Circular RNAs in neuroblastoma: Pathogenesis, potential biomarker, and therapeutic target.

Neuroblastoma (NB) is a common cancer in childhood responsible for 15 % of fatalities by pediatric cancers. Epigenetic factors play an important role in the pathogenesis of NB. Recently, it has been demonstrated that circular RNAs (circRNAs, ciRNAs), a newly identified class of non-coding RNAs, are also dysregulated in NB. CircRNAs mediate their functions by regulating gene expression mainly through microRNA (miRNA) sponging. The dysregulation (abnormal upregulation or downregulation) of circRNAs is involved in tumorigenesis of a variety of tumors including NB. It seems that the expression of some circRNAs is correlated with NB prognosis and clinical features. CircRNAs might be favorable as a diagnostic/prognostic biomarker and therapeutic target. However, due to the lack of studies, it is difficult to make a conclusion regarding the clinical benefits of circRNAs. In this review, we discussed the circRNAs that experimentally have been proved to be dysregulated in NB tissues and cancer cells.

Levetiracetam adjunct to quetiapine for the acute manic phase of bipolar disorder: a randomized, double-blind and placebo-controlled clinical trial of efficacy, safety and tolerability.

Unsatisfactory responses to bipolar disorder treatments have necessitated novel therapeutic approaches. Evidence of levetiracetam's effectiveness in mania was reported in previous studies. This study evaluated its efficacy, safety and tolerability as an adjunct to quetiapine in mania. Forty-four patients with Young Mania Rating Scale (YMRS) score ≥20 entered and were randomized to receive levetiracetam plus quetiapine or placebo plus quetiapine for 6 weeks. Patients were assessed using the YMRS and Beck Scale for Suicidal Ideations (BSSI) at baseline and weeks 2, 4 and 6. Changes in the scores, remission rates and response to treatment were compared between the groups. Forty patients completed the trial. The general linear model (GLM) repeated measures demonstrated a significant effect for time × treatment interaction on the YMRS score during the trial (P = 0.04). A greater reduction in YMRS scores was seen in the levetiracetam group compared with the placebo group from baseline to week 4 (P = 0.045). Response to treatment was significantly better in the levetiracetam group (P = 0.046). No significant effect for time × treatment interaction on BSSI score was seen in GLM repeated measures. Finally, there was no significant difference in the frequency of adverse events. Adjunctive levetiracetam is effective, safe and well-tolerated in patients with mania. Further high-quality, large-scale trials are recommended.

Medication adherence and its possible associated factors in patients with acne vulgaris: A cross-sectional study of 200 patients in Iran.

There are several etiologic factors involved in the pathogenesis of acne vulgaris. Therefore, current treatment guidelines recommend applying different classes of medications for it. This makes medication adherence a challenging issue in acne patients. The current study was designed to assess medication adherence and its possible associated factors in patients with acne vulgaris. This study was performed on patients with acne vulgaris in two dermatology clinics of Imam Khomeini Hospital and Razi Hospital. A validated questionnaire (ECOB, Elaboration d'un outil d'evaluation de l'observance des traitements medicamenteux) was applied to evaluate adherence to topical and oral therapies. We assessed relationship between patients' medication adherence and their sociodemographic, medication, and medical histories. A total of 200 patients, 136 females (68%), and 64 males (32%), with a mean age of 22 years were entered into the study. Overall, only 30 out of 200 patients (15%) were adherent to their treatments. Based on the bivariate analyses, food exacerbations, and severity of the disease by the patient's opinion was significantly associated with overall medication adherence (P = .03). Moreover, patients who were more adherent to topical treatment were more adherent to systemic treatment, as well (P = .007). The current study showed that treatment adherence was very low among patients with acne vulgaris. It is recommended to educate patients on the proper use of anti-acne medications. Besides, it is highly recommended that physicians and pharmacists use ECOB questionnaire regularly to guide patients accurately with the use of their drug regimens.

5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control.

