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Cognitive impairment is common in extracerebral diseases such as chronic kidney disease (CKD). Kidney transplantation reverses cognitive impairment, indicating that cognitive impairment driven by CKD is therapeutically amendable. However, we lack mechanistic insights allowing development of targeted therapies. Using a combination of mouse models (including mice with neuron-specific IL-1R1 deficiency), single cell analyses (single-nuclei RNA-sequencing and single-cell thallium autometallography), human samples and in vitro experiments we demonstrate that microglia activation impairs neuronal potassium homeostasis and cognition in CKD. CKD disrupts the barrier of brain endothelial cells in vitro and the blood-brain barrier in vivo, establishing that the uremic state modifies vascular permeability in the brain. Exposure to uremic conditions impairs calcium homeostasis in microglia, enhances microglial potassium efflux via the calcium-dependent channel K Ca 3.1, and induces p38-MAPK associated IL-1β maturation in microglia. Restoring potassium homeostasis in microglia using a K Ca 3.1-specific inhibitor (TRAM34) improves CKD-triggered cognitive impairment. Likewise, inhibition of the IL-1β receptor 1 (IL-1R1) using anakinra or genetically abolishing neuronal IL-1R1 expression in neurons prevent CKD-mediated reduced neuronal potassium turnover and CKD-induced impaired cognition. Accordingly, in CKD mice, impaired cognition can be ameliorated by either preventing microglia activation or inhibiting IL-1R-signaling in neurons. Thus, our data suggest that potassium efflux from microglia triggers their activation, which promotes microglia IL-1β release and IL-1R1-mediated neuronal dysfunction in CKD. Hence, our study provides new mechanistic insight into cognitive impairment in association with CKD and identifies possible new therapeutic approaches., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Glomerular-tubular crosstalk within the kidney has been proposed, but the paracrine signals enabling this remain largely unknown. The cold-shock protein Y-box binding protein 1 (YBX1) is known to regulate inflammation and kidney diseases but its role in podocytes remains undetermined. Therefore, we analyzed mice with podocyte specific Ybx1 deletion (Ybx1 ΔPod ). Albuminuria was increased in unchallenged Ybx1 ΔPod mice, which surprisingly was associated with reduced glomerular, but enhanced tubular damage. Tubular toll-like receptor 4 (TLR4) expression, node-like receptor protein 3 (NLRP3) inflammasome activation and kidney inflammatory cell infiltrates were all increased in Ybx1 ΔPod mice. In vitro, extracellular YBX1 inhibited NLRP3 inflammasome activation in tubular cells. Co-immunoprecipitation, immunohistochemical analyses, microscale cell-free thermophoresis assays, and blunting of the YBX1-mediated TLR4-inhibition by a unique YBX1-derived decapeptide suggests a direct interaction of YBX1 and TLR4. Since YBX1 can be secreted upon post-translational acetylation, we hypothesized that YBX1 secreted from podocytes can inhibit TLR4 signaling in tubular cells. Indeed, mice expressing a non-secreted YBX1 variant specifically in podocytes (Ybx1 PodK2A mice) phenocopied Ybx1 ΔPod mice, demonstrating a tubular-protective effect of YBX1 secreted from podocytes. Lipopolysaccharide-induced tubular injury was aggravated in Ybx1 ΔPod and Ybx1 PodK2A mice, indicating a pathophysiological relevance of this glomerular-tubular crosstalk. Thus, our data show that YBX1 is physiologically secreted from podocytes, thereby negatively modulating sterile inflammation in the tubular compartment, apparently by binding to and inhibiting tubular TLR4 signaling. Hence, we have uncovered an YBX1-dependent molecular mechanism of glomerular-tubular crosstalk., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) took place in person in Montréal, Canada, from June 24-28, 2023. The conference, held annually, highlighted cutting-edge advances in basic, translational, population and clinical sciences relevant to the Society. As for all ISTH congresses, we offered a special, congress-specific scientific theme; this year, the special theme was immunothrombosis. Certainly, over the last few years, COVID-19 infection and its related thrombotic and other complications have renewed interest in the concepts of thromboinflammation and immunothrombosis; namely, the relationship between inflammation, infection and clotting. Other main scientific themes of the Congress included Arterial Thromboembolism, Coagulation and Natural Anticoagulants, Diagnostics and Omics, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostatic System in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women's Health. Among other sessions, the program included 28 State-of-the-Art (SOA) sessions with a total of 84 talks given by internationally recognized leaders in the field. SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the Congress., (© 2023 Published by Elsevier Inc. on behalf of International Society on Thrombosis and Haemostasis.)

