A comparative, single-blind, randomized study on quetiapine and aripiperazole augmentation in treatment of selective serotonin reuptake inhibitor refractory obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder, of unknown etiology, that affects 2.5% of the population. An appropriate therapeutic response to conventional treatment is seen. Some studies use augmentative treatment by antipsychotics, glutamatergic, lithium, buspirone, and others agents to improve the therapeutic response. In this study, we aimed to evaluate the efficacy and tolerability of aripiprazole and quetiapine as augmentative treatments in patients with selective serotonin reuptake inhibitor (SSRI) refractory OCD. The OCD patients were initially treated for 12 weeks with a SSRI. If after 12 weeks their Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score was more than 16, they were randomly assigned to either the aripiprazole or the quetiapine augmentation group for an additional 12 weeks. There were no significant differences in age, sex, education, marital status, or score of Y-BOCS and Clinical Global Impression-Severity Scale (CGI-S) between groups (p > 0.05) at the outset of the study. Significant differences were noted after 1 month when compared with results at 2, 3, and 4 months in both groups (p < 0.001). Both quetiapine and aripiprazole may be effective and well-tolerated augmentative agents in the treatment of SSRI-refractory OCD. Because of positive results, aripiprazole may be considered more effective and may have a more rapid onset in terms of therapeutic response.

Mental Health and Disorders of Sex Development/Intersex Conditions in Iranian Culture: Congenital Adrenal Hyperplasia, 5-α Reductase Deficiency-Type 2, and Complete Androgen Insensitivity Syndrome.

Sixty-one patients (22 patients with congenital adrenal hyperplasia [CAH] with a mean age of 14.86 years [range, 5-23], 20 patients with 5-α reductase deficiency type 2 [5α-RD-2] with a mean age of 19.5 years [range, 5-29], and 19 patients with complete androgen insensitivity syndrome [CAIS] with a mean age of 18.26 years [range, 5-28]) were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia, the Structured Clinical Interview for DSM-IV Axis I, Axis II, and the Global Assessment Functioning Scale. All participants were female-assigned at birth. Ten patients (16.4%) transitioned to the male gender. Overall, 68% of patients had one or more lifetime Axis I disorders, including 63.6% of the CAH participants, 90% of 5α-RD-2 participants, and 52.6% of the CAIS participants. The most commonly observed were affective disorders (27.9%), gender identity disorder (27.9%), and anxiety (16.4%). Our study demonstrates that mental health of Iranian patients with DSD is at risk. This might be due to the fact that patients with DSD conditions are mostly treated medically and their mental health is often superficially addressed in developing countries such as Iran, at least in the past. We argue that it is important to pay attention to the mental health issues of patients with DSD and focus on specific issues, which may vary cross-culturally.

Childhood Sex-Typed Behavior and Gender Change in Individuals with 46,XY and 46,XX Disorders of Sex Development: An Iranian Multicenter Study.

Disorders of sex development (DSD) are congenital conditions in which the typical genetic and hormonal profiles are affected and thereby the usual process of sexual differentiation. Most of these studies, however, have been conducted in Western countries. In the present study, preschool sex-typed activities of Iranian individuals with DSD and their age-matched non-affected male and female relatives were assessed using the Pre-School Activities Inventory (PSAI) modified for retrospective self-report. A total of 192 individuals participated in our study, including 33 46,XX individuals with congenital adrenal hyperplasia (CAH; M age = 10.36, SD = 5.52), 15 46,XY individuals with complete androgen insensitivity syndrome (CAIS; M age = 19.8, SD = 7.14), and 16 46,XY individuals with 5-alpha reductase deficiency type-2 (5α-RD-2; M age = 17.31, SD = 7.28), as well as one age-matched non-affected male and female relative for each patient. With regard to PSAI scores, male-identifying participants with 5α-RD-2 and male controls reported similar levels of male-typical childhood play. Female-identifying participants with 5α-RD-2 and CAH showed comparable scores: significantly less masculine and more feminine than male controls, but significantly more masculine and less feminine than females with CAIS and female controls. These findings support the role of androgens in the development of sex-typical childhood play behavior, with those being exposed to higher levels of fetal functional androgens expressing more masculine behavior at preschool ages.

