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Objective: To investigate fetal sex dependency of maternal vascular adaptation to pregnancy as assessed by uteroplacental vascular resistance and maternal blood pressure.Design: Prospective population-based cohort study.Setting: Rotterdam, the Netherlands.Population: In total, 8224 liveborn singleton pregnancies were included.Methods: Maternal vascular adaptation was assessed in all trimesters of pregnancy. Pregnancies were stratified into being either complicated by the placental syndrome (i.e. pre-eclampsia, fetal growth restriction or preterm birth, n = 1229) or uncomplicated (n = 6995).Main Outcome Measures: First trimester: blood pressures. Second trimester: blood pressures, pulsatility index of the uterine artery (PI-UtA). Third trimester: blood pressures, PI-UtA, presence of notching in the uterine artery.Results: In women carrying a male fetus PI-UtA was higher than in women with a female fetus in the total group (second trimester P < 0.001, third trimester P = 0.005). Effect estimates differed between women with or without the placental syndrome. In the total group, women with a male fetus more often showed notching in the Doppler resistance pattern (odds ratio 1.42, 95% confidence interval 1.17-1.72). Different blood pressure patterns were observed between pregnant women with a male fetus and pregnant women with a female fetus and between complicated pregnancies and uncomplicated pregnancies.Conclusion: Fetal sex is significantly associated with maternal vascular adaptation to pregnancy with differential effects in uncomplicated pregnancies and in pregnancies complicated by the placental syndrome.Tweetable Abstract: Fetal sex is significantly associated with maternal vascular adaptation to pregnancy. [ABSTRACT FROM AUTHOR]

One out of five teens and adults has genital herpes-many of them women. How can you help stem the epidemic? By identifying patients at risk for acquiring and transmitting herpes simplex virus using type-specific serologic tests, say these experts. [ABSTRACT FROM AUTHOR]

The understanding of the variation of mechanical properties and microstructural changes of rocks due to chemical weathering is critical for prospection, extraction and storage of energy resources in the subsurface. Uniaxial and triaxial compression tests were conducted on fresh and chemically weathered oolitic limestone samples submerged in acidic solutions with pH5 and pH3 values for 30 and 50 days each. Results show that both, acid concentration and exposure period have a significant influence not only in changes of effective porosity, Young’s modulus and peak strength, but also in the development of stress-induced microstructures. While the change in effective porosity increased and the Young’s modulus decreased with exposure time, the peak strength decreased with exposure time and decreasing pH. Micro-fracturing, twinning, and rigid body rotation were the main mechanisms of the deformations observed. The highest density of microcracks and twinned grains were observed in samples subjected to longer exposure periods of time, suggesting that the exposure time constitutes an essential factor in rock softening. Microfracturing initiated at grain boundaries, where stress concentrations were higher. In agreement with previous work on limestone inelastic compaction, the mechanical contrast of allochemical components with respect to cement conditioned the spatial distribution of the microfractures.

Antimicrobial peptides (AMPs) are compounds with a variety of bioactive properties. Especially promising are their antibacterial activities, often toward drug-resistant pathogens. Across different AMP sources, AMPs expressed within plants are relatively underexplored with a limited number of plant AMP families identified. Recently, we identified the novel AMPs CC-AMP1 and CC-AMP2 in ghost pepper plants ( Capsicum chinense x frutescens ), exerting promising antibacterial activity and not classifying into any known plant AMP family. Herein, AMPs related to CC-AMP1 and CC-AMP2 were identified within both Capsicum annuum and Capsicum baccatum . In silico predictions throughout plants were utilized to illustrate that CC-AMP1-like and CC-AMP2-like peptides belong to two broader AMP families, with three-dimensional structural predictions indicating that CC-AMP1-like peptides comprise a novel subfamily of α-hairpinins. The antibacterial activities of several closely related CC-AMP1-like peptides were compared with a truncated version of CC-AMP1 possessing significantly more activity than the full peptide. This truncated peptide was further characterized to possess broad-spectrum antibacterial activity against clinically relevant ESKAPE pathogens. These findings illustrate the value in continued study of plant AMPs toward characterization of novel AMP families, with CC-AMP1-like peptides possessing promising bioactivity.

The contribution of the electron drift instability to anomalous electron transport is experimentally assessed in a Hall effect discharge. The transport is represented by an anomalous collision frequency, which is related through quasilinear theory to the energy and growth rate of the instability. The wave energy is measured directly with ion saturation probes, while estimates of the growth rate are employed based on both linearized theory and direct measurement. The latter measurement is performed with a bispectral analysis method. The wave-driven collision frequency is compared to measurements of the actual collision frequency inferred from a method based on laser-induced fluorescence. It is found that estimates for transport using linearized theory for the growth differ by over an order of magnitude from the actual anomalous collision frequency in the plasma. The wave-driven anomalous collision frequency with measured growth, however, is shown to agree with the electron collision frequency in magnitude and capture aspects of the trends in spatial variation. This result demonstrates experimentally that wave-driven effects ultimately can explain the observed cross-field transport in these devices. The implications of this finding are discussed in the context of the key lengthscales that drive the transport as well as the implications identifying reduced fidelity models that could be used to predict anomalous collision frequency.

Chemoproteomic profiling is a powerful approach to define the selectivity of small molecules and endogenous metabolites with the human proteome. In addition to mechanistic studies, proteome specificity profiling also has the potential to identify new scaffolds for biomolecular sensing. Here, we report a chemoproteomics-inspired strategy for selective sensing of acetyl-CoA. First, we use chemoproteomic capture experiments to validate the N-terminal acetyltransferase NAA50 as a protein capable of differentiating acetyl-CoA and CoA. A Nanoluc-NAA50 fusion protein retains this specificity and can be used to generate a bioluminescence resonance energy transfer (BRET) signal in the presence of a CoA-linked fluorophore. This enables the development of a ligand displacement assay in which CoA metabolites are detected via their ability to bind the Nanoluc-NAA50 protein "host" and compete binding of the CoA-linked fluorophore "guest". We demonstrate that the specificity of ligand displacement reflects the molecular recognition of the NAA50 host, while the window of dynamic sensing can be controlled by tuning the binding affinity of the CoA-linked fluorophore guest. Finally, we show that the method's specificity for acetyl-CoA can be harnessed for gain-of-signal optical detection of enzyme activity and quantification of acetyl-CoA from cellular samples. Overall, our studies demonstrate the potential of harnessing insights from chemoproteomics for molecular sensing and provide a foundation for future applications in target engagement and selective metabolite detection.

