Search

Background: Poor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR. Methods: In this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction. Results: After the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group. Conclusion: AST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis. Trial registration: Clinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870, registration date: 2023 March 16. [ABSTRACT FROM AUTHOR]

Objective: Astaxanthin (ASX) is a lipid-soluble keto-carotenoid with several biological effects. These effects may benefit polycystic ovarian syndrome (PCOS) patients. Imbalanced apoptosis/anti-apoptosis signaling has been considered the major pathogenesis of PCOS. In a randomized clinical trial, we tested the impact of ASX on the apoptotic pathway in PCOS granulosa cells (GCs). The present study hypothesizes that ASX may improve apoptosis in PCOS patients. Materials and Methods: This trial recruited patients with confirmed PCOS. A total of 58 patients were randomly assigned to take ASX (12 mg) or placebo for 8 weeks. Aspirated follicular fluid (FF) and blood samples were taken from both groups to measure BAX and BCL2 protein expression. Following FF aspiration, GCs from both groups were obtained; Real-Time PCR and Western blotting were used to evaluate the apoptotic pathway's gene and protein expression levels in GCs.BAXBCL2 Results: In GCs analysis, ASX reduced DR5 gene and protein expression after 8 weeks compared to placebo(p<0.05). Also, Caspase8 (p>0.05) and BAX (p<0.05) gene expression declined, although the difference was not statistically significant for Caspase8. Besides, ASX treatment contributed to an elevated BCL2 gene expression in GCs(p<0.05). In FF and serum analysis, a statistically significant increase was found in BCL2 concentration in the ASX group (p<0.05). Moreover, a reduction in BAX level was confirmed in both FF and serum of the ASX group; however, this change was not significant in the serum (p>0.05). Conclusion: It seems that ASX consumption among women with PCOS improved serum and FF levels of apoptotic factors and modulated genes and protein expression of the apoptosis pathway in GCs. Nevertheless, further investigations are needed to reveal the potential role of this compound in PCOS treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Differentiating between glioma and primary central nervous system lymphoma (PCNSL) is difficult, and current diagnostic methods are of limited efficacy. Liquid biopsies that detect circulating biomarkers, such as microRNAs (miRs), may provide valuable insights into diagnostic biomarkers. In this review, a systematic search was conducted, and 16 dysregulated miRs were identified, including miR-21, which was the most prominent miR with higher levels in PCNSL, followed by the glioma and control groups. The lowest levels of miR-16 and miR-205 were observed in glioma, followed by PCNSL and control groups, whereas miR-15b and miR-301 were higher in both tumor groups, with the highest levels observed in glioma patients. The levels of miR-711 were higher in glioma (including GBM patients) and downregulated in PCNSL compared to the control group. Using these six circulating microRNAs as liquid biomarkers with unique changing patterns could aid in better discrimination between glioma and PCNSL. Differentiating glioma from primary central nervous system lymphoma (PCNSL) can be challenging, and current diagnostic measures such as MRI and biopsy are of limited efficacy. Liquid biopsies, which detect circulating biomarkers such as microRNAs (miRs), may provide valuable insights into diagnostic biomarkers for improved discrimination. This review aimed to investigate the role of specific miRs in diagnosing and differentiating glioma from PCNSL. A systematic search was conducted of PubMed, Scopus, Web of Science, and Embase for articles on liquid biopsies as a diagnostic method for glioma and PCNSL. Sixteen dysregulated miRs were identified with significantly different levels in glioma and PCNSL, including miR-21, which was the most prominent miR with higher levels in PCNSL, followed by glioma, including glioblastoma (GBM), and control groups. The lowest levels of miR-16 and miR-205 were observed in glioma, followed by PCNSL and control groups, whereas miR-15b and miR-301 were higher in both tumor groups, with the highest levels observed in glioma patients. The levels of miR-711 were higher in glioma (including GBM) and downregulated in PCNSL compared to the control group. This review suggests that using these six circulating microRNAs as liquid biomarkers with unique changing patterns could aid in better discrimination between glioma, especially GBM, and PCNSL. [ABSTRACT FROM AUTHOR]

An experimental study was conducted to study the effects of rounded (RL) and squared leading edge (SL) on the time-averaged and temporal characteristics around a slanted-back Ahmed body. Measurements were conducted at two Reynolds numbers of Re H = 1.70 × 104 and 3.60 × 104. The results showed that sharpening the leading edge induces a larger recirculation region near the leading edge of the body, but slightly reduces the recirculation region in the wake region. In both leading and near wake of bodies, the recirculation length for SL cases was independent of ReH, but for the RL body, it decreases in the leading edge and increases in the wake region as ReH increases. The analysis of turbulent structures showed that the extent of the region of elevated integral timescale around the body is larger in the SL case than RL one. Statistical analysis showed that sharpening the leading edge suppresses downwash flow, which in turn reduces the shear layer interaction behind the body and decreases the dominant shedding frequency. The dominant frequencies obtained using velocity fluctuations, reverse flow area, and the coefficient of the first proper orthogonal decomposition confirmed that the dominant frequency near the leading edge and the wake region of the RL body increases with Re H , while it is insensitive to Re H for SL case. The analysis performed in the spanwise plane also revealed that a region with higher streamwise mean velocity forms in the wake region of the RL body, which originates from the higher flow deviation near the trailing edge of the body. [ABSTRACT FROM AUTHOR]

Astaxanthin (ASX), as a natural carotenoid compound, exists in various types of seafood and microorganisms. It has several possible beneficial therapeutic effects for patients with polycystic ovary syndrome (PCOS). Patients with PCOS also suffer from endoplasmic reticulum (ER) stress. In the present work, it was hypothesized that ER stress could be improved by ASX in PCOS patients. Granulosa cells (GCs) were obtained from 58 PCOS patients. The patients were classified into ASX treatment (receiving 12 mg/day for 60 days) and placebo groups. The expression levels of ER stress pathway genes and proteins were explored using Western blotting and quantitative polymerase chain reaction. To assess oxidative stress markers, follicular fluid (FF) was gained from all patients. The Student's t test was used to perform statistical analysis. After the intervention, ASX led to a considerable reduction in the expression levels of 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and X-box-binding protein 1 compared to the placebo group, though the reduction in the messenger RNA (mRNA) expression level of activating transcription factor 6 was not statistically significant. However, ASX significantly increased the ATF4 expression level. GRP78 and CHOP protein levels represented a considerable decrease in the treatment group after the intervention. In addition, a statistically significant increase was found in the FF level of total antioxidant capacity in the treatment group. Based on clinical outcomes, no significant differences were found between the groups in terms of the oocyte number, fertilization rate, and fertility rate, but the ASX group had higher rates of high-quality oocytes, high-quality embryo, and oocyte maturity compared to the placebo group. Our findings demonstrated that ER stress in the GCs of PCOS patients could be modulated by ASX by changing the expression of genes and proteins included in the unfolding protein response. Trial registration This study was retrospectively registered on the Iranian Registry of Clinical Trials website (www.irct.ir; IRCT-ID: IRCT20201029049183N, 2020-11-27). [ABSTRACT FROM AUTHOR]

