67 research outputs found
Defining the healthy "core microbiome" of oral microbial communities
<p>Abstract</p> <p>Background</p> <p>Most studies examining the commensal human oral microbiome are focused on disease or are limited in methodology. In order to diagnose and treat diseases at an early and reversible stage an in-depth definition of health is indispensible. The aim of this study therefore was to define the healthy oral microbiome using recent advances in sequencing technology (454 pyrosequencing).</p> <p>Results</p> <p>We sampled and sequenced microbiomes from several intraoral niches (dental surfaces, cheek, hard palate, tongue and saliva) in three healthy individuals. Within an individual oral cavity, we found over 3600 unique sequences, over 500 different OTUs or "species-level" phylotypes (sequences that clustered at 3% genetic difference) and 88 - 104 higher taxa (genus or more inclusive taxon). The predominant taxa belonged to Firmicutes (genus <it>Streptococcus</it>, family <it>Veillonellaceae</it>, genus <it>Granulicatella</it>), Proteobacteria (genus <it>Neisseria</it>, <it>Haemophilus</it>), Actinobacteria (genus <it>Corynebacterium</it>, <it>Rothia</it>, <it>Actinomyces</it>), Bacteroidetes (genus <it>Prevotella</it>, <it>Capnocytophaga, Porphyromonas</it>) and Fusobacteria (genus <it>Fusobacterium</it>).</p> <p>Each individual sample harboured on average 266 "species-level" phylotypes (SD 67; range 123 - 326) with cheek samples being the least diverse and the dental samples from approximal surfaces showing the highest diversity. Principal component analysis discriminated the profiles of the samples originating from shedding surfaces (mucosa of tongue, cheek and palate) from the samples that were obtained from solid surfaces (teeth).</p> <p>There was a large overlap in the higher taxa, "species-level" phylotypes and unique sequences among the three microbiomes: 84% of the higher taxa, 75% of the OTUs and 65% of the unique sequences were present in at least two of the three microbiomes. The three individuals shared 1660 of 6315 unique sequences. These 1660 sequences (the "core microbiome") contributed 66% of the reads. The overlapping OTUs contributed to 94% of the reads, while nearly all reads (99.8%) belonged to the shared higher taxa.</p> <p>Conclusions</p> <p>We obtained the first insight into the diversity and uniqueness of individual oral microbiomes at a resolution of next-generation sequencing. We showed that a major proportion of bacterial sequences of unrelated healthy individuals is identical, supporting the concept of a core microbiome at health.</p
Classification of Quantitative Light-Induced Fluorescence Images Using Convolutional Neural Network
Images are an important data source for diagnosis and treatment of oral
diseases. The manual classification of images may lead to misdiagnosis or
mistreatment due to subjective errors. In this paper an image classification
model based on Convolutional Neural Network is applied to Quantitative
Light-induced Fluorescence images. The deep neural network outperforms other
state of the art shallow classification models in predicting labels derived
from three different dental plaque assessment scores. The model directly
benefits from multi-channel representation of the images resulting in improved
performance when, besides the Red colour channel, additional Green and Blue
colour channels are used.Comment: Full version of ICANN 2017 submissio
A polymeric colchicinoid prodrug with reduced toxicity and improved efficacy for vascular disruption in cancer therapy
