Maternal folate status and placental vascular malperfusion: Findings from a high-risk US minority birth cohort.

INTRODUCTION: Maternal folate deficiency was associated with preeclampsia (PE) and PE was associated with placental maternal vascular malperfusion (MVM). However, no study has examined the association of maternal folate status with placental MVM. METHODS: We examined the association of maternal folate status and placental MVM in the Boston Birth Cohort. Primary exposure variables were maternal self-reported multivitamin supplement (<2, 3-5, >5 times/week) per trimester; and plasma folate levels (nmol/L) after birth. Primary outcome was presence/absence of placental MVM defined by the Amsterdam Placental Workshop Group standard classification. Covariates included demographics, chronic hypertension, clinically diagnosed PE, eclampsia and HELLP syndrome, gestational and pre-gestational diabetes, overweight/obesity, maternal cigarette smoking and alcohol use. Associations between folate and placental MVM were evaluated using multivariate logistic regressions. RESULTS: Of 3001 mothers in this study, 18.8% of mothers had PE, 37.5% had MVM. Mothers with the lowest self-reported frequency of folate intake had the highest risk of MVM (OR 1.45, 95% CI 1.03-2.05), after adjusting for the covariates. Consistently, among a subset of 939 mothers with plasma folate levels, folate insufficiency was associated with increased risk of MVM (OR 1.65, 95% CI 1.03-2.63), after adjusting for the covariables. As expected, mothers with low folate and placental MVM had highest rates of PE compared to those of high folate and no MVM (p < 0.001). DISCUSSION: In this high-risk birth cohort, low maternal folate status was associated with increased risk of placental MVM. Further investigation should explore the association between folate status, placental findings and the great obstetrical syndrome.

Successful treatment of stage IIIB intrahepatic cholangiocarcinoma using neoadjuvant therapy with the PD-1 inhibitor camrelizumab: A case report.

BACKGROUND: The prognosis of intrahepatic cholangiocarcinoma (ICC) with lymph node metastasis is poor. The feasibility of surgery is not certain, which is a contraindication according to the National Comprehensive Cancer Network guidelines. The role of immunotherapy as a neoadjuvant therapy for ICC is not clear. We herein describe a case of ICC with lymph node metastasis that was successfully treated with neoadjuvant therapy. CASE SUMMARY: A 60-year-old man with a liver tumor was admitted to our hospital. Enhanced computed tomography and magnetic resonance imaging revealed a space-occupying lesion in the right lobe of the liver. Multiple subfoci were found around the tumor, and the right posterior branch of the portal vein was invaded. Liver biopsy indicated poorly differentiated cholangiocytes. According to the American Joint Committee on Cancer disease stage classification, ICC with hilar lymph node metastasis (stage IIIB) and para-aortic lymph node metastasis was suspected. A report showed that two patients with stage IIIB ICC achieved a complete response (CR) 13 mo and 16 mo after chemotherapy with a PD-1 monoclonal antibody. After multidisciplinary consultation, the patient was given neoadjuvant therapy, surgical resection and lymph node dissection, and postoperative adjuvant therapy. After three rounds of PD-1 immunotherapy (camrelizumab) and two rounds of gemcitabine combined with cisplatin regimen chemotherapy, the tumor size was reduced. Therefore, a partial response was achieved. Exploratory laparotomy found that the lymph nodes of Group 16 were negative, and the tumor could be surgically removed. Therefore, the patient underwent right hemihepatectomy plus lymph node dissection. The patient received six rounds of chemotherapy and five rounds of PD-1 treatment postoperatively. After 8 mo of follow-up, no recurrence was found, and a CR was achieved. CONCLUSION: Neoadjuvant therapy combined with surgical resection is useful for advanced-stage ICC. This is the first report of successful treatment of stage IIIB ICC using neoadjuvant therapy with a PD-1 inhibitor.

Application Effects of SBAR Communication Mode in ICU Nursing Physical Restraint Shift.