Psychosexual Outcome Among Iranian Individuals With 5α-Reductase Deficiency Type 2 and Its Relationship With Parental Sexism.

INTRODUCTION: Few studies exist on the psychosexual outcome of homogeneous groups of individuals with 5α-reductase deficiency type 2 (5α-RD-2) and the relation between gender changes and parental hostile and benevolent sexism, which are two components of ambivalent sexism that assume a stereotypical approach toward women in an overtly negative way or a chivalrous, seemingly positive way. AIM: To report on the psychosexual outcome of individuals with 5α-RD-2 and to investigate its relation to the level of parental sexism in a relatively large sample of Iranians with 5α-RD-2. METHODS: Twenty participants (mean age = 19.5 years, SD = 6.345) with a molecularly confirmed diagnosis of 5α-RD-2 who were assigned the female gender at birth and raised as female were included in the study. Participants and their parents were interviewed and their medical records were assessed. Parents also completed the Ambivalent Sexism Inventory (ASI), which includes hostile and benevolent sexism subscales. MAIN OUTCOME MEASURES: Psychosexual outcome and parental hostile and benevolent sexism measurements. RESULTS: Twelve of 20 participants (60%) were diagnosed with gender identity disorder not otherwise specified (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision). Ten of these transitioned to the male gender. The other 10 participants (50%), including the two diagnosed with gender identity disorder not otherwise specified, continued living in a female gender role. When comparing the ASI subscale scores between families of participants who changed their gender and those who did not, no significant difference was found for ASI total and hostile sexism scores, but there was a difference for benevolent sexism (P = .049): those whose daughters had changed their gender had higher benevolent sexism scores. CONCLUSION: The high prevalence of gender change and gender dysphoria reported in the literature was confirmed in this relatively large and homogeneous sample of Iranians with 5-α-RD-2 raised as female. Prenatal exposure to testosterone is hypothesized to play a role in the development of gender identity and sexual orientation, but parental attitudes also might be important. Although gender change in individuals with 5-α-RD-2 is often attributed to high levels of hostile sexism in some cultures, our findings show this to be associated with benevolent sexism.

Intelligent berberine-loaded erythrocytes attenuated inflammatory cytokine productions in macrophages.

Erythrocytes are impressive tools for drug delivery, especially to macrophages. Therefore, berberine was loaded into erythrocytes using both hypotonic pre-swelling and endocytosis methods to target macrophages. Physicochemical and kinetic parameters of the resulting carrier cells, such as drug loading/release kinetics, osmotic fragility, and hematological indices, were determined. Drug loading was optimized for the study using Taguchi experimental design and lab experiments. Loaded erythrocytes were targeted to macrophages using ZnCl2 and bis-sulfosuccinimidyl-suberate, and targeting was evaluated using flow cytometry and Wright-Giemsa staining. Differentiated macrophages were stimulated with lipopolysaccharide, and the inflammatory profiles of macrophages were evaluated using ELISA, western blotting, and real-time PCR. Findings indicated that the endocytosis method is preferred due to its low impact on the erythrocyte's structural integrity. Maximum loading achieved (1386.68 ± 22.43 µg/ml) at 1500 µg/ml berberine treatment at 37 °C for 2 h. Berberine successfully inhibited NF-κB translation in macrophages, and inflammatory response markers such as IL-1ß, IL-8, IL-23, and TNF-α were decreased by approximately ninefold, sixfold, twofold, eightfold, and twofold, respectively, compared to the LPS-treated macrophages. It was concluded that berberine-loaded erythrocytes can effectively target macrophages and modulate the inflammatory response.

Nanocomposite of electrochemically reduced graphene oxide and gold nanourchins for electrochemical DNA detection.

