To compare the effects of stannous (Sn) and fluoride (F) ions and their combination on acquired enamel pellicle (AEP) protein composition (proteome experiment), and protection against dental erosion ...(functional experiment).
In the proteome experiment, bovine enamel specimens were incubated in whole saliva supernatant for 24h for AEP formation. They were randomly assigned to 4 groups (n=10), according to the rinse treatment: Sn (800ppm/6.7mM, SnCl2), F (225ppm/13mM, NaF), Sn and F combination (Sn+F) and deionized water (DIW, negative control). The specimens were immersed 3× in the test rinses for 2min, 2h apart. Pellicles were collected, digested, and analyzed for protein content using liquid chromatography electrospray ionization tandem mass spectrometry. In the functional experiment, bovine enamel specimens (n=10) were similarly treated for pellicle formation. Then, they were subjected to a five-day erosion cycling model, consisting of 5min erosive challenges (15.6 mM citric acid, pH 2.6, 6×/d) and 2min treatment with the rinses containing Sn, F or Sn+F (3×/d). Between the treatments, all specimens were incubated in whole saliva supernatant. Surface loss was determined by profilometry.
Our proteome approach on bovine enamel identified 72 proteins that were common to all groups. AEP of enamel treated with Sn+F demonstrated higher abundance for most of the identified proteins than the other groups. The functional experiment showed reduction of enamel surface loss for Sn+F (89%), Sn (67%) and F (42%) compared to DIW (all significantly different, p<0.05).
This study highlighted that anti-erosion rinses (e.g. Sn+F) can modify quantitatively and qualitatively the AEP formed on bovine enamel. Moreover, our study demonstrated a combinatory effect that amplified the anti-erosive protection on tooth surface.
Objective
To develop and test markers of neonatal severe morbidity for the identification of neonatal near‐miss cases.
Design
This is a database analysis of two World Health Organization ...cross‐sectional studies: the Global Survey on Maternal and Perinatal Health (WHOGS) and the Multicountry Survey on Maternal and Newborn Health (WHOMCS).
Setting
The WHOGS was performed in 373 health facilities in 24 countries (2004–2008). The WHOMCS was conducted in 359 health facilities in 29 countries (2010–2011).
Population
Data were collected from hospital records of all women admitted for delivery and their respective neonates.
Methods
Pragmatic markers (birthweight <1750 g, Apgar score at 5 minutes <7, and gestational age <33 weeks) were developed with WHOGS data and validated with WHOMCS data. The diagnostic accuracy of neonatal characteristics and management markers of severity was determined in the WHOMCS.
Results
This analysis included 290 610 liveborn neonates from WHOGS and 310 436 liveborn neonates from WHOMCS. The diagnostic accuracy of pragmatic and management markers of severity for identifying early neonatal deaths was very high: sensitivity, 92.8% (95% CI 91.8–93.7%); specificity, 92.7% (95% CI 92.6–92.8%); positive likelihood ratio, 12.7 (95% CI 12.5–12.9); negative likelihood ratio, 0.08 (95% CI 0.07–0.09); diagnostic odds ratio, 163.4 (95% CI 141.6–188.4). A positive association was found between the frequency of neonatal near‐miss cases and Human Development Index.
Conclusion
Newborn infants presenting selected markers of severity and surviving the first neonatal week could be considered as neonatal near‐miss cases. This definition and criteria may be seen as a basis for future applications of the near‐miss concept in neonatal health. These tools can be used to inform policy makers on how best to apply scarce resources for improving the quality of care and reducing neonatal mortality.
Background. The natural history of congenital cytomegalovirus (CMV) infection is scarcely known in populations with high maternal CMV seroprevalence. This study evaluated the birth prevalence, ...clinical findings at birth, and hearing outcome in CMV-infected children from such a population. Methods. Consecutively born infants were screened for the presence of CMV in urine and/or saliva specimens during the first 2 weeks after birth. Neonatal clinical findings were recorded, and CMV-infected children were tested to document hearing function during follow-up. A subset of mothers of CMV-infected infants were prenatally tested for the presence of anti-CMV immunoglobulin G antibodies. Results. Congenital CMV infection was confirmed in 87 (1.08%; 95% confidence interval CI, 0.86%-1.33%) of 8047 infants. Seven infants (8.1%; 95% CI, 3.3%-15.9%) had at least 1 clinical finding suggestive of CMV infection, and 4 (4.6%; 95% CI, 1.3%-11.3%) had >3 findings of systemic disease. Sensorineural hearing loss was found in 5 (8.6%; 95% CI, 2.9%-19.0%) of 58 children tested at a median age of 21 months. Bilateral profound hearing loss was observed in 2 children, and the hearing threshold was >60 decibels in all 5 children with hearing loss, including 2 children born to mothers with probable nonprimary CMV infection. Conclusions. The results of this large newborn screening study in a population with high CMV seroimmunity provide additional evidence that congenital CMV disease occurs in populations with high seroprevalence rates, with a similar incidence of CMV-related hearing loss to that reported in the offspring of women from populations in developed countries with lower rates of seroimmunity to CMV.
