The Excess Burden of Cytomegalovirus in African American Communities: A Geospatial Analysis.

Background.  Cytomegalovirus (CMV) is a common cause of birth defects and hearing loss in infants and opportunistic infections in the immunocompromised. Previous studies have found higher CMV seroprevalence rates among minorities and among persons with lower socioeconomic status. No studies have investigated the geographic distribution of CMV and its relationship to age, race, and poverty in the community. Methods.  We identified patients from 6 North Carolina counties who were tested in the Duke University Health System for CMV immunoglobulin G. We performed spatial statistical analyses to analyze the distributions of seropositive and seronegative individuals. Results.  Of 1884 subjects, 90% were either white or African American. Cytomegalovirus seropositivity was significantly more common among African Americans (73% vs 42%; odds ratio, 3.31; 95% confidence interval, 2.7-4.1), and this disparity persisted across the life span. We identified clusters of high and low CMV odds, both of which were largely explained by race. Clusters of high CMV odds were found in communities with high proportions of African Americans. Conclusions.  Cytomegalovirus seropositivity is geographically clustered, and its distribution is strongly determined by a community's racial composition. African American communities have high prevalence rates of CMV infection, and there may be a disparate burden of CMV-associated morbidity in these communities.

Epigenetic Basis of Centromere Maintenance and Inheritance

Centromeres are essential chromosomal loci at which kinetochore formation occurs for spindle fiber attachment during mitosis and meiosis, guiding proper segregation of chromosomes. In humans, centromeres are located at large arrays of alpha satellite DNA, contributing to but not defining centromere function. The histone variant CENP-A assembles at alpha satellite DNA, epigenetically defining the centromere. CENP-A containing chromatin exists as an essential domain composed of blocks of CENP-A nucleosomes interspersed with blocks of H3 nucleosomes, and is surrounded by pericentromeric heterochromatin. In order to maintain genomic stability, the CENP-A domain is propagated epigenetically over each cell division; disruption of propagation is associated with chromosome instabilities such as aneuploidy, found in birth defects and in cancer.

The CENP-A chromatin domain occupies 30-45% of the alpha satellite array, varying in genomic distance according to the underlying array size. However, the molecular mechanisms that control assembly and organization of CENP-A chromatin within its genomic context remain unclear. The domain may shift, expand, or contract, as CENP-A is loaded and dispersed each cell cycle. We hypothesized that in order to maintain genome stability, the centromere is inherited as static chromatin domains, maintaining size and position within the pericentric heterochromatin. Utilizing stretched chromatin fibers, I found that CENP-A chromatin is limited to a sub-region of the alpha satellite array that is fixed in size and location through the cell cycle and across populations.

The average amount of CENP-A at human centromeres is largely consistent, implying that the variation in size of CENP-A domains reflects variations in the number of CENP-A subdomains and/or the density of CENP-A nucleosomes. Multi-color nascent protein labeling experiments were utilized to examine the distribution and incorporation of distinct pools of CENP-A over several cell cycles. I found that in each cell cycle there is independent CENP-A distribution, occurring equally between sister centromeres across all chromosomes, in similar quantities. Furthermore, centromere inheritance is achieved through specific placement of CENP-A, following an oscillating pattern that fixes the location and size of the CENP-A domain. These results suggest that spatial and temporal dynamics of CENP-A are important for maintaining centromere and genome stability.

Hmx1 Function In Lateral Facial Development

Thesis (Master's)--University of Washington, 2016-08

Absence of prenatal ultrasound surveillance: Data from the Portuguese congenital anomalies registry

In Portugal, prenatal care guidelines advocate two prenatal ultrasound scans for all pregnant women. Not following this recommendation is considered inadequate prenatal surveillance. The National Registry of Congenital Anomalies (RENAC in Portuguese) is an active population-based registry and an important instrument for the epidemiological surveillance of congenital anomalies (CA) in Portugal. Regarding pregnancies with CA, this study aims to describe the epidemiology of absent prenatal ultrasound scans and factors associated with this inadequate surveillance.

