ALDH1A3-related congenital microphthalmia-8 due to a novel frameshift variant.

Microphthalmia (MCOP) is a group of rare developmental malformations of eye with often reduced size of the eyeball, leading to blindness. Affecting about 1 in 7000 live births, MCOP can occur due to either environmental or genetic factors. Isolated microphthalmia-8 (MCOP8) has been proved to be caused by autosomal recessive mutations of the ALDH1A3 gene (MIM*600463) encoding aldehyde dehydrogenase 1 family, member A3. Herein, we report an 8-year-old boy with vision problems since birth from a first-cousin consanguineous parents. The main symptoms of the patient included severe bilateral microphthalmia, cyst in the left eye and blindness. The child developed behavioral disorders at the age of 7. It should be noted that there is no family history of the disease. To identify the genetic factor underlying the pathogenesis in this case Whole Exome Sequencing (WES) was performed and followed by Sanger sequencing. A novel pathogenic variant, c.1441delA (p.M482Cfs*8), in the ALDH1A3 gene was detected by WES in the proband. Further prenatal diagnosis is highly suggested to the family for the future pregnancies.

Rheumatoid arthritis: current therapeutics compendium.

Rheumatoid arthritis is a common chronic inflammatory disease with substantial economic, social, and personal costs. Its pathogenesis is multifactorial and complex. The ultimate goal of rheumatoid arthritis treatment is stopping or slowing down the disease progression. In the past two decades, invention of new medicines, especially biologic agents, revolutionized the management of this disease. These agents have been associated with an improved prognosis and clinical remission, especially in patients who did not respond to traditional disease-modifying anti-rheumatic drugs (DMARDs). Improvement in the understanding of the rheumatoid arthritis pathogenesis leads to the development of novel biologic therapeutic approaches. In the present paper, we summarized the current therapeutics, especially biologic agents, available for the treatment of rheumatoid arthritis.

Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer

Background: Triple-negative breast cancer (TNBC) is determined by the absence of ERBB2, estrogen and progesterone receptors' expression. Cancer vaccines, as the novel immunotherapy strategies, have emerged as promising tools for treating the advanced stage of TNBC. The aim of this study was to evaluate Carcinoembryonic antigen (CEA), Metadherin (MTDH), and Mucin 1 (MUC-1) proteins as vaccine candidates against TNBC. Methods: In this research, a novel vaccine was designed against TNBC by using different immunoinformatics and bioinformatics approaches. Effective immunodominant epitopes were chosen from three antigenic proteins, namely CEA, MTDH, and MUC-1. Recombinant TLR4 agonists were utilized as an adjuvant to stimulate immune responses. Following the selection of antigens and adjuvants, appropriate linkers were chosen to generate the final recombinant protein. To achieve an excellent 3D model, the best predicted 3D model was required to be refined and validated. To demonstrate whether the vaccine/TLR4 complex is stable or not, we performed docking analysis and dynamic molecular simulation. Result: Immunoinformatics and bioinformatics evaluations of the designed construct demonstrated that this vaccine candidate could effectively be used as a therapeutic armament against TNBC. Conclusion: Bioinformatics studies revealed that the designed vaccine has an acceptable quality. Investigating the effectiveness of this vaccine can be confirmed by supplementary in vitro and in vivo studies.

Optical neural stimulation using the thermoplasmonic effect of gold nano-hexagon.

The use of nanoparticle photothermal effect as adjuvants in neuromodulation has recently received much attention, with many open questions about new nanostructures' effect on the action potential. The photothermal properties of hexagonal gold nanoparticles are investigated in this work, including the absorption peak wavelength and light-heat conversion rate, using both experimental and simulation methods. Furthermore, the ability to use these nanostructures in axonal neural stimulation and cardiac stimulation by measuring temperature changes of gold nano-hexagons under 532 nm laser irradiation is studied. In addition, their thermal effect on neural responses is investigated by modeling small-diameter unmyelinated axons and heart pacemaker cells. The results show that the increase in temperature caused by these nano-hexagons can successfully stimulate the small diameter axon and produce an action potential. Experiments have also demonstrated that the heat created by gold nano-hexagons affects toad cardiac rhythm and increases T wave amplitude. An increase in T wave amplitude on toad heart rhythm shows the thermal effect of nano hexagons heat on heart pacemaker cells and intracellular ion flows. This work demonstrates the feasibility of utilizing these nanostructures to create portable and compact medical devices, such as optical pacemakers or cardiac stimulation.

