Investigate the relationship between obstructive sleep apnea and cardiac arrhythmia after CABG surgery.

BACKGROUND AND OBJECTIVE: Heart rhythm disorder is one of the most common problems after coronary artery bypass graft surgery. Various factors, such as the history of sleep apnoea before the operation, may aggravate the occurrence of this disorder. The present study was conducted to determine the relationship between sleep apnoea before surgery and heart rhythm disorder after surgery in patients undergoing coronary Artery Bypass Grafting in 2019. METHODS: This analytical cross-sectional study was conducted on 192 patients who were selected by sequential sampling. The research tool included demographic information, a checklist of heart rhythm disorders, and the Berlin sleep apnoea questionnaire. Descriptive statistics and the Chi-square test, Fisher's exact test, Mann-Whitney's U-test, and logistic regression were used to analyze the data. RESULTS: A total of 71.35% of the samples were male, and the mean age of the participants was 57.8 ± 7.5 years. Also, 46.0% of the samples had sleep pane and 21.35% had rhythm disorder. The most frequent heart rhythm disorder in patients with obstructive sleep apnoea was atrial fibrillation. There was a significant relationship between the occurrence of rhythm disorder and a history of smoking (P = 0.021), and the regression model showed that a history of smoking is the only variable related to the occurrence of rhythm disorder after coronary Artery Bypass Grafting (P = 0.005, CI 95%: 6.566-1.386, OR = 3.017). CONCLUSIONS: The results showed that there is no statistically significant relationship between sleep apnea and rhythm disorder after coronary artery bypass surgery.

Geographical and Molecular Analysis of Haplotype Variations in Leishmania major Among Infected Iranian Phlebotomus papatasi.

PURPOSE: Leishmania major is main causative agent and Phlebotomus papatasi is only proven vector of Zoonotic Cutaneous Leishmaniasis (ZCL) in Iran. Human leishmaniasis is mostly susceptible to climatic conditions and molecular variations of Leishmania parasites within sandflies. METHODS: L. major was analyzed based on geographical, environmental, climatic changes and haplotype variations within P. papatasi. Molecular tools and different geographical aspects were employed using Arc-GIS software for mapping the geographic distribution of samples and other statistics tests. Fragments of ITS-rDNA, k-DNA, and microsatellite genes of Leishmania were used for PCR, RFLP, sequencing, and phylogenetic analyses. RESULTS: Totally 81 out of 1083 female P. papatasi were detected with Leishmania parasites: 70 and five were L. major and L. turanica, respectively. Golestan and Fars provinces had the highest (13.64%) and lowest (4.55%) infection rates, respectively. The infection rate among female P. papatasi collected from gerbil burrows was significantly higher (15.15%) than animal shelters, yards, and inside houses (4.48%) (P < 0.0%). Microsatellite was more sensitive (22.72%) than k-DNA (18.8%) and ITS-rDNA (7.48%). More molecular variations of L. major were found in Isfahan province. CONCLUSIONS: Arc-GIS software and other statistics tests were employed to find Leishmania positive and haplotype variations among sand flies. Geographical situations, altitude, climate, precipitation, humidity, temperature, urbanization, migrations, regional divergences, deforestation, global warming, genome instability, ecology, and biology of the sand flies intrinsically, and the reservoir hosts and neighboring infected locations could be reasons for increasing or decreasing the rate of Leishmania infection and haplotype variations.

Sustainable PET Waste Recycling: Labels from PET Water Bottles Used as a Catalyst for the Chemical Recycling of the Same Bottles.

We report using a waste material, poly(ethylene terephthalate) (PET) water bottle labels, for the chemical recycling of the same PET water bottles. The solid fillers used for the manufacturing of the packaging labels were recovered by thermolysis in an electrical furnace at 600, 800, and 1000 °C with 13.5, 12.0, and 10.4 wt % recovery. Characterization of the solid residue showed the presence of calcium carbonate, calcium oxide, and titanium dioxide, which are typical fillers used for packaging film manufacturing, such as water bottle labels. These solid residues were then used as a catalyst for PET depolymerization by glycolysis, in which the catalyst recovered from bottle labels and shredded PET reacted in the presence of excess ethylene glycol at 200 °C. The reaction mixtures were analyzed for PET conversion and the yield of the bis(2-hydroxyethyl)terephthalate (BHET) monomer as the final product of the glycolysis reaction to determine the efficiency of the catalyst. Our results show that the catalyst prepared at 800 °C (Cat-800) has the best performance and provides a 100% PET conversion with a 95.8% BHET yield with a 1.0 wt % loading in 1.5 h. The catalyst from the PET water bottle labels is nontoxic, readily available, cost-effective, environmentally friendly, and can be used as a model for the self-sufficient chemical recycling of PET via glycolysis.