A nanocomposite of graphene oxide and gold nanourchins has been used here to modify the surface of a screen-printed carbon electrode to enhance the sensitivity of the electrochemical DNA detection system. A specific single-stranded DNA probe was designed based on the target DNA sequence and was thiolated to be self-assembled on the surface of the gold nanourchins placed on the modified electrode. Doxorubicin was used as an electrochemical label to detect the DNA hybridisation using differential pulse voltammetry (DPV). The assembling process was confirmed using scanning electron microscopy (SEM) imaging, cyclic voltammetry (CV), and the EIS method. The high sensitivity of the proposed system led to a low detection limit of 0.16 fM and a wide linear range from 0.5 to 950.0 fM. The specificity of the DNA hybridisation and the signalling molecule (haematoxylin) caused very high selectivity towards the target DNA than other non-specific sequences.

Psychiatric morbidity among adult transgender people in Iran.

Psychiatric morbidity among transgender and gender diverse people is thought to be to an important extent related to socio-cultural intolerance, but such morbidity has been understudied in non-western socio-political contexts. This study aims to report the psychiatric profiles of clients who are seeking gender-affirming treatment in a gender clinic in Iran. All transgender people who were consecutively referred to the Mashhad University of Medical Sciences in Mashhad, Iran, between February 2015 and December 2016 were investigated. Clients were evaluated during at least four sessions when sociodemographic and psychiatric characteristics were collected. Out of 209 clients, 205 were included (transmen (TM), N = 110; transwomen (TW) N = 95). A subset of these were assessed using Structured Clinical Interview based for DSM-5 (n = 154). The mean age of participants was 24.41 (SD = 6.316; range, 15-43). There was no significant difference between transmen and transwomen (p = 0.960); 48% (80 out of 154) of participants were found to have at least one current psychiatric condition currently, and 67% (138 out of 205) during their lifetime. Depressive and trauma- and stressor-related disorders were the most common conditions. Prevalence rates were similar in both genders. In both TM and TW groups, as many as 70% of the clients reported that they had experienced suicidal ideation. These findings are surprisingly similar to those of western studies despite the more extreme difficulties Iranian transgender people face in their lives in a non-western socio-political context.

A potential hypothesis for 2019-nCoV infection therapy through delivery of recombinant ACE2 by red blood cell-hitchhiking.

A novel infectious disease, caused by 2019 Novel Coronavirus (2019-nCoV) is responsible for the recent outbreak of severe respiratory disease. The 2019-nCoV spread rapidly and reaching epidemic proportions in many countries of the world. ACE2 was identified as a key receptor for 2019-nCoV infections. Excessive form of soluble ACE2 rescues cellular ACE2 activity which has a protective role in acute lung failure and neutralizes the virus. The short half-life of ACE2 is a major limitation to its practical application. Nanoparticle-based drug delivery systems are one of the most widely investigated approaches for developing novel therapies for a variety of diseases. Nevertheless, nanoparticles suffer from the rapid removal from the bloodstream by the reticuloendothelial system (RES). A noncovalent attachment of nanoparticles to RBCs increases their half-life in blood and allows transient accumulation in the lungs, while decreases their uptake by the liver and spleen. Connecting the recombinant ACE2 into the surface of nanoparticles that were attached to RBCs can be a potential therapeutic approach for 2019-nCoV infection through increasing their lung targeting to naturalize the virus and also acting as a bioreactor in the blood circulation to decrease serum level of Angiotensin II and protects lungs from injury/ARDS.

Growth Factors as Tools in Photoreceptor Cell Regeneration and Vision Recovery.

