Effects of nasal septum deviation and concha bullosa surgery on the frequency and financial burden of acute rhinosinusitis.

BACKGROUND: Nasal septum deviation/concha bullosa (DNS)/(CB) are known to be predisposing factors in the pathophysiology of acute rhinosinusitis (ARS). However, the effects of surgical treatment of these pathologies on ARS have not been adequately investigated. AIMS: To reveal the effects of the surgical treatment of DNS and CB on the frequency of the ARS, the use of antibiotics (ABs), and the direct cost incurred. METHODS: Medical records of the patients who had undergone successful surgery for DNS/CB and were diagnosed with ARS in the preoperative and postoperative 3-year period were retrospectively analyzed. The average annual number of ARS examinations of the patients, the number of ABs prescribed, and prescription, examination, and total health system costs were compared. RESULTS: Fifty-three patients (33 men (62%) and 20 women (38%)) were included in the study. There was a statistically significant decrease in the mean annual number of examinations for ARS, the number of ABs prescribed, prescription, examination, and total health system costs (p < 0.05) in the postoperative period compared with the preoperative period. CONCLUSIONS: The present study determined that successful surgeries performed in patients with DNS/CB resulted in a significant decrease in the average annual number of examinations performed for ARS, number of AB prescriptions, and prescription, examination, and total health system costs. With these results, it seems beneficial to direct patients to surgery within the framework of the health policies of countries to reduce the frequency and financial burden of ARS in DNS/CB patients.

Evaluation of the intranasal steroid treatment outcomes in adenoid tissue hypertrophy with or without allergic rhinitis.

PURPOSE: To compare the intranasal steroid (INS) treatment outcomes in patients with adenoid tissue hypertrophy (ATH) with or without allergic rhinitis (AR). MATERIALS AND METHODS: Medical records of 96 children diagnosed with ATH were retrospectively examined. The pediatric version of the Score for Allergic Rhinitis (SFAR) questionnaire was used to determine the AR status of the patients and classify them. The children were divided into two groups based on the questionnaire: Group 1, low probability of AR (SFAR<9); and Group 2, high probability of AR (SFAR≥9). Intranasal mometasone furoate (100 µg/mL) was used to treat ATH for at least 3 months. The severity of nasal obstruction and snoring was evaluated using the visual analog scale (VAS) score, the adenoid/choana (A/C) ratios before and after treatment were compared, and the rate of patient referral to surgery was recorded among groups. RESULTS: The change in the A/C ratio within the group between before and after treatment was significant (both P < 0.001). However, the reduction in the adenoid size was more significant in Group 1 than in Group 2 (P = 0.025). A significant improvement in the VAS scores was observed between before and after treatment in both groups (P < 0.001). Furthermore, the rate of surgical referral of Group 1 was significantly lower than that of Group 2 (P = 0.035). CONCLUSIONS: INS treatment was found more successful for reducing A/C ratio in ATH without AR. Related with this, when considering the INS treatment for ATH, AR status should be kept in mind for predicting the treatment success.

A Quantitative Modular Modeling Approach Reveals the Effects of Different A20 Feedback Implementations for the NF-kB Signaling Dynamics.

Signaling pathways involve complex molecular interactions and are controled by non-linear regulatory mechanisms. If details of regulatory mechanisms are not fully elucidated, they can be implemented by different, equally reasonable mathematical representations in computational models. The study presented here focusses on NF-κB signaling, which is regulated by negative feedbacks via IκBα and A20. A20 inhibits NF-κB activation indirectly through interference with proteins that transduce the signal from the TNF receptor complex to activate the IκB kinase (IKK) complex. A number of pathway models has been developed implementing the A20 effect in different ways. We here focus on the question how different A20 feedback implementations impact the dynamics of NF-κB. To this end, we develop a modular modeling approach that allows combining previously published A20 modules with a common pathway core module. The resulting models are fitted to a published comprehensive experimental data set and therefore show quantitatively comparable NF-κB dynamics. Based on defined measures for the initial and long-term behavior we analyze the effects of a wide range of changes in the A20 feedback strength, the IκBα feedback strength and the TNFα stimulation strength on NF-κB dynamics. This shows similarities between the models but also model-specific differences. In particular, the A20 feedback strength and the TNFα stimulation strength affect initial and long-term NF-κB concentrations differently in the analyzed models. We validated our model predictions experimentally by varying TNFα concentrations applied to HeLa cells. These time course data indicate that only one of the A20 feedback models appropriately describes the impact of A20 on the NF-κB dynamics in this cell type.

It takes two to tango: IκBs, the multifunctional partners of NF-κB.

