Salivary Gland and Tooth Abnormalities Massively Increase Caries Susceptibility in A Mouse Model of Cleft Lip/Palate

Thesis (Ph.D.)--University of Washington, 2016-04

Health and developmental outcome of children following prenatal diagnosis of confined placental mosaicism

Objective To determine the long-term health and development of a cohort of children in whom confined placental mosaicism (CPM) was diagnosed at prenatal diagnosis. Methods A retrospective cohort study was performed comparing 36 children in whom CPM had been diagnosed prenatally with 195 controls subjects in whom a normal karyotype had been detected prenatally. Data comprising birth information, health, health service utilisation, growth, development, behaviour, and the family were collected by a maternal questionnaire administered when the subjects were aged between 4 and 11 years. Results CPM cases did not differ from controls across a broad range of health measures and there were no major health problems or birth defects among the CPM group. No increase was detected in the incidence of intrauterine growth retardation (IUGR) among CPM cases; however, postnatal growth was reduced compared with controls (p = 0.047). Development and behaviour in CPM cases was similar to that of controls. Conclusions The prenatal diagnosis of CPM is not associated with an increased risk of birth defects or developmental problems, but may be associated with decreased growth. Copyright (C) 2006 John Wiley & Sons, Ltd.

Mitochondrial dysmorphology in the neuroepithelium of rat embryos following a single dose of maternal hyperthermia during gestation

Hyperthermia is teratogenic to human and animal embryos and induces mainly anomalies of the nervous system. However, the teratogenic mechanism is poorly understood. Mammalian embryos are known to switch from anaerobic to aerobic metabolism around the time of neural tube closure. This critical event might be sensitive to hyperthermia. The objective of the present study was to evaluate the ultrastructural changes of the mitochondria of the neuroepithelium (NE) of rat embryos following maternal exposure to hyperthermia. Pregnant rats were heat stressed for an hour on gestation day (GD) 9 and embryos were examined by electron microscopy on GD 10. NE presented extensive apoptosis. Intercellular junctions were weakened and copious cellular debris projected into the ventricle. The mitochondria were of diverse size and shape. Most of them were swollen and had short cristae and electron dense matrix. Hydropic changes were also observed in numerous mitochondria. Lipid-laden mitochondria were found in the apical portions of neuroblasts. The mesenchyme (ME) of heat-treated embryos showed paucity of cells and only as frequent apoptosis as the controls. Their mitochondria also showed changes similar to those of the NE. Additionally extensive lipid accumulation was observed in and in the vicinity of mitochondria, often surrounded by short strands of endoplasmic reticulum. Whereas mitochondrial pathology was associated with profound apoptosis in the NE, growth restriction and lipid accumulation accompanied mitochondrial changes in the ME. The results of this study indicate that the embryonic response to maternal heat shock is tissue-specific and morphologically distinct in this species.

The prevalence and impact of overweight and obesity in an Australian obstetric population

Objective: To assess the prevalence and impact of overweight and obesity in an Australian obstetric population. Design, setting and participants: The Mater Mother's Hospital (MMH), South Brisbane, is an urban tertiary referral maternity hospital. We reviewed data for the 18401 women who were booked for antenatal care at the MMH, delivered between January 1998 and December 2002, and had a singleton pregnancy. Of those women, 14 230 had an estimated pre-pregnancy body mass index (BMI) noted in their record; 2978 women with BMI 40 kg/m(2)). Main outcome measures: Prevalence of overweight and obesity in an obstetric population; maternal, peripartum and neonatal outcomes associated with raised BMI. Results: Of the 14230 women, 6443 (45%) were of normal weight, and 4809 (34%) were overweight, obese or morbidly obese. Overweight, obese and morbidly obese women were at increased risk of adverse outcomes (figures represent adjusted odds ratio [AOR] [95% Cl]): hypertensive disorders of pregnancy (overweight 1.74 [1.45-2.15], obese 3.00 [2.40-3.74], morbidly obese 4.87 [3.27-7.24]); gestational diabetes (overweight 1.78 [1.25-2.52], obese 2.95 [2.05-4.25], morbidly obese 7.44 [4.42-12.54]); hospital admission longer than 5 days (overweight 1.36 [1.13-1.63], obese 1.49 [1.21-1.86], morbidly obese 3.18 [2.19-4.61]); and caesarean section (overweight 1.50 [1.36-1.66], obese 2.02 [1.79-2.29], morbidly obese 2.54 [1.94-3.321). Neonates born to obese and morbidly obese women had an increased risk of birth defects (obese 1.58 (1.02-2.46], morbidly obese 3.41 [1.67-6.94]); and hypoglycaemia (obese 2.57 [1.39-4.78], morbidly obese 7.14 [3.04-16.74]). Neonates born to morbidly obese women were at increased risk of admission to intensive care (2.77 [1.81-4.25]); premature delivery (< 34 weeks' gestation) (2.13 [1.13-4.01]); and jaundice (1.44 [1.09-1.89]). Conclusions: Overweight and obesity are common in pregnant women. Increasing BMI is associated with maternal and neonatal outcomes that may increase the costs of obstetric care. To assist in planning health service delivery, we believe that BMI should be routinely recorded on perinatal data collection sheets

The effects of peer teaching of infant massage on general elf-efficacy and mother infant attachment among mothers in a residential rehabilitation facility for drug addiction and substance abuse

