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1.
PLoS One ; 19(4): e0298365, 2024.
Article in English | MEDLINE | ID: mdl-38648215

ABSTRACT

BACKGROUND: Echogenic Intracardiac Foci (EIF) are non-structural markers identified during the routine 18-20-week foetal anomaly ultrasound scan yet their clinical significance on future outcomes for the infant is unclear. OBJECTIVE: To examine the association between EIF and risk of preterm birth, chromosomal abnormalities, and cardiac abnormalities. DESIGN: A review across four databases to identify English language journal articles of EIF using a cohort study design. All studies were reviewed for quality using the Critical Appraisal Skills Programme (CASP) checklist and data extracted for comparison and analysis. RESULTS: 19 papers from 9 different countries were included. Combining these studies showed 4.6% (95% CI = 4.55-4.65%) of all pregnancies had EIF which was on the left in 86% of cases, on the right in 3% of cases and bilaterally in 10%. There was no evidence that EIF was associated with higher rates of preterm birth. However, it is possible that infants with EIF were more likely to be terminated rather than be born preterm as there was a 2.1% (range 0.3-4.2%) rate of termination or death of the foetus after week 20 among those with EIF. There was no evidence that EIF alone is highly predictive of chromosomal abnormalities. There was evidence that EIF is associated with higher rates of minor cardiac abnormalities (e.g. ventricular septal defect, tricuspid regurgitation or mitral regurgitation)) with 5.1% (224 of 4385) of those with EIF showing cardiac abnormalities (3.08% in retrospective studies and 17.85% in prospective studies). However, the risk of cardiac defects was only higher with right-sided EIF and where the EIF persisted into the third trimester. However, this is a rare event and would be seen in an estimated 4 per 10,000 pregnancies. CONCLUSION: EIF alone was not associated with adverse outcomes for the infant. Only persistent EIF on the right side showed evidence of carrying a higher risk of cardiac abnormality and would warrant further follow-up.


Subject(s)
Heart Defects, Congenital , Pregnancy Trimester, Second , Ultrasonography, Prenatal , Female , Humans , Pregnancy , Chromosome Aberrations , Heart Defects, Congenital/diagnostic imaging , Pregnancy Outcome , Premature Birth , Ultrasonography, Prenatal/methods
2.
BMJ Open ; 14(1): e076711, 2024 01 18.
Article in English | MEDLINE | ID: mdl-38238056

ABSTRACT

PURPOSE: Using Wales's national dataset for maternity and births as a core dataset, we have linked related datasets to create a more complete and comprehensive entire country birth cohort. Data of anonymised identified persons are linked on the individual level to data from health, social care and education data within the Secure Anonymised Information Linkage (SAIL) Databank. Each individual is assigned an encrypted Anonymised Linking Field; this field is used to link anonymised individuals across datasets. We present the descriptive data available in the core dataset, and the future expansion plans for the database beyond its initial development stage. PARTICIPANTS: Descriptive information from 2011 to 2023 has been gathered from the National Community Child Health Database (NCCHD) in SAIL. This comprehensive dataset comprises over 400 000 child electronic records. Additionally, survey responses about health and well-being from a cross-section of the population including 2500 parents and 30 000 primary school children have been collected for enriched personal responses and linkage to the data spine. FINDINGS TO DATE: The electronic cohort comprises all children born in Wales since 2011, with follow-up conducted until they finish primary school at age 11. The child cohort is 51%: 49% female: male, and 7.8% are from ethnic minority backgrounds. When considering age distribution, 26.8% of children are under the age of 5, while 63.2% fall within the age range of 5-11. FUTURE PLANS: Born in Wales will expand by 30 000 new births annually in Wales (in NCCHD), while including follow-up data of children and parents already in the database. Supplementary datasets complement the existing linkage, including primary care, hospital data, educational attainment and social care. Future research includes exploring the long-term implications of COVID-19 on child health and development, and examining the impact of parental work environment on child health and development.