A loop-mediated isothermal amplification (LAMP) assay for detection of Toxoplasma gondii infection in women with spontaneous abortion.

The present study aimed to use the loop-mediated isothermal amplification (LAMP) technique in comparison with serological tests to determine the rate of T. gondii infection in women suffering from spontaneous abortion (SA). A total of 140 women suffering from their first SA were included in this study. The collected aborted fetal remains and blood samples from each patient were examined in sterilized conditions using the LAMP technique and ELISA. Of the 140 women, 80 (57.1%) tested seropositive for anti-Toxoplasma antibodies by ELISA, 72 (51.4%) women tested seropositive for the IgG antibody, 8 (5.7%) tested seropositive for the IgM antibody. Among the eight women who'd had their first SA who tested seropositive for IgM antibody by ELISA, only five cases (62.5%) reported positively to the LAMP test. The difference in the frequency distribution of the LAMP results for measuring the Toxoplasma infection in pregnant women under study was statistically significant (P < 0.001) from the results of the serological test (ELISA). Although there was a significant difference between age and positivity in the LAMP test (P = 0.017), no significant difference was observed between positivity in the LAMP test and other variables. The findings of the present investigation suggest that LAMP is a preferred method for determining Toxoplasma infection in pregnant women suffering from SA compared with other routine serological tests. Even in a field with limited facilities and equipment, this technique can be effective and efficient in accurately and specifically diagnosing Toxoplasma infections in women at high risk of SA.

Silibinin Inhibit Cell Migration through Downregulation of RAC1 Gene Expression in Highly Metastatic Breast Cancer Cell Line.

BACKGROUND: Triple negative breast cancer is the most invasive breast cancer subtype and possesses poor prognosis and survival. Rho GTPase famil, especially Rac1 participates in a number of signaling events in cells with crucial roles in malignancy, migration and invasion of tumor cells. Silibinin, a flavonoid antioxidant from milk thistle has attracted attention in the recent decades for chemoprevention and chemotherapy of tumor cells. In this study, the effect of silibinin on the migration capacity of MDA-MB-231 cells, a highly metastatic human breast cancer cell line was investigated by evaluation of Rac1 expression. METHOD: MTT wound healing and transwell assays were performed to evaluate the effects of silibinin on proliferation and migration of MDA-MB-231 cells. In addition, the influence of the silibinin on the expression of Rac1mRNAs was assessed by RT-PCR. RESULTS: Results indicated significant dose-dependent inhibitory effect of silibinin on proliferation and migration of MDA-MB-231 cells. It significantly inhibited the expression of Rac1 mRNA. CONCLUSION: In conclusion, the results demonstrate that the silibinin can be used as an experimental therapeutic for the management of TNBC metastatic cancer.

Recurrent Spontaneous Abortion (RSA) and Maternal KIR Genes: A Comprehensive Meta-Analysis.

Natural killer cells (NKs) are the most important cells in the fetomaternal immune tolerance induced through interaction of maternal killer-cell immunoglobulin-like receptors (KIR) and fetal human leucocyte antigens (HLA). Hence, we intend to perform a meta-analysis on the role of maternal KIR genes diversity in recurrent spontaneous abortion (RSA). The present paper is a meta-analysis of previous genetic association studies and our previous original study. The results showed that KIR3DL1 was a significantly protecting factor for RSA (p=0.044; OR=0.833 [0.698-0.995]; fixed effect model). KIR2DS2 (p=0.034; OR=1.195 [1.013-1.408]; fixed effect model) and KIR2DS3 (p=0.013; OR=1.246 [1.047-1.483]; fixed effect model) were significantly risk factors for RSA. For KIR2DS1 there was a high heterogeneity and publication bias. Briefly, the inhibitory gene KIR3DL1 was a protecting factor, and the activating genes KIR2DS2 and KIR2DS3 were risk factors for RSA. However, the effect sizes were not suitable. We suggest further studies on different causes of pregnancy loss, to find the role of KIR2DS1.

Toxoplasma Serology Status and Risk of Miscarriage, A Case-Control Study among Women with A History of Spontaneous Abortion.

