NIC Group Research Articles

Vitamin B12 supplementation improved memory impairment following nicotine withdrawal in adolescent male rats: The role of oxidative stress, inflammatory, BDNF, GFAP, and AChE activity

The present study aimed to assess the potential effect of vitamin B12 (Vit B12) on cognition impairment caused by nicotine (Nic) cessation in adolescent male rats. Adolescent male rats were categorized into two main groups as vehicle (normal saline, intraperitoneally), and Nic group in which received Nic (2 mg/kg) from 21 to 42 days of ages and then the Nic group were divided into three groups as withdrawal (the animals returned to regular diet without treatment), second and third groups received bupropion (20 mg/kg), and Vit B12 at three different doses including 0.5,1, and 1.5 mg/kg by oral gavage as treatments to attenuate Nic withdrawal symptoms. The last group including normal animals received the highest doses of Vit B12 just in the Nic abstinence period to compare the effect of that with vehicle. In MWM, Vit B12and bupropion increased the time spent in the target quadrant that is strongly associated with spatial memory as well as the more time spent with the NORT. Vit B12 and bupropion modulated both oxidant/antioxidant and inflammatory/anti-inflammatory balance, alongside inhibitory effect on AChE, and GFAP. However, BDNF and amyloid-B showed insignificant difference as compared to Vit B12 and bupropion. Considering the present results and similar related studies, Vit B12 can be introduced as a strong anti-oxidant, and anti-inflammatory agent by which probably improved memory impairment caused by Nic addiction accompanied by withdrawal. Further, other mechanisms including activity reduction of AChE, and GFAP should be considered; however, it needs further investigation and larger-scale evidences.

A propensity-matched cohort study of neoadjuvant immunotherapy combined with chemotherapy versus neoadjuvant chemotherapy for early-stage triple-negative breast cancer.

e13134 Background: Preferred neoadjuvant treatment (NAT) regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. This study compared the efficacy, safety and biomarker exploration of camrelizumab combined with chemotherapy and chemotherapy as neoadjuvant treatment for early-stage TNBC. Methods: This study included 2 cohorts with different NAT regimens, matched (2:1) according to age, clinical T and N stage, and Ki-67 status. Patients in the immune combination chemotherapy (NIC) cohort were recruited from a phase II clinical trial (NCT04676997). NIC patients received intravenous camrelizumab at a dose of 200mg and simultaneous chemotherapy consisted of platinum-free drugs, or platinum containing drugs. Patients in the neoadjuvant chemotherapy (NAC) cohort regimen comprised 4 cycles of paclitaxel 175 mg/m2, and 4 cycles of epirubicin (90 mg/m2, d1, q2w) + cyclophosphamide (600 mg/m2, d1, q2w). The indicators of this study include pCR, breast pCR (bpCR), axillary lymph node dissection (ALND) rate, breast conserving surgery (BCS) rate and tumor immune microenvironment (TIME) analysis of gene expression profiling. Results: Of 252 eligible patients, 162 patients were identified in the analysis after propensity score matching (PSM). Compared with NAC alone, the addition of camrelizumab brought higher pCR rates (64.81% versus 37.04%, p<0.05), ALND rates (38.89% versus 12.96%, p<0.05) and comparable BCS rates (20.37% versus 15.74%, p<0.05). Gene expression analysis was performed on tumor tissue samples from 12 patients receiving NAC and 16 patients receiving NIC before and after NAT. The results showed that the TIME status of the NIC and NAC groups before treatment was basically the same. Moreover, we respectively compared the TIME status of patients with pCR and non_pCR in NIC and NAC before NAT. The results found that there were 9 significantly different signatures (p<0.05) between pCR and non_pCR patients in the NIC group, and 1 signature (p<0.05) in the NAC group, respectively. Notably, we found 8 signatures (B Cells, CD8 T Cells, TIS, IFN Gamma, Lymphoid, T Cell, APM, Immunoproteasome), that were scored significantly higher only in pCR patients in the NIC group compared with non-pCR patients, and 8 signatures could promote response to immunotherapy. The common difference signature between the two groups is Treg cells. Conclusions: In patients with early-stage TNBC, neoadjuvant treatment with camrelizumab plus chemotherapy significantly improved pCR with an acceptable safety profile. Differences in TIME may affect response to treatment regimens. Future validation in prospective randomized controlled trials with larger sample sizes is needed. Clinical trial information: NCT04676997 .

Gender Disparities in Neurobehavioral Symptoms and the Role of Post-Traumatic Symptoms in US Service Members Following Mild Traumatic Brain Injury.

