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1.
Cell ; 165(7): 1672-1685, 2016 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-27315481

RESUMO

Long intergenic noncoding RNAs (lincRNAs) are important regulators of gene expression. Although lincRNAs are expressed in immune cells, their functions in immunity are largely unexplored. Here, we identify an immunoregulatory lincRNA, lincRNA-EPS, that is precisely regulated in macrophages to control the expression of immune response genes (IRGs). Transcriptome analysis of macrophages from lincRNA-EPS-deficient mice, combined with gain-of-function and rescue experiments, revealed a specific role for this lincRNA in restraining IRG expression. Consistently, lincRNA-EPS-deficient mice manifest enhanced inflammation and lethality following endotoxin challenge in vivo. lincRNA-EPS localizes at regulatory regions of IRGs to control nucleosome positioning and repress transcription. Further, lincRNA-EPS mediates these effects by interacting with heterogeneous nuclear ribonucleoprotein L via a CANACA motif located in its 3' end. Together, these findings identify lincRNA-EPS as a repressor of inflammatory responses, highlighting the importance of lincRNAs in the immune system.


Assuntos
Regulação da Expressão Gênica , Inflamação/genética , Macrófagos/imunologia , RNA Longo não Codificante/metabolismo , Animais , Cromátides/metabolismo , Deleção de Genes , Humanos , Listeria monocytogenes/fisiologia , Listeriose/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Macrófagos/virologia , Camundongos , Camundongos Endogâmicos C57BL , RNA Longo não Codificante/genética , Infecções por Respirovirus/imunologia , Vírus Sendai/fisiologia , Receptores Toll-Like/metabolismo , Transcriptoma
2.
Psychol Res ; 86(1): 209-233, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33590297

RESUMO

We report three experiments in which the events flanking a temporal interval were either related or unrelated, based on overlap in the letter identity of single letters (Experiment 1), in the conceptual congruency of color words and colored rectangles (Experiment 2), or in the conceptual congruency of sentence stems and their terminal words (Experiment 3). In all cases, we observed a bias for participants to judge the duration of temporal intervals as shorter when the flanking events were related. We draw an analogy between these temporal judgement distortions and those reported elsewhere (Alards-Tomalin et al. in J Exp Psychol Learn Mem Cogn 40(2):555-566, 2014) that revealed that the similarity in the relative magnitude of flanking events generate the same type of bias on duration judgements. The observation that non-magnitude dimensions of relatedness between flanking events can also bias duration judgements raise questions about the applicability of two influential theoretical frameworks for understanding the distorting effects that non-temporal stimulus dimensions can have on duration judgments, A Theory of Magnitude (Buetl and Walsh in Philos Trans R Soc B Biol Sci 12:1831-1840, 2009, Walsh in Trends Cogn Sci 7:483-488, 2003) and the Conceptual Metaphor Theory (e.g., Lakoff and Johnson in Philosophy in the flesh: the embodied mind and its challenge to western thought. Basic Books, New York, 1999). In our general discussion, we consider a number of alternative frameworks that may account for these findings.


Assuntos
Julgamento , Humanos
3.
Eur Spine J ; 26(11): 2941-2950, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28766018

RESUMO

STUDY DESIGN: A retrospective analysis of two consecutive patients who underwent a novel surgical technique. OBJECTIVE: A report of a novel surgical technique utilizing an electronic conductivity device guidance to aide placement of S2-Alar-Iliac (S2-AI) instrumentation. Electronic conductivity guidance for instrumentation of the thoracolumbar spine is an accepted means of improving intraoperative accuracy. Although commercially available for percutaneous techniques, there is a paucity of literature regarding its use. Percutaneous implantation of S2-AI screws has been previously described as another technique surgeons can avail, primarily employing fluoroscopy as a means of intraoperative feedback. We describe a novel technique that utilizes electronic conductivity as an added feedback measure to increase accuracy of percutaneous S2-AI fixation. METHODS: Two patients were treated by the senior author (FAS) who underwent surgery employing S2-AI fixation utilizing an electronic conductivity device (Pediguard cannulated probe, Spineguard, Paris, France). The surgical technique, case illustrations, and radiographic outcomes are discussed. RESULTS: Stable and accurate fixation was attained in both patients. There were no peri-operative complications related to hardware placement. CONCLUSION: To the authors' knowledge, this is the first reported literature combining S2-AI screws with electronic conductivity for immediate intraoperative feedback. This technique has the opportunity to provide surgeons with increased accuracy for placement of S2-AI screws while improving overall radiation safety. This feedback can be particularly helpful when surgeons are learning new techniques such as placement of S2AI screws.