The opioid overdose epidemic has caused over 600,000 deaths in the U.S. since 1999. Public access naloxone programs show great potential as a strategy for reducing opioid overdose-related deaths. However, their implementation within public transit stations, often characterized as opioid overdose hotspots, has been limited, partly because of a lack of understanding in how to structure such programs. Here, we propose a comprehensive framework for implementing public access naloxone programs at public transit stations to curb opioid overdose-related deaths. The framework, tailored to local contexts, relies on coordination between local public health organizations to provide naloxone at public access points and bystander training, local academic institutions to oversee program evaluation, and public transit organizations to manage naloxone maintenance. We use the city of Cambridge, Massachusetts as a case study to demonstrate how it and other municipalities may implement such an initiative., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians., Competing Interests: Conflict of interest Raman Puri: Boehringer Ingelheim, Novartis Vimal Mehta: Institutional research grants from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, LIB Therapeutics, Novo Nordisk, Torrent P Barton Duell: Advisory activities: Akcea/Ionis, Esperion, Novo Nordisk, Regeneron, Kaneka. Institutional grants: Regeneron, Regenxbio, Retrophin/Travere V Mohan: Research or educational grants from Abbott, AstraZeneca, Boehringer Ingelheim, Dr. Reddy's Lab, Johnson and Johnson, Lifescan, MSD, Novartis, Novo Nordisk, Roche Diabetes Care India Private Ltd, Sanofi-Aventis, USV, other Indian pharmaceutical companies S. S. Iyengar: Dr. Reddy's Lab, Amgen, Emcure, Glenmark, Boehringer Ingelheim, Pfizer, Novartis Vinod Mittal: Boehringer Ingelheim, USV, Cipla, Intas, Emcure, MacLeods S N Narasingan: USV, Novo Nordisk, Eris, Glenmark, Torrent, Boehringer Ingelheim J.B. Chemicals and Pharmaceuticals Nathan D. Wong: Amgen, Amarin, Novartis, Esperion SK Wangnoo: Sanofi- Aventis, Nova Nordisk, Boehringer Ingelheim, Astra Zeneca The other authors report no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Dysfunction of mesangial cells plays a major role in the pathogenesis of diabetic kidney disease (DKD), the leading cause of kidney failure. However, the underlying molecular mechanisms are incompletely understood. By unbiased gene expression analysis of glucose-exposed mesangial cells, we identified the transmembrane receptor CD248 as the most upregulated gene, and the maladaptive unfolded protein response (UPR) as one of the most stimulated pathways. Upregulation of CD248 was further confirmed in glucose-stressed mesangial cells in vitro, in kidney glomeruli isolated from diabetic mice (streptozotocin; STZ and db/db models, representing type 1 and type 2 diabetes mellitus, respectively) in vivo, and in glomerular kidney sections from patients with DKD. Time course analysis revealed that glomerular CD248 induction precedes the onset of albuminuria, mesangial matrix expansion and maladaptive UPR activation (hallmarked by transcription factor C/EBP homologous protein (CHOP) induction) but is paralleled by loss of the adaptive UPR regulator spliced X box binding protein (XBP1). Mechanistically, CD248 promoted maladaptive UPR signaling via inhibition of the inositol requiring enzyme 1α (IRE1α)-mediated transcription factor XBP1 splicing in vivo and in vitro. CD248 induced a multiprotein complex comprising heat shock protein 90, BH3 interacting domain death agonist (BID) and IRE1α, in which BID impedes IRE1α-mediated XBP1 splicing and induced CHOP mediated maladaptive UPR signaling. While CD248 knockout ameliorated DKD-associated glomerular dysfunction and reverses maladaptive unfolded protein response signaling, concomitant XBP1 deficiency abolished the protective effect in diabetic CD248 knockout mice, supporting a functional interaction of CD248 and XBP1 in vivo. Hence, CD248 is a novel mesangial cell receptor inducing maladaptive UPR signaling in DKD., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Pathogenic variants in the transmembrane sulfate transporter protein SLC26A2 are associated with different phenotypes of inherited chondrodysplasias. As limited data is published from India, in this study we sought to elucidate the molecular basis of inherited chondrodysplasias in an Indian cohort., Methods: Molecular screening of 32 fetuses with antenatally diagnosed lethal skeletal dysplasia was performed by next generation sequencing and Sanger sequencing. The genotype-protein phenotype characterization was done using computational biology techniques like homology modelling, stability and pathogenicity predictions., Results: We identified five rare autosomal recessive SLC26A2 [NM_000112.4] variants, including three homozygous c.796dupA(p.Thr266Asnfs*12), c.1724delA(p.Lys575Serfs*10), and c.1375_1377dup(p.Val459dup) and two heterozygous variants (c.532C > T(p.Arg178*)) and (c.1382C > T(p.Ala461Val)) in compound heterozygous form in a total of four foetuses. Genotype-protein phenotype annotations highlighted that the clinically severe achondrogenesis 1B causative c.796dupA(p.Thr266Asnfs*12) and c.1724delA(p.Lys575Serfs*10)variants impact SLC26A2 protein structure by deletion of the protein core and transmembrane STAS domains, respectively. In clinically moderate atelosteogenesis type 2 phenotype, the c.1382C > T(p.Ala461Val) variant is predicted to distort alpha helix conformation and alter the bonding properties and free energy dynamics of transmembrane domains and the c.532C > T(p.Arg178*) variant results in loss of both core transmembrane and STAS domains of the SLC26A2 protein. The c.1375_1377dup(p.Val459dup) variant identified in clinically milder atelosteogenesis type II-diastrophic dysplasia spectrum lethal phenotype is predicted to decrease the Qualitative Model Energy Analysis (QMean), which affects major geometrical aspects of the SLC26A2 protein structure., Conclusion: We expand the spectrum of SLC26A2 related lethal chondrodysplasia and report three novel variants correlating clinical severity and protein phenotype within the lethal spectrum of this rare dysplasia. We demonstrate the relevance of structural characterization to aid novel variant reclassification to provide better prenatal management and reproductive options to families with lethal antenatal skeletal disorder., Competing Interests: Declaration of competing interest There was no conflict of interest for any author., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objectives: India introduced BBV152/Covaxin and AZD1222/Covishield vaccines in January 2021. We estimated the effectiveness of these vaccines against severe COVID-19 among individuals aged ≥45 years., Methods: We did a multi-centric, hospital-based, case-control study between May and July 2021. Cases were severe COVID-19 patients, and controls were COVID-19 negative individuals from 11 hospitals. Vaccine effectiveness (VE) was estimated for complete (2 doses ≥ 14 days) and partial (1 dose ≥ 21 days) vaccination; interval between two vaccine doses and vaccination against the Delta variant. We used the random effects logistic regression model to calculate the adjusted odds ratios (aOR) with a 95% confidence interval (CI) after adjusting for relevant known confounders., Results: We enrolled 1143 cases and 2541 control patients. The