Adjuvant activity of CpG-ODN formulated as a liquid crystal

The adjuvants approved in human vaccine with recombinant/purified antigens induce weak cellular immune response and so the development of new adjuvant strategies is critical. CpG-ODN has successfully been used as an adjuvant (phase I–III clinical trials) but its bioavailability needs to be improved. We investigated the adjuvant ability of CpG-ODN formulated with a liquid crystal nanostructure of 6-O-ascorbyl palmitate (Coa-ASC16). Mice immunized with OVA/CpG-ODN/Coa-ASC16 elicited a potent specific IgG1, IgG2a, Th1 and Th17 cellular response without systemic adverse effects. These responses were superior to those induced by OVA/CpG-ODN (solution of OVA with CpG-ODN) and to those induced by the formulation OVA/CpG-ODN/Al(OH)₃. Immunization with OVA/CpG-ODN/Coa-ASC16 resulted in a long-lasting cell-mediated immune response (at least 6.5 months). Furthermore, Coa-ASC16 alone allows a controlled release of CpG-ODN in vitro and induces local inflammatory response, independent of TLR4 signaling, characterized by an influx of neutrophils and Ly6C^high monocytes and pro-inflammatory cytokines. Remarkably, the adjuvant capacity of CpG-ODN co-injected with Coa-ASC16 (OVA/CpG-ODN plus Coa-ASC16) was similar to the adjuvant activity of OVA/CpG-ODN, supporting the requirement for whole formulation to help CpG-ODN adjuvanticity. These results show the potential of this formulation, opening a new avenue for the development of better vaccines.     

Analysis of polymorphisms of the vitamin D receptor, estrogen receptor, and collagen Ialpha1 genes and their relationship with height in children with bone cancer

PURPOSE: The authors' objectives were to compare height at diagnosis of children with bone tumors with that of Spanish reference children; to analyze the frequency of the genotypes for the polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIalpha1) genes in patients and in healthy controls; and to test the relationship between the genetic markers and height. PATIENTS AND METHODS: Height and weight at diagnosis were measured in 58 osteosarcoma and 36 Ewing sarcoma patients and compared with standards published for Spanish reference children according to sex and age. For the molecular analysis, genetic polymorphisms of the VDR (Fok I, Apa I, and TaqI), ER (Pvu II and XbaI), and COLIalpha1 (Msc I) genes were characterized in 72 osteosarcoma and 53 Ewing sarcomas and in a group of 143 healthy matched children. RESULTS: Osteosarcoma and Ewing sarcoma patients were significantly taller than Spanish reference children. Osteosarcoma patients showed a significantly higher frequency of the Ff genotype for the Fok I polymorphism (VDR gene) than the control group. The odds ratio for this genotype was 1.78, with an increased relative risk of 78% for heterozygous Ff carriers. Among Ewing sarcoma patients, this same genotype was significantly associated with lower height than homozygotes (FF or ff). CONCLUSIONS: Children with bone cancer are significantly taller than the reference population, which may be influenced by the genotype for the Fok I polymorphism of the VDR gene.     

Prenatal diagnosis of Down syndrome: A 13-year retrospective study

Objective

The aim of this study is to summarize the experience on prenatal diagnosis of Down syndrome.

Troponins,heat shock proteins and glycogen phosphorylase BB in umbilical cord blood of complicated pregnancies

Purpose of the study: Heat shock proteins (Hsp) are evolutionary conserved molecules with a chaperone role in cell survival. We hypothesized that cord blood concentrations of molecules reflecting fetal cardiac muscle insult, including Hsp, troponins cTnI and cTnT, and glycol-phosphorylase BB (GP-BB) would be elevated in pregnancies complicated by gestational diabetes (GDM) or preeclampsia (PIH) compared to healthy controls.

Materials and methods: Pregnant women admitted for delivery at >28 weeks were divided into four groups: healthy patients delivered vaginally (VAG), healthy patients delivered by c-section (CS), patients with PIH, and patients with GDM. Demographics, clinical characteristics, and cord blood concentrations of Hsp, troponins cTnI and cTnT, and GP-BB were compared between groups. Statistical analyses included t-test, Chi square, and Wilcoxon rank sum as appropriate.

Results: cTnI concentrations were significantly higher in the PIH group compared to the GDM and VAG groups and they were higher in the CS group compared to the VAG group. Concentrations of Hsp70 were higher in the GDM group compared to the VAG and CS groups. Concentration of GP-BB was higher in the PIH group compared to the VAG group.

Conclusions: GP-BB and cTNI are the most sensitive markers for PIH-related fetal myocyte injury as is Hsp70 in pregnancies complicated by GDM.     