MOSQUITO-BORNE DISEASES IN S.C.

At least 61 different species of mosquitoes exist in South Carolina. Mosquitoes are pests that can cause itchy bites, but they can also cause serious health issues. Mosquitoes can carry harmful viruses and parasites that infect millions of people worldwide each year. Mosquito-borne diseases can cause brain inflammation (or encephalitis), birth defects, internal bleeding, complications from parasites and even death in some cases.

ENFERMEDADES TRANSMITIDAS POR MOSQUITOS EN C.S.

This sheet is printed in Spanish. At least 61 different species of mosquitoes exist in South Carolina. Mosquitoes are pests that can cause itchy bites, but they can also cause serious health issues. Mosquitoes can carry harmful viruses and parasites that infect millions of people worldwide each year. Mosquito-borne diseases can cause brain inflammation (or encephalitis), birth defects, internal bleeding, complications from parasites and even death in some cases.

Plantas y sustancias tóxicas para el ganado

Las pérdidas económicas ocasionadas por las intoxicaciones vegetales son muy difíciles de cuantificar, fundamentalmente porque son muy diversos los mecanismos de acción y las manifestaciones de toxicidad. Estas pueden producir graves mortandades en forma súbita, mermas en los índices reproductivos, malformaciones congénitas, merma en la ganancia o directamente pérdida de peso. No obstante a pesar de la dificultad en la evaluación, es muy claro que el efecto de las intoxicaciones repercute fuertemente en el resultado económico de los productores de carne. El objetivo de esta presentación es aportar información tendiente a facilitar el reconocimiento de las plantas tóxicas por parte del productor, y dar armas al Veterinario para diagnosticar en forma certera las intoxicaciones mediante el conocimiento de las alteraciones clínicas, parámetros bioquímicos y lesiones macroscópicas observables a la necropsia.

Investigating 22q11.2 Deletion and Other Chromosomal Aberrations in Fetuses With Heart Defects Detected by Prenatal Echocardiography

Congenital heart disease (CHD) is the most common birth defect and the leading cause of mortality in the first year of life. In fetuses with a heart defect, chromosomal abnormalities are very frequent. Besides aneuploidy, 22q11.2 deletion is one of the most recognizable chromosomal abnormalities causing CHD. The frequency of this abnormality varies in nonselected populations. This study aimed to investigate the incidence of the 22q11.2 deletion and other chromosomal alterations in a Brazilian sample of fetuses with structural cardiac anomalies detected by fetal echocardiography. In a prospective study, 68 fetuses with a heart defect were evaluated. Prenatal detection of cardiac abnormalities led to identification of aneuploidy or structural chromosomal anomaly in 35.3% of these cases. None of the fetuses with apparently normal karyotypes had a 22q11.2 deletion. The heart defects most frequently associated with chromosomal abnormalities were atrioventricular septal defect (AVSD), ventricular septal defect (VSD), and tetralogy of Fallot. Autosomal trisomies 18 and 21 were the most common chromosomal abnormalities. The study results support the strong association of chromosome alterations and cardiac malformation, especially in AVSD and VSD, for which a chromosome investigation is indicated. In fetuses with an isolated conotruncal cardiopathy, fluorescence in situ hybridization (FISH) to investigate a 22q11.2 deletion is not indicated.

