Effect of Back-Pressure Anesthesia on Postoperative Pain after the Endodontic Treatment in Patients with Symptomatic Irreversible Pulpitis: Randomized Double-Blind Clinical Trial.

INTRODUCTION: The present study evaluated the effect of 2 different back pressure-based supplemental anesthesia on postoperative pain in patients receiving endodontic treatment for a mandibular molar with symptomatic irreversible pulpitis. METHODS: One-hundred-thirty-five adult patients with symptomatic irreversible pulpits in a mandibular first or second molar, received an initial inferior alveolar nerve block (IANB) injection with 2% lidocaine with 1:80,000 epinephrine. Ten minutes following the injection, access to cavity preparation began. Lip numbness was a must for all patients. The Heft-Parker visual analogue scale (HP-VAS) was used to measure pain during endodontic therapy. Success of primary injections was defined as no or mild pain (less than 55 mm on HP-VAS) during access preparation. The patients with initial successful anesthesia served as control and received endodontic treatment. Ninety-five patients with unsuccessful primary anesthesia randomly received either intraligamentary injections of 2% lidocaine with 1:80,000 epinephrine or intrapulpal injections with similar anesthetic solution. Endodontic treatment was re-initiated and canals were instrumented till working length under copious irrigation. Intracanal medicament of calcium hydroxide was placed and teeth received a temporary restoration. Postoperative pain was measured at 2 hours, 4 hours, 6 hours, 24 hours, and 3 days. Data were analyzed using the Pearson chi-square test, one-way analysis of variance, and one-way repeated measures analysis of variance. RESULTS: The initial initial inferior alveolar nerve block was successful in 40 cases (out of 135). The intraligamentary injections were successful in 33 out of 47 cases (70%), and intrapulpal injections were successful in all cases (45/45). The patients receiving intraligamentary injections reported significantly higher pain scores at all intervals till 24 hours. After 3 days, the pain significantly reduced in all the groups with no significant difference between them. CONCLUSIONS: Patients receiving supplementary intraligamentary injections can experience increased postoperative pain till 24 hours after the endodontic treatment. The pain scores reduced to the level of the control group after 3 days.

Targeting an inflammation-amplifying cell population can attenuate osteoarthritis-associated pain.

BACKGROUND: Understanding of pain in osteoarthritis, its genesis, and perception is still in its early stages. Identification of precise ligand-receptor pairs that transduce pain and the cells and tissues in which they reside will elucidate new therapeutic approaches for pain management. Our recent studies had identified an inflammation-amplifying (Inf-A) cell population that is expanded in human OA cartilage and is distinctive in the expression of both IL1R1 and TNF-R2 receptors and active Jnk signaling cascade. METHODS: In this study, we have tested the function of the cartilage-resident IL1R1+TNF-R2+ Inf-A cells in OA. We have identified that the IL1R1+TNF-R2+ Inf-A cells expand in aged mice as well as after anterior cruciate ligament tear upon tibia loading and OA initiation in mice. We targeted and modulated the Jnk signaling cascade in InfA through competitive inhibition of Jnk signaling in mice and human OA explants and tested the effects on joint structure and gait in mice. RESULTS: Modulation of Jnk signaling led to attenuation of inflammatory cytokines CCL2 and CCL7 without showing any structural improvements in the joint architecture. Interestingly, Jnk inhibition and lowered CCL2 and 7 are sufficient to significantly improve the gait parameters in treated PTOA mice demonstrating reduced OA-associated pain. Consistent with the mice data, treatment with JNK inhibitor did not improve human OA cartilage explants. CONCLUSION: These studies demonstrate that Inf-A, an articular-cartilage resident cell population, contributes to pain in OA via secretion of CCL2 and 7 and can be targeted via inhibition of Jnk signaling.

Effect of Intraligamentary Tramadol Hydrochloride on Anesthetic Success During Endodontic Management of Mandibular Molars: A Randomized Clinical Controlled Trial.

