Efficacy and safety of adjunctive therapy with fingolimod in patients with schizophrenia: A randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVES: Studies have suggested that fingolimod, a sphingosine-1-phosphate receptor modulator, exerts neuroprotective and anti-inflammatory effects. Although fingolimod is approved for the treatment of relapsing-remitting multiple sclerosis, limited studies have investigated its effects in patients with schizophrenia. This study investigated the efficacy and safety of fingolimod adjuvant to risperidone in schizophrenia treatment. METHODS: This eight-week, randomized, double-blinded, placebo-controlled trial included 80 (clinical trials registry code: IRCT20090117001556N137) patients with chronic schizophrenia. Participants were assigned to two equal arms and received risperidone plus either fingolimod (0.5 mg/day) or a matched placebo. The positive and negative symptom scale (PANSS) was used to measure and compare the effectiveness of treatment strategies at baseline and weeks 2, 4, 6, and 8. Treatment side effects were also compared. RESULTS: Seventy participants completed the trial (35 in each arm). The baseline characteristics of the groups were comparable (P-value > 0.05). There were significant time-treatment interaction effects on negative symptoms (P-value = 0.003), general symptoms (P-value = 0.037), and the PANSS total score (P-value = 0.035), suggesting greater improvement in symptoms following the fingolimod adjuvant therapy. In contrast, the longitudinal changes in positive and depressive symptoms were similar between the groups (P-values > 0.05). Regarding the safety of treatments, there were no differences in extrapyramidal symptoms [assessed by the extrapyramidal symptom rating scale (ESRS)] or frequency of other complications between the fingolimod and the placebo groups (P-values > 0.05). CONCLUSIONS: This study indicated that fingolimod is a safe and effective adjuvant agent for schizophrenia treatment. However, further clinical trials are required to suggest extensive clinical application.

Knowledge, attitude, and practice regarding child maltreatment amongst Iranian medical students through internship course: an 18-month longitudinal study.

BACKGROUND: Child maltreatment has been a major worldwide problem and has remained a persistent public health challenge in all countries. Physicians have a significant role in the prevention and intervention of child maltreatment. An educated physician that can effectively identify and report child maltreatment can fill one of the most significant gaps in reducing child abuse. This study was performed to examine the knowledge, attitude, and practice regarding child maltreatment among Iranian medical students through an internship course. METHOD: All the medical students (235 students) of the Iran University of Medical Sciences who passed the internship entrance exam in the 2019-2020 academic year participated in this study. The participants completed a 49-item scale questionnaire built by combining three other validated questionnaires that evaluate their attitude, knowledge, and practice skills in the first month of their internship course and then completed the same questionnaire 18 months later, at the end-point of the internship period. RESULTS: One-hundred thirty nine (59.1%) participants were female, and 96 (40.9%) were male. The mean age of the subjects was 24.35 ± 0.76. Only 7 (3%) of them formerly received any education about child maltreatment. There was a significant improvement in scores of the knowledge of prevention (p-value = 0.001), the practice of prevention (p-value < 0.001) and the general subscale of the practice section (p-value < 0.001) during the internship course. However, the performance of participants decreased significantly in the subscales of the attitude towards diagnosis (p-value = 0.001) and the attitude towards reporting (p-value < 0.001) of child maltreatment. At the end of the study, the result of graduated physicians was: The total knowledge and attitude of participants were satisfactory, and the majority were at reasonable levels. Although in the practice subscale, 70.6% of the participants didn't identify, 84.7% didn't refer, and 86.4% didn't report a child abuse case in the past year. CONCLUSION: The knowledge and attitude of Iranian physicians regarding child maltreatment are at a satisfactory level. Although, the practice level has deficiencies. In addition, our findings show that Iranian interns have a shallow experience regarding child maltreatment, particularly despite the higher scores in attitude and knowledge, which can be the reason for deficiencies in the practice level.

Cognitive rehabilitation for improving cognitive functions and reducing the severity of depressive symptoms in adult patients with Major Depressive Disorder: a systematic review and meta-analysis of randomized controlled clinical trials.