VE of complete vaccination was 85% (95% CI: 79-89%) with AZD1222/Covishield and 71% (95% CI: 57-81%) with BBV152/Covaxin. The VE was highest for 6-8 weeks between two doses of AZD1222/Covishield (94%, 95% CI: 86-97%) and BBV152/Covaxin (93%, 95% CI: 34-99%). The VE estimates were similar against the Delta strain and sub-lineages., Conclusion: BBV152/Covaxin and AZD1222/Covishield were effective against severe COVID-19 among the Indian population during the period of dominance of the highly transmissible Delta variant in the second wave of the pandemic. An escalation of two-dose coverage with COVID-19 vaccines is critical to reduce severe COVID-19 and further mitigate the pandemic in the country., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: To investigate, using a validated questionnaire, the teaching of removable partial dentures (RPDs) in dental schools of Malaysia., Materials and Methods: A validated questionnaire to investigating trends in the teaching of RPDs in dental schools in Oceania was emailed (in English version form) to Heads of Restorative/Prosthodontics/course coordinators in the 13 dental schools in Malaysia. Follow-up reminders were sent and participants were given six weeks to complete and return the questionnaire. Data was entered into an Excel spreadsheet and results compiled and analyzed., Results: Completed questionnaires were received from 13 dental school - a 100% response rate. All schools (n = 13) provided a preclinical technical course in RPD design. In most schools (n = 9, 69.2%), course work was supervised by senior lecturers while rest of the institutions made use of associate professor/professors. There were significant differences (p<0.05) between dental schools in terms of the contact hours dedicated to preclinical teaching. Students received an average of 62 h of instruction. Didactic instruction was the primary focus with practical (78 h) and didactic teaching (32 h). All dental schools (n = 13) provided practical surveyor design teaching (8 h). The staff student ratio for formal lectures (1:61), tutorials (1:29) and lab demonstrations (1:12) were recorded. Majority of the schools (n = 11, 84.6%) employed paired teaching in clinical sessions. All schools (n = 13, 100%) emphasized on increased teaching of RPD design and prescription writing in future clinical RPD courses., Conclusion: Teaching of RPDs in Malaysia may be considered sufficient and comparable to the teaching in other parts of the world., Clinical Significance: Whilst the teaching of partial dentures at Dental Schools in Malaysia provides the core competencies involved in partial denture design and construction based on sound fundamental, scientific principles they should address the challenges of teaching partial dentures and other areas of dental education including improving working conditions for dental professionals., (Copyright © 2022. Published by Elsevier Ltd.)

The purpose of this trial was to study the effect on pain and mouth opening of intramuscular injection of botulinum toxin-A into masticatory muscles following surgical intervention in oral submucous fibrosis (OSMF) cases. Injections of either botulinum toxin A (BTX-A) (study group) or normal saline (control group) were given 2 weeks prior to surgical intervention in OSMF patients, into the bilateral masseter and temporalis muscles. All patients were evaluated for pain and ease of active physiotherapy at 1 week and 1, 3, and 6 months after surgery using a numerical rating scale and appropriate questionnaires, with comparisons made between the study and control group patients. Electromyographic studies of the masticator muscles were also carried out in all patients before injection, and at 1 month and 6 months after injection. 20 OSMF patients were equally divided into study and control groups (n = 10 each). At 1, 3, and 6 months after surgery, the study group patients showed significantly greater decreases in pain (p-values of 0.007, 0.001, and 0.005, respectively) and greater ease in physiotherapy compared with the control group. EMG recordings of masticator muscles showed a transient drop in microvolt value in the study group 1 month after injection, unlike the control group recordings. It was concluded that preoperative BTX-A injection was a good addition to surgical therapy in the patient group., Competing Interests: Declaration of competing interest None., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Aim: Genetic contribution in acute rheumatic fever (ARF)/rheumatic heart disease (RHD) has been suggested but not according to severity of the valve involvement. This study attempts to identify the relevance of CTLA-4 polymorphism with severity of the disease., Methods: In a case-control design, 291 healthy controls and 83 patients were genotyped for association between RHD and single-nucleotide polymorphisms -1661A/G of CTLA-4., Results: Segregation of patients on the basis of severity i.e., MVL (Mitral Valve Lesion) and CVL (Combined Valve Lesion) revealed that the frequency of CTLA-4 -1661G allele depleted as the disease progressed to CVL (p < 0.05). Patients in the age group of 31-45 years were significantly more susceptible (p < 0.046). Whereas, female patients were more susceptible than the male patients., Conclusion: Our study suggests the risk associated with decreased frequency of CTLA-4 -1661G allele in the CVL group and in females., Competing Interests: Declaration of competing interest All the authors state that they have no conflict interest to declare with respect to the present article titled “Susceptibility of CTLA-4 −1661A/G polymorphism towards severity of Rheumatic Heart Disease”., (Copyright © 2021 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Excess platelet activation by extracellular vesicles (EVs) results in trophoblast inflammasome activation, interleukin 1β (IL-1β) activation, preeclampsia (PE), and partial embryonic lethality. Embryonic thrombomodulin (TM) deficiency, which causes embryonic lethality hallmarked by impaired trophoblast proliferation, has been linked with maternal platelet activation. We hypothesized that placental TM loss, platelet activation, and embryonic lethality are mechanistically linked to trophoblast inflammasome activation. Here, we uncover unidirectional interaction of placental inflammasome activation and reduced placental TM expression: although inflammasome inhibition did not rescue TM-null embryos from lethality, the inflammasome-dependent cytokine IL-1β reduced trophoblast TM expression and impaired pregnancy outcome. EVs, known to induce placental inflammasome activation, reduced trophoblast TM expression and proliferation. Trophoblast TM expression correlated negatively with IL-1β expression and positively with platelet numbers and trophoblast proliferation in human PE placentae, implying translational relevance. Soluble TM treatment or placental TM restoration ameliorated the EV-induced PE-like phenotype in mice, preventing placental thromboinflammation and embryonic death. The lethality of TM-null embryos is not a consequence of placental NLRP3 inflammasome activation. Conversely, EV-induced placental inflammasome activation reduces placental TM expression, promoting placental and embryonic demise. These data identify a new function of placental TM in PE and suggest that soluble TM limits thromboinflammatory pregnancy complications., (© 2021 by The American Society of Hematology.)