BACKGROUND: Toxoplasma gondii is one of the major causes of abortion in pregnant women. Most cases of abortion occur in the acute phase of infection and early pregnancy. The purpose of this study was to investigate the association between spontaneous abortion and seropositive status of toxoplasmosis in women with first-time spontaneous abortion. MATERIALS AND METHODS: This research is a case-control study on 240 serum samples from women experiencing spontaneous abortion for the first time as the case group, and 240 serum samples from women who had a normal delivery with no history of abortion as the control group. The level of anti-Toxoplasma gondii IgM and IgG antibodies were assessed in serum samples using ELISA. To separate the acute and chronic infections, all IgM-positive samples in both groups and IgG-positive samples of the case group were examined using IgG avidity. RESULTS: The toxoplasmosis IgM antibody was detected in 3.3% (8/240) of the case group and 0.4% (1/240) of the control group, which was a statistically significant difference between the two groups [P=0.019, odds ratio (OR)=10.266]. Of all samples 47.5% and 46.3% of the case and control groups were positive for toxoplasmosis IgG antibody, respectively. Seven out of 8 (87.5%) IgM-positive serum samples from the case group had low IgG avidity, indicating acute infections, whereas all IgG-positive sera and 1 IgM-positive serum, which was related to the control group, showed a high IgG avidity, indicating chronic infections. CONCLUSION: Maternal acute toxoplasmosis during pregnancy is raised as one of the factors that increase the chance of spontaneous abortion. The necessary health training, especially on the parasite transmission ways to women before marriage, as well as the serological test in women before and during pregnancy is recommended. Polymerase chain reaction (PCR) and IgG avidity assays should be performed in the medical diagnostic laboratories for accurate distinguishing of the initial infection of toxoplasmosis in the pregnant women.

Association of vitamin D level and vitamin D deficiency with risk of preeclampsia: A systematic review and updated meta-analysis.

OBJECTIVES: Because of the immune modulatory effects of vitamin D3 in preeclampsia, we intend to have a systematic review and meta-analysis on association of both 25-hydroxy vitamin D (25-OHD) level (parametric approach) and 25-OHD deficiency (non-parametric approach) with preeclampsia. As well, for the parametric part, we used receiver operating characteristic (ROC) curve model. MATERIALS AND METHODS: We used Web of Science, PubMed and Science Direct data bases through searching in titles. Google Scholar search engine was used in order to find missing papers. Finally 23 studies were imported. Both random and fixed models were reported. RESULTS: Based on the forest plot, lower levels of 25-OHD were significantly associated with risk of preeclampsia (fixed and random P < 0.001). Based on the forest plot, vitamin D deficiency (25-OHD < 20 ng/ml) was significantly associated with risk of preeclampsia (fixed P < 0.0001; random P = 0.0029; fixed OR = 1.33; random OR = 1.54). Based on ROC curve results, we found 2 cutoffs of 10.60 and 20.05 ng/ml. CONCLUSION: Women with vitamin D deficiency at cutoff 20 ng/ml are more at risk of preeclampsia. This association can be specific up to 90% at 10.60 ng/ml cutoff. Treatment of vitamin D deficiency is necessary before pregnancy.

Client satisfaction of maternity care in Lorestan province Iran.

BACKGROUND: Client satisfaction is an important indicator for assessment of the quality of care provided. Detecting patients dissatisfaction and trying to find the most effective and costly services is the basic way for improvement of service quality. The purpose of this study was to determine the satisfaction level of women in the maternity care centers (hospitals) of Lorestan University of Medical Sciences, Iran. MATERIALS AND METHODS: In this descriptive cross-sectional study, the satisfaction level of 200 patients who received care during childbirth in province hospitals was assessed using a researcher-made questionnaire. Women in maternity care units completed the questionnaires. RESULTS: The mean maternity care satisfaction score was 66.6 ± 3.5. The lowest satisfaction level was related to getting to know the delivery room (64%) and vaginal examination (66%). The highest satisfaction score was related to confidentiality of the information (86%) and trusting the midwife (84%). Regarding the environmental factors, the lowest satisfaction was related to respecting silence in the pain room (69.5%) and the highest was related to cleanliness and hygiene of the delivery room (84%). CONCLUSIONS: Our results suggest the relative satisfaction of women receiving care in the health centers of Lorestan province; but this level of satisfaction does not mean that the delivery of care in this province is perfect. By reviewing the policies and the existing care programs regarding promoting the quality of services, managers can increase clients' satisfaction.

Normal and indeterminate pattern of fetal cardiotocography in admission test and pregnancy outcome.

