Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy
Glioblastomas shed large quantities of small, membrane-bound microvesicles into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Here, we describe a highly sensitive and rapid analytical technique for profiling circulating microvesicles directly from blood samples of patients with glioblastoma. Microvesicles, introduced onto a dedicated microfluidic chip, are labeled with target-specific magnetic nanoparticles and detected by a miniaturized nuclear magnetic resonance system. Compared with current methods, this integrated system has a much higher detection sensitivity and can differentiate glioblastoma multiforme (GBM) microvesicles from nontumor host cell–derived microvesicles. We also show that circulating GBM microvesicles can be used to analyze primary tumor mutations and as a predictive metric of treatment-induced changes. This platform could provide both an early indicator of drug efficacy and a potential molecular stratifier for human clinical trials.
Effects of Dioxins and Polychlorinated Biphenyls on Thyroid Hormone Status of Pregnant Women and Their Infants
Dioxins [polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF)] and polychlorinated biphenyls (PCB) are potentially hazardous compounds. Animal studies have demonstrated that PCDD, PCDF, and PCB can alter thyroid hormone homeostasis. We investigated thyroid hormone levels in 105 mother-infant pairs. To estimate maternal and infant exposure, four nonplanar PCB congeners were measured in maternal plasma during the last month of pregnancy and in umbilical cord plasma. Seventeen PCDD and PCDF congeners, three planar PCB congeners, and 23 nonplanar PCB congeners were measured in human milk. Higher PCDD, PCDF, and PCB levels in human milk, expressed as toxic equivalents, correlated significantly with lower plasma levels of maternal total triiodothyronine and total thyroxine, and with higher plasma levels of TSH in the infants in the 2nd wk and 3rd mo after birth. Infants exposed to higher toxic equivalents levels had also lower plasma free thyroxine and total thyroxine levels in the 2nd wk after birth. We conclude that elevated levels of dioxins and PCB can alter the human thyroid hormone status.
Real-time monitoring of cell apoptosis and drug screening using fluorescent light-up probe with aggregation-induced emission characteristics.
Real-time monitoring of cell apoptosis could provide valuable insights into early detection of therapy efficiency and evaluation of disease progression. In this work, we designed and synthesized a new live-cell-permeable, fluorescent light-up probe for real-time cell apoptosis imaging. The probe is comprised of a hydrophilic caspase-specific Asp-Glu-Val-Asp (DEVD) peptide and a hydrophobic tetraphenylethene (TPE) unit, a typical fluorogen with aggregation-induced emission characteristics. In aqueous solution, the probe is almost nonfluorescent but displays significant fluorescence enhancement in response to caspase-3/-7, which are activated in the apoptotic process and able to cleave the DEVD moieties. This fluorescence "turn-on" response is ascribed to aggregation of cleaved hydrophobic TPE residues, which restricts the intramolecular rotations of TPE phenyl rings and populates the radiative decay channels. The light-up nature of the probe allows real-time monitoring of caspase-3/-7 activities both in solutions and in living cells with a high signal-to-noise ratio. The probe provides a new opportunity to screen enzyme inhibitors and evaluate the apoptosis-associated drug efficacy.
Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments
Significance Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA, we obtained a bird’s eye view of the identities and contributions of these tissues to the circulating DNA pool. The tissue contributors and their relative proportions are identified by a bioinformatics deconvolution process that draws reference from DNA methylation signatures representative of each tissue type. We validated this approach in pregnant women, cancer patients, and transplant recipients. This method also allows one to identify the tissue of origin of genomic aberrations observed in plasma DNA. This approach has numerous research and diagnostic applications in prenatal testing, oncology, transplantation monitoring, and other fields. Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA and deconvolution of the sequencing data with reference to methylation profiles of different tissues, we developed a general approach for studying the major tissue contributors to the circulating DNA pool. We tested this method in pregnant women, patients with hepatocellular carcinoma, and subjects following bone marrow and liver transplantation. In most subjects, white blood cells were the predominant contributors to the circulating DNA pool. The placental contributions in the plasma of pregnant women correlated with the proportional contributions as revealed by fetal-specific genetic markers. The graft-derived contributions to the plasma in the transplant recipients correlated with those determined using donor-specific genetic markers. Patients with hepatocellular carcinoma showed elevated plasma DNA contributions from the liver, which correlated with measurements made using tumor-associated copy number aberrations. In hepatocellular carcinoma patients and in pregnant women exhibiting copy number aberrations in plasma, comparison of methylation deconvolution results using genomic regions with different copy number status pinpointed the tissue type responsible for the aberrations. In a pregnant woman diagnosed as having follicular lymphoma during pregnancy, methylation deconvolution indicated a grossly elevated contribution from B cells into the plasma DNA pool and localized B cells as the origin of the copy number aberrations observed in plasma. This method may serve as a powerful tool for assessing a wide range of physiological and pathological conditions based on the identification of perturbed proportional contributions of different tissues into plasma.