Context: Correct and effective handovers of patients' information during shift changes can ensure patients' safety and can help an incoming shift of nurses to continuously monitor patients' psychological problems and avoid unnecessary physical restraints. Development of a standard procedure for handover of patients who have been physically restrained has important clinical significance related to the smooth continuation of nursing work and assurance of the quality of care. Objective: The study intended to investigate the clinical effects of the situation-background-assessment-recommendation (SBAR) communication mode on the quality of the information passed during shift changes about patients in intensive care units (ICUs) who had been physically restrained and to compare it to the clinical effects obtained using traditional methods of communication. Design: The study was a retrospective analysis of the process used by nurses who were passing patient's information during shift changes when caring for patients who had been physically restrained. Setting: The study took place in an ICU at the Second Hospital of Hebei Medical University in Shijiazhuang, Hebei, China. Participants: Participants were 21 nurses caring for 239 ICU patients under physical restraint at the Second Hospital. Intervention: Of the 239 patients, 118 had been hospitalized between March 1 and March 15, 2018 and were assigned to the control group, and 121 had been hospitalized between June 1 and June 15, 2018 and were assigned to the intervention group. An ICU Physical Restraint Handover Order was established according to the SBAR communication mode. The intervention group used the SBAR communication mode and the control group used the hospital's routine communication mode for the physical restraint of a patient during a nursing shift. Outcome Measures: The study measured the differences between the groups in the nurses' passing rates based on standards for the use of physical restraints, the quality of handover of information during shift changes about patients under physical restraint, the quality of the documentation written by nurses about the physical restraint, and the nurses' satisfaction with the handover of information during a shift change. Results: Among the patient, 112 in the intervention group (92.56%) and 92 in the control group (77.97%) were qualified for physical restraint. A statistically significant difference existed between the two groups in the passing rate for the use of physical restraints (P = .001). The quality score for the handovers during shift changes of patients under physical restraint in the intervention group was 95.46 ± 2.50 and for the control group was 91.08 ± 3.57, with the difference being statistically significant (P = .030). The quality score for the nursing documentation for the intervention group, at 97.21 ± 1.49, was higher than that of the control group, at 90.78 ± 3.42, and the difference was statistically significant (P < .001). The nurses' satisfaction score for the intervention group, at 98.14 ± 1.01 was higher than that of the control group, at 92.57 ± 1.86, and the difference was statistically significant (P = .006). Conclusions: The use of the SBAR communication mode to improve the information passed to nurses about patients under physical restraint during a shift change can improve the quality of the physical restraint and nurses' satisfaction and has a better clinical-application effect than the traditional methods used during shift changes.

Maternal prenatal selenium levels and child risk of neurodevelopmental disorders: A prospective birth cohort study.

Selenium (Se) is an essential trace element involved in various biological processes, including neurodevelopment. Available literature indicates that both Se deficiency and excess may be detrimental to health. It is also known that Se can cross the placenta from maternal to fetal circulation. To date, the role of maternal Se status in child long-term neurodevelopment is largely unexplored. This study investigated the temporal and dose-response associations between maternal Se status and child risk of neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). It consisted of 1550 mother-infant dyads from the Boston Birth Cohort. Maternal red blood cell (RBC) Se levels were measured in samples collected within 72 h of delivery (biomarker of third trimester Se status). Pediatric neurodevelopmental diagnoses were obtained from electronic medical records. Data analyses showed that maternal RBC Se levels were positively associated with child risk of developing ASD, with an adjusted odds ratio of 1.49 for ASD (95% CI: 1.09, 2.02) per IQR increase in Se. There was also a positive association between maternal Se and ADHD (OR: 1.29; 95% CI: 1.04, 1.56, per IQR increase in Se). These associations remained robust even after adjusting for pertinent covariables; and there was no significant interaction between Se and these covariables. Our findings suggest that prenatal exposure to high maternal Se levels may adversely affect child neurodevelopment. Our findings warrant further investigation; if confirmed, optimizing maternal prenatal Se levels may be necessary to maximize its health benefits while preventing undue risk. LAY SUMMARY: Selenium (Se) is an essential nutrient for the health of the pregnant mother and her baby. While Se can readily cross the placenta from maternal to fetal circulation, little is known about maternal Se status on her child's neurodevelopmental outcomes. We studied over 1500 mother-child dyads from birth to school age of the child. We found that babies born from mothers with high blood Se levels may be at increased risk of developing autism spectrum disorder or attention deficit hyperactivity disorder. Given this is the first study of the kind, more study is needed to confirm our findings.