Subject(s)
Birth Cohort , Ethnicity , Pregnancy , Child , Humans , Male , Female , Wales/epidemiology , Life Change Events , Minority Groups , Information Storage and Retrieval , Parents
3.
PLoS One ; 18(12): e0273596, 2023.
Article in English | MEDLINE | ID: mdl-38079428

ABSTRACT

BACKGROUND: School readiness is a measure of a child's cognitive, social, and emotional readiness to begin formal schooling. Children with low school readiness need additional support from schools for learning, developing required social and academic skills, and catching-up with their school-ready peers. This study aims to identify the most significant risk factors associated with low school readiness using linked routine data for children in Wales. METHOD: This was a longitudinal cohort study using linked data. The cohort comprises of children who completed the Foundation Phase assessment between 2012 and 2018. Individuals were identified by linking Welsh Demographic Service and Pre16 Education Attainment datasets. School readiness was assessed via the binary outcome of the Foundation Phase assessment (achieved/not achieved). This study used multivariable logistic regression model and a decision tree to identify and weight the most important risk factors associated with low school readiness. RESULTS: In order of importance, logistic regression identified maternal learning difficulties (adjusted odds ratio 5.35(95% confidence interval 3.97-7.22)), childhood epilepsy (2.95(2.39-3.66)), very low birth weight (2.24(1.86-2.70), being a boy (2.11(2.04-2.19)), being on free school meals (1.85(1.78-1.93)), living in the most deprived areas (1.67(1.57-1.77)), maternal death (1.47(1.09-1.98)), and maternal diabetes (1.46(1.23-1.78)) as factors associated with low school readiness. Using a decision tree, eligibility for free school meals, being a boy, absence/low attendance at school, being born late in the academic year, being a low birthweight child, and not being breastfed were factors which were associated with low school readiness. CONCLUSION: This work suggests that public health interventions focusing on children who are: boys, living in deprived areas, have poor early years attendance, have parents with learning difficulties, have parents with an illness or have illnesses themselves, would make the most difference to school readiness in the population.


Subject(s)
Schools , Child , Male , Humans , Longitudinal Studies , Wales/epidemiology , Educational Status , Cohort Studies
4.
BMC Infect Dis ; 23(1): 594, 2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37697235

ABSTRACT

BACKGROUND: Multimorbidity, smoking status, and pregnancy are identified as three risk factors associated with more severe outcomes following a SARS-CoV-2 infection, thus vaccination uptake is crucial for pregnant women living with multimorbidity and a history of smoking. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage. METHODS: This cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was employed to examine and compare the length of time to vaccination uptake in pregnancy by considering multimorbidity, smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. The study also assessed the variation in uptake by multimorbidity, smoking status, and demographics, both jointly and separately for the independent conditions, using hazard ratios (HR) derived from the Cox regression model. RESULTS: Within the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.002). Women living with multimorbidity were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002). CONCLUSION: Younger women, living without multimorbidity, current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Pregnant individuals living with multimorbidity exhibit a slight but statistically significant reduction in vaccine hesitancy towards COVID-19 during pregnancy.


Subject(s)
COVID-19 Vaccines , COVID-19 , Pregnancy , Female , Humans , Cohort Studies , Vaccination Hesitancy , Wales/epidemiology , Multimorbidity , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Vaccination , Smoking
5.
BMJ Paediatr Open ; 7(1)2023 07.
Article in English | MEDLINE | ID: mdl-37433713

ABSTRACT

OBJECTIVES: The WHO recommends exclusive breastfeeding for the first 6 months of life. This study aimed to examine the impact the pandemic had on breastfeeding uptake and duration, and whether intention to breastfeed is associated with longer duration of exclusive breastfeeding. METHODS: A cohort study using routinely collected, linked healthcare data from the Secure Anonymised Information Linkage databank. All women who gave birth in Wales between 2018 and 2021 recorded in the Maternal Indicators dataset were asked about intention to breastfeed. These data were linked with the National Community Child Health Births and Breastfeeding dataset to examine breastfeeding rates. RESULTS: Intention to breastfeed was associated with being 27.6 times more likely to continue to exclusively breastfeed for 6 months compared with those who did not intend to breastfeed (OR 27.6, 95% CI 24.9 to 30.7). Breastfeeding rates at 6 months were 16.6% prepandemic and 20.5% in 2020. When compared with a survey population, the initial intention to breastfeed/not breastfeed only changes for about 10% of women. CONCLUSION: Women were more likely to exclusively breastfeed for 6 months during the pandemic compared with before or after the pandemic. Arguably, interventions which enable families to spend more time with their baby such as maternal and paternal leave may help improve breastfeeding duration. The biggest predictor of breastfeeding at 6 months was intention to breastfeed. Therefore, targeted interventions during pregnancy to encourage motivation to breastfeed could improve duration of breastfeeding.


