Withdrawal from repeated nicotine vapor exposure increases somatic signs of physical dependence, anxiety-like behavior, and brain reward thresholds in adult male rats.

In recent years, there has been a dramatic increase in nicotine vapor consumption via electronic nicotine delivery systems (i.e., e-cigarettes), particularly in adolescents. While recent work has focused on the health effects of nicotine vapor exposure, its effects on the brain and behavior remain unclear. In this study, we assessed the effects that cessation from repeated nicotine vapor exposure had on behavioral and neuronal measures of withdrawal. For Experiment 1, fifty-six adult male rats were tested for plasma cotinine levels, somatic withdrawal signs, and anxiety-like behavior in the elevated plus maze, immediately following precipitated withdrawal from repeated exposure to 12 or 24 mg/mL nicotine vapor. In Experiment 2, twelve adult male rats were tested for intracranial self-stimulation (ICSS) across 14 days of exposure to 24 mg/mL nicotine vapor and across the 14 days immediately following nicotine exposure. Results revealed that plasma cotinine, somatic signs, anxiety-like behavior, and ICSS stimulation thresholds were all observed to be elevated during withdrawal in the 24 mg/mL nicotine group, when compared to vehicle controls (50/50 vegetable glycerin/propylene glycol). The data suggest that cessation from repeated nicotine vapor exposure using our preclinical model leads to nicotine dependence and withdrawal, and demonstrates that the vapor system described in these experiments is a viable pre-clinical model of e-cigarette use in humans. Further characterization of the mechanisms driving nicotine vapor abuse and dependence is needed to improve policies and educational campaigns related to e-cigarette use.

Analysis of the mechanical resistance of cement with aggregates of petrous endocarp from macadamia nut

This research evaluates if adding crushed macadamia nutshell to a mixture of cement and sand could result in lighter and more resistant constructive materials. The mechanical resistance under compression of cement blocks made from two different experimental mixtures, in which a certain amount of sand is replaced with crushed nutshell, is compared against two control groups. Results show that blocks made from one of the proposed mixtures got an average resistance around 50% above the controls group while being 3% lighter. Additionally, the physical dependence of the strength of the blocks on the granulometry of the aggregated endocarp fragments, and their percentage to the volume of cement, was studied thanks to contour plots developed from a factorial design of the data.

Comparison of an Addictive Potential of μ-Opioid Receptor Agonists with G Protein Bias: Behavioral and Molecular Modeling Studies

Among different approaches to the search for novel—safer and less addictive—opioid analgesics, biased agonism has received the most attention in recent years. Some μ-opioid receptor agonists with G protein bias, including SR compounds, were proposed to induce diminished side effects. However, in many aspects, behavioral effects of those compounds, as well as the mechanisms underlying differences in their action, remain unexplored. Here, we aimed to evaluate the effects of SR-14968 and SR-17018, highly G protein-biased opioid agonists, on antinociception, motor activity and addiction-like behaviors in C57BL/6J mice. The obtained results showed that the compounds induce strong and dose-dependent antinociception. SR-14968 causes high, and SR-17018 much lower, locomotor activity. Both agonists develop reward-associated behavior and physical dependence. The compounds also cause antinociceptive tolerance, however, developing more slowly when compared to morphine. Interestingly, SR compounds, in particular SR-17018, slow down the development of antinociceptive tolerance to morphine and inhibit some symptoms of morphine withdrawal. Therefore, our results indicate that SR agonists possess rewarding and addictive properties, but can positively modulate some symptoms of morphine dependence. Next, we have compared behavioral effects of SR-compounds and PZM21 and searched for a relationship to the substantial differences in molecular interactions that these compounds form with the µ-opioid receptor.

Addiction withdrawal syndrome: Needs medications, education, counselling & support

Addiction is a feel good or euphoria like condition which is commonly associated with drug abuse (opioid & non-opioid), alcohol and nicotine intake. There are many reasons behind a man gets addicted to these substances such as recreation purpose, drugs used for long time for treatment of any disorder and gets addicted, unemployment, stress, emotions, professional pressure and social status. It provides enjoyable feelings which results in creating a strong urge to use the substances again and again. These drugs can cause physical dependence or psychological dependence or both. Over time, drug tolerance is produced which means to get the same effect more quantity of the drug is needed. These substances are very harmful physically, mentally, financially and socially too. If someone suddenly terminates using these substances after heavy or long term use, the body needs time to recover and number of withdrawal symptoms arises. These withdrawal symptoms can’t be treated by medications only but it needs counselling and support as well. This article reviews i. the drug abuse (opioid & non-opioid), alcohol and nicotine addictions with their withdrawal symptoms and medications used to treat these symptoms ii. Rehabilitation centers running and other steps taken by Government of India to aware people especially the youths of the country about the harmful effects of these substances.

