Comparative efficacy of pharmaceutical (Ibuprofen) and non-pharmaceutical (photobiomodulation, and chewing gum) interventions for pain reduction after elastomeric separator placement in orthodontic patients: a randomized clinical trial.

This study compared the efficacy of pharmaceutical (ibuprofen) and non-pharmaceutical (photobiomodulation and chewing gum) interventions for pain reduction after elastomeric separator placement in orthodontic patients. This 3-arm, parallel-group randomized clinical trial was conducted on 90 orthodontic patients. The level of anxiety and pain threshold of patients were measured at baseline using the Pain Catastrophizing Scale (PCS) and an algometer, respectively. The patients were randomly assigned to three groups (n = 30; equal number of males and females). In the laser group, 940 nm diode laser (Epic X, Biolase, USA, 12.35 J/cm2 energy density and 300 mW power in continuous-wave mode., The cross-sectional area of the laser handpiece tip was 1.7 cm2.) was irradiated to the buccal and lingual surfaces for 35 s each, prior to placement of separators. In the gum group, the patients were asked to chew a piece of sugar-free gum immediately after the placement of separators and repeat every 8 h for 5 min for one week in case of pain. In the ibuprofen group, patients received 400 mg ibuprofen (Hakim Pharmaceuticals, Tehran, Iran) after the placement of separators and were asked to take one tablet every 8 h for one week in case of pain. The pain score was recorded using the Modified McGill Pain Questionnaire (MPQ). The normality of data distribution was analyzed by the Kolmogorov-Smirnov test. ANOVA was applied to compare age, and the Chi-square and Monte Carlo Chi-square tests were used to compare gender and patient responses to the questions among the groups. Repeated measures ANOVA was used to compare the pain score at different time points and among the three groups. All statistical analyses were conducted using SPSS version 19 (SPSS Inc., Chicago, IL, USA) at 0.05 level of significance. Data analysis in this study had an intention to treat approach. Although the pain score was slightly lower in ibuprofen and gum groups, the difference among the three groups was not statistically significant (P > 0.05). 'Repeated measures ANOVA showed no significant effect of method of pain reduction on pain score (F = 1.520, P = 0.225). Time had a significant effect on pain score (F = 20.310, P < 0.001). The interaction effect of time and pain reduction method on pain score was not significant (F = 0.737, P = 0.651). patients experienced a lower level of pain in the ibuprofen and chewing gum groups, the difference in pain score was not significant among the three groups (P = 0.225). patients experienced a higher level of pain at 12 and 24 hours after the placement of separators in all groups. Considering the comparably equal analgesic efficacy of this modalities, non-pharmaceutical interventions can be used for pain reduction of elastomeric separator. The study protocol was registered in the Iranian Registry of Clinical Trials (IRCT20210927052611N1). Date of registration 2022/03/14.

Changes in paranasal sinus volumes, temporal bone pneumatization, internal acoustic canal and olfactory cleft dimensions over the centuries: a comparison of skulls from different epochs in Anatolia.

OBJECTIVES: Investigating changes in temporal bone pneumatization (TBP) and paranasal sinus volumes (PSV) across different eras may help understanding not only changes in skull anatomy but also pathophysiology of chronic otitis media and sinusitis, respectively, which are common health problems. METHODS: Eight skulls from the second century AD, 20 skulls were from the 10th-11th centuries AD, 20 skulls from the 16th-19th centuries AD, and 60 contemporary skulls were included in this cross-sectional observational study. Using computerized tomography (CT) scans, the PSV were calculated by multiplying the height, width, and antero-posterior distance of the sinuses. TBP was divided into three types. Internal acoustic canal (IAC) length and width, and olfactory cleft (OC) width were measured. RESULTS: No statistically significant differences were found between the paranasal sinus (frontal, maxillary, and sphenoid) volumes between the groups. However, TBP decreased statistically significantly over time on both sides of the skulls (p = 0.001). The contemporary IAC and OC measures were found to be significantly lower on both sides compared to the skulls from the other three eras (p < 0.001 for both). CONCLUSIONS: Although no significant change was observed in PSV, decreases were evident in TBP, OC width and IAC length and width over time. It appears a fair inference that changes in size of OC and IAC might be another indication of the fact that olfaction and hearing were more vital for survival in old eras. Since we do not know incidence of chronic ear problems in old eras, we cannot speculate outcome of increased TBP in terms of developing chronic ear diseases. On the contrary, increased TBP was likely to play a protective role in traumas in old ears. Additionally, the environmental influences may be crucial role in the development of paranasal sinuses.

