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Background: Tramadol is a synthetics 4-phenyl-piperidine analogue of codeine used for treating moderate to severe pain. Tramadol is a FDA pregnancy category C medication which induces release of serotonin and inhibits the reuptake of norepinephrine. Chronic use of this drug during pregnancy may lead to physical dependency and withdrawal syndrome in the neonate.Case presentation: We report the newborn of a woman admitted in the delivery ward of Mostafa Khomeini Hospital in Tehran, Iran in 2011. The mother suffered from chronic low back pain and headache and frequently took tramadol during pregnancy. The infant had a gestational age of 38.5 w, a birth weight of 2950 gr and an Apgar score of 9/10 at 1 and 5 minutes after birth. The first signs of withdrawal syndrome occurred after 24 h with nausea, vomiting, poor feeding, and tremor. Later, agitation, tremor, hyprertonicity, and repeated multifocal myoclonus, and generalized tonic-clonic seizures developed. Clinical signs of withdrawal syndrome waned under phenobarbital therapy.Conclusion: Drug withdrawal syndrome should be considered in the neonates of pregnant mothers who chronically take tramadol. Tramadol administration during pregnancy should be restricted to carefully selected cases.

Abstract Background Our purpose was to determine whether AFI Methods We performed a prospective cohort study of 95 singleton pregnancies complicated by preterm premature rupture of the membranes (PPROM) with delivery between 26 and 34 weeks gestation. Patients were categorized in two groups on the basis of amniotic fluid index2 and Fisher exact tests. Continuous data were evaluated for normal distribution and tested for significance with the student t test. All 2-sided p values < 0.05 were considered significant. Results Both groups were similar with respect to selected demographics, gestational age at rupture of the membranes, gestational age at the delivery, birth weight. Both groups were similar with respect to selected variable, latency until delivery, early onset neonatal sepsis, RDS and neonatal death. Patients with AFI Conclusions An AFI

The fundamental mechanism responsible for the aggressiveness of metastatic cancers such as triple-negative breast cancer (TNBC) is the epithelial-mesenchymal transition (EMT). In cancer microenvironments, the Phosphoinositide 3-kinases (PI3K)-Akt- mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in regulating the EMT mechanism. The current study focuses on the impacts of rapamycin, a newly retargeted chemotherapeutic agent against mTOR, and MicroRNA (miR)-122 on the aggressive behavior of TNBC.  The half-maximal inhibitory concentration (IC50) of rapamycin on 4T1 cells was determined using an MTT assay. Also, miR-122 was transiently transfected into 4T1 cells to study its effect on the pathway. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess the expression level of central mTOR and EMT-related cascade genes. Moreover, cell mobility and migration were evaluated using scratch and migration assays, respectively. Both rapamycin and miR-122 significantly decreased the expression levels of PI3K, AKT, and mTOR, as well as ZeB1 and Snail genes. However, no significant change was observed in Twist gene expression. Furthermore, scratch and migration assays revealed that the migration of 4T1 cells was markedly reduced, especially following miR-122 induction. Our experimental findings and gene enrichment studies indicated that miR-122 mainly operates on multiple metabolic pathways, as well as EMT and mTOR, while rapamycin has restricted targets in cancer cells.  Consequently, miR-122 can be considered a potential cancer microRNA therapy option, which can be validated in the future in animal studies to demonstrate its efficacy in cancer control.

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease with pulmonary and extra-pulmonary complications. Due to the disease's systemic nature, many investigations investigated the genetic alterations in various biological samples. We aimed to infer causal genes in COPD's pathogenesis in different biological samples using elastic-net logistic regression and the Structural Equation Model. Samples of small airway epithelial cells, bronchoalveolar lavage macrophages, lung tissue biopsy, sputum, and blood samples were selected (135, 70, 235, 143, and 226 samples, respectively). Elastic-net Logistic Regression analysis was implemented to identify the most important genes involved in COPD progression. Thirty-three candidate genes were identified as essential factors in the pathogenesis of COPD and regulation of lung function. Recognized candidate genes in small airway epithelial (SAE) cells have the highest area under the ROC curve (AUC = 97%, SD = 3.9%). Our analysis indicates that macrophages and epithelial cells are more influential in COPD progression at the transcriptome level.