Women are more directly involved in combat operations today than ever before, currently making up 18.6% of officers and 16.8% of enlisted personnel in the United States military. However, women continue to be under-represented in military research. Studies that do consider gender differences in traumatic brain injury (TBI) outcomes have shown that women report significantly more post-concussive symptoms than men. Conclusions for true gender differences related to TBI are hard to make without controlling for non-TBI factors. The effects previously identified in the literature may be an artifact of how men and women differ in their response to injury, unrelated to the neurological recovery process associated with TBI. The objective of this study was to examine the effects of gender specifics on mild TBI (mTBI) sequelae on injured and uninjured control groups, and to investigate the role of post-traumatic stress disorder (PTSD) on symptom reporting. It should be noted that the terms "gender" and "men/women" are used in this article in place of "sex" or "males/females" given that we are not discussing biological attributes. A total of 966 United States military service members and veterans were included in the study. Of the total sample, 455 men and 46 women were in the mTBI group, 285 men and 31 women were in the injured controls group (IC), and 111 men and 38 women in the non-injured controls group (NIC). Post-concussive and quality of life symptoms were compared for men and women while controlling for combat exposure. MTBI and IC groups were also stratified by PTSD presentation. Measures used included the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist (PCL-C), Traumatic Brain Injury Quality of Life (TBI-QOL), and Combat Exposure Scale. In the mTBI group, women had worse scores on NSI total, NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety, Fatigue, and Headache scales (n2 = 0.018-0.032, small to small-medium effect sizes). When PTSD was present, women had worse scores on the NSI Somatosensory cluster only (n2 = 0.029, small-medium effect size). In contrast, when PTSD was absent, women had worse scores than men on the NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety and Headache scales (n2 = 0.032-0.063, small to medium effect sizes). In the IC group, women had worse scores on the NSI Cognitive cluster and the TBI-QOL Fatigue and Pain Interference scales (n2 = 0.024-0.042, small to small-medium effect sizes). However, group differences were no longer found when stratified by PTSD sub-groups. In the NIC group, there were no significant group differences for any analyses. We were able to identify symptoms unique to women recovering from mTBI that were not present following other forms of physical injury or in healthy controls. However, the impact of PTSD exacerbates the symptom profile and its comorbidity with mTBI equates to most of the noted gender differences.

Serum GFAP, NfL, and tau concentrations are associated with worse neurobehavioral functioning following mild, moderate, and severe TBI: a cross-sectional multiple-cohort study.

The purpose of this study was to examine whether blood-based biomarkers associate with neurobehavioral functioning at three time points following traumatic brain injury (TBI). Participants were 328 United States service members and veterans (SMVs) prospectively enrolled in the Defense and Veterans Brain Injury Center-Traumatic Brain Injury Center of Excellence (DVBIC-TBICoE) 15-Year Longitudinal TBI Study, recruited into three groups: uncomplicated mild TBI (MTBI, n = 155); complicated mild, moderate, severe TBI combined (STBI, n = 97); non-injured controls (NIC, n = 76). Participants were further divided into three cohorts based on time since injury (≤12 months, 3-5 years, and 8-10 years). Participants completed the Minnesota Multiphasic Personality Inventory-2-Restructured Format (MMPI-2-RF) and underwent blood draw to measure serum concentrations of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau. A total of 11 MMPI-2-RF scales were examined (e.g., depression, anxiety, anger, somatic, cognitive symptoms). Stepwise hierarchical regression models were conducted within each group. Significant associations were found between biomarkers and MMPI-2-RF scales (all p < 0.05; R2Δ > 0.10). GFAP was inversely related to (a) neurological complaints in the MTBI group at ≤12 months, (b) demoralization, anger proneness in the STBI group at ≤12 months, and (c) head pain complaints in the STBI group at 8-10 years. NfL was (a) related to low positive emotions in the NIC group; and inversely related to (b) demoralization, somatic complaints, neurological complaints, cognitive complaints in the MTBI group at ≤12 months, (c) demoralization in the STBI group at ≤12 months, and (d) demoralization, head pain complaints, stress/worry in the STBI group at 3-5 years. In the STBI group, there were meaningful findings (R2Δ > 0.10) for tau, NFL, and GFAP that did not reach statistical significance. Results indicate worse scores on some MMPI-2-RF scales (e.g., depression, stress/worry, neurological and head pain complaints) were associated with lower concentrations of serum GFAP, NfL, and tau in the sub-acute and chronic phase of the recovery trajectory up to 5 years post-injury, with a reverse trend observed at 8-10 years. Longitudinal studies are needed to help elucidate any patterns of association between blood-based biomarkers and neurobehavioral outcome over the recovery trajectory following TBI.

Efficacy and Safety of Nicotinamide 10%, Associated with Magnesium Ascorbyl Phosphate 5% and Hyaluronic Acid 5%, Compared to Hydroquinone 4% in Women with Facial Melasma: A Randomized, Double-Blind, Controlled Clinical Trial.