In Utero Exposure to Heavy Metals and Trace Elements and Childhood Blood Pressure in a U.S. Urban, Low-Income, Minority Birth Cohort.

BACKGROUND: In utero exposure to heavy metals lead (Pb), mercury (Hg), and cadmium (Cd) may be associated with higher childhood blood pressure (BP), whereas trace elements selenium (Se) and manganese (Mn) may have protective antioxidant effects that modify metal-BP associations. OBJECTIVES: We examined the individual and joint effects of in utero exposure to Pb, Hg, Cd, Se, and Mn on childhood BP. METHODS: We used data from the Boston Birth Cohort (enrolled 2002-2013). We measured heavy metals and trace elements in maternal red blood cells collected 24-72 h after delivery. We calculated child BP percentile per the 2017 American Academy of Pediatrics Clinical Practice Guideline. We used linear regression models to estimate the association of each metal, and Bayesian kernel machine regression (BKMR) to examine metal coexposures, with child BP between 3 to 15 years of age. RESULTS: Our analytic sample comprised 1,194 mother-infant pairs (61% non-Hispanic Black, 20% Hispanic). Hg and Pb were not associated with child systolic BP (SBP). Se and Mn were inversely associated with child SBP percentiles, which, on average, were 6.23 points lower with a doubling of Se (95% CI: -11.51, -0.96) and 2.62 points lower with a doubling of Mn (95% CI: -5.20, -0.04). BKMR models showed similar results. Although Cd was not associated with child SBP overall, the inverse association between Mn and child SBP was stronger at higher levels of Cd (p-interaction=0.04). Consistent with this finding, in utero exposure to cigarette smoke modified the Mn-child SBP association. Among children whose mothers smoked during pregnancy, a doubling of Mn was associated with a 10.09-point reduction in SBP percentile (95% CI: -18.03, -2.15), compared with a 1.49-point reduction (95% CI: -4.21, 1.24) in children whose mothers did not smoke during pregnancy (p-interaction=0.08). CONCLUSION: Se and Mn concentrations in maternal red blood cells collected 24-72 h after delivery were associated with lower child SBP at 3 to 15 years of age. There was an interaction between Mn and Cd on child SBP, whereby the protective association of Mn on child SBP was stronger among mothers who had higher Cd. The association of Mn and child SBP was also modified by maternal cigarette smoking-a source of Cd-during pregnancy. Optimizing in utero Se levels, as well as Mn levels in women who had high Cd or smoked during pregnancy, may protect offspring from developing high BP during childhood. https://doi.org/10.1289/EHP8325.

Chemical compounds with a neuroprotective effect from the seeds of Celosia argentea L.

Oxidative stress plays a central role in the common pathophysiology of neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Compounds derived from natural sources may offer the potential for new treatment options. Semen Celosiae is a traditional Chinese edible herbal medicine with a long history in China and exhibits wide-reaching biological activities such as hepatoprotective, anti-tumor, anti-diarrheal, anti-diabetic, anti-oxidant, etc. In this study, nine saponins and two phenylacetonitrile glycosides were isolated from Semen Celosiae and their structures were identified using ESI-MS and NMR techniques. Among them, compounds 1 and 2 have not been previously reported. The total concentrations of the five triterpenoid saponins and the two phenylacetonitrile glycosides were 3.348 mg g-1 and 0.187 mg g-1, respectively, suggesting that Semen Celosiae is a novel viable source of the two kinds of compounds. These compounds were observed to significantly attenuate t-BHP-induced neuronal damage by effectively enhancing cell viability and decreasing reactive oxygen species generation and cell apoptosis rate in NSC-34 cells. Furthermore, compounds 1 and 7 reduced the ratios of cleaved caspase-3: caspase-3 and cleaved caspase-7: caspase-7 and the level of cytochrome C, while they increased the levels of SOD1 and Beclin 1. These findings suggest that compounds 1-11 are potent inhibitors of neuron injury elicited by t-BHP, possibly via inhibition of oxidative stress and apoptosis, and activation of autophagy; therefore they may be valuable leads for future therapeutic development.

A prospective birth cohort study on cord blood folate subtypes and risk of autism spectrum disorder.