Subject(s)
COVID-19 , Infant , Child , Pregnancy , Humans , Female , COVID-19/epidemiology , Breast Feeding , Pandemics , Cohort Studies , Wales/epidemiology
6.
BMJ Open ; 13(2): e063836, 2023 02 10.
Article in English | MEDLINE | ID: mdl-36764720

ABSTRACT

OBJECTIVE: Globally, 20 million children are born with a birth weight below 2500 g every year, which is considered as a low birthweight (LBW) baby. This study investigates the contribution of modifiable risk factors in a nationally representative Welsh e-cohort of children and their mothers to inform opportunities to reduce LBW prevalence. DESIGN: A longitudinal cohort study based on anonymously linked, routinely collected multiple administrative data sets. PARTICIPANTS: The cohort, (N=693 377) comprising of children born between 1 January 1998 and 31 December 2018 in Wales, was selected from the National Community Child Health Database. OUTCOME MEASURES: The risk factors associated with a binary LBW (outcome) variable were investigated with multivariable logistic regression (MLR) and decision tree (DT) models. RESULTS: The MLR model showed that non-singleton children had the highest risk of LBW (adjusted OR 21.74 (95% CI 21.09 to 22.40)), followed by pregnancy interval less than 1 year (2.92 (95% CI 2.70 to 3.15)), maternal physical and mental health conditions including diabetes (2.03 (1.81 to 2.28)), anaemia (1.26 (95% CI 1.16 to 1.36)), depression (1.58 (95% CI 1.43 to 1.75)), serious mental illness (1.46 (95% CI 1.04 to 2.05)), anxiety (1.22 (95% CI 1.08 to 1.38)) and use of antidepressant medication during pregnancy (1.92 (95% CI 1.20 to 3.07)). Additional maternal risk factors include smoking (1.80 (95% CI 1.76 to 1.84)), alcohol-related hospital admission (1.60 (95% CI 1.30 to 1.97)), substance misuse (1.35 (95% CI 1.29 to 1.41)) and evidence of domestic abuse (1.98 (95% CI 1.39 to 2.81)). Living in less deprived area has lower risk of LBW (0.70 (95% CI 0.67 to 0.72)). The most important risk factors from the DT models include maternal factors such as smoking, maternal weight, substance misuse record, maternal age along with deprivation-Welsh Index of Multiple Deprivation score, pregnancy interval and birth order of the child. CONCLUSION: Resources to reduce the prevalence of LBW should focus on improving maternal health, reducing preterm births, increasing awareness of what is a sufficient pregnancy interval, and to provide adequate support for mothers' mental health and well-being.


Subject(s)
Infant, Low Birth Weight , Substance-Related Disorders , Infant, Newborn , Pregnancy , Infant , Female , Child , Humans , Cohort Studies , Wales/epidemiology , Longitudinal Studies , Birth Weight , Risk Factors
7.
BMC Infect Dis ; 22(1): 932, 2022 Dec 12.
Article in English | MEDLINE | ID: mdl-36503414