Nicotinamide has demonstrated efficacy in the treatment of melasma. Topical antioxidants and humectants may enhance its performance. Currently, there is no controlled trial on the combination of 10% nicotinamide, 5% magnesium ascorbyl phosphate, and 5% hyaluronic acid, a dermo-cosmetic compound, in comparison to 4% hydroquinone for the treatment of melasma. This study aimed to explore the tolerability and efficacy of the association of the combined product versus hydroquinone. A randomized, double-blind trial involving women with facial melasma was conducted. Participants were instructed to apply the combined product (NIC group) twice daily or 4% hydroquinone for 60 days (HQ group) at night and placebo in the morning. Evaluations were performed at inclusion, after 14 and 60 days of treatment, measuring the modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life Scale (MELASQoL), and colorimetric luminosity. The Global Aesthetic Improvement Scale (GAIS) was assessed by a blinded evaluator. Both interventions led to a progressive improvement in mMASI, MELASQoL, and GAIS, without a difference between them on D14 and D60 (p>0.2). For NIC, the mean reduction (95% CI) in mMASI was 16% (8-24%) on D14 and 32% (23-41%) on D60, while for HQ, it was 10% (7-24%) on D14 and 43% (34-52%) on D60. Reduction in colorimetric luminosity was greater in the HQ group at D60 (p=0.01). No serious side effects were identified. Of the initially included 50 patients, one was lost to follow-up in the HQ group on D60, and one withdrew consent from the NIC group, both unrelated to treatment. The association of 10% nicotinamide, 5% magnesium ascorbyl phosphate, and 5% hyaluronic acid was safe and well-tolerated, although its overall clinical efficacy was numerically inferior to 4% hydroquinone. This regimen can be considered for patients with poor tolerability to hydroquinone. #RBR-4mkfmr8.

Nicotine plays a protective role in rats with induced viral pneumonia with polyinosinic-polycytidylic acid through α7nAChR

ObjectiveTo study the effect of nicotine in rat model of pneumonia induced by polyinosinic-polycytidylic acid [Poly (I:C)] and explore the underlying mechanism. MethodsTwenty-four healthy adult male Sprague-Dawley (SD) rats (200–250 g) were randomly divided into normal saline control group (NS group); Poly (I:C) group; nicotine group (NIC group); and α7 nicotinic acetylcholine receptor (α7nAChR) antagonist group (α-BGT group) (n = 6 each). Rats in the Poly (I: C), NIC, and α-BGT groups were administered 1.5 mg/mL 100 μL Poly (I:C) intranasally to establish pneumonia model. In α-BGT group, 1 μg/kg α-bungarotoxin (α-BGT) was intraperitoneally injected 45 min before intranasal Poly (I:C), and 400 μg/kg nicotine was intraperitoneally injected 15 min after α-BGT injection. The NIC group received an equal volume of NS in place of α-BGT while the other treatments were same. The Poly (I:C) group received equal volume of NS in place of nicotine while the other treatments were same as in NIC group. In the NS group, only NS was administered at all three time points. PaCO2, PaO2, and PaO2/FiO2 levels were determined 24 h after administration of Poly (I:C). After euthanization, rat lung tissues were extracted for pathological examination, and wet weight/dry weight (W/D ratio) was determined. Expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, and interferon (IFN)-γ in lung tissue was determined by ELISA. q-PCR was used to detect nuclear factor kappa-B P65 (NF-κBP65). ResultsCompared with NS group, Poly (I:C) and α-BGT groups showed significantly increased W/D ratio, PaCO2, TNF-α, IL-6, IL-1β, and IFN-γ content, NF-κB P65 expression, and reduced PaO2 and PaO2/FiO2 (p < 0.05), along with obvious signs of pathological injury. Nicotine pre-treatment reduced W/D ratio, PaCO2, proinflammatory cytokines, NF-κBP65 expression, and increased PaO2 and PaO2/FiO2 levels. The above effects were negated in α-BGT group. ConclusionPre-administration of nicotine improved Poly (I:C)-induced pneumonia by activating the cholinergic anti-inflammatory pathway.

Effect Of Surface Treatment on The Shear Bond Strength Between Nickel-Chromium Alloy and Veneering Porcelain

Nickel–chromium (Ni–Cr) alloys, have been used widely, due to their superior physical properties and economic issues in relation to other precious alloys. Many studies have been carried out on porcelain fused to metal restorations to enhance the bonding quality of the porcelain to Ni-Cr alloy, such as mechanical treatment by air abrasion particles or chemical treatment by acid etching to increase the longevity of the restoration. The purpose of this study is to investigate the effect of surface treatments sandblasting with Aluminum Oxide (Al2O3), acid etching with Potassium hydrogen difluoride acid (KHF2) and combination treatment on the shear bond strength between Nickel-chromium alloy substructure and porcelain veneer. Twenty-one cylindrical shaped samples have base of 5 mm in diameter and 1 mm in thickness and a cylinder with 4 mm in diameter and 4 mm in length were prepared from Ni – Cr alloy. The samples were divided into 3 groups (n=7) according to surface treatment: Nickel -chromium treated with sandblasting with 50μm Al2O3 group (c), Nickel – chromium etching with KHF2 group (k), and Nickel – chromium sandblasting with 50μm Al2O3 followed with acid etching with KHF2 group (comb). Then ceramic build up (opaque, dentin, enamel, and glaze Vita VMK Master opaque, dentin, enamel, and glaze Vita VMK Master) and sintering was performed according to manufacturer's instructions and the final dimension of porcelain cylinder (4 X 4X 1) were checked with a metal gauge. All samples were subjected to shear force in a universal testing machine at cross head speed 0.5 mm/min. and recorded in MPa. The fractured samples were checked under (DIGITAL MICROSCOPE) (X50) to evaluate the mode of failure, it was adhesive, cohesive and mixed failure modes. The shear bond strength values were analyzed with one-way ANOVA and LSD. The results showed that the highest mean of shear bond strength values was in Ni – Cr combination surface treatment group (26.11 ± 1.85), while the lowest mean was for Ni- Cr acid etched group (22.02 ± 1.5) and Nic group (20.85 ± 1.5). Within the limitation of the present study, the following conclusion can be drawn: Combination surface treatment produced the highest shear bond strength between Ni – Cr surface and veneering porcelain, followed by etching with KHF2, so combination method would increase longevity of porcelain fused to metal restorations.