The inhibitory IκB proteins have been discovered as fundamental regulators of the inducible transcription factor nuclear factor-κB (NF-κB). As a generally excepted model, stimulus-dependent destruction of inhibitory IκBs and processing of precursor molecules, both promoted by components of the signal integrating IκB kinase complex, are the key events for the release of various NF-κB/Rel dimers and subsequent transcriptional activation. Intense research of more than 20 years provides evidence that the extending family of IκBs act not simply as reversible inhibitors of NF-κB activation but rather as a complex regulatory module, which assures feedback regulation of the NF-κB system and either can inhibit or promote transcriptional activity in a stimulus-dependent manner. Thus, IκB and NF-κB/Rel family proteins establish a complex interrelationship that allows modulated NF-κB-dependent transcription, tailored to the physiological environment.

Evaluation of surface roughness and hardness of different glass ionomer cements.

OBJECTIVES: The aim of this study was to evaluate surface roughness and hardness of a nanofiller GIC, a resin-modified GIC, three conventional GICs, and a silver-reinforced GIC. METHODS: For each material, 11 spcecimens were prepared and then stored in distilled water at 37 °C for 24 h. The surface roughness of 5 specimens was measured using a surface profilometer before polishing and after polishing with coarse, medium, fine, superfine aluminum oxide abrasive Sof-Lex discs respectively. The hardness of the upper surfaces of the remaining 6 specimens was measured with a Vickers microhardness measuring instrument. RESULTS: All tested GICs showed lower surface roughness values after the polishing procedure. Surface finish of nanofiller GIC was smoother than the other tested GICs after polishing. This was followed by resin-modified GIC, Fuji II LC; then silver-reinforced GIC, Argion Molar, conventional GICs, Aqua Ionofil Plus, Fuji IX, and Ionofil Molar, respectively. The result of the hardness test indicated that the microhardness value of silver-reinforced GIC was greater than that of the other GICs. When the hardness values of all tested GICs were compared, the differences between materials (except Aqua Ionofil Plus with Ionofil Molar and Ketac N100 with Fuji II LC (P>.05)) were found statistically significant (P<.05). CONCLUSIONS: According to the results of this study, it can be concluded that the differences in the composition of GICs may affect their surface roughness and hardness.

The prevalence of TNFα-induced necrosis over apoptosis is determined by TAK1-RIP1 interplay.

Death receptor-induced programmed necrosis is regarded as a secondary death mechanism dominating only in cells that cannot properly induce caspase-dependent apoptosis. Here, we show that in cells lacking TGFß-activated Kinase-1 (TAK1) expression, catalytically active Receptor Interacting Protein 1 (RIP1)-dependent programmed necrosis overrides apoptotic processes following Tumor Necrosis Factor-α (TNFα) stimulation and results in rapid cell death. Importantly, the activation of the caspase cascade and caspase-8-mediated RIP1 cleavage in TNFα-stimulated TAK1 deficient cells is not sufficient to prevent RIP1-dependent necrosome formation and subsequent programmed necrosis. Our results demonstrate that TAK1 acts independently of its kinase activity to prevent the premature dissociation of ubiquitinated-RIP1 from TNFα-stimulated TNF-receptor I and also to inhibit the formation of TNFα-induced necrosome complex consisting of RIP1, RIP3, FADD, caspase-8 and cFLIP(L). The surprising prevalence of catalytically active RIP1-dependent programmed necrosis over apoptosis despite ongoing caspase activity implicates a complex regulatory mechanism governing the decision between both cell death pathways following death receptor stimulation.

A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-κB activation.

As part of the genotoxic stress response, cells activate the transcription factor NF-κB. The DNA strand break sensor poly(ADP-ribose)-polymerase-1 (PARP-1) and the kinase ataxia telangiectasia mutated (ATM) act as proximal signal mediators. PARP-1 assembles a nucleoplasmic signalosome, which triggers PIASy-mediated IKKγ SUMOylation. ATM-dependent IKKγ phosphorylation and subsequent ubiquitination were implicated to activate the cytoplasmic IκB kinase (IKK) complex by unknown mechanisms. We show that activated ATM translocates in a calcium-dependent manner to cytosol and membrane fractions. Through a TRAF-binding motif, ATM activates TRAF6, resulting in Ubc13-mediated K63-linked polyubiquitin synthesis and cIAP1 recruitment. The ATM-TRAF6-cIAP1 module stimulates TAB2-dependent TAK1 phosphorylation. Both nuclear PARP-1- and cytoplasmic ATM-driven signaling branches converge at the IKK complex to catalyze monoubiquitination of IKKγ at K285. Our data indicate that exported SUMOylated IKKγ acts as a substrate. IKKγ monoubiquitination is a prerequisite for genotoxic IKK and NF-κB activation, but also promotes cytokine signaling.