BACKGROUND: We previously reported that extremely high concentrations of maternal plasma folate were associated with increased risk of autism spectrum disorder (ASD) in children. This study explored whether specific types of folate in cord blood have differential association with ASD. OBJECTIVES: In the Boston Birth Cohort (BBC), we assessed the association between cord blood unmetabolized folic acid (UMFA), 5-methyl tetrahydrofolate (THF), and total folate and a child's ASD risk. In a subset, we explored whether the association between UMFA and ASD risk can be affected by the dihydrofolate reductase (DHFR) genotype and cord plasma creatinine. We also examined prenatal correlates of cord UMFA concentrations. METHODS: This report included 567 BBC children (92 ASD, 475 neurotypical), who were recruited at birth and prospectively followed at the Boston Medical Center. ASD was defined from International Classification of Diseases (ICD)-9 and ICD-10 codes documented in electronic medical records. RESULTS: Children with cord UMFA in the highest, versus lowest quartile, had a greater ASD risk (adjusted OR, aORquartile4: 2.26; 95% CI: 1.08, 4.75). When stratified by race/ethnicity, the association was limited to 311 (45 ASD) Black children (aORquartile4: 9.85; 95% CI: 2.53, 38.31); a test of interaction between race/ethnicity and cord UMFA concentrations was significant (P = 0.007). The UMFA-ASD association in Black children slightly attenuated after adjusting for cord plasma creatinine (P = 0.05). There was no significant association between cord 5-methyl THF, total folate, DHFR genotype, and ASD risk. Cord total folate and maternal supplement intake during second trimester were associated with higher cord UMFA. CONCLUSIONS: Higher concentrations of cord UMFA, but not 5-methyl THF or total folate, were associated with a greater risk of ASD in Black children. This study in a preterm-birth-enriched cohort raises more questions than it could answer and underscores the need for additional investigations on the sources and role of cord UMFA in children's neurodevelopmental outcomes and underlying mechanisms.

Raffinose synthase enhances drought tolerance through raffinose synthesis or galactinol hydrolysis in maize and Arabidopsis plants.

Raffinose and its precursor galactinol accumulate in plant leaves during abiotic stress. RAFFINOSE SYNTHASE (RAFS) catalyzes raffinose formation by transferring a galactosyl group of galactinol to sucrose. However, whether RAFS contributes to plant drought tolerance and, if so, by what mechanism remains unclear. In this study, we report that expression of RAFS from maize (or corn, Zea mays) (ZmRAFS) is induced by drought, heat, cold, and salinity stresses. We found that zmrafs mutant maize plants completely lack raffinose and hyper-accumulate galactinol and are more sensitive to drought stress than the corresponding null-segregant (NS) plants. This indicated that ZmRAFS and its product raffinose contribute to plant drought tolerance. ZmRAFS overexpression in Arabidopsis enhanced drought stress tolerance by increasing myo-inositol levels via ZmRAFS-mediated galactinol hydrolysis in the leaves due to sucrose insufficiency in leaf cells and also enhanced raffinose synthesis in the seeds. Supplementation of sucrose to detached leaves converted ZmRAFS from hydrolyzing galactinol to synthesizing raffinose. Taken together, we demonstrate that ZmRAFS enhances plant drought tolerance through either raffinose synthesis or galactinol hydrolysis, depending on sucrose availability in plant cells. These results provide new avenues to improve plant drought stress tolerance through manipulation of the raffinose anabolic pathway.

Trace Minerals, Heavy Metals, and Preeclampsia: Findings from the Boston Birth Cohort.