Autism is more prevalent in males and males on average score higher on measures of autistic traits. Placental function is affected significantly by the sex of the fetus. It is unclear if sex differences in placental function are associated with sex differences in the occurrence of autistic traits postnatally. To assess this, concentrations of angiogenesis-related markers, placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) were assessed in maternal plasma of expectant women in the late 1 st (mean= 13.5 [SD = 2.0] weeks gestation) and 2 nd trimesters (mean=20.6 [SD = 1.2] weeks gestation), as part of the Generation R Study, Rotterdam, the Netherlands. Subsequent assessment of autistic traits in the offspring at age 6 was performed with the 18-item version of the Social Responsiveness Scale (SRS). Associations of placental protein concentrations with autistic traits were tested in sex-stratified and cohort-wide regression models. Cases with pregnancy complications or a later autism diagnosis (n = 64) were also assessed for differences in placenta-derived markers. sFlt-1 levels were significantly lower in males in both trimesters but showed no association with autistic traits. PlGF was significantly lower in male pregnancies in the 1 st trimester, and significantly higher in the 2 nd trimester, compared to female pregnancies. Higher PlGF levels in the 2 nd trimester and the rate of PlGF increase were both associated with the occurrence of higher autistic traits (PlGF-2 nd : n = 3469,b = 0.24 [SE = 0.11], p = 0.03) in both unadjusted and adjusted linear regression models that controlled for age, sex, placental weight and maternal characteristics. Mediation analyses showed that higher autistic traits in males compared to females were partly explained by higher PlGF or a faster rate of PlGF increase in the second trimester (PlGF-2 nd : n = 3469, ACME: b = 0.005, [SE = 0.002], p = 0.004). In conclusion, higher PlGF levels in the 2 nd trimester and a higher rate of PlGF increase are associated with both being male, and with a higher number of autistic traits in the general population., (© 2023. The Author(s).)

The linear growth and nonlinear energy transfer of the electron drift instability (EDI) are experimentally measured in the plume of a low-temperature, Hall effect discharge. A frequency-based bispectral analysis technique applied to fast ion density fluctuation measurements shows a growth rate function that is qualitatively similar to predictions from the linear instability dispersion relation, but an order of magnitude smaller. Calculation of the nonlinear transfer function indicates multiple three-wave interactions between high-frequency resonances of the instability in addition to an inverse energy cascade toward lower-frequency modes. These results are discussed in the context of recent theoretical, numerical, and experimental efforts on the EDI in Hall effect discharges and how the EDI may impact anomalous cross field transport.

Those with insulin resistance often display increased circulating branched-chain amino acids (BCAA), which has been largely attributable to reduced BCAA catabolic capacity. Metabolic stimuli such as exercise activates AMP-activated kinase (AMPK), which promotes the metabolism of BCAA and induction/activation of BCAA catabolic enzymes. Though much attention has been paid to BCAA catabolic machinery, few studies have assessed the effect of AMPK activation on the predominant BCAA transporter, L-type amino acid transporter 1 (LAT1). This study assessed the effect of AMPK activation on LAT1 expression via common chemical AMPK activators in a cell model of skeletal muscle. C2C12 myotubes were treated with either 1 mM AICAR, 1 mM Metformin, or filter-sterilized water (control) for 24 h with either low- (5 mM) or high-glucose (25 mM) media. LAT1 and pAMPK protein content were measured via western blot. BCAA media content was measured using liquid chromatography-mass spectrometry. AICAR treatment significantly increased pAMPK and reduced LAT1 expression. Collectively, pAMPK and LAT1 displayed a significant inverse relationship independent of glucose levels. During low-glucose experiments, AICAR-treated cells had higher BCAA media content compared to other groups, and an inverse relationship between LAT1 and BCAA media content was observed, however, these effects were not consistently observed during high-glucose conditions. Further investigation with AICAR with and without concurrent LAT1 inhibition (via JPH203) also revealed reduced BCAA utilization in AICAR-treated cells regardless of LAT1 inhibition (which also independently reduced BCAA utilization). pAMPK activation via AICAR (but not Metformin) may reduce LAT1 expression and BCAA uptake in a glucose-dependent manner., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: In women with singleton pregnancies, maternal adaptation is considered a stress test for later life cardiovascular disease. The aim of this study was to assess maternal adaptation in women with twin pregnancies compared to women carrying singletons during and after pregnancy., Methods: This was a population based prospective cohort study of 91 women with twin pregnancies and 8107 women carrying singletons. The association of twin pregnancy and maternal adaptation was examined using regression analyses. In pregnancy, we measured soluble fms-like tyrosine kinase-1 (sFLT-1), placental growth (PGF) factor, systolic (SBP) and diastolic blood pressure (DBP), and the occurrence of pre-eclampsia (PE). After pregnancy, measurements were obtained on SBP and DBP, cardiac function, retinal calibres, intima media thickness and distensibility of the common carotid artery., Results: sFLT-1 and PGF concentrations were higher in early (13.4 weeks) and mid-pregnancy (20.4 weeks) in women with twin pregnancies compared to women with singleton pregnancies. Women with twin pregnancies had a different DBP pattern in pregnancy. Women with twin pregnancies were more likely to have PE (odds ratio 3.63; 95% CI [1.76 to 7.48]). Six and ten years after pregnancy, no differences in maternal adaptation were observed., Conclusions: Women with twin pregnancies show an altered adaptation during pregnancy compared to women with singleton pregnancies. This is associated with a substantially increased incidence of PE, but does not lead to persistent altered maternal adaptation years after pregnancy.