OBJECTIVE: Tramadol hydrochloride has shown local anesthetic properties similar to lidocaine, apart from a central analgesic effect. The present study evaluated the effect of the administration of tramadol alone or in addition to 2% lidocaine, as supplementary intraligamentary injections. METHODS: One hundred and five patients, with a failed primary inferior alveolar nerve block (IANB), were randomly allocated to one of the three supplementary intraligamentary groups: 2% lidocaine with 1: 80,000 epinephrine; tramadol hydrochloride (50 mg/mL); and 2% lidocaine with 1: 80,000 epinephrine plus tramadol hydrochloride. Patients received 1.2 mL doses (0.6 mL of each root). Patients reporting pain ≤54 on Heft Parker visual analogue scale (Heft-Parker VAS), were categorized as successful anesthesia. A finger pulse oximeter was used to measure the heart rates. The anesthetic success rates, gender, and type of tooth were compared using the Pearson chi-square test. The heart rates and age were statistically evaluated using the one-way analysis of variance test. The level of significance was set at 0.05 (p=0.05). RESULTS: The initial IANB was successful in 31% of cases. There were significant differences in the anesthetic success rates of different supplementary intraligamentary injections (χ2= 33.6, p<0.001, df=2). The 2% lidocaine-plus-tramadol resulted in significantly higher success rates than the two groups. There were no significant changes in the baseline heart rates of all groups (p>0.05). CONCLUSION: The addition of tramadol to 2% lidocaine with 1: 80,000 epinephrine, given as supplementary intraligamentary injection, can help in achieving successful anesthesia during the endodontic management of mandibular molars with irreversible pulpitis resistant to IANB injections.

TET1 Regulates Skeletal Stem-Cell Mediated Cartilage Regeneration.

OBJECTIVE: Adult skeletal stem cells (SSCs) that give rise to chondrocytes, osteocytes, and stromal cells as progeny have been shown to contribute to cartilage regeneration in osteoarthritis (OA). Understanding extrinsic and intrinsic regulators of SSC fate and function can therefore identify putative candidate factors to enhance cartilage regeneration. This study explores how the DNA hydroxymethylase Tet1 regulates SSC function in OA. METHODS: We investigated the differences in the SSC lineage tree and differentiation potential in neonatal and adult Tet1+/+ and Tet1-/- mice with and without injury and upon OA induction and progression. Using RNA sequencing, the transcriptomic differences between SSCs and bone cartilage stroma progenitor cells (BCSPs) were identified in Tet1+/+ mice and Tet1-/- mice. RESULTS: Loss of Tet1 skewed the SSC lineage tree by expanding the SSC pool and enhanced the chondrogenic potential of SSCs and BCSPs. Tet1 inhibition led to enhanced chondrogenesis in human SSCs and chondroprogenitors isolated from human cartilage. Importantly, TET1 inhibition in vivo in late stages of a mouse model of OA led to increased cartilage regeneration. Transcriptomic analyses of SSCs and BCSPs lacking Tet1 revealed pathway alterations in transforming growth factor ß signaling, melatonin degradation, and cartilage development-associated genes. Lastly, we report that use of the hormone melatonin can dampen inflammation and improve cartilage health. CONCLUSION: Although Tet1 is a broad epigenetic regulator, melatonin can mimic the inhibition ability of TET1 to enhance the chondrogenic ability of SSCs. Melatonin administration has the potential to be an attractive stem cell-based therapy for cartilage regeneration.

Sub-operon promoter arrangement of disA facilitates c-di-AMP homeostasis and selective stress responses in Mycobacterium smegmatis.

Bacterial second messenger signaling often plays an important role in cellular physiology. In this study, we have attempted to understand how c-di-AMP synthesis and degradation are transcriptionally regulated in Mycobacterium smegmatis. We found that although a c-di-AMP synthesis gene, disA, exists in a multi-gene operon, a sub-operon promoter arrangement facilitates disA gene expression under normal conditions to maintain intracellular c-di-AMP concentration and is induced further during certain stress adaptations. Individual gene-specific promoters also play a key role under various genotoxic stress conditions to shut down c-di-AMP synthesis, which could otherwise be detrimental for cells. Further, we learned that a high c-di-AMP concentration plays a role in the autoregulation of the disA promoter to limit intracellular c-di-AMP concentration. This study was helpful to understand how c-di-AMP synthesis is regulated under normal and stress conditions linked to its physiological relevance in M. smegmatis.