ABSTRACT

BACKGROUND: Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. This study aimed to (1) estimate COVID-19 vaccination rates among pregnant women in Wales and their association with age, ethnicity, and area of deprivation, using electronic health record (EHR) data linkage, and (2) explore pregnant women's views on receiving the COVID-19 vaccine during pregnancy using data from a survey recruiting via social media (Facebook, Twitter), through midwives, and posters in hospitals (Born-In-Wales Cohort). METHODS: This was a mixed-methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) Databank (Objective 1) and the Born-In-Wales Birth Cohort participants (Objective 2). Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnic group, and deprivation area was examined using hazard ratios (HR) from Cox regression. Survey respondents were women who had a baby during the COVID-19 pandemic or were pregnant between 1st November 2021 and 24th March 2022 and participating in Born-In-Wales. Codebook thematic analysis was used to generate themes from an open-ended question on the survey. RESULTS: Population-level data linkage (objective 1): Within the population cohort, 8203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, 8572 (34.1%) remained unvaccinated throughout the follow-up period, and 8336 (33.2%) received the vaccine postpartum. Younger women (< 30 years) were less likely to have the vaccine, and those living in areas of high deprivation were also less likely to have the vaccine (HR = 0.88, 95% CI 0.82 to 0.95). Asian and Other ethnic groups were 1.12 and 1.18 times more likely to have the vaccine in pregnancy compared with White women (HR = 1.12, 95% CI 1.00 to 1.25) and (HR = 1.18, 95% CI 1.03 to 1.37) respectively. Survey responses (objective 2): 207 (69%) of participants stated that they would be happy to have the vaccine during pregnancy. The remaining 94 (31%) indicated they would not have the vaccine during pregnancy. Reasons for having the vaccine included protecting self and baby, perceived risk level, and receipt of sufficient evidence and advice. Reasons for vaccine refusal included lack of research about long-term outcomes for the baby, anxiety about vaccines, inconsistent advice/information, and preference to wait until after the pregnancy. CONCLUSION: Potentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation areas.


Subject(s)
COVID-19 Vaccines , COVID-19 , Pregnancy , Infant , Female , Humans , Male , Birth Cohort , Pandemics , COVID-19/epidemiology , COVID-19/prevention & control , Vaccination
8.
PLoS One ; 17(5): e0267176, 2022.
Article in English | MEDLINE | ID: mdl-35609019

ABSTRACT

BACKGROUND: Pregnancy can be a stressful time and the COVID-19 pandemic has affected all aspects of life. This study aims to investigate the pandemic impact on pregnancy experience, rates of primary childhood immunisations and the differences in birth outcomes in during 2020 to those of previous years. METHODS: Self-reported pregnancy experience: 215 expectant mothers (aged 16+) in Wales completed an online survey about their experiences of pregnancy during the pandemic. The qualitative survey data was analysed using codebook thematic analysis. Population-level birth outcomes in Wales: Stillbirths, prematurity, birth weight and Caesarean section births before (2016-2019) and during (2020) the pandemic were compared using anonymised individual-level, population-scale routine data held in the Secure Anonymised Information Linkage (SAIL) Databank. Uptake of the first three scheduled primary childhood immunisations were compared between 2019 and 2020. FINDINGS: The pandemic had a negative impact on the mental health of 71% of survey respondents, who reported anxiety, stress and loneliness; this was associated with attending scans without their partner, giving birth alone, and minimal contact with midwives. There was no significant difference in annual outcomes including gestation and birth weight, stillbirths, and Caesarean sections for infants born in 2020 compared to 2016-2019. There was an increase in late term births (≥42 weeks gestation) during the first lockdown (OR: 1.28, p = 0.019) and a decrease in moderate to late preterm births (32-36 weeks gestation) during the second lockdown (OR: 0.74, p = 0.001). Fewer babies were born in 2020 (N = 29,031) compared to 2016-2019 (average N = 32,582). All babies received their immunisations in 2020, but there were minor delays in the timings of immunisations. Those due at 8-weeks were 8% less likely to be on time (within 28-days) and at 16-weeks, they were 19% less likely to be on time. INTERPRETATION: Whilst the pandemic had a negative impact on mothers' experiences of pregnancy. Population-level data suggests that this did not translate to adverse birth outcomes for babies born during the pandemic.