Background: Since the placenta also has a sex, fetal sex-specific differences in the occurrence of placenta-mediated complications could exist., Objective: To determine the association of fetal sex with multiple maternal pregnancy complications., Search Strategy: Six electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies., Selection Criteria: Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies., Data Collection and Analyses: Data were extracted by 2 independent reviewers using a predesigned data collection form., Main Results: From 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition., Conclusion: This meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular and metabolic load for the mother in the presence of a male fetus., Funding: None.

Background: Small for gestational age (SGA) is frequently used to define fetal growth restriction (FGR). However, FGR describes a slowdown in fetal growth and is not synonymous with SGA, which may introduce misclassification. We investigated the effect of both on delivery and childhood outcomes., Methods: From a prospective population-based cohort study we included 7959 live singleton births with data available on second trimester estimated fetal weight (EFW) and birth weight. We used a decrease in growth of > 40 percentiles between second trimester EFW and birthweight to define a deceleration in growth. SGA was defined as birthweight

Background: Angiogenic placental growth factor (PlGF) concentrations rise during pregnancy, peaking at the end of midpregnancy. Low PlGF concentrations during pregnancy are associated with pregnancy complications with recognized later-life cardiovascular risk. We hypothesized that low PlGF concentrations, especially in midpregnancy, identify not only a subset of women at risk for pregnancy complications but also women with greater cardiovascular risk factor burden after pregnancy regardless of pregnancy outcome., Methods: In a population-based prospective cohort study of 5475 women, we computed gestational age-adjusted multiples of the medians of early pregnancy and midpregnancy PlGF concentrations. Information on pregnancy complications (preeclampsia, small for gestational age, and spontaneous preterm birth) was obtained from hospital registries. Six years after pregnancy, we measured maternal systolic and diastolic blood pressures, cardiac structure (aortic root diameter, left atrial diameter, left ventricular mass, and fractional shortening), carotid-femoral pulse wave velocity, and central retinal arteriolar and venular calibers. Blood pressure was also measured 9 years after pregnancy., Results: Women were on average 29.8 (SD, 5.2) years of age in pregnancy, were mostly European (55.2%), and 14.8% developed a pregnancy complication. Quartile analysis showed that especially women with midpregnancy PlGF in the lowest quartile (the low-PlGF subset) had a larger aortic root diameter (0.40 mm [95% CI, 0.08-0.73]), left atrial diameter (0.34 mm [95% CI, -0.09 to 0.78]), left ventricular mass (4.6 g [95% CI, 1.1-8.1]), and systolic blood pressure (2.3 mm Hg [95% CI, 0.93-3.6]) 6 years after pregnancy than women with the highest PlGF. Linear regression analysis showed that higher midpregnancy PlGF concentrations were associated with a smaller aortic root diameter (-0.24 mm [95% CI, -0.39 to -0.10]), smaller left atrial diameter (-0.75 mm [95% CI, -0.95 to -0.56]), lower left ventricular mass (-3.9 g [95% CI, -5.5 to -2.3]), and lower systolic blood pressure (-1.1 mm Hg [95% CI, -1.7 to -0.46]). These differences persisted after the exclusion of women with complicated pregnancies., Conclusions: Women with low PlGF in midpregnancy have a greater aortic root diameter, left atrial diameter, and left ventricular mass and higher systolic blood pressure 6 and 9 years after pregnancy compared to women with higher PlGF, including women with uncomplicated pregnancies. The pathophysiological implications of lower PlGF concentrations in midpregnancy might provide insight into the identification of pathways contributing to greater cardiovascular risk factor burden.

Objective: We assessed whether umbilical cord blood placental growth factor (PlGF) levels at delivery are associated with fetal growth., Methods: From a prospective population-based cohort study we included 3,461 live singleton births. Fetal growth was assessed by birth weight, fetal growth pattern, and fetal growth restriction (FGR; decrease in growth between the second trimester and birth of ≥40 percentiles). In all analyses the highest PlGF multiple of the median (MoM) quintile was used as the reference category., Results: Umbilical cord PlGF was neither correlated with maternal second-trimester PlGF (p = 0.08) nor placental weight (p = 0.18), suggesting that PlGF from umbilical cord blood was of fetal origin. Lower PlGF MoM quintiles were associated with a lower birth weight (lowest quintile -0.60 standard deviation [95% confidence interval -0.71 to -0.48, p for trend <0.001]) and a different fetal growth pattern (p < 0.001). Finally, lower PlGF MoM quintiles were associated with FGR (lowest quintile odds ratio 2.00 [95% confidence interval 1.25 to 3.21, p for trend <0.001])., Conclusion: Lower umbilical cord PlGF levels are associated with lower birth weight, deviating fetal growth patterns, and a higher odds of FGR. Hence, cord blood PlGF might be a promising biomarker to determine deviations in fetal growth and FGR retrospectively, enabling follow-up of these neonates., (© 2017 S. Karger AG, Basel.)

Background: The objective of this study was to assess whether sex-specific differences in fetal and infant growth exist., Methods: This study was embedded in the Generation R Study, a population-based prospective birth cohort. In total, 8556 live singleton births were included. Fetal growth was assessed by ultrasound. During the first trimester, crown-rump-length (CRL) was measured. In the second and third trimester of pregnancy head circumference (HC), abdominal circumference (AC) and femur length (FL) were assessed. Information on infant growth during the first 2 years of life was obtained from Community Health Centers and included HC, body weight and length., Results: In the first trimester, male CRL was larger than female CRL (0.12 SD [95% CI 0.03,0.22]). From the second trimester onwards, HC and AC were larger in males than in females (0.30 SD [95% CI 0.26,0.34] and 0.09 SD [95% CI 0.05,0.014], respectively). However, FL in males was smaller compared to female fetuses (0.21 SD [95% CI 0.17,0.26]). Repeated measurement analyses showed a different prenatal as well as postnatal HC growth pattern between males and females. A different pattern in body weight was observed with a higher body weight in males until the age of 12 months where after females have a higher body weight., Conclusions: Sex affects both fetal as well as infant growth. Besides body size, also body proportions differ between males and females with different growth patterns. This sexual dimorphism might arise from differences in fetal programming with sex specific health differences as a consequence in later life.