Magnetic ionic liquid catalyst functionalized with antimony (III) bromide for effective glycolysis of polyethylene terephthalate.

In a previous study, we demonstrated the efficient depolymerization of polyethylene terephthalate (PET) through glycolysis using antimony (III) oxide, a commonly used catalyst in PET synthesis. In the present research, we introduce a novel approach involving the synthesis of a magnetic bifunctional ionic liquid, Fe3O4@PMIM.SbBr4, containing only 2.2 wt% of antimony. The aim is to reduce the required antimony dosage for the reaction and enable its facile recovery and reuse. By employing this catalyst in PET chemical recycling through glycolysis to generate bis (2-hydroxyethyl) terephthalate (BHET) monomer, we achieved 100% PET conversion with a 96.4% yield and selectivity for BHET. This outcome was obtained using a catalyst loading of 6.0 wt% at 200 °C and 0.6 bar in a high-pressure reactor. We explored the impact of catalyst loading on BHET yield and conducted a comparative assessment of the Fe3O4@PMIM.SbBr4 catalyst against antimony (III) bromide, and another synthesized unsupported antimony-containing ionic liquid. Our results revealed the superior catalytic activity of the magnetic ionic liquid catalyst in PET glycolysis. The utilization of this catalyst offers promising potential for PET glycolysis due to its effortless separation using an external magnet, ability to produce highly pure BHET, and recyclability for repetitive use.

Controlled Glycolysis of Poly(ethylene terephthalate) to Oligomers under Microwave Irradiation Using Antimony(III) Oxide.

We report here the production of higher-order oligomers from the glycolysis of poly(ethylene terephthalate) (PET) by using microwave irradiation in a controlled fashion, instead of its fully glycolyzed product, bis(2-hydroxyethyl)terephthalate (BHET). We show that different catalysts can generate either BHET as the ultimate glycolysis product or higher oligomers of PET under microwave irradiation. Depolymerization of waste PET with an average degree of polymerization (DP) of 417 from water bottles was performed in the presence of 0.25 wt % antimony(III) oxide (Sb2O3) as the catalyst at 240 °C and 400 W microwave power, resulting in an oligomer yield of 96.7% with an average DP of 37. Under these conditions, the conversion of PET to oligomers reached 100% in only 5 min at 240 °C (with a 10 min ramping time) and with a ethylene glycol to PET weight ratio of 2.5. In comparison, under the same reaction conditions, 0.04 wt % of zinc acetate (Zn(OAc)2), a well-known catalyst for PET glycolysis, produces only the BHET monomer in 96.3% yield. Our results demonstrated that by using Sb2O3, the same catalyst that is used extensively for PET synthesis from BHET, under microwave irradiation, the PET glycolysis can be controlled to produce higher PET oligomers as an alternative for a complete chemical depolymerization to the BHET monomer. These oligomers are more suitable for being used as additives for many applications and to produce high-quality second-generation products, including regenerated PET.

Pharmacological Effects of Ginseng: Multiple Constituents and Multiple Actions on Humans.

Ginseng is a very commonly used natural product in the world, and its two main species are Asian ginseng and American ginseng. Ginseng is an adaptogenic botanical that reportedly protects the body against stress, stabilizes physiological processes, and restores homeostasis. Previously, different animal models and contemporary research methodologies have been used to reveal ginseng's biomedical activities in different body systems and the linked mechanisms of actions. However, human clinical observation data on ginseng effects have attracted more attention from the general public and medical community. In this paper, after an introduction of the phytochemistry of ginseng species, we review positive ginseng clinical studies, mainly conducted in developed countries, performed over the past 20 years. The reported effects of ginseng are presented in several sections, and conditions impacted by ginseng include diabetes; cardiovascular disorders; cognition, memory, and mood; the common cold and flu; cancer fatigue and well-being; quality of life and social functioning, etc. Administration of ginseng demonstrated a good safety record in humans. Although encouraging beneficial effects obtained from clinical data, using the study treatment regimen, the reported ginseng effects in general only ranged from mild to moderate. Nonetheless, these beneficial effects of ginseng could be a valuable add-on therapy for patients receiving standard drug treatments. Additionally, as a dietary supplement, ginseng possesses an important role in maintaining and promoting human health. We believe that the quality of future ginseng trials should be improved, particularly by providing detailed herbal phytochemistry and quality control information. With solid effectiveness data obtained from a well-designed, carefully executed ginseng clinical trial, this meritoriously herbal medicine will be widely used by consumers and patients.