Background Preeclampsia is a leading contributor to maternal and perinatal morbidity and mortality. In mice experiments, manganese (Mn) and selenium (Se) are protective whereas cadmium (Cd) is promotive for preeclampsia. Epidemiologic findings on these chemical elements have been inconsistent. To confirm experimental findings in mice, we examined associations of trace minerals (Mn and Se) and heavy metals (Cd, lead [Pb], and mercury [Hg]) with preeclampsia in a birth cohort. Methods and Results A total of 1274 women from the Boston Birth Cohort (enrolled since 1998) had complete data on the exposures and outcome. We measured Mn, Se, Cd, Pb, and Hg from red blood cells collected within 24 to 72 hours after delivery. We ascertained preeclampsia diagnosis from medical records. We used Poisson regression with robust variance models to estimate prevalence ratios (PRs) and 95% CIs. A total of 115 (9.0%) women developed preeclampsia. We observed evidence of a dose-response trend for Mn (P for trend<0.001) and to some extent for Cd (P for trend=0.009) quintiles. After multivariable adjustment, a 1 SD increment in Mn was associated with 32% lower risk of developing preeclampsia (PR=0.68; 95% CI, 0.54-0.86), whereas a 1 SD increment in Cd was associated with 15% higher risk of preeclampsia (PR=1.15; 95% CI, 0.98-1.36). Null associations were observed for Se, Pb, and Hg. Conclusions Findings from our cohort, consistent with evidence from mice experiments and human studies, indicate that women with lower blood concentration of Mn or higher Cd are more likely to develop preeclampsia.

Vitamin D Trajectories From Birth to Early Childhood and Elevated Systolic Blood Pressure During Childhood and Adolescence.

Vitamin D deficiency is associated with hypertension in adults. It is unknown to what degree vitamin D status in early life can affect blood pressure (BP) a decade later. This study investigated the effect of vitamin D trajectory through early life on systolic BP (SBP) in childhood. This is a prospective birth cohort study of 775 children enrolled from 2005 to 2012 and followed prospectively up to age 18 years at the Boston Medical Center, Boston, MA. Persistent low vitamin D status is defined as plasma 25(OH)D <11 ng/mL at birth and <25 ng/mL in early childhood. Elevated SBP is defined as SBP ≥75th percentile. Low vitamin D status at birth was associated with higher risk of elevated SBP at ages 3 to 18 years: odds ratio, 1.38; (95% CI, 1.01-1.87) compared to those with sufficient vitamin D. Low vitamin D status in early childhood was associated with a 1.59-fold (95% CI, 1.02-2.46) higher risk of elevated SBP at age 6 to 18 years. Persistent low vitamin D status from birth to early childhood was associated with higher risk of elevated SBP (odds ratio, 2.04; [95% CI, 1.13-3.67]) at ages 3 to 18 years. These results suggest that low vitamin D status and trajectory in early life were associated with increased risk of elevated SBP during childhood and adolescence. Our findings will help inform future clinical and public health strategies for vitamin D screening and supplementation in pregnancy and childhood to prevent or reduce risk of elevated BP across the lifespan and generations.

Genomic Prediction using Existing Historical Data Contributing to Selection in Biparental Populations: A Study of Kernel Oil in Maize.

Maize ( L.) kernel oil provides high-quality nutrition for animal feed and human health. A certain number of maize breeding programs seek to enhance oil concentration and composition. Genomic selection (GS), which entails selection based on genomic estimated breeding values (GEBVs), has proven to be efficient in breeding programs. Here, we estimate the robustness of predictions for the oil traits of maize kernels in biparental recombination inbred lines (RILs) using a GS model built based on an association population. Most statistical models, including ridge regression-best linear unbiased prediction (RR-BLUP), showed high prediction accuracy in the training population through a cross validation procedure. The training population size was more important than marker density and a statistical model for prediction performance. Using the optimized GS model, prediction of the biparental RIL population showed medium-high prediction accuracy (0.68) compared with prediction using only oil associated markers ( = 0.43). The potential to apply the GS model to another RIL population that is genetically less related to the training population was also examined, showing promising prediction accuracy in the top selected lines. Our results proved that genomic prediction using existing data is robust for the prediction of polygenic traits with moderate to high heritability.

Maternal postpartum plasma folate status and preterm birth in a high-risk US population.

