RESUMEN
The present study applied the Simon effect task to examine the pattern of functional brain reorganization in individuals with Friedreich ataxia (FRDA), using functional magnetic resonance imaging (fMRI). Thirteen individuals with FRDA and 14 age and sex matched controls participated, and were required to respond to either congruent or incongruent arrow stimuli, presented either to the left or right of a screen, via laterally-located button press responses. Although the Simon effect (incongruent minus congruent stimuli) showed common regions of activation in both groups, including the superior and middle prefrontal cortices, insulae, superior and inferior parietal lobules (LPs, LPi), occipital cortex and cerebellum, there was reduced functional activation across a range of brain regions (cortical, subcortical and cerebellar) in individuals with FRDA. The greater Simon effect behaviourally in individuals with FRDA, compared with controls, together with concomitant reductions in functional brain activation and reduced functional connectivity between cortical and sub-cortical regions, implies a likely disruption of cortico-cerebellar loops and ineffective engagement of cognitive/attention regions required for response suppression.
Asunto(s)
Encéfalo/fisiopatología , Ataxia de Friedreich/fisiopatología , Adulto , Atención , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Desempeño Psicomotor , Análisis y Desempeño de TareasRESUMEN
Friedreich ataxia (FRDA) is the most common of the genetically inherited ataxias. We recently demonstrated that people with FRDA have impairment in motor planning - most likely because of pathology affecting the cerebral cortex and/or cerebello-cortical projections. We used the Simon interference task to examine how effective 13 individuals with FRDA were at inhibiting inappropriate automatic responses associated with stimulus-response incompatibility in comparison with control participants. Participants had to respond to arrow targets according to two features which were either congruent or incongruent. We found that individuals with FRDA were differentially affected in reaction time to incongruent, compared with congruent stimuli, when compared with control participants. There was a significant negative correlation between age of onset and the incongruency effect, suggesting an impact of FRDA on the developmental unfolding of motor cognition, independent of the effect of disease duration. Future neuroimaging studies will be required to establish whether this dysfunction is due to cerebellar impairment disrupting cerebro-ponto-cerebello-thalamo-cerebral loops (and thus cortical function), direct primary cortical pathology, or a possible combination of the two.
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Cerebelo/fisiopatología , Ataxia de Friedreich/fisiopatología , Inhibición Psicológica , Desempeño Psicomotor/fisiología , Adulto , Análisis de Varianza , Cognición/fisiología , Humanos , Pruebas Neuropsicológicas , Tiempo de Reacción/fisiologíaRESUMEN
BACKGROUND: It has become established that Helicobacter pullorum could be isolated from raw chicken meat. AIMS: This study was aimed to develop a novel culture method (protocol B) to isolate H. pullorum from chicken meat by adding some modifications to the traditional culture method (protocol A), and as a consequence to compare their sensitivity, specificity, and the accuracy of these methods with polymerase chain reaction (PCR) test. METHODS: 400 chicken meat samples were collected from various retail markets and supermarkets. Each sample was processed by protocol A, protocol B, and PCR test. RESULTS: Out of 400 samples, 77 (19.25%), and 163 (40.75%) were culture-positive by protocol A and protocol B, respectively. Using PCR test as a gold standard, 196 (49%) samples were identified as H. pullorum. The specificity for both protocols was determined 100%, while the sensitivity of protocol B and protocol A was assessed 83% and 39%, respectively. Also, the higher and lower accuracy belonged to protocol B (92%) and protocol A (70%), respectively. CONCLUSION: The methodology designed herein can provide a suitable, approximately sensitive, specific, and accurate method to cultivate H. pullorum from chicken meat.
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CD8 T cells protect the liver against viral infection, but can also cause severe liver damage that may even lead to organ failure. Given the lack of mechanistic insights and specific treatment options in patients with acute fulminant hepatitis, we develop a mouse model reflecting a severe acute virus-induced CD8 T cell-mediated hepatitis. Here we show that antigen-specific CD8 T cells induce liver damage in a perforin-dependent manner, yet liver failure is not caused by effector responses targeting virus-infected hepatocytes alone. Additionally, CD8 T cell mediated elimination of cross-presenting liver sinusoidal endothelial cells causes endothelial damage that leads to a dramatically impaired sinusoidal perfusion and indirectly to hepatocyte death. With the identification of perforin-mediated killing as a critical pathophysiologic mechanism of liver failure and the protective function of a new class of perforin inhibitor, our study opens new potential therapeutic angles for fulminant viral hepatitis.