Molecular mechanisms and therapeutic application of extracellular vesicles from plants.

Small extracellular vesicles (sEVs) isolated from animal sources are among the most investigated types of cell-free therapeutic tools to cure different diseases. sEVs have been isolated from a variety of sources, ranging from prokaryotes to animals and plants. Human-derived sEVs have many uses in pre- and clinical studies in medicine and drug delivery, while plant-derived EVs, also known as plant-derived nanovesicles (PDNVs), have not been widely investigated until the second decade of the 21st century. For the past five years, there has been a rapid rise in the use of plant EVs as a therapeutic tool due to the ease of massive production with high efficacy and yield of preparation. Plant EVs contain various active biomolecules such as proteins, regulatory RNAs, and secondary metabolites and play a key role in inter-kingdom communications. Many studies have already investigated the potential application of plant EVs in preventing and treating cancer, inflammation, infectious diseases, and tissue regeneration with no sign of toxicity and are therefore considered safe. However, due to a lack of universal markers, the properties of plant EVs have not been extensively studied. Concerns regarding the safety and therapeutic function of plant EVs derived from genetically modified plants have been raised. In this paper, we review the physiological role of EVs in plants. Moreover, we focus on molecular and cellular mechanisms involved in the therapeutic effects of plant EVs on various human diseases. We also provide detailed information on the methodological aspects of plant EV isolation and analysis, which could pave the way for future clinical translation.

Association between alcohol dehydrogenase polymorphisms (rs1229984, rs1573496, rs1154460, and rs284787) and susceptibility to head and neck cancers: A systematic review and meta-analysis.

OBJECTIVE: Head and neck cancer (HNC) is a prevalent and complex group of malignancies with increasing incidence globally. Alcohol dehydrogenases (ADHs) play a crucial role in alcohol metabolism, and their polymorphisms have been linked to HNC risk. This systematic review and meta-analysis aims to evaluate the association between ADH polymorphisms and susceptibility to HNCs, incorporating additional analyses and adding more studies to increase power and accuracy of the results. DESIGN: Subgroup analysis, meta-regression analysis, and sensitivity analyses were conducted to explore potential differences within the data and assess the stability of pooled odds ratios (ORs). To mitigate the risk of false conclusions from meta-analyses, a trial sequential analysis was performed. RESULTS: For ADH1B rs1229984, the pooled OR (95 % confidence interval (CI)) was 0.73 (0.65, 0.82), 0.42 (0.35, 0.50), 0.57 (0.44, 0.73), 0.56 (0.50, 0.62), and 0.80 (0.73, 0.88), as well as for ADH7 rs1573496, the pooled OR was 0.72 (0.62, 0.85), 0.36 (0.17, 0.74), 0.76 (0.64, 0.91), 0.80 (0.71, 0.91), and 0.38 (0.18, 0.78) with a p < 0.05 in all allelic, homozygous, heterozygous, recessive, and dominant models, respectively. However, no significant association was found between the ADH7 rs1154460 and rs284787 polymorphisms and the risk of HNC with pooled ORs of 1.11 (p = 0.19) and 1.09 (p = 0.24) for the recessive model, respectively. The ethnicities, tumor subsites, control sources, sample sizes, quality scores, and Hardy-Weinberg equilibrium statuses were confounding factors. CONCLUSION: The ADH1B rs1229984 and ADH7 rs1573496 polymorphisms are significantly associated with a reduced risk of HNC.

Relationship between the amount of mesial movement of the mandibular first molar and angular changes of the mandibular third molar: A retrospective comparative study in growing patients with and without first premolar extraction.