Vitamin B12 reversed anxiety and depression induced by adolescent nicotine withdrawal through alteration the inflammatory, oxidative and serotoninergic profiles in male rats

BackgroundThe present study aims to assess the effect of vitamin B12 (Vit B12) on depression-like behavior caused by nicotine (Nic) withdrawal, which is more likely due to the anxiogenic effect of Nic in adolescent male rats, through assessing behavioral and biochemical analysis. MethodsAdolescent male rats were divided into vehicle (received normal saline), and experimental groups that received Nic (2 mg/kg, intraperitoneally (i.p.)) for three consecutive weeks and after that, the group that received normal saline was divided into two groups, one of which returned to a regular diet, and the second one received Vit B12 (1.5 mg/kg). The Nic group was divided into five groups, one of which received bupropion (Bup, 20 mg/kg), three of which received different doses of Vit B12 (0.5, 1, and 1.5 mg/kg), and the last one returned to a normal diet without treatment, which was considered as the withdrawal period. ResultsBehavioral analysis showed that Nic withdrawal induced anxiety and depression. Vit B12 and Bup reduced anxiety and depression induced by Nic withdrawal. The biochemical analysis demonstrated the more activity of oxidative stress factors and pro-inflammatory cytokines in which Nic was administered, whereas both Vit B12 and Bup reversed the results and improved the activity of both antioxidant and anti-inflammatory parameters. Furthermore, both serum and cortical Vit B12 levels dramatically decreased in nicotine group, whereas treatment with both Vit B12 and Bup as desirable treatments corrected Vit B12 levels. ConclusionAccording to the present findings, the results revealed that Vit B12 is comparable with Bup in attenuation of Nic withdrawal symptoms. In addition, both Bup and Vit B12 improved the decreased serum and cortical levels of Vit B12, which caused by nicotine. Administration of Vit B12 in normal animals demonstrated better results in reducing antioxidant and anti-inflammatory parameters, which explores new hope to introduce Vit B12 as a novel antioxidant and anti-inflammatory agent to treat not only withdrawal, but also other diseases related to the prominent role of oxidative stress or inflammatory pathways, such as Alzheimer’s disease.

Serum Tau, Neurofilament Light Chain, Glial Fibrillary Acidic Protein, and Ubiquitin Carboxyl-Terminal Hydrolase L1 Are Associated with the Chronic Deterioration of Neurobehavioral Symptoms after Traumatic Brain Injury.

The purpose of this study was to examine the association of serum tau, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCHL-1) concentrations evaluated within the first 12 months after a military-related TBI, with longitudinal changes in neurobehavioral functioning extending two or more years post-injury. Participants were 84 United States service members and veterans (SMVs) prospectively enrolled in the Defense and Veterans Brain Injury Center of Excellence/Traumatic Brain Injury Center 15-Year Longitudinal TBI Study, separated into three discreet groups: (a) uncomplicated mild TBI (MTBI; n = 28), (b) complicated mild, moderate, severe, and penetrating TBI combined (STBI; n = 29], and (c) non-injured controls (NIC, n = 27). Participants completed a battery of self-report neurobehavioral symptom measures (e.g., depression, post-traumatic stress disorder [PTSD], post-concussion, anxiety, somatic, cognitive, and neurological symptoms) within 12 months of injury (baseline), and then again at two or more years post-injury (follow-up). At baseline, participants also completed a blood draw to determine serum concentrations of tau, NFL, GFAP, and UCHL-1 using an ultra-sensitivity assay method. In the MTBI and STBI groups (using hierarchical regression analyses), (1) baseline tau concentrations predicted the deterioration of neurobehavioral symptoms from baseline to follow-up on measures of anxiety, PTSD, depression, post-concussion, somatic, and neurological symptoms (accounting for 10-28% of the variance); (2) NFL predicted the deterioration of depression, post-concussion, somatic, cognitive, and neurological symptoms (10-32% variance); (3) GFAP predicted the deterioration of post-concussion, PTSD, depression, anxiety, somatic, neurological, and cognitive symptoms (11-43% variance); and (4) UCHL-1 predicted the deterioration of anxiety, somatic, and neurological symptoms (10-16% variance). In the NIC group, no meaningful associations were found between baseline biomarker concentrations and the deterioration of neurobehavioral symptoms on the majority of measures. This study reports that elevated tau, NFL, GFAP, and UCHL-1 concentrations within the first 12 months of injury are associated with the deterioration of neurobehavioral symptoms that extends to the chronic phase of recovery after a TBI. These findings suggest that a blood-based panel including these biomarkers could be a useful prognostic tool to identifying those individuals at risk of poor future outcome after TBI.