In our recent studies, we have shown that in vivo–acquired enamel pellicle is a sophisticated biological structure containing a significant portion of naturally occurring salivary peptides. From a ...functional aspect, the identification of peptides in the acquired enamel pellicle is of interest because many salivary proteins exhibit functional domains that maintain the activities of the native protein. Among the in vivo–acquired enamel pellicle peptides that have been newly identified, 5 peptides are derived from statherin. Here, we assessed the ability of these statherin pellicle peptides to inhibit hydroxyapatite crystal growth. In addition, atomistic molecular dynamics (MD) simulations were performed to better understand the underlying physical mechanisms of hydroxyapatite growth inhibition. A microplate colorimetric assay was used to quantify hydroxyapatite growth. Statherin protein, 5 statherin-derived peptides, and a peptide lacking phosphate at residues 2 and 3 were analyzed. Statherin peptide phosphorylated on residues 2 and 3 indicated a significant inhibitory effect when compared with the 5 other peptides (P < 0.05). MD simulations showed a strong affinity and fast adsorption to hydroxyapatite for phosphopeptides, whereas unphosphorylated peptides interacted weakly with the hydroxyapatite. Our data suggest that the presence of a covalently linked phosphate group (at residues 2 and 3) in statherin peptides modulates the effect of hydroxyapatite growth inhibition. This study provides a mechanism to account for the composition and function of acquired enamel pellicle statherin peptides that will contribute as a base for the development of biologically stable and functional synthetic peptides for therapeutic use against dental caries and/or periodontal disease.
A neighborhood-restricted mixed Gibbs sampling (MGS)-based approach is proposed for low-complexity high-order modulation large-scale multiple-input multiple-output (LS-MIMO) detection. The proposed ...LS-MIMO detector applies a neighborhood limitation (NL) on the noisy solution from the MGS at a distance
d
— thus, named
d
-simplified MGS (
d
-sMGS) — in order to mitigate its impact, which can be harmful when a high-order modulation is considered. Numerical simulation results considering 64-QAM demonstrated that the proposed detection method can substantially improve the MGS algorithm convergence, whereas no extra computational complexity per iteration is required. The proposed
d
-sMGS-based detector suitable for high-order modulation LS-MIMO further exhibits improved performance × complexity tradeoff when the system loading is high, i.e., when
K
N
≥
0.75
. Also, with increasing the number of dimensions, i.e., increasing number of antennas and/or modulation order, a smaller restriction of 2-sMGS was shown to be a more interesting choice than 1-sMGS.
Human cytomegalovirus (HCMV) is the leading cause of birth defects associated with infections and a leading cause of transplantation failure. This study reveals the patterns and limits of HCMV ...genomic diversity by performing a large-scale analysis of HCMV sequences sampled from human hosts, identifying the hot and cold spots of variability. We find that the diversity is unevenly distributed across three host compartments and show that HCMV populations of vascular compartments are genetically constrained while enriched for polymorphisms of glycoproteins and regulatory proteins. This work significantly advances our understanding of the genomic diversity of HCMV in humans and has clear implications for the development of therapeutics against HCMV.
Human cytomegalovirus (HCMV) exhibits surprisingly high genomic diversity during natural infection although little is known about the limits or patterns of HCMV diversity among humans. To address this deficiency, we analyzed genomic diversity among congenitally infected infants. We show that there is an upper limit to HCMV genomic diversity in these patient samples, with â¼25% of the genome being devoid of polymorphisms. These low diversity regions were distributed across 26 loci that were preferentially located in DNA-processing genes. Furthermore, by developing, to our knowledge, the first genome-wide mutation and recombination rate maps for HCMV, we show that genomic diversity is positively correlated with these two rates. In contrast, median levels of viral genomic diversity did not vary between putatively single or mixed strain infections. We also provide evidence that HCMV populations isolated from vascular compartments of hosts from different continents are genetically similar and that polymorphisms in glycoproteins and regulatory proteins are enriched in these viral populations. This analysis provides the most highly detailed map of HCMV genomic diversity in human hosts to date and informs our understanding of the distribution of HCMV genomic diversity within human hosts.
Light sensing has been extensively characterized in the human pathogen
at environmental temperatures. However, the influence of light on the physiology and pathogenicity of human bacterial pathogens ...at temperatures found in warm-blooded hosts is still poorly understand. In this work, we show that
,
, and
(ESKAPE) priority pathogens, which have been recognized by the WHO and the CDC as critical, can also sense and respond to light at temperatures found in human hosts. Most interestingly, in these pathogens, light modulates important pathogenicity determinants as well as virulence in an epithelial infection model, which could have implications in human infections. In fact, we found that alpha-toxin-dependent hemolysis, motility, and growth under iron-deprived conditions are modulated by light in
Light also regulates persistence, metabolism, and the ability to kill competitors in some of these microorganisms. Finally, light exerts a profound effect on the virulence of these pathogens in an epithelial infection model, although the response is not the same in the different species; virulence was enhanced by light in
and
, while in
and
it was reduced. Neither the BlsA photoreceptor nor the type VI secretion system (T6SS) is involved in virulence modulation by light in
Overall, this fundamental knowledge highlights the potential use of light to control pathogen virulence, either directly or by manipulating the light regulatory switch toward the lowest virulence/persistence configuration.
Pathogenic bacteria are microorganisms capable of producing disease. Dangerous bacterial pathogens, such as
,
, and
, are responsible for serious intrahospital and community infections in humans. Therapeutics is often complicated due to resistance to multiple antibiotics, rendering them ineffective. In this work, we show that these pathogens sense natural light and respond to it by modulating aspects related to their ability to cause disease; in the presence of light, some of them become more aggressive, while others show an opposite response. Overall, we provide new understanding on the behavior of these pathogens, which could contribute to the control of infections caused by them. Since the response is distributed in diverse pathogens, this notion could prove a general concept.
The Poiano karst spring is located in the North Apennines (Italy) and it drains Triassic evaporite rocks with a mean discharge of hundreds of liters/second. Two hydrogeological conceptual models have ...been proposed (and published) for the spring based on tracer tests. Both models highlighted the contribution of the local streams to recharge of the karst aquifer system, through sinking-stream processes, as well as recharge through rainfall; however, those studies differed in the water courses selected to monitor the recharge processes. The aim of the present research is to increase knowledge about the groundwater recharge processes of the Poiano karst spring with new surveys and analyses, resulting in a large dataset of temporal water stable isotope analyses (δ
18
O, δ
2
H), temporal stream discharge measurements, and temporal water tritium isotope data (T). A new hydrogeological conceptual model for the Poiano karst spring is proposed, within which a new list of streams becomes involved in the recharge-processes model based on different sources of water. In addition, the research identifies and confirms the occurrence of groundwater flow processes inside the karst system, such as the piston effect.
HIV-exposed uninfected infants (HEU) have increased morbidity and mortality due to infections in the first 6 months of life that tapers down to 2 years of life. The underlying immunologic defects ...remain undefined. We investigated antigen-presenting cells (APC) by comparing the phenotype of unstimulated APC, responses to toll-like receptor (TLR) stimulation, and ability to activate natural killer (NK) cells in 24 HEU and 64 HIV-unexposed infants (HUU) at 1-2 days of life (birth) and 28 HEU and 45 HUU at 6 months of life. At birth, unstimulated APC showed higher levels of activation and cytokine production in HEU than HUU and stimulation with TLR agonists revealed lower expression of inflammatory cytokines and activation markers, but similar expression of IL10 regulatory cytokine, in APC from HEU compared to HUU. Differences were still present at 6 months of life. From birth to 6 months, APC underwent extensive phenotypic and functional changes in HUU and minimal changes in HEU. TLR stimulation also generated lower NK cell expression of CD69 and/or IFNγ in HEU compared with HUU at birth and 6 months.
experiments showed that NK IFNγ expression depended on APC cytokine secretion in response to TLR stimulation.
IL10 supplementation decreased APC-mediated NK cell activation measured by IFNγ expression. We conclude that APC maturation was stunted or delayed in the first 6 months of life in HEU compared with HUU. Deficient inflammatory APC responses and/or the imbalance between inflammatory and regulatory responses in HEU may play an important role in their increased susceptibility to severe infections.
The combined use of hydrogeological and hydrogeochemical methods can provide relevant information about the characteristics of aquifers in studies focused on groundwater protection and management. In ...the present study, spring discharge monitoring coupled with stable and unstable water isotopes was used to compare the behaviour of adjacent fractured and porous aquifers hosted in a 4.5 km
2
area along the same slope in the northern Apennines, Italy. Based on stable isotope analyses of four springs, a plausible local meteoric water line and a local vertical isotopic gradient were identified. Additionally, tritium contents revealed a recent meteoric origin for groundwater via infiltration in the area. The results of monthly stable isotope monitoring, hourly spring discharge monitoring, hourly rainfall monitoring, and statistical analyses (time series analysis) suggested that although the adjacent aquifers exhibited pronounced geological and hydrogeological differences, few discrepancies were observed regarding groundwater infiltration and release processes. Notably, they exhibited similar temporal delays associated with the response to precipitation events due to the roles of macro-fractures and macro-porosity. Groundwater circulation was characterized by piston and memory effects in both the fractured and porous aquifers, and these effects reflect the roles of micro-fractures/fissures and micro-porosity. The study highlights the relevant contributions of isotopes in studies that focus on spring vulnerability and aquifer processes. Moreover, results obtained in the Pietra di Bismantova site are useful to increase hydrological knowledge on the quite relevant aquifers hosted in Epi-ligurian rock slabs and the surrounding slope deposits in the northern Apennines of Italy.
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