Multi-institutional clinical experience with the Calypso System in localization and continuous, real-time monitoring of the prostate gland during external radiotherapy.
PURPOSE To report the clinical experience with an electromagnetic treatment target positioning and continuous monitoring system in patients with localized prostate cancer receiving external beam radiotherapy. METHODS AND MATERIALS The Calypso System is a target positioning device that continuously monitors the location of three implanted electromagnetic transponders at a rate of 10 Hz. The system was used at five centers to position 41 patients over a full course of therapy. Electromagnetic positioning was compared to setup using skin marks and to stereoscopic X-ray localization of the transponders. Continuous monitoring was performed in 35 patients. RESULTS The difference between skin mark vs. the Calypso System alignment was found to be >5 mm in vector length in more than 75% of fractions. Comparisons between the Calypso System and X-ray localization showed good agreement. Qualitatively, the continuous motion was unpredictable and varied from persistent drift to transient rapid movements. Displacements > or =3 and > or =5 mm for cumulative durations of at least 30 s were observed during 41% and 15% of sessions. In individual patients, the number of fractions with displacements > or =3 mm ranged from 3% to 87%; whereas the number of fractions with displacements > or =5 mm ranged from 0% to 56%. CONCLUSION The Calypso System is a clinically efficient and objective localization method for positioning prostate patients undergoing radiotherapy. Initial treatment setup can be performed rapidly, accurately, and objectively before radiation delivery. The extent and frequency of prostate motion during radiotherapy delivery can be easily monitored and used for motion management.
Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections
In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, initially termed 2019-nCoV and subsequently SARS-CoV-2. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.
ALOS PALSAR: A Pathfinder Mission for Global-Scale Monitoring of the Environment
The Advanced Land Observing Satellite (ALOS) is Japan's new-generation Earth Observation satellite, launched in January 2006 by the Japan Aerospace Exploration Agency. ALOS carries two optical instruments (Panchromatic Remote-sensing Instrument for Stereo Mapping and Advanced Visible and Near-Infrared Radiometer type 2) and, to maintain Japan's commitment to spaceborne L-band Synthetic Aperture Radar (SAR), the Phased Array L-band SAR (PALSAR). The successor to the SAR onboard the Japanese Earth Resources Satellite (1992-1998), the PALSAR instrument provides enhanced sensor characteristics, including full polarimetry, variable off-nadir viewing, and ScanSAR operations, as well as significantly improved radiometric and geometric performance. As important as the technical improvements and the reason PALSAR here is referred to as a pathfinder mission for global environmental monitoring is the systematic data-acquisition strategy which has been implemented for ALOS. With a priority second only to emergency observations, the PALSAR observation strategy has been designed to provide consistent, wall-to-wall observations at fine resolution of all land areas on the Earth on a repetitive basis, in a manner which has earlier been conceived only for coarse- and medium-resolution instruments.
Real-time monitoring of cell apoptosis and drug screening using fluorescent light-up probe with aggregation-induced emission characteristics.
Real-time monitoring of cell apoptosis could provide valuable insights into early detection of therapy efficiency and evaluation of disease progression. In this work, we designed and synthesized a new live-cell-permeable, fluorescent light-up probe for real-time cell apoptosis imaging. The probe is comprised of a hydrophilic caspase-specific Asp-Glu-Val-Asp (DEVD) peptide and a hydrophobic tetraphenylethene (TPE) unit, a typical fluorogen with aggregation-induced emission characteristics. In aqueous solution, the probe is almost nonfluorescent but displays significant fluorescence enhancement in response to caspase-3/-7, which are activated in the apoptotic process and able to cleave the DEVD moieties. This fluorescence "turn-on" response is ascribed to aggregation of cleaved hydrophobic TPE residues, which restricts the intramolecular rotations of TPE phenyl rings and populates the radiative decay channels. The light-up nature of the probe allows real-time monitoring of caspase-3/-7 activities both in solutions and in living cells with a high signal-to-noise ratio. The probe provides a new opportunity to screen enzyme inhibitors and evaluate the apoptosis-associated drug efficacy.
