Effect of the treatment of root surface-adhered necrotic periodontal ligament with propolis or fluoride in delayed rat tooth replantation

Objectives

The purpose of this study was to evaluate the application of 15 % propolis and 2 % acidulated-phosphate sodium fluoride solutions on the root surface-adhered necrotic cemental periodontal ligament in delayed tooth replantation.

Materials and methods

Thirty Wistar rats (Rattus norvegicus, albinus) had their right upper incisor extracted and maintained in dry storage for 60 min. After this period, the dental papilla, enamel organ, and pulp tissue were removed, and the animals were randomly assigned to three groups: group I = immersion in saline for 10 min; group II = immersion in a 2 % acidulated-phosphate sodium fluoride solution for 10 min; and group III = immersion in a 15 % propolis and propylene glycol solution for 10 min. The root canals were filled with a calcium hydroxide paste and the teeth were replanted.

Results

Inflammatory resorption, replacement resorption, and ankylosis were observed in all groups without a statistically significant difference (p?>?0.05) among them.

Conclusions

Under the tested conditions, the application of fluoride or propolis on root surface-adhered necrotic periodontal ligament did not favor the healing process in delayed tooth replantation.     

Licensed human natural killer cells aid dendritic cell maturation via TNFSF14/LIGHT

Interactions between natural killer (NK) cells and dendritic cells (DCs) aid DC maturation and promote T-cell responses. Here, we have analyzed the response of human NK cells to tumor cells, and we identify a pathway by which NK–DC interactions occur. Gene expression profiling of tumor-responsive NK cells identified the very rapid induction of TNF superfamily member 14 [TNFSF14; also known as homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT)], a cytokine implicated in the enhancement of antitumor responses. TNFSF14 protein expression was induced by three primary mechanisms of NK cell activation, namely, via the engagement of CD16, by the synergistic activity of multiple target cell-sensing NK-cell activation receptors, and by the cytokines IL-2 and IL-15. For antitumor responses, TNFSF14 was preferentially produced by the licensed NK-cell population, defined by the expression of inhibitory receptors specific for self-MHC class I molecules. In contrast, IL-2 and IL-15 treatment induced TNFSF14 production by both licensed and unlicensed NK cells, reflecting the ability of proinflammatory conditions to override the licensing mechanism. Importantly, both tumor- and cytokine-activated NK cells induced DC maturation in a TNFSF14-dependent manner. The coupling of TNFSF14 production to tumor-sensing NK-cell activation receptors links the tumor immune surveillance function of NK cells to DC maturation and adaptive immunity. Furthermore, regulation by NK cell licensing helps to safeguard against TNFSF14 production in response to healthy tissues.Natural killer (NK) cells play an important role in protecting the host against viral infection and cancer. As well as having potent cytotoxic activity, NK cells are endowed with immunoregulatory activity (1, 2). For example, NK cell activation induces the production of chemokines, such as macrophage inflammatory protein-1α (MIP-1α) and IL-8, and proinflammatory cytokines, such as IFN-γ, GM-CSF, and TNF-α. These molecules regulate the recruitment and activity of numerous immune cell types (1, 2). Importantly, NK cells can promote development of T-cell responses via NK–dendritic cell (DC) interactions that favor both DC maturation and NK-cell activation (3–5), with NK cell-derived IFN-γ skewing T-cell differentiation toward the Th1 phenotype (6, 7).Cytotoxic activity and cytokine production are coupled to signaling pathways downstream of a repertoire of activating and inhibitory receptors; signals from activating receptors (including NKG2D, DNAM-1, and 2B4, as well as the natural cytotoxicity receptors NKp30, NKp44, and NKp46) compete with signals from inhibitory receptors such as the killer cell immunoglobulin-like receptors (KIRs) and CD94/NKG2A heterodimers to regulate activation. In addition, NK cells express CD16, the low-affinity receptor for IgG, conferring antibody-dependent cellular cytotoxicity (8–10). Activation thus coordinates the killing of target cells, the induction of inflammation, and the promotion of adaptive immunity. This potent cytotoxicity and proinflammatory activity must be strictly controlled to minimize damage to healthy tissue. Functional competency of unstimulated NK cells is achieved via a process termed “licensing” or “education” (11–14). Licensing ensures that only those NK cells expressing inhibitory receptors for self-MHC class I can respond to target cells and NK cells that lack inhibitory receptors for self-MHC class I molecules are rendered hyporesponsive, preventing them from attacking healthy cells expressing normal levels of MHC class I molecules.We have analyzed the consequences of human NK cell activation by tumor cells. Our results reveal induction of the TNF superfamily member 14 (TNFSF14), also known as homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT) (15). We show that activated NK cells produce TNFSF14 in response to different stimuli, that tumor cells induce TNFSF14 production by licensed NK cells, and that TNFSF14-producing NK cells aid DC maturation during NK–DC cross-talk.     