Roles of alpha-7 nicotinic acetylcholine receptors and spleen in the lung injury induced by a repeated saline lavage in rat

BackgroundThe study aimed to determine whether or notα7 nicotinic acetylcholine receptors (α7nAChR) induce anti-inflammatory effects directly in the lung or through the spleen pathway in a sterile model of lung injury by saline lavage.MethodsMale Sprague Dawley rats were divided into seven groups; Sham, splenectomy (SPX), saline lavage (LAV), LAV treated with α7nAChR agonist nicotine (LAV + NIC), and LAV treated with NIC and a selective α7nAChR antagonist MLA (LAV+MLA+NIC), LAV and splenectomy (LAV+SPX), and LAV+SPX treated with nicotine (LAV+SPX+NIC). Tracheostomy and catheterization of the femoral artery were performed under deep anesthesia. Animals were subjected to volume-controlled ventilation and lung injury by 10 repeated saline lavages. Splenectomy was achieved one week before the induction of lung injury. The recovery phase lasted for 3 h, and drugs were injected 1 h after the last lavage.ResultsMean arterial blood pressure (MBP), heart rate (HR), PaO2, PaO2/FiO2 ratio, and pH decreased, whereas, maximal inspiratory (MIP) and expiratory (MEP) pressures, and PaCO2 increased 1 h after the saline lavage. Nicotine corrected entirely all the above parameters in the LAV + NIC group. MLA or SPX prevented the effects of nicotine on the above parameters, except that MLA had no extra effect on MIP or MEP. In addition, nicotine improved lung compliance in the LAV + NIC and LAV + SPX + NIC groups, though it was inhibited by MLA in the LAV + MLA + NIC group. The increases of plasma and lung tissue malondialdehyde (MDA) in the LAV group were diminished by nicotine, whereas, MLA and SPX prevented these reductions. Besides, nicotine could reduce plasma MDA in the LAV + SPX + NIC group. Total BAL cell count, protein BAL/protein plasma ratio, and lung histological scores were attenuated by nicotine in the LAV + NIC group, whereas, MLA reversed the mentioned alterations in the LAV + MLA + NIC group. However, splenectomy could not stop the decreasing effect of nicotine on the total BAL cell in the LAV + SPX + NIC group.ConclusionsIn this study, we indicated that α7nAChR and spleen play roles in cholinergic anti-inflammatory pathways in saline lavage-induced lung injury. However, our results are in favor of at least some direct effects of α 7nAChR in the lung.

Childhood Imaginary Companion and Schizotypy in Adolescents and Adults

Objective: This study evaluated the association of Childhood Imaginary Companion (CIC) status and schizotypy levels of adolescents and adults within the framework of the Hierarchical Taxonomy of Psychopathology (HiTOP). Method: The sample included 255 Iranian adolescents and adults, grouped according to their CIC status, who responded mostly via e-questionnaires on a website. Schizotypy dimensions were compared between these two groups. Two measures compatible with the HiTOP model were also evaluated both in relation to the short scale of the Oxford-Liverpool Inventory of Feelings and Experiences (sO-LIFE) schizotypy dimensions and the CIC status of participants; one scale used exclusively with adolescents (i.e., the Achenbach System of Empirically-Based Assessment-Youth Self-Report [ASEBA-YSR]), and another with adults (i.e., the NEO-Five Factor Inventory [NEO-FFI]). Results: Scores on the unusual experiences (UnEx) the impulsive nonconformity (ImpNon) dimensions, and the total score of the sO-LIFE were higher for the CIC group. For adolescents, the UnEx dimension and the Thought Problems subscale of the ASEBA-YSR correlated. Scores on three subscales of the ASEBA-YSR (i.e., Thought Problems, Obsessive-Compulsive Problems, and PTSD Problems) were significantly higher for the CIC group. For adults, the neuroticism domain of the NEO-FFI correlated strongly with total score of the sO-LIFE and the cognitive disorganization (CogDis) dimension. This domain of the NEO-FFI was the only one in which CIC adults scored higher than the NIC group. Conclusion: CIC in adolescents and adults is associated with a set of schizotypy dimensions in line with the concept of the “happy schizotype.”

Understanding the stimulus effects of nicotine and bupropion in a drug-drug discriminated goal-tracking task.