A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IkappaB kinase activation.

Upon genotoxic stresses, cells activate IkappaB kinases (IKKs) and the transcription factor NF-kappaB to modulate apoptotic responses. The SUMO-1 ligase PIASy and the kinase ataxia talengiectasia mutated (ATM) have been implicated to SUMOylate and phosphorylate nuclear IKKgamma (NEMO) in a consecutive mode of action, which in turn results in activation of cytoplasmic IKK holocomplexes. However, the nuclear signals and scaffold structures that initiate IKKgamma recruitment and activation are unknown. Here, we show that poly(ADP-ribose)-polymerase-1 (PARP-1) is the DNA proximal regulator, which senses DNA strand breaks and, through poly(ADP-ribose) (PAR) synthesis, assembles IKKgamma, PIASy, and ATM in a dynamic manner. Signalosome formation involves direct protein-protein interactions and binding to ADP-ribose polymers through PAR binding motifs (PARBM). Activated PARP-1 and a PARBM in PIASy are required to trigger IKKgamma SUMOylation, which in turn permits IKK and NF-kappaB activation, as well as NF-kappaB-regulated resistance to apoptosis.

Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation.

Triggering of antigen receptors on lymphocytes is critical for initiating adaptive immune response against pathogens. T-cell receptor (TCR) engagement induces the formation of the Carma1-Bcl10-Malt1 (CBM) complex that is essential for activation of the IkappaB kinase (IKK)/NF-kappaB pathway. However, the molecular mechanisms that link CBM complex formation to IKK activation remain unclear. Here we report that Malt1 is polyubiquitinated upon T-cell activation. Ubiquitin chains on Malt1 provide a docking surface for the recruitment of the IKK regulatory subunit NEMO/IKKgamma. TRAF6 associates with Malt1 in response to T-cell activation and can function as an E3 ligase for Malt1 in vitro and in vivo, mediating lysine 63-linked ubiquitination of Malt1. Multiple lysine residues in the C-terminus of Malt1 serve as acceptor sites for the assembly of polyubiquitin chains. Malt1 mutants that lack C-terminal ubiquitin acceptor lysines are impaired in rescuing NF-kappaB signaling and IL-2 production in Malt1-/- T cells. Thus, our data demonstrate that induced Malt1 ubiquitination is critical for the engagement of CBM and IKK complexes, thereby directing TCR signals to the canonical NF-kappaB pathway.

Fracture resistance of roots obturated with three different materials.

OBJECTIVE: The aim of this study was to compare the fracture resistance of roots obturated with different materials. STUDY DESIGN: Sixty root canals were instrumented and divided into 4 equal groups (n = 15 each). The root canals in group 1 were filled with AH26 sealer and gutta-percha, in group 2 with Resilon and Epiphany, and in group 3 with Ketac-Endo Aplicap and gutta-percha. Fifteen root canals had no obturation. The force required to fracture was recorded. The data was analyzed with analysis of variance and Duncan test. RESULTS: The mean force of fracture for group 1 was significantly higher than for the other 3 groups (P < .05). There was significant difference between group 2 and group 3 (P < .05). Group 2 and group 3 were not significantly different from the control group (P > .05). CONCLUSION: The use of AH26 + gutta-percha increased the fracture resistance of instrumented root canals compared with Resilon + Epiphany and Ketac-Endo Aplicap + gutta-percha.

Signal responsiveness of IkappaB kinases is determined by Cdc37-assisted transient interaction with Hsp90.

The IkappaB kinase (IKK) holocomplex, containing the kinases IKKalpha, IKKbeta, and the scaffold NEMO (NF-kappaB essential modifier), mediates activation of NF-kappaB by numerous physiological stimuli. Heat shock protein 90 (Hsp90) and the co-chaperone Cdc37 have been indicated as additional subunits, but their specific functions in signal transduction are indistinct. Using an RNA interference approach, we demonstrate that Cdc37 recruits Hsp90 to the IKK complex in a transitory manner, preferentially via IKKalpha. Binding is conferred by N-terminal as well as C-terminal residues of Cdc37. Cdc37 is essential for the maturation of de novo synthesized IKKs into enzymatically competent kinases but not for assembly of an IKK holocomplex. Mature IKKs, T-loop-phosphorylated after stimulation either by receptor-mediated signaling or upon DNA damage, further require Hsp90-Cdc37 to generate an activated state. Thus, the present data denote Hsp90-Cdc37 as a transiently acting essential regulatory component of IKK signaling.