Subject(s)
COVID-19 , Premature Birth , Birth Weight , COVID-19/epidemiology , Cesarean Section , Child , Communicable Disease Control , Female , Humans , Infant , Infant, Newborn , Mothers , Pandemics , Pregnancy , Premature Birth/epidemiology , Stillbirth/epidemiology , Wales/epidemiology
9.
PLoS One ; 16(12): e0260640, 2021.
Article in English | MEDLINE | ID: mdl-34910753

ABSTRACT

COVID-19 infection and the resultant restrictions has impacted all aspects of life across the world. This study explores factors that promote or support wellbeing for young people during the pandemic, how they differ by age, using a self-reported online survey with those aged 8-25 in Wales between September 2020 and February 2021. Open-ended responses were analysed via thematic analysis to provide further context. A total of 6,291 responses were obtained from 81 education settings across Wales (including primary and secondary schools as well as sixth form, colleges and universities). Wellbeing was highest in primary school children and boys and lowest in those who were at secondary school children, who were girls and, those who preferred not to give a gender. Among primary school children, higher wellbeing was seen for those who played with lots of others (rather than alone), were of Asian ethnicity (OR 2.17, 95% CI: 1.26 to 4.3), had a safe play area (OR: 2.4, 95% CI: 1.67 to 2.56) and had more sleep. To support their wellbeing young people reported they would like to be able to play with their friends more. Among secondary school children those who were of mixed ethnicity reported lower wellbeing (OR: 5.14, 95% CI: 1.68 to 15.79). To support their wellbeing they reported they would like more support with mental health (due to anxiety and pressure to achieve when learning online). This study found self-reported wellbeing differed by gender, ethnicity and deprivation and found younger children report the need for play and to see friends to support wellbeing but older children/young people wanted more support with anxiety and educational pressures.


Subject(s)
COVID-19 , Adolescent , Anxiety Disorders , Child , Humans
10.
PLoS One ; 14(5): e0212242, 2019.
Article in English | MEDLINE | ID: mdl-31150409

ABSTRACT

The relationship between child health, wellbeing and education demonstrates that healthier and happier children achieve higher educational attainment. An engaging curriculum that facilitates children in achieving their academic potential has strong implications for educational outcomes, future employment prospects, and health and wellbeing during adulthood. Outdoor learning is a pedagogical approach used to enrich learning, enhance school engagement and improve pupil health and wellbeing. However, its non-traditional means of achieving curricular aims are not yet recognised beyond the early years by education inspectorates. This requires evidence into its acceptability from those at the forefront of delivery. This study aimed to explore headteachers', teachers' and pupils' views and experiences of an outdoor learning programme within the key stage two curriculum (ages 9-11) in South Wales, United Kingdom. We examine the process of implementation to offer case study evidence through 1:1 interviews with headteachers (n = 3) and teachers (n = 10) and focus groups with pupils aged 9-11 (n = 10) from three primary schools. Interviews and focus groups were conducted at baseline and six months into implementation. Schools introduced regular outdoor learning within the curriculum. This study found a variety of perceived benefits for pupils and schools. Pupils and teachers noticed improvements in pupils' engagement with learning, concentration and behaviour, as well as positive impacts on health and wellbeing and teachers' job satisfaction. Curriculum demands including testing and evidencing work were barriers to implementation, in addition to safety concerns, resources and teacher confidence. Participants supported outdoor learning as a curriculum-based programme for older primary school pupils. However, embedding outdoor learning within the curriculum requires education inspectorates to place higher value on this approach in achieving curricular aims, alongside greater acknowledgment of the wider benefits to children which current measurements do not capture.


Subject(s)
Curriculum , Faculty , Schools , Students , Attitude , Child , Female , Humans , Learning , Male
11.
Rheumatology (Oxford) ; 55(10): 1736-45, 2016 10.
Article in English | MEDLINE | ID: mdl-27288209

