Oral administration of coenzyme Q10 ameliorates memory impairment induced by nicotine-ethanol abstinence through restoration of biochemical changes in male rat hippocampal tissues.

Substance abuse among adolescents has become a growing issue throughout the world. The significance of research on this life period is based on the occurrence of neurobiological changes in adolescent brain which makes the individual more susceptible for risk-taking and impulsive behaviors. Alcohol and nicotine are among the most available drugs of abuse in adolescents. Prolonged consumption of nicotine and alcohol leads to drug dependence and withdrawal which induce various dysfunctions such as memory loss. Coenzyme Q10 (CoQ10) is known to improve learning and memory deficits induced by various pathological conditions such as Diabetes mellitus and Alzheimer's disease. In the present study we investigated whether CoQ10 treatment ameliorates memory loss following a nicotine-ethanol abstinence. Morris water maze and novel object recognition tests were done in male Wistar rats undergone nicotine-ethanol abstinence and the effect of CoQ10 was assessed on at behavioral and biochemical levels. Results indicated that nicotine-ethanol abstinence induces memory dysfunction which is associated with increased oxidative and inflammatory response, reduced cholinergic and neurotrophic function plus elevated Amyloid-B levels in hippocampi. CoQ10 treatment prevented memory deficits and biochemical alterations. Interestingly, this ameliorative effect of CoQ10 was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration. CoQ10 treatment could effectively improve memory defects induced by nicotine-ethanol consumption through attenuation of oxidative damage, inflammation, amyloid-B level and enhancement of cholinergic and neurotrophic drive. Further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects.

Comparative Analysis of the Prognostic Significance of IDH,TERT, EGFR and MGMT Status in Patients with Adult Non-H3-Altered Grade 4 Gliomas: A Prospective Cohort Study.

INTRODUCTION: Gliomas continue to have a dismal prognosis. A myriad of genetic alterations has been described in this subset of tumors over the last decades. The integrative interpretation of the biomarker constellation for individual patients remains unclear. This study aims to evaluate the impact of some known genetic factors as prognostic biomarkers in grade 4 gliomas. METHODS: Adult non-H3-altered grade 4 gliomas who underwent maximal safe resection accompanied by adjuvant therapy were successively enrolled since January 2019 till January 2021. Patient data were documented preoperatively and during the follow-up visits. The genetic profiling of the tumors included Isocitrate Dehydrogenase (IDH)-1 and IDH-2 mutation, MGMT promoter methylation rate, EGFR gene amplification and telomerase reverse transcriptase gene promoter (TERTp) mutation. RESULTS: Mean Overall survival (OS) and Progression-free survival (PFS) were 14.45 ± 5.13 months (3-24 months) and 10.66 ± 4.87 months respectively. TERTp-mutant group had a significantly lower OS (10.9 vs. 15.9) and PFS (6.9 vs. 12.3) than TERTp wildtype group. In the TERT-mutant group, those with concomitant IDH wildtype tumor had higher OS and PFS, comparable to those with both TERTp and IDH wildtype tumors. In multivariate analysis, IDH mutation and TERTp wildtype status were predictive of longer OS and PFS. While IDH and absence of TERTp mutation were associated with KPS > 80 across the follow-ups, their predictive values were inferior to preoperative KPS scores. CONCLUSIONS: TERTp mutation and IDH-wildtype status were associated with worse OS and PFS and lower follow-up KPS score in surgically resected gliomas, while MGMT and EGFR status did not have considerable prognostic value in this study.

Alteration of anxiety and depression after awake craniotomy: a prospective study on patients with language eloquent high-grade glioma.

