The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother‐to‐infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, ...multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)– and hepatitis B e antigen–positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30‐32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF‐group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. Conclusions: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375–386
Background & Aims Mother-to-infant transmission is the major cause of hepatitis B virus (HBV) infection among immunized children. There has been much debate about screening pregnant women and ...administering hepatitis B immunoglobulin (HBIG) to newborns. We analyzed the rate of HBV infection among children born to hepatitis B surface antigen (HBsAg)-positive mothers and whether HBIG administration reduces transmission. Methods We analyzed data from 2356 children born to HBsAg-positive mothers, identified through prenatal maternal screens. In addition to HBV vaccines, HBIG was given to all 583 children with hepatitis B e antigen (HBeAg)-positive mothers and to 723 of 1773 children with HBeAg-negative mothers. Serology tests for HBV were performed from 2007 to 2009, when children were 0.5–10 years old. Results A significantly greater percentage of children with HBeAg-positive mothers tested positive for antibodies against the hepatitis B core protein (16.76%) and HBsAg (9.26%) than children with HBeAg-negative mothers (1.58% and 0.29%, respectively; P < .0001 and <.001). Among the HBV-infected children, the rate of chronicity also was higher among children with HBeAg-positive mothers than children with HBeAg-negative mothers (54% vs 17%; P = .002). Similar rates of antibodies against the hepatitis B core protein (0.99% and 1.88%; P = .19) and HBsAg (0.14% and 0.29%; P = .65) were noted in children born to HBeAg-negative mothers who were or were not given HBIG. Infantile fulminant hepatitis developed in 1 of 1050 children who did not receive HBIG (.095%). Conclusions Children born to HBeAg-positive mothers are at greatest risk for chronic HBV infection (9.26%), despite immunization. Administration of HBIG to infants born to HBeAg-negative mothers did not appear to reduce the rate of chronic HBV infection, but might prevent infantile fulminant hepatitis. Screening pregnant women for HBsAg and HBeAg might control mother-to-infant transmission of HBV.
Gold nanoparticles (Au-NPs) are being increasingly used as constituents in cosmetics, biosensors, bioimaging, photothermal therapy, and targeted drug delivery. This elevated exposure to Au-NPs poses ...systemic risks in humans, particularly risks associated with the biodistribution of Au-NPs and their potent interaction with biological barriers. We treated human umbilical vein endothelial cells with Au-NPs and comprehensively examined the expression levels of tight junction (TJ) proteins such as occludin, claudin-5, junctional adhesion molecules, and zonula occludens-1 (ZO-1), as well as endothelial paracellular permeability and the intracellular signaling required for TJ organization. Moreover, we validated the effects of Au-NPs on the integrity of TJs in mouse brain microvascular endothelial cells in vitro and obtained direct evidence of their influence on blood-brain barrier (BBB) permeability in vivo. Treatment with Au-NPs caused a pronounced reduction of PKCζ-dependent threonine phosphorylation of occludin and ZO-1, which resulted in the instability of endothelial TJs and led to proteasome-mediated degradation of TJ components. This impairment in the assembly of TJs between endothelial cells increased the permeability of the transendothelial paracellular passage and the BBB. Au-NPs increased endothelial paracellular permeability in vitro and elevated BBB permeability in vivo. Future studies must investigate the direct and indirect toxicity caused by Au-NP-induced endothelial TJ opening and thereby address the double-edged-sword effect of Au-NPs.
Summary
Background
Maternal anti‐viral treatment prevents mother‐to‐infant transmission of hepatitis B virus (HBV), but the role of neonatal viremia on subsequent HBV infection is not clear.
Aims
To ...investigate the effect of maternal anti‐viral treatment on neonatal serum HBV DNA and hepatitis B surface antigen (HBsAg) in infants born to highly viremic mothers and the roles of neonatal markers in predicting chronic HBV infection in children.
Methods
Serum HBV DNA and HBsAg were tested in children. Of the 201 pregnant mothers, 110 received tenofovir during the third trimester. Chronic infection in children was defined by HBsAg seropositivity at 6 or 12 months lasting more than 6 months.
