Sex Differences in Withdrawal-Induced Anxiety in Rats After Exposure to Tobacco Smoke.

Nicotine, a component of cigarettes, possesses strong reinforcing properties and improves cognitive function, which can lead to dependence. Upon cigarette smoking cessation, withdrawal symptoms occur and may cause an individual to relapse. Affective withdrawal symptoms, such as anxiety, is of great concern as studies have shown its ability to cause relapse in men and women. In this in vivo study, anxiety resulting from smoking cessation after 2-day smoke-free intervals per week for the duration of 4 weeks was investigated in 8 male and 8 female rats after their exposure to cigarette smoke compared to unexposed control rats (8 males and 8 female rats). The anxiety in rats during smoke-free intervals was investigated using an elevated plus-maze (EPM), open-field (OF), and light/dark test (LD). In all tests male rats exhibited significantly higher anxiety symptoms compared to female rats during nicotine withdrawal, despite control rats showing no differences. In the EPM, male rats spent less time in open arm as well having as lower number of crossings than female rats. As for the OFT, the amount of time spent in the center of the open field was also lower in male rats than female rats. In the LD test, the time spent in the light chamber and the latency (delay) to enter the dark chamber was lower in male rats compared to female rats. Our study showed that male rats show greater nicotine withdrawal effects, in terms of anxiety-like behavior than female rats.

Assessment of Zonular Integrity in Phakic Eyes Following Pars Plana Vitrectomy Using Ultrasound Biomicroscopy: A Prospective Paired Eye Comparative Study.

PURPOSE: To assess zonular integrity in phakic patients post vitrectomy using ultrasound biomicroscopy (UBM). DESIGN: Prospective, comparative, nonrandomized, double-masked, paired eye study. METHODS: We used ultrasound biomicroscopy (UBM) to evaluate phakic patients with a history of unilateral pars-plana vitrectomy. INCLUSION CRITERIA: (1) phakic patients with history of pars plana vitrectomy in one eye as the only procedure; (2) normal unoperated fellow eye; and (3) complete gas or air resolution from the vitreous cavity at the time of UBM assessment. EXCLUSION CRITERIA: (1) monocular patients; (2) history of intraoperative lenticular trauma; (3) the use of silicone oil tamponade; (4) history of trauma or pseudoexfoliation in either eye; (5) history of other ocular conditions that can affect the integrity of zonules, such as uveitis or ectopia lentis; (6) eyes with extreme myopia or long axial length (> -8.00 D or >30.0 mm); (7) history of intravitreal injection in either eye; (8) age <18 years. TECHNIQUE: A high-frequency (50 MHz) UBM device was used by a masked technician to obtain radial section images from zonular bundles at 8 different clock positions. Image quality was assessed in real time, captured, and saved. Two experienced masked observers (H.C. and C.B.) then assessed the quality of the images and graded the zonular findings. Only patients with adequate studies have been included. A unique grading system that was specifically devised for this study was used as the following: (0) clear, well-defined zonule(s); (1) uneven, disrupted zonules or stretched zonules; and (2) extensive loss of zonules. Each clock hour was graded according to this system and the total score was then calculated for each eye. In the primary outcome, 2 main groups were analyzed: vitrectomized eyes and healthy contralateral nonvitrectomized eyes. The mean total UBM score (TUS) from each group was compared and analyzed. RESULTS: Thirty-five patients were recruited into this study. Eleven patients were male and 24 were female. The mean age was 66.3 years. Thirty patients had vitrectomy for vitreomacular interface disorders (either macular hole or epiretinal membrane), 1 patient had vitreous hemorrhage and the remaining 4 patients had rhegmatogenous retinal detachments. With regard to tamponade agents, SF6 was used in 21 (60%) patients, air in 9 (26%) patients, and C3F8 in 5 (14%) patients. The mean TUS in the vitrectomized eyes was 2.28 (SD 1.83) vs 2.24 (SD 1.77) in the nonvitrectomized eyes (P = .9531). Overall, in the comparative analysis of mean scores based on 2 graders' assessments for each clock position in vitrectomized and nonvitrectomized eyes, there were no significant differences noted between the groups. CONCLUSION: This study found no evidence for a difference in the mean total UBM score in eyes following vitrectomy when compared to their contralateral healthy, nonvitrectomized eyes. This likely indicates that vitrectomy may not affect the integrity of zonules in phakic patients, at least for patients with vitreomacular interface disorders undergoing uncomplicated surgery.

