A large proportion of pregnancy losses occur during the pre-implantation period, when the developing embryo is elongating rapidly and signalling its presence to the maternal system. The molecular ...mechanisms that prevent luteolysis and support embryo survival within the maternal environment are not well understood. To gain a more complete picture of these molecular events, genome-wide transcriptional profiles of reproductive day 17 endometrial tissue were determined in pregnant and cyclic Holstein-Friesian dairy cattle.
Microarray analyses revealed 1,839 and 1,189 differentially expressed transcripts between pregnant and cyclic animals (with > or = 1.5 fold change in expression; P-value < 0.05, MTC Benjamini-Hochberg) in caruncular and intercaruncular endometrium respectively. Gene ontology and biological pathway analysis of differentially expressed genes revealed enrichment for genes involved in interferon signalling and modulation of the immune response in pregnant animals.
The maternal immune system actively surveys the uterine environment during early pregnancy. The embryo modulates this response inducing the expression of endometrial molecules that suppress the immune response and promote maternal tolerance to the embryo. During this period of local immune suppression, genes of the innate immune response (in particular, antimicrobial genes) may function to protect the uterus against infection.
Racism is a determinant of individual and offspring health. Accelerated telomere shortening, an indicator of cellular aging, is a potential mechanism through which parental experience of racism could ...affect offspring. Here we longitudinally evaluated the relationship between maternal lifetime experience of an ethnically-motivated verbal or physical attack, as reported in pregnancy, with offspring telomere length in 4.5-year-old children. We also explored the potential association between positive feelings about one's culture and offspring telomere length. Data come from a nationally representative, multi-ethnic birth cohort in Aotearoa New Zealand (NZ) (Māori N = 417, Pacific N = 364, Asian N = 381). In models adjusting for covariates, including socioeconomic status and health status, Māori mothers who experienced an ethnically-motivated physical attack had children with significantly shorter telomere length than children of Māori mothers who did not report an attack (B = - 0.20, p = 0.01). Conversely, Māori mothers who had positive feelings about their culture had offspring with significantly longer telomeres (B = 0.25, p = 0.02). Our results suggest that ethnicity-based health inequities are shaped by racism, with impacts for clinical care and policy. Future research should also evaluate the potential protective effects of positive cultural identity.
This paper describes the results of recent research carried out with the UK energy sector to assess low-carbon related skills gaps and training requirements at the masters-level. Via iterative ...engagement across the industry, the characteristics of the market for new ‘needs-driven’ industry-focussed masters-level training offerings were defined. The results, taken together with the outcomes of a gap analysis of existing masters-level training, support the creation of a new framework for masters-level energy education that will more effectively meet the growing unmet need for such skills in the UK and beyond. The outcomes of the research indicate that flexibility in both delivery mode and curriculum content across both technical and non-technical disciplines is essential, along with improved supplier agility to rapidly develop new courses in evolving engineering specialisations. Without responding effectively to such demands from industry, we conclude that the advanced skills needed across the highly dynamic UK and global energy engineering sector will be in increasingly short supply.
Chronic otitis media with effusion (COME) in children can cause prolonged hearing loss, which is associated with an increased risk of learning delays and behavioural problems. Dispersal of bacterial ...pathogens from the nasal passages to the middle ear is implicated in COME. We sought to determine whether there is an association between nasal microbial composition and COME in children.
A case-control study of children aged 3 and 4 years was conducted. Cases undergoing placement of tympanostomy tubes for COME were compared to healthy controls. Nasal swabs were collected and a questionnaire was administered. The V1-3 region of the 16S rRNA gene was amplified, and sequenced on the Illumina MiSeq.
73 children with COME had a lower Shannon diversity index than 105 healthy controls (1.62 .80 versus 1.88 .84, respectively; P = .046). The nasal microbiota of cases and controls differed in composition using Bray-Curtis dissimilarity (p = 0.002). Children with COME had a higher abundance of otopathogens and lower abundance of commensals including alpha haemolytic Streptococci and Lactococcus. Cluster analysis revealed 4 distinct nasal microbial profiles. Profiles that were Corynebacterium-dominated (aOR 4.18 95%CI, 1.68-10.39, Streptococcus-dominated (aOR 3.12 95%CI, 1.08-9.06, or Moraxella-dominated (aOR 4.70 95%CI, 1.73-12.80 were associated with COME, compared to a more mixed microbial profile when controlling for age, ethnicity, and recent antibiotics use.
Children with COME have a less diverse nasal microbial composition with a higher abundance of pathogens, compared to healthy children who have a more mixed bacterial profile with a higher abundance of commensals. Further research is required to determine how nasal microbiota may relate to the pathogenesis or maintenance of COME, and whether modification of the nasal microbiota can prevent or treat children at risk of COME.
