The Effect of Photodynamic Therapy in Root Canal Disinfection: A Systematic Review

Introduction

Effective root canal disinfection is a fundamental component of successful root canal treatment. Photodynamic therapy (PDT) has been proposed as a new adjunctive method for additional disinfection of the root canal system with the possibility of improved treatment outcomes. The aim of this systematic review was to investigate the effect of PDT on bacterial load reduction during root canal disinfection.

Methods

Two reviewers independently conducted a comprehensive literature search using a combination of medical subject heading terms and key words to identify studies relevant to the Population Intervention Control Outcome question. The selection of articles for inclusion was performed in 2 phases based on predetermined eligibility criteria according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inter-reviewer agreement for each phase was recorded. The effect of PDT on bacterial load reduction during root canal disinfection was evaluated as the primary outcome variable during data extraction.

Results

The literature search provided 57 titles and abstracts. Three articles met the inclusion criteria and were selected for this systematic review. The reasons for study exclusion in each phase were recorded. Because of the heterogeneity in clinical indications and PDT protocols among the included studies, a meta-analysis could not be performed. All included studies showed a positive effect of PDT in the reduction of microbial load in root canal treatment ranging from 91.3%–100%.

Conclusions

Limited clinical information is currently available on the use of PDT in root canal disinfection. If supported by future clinical research, PDT may have efficacy for additional root canal disinfection, especially in the presence of multi–drug-resistant bacteria.     