C-4-Modified Isotetrones Prevent Biofilm Growth and Persister Cell Resuscitation in Mycobacterium smegmatis.

Hyperphosphorylated nucleotide (p)ppGpp, synthesized by Rel protein, regulates the stringent response pathway responsible for biofilm and persister cell growth in mycobacteria. The discovery of vitamin C as an inhibitor of Rel protein activities raises the prospect of tetrone lactones to prevent such pathways. The closely related isotetrone lactone derivatives are identified herein as inhibitors of the above processes in a mycobacterium. Synthesis and biochemical evaluations show that an isotetrone possessing phenyl substituent at C-4 inhibit the biofilm formation at 400 µg mL-1, 84 h post-exposure, followed by moderate inhibition by the isotetrone possessing the p-hydroxyphenyl substituent. The latter isotetrone inhibits the growth of persister cells at 400 µg mL-1 f.c. when monitored for 2 weeks, under PBS starvation. Isotetrones also potentiate the inhibition of antibiotic-tolerant regrowth of cells by ciprofloxacin (0.75 µg mL-1) and thus act as bioenhancers. Molecular dynamics studies show that isotetrone derivatives bind to the RelMsm protein more efficiently than vitamin C at a binding site possessing serine, threonine, lysine, and arginine.

Elucidating the role of c-di-AMP in Mycobacterium smegmatis: Phenotypic characterization and functional analysis.

Cyclic-di-AMP (c-di-AMP) is an important secondary messenger molecule that plays a critical role in monitoring several important cellular processes, especially in several Gram-positive bacteria. In this study, we seek to unravel the physiological significance of the molecule c-di-AMP in Mycobacterium smegmatis under different conditions, using strains with altered c-di-AMP levels: c-di-AMP null mutant (ΔdisA) and a c-di-AMP over-expression mutant (Δpde). Our thorough analysis of the mutants revealed that the intracellular concentration of c-di-AMP could determine many basic phenotypes such as colony architecture, cell shape, cell size, membrane permeability etc. Additionally, it was shown to play a significant role in multiple stress adaptation pathways in the case of different DNA and membrane stresses. Our study also revealed how the biofilm phenotypes of M. smegmatis cells are altered with high intracellular c-di-AMP concentration. Next, we checked how c-di-AMP contributes to antibiotic resistance or susceptibility characteristics of M. smegmatis, which was followed by a detailed transcriptome profile analysis to reveal key genes and pathways such as translation, arginine biosynthesis, cell wall and plasma membrane are regulated by c-di-AMP in mycobacteria.

Erratum: Addendum: Addition of 2 mg dexamethasone to improve the anesthetic efficacy of 2% lidocaine with 1:80,000 epinephrine administered for inferior alveolar nerve block to patients with symptomatic irreversible pulpitis in the mandibular molars: a randomized double-blind clinical trial.

[This corrects the article on p. 305 in vol. 22, PMID: 35991360.].

An observational multi-centric COVID-19 sequelae study among health care workers.

Background: India has seen more than 43 million confirmed cases of COVID-19 as of April 2022, with a recovery rate of 98.8%, resulting in a large section of the population including the healthcare workers (HCWs), susceptible to develop post COVID sequelae. This study was carried out to assess the nature and prevalence of medical sequelae following COVID-19 infection, and risk factors, if any. Methods: This was an observational, multicenter cross-sectional study conducted at eight tertiary care centers. The consenting participants were HCWs between 12 and 52 weeks post discharge after COVID-19 infection. Data on demographics, medical history, clinical features of COVID-19 and various symptoms of COVID sequelae was collected through specific questionnaire. Finding: Mean age of the 679 eligible participants was 31.49 ± 9.54 years. The overall prevalence of COVID sequelae was 30.34%, with fatigue (11.5%) being the most common followed by insomnia (8.5%), difficulty in breathing during activity (6%) and pain in joints (5%). The odds of having any sequelae were significantly higher among participants who had moderate to severe COVID-19 (OR 6.51; 95% CI 3.46-12.23) and lower among males (OR 0.55; 95% CI 0.39-0.76). Besides these, other predictors for having sequelae were age (≥45 years), presence of any comorbidity (especially hypertension and asthma), category of HCW (non-doctors vs doctors) and hospitalisation due to COVID-19. Interpretation: Approximately one-third of the participants experienced COVID sequelae. Severity of COVID illness, female gender, advanced age, co-morbidity were significant risk factors for COVID sequelae. Funding: This work is a part of Indian Council for Medical Research (ICMR)- Rational Use of Medicines network. No additional financial support was received from ICMR to carry out the work, for study materials, medical writing, and APC.

