Visualization of both proximal M2-MCA segments in patients (the Tilted-V Sign) with acute M1-MCA occlusion stroke is associated with better procedural and prognostic outcomes

IntroductionWe aimed to assess the clinical significance of M1-MCA occlusion with visualization of both MCA-M2 segments [“Tilted-V sign” (TVS)] on initial CT angiography (CTA) in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT).MethodsData for patients with consecutive AIS undergoing EVT for large vessel occlusion (LVO) in two academic centers are recorded in ongoing databases. Patients who underwent EVT for M1-MCA occlusions ≤ 6 h from symptom onset were included in this retrospective analysis.ResultsA total of 346 patients met the inclusion criteria; 189 (55%) had positive TVS. Patients with positive TVS were younger (68 ± 14 vs. 71 ± 14 years, P = 0.028), with similar rates of vascular risk factors and baseline modified Rankin scores (mRS) 0–2. The rates of achieving thrombolysis in cerebral ischemia (TICI) 2b-3 were similar to the two groups (79%), although successful first-pass recanalization was more common with TVS (64 vs. 36%, p = 0.01). On multivariate analysis, higher collateral score [odds ratio (OR) 1.38 per unit increase, p = 0.008] and lower age (OR 0.98 per year increase, p = 0.046) were significant predictors of TVS. Patients with positive TVS had higher post-procedural Alberta Stroke Program Early CT Score (ASPECTS; 6.9 ± 2.2 vs. 5.2 ± 2.3, p = 0.001), were discharged with lower National Institutes of Health Stroke Score (NIHSS; 6±6 vs. 9±7, p = 0.003) and higher rates of mRS 0–2 (29.5 vs. 12%, p = 0.001), and had lower rates of 90-day mortality (13.2 vs. 21.6%, p = 0.038). However, TVS was not an independent predictor of functional independence (OR 2.51; 95% CI 0.7–8.3).ConclusionTilted-V Sign, an easily identifiable radiological marker, is associated with fewer recanalization attempts, better functional outcomes, and reduced mortality

Novel use of an exchange catheter to facilitate intubation with an Aintree catheter in a tall patient with a predicted difficult airway: a case report

<p>Abstract</p> <p>Introduction</p> <p>The Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) has been shown to successfully facilitate difficult intubations when other methods have failed. The Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) has a fixed length of 56 cm, and it has been suggested in the literature that it may be too short for safe use in patients who are tall.</p> <p>Case presentation</p> <p>We present the case of a 32-year-old, 180 cm tall Caucasian woman with a predicted difficult airway who presented to our facility for an emergency cesarean section. After several failed intubation attempts via direct laryngoscopy, an airway was established with a laryngeal mask airway. After delivery of a healthy baby, our patient's condition necessitated tracheal intubation. A fiber-optic bronchoscope loaded with an Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) was passed through the laryngeal mask airway into the trachea until just above the carina, but was too short to safely allow for the passage of an endotracheal tube.</p> <p>Conclusions</p> <p>We present a novel technique in which the Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) was replaced with a longer (100 cm) exchange catheter, over which an endotracheal tube was passed successfully into the trachea.</p

A DJ-1 Based Peptide Attenuates Dopaminergic Degeneration in Mice Models of Parkinson's Disease via Enhancing Nrf2.

Drugs currently used for treating Parkinson's disease patients provide symptomatic relief without altering the neurodegenerative process. Our aim was to examine the possibility of using DJ-1 (PARK7), as a novel therapeutic target for Parkinson's disease. We designed a short peptide, named ND-13. This peptide consists of a 13 amino acids segment of the DJ-1-protein attached to 7 amino acids derived from TAT, a cell penetrating protein. We examined the effects of ND-13 using in vitro and in vivo experimental models of Parkinson's disease. We demonstrated that ND-13 protects cultured cells against oxidative and neurotoxic insults, reduced reactive oxygen species accumulation, activated the protective erythroid-2 related factor 2 system and increased cell survival. ND-13 robustly attenuated dopaminergic system dysfunction and in improved the behavioral outcome in the 6-hydroxydopamine mouse model of Parkinson's disease, both in wild type and in DJ-1 knockout mice. Moreover, ND-13 restored dopamine content in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model. These findings validate DJ-1 as a promising therapeutic target in Parkinson's disease and identify a novel peptide with clinical potential, which may be significant for a broader range of neurological diseases, possibly with an important impact for the neurosciences

Frequência de lesões sugestivas de toxoplasmose ocular em uma população rural do Estado do Rio de Janeiro Frequency of lesions suggestive of ocular toxoplasmosis among a rural population in the State of Rio de Janeiro