Investigation of Copy Number Variation in Children with Conotruncal Heart Defects

Background:Congenital heart defects (CHD) are the most prevalent group of structural abnormalities at birth and one of the main causes of infant morbidity and mortality. Studies have shown a contribution of the copy number variation in the genesis of cardiac malformations.Objectives:Investigate gene copy number variation (CNV) in children with conotruncal heart defect.Methods:Multiplex ligation-dependent probe amplification (MLPA) was performed in 39 patients with conotruncal heart defect. Clinical and laboratory assessments were conducted in all patients. The parents of the probands who presented abnormal findings were also investigated.Results:Gene copy number variation was detected in 7/39 patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2 duplication, 19p deletion, 15q and 8p23.2 duplication with 10p12.31 duplication. The clinical characteristics were consistent with those reported in the literature associated with the encountered microdeletion/microduplication. None of these changes was inherited from the parents.Conclusions:Our results demonstrate that the technique of MLPA is useful in the investigation of microdeletions and microduplications in conotruncal congenital heart defects. Early diagnosis of the copy number variation in patients with congenital heart defect assists in the prevention of morbidity and decreased mortality in these patients.

Congenital heart defects in Europe: prevalence and perinatal mortality, 2000 to 2005.

BACKGROUND: This study determines the prevalence of Congenital Heart Defects (CHD), diagnosed prenatally or in infancy, and fetal and perinatal mortality associated with CHD in Europe. METHODS AND RESULTS: Data were extracted from the European Surveillance of Congenital Anomalies central database for 29 population-based congenital anomaly registries in 16 European countries covering 3.3 million births during the period 2000 to 2005. CHD cases (n=26 598) comprised live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly (TOPFA). The average total prevalence of CHD was 8.0 per 1000 births, and live birth prevalence was 7.2 per 1000 births, varying between countries. The total prevalence of nonchromosomal CHD was 7.0 per 1000 births, of which 3.6% were perinatal deaths, 20% prenatally diagnosed, and 5.6% TOPFA. Severe nonchromosomal CHD (ie, excluding ventricular septal defects, atrial septal defects, and pulmonary valve stenosis) occurred in 2.0 per 1000 births, of which 8.1% were perinatal deaths, 40% were prenatally diagnosed, and 14% were TOPFA (TOPFA range between countries 0% to 32%). Live-born CHD associated with Down syndrome occurred in 0.5 per 1000 births, with > 4-fold variation between countries. CONCLUSION: Annually in the European Union, we estimate 36 000 children are live born with CHD and 3000 who are diagnosed with CHD die as a TOFPA, late fetal death, or early neonatal death. Investing in primary prevention and pathogenetic research is essential to reduce this burden, as well as continuing to improve cardiac services from in utero to adulthood.

Long term trends in prevalence of neural tube defects in Europe: population based study.

STUDY QUESTION: What are the long term trends in the total (live births, fetal deaths, and terminations of pregnancy for fetal anomaly) and live birth prevalence of neural tube defects (NTD) in Europe, where many countries have issued recommendations for folic acid supplementation but a policy for mandatory folic acid fortification of food does not exist? METHODS: This was a population based, observational study using data on 11 353 cases of NTD not associated with chromosomal anomalies, including 4162 cases of anencephaly and 5776 cases of spina bifida from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries covering approximately 12.5 million births in 19 countries between 1991 and 2011. The main outcome measures were total and live birth prevalence of NTD, as well as anencephaly and spina bifida, with time trends analysed using random effects Poisson regression models to account for heterogeneities across registries and splines to model non-linear time trends. SUMMARY ANSWER AND LIMITATIONS: Overall, the pooled total prevalence of NTD during the study period was 9.1 per 10 000 births. Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991. Estimates from Poisson models that took registry heterogeneities into account showed an annual increase of 4% (prevalence ratio 1.04, 95% confidence interval 1.01 to 1.07) in 1995-99 and a decrease of 3% per year in 1999-2003 (0.97, 0.95 to 0.99), with stable rates thereafter. The trend patterns for anencephaly and spina bifida were similar, but neither anomaly decreased substantially over time. The live birth prevalence of NTD generally decreased, especially for anencephaly. Registration problems or other data artefacts cannot be excluded as a partial explanation of the observed trends (or lack thereof) in the prevalence of NTD. WHAT THIS STUDY ADDS: In the absence of mandatory fortification, the prevalence of NTD has not decreased in Europe despite longstanding recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification. FUNDING, COMPETING INTERESTS, DATA SHARING: The study was funded by the European Public Health Commission, EUROCAT Joint Action 2011-2013. HD and ML received support from the European Commission DG Sanco during the conduct of this study. No additional data available.

