ABSTRACT
Nuclear reprogramming mediated by somatic cell nuclear transfer (SCNT) has many applications in medicine. However, animal clones show increased rates of abortion and reduced neonatal viability. Herein, we used exosomal-miRNA profiles as a non-invasive biomarker to identify pathological pregnancies. MiRNAs play important roles in cellular proliferation and differentiation during early mammalian development. Thus, the aim of this study was to identify exosomal-miRNAs in maternal blood at 21 days of gestation that could be used for diagnosis and prognosis during early clone pregnancies in cattle. Out of 40 bovine-specific miRNAs, 27 (67.5%) were with low abundance in the C-EPL (Clone - Early pregnancy loss) group compared with the C-LTP (Clone - Late pregnancy) and AI-LTP (Artificial Insemination - Late pregnancy) groups, which had similar miRNAs levels. Bioinformatics analysis of the predicted target genes demonstrated signaling pathways and functional annotation clusters associated with critical biological processes including cell proliferation, differentiation, apoptosis, angiogenesis and embryonic development. In conclusion, our results demonstrate decreased exosomal-miRNAs in maternal blood at 21 days of gestation in cloned cattle pregnancies that failed to reach term. Furthermore, the predicted target genes regulated by these 27 miRNAs are strongly associated with pregnancy establishment and in utero embryonic development.
Subject(s)
Abortion, Spontaneous/genetics , Cell-Free Nucleic Acids/metabolism , Exosomes/metabolism , MicroRNAs/metabolism , Animals , Cattle , Cell Differentiation , Cell Proliferation/genetics , Cell-Free Nucleic Acids/genetics , Cellular Reprogramming , Cloning, Organism , Computational Biology , Embryonic Development , Female , Gene Expression Profiling , Insemination, Artificial , MicroRNAs/genetics , Molecular Sequence Annotation , Mothers , Nuclear Transfer Techniques , Pregnancy , Signal TransductionABSTRACT
El abuso infantil es la causa más común de lesión cefálica grave en los niños de corta edad. A pesar de ello, el traumatismo cefálico abusivo con frecuencia es subdiagnosticado y subinformado. Esto se relaciona parcialmente con el entrenamiento inadecuado que los profesionales de la salud reciben en el reconocimiento y enfoque del abuso infantil. Actualmente, está disponible el contenido curricular para las universidades médicas y programas de residencia. Dadas las altas tasas de muerte y deterioro neurológico grave asociado con el traumatismo cefálico abusivo, la prevención se ha convertido en el centro de atención. Algunas estrategias de prevención mostraron resultados promisorios en mejorar la educación de los padres y en reducir la incidencia de lesiones. Este artículo revisa la epidemiología, las características clínicas y el desenlace del traumatismo cefálico abusivo en los niños de corta edad. También analiza las estrategias de prevención, como la educación y el contenido curricular para los profesionales de la salud.(AU)
Child abuse is the most common cause of serious head injury in young children. Despite this, abusive headtrauma is often under-recognized and under-reported. This is partly related to the inadequate trainingthat health professionals receive in child abuse recognition and management. Published curricula are nowavailable for medical school and residency education. Given the high rates of death and serious neurolo-gical impairment associated with abusive head trauma, prevention has become a focus. Some preventionstrategies show promising results in improving parent education and reducing the incidence of injury. Thisarticle reviews the epidemiology, clinical characteristics, and outcomes of abusive head trauma in youngchildren. It also discusses prevention strategies, including education and curricula for health professionals.(AU)
Subject(s)
Female , Infant , Child, Preschool , Child , Child Abuse/diagnosis , Child Abuse/trends , Child Abuse/therapy , Brain Injuries, Traumatic/diagnosis , Brain Injuries, Traumatic/prevention & control , Shaken Baby Syndrome/diagnosis , Shaken Baby Syndrome/prevention & controlABSTRACT
El abuso infantil es la causa más común de lesión cefálica grave en los niños de corta edad. A pesar de ello, el traumatismo cefálico abusivo con frecuencia es subdiagnosticado y subinformado. Esto se relaciona parcialmente con el entrenamiento inadecuado que los profesionales de la salud reciben en el reconocimiento y enfoque del abuso infantil. Actualmente, está disponible el contenido curricular para las universidades médicas y programas de residencia. Dadas las altas tasas de muerte y deterioro neurológico grave asociado con el traumatismo cefálico abusivo, la prevención se ha convertido en el centro de atención. Algunas estrategias de prevención mostraron resultados promisorios en mejorar la educación de los padres y en reducir la incidencia de lesiones. Este artículo revisa la epidemiología, las características clínicas y el desenlace del traumatismo cefálico abusivo en los niños de corta edad. También analiza las estrategias de prevención, como la educación y el contenido curricular para los profesionales de la salud.