Photoreceptor loss is a major cause of blindness around the world. Stem cell therapy offers a new strategy in retina degenerative disease. Retinal progenitors can be derived from embryonic stem cells (ESC) in vitro, but cannot be processed to a mature state. In addition, the adult recipient retina presents a very different environment than the photoreceptor precursor donor. It seems that modulation of the recipient environment by ectopic development regulated growth factors for transplanted cells could generate efficient putative photoreceptors. The purpose of this review article was to investigate the signaling pathway of growth factors including: insulin-like growth factors (IGFs), fibroblast growth factors (FGF), Nerve growth factor (NGF), Brain-derived neurotrophic factor (BDNF), Taurin and Retinoic acid (RA) involved in the differentiation of neuroretina cell, like; photoreceptor and retinal progenitor cells. Given the results available in the related literature, the differentiation efficacy of ESCs toward the photoreceptor and retinal neurons and the important role of growth factors in activating signaling pathways such as Akt, Ras/Raf1/ and ERKs also inhibit the ASK1/JNK apoptosis pathway. Manipulating differentiated culture, growth factors can influence photoreceptor transplantation efficiency in retinal degenerative disease.

Taguchi Experimental Design for Optimization of Recombinant Human Growth Hormone Production in CHO Cell Lines and Comparing its Biological Activity with Prokaryotic Growth Hormone.

Growth hormone deficiency results in growth retardation in children and the GH deficiency syndrome in adults and they need to receive recombinant-GH in order to rectify the GH deficiency symptoms. Mammalian cells have become the favorite system for production of recombinant proteins for clinical application compared to prokaryotic systems because of their capability for appropriate protein folding, assembly, post-translational modification and proper signal. However, production level in mammalian cells is generally low compared to prokaryotic hosts. Taguchi has established orthogonal arrays to describe a large number of experimental situations mainly to reduce experimental errors and to enhance the efficiency and reproducibility of laboratory experiments.In the present study, rhGH was produced in CHO cells and production of rhGH was assessed using Dot blotting, western blotting and Elisa assay. For optimization of rhGH production in CHO cells using Taguchi method An M16 orthogonal experimental design was used to investigate four different culture components. The biological activity of rhGH was assessed using LHRE-TK-Luciferase reporter gene system in HEK-293 and compared to the biological activity of prokaryotic rhGH.A maximal productivity of rhGH was reached in the conditions of 1%DMSO, 1%glycerol, 25 µM ZnSO4 and 0 mM NaBu. Our findings indicate that control of culture conditions such as the addition of chemical components helps to develop an efficient large-scale and industrial process for the production of rhGH in CHO cells. Results of bioassay indicated that rhGH produced by CHO cells is able to induce GH-mediated intracellular cell signaling and showed higher bioactivity when compared to prokaryotic GH at the same concentrations.

A highly sensitive miR-195 nanobiosensor for early detection of Parkinson's disease.

Early detection of Parkinson's disease (PD), as a dangerous neurodegenerative disease, is a key factor in the therapy or prevention of further development of this disease. We developed an electrochemical nanobiosensor for early detection of PD based on the quantification of circulating biomarker, miR-195. Exfoliated graphene oxide (EGO) and gold nanowires (GNWs) were used to modify the surface of screen-printed carbon electrode. A single-strand thiolated probe was designed for specific hybridization with target miRNA (miR-195), and doxorubicin was used as an electrochemical indicator for differential pulse voltammetry measurements. The results of scanning electron microscope imaging and cyclic voltammetry experiments confirmed the accuracy of the working electrode modification steps. The results of analytical performance nanobiosensor showed a high sensitivity of the biosensing with 2.9 femtomolar detection limit and dynamic range of 10.0-900.0 femtomolar. In addition, good selectivity for target miRNA over non-specific oligonucleotides (one and three base replacement in target miRNA, and non-complementary) was achieved. The results of real human serum analysis did not show any interference in the function of the biosensor. Based on the results, the miR-195 electrochemical nanobiosensor could be suggested for clinicians in the medical diagnosis of PD.

A nanobiosensor composed of Exfoliated Graphene Oxide and Gold Nano-Urchins, for detection of GMO products.