An experimental study was performed on two elongated bluff bodies with underbody gaps, a square-back Ahmed body and a cuboid, to investigate the effects of geometry and the approach flow conditions on the time-averaged and temporal characteristics. The flow fields produced from two approach turbulent boundary layers with moderate (∼4%) and high (∼7%) turbulence levels were studied using time-resolved and double-frame particle image velocimetry systems. With the moderate turbulence, the wake topology and the loci of the centroid of vortices exhibit the well-known toroidal structure behind the Ahmed body, though it is skewed away from the wall. Also, the regions of elevated Reynolds stresses are considerably larger in the upper shear layer compared to the lower shear layer due to the reduced underbody velocity. The dominant frequencies obtained from the velocity fluctuations, reverse flow area, and the coefficient of the first proper orthogonal decomposition (POD) mode are identical. The flow structures are more complex behind the cuboid and the Ahmed body mounted in the high turbulent flow due to the enhanced interaction between the lower and upper shear layers, which is also evident from the shape of the turbulent structures in these shear layers. Consequently, the dominant vortex shedding frequencies varied as the streamwise distance from the bodies increased. The probability density function of the reverse flow area and the POD analysis performed in the spanwise plane revealed that the bi-stability phenomenon is absent in the present study due to the significant modification of the wake topology. [ABSTRACT FROM AUTHOR]

Objective: Sulforaphane (SFN) is a natural free radical scavenger that can reduce oxidative stress (OS) through mediating nuclear factor (erythroid-derived 2)-like 2 (NF-E2-related factor 2 or NRF2)/antioxidant response element (ARE) signaling pathway and the downstream antioxidant enzymes. Here, we intended to study the role of SFN in OS- induced human granulosa cells (GCs) by investigating the intracellular levels of reactive oxygen species (ROS), cell death, and NRF2-ARE pathway. Materials and Methods: This experimental study was conducted on GCs of 12 healthy women who had normal menstrual cycles with no history of polycystic ovary syndrome (PCOS), endometriosis, menstrual disorders, hyperprolactinemia, or hormonal therapy. After isolation of GCs, the MTT assay was performed to explore GCs viability after treatment with SFN in the presence or absence of H2O2. Flow cytometry was utilized to determine the intracellular ROS production and the apoptosis rate. Evaluation of the mRNA and protein expression levels of NRF2 and phase II enzymes including superoxide dismutase (SOD) and catalase (CAT) was performed by quantitative real-time polymerase chain reaction (PCR) and western blotting. Finally, the data were analyzed by SPSS software using One-way ANOVA and the suitable post-hoc test. Significance level was considered as P<0.05. Results: Pretreatment of GCs with SFN attenuated intracellular ROS production and apoptosis rate in the H2O2-exposed cells. Moreover, SFN treatment increased the mRNA expression level of NRF2, SOD, and CAT . Higher expression of NRF2 and SOD was also observed at the protein level. Conclusion: Our study demonstrated that SFN protects human GCs against H 2O2 induced-OS by reducing the intracellular ROS production and the following apoptosis through a mechanism by which NRF2 increases the antioxidant enzymes such as SOD and CAT. This result may have a potential application in aassisted reproduction cycles by improving the quality of GCs and the embedded oocyte, especially in PCOS patients. [ABSTRACT FROM AUTHOR]

• Cf-mtDNA in follicular fluid of PCOS patients was significantly lower than non-PCOS women. • We found that cf-mtDNA in follicular fluid of women with different reproductive status has not an equal efficiency regarding biomarker of ART outcome. • Cf-mtDNA is not an appropriate biomarker for ART outcome in PCOS patients. • Our data suggests that elevation of cf-mtDNA in follicular fluid might result from impairment of mtDNA packaging by TFAM , and the consequence of this event will be triggered by induction of inflammatory cytokines. Lack of reliable biomarkers for estimating the outcome is one of the current gaps in ART. In this study, we assessed whether cell-free mitochondrial DNA within the follicular fluid (FF cf-mtDNA) of PCOS patients has biomarker applicability or not. Furthermore, probable involved mechanisms in the FF cf-mtDNA pathway were evaluated. The level of FF cf-mtDNA was compared between 50 PCOS patients and 50 women without any certain reproductive disorder, and analyzed for correlations with ART outcome. The associations between levels of FF cf-mtDNA and TFAM , POLG , and RNase H1 genes expression in mural granulosa cells (MGCs), as well as IL-6, and TNFα in follicular fluid (FF) were assessed. We identified that FF cf-mtDNA level was significantly lower in PCOS women and was accompanied by a reduction in the expression of mtDNA biogenesis genes in MGCs of the patients. Although a significant association between FF cf-mtDNA level and ART outcome was observed in the control group, no correlation could be proved in the PCOS group. Moreover, the expression level of TFAM was negatively associated, while amounts of IL-6 and TNFα were positively correlated with FF cf-mtDNA level in both groups. PCOS patients present a lower FF cf-mtDNA level in comparison with non-PCOS women. FF cf-mtDNA has biomarker applicability for ART outcome in women without any certain reproductive disorder, but not for those with PCOS. It seems that mtDNA packaging dysfunction results in elevated FF cf-mtDNA, and subsequent effects are triggered by increasing the inflammatory cytokines. [ABSTRACT FROM AUTHOR]

In this study, selenite ions were reduced to selenium nanoparticles using a leaf extract of barley (Hordeum vulgare L.) plants. Characterization of synthesized nanoparticles using Scanning Electron Microscopy (SEM) and UV-visible spectrophotometry indicated the formation of variable size of selenium nanoparticles, suggesting that leaf extract could form polydispersed nanoparticles. Then we used these synthesized selenium nanoparticles to mitigate salt stress in barley plants under hydroponic conditions. Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) analyses suggested that the hydroponically nano-Se application resulted in direct accumulation of Se in the leaves of barley. Shoot growth was negatively affected by salinity levels up to 100 mM, whereas this reduction was mitigated by application of exogenous Se nanoparticles. Our results indicated that high salinity stress decreased the activity of superoxide dismutase (SOD), and enhanced the levels of malondialdehyde (MDA) in the leaves of barley seedlings, whereas application of Se nanoparticles increased total phenolic levels, and also resulted in a significant reduction of MDA (a marker for the ROS-mediated cell membrane damage) contents, which could influence the metabolism and be responsible for the increasing shoot dry weight. These results provided the first evidence that the green Se nanoparticles promote the growth of barley seedlings under salt stress. [ABSTRACT FROM AUTHOR]

Turbulent flows are investigated in the bypass of a bar rack system to understand the effects of weirs placed at the bypass entrance on hydraulic conditions used to guide fish moving downstream. Three test cases were studied: (a) no weir (reference case), (b) arc-shaped weir and (c) triangular weir. A stereo particle image velocimetry system was employed to acquire the three velocity components in the mid-plane of the bypass and examine various statistics including mean velocities, Reynolds stresses, turbulent kinetic energy as well as turbulence eddies and swirling strength. The weirs deflect the flow away from the channel bed due to the blockage effect and increase the bypass velocity significantly, though remains under the suggested critical value of 1 m s−1 when the approach velocity was 0.38 m s−1. In the wake region of the triangular weir, a distinct recirculation bubble forms which may negatively affect fish migration. There is an increase in the level of Reynolds stresses and turbulent kinetic energy in the upstream vicinity of the weirs and the shear layers issuing from their tips. It is shown that the topology of the turbulence eddies is greatly modified by the weirs which can more readily assist fish guidance toward the bypass. Also, the swirling strength of the turbulence eddies behind the triangular weir is more pronounced compared to the arc-shaped weir. For the reference case, the swirling strength of the eddies is the weakest. • Effects of weirs at bypass entrance of bar rack systems on fish guidance effectiveness and swimming behavior are studied. • Key variables including velocities, spatial acceleration, Reynolds stresses, TKE as well as turbulence eddies are examined. • Mean velocities, spatial acceleration, Reynolds stresses and TKE enhanced significantly with the insertion of weirs. • Turbulence eddies are modified substantially around the weirs which helps fish pass downstream more readily. [ABSTRACT FROM AUTHOR]