Results
The maternal HBV viral loads from baseline to delivery were 8.25 ± 0.48 to 4.29 ± 0.98 log10 IU/mL; and 8.29 ± 0.49 to 8.12 ± 0.68 log10 IU/mL in the tenofovir and control group respectively. Of the 208 children, those in the tenofovir group had a lower rate of neonatal HBV DNA seropositivity at birth (5.22% vs 30.11%, P < 0.0001) and HBsAg seropositivity at 6 months (1.74% vs 11.83%, P = 0.003) and 12 months (1.74% vs 10.75%, P = 0.007). In a first multivariate analysis, maternal HBV DNA level at delivery (odds ratio = 1.70, P = 0.0172) and neonatal HBsAg positivity (odds ratio = 19.37, P < 0.0001) were significantly associated with children's chronic HBV infection. In a second model, neonatal HBV DNA positivity was a strong independent influence variable (odds ratio = 61.89, P = 0.0002).
Conclusions
Maternal tenofovir therapy decreased maternal viral load and neonatal viremia. Positive neonatal HBV DNA was highly correlated with chronic HBV infection in children. Clinical Trial Identifier: NCT01312012.
Adequate migration of Schwann cells (Sc) is crucial for axon-guidance in the regenerative process after peripheral nerve injury (PNI). Considering neuregulin-erbB-FAK signaling is an essential ...pathway participating in the regulation of Sc migration during development, the present study is aimed to examine whether neuregulin would exert its beneficial effects on adult following PNI and further determine the potential changes of downstream pathway engaged in neuro-regeneration by both in vitro and in vivo approaches.
Cultured RSC96 cells treated with neuregulin were processed for erbB2/3 immunofluorescence and FAK immunoblotings. The potential effects of neuregulin on Sc were assessed by cell adherence, spreading, and migration assays. In order to evaluate the functional significance of neuregulin on neuro-regeneration, the in vivo model of PNI was performed by chronic end-to-side neurorrhaphy (ESN). In vitro studies indicated that after neuregulin incubation, erbB2/3 were not only expressed in cell membranes, but also distributed throughout the cytoplasm and nucleus of RSC96 cells. Activation of erbB2/3 was positively correlated with FAK phosphorylation. Neuregulin also increases Sc adherence, spreading, and migration by 127.2 ± 5.0%, 336.8 ± 3.0%, and 80.0 ± 5.7%, respectively. As for in vivo study, neuregulin significantly accelerates the speed of Sc migration and increases Sc expression in the distal stump of injured nerves. Retrograde labeling and compound muscle action potential recordings (CMAP) also showed that neuregulin successfully facilitates nerve regeneration by eliciting noticeably larger CMAP and promoting quick re-innervation of target muscles.
As neuregulin successfully improves axo-glial interaction by speeding Sc migration via the erbB2/3-FAK pathway, therapeutic use of neuregulin may thus serve as a promising strategy to facilitate the progress of nerve regeneration after PNI.
Aberrant glycosylation is frequently observed in cancers. Core 1 β1,3-galactosyltransferase (C1GALT1) is an exclusive enzyme in humans that catalyzes the biosynthesis of core 1 O-glycan structure, ...Gal-GalNAc-O-Ser/Thr, whose expression is commonly up-regulated during tumorigenesis. Little is known about the function of C1GALT1 in breast cancer. This study aims to determine the correlation between C1GALT1 expression and breast cancer clinicopathological features and roles of C1GALT1 in breast cancer malignant phenotypes. Public databases and our data showed that C1GALT1 mRNA and C1GALT1 protein are frequently up-regulated in breast cancer; and increased C1GALT1 expression correlates with higher histological grade and advanced tumor stage. Overexpression of C1GALT1 enhanced breast cancer cell growth, migration, and invasion in vitro as well as tumor growth in vivo. Conversely, C1GALT1 knockdown suppressed these malignant phenotypes. Furthermore, C1GALT1 modulates O-glycan structures on Mucin (MUC) 1 and promotes MUC1-C/β-catenin signaling in breast cancer cells. These findings suggest that C1GALT1 enhances breast cancer malignant progression through promoting MUC1-C/β-catenin signaling pathway. Unveiling the function of C1GALT1 in breast cancer opens new insights to the roles of C1GALT1 and O-glycosylation in tumorigenesis and renders the potential of C1GALT1 as a target of novel therapeutic agent development.
The relationship between concurrent or previous postnatal pain and depressive symptoms remains controversial. To the best of our knowledge, no previous study has used validated measures and multiple ...scales to evaluate perineal pain, or examined its relationship with depressive symptoms during the postpartum period.
We investigated the association between pain and previous postnatal pain with depression during the 6-month postpartum period, and the influence of previous postnatal depressive symptoms.
A prospective cohort study design was used.
Maternity unit of a medical center.
This study included 432 participants; data regarding demographic characteristics, perineal pain, and any pain and depression during the 6-month postpartum period were collected.