Although it is increasingly being recognized that roots play a key role in soil carbon (C) dynamics, the magnitude and direction of these effects are unknown. Roots can accelerate soil C losses by provisioning microbes with energy to decompose organic matter or impede soil C losses by enhancing microbial competition for nutrients. We experimentally reduced belowground C supply to soils via tree girdling, and contrasted responses in control and girdled plots for three consecutive growing seasons. We hypothesized that decreases in belowground C supply would have stronger effects in plots dominated by ectomycorrhizal (ECM) trees rather than arbuscular mycorrhizal (AM) trees. In ECM-dominated plots, girdling decreased the activity of enzymes that break down soil organic matter (SOM) by c. 40%, indicating that, in control plots, C supply from ECM roots primes microbial decomposition. In AM-dominated plots, girdling had little effect on SOM-degrading enzymes, but increased the decomposition of AM leaf litter by c. 43%, suggesting that, in control plots, AM roots may intensify microbial competition for nutrients. Our findings indicate that root-induced changes in soil processes depend on forest composition, and that shifts in the distribution of AM and ECM trees owing to climate change may determine soil C gains and losses., (© 2015 The Authors New Phytologist © 2015 New Phytologist Trust.)

Introduction: Our objective was to assess fetal sex specific differences in first trimester placental biomarkers of both physiological and pathological pregnancies and their interaction with environmental influences. This study is embedded in the Generation R Study, a prospective cohort study., Methods: Only live singleton births were included. Linear regression was performed to assess the effect of sex on first trimester placental biomarkers. Interaction analyses were performed to assess interaction of fetal sex with environmental influences. First trimester soluble fms-like tyrosine kinase (s-Flt1), placental growth factor (PLGF), plasminogen activator inhibitor (PAI-2) and homocysteine levels were assessed., Results: Significant fetal sex specific differences in placental biomarkers were observed. S-Flt1, PAI-2 and PLGF log transformated concentrations were 0.08 ng/mL (95% CI 0.05; 0.11), 0.07 ng/mL (95% CI 0.06; 0.09) and 0.04 pg/mL (95% CI 0.01; 0.06) higher in case of female as compared to male placentas. In pregnancies complicated by pre-eclampsia (PE), preterm birth (PTB) or a newborn being small for gestational age (SGA) no fetal sex specific differences were observed. Interaction analyses suggest that concentrations of s-Flt1, PLGF and PAI-2 decrease in male placentas in the case of hyperhomocysteinemia but remain equal in female placentas., Discussion: Fetal sex affects early placentation processes with discrepancies regarding pregnancies complicated by PE, PTB or a newborn being SGA. This suggests that other mechanisms causing these complications may dominate the fetal sex effect. The differences concerning homocysteine suggest that fetal sex dependent placental gene-environment interactions exist., Conclusion: Fetal sex specific differences in placental biomarkers exist., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To assess the effects of aging on the features of polycystic ovary syndrome (PCOS)., Design: Retrospective longitudinal follow-up study., Setting: Tertiary care center., Patient(s): Patients with PCOS, diagnosed according to the 2003 Rotterdam criteria, who visited the outpatient clinic on consecutive occasions with a minimum interval of 6 months., Intervention(s): Comparisons were made between the first visit and the consecutive visit grouped by intervals., Main Outcome Measure(s): Changes in clinical and endocrine characteristics., Result(s): A total of 254 women visited the outpatient clinic on 2 occasions each. Consecutive visits were grouped into 0.5 to 3.9 years (n = 172; mean follow-up, 2.6 years) and 4.0 to 7.0 years (n = 82; mean follow-up, 5.5 years). At their second visit, significantly more women had regained a regular cycle. The total antral follicle count was similar. Serum levels of testosterone, androstenedione, and dehydroepiandrosterone sulfate had decreased significantly. Plasma glucose levels had increased, whereas serum insulin levels and homeostasis model assessment score had significantly decreased., Conclusion(s): The PCOS phenotype changed with aging, suggesting an amelioration of the phenotype and ovarian dysfunction as indicated by the increase in number of regular menstrual cycles, decrease in serum androgen levels, and decrease in insulin resistance., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Cobalt cyanide complexes often result when ore is treated with cyanide solutions to extract gold and other metals. These have recently been discovered in low but significant concentrations in effluents from gold leach operations. This study was conducted to determine the potential toxicity of cobalt-cyanide complexes to freshwater organisms and the extent to which ultraviolet radiation (UV) potentiates this toxicity. Tests were also conducted to determine if humic acids or if adaptation to UV influenced sensitivity to the cyanide complexes., Methods: Rainbow trout (Oncorhynchus mykiss), Daphnia magna, and Ceriodaphnia dubia were exposed to potassium hexacyanocobaltate in the presence and absence of UV radiation, in the presence and absence of humic acids. Cyano-cobalt exposures were also conducted with C. dubia from cultures adapted to elevated UV., Results: With an LC50 concentration of 0.38 mg/L, cyanocobalt was over a 1000 times more toxic to rainbow trout in the presence of UV at a low, environmentally relevant irradiance level (4 microW/cm2 as UVB) than exposure to this compound in the absence of UV with an LC50 of 112.9 mg/L. Toxicity was immediately apparent, with mortality occurring within an hour of the onset of exposure at the highest concentration. Fish were unaffected by exposure to UV alone. Weak-acid dissociable cyanide concentrations were observed in irradiated aqueous solutions of cyanocobaltate within hours of UV exposure and persisted in the presence of UV for at least 96 hours, whereas negligible concentrations were observed in the absence of UV. The presence of humic acids significantly diminished cyanocobalt toxicity to D. magna and reduced mortality from UV exposure. Humic acids did not significantly influence survival among C. dubia. C. dubia from UV-adapted populations were less sensitive to metallocyanide compounds than organisms from unadapted populations., Conclusions: The results indicate that metallocyanide complexes may pose a hazard to aquatic life through photochemically induced processes. Factors that decrease UV exposure such as dissolved organic carbon or increased pigmentation would diminish toxicity.