Background: HIV-infected children are at a higher risk of Invasive Pneumococcal Disease (IPD) and its mortality, even in the era of antiretroviral therapy. Therefore, an effective vaccination strategy would be beneficial. To investigate the effectiveness of Pneumococcal Conjugate Vaccination (PCV) against IPD among HIV-Infected and HIV-Uninfected Children through a systematic review and meta-analysis., Methods: Observational studies and randomized trials on 7 years old or older children were searched in the Cochrane Library, Web of Science core collection, Embase, Medline/PubMed, and Google Scholar. Critical appraisal was done using the Cochrane risk of bias tool and the Newcastle-Ottawa quality assessment form. Effectiveness and efficacy of at least one dose of PCV was investigated among children with and without HIV considering subgroups of pneumococcal serotypes. We meta-analyzed the effect sizes using random-effects modeling., Results: Efficacy of PCV was estimated as 45.0% (31.2, 56.1) and 52.6% (25.7, 69.8) among HIV-infected and HIV-uninfected children, respectively. Effectiveness of PCV among HIV-infected children as - 6.2% (- 67.6, 32.7) was significantly lower than HIV-uninfected children 65.1% (47.3, 76.9). Effectiveness of PCV among HIV-infected children for IPDs caused by vaccine serotypes was estimated as 7.7(- 66.7, 48.9), and for IPDs caused by non-vaccine serotypes was estimated as - 402.8(- 1856, - 29.2)., Conclusion: Unlike the evidence on the efficacy of PCV against IPD among both of HIV-infected and HIV-uninfected children, its effectiveness against IPD among HIV-infected children is much less limited., Review Registration: The study protocol was registered at PROSPERO (registration ID: CRD42018108187).

Sulfur mustard (SM) is a mutagenic compound that targets various organs. Although it causes a wide range of abnormalities, cellular and molecular mechanisms of its action are not-well-understood. Oxidation of DNA, proteins, lipids, as well as depletion of cellular nicotinamide adenine dinucleotide (NAD), antioxidants and increase of intracellular calcium are the hypothesized mechanisms of its action at the acute phase of injury. In this review, the proteome analysis of SM toxicity has been considered. We selected articles that considered proteomics analysis of SM toxicity with two-dimensional gel electrophoresis (2DE) followed by mass spectrometry. Our search yielded nine related articles, four original in vitro and five human studies. The results of these studies have revealed a change in expression pattern of various proteins such as haptoglobin, amyloid A1, surfactant proteins, S100 proteins, apolipoprotein, Vit D binding protein, transferrin, alpha 1 antitrypsin, protein disulfide isomerase and antioxidant enzymes in patients who were exposed to SM about 30 years ago. Most of these proteins are up- or down-regulated in response to excessive production of reactive oxygen species (ROS) and oxidative stress (OS). There is a tight link between the expression pattern of these proteins with accumulation of leukocytes, inflammatory conditions, antioxidant depletion, mitochondrial deficiency, as well as increased expression or activity of several proteases such as caspases and matrix metalloproteinases (MMPs). Therefore, excessive production of ROS and OS along with chronic inflammatory may be the long-term toxic effects of SM following acute exposure.

Sulfur mustard (SM) is a chemical alkylating compound that primary targets lung tissue. It causes a wide variety of pathological effects in respiratory system such as chronic bronchitis, bronchiolitis obliterans, necrosis of the mucosa and inflammation, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. However, molecular and cellular mechanisms for these pathologies are still unclear. Oxidative stress (OS) induced by reactive oxygen species (ROS) is likely a significant mechanism by which SM leads to cell death and tissues injury. SM can trigger various molecular and cellular pathways that are linked to ROS generation, OS, and inflammation. Hypoxia-induced oxidative stress, reduced activity of enzymatic antioxidants, depletion of intercellular glutathione (GSH), decreased productivity of GSH-dependent antioxidants, mitochondrial dysfunction, accumulation of leukocytes and proinflammatory cytokines, and increased expression of ROS producing-related enzymes and inflammatory mediators are the major events in which SM leads to massive production of ROS and OS in pulmonary system. Therefore, understanding of these molecules and signaling pathways gives us valuable information about toxicological effects of SM on injured tissues and the way for developing a suitable clinical treatment. In this review, we aim to discuss the possible mechanisms by which SM induces excessive production of ROS, OS, and antioxidants depletion in lung tissue of exposed patients.