Opioid receptor antagonists reduce motivated wheel-running behavior in mice.

We hypothesized that opioid receptor antagonists would inhibit motivated behavior produced by a natural reward. To evaluate motivated responses to a natural reward, mice were given access to running wheels for 71.5 h in a multi-configuration testing apparatus. In addition to a running wheel activity, locomotor activity (outside of the wheel), food and water intake, and access to a food container were measured in the apparatus. Mice were also tested separately for novel-object exploration to investigate whether naloxone affects behavior unrelated to natural reward. In untreated mice wheel running increased from day 1 to day 3. The selective µ-opioid receptor antagonist ß-funaltrexamine (ß-FNA) (5 mg/kg) slightly decreased wheel running, but did not affect the increase in wheel running from day 1 to day 3. The non-selective opioid receptor antagonist naloxone produced a greater reduction in wheel running than ß-FNA and eliminated the increase in wheel running that occurred over time in the other groups. Analysis of food access, locomotor behavior, and behavior in the novel-object test suggested that the reduction in wheel running was selective for this highly reinforcing behavior. These results indicate that opioid receptor antagonism reduces responses to the natural rewarding effects of wheel running and that these effects involve multiple opioid receptors since the non-selective opioid receptor antagonist had greater effects than the selective µ-opioid receptor antagonist. It is possible that at the doses employed, other receptor systems than opioid receptors might be involved, at least in part, in the effect of naloxone and ß-FNA.

Triglyceride Glucose Index as an Indicator of Cardiovascular Risk in Syrian Refugees.

Background: The triglyceride glucose (TyG) index is a quick and inexpensive approach to measure insulin resistance. The aim of this study was to evaluate the TyG index's ability to predict cardiovascular risk and determine the TyG index cutoff values in Syrian refugees. Methods: A retrospective research study was conducted with 756 Syrian refugees. Data on demographics and clinical laboratory assessments were obtained from refugee's files. The formula Ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg (dL)/2] was used to calculate the TyG index. The Framingham risk score was used to calculate ten-year cardiovascular risk. The TyG index cutoff point was determined using the receiver operating characteristic curve (ROC). Results: Included participants had a mean age of 56.76 ± 10.78 years and a mean body mass index (BMI) of 27.42 ± 4.03 kg/m2. 28.57% of the subjects were smokers, and the majority were female (56.75%). A significant moderate correlation was observed between TyG index and Framingham score (r = 0.428, p < 0.001). ROC curve analysis for TyG index and Framingham score showed an area under the curve (AUC) of 0.741 (95% CI = 0.691-0.791; p < 0.001). The cutoff value of the TyG index to recognize intermediate/high risk Framingham risk score was 9.33, with a sensitivity of 64.3%, and specificity of 75.0%. Conclusion: Our findings determine that, given a TyG index cutoff value of 9.33, the TyG index has a predictive ability to assess ten-year cardiovascular risk by comparison to the Framingham risk score in a high-risk group of Syrian refugees and can be used as an independent indicator of cardiovascular risk.

A Computed Tomography Scan Near Miss of an Intraorbital Wooden Foreign Body.

When intraorbital wooden foreign bodies are missed, the consequences can be devastating. While the gold standard diagnostic imaging is computed tomography (CT), it has low sensitivity. We present a 61-year-old man with a bamboo injury to his right eye. He underwent two CT scans that failed to raise the possibility of intraorbital foreign bodies. Upon additional review, a rectangular-shaped pocket of air was identified in the orbit which was most consistent with wooden foreign bodies based on the clinical history. A combined mid-lid approach followed by a transconjunctival and transcaruncular extension were employed to remove several wooden splinters. Postoperatively, due to recurrent orbital compartment syndrome, he required a second decompression with an inferior rim osteotomy. He had good recovery at 3 months follow-up. Overall, intraorbital wooden foreign bodies are challenging to diagnose due to imaging limitations. Providing a clear history and suspected diagnosis to radiology is critical for diagnosis.

