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The effects of the charged ion species 4He, 12C and 20Ne on glioblastoma multiforme (GBM) T98G, U87 and LN18 cell lines were compared with the effects of 200 kVp X-rays (1.7 keV/μm). These cell lines have different genetic profiles. Individual GBM relative biological effectiveness (RBE) was estimated in two ways: the RBE10 at 10% survival fraction and the RBE2Gy after 2 Gy doses. The linear quadratic model radiosensitivity parameters α and β and the α/β ratio of each ion type were determined as a function of LET. Mono-energetic 4He, 12C and 20Ne ions were generated by the Heavy Ion Medical Accelerator at the National Institute of Radiological Sciences in Chiba, Japan. Colony-formation assays were used to evaluate the survival fractions. The LET of the various ions used ranged from 2.3 to 100 keV/μm (covering the depth-dose plateau region to clinically relevant LET at the Bragg peak). For U87 and LN18, the RBE10 increased with LET and peaked at 85 keV/μm, whereas T98G peaked at 100 keV/μm. All three GBM α parameters peaked at 100 keV/μm. There is a statistically significant difference between the three GBM RBE10 values, except at 100 keV/μm (P < 0.01), and a statistically significant difference between the α values of the GBM cell lines, except at 85 and 100 keV/μm. The biological response varied depending on the GBM cell lines and on the ions used.

Between 35% to 50% of traumatic brain injury (TBI) patients are under the influence of alcohol. Alcohol intoxication may limit the ability of the Glasgow Coma Scale (GCS) to accurately assess severity of TBI. We hypothesized that alcohol intoxication significantly depresses GCS scores of TBI patients.A 10-year, retrospective analysis of a Level I trauma center registry was undertaken. The study population consisted of all blunt injured TBI patients tested for blood alcohol concentration (BAC, n = 1,075). Patients were divided into two groups; intoxicated (mean BAC 202 +/- 77 mg/dL, n = 504) and nonintoxicated (BAC = 0, n = 571). TBI was classified using ICD-9 codes as concussion alone (ICD-9 850, n = 90) and intracranial injury (ICI, ICD-9 851-854, n = 985). Severity was further classified using the Abbreviated Injury Score (AIS). Mean GCS score was compared between the two groups. Patients who were either intubated or hypotensive upon arrival were analyzed separately to rule out confounding effects on GCS score. Severely intoxicated patients (BAC >250 mg/dL, [mean +/- SD] 309 +/- 54 SD, n = 118) were similarly compared. Finally, multivariate linear regression analysis was undertaken to determine whether BAC level was an independent predictor of GCS score while controlling for confounding factors.Intoxicated and nonintoxicated TBI patients were clinically similar. Alcohol intoxication had little effect on GCS score, with less than a single point difference in all types of TBI, except the most severely injured (AIS 5 injuries, GCS score difference 1.4 points). These results were not altered by endotracheal intubation, systemic hypotension, or severe intoxication. Similarly, BAC was not a significant independent predictor of GCS score in a multivariate model.Alcohol intoxication does not result in clinically significant changes in GCS score for patients with blunt TBI. Hence, alterations in GCS score after TBI should not be attributed to alcohol intoxication, as doing so might result in inappropriate delays in monitoring and therapeutic interventions.

We present a protocol for the biosensor Cell-Fit-HD4D. It enables long-term monitoring and correlation of single-cell fate with subcellular-deposited energy of ionizing radiation. Cell fate tracking using widefield time-lapse microscopy is uncoupled in time from confocal ion track imaging. Registration of both image acquisition steps allows precise ion track assignment to cells and correlation with cellular readouts. For complete details on the use and execution of this protocol, please refer to Niklas et al. (2022).

Prenatal ethanol exposure is associated with, and is a risk factor for, developmental disorders with abnormal social behaviors, including autism spectrum disorders. We hypothesize that the specific effects of ethanol on social behavior are defined by the timing of the exposure as well as subsequent changes in brain regions such as the amygdala and ventral striatum. We recently reported that in utero ethanol exposure on gestational day 12 alters social behaviors of weanling [postnatal day (P) 28], adolescent (P42), and young adult (P75) rats. Male, but not female, offspring of the ethanol-exposed dams showed significant decreases in social investigation (sniffing of a social partner), contact behavior (grooming or crawling over/under the partner), and play fighting (following, chasing, nape attacks, or pinning) at all ages tested with maximal effects at P28 and P42. Furthermore, ethanol-exposed males and females showed evidence of social avoidance at P42 and P75. The present study sought to test whether a form of social enrichment could normalize any of the social deficits and what the molecular mechanisms of such effects might be. We found that housing rats with nonmanipulated control rats normalized the social avoidance phenotype normally seen when they are housed with sex-matched prenatal ethanol-exposed littermates. There was no mitigation of the other ethanol-induced behavioral deficits. Conversely, male control-treated rats housed with nonlittermates showed deficits in play fighting, social investigation and contact behavior. Molecular analyses of the amygdala and ventral striatum of adolescent rats following fetal ethanol exposure indicated several specific neurotransmitter systems and pathways that might underlie the social avoidance phenotype as well as its reversal.