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Células Endoteliales/efectos de los fármacos , Hepatitis Viral Animal/tratamiento farmacológico , Hígado/efectos de los fármacos , Proteínas Citotóxicas Formadoras de Poros/antagonistas & inhibidores , Sustancias Protectoras/farmacología , Sulfonamidas/farmacología , Adenoviridae/genética , Adenoviridae/inmunología , Adenoviridae/patogenicidad , Animales , Anticuerpos/administración & dosificación , Antígenos CD40/antagonistas & inhibidores , Antígenos CD40/genética , Antígenos CD40/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Capilares/efectos de los fármacos , Capilares/virología , Modelos Animales de Enfermedad , Células Endoteliales/inmunología , Células Endoteliales/virología , Expresión Génica , Genes Reporteros , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Hepatitis Viral Animal/inmunología , Hepatitis Viral Animal/virología , Hepatocitos/efectos de los fármacos , Hepatocitos/inmunología , Hepatocitos/virología , Humanos , Hígado/irrigación sanguínea , Hígado/patología , Hígado/virología , Luciferasas/genética , Luciferasas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ovalbúmina/administración & dosificación , Poli I-C/administración & dosificación , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/inmunologíaRESUMEN
Introduction. Secure airway for proper ventilation during anesthesia is one important component of a successful surgery. Endotracheal intubation is one of the most important methods in this context. Intubation method and used medication are considerably important in attenuating complications. This research aimed to investigate the impact of two different doses of dexmedetomidine in mitigating cardiovascular responses to endotracheal intubation in candidate cases supporting voluntary operation. Methods. The current research contained 90 cases in the range of 18 and 50 old, with ASA I,II supporting voluntary operation, who were randomly classified into three teams, each group consisting of 30 cases. The first set (A) got 0.5 µg/ kg dexmedetomidine, the second set (B) got 1 µg/ kg dexmedetomidine and the third set (C) got an equal volume of saline as placebo, 600 seconds earlier the initiation of anesthesia. Hemodynamic parameters were recorded at baseline (T0), then after the injection and the earlier initiation of anesthesia (T1), after the induction of anesthesia and before the endotracheal intubation (T2), promptly after tracheal intubation, 180, and 300 after endotracheal intubation (T4, T5). Data was analyzed and p < 0.05 was supposed notable. Findings. In this research, 3 teams were similar regarding weight, age, height, sex and duration of laryngoscopy. The diastolic mean arterial pressure, heart rate, and systolic arterial pressure were significantly lower in dexmedetomidine teams (A,B) at all times after the endotracheal intubation compared to group C. There were no significant differences in hemodynamic factors among group A, B. Conclusion. Dexmedetomidine effectively and significantly attenuates cardiovascular and hemodynamic responses during endotracheal intubation. In addition, different doses of dexmedetomidine did not cause any significant distinct result in mitigating cardiovascular responses.
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Friedreich's ataxia (FRDA) is the most common form of hereditary ataxia. In addition to proximal spinal cord and brain stem atrophy, mild to moderate atrophy of the cerebellum has been reported in advanced FRDA. The aim of this study was to examine dysfunction in motor-related areas involved in the execution of finger tapping tasks in individuals with FRDA, and to investigate functional re-organization of cortico-cerebellar, cortico-striatal and parieto-frontal loops as a result of the cerebellar pathology. Thirteen right-handed individuals with FRDA and fourteen right-handed controls participated. Functional MRI images were acquired during four different finger tapping tasks consisting of visually cued regular and irregular single finger tapping tasks, a self-paced regular finger tapping task, and a visually cued multi-finger tapping task. Both groups showed significant activation of the motor-related network including the pre-central cortex and supplementary motor area bilaterally; the left primary motor cortex, somatosensory cortex and putamen; and the right cerebellum. During the visually cued regular finger tapping task, the right hemisphere of the cerebellar cortex, bilateral supplementary motor areas and right inferior parietal cortex showed higher activation in the healthy control group, while in individuals with FRDA the left premotor cortex, left somatosensory cortex and left inferior parietal cortex were more active. In addition, during the visually cued irregular finger tapping task, the right middle temporal gyrus in the control group and the right superior parietal lobule and left superior and middle temporal gyri in the individuals with FRDA showed higher activation. During visually cued multi-finger tapping task, the control group showed higher activation in the bilateral middle frontal gyri, bilateral somatosensory cortices, bilateral inferior parietal lobules, left premotor cortex, left supplementary area, right superior frontal gyrus and right cerebellum, while individuals with FRDA showed increased activity in the left inferior parietal lobule, left primary motor cortex, left middle occipital gyrus, right somatosensory cortex and the left cerebellum. Only the right crus I/II of the cerebellum showed higher activation in individuals with FRDA during the self-paced regular finger tapping task, whereas wide-spread regions including the left superior frontal gyrus, left central opercular cortex, left somatosensory cortex, left putamen, right cerebellum, bilateral primary motor cortices, bilateral inferior parietal lobules and the left insula were more active in the control group. Although the pattern of the BOLD signal from the putamen was different during the self-paced regular finger tapping task to the other tasks in controls, in individuals with FRDA there was no distinction of the signal between the tasks suggesting that primary cerebellar pathology may cause secondary basal ganglia dysregulation. While individuals with FRDA tapped at a slightly lower rate (0.59Hz) compared with controls (0.74Hz) they showed significantly decreased activity of the SMA and the inferior parietal lobule, which may suggest disruption to the fronto-parietal connections. These findings suggest that the motor impairments in individuals with FRDA result from dysfunction extending beyond the spinal cord and cerebellum to include sub-cortical and cortical brain regions.