Child abuse is the most common cause of serious head injury in young children. Despite this, abusive headtrauma is often under-recognized and under-reported. This is partly related to the inadequate trainingthat health professionals receive in child abuse recognition and management. Published curricula are nowavailable for medical school and residency education. Given the high rates of death and serious neurolo-gical impairment associated with abusive head trauma, prevention has become a focus. Some preventionstrategies show promising results in improving parent education and reducing the incidence of injury. Thisarticle reviews the epidemiology, clinical characteristics, and outcomes of abusive head trauma in youngchildren. It also discusses prevention strategies, including education and curricula for health professionals.
Subject(s)
Female , Infant , Child, Preschool , Child , Child Abuse/diagnosis , Child Abuse/trends , Child Abuse/therapy , Shaken Baby Syndrome/diagnosis , Shaken Baby Syndrome/prevention & control , Brain Injuries, Traumatic/diagnosis , Brain Injuries, Traumatic/prevention & controlABSTRACT
We explored the association between caries development, colonization with caries-associated microflora, and immunity as children begin the transition to mixed dentition. Forty children received dental examinations at 3-4 years of age, repeated a year later. Children were grouped into caries-free (n = 23; CF) and caries-active (n = 17; CA ≥3 new lesions on follow-up). Salivary IgA and IgA antibody to Streptococcus mutans virulence epitopes were measured by Luminex assay. Mutans streptococci (MS), lactobacilli and total microorganisms were enumerated on selective media from plaque samples. There was no significant difference in baseline levels of MS or lactobacilli between CF and CA groups. However, both MS and lactobacilli levels were higher at follow-up in the CA group. Furthermore, children with detectable lactobacilli at baseline had significantly higher caries risk. Salivary IgA concentrations increased significantly in both groups during the study. Both CF and CA groups also displayed significant increases in salivary IgA antibody levels to glucosyltransferase, glucan-binding protein (Gbp) and antigen I/II salivary binding region. CF antibody levels to seven peptides associated with domains of biological importance increased at follow-up, in contrast to increases to only three peptides in CA saliva samples. Multivariate modeling showed that a lower baseline level of salivary IgA anti-GbpB was associated with higher caries risk. These data indicate that MS and lactobacilli are associated with caries in this population, that the secretory immune system is undergoing significant maturation during this period, and that the breadth of mucosal IgA response to epitopes of S. mutans virulence components may influence the degree to which these cariogenic microorganisms can cause disease.
Subject(s)
Dental Caries/immunology , Dental Caries/microbiology , Dental Plaque/microbiology , Lactobacillus/immunology , Saliva/immunology , Streptococcus mutans/immunology , Adhesins, Bacterial/immunology , Antibodies, Bacterial/analysis , Carrier Proteins/analysis , Child, Preschool , Dentition, Mixed , Humans , Immunity, Mucosal , Immunoglobulin A, Secretory/analysis , Lectins/analysis , Logistic Models , Multivariate Analysis , Statistics, Nonparametric , Virulence Factors/immunologyABSTRACT
The interplay between mucosal immune responses to natural exposure to mutans streptococci and the incorporation and accumulation of these cariogenic microorganisms in oral biofilms is unclear. An initial approach to explore this question would be to assess the native secretory immunity emerging as a consequence of Streptococcus mutans infection. To this end, we analyzed salivary immunoglobulin A (IgA) antibody to mutans streptococcal glucosyltransferase (Gtf) and glucan binding protein B (GbpB) and to domains associated with enzyme function and major histocompatibility complex (MHC) class II binding in two experiments. Salivas were collected from approximately 45-day-old Sprague-Dawley rats, which were then infected with S. mutans SJ32. Infection was verified and allowed to continue for 2 to 2.5 months. Salivas were again collected following the infection period. Pre- and postinfection salivas were then analyzed for IgA antibody activity using peptide- or protein-coated microsphere Luminex technology. S. mutans infection induced significant levels of salivary IgA antibody to Gtf (P < 0.002) and GbpB (P < 0.001) in both experiments, although the levels were usually far lower than the levels achieved when mucosal immunization is used. Significantly (P < 0.035 to P < 0.001) elevated levels of postinfection salivary IgA antibody to 6/10 Gtf peptides associated with either enzyme function or MHC binding were detected. The postinfection levels of antibody to two GbpB peptides in the N-terminal region of the six GbpB peptides assayed were also elevated (P < 0.031 and P < 0.001). Interestingly, the patterns of the rodent response to GbpB peptides were similar to the patterns seen in salivas from young children during their initial exposure to S. mutans. Thus, the presence of a detectable postinfection salivary IgA response to mutans streptococcal virulence-associated components, coupled with the correspondence between rat and human mucosal immune responsiveness to naturally presented Gtf and GbpB epitopes, suggests that the rat may be a useful model for defining mucosal responses that could be expected in humans. Under controlled infection conditions, such a model could prove to be helpful for unraveling relationships between the host response and oral biofilm development.