Background: Cervical ectopic pregnancy (CEP) is a rare and dangerous form of ectopic pregnancy in which the blastocyst is installed within the endo-cervical canal. CEP diagnosis requires special awareness to evaluate patient precisely. Individualizing controversial medical and surgical management strategies is of importance in medical practice. Case: A 35-year-old nulliparous woman on her 9th week of pregnancy was referred to our hospital with vaginal bleeding preliminary misdiagnosed as aborting intrauterine pregnancy. Transvaginal ultrasound revealed an empty uterus and a viable triplet pregnancy just below the level of internal os. Cervical curettage after cerclage suture placement procedure removed conception tissues completely. Consequently, in the next few hours vaginal bleeding decreased to minimal amount and vital signs remained within normal limits and there was no hematocrit change. On follow-up day 32, serum B-HCG became negative. Conclusion: CEP diagnosis requires special attention and awareness to evaluate patient precisely along with skillful assessment of possible risk factors. Lifesaving treatment beside fertility preservation was successful with pre-curettage cerclage. [ABSTRACT FROM AUTHOR]

• Mean and turbulent quantities of twin round jets presented at different Re. • Swirling strength analysis performed to study vortical structures of twin jets. • Turbulent/non-turbulent interface examined in jet's inner and outer shear layers. • Twin round and plane jets were compared. The aim of the current study is to delineate the effects of Reynolds number (Re = 5000–20,000) on the mean and turbulent properties as well as the turbulent structures of the flow issuing from twin round jets with nozzle spacing of 2.8 nozzle diameter (d). The measurements were performed using a high-resolution particle image velocimetry from the jet exit up to x/d = 40 to examine the merging, converging and combined regions of the twin jets. The results show that the velocity decay and jet spread rates, and the combined point location become Re -independent at Re > 10,000 while the merging points shift downstream as Re increases. Upstream of the merging point, the levels of Reynolds stresses and turbulent kinetic energy production are higher and vortical structures are more intense in the inner shear layers compared to the outer shear layers. At the merging point they equal each other and beyond this point the trends are opposite of those at the upstream. The flow analysis at turbulent/non-turbulent interface of the outer shear layer reveals that conditional streamwise velocity and spanwise vorticity are Re -independent while significantly larger transverse velocity is observed at the lowest Re. At the inner shear layer interface, on the other hand, the conditional properties do not show any dependence on Re. Two-point correlation functions exhibit the presence of larger structures in the outer shear layers due to more exposure to the ambient fluid compared to the inner shear layers. The size of the structures also decreased as Re increased indicating the effect of Re on large-scale engulfment. Joint and weighted joint probability density functions are presented to examine the flow behaviors in more details. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of endometrial preparation by exogenous steroids, with and without pretreatment by the use of GnRH agonist. Materials and methods: This randomized interventional study was conducted on 100 women who underwent a FTET that were randomly assigned to receive GnRH agonist (buserelin) in the luteal phase or no receive this medication. In both groups endometrial preparation was achieved by the use of estradiol valerate pill started from the second day of the menstruation and used every day, with an initial dose of 2mg/d and every 3 days increased to 4 mg/d and 6 mg/d, respectively. Endometrial thickness was evaluated by vaginal ultrasound. Forty eight hours after beginning of progesterone administration 2 to 3 embryos surviving in freezing procedure were transferred. Results: the two groups were similar in mean age, body mass index, duration of infertility, type of infertility, number of embryos transferred and endometrial thickness on the day of beginning progesterone therapy. Comparing outcome of FTET between the two groups scheduled for receiving GnRH agonist showed no significant difference in the rate of implantation (6.7% versus 10.0%), the rate of chemical pregnancy (21.7% versus 22.5%), clinical pregnancy rate (15.0% versus 17.5%), and also ongoing pregnancy (13.3% versus 12.5%). Conclusion: Endometrial preparation for FTET using GnRH agonists appears to be as effective as FTET without administrating these agonists. [ABSTRACT FROM AUTHOR]

A growing number of studies implicate the brain's reward circuitry in aggressive behavior. However, the cellular and molecular mechanisms within brain reward regions that modulate the intensity of aggression as well as motivation for it have been underexplored. Here, we investigate the cell-type-specific influence of ΔFosB, a transcription factor known to regulate a range of reward and motivated behaviors, acting in the nucleus accumbens (NAc), a key reward region, in male aggression in mice. We show that ΔFosB is specifically increased in dopamine D1 receptor (Drd1)-expressing medium spiny neurons (D1-MSNs) in NAc after repeated aggressive encounters. Viral-mediated induction of ΔFosB selectively in D1-MSNs of NAc intensifies aggressive behavior without affecting the preference for the aggression-paired context in a conditioned place preference (CPP) assay. In contrast, ΔFosB induction selectively in D2-MSNs reduces the time spent exploring the aggression-paired context during CPP without affecting the intensity of aggression per se. These data strongly support a dissociable cell-type-specific role for ΔFosB in the NAc in modulating aggression and aggression reward. [ABSTRACT FROM AUTHOR]

Aggression is an innate behavior that helps individuals succeed in environments with limited resources. Over the past few decades, neurobiologists have identified neural circuits that promote and modulate aggression; however, far less is known regarding the motivational processes that drive aggression. Recent research suggests that aggression can activate reward centers in the brain to promote positive valence. Here, we review major recent findings regarding neural circuits that regulate aggression, with an emphasis on those regions involved in the rewarding or reinforcing properties of aggressive behavior. [ABSTRACT FROM AUTHOR]

Introduction: Progesterone can be used instead of GnRH agonists and antagonists in order to avert a premature LH surge during controlled ovarian stimulation (COS) protocol. Nonetheless, there is limited knowledge regarding its utilization. Thus, this study compared the effects of progesterone and GnRH antagonists (GnRH-ant) on premature LH surges and assisted reproductive technology (ART) results in infertile women undergoing ART. Materials and methods: In this clinical trial, the progesterone protocol (study group) and GnRH-ant protocol (control group) were tested in 300 infertile individuals undergoing IVF/ICSI. The main outcome was the number of oocytes retrieved. The secondary outcomes included premature LH rise/surge, the quantity of follicles measuring ≥ 10 and 14 mm, oocyte maturity and fertilization rate, the number of viable embryos, high-quality embryo rate and pregnancy outcomes. Results: The study group exhibited a statistically significant increase in the number of retrieved oocytes, follicles measuring 14 mm or greater, and viable embryos compared to the control group (P < 0.05). The study group also increased oocyte maturity, chemical pregnancy rate, and clinical pregnancy rate (P < 0.05). Both groups had similar mean serum LH, progesterone, and E2 levels on trigger day. The control group had more premature LH rise than the study group, although this difference was not statistically significant. Conclusion: In conclusion, it can be stated that the progesterone protocol and the GnRH-ant protocol exhibit similar rates of sudden premature LH surge in infertile patients. However, it is important to note that the two regiments differ in their outcomes in ART. Trial registration: This study was retrospectively registered in the Iranian website (www.irct.ir) for clinical trials registration (http://www.irct.ir: IRCT-ID: IRCT20201029049183N, 2020-11-27). [ABSTRACT FROM AUTHOR]