Perennial grasslands enhance biodiversity and multiple ecosystem services in bioenergy landscapes

Agriculture is being challenged to provide food, and increasingly fuel, for an expanding global population. Producing bioenergy crops on marginal lands—farmland suboptimal for food crops—could help meet energy goals while minimizing competition with food production. However, the ecological costs and benefits of growing bioenergy feedstocks—primarily annual grain crops—on marginal lands have been questioned. Here we show that perennial bioenergy crops provide an alternative to annual grains that increases biodiversity of multiple taxa and sustain a variety of ecosystem functions, promoting the creation of multifunctional agricultural landscapes. We found that switchgrass and prairie plantings harbored significantly greater plant, methanotrophic bacteria, arthropod, and bird diversity than maize. Although biomass production was greater in maize, all other ecosystem services, including methane consumption, pest suppression, pollination, and conservation of grassland birds, were higher in perennial grasslands. Moreover, we found that the linkage between biodiversity and ecosystem services is dependent not only on the choice of bioenergy crop but also on its location relative to other habitats, with local landscape context as important as crop choice in determining provision of some services. Our study suggests that bioenergy policy that supports coordinated land use can diversify agricultural landscapes and sustain multiple critical ecosystem services.In agricultural landscapes, balancing the provisioning of food and energy with maintenance of biodiversity and ecosystem functions is a global challenge. To avoid impacts on food production, attention is increasingly being focused on the potential for marginal lands to support bioenergy production (1). Marginal lands, those suboptimal for food production, may consist of relatively small areas within generally productive landscapes or larger regions where conditions generally limit crop productivity. However, there is increasing recognition that these lands are already performing a variety of useful functions, and their conversion to bioenergy cropping could reduce these services. For example, in the north central United States, rising commodity prices are predicted to bring marginal croplands—including Conservation Reserve Program lands—into annual crop production with negative impacts on wildlife habitat and water quality (2, 3). With 2013 corn plantings at recent record highs (4) and new reports of grassland and wetland conversion to cropland (5, 6), this may be occurring already.An alternative to annual cropping is conversion of marginal croplands to perennial, cellulosic crops for bioenergy. Although current US biofuel production centers on grain ethanol derived from annual monocultures of maize (Zea mays), this situation could change with full implementation of the 2007 US Energy Independence and Security Act (7), which calls for increased production of cellulosic biofuels. In the Midwest United States, perennial grasses and forbs grown on marginal lands could provide up to 25% of national targets for cellulosic biofuel, with substantial greenhouse gas (GHG) benefits (8). Moreover, increasing the area of perennial cover on the landscape is predicted to positively affect a diverse array of organisms and ecological functions (9–11), leading to important synergies that have not yet informed the ongoing bioenergy debate. Here we provide the most comprehensive empirical evaluation of this hypothesis to date, reporting data that elucidate the impacts of different bioenergy cropping systems on a wide variety of organisms and the ecosystem functions they perform.Previous studies have examined the ability of select bioenergy crops to support specific taxa (12) or individual services such as energy production (13) or GHG mitigation (14), without consideration of the tradeoffs or synergies that can arise when considering entire suites of organisms and ecosystem functions. We report on a unique multidisciplinary study of matched sets of organisms and ecosystem services and show that perennial grass energy crops (switchgrass, Panicum virgatum, and mixed prairie plantings) synergistically enhance diversity of a variety of organisms and levels of the services they provide. We further quantify the importance of landscape context on service provisioning, suggesting that policy supporting intentional design of bioenergy landscapes could increase sustainability of both food and energy production.     