Effects of eight-week high-intensity interval training on some metabolic, hormonal and cardiovascular indices in women with PCOS: a randomized controlled trail.

BACKGROUND: Studies have revealed that high-intensity interval training (HIIT) has beneficial effect on hormonal, cardiovascular indices in women with polycystic ovary syndrome (PCOS). There, however, is still no comprehensive data on the type, intensity and duration of training for these women. OBJECTIVE: The current study aimed to investigate the effects of high-intensity interval training (HIIT) on metabolic, hormonal and cardiovascular indices in women with PCOS compared to a control group. METHODS: In a randomized controlled study, 28 patients (age: 23.8 ± 5.3 years, weight: 82.4 ± 9.7 kg, BMI: 30.33 ± 3.99 kg/m2) were divided into two groups including HIIT (n = 14) and the control (n = 14). The training protocol was performed with 100-110 maximum aerobic velocity (MAV), 4-6 sets, 4 laps, 3 sessions per week for eight weeks. Anthropometric indices, aerobic performance, insulin resistance and sensitivity, lipid profiles, testosterone, cortisol and hs-CRP were evaluated. RESULTS: The HIIT intervention decreased BMI, waist to hip ratio (WHR), visceral fat, insulin, insulin resistance, low density lipoprotein (LDL), atherogenic index, cholesterol and cortisol (P < 0.05). All variables remained unchanged in the control group (P > 0.05). Except for VAI, FBG, HDL, TG and AIP, the rest of the variables in the training and control groups show a significant difference (P < 0.05). CONCLUSION: The results of the present study indicate that eight weeks of HIIT has beneficial effects on anthropometric, insulin sensitivity, fat profile, and inflammatory and cardiovascular indices in PCOS patients. It seems that the intensity of HIIT (100-110 MAV) is a determining factor in creating optimal adaptations in PCOS patients. TRAIL REGISTRATION: IRCT20130812014333N143. Registration date: 22/03/2020. URL: https://en.irct.ir/trial/46295 .

Spontaneous idiopathic spinal subdural hemorrhage in a 16-year-old boy: A rare case in pediatrics and review of literature.

Idiopathic spinal subdural hematoma (SSDH) is a rare phenomenon. Here, we present a 16-year-old-boy who presented with acute sudden onset weakness and brown squared syndrome; the cervical MRI findings showed acute subdural hematoma from C2 to C6. Emergent surgical intervention was performed, and significant improvement was seen in follow-ups.

A Turn Off Fluorescence Probe Based on Carbon Dots for Highly Sensitive Detection of BRCA1 Gene in Real Samples and Cellular Imaging.

In this research, DNA-modified carbon dots (CDs) were exploited to construct a fluorescence assay for breast cancer genes (BRCA1, a potential marker for cancer diagnosis) detection. For this purpose, water-soluble synthesized CDs were functionalized with 19 mer-modified oligonucleotides (capture probe). By adding the DNA target, the specific binding between the DNA probe and DNA target causes fluorescence quenching. The assay displayed a fine capability of sensing the BRCA1 gene with a linear range (R2 = 0.9918) of 36 attomolar (aM) to 532 femtomolar (fM) and a detection limit of 2 attomolar. This homogeneous process does not need additional separation and washing steps of un-hybridized DNA. To assess the selectivity, the prepared biosensor responses were evaluated in solutions containing single-base mismatched DNA sequences, three-base mismatched DNA sequences, or non-complementary DNA sequences, separately. To demonstrate the practical application of the designed biosensor, the extracted DNA from blood samples of breast cancer patients was utilized as real samples. When the CDs-DNA bioassay was exploited in the imaging of MCF-7 cancer cells, strong fluorescence emission was observed. After incubation times, both the cells' size and shape remained unchanged. The results validated that the CDs are an extremely great bioimaging candidate in disease diagnosis, biomedicine investigation, and managing cancer diseases.