OBJECTIVES: The main objective of this study was to assess the relationship of the amount of mesial movement of mandibular first molar (MFM) and angular changes of the mandibular third molar (MTM) in orthodontic patients. The secondary objective of this study was to compare the obtained values in extraction and non-extraction orthodontic patients. MATERIAL AND METHODS: In this cross-sectional retrospective study were enrolled all the eligible patients (12-16 years) with and without first premolar extraction that met the inclusion criteria. The angle between the longitudinal axis of MTM and horizontal reference plane (HRP) (to calculate the angular change of MTM), and the distance between the cementoenamel junction of the mesial surface of MFM and the bisector of the anterior nasal spine and nasal septum (to determine the amount of mesial movement of MFM) were measured on pre- and post-treatment panoramic radiographs. The correlation between the two variables was analysed and compared between extraction and non-extraction patients using STATA v. 14.2 software. RESULTS: A total of 100 fixed orthodontic patients with and without first premolar extraction (n=50) whose treatment had been accomplished were included in the study. In the non-extraction group, the mean amount of mesial movement of MFM was 1.45mm and the mean angular change of MTM was 4.28 degrees; this correlation was significant (P<0.05). These values were 2.98mm and 7.17 degrees in the first premolar extraction group, respectively, with a significant correlation (P<0.05). However, the difference in this respect was not significant between the two groups (P>0.05). According to the regression model, 1mm mesial movement of MFM would averagely cause 2.2-degree angular change in MTM, adjusting for the effect of extraction/non-extraction treatment plan. CONCLUSION: The mesial movement of MFM was significantly correlated with the angular changes of MTM in extraction and non-extraction orthodontic patients, with no significant difference between them.

Role of A Single Nucleotide Polymorphism in Thrombospondine 4 Gene in Premature Myocardial Infarction among Population of Southern Iran.

BACKGROUND: Coronary Artery Diseases (CAD) are the leading cause of Myocardial Infarction (MI). However, their underlying etiology can be found in the interplay between environmental and genetic factors. On the other hand, it has been shown that Extracellular Matrix (ECM) proteins, such as Thrombospondins (TSP), play a crucial regulatory role in vascular pathologies, including atherogenesis. TSPs are extracellular proteins responsible for intercellular and cell-ECM interactions and are involved in regulating functional responses. Recently, a missense mutation in the TSP-4 gene has been reported to potentially increase the risk of CADs. The present study aimed to investigate the role of rs1866389 Guanosine to Cytosine (G/C) Single Nucleotide Polymorphism (SNP) of the TSP-4 gene on the prevalence of premature MI in southern Iran. METHOD: The present case-control study included 100 patients with premature MI and 100 healthy individuals. The DNA extracted from the blood samples of the participants underwent Polymerase Chain Reaction (PCR) for the sequence of the TSP-4 gene. Afterward, the frequency of C (mutated) and G (normal) alleles of the TSP-4 gene was evaluated in the case and control groups. RESULTS: According to our findings, there was no significant intergroup difference in gender, age, and smoking status. However, the case group was significantly higher in the prevalence of Diabetes mellitus (DM), Hyperlipidemia (HLP), and Hypertension (HTN) compared to the control group. Moreover, 22%, 49%, and 29% of the case group had CC, GC, and GG genotypes in the TSP-4 gene, respectively, while the prevalence of CC, GC, and GG genotypes were 10%, 44%, and 46% in the control group. Also, the prevalence of allele C was significantly higher in the case group (47%) compared to the control group (33%, P=0.043), showing its significant association with the increased risk of premature MI (OR = 1.80; 95% CI = 1.01-3.19). CONCLUSIONS: The rs1866389 G/C SNP of the TSP-4 gene significantly increased the risk of premature MI in the population of southern Iran. Thus, such mutated gene can be used as a target for gene therapy or a marker for early detection of individuals at high risk for CADs.

Effect of Serum Level of Vitamin D on External Apical Root Resorption in Maxillary Anterior Teeth in Patients under Fixed Orthodontic Treatment.

Introduction: This study aimed to assess the effect of serum level of vitamin D on external apical root resorption (EARR) in maxillary anterior teeth in patients under fixed orthodontic treatment. Materials and Methods: This retrospective cohort was conducted on patients under fixed orthodontic treatment who were between 12 to 30 years of age. All patients underwent the same treatment technique by the same orthodontist using a 0.022 MBT system. EARR in maxillary anterior teeth was evaluated on pre- and postoperative panoramic radiographs. Blood samples were also collected from patients, and their serum level of vitamin D was measured after the completion of treatment. Data were analyzed by independent t-test and Chi-square test (alpha = 0.05). Results: A reduction in root length was noted in all patients, which was significant (P < 0.0001); 75% of patients showed EARR in at least one maxillary incisor. EARR had no significant correlation with the serum level of vitamin D (P=0.423). Conclusions: Serum level of vitamin D had no significant correlation with the occurrence of EARR. However, the high prevalence of EARR calls for measures to minimize it.

