RESUMO
Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support 'normal life' following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.'s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).
RESUMO
The health impacts of the BP oil spill are yet to be further revealed as the toxicological effects of oil products and dispersants on human respiratory system may be latent and complex, and hence difficult to study and follow up. Here we performed RNA-seq analyses of a system of human airway epithelial cells treated with the BP crude oil and/or dispersants Corexit 9500 and Corexit 9527 that were used to help break up the oil spill. Based on the RNA-seq data, we then systemically analyzed the transcriptomic perturbations of the cells at the KEGG pathway level using two pathway-based analysis tools, GAGE (generally applicable gene set enrichment) and GSNCA (Gene Sets Net Correlations Analysis). Our results suggested a pattern of change towards carcinogenesis for the treated cells marked by upregulation of ribosomal biosynthesis (hsa03008) (p=1.97E-13), protein processing (hsa04141) (p=4.09E-7), Wnt signaling (hsa04310) (p=6.76E-3), neurotrophin signaling (hsa04722) (p=7.73E-3) and insulin signaling (hsa04910) (p=1.16E-2) pathways under the dispersant Corexit 9527 treatment, as identified by GAGE analysis. Furthermore, through GSNCA analysis, we identified gene co-expression changes for several KEGG cancer pathways, including small cell lung cancer pathway (hsa05222, p=9.99E-5), under various treatments of oil/dispersant, especially the mixture of oil and Corexit 9527. Overall, our results suggested carcinogenic effects of dispersants (in particular Corexit 9527) and their mixtures with the BP crude oil, and provided further support for more stringent safety precautions and regulations for operations involving long-term respiratory exposure to oil and dispersants.
Assuntos
Carcinógenos/toxicidade , Lipídeos/toxicidade , Poluição por Petróleo/efeitos adversos , Petróleo/toxicidade , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Tensoativos/toxicidade , Poluentes Químicos da Água/toxicidadeRESUMO
Neck lumbar traction bed is through the computer control motor and hydraulic transmission device, implementation of traditional Chinese medicine traction, Angle rotation and manual reduction action of a device, etc. Saving time and effort can well meet the needs of the treatment on lumbar disease. Based on the failure phenomenon of traction bed hydraulic transmission device, the composition and working principle analysis of the hydraulic system, concluded that failure of the hydraulic transmission device is due to the pressure gauge damaged or blocked between the tubing and the overflow valve, which allows users to quickly troubleshoot.
RESUMO
Phineas Gage es a no dudar, uno de los pacientes más famosos de la historia de la neurología, una cita indefectible en textos neurológicos y objeto de numerosos artículos científicos a lo largo de más de ciento cincuenta años. Este caso tan excepcional ha permitido establecer el papel principal que en el pensamiento y en la capacidad de sociabilizar tienen las regiones frontales del cerebro, especialmente la porción ventromedial, así como los circuitos y sistemas relacionados con las emociones, cuya activación conjunta con las regiones frontales, participa de forma fundamental en la planificación y toma de decisiones, y contribuye a determinar el tono afectivo de nuestras relaciones sociales. Una revisión sumaria de la historia de la medicina nos indica que es inusual que el nombre de un paciente y no el del médico que describe una situación clínica, sea mencionado para la posteridad. ¿Por qué entonces se recuerda el nombre de Gage y no el de su médico tratante y acusioso descriptor de su insania, John Martyn Harlow? Quizá porque el caso es todavía considerado como una de las mejores descripciones de un desorden "psicopático" del comportamiento relacionado con una lesión traumática del córtex prefrontal, donde la correlación anatomoclínica ha sido intentada empleando diversas concepciones y métodos a la usanza de los diversos momentos históricos. La ocasión de este relato permitirá al lector pasearse a través de la fascinante evolución y perfeccionamiento de las ideas que han llevado al conocimiento actual de la localización de las funciones neurológicas, y a atisbar el desentrañamiento de los loci de la mente y del espíritu
Phineas Gage is doubtless one of the most famous patients in the history of neurology. An infallible quote in neurology textbooks and the object of numerous scientific articles for over one hundred and fifty years. This exceptional case has allowed investigators to establish the role of the frontal cortex, specifically its ventromedial portion in the development of human thought and his/her capacity to socialize and also the close relationship of these structures with emotion-related circuits and systems which participate in the decision-making process and contributes to determine the affective tone of social interaction. A brief glance at the history of medicine shows it is exceedingly infrequent for a patient's name to transcend into posterity. Why then is the name Gage remembered instead of John Martin Harlow's, the keen describer of Gage's insanity? Perhaps because Gage's case is still considered one of the salient descriptions of a "psychopathic" disorder of behavior directly related to a traumatic lesion of the prefrontal cortex in which an anatomoclinical correlation has been attempted through diverse conceptions and methods tailored to each historical period of time. Gage's tale will take the reader for a ride along the fascinating evolutional pathways of medical thinking that have permitted the acquisition of knowledgeable localization of neurological function and allowed scientists to peep into the entangled realm of the mind and spirit