During the past seven years, several states within the US have enacted regulations that limit the amounts of selected non-nutritive elements in fertilizers. Internationally, several countries, including Japan, China, and Australia, and the European Union also limit the amount of selected elements in fertilizers. The elements of interest include As, Cd, Co, Cr, Cu, Hg, Mo, Ni, Pb, Se, and Zn. Fertilizer manufacturers and state regulatory authorities, faced with meeting and verifying these limits, need to develop analytical methods for determination of the elements of concern and to validate results obtained using these methods. Until now, there were no certified reference materials available with certified mass fraction values for all elements of interest in a blended, multi-nutrient fertilizer matrix. A new standard reference material (SRM) 695 trace elements in multi-nutrient fertilizer, has been developed to help meet these needs. SRM 695 has recently been issued with certified mass fraction values for seventeen elements, reference values for an additional five elements, and information values for two elements. The certificate of analysis includes an addendum listing percentage recovery for eight of these elements, determined using an acid-extraction inductively-coupled plasma optical-emission spectrometry (ICP-OES) method recently developed and tested by members of the Association of American Plant Food Control Officials.

Varicella zoster virus (VZV) infection can be serious for pregnant women and their babies, although it is rare. The implications of primary VZV infection vary with the gestational age at infection. For the mother, the risk of severe illness is greatest after mid-pregnancy, when she is relatively immunocompromised. For the fetus, the risk of congenital infection is greatest when maternal infection occurs in the first or second trimester. Maternal infection is preventable by preconception vaccination.

Genital herpes is common and is becoming more so, with a seroprevalence of 25% in middle class primary care settings. Primary genital herpes in pregnancy most often is subclinical, but it also can cause severe illness. Further, active genital herpes at the time of vaginal delivery poses significant risk of neonatal infection, especially if the mother acquired the infection in the third trimester. It is important to prevent genital herpes acquisition in pregnancy and to diagnose recurrent genital herpes to prevent neonatal herpes.

Background: Nephropathy complicates 5% to 10% of pregnancies in women with diabetes and is associated with adverse outcomes. Given the importance of blood pressure (BP) control in reducing cardiovascular and renal complications outside of pregnancy, we hypothesized that poorly controlled hypertension in early pregnancy among women with diabetic nephropathy would be associated with adverse outcomes., Methods: To examine the impact of hypertensive control in early pregnancy on perinatal outcomes, we performed a retrospective cohort study of pregnancies complicated by diabetic nephropathy with "Above Target" mean arterial pressure (> or = 100 mm Hg; N = 21) and "Below Target" mean arterial pressure (< 100 mm Hg; N = 22), which approximates the American Diabetes Association and the Seventh Report of the Joint National Committee recommended target of 130/80 mm Hg, measured at < 20 weeks' gestation., Results: There were no differences in maternal age (mean +/- SEM: 27.2 +/- 1.2 v 29.5 +/- 1.0 years), duration of diabetes (median, range: 17.5, 13 to 24 v 16, 1 to 25 years), or glucose control (glycosylated hemoglobin [HbA1c] 8.0% +/- 0.3% v 8.1% +/- 0.4%) between the Above and Below Target groups. The Above Target group had more proteinuria (4.69 +/- 1.08 v 1.65 +/- 0.43 g/24 h; P = .007) and higher serum creatinine levels (1.23 +/- 0.17 v 0.85 +/- 0.06 mg/dL; P = .02). The Above Target group was more likely to deliver at < 32 weeks' gestation (38.1% v 4.6%; P = .007). The increased risk of preterm delivery remained significant after adjusting for duration of diabetes and glucose control., Conclusions: Suboptimal control of hypertension in early pregnancy in women with diabetic nephropathy is associated with a significant risk of preterm delivery. Improved preconceptional control of hypertension may reduce adverse perinatal outcomes in women with diabetic nephropathy.

Neonatal herpes is a devastating disease, the most serious complication of genital herpes, one of the most common serious congenital or perinatal infections, and the most frequent complication of sexually transmitted infections among children. Nevertheless, neonatal herpes is not reportable to health authorities in most states. The potential for prevention has been enhanced by recent diagnostic and therapeutic advances, and the disease meets widely accepted criteria for reporting, including incidence rates that exceed those of comparable conditions, epidemiologic instability, disease severity, direct and indirect socioeconomic costs, concern by persons at risk, the potential for prevention by public health interventions, and the prospect that the resulting data would influence public health policy. The absence of national surveillance contributes to beliefs by healthcare providers and the public health community that genital and neonatal herpes are uncommon conditions that affect small segments of society, beliefs that directly interfere with prevention. Neonatal herpes should be a reportable condition.

In recent proficiency testing of herpes simplex virus type-specific serologic evidence by the College of American Pathologists, commercially available herpes simplex virus antibody assays that were not glycoprotein-G based demonstrated high false-positive rates (14%-88%) for herpes simplex virus type-2 antibodies in sera that were positive for herpes simplex virus type-1 antibodies but negative for herpes simplex virus type-2 antibodies. Herpes simplex virus serologic testing should be performed with only glycoprotein-G-based tests.