Manquer des corps étrangers intraorbitaires en bois peut avoir des conséquences désastreuses. L'imagerie diagnostique de référence est la tomodensitométrie (TDM) mais sa sensibilité est faible. Nous présentons le cas d'un homme de 61 ans ayant une plaie par morceau de bambou dans son œil droit. Il a bénéficié de deux tomodensitométrie qui n'ont pas réussi à donner l'alarme sur la possibilité de corps étrangers intraorbitaires. Lors d'un réexamen supplémentaire, une poche d'air de forme rectangulaire a été identifiée dans l'orbite; cette poche était très compatible avec des corps étrangers en bois, selon l'histoire clinique. Un abord combiné à mi-paupière, suivi d'une extension transconjonctivale et transcaronculaire, a été employé pour retirer plusieurs échardes en bois. En postopératoire, le patient a nécessité une deuxième décompression avec ostéotomie du bord inférieur en raison d'un syndrome du compartiment orbitaire récidivant. La récupération a été bonne au suivi de trois mois. Globalement, les corps étrangers intraorbitaires en bois sont difficiles à diagnostiquer en raison des limites de l'imagerie. Fournir au radiologue une histoire claire et un diagnostic suspecté est essentiel au diagnostic.

Comparison of long-term outcomes of simultaneous accelerated corneal crosslinking combined with intracorneal ring segment or topography-guided PRK.

PURPOSE: To compare long-term outcomes of simultaneous accelerated corneal crosslinking (CXL) with intrastromal corneal ring segments (CXL-ICRS) with simultaneous accelerated CXL with topography-guided photorefractive keratectomy (CXL-TG-PRK) in progressive keratoconus (KC). SETTING: Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada. DESIGN: Prospective nonrandomized interventional study. METHODS: The change in visual and topographical outcomes of CXL-ICRS and CXL-TG-PRK 4 to 5 years postoperatively were compared using linear regression models adjusted for preoperative corrected distance visual acuity (CDVA) and maximum keratometry (Kmax). RESULTS: 57 eyes of 43 patients with progressive KC who underwent simultaneous accelerated (9 mW/cm 2 , 10 minutes) CXL-ICRS (n = 32) and CXL-TG-PRK (n = 25) were included. Mean follow-up duration was 51.28 (9.58) and 54.57 (5.81) months for the CXL-ICRS and CXL-TG-PRK groups, respectively. Initial mean Kmax was higher in the CXL-ICRS group compared with the CXL-TG-PRK group (60.68 ± 6.81 diopters [D] vs 57.15 ± 4.19 D, P = .02). At the last follow-up, change (improvement) in logMAR uncorrected distance visual acuity (UDVA) compared with that preoperatively was significant with CXL-ICRS (-0.31 ± 0.27, P < .001, which is equivalent to approximately 3 lines) and not significant with CXL-TG-PRK (-0.06 ± 0.42, P = .43). The logMAR CDVA improved significantly with CXL-ICRS (-0.22 ± 0.20, P < .001), but not with CXL-TG-PRK (-0.05 ± 0.22, P = .25). Adjusting for baseline Kmax and CDVA, the improvement in UDVA was significantly greater with CXL-ICRS than with CXL-TG-PRK (-0.27, 95% CI, 0.06-0.47, P = .01). Improvement in CDVA was not significantly different. CONCLUSIONS: In this cohort of progressive KC with long-term follow-up, UDVA showed more improvement with accelerated CXL-ICRS than with CXL-TG-PRK.

Role of glycogen synthase kinase-3ß in dependence and abuse liability of alcohol.