On the basis of numerous previous studies, the serotonergic system plays a role in the pathogenesis of obsessive-compulsive disorder (OCD) and effective agents in this pathway, such as 5-hydroxytryptophan, can potentially contribute to treatment of patients with this disorder. Evaluating the efficacy of 5-hydroxytryptophan in treating OCD was the aim of the present randomized, double-blind, placebo-controlled 12-week trial. In a 12-week, randomized double-blind study, 60 patients with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of moderate to severe OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of >21 were randomly assigned to receive either fluoxetine plus placebo or fluoxetine plus 5-hydroxytryptophan (100 mg twice daily). All patients, regardless of their treatment group, received fluoxetine at 20 mg/day for the initial 4 weeks of the study followed by 60 mg/day of fluoxetine for the rest of the trial course. Symptoms were assessed using the Y-BOCS at baseline and weeks 4, 8 and 12. General linear model repeated measure showed significant effects for time × treatment interaction on total Y-BOCS (F = 12.07, df = 2.29, P-value <0.001), obsession (F = 8.25, df = 1.91, P-value = 0.001) and compulsion subscale scores (F = 6.64, df = 2.01, P-value = 0.002). 5-Hydroxytryptophan augmentation therapy demonstrated higher partial and complete treatment response rate (P = 0.032 and P = 0.001, respectively) according to the Y-BOCS total scores. The results of this study confirm that 5-hydroxytryptophan may be effective as an augmentative agent in treatment of moderate-to-severe OCD.

Inadequate achievement of ABC goals (HbA1c, blood pressure, LDL-C) among patients with type 2 diabetes in an Iranian population, 2012-2017.

AIMS: This study was designed to evaluate the meeting of ABC goals in patients with type 2 diabetes. The ABC goals were defined as meeting the HbA1c <7%, systolic blood pressure <130 mmHg and diastolic blood pressure <80 mmHg, and LDL-C <100 mg/dL. We also determined the associated factors with meeting the ABC goals, as well as the effectiveness of statin therapy. METHODS: We designed a cross-sectional study of 2008 type 2 diabetes patients attending the diabetes clinics of Valiasr Hospital of Imam Khomeini Hospital Complex. Meeting ABC goals and their associated factors were analyzed from the registered data. RESULTS: At the end of the year 2014, 61.3% of patients met the HbA1c goal, which increased to 77.8% in 2017. Blood pressure of 79.5% of patients met the ADA recommendations by the end of the year 2014, reaching 86.6% in 2017. Moreover, 84.5% and 93.8% could reach the LDL-C goal in 2014 and 2017, respectively. The proportion for the patients meeting all three ABC goals were 23.2% and 42.1% in 2014 and 2017, respectively. CONCLUSIONS: The level of achievement of ABC goals in Iran is lower than expected and it requires a lot of programming effort and follow-up. As patients are followed over the years, controlling ABC becomes much more favorable.

Comparison of vortioxetine and sertraline for treatment of major depressive disorder in elderly patients: A double-blind randomized trial.

WHAT IS KNOWN AND OBJECTIVE: Major depressive disorder (MDD) is a complex disease and one of the leading contributors to disease burden throughout the world. In the current study, we explored the efficacy and tolerability of vortioxetine versus sertraline on symptoms of depression in elderly patients with MDD. METHODS: Sixty patients diagnosed with MDD (based on DSM-5) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were entered into a randomized double-blind study and were randomized to receive either vortioxetine (15 mg daily) or sertraline (75 mg daily) for six weeks. Patients were assessed using the HAM-D scale at baseline and weeks 3 and 6. Changes in HAM-D score, response rates, remission rate and time to response or remission were also compared between the two study groups. RESULTS AND DISCUSSION: Fifty patients completed the trial after six weeks. General linear model repeated measures demonstrated no difference in trend of the two treatment groups (P = .897). There was no significantly different improvement in the HDRS scores from baseline to weeks 3 and 6, as well. Differences in response rate, remission rate, time to response and time to remission periods were not statistically significant. Finally, there was not any significantly difference between the two study groups in the frequency of adverse events. WHAT IS NEW AND CONCLUSION: This study showed no significant differences in the efficacy and safety of vortioxetine in comparison with sertraline in order for it to be used safely for treatment of major depressive disorder in elderly patients.