Effects of differential habitat warming on complex communities

Food webs unfold across a mosaic of micro and macro habitats, with each habitat coupled by mobile consumers that behave in response to local environmental conditions. Despite this fundamental characteristic of nature, research on how climate change will affect whole ecosystems has overlooked (i) that climate warming will generally affect habitats differently and (ii) that mobile consumers may respond to this differential change in a manner that may fundamentally alter the energy pathways that sustain ecosystems. This reasoning suggests a powerful, but largely unexplored, avenue for studying the impacts of climate change on ecosystem functioning. Here, we use lake ecosystems to show that predictable behavioral adjustments to local temperature differentials govern a fundamental structural shift across 54 food webs. Data show that the trophic pathways from basal resources to a cold-adapted predator shift toward greater reliance on a cold-water refuge habitat, and food chain length increases, as air temperatures rise. Notably, cold-adapted predator behavior may substantially drive this decoupling effect across the climatic range in our study independent of warmer-adapted species responses (for example, changes in near-shore species abundance and predator absence). Such modifications reflect a flexible food web architecture that requires more attention from climate change research. The trophic pathway restructuring documented here is expected to alter biomass accumulation, through the regulation of energy fluxes to predators, and thus potentially threatens ecosystem sustainability in times of rapid environmental change.Natural systems are inherently complex entities, wherein organisms act as agents of material and biomass transport (1) weaving food webs through a mosaic thermal environment. Direct temperature effects on trophic interactions arise through thermal regulation of an organism’s physiology and behavior (2–5). For ecotherms (that is, organisms whose body temperature is aligned with ambient temperature), several biological rates show unimodal responses to temperature (2, 3, 6), and correspondingly, studies have shown that consumption rates initially rise with warming to a peak rate and then fall rapidly approaching a critical temperature (6). Understanding the ways that these organism responses alter food webs, and how these food web responses affect ecosystem function, are key requirements to predicting climate change impacts on ecosystems (7–11).A simple way to think about temperature’s effects on any single trophic interaction is through the general linear consumption function:Consumption(per?capita) = a?t_s?R, [1]where a is the attack rate, t_s is the time searching, and R is the resource biomass density. The direct effects of temperature on an organism’s ability to encounter and capture resources in a given habitat may largely depend on a, and t_s (with potential indirect effects relative to the consumer through temperature influences on R). The argument for the temperature dependence of attack rate (a) is relatively straightforward. Temperature mediates foraging velocity (3), and considering all else equal, velocity determines encounter rates and prey capture success. The influence of temperature on time searching is a little more complex, but the general expectation is that its influence will be shaped by the requirement that the organism allocate its feeding time in different patches or habitats to increase its fitness (5). Such thermal limitation of search time would lead to reductions of interaction strength in warming habitats—in effect, temperature would mediate prey availability (e.g., when temperature exceeds physiological limits). What remains to complete the consumption equation above is the effect of temperature on R, both the direct effects (for example, the impact of warming on R’s productivity) and indirect effects (for example, impact of warming on the number and consumption capabilities of consumers competing for R) (12, 13). Note that the numerical response (i.e., biomass accumulation) of the consumer may depend on additional vital rates (e.g., conversion efficiency). The conversion of prey biomass to predator biomass (often denoted e) may not change with temperature (2, 3), although recent research suggests that e may be temperature dependent if consumers switch among resources with different elemental composition to balance changing metabolic and somatic demands (14). Nevertheless, we focus on consumption (a, t_s, R) as a means to build an argument for temperature’s influence on trophic structure.Here, we extend the logic that underlies this simple representation of temperature-dependent consumption to develop hypotheses that link temperature differentials, through direct and indirect means, to spatial food web structure. Spatially simple laboratory studies of food webs suggest that larger-bodied, higher trophic level organisms are likely to have high extinction risk with ambient warming (15). In natural systems, these higher-order predators provide a spatially unifying component to food webs: their high mobility enables them to forage among different habitats, coupling food chains with unique basal resource groups (16–18). This coupling structure can be an important part of sustaining higher-order consumers with consequences for food chain length, trophic control, and ecosystem stability (16, 19–21). For example, theory argues that reduced access to a novel resource compartment may decrease a consumer’s biomass (19, 20), thereby increasing the chance of local extinction from a random event. When accessibility is limited, reduced coupling may alter food chain length if habitats contain prey that differ in trophic position (22) or if higher level prey increase, with reduced trophic control, and consequently predators become less omnivorous (19, 21). Given that temperature change can drive asymmetric responses in species that differ in thermal tolerance, the influence of spatially structuring elements on the response of a food web to warming will depend not only on the direct responses of consumers to temperature (2, 3, 5) but also those responses of other interacting community members (i.e., resources and competing predators) (12, 13, 23). We test notions of the structuring effects of differential temperature on spatially coupled food webs (thermal-accessibility hypothesis), using boreal lakes as a natural study system (Fig. 1). To make this test, we assembled one of the largest comparative food web datasets on record: 54 ecosystems, characterized using >3,000 isotope (N and C) samples.Open in a separate windowFig. 1.Simple schematic showing expected effects of differential warming on habitat coupling (horizontal axis) and habitat use (vertical axis) by lake trout in cold (Upper) and warm (Lower) lakes. A thermal accessibility argument predicts that lake trout couple into the thermally exposed near-shore resource channel less and should use (proportionally) that habitat less under warmer conditions (indicated by lake trout position). The arrow direction and thickness indicate coupling direction and strength. The letters in the upper diagram identify trophic groups used in both cold (Upper) and warm (Lower) lake depictions: lake trout (a), pelagic forage fish (b), pelagic invertebrates (c), pelagic phytoplankton (d), littoral fish (e), littoral invertebrates (f), and benthic algae (g). To the right in the diagram, we show thermal profile data contrasting temperature at depth from Victoria Lake [cold; summer air temperature, 15.5 °C; latitude (lat), 49.62306; longitude (long), −91.54889] and Charleston Lake (warm; summer air temperature, 19.7 °C; lat, 44.53611; long, −76.01194) taken at the time of sampling. Temperature is visually highlighted with darker blue (cold) and darker red (warm) hues. These lakes experience temperatures near the cold and warm endpoints for our dataset and are of the same order of magnitude in size, and both had thermal profiles recorded to 30 m.Freshwater lakes are particularly sensitive to climate change as lake habitats are structured by climate-driven water temperature and many biota are vulnerable to ambient temperature change (24). A key habitat feature of boreal lakes is thermal stratification, an effect of antagonistic physical forces of mixing by wind energy and resistance to mixing by solar heating that separates cold, more dense water (hypolimnion) from warmer, less dense surface water (epilimnion) (25). The stratification process creates a potential for temperature differentials between deeper offshore and shallower near-shore subhabitats within a lake, as temperatures remain relatively constant in deep habitats, whereas shallower near-shore temperatures are strongly influenced by air temperatures (26). Monitoring in the boreal region (27, 28) has shown that rising air temperature warms surface waters, accelerates the stratification process, and extends the duration of stratification; thus, air temperature is a primary determinant of lake thermal heterogeneity.Most aquatic organisms (e.g., invertebrates, amphibians, fish) are ectotherms; therefore, the demands of the thermal environment arguably form the most influential set of abiotic factors aquatic organisms must satisfy (29, 30) (including increased oxygen requirements in warmer water). Thermal differentiation in lakes typically corresponds with the species differences that characterize offshore and near-shore habitats. Conveniently, biomass flow from these habitats through a food web can be traced using stable carbon and nitrogen isotope ratios due to isotope differences at the base of the food web between phytoplankton (offshore) and benthic algae (near-shore) (18, 22, 31, 32).We focus our study on the trophic pathways that flow from basal resources to lake trout (Salvelinus namaycush), a vulnerable, cold-adapted (10–12 °C preference) apex predator (33) estimated to reside in 66,500 Canadian lakes (34) (Fig. 1). Previous studies show that lake trout play a keystone structural role in integrating resource pools in offshore and near-shore habitats (18, 21, 22, 31). In what follows, we test the direct and indirect effects of differential warming on this natural system (lake trout food web) across a summer mean temperature gradient ranging 15–20 °C. At the warmer end of this range, surface water temperatures will often exceed the physiological tolerance of lake trout and should restrict accessibility into the near-shore habitat (Fig. 1, Lower). Given this thermal mechanism, we predict that lake trout in warmer climates may change their habitat use to deeper waters and this spatial behavior may shift the degree that near-shore resource pools are coupled by this predator relative to cooler climates (Fig. 1). We further consider whether spatial responses are associated with a shift in the length of the apex predator’s food chain. This thermal-accessibility–mediated restructuring of fundamental food web structure is considered along with complementary notions of warm-tolerant competitor effects and relative prey abundance changes with climate.     