Pharmacists on rounding teams reduce preventable adverse drug events in hospital general medicine units.
BACKGROUND Previous studies found that medication errors result from lack of sufficient information during the prescribing step. Therefore, it is proposed that having a pharmacist available when patients are evaluated during the rounding process may reduce the likelihood of preventable adverse drug events (ADEs). The objectives of this study were to evaluate the impact of having a pharmacist participate with a physician rounding team on preventable ADEs in general medicine units and to document pharmacist interventions made during the rounding process. METHODS A single-blind, standard care-controlled study design was used to compare patients receiving care from a rounding team including a pharmacist with patients receiving standard care (no pharmacist on rounding team). Patients admitted to and discharged from the same general medicine unit were included in the study. The main outcome measure of this study was preventable ADEs. Patient records were randomly selected and evaluated by a blinded process involving independent senior pharmacist specialists and a senior staff physician. Interventions made by the pharmacists in the treatment group were documented. RESULTS The rate of preventable ADEs was reduced by 78%, from 26.5 per 1000 hospital days to 5.7 per 1000 hospital days. There were 150 documented interventions recommended during the rounding process, 147 of which were accepted by the team. The most common interventions were (1) dosing-related changes and (2) recommendations to add a drug to therapy. CONCLUSION Pharmacist participation with the medical rounding team on a general medicine unit contributes to a significant reduction in preventable ADEs.
Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial.
BACKGROUND Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants. METHODS The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing. FINDINGS Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups. INTERPRETATION A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants. FUNDING National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.
Influenza vaccination of pregnant women and protection of their infants.
BACKGROUND There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus (HIV) infection and protection of their infants. METHODS We conducted two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccine (IIV3) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected. The immunogenicity, safety, and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth. Immune responses were measured with a hemagglutination inhibition (HAI) assay, and influenza was diagnosed by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays of respiratory samples. RESULTS The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV. At 1 month after vaccination, seroconversion rates and the proportion of participants with HAI titers of 1:40 or more were higher among IIV3 recipients than among placebo recipients in both cohorts. Newborns of IIV3 recipients also had higher HAI titers than newborns of placebo recipients. The attack rate for RT-PCR-confirmed influenza among both HIV-uninfected placebo recipients and their infants was 3.6%. The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5 to 71.2) and 48.8% (95% CI, 11.6 to 70.4). Among HIV-infected women, the attack rate for placebo recipients was 17.0% and the rate for IIV3 recipients was 7.0%; the vaccine-efficacy rate for these IIV3 recipients was 57.7% (95% CI, 0.2 to 82.1). CONCLUSIONS Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov numbers, NCT01306669 and NCT01306682.).
Effect of maternal cigarette smoking on pregnancy complications and sudden infant death syndrome.
BACKGROUND The purpose of this study was to estimate the annual morbidity and mortality among fetuses and infants that can be attributed to the use of tobacco products by pregnant women. METHODS Published research reports identified by literature review were combined in a series of meta-analyses to compute pooled risk ratios, which, in turn, were used to determine the population attributable risk. RESULTS Each year, use of tobacco products is responsible for an estimated 19,000 to 141,000 tobacco-induced abortions, 32,000 to 61,000 infants born with low birthweight, and 14,000 to 26,000 infants who require admission to neonatal intensive care units. Tobacco use is also annually responsible for an estimated 1900 to 4800 infant deaths resulting from perinatal disorders, and 1200 to 2200 deaths from sudden infant death syndrome (SIDS). CONCLUSIONS Tobacco use is an important preventable cause of abortions, low birthweight, and deaths from perinatal disorders and SIDS. All pregnant women should be advised that smoking places their unborn children in danger. The low success rate of smoking cessation among pregnant women suggests that efforts to reduce the complications of pregnancy attributable to tobacco use by pregnant women should focus on preventing nicotine addiction among teenaged girls.
Fetal cells in the blood of pregnant women: detection and enrichment by fluorescence-activated cell sorting.