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases., Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

According to significant improvements in the tissue engineering field over the past several years, lung tissue cells have recently attracted more attention due to the high prevalence and diversity in related diseases. However, selection of an appropriate cell type, screening of suitable conditions for growth and proliferation, as well as subsequent implantation into the body to repair and regenerate damaged tissues are considered as important issues in this context. It should also be noted that most studies have been described in animal models, but not in humans. Because of the high regenerative capacity, predominant immunomodulatory feature, and inhibition of T-lymphocyte proliferation, mesenchymal stem cells (MSCs) may play an important role in the reconstruction of damaged tissues including bronchioles in pulmonary diseases. Interestingly, clinical trial studies demonstrated that MSCs have the significant potential to treat a wide variety of diseases including acute myocardial infarction (AMI), liver cirrhosis, crohn's disease, and graft-versus-host disease (GVHD).

Context: The main objectives of triage are securing patient safety during the process of emergency diagnosis and treatment, and reduction of waiting time for medical services and transport. To date, there is no triage system for nerve agent victims., Evidence Acquisition: This systematic review proposes a new triage system for patients exposed to nerve agents. Information regarding clinical signs and symptoms of intoxication with nerve agents, primary treatments, and classification of patients were extracted from the literature. All related articles were reviewed. Subsequently, specialists from different disciplines were invited to discuss and draft protocols., Results: Finalized triage tables summarizing the classification methods and required protocols in the field were designed after several meetings., Conclusions: The proposed triage protocol encompasses aspects from most of the existing triage systems to create a single overarching guide for unifying the triage process. The proposed protocol can serve as a base for the designing future guidelines.

Introduction: RNA interference is a sequence-specific gene silencing phenomenon in which small interfering RNAs (siRNAs) can trigger gene transcriptional and post-transcriptional silencing. This phenomenon represents an emerging therapeutic approach for in vivo studies by efficient delivery of specific synthetic siRNAs against diseases. Therefore, simultaneous development of synthetic siRNAs along with novel delivery techniques is considered as novel and interesting therapeutic challenges., Areas Covered: This review provides a basic explanation to siRNA signaling pathways and their therapeutic challenges. Here, we provide a comprehensive explanation to failed and successful trials and their in vivo challenges., Expert Opinion: Specific, efficient and targeted delivery of siRNAs is the major concern for their in vivo administrations. Also, anatomical barriers, drug stability and availability, immunoreactivity and existence of various delivery routes, different genetic backgrounds are major clinical challenges. However, successful administration of siRNA-based drugs is expected during foreseeable features. But, their systemic applications will depend on strong targeted drug delivery strategies.

Human immune system includes variety of different cells and molecules correlating with other body systems. These instances complicate the analysis of the system; particularly in postgenomic era by introducing more amount of data, the complexity is increased and necessity of using computational approaches to process and interpret them is more tangible.Immunoinformatics as a subset of bioinformatics is a new approach with variety of tools and databases that facilitate analysis of enormous amount of immunologic data obtained from experimental researches. In addition to directing the insight regarding experiment selections, it helps new thesis design which was not feasible with conventional methods due to the complexity of data. Considering this features immunoinformatics appears to be one of the fields that accelerate the immunological research progression.In this study we discuss advances in genomics and vaccine design and their relevance to the development of effective vaccines furthermore several division of this field and available tools in each item are introduced.

Cancer is now the main cause of increasing mortality throughout the world. Minor alterations in the cell cycle which are inherited and not removed by apoptosis are important risk factors. Blood cancers are asmong the types which most readily cause death. Here in this study, usual but important factors such as age, gender, Rh and ABO blood typing, weight, and platelet counts are analyzed for impact on blood cancers. Frequencies and distributions, correlations and chi-square test were utilized in order to clarify the perspective of important factors. Our statistical results show males and females to have same risk in blood cancer but A blood type (40%) along with positive Rh (73%) had the highest risk. Low platelet counts are related to more than 80% of cases. Obesity has a statistically ignorable role in blood cancer prevalence. The fact that blood cancer cases increase during the second decade of life (45.7%) which might be because of involvement of maturation processes.

