Mid-pregnancy poly(I:C) viral mimic disrupts placental ABC transporter expression and leads to long-term offspring motor and cognitive dysfunction.

Limited information is available about the effect of mid-pregnancy viral infections on the placental expression of efflux transporters and offspring behavior. We hypothesized that maternal exposure to polyinosinic-polycytidylic acid [poly(I:C)], a synthetic double-stranded RNA viral mimic, would impair placental cell turnover, the expression of selected ABC transporters and adult offspring behavior. C57BL/6 mice were administered poly(I:C) (10 mg/Kg;ip) or vehicle at gestational day (GD) 13.5 (mid-pregnancy). Dams were euthanized for blood collection 4 h after injection, fetal and placental collection at GD18.5 or allowed to deliver spontaneously at term. At GD 13.5, poly(I:C) induced an acute pro-inflammatory response characterized by an increase in maternal plasma levels of IL-6, CXCL-1 and CCL-2/MCP-1. At GD 18.5, poly(I:C) decreased cell proliferation/death in the labyrinthine and increased cell death in the junctional zones, characterizing a disruption of placental cell turnover. Abca1 and Abcg1 immunolabelling was decreased in the labyrinthine zone, whereas Abca1, Abcg1 and breast cancer resistance transporter (Bcrp) expression increased in the junctional zone. Moreover, adult offspring showed motor and cognitive impairments in the Rotarod and T-water maze tests. These results indicate that viral infection during mid-pregnancy may disrupt relevant placental efflux transporters, as well as placental cell turnover and offspring behavior in adult life.

Characterizing the Subcortical Structures in Youth with Congenital Heart Disease.

BACKGROUND AND PURPOSE: Congenital heart disease is a leading cause of neurocognitive impairment. Many subcortical structures are known to play a crucial role in higher-order cognitive processing. However, comprehensive anatomic characterization of these structures is currently lacking in the congenital heart disease population. Therefore, this study aimed to compare the morphometry and volume of the globus pallidus, striatum, and thalamus between youth born with congenital heart disease and healthy peers. MATERIALS AND METHODS: We recruited youth between 16 and 24 years of age born with congenital heart disease who underwent cardiopulmonary bypass surgery before 2 years of age (n = 48) and healthy controls of the same age (n = 48). All participants underwent a brain MR imaging to acquire high-resolution 3D T1-weighted images. RESULTS: Smaller surface area and inward bilateral displacement across the lateral surfaces of the globus pallidus were concentrated anteriorly in the congenital heart disease group compared with controls (q < 0.15). On the lateral surfaces of bilateral thalami, we found regions of both larger and smaller surface areas, as well as inward and outward displacement in the congenital heart disease group compared with controls (q < 0.15). We did not find any morphometric differences between groups for the striatum. For the volumetric analyses, only the right globus pallidus showed a significant volume reduction (q < 0.05) in the congenital heart disease group compared with controls. CONCLUSIONS: This study reports morphometric alterations in youth with congenital heart disease in the absence of volume reductions, suggesting that volume alone is not sufficient to detect and explain subtle neuroanatomic differences in this clinical population.

Breast cancer resistance protein (Bcrp/Abcg2) is selectively modulated by lipopolysaccharide (LPS) in the mouse yolk sac.

Bacterial infection alters placental ABC transporters expression. These transporters provide fetal protection against circulating xenobiotics and environmental toxins present in maternal blood. We hypothesized that lipopolysaccharide (LPS-bacterial mimic) alters the yolk sac morphology and expression of key ABC transporters in a gestational-age dependent manner. Yolk sac samples from C57BL/6 mice were obtained at gestational ages (GD) 15.5 and GD18.5, 4 or 24 h after LPS exposure (150ug/kg; n = 8/group). Samples underwent morphometrical, qPCR and immunohistochemistry analysis. The volumetric proportions of the histological components of the yolk sac did not change in response to LPS. LPS increased Abcg2 expression at GD15.5, after 4 h of treatment (p < 0.05). No changes in Abca1, Abcb1a/b, Abcg1, Glut1, Snat1, Il-1ß, Ccl2 and Mif were observed. Il-6 and Cxcl1 were undetectable in the yolk sac throughout pregnancy. Abca1, breast cancer resistance protein (Bcrp, encoded by Abcg2) and P-glycoprotein (P-gp/ Abcb1a/b) were localized in the endodermal (uterine-facing) epithelium and to a lesser extent in the mesothelium (amnion-facing), whereas Abca1 was also localized to the endothelium of the yolk sac blood vessels. LPS increased the labeling area and intensity of Bcrp in the yolk sac's mesothelial cells at GD15.5 (4 h), whereas at GD18.5, the area of Bcrp labeling in the mesothelium (4 and 24 h) was decreased (p < 0.05). Bacterial infection has the potential to change yolk sac barrier function by affecting Bcrp and Abcg2 expression in a gestational-age dependent-manner. These changes may alter fetal exposure to xenobiotics and toxic substances present in the maternal circulation and in the uterine cavity.

Physical activity, functional ability, and quality of life after breast cancer surgery.