Objective: The purpose of this study was to assess the efficacy of acyclovir in the reduction of herpes simplex virus culture and polymerase chain reaction positivity and cesarean delivery., Study Design: Women with recurrent genital herpes simplex virus were randomized to acyclovir 400 mg three times daily or placebo from 36 weeks of gestation until delivery. A subset of daily specimens for herpes simplex virus culture and DNA polymerase chain reaction was self-collected. Analyses used chi(2), Fisher exact, and Mann-Whitney U tests., Results: Lesions occurred at delivery among 11 of 78 women (14%) who received placebo and 4 of 84 women (5%) who received acyclovir (P =.08). Herpes simplex virus culture and polymerase chain reaction positivity near delivery occurred in 7% and 34% women in the placebo group and 0 and 2% in the acyclovir group (P =.03 and <.01, respectively). Cesarean delivery for herpes simplex virus occurred in 8 of the women (10%) in the placebo group and in 3 of the women (4%) in the acyclovir group (P =.17). Despite reductions in herpes simplex virus detection, 6% of the women who received acyclovir had herpes simplex virus detected by polymerase chain reaction on >20% of days. Neonatal outcomes were similar between groups., Conclusion: Acyclovir significantly reduced, but did not eliminate, herpes simplex virus lesions and detection in late pregnancy.

Context: Neonatal herpes most commonly results from fetal exposure to infected maternal genital secretions at the time of delivery. The risk of transmission from mother to infant as it relates to maternal herpes simplex virus (HSV) serologic status and exposure to HSV in the maternal genital tract at the time of labor has not been quantified. Furthermore, no data exist on whether cesarean delivery, the standard of care for women with genital herpes lesions at the time of delivery, reduces HSV transmission., Objective: To determine the effects of viral shedding, maternal HSV serologic status, and delivery route on the risk of transmission of HSV from mother to infant., Design: Prospective cohort of pregnant women enrolled between January 1982 and December 1999., Settings: A university medical center, a US Army medical center, and 5 community hospitals in Washington State., Patients: A total of 58 362 pregnant women, of whom 40 023 had HSV cultures obtained from the cervix and external genitalia and 31 663 had serum samples tested for HSV., Main Outcome Measure: Rates of neonatal HSV infection., Results: Among the 202 women from whom HSV was isolated at the time of labor, 10 (5%) had neonates with HSV infection (odds ratio [OR], 346; 95% confidence interval [CI], 125-956 for neonatal herpes when HSV was isolated vs not isolated). Cesarean delivery significantly reduced the HSV transmission rate among women from whom HSV was isolated (1 [1.2%] of 85 cesarean vs 9 [7.7%] of 117 vaginal; OR, 0.14; 95% CI, 0.02-1.08; P =.047). Other risk factors for neonatal HSV included first-episode infection (OR, 33.1; 95% CI, 6.5-168), HSV isolation from the cervix (OR, 32.6; 95% CI, 4.1-260), HSV-1 vs HSV-2 isolation at the time of labor (OR, 16.5; 95% CI, 4.1-65), invasive monitoring (OR, 6.8; 95% CI, 1.4-32), delivery before 38 weeks (OR, 4.4; 95% CI, 1.2-16), and maternal age less than 21 years (OR, 4.1; 95% CI, 1.1-15). Neonatal HSV infection rates per 100 000 live births were 54 (95% CI, 19.8-118) among HSV-seronegative women, 26 (95% CI, 9.3-56) among women who were HSV-1-seropositive only, and 22 (95% CI, 4.4-64) among all HSV-2-seropositive women., Conclusion: Neonatal HSV infection rates can be reduced by preventing maternal acquisition of genital HSV-1 and HSV-2 infection near term. It can also be reduced by cesarean delivery and limiting the use of invasive monitors among women shedding HSV at the time of labor.

It is now known that the physical presentation of genital herpes simplex (HSV) infection can be misleading in making the diagnosis of genital herpes. An incorrect diagnosis can be particularly damaging in pregnancy where it may result in extended exposure of the fetus to antiviral agents, an inappropriate route and timing of delivery and a significant increase in fetal exposure to HSV during labour and delivery. Case 1 describes a 32-year-old woman at 30 weeks in her first pregnancy who had the appearance and clinical course typically ascribed to primary genital HSV infection. In contrast, Case 2, a 24-year-old woman at 34 weeks' gestation, had the physical appearance of a recurrent episode. Type-specific serological testing revealed that what Case 1 was actually experiencing was the first symptomatic reactivation of genital herpes, whereas Case 2 had a true primary genital HSV-2 infection that was accompanied by minimal symptoms. Had serology testing not been available, Case 1 would probably have delivered unnecessarily by Caesarean section, and Case 2 would have been managed as a recurrent infection and allowed to deliver vaginally with potentially disastrous results. These cases illustrate the usefulness of a type-specific serology in diagnosing genital herpes in pregnant women.

Objective: Glycemic control, perinatal outcome, and health care costs were evaluated among women with type 1 diabetes mellitus who began insulin pump therapy during pregnancy (group 1, n = 24), were treated with multiple insulin injections (group 2, n = 24), or were already using an insulin pump before pregnancy (group 3, n = 12). Patient satisfaction and continuation of pump therapy post partum were assessed., Study Design: A retrospective review of maternal and neonatal medical records was performed, and a questionnaire was sent to patients after delivery. Patients in groups 1 and 2 were matched for age, age at onset and duration of diabetes mellitus, White class, and date of delivery., Results: No differences in glycosylated hemoglobin A levels were observed among groups 1, 2 or 3 in the first, second, or third trimester. Patients in group 1 started pump therapy at a mean of 16.8 weeks' gestation, and 17 (70.8%) began therapy as outpatients. No deterioration in glycemic control was noted during the 2- to 4-week period after the start of pump treatment. Among the women in group 1 eight had at least one episode of severe hypoglycemia before starting pump therapy, but only one had such an episode after this treatment was begun. Two episodes of ketoacidosis occurred in group 1, and no episodes occurred in groups 2 and 3. No significant differences in perinatal outcomes or health care costs were observed among groups 1, 2, and 3. After delivery 94. 7% of the women in group 1 continued to use the pump because it provided better glycemic control and a more flexible lifestyle. Postpartum glycosylated hemoglobin A values were 7.2% in group 1 and 9.1% in group 2, a significant difference., Conclusions: Insulin pump therapy was initiated during pregnancy without a deterioration of glycemic control and was associated with maternal and perinatal outcomes and health care costs comparable to those among women who were already using the pump before pregnancy or who received multiple-dose insulin therapy. Women who began pump therapy in pregnancy were highly likely to continue pump use after delivery and preferred the flexible lifestyle that this treatment allowed.