Objectives: The extent to which dentists are happy with their profession and their life has not been well studied. The present study aimed to explore the level of happiness, satisfaction with life and psychological well-being among a sample of dental professionals from 21 countries., Materials and Methods: The sample comprised 2,200 dentists from 21 countries. Three scales - Subjective Happiness Scale (SHS), Satisfaction With Life Scale (SWLS), and Affect Balance Scale (ABS) - were used to measure the subjective responses. Data related to demographic and social characteristics were recorded. Mann-Whitney and Kruskal-Wallis tests were used as appropriate. Scales were correlated, and multiple linear regression analyses were employed to identify the independent determinants of SHS, SWLS and ABS. Data were analysed using the SPSS software program; a value of P <0.05 was considered significant., Results: The overall mean scores of SHS, SWLS and ABS were 18.53 ± 5.06, 23.06 ± 6.25 and 1.26 ± 2.40, respectively, with significant differences found across countries: dentists working in Croatia, Peru and Serbia recorded the highest scores, unlike dentists practicing in Yemen, Syria, and Iraq, who recorded the lowest scores. There were significant, moderately positive correlations between the various scales: SHS and SWLS: r = 0.535, P < 0.001; SHS and ABS: r = 0.58, P < 0.001; and SWLS and ABS: r = 0.533, P < 0.001. Country of practice, age, qualification and monthly income were the significant independent predictors of SHS, SWLS and ABS., Conclusion: Country of residence and social characteristics were associated with dentists' responses regarding their feelings and subjective well-being., (© 2020 FDI World Dental Federation.)

Purpose: Enterococci express high degree of resistance towards wide range of antibiotics. Production of biofilm and many virulence factors along with drug resistance makes it difficult to eradicate the infection from urinary tract. The present study detected the expression of such factors including biofilm production by multidrug-resistant (MDR) enterococci., Materials and Methods: Drug susceptibility of 103 uropathogenic enterococci was performed followed by estimation of minimum inhibitory concentration of high-level gentamicin and vancomycin by microbroth dilution method. Vancomycin-resistant genes were detected by multiplex polymerase chain reaction. Production of virulence factors such as haemagglutination, caseinase, lipase, gelatinase, haemolysin and β-lactamase was detected by phenotypic methods in MDR strains. Biofilm production was detected by calcofluor-white fluorescence staining and semi-quantitative adherence assay., Results: 45% and 18.4% of the isolates were high-level gentamicin-resistant and vancomycin-resistant enterococci (VRE), respectively. vanA gene was detected in 14 and vanB gene in 5 strains. Biofilm, caseinase and gelatinase were the most expressed virulence factor. Expression of caseinase, gelatinase and lipase was significantly higher in Enterococcus faecalis (P < 0.05). Expression of haemagglutination, gelatinase and haemolysin among the vancomycin-resistant isolates was significantly higher (P < 0.05)., Conclusion: VanA and vanB are the prevalent genotypes responsible for vancomycin resistance. The high prevalence of MDR enterococcal strains producing biofilm and virulence determinants raises concern. asa1, hyl, esp, gelE, cyl and other genes are known to express these factors and contribute to biofilm formation. Most uropathogenic enterococci expressed biofilm at moderate level and can be detected effectively by calcofluor-white staining. No correlation was noted between vancomycin resistance and biofilm production., Competing Interests: None

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 (χ 2  = 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., (Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Takayasu arteritis (TA) is an idiopathic chronic inflammatory disease of the aorta and its branches, leading to stenosis, occlusion, and aneurysmal dilatation. Tumor necrosis factor-alpha (TNF-α) is a cytokine with pleomorphic actions and plays a pivotal role in inflammation; the serum level of TNF-α is genetically determined. However, the literature lacks adequate information on the association of TNF-α polymorphisms with TA. Hence, the present study investigates the contribution of TNF-α polymorphism toward the complex etiology of TA., Methods: A cross-sectional study was performed in 87 patients with TA and 90 controls. A promoter region polymorphism of TNF-α, rs1800629 G/A, or -308G/A was genotyped in all the study subjects followed by a case-control association study. Furthermore, to understand the biomarker profile, levels of specific markers such as erythrocyte sedimentation rate, serum high-sensitivity C-reactive protein, interleukin-18, interleukin-6, and TNF-α were measured in all the study subjects., Results: All the inflammatory markers were significantly higher in the TA patients than in the controls. The genetic study (available for 57 TA patients and 36 controls) revealed that the TNF-α -308A allele was overrepresented in the TA patients (12% vs 7%). The TNF-α -308A allele correlated with the increased TNF-α levels, but it could not attain significance because of a small sample size., Conclusion: The TNF-α -308G/A polymorphism is associated with TNF-α levels in Indian population, which might have implications for clinical risk stratification and treatment. The different TNF-α gene promoter polymorphism might contribute to the molecular pathogenesis of