Behavioral coping strategies are critical for active resilience to stress and depression; here we describe a role for neuroligin-2 (NLGN-2) in the nucleus accumbens (NAc). Neuroligins (NLGN) are a family of neuronal postsynaptic cell adhesion proteins that are constituents of the excitatory and inhibitory synapse. Importantly, NLGN-3 and NLGN-4 mutations are strongly implicated as candidates underlying the development of neuropsychiatric disorders with social disturbances such as autism, but the role of NLGN-2 in neuropsychiatric disease states is unclear. Here we show a reduction in NLGN-2 gene expression in the NAc of patients with major depressive disorder. Chronic social defeat stress inmice also decreases NLGN-2 selectively in dopamine D1-positive cells, but not dopamine D2-positive cells, within the NAc of stress-susceptible mice. Functional NLGN-2 knockdown produces bidirectional, cell-type-specific effects: knockdown in dopamine D1-positive cells promotes subordination and stress susceptibility, whereas knockdown in dopamine D2-positive cells mediates active defensive behavior. These findings establish a behavioral role for NAc NLGN-2 in stress and depression; provide a basis for targeted, cell-type specific therapy; and highlight the role of active behavioral coping mechanisms in stress susceptibility. [ABSTRACT FROM AUTHOR]

Background: The effect of elevated progesterone level on human chorionic gonadotropin (HCG) day in in vitro fertilization cycles is controversial. Some suppose that rise in progesterone level seems to have a negative impact on implantation and pregnancy by desynchronizing the endometrium, while others disagree. Objective: To evaluate the superiority of the frozen cycle over fresh cycle on live birth in patients with elevated progesterone level on HCG day. Materials and Methods: In this double-blind, randomized clinical trial, 72 women undergoing assisted reproductive technology with elevated progesterone level (=1.8 ng/dl) on HCG day were included. The participants were grouped by fresh versus frozen embryo transfer, randomly. Finally, the clinical pregnancy and live birth rate were compared. Results: The implantation rate was 21.51%. The clinical pregnancy rate was 47.22% in fresh embryo transfer group (17/36) and 41.66% in frozen group (15/36) (p=0. 40). The live birth rate was not significantly difference between two groups (p=0.56). Conclusion: None of the fresh and frozen cycles are superior to the other and we recommend individualizing the decision for each patient. The frozen cycle may impose more emotional stress on patients. [ABSTRACT FROM AUTHOR]

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication, which can cause high morbidity and mortality. Use of gonadotropin releasing hormone (GnRH) agonist instead of human chorionic gonadotropin (hCG) in GnRH antagonist cycles causes luteinizing hormone surge by GnRH stimulation which reduces the risk of OHSS by reducing the total amount of gonadotropin; however, there is no possibility of transferring fresh embryos. Objective: The current study aimed to evaluate the effect of hCG along with GnRH agonist administration in the occurrence of OHSS and pregnancy rate in females undergoing in vitro fertilization. Materials and Methods: The current randomized clinical trial was conducted on 80 cases in 2 groups. Gonal-F was used to stimulate the oocyte from the second day of menstruation. When follicle size was 12-14 mm, GnRH antagonist was added to the protocol till the detection of more than two follicles greater than 18 mm. Then, GnRH agonist was added to the protocol as a trigger. In group A, 35 hr after the administration of GnRH agonist, the low-dose human hCG, 1500 IU, was used. In group B, low-dose hCG, 1500 IU, was used at the same time by GnRH agonist administration. The rate of pregnancy, OHSS, and its severity were compared between 2 groups within 2 wk. Results: There was no significant difference regarding chemical and clinical pregnancies between the 2 groups. Severe OHSS was significantly higher in group B (p= 0.03). Conclusion: Administration of hCG 35 hr after GnRH agonist administration results in lower rate of severe OHSS. [ABSTRACT FROM AUTHOR]

Inter-male aggression is an essential component of social behavior in organisms from insects to humans. However, when expressed inappropriately, aggression poses significant threats to the mental and physical health of both the aggressor and the target. Inappropriate aggression is a common feature of numerous neuropsychiatric disorders in humans and has been hypothesized to result from the atypical activation of reward circuitry in response to social targets. The lateral habenula (LHb) has recently been identified as a major node of the classical reward circuitry and inhibits the release of dopamine from the midbrain to signal negative valence. Here, we discuss the evidence linking LHb function to aggression and its valence, arguing that strong LHb outputs to the ventral tegmental area (VTA) and the dorsal raphe nucleus (DRN) are likely to play roles in aggression and its rewarding components. Future studies should aim to elucidate how various inputs and outputs of the LHb shape motivation and reward in the context of aggression. [ABSTRACT FROM AUTHOR]

Background: There are only a few reports concerning the genetic risk factors for coronary artery disease (CAD). However, 2 polymorphisms of rs10757274 and rs2383206 on chromosome 9p21.3 have been shown recently to be associated with CAD in certain populations. This is the 1st study to investigate their validity and association with CAD in a sample of the Iranian population. Methods: Genomic DNA was extracted from the peripheral blood of all participants, consisting of 111 cases with CAD and 100 normal controls with normal coronary angiographies. Genotyping of rs10757274 and rs2383206 was performed in the cases and controls using designed mismatch primers via the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Statistical analysis presented a significant association between the rs10757274 GG (p value = 0.029, χ² = 7.078) and rs2383206 GG (p value = 0.036, χ² =6.658) genotypes and CAD among the cases as compared with the normal controls. Haplotype analysis of rs10757274 and rs2383206 polymorphisms showed 43% GG/GG haplotype with a significant association with CAD (p value = 0.014, χ² = 6.058). Conclusion: The results of this study provide an insight into the underlying molecular mechanism of CAD pathogenesis and pave the way for future functional studies on these variants. [ABSTRACT FROM AUTHOR]

We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3-4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1 x C57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening did not develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1 x D1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression. [ABSTRACT FROM AUTHOR]

Objective: MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) that transcriptionally or post-transcriptionally regulate gene expression through degradation of their mRNA targets and/or translational suppression. However, there are a few reports on miRNA-mediated expression regulation of long ncRNAs (lncRNAs). We have previously reported a significant upregulation of the lncRNA SOX2OT and its intronic coding gene, SOX2, in esophageal squamous cell carcinoma (ESCC) tissue samples. In this study, we aimed to evaluate the effect of induced overexpression of miR-211 on SOX2OT and SOX2 expression in vitro. Materials and Methods: In this experimental study, we performed both bioinformatic and experimental analyses to examine whether these transcripts are regulated by miRNAs. From the list of potential candidate miRNAs, miR-211 was found to have complementary sequences to SOX2OT and SOX2 transcripts. To validate our finding experimentally, we transfected the NT-2 pluripotent cell line (an embryonal carcinoma stem cell) with an expression vector overexpressing miR-211. The expression changes of miR-211, SOX2OT, and SOX2 were then quantified by a real-time polymerase chain reaction (RT-PCR) approach. Results: Compared with mock-transfected cells, overexpression of miR-211 caused a significant down-regulation of both genes (P<0.05). Furthermore, flow-cytometry analysis revealed a significant elevation in sub-G1 cell population following ectopic expression of miR-211 in NT-2 cells. Conclusion: We report here, for the first time, the down-regulation of SOX2OT and SOX2 genes by an miRNA. Considering the vital role of SOX2OT and SOX2 genes in pluripotency and tumorigenesis, our data suggest an important and inhibitory role for miR-211 in the aforementioned processes. [ABSTRACT FROM AUTHOR]