Approximately 200 million people, 5% aged 15-64 worldwide are illicit drug or substance abusers (World Drug Report, 2006). Between 2002 and 2005, an average of 8.2% of 12 year olds and older in the Miami, Fort Lauderdale metropolitan areas used illicit drugs (SAMHSA, 2007). Eight percent of pregnant women, aged 15 to 25, were more likely to have used illicit drugs during pregnancy than pregnant women aged 26 to 44. Alcohol use was 9.8% and cigarette use was 18% for pregnant women aged 15 to 44 (SAMHSA, 2005). Approximately a quarter of annual birth defects are attributed to the exposure of drugs or substance abuse in utero (General Accounting Office, 1991). Physical, psychological and emotional challenges may be present for the illicit drug/substance abuse (ID/SA) mother and infant placing them at a disadvantage early in their relationship (Shonkoff & Marshall, 1990). Mothers with low self efficacy have insecurely attached infants (Donovan, Leavitt, & Walsh, 1987). As the ID/SA mother struggles with wanting to be a good parent, education is needed to help her care for her infant. In this experimental study residential rehabilitating ID/SA mothers peer taught infant massage. Massage builds bonding/attachment between mother and infant (Reese & Storm, 2008) and peer teaching is effective because participants have faced similar challenges and speak the same language (Boud, Cohen, & Sampson 2001). Quantitative data were collected using the General Self-Efficacy and Maternal Attachment Inventory-Revised Scale before and after the 4-week intervention program. A reported result of this study was that empowering ID/SA mothers increased their self-efficacy, which in turn allowed the mothers to tackle challenges encountered and created feelings of being a fit mother to their infants. This research contributes to the existing database promoting evidence-based practice in drug rehabilitation centers. Healthcare personnel, such as nurse educators and maternal-child health practitioners, can develop programs in drug rehabilitation centers that cultivate an environment where the ID/SA rehabilitating mothers can peer teach each other, while creating a support system. Using infant massage as a therapeutic tool can develop a healthy infant and nurture a more positive relationship between mother and infant.

Characterization of a Novel Mouse Phenotype with Marked Hydrocephalus

In multigenic diseases, disorders where mutations in multiple genes affect the expressivity of the disease, genetic interactions play a major role in prevalence and phenotypic severity. While studying the genetic interactions between Pax3 and EdnrB in the melanocyte lineage, a new phenotype was noted in 80% of Pax3 mutants that we believe to be a novel murine model for hydrocephalus. Hydrocephalus, an accumulation of cerebrospinal fluid in the cranial cavity due to obstruction of flow in and out of the cavity, is one of the most common birth defects surpassing Down syndrome. Characteristic to hydrocephalus is a "domed" head appearance, expansion of the ventricles of the brain, and loss of neurons with hyperproliferation of glial cell types all three of which were seen in the mutant mice. The phenotype also consisted of craniofacial deformities coupled with skeletal defects including, but not limited to kyphosis, lordosis, and an apparent shortening of the some limbs. For the cellular analysis of the hydrocephalus phenotype, brains were removed and stained with two antibodies: Glial Fibrillary Acidic Protein (GFAP) and Neurofilament (NF), which are astrocyte- and neuron- specific respectively. A higher number of cells expressing GF AP and a lower number of cells expressing NF were seen in the mutant brain, when compared to control. For skeletal deformity analysis, affected mice skeletons were stained with Alizarin Red and Alcian Blue showing no apparent difference in ossification. Future genetic analysis of these mutant mice has the potential to identify novel gene modifiers involved in the promotion of this particular phenotype.

The Effects of Peer Teaching of Infant Massage on General Self-Efficacy and Mother Infant Attachment Among Mothers in a Residential Rehabilitation Facility for Drug Addiction and Substance Abuse

Approximately 200 million people, 5% aged 15-64 worldwide are illicit drug or substance abusers (World Drug Report, 2006). Between 2002 and 2005, an average of 8.2% of 12 year olds and older in the Miami, Fort Lauderdale metropolitan areas used illicit drugs (SAMHSA, 2007). Eight percent of pregnant women, aged 15 to 25, were more likely to have used illicit drugs during pregnancy than pregnant women aged 26 to 44. Alcohol use was 9.8% and cigarette use was 18% for pregnant women aged 15 to 44 (SAMHSA, 2005). Approximately a quarter of annual birth defects are attributed to the exposure of drugs or substance abuse in utero (General Accounting Office, 1991). Physical, psychological and emotional challenges may be present for the illicit drug/substance abuse (ID/SA) mother and infant placing them at a disadvantage early in their relationship (Shonkoff & Marshall, 1990). Mothers with low self efficacy have insecurely attached infants (Donovan, Leavitt, & Walsh, 1987). As the ID/SA mother struggles with wanting to be a good parent, education is needed to help her care for her infant. In this experimental study residential rehabilitating ID/SA mothers peer taught infant massage. Massage builds bonding/attachment between mother and infant (Reese & Storm, 2008) and peer teaching is effective because participants have faced similar challenges and speak the same language (Boud, Cohen, & Sampson 2001). Quantitative data were collected using the General Self-Efficacy and Maternal Attachment Inventory-Revised Scale before and after the 4-week intervention program. A reported result of this study was that empowering ID/SA mothers increased their self-efficacy, which in turn allowed the mothers to tackle challenges encountered and created feelings of being a fit mother to their infants. This research contributes to the existing database promoting evidence-based practice in drug rehabilitation centers. Healthcare personnel, such as nurse educators and maternal-child health practitioners, can develop programs in drug rehabilitation centers that cultivate an environment where the ID/SA rehabilitating mothers can peer teach each other, while creating a support system. Using infant massage as a therapeutic tool can develop a healthy infant and nurture a more positive relationship between mother and infant.

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.