An integrated approach for evaluating and improving the performance of surgical theaters with resilience engineering.

Operating rooms are among the most high-risk and vital parts of a hospital. Therefore, one of the most fundamental tasks of risk management is maintaining the safety of operating rooms. Resilience engineering (RE) can be introduced as a model for overcoming problems, and it seeks ways to raise success rates by focusing on and addressing complexities. To this end, an RE-based framework is presented to evaluate the performance of operating rooms. First, the RE indicators are identified, and the relative importance of each is calculated via the best-worst method (BWM). Subsequently, the required data are collected from operating room experts using a standard questionnaire. Next, a data envelopment analysis (DEA) method is employed to evaluate the performance of operating rooms in the study case. Lastly, drawing upon the sensitivity analysis and statistical tests, the effect of each RE indicator is examined on the surgical department. Accordingly, some improvement approaches are proposed. Besides, SWOT (strengths, weaknesses, opportunities, and threats) analysis is used to extract appropriate strategies to improve performance. To the best of our knowledge, this paper is the first to evaluate the performance of operating rooms quantitatively in terms of RE indicators, and the framework presented in this paper can have practical applications in different operating rooms.

Right ventricular free wall strain for detection of anthracycline induced cardiac toxicity.

Anthracycline agents are routinely used for treatment of many types of malignancy, while imposing the risk for cardiotoxicity (AT-CMP). Although the right ventricle (RV) is more susceptible to cardiotoxicity, most of the studies have focused on left ventricle (LV) function for monitoring AT-CMP. In this study, we have focused on RV function before and after chemotherapy using two-dimensional speckle tracking Echocardiography. In this prospective study, newly diagnosed and untreated cancerous patients without previous cardiovascular diseases were enrolled. For all patients, baseline echocardiography was performed before the initiation of the anthracycline regimen and after 6 months of follow up when the chemotherapy was stopped. Several parameters of LV and RV function were measured using 3D echocardiography and STE techniques. 60 patients were enrolled in the study. There was a significant decrease (P = 0.001) in RV fractional area change (53.57% ± 4.36 vs. 45.66% ± 6.19), RV Global longitudinal strain (GLS) (- 22.93% ± 1.95 vs. - 18.53 ± 2.75), and RV free wall strain (FWLS) (- 25.75% ± 3.01 VS. - 20.30 ± 3.78). There was a significant decline in LVEF (59.42 ± 6.36% vs. 51.1 ± 6.31%) and LV-GLS (- 21.1 ± 1.8% vs - 18.6 ± 2.6%) (both P = 0.001) as well. Among the parameters changed following chemotherapy, RV-FWLS was dropped to a pathological level in 25% of patients showing the highest potential for detection of anthracyclines effect on the myocardium. Anthracycline therapy can induce subclinical RV dysfunction. In this clinical setting, RV free wall strain shows a great ability to exhibit deleterious effects of anthracyclines on the myocardium. This finding needs to be confirmed in future and larger studies.

Tooth alignment and pain experience with A-NiTi versus Cu-NiTi: a randomized clinical trial.

BACKGROUND: Nickel-titanium (NiTi) archwires are routinely used for initial leveling and alignment of teeth in orthodontic treatment. This study aimed to clinically compare the level of pain and tooth alignment in orthodontic treatment with A-NiTi versus Cu-NiTi archwires. METHODS: In this parallel randomized clinical trial, 88 orthodontic patients (12-25 years) with an irregularity index > 2 mm in the anterior site of the lower dental arch who required non-extraction orthodontic treatment of the lower arch were randomized into two age- and sex-matched groups (n = 44) for treatment with A-NiTi and Cu-NiTi initial archwires. Each archwire was used for 6 weeks. After 6 weeks, the irregularity index was measured, and the level of pain was scored using the Modified McGill pain questionnaire (MPQ) and visual analog scale (VAS) according to the time of onset and duration of pain, and analgesic intake. Data were analyzed by paired t test, independent samples t test, and Chi-square test (P < 0.05). RESULTS: The irregularity index significantly decreased in both groups after 6 weeks of treatment (P < 0.001). However, the difference in this respect was not significant between the two groups (P > 0.05). Pain perception (P = 0.487), duration of pain (P = 0.546), and analgesic intake (P = 0.102) were not significantly different between the two groups either. CONCLUSION: Both A-NiTi and Cu-NiTi archwires are equally effective for tooth alignment in the anterior site of the lower dental arch and have no significant difference with regard to the level of pain experienced by patients. TRIAL REGISTRATION NUMBER: IRCT20190705044102N1 and Name of the registry: Iranian registry of clinical trials (https://irct.ir/) Date of registration: September, 26, 2019.