ABSTRACT

OBJECTIVE: RA typically features rheumatoid cachexia [loss of muscle mass (MM) and excessive total fat mass (TFM), especially trunk FM], which contributes to physical disability. Since rheumatoid cachexia is driven by inflammation, it would be anticipated that the success of tight control of disease activity, such as treat-to-target (T2T), in attenuating inflammation would benefit body composition and physical function. This aim of this cross-sectional study was to assess the impact of T2T on body composition and objectively assessed function in RA patients. METHODS: A total of 82 RA patients exclusively treated by T2T, were compared with 85 matched sedentary healthy controls (HCs). Body composition was estimated by DXA, with appendicular lean mass the surrogate measure of total MM. Physical function was assessed by knee extensor strength, handgrip strength, 30 s sit-to-stands, 8' up and go, and 50' walk (tests which reflect the ability to perform activities of daily living). RESULTS: Although generally well treated (mean DAS28 = 2.8, with 49% in remission), RA patients had ∼10% proportionally less appendicular lean mass and were considerably fatter (by ∼27%), particularly in the trunk (∼32%), than HCs. All measures of function were 24-34% poorer in the RA patients relative to HC. CONCLUSIONS: Despite marked improvements in disease control (most patients achieving or approaching remission), the relative loss of MM and increased adiposity in RA patients compared with matched HCs was similar to that observed pre-T2T. Additionally, performance of objective function tests was unchanged from that reported by our group for pre-T2T RA patients. Thus T2T, even in responsive RA patients, did not attenuate rheumatoid cachexia or improve objectively assessed function.


Subject(s)
Arthritis, Rheumatoid/prevention & control , Body Composition/physiology , Activities of Daily Living , Arthritis, Rheumatoid/physiopathology , Cachexia/physiopathology , Cachexia/prevention & control , Case-Control Studies , Cross-Sectional Studies , Disabled Persons , Exercise/physiology , Female , Hand Strength/physiology , Health Status , Humans , Male , Middle Aged , Muscle Strength/physiology , Muscle, Skeletal/physiopathology , Treatment Outcome , Waist Circumference/physiology
12.
Genetics ; 186(4): 1161-73, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20837992

ABSTRACT

Gross chromosomal rearrangements (GCRs) are large scale changes to chromosome structure and can lead to human disease. We previously showed in Saccharomyces cerevisiae that nearby inverted repeat sequences (∼20-200 bp of homology, separated by ∼1-5 kb) frequently fuse to form unstable dicentric and acentric chromosomes. Here we analyzed inverted repeat fusion in mutants of three sets of genes. First, we show that genes in the error-free postreplication repair (PRR) pathway prevent fusion of inverted repeats, while genes in the translesion branch have no detectable role. Second, we found that siz1 mutants, which are defective for Srs2 recruitment to replication forks, and srs2 mutants had opposite effects on instability. This may reflect separate roles for Srs2 in different phases of the cell cycle. Third, we provide evidence for a faulty template switch model by studying mutants of DNA polymerases; defects in DNA pol delta (lagging strand polymerase) and Mgs1 (a pol delta interacting protein) lead to a defect in fusion events as well as allelic recombination. Pol delta and Mgs1 may collaborate either in strand annealing and/or DNA replication involved in fusion and allelic recombination events. Fourth, by studying genes implicated in suppression of GCRs in other studies, we found that inverted repeat fusion has a profile of genetic regulation distinct from these other major forms of GCR formation.


Subject(s)
Chromosomes, Fungal , DNA Replication , Inverted Repeat Sequences , Saccharomycetales/genetics , DNA Helicases/genetics , DNA Helicases/metabolism , Gene Expression Regulation , Protein Transport , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Ubiquitin-Protein Ligases/genetics
13.
Genes Dev ; 23(24): 2861-75, 2009 Dec 15.
Article in English | MEDLINE | ID: mdl-20008936

ABSTRACT

Large-scale changes (gross chromosomal rearrangements [GCRs]) are common in genomes, and are often associated with pathological disorders. We report here that a specific pair of nearby inverted repeats in budding yeast fuse to form a dicentric chromosome intermediate, which then rearranges to form a translocation and other GCRs. We next show that fusion of nearby inverted repeats is general; we found that many nearby inverted repeats that are present in the yeast genome also fuse, as does a pair of synthetically constructed inverted repeats. Fusion occurs between inverted repeats that are separated by several kilobases of DNA and share >20 base pairs of homology. Finally, we show that fusion of inverted repeats, surprisingly, does not require genes involved in double-strand break (DSB) repair or genes involved in other repeat recombination events. We therefore propose that fusion may occur by a DSB-independent, DNA replication-based mechanism (which we term "faulty template switching"). Fusion of nearby inverted repeats to form dicentrics may be a major cause of instability in yeast and in other organisms.