BACKGROUND: Alcohol is a major abused drug worldwide that contributes substantially to health and social problems. These problems result from acute alcohol overuse as well as chronic use, leading to alcohol use disorder (AUD). A major goal of this field is to establish a treatment for alcohol abuse and dependence in patients with AUD. The central molecular mechanisms of acute alcohol actions have been extensively investigated in rodent models. AIMS: One of the central mechanisms that may be involved is glycogen synthase kinase-3ß (GSK-3ß) activity, a key enzyme involved in glycogen metabolism but which has crucial roles in numerous cellular processes. Although the exact mechanisms leading from acute alcohol actions to these chronic changes in GSK-3ß function are not yet clear, GSK-3ß nonetheless constitutes a potential therapeutic target for AUD by reducing its function using GSK-3ß inhibitors. This review is focused on the correlation between GSK-3ß activity and the degree of alcohol consumption. METHODS: Research articles regarding investigation of effect of GSK-3ß on alcohol consumption in rodents were searched on PubMed, Embase, and Scopus databases using keywords "glycogen synthase kinase," "alcohol (or ethanol)," "intake (or consumption)," and evaluated by changes in ratios of pGSK-3ßSer9/pGSK-3ß. RESULTS: In animal experiments, GSK-3ß activity decreases in the brain under forced and voluntary alcohol consumption while GSK-3ß activity increases under alcohol-seeking behavior. CONCLUSIONS: Several pieces of evidence suggest that alterations in GSK-3ß function are important mediators of chronic ethanol actions, including those related to alcohol dependence and the adverse effects of chronic ethanol exposure.

Glycogen Synthase Kinase-3 Inhibitors Block Morphine-Induced Locomotor Activation, Straub Tail, and Depression of Rearing in Mice Via a Possible Central Action.

We investigated morphine-induced Straub's tail reaction (STR) in mice pretreated with or without glycogen synthase kinase-3 (GSK-3) inhibitors (SB216763 and AR-A014418) by using a newly modified, infrared beam sensor-based automated apparatus. Mice treated with a single injection of morphine (30 mg/kg, i.p.) showed a significant STR with a plateau level at a time point of 20 min after morphine challenge. Pretreatment of mice with SB216763 (5 mg/kg, s.c.) or AR-A014418 (3 mg/kg, i.p.) significantly inhibited morphine-induced STR and attenuated the duration of STR in a dose-dependent fashion. In the striatum and the nucleus accumbens, expression of pGSK-3ßTyr216 but not GSK3ß or pGSK-3ßSer9 was largely but not significantly reduced after treatment with SB216763 (5 mg/kg, s.c.) in combination with/without morphine, indicating that the inhibitory effect of GSK-3 inhibitors on morphine-induced STR and hyperlocomotion might not depend on the direct blockade of GSK-3ß function. In constipated mice after morphine challenge (30 mg/kg), the effect of GSK-3 inhibitors on gastrointestinal transit was examined to reveal whether the action of GSK-3 inhibitors on morphine effects was central and/or peripheral. Pretreatment with SB216763 (5 mg/kg) did not block constipation in morphine-injected mice. The mechanism of action seems to be central but not peripheral, although the underlying subcellular mechanism of GSK-3 inhibitors is not clear. Our measurement system is a useful tool for investigating the excitatory effects of morphine in experimental animals.

Role for µ-opioid receptor in antidepressant effects of δ-opioid receptor agonist KNT-127.

Previous pharmacological data have shown the possible existence of functional interactions between µ- (MOP), κ- (KOP), and δ-opioid receptors (DOP) in pain and mood disorders. We previously reported that MOP knockout (KO) mice exhibit a lower stress response compared with wildtype (WT) mice. Moreover, DOP agonists have been shown to exert antidepressant-like effects in numerous animal models. In the present study, the tail suspension test (TST) and forced swim test (FST) were used to examine the roles of MOP and DOP in behavioral despair. MOP-KO mice and WT mice were treated with KNT-127 (10 mg/kg), a selective DOP agonist. The results indicated a significant decrease in immobility time in the KNT-127 group compared with the saline group in all genotypes in both tests. In the saline groups, immobility time significantly decreased in MOP-KO mice compared with WT mice in both tests. In female MOP-KO mice, KNT-127 significantly decreased immobility time in the TST compared with WT mice. In male MOP-KO mice, however, no genotypic differences were found in the TST after either KNT-127 or saline treatment. Thus, at least in the FST and TST, the activation of DOP and absence of MOP had additive effects in reducing measures of behavioral despair, suggesting that effects on this behavior by DOP activation occur independently of MOP.

Are We Overoperating on Isolated Orbital Floor Fractures?