Effect of Cooling of Lidocaine with Epinephrine on the Anesthetic Success of Supplementary Intraligamentary Injection after a Failed Primary Inferior Alveolar Nerve Block: A Randomized Controlled Trial.

OBJECTIVE: The purpose of this prospective, randomized clinical trial was to evaluate the effect of cooling a 2% lidocaine solution with 1: 200,000 epinephrine, administered as a supplementary intraligamentary injection to overcome a failed primary inferior alveolar nerve block (IANB). METHODS: The study was preceded by a pilot study to evaluate the anesthetic efficacy of plain lidocaine solutions given as intraligamentary injections. In the subsequent randomized clinical trial, one hundred and thirty-eight patients received IANB with 2% lidocaine with 1: 80,000 epinephrine for endodontic man- agement of a mandibular molar with symptomatic irreversible pulpitis. Eighty-eight patients reported pain greater than 54 mm on a visual analog scale (Heft-Parker VAS) were categorized as unsuccessful anesthesia. These patients received either of the following intraligamentary injections: 2% lidocaine with 1: 200,000 epinephrine at room temperature; or 2% lidocaine with 1: 200,000 epinephrine at 4°C. Anes- thetic success was again evaluated after re-initiation of the endodontic treatment. The heart rates of the patients were measured using a finger pulse oximeter. The categorical success rates were statistically analyzed with the Pearson chi-square test at 5% significance levels. The heart rate measurements were analyzed using a t-test. RESULTS: The intraligamentary injections with anesthetic solutions at room temperature presented a suc- cess rate of 59.1%, while the injections with a solution at 4°C gave a success rate of 52.27%. There were no significant differences between the success rates of the groups (χ2=0.41, p=0.52). Regarding the heart rates, there were no differences between the two solutions at baseline (T=1.2, p=0.2) or after injections (T=0.64, p=0.52). CONCLUSION: Reducing the temperature of 2% lidocaine with 1: 200,000 epinephrine to 4°C does not affect the anesthetic efficacy of supplemental intraligamentary injections, given after a failed primary IANB. (EEJ-2023-03-044).

Addition of 2 mg dexamethasone to improve the anesthetic efficacy of 2% lidocaine with 1:80,000 epinephrine administered for inferior alveolar nerve block to patients with symptomatic irreversible pulpitis in the mandibular molars: a randomized double-blind clinical trial.