L-Carnosine combination therapy for major depressive disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Evidence for antidepressant effects of L-Carnosine was shown in some experimental studies. In this study we tried to evaluate the efficacy and tolerability of L-Carnosine combination therapy in treatment of patients with major depressive disorder (MDD). METHODS: Fifty-eight patients with MDD (DSM-V) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 400 mg twice daily L-Carnosine or placebo in addition to citalopram (maximum dosage of 40 mg/day) for six weeks in a randomized double-blind, and placebo-controlled study. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6. RESULTS: Fifty-two patients completed the trial. General linear model repeated measure showed significant difference for time × treatment on HAM-D score [F = 3.17, df = 2.39, p-value = 0.03]. Significantly greater improvement was detected in HAM-D score of the L-Carnosine group compared with the placebo group from baseline to weeks 2, 4 and 6 [Ps = 0.013, 0.028 and 0.023; respectively]. Patients in the L-Carnosine group experienced significantly greater response and remission rate than the placebo group [Ps = 0.023 and 0.012; respectively]. There was no significant difference between the two groups in baseline parameters and frequency of side effects. LIMITATIONS: Short follow-up period and small population size were two important limitations of this study. CONCLUSIONS: L-Carnosine combination therapy with citalopram can effectively improve symptoms of patients with major depressive disorder. Rapid-onset antidepressant effects of L-Carnosine were also shown which need further investigation.

Crocus sativus L. Versus Methylphenidate in Treatment of Children with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Pilot Study.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders of childhood and adolescence. About 30% of patients do not respond to stimulants or cannot tolerate their side effects. Thus, alternative medication, like herbal medicine, should be considered. The aim of this trial is to compare the safety and efficacy of Crocus sativus (saffron) versus methylphenidate in improving symptoms of children with ADHD. METHODS: In a 6-week randomized double-blind study, 54 patients (children 6-17 years old) with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ADHD were randomly assigned to receive either 20-30 mg/d (20 mg/d for <30 kg and 30 mg/d for >30 kg) methylphenidate (MPH) or 20-30 mg/d saffron capsules depending on weight (20 mg/d for <30 kg and 30 mg/d for >30 kg). Symptoms were assessed using the Teacher and Parent Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) at baseline and weeks 3 and 6. RESULTS: Fifty patients completed the trial. General linear model repeated measures showed no significant difference between the two groups on Parent and Teacher Rating Scale scores (F = 0.749, df = 1.317, p = 0.425, and F = 0.249, df = 1.410, p = 0.701, respectively). Changes in Teacher and Parent ADHD Rating Scale scores from baseline to the study end were not significantly different between the saffron group and the MPH group (p = 0.731 and p = 0.883, respectively). The frequency of adverse effects was similar between saffron and MPH groups. CONCLUSION: Short-term therapy with saffron capsule showed the same efficacy compared with methylphenidate. Nevertheless, larger controlled studies with longer treatment periods are necessary for future studies.

Amantadine as adjuvant therapy in the treatment of moderate to severe obsessive-compulsive disorder: A double-blind randomized trial with placebo control.

AIM: The role of the glutamatergic system in the pathogenesis of obsessive-compulsive disorder (OCD) has been shown by numerous studies. The aim of the present randomized, double-blind, placebo-controlled, 12-week trial was to assess the efficacy and tolerability of amantadine as an adjuvant to fluvoxamine in the treatment of patients with moderate to severe OCD. METHODS: One hundred patients diagnosed with moderate to severe OCD were randomized into two parallel groups to receive fluvoxamine (100 mg twice a day) plus placebo or fluvoxamine (100 mg twice a day) plus amantadine (100 mg daily) for 12 weeks. All patients received 100 mg/day fluvoxamine for 28 days followed by 200 mg/day for the rest of the trial, regardless of their treatment groups. Patients were evaluated for response to treatment using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline and at Weeks 4, 10, and 12. The main outcome measure was to assess the efficacy of amantadine in improving the OCD symptoms. RESULTS: Repeated-measure analysis of variance showed a significant effect for Time × Treatment interaction (Greenhouse-Geisser corrected: F = 3.84, d.f. = 1.50, P = 0.03) in the Y-BOCS total score and a significant effect for Time × Treatment interaction (Greenhouse-Geisser corrected: F = 5.67, d.f. = 1.48, P < 0.01) in the Y-BOCS Obsession subscale score between the two groups. CONCLUSION: The results of this study suggest that amantadine may be effective as an augmentative agent in the treatment of moderate-to-severe OCD.