Bupropion is a non-nicotine medication for smoking cessation that has overlapping stimulus effects with nicotine as demonstrated in drug discrimination studies. Whether these shared stimulus effects will alter acquisition or maintenance of a discrimination between nicotine and bupropion is unknown. We sought to test this possibility using the drug discriminated goal-tracking (DGT) task and whether discrimination training history affected generalization and substitution tests. Sixty adult Sprague-Dawley rats (30M/30F) were equally split into three discrimination training groups: SAL-0.4NIC, 10BUP-0.4NIC, and 20BUP-0.4NIC. On nicotine days, all rats were administered subcutaneously 0.4mg/kg nicotine and had intermittent access to liquid sucrose. On intermixed non-reinforced days, rats were administered intraperitoneally saline, 10 or 20mg/kg bupropion. Upon completion, a range of nicotine and bupropion doses were assessed before substitution tests with varenicline and sazetidine-A were conducted. The SAL-0.4NIC and 10BUP-0.4NIC groups readily discriminated by session 8, as evidenced by increased dipper entries (goal-tracking) on nicotine days. The 20BUP-0.4NIC group was slower to acquire the discrimination. Female rats, regardless of group, had higher conditioned responding evoked by the lowest dose of nicotine (0.025mg/kg) in the dose-effect curve. The discrimination required rats to learn to withhold responding to the training dose of bupropion. This withholding of excitatory dipper entries generalized to other doses. Varenicline and sazetidine-A partially substituted for the nicotine stimulus, and this pattern did not differ with training history. We are the first to study a drug-drug discrimination using the DGT task. Females appeared to have a lower discrimination threshold for nicotine that was not impacted by the learning history. Further work on the importance of sex as a biological variable and how the complex interoceptive stimulus effects of nicotine can vary with training histories is needed.

Oropharynx microbiota transitions in hypopharyngeal carcinoma treatment of induced chemotherapy followed by surgery

AimsTo analyze changes in oropharynx microbiota composition after receiving induced chemotherapy followed by surgery for hypopharyngeal squamous cell carcinoma (HPSCC) patients.MethodsClinical data and swab samples of 38 HPSCC patients (HPSCC group) and 30 patients with benign disease (control group, CG) were enrolled in the study. HPSCC group was stratified into two groups: induced chemotherapy group (IC) of 10 patients and non-induced chemotherapy group (nIC) of 28 patients. The microbiota from oropharyngeal membrane was analyzed through 16S rRNA sequencing.ResultsAlpha-diversity (Shannon and Ace indexes) and weighted UniFrac based beta-diversity severely decreased in the HPSCC group when compared with CG. In pre-operative comparisons, PCoA and NMDS analyses showed microbial structures in the IC group were more similar to CG than nIC. Both IC group and nIC group yielded significantly diverse post-operative communities in contrast to their pre-operative counterparts, evident by the decrease in genera Veillonella and Fusobacterium and increase in genera Streptococcus and Gemella. Given that post-operative oropharynx microbiota showed no difference between IC and nIC groups, the IC group showed less accumulation in anaerobic communities. The abundance of genera Fusobacterium, Parvimonas, Actinomyces were enhanced in the advanced stages (III/IV).ConclusionsOropharynx microbiota in the HPSCC group presents dysbiosis with low diversity and abundance. Induced chemotherapy is beneficial in adjusting the oropharynx microbial environment leading to fewer amounts of anaerobe accumulation after operation. Higher amounts of Fusobacterium in advanced stages (III/IV) may influence the progression of HPSCC.

Nicotine supplementation enhances simulated game performance of archery athletes

BackgroundNicotine is beneficial to mood, arousal and cognition in humans. Due to the importance of cognitive functioning for archery athletes, we investigated the effects of nicotine supplementation on the cognitive abilities, heart rate variability (HRV), and sport performance of professional archers.MethodsEleven college archers were recruited and given 2 mg of nicotine supplementation (NIC group) and placebo (PLA group) in a crossover design.ResultsThe results showed that at 30 min after the intake of nicotine gum, the “correct rejection” time in the NIC group was significantly lower than that of the PLA group (7.29 ± 0.87 vs. 8.23 ± 0.98 msec, p < 0.05). In addition, the NIC group completed the grooved pegboard test in a shorter time than the PLA group (48.76 ± 3.18 vs. 53.41 ± 4.05 s, p < 0.05), whereas motor reaction times were not different between the two groups. Saliva α-amylase activity was significantly lower after nicotine supplementation (p < 0.01) but increased immediately after the archery test in the NIC group (p < 0.05). In addition, nicotine supplementation significantly decreased HRV and increased the archery score (290.58 ± 10.09 vs. 298.05 ± 8.56, p < 0.01).ConclusionsNicotine enhances the performance of archery athletes by increasing cognitive function and stimulating the sympathetic adrenergic system.