Introduction: This clinical trial aimed to evaluate the anesthetic effect of the addition of 2 mg (4 mg/ml) of dexamethasone to 2% lidocaine (plain or with 1:80,000 epinephrine). The solutions were injected for a primary inferior alveolar nerve block (IANB) to provide mandibular anesthesia for the endodontic treatment of mandibular molars with symptomatic irreversible pulpitis. Methods: In a double-blinded setup, 124 patients randomly received either of the following injections: 2% lidocaine with 1:80,000 epinephrine, 2% lidocaine with 1:80,000 epinephrine mixed with 2 mg dexamethasone, or plain 2% lidocaine mixed with 2 mg dexamethasone, which were injected as a primary IANB. Ten minutes after injection, patients with profound lip numbness underwent electric and thermal pulp sensibility tests. Patients who responded positively to the tests were categorized as "failed" anesthesia and received supplemental anesthesia. The remaining patients underwent endodontic treatment using a rubber dam. Anesthetic success was defined as "no pain or faint/weak/mild pain" during endodontic access preparation and instrumentation (HP visual analog scale score < 55 mm). The effect of the anesthetic solutions on the maximum change in heart rate was also evaluated. The Pearson chi-square test at 5% and 1% significance was used to analyze anesthetic success rates. Results: The 2% lidocaine with 1:80,000 epinephrine, 2% lidocaine with 1:80,000 epinephrine mixed with 2 mg dexamethasone, and plain 2% lidocaine mixed with 2 mg dexamethasone groups had anesthetic success rates of 34%, 59%, and 29%, respectively. The addition of dexamethasone resulted in significantly better results (P < 0.001, χ2 = 9.07, df = 2). Conclusions: The addition of dexamethasone to 2% lidocaine with epinephrine, administered as an IANB, can improve the anesthetic success rates during the endodontic management of symptomatic mandibular molars with irreversible pulpitis.

Does the presence and amount of epinephrine in 2% lidocaine affect its anesthetic efficacy in the management of symptomatic maxillary molars with irreversible pulpitis?

BACKGROUND: This was a randomized controlled clinical trial that aimed to evaluate the anesthetic efficacy of 2% lidocaine combined with different concentrations of epinephrine (plain, 1:200,000 and 1:80,000) during endodontic treatment of maxillary molars with symptomatic irreversible pulpitis. METHODS: The trial included 144 adult patients who were randomly allocated to three treatment groups. All patients received buccal-plus-palatal infiltration. After 10 min, pulp sensibility testing was performed using an electric pulp test (EPT). If a tooth responded positively, anesthesia was considered to have failed. In the case of a negative EPT response, endodontic access was initiated under rubber dam isolation. The success of anesthesia was defined as having a pain score less than 55 on the Heft Parker visual analog scale (HP VAS), which was categorized as 'no pain' or 'faint/weak/mild' pain on the HP VAS. Baseline pre-injection and post-injection maximum heart rates were recorded. The Pearson chi-square test was used to analyze the anesthetic success rates at 5% significance. RESULTS: Plain 2% lidocaine and 2% lidocaine with 1:200,000 epinephrine and 1:80,000 epinephrine had anesthetic success rates of 18.75%, 72.9%, and 82.3%, respectively. Statistical analysis indicated significant differences between the groups (P < 0.001, χ2 = 47.5, df = 2). The maximum heart rate increase was seen with 2% lidocaine solution with epinephrine. CONCLUSION: Adding epinephrine to 2% lidocaine significantly improves its anesthetic success rates during the root canal treatment of maxillary molars with symptomatic irreversible pulpitis.

A Quick and Efficient Method for the Generation of Immunomodulatory Mesenchymal Stromal Cell from Human Induced Pluripotent Stem Cell.

Mesenchymal stromal cells (MSCs) have been widely investigated for their regenerative capacity, anti-inflammatory properties and beneficial immunomodulatory effects across multiple clinical indications. Nevertheless, their widespread clinical utilization is limited by the variability in MSC quality, impacted by donor age, metabolism, and disease. Human induced pluripotent stem cells (hiPSCs) generated from readily accessible donor tissues, are a promising source of stable and rejuvenated MSC but differentiation methods generally require prolonged culture and result in low frequencies of stable MSCs. To overcome this limitation, we have optimized a quick and efficient method for hiPSC differentiation into footprint-free MSCs (human induced MSCs [hiMSCs]) in this study. This method capitalizes on the synergistic action of growth factors Wnt3a and Activin A with bone morphogenetic protein-4 (BMP4), leading to an enrichment of MSC after only 4 days of treatment. These hiMSCs demonstrate a significant upregulation of mesenchymal stromal markers (CD105+, CD90+, CD73, and cadherin 11) compared with bone marrow-derived MSCs (bmMSCs), with reduced expression of the pluripotency genes (octamer-binding transcription factor [Oct-4], cellular myelocytomatosis oncogene [c-Myc], Klf4, and Nanog homebox [Nanog]) compared with hiPSC. Moreover, they show improved proliferation capacity in culture without inducing any teratoma formation in vivo. Osteogenesis, chondrogenesis, and adipogenesis assays confirmed the ability of hiMSCs to differentiate into the three different lineages. Secretome analyses showed cytokine profiles compared with bmMSCs. Encapsulated hiMSCs in alginate beads cocultured with osteoarthritic (OA) cartilage explants showed robust immunomodulation, with stimulation of cell growth and proteoglycan production in OA cartilage. Our quick and efficient protocol for derivation of hiMSC from hiPSC, and their encapsulation in microbeads, therefore, presents a reliable and reproducible method to boost the clinical applications of MSCs.