Carbon dots hybrid for dual fluorescent detection of microRNA-21 integrated bioimaging of MCF-7 using a microfluidic platform.

BACKGROUND: MicroRNAs have short sequences of 20 ~ 25-nucleotides which are similar among family members and play crucial regulatory roles in numerous biological processes, such as in cell development, metabolism, proliferation, differentiation, and apoptosis. RESULTS: We reported a strategy for the construction of a dual-emission fluorescent sensor using carbon dots (CDs) and confirmed their applications for ratiometric microRNA-21 sensing and bioimaging of cancer cells in a microfluidic device. The composition of blue CDs (B-CDs) and yellow CDs (Y-CDs) depicts dual-emission behavior which is centered at 409 and 543 nm under an excitation wavelength of 360 nm. With increasing microRNA-21 concentration, the robust and specific binding of DNA probe functionalized B-CDs to complementary microRNA-21 target induced perturbations of probe structure and led to changing fluorescence intensity in both wavelengths. Consequently, the ratio of turn-on signal to turn-off signal is greatly altered. With monitoring of the inherent ratiometric fluorescence variation (ΔF540nm/ΔF410nm), as-prepared BY-CDs were established as an efficient platform for ratiometric fluorescent microRNA-21 sensing, with a wide linear range of 0.15 fM to 2.46 pM and a detection limit of 50 aM. CONCLUSIONS: Furthermore, the proposed assay was applied for detecting microRNA-21 in dilute human serum samples with satisfactory recovery and also in MCF-7 cell lines in the range 3000 to 45,000 (cell mL-1) with a detection limit (3 cells in 10 µL), demonstrating the potential of the assay for clinic diagnosis of microRNA-associated disease. More importantly, the images revealed that MCF-7 cells well labeled with BY-CDs could exhibit the applicability of the proposed microfluidic system as an effective cell trapping device in bioimaging.

A Chelation-enhanced Fluorescence Assay using Thiourea Capped Carbonaceous Fluorescent Nanoparticles for As (III) Detection in Water Samples.

Herein, we designed a sensitive and selective "Turn-On" fluorescence nanosensor using water-soluble carbonaceous fluorescent nanomaterials (CFNs) functionalized with thiourea (CFNs-Thiourea) for efficient detection of trace concentrations of arsenic (III) in aqueous samples. The CFNs and CFNs-Thiourea were characterized by transmission electron microscopy (TEM), UV-visible spectroscopy (UV-vis) and fourier transformed infrared spectroscopy (FTIR). The emission peak intensity of proposed nanosensor at 425 nm was gradually enhanced on arsenite addition in a wide detection range (3.3-828.5 µg L-1) attributed to the binding of arsenite species with sulfur groups of CFNs-Thiourea. The limit of detection (LOD) was 0.48 µg L-1 being much lower than the World Health Organization (WHO) recommended threshold value of 10 µg L-1. Furthermore, the as-prepared CFNs-Thiourea exhibited a superb selectivity for As (III) compared to various cations and anions, such as; NO3-, NO2-, F-, Ni2+, Fe3+, Cu2+, Ca2+, Mg2+, Zn2+, Fe2+, Hg2+, Pb2+, F-, Cl-, Mn2+, Cr3+, Co2+, Cd2+, Bi3+, Al3+ and As (V) at 100 folds concentration of As (III). The turn on fluorescence nanosensor was successfully exploited for quantification of arsenic in spiked water samples with acceptable efficiencies.

An overview of modeling and behavioral assessment of autism in the rodent.

Autism Spectrum Disorders (ASDs) are common neurodevelopmental disorders with a growing incidence that generally present in the first 3 years of life. Behavioral symptoms, including impaired social interaction and increased repetitive or stereotypic movements, are hallmark characteristics of autism. Animal models are research tools used to study the biology of the disease and to develop new therapeutic approaches. The complexity of the etiology of autism makes it challenging to develop a comprehensive animal model that accurately mimics different clinical aspects of autism. Here, we reviewed the literature on modeling and behavioral assessment of autism in the rodent, and focused on ASD behavioral phenotypes that can be modeled in rodents. These animal models can be effective in gaining a better understanding of the pathophysiology of the disease.