Aims: Pharmacological activation of the adaptive response to hypoxia is a therapeutic strategy of growing interest for neurological conditions, including stroke, Huntington's disease, and Parkinson's disease. We screened a drug library with known safety in humans using a hippocampal neuroblast line expressing a reporter of hypoxia-inducible factor (HIF)-dependent transcription. Results: Our screen identified more than 40 compounds with the ability to induce hypoxia response element-driven luciferase activity as well or better than deferoxamine, a canonical activator of hypoxic adaptation. Among the chemical entities identified, the antihelminthic benzimidazoles represented one pharmacophore that appeared multiple times in our screen. Secondary assays confirmed that antihelminthics stabilized the transcriptional activator HIF-1α and induced expression of a known HIF target gene, p21cip1/waf1, in post-mitotic cortical neurons. The on-target effect of these agents in stimulating hypoxic signaling was binding to free tubulin. Moreover, antihelminthic benzimidazoles also abrogated oxidative stress-induced death in vitro, and this on-target effect also involves binding to free tubulin. Innovation and Conclusions: These studies demonstrate that tubulin-binding drugs can activate a component of the hypoxic adaptive response, specifically the stabilization of HIF-1α and its downstream targets. Tubulin-binding drugs, including antihelminthic benzimidazoles, also abrogate oxidative neuronal death in primary neurons. Given their safety in humans and known ability to penetrate into the central nervous system, antihelminthic benzimidazoles may be considered viable candidates for treating diseases associated with oxidative neuronal death, including stroke. Antioxid. Redox Signal. 22, 121-134. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the outcomes of adding low-dose hCG (human chorionic gonadotropin), as an LH active supplement, to a GnRH antagonist protocol in patients undergoing assisted reproduction techniques. In this parallel-group randomized clinical trial, 137 infertile female outpatients aged 20 - 39 years were randomized into two groups: hCG group and non-hCG group. All patients received r-FSH (150-300 IU) and then a GnRH-antagonist, Cetrorelix (0.25 mg/day). Concomitantly with Cetrorelix, patients in the hCG group received low-dose hCG (200 IU daily), but the patients in the non-hCG group did not. 10,000 IU Urinary hCG (10,000 IU) was injected to all patients, and ICSI was performed after oocyte retrieval. The primary outcome of this study was comparing the pregnancy rates between two study groups. Other differences between two groups such as serum estradiol concentration, fertilization rate, etc. were considered as secondary outcomes. A total of 130 patients completed this trial. No significant difference was detected between pregnancy rates of the two groups (P=0.52) as well as the fertilization, implantation and ongoing pregnancy rates (P=0.11, P=0.75 and P=0.06 respectively). The only significant difference between two groups was a higher concentration of estradiol in the hCG-treated patients (P<0.05). HCG-treated patients experienced a shorter treatment duration and a lower r-FSH required dose than the non-hCG group, but none of these differences were statistically significant (P=0.19 and P=0.10, respectively). The findings of the current study did not support advantages of adding low-dose hCG to GnRH antagonist plus r-FSH protocol in an unselected population of patients. Well-designed trials with a larger sample size for specific patients' subgroups are warranted. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is characterized by autoimmune destruction of pancreatic beta cells, leading to decreased insulin production. Differentiation of mesenchymal stem cells ( MSCs) into insulin-producing cells offers novel ways of diabetes treatment. MSCs can be isolated from the human umbilical cord tissue and differentiate into insulin-secreting cells. Human umbilical cord-derived stem cells (h UDSCs) were obtained after birth, selected by plastic adhesion, and characterized by flow cytometric analysis. h UDSCs were transduced with nonintegrated lentivirus harboring PDX1 (nonintegrated LV- PDX1) and was cultured in differentiation medium in 21 days. Pancreatic duodenum homeobox protein-1 ( PDX1) is a transcription factor in pancreatic development. Significant expressions of PDX1, neurogenin3 (Ngn3), glucagon, glucose transporter2 (Glut2), and somatostatin were detected by quantitative RT- PCR ( P < 0.05). PDX1 and insulin proteins were shown by immunocytochemistry analysis. Insulin secretion of h UDSCsPDX1+ in the high-glucose medium was 1.8 μU/mL. They were used for treatment of diabetic rats and could decrease the blood glucose level from 400 mg/dL to a normal level in 4 days. In conclusion, our results demonstrated that h UDSCs are able to differentiate into insulin-producing cells by transduction with nonintegrated LV- PDX1. These h UDSCsPDX1+ have the potential to be used as a viable resource in cell-based gene therapy of type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Subclinical hypothyroidism may adversely affect In Vitro Fertilization (IVF) outcomes. However the cutoff of thyroid-stimulating hormone (TSH) for diagnosis and treatment is controversal. The aim of this study was to find the association of clinical pregnancy rate with regard to TSH levels in women undergoing IVF. Methods: A historical cohort study of 816 infertile patients who underwent IVF in 2011 and 2012 was conducted. The study subjects were categorized in two groups according to their baseline TSH level; one with 0.5 ≤TSH< 2.5 mIU/L and other with 2.5 ≤TSH< 4.5 mIU/L. All patients were followed up for 6 weeks after embroyonic transfer. The outcomes of the study were consisted of rates for Human Chorionic Gonadotropin (HCG) and evaluation of their clinical pregnancies. Results: About 60% of the study subjects had serum TSH level < 2.5 mIU/L and 40% ≥ 2.5 mIU/L. There were no statistically significant differences in age, years of infertility, BMI, baseline FSH and estradiol level of patients and the type of induction protocols between the study groups. The HCG rise was occurred in 30.4% of the subjects with TSH level < 2.5 mIU/L versus 26.3% of the subjects with TSH ≥ 2.5 mIU/L (p value= 0.2). The clinical pregnancy rates in the group of patients with TSH < 2.5 mIU/L and those with ≥ 2.5 mIU/L were 27.1% and 23.9% respectively (p value= 0.3). Conclusion: Our results were similar to various studies in which reported lack of association between TSH level in the range of 0.5- 4.5 mIU/L and IVF outcomes. It seems that lowering the upper limit of normal TSH should be still considered as a scientific debate. [ABSTRACT FROM AUTHOR]

We present the application of two-photon fluorescence (TPF) imaging to monitor intracellular hydrogen peroxide (H2O2) production in brain cells. For selective imaging of H2O2 over other reactive oxygen species, we employed small-molecule fluorescent probes that utilize a chemoselective boronate deprotection mechanism. Peroxyfluor-6 acetoxymethyl ester detects global cellular H2O2 and mitochondria peroxy yellow 1 detects mitochondrial H2O2. Two-photon absorption cross sections for these H2O2 probes are measured with a mode-locked Ti:sapphire laser in the wavelength range of 720 to 1040 nm. TPF imaging is demonstrated in the HT22 cell line to monitor both cytoplasmic H2O2 and localized H2O2 production in mitochondria. Endogenous cytoplasmic H2O2 production is detected with TPF imaging in rat astrocytes modified with D-amino acid oxidase. The TPF H2O2 imaging demonstrated that these chemoselective probes are powerful tools for the detection of intracellular H2O2. [ABSTRACT FROM AUTHOR]