Factors associated with unintended pregnancy in Brazil: cross-sectional results from the Birth in Brazil National Survey, 2011/2012

Background

Unintended pregnancy, a pregnancy that have been either unwanted or mistimed, is a serious public health issue in Brazil. It is reported for more than half of women who gave birth in the country, but the characteristics of women who conceive unintentionally are rarely documented. The aim of this study is to analyse the prevalence and the association between unintended pregnancy and a set of sociodemographic characteristics, individual-level variables and history of obstetric outcomes.

Methods

Birth in Brazil is a cross-sectional study with countrywide representation that interviewed 23,894 women after birth. The information about intendedness of pregnancy was obtained after birth at the hospital and classified into three categories: intended, mistimed or unwanted. Multinomial regression analysis was used to estimate the associations between intendedness of a pregnancy, and sociodemographic and obstetric variables, calculating odds ratios and 95 % confidence intervals. All significant variables in the bivariate analysis were included in the multinomial multivariate model and the final model retaining variables that remained significant at the 5 % level.

Results

Unintended pregnancy was reported by 55.4 % of postpartum women. The following variables maintained positive and significant statistical associations with mistimed pregnancy: maternal age?<?20 years (OR?=?1.89, 95 % CI: 1.68–2.14); brown (OR?=?1.15, 95 % CI: 1.04–1.27) or yellow skin color (OR?=?1.56, 95 % CI: 1.05–2.32); having no partner (OR?=?2.32, 95 % CI: 1.99–2.71); having no paid job (OR?=?1.15, 95 % CI: 1.04–1.27); alcohol abuse with risk of alcoholism (OR?=?1.25, 95 % CI: 1.04–1.50) and having had three or more births (OR?=?2.01, 95 % CI: 1.63–2.47). The same factors were associated with unwanted pregnancy, though the strength of the associations was generally stronger. Women with three or more births were 14 times more likely to have an unwanted pregnancy, and complication in the previous pregnancies and preterm birth were 40 % and 19 % higher, respectively. Previous neonatal death was a protective factor for both mistimed (OR?=?0.61, 95 % CI: 0.44–0.85) and unwanted pregnancy (OR?=?0.44, 95 % CI: 0.34–0.57).

Conclusions

This study confirms findings from previous research about the influence of socioeconomic and individual risk factors on unintended pregnancy. It takes a new approach to the problem by showing the importance of previous neonatal death, preterm birth and complication during pregnancy as risk factors for unintended pregnancy.

     

Factors associated with the use of supplemental oxygen or positive pressure ventilation in the delivery room,in infants born with a gestational age ≥ 34 weeks

Background

Approximately 5–10 % of newborns require some form of resuscitationupon delivery; several factors, such as maternal abnormal conditions, gestational age and type of delivery could be responsible for this trend. This study aimed to describe the factors associated with the need for positive pressure ventilation (PPV) via a mask or endotracheal tube and the use of supplemental O2 in newborns with a gestational age greater than 34 weeks in Brazil.

Methods

We performed a cross-sectional study and obtained data from the Birth in Brazil Survey. The inclusion criterion was a gestational age ≥34 weeks. Exclusion criteria were newborns with congenital malformations, and cases with undetermined gestational age or type of delivery (vaginal, pre labor cesarean section and cesarean section during labor). The primary outcomes were need of PPV via a mask or endotracheal tube and the use of supplemental oxygen without PPV. Confounding variables, including maternal age, source of birth payment, years of maternal schooling, previous birth, newborn presentation, multiple pregnancy, and maternal obstetric risk, were analyzed.

Results

We included 22,720 newborns. Of these, 2974 (13.1 %) required supplementary oxygen. PPV with a bag and mask was used for 727 (3.2 %) newborns and tracheal intubation for 192 (0.8 %) newborns. Chest compression was necessary for 136 (0.6 %) newborns and drugs administered in 114 (0.5 %). 51.3 % of newborns were delivered by cesarean section, with the majority of cesarean sections (88.7 %) being performed prior to labor. Gestational age (late preterm infants: (Relative Risk-(RR) 2.46; 95 % (Confidence interval-CI 1.79–3.39), maternal obstetric risk (RR 1.59; 95 % CI1.30–1.94), and maternal age of 12–19 years old (RR 1.36; 95 % CI1.06–1.74) contributed to rates of PPV in the logistic regression analysis. Newborns aged between 37–38 weeks of gestaional age weren´t less likely to require PPV compared with those aged 39–41 weeks of gestational age.

Conclusions

Late preterm infants, previous maternal obstetric risks and maternal age contributed to the higher needs of PPV and use of O2 in the delivery room. These variables need to be considered in planning care in the delivery room.