AIM: The aim of this study was to evaluate the prognostic value of normal and indeterminate patterns of cardiotocography in admission test (AT) and pregnancy outcome. MATERIAL AND METHODS: A prospective study enrolled 818 intrapartum singleton pregnancies with gestational age of >34 weeks, in the latent phase and with intact membrane. Cases were divided into the high- and low-risk groups. Non-Stress Test was interpreted according to the 2008 National Institute of Child Health and Human Development workshop. Adverse pregnancy outcomes were compared between groups based on AT interpretation. RESULTS: Out of 818 patients, 492 (60%) were categorized as low-risk and 326 (40%) as high-risk pregnancies. In low-risk patients, 410 (83.3%) had normal and 82 (16.7%) had indeterminate AT. These figures were 249 (76.4%) and 77 (23.6%) in high-risk patients, respectively, and two cases (0.6%) had abnormal AT. In both groups, thick meconium staining, non-reassuring fetal heart rate pattern, cesarean section and cesarean section due to non-reassuring fetal heart rate pattern were significantly more frequent in indeterminate AT than normal ones (P < 0.001). In high-risk pregnancies with indeterminate AT, the risk of low birthweight and neonatal intensive care unit (NICU) admission increased. The positive predictive value was less than 30% in predicting thick meconium staining, non-reassuring fetal heart rate pattern, PH ≤ 7.2 and NICU admission in both groups. Overall, negative predictive value of AT for neonatal death and NICU admission was 100% and 96%, respectively. CONCLUSIONS: Indeterminate patterns of cardiotocography can predict adverse pregnancy outcomes and when facing this condition, obstetricians should act cautiously.

Effect of different maternal metabolic characteristics on fetal growth in women with gestational diabetes mellitus.

BACKGROUND: Fetal growth in diabetic pregnancies is a complex process and probably abnormalities in other metabolic pathways such as protein and lipid, as well as carbohydrate are responsible for delivering of macrosomic newborn. OBJECTIVE: The purpose of this study was to investigate the association between fetal growth and different maternal metabolic parameters in women with gestational diabetes mellitus (GDM) in comparison to control group. MATERIALS AND METHODS: This was a prospective cohort study conducted between March 2011 and May 2012, on 112 pregnant women with GDM and 159 healthy pregnant women. In order to determine of lipids or lipoproteins changes during pregnancy and to investigate any possible effects on fetal growth, lipid components, glucose and insulin levels were obtained in maternal serum three times in third trimester. RESULTS: Maternal serum glucose, total cholesterol (TC), low and high density lipoprotein (LDL-c, HDL-c) levels did not show any significant difference between two groups. While insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and triglyceride (TG) values were detected to be significantly higher in the GDM cases especially after 32 weeks of gestation (p<0.001). After adjustment for confounding variables, maternal hypertriglyceridemia remained as a significant risk factor for delivering large for gestational age (LGA) newborns (p=0.04); and according to spearman test the increase of TG level was correlated with increase of insulin resistance and HOMA-IR (p<0.001, CI: 0.312). CONCLUSION: Due to positive correlation of hypertriglyceridemia and hyperinsulinemia with newborn weight, it is possible to assume that elevated TGs levels in GDM cases is a reflection of variation in maternal insulin levels.

Metformin compared with insulin in the management of gestational diabetes mellitus: a randomized clinical trial.

AIMS: To evaluate the effect of metformin and insulin in glycemic control and compare pregnancy outcome in women with gestational diabetes mellitus (GDM). METHODS: This randomized controlled trial was conducted in GDM women with singleton pregnancy and gestational age between 20 and 34 weeks who did not achieve glycemic control on diet were assigned randomly to receive either metformin (n=80) or insulin (n=80). The primary outcomes were maternal glycemic control and birth weight. The secondary outcomes were neonatal and obstetric complications. RESULTS: Two groups were comparable regarding the maternal characteristics. Two groups were similar in mean FBS (P=0.68) and postprandial measurements (P=0.87) throughout GDM treatment. The neonates of metformin group had less rate of birth weight centile >90 than insulin group (RR: 0.5, 95% CI: 0.3-0.9, P=0.012). Maternal weight gain was reduced in the metformin group (P<0.001). Two groups were comparable according to neonatal and obstetric complications (P>0.05). In metformin group 14% of women needed to supplemental insulin to achieve euglycemia. CONCLUSION: Metformin is an effective and safe alternative treatment to insulin for women with GDM. This study does not show significant risk of maternal or neonatal adverse outcome with the use of metformin.

Cushing's syndrome during pregnancy secondary to adrenal adenoma.