Risk-reducing laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for low-grade appendiceal mucinous neoplasm: early outcomes and technique

Background

Low-grade appendiceal mucinous neoplasm (LAMN) is a precursor lesion of pseudomyxoma peritonei, which, if treated suboptimally, may later disseminate throughout the abdominal cavity. We previously demonstrated the role of cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) to reduce the dissemination risk. Here we describe the feasibility and safety of minimal access cytoreductive surgery (MACRS) and HIPEC as an alternative to the open approach.

Methods

We evaluated patients with LAMNs at risk of dissemination (known as LAMN II) who were referred to a national treatment centre between 2010 and 2012 and comparison is made between this group and patients undergoing open CRS and HIPEC for the same pathology over the same time period.

Results

Of the 39 patients with LAMN II, 10 patients were treated by MACRS and HIPEC and 7 were treated by an open approach. Among the MACRS procedures, there were no conversions to open surgery; median procedure length, median length of stay, and complication rates were similar between groups and there were no 30-day deaths. After 3- and 11-months median follow-up respectively, no patients have evidence of disease progression.

Conclusions

The present series demonstrates that MACRS and HIPEC is a feasible and safe alternative to the open procedure with the advantage of smaller abdominal wounds and comparable morbidity and inpatient stay. Longer follow-up is needed to assess the impact on disease progression.     

Validation of the Maryland Aggregate Pathology Index (MAPI), a pre‐implantation scoring system that predicts graft outcome

Predicting graft outcome after renal transplantation based on donor histological features has remained elusive and is subject to institutional variability. We have shown in a retrospective study that the Maryland Aggregate Pathology Index score reliably predicts graft outcome. We sought to validate the scoring system in our center and a second transplant center. We analyzed 140 deceased donor kidneys pre‐implantation biopsies from center 1 and 65 from center 2. The patients had a mean follow‐up of 695 ± 424 and 656 ± 305 d respectively. Although MAPI scores were similar, there were significant differences in donor and recipient parameters between both centers. Despite this, MAPI was predictive of graft outcome for both centers by Cox univariate, multivariate and time dependent ROC analysis. For center 1 and 2, three yr graft survival within each MAPI group was statistically equivalent. The three‐yr graft survival at center 1 for low, intermediate, and high MAPI groups were 84.3%, 56.5%, and 50.0%, respectively, p ≤ 0.0001, and at center 2 were 83.3%, 33.3%, and 33.3%, p = 0.006. MAPI, which is based on a pre‐implantation biopsy, demonstrated similar predictive and outcome results from both centers. As expanded criteria donors (ECD) criteria have redefined marginal kidneys, MAPI has the potential to further define ECD kidneys, increase utilization, and ultimately improve outcomes.     