A classic of medieval studies, The Resurrection of the Body in Western Christianity, 200–1336 traces ideas of death and resurrection in early and medieval Christianity. Caroline Walker Bynum explores ...problems of the body and identity in devotional and theological literature, suggesting that medieval attitudes toward the body still shape modern notions of the individual. This expanded edition includes her 1995 article "Why All the Fuss About the Body? A Medievalist's Perspective," which takes a broader perspective on the book's themes. It also includes a new introduction that explores the context in which the book and article were written, as well as why the Middle Ages matter for how we think about the body and life after death today.
•Human papillomaviruses modulate epithelial homeostasis to ensure persistent infection in the epithelial basal layer.•Viral papillomas are self-limiting structures with a modified pattern of ...homeostatic regulation.•The cervical transformation zone is regulated by two cell types, with cervical reserve cells able to form a stratified squamous epithelium.•HPV infection of cells that are able to undergo metaplasia appears central to the development of cervical neoplasia.•The cellular targets of high-risk HPV types appear to be important modulators of epithelial homeostasis.
Human papillomaviruses establish a reservoir of infection in the epithelial basal layer. To do this they limit their gene expression to avoid immune detection and modulate epithelial homeostasis pathways to inhibit the timing of basal cell delamination and differentiation to favour persistence. For low-risk Alpha papillomaviruses, which cause benign self-limiting disease in immunocompetent individuals, it appears that cell competition at the lesion edge restricts expansion. These lesions may be considered as self-regulating homeostatic structures, with epithelial cells of the hair follicles and sweat glands, which are proposed targets of the Beta and Mu papillomaviruses, showing similar restrictions to their expansion across the epithelium as a whole. In the absence of immune control, which facilitates deregulated viral gene expression, such lesions can expand, leading to problematic papillomatosis in afflicted individuals. By contrast, he high-risk Alpha HPV types can undergo deregulated viral gene expression in immunocompetent hosts at a number of body sites, including the cervical transformation zone (TZ) where they can drive the formation of neoplasia. Homeostasis at the TZ is poorly understood, but involves two adjacent epithelial cell population, one of which has the potential to stratify and to produce a multilayed squamous epithelium. This process of metaplasia involves a specialised cell type known as the reserve cell, which has for several decades been considered as the cell of origin of cervical cancer. It is becoming clear that during evolution, HPV gene products have acquired functions directly linked to their requirements to modify the normal processes of epithelial homestasis at their various sites of infection. These protein functions are beginning to provide new insight into homeostasis regulation at different body sites, and are likely to be central to our understanding of HPV epithelial tropisms.
Telomeres are repetitive DNA sequences at the end of chromosomes that function to protect chromosomes from degradation. Throughout the life course, telomere length decreases with age and is ...influenced by environmental factors and health conditions. This study aimed to determine the relative telomere lengths in a diverse cohort of about 4000 four-year-old children in New Zealand. Linear regression was used to investigate the relationship between telomere length, child gender, ethnicity, paternal age and deprivation. We observed substantial variation in telomere length according to sex and self-identified ethnicity. Telomere length was longer in females compared to males (coefficient of 0.042, 95% confidence interval (CI) 0.024-0.060). European children had shorter telomere than both the indigenous Māori (coefficient of 0.03, CI 0.007-0.055) and Pacific children (coefficient of 0.15, CI 0.12-0.18). The data suggest that telomere lengths are highly variable and variability between individuals arise from early age, influenced partly by sex and ethnicity. Longer telomeres in indigenous Māori and Pacific children may reflect the heritability of telomere length in genetically less complex populations. This study increases our understanding of telomere dynamics in young children since the majority of telomere studies are conducted in adults.
It has been argued that rare diseases should be recognized as a public health priority. However, there is a shortage of epidemiological data describing the true burden of rare diseases. This study ...investigated hospital service use to provide a better understanding of the collective health and economic impacts of rare diseases.
Novel methodology was developed using a carefully constructed set of diagnostic codes, a selection of rare disease cohorts from hospital administrative data, and advanced data-linkage technologies. Outcomes included health-service use and hospital admission costs.
In 2010, cohort members who were alive represented approximately 2.0% of the Western Australian population. The cohort accounted for 4.6% of people discharged from hospital and 9.9% of hospital discharges, and it had a greater average length of stay than the general population. The total cost of hospital discharges for the cohort represented 10.5% of 2010 state inpatient hospital costs.
This population-based cohort study provides strong new evidence of a marked disparity between the proportion of the population with rare diseases and their combined health-system costs. The methodology will inform future rare-disease studies, and the evidence will guide government strategies for managing the service needs of people living with rare diseases.Genet Med advance online publication 22 September 2016.
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