A-117 Sleep Disruption has a Stronger Influence on Self-reported Neurobehavioral Status than Traumatic Brain Injury in U.S. Military Service Members and Veterans

Abstract Objective To examine the relation between sleep disruption and neurobehavioral outcome following mild, moderate, and severe traumatic brain injury (TBI). Methods Participants were 509 U.S. military service members/veterans divided into four groups: uncomplicated mild TBI (n = 183; MTBI); complicated mild TBI and moderate–severe TBI (n = 96; STBI); injured controls (n = 138; IC); and non-injured controls (n = 92; NIC). Participants completed a 2-hour neurobehavioral test battery 12 or more months post-injury that included the PTSD Checklist and 13 scales from the TBI-Quality of Life (TBI-QOL). Using the TBI-QOL Sleep Disturbance scale, participants were classified into two ‘Sleep’ subgroups: Poor Sleep (55 T or higher) or Good Sleep (50 T or lower). Results A higher proportion of the MTBI group was classified as having Poor Sleep (79.2%) compared to the IC (64.5%) and STBI (58.3%) groups; and all were higher than the NIC group (40.2%). In each group separately, participants with Poor Sleep had significantly worse scores on all TBI-QOL scales compared to those with Good Sleep (all p’s &amp;lt; .001, d = .68 to d = 1.98). Participants with Poor Sleep consistently had worse TBI-QOL scores regardless of TBI severity or the presence/absence of TBI (all p’s &amp;lt; .05). Additionally, there was a significant interaction between Sleep and PTSD. Both factors combined resulted in worse outcome than either factor alone (p’s &amp;lt; .05). Conclusions Poor Sleep had a very strong influence on self-reported neurobehavioral outcome, and a greater influence on outcome than TBI severity or the presence/absence of TBI. Poor Sleep may be a useful ‘risk factor’ that can be used clinically to identify individuals in need of early intervention.

Menthol blunts the interoceptive discriminative stimulus effects of nicotine in female but not male rats.

Menthol is a widely used tobacco constituent that has shown to enhance nicotine's reinforcing effects. To determine whether injected menthol also alters nicotine's stimulus effects, we used a drug discrimination task. A total of 57 adult Sprague-Dawley rats (28M, 29F) received 20 positive and 20 negative days (intermixed) of discrimination training. On positive days, rats received a group-specific menthol and nicotine injection (VEH + 0.1 NIC, 1 M + 0.1 NIC, 5 M + 0.1 NIC, VEH + 0.4 NIC, 1 M + 0.4 NIC, 5 M + 0.4 NIC; mg/kg) before eight 15-s cue light presentations (conditioned stimulus (CS)), each followed by 4-s sucrose access. On negative days, all rats were injected with vehicle and saline before eight non-reinforced CS presentations. Next, rats underwent generalization testing with 30 dose combinations of menthol and nicotine. The change in drug-mediated anticipatory goal tracking during the CS was calculated as a difference score (CS minus pre-CS responding). All groups readily acquired drug discrimination. However, difference scores for the 5M + 0.1 NIC group were lower for females. Additionally, females had lower scores for 0.05, 0.1, and 0.4 mg/kg nicotine generalization tests. The lowest nicotine dose discriminable from saline was 0.05 mg/kg for females but 0.025 mg/kg for males. Co-administration with 5 or 10 mg/kg menthol weakened discrimination performance between 0.1 and 0.4 mg/kg and between 0.1 and 0.05 mg/kg nicotine for 0.1 mg/kg nicotine training groups. Female rats that were trained with 0.1 mg/kg nicotine were more sensitive to menthol's modulatory effects on nicotine's stimulus effects. This highlights the importance of taking sex and training dose into account when evaluating the interoceptive stimulus effects of nicotine and menthol.

Traumatic Brain Injury and Its Relationship to Previous Convictions, Aggression, and Psychological Functioning in Dutch Detainees

ABSTRACT Objective: Higher prevalence of traumatic brain injury (TBI) has been reported for detained individuals. TBI may result in erroneously interpreting situations in everyday life, impair problem-solving abilities through dialogue, or negotiation, which may increase aggressive behavior. Knowledge of TBI and its consequences in Dutch penitentiaries is lacking, as virtually no screening, supervision, or treatment is currently provided. Method: The current manuscript assesses differences in self-reported aggression, impulsivity, indication for mild intellectual disability, history of childhood trauma, and emotion regulation in detainees (n = 283) and non-incarcerated controls (NIC; n = 51), with and without a history of TBI. Result: A total of 45.2% of detainees reported a TBI, compared to 29.4% in the NIC group. ANCOVA results revealed no interaction between group and TBI history, indicating that TBI history did not affect behavior in detainees and NIC differently. The main effects revealed higher levels of aggression in detainees compared to NICs, and in participants with TBI compared to those without. Separate ANCOVA’s per group reveal that TBI history in detainees was associated with more aggression – also when correcting for violence as the cause of TBI. A logistic regression revealed that detainees with TBI have a higher chance (odds ratio = 3.3) of having at least one prior conviction. Conclusions: TBI history was related to aggressive behavior in Dutch inmates, future studies should assess if TBI history is predictive of in-prison infractions and recidivism rates, and if screening and providing neuro-rehabilitative measures or improved supervision may improve TBI related deficits.