Assuntos
Condutividade Elétrica , Ílio/cirurgia , Monitorização Intraoperatória/métodos , Parafusos Pediculares , Sacro/cirurgia , Fusão Vertebral/métodos , Humanos , Estudos Retrospectivos
4.
Front Immunol ; 12: 605930, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854495

RESUMO

Detection of DNA is an important determinant of host-defense but also a driver of autoinflammatory and autoimmune diseases. Failure to degrade self-DNA in DNAseII or III(TREX1)-deficient mice results in activation of the cGAS-STING pathway. Deficiency of cGAS or STING in these models ameliorates disease manifestations. However, the contribution of the cGAS-STING pathway, relative to endosomal TLRs, in systemic lupus erythematosus (SLE) is controversial. In fact, STING deficiency failed to rescue, and actually exacerbated, disease manifestations in Fas-deficient SLE-prone mice. We have now extended these observations to a chronic model of SLE induced by the i.p. injection of TMPD (pristane). We found that both cGAS- and STING-deficiency not only failed to rescue mice from TMPD-induced SLE, but resulted in increased autoantibody production and higher proteinuria levels compared to cGAS STING sufficient mice. Further, we generated cGASKOFaslpr mice on a pure MRL/Faslpr background using Crispr/Cas9 and found slightly exacerbated, and not attenuated, disease. We hypothesized that the cGAS-STING pathway constrains TLR activation, and thereby limits autoimmune manifestations in these two models. Consistent with this premise, mice lacking cGAS and Unc93B1 or STING and Unc93B1 developed minimal systemic autoimmunity as compared to cGAS or STING single knock out animals. Nevertheless, TMPD-driven lupus in B6 mice was abrogated upon AAV-delivery of DNAse I, implicating a DNA trigger. Overall, this study demonstrated that the cGAS-STING pathway does not promote systemic autoimmunity in murine models of SLE. These data have important implications for cGAS-STING-directed therapies being developed for the treatment of systemic autoimmunity.


Assuntos
Autoimunidade , Suscetibilidade a Doenças , Lúpus Eritematoso Sistêmico/etiologia , Proteínas de Membrana/metabolismo , Nucleotidiltransferases/metabolismo , Transdução de Sinais , Animais , Autoanticorpos/imunologia , Autoimunidade/genética , Biomarcadores , Modelos Animais de Doenças , Expressão Gênica , Imunofenotipagem , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Nucleotidiltransferases/genética
5.
Neurosurg Clin N Am ; 30(3): 313-322, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078232

RESUMO

Spondylolisthesis is a common cause of lower back pain in people of all ages. When nonsurgical management is unsuccessful in treatment for lumbar spondylolisthesis, surgical treatment algorithms can be used. This article focuses on lateral lumbar interbody fusion (LLIF). It represents a minimally invasive approach that affords surgeons an increased ability to restore disc height, indirectly decompress the neural elements, and affect global spinal alignment. As the role for circumferential minimally invasive spine surgery continues to expand, the use of LLIF in the setting of spondylolisthesis-and other pathologies-will continue to represent a robust fusion option.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Espondilolistese/cirurgia , Resultado do Tratamento , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fusão Vertebral/métodos , Espondilolistese/diagnóstico por imagem
6.
Can J Exp Psychol ; 73(1): 64-68, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30883179

RESUMO

On the event of his recent passing, this article provides a personal discussion of Bruce Whittlesea's contributions and career from the perspective of one of his former students. It summarizes the basic tenets of the theoretical framework he developed, the Selective Construction and Preservation of Experience (SCAPE) Account of Memory (Whittlesea, 1997). (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Ciência Cognitiva/história , Memória/fisiologia , Psicologia/história , História do Século XX , História do Século XXI , Humanos
7.
J Clin Neurosci ; 61: 124-129, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30552048

RESUMO

BACKGROUND: Complications associated with the lateral lumbar transpsoas approach largely comprise various nerve-related syndromes particularly at L4-5. Quadriceps weakness can occur from stretch injury to the femoral nerve during retraction. OBJECTIVE: The purpose of this study is to evaluate the role of retraction time in the development of postoperative neuropathic motor weakness at the L4-5 level. METHODS: A retrospective review of a prospectively collected database at a single institution was reviewed over a two-year period (March 2014-2016) for a single surgeon. Twenty-six patients undergoing single level LLIF at L4-5 were identified. Pre- and postoperative data collection obtained included motor function grading (0-5/5) with a minimum of 3-month postoperative follow-up. Intraoperative data collection included retraction time (RT) defined as the time the retraction system was affixed to the spine and expanded to the time of closure and removal. Two-Tailed T-Test was used to determine clinical significance. RESULTS: 50% of patients had leg weakness after surgery (13/26). All postoperative motor deficits were at least antigravity strength (>3/5) and all deficits resolved. The mean RT for the motor dysfunction cohort was 29 min (14-51) compared to 27.5 min for the cohort without postoperative weakness (19-37) (p = 0.685). CONCLUSION: The results of this study suggest that longer retraction time (within a range of 14-51 min) did not correlate with a greater risk of postoperative neuropathic quadriceps muscle dysfunction for lateral lumbar interbody fusions performed at L4-5. Other factors may contribute to postoperative neurologic dysfunction regardless of RT. Motor deficits resolved quickly after surgery.