Colchicinoids are very potent tubulin-binding compounds, which interfere with microtubule formation, giving them strong cytotoxic properties, such as cell mitosis inhibition and induction of microcytoskeleton depolymerization. While this makes them promising vascular disrupting agents (VDAs) in cancer therapy, their dose-limiting toxicity has prevented any clinical application for this purpose. Therefore, colchicinoids are considered attractive lead molecules for the development of novel vascular disrupting nanomedicine. In a previous study, a polymeric colchicinoid prodrug that showed favorable hydrolysis characteristics at physiological conditions was developed. In the current study, this polymeric colchicinoid prodrug was evaluated in vitro and in vivo for its toxicity and vascular disrupting potential. Cell viability studies with human umbilical vein endothelial cells, as an in vitro measure for colchicine activity, reflected the degradation kinetics of the prodrug accordingly. Upon intravenous treatment, in vivo, of B16F10 melanoma-bearing mice with colchicine or with the polymeric colchicinoid prodrug, apparent vascular disruption and consequent tumor necrosis was observed for the prodrug but not for free colchicine at an equivalent dose. Moreover, a five-times-higher dose of the prodrug was well tolerated, indicating reduced toxicity. These findings demonstrate that the polymeric colchicinoid prodrug has a substantially improved efficacy/toxicity ratio compared with that of colchicine, making it a promising VDA for cancer therapy
Π’Π΅ΠΎΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΎΡΠ΅Π½ΠΊΠ° ΡΠ°Π·ΡΠ΅ΡΠ°ΡΡΠ΅ΠΉ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΏΡΠ΅ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ ΠΡΠ°ΡΡΠΌΠ°Π½Π° Π² ΡΠΈΡΡΠ΅ΠΌΠ°Ρ ΠΊΠΎΠ΄ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠ²Π΅ΡΠ°, ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΠΌΡΡ Π² Π°Π²ΠΈΠΎΠ½ΠΈΠΊΠ΅
Π Π°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°Π΅ΡΡΡ Π·Π°Π΄Π°ΡΠ° ΠΎΡΠ΅Π½ΠΊΠΈ ΡΠ°Π·ΡΠ΅ΡΠ°ΡΡΠ΅ΠΉ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ ΠΡΠ°ΡΡΠΌΠ°Π½Π°, ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠ΅Π³ΠΎ ΠΊΠΎΠΎΡΠ΄ΠΈΠ½Π°ΡΡ ΡΠ²Π΅ΡΠ½ΠΎΡΡΠΈ Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
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ΠΊΠΎΠ΄ΠΈΡΠΎΠ²Π°Π½ΠΈΡ: RGB ΠΈ XY. ΠΡΠΈΠ²ΠΎΠ΄ΡΡΡΡ ΠΏΡΠΈΠΌΠ΅ΡΡ Π³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΠΉ ΡΠ²Π΅ΡΠΎΠ² ΠΈ ΠΎΡΡΠ΅Π½ΠΊΠΎΠ² Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΠΈΡΡΠ΅ΠΌΠ°Ρ
ΠΊΠΎΠ΄ΠΈΡΠΎΠ²Π°Π½ΠΈΡ. ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ Π²ΡΠ²ΠΎΠ΄ ΡΠΎΡΠΌΡΠ»Ρ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΠ°Π·ΡΠ΅ΡΠ°ΡΡΠ΅ΠΉ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΏΡΠ΅ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ ΠΡΠ°ΡΡΠΌΠ°Π½Π°, ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΡΡΠ΅ΠΉ Π²Π΅Π»ΠΈΡΠΈΠ½Ρ ΠΌΠΈΠ½ΠΈΠΌΠ°Π»ΡΠ½ΠΎ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠ³ΠΎ (Π½Π΅ Π½ΡΠ»Π΅Π²ΠΎΠ³ΠΎ) ΠΌΠΎΠ΄ΡΠ»Ρ Π΄ΠΈΡΠΊΡΠ΅ΡΠ° ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ (x,y)-ΠΊΠΎΠΎΡΠ΄ΠΈΠ½Π°Ρ ΡΠ²Π΅ΡΠ½ΠΎΡΡΠΈ ΠΏΠΎ ΠΎΡΡΠΌ XY ΠΏΡΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΈ ΠΊΠΎΠ΄Π° RGB Π½Π° ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ»ΡΠ½ΡΡ Π²Π΅Π»ΠΈΡΠΈΠ½Ρ ΠΏΠΎ Π»ΡΠ±ΠΎΠΌΡ ΠΈΠ· ΡΡΠ΅Ρ
ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ² R, G, B. Π Π°ΡΡΡΠΈΡΠ°Π½Ρ ΡΠΈΡΠ»ΠΎΠ²ΡΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΡΠ°Π·ΡΠ΅ΡΠ°ΡΡΠ΅ΠΉ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Ρ Π·Π½Π°ΡΠ΅Π½ΠΈΡ Π½Π°ΡΠ°Π»ΡΠ½ΡΡ
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ΠΊΠΎΠ΄ΠΎΠ² RGB, ΠΏΡΠΈ ΠΊΠΎΡΠΎΡΡΡ
Π΄ΠΎΡΡΠΈΠ³Π°Π΅ΡΡΡ ΠΌΠΈΠ½ΠΈΠΌΡΠΌ ΠΏΡΠΈΡΠ°ΡΠ΅Π½ΠΈΠΉ DΡ
, Dy Π΄Π»Ρ Π΅Π΄ΠΈΠ½ΠΈΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΈΡΠ°ΡΠ΅Π½ΠΈΡ ΠΊΠΎΠ΄Π° RGB ΠΈ Π²ΠΎΡΡΠΌΠΈΠ±ΠΈΡΠ½ΠΎΠ³ΠΎ ΠΊΠΎΠ΄ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΊΠ°ΠΆΠ΄ΠΎΠ³ΠΎ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ° R, G, B
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Macrophages support pathological erythropoiesis in Polycythemia Vera and Beta-Thalassemia