Programming of hepatic lipid metabolism in a rat model of postnatal nicotine exposure – Sex-related differences

Maternal nicotine exposure during lactation induces liver damage in adult male rats. However, the mechanism in males is unknown and females have not been tested. Here, we determined the liver lipid composition and lipogenic enzymes in male and female offspring at two ages in a model of postnatal nicotine exposure. Osmotic minipumps were implanted in lactating Wistar rat dams at postnatal day (PND) 2 to release 6 mg/kg/day of nicotine (NIC group) or saline (CON group) for 14 days. Offspring received a standard diet from weaning until euthanasia at PND120 (1 pup/litter/sex) or PND180 (2 pups/litter/sex). At PND120, NIC males showed lower plasma triglycerides (TG), steatosis degree 1, higher hepatic cholesterol (CHOL) ester, free fatty acids, monoacylglycerol content as well as acetyl-coa carboxylase-1 (ACC-1) and fatty acid synthase (FAS) protein expression in the liver compared to CON males. At this age, NIC females had preserved hepatocytes architecture, higher plasma CHOL, higher CHOL ester and lower total CHOL content in the liver compared to CON females. At PND180, NIC males showed steatosis degrees 1 and 2, higher TG, lower free fatty acids and total CHOL content in the liver and an increase in ACC-1 hepatic protein expression. NIC females had higher plasma TG and CHOL levels, no change in hepatic morphology, lower CHOL ester and free fatty acids in the liver, which also showed higher total ACC-1 and FAS protein expression. Maternal nicotine exposure induces long-term liver dysfunction, with an alteration in hepatic cytoarchitecture that was aggravated with age in males. Concerning females, despite unchanged hepatic cytoarchitecture, lipid metabolism was compromised, which deserves further attention.

Oral inoculation of ultraviolet-irradiated Eimeria species oocysts protects chickens against coccidiosis.

Prevention of coccidiosis is one of the best ways of controlling disease. Therefore, the present study was carried out to evaluate the protective effect of ultraviolet (UV)-irradiated sporulated oocysts of Eimeria species against coccidiosis in layer chickens. One hundred forty-four one-day-old layer chicks were randomly divided into 4 groups (n = 36), including non-immunized/non-challenged negative control group (NC group), non-immunized/challenged control group (NIC group), non-irradiated sporulated oocyst/challenged group (CA group), and UV-irradiated sporulated oocyst/challenged (UV group). At the age of 4days, chickens in groups UV and CA were both orally inoculated with 1.0 × 104 UV-irradiated and non-irradiated sporulated oocysts of Eimeria species, respectively. Chickens in groups NIC and NC were served as positive and negative controls, respectively. Chickens in all groups were orally challenged with 7.5 × 104 sporulated oocysts of Eimeria species except the NC group at the age of 21days. The results revealed that chicks receiving UV-irradiated sporulated oocysts had no signs of illness with minimal or no changes in the cecal integrity and a significantly lower oocyst shedding (OPG) than in the NIC group. Additionally, the cytokine gene expression profiles were evaluated. Expression levels of IL-2, IL-12, and IFN-γ were significantly higher in the spleen of chicks in the UV and CA groups than in the NC group post-challenge. As expected, treatment with irradiated oocysts resulted in a significant reduction in oocyst shedding and maintenance of cecal mucosal integrity. Furthermore, the body weight was higher in chickens inoculated with UV-irradiated oocysts than their non-irradiated counterparts. In conclusion, our results demonstrate that inoculation with UV-irradiated sporulated oocysts of Eimeria species can produce a substantial reduction in infection symptoms.

Reduced adolescent risk-assessment and lower nicotinic beta-2 expression in rats exposed to nicotine through lactation by forcedly drinking dams

Few animal studies focus on consequences of nicotine postnatal exposure, particularly through lactation. We have recently shown that forced nicotine drinking elevates maternal care, paradoxically provoking arousal and stress in pups. Present work aimed to evaluate the specific contribution of altered maternal cares, compared to the sequelae merely due to nicotine effects. Two groups were compared to water-drinking control dams: (i) free-choice dams (H2O+NIC group) drinking from two bottles, containing either nicotine or water; (ii) forced dams (NIC+NIC group) drinking from two bottles, both containing nicotine. We previously demonstrated that nicotine was indeed transferred to the lactating offspring. Regarding behavioural consequences at adolescence, both H2O+NIC and NIC+NIC rats were slower than controls in discovering a novel over a familiar compartment, whilst only NIC+NIC rats exhibited reduced risk-related avoidance and assessment behaviour. Brain analyses at adulthood suggest that, in prefrontal cortex, nicotine per se reduced serotonin, while the maternal overcare reduced CHRN-B2 gene-expression. As a whole, unescapable nicotine-enhanced maternal care could have an impact on the offspring arousal by acting on prefrontal CHRN-B2 gene-expression. When present results are translated to consequences of non-voluntary exposure in humans, we propose that children receiving altered attentions by a smoking caregiver might undergo a neuro-behavioural development biased towards emotional shyness.