Assuntos
Nervo Femoral/lesões , Debilidade Muscular/etiologia , Complicações Pós-Operatórias/etiologia , Fusão Vertebral/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fusão Vertebral/métodos
8.
Chin Neurosurg J ; 5: 22, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32922921

RESUMO

BACKGROUND: As chordomas are slow growing and locally invasive with high recurrence rates, initial recommendations include complete surgical resection with or without radiation therapy. A large proportion of recurrences occur years after initial resection necessitating lengthy follow-up. The novel biomarker brachyury and the repurposing of pharmaceutical products have the potential to substantially impact long-term recurrence rates. CASE PRESENTATION: A 43-year-old woman presented with an isolated, cervical extraosseous intradural extramedullary chordoma attached to a nerve root underwent a C3-5 laminectomy, C3-5 lateral mass screw instrumentation, and mass resection. All symptoms resolved by the 12-month postoperative follow-up visit. CONCLUSIONS: This is the first report of an isolated, cervical extraosseous intradural extramedullary chordoma attached to a nerve root, and this case adds to the previous six Type IV chordomas in the literature. Unfortunately, the very rare form of extraosseous intradural chordoma is poorly understood: the lack of detailed knowledge in how they are differentiated from other forms of chordoma confounds the development of optimal treatment strategies and follow-up guidelines.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30675388

RESUMO

Introduction: Spinal cord injury is one of the leading causes of paralysis and permanent morbidity. High cervical spine injuries, in particular, have the potential to be fatal and debilitating due to injury to multiple components, including but not limited to, discoligamentous disruption, vascular insult and spinal cord injury. To date, no unifying algorithm exists making it challenging to guide treatment decisions. Case presentation: We present the case of a 29-year-old polytrauma patient with an unstable C2-C3 fracture subluxation secondary to hyperextension and rotation injury with complete ligamentous dissociation and vertebral artery dissection after a high-velocity injury. We review the literature on injury patterns, associated complications and neurological outcomes in subaxial cervical spine injuries. Discussion: Our patient's injuries had several components including fracture subluxation, ligamentous disruption, central cord syndrome, and vascular insult. The lack of a unifying algorithm to guide treatment decisions highlights the variations in pathology and subsequent limitations in generalizability of current literature. Our patient underwent an open anterior C2-C3 reduction and discectomy with fusion and plating and a subsequent C2-C4 posterior instrumented fusion. The patient regained some motor function postoperatively and through rehabilitation. Careful consideration of multiple components is crucial when treating subaxial spine injuries.


Assuntos
Vértebra Cervical Áxis/lesões , Fratura-Luxação/cirurgia , Ligamentos Longitudinais/lesões , Traumatismo Múltiplo/cirurgia , Radiculopatia/cirurgia , Compressão da Medula Espinal/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Dissecação da Artéria Vertebral/tratamento farmacológico , Adulto , Vértebra Cervical Áxis/cirurgia , Infarto Encefálico/diagnóstico por imagem , Vértebras Cervicais/lesões , Vértebras Cervicais/cirurgia , Angiografia por Tomografia Computadorizada , Discotomia , Fratura-Luxação/complicações , Fratura-Luxação/diagnóstico por imagem , Humanos , Masculino , Transferência de Nervo , Inibidores da Agregação Plaquetária/uso terapêutico , Radiculopatia/complicações , Compressão da Medula Espinal/etiologia , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fusão Vertebral , Artéria Vertebral/lesões , Dissecação da Artéria Vertebral/complicações , Dissecação da Artéria Vertebral/diagnóstico por imagem
10.
Acta Psychol (Amst) ; 182: 138-153, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29179019

RESUMO

The negative priming effect occurs when withholding a response to a stimulus impairs generation of subsequent responding to a same or a related stimulus. Our goal was to use the negative priming procedure to obtain insights about the memory representations generated by ignoring vs. attending/responding to a prime stimulus. Across three experiments we observed that ignoring a prime stimulus tends to generate higher identity-independent, non-specific repetition effects, owing to an overlap in the coarse perceptual form of a prime distractor and a probe target. By contrast, attended repetition effects generate predominantly identity-specific sources of facilitation. We use these findings to advocate for using laboratory phenomena to illustrate general principles that can be of practical use to non-specialists. In the case of the negative priming procedure, we propose that the procedure provides a useful means for investigating attention/memory interactions, even if the specific cause (or causes) of negative priming effects remain unresolved.