Background & Objective: Fragile X syndrome is one of the most common causes of inherited mental retardation in males after Down syndrome. To date less attention was to study secondary genetic factor that may play role in fragile X neuropathology. In central nervous system, folic acid derivatives participate in different process such as neural development and function, synthesis of neurotransmitters and DNA methylation. This study aimed to assess the possible association of three common polymorphisms of folate pathway key enzymes, methylentetra hydrofolate reductase, MTHFR (C677T and A1298C), and methionine synthase reductase, MTRR (A66G), polymorphisms with the development of fragile X syndrome. Methods: Genetic polymorphisms were examined in a case-control study of 38 unrelated male patients and 60 age/sex matched unrelated controls using PCR-RFLP method. Allele frequencies and genotypes were calculated by chi-square test. Results: significantly increased frequencies of the 677T allele and the 677CT genotype in patients were observed compared to control (p=0.010; OR=2.459 for T allele frequency; p=0.028; OR=2.608 for CT genotype frequency). The statistical analysis demonstrated the significant correlation between C677T MTHFR polymorphism and fragile X syndrome in Iranian population (p=0.018). However, no significant case-control differences were found for A1298C MTHFR and A66G MTRR polymorphisms. Conclusions: The association between C677T MTHFR polymorphism and fragile X syndrome has been demonstrated for the first time in Iran population. This study may be important in better understanding of molecular pathology of fragile X syndrome. Further studies need to be undertaken to evaluate these preliminary results in other populations. [ABSTRACT FROM AUTHOR]

Background Granisetron is a first-generation 5-HT3-receptor antagonist that has shown efficacy in preventing postoperative nausea and vomiting (PONV). In this randomized doubleblind parallel-group clinical trial, we assessed the efficacy of generic granisetron versus Kytril®, in the prevention of PONV in patients undergoing general anesthesia for gynaecological surgeries. Method One hundred and twenty patients who were supposed to undergo major gynaecological surgeries (myomectomy and hysterectomy) in Dr. Shariati Teaching Hospital, Tehran, Iran were randomly assigned to either single dose generic granisetron (40 mcg/kg), or Kytril® (40 mcg/kg) at the end of the surgery. Two episodes of emetic symptoms (nausea and vomiting) were recorded by a gynaecologist who had no knowledge of which treatment each patient had received. This gynaecologist observed the patients at three different intervals: 6, 12 and 18 h post surgery. At the end of the observation period each patient evaluated the satisfaction with the study drug, and the gynaecologist evaluated sedation of the patients. Results In the generic granisetron group 47 and 13 patients, and in the Kytril® group 45 and 15 patients underwent hysterectomy and myomectomy respectively. No difference was observed between two treatment groups regarding postoperative nausea and vomiting control during 18 hours after the drugs administration. Also there were no differences in the satisfaction with the study drug between the generic granisetron and Kytril®. No difference in sedation scores was observed between two groups. Conclusion Generic granisetron exerts efficacy against PONV after gynaecological surgeries which is non-inferior to that of Kytril®. [ABSTRACT FROM AUTHOR]

Background: Histones are replaced by protamines to condensate and package DNA into the sperm head during mammalian spermatogenesis. Protamine genes defects have been reported to cause sperm DNA damage and male infertility. Objective: In this study relationship among some protamines genes family SNPs include PRMI (C321A), PRM2 (C248T) and TNP2 (T1019C), (G1272C), (G del in 1036 and 1046 bp) were studied in 96 idiopathic infertile men with azoospermia or oligospermia and 100 normal control men. Materials and Methods: Analysis of SNPs was performed using restriction fragment length polymorphism (PCR-RFLP), single strand conformational polymorphism (PCR-SSCP) and PCR sequencing. Results: No polymorphisms were found for tested SNPs except for PRM 1 (C321A) and TNP2 (G1272C) in which frequency of altered AA and GG genotypes were slightly higher in infertile case group. Statistical analysis showed no significant association related to PRM1 (C321A) p=0.805 and TNP2 (G1272C) loci p=0.654. Conclusion: These results are consistent with previous studies and indicating that all tested SNPs was not associated with oligospermia and azospermia and idiopatic male infertility in Iranian population. [ABSTRACT FROM AUTHOR]

Pancreatic duodenum homeobox protein-1 (PDX1) is a master regulatory gene in pancreatic development. Reprogramming of mesenchymal stem cells (MSCs) is a promising tool for producing insulin-producing cells. In this study, lentivirus harboring PDX1 (LV-PDX1) has been used for persistence gene expression in MSCs. The objective of this study was to evaluate the potential of lentivirus to introduce the PDX1 gene into MSCs to produce insulin-secreting cells and apply it for treatment of hyperglycemia in diabetic rats. MSCs were isolated from rat bone marrow, characterized, and transduced by LV-PDX1. Significant expressions of PDX1, neurogenin3, glucagon, glucose transporter2 (Glut2), and insulin were detected by quantitative reverse transcription-polymerase chain reaction ( P < 0.05). PDX1 and insulin were detected at the protein level by immunofluorescence analysis. PDX1 could trigger a gene expression cascade that involved pancreatic endocrine differentiation and also revealed the glucose sensing ability by expressing Glut2 in high-glucose medium. The insulin secretion of MSCsPDX1+ in the high-glucose medium was 1.75-fold higher than that secreted in the low-glucose medium ( P < 0.05). MSCsPDX1+ implanted into diabetic rats could decrease the blood glucose level from 485 mg/dL to the normal level in 3 days. This study showed MSCsPDX1+ have the potential to be used as a viable resource in cell-based gene therapy of type 1 diabetes. [ABSTRACT FROM AUTHOR]

Abstract- This study aimed to assess the relationship between the serum levels of anti-mullerian hormone (AMH) and other hormonal markers and results of assisted reproductive techniques (ART) in polycystic ovary syndrome (PCOS) patients. This cohort study was conducted on 60 PCOS patients who were candidates for assisted reproductive techniques. In all patients the serum levels of AMH, follicle stimulating hormone (FSH) and luteinizing hormone (LH), estradiol (E2), free testosterone (fT), testosterone (T) and inhibin B were measured in the 3rd day of menstrual cycle. The relationship between serum level of measured hormonal markers with retrieved oocytes, mature oocytes, the number of transferred fetus and pregnancy rate were assessed. The cut-off value for the serum level of AMH and retrieved oocytes were determined. There was a significant direct correlation between the serum mullerian inhibiting substance (MIS) level with number of total picked up oocytes (r=0.412), mature oocytes (r=0.472) and embryo transfer (r=0.291). There was a linear and significant correlation between inhibin B and fertilization (r=0.283) Cut-off point for AMH level according to presence or absence of pregnancy was 4.8 ng/ml and it was not statistically significant (P=0.655). Area under curve (AUC) was 0.543. Cut-off point for MIS according to picked up oocytes was 2.7 ng/ml with area under the curve (ROC curve) of 0.724 (CI= 0.591-0.831) (P=0.002). Patients with PCOS who had AMH more than 2.7 ng/ml, the number of retrieved oocytes (6 or more) was higher than MIS/AMH <2.7 ng/ml (P=0.002). As a marker of ovarian responsiveness to controlled ovarian hyperstimulation (COH) and despite a small sample size of our study, it is revealed that pretreatment MIS/AMH is highly associated with the number of mature oocytes retrieved during COH in PCOS women. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the correlation between the levels of vitamin D in follicular fluid and serum, and to determine whether the level of 25-hydroxyvitamin D (25OH-D) in follicular fluid of infertile women undergoing assisted reproductive technology (ART) is associated with the outcome. Study design: Eighty-two infertile women undergoing ART at an academic tertiary care centre were recruited for a prospective cohort study. Levels of 25OH-D in follicular fluid and serum were measured. Standardized regimens for pituitary downregulation and controlled ovarian hyperstimulation were employed. Patient and cycle parameters, and clinical pregnancy (defined as evidence of intra-uterine gestation sac plus heart rate on ultrasound) were determined. Results: A significant correlation was found between the levels of vitamin D in follicular fluid and serum (r =0.767, p =0.001). The overall rates of chemical, clinical and ongoing pregnancy were 35.5% (n =29), 29.3% (n =24) and 23.2% (n =19), respectively. No significant difference was found in these pregnancy rates between the tertiles of 25OH-D level in follicular fluid (p =0.959, 0.995 and 0.604, respectively). The median serum level of vitamin D was 8.13 (range 5.37–13.62)ng/ml in the clinically pregnant group and 8.29 (range 5.93–21.23)ng/ml in the non-pregnant group (p =0.235). Interestingly, the median level of vitamin D in follicular fluid was 9.19 (range 5.25–19.51)ng/ml in the clinically pregnant group and 10.34 (range 5.89–29.69)ng/ml in the non-pregnant group (p =0.433). The fertilization rate decreased significantly and the implantation rate increased (not significantly) with increasing tertiles of 25OH-D level in follicular fluid. Conclusions: The level of 25OH-D in follicular fluid is reflective of body stores of vitamin D. Most subjects in this study were deficient in vitamin D, but this study found that vitamin D deficiency does not play a pivotal role in the outcome of ART. [Copyright &y& Elsevier]