Fetal cells, potentially usable for prenatal diagnosis, were sorted from maternal blood samples taken as early as 15 weeks of gestation. Immunogenetic and cytogenic criteria established the fetal origin of the observed cells: Y-chromatin-containing (male) cells were detected in the sorted sample if and only if the newborn proved to be male and carried cell-surface antigens detected by the fluorescent-labeled antibody used for sorting with the fluorescence-activated cell sorter.
Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection.
BACKGROUND Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery. METHODS We screened pregnant women for trichomoniasis by culture of vaginal secretions. We randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation. RESULTS Between randomization and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group (92.6 percent) and 92 of 260 women with follow-up cultures in the placebo group (35.4 percent). Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group. Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and 31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable primarily to an increase in preterm delivery resulting from spontaneous preterm labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence interval, 1.5 to 5.9). CONCLUSIONS Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended.
Research Methods for Organizational Studies
Contents: Preface. Part I: Overview. Introduction. A Model of Empirical Research. Part II: Measurement: Understanding Construct Validity. Measurement Foundations: Validity and Validation. Measurement Applications: Research Questionnaires. Part III: Design: Addressing Internal Validity. Research Design Foundations. Design Applications: Experiments and Quasi-Experiments. Design Applications: Field Studies and Surveys. Part IV: Analysis: Investigating Empirical Relationships. Data Analysis Foundations. Analysis Applications: Describing Scores on a Single Variable. Analysis Applications: Simple Correlation and Regression. Analysis Applications: Multiple Correlation and Regression. Part V: Statistical Validation. Statistical Inference Foundations. Statistical Inference Applications. Part VI: Generalization: Addressing External Validity. External Validity. Part VII: Research Reports. Research Report Writing. Part VIII: Extensions. On Incomplete Data. On Reliability. On Multicollinearity. On Casual Models and Statistical Modeling. On Statistical Modeling Challenges. On Good Research.
Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads <1000 copies/ml.
In a collaboration of 7 European and United States prospective studies, 44 cases of vertical human immunodeficiency virus type 1 (HIV-1) transmission were identified among 1202 women with RNA virus loads <1000 copies/mL at delivery or at the measurement closest to delivery. For mothers receiving antiretroviral treatment during pregnancy or at the time of delivery (or both), there was a 1.0% transmission rate (8 of 834; 95% confidence interval [CI], 0.4%-1.9%), compared with 9.8% (36 of 368; 95% CI, 7.0%-13.4%) for untreated mothers (risk ratio, 0.10; 95% CI, 0.05-0.21). In multivariate analysis adjusting for study, transmission was lower with antiretroviral treatment (odds ratio [OR], 0.10; P<.001), cesarean section (OR, 0.30; P=.022), greater birth weight (P=.003), and higher CD4 cell count (P=.039). In 12 of 44 cases, multiple RNA measurements were obtained during pregnancy or at the time of delivery or within 4 months after giving birth; in 10 of the 12 cases, the geometric mean virus load was >500 copies/mL. Perinatal HIV-1 transmission occurs in only 1% of treated women with RNA virus loads <1000 copies/mL and may be almost eliminated with antiretroviral prophylaxis accompanied by suppression of maternal viremia.
Chemical Stability of Pharmaceuticals: A Handbook for Pharmacists
PRINCIPLES. Stability Calculations. Interpretation of Kinetic Data. Hydrolysis and Other Acyl Transfers. Oxidation and Photolysis. Solid-State Chemical Decompostion. Strategy and Tactics of Stability Testing. STABILITY MONOGRAPHS. Appendixes. Index.
The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-saharan Africa.
In sub-Saharan Africa, human immunodeficiency virus (HIV) and malaria are among the leading causes of morbidity during pregnancy. We reviewed available information collected since the first report 15 years ago that HIV impaired the ability of pregnant women to control malaria parasitemia. Results from 11 studies showed that HIV-infected women experienced consistently more peripheral and placental malaria (summary relative risk = 1.58 and 1.66, respectively), higher parasite densities, and more febrile illnesses, severe anemia, and adverse birth outcomes than HIV-uninfected women, particularly in multigravidae. Thus, HIV alters the typical gravidity-specific pattern of malaria risk by shifting the burden from primarily primigravidae and secundigravidae to all pregnant women. The proportional increase of malaria during pregnancy attributable to HIV was estimated to be 5.5% and 18.8% for populations with HIV prevalences of 10% and 40%, respectively. Maternal malaria was associated with a two-fold higher HIV-1 viral concentrations. Three studies investigating whether placental malaria increased mother-to-child HIV-1 transmission showed conflicting results, possibly reflecting a complex balance between placental malarial immune responses and stimulation of HIV-1 viral replication. Further investigations of interactions between antiretroviral drugs, prophylaxis with cotrimoxazole, and antimalarial drugs in pregnant women are urgently needed. Although much has been learned in the past 15 years about the interaction between malaria and HIV-1 during pregnancy, many issues still require further information to improve our understanding. There is a clear need to strengthen the deployment of existing malaria and HIV prevention and intervention measures for pregnant women.