Assuntos
Atenção/fisiologia , Cognição/fisiologia , Memória de Curto Prazo/fisiologia , Atividade Motora/fisiologia , Adulto , Feminino , Humanos , Masculino , Resolução de Problemas , Tempo de Reação/fisiologia , Adulto Jovem
11.
Can J Exp Psychol ; 72(2): 91-104, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29389144

RESUMO

There are several independent demonstrations that attentional phenomena can be controlled in a context-dependent manner by cues associated with differing attentional control demands. The present set of experiments provide converging evidence that attention-capture phenomena can be modulated in a context-dependent fashion. We determined whether methods from the proportion congruent literature (listwide and item- and context-specific proportion congruent designs) that are known to modulate distractor interference effects in Stroop and flanker tasks are capable of modulating attention capture by salient feature singletons. Across experiments we found evidence that attention capture can be modulated by listwide, item-specific, and context-specific manipulations of proportion congruent. We discuss challenges associated with interpreting results from proportion congruent studies but propose that our findings converge with existing work that has demonstrated context-dependent control of attention capture. (PsycINFO Database Record


Assuntos
Atenção/fisiologia , Percepção de Cores/fisiologia , Sinais (Psicologia) , Reconhecimento Visual de Modelos/fisiologia , Análise de Variância , Discriminação Psicológica , Feminino , Humanos , Masculino , Estimulação Luminosa , Tempo de Reação , Estudantes , Universidades
12.
Neurosurg Clin N Am ; 28(1): 157-162, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27886877

RESUMO

The role for minimally invasive surgery (MIS) continues to expand in the management of spinal pathology. In the setting of trauma, operative techniques that can minimize morbidity without compromising clinical efficacy have significant value. MIS techniques are associated with decreased intraoperative blood loss, operative time, and morbidity, while providing patients with comparable outcomes when compared with conventional open procedures. MIS interventions further enable earlier mobilization, decreased hospital stay, decreased pain, and an earlier return to baseline function when compared with traditional techniques. This article reviews patient selection and select MIS techniques for those who have suffered traumatic spinal injury.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fraturas da Coluna Vertebral/cirurgia , Humanos , Cuidados Pós-Operatórios , Resultado do Tratamento
13.
Cureus ; 7(12): e394, 2015 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-26798570

RESUMO

STUDY DESIGN: Retrospective chart analysis. OBJECTIVE: The objective of this study is to describe the senior author's (MNN) experience applying a widely available surgical drape as a postoperative sterile surgical site dressing for both cranial and spinal procedures. SUMMARY OF BACKGROUND DATA: Surgical site infection (SSI) is an important complication of spine surgery that can result in significant morbidity. There is wide variation in wound care management in practice, including dressing type. Given the known bactericidal properties of the surgical drape, there may be a benefit of continuing its use immediately postoperatively. METHODS: All of the senior author's cases from September 2014 through September 2015 were reviewed. These were contrasted to the previous year prior to the institution of a sterile surgical drape as a postoperative dressing. RESULTS: Only one surgical case out of 157 operative interventions (35 cranial, 124 spinal) required operative debridement due to infection. From September 2013 to September 2014, prior to the institution of a sterile surgical drape as dressing, the author had five infections out of 143 operations (46 cranial, 97 spinal) requiring intervention. CONCLUSION: The implementation of a sterile surgical drape as a closed postoperative surgical site dressing has led to a decrease in surgical site infections. The technique is simple and widely available, and should be considered for use to diminish surgical site infections.

14.
J Exp Psychol Learn Mem Cogn ; 40(2): 555-66, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24274384

RESUMO

The relative magnitude (or intensity) of an event can have direct implications on timing estimation. Previous studies have found that greater magnitude stimuli are often reported as longer in duration than lesser magnitudes, including Arabic digits (Xuan, Zhang, He, & Chen, 2007). One explanation for these findings is that different quantitative dimensions (size, intensity, number) are processed and represented according to a common analog magnitude system (Walsh, 2003). In the current study, we examined whether there were commonalities in how people judge the intervals of time occurring between discrete stimuli of different magnitudes across a variety of quantitative dimensions, which included number, size, and color saturation. It was found that duration judgments increased systematically as the overall magnitude difference between sequentially presented stimuli increased. This finding was robust against manipulations to the direction of the sequence, or whether the sequence followed ordered (continuous) or nonordered (discontinuous) pattern trajectories.


Assuntos
Percepção de Cores/fisiologia , Matemática , Reconhecimento Visual de Modelos/fisiologia , Percepção Espacial/fisiologia , Análise de Variância , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estimulação Luminosa , Tempo de Reação/fisiologia , Adulto Jovem
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