increase the likelihood of resorption include the initial size of the herniation, sequestration, percentage of rim enhancement on initial gadolinium-based magnetic resonance imaging (MRI), composition of inflammatory mediators, and involvement of the posterior longitudinal ligament. CONCLUSION: Heterogeneity in imaging and morphologic factors has led to uncertainty in the identification of which lumbar herniations will resorb. Current factors that increase the likelihood of disk resorption include the initial size of the herniation, sequestration, percentage of rim enhancement on initial MRI, composition of cellular and inflammatory mediators present, and involvement of the posterior longitudinal ligament. This review article highlights the role of disk resorption after herniation without surgical intervention and questions the role of traditional noninflammatory medications after acute herniation. Further research is warranted to refine the ideal patient profile for disk resorption to ultimately avoid unnecessary treatment, thus individualizing patient care.


Assuntos
Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/terapia , Deslocamento do Disco Intervertebral/patologia , Imageamento por Ressonância Magnética/métodos , Região Lombossacral
16.
J Orthop Res ; 41(1): 206-214, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35398932

RESUMO

Modic changes (MC) and endplate abnormalities (EA) have been shown to impact preoperative symptoms and outcomes following spinal surgery. However, little is known about how these phenotypes impact cervical alignment. This study aimed to evaluate the impact that these phenotypes have on preoperative, postoperative, and changes in cervical alignment in patients undergoing anterior cervical discectomy and fusion (ACDF). We performed a retrospective study of prospectively collected data of ACDF patients at a single institution. Preoperative magnetic resonance imagings (MRIs) were used to assess for the MC and EA. Patients were subdivided into four groups: MC-only, EA-only, the combined Modic-Endplate-Complex (MEC), and patients without either phenotype. Pre and postoperative MRIs were used to assess alignment parameters. Associations with imaging phenotypes and alignment parameters were assessed, and statistical significance was set at p < 0.5. A total of 512 patients were included, with 84 MC-only patients, 166 EA-only patients, and 71 patients with MEC. Preoperative MC (p = 0.031) and the MEC (p = 0.039) had significantly lower preoperative T1 slope compared to controls. Lower preoperative T1 slope was a risk factor for MC (p = 0.020) and MEC (p = 0.029) and presence of MC (Type II) and the MEC (Type III) was predictive of lower preoperative T1 slope. There were no differences in postoperative alignment measures or patient reported outcome measures. MC and endplate pathologies such as the MEC appear to be associated with worse cervical alignment at baseline relative to patients without these phenotypes. Poor alignment may be an adaptive response to these degenerative findings or may be a risk factor for their development.


Assuntos
Vértebras Cervicais , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Humanos , Imageamento por Ressonância Magnética
17.
J Phys Chem A ; 116(40): 9928-33, 2012 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-22994311

RESUMO

We designed a strategy to activate fluorescence under the influence of optical stimulations based on the intermolecular transfer of protons. Specifically, the illumination of a 2-nitrobenzyl derivative at an activating wavelength is accompanied by the release of hydrogen bromide. In turn, the photogenerated acid encourages the opening of an oxazine ring embedded within a halochromic compound. This structural transformation extends the conjugation of an adjacent coumarin fluorophore and enables its absorption at an appropriate excitation wavelength. Indeed, this bimolecular system offers the opportunity to activate fluorescence in liquid solutions, within rigid matrixes and inside micellar assemblies, relying on the interplay of activating and exciting beams. Furthermore, this strategy permits the permanent imprinting of fluorescent patterns on polymer films, the monitoring of proton diffusion within such materials in real time on a millisecond time scale, and the acquisition of images with spatial resolution at the nanometer level. Thus, our operating principles for fluorescence activation can eventually lead to the development of valuable photoswitchable probes for imaging applications and versatile mechanisms for the investigation of proton transport.


Assuntos
Fluorescência , Ácido Bromídrico/química , Prótons , Processos Fotoquímicos
18.
J Orthop Res ; 40(2): 449-459, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33749924