The Macrophage Mediates the Renoprotective Effects of Endotoxin Preconditioning

Preconditioning is a preventative approach, whereby minimized insults generate protection against subsequent larger exposures to the same or even different insults. In immune cells, endotoxin preconditioning downregulates the inflammatory response and yet, preserves the ability to contain infections. However, the protective mechanisms of preconditioning at the tissue level in organs such as the kidney remain poorly understood. Here, we show that endotoxin preconditioning confers renal epithelial protection in various models of sepsis in vivo. We also tested the hypothesis that this protection results from direct interactions between the preconditioning dose of endotoxin and the renal tubules. This hypothesis is on the basis of our previous findings that endotoxin toxicity to nonpreconditioned renal tubules was direct and independent of immune cells. Notably, we found that tubular protection after preconditioning has an absolute requirement for CD14-expressing myeloid cells and particularly, macrophages. Additionally, an intact macrophage CD14-TRIF signaling pathway was essential for tubular protection. The preconditioned state was characterized by increased macrophage number and trafficking within the kidney as well as clustering of macrophages around S1 proximal tubules. These macrophages exhibited increased M2 polarization and upregulation of redox and iron-handling molecules. In renal tubules, preconditioning prevented peroxisomal damage and abolished oxidative stress and injury to S2 and S3 tubules. In summary, these data suggest that macrophages are essential mediators of endotoxin preconditioning and required for renal tissue protection. Preconditioning is, therefore, an attractive model to investigate novel protective pathways for the prevention and treatment of sepsis.     

α-Tocopherol protected against cobalt nanoparticles and cocl2 induced cytotoxicity and inflammation in Balb/3T3 cells

Context: Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and cobalt ions (Co²⁺) are the most serious adverse effect in the patients with metal-on-metal hip prostheses. Therefore, an urgent need exists for the identification of the mechanisms and the development of therapeutic strategies to limit it.