Para determinar a prevalência da toxoplasmose ocular na população em geral do bairro de Santa Rita de Cássia, Barra Mansa, RJ, foi realizado um estudo seccional no qual 1.071 indivíduos foram submetidos a testes sorológicos (IgG e IgM anti-Toxoplasma) e a exame físico e oftalmológico. O diagnóstico da toxoplasmose ocular presumida foi baseado em critérios clínicos, sorológicos e aspecto da lesão retinocoroidiana. As lesões foram classificadas em três tipos morfológicos: 1. Limites marcados com halo de hiperpigmentação e área de atrofia coriorretiniana central. 2. Halo hipopigmentado e área central hiperpigmentada e 3. Hiperpigmentadas ou hipopigmentadas. A prevalência de lesões cicatrizadas compatíveis com toxoplasmose ocular foi de 3,8% na população em geral e 5,8% entre os indivíduos com sorologia positiva para Toxoplasma gondii (65,9% dos indivíduos analisados), com predominância de: lesões do tipo 1 (41,5%), sexo feminino (68,3%), periféricas (58,5%) e menores que 3 diâmetros de disco (87,8%).<br>To determine the prevalence of ocular toxoplasmosis among the general population of the district of Santa Rita de Cassia, Barra Mansa, State of Rio de Janeiro, a cross-sectional study on 1,071 individuals was performed. These subjects underwent serological tests (anti-Toxoplasma IgG and IgM) and physical and ophthalmological examinations. The diagnosis of presumed ocular toxoplasmosis was based on clinical and serological criteria and the appearance of the retinochoroidal lesion. The lesions were classified into three morphological types: 1. Limits marked with a halo of hyperpigmentation and an area of central chorioretinal atrophy; 2. Hypopigmented halo and hyperpigmented central area; and 3. Hyperpigmented or hypopigmented. The prevalence of healed lesions compatible with ocular toxoplasmosis was 3.8% among the general population and 5.8% among individuals who were seropositive for Toxoplasma gondii (65.9% of the individuals evaluated). Type-1 lesions (41.5%), female sex (68.3%), peripheral lesions (58.5%) and lesions smaller than three disc diameters predominated

ND-13 increased activation of the Nrf2 after exposure to 6-OHDA.

<p>(A) Quantitative real time PCR analysis of the mRNA levels of Nrf2, (B) HO-1, (C) NQO-1 and (D) GCLC levels of PC-12 cells, 5 hours after exposure to increasing doses of 6-OHDA (0–50 μM). Real time PCR was done in triplicate. GAPDH was used as a housekeeping gene. Real time PCR was done by the ddCT method. Experiments were repeated 3 times. Results are shown as averages ±SD. * p<0.05.</p

ND-13 restores dopamine levels and tyrosine hydroxylase in 6-OHDA hemiparkinsonian mice.

<p>(A) Dopamine levels in brains of naïve (control) mice or mice lesioned by 6-OHDA were measured by HPLC. Dopamine level in the right (6-OHDA lesioned) hemisphere is presented as percentage of the normal left hemisphere. IV injection of the ND-13 (1.5 mg/Kg dissolved in 200 μl, 4 hours before 6-OHDA) or SC injection of ND-13 (3 mg/Kg dissolved in 100 μl saline, 6 hours before and 1 hour after 6-OHDA lesioning) restored dopamine levels as compared to vehicle treated 6-OHDA mice (# p<0.05, as compared to naïve mice, * p<0.05, as compared to vehicle-treated 6-OHDA mice). (B) IV administration of ND-13 (1.5 mg/Kg dissolved in 200μl saline, 4 hours before 6-OHDA lesioning) markedly reduced the loss of tyrosine hydroxylase (TH) staining in the 6-OHDA-lesioned (right) substantia nigra in wild type c57/bl6 mice, as compared to vehicle-treated 6-OHDA mice. TH staining in the left (unlesioned) substantia nigra did not show significant differences.</p

ND-13 administration attenuates 6-OHDA toxicity in DJ-1 knockout mice.