Subject(s)
Chromosomes, Fungal/genetics , DNA Replication/genetics , DNA, Fungal/genetics , Genomic Instability , Inverted Repeat Sequences/genetics , Saccharomyces cerevisiae/genetics , DNA Breaks , Saccharomyces cerevisiae Proteins/metabolism
14.
J Neurotrauma ; 22(8): 929-35, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16083359

ABSTRACT

Spinal cord injury (SCI) releases a cascade of events that leads to the onset of an inhibitory milieu for axonal regeneration. Some of these changes result from the presence of repulsive factors that may restrict axonal outgrowth after trauma. The Eph receptor tyrosine kinase (RTK) family has emerged as a key repellent cue known to be involved in neurite outgrowth, synapse formation, and axonal pathfinding during development. Given the nonpermissive environment for axonal regeneration after SCI, we questioned whether re-expression of one of these molecules occurs during regenerative failure. We examined the expression profile of EphA3 at the mRNA and protein levels after SCI, using the NYU contusion model. There is a differential distribution of this molecule in the adult spinal cord and EphA3 showed an increase in expression after several injury models like optic nerve and brain injury. Standardized semi-quantitative RT-PCR analysis demonstrated a time-dependent change in EphA3 mRNA levels, without alterations in beta-actin levels. The basal level of EphA3 mRNA in the adult spinal cord is low and its expression was induced 2 days after trauma (the earliest time point analyzed) and this upregulation persisted for 28 days post-injury (the latest time point examined). These results were corroborated at the protein level by immunohistochemical analysis and the cell phenotype identified by double labeling studies. In control animals, EphA3 immunoreactivity was observed in motor neurons of the ventral horn but not in lesioned animals. In addition, GFAP-positive cells were visualized in the ventral region of injured white matter. These results suggest that upregulation of EphA3 in reactive astrocytes may contribute to the repulsive environment for neurite outgrowth and may be involved in the pathophysiology generated after SCI.


Subject(s)
Receptor Protein-Tyrosine Kinases/metabolism , Spinal Cord Injuries/metabolism , Spinal Cord/metabolism , Up-Regulation/physiology , Animals , Anterior Horn Cells/metabolism , Astrocytes/metabolism , Brain Injuries/genetics , Brain Injuries/metabolism , Brain Injuries/physiopathology , Cell Communication/physiology , Disease Models, Animal , Female , Gene Expression Regulation/physiology , Glial Fibrillary Acidic Protein/metabolism , Growth Cones/metabolism , Growth Inhibitors/genetics , Growth Inhibitors/metabolism , Nerve Regeneration/physiology , Neural Pathways/metabolism , Neural Pathways/physiopathology , Optic Nerve Injuries/genetics , Optic Nerve Injuries/metabolism , Optic Nerve Injuries/physiopathology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptor Protein-Tyrosine Kinases/genetics , Spinal Cord/physiopathology , Spinal Cord Injuries/genetics , Spinal Cord Injuries/physiopathology
15.
Am J Occup Ther ; 57(3): 342-6, 2003.
Article in English | MEDLINE | ID: mdl-12785674

ABSTRACT

OBJECTIVE: The purpose of this study was to provide information regarding the validity of using the Allen Cognitive Levels Screen (ACL-90 version) by comparing functional cognitive performance between adolescents living in the community and adolescents residing in mental health facilities. METHOD: Sixty-three adolescents were assessed using the ACL-90: 32 adolescents living in the community, and 28 adolescents residing in residential mental health facilities. RESULTS: Using a one-tailed t test, performance scores for adolescents residing in the community were statistically higher than those for adolescents living in residential mental health facilities (t(34) = 4.3, p < .001). CONCLUSION: This study suggests the validity of the ACL-90 as an assessment to use for screening the cognitive functional performance of adolescents.


Subject(s)
Adolescent Behavior , Cognition Disorders/diagnosis , Mass Screening , Occupational Therapy , Psychiatric Status Rating Scales , Adolescent , Child , Female , Humans , Male , Mental Disorders , Sensitivity and Specificity
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