Does additional support by nurses enhance the effect of a brief smoking cessation intervention in people with moderate to severe chronic obstructive pulmonary disease? A randomised controlled trial

BACKGROUND: Smoking cessation is the primary disease modifying intervention for chronic obstructive pulmonary disease (COPD). SETTING: A Regional Respiratory Centre (RRC) out-patient department in Northern Ireland. METHODS: A randomised controlled trial (RCT) evaluated the effectiveness of brief advice alone or accompanied by individual nurse support or group support facilitated by nurses. Smoking status was biochemically validated and stage of change, nicotine addiction and dyspnoea were recorded at 2, 3, 6, 9 and 12 months. PARTICIPANTS: Ninety-one cigarette smokers with COPD were enrolled in the study (mean age 61 years, 47 female). RESULTS: After 12 months cessation rates were not significantly different between groups (p=0.7), but all groups had a significant reduction in their nicotine addiction (p=0.03-0.006). No changes in subjects' motivation or dyspnoea were detected over the 12 months. CONCLUSION: Patients with COPD were unable to stop smoking regardless of the type of support they received. Harm reduction may be a more appropriate goal than complete cessation for intractable smokers and nurses must evaluate their role in this arena.     

A three-step method of self-reflection using reflective journal writing

Fiscal and financial constraints present a challenge for nurse educators to broaden the diversity and scope of teaching/learning methodologies. One method designed to promote autonomy and self-direction of nursing students is self-reflection combined with reflective journal writing. This paper describes a three-step process of self-reflection encompassing critical appraisal, peer group discussion and self-awareness. This process of self-reflection was initiated with one group of clinical nursing students. Using student and teacher feedback, implications for employing this teaching/learning strategy in clinical practice are suggested.     

Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8⁺ T cell populations in Mamu-A*01⁺ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8⁺ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8⁺ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection.The global HIV pandemic demands an effective vaccine. However, while immunogenic vectors enter advanced clinical trials, the parameters on which to base measurements of efficacious immunity in a prospective manner remain unclear. Indeed, the recent Merck STEP trial failure has exposed our rudimentary understanding of protective determinants within the adaptive T cell response to HIV (1–3). It is established that specific CD8⁺ T cell immunity suppresses HIV replication in vivo and that certain patterns with respect to antigen targeting and MHC class I restriction are consistently associated with low levels of virus load (4–6). However, simple quantitative correlates, at least in peripheral blood, have proved elusive (7, 8). This paradox is exemplified by the SIV model, in which CD8⁺ T cell responses to the structurally constrained Gag CM9 epitope restricted by Mamu-A*01 are protective yet insufficient in terms of magnitude alone to define outcome (9, 10).In the absence of consistent numerical correlates of immune control, recent observational studies have focused on functional profiling in attempts to identify the properties that demarcate effective HIV-specific CD8⁺ T cell responses (11–15). Indeed, a broad consensus indicates that polyfunctionality within pathogen-specific T cell populations, which is related to the sensitivity of antigen recognition among other parameters, correlates with improved outcome measures (3, 16). However, the qualitative properties of CD8⁺ T cell populations are clearly affected by viral replication, and the extent to which such functional associates reflect deterministic attributes remains uncertain. Similarly, phenotypic analyses of HIV-specific CD8⁺ T cell populations have yet to provide definitive indicators of immune control (3). At a more fundamental level, a given cognate T cell response is defined by the nature of its constituent clonotypes, which are defined on the basis of their expressed TCRs and can be considered the elemental units of any antigen-specific T cell population. Thus, the primary interface between the virus and adaptive T cell immunity occurs at the level of TCR-mediated recognition of peptide-MHC antigen; these signal transduction events, in turn, dictate the ontogeny and biological characteristics of individual cognate T cells in vivo. Given the seminal importance of clonotype-dependent TCR-mediated recognition events, it is not unreasonable to propose that the potential efficacy of a composite virus-specific CD8⁺ T cell population might depend on the idiosyncrasies with which individual cognate TCRs engage the targeted viral antigen.In a previous study, we examined the clonotypic composition of immunodominant CD8⁺ T cell populations in acute SIV infection to illuminate the role of TCR usage in the process of mutational immune escape (17). In the present study, we conducted a detailed prospective study of vaccine-induced SIV-specific CD8⁺ T cell responses to the same immunodominant epitopes to establish whether the mobilized antigen-specific TCR repertoire can influence virologic outcome.