The most devastating consequence of genital herpes is neonatal herpes. It is clear that the majority of newborns acquire their infection by contact with infected genital secretions during delivery from an asymptomatic mother who acquired a first episode of genital herpes near the time of labour. Since the majority of cases of first episode genital herpes during pregnancy are unrecognised, the prevention of neonatal transmission will depend upon the identification of the HSV serologically discordant couple and the institution of appropriate interventions by mid pregnancy. Therefore, the précis of this discussion paper is that universal HSV serological testing should be performed at the first prenatal visit. As a corollary, type specific HSV serology will need to be commercially available and relatively inexpensive. In any country, pregnant women and their partners represent a broad, cross section of sexually active adults. The vast majority present themselves to the health care system for care during their pregnancies which is a period of time in which the focus of care is primarily preventive and during which women are generally motivated and compliant. This is truly the 'golden opportunity' to identify patients already infected as well as those at risk for acquiring genital herpes. Information regarding genital herpes and methods of preventing transmission to susceptible partners and newborn infants can easily be added to educational programmes which have already become an institution within prenatal care., (Copyright 2000 John Wiley & Sons, Ltd.)

The seroprevalence of herpes simplex virus type 2 (HSV-2) infections among reproductive-aged women in the United States in prevalent. This article discusses HSV and how it effects the pregnant women and neonates. Management of the disease is reviewed, and recommendations for management of HSV during pregnancy are given.

Objective: To determine why women with diabetes generally do not plan their pregnancies, consequently entering their pregnancies with poor blood glucose control and greatly increasing the risk of birth defects in their infants., Research Design and Methods: A population-based sample of 85 women with diabetes diagnosed before the index pregnancy were recruited within 6 months postpartum from 15 hospitals in the state of Washington. Women with planned and unplanned pregnancies were compared using qualitative and quantitative analysis of personal interviews, self-administered questionnaires, and medical record review., Results: Although most women (79%) knew they should optimize their blood glucose levels before conception, fewer than half (41%) of their pregnancies were planned. Women with planned pregnancies had significantly higher income and more education; were more likely to have private health insurance, to see an endocrinologist before pregnancy, to be happily married, and to be Caucasian; and were less likely to use tobacco. Most unplanned pregnancies were not contraceptive failures, but may have been consciously or subconsciously intended. Women with planned pregnancies generally described an ongoing and positive relationship with their health care providers. Women who felt that their doctors discouraged pregnancy were more likely to have an unplanned pregnancy than were women who had been reassured they could have a healthy baby., Conclusions: Many women with diabetes still perceive negative messages about pregnancies and become pregnant without optimal planning. We believe there are many opportunities for increasing the proportion of women with diabetes who plan their pregnancies, particularly in the areas of prepregnancy information, support that women are given, and the quality of the relationships they experience within the health care system. It is crucial that couples be reassured that with pre-conception glucose control, almost all women with diabetes can have healthy babies.

Background: The acquisition of genital herpes during pregnancy has been associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. The frequency of seroconversion, maternal symptoms of the disease, and the timing of its greatest effect on the outcome of pregnancy have not been systematically studied., Methods: We studied 7046 pregnant women whom serologic tests showed to be at risk for herpes simplex virus (HSV) infection. Serum samples obtained at the first prenatal visit, at approximately 16 and 24 weeks, and during labor were tested for antibodies to HSV types 1 and 2 (HSV-1 and HSV-2) by the Western blot assay, and the results were correlated with the occurrence of antenatal genital infections., Results: Ninety-four of the women became seropositive for HSV; 34 of the 94 women (36 percent) had symptoms consistent with herpes infection. Women who were initially seronegative for both HSV-1 and HSV-2 had an estimated chance of seroconversion for either virus of 3.7 percent; those who were initially seropositive only for HSV-1 had an estimated chance of HSV-2 seroconversion of 1.7 percent; and those who were initially HSV-2-seropositive had an estimated chance of zero for acquiring HSV-1 infection. Among the 60 of the 94 pregnancies for which the time of acquisition of HSV infection was known, 30 percent of the infections occurred in the first trimester, 30 percent in the second, and 40 percent in the third. HSV seroconversion completed by the time of labor was not associated with an increase in neonatal morbidity or with any cases of congenital herpes infection. However, among the infants born to nine women who acquired genital HSV infection shortly before labor, neonatal HSV infection occurred in four infants, of whom one died., Conclusions: Two percent or more of susceptible women acquire HSV infection during pregnancy. Acquisition of infection with seroconversion completed before labor does not appear to affect the outcome of pregnancy, but infection acquired near the time of labor is associated with neonatal herpes and perinatal morbidity.

Objective: Our purpose was to determine whether pregnant women infected with human immunodeficiency virus-1 have an increased risk of herpes simplex virus-2 seropositivity and herpes simplex virus reactivation at delivery., Study Design: Sixty women infected with human immunodeficiency virus and 8408 other patients who were delivered at the University of Washington between 1989 and 1995 had herpes simplex virus serologic determinations at delivery. Genital herpes simplex virus cultures were obtained for 48 (80%) of the human immunodeficiency virus-infected women and 5567 (66%) of the controls. Logistic regression was used to adjust for possible confounding factors., Results: Forty-five (75%) of human immunodeficiency virus-infected women and 2709 (32%) controls were seropositive for herpes simplex virus-2 (p < 0.0001). Eight percent of human immunodeficiency virus-infected women and 2% of controls had herpes simplex virus reactivation in labor (p < 0.05)., Conclusions: Infection with herpes simplex virus-2 is common among pregnant women infected with human immunodeficiency virus. Herpes simplex virus reactivation complicates labor in this group more often than in other obstetric patients. The role of herpes simplex virus in perinatal human immunodeficiency virus transmission warrants further study.

