Buccal versus buccal palatal infiltration for pulpal anesthesia using 2% lidocaine and 4% articaine: A randomized controlled trial.

Background: The inability in achieving complete pulpal anesthesia with standard buccal infiltration especially in cases with SIP used for maxillary teeth. The study aimed to compare the anesthetic efficacy of buccal and buccal plus palatal infiltration technique using 2% lidocaine and 4% articaine in permanent maxillary first molars with the diagnosis of symptomatic irreversible pulpitis (SIP). Material and method: One hundred and twenty-three patients with clinical diagnosis of SIP, aged 18-50 years were randomly allocated to three treatment groups (N = 41). Group 1(BIL): Buccal infiltration technique using 2% lidocaine with 1:80,000 adrenaline. Group 2(BPIL): combination of buccal plus palatal infiltration using 2% Lidocaine with 1:80,000 adrenaline. Group 3(BIA): Buccal infiltration using 4% articaine with 1:100,000 adrenaline. Pain intensity of patients were recorded before and after the administration of local anesthesia during endodontic procedure that is during caries removal, access preparation and pulp removal using Heft-Parker Visual Analog Scale (HP-VAS). Success was defined by "no pain (0 mm)" or "mild pain (0-54 mm)" during endodontic procedure. The anesthetic efficacy rates were analyzed using chi-square tests, age differences using one-way ANOVA. Results: The final analysis included total of 117 patients. Higher success was observed in group II (85%) in comparison to group I (69%) and group III (74%), but the difference was statistically nonsignificant (p > 0.05). Our results demonstrated a nonsignificant difference between genders in all three groups (p > 0.05). Conclusion: The use of buccal plus palatal infiltration and 4% articaine can provide effective anesthesia as standard buccal infiltration and 2% lidocaine for patients with SIP in maxillary first molars.

Latent sub-structural resilience mechanisms in temporal human mobility networks during urban flooding.

In studying resilience in temporal human networks, relying solely on global network measures would be inadequate; latent sub-structural network mechanisms need to be examined to determine the extent of impact and recovery of these networks during perturbations, such as urban flooding. In this study, we utilize high-resolution aggregated location-based data to construct temporal human mobility networks in Houston in the context of the 2017 Hurricane Harvey. We examine motif distribution, motif persistence, temporal stability, and motif attributes to reveal latent sub-structural mechanisms related to the resilience of human mobility networks during disaster-induced perturbations. The results show that urban flood impacts persist in human mobility networks at the sub-structure level for several weeks. The impact extent and recovery duration are heterogeneous across different network types. Also, while perturbation impacts persist at the sub-structure level, global topological network properties indicate that the network has recovered. The findings highlight the importance of examining the microstructures and their dynamic processes and attributes in understanding the resilience of temporal human mobility networks (and other temporal networks). The findings can also provide disaster managers, public officials, and transportation planners with insights to better evaluate impacts and monitor recovery in affected communities.

Erratum: Addendum: Effect of pre-operative medication with paracetamol and ketorolac on the success of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a double-blind randomized clinical trial.

[This corrects the article on p. 441 in vol. 21, PMID: 34703893.].

Effect of pre-operative medication with paracetamol and ketorolac on the success of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a double-blind randomized clinical trial.

BACKGROUND: The efficacy of local anesthesia decreases in patients with symptomatic irreversible pulpitis. Therefore, it was proposed that the use of premedication with an anti-inflammatory drug might increase the success rate of pulpal anesthesia in mandibular posterior teeth with vital inflamed pulp. METHODS: One hundred thirty-four patients who were actively experiencing pain willingly participated in this study. The Heft Parker (HP) visual analog scale (VAS) was used to record the initial pain intensity. Patients were randomly allocated to receive a placebo, 10 mg of ketorolac, and 650 mg of paracetamol. The standard inferior alveolar nerve block (IANB) was administered to all patients using 2% lidocaine with 1:200,000 adrenaline after one hour of medication. After 15 min, the patient was instructed to rate the discomfort during each step of the treatment procedure, such as access to remaining dentin, access to the pulp chamber, and during canal instrumentation on the HP VAS. IANB was considered successful if the patient reported no or mild pain during access preparation and instrumentation. Moderate or severe pain was classified as a failure of IANB and another method of anesthesia was used before continuing the treatment. RESULTS: The rate of successful anesthesia in the placebo, paracetamol, and ketorolac groups was 29%, 33%, and 43%, respectively, and no statistically significant difference was found between the groups. CONCLUSION: Preoperative administration of paracetamol or ketorolac did not significantly affect the success rate of IANB in patients with irreversible pulpitis. No significant difference was observed between the paracetamol and ketorolac groups.

Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation.

Ubiquitination is a central process affecting all facets of cellular signalling and function. A critical step in ubiquitination is the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to a substrate or a growing ubiquitin chain, which is mediated by E3 ubiquitin ligases. RING-type E3 ligases typically facilitate the transfer of ubiquitin from the E2 directly to the substrate. The RING-between-RING (RBR) family of RING-type E3 ligases, however, breaks this paradigm by forming a covalent intermediate with ubiquitin similarly to HECT-type E3 ligases. The RBR family includes Parkin and HOIP, the central catalytic factor of the LUBAC (linear ubiquitin chain assembly complex). While structural insights into the RBR E3 ligases Parkin and HHARI in their overall auto-inhibited forms are available, no structures exist of intact fully active RBR E3 ligases or any of their complexes. Thus, the RBR mechanism of action has remained largely unknown. Here we present the first structure, to our knowledge, of the fully active human HOIP RBR in its transfer complex with an E2~ubiquitin conjugate, which elucidates the intricate nature of RBR E3 ligases. The active HOIP RBR adopts a conformation markedly different from that of auto-inhibited RBRs. HOIP RBR binds the E2~ubiquitin conjugate in an elongated fashion, with the E2 and E3 catalytic centres ideally aligned for ubiquitin transfer, which structurally both requires and enables a HECT-like mechanism. In addition, three distinct helix-IBR-fold motifs inherent to RBRs form ubiquitin-binding regions that engage the activated ubiquitin of the E2~ubiquitin conjugate and, surprisingly, an additional regulatory ubiquitin molecule. The features uncovered reveal critical states of the HOIP RBR E3 ligase cycle, and comparison with Parkin and HHARI suggests a general mechanism for RBR E3 ligases.

Karyotype, Pedigree and cone-beam computerized tomography analysis of a case of nonsyndromic pandental anomalies.

This case report presented a karyotype and pedigree analysis of a case with unusual combination of dental anomalies: Generalized short roots, talon cusps, dens invagination, low alveolar bone heights, very prominent cusp of carabelli and protostylid on first permanent molars, taurodontism of second permanent molars, rotated, missing and impacted teeth. None of the anomalies alone are rare. However, until date, nonsyndromic pandental anomalies that are affecting entire dentition with detailed karyotype, pedigree and cone-beam computerized tomography analysis have not been reported. The occurrence of these anomalies is probably incidental as the conditions are etiologically unrelated.

Management of a rare combination of avulsion and intrusive luxation: A case report.

In traumatic dental injury, concomitant occurrence of avulsion and intrusive luxation is exceptional. This is because the vectors of forces responsible for both avulsive and intrusive injuries are in different directions. The present case report reviews the management of a rare combination of avulsion in right maxillary lateral incisor (tooth #12) and intrusive luxation in right maxillary central incisor (tooth #11) in a 22-year-old Asian male. Clinical and radiographic evaluation was done at 12-month follow-up. Various treatment modalities and complications associated with both avulsion and intrusion are also discussed in the paper.

Type III talon cusp and Type III B dens invaginatus occurring simultaneously in a mandibular lateral incisor.