Congenital upper limb defects in Finland 1993-2005

Background: Interest in limb defects has grown after the thalidomide tragedy in the 1960s. As a result, congenital malformation registries, monitoring changes in birthprevalence and defect patterns, have been established in several countries. However, there are only a few true population based studies on birth prevalence of upper limb defects. The burden of hospital care among these children, specifically in terms of the number of admissions and total time spent in hospital, is also unknown. Aims and Methods: This study is based on information gathered from the Finnish Register of Congenital malformations (FRM) and the Finnish Hospital Discharge Register (FHDR). A total of 417 children born between 1993 and 2005 with an upper limb defect were gathered from the FRM. The upper limb defects were classified using the International Federation of Societies for Surgery of the Hand -classification that enables comparison with previous and future studies. Birth and live birth prevalence, sex and side distribution, frequency of associated anomalies as well as the proportion of perinatal and infant deaths according to the different subtypes were calculated. The number of hospital admissions, days spent in hospital, number and type of surgical operations were collected from the FHDR. Special features of two subgroups, radial ray defects (RRD) and constriction band syndrome (CBS), were explored. Results: Upper limb defects were observed in 417 of 753 342 consecutive births and in 392 of 750 461 live births. Birth prevalence was 5.5 per 10 000 births and 5.2 per 10 000 live births. Multiple anomalies or a known syndrome was found in 250 cases (60%). Perinatal mortality was 139 per 1000 births and infant mortality 135 per 1000 live births (overall Finnish perinatal mortality <5 per 1000 births and infant mortality 3.7 per 1000 live births). Altogether, 138 infants had RRD and 120 (87%) of these had either a known syndrome or multiple major anomalies. The proportion of perinatal deaths in RRD group was 29% (40/138) and infant deaths 35% (43/123). Fifty-one children had CBS in upper limbs. Fifteen of these (29%) had other major anomalies associated with constriction rings. The number of hospital admissions per year of children with congenital upper limb defects was 11-fold and the time spent in hospital 13-fold as compared with the general paediatric population. Conclusions: Birth prevalence of congenital upper limb defects was 5.5 per 10 000 births and 5.2 per 10 000 live births. RRD was especially associated with other major anomalies and high mortality. Nearly one third of the children with CBS also had other major anomalies suggesting different aetiologies inside the group. The annual burden of hospital care of children with congenital upper limb defects was at least 11-fold as compared with the general paediatric population.

Enzyme replacement prevents enamel defects in hypophosphatasia mice

Hypophosphatasia (HPP) is the inborn error of metabolism characterized by deficiency of alkaline phosphatase activity, leading to rickets or osteomalacia and to dental defects. HPP occurs from loss-of-function mutations within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). TNAP knockout (Alpl-/-, aka Akp2-/-) mice closely phenocopy infantile HPP, including the rickets, vitamin B6-responsive seizures, improper dentin mineralization, and lack of acellular cementum. Here, we report that lack of TNAP in Alpl-/- mice also causes severe enamel defects, which are preventable by enzyme replacement with mineral-targeted TNAP (ENB-0040). Immunohistochemistry was used to map the spatiotemporal expression of TNAP in the tissues of the developing enamel organ of healthy mouse molars and incisors. We found strong, stage-specific expression of TNAP in ameloblasts. In the Alpl-/- mice, histological, mu CT, and scanning electron microscopy analysis showed reduced mineralization and disrupted organization of the rods and inter-rod structures in enamel of both the molars and incisors. All of these abnormalities were prevented in mice receiving from birth daily subcutaneous injections of mineral-targeting, human TNAP at 8.2?mg/kg/day for up to 44 days. These data reveal an important role for TNAP in enamel mineralization and demonstrate the efficacy of mineral-targeted TNAP to prevent enamel defects in HPP. (C) 2012 American Society for Bone and Mineral Research.

Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm

Fgfrl1 (also known as Fgfr5; OMIM 605830) homozygous null mice have thin, amuscular diaphragms and die at birth because of diaphragm hypoplasia. FGFRL1 is located at 4p16.3, and this chromosome region can be deleted in patients with congenital diaphragmatic hernia (CDH). We examined FGFRL1 as a candidate gene for the diaphragmatic defects associated with 4p16.3 deletions and re-sequenced this gene in 54 patients with CDH. We confirmed six known coding single nucleotide polymorphisms (SNPs): c.209G > A (p.Pro20Pro), c.977G > A (p.Pro276Pro), c.1040T > C (p.Asp297Asp), c.1234C > A (p.Pro362Gln), c.1420G > T (p.Arg424Leu), and c.1540C > T (p.Pro464Leu), but we did not identify any gene mutations. We genotyped additional CDH patients for four of these six SNPs, including the three non-synonymous SNPs, to make a total of 200 chromosomes, and found that the allele frequency for the four SNPs, did not differ significantly between patients and normal controls (p > or = 0.05). We then used Affymetrix Genechip Mouse Gene 1.0 ST arrays and found eight genes with significantly reduced expression levels in the diaphragms of Fgfrl1 homozygous null mice when compared with wildtype mice-Tpm3, Fgfrl1 (p = 0.004), Myl2, Lrtm1, Myh4, Myl3, Myh7 and Hephl1. Lrtm1 is closely related to Slit3, a protein associated with herniation of the central tendon of the diaphragm in mice. The Slit proteins are known to regulate axon branching and cell migration, and inhibition of Slit3 reduces cell motility and decreases the expression of Rac and Cdc42, two genes that are essential for myoblast fusion. Further studies to determine if Lrtm1 has a similar function to Slit3 and if reduced Fgfrl1 expression can cause diaphragm hypoplasia through a mechanism involving decreased myoblast motility and/or myoblast fusion, seem indicated.

The Rendez-vous technique for treatment of caesarean scar defects: a novel combined endoscopic approach.

BACKGROUND A caesarean scar defect is a late complication of caesarean birth with a wide range of prevalence between 56 and 84 % depending on which diagnostic tool and which definition is used [1]. The referred symptoms which include postmenstrual spotting and infertility are fortunately rare. Moreover, severe complications such as caesarean scar pregnancy and uterine rupture in the following pregnancy may occur. Given the increasing incidence of caesarean births, the potential morbidity associated with caesarean scars is likely to become more important. Recently, a few repair techniques were described in the literature including the hysteroscopic resection of scarred tissue or the laparoscopic repair with or without robotic assistance [2, 3]. METHODS Between June 2009 and February 2014, 21 women with caesarean scar defects were operated with the Rendez-vous technique, a minimally invasive surgery combining the laparoscopic and hysteroscopic approach. Data were retrospectively collected. The indications for this surgery included secondary infertility, previous caesarean scar pregnancy, recurrent miscarriage and postmenstrual spotting. Prior to operation, a transvaginal ultrasound was performed to examine the uterine wall defect. RESULTS The patient characteristics are provided in Table 1. In all cases, the operation was successfully completed laparoscopically. The median operation time was 125 min. One case was complicated by recurrence of the scar defect 6 weeks after the operation. No other intra- or post-operative complications were observed, and the median in-patient stay was 3 days. CONCLUSIONS The benefits of the technique include the feasibility and safety of the procedure, the "Halloween sign" (Fig. 1) which indicates the exact extent and localization of the scar defect and the immediate assessment of repair through the hysteroscopy at the end of the surgery. However, before further studies evaluate the efficacy of this method, the routine repair of caesarean scar defects cannot be recommended. A video of the technique is presented.