RESUMO

This study describes a novel, combined Modic changes (MC) and structural endplate abnormality phenotype of the cervical spine, which we have termed the Modic-Endplate-Complex (MEC), and its association with preoperative symptoms and outcomes in anterior cervical discectomy and fusion (ACDF) patients. This was a retrospective study of prospectively collected data at a single institution. Preoperative cervical magnetic resonance imagings were used to assess the presence of MC and endplate abnormalities. Patients were divided into four groups: MC-only, endplate abnormality-only, the MEC and controls. The MEC was defined as the presence of both a MC and endplate abnormality in the cervical spine. Phenotypes were further stratified by location and compared to controls. Associations with patient-reported outcome measures were assessed using regression controlling for baseline characteristics. A total of 628 patients were included, with 84 MC-only, 166 endplate abnormality-only, and 187 MEC patients. Both MC (p < 0.001) and endplate abnormalities (p < 0.001) were independently associated with one another. MC at the adjacent level (p = 0.018), endplate abnormalities (regardless of location) (p = 0.001), and the MEC within the fusion segment (p = 0.027) were all associated with higher Neck Disability Index scores. Both MC within the fusion segment (p = 0.008) and endplate abnormalities within the fusion segment (p = 0.017) associated with lower Veteran's Rand 12-item scores. MC and structural endplate abnormalities commonly manifest concomitantly in patients indicated for ACDF for degenerative pathology. Patients with the endplate pathology, including the MEC phenotype, reported significantly higher levels of postoperative disability following ACDF. These findings add valuable data to the prognostic assessment of degenerative cervical spine patients.


Assuntos
Degeneração do Disco Intervertebral , Fusão Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Fenótipo , Estudos Retrospectivos , Resultado do Tratamento
19.
Int J Spine Surg ; 15(4): 669-675, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34266929

RESUMO

BACKGROUND: YouTube has become a popular source for patient education, though there are concerns regarding the quality and reliability of videos related to orthopaedic and neurosurgical procedures. This study aims to evaluate the credibility and educational content of videos on YouTube related to cervical fusion. Secondarily, the study aims to identify factors predictive of higher or lower quality videos. METHODS: A YouTube query using the search terms "cervical fusion" was performed, and the first 50 videos were included for analysis. Reliability was assessed using the Journal of the American Medical Association (JAMA) criteria. Educational quality was assessed using the Global Quality Score (GQS) and the Cervical Fusion Content Score (CFCS). Videos were stratified by content and source, and differences in JAMA, GQS, and CFCS scores were assessed. Multivariable linear regression was used to identify predictors of higher or lower JAMA, GQS, and CFCS scores. Statistical significance was established at P < 0.05. RESULTS: Total number of views was 6 221 816 with a mean of 124 436.32 ± 412 883.32 views per video. Physicians, academic, and medical sources had significantly higher mean JAMA scores (P = 0.042). Exercise training and nonsurgical management videos had significantly higher mean CFCS scores (P = 0.018). Videos by physicians (ß = 0.616; P = 0.025) were independently associated with higher JAMA scores. Advertisements were significant predictors of worse CFCS (ß = -3.978; P = 0.030), and videos by commercial sources predicted significantly lower JAMA scores (ß = -1.326; P = 0.006). CONCLUSIONS: While videos related to cervical fusion amassed a large viewership, they were poor in both quality and reliability. Videos by physicians were associated with higher reliability scores relative to other sources, whereas commercial sources and advertisements had significantly lower reliability and educational content scores. Currently, YouTube seems to be an unreliable source of information on cervical fusion for patients. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: The results of this study aid surgeons in counseling patients interested in cervical fusion, and suggest that publicly available videos regarding cervical fusion may not be an adequate tool for patient education at this time.

20.
Neurospine ; 17(1): 190-203, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32252168

RESUMO

OBJECTIVE: To assess the impact of Modic changes (MC) on preoperative symptoms, and postoperative outcomes in anterior cervical discectomy and fusion (ACDF) patients. METHODS: We performed a retrospective study of prospectively collected data of ACDF patients at a single institution. Preoperative magnetic resonance imagings were used to assess the presence of MC. MC were stratified by type and location, and compared to patients without MC. Associations with symptoms, patient-reported measures, and surgical outcomes were assessed. RESULTS: A total of 861 patients were included, with 356 patients with MC (41.3%). MC more frequently occurred at C5-6 (15.1%), and type II was the most common type (61.2%). MC were associated with advanced age (p < 0.001), more levels fused (p < 0.001), a longer duration of symptoms, but not with specific symptoms. MC at C7-T1 resulted in higher postoperative disability (p < 0.001), but did not increase risk of adjacent segment degeneration or reoperation. CONCLUSION: This study is the first to systematically examine the impact of cervical MC, stratified by type and location, on outcomes in ACDF patients. Patients with MC were generally older, required larger fusions, and had longer duration of preoperative symptoms. While MC may not affect specific outcomes following ACDF, they may indicate a more debilitating preoperative state for patients.

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