Pregnancy rarely occurs in untreated cases of Cushing's syndrome (CS) , because most of them are infertile due to significant maternal and fetal complications during pregnancy. Diagnosis of CS may be difficult during pregnancy. Since physiological changes of pregnancy are overlapped by classical presentation and biological confirmation of CS. Therefore the high clinical suspicious is needed for diagnosis. We present a 33 years old pregnant woman with a history of chronic hypertension from 10 years ago that referred to Imam Khomeini hospital for uncontrolled hypertension, gestational diabetes and fetal tachycardia at the 30 weeks of gestation. After initial studies abdominal MRI detected a 43 x 35 x 29 mm right adrenal mass. She was treated by anti-hypertensive drugs. But at 31.5 weeks of gestational age cesarean section was performed due to severe preeclampsia. Then two weeks after delivery open right adrenalectomy was carried out without any complications and in the histopathological evaluation benign adrenocortical adenoma was reported. CS is associated with considerable fetal and maternal morbidity and mortality. Selection of treatment method is variable and it depends on gestational age. Medical and surgical approaches have been used in managing CS in pregnancy. Surgical treatment is the first choice for CS which is recommended at the second trimester and in the late pregnancy medical treatment is preferred.

Comparing of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles.

BACKGROUND: Clomiphene citrate (CC) an agonist and antagonist of estrogen, is the first line treatment in ovarian stimulation. Anti-estrogenic effect of CC in endometrial thickness and cervical mucus has negative effect on pregnancy rate. Letrozole is an Aromatase Inhibitor has been seen that has acceptable pregnancy rate compared to CC. OBJECTIVE: The aim of this study was to compare the efficacy of letrozole and clomiphene citrate (CC) with gonadotropins for ovarian stimulation in women candidate for intrauterine insemination (IUI). MATERIALS AND METHODS: One hundred sixty patients eligible to IUI therapy enrolled in this study. Patients randomized to two groups: group A (received letrozole-gonadotropin) and group B (received CC-gonadotropin). In group A (n=80) letrozole was given on days 3-7 of the menstrual cycles. In group B clomiphen citrate was given like letrozole combined with human menopausal gonadotropin (hMG) administered every day starting on day 8. Ovulation was triggered with urinary HCG when the leading follicle (s) reached 18 mm in diameter. A single IUI was performed 36-40 hours later. The ovarian stimulation response (E2 levels and number of follicles, clinical pregnancy and endometrial thickness) was primary outcome. RESULTS: Both groups were similar in demographic characteristics. There was a significantly lower peak serum E2 level in the letrozole group compared with CC. (236±86 Vs. 283±106 pg/mL, respectively; p<0.002). The number of mature (>18 mm) preovulatory follicles was significantly higher in CC group than letrozole group (2.2±.68 Vs. 2.02±0.63 respectively; p=0.025). Endometrial thickness measured at the time of hCG administration was significantly higher in letrozole group. (9.08±1.2 mm Vs. 8.1±1.9 mm; p=0.0001). The clinical pregnancy rate was comparable between two groups. Conclusion : Letrozole is a good and cost-effective alternative to CC in IUI cycles.

Impact of prophylactic iron supplementation in healthy pregnant women on maternal iron status and birth outcome.

BACKGROUND: In spite of the beneficial effect of iron supplementation in iron-deficient pregnant women, iron supplementation may not be needed for women who are iron replete or not anemic. Moreover, the theoretical possibility of adverse effects, such as oxidative damage,from administration of iron supplements during pregnancy has been raised. OBJECTIVE: To determine the effect of prophylactic iron supplementation on iron status and birth outcomes among nonanemic pregnant women. METHODS. A randomized, triple-blind clinical trial was conducted. One hundred forty-eight nonanemic pregnant women with hemoglobin > 110 g/L, serum ferritin > 12 microg/L, and gestational age < 20 weeks were randomly assigned to receive either ferrous sulfate (60 mg elemental iron) (n = 70) or placebo (n = 78) until delivery. Hemoglobin concentration and serum ferritin were measured by electronic counter and radioimmunoassay, respectively. Data were analyzed by independent t-tests, ANCOVA, and repeated measures. RESULTS: At delivery, the incidence of iron deficiency was significantly lower in the iron than in the placebo group. There were no significant differences between the two groups in maternal hemoglobin and ferritin concentrations at delivery or in the infant's birthweight, birth length, or length of gestation. CONCLUSIONS: Iron supplementation during pregnancy in nonanemic women with low serum ferritin may have benefits beyond the prevention of iron-deficiency anemia.