Preoperative Intraligamentary Injection of Dexamethasone Can Improve the Anesthetic Success Rate of 2% Lidocaine during the Endodontic Management of Mandibular Molars with Symptomatic Irreversible Pulpitis.

INTRODUCTION: The aim of this randomized, double-blind clinical trial was to evaluate the effect of preoperative administration of intraligamentary injections of diclofenac sodium and dexamethasone on the anesthetic efficacy of 2% lidocaine given as an inferior alveolar nerve block in the endodontic management of symptomatic irreversible pulpitis. METHODS: One hundred seventeen patients randomly received 1 of the 3 intraligamentary injections before the endodontic treatment: 0.9% normal saline, 25 mg/mL diclofenac sodium, or 4 mg/mL dexamethasone. After 30 minutes, patients received an inferior alveolar nerve block with 2% lidocaine and 1:80,000 epinephrine. The teeth were tested with electric pulp testing after 10 minutes. In case of a positive response, the anesthesia was considered as "failed." If the electric test response was negative, a rubber dam was applied, and endodontic treatment was started. Any pain during the treatment was recorded. The anesthesia was considered successful if the patients experienced no pain or faint/weak/mild pain during root canal access preparation and instrumentation (Heft-Parker visual analog scale score <55 mm). The effect of intraligamentary injections on maximum heart rates was also recorded. The anesthetic success rates were analyzed with the Pearson chi-square test at 5% significance. RESULTS: The control, diclofenac sodium, and dexamethasone groups had anesthetic success rates of 32%, 37%, and 73%, respectively. Dexamethasone was significantly more successful than the control and diclofenac sodium groups (P < .001, χ22 = 14.7). There were no differences between the control and diclofenac groups (P > .05). All the solutions did not significantly affect heart rates. CONCLUSIONS: The administration of an intraligamentary injection of dexamethasone before endodontic intervention of mandibular molars with symptomatic irreversible pulpitis increases the success rates of an inferior alveolar nerve block with 2% lidocaine.

Anaesthetic efficacy of 2% lidocaine with different concentrations of epinephrine (1:80,000 and 1:200,000) in intraligamentary injection after a failed primary inferior alveolar nerve block: a randomized double-blind study.

Introduction: The present study evaluated the anaesthetic efficacy of 2% lidocaine with 1:80,000 epinephrine vs. 2% lidocaine with 1:200,000 given as supplemental intraligamentary injections after a failed inferior alveolar nerve block (IANB) in patients with symptomatic irreversible pulpitis. The effect of these solutions on the heart rate was also evaluated.Methods: One-hundred-eighteen adult patients with symptomatic irreversible pulpits in a mandibular first or second molar, received an initial IANB with 2% lidocaine with 1:80,000 epinephrine. Pain during the endodontic treatment was assessed using a visual analogue scale (Heft-Parker VAS). Eighty-eight patients with unsuccessful anaesthesia were randomly allocated to one of the two treatment groups: one group received 0.6 mL/root of supplementary intraligamentary injection of 2% lidocaine with 1:80,000 epinephrine; while the second group received 2% lidocaine with 1:200,000 epinephrine. Endodontic treatment was re-initiated. Success after primary injection or supplementary injection was defined as no or mild pain (pain score ≤54 mm on HP VAS) during access preparation and root canal instrumentation. Heart rate was monitored using a finger pulse oximeter. The anaesthetic success rates were analyzed with the Pearson chi-square test at 5% significance levels. The heart rate changes were analyzed using the t-test.Results: The anaesthetic success rate in patients receiving supplementary intraligamentary injections in 1:80,000 epinephrine group was 82%, while the intraligamentary injections with 2% lidocaine with 1:200,000 epinephrine were successful in 57% of cases. The difference was statistically significant (χ2=6.4, p = .011). There was no significant effect of both the anaesthetic agents on the mean heart rate.Conclusions: Both 2% lidocaine with 1:80,000 epinephrine and 2% lidocaine with 1:200,000 epinephrine improved the success rates after a failed primary anaesthetic injection. The 1:80,000 epinephrine group was significantly more successful.