Objective: We aimed to explore the mechanisms of cytotoxicity of CoNPs and Co²⁺ and developed strategies to reduce this cytotoxicity with α-tocopherol treatment.

Methods: To evaluate the protective effect of α-tocopherol, Balb/3T3 cells were pretreated with 10?μM α-tocopherol for 24?h. The cells were then exposed to different concentrations of CoNPs and Co²⁺ for 12?h, 24?h and 48?h. The cell viabilities, reactive oxygen species (ROS), inflammatory cytokines and MAP kinase (MAPK) levels were measured.

Results: CoNPs and Co²⁺ can induce the increase of ROS and inflammatory cytokines in Balb/3T3 cells, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). However, α-tocopherol pretreatment can significantly prevent cytotoxicity induced by CoNPs and Co²⁺, decrease ROS production and decrease levels of inflammatory cytokines in Balb/3T3 cells. Additionally, MAPK pathway may be involved in the protection of α-tocopherol against cytotoxicity induced by CoNPs and Co²⁺ in vitro.

Conclusions: Our results provide new insights into the potential therapeutic use of α-tocopherol in the prevention and treatment of various oxidative- or inflammatory stress-related inflammation and injuries.     

Phylogenomics with paralogs

Phylogenomics heavily relies on well-curated sequence data sets that comprise, for each gene, exclusively 1:1 orthologos. Paralogs are treated as a dangerous nuisance that has to be detected and removed. We show here that this severe restriction of the data sets is not necessary. Building upon recent advances in mathematical phylogenetics, we demonstrate that gene duplications convey meaningful phylogenetic information and allow the inference of plausible phylogenetic trees, provided orthologs and paralogs can be distinguished with a degree of certainty. Starting from tree-free estimates of orthology, cograph editing can sufficiently reduce the noise to find correct event-annotated gene trees. The information of gene trees can then directly be translated into constraints on the species trees. Although the resolution is very poor for individual gene families, we show that genome-wide data sets are sufficient to generate fully resolved phylogenetic trees, even in the presence of horizontal gene transfer.Molecular phylogenetics is primarily concerned with the reconstruction of evolutionary relationships between species based on sequence information. To this end, alignments of protein or DNA sequences are used, whose evolutionary history is believed to be congruent to that of the respective species. This property can be ensured most easily in the absence of gene duplications and horizontal gene transfer (HGT). Phylogenetic studies judiciously select families of genes that rarely exhibit duplications (such as rRNAs, most ribosomal proteins, and many of the housekeeping enzymes). In phylogenomics, elaborate automatic pipelines such as HaMStR (1), are used to filter genome-wide data sets to at least deplete sequences with detectable paralogs (homologs in the same species).In the presence of gene duplications, however, it becomes necessary to distinguish between the evolutionary history of genes (gene trees) and the evolutionary history of the species (species trees) in which these genes reside. Leaves of a gene tree represent genes. Their inner nodes represent two kinds of evolutionary events, namely the duplication of genes within a genome—giving rise to paralogs—and speciations, in which the ancestral gene complement is transmitted to two daughter lineages. Two genes are (co)orthologous if their last common ancestor in the gene tree represents a speciation event, whereas they are paralogous if their last common ancestor is a duplication event; see refs. 2 and 3 for a more recent discussion on orthology and paralogy relationships. Speciation events, in turn, define the inner vertices of a species tree. However, they depend on both the gene and the species phylogeny, as well as the reconciliation between the two. The latter identifies speciation vertices in the gene tree with a particular speciation event in the species tree and places the gene duplication events on the edges of the species tree. Intriguingly, it is nevertheless possible in practice to distinguish orthologs with acceptable accuracy without constructing either gene or species trees (4). Many tools of this type have become available over the last decade; see refs. 5 and 6 for a recent review. The output of such methods is an estimate Θ of the true orthology relation Θ^?, which can be interpreted as a graph G_Θ whose vertices are genes and whose edges connect estimated (co)orthologs.Recent advances in mathematical phylogenetics suggest that the estimated orthology relation Θ contains information on the structure of the species tree. To make this connection, we combine here three abstract mathematical results that are made precise in Materials and Methods below.