Talon cusp and dens invaginatus are developmental anomalies of the human dentition. They not only affect the esthetic appearance of teeth but also may create difficulties during dental treatment and lead to a number of dental problems. Both anomalies are observed most commonly in the lateral maxillary incisor and rarely in the mandibular dentition. The simultaneous occurrence of talon cusp and dens invaginatus in a single tooth is very rare in the mandibular dentition and, to the authors' knowledge, has not yet been reported in a mandibular lateral incisor. This article presents a rare case of dens invaginatus and talon cusp occurring concurrently in a mandibular lateral incisor. Three-dimensional imaging modality was used to describe the complex internal anatomy.

Assessment of dentinal damage during canal preparation using reciprocating and rotary files.

INTRODUCTION: The role of motion kinematics in creating dentinal damage during instrumentation is not very clear. The purpose of this study was to compare the formation of dentinal cracks with instruments working in continuous rotation and reciprocating motion. METHODS: One hundred twenty extracted human mandibular premolars were selected for the study. Thirty teeth served as controls, and the remaining 90 teeth were divided into 3 groups depending on the root canal preparation technique. Group 1 samples were treated with WaveOne primary files (Dentsply Maillefer, Ballaigues, Switzerland), group 2 samples with single F2 ProTaper (Dentsply Maillefer) working in reciprocating motion, and group 3 samples were prepared with sequential ProTaper (Dentsply Maillefer) until F2 working in continuous rotation motion. Roots were then sectioned at 3, 6, and 9 mm from the apex, and the cut surface was observed under a stereomicroscope for the presence of dentinal microcracks. RESULTS: The control group and WaveOne, single F2 ProTaper in reciprocating motion, and continuous ProTaper groups caused cracks in 0%, 15%, 26%, and 53% of samples, respectively. A statistically significant difference was found between 2 reciprocating file groups (WaveOne and single F2 ProTaper in reciprocating motion) and the continuous rotation group (ProTaper) (P < .05). However, no significant difference was found among the 2 reciprocating file groups (P > .05). CONCLUSIONS: Dentinal cracks are produced irrespective of motion kinematics. Within the limits of this study and the current literature, such incidence is less with instruments working in reciprocating motion compared with those working in continuous rotation.

bNAber: database of broadly neutralizing HIV antibodies.

The discovery of broadly neutralizing antibodies (bNAbs) has provided an enormous impetus to the HIV vaccine research and to entire immunology. The bNAber database at http://bNAber.org provides open, user-friendly access to detailed data on the rapidly growing list of HIV bNAbs, including neutralization profiles, sequences and three-dimensional structures (when available). It also provides an extensive list of visualization and analysis tools, such as heatmaps to analyse neutralization data as well as structure and sequence viewers to correlate bNAbs properties with structural and sequence features of individual antibodies. The goal of the bNAber database is to enable researchers in this field to easily compare and analyse available information on bNAbs thereby supporting efforts to design an effective vaccine for HIV/AIDS. The bNAber database not only provides easy access to data that currently is scattered in the Supplementary Materials sections of individual papers, but also contributes to the development of general standards of data that have to be presented with the discovery of new bNAbs and a universal mechanism of how such data can be shared.

Successful management of pulpo-periodontal lesion in maxillary lateral incisor with palatogingival groove using CBCT scan.

Palatogingival groove is a rare developmental anomaly involving the lingual surface of the maxillary incisor and resulting in severe endodontic and periodontal lesions. This case report describes a multidisciplinary approach for the combined management of the endodontic and periodontal problems for successful rehabilitation of the involved tooth. Cone-beam computed tomography (CBCT) helped in correct diagnosis of the lesion and hence enabled effective treatment.

RIG-I RNA helicase activation of IRF3 transcription factor is negatively regulated by caspase-8-mediated cleavage of the RIP1 protein.