BACKGROUND: Orbital floor fracture defect size and inferior rectus (IR) rounding index are currently accepted indications for surgery to prevent late enophthalmos. The authors analyzed the positive predictive value (PPV) of these indications. METHODS: Twenty-eight patients with orbital floor fractures presenting without enophthalmos underwent Hertel exophthalmometry at presentation and at weeks 1, 2, 3, 6, 13, 26, and 52 or more after injury. Orbital defect size and IR rounding index were measured from computed tomographic scans, and PPVs of defects of 1.5 to 2 cm 2 or larger and IR rounding index of 1 or higher for enophthalmos (≥2 mm) were calculated. RESULTS: Nineteen patients had isolated orbital floor fractures (group A), three had noncontinuous orbital floor and medial wall fractures (group B), and six had continuous orbital floor with medial wall fractures (group C). Mean follow-up time was 440 days. Of all patients, 20 had a defect size of 1.5 cm 2 or larger, 12 had a defect of 2.0 cm 2 or larger, and 13 had an IR rounding index of 1 or higher. Of the 28 patients, only one from group A and two from group C developed enophthalmos of 2 mm only. The PPVs of orbital floor defect size of 1.5 cm 2 or larger and 2 cm 2 or larger (groups A and B only) for late enophthalmos were 6.7% and 0%, respectively. The PPV of IR rounding index of 1 or higher for late enophthalmos (all groups) was 0%. CONCLUSIONS: For patients with orbital floor fractures presenting without enophthalmos, defects of 1.5 cm 2 or larger and 2 cm 2 or larger, and IR rounding index of 1 or higher, are weakly predictive of late enophthalmos. Furthermore, patients who do not develop enophthalmos within 3 weeks of injury are unlikely to develop significant (>2 mm) late enophthalmos. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

A randomized controlled trial comparing femtosecond-enabled deep anterior lamellar keratoplasty and standard deep anterior lamellar keratoplasty (FEDS Study).

OBJECTIVES: To compare outcomes of femtosecond-enabled deep anterior lamellar keratoplasty (FE-DALK) and standard deep anterior lamellar keratoplasty (S-DALK). METHODS: An open label, randomized controlled trial (Kensington Eye Institute, Toronto, ON, Canada) including 100 eyes of 97 participants with either keratoconus or corneal scarring, randomized to either FE-DALK (n = 48) or S-DALK (n = 49). PRIMARY OUTCOMES: postoperative astigmatism and surgically induced corneal astigmatism (SIA) - both at 15 months. SECONDARY OUTCOMES: 6-, 12- and 15-month postoperative uncorrected- and best spectacle-corrected visual acuity, steep and flat keratometry, manifest sphere and astigmatism, rate of conversion to penetrating keratoplasty (PK), big-bubble success, central corneal thickness, endothelial cell count and complications. RESULTS: In intention-to-treat analysis, mean postoperative astigmatism in the FE-DALK (n = 30) and S-DALK (n = 30) groups at 15 months was 7.8 ± 4.4 D and 6.3 ± 5.0 D, respectively (p = 0.282) with an adjusted mean difference of 1.3 D (95% CI -1.08, +3.65). Mean SIA (arithmetic) was 9.2 ± 7.8 and 8.8 ± 5.4 D, respectively (p = 0.838) with a mean difference of 0.4 D (95% CI -3.13, +3.85). In an analysis of successful DALK cases only, mean postoperative astigmatism in the FE-DALK (n = 24) and S-DALK (n = 20) groups at 15 months (after excluding 4 eyes with AEs) was 7.3 ± 4.4 and 6.2 ± 4.9 D, respectively (p = 0.531) with an adjusted mean difference of 0.9 D (95% CI -1.94, +3.71). Mean SIA (arithmetic) was 9.1 ± 7.8 and 7.9 ± 4.6 D, respectively (p = 0.547) with a mean difference of 1.2 D (95% CI -2.70,+5.02). Comparison of secondary outcomes showed only weak statistical evidence. CONCLUSIONS: In this randomized controlled trial, FE-DALK and S-DALK showed comparable functional and anatomical outcomes.