• i)Building upon the theory of symbolic ultrametrics (7), we showed that in the absence of horizontal gene transfer, the orthology relation of each gene family is a cograph (8). Cographs can be generated from the single-vertex graph K₁ by complementation and disjoint union (9). This special structure of cographs imposes very strong constraints that can be used to reduce the noise and inaccuracies of empirical estimates of orthology from pairwise sequence comparison. To this end, the initial estimate of G_Θ is modified to the closest correct orthology relation G_Θ^? in such a way that a minimal number of edges (i.e., orthology assignments) are introduced or removed. This amounts to solving the cograph-editing problem (10, 11).
• ii)It is well known that each cograph is equivalently represented by its cotree (9). The cotree is easily computed for a given cograph. In our context, the cotree of G_Θ^? is an incompletely resolved event-labeled gene tree. That is, in addition to the tree topology, we know for each internal branch point whether it corresponds to a speciation or a duplication event. Even though adjacent speciations or adjacent duplications cannot be resolved, the tree faithfully encodes the relative order of any pair of duplication and speciation (8). In the presence of horizontal gene transfer, G_Θ may deviate from the structural requirements of a cograph. Still, the situation can be described in terms of edge-colored graphs whose subgraphs are cographs (7, 8), so that the cograph structure remains an acceptable approximation.
• iii)Every triple (rooted binary tree on three leaves) in the cotree that has leaves from three species and is rooted in a speciation event also appears in the underlying species tree (12). Thus, the estimated orthology relation, after editing to a cograph and conversion to the equivalent event-labeled gene tree, provides much information on the species tree. This result allows us to collect, from the cotrees for each gene family, partial information on the underlying species tree. Interestingly, only gene families that harbor duplications, and thus have a nontrivial cotree, are informative. If no paralogs exist, then the orthology relation G_Θ is a clique (i.e., every family member is orthologous to every other family member) and the corresponding cotree is completely unresolved, and hence contains no triple. On the other hand, full resolution of the species tree is guaranteed if at least one duplication event between any two adjacent speciations is observable. The achievable resolution therefore depends on the frequency of gene duplications and the number of gene families.

Despite the variance reduction due to cograph editing, noise in the data, as well as the occasional introduction of contradictory triples as a consequence of horizontal gene transfer, is unavoidable. The species triples collected from the individual gene families thus will not always be congruent. A conceptually elegant way to deal with such potentially conflicting information is provided by the theory of supertrees in the form of the largest set of consistent triples (13, 14). The data will not always contain a sufficient set of duplication events to achieve full resolution. To this end, we consider trees with the property that the contraction of any edge leads to the loss of an input triple. There may be exponentially many alternative trees of this type. They can be listed efficiently using Semple’s algorithms (15). To reduce the solution space further, we search for a least resolved tree in the sense of ref. 16, i.e., a tree that has the minimum number of inner vertices. It constitutes one of the best estimates of the phylogeny without pretending a higher resolution than actually supported by the data. In SI Appendix, we discuss alternative choices.The mathematical reasoning summarized above, outlined in Materials and Methods, and presented in full detail in SI Appendix, directly translates into a computational workflow, Fig. 1. It entails three NP-hard combinatorial optimization problems: cograph editing (11), maximal consistent triple set (17–19), and least resolved supertree (16). We show here that they are nevertheless tractable in practice by formulating them as Integer Linear Programs (ILP) that can be solved for both artificial benchmark data sets and real-life data sets, comprising genome-scale protein sets for dozens of species, even in the presence of horizontal gene transfer.Open in a separate windowFig. 1.Outline of the computational framework. Starting from an estimated orthology relation Θ, its graph representation G_Θ is edited to obtain the closest cograph G_Θ^*, which, in turn, is equivalent to a (not necessarily fully resolved) gene tree T and an event labeling t. From (T, t), we extract the set ?? of all relevant species triples. As the triple set ?? need not be consistent, we compute the maximal consistent subset ??^? of ??. Finally, we construct a least resolved species tree from ??^?.