Pain and depressive symptoms were measured using the Short Form-McGill Pain Questionnaire and Center for Epidemiologic Studies Depression Scale, respectively. A generalized estimating equation was used to examine factors associated with postpartum depression.
After adjusting for covariates, women who had perineal pain at 4–6 weeks postpartum showed an increased risk for depression at 4–6 weeks (risk ratio RR: 1.9, 95% confidence limits CL: 1.2, 3.2) and 6 months (RR: 1.9, 95% CL: 1.1, 3.3) compared to those with no perineal pain. Perineal pain severity, 4–6 weeks postpartum, also predicted depressive symptoms at 6 months postpartum (β=0.63, p=0.02). Any pain intensity score at 3–5 days postpartum predicted depression at 3 months (β=0.01, p=0.04). Women with high depression scores at 3–5 days had a two- or three-fold higher risk for depression at 4–6 weeks and 3 and 6 months, respectively, compared to those with low depression scores (RR: 3.5, 95% CL: 2.2, 5.4; RR: 2.2, 95% CL: 1.3, 3.4; and RR: 2.8, 95% CL: 1.7, 4.8, respectively).
Our study provides robust evidence that perineal pain 4–6 weeks postpartum is associated with depressive symptoms 4–6 weeks and 6 months postpartum; pain at 3–5 days postpartum predicts depressive symptoms at 3 months postpartum; and previous postnatal depressive symptoms, particularly depressive symptoms 3–5 days postpartum, predict depressive symptoms during the 6-month postpartum period.
The enzyme 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD) is involved in the synthesis of active steroid hormones. Two human 3β-HSD isoforms are expressed in a tissue-specific pattern. HSD3B1 ...(type I) expression is essential to produce progesterone for pregnancy maintenance. To understand the mechanisms of human HSD3B1 activation in the placenta, 2.2 kb of 5'-flanking sequence and 5'-deletions were fused to the luciferase reporter gene and transfected into human JEG-3 cells. The proximal -238/+337 sequence had the highest promoter activity. Two GATA elements were identified at -106/-99 and -52/-45. Mutations of either sites greatly reduced promoter activity in JEG-3 cells, demonstrating the importance of GATA sites. EMSA revealed the specific binding of GATA2 and GATA3 to the GATA sequences at -106/-99 and -52/-45. ChIP assays demonstrated the association of GATA2 but not GATA3 with the GATA-binding regions of the HSD3B1 promoter in JEG-3 cells. GATA2 knockdown significantly reduced HSD3B1 expression in JEG-3 cells; however, GATA3 knockdown increased HSD3B1 expression. Western blot analysis revealed high levels of GATA2 but not GATA3 in human placental tissues. This study identified GATA motifs as essential control elements for HSD3B1 transcription and GATA2 as a novel transcriptional regulator of HSD3B1 expression in the human placenta.
A case of placenta percreta was referred at 31 weeks' gestation. We performed a cesarean hysterectomy preceded by placement of occlusive balloon catheters at bilateral common iliac arteries at 34 ...weeks' gestation. This simple and safe technique provides satisfactory efficacy for control of profuse bleeding during operation, with blood loss estimated at 800 mL.
Aim
In this study, we collected group B streptococcus (GBS) screening data and analyzed screening rate, antimicrobial resistance rate, and neonatal observation room (NOR) admission rate due to ...inadequate chemoprophylaxis.
Methods
The GBS screening data for January 2006–December 2013 were retrospectively collected and analyzed. We also collected data for neonates admitted to NOR due to inadequate chemoprophylaxis during the period 1 April 2010–31 December 2013.
Results
A total of 12 200 pregnant women received rectovaginal culture during the 8‐year study period. The overall screening rate was 53.8% and maternal colonization rate was 20.7%. The GBS screening rate increased remarkably, from 23.2% in 2006 to 70% in 2013. Antimicrobial resistance was common. The resistance rates for each antimicrobial used in pregnancy were as follows: clindamycin, 49.51%; erythromycin, 49.51%. A total of 297 neonates were admitted to NOR due to inadequate antibiotic prophylaxis during 1 April 2010–31 December 2013. The overall NOR admission rate due to inadequate chemoprophylaxis was 2.67%, and the inadequate chemoprophylaxis rate for those GBS colonized mothers was 19.6%. None of these 297 infants had positive blood culture for GBS sepsis.
Conclusion
The GBS screening rate increased remarkably, reaching 70% in 2013. The NOR admission rate due to inadequate chemoprophylaxis was 2.67% and there was no early onset GBS disease in a total of 11 123 deliveries in this 4‐year cohort study.
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