Post-traumatic Fungal Keratitis and Endophthalmitis Caused by Coniochaeta Hoffmannii with Late Recurrence following Therapeutic Full-thickness Penetrating Keratoplasty.

BACKGROUND: To report a rare case of fungal keratitis and endophthalmitis due to Coniochaeta hoffmannii. METHODS: Case report. RESULTS: A 71-year-old immunocompetent male sustained a corneal laceration, traumatic cataract, and retinal detachment due to penetrating injury from a nail pulled from a wooden deck. The patient's postoperative course was complicated by infectious keratitis. Fungal cultures, DNA sequencing and analysis of the internal transcribed spacer sequence confirmed Coniochaeta hoffmannii. Topical and oral voriconazole treatments were initiated; however, due to impending perforation, a therapeutic corneal transplant was required. One year later, the patient developed a new corneal infiltrate at the graft-host junction: Corneal scrapings were culture positive for Coniochaeta hoffmannii. This was treated with topical and intrastromal voriconazole along with oral itraconazole 200 mg once daily for 8 months. CONCLUSIONS: Coniochaeta hoffmannii may cause recalcitrant keratitis and endophthalmitis, which required longstanding antifungal treatment.

Comparative evaluation of four Descemet membrane endothelial keratoplasty graft preparation techniques.

OBJECTIVE: To compare subjective and objective outcomes of 4 different Descemet membrane endothelial keratoplasty (DMEK) peeling techniques performed by novice surgeons at different stages in their surgical career. DESIGN: An ex vivo prospective study. METHODS: In the first round, 2 DMEK peeling techniques were pitched against each other: the peripheral scoring and Sinskey dissection technique with the peripheral scoring and microhoe dissection and the peripheral blunt microhoe dissection against the scleral spurectomy and microhoe dissection. Three surgeons with different operative experience performed the peeling. Outcome measures included graft peeling time, surgeon's peeling difficulty grading (on a scale of 1-10, 1 being the easiest and 10 the hardest), number of radial and circumferential tears before and after trephination, and tissue loss. The 2 techniques that performed the best from the first round proceeded to the final round to identify the best overall technique. RESULTS: In total, 90 tissues (45 pairs) were peeled by 3 surgeons. Following the first-round results, the peripheral scoring and Sinskey dissection and peripheral blunt microhoe dissection proceeded to the final round. There were no significant differences between the groups in terms of peeling times, subjective feeling of difficulty, post-trephination tears, and peeling success rates (P > 0.05 for all). However, the peripheral scoring and Sinskey dissection technique had significantly fewer pretrephination radial tears (1.3 ± 1.3 vs 6.1 ± 5.2, P = 0.007) and circumferential tears (0.6 ± 0.9 vs 1.8 ± 2.1, P = 0.02). CONCLUSIONS: This study demonstrates that the learning curve can be overcome quickly with appropriate DMEK peeling techniques. The peripheral scoring and Sinskey dissection peeling technique allows efficient peeling with fewer related tears.

Effect of amoxicillin/clavulanic acid in attenuating pregabalin-induced condition place preference.

Substance abuse is a worldwide problem with serious repercussions for patients and the communities where they live. Pregabalin (Lyrica), is a medication commonly used to treat neuropathic pain. Like other analgesic medications there has been concern about pregabalin abuse and misuse. Although it was initially suggested that pregabalin, like other gabapentinoids, has limited abuse liability, questions still remain concerning this inquiry. Changes in glutamate system homeostasis are a hallmark of adaptations underlying drug dependence, including down-regulation of the glutamate transporter 1 (GLT-1; SLC1A2) and the cystine/glutamate antiporter (xCT; SLC7A11). In this study, it was found that pregabalin (90 mg/kg) produces a conditioned place preference (CPP), indicative of reinforcing effects that suggest a potential for abuse liability. Moreover, like other drugs of abuse, pregabalin also produced alterations in glutamate homeostasis, reducing the mRNA expression of Slc1a2 and Slc7a11 in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). Amoxicillin clavulanic acid, a ß-lactam antibiotic, blocked the reinforcing effects of pregabalin and normalized glutamate homeostasis. These results suggest that pregabalin has abuse potential that should be examined more critically, and that, moreover, the mechanisms underlying these effects are similar to those of other drugs of abuse, such as heroin and cocaine. Additionally, these results support previous findings showing normalization of glutamate homeostasis by ß-lactam drugs that provides a novel potential therapeutic approach for the treatment of drug abuse and dependence.