Efficacy of Articaine Versus Lidocaine Administered as Supplementary Intraligamentary Injection after a Failed Inferior Alveolar Nerve Block: A Randomized Double-blind Study.

INTRODUCTION: The present study comparatively evaluated the anesthetic efficacy of 4% articaine versus 2% lidocaine given as supplemental intraligamentary injections after a failed inferior alveolar nerve block. METHODS: One hundred six adult patients with symptomatic irreversible pulpitis in a mandibular first or second molar received an initial inferior alveolar nerve block with 2% lidocaine with 1:80,000 epinephrine. Pain during the endodontic treatment was assessed using the Heft-Parker visual analog scale. Eighty-two patients with unsuccessful anesthesia were randomly allocated to 2 treatment groups: 1 group received 0.6 mL/root of supplementary intraligamentary injection of 4% articaine with 1:100,000 epinephrine, and the second group received 2% lidocaine with 1:80,000 epinephrine. Endodontic treatment was reinitiated. Success after the primary injection or supplementary injection was defined as no or mild pain (less than 55 mm on the Heft-Parker visual analog scale) during access preparation and root canal instrumentation. Patients' heart rate was monitored using a finger pulse oximeter. The anesthetic success rates were analyzed with the Pearson chi-square test at 5% significance levels. The heart rate changes were analyzed using the t test. RESULTS: The patients receiving supplementary intraligamentary injections of 4% articaine had a success rate of 66%, whereas 2% lidocaine injections were successful in 78% of cases. The difference was statistically nonsignificant (χ2 = 1.51, P = .2). There was no significant effect of the different anesthetic agents on the heart rate. CONCLUSIONS: Both 4% articaine and 2% lidocaine improved the success rates after a failed primary anesthetic injection, with no significant difference between them.

Effect of polyethylene fiber reinforcement on marginal adaptation of composite resin in Class II preparations.

The aim of this study was to evaluate the effect of polyethylene fibers incorporated in a composite resin matrix on the gingival marginal adaptation of Class II slot restorations. Sixty Class II slot cavity preparations were divided into 2 groups. A fiber-reinforced resin (FRR) group received restorations of composite resin mixed with strips of polyethylene fiber, and an unreinforced resin (UR) group was restored with only composite resin. The groups were subdivided on the basis of the adhesive system (etch-and-rinse or self-etch) that was used. Shrinkage stress was evaluated by placing a strain gauge at the buccal surface of the teeth. A scanning electron microscope was used to evaluate marginal adaptation in terms of a continuous margin (CM) at the gingival margin. Statistical analysis included a 2-way analysis of variance with the Holm-Sidak correction for multiple comparisons at a significance level of 0.05. The mean strain value was significantly smaller in the FRR group (185 [SD 37] µm/m) than in the UR group (295 [SD 21] µm/m). The FRR group presented with a mean CM value of 80.2% (SD 4.6%), which was significantly higher than that of the UR group, which had an overall CM value of 64.4% (SD 4.2%). There was no statistically significant difference between the adhesive subgroups with regard to strain or percentage of CM. The results showed that the incorporation of polyethylene fibers in a composite resin matrix can help to improve gingival marginal adaptation in Class II cavities.

Effect of root canal obturation with calcium silicate materials on pH change in simulated root resorption defects.