TA. However, further study of the underlying mechanism is warranted., (Copyright © 2018 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this prospective, randomized, comparative clinical study was to compare treatment outcome of removal of foci and incision and drainage, with or without oral antibiotic therapy, in the management of single primary maxillofacial space infection with a known focus., Materials and Methods: A total of 40 patients with single primary maxillofacial space infection with a known infectious focus were divided into two groups, one treated with incision and drainage only, and the other with incision and drainage along with oral antibiotics. The focus of infection was addressed in both groups. Parameters evaluated included pain score, maximum mouth opening, swelling, purulent discharge and return to normal life, which were assessed on days 1, 2, 3, 5 and 7. The patients were followed up until they reported return to normal life as assessed by a questionnaire., Results: All of the patients rapidly responded to treatment as observed by a reduction in pain, swelling, discharge, and improvement in mouth opening. Pus discharge stopped within first 3 days in 75% of patients. The patients who underwent immediate extraction showed a faster resolution of infection (mean return to normal life = 9 days) than others (mean = 11.2 days). There was no statistically significant difference between the two groups for the five study parameters (p < 0.05). Of the total pus specimens, 75% had no significant bacterial growth, or grew 'oral flora'/contaminants, while only 25% grew specific bacteria., Conclusion: This study questions the conventional practice by dental practitioners and surgeons of prescribing antibiotics to all patients with odontogenic infection. Microbial culture and antibiotic sensitivity is of little therapeutic value in selected patient groups., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The study focuses on potential of combined pre-soaking treatment of 24-Epibrassinolide (EBL) and Salicylic acid (SA) in alleviating Pb phytotoxicity in Brassica juncea L. plants. The seeds after treatment with combination of both the hormones were sown in mixture of soil, sand and manure (3:1:1) and were exposed to Pb concentrations (0.25mM, 0.50mM and 0.75mM). After 30 days of growth, the plants were harvested and processed, for quantification of various metabolites. It was found that pre-sowing of seeds in combination of EBL and SA, mitigated the adverse effects of metal stress by modulating antioxidative defense response and enhanced osmolyte contents. Dry matter content and heavy metal tolerance index were enhanced in response to co-application of EBL and SA. The levels of superoxide anions, hydrogen peroxide and malondialdehyde were lowered by the combined treatment of hormones. Enhancement in activities of guaiacol peroxidase, catalase, glutathione reductase and glutathione-s-transferase were recorded. Contents of glutathione, tocopherol and ascorbic acid were also enhanced in response to co-application of both hormones. Expression of POD, CAT, GR and GST1 genes were up-regulated whereas SOD gene was observed to be down-regulated. Contents of proline, trehalose and glycine betaine were also reported to be elevated as a result of treatment with EBL+SA. The results suggest that co-application of EBL+SA may play an imperative role in improving the antioxidative defense expression of B. juncea plants to combat the oxidative stress generated by Pb toxicity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cytoprotection by activated protein C (aPC) after ischemia-reperfusion injury (IRI) is associated with apoptosis inhibition. However, IRI is hallmarked by inflammation, and hence, cell-death forms disjunct from immunologically silent apoptosis are, in theory, more likely to be relevant. Because pyroptosis (ie, cell death resulting from inflammasome activation) is typically observed in IRI, we speculated that aPC ameliorates IRI by inhibiting inflammasome activation. Here we analyzed the impact of aPC on inflammasome activity in myocardial and renal IRIs. aPC treatment before or after myocardial IRI reduced infarct size and Nlrp3 inflammasome activation in mice. Kinetic in vivo analyses revealed that Nlrp3 inflammasome activation preceded myocardial injury and apoptosis, corroborating a pathogenic role of the Nlrp3 inflammasome. The constitutively active Nlrp3 A350V mutation abolished the protective effect of aPC, demonstrating that Nlrp3 suppression is required for aPC-mediated protection from IRI. In vitro aPC inhibited inflammasome activation in macrophages, cardiomyocytes, and cardiac fibroblasts via proteinase-activated receptor 1 (PAR-1) and mammalian target of rapamycin complex 1 (mTORC1) signaling. Accordingly, inhibiting PAR-1 signaling, but not the anticoagulant properties of aPC, abolished the ability of aPC to restrict Nlrp3 inflammasome activity and tissue damage in myocardial IRI. Targeting biased PAR-1 signaling via parmodulin-2 restricted mTORC1 and Nlrp3 inflammasome activation and limited myocardial IRI as efficiently as aPC. The relevance of aPC-mediated Nlrp3 inflammasome suppression after IRI was corroborated in renal IRI, where the tissue protective effect of aPC was likewise dependent on Nlrp3 inflammasome suppression. These studies reveal that aPC protects from IRI by restricting mTORC1-dependent inflammasome activation and that mimicking biased aPC PAR-1 signaling using parmodulins may be a feasible therapeutic approach to combat IRI., (© 2017 by The American Society of Hematology.)