This cross-sectional study aimed to assess the influence of different surgical treatment modalities on the level of physical activity, functional capacity, and quality of life of breast cancer survivors. One hundred eighty women aged 30-60 years old were selected and allocated to control group (CG, women without breast cancer, n = 45), breast-conserving surgery group (BCG, n = 45), mastectomy group (MG, n = 45), and breast reconstruction group (BRG, n = 45). Physical activity, functional capacity, and quality of life were assessed, respectively, using the following self-report questionnaires validated for use in Brazil: International Physical Activity Questionnaire (IPAQ), Stanford Health Assessment Questionnaire (HAQ-20), and Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). The groups were homogeneous relative to sociodemographic variables. The scores for physical activity (IPAQ) did not differ between CG and BRG, whereas they were better for CG than for BCG and MG (p = 0.0270). The results for functional capacity (HAQ-20) were better for CG than for MG (p = 0.0450), with no difference between the remaining groups. Differences were found for the SF-36 domains "physical functioning" (p < 0.01), "physical role functioning" (p < 0.001), "emotional role functioning" (p = 0.0174), and "general health" (p = 0.0307). CG and BRG differed significantly relative to the domains "physical role functioning" and "emotional role functioning" only. We concluded that patients who underwent breast reconstruction exhibited higher levels of physical activity and quality of life than patients subjected to mastectomy alone or breast-conserving surgery.

Dysregulation of placental ABC transporters in a murine model of malaria-induced preterm labor.

Malaria in Pregnancy (MiP) is characterized by placental accumulation of Plasmodium-infected erythrocytes, intrauterine growth restriction (IUGR) and preterm delivery (PTD). Placental ATP-binding cassette (ABC) transporters mediate the efflux of nutrients, cytokines and xenobiotics. The expression and activity of these transporters are highly responsive to infection. We hypothesized that MiP would perturb the expression of placental ABC transporters, promoting PTD. Peripheral blood, spleens, livers and placentas of pregnant mice, infected with Plasmodium berghei ANKA on gestational day (GD) 13.5, were collected and analyzed on GD18.5. The primary consequences of human MiP, including IUGR, PTD (20%) and placental inflammation, were recapitulated in our mouse model. Electron microscopy revealed attenuated presence of labyrinthine microvilli and dilated spongiotrophoblasts -granular endoplasmic reticulum cisternae. Additionally, a decrease in placental Abca1 (ABCA1), Abcb1b (P-glycoprotein), Abcb9 and Abcg2 (BCRP) expression was observed in MiP mice. In conclusion, MiP associated with PTD impairs placental ABC transporters' expression, potentially modulating placental nutrient, environmental toxin and xenobiotic biodistribution within the fetal compartment, and may, at some degree, be involved with pregnancy outcome in MiP.

Hemostasia e incisão do pedículo ovariano de gatas submetidas à ovariossalpingo-histerectomia eletiva por meio da técnica das três pinças ou do eletrobisturi bipolaar. Estudo comparativo / Hemostasis and incision into the ovary pedicle of cats undergone elective ovariosalpingohysterectomy using the technique of the three bipolar forceps or eletrobisturi. Comparative study

Na cirurgia de ovariossalpingo-histerectomia (OSH), há várias técnicas para realização da hemostasia e da secção do pedículo ovariano, sendo mais comum a técnica das três pinças. O eletrobisturi bipolar pode ser utilizado com eficácia para hemostasia e corte de tecidos. Objetivou-se nesta pesquisa comparar, em gatas, a hemostasia e a secção do pedículo ovariano mediante o uso do eletrobisturi bipolar com a técnica das três pinças, ambas via celiotomia mediana, em relação ao tempo cirúrgico e à eficiência hemostática (hematócrito). Quarenta gatas, com idade de seis meses a sete anos, peso entre 1,68 e 4,14kg, foram submetidas à hemostasia e à secção desse pedículo, sendo 20 pela técnica convencional e 20 por meio do eletrobisturi bipolar. Na análise estatística, observou-se que o uso do eletrobisturi bipolar gera uma diminuição média significativa na duração da cirurgia, quando comparado com o outro método, sem diferenças quanto à comparação de hematócritos pré e pós-cirúrgicos. Por meio do modelo de regressão múltiplo, verificou-se que as variáveis: idade, peso, número de gestações, número de partos e número de cios não influenciaram significativamente no tempo. Concluiu-se, portanto, que o eletrobisturi bipolar oferece eficiência e maior rapidez na realização da hemostasia e da diérese do pedículo ovariano de gatas submetidas à OSH eletiva...

In ovariosalpingohisterectomy (OSH) surgery, there are several techniques for hemostasis and resection of ovarian pedicle, the most common being the three tweezers technique. The bipolar eletrobisturi can be used effectively for hemostasis and cutting tissue. The aim of this research was to compare, in cats, hemostasis and resection of ovarian pedicle eletrobisturi with bipolar forceps and the three techniques, both via median celiotomy, in relation to time and surgical hemostatic efficiency (hematocrit). Forty cats aged six months to seven years, weighing between 1.68 and 4.14kg, underwent hemostasis and pedicle of this section, 20 with the conventional technique and 20 with eletrobisturi bipolar. Statistical analysis showed that the use of bipolar eletrobisturi generates a significant decrease in the mean duration of surgery when compared with a method without differences in hematocrit comparing pre-and post-surgery. Through the multiple regression model we found that the variables age, weight, number of pregnancies, number of births and number of cycles did not significantly influence the time. We conclude, therefore, that the bipolar eletrobisturi is efficient and fast for hemostasis and dieresis ovarian pedicle of cats undergoing elective ovariohysterectomy...