Predictive value of initial CT scan for various adverse outcomes in patients with COVID-19 pneumonia.

BACKGROUND: Chest computed tomography (CT) scan is frequently used in the diagnosis of COVID-19 pneumonia. OBJECTIVES: This study investigates the predictive value of CT severity score (CSS) for length-of-stay (LOS) in hospital, initial disease severity, ICU admission, intubation, and mortality. METHODS: In this retrospective study, initial CT scans of consecutively admitted patients with COVID-19 pneumonia were reviewed in a tertiary hospital. The association of CSS with the severity of disease upon admission and the final adverse outcomes was assessed using Pearson's correlation test and logistic regression, respectively. RESULTS: Total of 121 patients (60±16 years), including 54 women and 67 men, with positive RT-PCR tests were enrolled. We found a significant but weak correlation between CSS and qSOFA, as a measure of disease severity (r: 0.261, p = 0.003). No significant association was demonstrated between CSS and LOS. Patients with CSS>8 had at least three-fold higher risk of ICU admission, intubation, and mortality. CONCLUSIONS: CSS in baseline CT scan of patients with COVID-19 pneumonia can predict adverse outcomes and is weakly correlated with initial disease severity.

Clinical characteristics, outcomes, and risk factors for mortality in hospitalized patients with COVID-19 and cancer history: a propensity score-matched study.

BACKGROUND: COVID-19 has caused great concern for patients with underlying medical conditions. We aimed to determine the prognosis of patients with current or previous cancer with either a PCR-confirmed COVID-19 infection or a probable diagnosis according to chest CT scan. METHODS: We conducted a case control study in a referral hospital on confirmed COVID-19 adult patients with and without a history of cancer from February25th to April21st, 2020. Patients were matched according to age, gender, and underlying diseases including ischemic heart disease (IHD), diabetes mellitus (DM), and hypertension (HTN). Demographic features, clinical data, comorbidities, symptoms, vital signs, laboratory findings, and chest computed tomography (CT) images have been extracted from patients' medical records. Multivariable logistic regression was used to estimate odd ratios and 95% confidence intervals of each factor of interest with outcomes. RESULTS: Fifty-three confirmed COVID-19 patients with history of cancer were recruited and compared with 106 non-cancerous COVID-19 patients as controls. Male to female ratio was 1.33 and 45% were older than 65. Dyspnea and fever were the most common presenting symptoms in our population with 57.86 and 52.83% respectively. Moreover, dyspnea was significantly associated with an increased rate of mortality in the cancer subgroup (p = 0.013). Twenty-six patients (49%) survived among the cancer group while 89 patients (84%) survived in control (p = 0.000). in cancer group, patients with hematologic cancer had 63% mortality while patients with solid tumors had 37%. multivariate analysis model for survival prediction showed that history of cancer, impaired consciousness level, tachypnea, tachycardia, leukocytosis and thrombocytopenia were associated with an increased risk of death. CONCLUSION: In our study, cancer increased the mortality rate and hospital stay of COVID-19 patients and this effect remains significant after adjustment of confounders. Compared to solid tumors, hematologic malignancies have been associated with worse consequences and higher mortality rate. Clinical and para-clinical indicators were not appropriate to predict death in these patients.

Clinical characteristics and outcomes of diabetics hospitalized for COVID-19 infection: a single-centered, retrospective, observational study.

Some debates exist regarding the association of diabetes mellitus (DM) with COVID-19 infection severity and mortality. In this study, we aimed to describe and compare the clinical characteristics and outcomes of hospitalized COVID-19 patients with and without DM. In this single-centered, retrospective, observational study, we enrolled adult patients with COVID-19 who were admitted to the Shariati hospital, Tehran, Iran, from February 25, 2020, to April 21, 2020. The clinical and paraclinical information as well as the clinical outcomes of patients were collected from inpatient medical records. A total of 353 cases were included (mean age, 61.67 years; 57.51 % male), of whom 111 patients were diabetics (mean age, 63.66 years; 55.86 % male). In comparison to those without DM, diabetic patients with COVID-19 were more likely to have other comorbidities, elevated systolic blood pressure (SBP), elevated blood sugar (BS), lower estimated glomerular filtration rate (eGFR) and elevated blood urea nitrogen (BUN). The association of DM with severe outcomes of COVID-19 infection (i.e. mechanical ventilation, median length of hospital stay and mortality) remained non-significant before and after adjustments for several factors including age, sex, body mass index (BMI), smoking status, and comorbidities. Based on our results DM has not been associated with worse outcomes in hospitalized patients for COVID-19 infection.