INTRODUCTION: Nearly 40% of patients with Major Depressive Disorder (MDD) have been found to experience cognitive impairment in at least one domain. Cognitive impairment associated with MDD is disproportionately represented in patients that have not fully returned to psychosocial functioning. As awareness regarding cognitive dysfunction in MDD patients grows, so does the interest in developing newer treatments that specifically address these deficits. METHOD: In the present study, we conduct a systematic review of controlled randomized clinical trials that used cognitive training and remediation interventions for improving cognitive functions and reducing symptom severity in adult patients with MDD. We selected studies published before March 2022 using search databases including PubMed, ScienceDirect, Scopus, and Google scholar. For conducting the meta-analysis, standard differences in means with the random effect model and with a 95% confidence interval of change in outcome measures from baseline to post-intervention between the cognitive rehabilitation and the control groups were calculated. RESULTS: The database search resulted in identifying 756 studies of interest, which ultimately 15 studies with 410 participants in the cognitive rehabilitation group and 339 participants in the control group were included. The meta-analysis of the data extracted from these studies, shows a moderate and significant effect on the executive function (d = 0.59 (95% CI, 0.25 to 0.93) p-value = 0.001, I2 = 15.2%), verbal learning (d = 0.45 (95% CI, 0.12 to 0.78) p-value = 0.007, I2 = 0.00%), and working memory (d = 0.41 (95% CI, 0.18 to 0.64) p-value < 0.001, I2 = 33%) of MDD patients. Although, there were no significant difference between intervention and control group in attention (d = 0.32 (95% CI, -0.01 to 0.66) p-value = 0.058, I2 = 0.00%) or depressive symptoms. CONCLUSION: This systematic review and meta-analysis indicate that cognitive rehabilitation is an effective intervention for the executive function, verbal learning, and working memory of MDD patients. Due to the importance of these neuropsychological deficits in day-to-day life and the core symptoms of MDD, cognitive rehabilitation should be considered an important part of treating MDD. Further research in this area and concentrated on these particular deficits is warranted.

Granisetron-mediated augmentation of sertraline therapeutic effect in obsessive-compulsive disorder: a double-blind placebo-controlled, randomized clinical trial.

BACKGROUND: Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually relieve the severity of symptoms by as much as 20-30%, and satisfactory treatment is obtained in 40-60% of patients with OCD. Nevertheless, the remaining symptoms continue to impair the patients' function. Therefore, it is necessary to investigate possible strategies to improve the mitigation of symptoms. In this study, the main objective was to examine and investigate the effectiveness of granisetron, which is a serotonin 5-hydroxytryptamine receptor type 3 (5-HT3) antagonist, as an adjunct therapy to selective serotonin reuptake inhibitors, for the purpose of ameliorating OCD symptoms. METHODS: fifty-eight patients diagnosed with OCD, based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, who had a Yale-Brown obsessive-compulsive scale (Y-BOCS) score of more than 21 were recruited in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either granisetron (1 mg twice daily) and sertraline (100 mg daily initially followed by 200 mg daily after week 4) or placebo and sertraline. The primary outcome was OCD symptoms measured by the Y-BOCS. RESULTS: Y-BOCS total score significantly dropped in both groups (28.9 to 17.7 for granisetron plus sertraline and 27.5 to 19.3 for placebo plus sertraline group with a slightly greater drop for granisetron plus sertraline group), while the granisetron plus sertraline group experienced a significantly greater reduction in obsession scores (Greenhouse-Geisser F(2.32,97.57) = 4.52,p-value = 0.01). Moreover, in comparison with the placebo plus sertraline group, the proportion of the patients showing complete response was considerably higher among the granisetron plus sertraline group (P-value < 0.01). No major adverse effects were observed in any of the groups. CONCLUSION: The results suggest that granisetron augmentation of sertraline may increase the rate of response in patients with moderate to severe non-refractory OCD. Further studies are suggested in this regard.

A modified quick-easy-cheap-effective-rugged-and-safe method involving carbon nano-onions-based dispersive solid-phase extraction and dispersive liquid-liquid microextraction for pesticides from grapes.

A combination of modified quick easy cheap effective rugged and safe extraction approach with carbon nano-onions-based dispersive solid-phase extraction and dispersive liquid-liquid microextraction was developed for the extraction of several pesticides (diazinon, chlorpyrifos, tebuconazole, deltamethrin, permethrin, haloxyfop-methyl, penconazole, and cyhalothrin) from grape before their analysis by gas chromatography-flame ionization detection. In the extraction approach, an aliquot of grape sample is chopped and after separating its juice, the pesticides that remained in the refuse are extracted by the quick, easy, cheap, effective, rugged, and safe extraction method. The obtained acetonitrile phase is mixed with juice and the analytes are extracted by the carbon nano-onions-based dispersive solid-phase extraction. The analytes are concentrated using the microextraction procedure to obtain high enrichment factors. The results showed low limits of detection (0.5-1.6 ng/g) and quantification (1.8-5.4 ng/g) with satisfactory linearity of the calibration curves (determination coefficient, r2 ≥ 0.994). The precision of the developed method expressed as relative standard deviations was good (≤7.2%). The method provided high enrichment factors (350-410) and extraction recoveries (70-82%). Finally, seven grape samples were analyzed successfully.