Objective: Birth trauma at delivery is a rare but significant prenatal complication. The aim of this study was to determine the incidence of birth trauma and risk factors related to fetal injury., Materials and Methods: Birth trauma was evaluated in singleton fetuses with no major anomalies and with vertex presentations over a 3-year period from 2002 to 2005. One hundred and forty-eight neonates, who experienced birth trauma, were prospectively identified and compared with 280 normal neonates. Both groups were delivered vaginally. Maternal and infant characteristics were evaluated as possible risk factors for fetal injury., Results: Among the 148 infants with birth trauma, nine had multiple injuries. The most common injury was cephalohematoma (n = 77). Other injuries included clavicle fractures (n = 56), brachial plexus paralysis (n = 13), asphyxia (n = 7), facial lacerations (n = 4), brain hemorrhage (n = 1), and skin hematoma (n = 2). Multiple regression analysis identified premature rupture of membranes, instrumental delivery, birth weight, gestational age, induction of labor, and academic degree of attendant physician at delivery as the most significant risk factors for birth trauma., Conclusion: The incidence of birth trauma was 41.16 per 1,000 vaginal deliveries. Induction of labor, premature rupture of membranes, academic degree of attendant physician at delivery, higher birth weight, and gestational age were associated with fetal injuries., (Copyright 2010 Taiwan Association of Obstetrics and Gynecology. Published by Elsevier B.V. All rights reserved.)

Background: The aim of this study was to evaluate the outcome of pregnancies in Iranian women with immune thrombocytopenic purpura (ITP)., Methods: In a historical cohort study, maternal and neonatal outcomes were studied in 30 pregnant women with ITP at a hospital in Tehran, from January 1994 through November 2003., Results: Twenty-two cases were diagnosed as ITP before and 8 during pregnancy. Thrombocytopenia (platelet count <150 x 10(9)/L) occurred in 22 pregnancies. Eleven (37%) had vaginal delivery and 19 (63%) underwent elective cesarean section. Eight women had severe postpartum hemorrhage. All live-born neonates were delivered in good condition at term. Neonatal thrombocytopenia occurred in 20 (67%) neonates. No bleeding complications occurred in any of the neonates., Conclusion: The outcome of pregnancy in pregnant women with ITP is generally good. Cesarean section should only be performed for obstetric indications. Postpartum hemorrhage is common in these women. Postpartum hemorrhage is unrelated to the mode of delivery. Severe thrombocytopenia and bleeding in the offspring are uncommon.

BACKGROUND: Our purpose was to determine whether AFI<5 cm after preterm premature rupture of the membranes (PPROM) is associated with an increased risk of perinatal morbidity. METHODS: We performed a prospective cohort study of 95 singleton pregnancies complicated by preterm premature rupture of the membranes (PPROM) with delivery between 26 and 34 weeks gestation.Patients were categorized in two groups on the basis of amniotic fluid index<5, (AFI<5 cm)(n = 26) or AFI >/= 5 cm (n = 69). Categorical data were tested for significance with the chi2 and Fisher exact tests. Continuous data were evaluated for normal distribution and tested for significance with the student t test.All 2-sided p values < 0.05 were considered significant. RESULTS: Both groups were similar with respect to selected demographics, gestational age at rupture of the membranes, gestational age at the delivery, birth weight. Both groups were similar with respect to selected variable, latency until delivery, early onset neonatal sepsis, RDS and neonatal death. Patients with AFI<5 cm demonstrated greater frequency of C/S delivery for non reassuring fetal tests (23%vs 2.8%) (p = 0.001). Our study demonstrated that patients in group I had a significant increase in the frequency of clinical chorioamnionitis (P < 0/001). Post partum infections were not seen in 2 groups. CONCLUSIONS: An AFI<5 cm after PPROM between 26 and 34 weeks gestation is associated with an increased risk of maternal infections and frequency of C/S.