Sleep Duration as the Main Indicator of Self-Rated Wellness and Health among Healthcare Workers Involved in the COVID-19 Pandemic.

OBJECTIVE: This study was performed during the COVID-19 pandemic to better understand the indicators of self-rated wellness and health among healthcare workers. METHODS: Sleep pattern, mood status, nutritional condition, physical activity, habits and the subjective wellness and health index of the healthcare workers of a university affiliated hospital were surveyed. Paired t-tests were performed to compare the participants' quality of life before and after the outbreak of COVID-19. Multivariable linear regression models with a backward elimination stepwise process determined the parameters that significantly correlated with self-reported wellness and health. RESULTS: Of the 200 healthcare workers who participated in this study, 119 (60%) were female and 81 (40%) were male, with a mean (SD) age of 28.8 (5.9) years. We found that the COVID-19 pandemic significantly changed many lifestyle factors compared to the pre-pandemic states. The scores of sleep quality, mood status, pre-planned physical activity and social activity were reduced by 30%, 40%, 50% and 70%, respectively. The average night sleep duration before the pandemic was 7 h and 22 min, whereas during the pandemic it decreased to 6 h and 44 min, a debt of 38 min in sleep duration every night. As found by multivariable regression modelling, self-reported wellness and health before the pandemic period was associated with wake-up time, mood status, physical activity and diet. During the pandemic period, in addition to these variables, night sleep duration (ß = 0.049, p = 0.049) and nap duration (ß = 0.009, p = 0.01) were left in the final multivariable model and correlated significantly with the wellness and health index. CONCLUSION: COVID-19 has detrimentally affected healthcare workers' well-being and quality of life. Sleep duration was the main factor correlated with subjective wellness and health index during the current COVID-19 pandemic.

Prevalence of coronavirus disease 2019 in rheumatic patients and evaluation of the effect of disease-modifying anti-rheumatic drugs.

One of the most controversial issues among rheumatologists is the best approach to managing a rheumatic patient (RP) with coronavirus disease 2019 (COVID-19). This study aims to evaluate the prevalence of COVID-19 in RPs compared to the general population and to relatively assess the potential role of RPs' treatment regimen against COVID-19. In a cross-sectional study, all RPs with an updated medical record between December 1, 2019, and February 29, 2020, at the rheumatology clinic of Shahid Beheshti Hospital, Qom, Iran were included (as the case group), and the prevalence of COVID-19 was compared to the paired control group-individuals without RDs, randomly selected from the Qom Health Network's database. Qom was the first city in Iran in which COVID-19 was identified and spread rapidly. Both groups were paired regarding sex, age, and underlying severe conditions. The prevalence of COVID-19 was lower in RPs than the control group (p = 0.028). Moreover, patients who were under treatment with disease-modifying anti-rheumatic drugs (DMARDs) and biologic agents seemed to possess a lower risk for COVID-19. Two RPs died from COVID-19, both of whom had granulomatosis and polyangiitis (GPA). The prevalence of COVID-19 in the RPs was lower than the control group, which could be associated with more adherence to the quarantine and social distancing rules by RPs and stricter routine follow-ups than the general population. Besides, taking DMARDs, such as leflunomide, might possess a protective effect against severe COVID-19, probably as a result of preventing cytokine storm.

A 3D hydrogel based on chitosan and carbon dots for sensitive fluorescence detection of microRNA-21 in breast cancer cells.

Hydrogels are 3D polymeric networks with great swelling capability in water and appropriate chemical, mechanical and biological features which make it feasible to maintain bioactive substances. Herein, we fabricated carbon dots-chitosan nanocomposite hydrogels via reacting carbon dots synthesized from various aldehyde precursors with chitosan after that functionalized with ssDNA probe for detection of microRNA-21 in MCF-7 cancer cells. More importantly, three fluorescent hydrogels were produced using schiff base reaction (forming imine bonds) among the amine in chitosan and aldehyde groups on the CDs surface. Furthermore, the hydrogel films, CDs and CDs-chitosan nanocomposite hydrogels were characterized by UV-vis absorption and fluorescence spectra, FT-IR, scanning electron microscope (SEM) and transmission electron microscopy (TEM). The DNA hydrogel bioassay strategy revealed a great stability and a superb sensitivity for microRNA-21, with a suitable linear range (0.1-125 fM) and a detection limit (0.03 fM). For sample analysis, the biosensors exhibited good linearity with MCF-7 cancer cell concentrations from 1000 to 25000, 1000-25000 and 1000-6000 cells mL-1 and detection limit of 310, 364 and 552 cells mL-1, for glutaraldehyde, nitrobezaldehyde and benzaldehyde based nanocomposite hydrogels, respectively. In addition, cell viability consequences demonstrated low probe cytotoxicity, so nanocomposite hydrogels was utilized to multicolor imaging of MCF-7 cancer cells.