The use of alcohol has been associated with both an increased risk of acquisition of HIV‐1 infection and an increased rate of disease progression among those already infected by the virus. The potential for alcohol to exacerbate the effects of HIV infection is especially important in the central nervous system (CNS) because this area is vulnerable to the combined effects of alcohol and HIV infection. The effects of alcohol on glial cells are mediated through receptors such as Toll‐like receptor 4 and N‐methyl‐d‐aspartate receptor. This causes the activation of signaling molecules such as interleukin‐1 receptor‐associated kinase and various members of the P38 mitogen‐activated protein kinase family and subsequent activation of transcription factors such as nuclear factor‐kappa beta and activator protein 1. The eventual outcome is an increase in pro‐inflammatory cytokine production by glial cells. Alcohol also induces higher levels of NADPH oxidase in glial cells, which leads to an increased production of reactive oxygen species (ROS). Viral invasion of the CNS occurs early after infection, and HIV proteins have also been demonstrated to increase levels of pro‐inflammatory cytokines and ROS in glial cells through activation of some of the same pathways activated by alcohol. Both cell culture systems and animal models have demonstrated that concomitant exposure to alcohol and HIV/HIV proteins results in increased levels of expression of pro‐inflammatory cytokines such as interleukin‐1 beta and tumor necrosis factor‐alpha, along with increased levels of oxidative stress. Clinical studies also suggest that alcohol exacerbates the CNS effects of HIV‐1 infection. This review focuses on the mechanisms by which alcohol causes increased CNS damage in HIV‐1 infection.

The opioid antagonist, naltrexone, reduces intake of, and operant responding for, ethanol, but reports of how the opioid agonist morphine alters these effects are conflicting. We examined the discrimination and plasma levels of ethanol with naltrexone and morphine pretreatments. Rats were trained to discriminate ethanol (1.5 g/kg; i.g.) from water, under a two-lever, food-reinforced procedure. Ethanol and pentobarbital, but not amphetamine, substituted for ethanol in a dose-related manner. Naltrexone reduced ethanol-induced, ethanol-appropriate responding to about 35%, but the peripherally-acting antagonist, naltrexone methobromide, was without effect. Morphine neither substituted for nor enhanced ethanol-appropriate responding. Rather, ethanol-induced, ethanol-appropriate responding was attenuated in a dose-related manner by morphine administration. Neither naltrexone nor morphine altered ethanol-appropriate responding to the substitution with pentobarbital. In another group of rats, both naltrexone and morphine decreased plasma ethanol levels, and delayed the time of peak concentrations, suggesting that opiates alter the behavioral effects of ethanol through both pharmacokinetic and pharmacodynamic mechanisms. The similarities between an opioid agonist and an antagonist suggest that either naltrexone has opioid agonist-like effects, or that these effects occur through non-opioidergic mechanisms.

Impaired motor function in children with histories of prenatal exposure to alcohol has been previously reported but, to date, no studies using quantitatively based analyses have been performed to assess gait in these children.Gait of children with (n = 18) or without (n = 26) prenatal alcohol exposure was assessed using an electronically instrumented walkway. Children completed blocks of trials traversing the walkway with different combinations of walking condition (increased, self-paced, and decreased cadence) and direction (forward and backward). Gait velocity, cadence, stride length, step width, foot angle, and double support time, as well as the variability of these temporal-spatial markers, were used to assess gait.Results indicated that, in comparison with typically developing children, alcohol-exposed children produced exaggerated foot angle and increased step width. Additionally, alcohol-exposed children produced greater intrasubject variability of gait velocity and walking cadence while walking forward and backward, and greater variability in step width when walking backward and for all 3 walking conditions.The results indicate that selected gait markers are adversely affected by prenatal exposure to alcohol. Clinicians and front-line personnel (e.g., teachers) should provide movement enriched experiences to help ameliorate these alcohol-related deficits.

The aim of this study is to provide an overview of deaths caused by poisoning (especially illicit drugs) in Estonia from 2000 to 2009. The data on poisoning deaths (N = 4132) were collected from the autopsy reports of the Estonian Forensic Science Institute. Ethanol poisoning was the most frequent cause of death (N = 1449, 35.1%), followed by carbon monoxide (N = 1151, 27.9%) and poisoning from illicit drugs (N = 888, 21.5%). The study included 3267 male (79.1%) and 865 female fatalities, with the prevalent age group being 35-64 years. Since 2002, deaths from fentanyles have increased sharply and remained at a high level - from 63 cases in 2002 to 138 cases in 2009. This high number indicates that in spite of the state's drug policies, illegal drugs remain easily available and that this area requires more attention. Alcohol abuse prevention policies - restrictions on alcohol advertisements in the media, limitations on sale times and anti-alcohol campaigns concerning traffic - have not brought about a significant decrease in ethanol poisoning.