Effect of bleaching with carbamide peroxide on shear bond strength of orthodontic brackets: A meta-analysis of in vitro studies.

INTRODUCTION: This study aimed to evaluate the effect of bleaching with carbamide peroxide (CP) according to different doses and intervals between bleaching and bonding on shear bond strength (SBS) of orthodontic brackets. METHODS: Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PubMed, and Scopus were searched for articles published up to June 2018. After removing the duplicates, two of the authors screened the titles and abstracts independently. Assessing the eligibility of the selected full texts was also conducted by two of the authors independently. Disagreements were resolved by discussion. Modified version of Cochrane's risk of bias tool was used to assess the quality of studies. Fifteen studies were selected. RESULTS: Overall, bleaching with CP decreased the SBS by around 2MPa (P<0.0001). Using 10% CP decreased the SBS of the immediately bonded brackets by 5.13MPa (P<0.005). This value was 1.67MPa when the bonding procedure was postponed by one day (P<0.0001). Postponing the bonding procedure for longer periods did not cause a statistically significant change in SBS. Using 11-16% CP, the reduction in SBS of the immediately bonded brackets was 8.51MPa (P<0.01). The SBS decreased by 4.12MPa when the bonding procedure was postponed for 20days (P<0.05). According to one study, use of CP with>16% concentration seemed not to affect the SBS. CONCLUSIONS: Bleaching with CP decreases the SBS, especially if the bracket bonding is performed shortly after bleaching. However, given the small number of articles interpretation should be made with caution.

In vitro bleaching effect of hydrogen peroxide with different time of exposition and concentration on shear bond strength of orthodontic brackets to human enamel: A meta-analysis of in vitro studies.

INTRODUCTION: Controversy exists regarding the effect of bleaching on shear bond strength (SBS) of orthodontic brackets to enamel. This study aims to do a review and meta-analysis on the effect of bleaching with hydrogen peroxide on SBS according to the interval between bleaching and bonding to human enamel and the concentration of Hydrogen Peroxide. METHODS: An electronic search of the literature was performed in Scopus, PubMed and Cochrane databases including CENTRAL and Cochrane library for relevant in vitro studies on the effect of bleaching with hydrogen peroxide on shear bond strength of human enamel, published until June 2018. Modified Cochrane Risk of Bias tool was used to assess the quality of the individual studies. AMSTAR tool was used for assessing the quality of the study. RESULTS: Nineteen studies were included in the qualitative analysis. Regardless of the interval between bleaching and bonding, reduction in SBS was not statistically significant when the hydrogen peroxide of less than 35% is used. Bleaching with 35% hydrogen reduces SBS when the bonding is conducted immediately (P<0.0001) or the time interval was shorter than one day (P<0.0005). On the other hand, use of high dose hydrogen peroxide resulted in a statistically significant reduction in SBS irrespective of the time interval between the procedures (P<0.05 for all categories of time interval). CONCLUSION: Bleaching with hydrogen peroxide decreases the SBS of brackets in patients undergoing orthodontic treatment especially if the time interval between bleaching and bonding procedures is short and a high concentration of hydrogen peroxide is used.

Electrophysiological study of the response of ventral tegmental area non-dopaminergic neurons to nicotine after concurrent blockade of orexin receptor-2 and cannabinoid receptors-1.