Regulation of erythropoiesis is achieved by integration of distinct signals. Among these, macrophages are emerging as erythropoietin-complementary regulators of erythroid development, particularly under stress conditions. We investigated the contribution of macrophages for physiological and pathological conditions of enhanced erythropoiesis. We utilized mouse models of induced anemia, Polycythemia vera and Ξ²-thalassemia in which macrophages were chemically depleted. Our data indicate that macrophages contribute decisively for recovery from induced anemia as well as the pathological progression of Polycythemia vera and Ξ²-thalassemia by modulating erythroid proliferation and differentiation. We validated these observations in primary human cultures, showing a critical direct impact of macrophages on proliferation and enucleation of erythroblasts from healthy individuals and Polycythemia vera or Ξ²-thalassemic patients. In summary, we identify a new mechanism that we named βStress Erythropoiesis Macrophage-supporting Activityβ (SEMA) that contributes to the pathophysiology of these disorders and will have critical scientific and therapeutic implications in the near future
A biodegradable antibiotic delivery system based on poly-(trimethylene carbonate) for the treatment of osteomyelitis
Background and purpose Many investigations on biodegradable materials acting as an antibiotic carrier for local drug delivery are based on poly(lactide). However, the use of poly(lactide) implants in bone has been disputed because of poor bone regeneration at the site of implantation. Poly(trimethylene carbonate) (PTMC) is an enzymatically degradable polymer that does not produce acidic degradation products. We explored the suitability of PTMC as an antibiotic releasing polymer for the local treatment of osteomyelitis
Exploring the oral microbiota of children at various developmental stages of their dentition in the relation to their oral health
<p>Abstract</p> <p>Background</p> <p>An understanding of the relation of commensal microbiota to health is essential in preventing disease. Here we studied the oral microbial composition of children (N = 74, aged 3 - 18 years) in natural transition from their deciduous to a permanent dentition and related the microbial profiles to their oral health status. The microbial composition of saliva was assessed by barcoded pyrosequencing of the V5-V6 hypervariable regions of the 16 S rRNA, as well as by using phylogenetic microarrays.</p> <p>Results</p> <p>Pyrosequencing reads (126174 reads, 1045 unique sequences) represented 8 phyla and 113 higher taxa in saliva samples. Four phyla - Firmicutes, Bacteriodetes, Proteobacteria and Actinobacteria - predominated in all groups. The deciduous dentition harboured a higher proportion of Proteobacteria (Gammaproteobacteria, Moraxellaceae) than Bacteroidetes, while in all other groups Bacteroidetes were at least as abundant as Proteobacteria. Bacteroidetes (mainly genus <it>Prevotella</it>), Veillonellaceae family, Spirochaetes and candidate division TM7 increased with increasing age, reflecting maturation of the microbiome driven by biological changes with age.</p> <p>Microarray analysis enabled further analysis of the individual salivary microbiota. Of 350 microarray probes, 156 gave a positive signal with, on average, 77 (range 48-93) probes per individual sample.</p> <p>A caries-free oral status significantly associated with the higher signal of the probes targeting <it>Porphyromonas catoniae </it>and <it>Neisseria flavescens</it>.</p> <p>Conclusions</p> <p>The potential role of <it>P. catoniae </it>and <it>N. flavescens </it>as oral health markers should be assessed in large-scale clinical studies. The combination of both, open-ended and targeted molecular approaches provides us with information that will increase our understanding of the interplay between the human host and its microbiome.</p
Seven-Valent Pneumococcal Conjugate Vaccine and Nasopharyngeal Microbiota in Healthy Children
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