BACKGROUND: Awake craniotomy (AC) is considered to achieve maximal safe resection of language eloquent gliomas. Impact of AC on the psychological status of patients (mainly anxiety, and post-traumatic stress disorder [PTSD]) is a potential concern. Despite the studies reporting the early postoperative patient's perception after AC, this study has been performed to quantitatively evaluate the long-term influence of AC on the level of anxiety/depression after surgery. METHODS: Patients who underwent AC for suspected language eloquent high-grade glioma were enrolled in this study. The anxiety, depression and PTSD of the patients were evaluated via hospital anxiety and depression scale (HADS) one week before and 1 and 6 months after the operation. PTSD symptoms were assessed according to the DSM-V checklist and confirmed by a structured clinical interview for DSM-V. RESULTS: Twenty-eight patients (22 men, six women) with the mean age of 39.2 years were enrolled. The mean preoperative depressive and anxiety score was 4.9±5.9 and 7.7±5.8 respectively. One month after surgery they were 6±4.9 and 7.4±6.2 and at 6 months' follow-up 5.5±5.1 and 5.4±4.2 respectively. There was no statistically significant trend for alterations of the anxiety/depression levels before and after surgery. Female patients, those suspected to have glioblastoma and patients presenting with speech disturbance had remarkably higher preoperative anxiety levels. Three patients had PTSD symptoms 3 months after AC while at 6 months there was no indication of PTSD. The decremental trend of PTSD score within 6 months was statistically significant. CONCLUSIONS: Judicious application of AC is not associated with an escalation of the anxiety/depression level among the patients. Even patients with high preoperative anxiety levels could be managed with AC without severe psychological deterioration.

Changes in Cognitive Functioning After Surgical Resection of Language-related, Eloquent-area, High-grade Gliomas Under Awake Craniotomy.

BACKGROUND: Dominant-hemisphere tumors, especially gliomas, as infiltrative tumors, frequently affect cognitive functioning. Establishing a balance between extensive resection, which is proven to result in longer survival, and less extensive resection, in order to maintain more cognitive abilities, is challenging. OBJECTIVE: To evaluate changes in cognitive functioning before and after surgical resection of language-related, eloquent-area, high-grade gliomas under awake craniotomy. METHOD: We provided individuals with newly diagnosed high-grade gliomas of the language-related eloquent areas with the same standard of care, including surgical resection of the glioma using intraoperative sensory-motor and cognitive mapping under awake craniotomy, and the same protocol for chemoradiotherapy. Cognitive functioning was assessed using Addenbrooke's Cognitive Examination-Revised (ACE-R) at four time points (preoperatively, early after surgery, and 3 and 6 months postoperatively). RESULTS: The preoperative evaluation revealed a range of cognitive impairments in 70.7% of the individuals, affecting all of the cognitive subdomains (mostly attention and visuospatial abilities). Overall cognitive functioning (ie, ACE-R score) dropped by 13.5% (P = 0.169) early postoperatively. At the 3-month evaluation, an average of 15.3% (P = 0.182) recovery in cognitive functioning was observed (mostly in verbal fluency: 39.1%). This recovery improved further, reaching 29% (P < 0.001) at the 6-month evaluation. The greatest improvement occurred in verbal fluency: 68.8%, P = 0.001. CONCLUSION: Extensive resection of eloquent-area gliomas with the aid of modern neuroimaging and neuromonitoring techniques under awake craniotomy is possible without significant long-term cognitive sequela.

Mandibular first and second molars with three mesial canals: a case series.

Adequate cleaning, shaping and filling of the root canal system are mandatory for successful root canal treatment. Thorough knowledge of root canal morphology and unusual anatomy of the tooth is critical for the practitioner. The occurrence and location of the third mesial canal (Middle Mesial Canal) in mandibular first and second molars in relation to other two mesial canals that were treated in private practice were studied. In 27 clinical cases, the presence of a middle mesial canal was demonstrated. The third canal was located in the middle of the distance between the mesiobuccal and mesiolingual canals. This canal configuration was found in six second lower molars and twenty one first molars. Middle mesial canal in all of our cases joined to mesiobuccal or mesiolingual canals. None of the teeth consisted of three independent canals with three apical foramina. In conclusion, every attempt should be made to find and treat all root canals of a tooth.