Cadmium(II) toxicity is a serious environmental issue warranting effective measures for its mitigation. In the present study, ameliorative effects of a bioactive brassinosteroid, castasterone (CS) and low molecular weight organic acid, citric acid (CA) against the Cd(II) toxicity to Brassica juncea L. were evaluated. Seeds of B. juncea treated with CS (0, 0.01, 1 and 100nM) were sown in cadmium spiked soils (0 and 0.6mmolkg -1 soil). CA (0.6mmolkg -1 soil) was added to soil one week after sowing seeds. Plants were harvested 30 days after sowing. Phytotoxicity induced by Cd(II) was evident from stunted growth of the plants, malondialdehyde accumulation, reduction in chlorophyll and carotenoid contents, and leaf gas exchange parameters. Cd(II) toxicity was effectively alleviated by seed soaking with CS (100nM) and/ or soil amendment with CA (0.6mMkg -1 soil). Relative gene expression of genes encoding for some of the key enzymes of pigment metabolism were also analysed. Expression of chlorophyllase (CHLASE) was reduced, while that of phytoene synthase (PSY), and chalcone synthase (CHS) genes were enhanced with CS and/or CA treatments with respect to plants treated with Cd(II) only. Cd also affected the activities of antioxidative enzymes. Plants responded to Cd(II) by accumulation of total sugars. CS (100nM) and CA treatments further enhanced the activities of these parameters and induced the contents of secondary plant pigments (flavonoids and anthocyanins) and proline. The results imply that seed treatment with CS and soil application with CA can effectively alleviate Cd(II) induced toxicity in B. juncea by strengthening its antioxidative defence system and enhancing compatible solute accumulation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Animals from different phyla including arthropods tolerate water stress to different extent. This tolerance is accompanied by biochemical changes which in turn are due to transcriptional alteration. The changes in transcription can be an indirect effect on some of the genes, ensuing from the effect of stress on the regulators of transcription including epigenetic regulators. Within this paradigm, we investigated the correlation between stress response and epigenetic modification underlying gene expression modulation during desiccation stress in Canton-S. We report altered resistance of flies in desiccation stress for heterozygote mutants of PcG and TrxG members. Pc/+ mutant shows lower survival, while ash1/+ mutants show higher survival under desiccation stress as compared to Canton-S. We detect expression alteration in stress related genes as well the genes of the Polycomb and trithorax complex in Canton-S subjected to desiccation stress. Concomitant with this, there is an altered enrichment of H3K27me3 and H3K4me3 at the upstream regions of the stress responsive genes. The enrichment of activating mark, H3K4me3, is higher in non-stress condition. H3K27me3, the repressive mark, is more pronounced under stress condition, which in turn, can be correlated with the binding of Pc. Our results show that desiccation stress induces dynamic switching in expression and enrichment of PcG and TrxG in the upstream region of genes, which correlates with histone modifications. We provide evidence that epigenetic modulation could be one of the mechanisms to adapt to the desiccation stress in Drosophila. Thus, our study proposes the interaction of epigenome and environmental factors., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Coagulation proteases have increasingly recognized functions beyond hemostasis and thrombosis. Disruption of activated protein C (aPC) or insulin signaling impair function of podocytes and ultimately cause dysfunction of the glomerular filtration barrier and diabetic kidney disease (DKD). We here show that insulin and aPC converge on a common spliced-X-box binding protein-1 (sXBP1) signaling pathway to maintain endoplasmic reticulum (ER) homeostasis. Analogous to insulin, physiological levels of aPC maintain ER proteostasis in DKD. Accordingly, genetically impaired protein C activation exacerbates maladaptive ER response, whereas genetic or pharmacological restoration of aPC maintains ER proteostasis in DKD models. Importantly, in mice with podocyte-specific deficiency of insulin receptor (INSR), aPC selectively restores the activity of the cytoprotective ER-transcription factor sXBP1 by temporally targeting INSR downstream signaling intermediates, the regulatory subunits of PI3Kinase, p85α and p85β. Genome-wide mapping of condition-specific XBP1-transcriptional regulatory patterns confirmed that concordant unfolded protein response target genes are involved in maintenance of ER proteostasis by both insulin and aPC. Thus, aPC efficiently employs disengaged insulin signaling components to reconfigure ER signaling and restore proteostasis. These results identify ER reprogramming as a novel hormonelike function of coagulation proteases and demonstrate that targeting insulin signaling intermediates may be a feasible therapeutic approach ameliorating defective insulin signaling., (© 2017 by The American Society of Hematology.)

