Roberto Romero

Bio: Roberto Romero is an academic researcher from National Institutes of Health. The author has contributed to research in topic(s): Amniotic fluid & Chorioamnionitis. The author has an hindex of 151, co-authored 1516 publication(s) receiving 108321 citation(s). Previous affiliations of Roberto Romero include University of Michigan & Weizmann Institute of Science.

Epidemiology and causes of preterm birth

Abstract: Summary This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12–13% in the USA and 5–9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM—together called spontaneous preterm births—are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.

Soluble endoglin contributes to the pathogenesis of preeclampsia.

Abstract: Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Maternal endothelial dysfunction mediated by excess placenta-derived soluble VEGF receptor 1 (sVEGFR1 or sFlt1) is emerging as a prominent component in disease pathogenesis. We report a novel placenta-derived soluble TGF-beta coreceptor, endoglin (sEng), which is elevated in the sera of preeclamptic individuals, correlates with disease severity and falls after delivery. sEng inhibits formation of capillary tubes in vitro and induces vascular permeability and hypertension in vivo. Its effects in pregnant rats are amplified by coadministration of sFlt1, leading to severe preeclampsia including the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome and restriction of fetal growth. sEng impairs binding of TGF-beta1 to its receptors and downstream signaling including effects on activation of eNOS and vasodilation, suggesting that sEng leads to dysregulated TGF-beta signaling in the vasculature. Our results suggest that sEng may act in concert with sFlt1 to induce severe preeclampsia.

Soluble endoglin and other circulating antiangiogenic factors in preeclampsia.

Abstract: Background Alterations in circulating soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and placental growth factor (PlGF), a proangiogenic protein, appear to be involved in th...

The preterm parturition syndrome

Abstract: The implicit paradigm that has governed the study and clinical management of preterm labour is that term and preterm parturition are the same processes, except for the gestational age at which they occur. Indeed, both share a common pathway composed of uterine contractility, cervical dilatation and activation of the membranes/decidua. This review explores the concept that while term labour results from physiological activation of the components of the common pathway, preterm labour arises from pathological signalling and activation of one or more components of the common pathway of parturition. The term "great obstetrical syndromes" has been coined to reframe the concept of obstetrical disease. Such syndromes are characterised by: (1) multiple aetiology; (2) long preclinical stage; (3) frequent fetal involvement; (4) clinical manifestations that are often adaptive in nature; and (5) gene-environment interactions that may predispose to the syndromes. This article reviews the evidence indicating that the pathological processes implicated in the preterm parturition syndrome include: (1) intrauterine infection/inflammation; (2) uterine ischaemia; (3) uterine overdistension; (4) abnormal allograft reaction; (5) allergy; (6) cervical insufficiency; and (7) hormonal disorders (progesterone related and corticotrophin-releasing factor related). The implications of this conceptual framework for the prevention, diagnosis, and treatment of preterm labour are discussed.

Preterm labor: One syndrome, many causes

Abstract: Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment.

limma powers differential expression analyses for RNA-sequencing and microarray studies

Abstract: limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

Standards of Medical Care in Diabetes

Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets.

Abstract: Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein-protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein-protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.

Epidemiology and causes of preterm birth

Abstract: Summary This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12–13% in the USA and 5–9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM—together called spontaneous preterm births—are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.