An in vitro model of folate-deficient erythropoiesis has been developed using proerythroblasts isolated from the spleens of Friend virus-infected mice fed an amino acid-based, folate-free diet. Control proerythroblasts were obtained from Friend virus-infected mice fed the same diet plus 2 mg folic acid/kg diet. Our previous studies showed that, after 20 to 32 hours of culture in folate-deficient medium with 4 U/mL of erythropoietin, the folate-deficient proerythroblasts underwent apoptosis, whereas control erythroblasts survived and differentiated into reticulocytes over a period of 48 hours. The addition of folic acid or thymidine to the folate-deficient medium prevented the apoptosis of the folate-deficient erythroblasts, thereby implicating decreased thymidylate synthesis as the main cause of apoptosis in the folate-deficient erythroblasts. In the study reported here, we examined intracellular folate levels, uracil misincorporation into DNA, p53 and p21 proteins, and reticulocyte formation in erythroblasts cultured in folate-deficient or control medium. In all experiments, the folate-deficient erythroblasts cultured in folate-deficient medium gave results that varied significantly from folate-deficient erythroblasts cultured in control medium or control erythroblasts cultured in either folate-deficient or control media. Folate-deficient erythroblasts cultured in folate-deficient medium had marked decreases in all coenzyme forms of folate that persisted throughout culture, increased uracil misincorporation into DNA, persistent accumulations of p53 and p21, and decreased reticulocyte production but increased size of individual reticulocytes. A model of folate-deficient erythropoiesis based on apoptosis of late stage erythroblasts is presented. This model provides explanations for the clinical findings in megaloblastic anemia.

Objectives: Our goal was to define the frequency of asymptomatic herpes simplex virus type 2 shedding by culture and polymerase chain reaction and to correlate our findings with cervical anti-herpes simplex virus type 2 immunoglobulin A production., Study Design: Women who were seropositive for herpes simplex virus type 2 collected daily genital tract samples during the third trimester for culture and deoxyribonucleic acid quantitation by polymerase chain reaction. Cervical secretions were collected weekly for anti-herpes simplex virus type 2 immunoglobulin A. Asymptomatic shedding by culture versus polymerase chain reaction and anti-herpes simplex virus type 2 immunoglobulin A detection with and without genital shedding were compared by means of McNemar's chi 2 test., Results: Asymptomatic shedding was more frequent by polymerase chain reaction than by culture (13.8% vs 2.3%, p < 0.0001). When cervical anti-herpes simplex virus type 2 immunoglobulin A was present, patients were more likely to have negative results by polymerase chain reaction than positive results (66.7% vs 26.7%, p = 0.001). Anti-herpes simplex virus type 2 immunoglobulin A was detected beyond 37 weeks in only one subject., Conclusions: Polymerase chain reaction was more sensitive than culture for detecting asymptomatic genital herpes simplex virus. The role of immunoglobulin A in clearing genital herpes simplex virus remains to be determined.

Objective: To determine if fetal growth restriction and prematurity are observed with subclinical shedding of herpes simplex virus (HSV) at the onset of labor., Methods: Within 48 hours of delivery, cultures were taken from the cervix and external genitalia of 15,923 asymptomatic pregnant women without symptoms or signs of genital HSV infection; results were positive for HSV in 57. Each of these 57 women were compared with a control group composed of the three culture-negative women delivering immediately before and the three delivering immediately after each woman shedding HSV., Results: The median birth weight for infants born to the 57 women with asymptomatic shedding was 3050 g, compared with 3360 g among the 342 women without asymptomatic shedding, a statistically significant difference (P < .002). These differences were due to very low birth weight (LBW) among the five infants of women with subclinical viral shedding secondary to recently acquired primary genital herpes; these five infants had a median gestational age of 33 weeks, compared with 37 weeks for the 14 infants of mothers with nonprimary, first-episode disease and 39 weeks for the 33 infants of women with reactivation disease, also a significant difference (P = .018)., Conclusions: Asymptomatic genital shedding of HSV at the onset of labor because of subclinical primary genital HSV infection is associated with preterm delivery. Women who acquire genital HSV-2 before pregnancy and are shedding subclinically at the onset of labor experience no increase in adverse outcome. Thus, prevention of the prematurity and LBW associated with genital herpes means that acquisition of the infection in late pregnancy must be prevented.

Objective: All women seropositive for herpes simplex virus-2 are at risk for asymptomatic viral shedding at the onset of labor and neonatal transmission of the virus. Unfortunately, only 20% to 35% of seropositive adults give a history consistent with genital herpes. We evaluated whether more detailed questioning during pregnancy might elucidate symptoms predictive of seropositivity and therefore better identify women at risk for herpes simplex virus shedding at delivery., Study Design: During pregnancy 201 randomly selected women were asked in-depth questions about recurrent genital symptoms and whether they "currently have or have ever had genital herpes." An assessment was made whether the patient had a history compatible with genital herpes. This assessment and the "yes/no" history of genital herpes obtained by physicians at the initial prenatal visit were both compared with herpes simplex virus serologic studies by Western blot., Results: Of 201 patients interviewed, 177 gave no history of genital herpes. Of these, 30.4% were seropositive for herpes simplex virus-2. Detailed histories on these 177 patients indicated that among the 159 subjects without suggestive symptoms or with somewhat suggestive symptoms the corresponding rates of seropositivity were 28% and 30%. Among the 18 (10.2%) subjects with highly suggestive symptoms, only 50% were seropositive. The positive predictive values for recurrent genital symptoms to predict herpes simplex virus-2 seropositivity ranged from 30% to 57%., Conclusion: A detailed history of genital symptoms is no better at identifying an herpes simplex virus-2 seropositive patient than is simply asking if she has ever had genital herpes. Serologic screening is a more accurate method of identifying women with past genital herpes or those who are at risk for acquiring genital herpes during pregnancy.