OBJECTIVE: While maternal folate deficiency has been linked to poor pregnancy outcomes such as neural tube defects, anaemia and low birth weight, the relationship between folate and preterm birth (PTB) in the context of the US post-folic acid fortification era is inconclusive. We sought to explore the relationship between maternal folate status and PTB and its subtypes, i.e. spontaneous and medically indicated PTB. DESIGN: Observational study. SETTING: Boston Birth Cohort, a predominantly urban, low-income, race/ethnic minority population at a high risk for PTB.ParticipantsMother-infant dyads (n 7675) enrolled in the Boston Birth Cohort. A sub-sample (n 2313) of these dyads had maternal plasma folate samples collected 24-72 h after delivery. RESULTS: Unadjusted and adjusted logistic regressions revealed an inverse relationship between the frequency of multivitamin supplement intake and PTB. Compared with less frequent use, multivitamin supplement intake 3-5 times/week (adjusted OR (aOR) = 0·78; 95 % CI 0·64, 0·96) or >5 times/week (aOR = 0·77; 95 % CI 0·64, 0·93) throughout pregnancy was associated with reduced risk of PTB. Consistently, higher plasma folate levels (highest v. lowest quartile) were associated with lower risk of PTB (aOR = 0·74; 95 % CI 0·56, 0·97). The above associations were similar among spontaneous and medically indicated PTB. CONCLUSIONS: If confirmed by future studies, our findings raise the possibility that optimizing maternal folate levels across pregnancy may help to reduce the risk of PTB among the most vulnerable US population in the post-folic acid fortification era.

Folate Nutrition Status in Mothers of the Boston Birth Cohort, Sample of a US Urban Low-Income Population.

OBJECTIVES: To examine maternal folic acid supplementation and plasma folate concentrations in the Boston Birth Cohort, a predominantly urban, low-income, minority population in Boston, Massachusetts. METHODS: This report includes 7612 mothers with singleton live births (3829 Black, 2023 Hispanic, 865 White, and 895 others) enrolled in the Boston Birth Cohort at the Boston Medical Center, during 1999 to 2014. Folic acid supplementation during preconception and each trimester was obtained via interview questionnaire. In a subset (n = 2598), maternal plasma folate concentrations were measured in blood samples drawn within a few days of delivery. RESULTS: The percentage of mothers taking folic acid supplementation almost daily during preconception and the first, second, and third trimesters were 4.3%, 55.9%, 59.4%, and 58.0%, respectively. Most striking, we observed a wide range of maternal plasma folate concentrations, with approximately 11% insufficient (< 13.4 nmol/L) and 23% elevated (> 45.3 nmol/L). CONCLUSIONS: Findings indicate that fewer than 5% of mothers in the Boston Birth Cohort started folic acid supplements before pregnancy, and approximately one third of mothers had either too low or too high plasma folate levels, which may have important health consequences on both the mother and the child.

Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring.

BACKGROUND: To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B12 levels at birth and child's Autism Spectrum Disorder (ASD) risk. METHODS: This report included 1257 mother-child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B12 were measured from samples taken 2-3 days after birth. RESULTS: Moderate (3-5 times/week) self-reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B12 (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5). CONCLUSION: There was a 'U shaped' relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B12 levels at birth were associated with ASD risk. This hypothesis-generating study does not question the importance of consuming adequate folic acid and vitamin B12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B12 exposure in-utero on early brain development.

ACC GABA levels are associated with functional activation and connectivity in the fronto-striatal network during interference inhibition in patients with borderline personality disorder.

Impulsivity often develops from disturbed inhibitory control, a function mainly regulated by γ-Aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) and the fronto-striatal system. In this study, we combined MRS GABA measurements and fMRI to investigate neurochemical and neurofunctional correlates of interference inhibition, further emphasizing the direct relationship between those two systems, as well as their relations to impulsivity in patients with BPD. In addition to BOLD activation, task-dependent functional connectivity was assessed by a generalized psychophysiological interactions approach. Full factorial analyses were performed via SPM to examine the main effect (within-group associations) as well as the interaction term (group differences in the association slope). The UPPS scales were used to evaluate impulsivity traits. Compared to healthy controls (HCs), BPD patients exhibited significantly less ACC-caudate functional connectivity during interference inhibition. ACC GABA levels in BPD patients but not in HCs were positively related to the magnitude of activation in several fronto-striatal regions (e.g. ACC, frontal regions, putamen, caudate,) and the strength of ACC-caudate functional connectivity during interference inhibition. The strength of the correlations of GABA with connectivity significantly differs between the two groups. Moreover, among all the UPPS impulsivity subscales, UPPS sensation seeking in the BPD group was related to GABA and was also negatively related to the task-dependent BOLD activation and functional connectivity in the fronto-striatal network. Finally, mediation analyses revealed that the magnitude of activation in the caudate and the strength of ACC-caudate functional connectivity mediated the relationship between ACC GABA levels and UPPS sensation seeking in patients with BPD. Our findings suggest a disconnectivity of the fronto-striatal network in BPD patients during interference inhibition, particularly for patients with higher impulsivity. The ACC GABAergic system seems to play a crucial role in regulating regional BOLD activations and functional connectivity in this network, which are further associated with impulsive sensation seeking in BPD.