A hierarchical 3D camellia-like molybdenum tungsten disulfide architectures for the determination of morphine and tramadol.

A practical technique was applied to fabricate MoWS2 nanocomposite through a one-pot hydrothermal method for use as the electrocatalyst. The characterization of MoWS2 nanocomposite was investigated by several techniques to identify the size, crystal structure, and elemental composition. MoWS2 nanocomposite exhibited a unique and well-defined hierarchical structure with neatly and densely piled nanopetals acting as the active sites in the electrocatalytic reactions. A carbon screen-printed electrode (CSPE) modified with interesting MoWS2 nanopetals (MoWS2/CSPE) was constructed. Subsequently, the electrochemical oxidation of morphine on fabricated MoWS2/CSPE was studied. Experimental results confirm that under optimized conditions, the maximum oxidation current of morphine occurs at 275 mV in the case of MoWS2/CSPE that is around 100 mV more negative than that observed in the case of the unmodified CSPE and about 2.6 times increase was observed for the oxidation peak current. The analytical approach was obtained by differential pulse voltammetry in accordance with the relationship between the oxidation peak current and the morphine concentration. The oxidation peak currents for morphine were found to vary linearly with its concentrations in the range of 4.8 × 10-8-5.05 × 10-4 M with the detection limit of 1.44 × 10-8 M. Two completely separated signals occured at the potentials of 275 mV and 920 mV for oxidation of morphine and tramadol at the surface of MoWS2/CSPE which are sufficient for determination of morphine in the presence of tramadol. The presence of morphine was also detected in real samples using the introduced approach. Graphical abstract Schematic representation of fabrication of the MoWS2 nanocomposite through a one-pot hydrothermal method for use as the electrocatalyst. A carbon screen-printed electrode was modified with MoWS2 nanocomposite. Subsequently, the electrochemical oxidation of morphine on the fabricated electrode was studied.

Improvement of autistic-like behaviors in adult rats prenatally exposed to valproic acid through early suppression of NMDA receptor function.

RATIONALE: Autism spectrum disorder (ASD), the fastest growing neurodevelopmental disorder, is characterized by social deficits, repetitive/stereotypic activity, and impaired verbal and nonverbal communication and is commonly diagnosed at early stages of life. Based on the excitatory-inhibitory imbalance theory of autism, some recent animal experiments have reported amelioration in autistic-like phenotypes in adult animals following acute treatment of NMDA antagonists. However, we suggested the neonatal period as a critical period for NMDA antagonist intervention. OBJECTIVES: This experiment was designed to determine the role of postnatal MK-801, an NMDA receptor blocker, in the prenatal valproic acid (VPA) rat model of ASD. METHODS: The model of autism was induced by subcutaneous administration of valproic acid (600 mg/kg) to pregnant rats at gestational day 12.5. The effects of MK-801 (0.03 mg/kg, from postnatal day 6-10) in correcting ASD-associated behaviors in male offspring were assessed by open-field, three-chambered social interaction tests. Moreover, the nociceptive threshold was measured by tail flick and hot plate. Behavioral tests were performed on PND 55-60. Nissl staining was performed to confirm the safety of 0.03 mg/kg MK-801 for the brain. RESULTS: We reported that MK-801 rescued social deficits, repetitive behaviors (self-grooming), anxiety-related behavior, and the low nociceptive threshold in the VPA-treated rats. Further, histological examination showed that there were no significant differences among all the groups in terms of the neuronal survival rate. CONCLUSIONS: Our results showed that postnatal low-dose MK-801 improved ASD-associated behaviors in the VPA-treated rats and that early exposure to NMDA antagonist resulted in permanent changes in adult behavior.