This study evaluated the effect of 3 commercially available calcium silicate materials (CSMs) on pH changes in simulated root resorption defects. Simulated root resorption defects were prepared on the facial root surface of 40 mandibular premolars. The depth of each defect was individually calculated to standardize the remaining dentin thickness to 1 mm. Prepared canals were obturated with the 3 CSMs. Ten specimens were kept as controls, filled with unbuffered normal saline. The pH measurements were taken at 1 hour, 6 hours, 1 day, 1 week, 2 weeks, 3 weeks, 1 month, and 2 months. All CSM groups exhibited an initial alkaline pH of 9.0-9.7. The pH decreased to 8.0-8.5 after 2 months of storage. There were no significant differences between pH measurements at other time intervals. The CSM groups exhibited higher pH levels than the control group. The results showed that intracanal placement of the CSMs maintained initial pH levels of 9.0-9.7 inside the simulated resorption defects; these measurements gradually decreased to 8.0-8.5 over the span of 2 months.

Epithelial to mesenchymal transition induces stem cell like phenotype in renal cell carcinoma cells.

BACKGROUND: Metastatic dissemination of solid tumors is often initiated by reactivation of an embryonic development program, epithelial-to-mesenchymal-transition (EMT). EMT has been associated with acquiring invasiveness and resistance to conventional therapies. However, the precise role of EMT during renal cell carcinoma is still debatable and is under investigation. In this context, our study is designed to evaluate the role of cyclosporine (CsA) and transforming growth factor-ß (TGFß) administration in inducing EMT-like state in renal carcinoma cells. We also studied the associated phenotypic changes which may lead to tumor metastasis. METHODS: The morphological changes in renal cell carcinoma cells (A498) treated with TGF-ß/CsA were observed by microscopy. Atomic force microscope was used to evaluate the changes in elasticity of cells treated with TGF-ß/CsA. The expression of mesenchymal and chemoresistance genes were checked by RT-PCR. Assays for migration, invasion, sphere formation ability and expression of cancer stem cell-like phenotypes were done to evaluate the metastatic potential of these cells. Lineage specific differentiations were also done to determine the acquisition of stem-cell like phenotype. RESULTS: Our results showed that treatment with TGF-ß/CsA led to loss of epithelial characteristics and gain of mesenchymal phenotype in vitro. Changes in shape and elastic properties of the cancer cells favoured metastatic progression, increased tumorisphere formation and invasiveness post treatment. We also observed higher expression of chemoresistance and stemness markers in EMT-induced cells. These cells also differentiated to various lineages like osteoblasts, adipocytes, neural and hepatic cells when induced with the respective differentiation media. CONCLUSION: We concluded that TGF-ß/CsA treatment led to acquisition of EMT-like cancer stem cells phenotype that enhanced local invasion and dissemination of renal carcinoma cells. This subpopulation of cells with EMT-like phenotype a can provide a better perception of the metastatic process. This can provide an in vitro system for testing pharmaceuticals for modulating EMT as a viable strategy within the therapeutic armamentarium for RCC patients. The results of our findings also suggest that CsA directly induced EMT like changes in epithelial cell which may be responsible for the potential risk of malignancy in transplant patients.

Effect of relative head position on the anesthetic efficacy of inferior alveolar nerve block during endodontic treatment of patients with irreversible pulpitis.

BACKGROUND: The purpose of this prospective randomized single-blind clinical trial was to evaluate the effect of tilting the head on the anesthetic efficacy of inferior alveolar nerve block (IANB) in patients with symptomatic irreversible pulpitis. METHODS: Ninety-two patients were divided into two groups: the first group received IANB and the head was tilted in the direction of the block for 15 min, whereas the second group received IANB and the head was tilted to the opposite side. Access cavity preparation was initiated after 15 min. Success was defined as no pain or faint/weak/mild pain during endodontic access preparation and instrumentation. The anesthetic success rates were analyzed by Pearson chi-square test at 5% significance levels. RESULTS: The same side position and opposite side position yielded 41% and 30% anesthetic success rates, respectively; there was no significant difference between the two sides. CONCLUSIONS: Relative head position has no effect on the anesthetic success rate of IANB.