[Chemical constituents from flowers of Scabiosa tschilliensis].

Twenty-two compounds were isolated from the flowers of Scabiosa tschilliensis. Their structures were identified by spectroscopic methods as octacosanol (1), stearic acid (2), ß-sitosterol (3), oleanolic acid (4), apigenin (5), luteolin (6), daucosterol (7), kaempferol-3-O-ß-D-6-O-(p-hydroxycinnamoyl) -glucopyranoside (8), kaempferol-3-O-ß-D- (3, 6-di-p-(hydroxycinnamoyl) -glucopyranoside (9), apigenin-7-O-ß-D-glucopyranoside (10), luteolin-4'-O-ß-D-glucopyranoside (11), apigenin-7-O-rutinoside (12), luteolin-7-O-ß-D-glucopyranoside (13), apigenin-4'-O-ß-D-glucopyranoside (14), caffeic acid methyl ester (15), loganin (16), adenosine (17), luteolin-6-C-ß-D-glycopyranosyl (18), sweroside (19), sylvestrosides I (20), sylvestrosides II (21), urceolide (22). Among them, compounds 1, 2, 7-9, 12, 15, 17-18, 20-22 were isolated from the genus Scabiosa for the first time, and compounds 1-4, 6-9, 11-12, 14-22 were isolated from this plant for the first time. 13C-NMR data of 22 were reported for the first time.

Hormonal interactions during cluster-root development in phosphate-deficient white lupin (Lupinus albus L.).

This study addresses hormonal interactions involved in cluster-root (CR) development of phosphate (Pi)-deficient white lupin (Lupinus albus), which represents the most efficient plant strategy for root-induced mobilisation of sparingly soluble soil phosphorus (P) sources. Shoot-to-root translocation of auxin was unaffected by P-limitation, while strong stimulatory effects of external sucrose on CR formation, even in P-sufficient plants, suggest sucrose, rather than auxins, acts as a shoot-borne signal, triggering the induction of CR primordia. Ethylene may act as mediator of the sucrose signal, as indicated by moderately increased expression of genes involved in ethylene biosynthesis in pre-emergent clusters and by strong inhibitory effects of the ethylene antagonist CoCl2 on CR formation induced by sucrose amendments or P-limitation. As reported in other plants, moderately increased production of brassinosteroids (BRs) and cytokinin, in pre-emergent clusters, may be required for the formation of auxin gradients necessary for induction of CR primordia via interference with auxin biosynthesis and transport. The well-documented inhibition of root elongation by high doses of ethylene may be involved in the growth inhibition of lateral rootlets during CR maturation, indicated by a massive increased expression of gene involved in ethylene production, associated with a declined expression of transcripts with stimulatory effects (BR and auxin-related genes).

Liquid Chromatography-Tandem Mass Spectrometry Screening Method for the Detection of Radical-Scavenging Natural Antioxidants from the Whole Scutellariae (Radix, Stem and Leaf).

A novel free radical reaction combined with high-performance LC-photodiode array-ESI-MS/MS screening method was developed for the detection and identification of natural antioxidants from whole Scutellariae. Six compounds and whole Scutellariae extracts were found to possess a potential antioxidant capacity, and their free radical-scavenging activities were investigated in detail. The six compounds were identified as baicalin, baicalein, scutellarin, scutellarein, wogonoside and chrystin-7-glucoronide. The present study reveals that the radical-scavenging capacities of the whole Scutellariae extracts are as follows: hydroxyl radical > superoxide radical > peroxy radical. Wogonoside showed the strongest capability for scavenging hydroxyl radical. Baicalein not only showed the strongest capability for scavenging superoxide radical but also showed capability for lipid radical; Scutellarein (Peak 5) exhibited the highest reactivity in the lipid peroxidation processes. Based on these studies, the current paper accomplishes the evaluation of activities of some important anti-radical substances extracted from the radix, stem and leaf of the whole Scutellariae.