<p>(A) IV administration of ND-13 (1.5 mg/Kg dissolved in 200μl saline, 4 hours before 6-OHDA lesioning) significantly reduced the rotational behavior induced by amphetamine injection, 2 and 4 weeks after 6-OHDA striatal lesioning in 6-OHDA hemiparkinsonian transgenic DJ-1 knockout mice. Results are shown as averages ± SD. (# p<0.05, as compared to naïve mice, * p<0.05, as compared to vehicle-treated 6-OHDA mice). (B) IV administration of ND-13 restores dopamine levels, as measured by HPLC in 6-OHDA lesioned DJ-1 knockout mice. Dopamine levels were measured in each cerebral hemisphere of naïve DJ-1 knockout mice (control), or mice lesioned by 6-OHDA treated by ND-13 or vehicle. The dopamine level in the right (6-OHDA lesioned) hemisphere is presented as a percentage of the normal left hemisphere. IV administration of ND-13 (1.5 mg/Kg dissolved in 200 μl, 4 hours before 6-OHDA) statistically restored dopamine levels, as compared to vehicle-treated 6-OHDA mice. Results are shown as averages ± SD. * p<0.05 as compared to vehicle-treated 6-OHDA DJ-1 knockout mice.</p

ND-13 reduced the accumulation of intracellular reactive oxygen species and activated the Nrf2 anti-oxidant system.

<p>(A) Exposure to hydrogen peroxide resulted in intracellular accumulation of reactive oxygen species, as quantified by the DCF assay. Pretreatment with ND-13 resulted in significantly decreased accumulation of reactive oxygen species. The time dependent effect was examined by increasing the time between ND-13 treatment and the oxidative insult. ND-13 showed significant effects when applied up to 6 hours before hydrogen peroxide exposure. Cells were washed before toxin application. (B) ND-13 induced nuclear translocation of Nrf-2, as quantified by cell fractionation and the Nrf2 activity kit (TransAM) on nuclear extracts. Results are shown as averages ± SD. * p<0.05. (C-F) Pretreatment with ND-13 induced early and increased expression of Nrf-2-dependent mRNA of antioxidant genes when cells were exposed to the neurotoxin 6-OHDA. (C) Quantitative real time PCR analysis of the mRNA levels of Nrf2, (D) NAD(P)H quinine oxidoreductase-1, GCLC (E) and HO-1 (F) levels in PC-12 cells, 2 hours after exposure to increasing doses of 6-OHDA (0–50 μM). Real time PCR was done in triplicate, by the ddCT method, with glyceraldehyde 3-phosphate dehydrogenase used as a housekeeping gene. Experiments were repeated 3 times. Results are shown as averages ±SD. * p<0.05. (G, H) Western blots of HO-1 protein levels in cells exposed to increasing doses of 6-OHDA (0–50 μM) for 8 hours. ND-13 pretreated cells showed increased HO-1 protein levels (normalized versus beta-actin levels) after exposure to 6-OHDA.</p

ND-13 attenuates toxicity of trophic factors depletion, oxidative insults and neurotoxins.

<p>SH-SY5Y, human neuroblastoma cells, were exposed to increasing doses of hydrogen peroxide (H₂O₂, 0–60 μM), 6-OHDA (0–25 μM) or dopamine (0–10 μM) for 24 hours. ND-13 (4 μM) or vehicle were applied 1 hour before the toxic insults. (A) ND-13 attenuated H₂O₂-induced cell death, measured by LDH cytotoxicity assay and (B) restored H₂O₂-induced metabolic changes, measured by Alamar blue. As controls we used cells treated with vehicle (phosphate buffered saline) or short peptides (ND-6 and ND-8) with sequences similar to ND-13, attached to the same cell penetrating peptide as ND-13. (C) ND-13 attenuated 6-OHDA and (D) against dopamine toxicity, as measured by the LDH cytotoxicity assay. (E) ND-13 preserved viability of human neuroblastoma cells SH-SY5Y exposed to trophic factors depletion (done by serum deprivation for 48 hours, * p<0.05 as compared to cell culture with serum, # p<0.05 as compared to cell culture without serum or ND-13). (F) ND-13 does not induce cell proliferation. Human neuroblastoma cells (SH-SY5Y) were exposed to 4 μM ND-13 or vehicle for 24 hours. Cell proliferation was quantified by BrdU assay. No significant differences were observed between ND-13 treated cells and vehicle treated cells. Data are presented as means ± S.D. * p<0.05 as compared to cells exposed to vehicle and the same toxic dose. The experiments were repeated 3 times in triplicates.</p

ND-13 blood-brain-barrier penetration.

<p>C57/bl6 mice were injected with FITC-Albumin (FITC-Alb) to visualize intact blood vessels. FITC conjugated TAT peptide (FITC-TAT), FITC conjugated ND-13 lacking the TAT sequence (ND-13C-FITC) or FITC conjugated full length ND-13 (ND-13-FITC) were injected subcutaneous (SC) and monitored by CellVizio system for additional 30 min. Time dependent accumulation of the fluorescent signal in the brain parenchyma around the blood vessels was observed when mice were administrated with either TAT-FITC or ND-13-FITC but not with ND-13C, indicating that the TAT-derived cell penetrating peptide enables ND-13 to penetrate the BBB.</p