Methamphetamine-induced lethal toxicity in zebrafish larvae.

RATIONALE: The use of novel psychoactive substances has been steadily increasing in recent years. Given the rapid emergence of new substances and their constantly changing chemical structure, it is necessary to develop an efficient and expeditious approach to examine the mechanisms underlying their pharmacological and toxicological effects. Zebrafish (Danio rerio) have become a popular experimental subject for drug screening due to their amenability to high-throughput approaches. OBJECTIVES: In this study, we used methamphetamine (METH) as an exemplary psychoactive substance to investigate its acute toxicity and possible underlying mechanisms in 5-day post-fertilization (5 dpf) zebrafish larvae. METHODS: Lethality and toxicity of different concentrations of METH were examined in 5-dpf zebrafish larvae using a 96-well plate format. RESULTS: METH induced lethality in zebrafish larvae in a dose-dependent manner, which was associated with initial sympathomimetic activation, followed by cardiotoxicity. This was evidenced by significant heart rate increases at low doses, followed by decreased cardiac function at high doses and later time points. Levels of ammonia in the excreted water were increased but decreased internally. There was also evidence of seizures. Co-administration of the glutamate AMPA receptor antagonist GYKI-52466 and the dopamine D2 receptor antagonist raclopride significantly attenuated METH-induced lethality, suggesting that this lethality may be mediated synergistically or independently by glutamatergic and dopaminergic systems. CONCLUSIONS: These experiments provide a baseline for the study of the toxicity of related amphetamine compounds in 5-dpf zebrafish as well as a new high-throughput approach for investigating the toxicities of rapidly emerging new psychoactive substances.

Misconceptions Related to COVID 19 Vaccines Among the Jordanian Population: Myth and Public Health.

OBJECTIVE: This study assesses misconceptions about coronavirus disease 2019 (COVID-19) vaccine and the factors associated with misconception among Jordanians. METHODS: A cross-sectional online survey was conducted. The survey was formulated on Google Forms, and was hosted on an online platform. These questions were created based on extensive review of online information about the vaccines. Frequencies and percentages (%) were used for categorical variables, while means and standard deviations (SDs) were used for continuous variables. Stepwise binary logistic regression was conducted to evaluate variables associated with participant's misconception questions. RESULTS: Of 1195 survey respondents who participated in the study, 41.3% had received the COVID-19 vaccine. The mean misconception score was (60.0 ± 19.1). The statement with the highest mean was "The vaccine hasn't been tested on enough people" (3.6 ± 1.0). The statement with the lowest mean was "The COVID-19 vaccine includes a microchip to control us" (2.2 ± 1.1) in the conspiracy theory portion. Females, 18- to 29-age group, higher educational level, living in a city, the participants who took lectures about the COVID-19 vaccine and vaccinated participants had higher odds of being in the low misconception level group. CONCLUSION: Targeted campaigns and vaccine safety information should be part of a broader health education campaign to alleviate vaccination safety concerns.

Effects of waterpipe tobacco smoke and ceftriaxone treatment on the expression of endocannabinoid receptors in mesocorticolimbic brain regions.