Purpose: The length of GT-repeats polymorphic region in the promoter of human Heme oxygenase-1 gene (HO-1) alters the level of its transcriptional activity in response to oxidative stresses. Decreased level of HO-1 protein in the seminal plasma has been reported to be associated with oligospermia and azoospermia in male infertility. This is the first study to investigate the association between GT-repeats expansion in the promoter of the HO-1 gene and male infertility. Methods: The frequencies of different GT-repeats alleles in the promoter of HO-1 gene were determined in 100 cases and 100 normal controls using PCR-PAGE, ABI fragment analysis genotyping and sequencing analysis. Results: All alleles were classified into S and L alleles. S alleles were specified as number 0 to 3 with <27 GT-repeats and L alleles were specified as number 4 to 6 with >27 repeats. The L allele frequency was significantly higher among case group (54.5%) than that was obtained in the normal control group (37.5%). Statistical analysis provided a significant relationship between L allele and male infertility ( P < 0.001). Conclusions: This study shows for the first time that GT-repeats expansion in promoter of the HO-1 gene is associated with oligospermia and azoospermia among Iranian infertile cases. [ABSTRACT FROM AUTHOR]

Human (hMPV) infection plays an important role in the pediatric respiratory infections. The aim of this study was to determine the relationship between asthma and wheezing with hMPV in hospitalized children. Nasal pharyngeal swabs obtained from 120 children aged 1-60 months, hospitalized during a one year period, were tested for the hMPV by RT-PCR. HMPV was detected in 20 (16.6%) of patients suffering from wheezing. Some patients in addition to wheezing had asthma 10.8%. This infection occurred predominantly from October 2008 to September 2009. [ABSTRACT FROM AUTHOR]

Background: Anti-mullerian hormone (AMH) levels may represent the ovarian follicular pool and could be a useful marker of ovarian reserve. The clinical application of AMH measurement has been proposed in the prediction of quantitative and qualitative aspects in assisted reproductive technologies. Objective: This study aimed to assess the relationship between the serum levels of AMH and results of assisted reproductive technique (ART) outcome in polycystic ovary syndrome (PCOS) patients versus control group. Materials and Methods: This cohort study was conducted on 61 (PCOS) patients and 28 patients without PCOS (controls) candidates for assisted reproductive technique. Serum levels of AMH were measured on the 3rd day of menstrual cycle and all the patients underwent controlled ovarian hyper stimulation and ART. The relationship between AMH serum level with retrieved oocytes, mature oocytes and pregnancy rate were assessed. Results: There was significant correlation between the AMH level with number of total retrieved oocytes and mature oocytes in patients with PCOS and controls (p=0.001). In PCOS and control groups AMH level in pregnant patients was higher, but it was not statistically significant (p=0.65, p=0.46, respectively). The major outcome of the study (pregnancy) did not differ significantly between two groups. Conclusion: This study revealed that AMH level was higher in pregnant patients undergoing ART; but AMH may not be an accurate predictor for pregnancy in PCOS patients. [ABSTRACT FROM AUTHOR]

Background: Some complications of pregnancy such as abortion, gestational diabetes mellitus, preeclampsia, and preterm delivery are more common among women with polycystic ovary syndrome (PCOS). Recently it has been reported that metformin treatment during pregnancy reduces pregnancy complications, so this study was conducted to demonstrate the possible effects of metformin on the uteroplacental circulation and pregnancy complications. Methods: Seventy pregnant women with polycystic ovary syndrome (PCOS) from 1386 to 1388 were enrolled in a randomized, double-blind, placebo-controlled trial of metformin during pregnancy in Shariati hospital. Doppler ultrasound examinations of the uterine arteries and umbilical artery were performed at 12th and 20th weeks of gestation. All patients were followed up to the end of pregnancy, then the effect of metformin on the uteroplacental circulation was evaluated by the comparison of the pulsatility index (PI) of uterine arteries and prevalence of obstetric complications between two groups. Results: The mean reduction of PI in metformin group from 12th to 20th weeks of gestation was 0.38 versus 0.16 in placebo group (p=0.016). Gestational diabetes mellitus, pre-eclampsia and preterm delivery, were more common in pregnant women in placebo group but the difference was not statistically significant. Conclusions: Metformin treatment in pregnancy accompanied with reduced uterine artery impedance between 12 and 20 weeks of gestation but this reduction showed no effect on the pregnancy complications such as preterm delivery, preeclampsia and gestational diabetes. [ABSTRACT FROM AUTHOR]

Aim: Gonadotropin-releasing hormone (GnRH) antagonists have reduced the incidence of severe ovarian hyper stimulation syndrome (OHSS) and rate of hospitalization due to severe OHSS, especially in polycystic ovarian syndrome (PCOS) patients. The present study aimed to compare the outcomes of patients with PCOS undergoing controlled ovarian hyperstimulation (COH) with GnRH agonist versus GnRH antagonist protocols for assisted reproduction cycles. Methods: The present clinical trial compared GnRH antagonist (cetrorelix) and GnRH agonist (buserelin) protocols during COH of 112 infertile PCOS patients entering assisted reproduction cycles. The primary outcome measure was pregnancy occurrence. Basal characteristics of the participants, stimulation cycle responses, pregnancy outcomes, incidence of OHSS and types of OHSS were considered in both groups. Results: Regarding chemical and clinical pregnancy rates, the number of retrieved oocytes was significantly higher and OHSS was significantly lower in the antagonist group. Follicle stimulating hormone (FSH), luteinizing hormone (LH) levels, number of follicles, number of follicles >18 mm, relative frequency of mature oocytes, number and days of gonadotropin injections, day of human chorionic gonadotropin (HCG) administration, estradiol level and abortion were similar between the two groups. Conclusion: GnRH antagonists are more effective, safe and a well tolerated alternative to agonists for assisted reproduction cycles in PCOS patients. GnRH antagonists are associated with a reduction in the incidence of OHSS in these patients. [ABSTRACT FROM AUTHOR]

Loss-of-function DJ-1 (PARK7) mutations have been linked with a familial form of early onset Parkinson disease. Numerous studies have supported the role of DJ-1 in neuronal survival and function. Our initial studies using DJ-1-deficient neurons indicated that DJ-1 specifically protects the neurons against the damage induced by oxidative injury in multiple neuronal types and degenerative experimental paradigms, both in vitro and in vivo. However, the manner by which oxidative stress-induced death is ameliorated by DJ-1 is not completely clear. We now present data that show the involvement of DJ-1 in modulation of AKT, a major neuronal prosurvival pathway induced upon oxidative stress. We provide evidence that DJ-1 promotes AKT phosphorylation in response to oxidative stress induced by H2O2 in vitro and in vivo following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Moreover, we show that DJ-1 is necessary for normal AKT-mediated protective effects, which can be bypassed by expression of a constitutively active form of AKT. Taken together, these data suggest that DJ-1 is crucial for full activation of AKT upon oxidative injury, which serves as one explanation for the protective effects of DJ-1. [ABSTRACT FROM AUTHOR]