Excessive responses to pattern-recognition receptors are prevented by regulatory mechanisms that affect the amounts and activities of the downstream signaling proteins. We report that activation of the transcription factor IRF3 by the ribonucleic acid sensor RIG-I was restricted by caspase-8-mediated cleavage of the RIP1 protein, which resulted in conversion of RIP1 from a signaling enhancer to a signaling inhibitor. The proteins RIP1 and caspase-8 were recruited to the RIG-I complex after viral infection and served antagonistic regulatory roles. Conjugation of ubiquitin chains to RIP1 facilitated assembly of the RIG-I complex, resulting in enhanced phosphorylation of IRF3. However, the ubiquitination of RIP1 also rendered it susceptible to caspase-8-mediated cleavage that yielded an inhibitory RIP1 fragment. The dependence of RIP1 cleavage on the same molecular change as that facilitating RIG-I signaling allows for RIG-I signaling to be restricted in its duration without compromising its initial activation.

Complicated crown-root fracture treated using reattachment procedure: a single visit technique.

Complicated crown-root fracture of maxillary central and lateral incisors is common in case of severe trauma or sports-related injury. It happens because of their anterior positioning in oral cavity and protrusive eruptive pattern. On their first dental visit, these patients are in pain and need emergency care. Because of impaired function, esthetics, and phonetics, such patients are quite apprehensive during their emergency visit. Successful pain management with immediate restoration of function, esthetics and phonetics should be the prime objective while handling such cases. This paper describes immediate treatment of oblique crown root fracture of maxillary right lateral incisor with reattachment procedure using light transmitting fiber post. After two and half years, the reattached fragment still has satisfying esthetics and excellent function.

In vitro study comparing fracture strength recovery of teeth restored with three esthetic bonding materials using different techniques.

Reattachment of the fractured fragment of a traumatized tooth (whenever available and usable) has become the treatment of choice in cases of uncomplicated crown fractures. Despite the presence of various bonding materials and techniques, laboratory data evaluating the biomechanical aspects of such procedures is largely lacking in the literature. The objective of this in vitro study was to evaluate the fracture strength recovery of incisors, following fragment restoration with three different techniques. A total of 90 extracted human maxillary central incisors were subjected to crown fractured under standard conditions. This was carried out by applying a compressive force from the buccal aspect of the clinical crown using a universal strength testing machine. The fractured teeth were equality distributed in three groups, defined on the basis of the technique used for reattachment: i) overcontour, ii) internal dentinal groove and iii) direct buildup. Each group was further subdivided into three subgroups on the basis of the intermediate restorative material used for reattachment, namely: i) hybrid composite (Filtek Z100 Universal Restorative, ii) nanocomposite (Filtek Z350) and iii) Ormocer (Voco Admira). Following reattachment, the crowns were re-fractured under standard conditions. The force required for fracture was recorded and was expressed as a percentage of the fracture strength of the intact tooth. The data was expressed as a percentage of the fracture strength of the intact tooth. The data was analyzed using two-way ANOVA and Bonferroni tests for pair-wise comparison. The results showed no statistically significant differences in fractures strength between the three groups (P > 0.05). However, comparison of the subgroups revealed statistically significant higher strength recovery percentages for the hybrid and the nanocomposite compared with the Ormocer material (P < 0.05). It was concluded that material properties have a significant influence on the success of reattachment procedures.

Anti-inflammatory functions of the "apoptotic" caspases.

The two main known functions of the caspases act antagonistically in regulating inflammation. "Inflammatory" caspases trigger inflammation by catalyzing the processing of IL-1ß precursors and other proinflammatory cytokines. In contrast, "apoptotic" caspases safeguard against the triggering of inflammation by imposing a cell-death form that withholds release of alarmins by dying cells and dictates generation of anti-inflammatory mediators. These antagonizing functions are exerted by evolution-related mechanisms. Studies of the function of caspase-8, an enzyme-mediating apoptotic cell-death induction in response to TNF-family ligands, reveal that it blocks inflammation in additional ways. One way is by restricting activation of the RIG-I complex by foreign ribonucleic acid. Chronic skin inflammation in mice with caspase-8-deficient epidermis is associated with constitutive activation of the RIG-I complex in keratinocytes. This activation is apparently prompted by nucleic acids released from epidermal cells that disintegrate during cornification, and becomes chronic because it is not restricted by caspase-8.

Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease.

Expression of enzymatically inactive caspase-8, or deletion of caspase-8 from basal epidermal keratinocytes, triggers chronic skin inflammation in mice. Unlike similar inflammation resulting from arrest of nuclear factor kappaB activation in the epidermal cells, the effect induced by caspase-8 deficiency did not depend on TNF, IL-1, dermal macrophage function, or expression of the toll-like receptor adapter proteins MyD88 or TRIF. Both interferon regulatory factor (IRF) 3 and TANK-binding kinase were constitutively phosphorylated in the caspase-8-deficient epidermis, and knockdown of IRF3 in the epidermis-derived cells from these mice abolished the expression of up-regulated genes. Temporal and spatial analyses of the alterations in gene expression that result from caspase-8 deficiency reveal that the changes are initiated before birth, around the time that cornification develops, and occur mainly in the suprabasal layer. Finally, we found that caspase-8-deficient keratinocytes display an enhanced response to gene activation by transfected DNA. Our findings suggest that an enhanced response to endogenous activators of IRF3 in the epidermis, presumably generated in association with keratinocyte differentiation, contributes to the skin inflammatory process triggered by caspase-8 deficiency.

Uncomplicated crown fracture, complicated crown-root fracture, and horizontal root fracture simultaneously treated in a patient during emergency visit: a case report.

Complicated crown fractures are not uncommon in cases of severe trauma or sports related injury. Such patients report with pain because of exposed pulp and need emergency care. Because of impaired function, esthetics, and phonetics, such patients are quite apprehensive during their emergency visit. Successful pain management with immediate restoration of function, esthetics, and phonetics should be the prime objective when handling such cases. This article describes immediate treatment of oblique crown root fracture of maxillary left central incisor, horizontal root fracture of maxillary left lateral incisor, and uncomplicated crown fracture of maxillary right central incisor. Maxillary left central incisor was treated with reattachment procedure using light-transmitting fiber post (D.T. Light Post; Bisco, Schaumburg, IL, USA); maxillary left lateral incisor subsequently healed after splinting for 7 weeks, and direct composite build-up was done on maxillary right central incisor. After 2 years, the reattached fragment had satisfying esthetics and excellent function and pulp was still vital in maxillary left lateral incisor and maxillary right central incisor. Various treatment modalities for traumatically injured incisors are shown in this article.

How are the regulators regulated? The search for mechanisms that impose specificity on induction of cell death and NF-kappaB activation by members of the TNF/NGF receptor family.

Signals emanating from receptors of the tumor necrosis factor/nerve growth factor (TNF/NGF) family control practically all aspects of immune defense and, as such, constitute potential targets for therapeutic intervention through rational drug design. Indeed, arrest of these signals by blocking ligand-receptor interactions enables effective suppression of a variety of activities that are implicated in various pathologies, such as T and B lymphocyte activation and growth, inflammation, fibroblast proliferation, and cell death. To be therapeutically useful, however, inhibition of signaling should be restricted by determinants of specificity, at least to the same degree observed when blocking activation of individual receptors. In spite of their broad range of functions, receptors of the TNF/NGF family are known to activate just a few signaling pathways. Of these, the most extensively studied are the activation of the caspase protease cascade, which leads to cell death, and the activation of NF-kappaB (nuclear factor-kappaB) transcription factors through protein phosphorylation cascades. Until recently, most studies of the two pathways have solely focused on the core signaling complexes that are shared by the different receptors: death-inducing complexes containing the cysteine proteases caspase-8 and caspase-10, bound to the adapter protein MORT1/FADD (mediator of receptor-induced toxicity/Fas-associated DD protein), and the NF-kappaB-activating complex, composed of the protein kinases IKK1 (IkappaB kinase 1) and IKK2 (IkappaB kinase 2) and the regulatory subunit NEMO (NF-kappaB essential modulator; the 'IKK signalosome'). Knowledge has begun to emerge of additional molecules and mechanisms that affect these basic signaling complexes and impose specificity on their function.