Purpose: Originally introduced for mandibular reconstruction more than 40 years ago, the sternoclavicular graft (SCG) has gained widespread popularity for the reconstruction of the ramus-condyle unit (RCU) owing to its anatomic and histological likeness to the normal mandibular condyle. Conventional longitudinal osteotomy design for its harvest has been fraught with considerable complications at the donor site including fracture clavicle and major neurovascular injury. In an attempt to alleviate these ill effects, a new technique for procuring the sternoclavicular graft is presented., Material and Methods: A split-thickness cortico-cancellous graft was harvested form the sternal end of the clavicle along with the articular disk with the osteotomy cut oriented parallel to the coronal plane, with limited soft tissue dissection. Donor site complications were assessed in terms of incidence of clavicle fracture, neurovascular injury, pleural tear and radiographic healing as seen in the six-month postoperative chest radiograph., Results: 17 patients suffering from unilateral temporomandibular joint ankylosis underwent SCG harvesting for RCU reconstruction following osteoarthrectomy. No adverse events were seen in the intra- and post-operative period in any patient and satisfactory radiographic osseous healing was observed after six months., Conclusion: The proposed harvest technique for SCG results in reduced donor site morbidity and favourable healing and greater patient comfort., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Acute necrotizing encephalopathy (ANE) is a rare disorder characterized by encephalopathy following a febrile illness, mostly viral. Most cases are sporadic; however, recurrent and familial cases have been linked to RANBP2 mutation., Description of the Case: This is a description of a three and half years old girl with recurrent ANE with RANBP2 mutation (c.1754 C>T (p.T585M)). She had two episodes of encephalopathy, each following a short non-specific febrile illness. Neuroradiologically, she had typical findings involving bilateral thalami during the first episode and involving bilateral temporal and occipital lobes, bilateral cerebellar hemispheres and brainstem during the second episode. She was managed with intravenous gamma globulin and dexamethasone during both the episodes. She recovered significantly with residual deficits in her cognitive and language domains., Conclusions: In relevant clinic-radiological scenarios both isolated and recurrent ANE should be considered because of treatment and long-term outcome related implications., (Copyright © 2016. Published by Elsevier B.V.)

Preeclampsia (PE) is a placenta-induced inflammatory disease associated with maternal and fetal morbidity and mortality. The mechanisms underlying PE remain enigmatic and delivery of the placenta is the only known remedy. PE is associated with coagulation and platelet activation and increased extracellular vesicle (EV) formation. However, thrombotic occlusion of the placental vascular bed is rarely observed and the mechanistic relevance of EV and platelet activation remains unknown. Here we show that EVs induce a thromboinflammatory response specifically in the placenta. Following EV injection, activated platelets accumulate particularly within the placental vascular bed. EVs cause adenosine triphosphate (ATP) release from platelets and inflammasome activation within trophoblast cells through purinergic signaling. Inflammasome activation in trophoblast cells triggers a PE-like phenotype, characterized by pregnancy failure, elevated blood pressure, increased plasma soluble fms-like tyrosine kinase 1, and renal dysfunction. Intriguingly, genetic inhibition of inflammasome activation specifically in the placenta, pharmacological inhibition of inflammasome or purinergic signaling, or genetic inhibition of maternal platelet activation abolishes the PE-like phenotype. Inflammasome activation in trophoblast cells of women with preeclampsia corroborates the translational relevance of these findings. These results strongly suggest that EVs cause placental sterile inflammation and PE through activation of maternal platelets and purinergic inflammasome activation in trophoblast cells, uncovering a novel thromboinflammatory mechanism at the maternal-embryonic interface., (© 2016 by The American Society of Hematology.)

Introduction: The purpose of this study was to compare the effectiveness of mental incisive nerve block (MINB) and inferior alveolar nerve block (IANB) that were given alone or in combination to provide anesthesia to symptomatic mandibular premolars., Methods: One hundred fifty-three patients participated in this randomized, double-blind clinical trial. The patients were divided into 3 groups; first group received MINB with 2 mL 2% lidocaine with 1:200,000 epinephrine and a mock IANB with 2 mL sterile saline, patients in group 2 received mock MINB and an IANB with 2 mL 2% lidocaine, and patients in group 3 received both MINB and IANB with 2 mL each of 2% lidocaine. Access cavity preparation was initiated after 10 minutes. Success was defined as no pain or faint/weak/mild pain during endodontic access preparation and instrumentation. The anesthetic success rates were analyzed with Pearson χ(2) test at 5% significance levels., Results: The MINB and IANB gave 53% and 47% anesthetic success rates, respectively, with no significant difference between them. Adding an IANB to MINB significantly improved the success rates to 82%., Conclusions: A combination of MINB and IANB can provide improved local anesthesia for symptomatic mandibular premolars., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Maple syrup urine disease (MSUD) is caused by mutations in genes BCKDHA, BCKDHB, DBT encoding E1α, E1β, and E2 subunits of enzyme complex, branched-chain alpha-ketoacid dehydrogenase (BCKDH). BCKDH participates in catabolism of branched-chain amino acids (BCAAs) - leucine, isoleucine and valine in the energy production pathway. Deficiency or defect in the enzyme complex causes accumulation of BCAAs and keto-acids leading to toxicity. Twenty-four patients with MSUD were enrolled in the study for molecular characterization and genotype-phenotype correlation. Molecular studies were carried out by sequencing of the 3 genes by Sanger method. Bioinformatics tools were employed to classify novel variations into pathogenic or benign. The predicted effects of novel changes on protein structure were elucidated by 3D modeling. Mutations were detected in 22 of 24 patients (11, 7 and 4 in BCKDHB, BCKDHA and DBT genes, respectively). Twenty mutations including 11 novel mutations were