Placental transfer and concentrations of cadmium, mercury, lead, and selenium in mothers, newborns, and young children.

There is an emerging hypothesis that exposure to cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in utero and early childhood could have long-term health consequences. However, there are sparse data on early life exposures to these elements in US populations, particularly in urban minority samples. This study measured levels of Cd, Hg, Pb, and Se in 50 paired maternal, umbilical cord, and postnatal blood samples from the Boston Birth Cohort (BBC). Maternal exposure to Cd, Hg, Pb, and Se was 100% detectable in red blood cells (RBCs), and there was a high degree of maternal-fetal transfer of Hg, Pb, and Se. In particular, we found that Hg levels in cord RBCs were 1.5 times higher than those found in the mothers. This study also investigated changes in concentrations of Cd, Hg, Pb, and Se during the first few years of life. We found decreased levels of Hg and Se but elevated Pb levels in early childhood. Finally, this study investigated the association between metal burden and preterm birth and low birthweight. We found significantly higher levels of Hg in maternal and cord plasma and RBCs in preterm or low birthweight births, compared with term or normal birthweight births. In conclusion, this study showed that maternal exposure to these elements was widespread in the BBC, and maternal-fetal transfer was a major source of early life exposure to Hg, Pb, and Se. Our results also suggest that RBCs are better than plasma at reflecting the trans-placental transfer of Hg, Pb, and Se from the mother to the fetus. Our study findings remain to be confirmed in larger studies, and the implications for early screening and interventions of preconception and pregnant mothers and newborns warrant further investigation.

Loading of free radicals on the functional graphene combined with liquid chromatography-tandem mass spectrometry screening method for the detection of radical-scavenging natural antioxidants.

A novel free radical reaction combined with liquid chromatography electrospray ionization tandem mass spectrometry (FRR-LC-PDA-ESI/APCI-MS/MS) screening method was developed for the detection and identification of radical-scavenging natural antioxidants. Functionalized graphene was prepared by chemical method for loading free radicals (superoxide radical, peroxyl radical and PAHs free radical). Separation was performed with and without a preliminary exposure of the sample to specific free radicals on the functionalized graphene, which can facilitate reaction kinetics (charge transfers) between free radicals and potential antioxidants. The difference in chromatographic peak areas is used to identify potential antioxidants. The structure of the antioxidants in one sample (Swertia chirayita) is identified using MS/MS and comparison with standards. Thirteen compounds were found to possess potential antioxidant activity, and their free radical-scavenging capacities were investigated. The thirteen compounds were identified as 1,3,5-trihydroxyxanthone-8-O-ß-D-glucopyranoside (PD1), norswertianin (PD2), 1,3,5,8-tetrahydroxyxanthone (PD3), 3, 3', 4', 5, 8-penta hydroxyflavone-6-ß-D-glucopyranosiduronic acid-6'-pentopyranose-7-O-glucopyranoside (PD4), 1,5,8-trihydroxy-3-methoxyxanthone (PD5), swertiamarin (PS1), 2-C-ß-D-glucopyranosyl-1,3,7-trihydroxylxanthone (PS2), 1,3,7-trihydroxylxanthone-8-O-ß-D-glucopyranoside (PL1), 1,3,8-trihydroxyl xanthone-5-O-ß-D-glucopyranoside (PL2), 1,3,7-trihydroxy-8-methoxyxanthone (PL3), 1,2,3-trihydroxy-7,8-dimethoxyxanthone (PL4), 1,8-dihydroxy-2,6-dimethoxy xanthone (PL5) and 1,3,5,8-tetramethoxydecussatin (PL6). The reactivity and SC50 values of those compounds were investigated, respectively. PD4 showed the strongest capability for scavenging PAHs free radical; PL4 showed prominent scavenging capacities in the lipid peroxidation processes; it was found that all components in S. chirayita exhibited weak reactivity in the superoxide radical scavenging capacity. The use of the free radical reaction screening method based on LC-PDA-ESI/APCI-MS/MS would provide a new approach for rapid detection and identification of radical-scavenging natural antioxidants from complex matrices.