Background: Reviewing the literature, reveals that pentoxifylline (PTX) plus tocopherol (vitamin E) are used mainly to promote sperm quality. However trials focusing on the effects of these drugs in female partner are limited. Combination of pentoxifylline and vitamin E appeared to improve the pregnancy rate in patients with a thin endometrium by increasing the endometrial thickness and improving ovarian function. Objective: To determine whether combined PTX and tocopherol treatment can improve clinical pregnancy rate. Materials and Methods: One hundred twelve infertile women undergoing standardized controlled ovarian hyperstimulation for ICSI- ZIFT entered this randomized clinical trial. Patients were randomized to equal groups of combined PTX and tocopherol therapy or none (not receiving PTX and tocopherol). These drugs were administered to the intervention group for two cycles before starting ICSI-ZIFT cycle. Main outcome measure was clinical pregnancy rate. SPSS.11 software (SPSS Inc. Chicago IL.) was used for data collection and analysis. Results: The clinical pregnancy was higher in the intervention (combined PTX and tocopherol) group in comparison to the other group (57.14% vs 39.29%, p=0.01). However, there was no difference in the mean endometrial thickness, number of retrieved oocytes, the number of metaphase II oocytes and grade of them in both groups. Conclusion: This study showed that PTX plus tocopherol could improve the ZIFT outcome in infertile couples. Local effects and anti oxidative characteristics of these drugs may be the cause of better results. [ABSTRACT FROM AUTHOR]

Endometriosis is an estogen dependent disease. Levels of Cancer antigen-125 are significantly higher in women with moderate to severe endometriosis. However, patients with unruptured endometriosis rarely have serum CA-125 levels more the 1000 U/mL. This case report presents a diffuse, unruptured overian endometrioma an a 29-year-old-woman, leading to an extraordinary high serum CA-125 and CA19-9 levels; usually typical of advaned ovarian carcinoma. Our experience emphasizes on benign gynecologic conditions such us endometrioma, which should be taken into account as a possible differential diagnosis in women with exaggerated elevation of the serum CA-125 level. [ABSTRACT FROM AUTHOR]

Recent evidence has indicated that common mechanisms play roles among multiple neurological diseases. However, the specifics of these pathways are not completely understood. Stroke is caused by the interruption of blood flow to the brain, and cumulative evidence supports the critical role of oxidative stress in the ensuing neuronal death process. DJ-1 (PARK7) has been identified as the gene linked to early-onset familial Parkinson's disease. Currently, our work also shows that DJ-1 is central to death in both in vitro and in vivo models of stroke. Loss of DJ-1 increases the sensitivity to excitotoxicity and ischemia, whereas expression of DJ-1 can reverse this sensitivity and indeed provide further protection. Importantly, DJ-1 expression decreases markers of oxidative stress after stroke insult in vivo, suggesting that DJ-1 protects through alleviation of oxidative stress. Consistent with this finding, we demonstrate the essential role of the oxidation-sensitive cysteine-106 residue in the neuroprotective activity of DJ-1 after stroke. Our work provides an important example of how a gene seemingly specific for one disease, in this case Parkinson's disease, also appears to be central in other neuropathological conditions such as stroke. It also highlights the important commonalities among differing neuropathologies. [ABSTRACT FROM AUTHOR]

Nuclear factor κB (NFκB) is a dynamically modulated transcription factor with an extensive literature pertaining to widespread actions across species, cell types and developmental stages. Analysis of NFκB in a complex environment such as neural tissue suffers from a difficulty in simultaneously establishing both activity and location. Much of the available data indicate a profound recalcitrance of NFκB activation in neurons, as compared with most other cell types. Few studies to date have sought to distinguish between the various combinatorial dimers of NFκB family members. Recent research has illuminated the importance of these problems, as well as opportunities to move past them to the nuances manifest through variable activation pathways, subunit complexity and target sequence preferences. [ABSTRACT FROM AUTHOR]

Previous studies have shown that DNA damage-evoked death of primary cortical neurons occurs in a p53 and cyclin-dependent kinase-dependent (CDK) manner. The manner by which these signals modulate death is unclear. Nuclear factor-κB (NF-κB) is a group of transcription factors that potentially interact with these pathways. Presently, we show that NF-κB is activated shortly after induction of DNA damage in a manner independent of the classic IKB kinase (IKK) activation pathway, CDKs, ATM, and p53. Acute inhibition of NF-κB via expression of a stable IκB mutant, downregulation of the p65 NF-κB subunit by RNA interference (RNAi), or pharmacological NF-κB inhibitors significantly protected against DNA damage-induced neuronal death. NF-κB inhibition also reduced p53 transcripts and p53 activity as measured by the p53-inducible messages, Puma and Noxa, implicating the p53 tumor suppresser in the mechanism of NF-κB-mediated neuronal death. Importantly, p53 expression still induces death in the presence of NF-κB inhibition, indicating that p53 acts downstream of NF-κB. Interestingly, neurons cultured from p65 or p50 NF-κB-deficient mice were not resistant to death and did not show diminished p53 activity, suggesting compensatory processes attributable to germline deficiencies, which allow p53 activation still to occur. In contrast to acute NF-κB inhibition, prolonged NF-κB inhibition caused neuronal death in the absence of DNA damage. These results uniquely define a signaling paradigm by which NF-κB serves both an acute p53-dependent pro-apoptotic function in the presence of DNA damage and an anti-apoptotic function in untreated normal neurons. [ABSTRACT FROM AUTHOR]

Maps loci from human chromosome 12 in cattle to compare the gene order between species. Selection of homologous genes for comparative mapping; Single-strand conformational analysis; Polymorphisms detected; Level of variation detected in the amplified cattle DNA.

Background: The purpose of this prospective study was to compare the ovarian response and pregnancy outcomes in the infertile women with endometrioma undergoing assisted reproductive technologies (ART) in two groups, who were underwent laparoscopic cystectomy and received gonadotropin releasing hormone-agonist (GnRH-agonist) and who only received GnRH-agonist without any surgery. Materials and Methods: In this prospective study, 79 infertile women with asymptomatic endometriomas cyst (2-6 cm) were enrolled and randomly assigned to two groups. First group underwent laparoscopic cystectomy and received GnRH-agonist. Second group only received GnRH-agonist without any surgery. Following ovulation induction, all patients underwent intracytoplasmic sperm injection (ICSI). Different parameters such as the number of retrieved oocytes and embryos; were made our outcomes that analyzed using SPSS. Results: The pregnancy rate, chemical and clinical, and live birth rate were higher in the combined group, although these differences were not statistically significant (48.48% vs. 30.8%, P=0.12, 36.36% vs. 25.6%, P=0.32, 36.36% vs. 23.1%, P=0.29). The number of injections, antral follicles, retrieved oocytes, mature oocytes, total embryos, transferred embryos and duration of stimulation were similar in two groups. Conclusion: Laparoscopic cystectomy followed by receiving GnRH-agonist improves pregnancy outcomes in endometrioma prior to treatment with ART (registration number: IRCT201106116689N2). [ABSTRACT FROM AUTHOR]