Potential neuroprotective therapies in traumatic acute spinal injury: an integrative review

Introduction: Acute traumatic spinal cord injury is a complex injury affecting the nervous tissue of the spinal cord, vertebrae, joints, innervation and local vasculature, resulting in high mortality, physical dependence, stress, financial losses, lifelong risk of medical complications and reduced longevity. The complexity of the clinical repercussions of acute spinal cord trauma (SCI) makes early interventions necessary to ensure better prognosis. Emerging therapies with neuroprotective agents emerge 1,2,3 Methodology: For the integrative literature review, the PubMed databases were used, Scielo, Google Scholar, Cochrane and the descriptors “spinal injury”; “spinal cord trauma”; “neuroprotective” and “drug therapy”. Results: Therapies with corticosteroids, ion channel blockers, agonists and antagonists of neurotransmitters, cellular and genetic agents, vitamin D, progesterone, erythropoietin and caspase inhibitors demonstrated different neuroprotective effects involving reduction of secondary spinal cord injury and acceleration of neuronal recovery. in uneven research phases. Conclusion: It is concluded that preclinical studies with neuroprotectors as a potential treatment for TRM are promising, however, not all of them evolve into clinical trials, which limits the application of these therapies in humans. Therefore, it is necessary to improve research and clinical trials related to the use of neuroprotective agents in the management of traumatic acute spinal cord injury.

Disturbances in the Ether

<p>We criticise the current philosophical practice of invoking causation as a solution to various problems in various fields of philosophy. Our specific concern is that many of these solutions to problems rely on the intuition that causation is "the cement of the universe". We question whether several different analyses of causation which are supposed to substantiate this intuition (or at least are treated as if they substantiate this intuition) in fact substantiate this intuition. We begin by establishing a basic desideratum for such an analysis of causation - that causal dependence ought to track physical dependence in this universe. We investigate in turn a Lewis-style counterfactual analysis of causation, the transference analysis developed by Aronson, Fair and Heathcote, and the process analyses developed by Salmon and Dowe. Rather to our surprise, none of the analyses fulfil our basic desideratum. Although this is not in itself conclusive grounds for scepticism about causation, our results speak against casually invoking analyses of causation in order to solve particular varieties of philosophical problems.</p>

Disturbances in the Ether

<p>We criticise the current philosophical practice of invoking causation as a solution to various problems in various fields of philosophy. Our specific concern is that many of these solutions to problems rely on the intuition that causation is "the cement of the universe". We question whether several different analyses of causation which are supposed to substantiate this intuition (or at least are treated as if they substantiate this intuition) in fact substantiate this intuition. We begin by establishing a basic desideratum for such an analysis of causation - that causal dependence ought to track physical dependence in this universe. We investigate in turn a Lewis-style counterfactual analysis of causation, the transference analysis developed by Aronson, Fair and Heathcote, and the process analyses developed by Salmon and Dowe. Rather to our surprise, none of the analyses fulfil our basic desideratum. Although this is not in itself conclusive grounds for scepticism about causation, our results speak against casually invoking analyses of causation in order to solve particular varieties of philosophical problems.</p>

Benzodiazepines: Uses, Dangers, and Clinical Considerations

Benzodiazepines (BZDs) are among one of the most widely prescribed drug classes in the United States. BZDs are a class of psychoactive drugs known for their depressant effect on the central nervous system (CNS). They quickly diffuse through the blood–brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects. Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. One of the debilitating side effects of BZDs is their addictive potential. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal. Some of these withdrawal symptoms can be life threatening. The current treatment for withdrawal is through tapering with clonazepam. Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States.

P.190 Choosing Endovascular Treatment or Thrombolysis in Patients with Pre-stroke Comorbidities: UNMASK EVT, a Worldwide Survey

Background: Decisions to treat large-vessel occlusion with endovascular therapy(EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients’ pre-stroke comorbidities. Methods: In an international survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case-scenarios. Five included comorbidities(metastatic/non-metastatic cancer, cardiac/respiratory/renal disease, non-disabling/mild cognitive impairment[MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions. Results: Among 607 physicians(38 countries), EVT was favoured in 1,097/1,379(79.6%) responses for comorbidity-related scenarios under current resources versus 1,510/1,657(91.1%,OR:0.38, 95%CI.0.31-0.47) for six “level-1A” scenarios (assuming ideal conditions:82.7% vs 95.1%,OR:0.25,0.19-0.33). However, this was reversed on including all other scenarios(e.g. under current resources:3,489/4,691[74.4%], OR:1.34,1.17-1.54). Responses favouring alteplase for comorbidity-related(e.g.75.0% under current resources) scenarios were comparable to level-1A scenarios(72.2%) and higher than all others(60.4%). No comorbidity-related factor independently diminished EVT-odds. MCI and dependence carried higher alteplase-odds; cancer and cardiac/respiratory/renal disease had lower odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT, lower alteplase-odds), practicing in East-Asia (higher EVT-odds), and in interventional neuroradiology(lower alteplase-odds vs neurology). Conclusions: Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT.