Delay In Maturation Research Articles

Advances in Understanding the Relationship between Sleep and Attention Deficit-Hyperactivity Disorder (ADHD).

Starting from the consolidated relationship between sleep and cognition, we reviewed the available literature on the association between Attention Deficit-Hyperactivity Disorder (ADHD) and sleep. This review analyzes the macrostructural and microstructural sleep features, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria (PRISMA). We included the polysomnographic studies published in the last 15 years. The results of macrostructural parameters are mixed. Almost half of the 18 selected investigations did not find differences between sleep architecture of children with ADHD and controls. Five studies observed that children with ADHD show a longer Rapid Eye Movement (REM) sleep duration than controls. Eight studies included microstructural measures. Remarkable alterations in sleep microstructure of ADHD are related to slow wave activity (SWA) and theta oscillations, respectively, during Non-REM (NREM) and REM sleep. Specifically, some studies found higher SWA in the ADHD group than controls. Similarly, higher theta activity appears to be detrimental for memory performance and inhibitory control in ADHD. These patterns could be interpreted as a maturational delay in ADHD. Also, the increased amount of these activities would be consistent with the hypothesis that the poor sleep could imply a chronic sleep deprivation in children with ADHD, which in turn could affect their cognitive functioning.

Bistable Wave Fronts in a Stage-Structured Reaction–Diffusion Model for a Single Species with Distributed Maturation Delay

This paper is concerned with bistable wave fronts in a class of nonlocal reaction diffusion model for a single species with stage structure and distributed maturation delay. By choosing the strong and weak kernel functions to transform system with delays to a two- or three-dimensional system without any delays, the existence of traveling wave fronts is established by abstract results. Then we prove the asymptotic stability (up to translation) of bistable wave fronts and the uniqueness of wave speeds by spectral analysis and upper and lower solution technique, respectively. At last, we apply these results to a single species model with special nonlinearity.

Delay growth model augmented with physical and human capitals

Abstract A growth model with a special production function augmented with physical capital and human capital is modified and used to explain the birth of cyclical dynamics. Crucial feature of the model is the assumption that there are a gestation delay and a maturation delay in constructing physical capital and human capital, respectively. Dynamics is described by a continuous time system of delay differential equations. Stability switching curves and directions of stability switches are analytically derived where stability of the model might be lost and regained. Its shape is numerically verified and it is confirmed that the two-delay model can generate a wide variety of dynamics from simple dynamics to complex dynamics.

Tank contamination with dicamba and 2,4-D influences dry edible bean

AbstractThe occurrence of herbicide tank contamination with dicamba or 2,4-D will likely increase with the recent commercialization of dicamba- and 2,4-D-resistant soybean. High-value sensitive crops, including dry bean, will be at higher risks for exposure. In 2017 and 2018, two separate field experiments were conducted in Michigan to understand how multiple factors may influence dry bean response to dicamba and 2,4-D herbicides, including 1) the interaction between herbicides applied POST to dry bean and dicamba or 2,4-D, and 2) the impact of low rates of glyphosate with dicamba or 2,4-D. Dry bean injury was 20% and 2% from POST applications of dicamba (5.6 h ae ha−1) and 2,4-D (11.2 g ae ha−1), respectively, 14 days after treatment (DAT). The addition of glyphosate (8.4 g ae ha−1) did not increase dry bean injury from dicamba or 2,4-D. Over 2 site-years the addition of dry bean herbicides to dicamba or dicamba + glyphosate (8.4 g ae ha−1) increased dry bean injury and reduced yield by 6% to 10% more than when dicamba or dicamba + glyphosate was applied alone. The interaction between 2,4-D (11.2 g ae ha−1) and dry bean herbicides was determined to be synergistic. However, 2,4-D (11.2 g ae ha−1) had little effect on dry bean with or without the addition of a dry bean herbicide program. These studies document that synergy also occurs between dicamba and dicamba + glyphosate and both common dry bean herbicide programs tested: 1) imazamox (35 g ha−1) + bentazon (560 g ha−1), and 2) fomesafen (280 g ha−1). The synergy between dry bean herbicide and dicamba and dicamba + glyphosate can increase plant injury, delay maturity, and reduce yield to a greater extent than dicamba or dicamba + glyphosate alone. This work emphasizes the need to properly clean out sprayers after applications of dicamba to reduce the risk of exposure to other crops.

Sensitivity of dry edible bean to dicamba and 2,4-D

AbstractDicamba and 2,4-D exposure to sensitive crops, such as dry bean, is of great concern with the recent registrations of dicamba- and 2,4-D–resistant soybean. In 2017 and 2018, field experiments were conducted at two Michigan locations to understand how multiple factors, including dry bean market class, herbicide rate, and application timing, influence dry bean response to dicamba and 2,4-D. Dicamba and 2,4-D at rates of 0.1%, 1%, and 10% of the field use rate for dicamba and 2,4-D choline were applied to V2 and V8 black and navy bean. Field-use rates for dicamba and 2,4-D choline were 560 and 1,120 g ae ha−1, respectively. There were few differences between market classes or application timings when dry bean was exposed to dicamba or 2,4-D. Estimated rates to cause 20% dry bean injury 14 d after treatment were 4.5 and 107.5 g ae ha−1 for dicamba and 2,4-D, respectively. When dicamba was applied at 56 g ae ha−1, light interception was reduced up to 51% and maturity was delayed up to 16 d. Although both herbicides caused high levels of injury to dry bean, yield reductions were not consistently observed. At four site-years, 2,4-D did not reduce dry bean yield or seed weight with any rate tested. However, when averaged over site-years, dicamba rates of 3.7, 9.8 and 17.9 g ae ha−1 were estimated to cause 5%, 10%, and 15% yield loss, respectively. Dicamba also reduced seed weight by 10% when 56 g ae ha−1 was applied. However, the germination of harvested seed was not affected by dicamba or 2,4-D. Long delays in dry bean maturity from dicamba injury can also indirectly increase losses in yield and quality due to harvestability issues. This work further stresses the need for caution when using dicamba or 2,4-D herbicides near sensitive crops.

A West Nile Virus Model with Vertical Transmission and Periodic Time Delays

Seasonal change has played a critical role in the evolution dynamics of West Nile virus transmission. In this paper, we formulate and analyze a novel delay differential equation model, which incorporates seasonality, the vertical transmission of the virus, the temperature-dependent maturation delay and the temperature-dependent extrinsic incubation period in mosquitoes. We first introduce the basic reproduction ratio $$R_0$$ for this model and then show that the disease is uniformly persistent if $$R_0>1$$. It is also shown that the disease-free periodic solution is attractive if $$R_0<1$$, provided that there is only a small invasion. In the case where all coefficients are constants and the disease-induced death rate of birds is zero, we establish a threshold result on the global attractivity in terms of $$R_0$$. Numerically, we study the West Nile virus transmission in Orange County, California, USA.

Microglia Regulate Pruning of Specialized Synapses in the Auditory Brainstem.

The assembly of uniquely organized sound localization circuits in the brainstem requires precise developmental mechanisms. Glial cells have been shown to shape synaptic connections in the retinogeniculate system during development, but their contributions to specialized auditory synapses have not been identified. Here we investigated the role of microglia in auditory brainstem circuit assembly, focusing on the formation and pruning of the calyx of Held in the medial nucleus of the trapezoid body (MNTB). Microglia were pharmacologically depleted in mice early in development using subcutaneous injections of an inhibitor of colony stimulating factor 1 receptor, which is essential for microglia survival. Brainstems were examined prior to and just after hearing onset, at postnatal days (P) 8 and P13, respectively. We found that at P13 there were significantly more polyinnervated MNTB neurons when microglia were depleted, consistent with a defect in pruning. Expression of glial fibrillary acidic protein (GFAP), a mature astrocyte marker that normally appears in the MNTB late in development, was significantly decreased in microglia-depleted mice at P13, suggesting a delay in astrocyte maturation. Our results demonstrate that monoinnervation of MNTB neurons by the calyx of Held is significantly disrupted or delayed in the absence of microglia. This finding may reflect a direct role for microglia in synaptic pruning. A secondary role for microglia may be in the maturation of astrocytes in MNTB. These findings highlight the significant function of glia in pruning during calyx of Held development.

Cortical development in fetuses with congenital heart defects using an automated brain-age prediction algorithm.

Congenital heart defects are associated with neurodevelopmental delay. It is hypothesized that fetuses affected by congenital heart defect have altered cerebral oxygen perfusion and are therefore prone to delay in cortical maturation. The aim of this study was to determine the difference in fetal brain age between consecutive congenital heart defect cases and controls in the second and third trimester using ultrasound. Since 2014, we have included 90 isolated severe congenital heart defect cases in the Heart And Neurodevelopment (HAND)-study. Every 4weeks, detailed neurosonography was performed in these fetuses, including the recording of a 3D volume of the fetal brain, from 20weeks onwards. In all, 75 healthy fetuses underwent the same protocol to serve as a control group. The volumes were analyzed by automated age prediction software which determines gestational age by the assessment of cortical maturation. In total, 477 volumes were analyzed using the age prediction software (199 volumes of 90 congenital heart defect cases; 278 volumes of 75 controls). Of these, 16 (3.2%) volume recordings were excluded because of imaging quality. The age distribution was 19-33weeks. Mixed model analysis showed that the age predicted by brain maturation was 3days delayed compared with the control group (P=.002). This study shows that fetuses with isolated cases of congenital heart defects show some delay in cortical maturation as compared with healthy control cases. The clinical relevance of this small difference is debatable. This finding was consistent throughout pregnancy and did not progress during the third trimester.

Shooting a high-density electroencephalographic picture on sleep in children with attention-deficit/hyperactivity disorder.

Sleep-related slow-wave activity (SWA) has been recognized as a marker of synaptic plasticity. In children affected by attention deficit hyperactivity disorder (ADHD), SWA is mainly located in the central rather than frontal regions, reflecting a maturational delay. A detailed subjective and objective sleep investigation, including a full night video-polysomnography (PSG-HD-EEG), was performed on 30 consecutive drug naïve outpatients with a diagnosis of ADHD. They received a diagnosis of sleep disorders in 29/30 cases, and most of them had a past history of sleep problems. They had a higher apnea-hypopnea index at PSG, and slept less than 9 hr at actigraphy. We aimed to describe the SWA behavior in the same group of children with ADHD. The full-night PSG-HD EEG of children with ADHD was compared with the one of the 25 healthy controls. The scalp SWA mapping, the decrease of SWA during the night, and the EEG source of SWA were analyzed. At scalp topography, the focus of SWA was observed over the centro-parietal-occipital regions in participants with ADHD (p < 0.01), which remained significant in the subgroups divided between subgroups according to the sleep diagnosis (p < 0.01). The physiological decrease in SWA was more evident in control participants. The source analysis revealed a greater delta power over the posterior cingulate in participants with ADHD (p < 0.01). Our results confirm static and dynamic changes in SWA behavior in children with ADHD, which may reflect a maturational delay occurring at a vulnerable age, as a consequence of chronic sleep deprivation.

Diffusive spatial movement with memory and maturation delays

A single species spatial population model that incorporates Fickian diffusion, memory-based diffusion, and reaction with maturation delay is formulated. The stability of a positive equilibrium and the crossing curves in the two-delay parameter plane on which the characteristic equation has purely imaginary roots are studied. With Neumann boundary condition, the crossing curve that separates the stable and unstable regions of the equilibrium may consist of two components, where spatially homogeneous and inhomogeneous periodic solutions are generated through Hopf bifurcation respectively. This phenomenon rarely emerges from standard partial functional differential equations with Neumann boundary condition, which indicates that the memory-based diffusion can induce more complicated spatiotemporal dynamics.

The effect of nitrogen fertilization on the incidence of olive fruit fly, olive leaf spot and olive anthracnose in two olive cultivars grown in rainfed conditions

Pests and diseases can cause significant loss of olive yield and/or justify control measures with pesticides which are harmful to the environment. Several agroecological variables, such as fertilization, can favour or limit the incidence of pests and diseases. However, in olive, few studies exist on the subject than can assist in the implementation of more sustainable phytosanitary measures. In this study the effect of nitrogen fertilization (0, 20, 40 and 120 kg N ha−1) on the incidence of olive fruit fly (Bactrocera oleae), olive leaf spot (Spilocaea oleaginea) and olive anthracnose (Colletotrichum gloeosporioides) was evaluated in two olive orchards of the cultivars ‘Cobrançosa’ and ‘Madural’. The study took place in 2017 and 2018 in Lombo, NE Portugal. Nitrogen fertilization significantly increased olive yield and nitrogen concentrations in plant tissues and induced a delay in fruit maturity. The incidence of the olive fruit fly was significantly lower in the more fertilized treatments of both cultivars. However, ‘Madural’ showed itself to be more susceptible than ‘Cobrançosa’ to olive fruit fly. The effect of nitrogen on the reduction of the incidence of the olive fruit fly was attributed to the delay caused in fruit maturation, which might have desynchronized the attractiveness of the fruits for insects to lay their eggs on their flight curve. In contrast, olive leaf spot and olive anthracnose were not influenced by nitrogen fertilization. As a result, nutrient management in olive groves must balance carefully the requirements of economic rationality with environmental preservation, particularly with regard to the harmful relationship between the use of excessive nitrogen rates and several adverse environmental effects.

R0 and sensitivity analysis of a predator-prey model with seasonality and maturation delay

Coexistence and seasonal fluctuations of predator and prey populations are common and well documented in ecology. Under what conditions can predators coexist with prey in a seasonally changing environment? What factors drive long-term population cycles of some predator and prey species? To answer these questions, we investigate an improved predator-prey model based on the Rosenzweig–MacArthur [1] model. Our model incorporates seasonality and a predator maturation delay, leading to a system of periodic differential equations with a time delay. We define the basic reproduction ratio R0 and show that it is a threshold parameter determining whether the predators can coexist with the prey. We show that if R0 < 1, then the prey population has seasonal variations and the predator population goes extinct. If R0 > 1, then the prey and the predators coexist and fluctuate seasonally. As an example, we study a Daphnia-algae system and explore possible mechanisms for seasonal population cycles. Our numerical simulations indicate that seasonal Daphnia-algae cycles are attributed to seasonality rather than Daphnia maturation delay or Daphnia-algae interaction. The Daphnia maturation delay, the amplitude of algae growth rate and the amplitude of the carrying capacity are found to affect the amplitude of cycles and average population levels. Our sensitivity analysis shows that R0 is most sensitive to Daphnia death rate.

Long-term exposure to moderate noise induces neural plasticity in the infant rat primary auditory cortex

ABSTRACTPrevious studies have reported that rearing infant rat pups in continuous moderate-level noise delayed the formation of topographic representational order and the refinement of response selectivity in the primary auditory (A1) cortex. The present study further verified that exposure to long-term moderate-intensity white noise (70 dB sound pressure level) from postnatal day (P) 12 to P30 elevated the hearing thresholds of infant rats. Compared with age-matched control rats, noise exposure (NE) rats had elevated hearing thresholds ranging from low to high frequencies, accompanied by decreased amplitudes and increased latencies of the two initial auditory brainstem response waves. The power of raw local field potential oscillations and high-frequency β oscillation in the A1 cortex of NE rats were larger, whereas the power of high-frequency γ oscillation was smaller than that of control rats. In addition, the expression levels of five glutamate receptor (GluR) subunits in the A1 cortex of NE rats were decreased with laminar specificity. These results suggest that the altered neural excitability and decreased GluR expression may underlie the delay of functional maturation in the A1 cortex, and may have implications for the treatment of hearing impairment induced by environmental noise.

The Genetic Basis of Delayed Puberty.

Delayed pubertal onset has many etiologies, but on average two-thirds of patients presenting with late puberty have self-limited (or constitutional) delayed puberty. Self-limited delayed puberty often has a strong familial basis. Segregation analyses from previous studies show complex models of inheritance, most commonly autosomal dominant, but also including autosomal recessive, bilineal, and X-linked. Sporadic cases are also observed. Despite this, the neuroendocrine mechanisms and genetic regulation remain unclear in the majority of patients with self-limited delayed puberty. Only rarely have mutations in genes known to cause aberrations of the hypothalamic-pituitary-gonadal axis been identified in cases of delayed puberty, and the majority of these are in relatives of patients with congenital hypogonadotropic hypogonadism (CHH), for example in the FGFR1 and GNRHR genes. Using next generation sequencing in a large family with isolated self-limited delayed puberty, a pathogenic mutation in the CHH gene HS6ST1 was found as the likely cause for this phenotype. Additionally, a study comparing the frequency of mutations in genes that cause GnRH deficiency between probands with CHH and probands with isolated self-limited delayed puberty identified that a significantly higher proportion of mutations with a greater degree of oligogenicity were seen in the CHH group. Mutations in the gene IGSF10 have been implicated in the pathogenesis of familial late puberty in a large Finnish cohort. IGSF10 disruption represents a fetal origin of delayed puberty, with dysregulation of GnRH neuronal migration during embryonic development presenting for the first time in adolescence as late puberty. Some patients with self-limited delayed puberty have distinct constitutional features of growth and puberty. Deleterious variants in FTO have been found in families with delayed puberty with extremely low BMI and maturational delay in growth in early childhood. Recent exciting evidence highlights the importance of epigenetic up-regulation of GnRH transcription by a network of miRNAs and transcription factors, including EAP1, during puberty. Whilst a fascinating heterogeneity of genetic defects have been shown to result in delayed and disordered puberty, and many are yet to be discovered, genetic testing may become a realistic diagnostic tool for the differentiation of conditions of delayed puberty.

The value of ABR- and ASSR-based hearing estimation in young children with congenital monaural malformation (atresia)

Background: The electrophysiology of auditory nerve mature is particularly important for unilateral hearing loss.Objectives: To assess the hearing status in young children with congenital monaural malformation and evaluate their potential for practical use in the functional maturation parameters of the auditory pathway.Materials and methods: ABR (auditory brainstem responses) and ASSR (auditory steady-state responses) threshold measurements were performed in 21 young children with congenital monaural atresia.Results: The average electrophysiologic thresholds for the ABR were 65 dB nHL ± 1.20 in malformed ears and 25 dB nHL ± 0.48 in normal ones. All 21 atretic ears presented with typical conductive hearing loss. There was no statistic positive correlation in hearing-impaired ears between the methods of ABR and ASSR responses (r = 0.12, 0.20 and 0.17). The IPL (interpeak latency) of I–III, III–V and I–V of atretic ears in ABR test was decreased relative to normal ears. Furthermore, a shortening of the IPLs I–III, III–V, I–V can be observed with increasing age of the children in malformed ears.Conclusions and significance: The ABR- and ASSR-based hearing evaluation in young children with congenital monaural malformation should be viewed as complementary technologies. Besides, there was no delay of functional maturation at brainstem level although unilateral hearing was deprived during their early years of life.

Periodic Phenomena and Driving Mechanisms in Transmission of West Nile Virus with Maturation Time

West Nile virus (WNv) transmission shows both seasonal pattern in every single year and cyclic pattern over years. In this paper we formulate a compartmental model with bird demographics and maturation time of mosquitoes during metamorphosis to study the impact of ambient temperature on the transmission and recurrence of disease. We show that avian birds serve as a reservoir of viruses, whilst maturation time affects disease transmission in sophisticated ways. It turns out that large maturation delay will lead to the extinction of mosquitoes and the disease; small maturation delay will stabilize the epidemic level of the disease; and intermediate maturation delay will cause sustainable oscillations of mosquito population, recurrence of diseases, and even mixed-mode oscillation of diseases with an alternation between oscillations of distinct large and small amplitudes. With bifurcation theory, we prove that temperature can drive the oscillation of mosquito population, which leads recurrence of WNv through the incidence interaction between mosquitoes and hosts, while the biting and transmission process itself will not generate sustained oscillations. Our results provide a sound explanation for understanding interactions between vectors and hosts, and driving mechanisms of periodic phenomena in the transmission of WNv and other mosquito-borne diseases.

PF570 CARFILZOMIB TREATMENT CAUSES RETICULOCYTOSIS BY IMPAIRING TERMINAL ERYTHROID MATURATION IN PATIENTS WITH MULTIPLE MYELOMA

Background:The ubiquitin‐proteasome system (UPS) is crucial for cellular protein homeostasis by ensuring the degradation of redundant or misfolded proteins. In addition to its pleiotropic effects, the UPS also plays an important role in different steps of erythropoiesis. Proteasome inhibition constitutes one of the cornerstones of current multiple myeloma (MM) treatment, with three proteasome inhibitors (PI) approved for clinical use, including the reversible proteasome inhibitors (PI) bortezomib, ixazomib and irreversible PI carfilzomib. Based on a clinical observation of increased reticulocyte counts in patients with MM under treatment with carfilzomib, we hypothesized that PI can affect erythroid maturation.Aims:To address the effects of PIs on erythroid differentiation and maturation.Methods:We first retrospectively assessed the effect of carfilzomib treatment on the red cell parameters in 40 patients treated with a carfilzomib‐based regimen (carfilzomib‐dexamethasone (Kd) or carfilzomib‐lenalidomide‐dexamethasone (KRd)). Data were compared to matched cohorts of patients treated with bortezomib and the immunomodulatory drug (IMiD) lenalidomide. To address the effect of PI on erythroid differentiation in vitro, we differentiated CD34+ hematopoietic progenitor cells (HPC) into erythroid cells as previously described by the Douay group (Nature Biotechnology, 2002) in the presence of carfilzomib. To evaluate the effect of PI on terminal erythroid maturation, we purified reticulocytes from the peripheral blood of healthy volunteers, and performed ex vivo maturation in the presence the of PIs carfilzomib, bortezomib, ixazomib and MG‐132. Finally, we performed a quantitative proteomics analysis using liquid chromotrography‐mass spectrometry (LC‐MS/MS) on maturing reticulocytes to identify proteins involved in erythroid maturation.Results:We observed a specific and highly significant increase in the reticulocyte count (p &lt; 0.001) during treatment with carfilzomib‐based regimens in patients with relapsed MM, an observation not made in a matched cohort of bortezomib‐ or lenalidomide‐treated patients. Surprisingly, this reticulocytosis was neither associated with improved hemoglobin levels nor with hemolysis. Moreover, carfilzomib treatment was not associated with increased EPO levels. Subsequent in vitro experiments demonstrated that carfilzomib did not alter the proportion of mature erythroid cells that were produced in vitro during differentiation experiments starting from CD34+ HPCs. In contrast, both continuous and pulse exposure to carfilzomib significantly impaired the terminal maturation of purified reticulocytes toward mature erythrocytes (p &lt; 0.01). A similar effect could only be observed with reversible PI during continuous, but not during short‐term exposure. Subsequent quantitative proteomics analysis identified the RNA‐stabilizing protein PABPC1 as a candidate regulator of mRNA stabilization in terminal erythroid maturation.Summary/Conclusion:Our results indicate that proteasome inhibition with carfilzomib causes a delay of terminal erythroid maturation, which might be explained by increased mRNA stabilization through PABPC1 upregulation. This not only demonstrates the first pharmacologically induced delay in erythroid maturation but also provides new insights on physiological erythroid maturation. Moreover, delayed reticulocyte maturation should be considered as a differential diagnosis, aside from hemolytic anemia, in MM patients treated with carfilzomib.

Usulan Perbaikan Sistem Untuk Meningkatkan Kualitas Layanan Sistem Administrasi Gudang Online (AGO) Menggunakan Standar ISO/IEC 9126 di PT. PLN (Persero) Rayon Duri

In building a system, it was needed a quality guarantee. A system could be stated well qualified, if it met the user needs. The quality could be measured from various points of views. One point of views to measure the software quality was focusing on user satisfaction (user based). To know the quality of a system, it was needed a quality analysis of its system. There was a lack of service when online warehouse administration system used to manage the warehouse material inventory in PT. PLN (Persero) Duri Rayon was used. This research aimed at finding proposed improvements for increasing the service quality percentage of online warehouse administration system based on ISO/IEC 9126 standard. The methods of collecting the data were using interview and questionnaire to know user complaints to the user. Maturity Model and Delay approaches were used to process the data. In testing the reliability level, online warehouse administration system was on the first level (the system was computerized, but it was not standardized yet). In testing the delay, all the delays in input were on good category and it could beunderstandable. Based on the levels of maturity and delay, the test showed that there was a need to improve and maintenance the online warehouse administration system to increase the performance of system service quality for users. so that the existence of repairs and maintenance systems can increase 26% to 41% the percentage of the quality of an information technology system.

In Vitro Performance of Bioinspired Phenolic Nanocoatings for Endosseous Implant Applications.

In the quest for finding new strategies to enhance tissue integration and to reduce the risk of bacterial colonization around endosseous implants, we report the application of auto-oxidative phenolic coatings made of tannic acid and pyrogallol to titanium surfaces. The functionalized surfaces were screened for their biological performance using cultures of primary human osteoblasts and biofilm-forming bioluminescent staphylococci S. epidermidis Xen43 and S. aureus Xen29. No toxic effect of the coatings on osteoblasts was detected. While tannic acid coatings seemed to induce a delay in osteoblast maturation, they revealed anti-inflammatory potential. Similar effects were observed for pyrogallol coatings deposited for 24 h. Thin pyrogallol coatings deposited for 2 h seemed to promote osteoblast maturation and revealed increased calcium deposition. The effects on osteoblast were found to be related to the release of phenolic compounds from the surfaces. While the phenolic coatings could not inhibit staphylococcal biofilm formation on the titanium surfaces, released phenolic compounds had an inhibitory effect the growth of planktonic bacteria. In conclusion, the assessed coating systems represent a versatile functionalization method which exhibit promising effects for endosseous implant applications.

Phenotype and functions of human dendritic cells derived from CD14+ monocyte subsets opposed to CD16 expression

The aim of the study was to analyze the relationship between monocyte subpopulations and phenotype/ functions of monocyte-derived dendritic cells (DCs), as well as DC sensitivity to the tolerogenic effect of dexamethasone.Materials and methods. The study included 15 healthy donors. DCs were generated by cultivating enriched fractions of CD14+ monocytes with or without CD16+cell depletion (CD16-Mo-DCs or CD16+Mo-DCs, respectively) in the presence of interferon alpha (IFNα) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte subpopulations were obtained by immunomagnetic negative selection.Results. CD16+Mo-DCs were characterized by higher percentage of mature (CD83+CD14-) and lower number of semi-mature (CD14+CD83+) cells, but were similar to CD16-Mo-DCs by HLA-DR and CD86 expression, involved in the presentation of antigens and activation of naive T-cells. and also to co-inhibitory/ tolerogenic molecules B7-H1 and TLR-2. CD16+Mo-DCs displayed higher allostimulatory activity, which was positively correlated with CD86 expression (rS = 0.69; p = 0.027) and negatively – with TLR-2 expression (rS = -0.72; p = 0.1). Allostimulatory activity of CD16-Mo-DCs was positively correlated with the number of mature CD14-CD83+DCs and semi-mature CD14+CD83+DCs. Addition of dexamethasone (10-6 M) into CD16-Mo-DCs and CD16+Mo-DCs cultures led to the delay of DC maturation, the decrease of CD86 and the increase of TLR-2 expression, as well as the increase of cells with co-inhibitory CD86- B7-H1+ phenotype that was positively correlated with the reduction of DC allostimulatory activity. The decrease of CD86+/TLR-2+ index in CD16+Mo-DC population was due to the reduction of CD86+DCs and in CD16-Mo-DC population – to the increase of TLR-2+cells. Dexamethasone possessed higher inhibitory effect on DC maturation in the CD16+Mo-DC cultures.Conclusion. CD14+ monocytes, both contained and depleted by CD16+ cells, can differentiate into DCs when cultured with IFNα. The presence of CD16+ cells in whole blood monocyte pool is associated with generation of DCs showed a more mature phenotype and higher allostimulatory activity. Both CD16- and CD16+ monocyte-derived DCs are sensitive to suppressive effect of dexamethasone. However, dexamethasone tolerogenic effect involves different mechanisms in CD16-Mo-DCs and CD16+Mo-DCs.