Chronic tobacco exposure can alter the endocannabinoid (eCB) system, consequently leading to an anxiety state. In this study, we investigated the effects of waterpipe tobacco smoke (WTS) on cannabinoid receptor 1 and 2 (CBR1 and CBR2) gene and protein expression in mesocorticolimbic brain regions. Using elevated plus maze (EPM) and open field (OF) tests, the effects of WTS exposure on withdrawal-induced anxiety-like behavior were examined. The effect of ceftriaxone (CEF), a ß-lactam known to upregulate glutamate transporter 1 (GLT-1), on anxiety and the expression of cannabinoid receptors was also determined. Male Sprague-Dawley rats were randomly assigned to four groups: 1) the Control group was exposed only to standard room air; 2) the WTS group was exposed to tobacco smoke and treated with saline vehicle; 3) the WTS-CEF group was exposed to WTS and treated with ceftriaxone; and 4) the CEF group was exposed only to standard room air and treated with ceftriaxone. Rats were exposed to WTS (or room air) for two hours per day, five days per week for a period of four weeks. Behavioral tests (EPM and OF) were conducted weekly during acute withdrawal, 24 h following WTS exposure. Rats were given either saline or ceftriaxone (200 mg/kg i.p.) for five days during Week 4, 30 min prior to WTS exposure. Withdrawal-induced anxiety was induced by WTS exposure but was reduced by ceftriaxone treatment. WTS exposure decreased CBR1 mRNA and protein expression in the NAc and VTA, but not PFC, and ceftriaxone treatment attenuated these effects. WTS exposure did not change CBR2 mRNA expression in the NAc, VTA, or PFC. These findings demonstrate that WTS exposure dysregulated the endocannabinoid system and increased anxiety-like behavior, and these effects were reversed by ceftriaxone treatment, which suggest the involvement of glutamate transporter 1 in these effects.

Are Histamine H3 Antagonists the Definitive Treatment for Acute Methamphetamine Intoxication?

BACKGROUND: Methamphetamine (METH) is classified as a Schedule II stimulant drug under the United Nations Convention on Psychotropic Substances of 1971. METH and other amphetamine analogues (AMPHs) are powerful addictive drugs. Treatments are needed to treat the symptoms of METH addiction, chronic METH use, and acute METH overdose. No effective treatment for METH abuse has been established because alterations of brain functions under the excessive intake of abused drug intake are largely irreversible due in part to brain damage that occurs in the course of chronic METH use. OBJECTIVE: Modulation of brain histamine neurotransmission is involved in several neuropsychiatric disorders, including substance use disorders. This review discusses the possible mechanisms underlying the therapeutic effects of histamine H3 receptor antagonists on symptoms of methamphetamine abuse. CONCLUSION: Treatment of mice with centrally acting histamine H3 receptor antagonists increases hypothalamic histamine contents and reduces high-dose METH effects while potentiating lowdose effects via histamine H3 receptors that bind released histamine. On the basis of experimental evidence, it is hypothesized that histamine H3 receptors may be an effective target for the treatment METH use disorder or other adverse effects of chronic METH use.

Protective role of lactic acid bacteria and yeasts as dietary carcinogen-binding agents - a review.

The importance of food contaminants in the link between diet and cancer has been widely demonstrated. Therefore, different physical and chemical strategies for the control of human exposure to such dietary carcinogens has been explored; however, most of these strategies are complex, costly, and have low efficiency which limited their applications. Hence, microbiological methods have been receiving more attention. Recent in vitro and in vivo studies have indicated that lactic acid bacteria (LAB) and yeast may act as dietary carcinogen-binding agents. This review describes the promising protective role of strains belonging mainly to the Lactobacillus, Bifidobacterium and Saccharomyces genera by acting as dietary carcinogen-binding agents. This property suggests that these microorganisms may have a protective role by reducing the bioaccessibility of dietary carcinogens, thereby decreasing their toxic effects. The mechanisms by which the binding process takes place have not been completely elucidated; thus, the possible underlying mechanisms and factors influencing carcinogens-binding will be addressed.

FACTORS CONTRIBUTING TO THE ESCALATION OF ALCOHOL CONSUMPTION.

Understanding factors that contribute to the escalation of alcohol consumption is key to understanding how an individual transitions from non/social drinking to AUD and to providing better treatment. In this review, we discuss how the way ethanol is consumed as well as individual and environmental factors contribute to the escalation of ethanol consumption from intermittent low levels to consistently high levels. Moreover, we discuss how these factors are modelled in animals. It is clear a vast array of complex, interacting factors influence changes in alcohol consumption. Some of these factors act early in the acquisition of ethanol consumption and initial escalation, while others contribute to escalation of ethanol consumption at a later stage and are involved in the development of alcohol dependence. There is considerable need for more studies examining escalation associated with the formation of dependence and other hallmark features of AUD, especially studies examining mechanisms, as it is of considerable relevance to understanding and treating AUD.