Subject(s)
Antibodies, Bacterial/immunology , Saliva/immunology , Streptococcus mutans/immunology , Virulence Factors/immunology , Animals , Antibodies, Bacterial/analysis , Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Glucosyltransferases/immunology , Glycoproteins/immunology , Immunoglobulin A/analysis , Immunoglobulin A/immunology , Rats , Rats, Sprague-Dawley , Saliva/chemistry , Streptococcal Infections/immunologyABSTRACT
Early mutans streptococci (MS) infection has been associated with higher caries activity in childhood. Since colonization with MS does not always lead to caries activity, additional factors may be involved in MS cariogenicity. For example, MS may differ in virulence traits such as the potential to synthesize glucan polymers from sucrose. In the present study, we tested the hypothesis that caries activity can be associated with variations in virulence factor expression of MS-infecting strains. At baseline, levels of MS obtained by the tongue-blade sampling method, and the presence of visible plaque on upper incisors, were measured in 101 12- to 30-month-old children. Dental caries lesions were diagnosed at baseline and after one year. Caries incidence data were then used to select ten caries-free and nine caries-active children from whom a total of 20 MS fresh isolates was studied. Water-insoluble glucan (WIG) synthesis, final pH, and sucrose-dependent adherence on glass surfaces were measured in these MS isolates. Concentrated culture supernatants were separated in duplicate SDS-PAGE gels, which were then either stained for protein or incubated with 5% sucrose. The intensities of the WIG bands developed in the 5% sucrose PAGE gels and the corresponding protein-stained GTF bands were measured by scanning densitometry. High MS levels (> or = 100 CFU) were associated with high caries incidence (p < 0.01). The presence of visible plaque did not correlate with caries incidence. The intensities of WIG bands were positively correlated with caries incidence (p < 0.05) and with the ability of MS to adhere to glass surfaces (p < 0.05). Analysis of our data suggests that the ability to synthesize WIG is an important virulence factor in initial caries development by increasing MS adherence and accumulation in the plaque of young children.
Subject(s)
Dental Caries/microbiology , Glucans/biosynthesis , Polysaccharides, Bacterial/biosynthesis , Streptococcus mutans/metabolism , Bacterial Adhesion , Brazil , Child, Preschool , DMF Index , Dental Caries/etiology , Dental Plaque/microbiology , Electrophoresis, Polyacrylamide Gel , Female , Follow-Up Studies , Glucosyltransferases/analysis , Humans , Hydrogen-Ion Concentration , Incidence , Infant , Male , Solubility , Streptococcus mutans/enzymology , Streptococcus mutans/pathogenicity , Sucrose/metabolism , Tongue/microbiology , Virulence , WaterABSTRACT
OBJECTIVE: To determine total and functional serogroup C antibody response after vaccination with a quadrivalent meningococcal polysaccharide vaccine. DESIGN: Prospective, before and after intervention study. SUBJECTS: Study subjects were between the ages of 0.5 and 19.9 years, and were eligible for a community-wide public health immunization campaign against Neisseria meningitidis serogroup C. METHODS: Total and functional antibody response was measured by enzyme-linked immunosorbent assay and bactericidal assay, respectively. RESULTS: One month after vaccination, total capsular polysaccharide antibody significantly increased in all age groups; a significant rise in bactericidal antibody, that correlated with total capsular polysaccharide antibody, was seen in children 18 months of age and older. At 1 year bactericidal antibody titers were maintained but capsular polysaccharide antibody declined substantially in children younger than 5 years. CONCLUSION: Total capsular polysaccharide antibody concentration appears to be a useful surrogate measure of bactericidal antibody in children 18 months and older. Children who originally received the vaccine at less than 18 months of age should be considered for revaccination if there is a new or continuing risk of disease. Because of the differences in the total and bactericidal antibodies formed, vaccine efficacy trials are required to define which serologic measures are associated with protection.
Subject(s)
Bacterial Vaccines/immunology , Meningococcal Infections/immunology , Neisseria meningitidis/immunology , Polysaccharides, Bacterial/immunology , Adolescent , Adult , Antibody Formation , Bacterial Vaccines/therapeutic use , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunotherapy, Active , Infant , Male , Meningococcal Infections/prevention & control , Neisseria meningitidis/isolation & purification , Polysaccharides, Bacterial/therapeutic use , Prospective Studies , VaccinationABSTRACT
We explored, during an outbreak of meningococcal disease, whether children of parents with workplace exposure to children were at increased risk of oropharyngeal colonization with Neisseria meningitidis. In comparison with children of parents without workplace exposure to children, the risk of colonization was not increased (odds ratio = 1.62; 95% confidence interval, 0.56 to 4.72). Therefore a parent's occupation does not appear to increase the risk of their children's colonization with N. meningitidis.