The Generation R Study: Design and cohort profile
The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioral and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Of all eligible children at birth, 61% participate in the study. Data collection in the prenatal phase included physical examinations, questionnaires, fetal ultrasound examinations and biological samples. In addition, more detailed assessments are conducted in a subgroup of 1232 pregnant women and their children. The children form a prenatally recruited birth-cohort that will be followed until young adulthood. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.
Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women
The prevalence and natural course of chronic hepatitis C virus (HCV) infection was evaluated in 15,250 consecutive pregnant women. The rate of HCV vertical and perinatal transmission was also assessed. The presence of anti‐HCV was tested by means of EIA III and confirmed by recombinant immunoblot assay III. Alanine transaminase (ALT), anti–human immunodeficiency virus (HIV), and HCV‐RNA were tested during the first month and third trimester of pregnancy, and 6 months after delivery; the same tests were made in all of the newborns of anti‐HCV–positive mothers at birth (on cord blood samples) and then at 4‐month intervals. Anti‐HCV positivity was found in 370 cases (2.4%), 72% of whom were also HCV‐RNA–positive. The proportion of women with hypertransaminases decreased from 56.4% at the first examination during the first month of pregnancy to 7.4% in the last trimester, and then increased again after delivery (54.5%), without any concomitant changes in the proportion of those with viremia. The proportion of anti‐HCV– and HCV‐RNA–positive newborns was 5.1% after 1 year (8 of 155), all of whom had the same genotype as their mother. The rate of HCV transmission was not affected by the type of delivery or feeding, or the HIV status of the mother. The results of this large‐scale study confirm previous data in smaller series concerning the prevalence of HCV infection in pregnant women, and strongly support the hypothesis of a favorable (possibly immunomediated) effect of pregnancy on liver cell necrosis in anti‐HCV–positive women.
sensor network wireless sensor network wireless sensor monitoring system magnetic resonance health monitoring synthetic aperture radar state estimation confidence interval markov random field systematic review bragg grating fiber bragg grating risk factor fiber bragg physical activity high throughput magnetic resonance image real-time monitoring power law resonance image fully automated diabetes mellitu bragg grating sensor real-time monitoring system brain tissue automated method living cell monitoring and analysi aerospace exploration agency analysis application hiv infection japan aerospace exploration odds ratio adverse event controlled trial variational baye health professional high resolution radiometer drug release pregnant woman partial volume exploration agency human immunodeficiency viru adverse drug event aerospace exploration japan aerospace cohort study tissue classification immunodeficiency viru human immunodeficiency power law distribution depressive disorder cell count birth weight plasmodium falciparum law distribution thyroid disease anxiety disorder randomised controlled trial randomised controlled body tissue real-time state intervention group fully automated method gestational diabetes maternal mortality local noise black woman middle east respiratory virus type automated model-based brain tissue classification cesarean section gestational diabetes mellitu randomised trial pregnancy outcome immunodeficiency virus type compliance behavior prospective cohort study toxoplasma gondii status epilepticu tissue classification based northern united state cell apoptosi gradient variational baye umbilical cord blood vitamin d deficiency coronavirus infection follow-up report preterm delivery white woman prenatal vitamin cessation of life one thousand confirmation - responselevel hypertensive disease diabetes mellitus, insulin-dependent adverse reaction to drug cessation of smoking infant, newborn morbidity - disease rate illness (finding) physiological sexual disorder immunologic deficiency syndrome appetite depressant got worse contraceptive method umbilicus (anatomy) premature obstetric labor birth injury vertical disease transmission sudden infant death syndrome spontaneous abortion immunoglobulin m fetal death multivitamin preparation non-clinical gestation trial phase united state