Genetically Modified Organisms, have been entered our food chain and detection of these organisms in market products are still the main challenge for scientists. Among several developed detection/quantification methods for detection of these organisms, the electrochemical nanobiosensors are the most attended which are combining the advantages of using nanomaterials, electrochemical methods and biosensors. In this research, a novel and sensitive electrochemical nanobiosensor for detection/quantification of these organisms have been developed using nanomaterials; Exfoliated Graphene Oxide and Gold Nano-Urchins for modification of the screen-printed carbon electrode, and also applying a specific DNA probe as well as hematoxylin for electrochemical indicator. Application time period and concentration of the components have been optimized and also several reliable methods have been used to assess the correct assembling of the nanobiosensor e.g. field emission scanning electron microscope, cyclic voltammetry and electrochemical impedance spectroscopy. The results shown the linear range of the sensor was 40.0-1100.0 femtomolar and the limit of detection calculated as 13.0 femtomolar. Besides, the biosensor had good selectivity towards the target DNA over the non-specific sequences and also it was cost and time-effective and possess ability to be used in real sample environment of extracted DNA of Genetically Modified Organism products. Therefore, the superiority of the aforementioned specification to the other previously published methods was proved adequate.

Sexual orientation and medical history among Iranian people with Complete Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia.

OBJECTIVE: To report sexual orientation, relationship status and medical history of Iranian people with Differences of Sex Development (DSD) who were raised female. METHODS: Our participants consisted of nineteen 46,XY individuals with Complete Androgen Insensitivity Syndrome (CAIS) and eighteen 46,XX individuals with Congenital Adrenal Hyperplasia (CAH) who were raised as females and older than 13years. As well as their relationship status and detailed medical history, an expert psychiatrist assessed their sexual orientation by a semi-structured psychiatric interview with them and, where applicable, their parents. RESULTS: Five percent of CAH participants and 42% of CAIS participants were in a relationship, which was significantly different. All CAH individuals had been diagnosed at birth; 89% of CAIS had been diagnosed after puberty and due to primary amenorrhea and 11% were diagnosed in childhood due to inguinal hernia. Genital reconstructive surgery had been performed in 100% of CAH participants and 37% of CAIS. Regarding sexual contact experiences and sexual fantasies (androphilic, gynephilic or both), no significant differences were found. However, CAH females had significantly more gynephilic dreams (P=0.045). CONCLUSION: This study, notable as one of the rare from a non-western culture, described sexual, medical and socioeconomic status of 46,XX CAH and 46,XY CAIS individuals living in Iran. Although broadly in line with previous findings from Western cultures, Iranian CAH individuals had fewer romantic relationships, but in contrast to previous studies their sexual orientation was only different from CAIS in the contents of sexual dreams.

Investigating the Interaction of Fe Nanoparticles with Lysozyme by Biophysical and Molecular Docking Studies.

Herein, the interaction of hen egg white lysozyme (HEWL) with iron nanoparticle (Fe NP) was investigated by spectroscopic and docking studies. The zeta potential analysis revealed that addition of Fe NP (6.45±1.03 mV) to HEWL (8.57±0.54 mV) can cause to greater charge distribution of nanoparticle-protein system (17.33±1.84 mV). In addition, dynamic light scattering (DLS) study revealed that addition of Fe NP (92.95±6.11 nm) to HEWL (2.68±0.37 nm) increases suspension potential of protein/nanoparticle system (51.17±3.19 nm). Fluorescence quenching studies reveled that both static and dynamic quenching mechanism occur and hydrogen bond and van der Waals interaction give rise to protein-NP system. Synchronous fluorescence spectroscopy of HEWL in the presence of Fe NP showed that the emission maximum wavelength of tryptophan (Trp) residues undergoes a red-shift. ANS fluorescence data indicated a dramatic exposure of hydrophobic residues to the solvent. The considerable reduction in melting temperature (T(m)) of HEWL after addition of Fe NP determines an unfavorable interaction system. Furthermore circular dichoroism (CD) experiments demonstrated that, the secondary structure of HEWL has not changed with increasing Fe NP concentrations; however, some conformational changes occur in tertiary structure of HEWL. Moreover, protein-ligand docking study confirmed that the Fe NP forms hydrogen bond contacts with HEWL.

The "Reading the Mind in the Eyes" Test: Investigation of Psychometric Properties and Test-Retest Reliability of the Persian Version.