The ventral tegmental area (VTA) is a key brain region, involved in the dependency on nicotine. Studies have shown that orexin and cannabinoids are likely to play an important role in nicotine dependency. In this study, the effect of orexin receptor-2 (OX2R) and cannabinoid receptor-1 (CB1R) blockade were investigated in response to nicotine in male rats, on the neural activity of VTA. Nicotine was injected subcutaneously and its effect on the firing of VTA non-dopaminergic (ND) neurons was investigated, using in vivo extracellular single unit recording. Nicotine increased the ND neuronal activity of the VTA. AM251 (0.18, 0.9, 1.8 nmol/0.3 µL), as a selective cannabinoid CB1R antagonist, and TCS-OX2-29 (0.5, 1, 5 nmol/0.3 µL), as a selective OX2R antagonist, individually or simultaneously were microinjected into the VTA. The results revealed that blockade of OX2R and CB1R in the VTA could prevent the increased firing rate, caused by nicotine. Concurrent administration of TCS-OX2-29 and AM251 could decrease responsiveness of VTA-ND neurons to nicotine, but it did not show a greater response than their single application. Because the synergistic effect was not observed in the simultaneous blockade of these two receptors, therefore, in order to detect the interactions of these two receptors, further studies are needed in the field of intracellular signaling.

Association of Omentin rs2274907 and FTO rs9939609 gene polymorphisms with insulin resistance in Iranian individuals with newly diagnosed type 2 diabetes.

BACKGROUND: Insulin resistance (IR) and fat accumulation in visceral adipose tissue are key players in developing type 2 diabetes (T2D). Several adipose tissue derived-gene polymorphisms are related to higher body mass index (BMI), insulin resistance and T2D. The association of omentin rs2274907 (Val109Asp) and fat-mass and obesity-associated (FTO) rs9939609 gene polymorphisms with overweight/obesity and T2D is controversial. The aim of this study was to determine the association between omentin Val109Asp and FTO rs9939609 polymorphisms and insulin resistance in newly-diagnosed T2D patients. METHODS: The case-control study included 83 newly-diagnosed T2D patients and 85 healthy matched controls, aged 20-80 years. Fasting blood glucose and insulin levels were measured by the enzymatic method and enzyme-linked-immunosorbent assay, respectively. Insulin resistance was calculated using the homeostasis model assessment (HOMA) index. Genotyping was examined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: There are significant differences between both omentin Val109Asp and FTO rs9939609 polymorphisms and studied individuals (P = 0.011 and P = 0.0001, respectively). Both genetic polymorphisms of omentin Val109Asp and FTO rs9939609 (T/A) are significantly related to higher HOMA index (P = 0.030 and P = 0.046, respectively). However, omentin Val109Asp polymorphism was only related to individuals who were overweight/obese. Additionally, both omentin Val109Asp and FTO rs9939609 polymorphisms were significantly positively correlated to familial history of diabetes (P = 0.046 and P = 0.024, respectively). CONCLUSIONS: Omentin V109D and FTO rs9939609 genetic variations may change insulin metabolism and have key roles in developing T2D through insulin resistance. Thus, the evaluation of these polymorphic regions may be helpful for predicting type 2 diabetes.

Orexin type-2 receptor blockade prevents the nicotine-induced excitation of nucleus accumbens core neurons in rats: An electrophysiological perspective.

BACKGROUND: The nucleus accumbens core (NAcc) expresses both orexin and nicotinic acetylcholine receptors (nAChRs). Orexin is among important neurotransmitters, which regulates addictive properties of drugs of abuse including nicotine. The role of orexin-2 receptor (OX2R) in the regulation of NAcc neural activity in response to nicotine has not yet been studied. Hence, in this study, we examined whether the OX2R antagonist (TCS-OX2-29) can adjust the effects of nicotine on electrical activity of NAcc neurons, in urethane-anesthetized rats, using the single unit recording. METHODS: Neuronal firing of NAcc was recorded for 15 min, then TCS-OX2-29 (OX2R-antagonist; 1, 3 and 10 ng/rat) or DMSO were microinjected into NAcc, just 5 min before subcutaneous (sc) administration of nicotine (0.5 mg/kg) or saline. The spontaneous firing activity was recorded for 70 min, after nicotine injection. RESULTS: The results demonstrated that nicotine significantly excites the NAcc neurons and interestingly, the administration of TCS-OX2-29 (3 and 10 ng/rat) into the NAcc, inhibited nicotine-induced increases of NAcc neuronal responses. Furthermore, administration of TCS-OX2-29 (10 ng/rat), just 5 min before sc administration of saline instead of nicotine, did not significantly alter the neuronal responses, compared to the saline-control group. CONCLUSION: Our results showed that, although OX2R blockade alone did not affect neuronal activity in the NAcc, it was able to prevent the exciting effects of nicotine on NAcc neuronal activity. Therefore, we proposed that orexin has a potential modulator effect, in response to nicotine.