Memantine augmentation of sertraline in the treatment of symptoms and executive function among patients with obsessive-compulsive disorder: A double-blind placebo-controlled, randomized clinical trial.

BACKGROUND: Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually decrease the severity of the symptoms by 20-30%; however, 40-60% of OCD patients do not achieve a satisfactory response. Our main objective was to investigate the effectiveness of memantine, a non-competitive N-Methyl-D-aspartate (NMDA) receptor antagonist, as an adjunct therapy to sertraline, a selective serotonin reuptake inhibitor (SSRI), to improve severity of symptoms and executive function among patients with obsessive-compulsive disorder. METHODS: Seventy patients with OCD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and a Yale-Brown obsessive compulsive scale (Y-BOCS) score of more than 21 were recruited to the study. They received sertraline (100 mg daily initially followed by 200 mg daily after week 4) and either memantine (10 mg twice daily) or placebo in a placebo controlled, double-blinded, parallel-group, clinical trial of 12 weeks. The primary outcome was OCD symptoms measured by the Y-BOCS. Moreover, executive function of participants was measured by the Wisconsin Card Sorting Test (WCST). RESULTS: The total score, and obsession and compulsion subscales of Y-BOCS significantly dropped in both groups with no significant difference between the two groups. However, memantine group showed a greater response in the number of completed categories subscale of the WCST (p value<0.001). We did not observe any major adverse effects in any of the groups. CONCLUSION: Memantine has an acceptable safety and tolerability in patients with OCD and might have a positive effect on their executive function. Nevertheless, the current results don`t support the efficacy of memantine as an adjunctive agent to sertraline for symptoms in patients with OCD. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials on 04/10/2019 ( www.irct.ir ; IRCT ID: IRCT20170123032145N4).

Iranian students' attitudes toward premarital sex, marriage, and family in different college majors.

ObjectiveThis study is performed to examine the attitudes regarding marriage, family, and premarital sex among the students of different majors. Participants: Four hundred fifty-seven students from four majors studying Medical Sciences, Arts, Humanities, and Mathematics/Engineering within the age range of 18- to 24-year old. Method: Participants were selected from different universities in Tehran using stratified nonprobability sampling method. Attitudes of our participants were examined using the premarital sexual, marital, child-rearing, and family attitude Survey and demographic variables, including major, age, gender, religious beliefs, family socioeconomic level, and marital status were evaluated. Results: Most of the results of the survey showed significant differences between different majors. Art students were open to premarital sex more than other students and believed that premarital sex would cause no harm in reputation for females. By contrast, Medical sciences students had the highest agreement regarding the bad influence on the reputation of females because of premarital sex and also regarding men's tendency to virgin girls. Art students mostly approved the acceleration of the divorce process while the highest disapproval in this regard was reported from Medical sciences students. Conclusion: Art students' beliefs about premarital sex were more liberal, while Medical sciences students' beliefs in this matter were more conservative.

The attenuation of the toxic effects of LPS on mouse pre-implantation development by alpha-lipoic acid.

The present study was conducted to evaluate the effects of alpha-lipoic acid (ALA) on quantitative and qualitative indices of mouse embryos challenged by lipopolysaccharide (LPS). Having determined the effective concentrations of LPS (1 mg/mL) that could reduce blastocyst formation rate by around 50% and the optimal concentration of ALA (10 µM) that could attenuate the toxic effects of LPS on blastocyst formation, the following indices were defined: inner cell mass and trophectoderm cell numbers, blastocyst mitochondrial distribution, ROS and GSH levels, as well as the relative expression of Tlr-4. Nrf-2 and Tnf-RI/P-60 receptor involved in inflammatory pathways. Finally, embryos derived from the experimental and control groups were transferred to synchronized recipients and their implantation rate and post-implantation capacity were determined. Treatment with LPS resulted in an increase in intracellular ROS level (P ≤ 0.05), and remarkable decreases (P ≤ 0.05) in intracellular GSH content, mitochondrial mass, and blastocyst quality. ALA attenuated all the aforementioned negative effects of LPS. The relative expression levels of Nrf-2 and Tnf-RI/P-60 receptor (P ≤ 0.05) significantly increased in response to LPS, and treatment with ALA significantly reduced the relative expression of Tnf-RI/P-60. ALA also improved the post-implantation developmental capacity of embryos treated with LPS. In conclusion, our findings indicate that the reproductive toxicity of LPS could be overcome by ALA treatment. These effects were mainly due to the improvements made in intracellular antioxidant capacity as well as suppression of some inflammatory elements, especially the main receptor of TNF-α, the Tnf-RI/P-60, involved in induction of apoptosis. These observations have important implications for dairy farming and treatment of infertility.