The psychometric properties of the Persian "Reading the Mind in the Eyes" test were investigated, so were the predictions from the Empathizing-Systemizing theory of psychological sex differences. Adults aged 16-69 years old (N = 545, female = 51.7 %) completed the test online. The analysis of items showed them to be generally acceptable. Test-retest reliability, as measured by Intra-class correlation coefficient, was 0.735 with a 95 % CI of (0.514, 0.855). The percentage of agreement for each item in the test-retest was satisfactory and the mean difference between test-retest scores was -0.159 (SD = 3.42). However, the internal consistency of Persian version, calculated by Cronbach's alpha (0.371), was poor. Females scored significantly higher than males but academic degree and field of study had no significant effect.

Validation of serum IGF-I as a biomarker to monitor the bioactivity of exogenous growth hormone agonists and antagonists in rabbits.

The development of new growth hormone (GH) agonists and growth hormone antagonists (GHAs) requires animal models for pre-clinical testing. Ideally, the effects of treatment are monitored using the same pharmacodynamic marker that is later used in clinical practice. However, intact rodents are of limited value for this purpose because serum IGF-I, the most sensitive pharmacodynamic marker for the action of GH in humans, shows no response to treatment with recombinant human GH and there is little evidence for the effects of GHAs, except when administered at very high doses or when overexpressed. As an alternative, more suitable model, we explored pharmacodynamic markers of GH action in intact rabbits. We performed the first validation of an IGF-I assay for the analysis of rabbit serum and tested precision, sensitivity, linearity and recovery using an automated human IGF-I assay (IDS-iSYS). Furthermore, IGF-I was measured in rabbits of different strains, age groups and sexes, and we monitored IGF-I response to treatment with recombinant human GH or the GHA Pegvisomant. For a subset of samples, we used LC-MS/MS to measure IGF-I, and quantitative western ligand blot to analyze IGF-binding proteins (IGFBPs). Although recovery of recombinant rabbit IGF-I was only 50% in the human IGF-I assay, our results show that the sensitivity, precision (1.7-3.3% coefficient of variation) and linearity (90.4-105.6%) were excellent in rabbit samples. As expected, sex, age and genetic background were major determinants of IGF-I concentration in rabbits. IGF-I and IGFBP-2 levels increased after single and multiple injections of recombinant human GH (IGF-I: 286±22 versus 434±26 ng/ml; P<0.01) and were highly correlated (P<0.0001). Treatment with the GHA lowered IGF-I levels from the fourth injection onwards (P<0.01). In summary, we demonstrated that the IDS-iSYS IGF-I immunoassay can be used in rabbits. Similar to rodents, rabbits display variations in IGF-I depending on sex, age and genetic background. Unlike in rodents, the IGF-I response to treatment with recombinant human GH or a GHA closely mimics the pharmacodynamics seen in humans, suggesting that rabbits are a suitable new model to test human GH agonists and antagonists.

Efficacy of integrating stress coping skills training with detoxification on social adjustment of addicted women.

BACKGROUND: Addiction as a biopsychosocial problem has been dramatically increased in our country. Adverse consequences of the addiction in women have been shown to be more than men, which in turn can affect family members' health and wellbeing. The current study examined the efficacy of stress coping skills training in addicted women referring to an outpatient centre of addiction prevention located in Welfare Organization of Gorgan, Iran. METHODS: 30 women with low levels of social adjustment measured by Social Adjustment Scale were randomly assigned to coping skills training with detoxification treatments (experimental) or detoxification alone groups. Both groups (n = 15) completed pre-post assessments of Bell's adjustment Inventory. Experimental group received coping skills training program in ten sessions, each session last 90 minutes. FINDINGS: Social adjustment was considerably improved more in addicted women who followed coping skills training program with detoxification treatment in comparison with the women who was undergone only detoxification treatment. CONCLUSION: Skills training program can help addicted women to better cope with their adjustment problem and these skills should be integrated into detoxification programs for this population.