identified. Protein modeling in novel mutations showed alteration of structure and function of these subunits. Mutations, c.1065 delT (BCKDHB gene) and c.939G > C (DBT gene) were noted to be recurrent, identified in 6 of 22 alleles and 5 of 8 alleles, respectively. Two-third patients were of neonatal classical phenotype (16 of 24). BCKDHB gene mutations were present in 10 of these 16 patients. Prenatal diagnoses were performed in 4 families. Consanguinity was noted in 37.5% families. Although no obvious genotype-phenotype correlation could be found in our study, most cases with mutation in BCKDHB gene presented in neonatal period. Large number of novel mutations underlines the heterogeneity and distinctness of gene pool from India., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Proper function, esthetics, and cost are the prime factors to be considered while selecting bridge veneering materials. The purpose of the study is to evaluate color durability of acrylic veneer materials after immersion in common beverages at different time intervals., Methods: Spectrophotometer was used for taking color measurements based on the transmission of light through the specimens made of the selected materials which were Tooth moulding powder (DPI) and Acrylux (Ruthinium). Thirty specimens of standardized dimensions were prepared from each material. The specimens were divided into three groups of 10 each. One group of each material was immersed in tea (TajMahal) and another group of each material in cola (Pepsi) as the staining solutions. The remaining group of 10 from each material served as control and was stored in distilled water. Color measurements were obtained pre-immersion, and after 1, 15, and 30 days of immersion., Results: Tooth moulding powder displayed better color durability than Acrylux over the 1 month immersion period in both staining solutions. Tea resulted in more discoloration compared to cola (Pepsi)., Conclusion: The difference in the color durability of Acrylux and Tooth moulding powder may be attributed to the differences in the composition of tested resin veneering materials, i.e. their polar properties, which contribute to the absorption of staining solution, and the different brands and the strengths of the solutions.

Objectives: Heart is an organ which is under a constant work load that generates numerous stress responses. Heart failure is associated with increased plasma norepinephrine (NE) and hypertrophic cell death. Within the current study we try to understand the concentration dependent molecular switch from hypertrophy to apoptosis under stress., Methods: The effect of increasing concentration of NE on cell death was studied using MTT assay based on which further experimental conditions were decided. Trypan Blue staining and TUNEL assay were done at selected concentrations of NE. Cellular and nuclear morphology at these concentrations was studied using Haematoxylin-Eosin, DAPI and PI stains. The molecular switch between hypertrophy and cell death was studied by expression analysis of β-MyHC and TNF-α. Rhodamine and DCFH-DA staining were done to evaluate the role of mitochondria and ROS under these conditions. Role of caspases under these transitions was also evaluated., Result: NE shows steep falls in cell viability at 50 μM and 100 μM concentrations. The cellular and nuclear morphology is altered at these concentrations along with alterations at molecular level showing a shift from hypertrophy towards cell death. Altered mitochondrial membrane potential and increase in ROS support this which leads to caspase dependent activation of cell death., Conclusion: We show that at 50 μM NE, there occurs a transition from cellular hypertrophy towards death. This could be beneficial to prevent hypertrophy induced cardiac cell death and evaluating cardio protective therapeutic targets in vitro., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammasome activation has recently been shown, but the pathophysiological relevance of this finding remains unknown. Within glomeruli, inflammasome activation was detected in endothelial cells and podocytes in diabetic humans and mice and in glucose-stressed glomerular endothelial cells and podocytes in vitro. Abolishing Nlrp3 or caspase-1 expression in bone marrow-derived cells fails to protect mice against diabetic nephropathy. Conversely, Nlrp3-deficient mice are protected against diabetic nephropathy despite transplantation of wild-type bone marrow. Pharmacological IL-1R antagonism prevented or even reversed diabetic nephropathy in mice. Mitochondrial reactive oxygen species (ROS) activate the Nlrp3 inflammasome in glucose or advanced glycation end product stressed podocytes. Inhibition of mitochondrial ROS prevents glomerular inflammasome activation and nephropathy in diabetic mice. Thus, mitochondrial ROS and Nlrp3-inflammasome activation in non-myeloid-derived cells aggravate diabetic nephropathy. Targeting the inflammasome may be a potential therapeutic approach to diabetic nephropathy.

Tea is one of the most popularly consumed beverage. Depending on the manufacturing process, different varieties of tea can be produced. The antioxidative and antimutagenic potential of tea in cardiovascular diseases, cancer and obesity have long been studied. These therapeutic and nutritional benefits of tea can be attributed to the presence of flavanoids. However, these flavanoids also have certain detrimental effects on human health when their consumption exceeds certain limits. The toxicity of these flavanoids can be attributed to the formation of reactive oxygen species in the body which causes damage to the DNA, lipid membranes etc. The aim of this review is to summarize briefly, the less studied evidences of various forms of toxicity associated with tea and its harmful effects on human health., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The study tested the hypothesis that augmentation of the left ventricular (LV) wall thickness with direct intramyocardial injections of alginate hydrogel implants (AHI) reduces LV cavity size, restores LV shape, and improves LV function in dogs with heart failure (HF)., Background: Progressive LV dysfunction, enlargement, and chamber sphericity are features of HF associated with increased mortality and morbidity., Methods: Studies were performed in 14 dogs with HF produced by intracoronary microembolizations (LV ejection fraction [EF] <30%). Dogs were randomized to AHI treatment (n = 8) or to sham-operated control (n = 6). During an open-chest procedure, dogs received either intramyocardial injections of 0.25 to 0.35 ml of alginate hydrogel (Algisyl-LVR, LoneStar Heart, Inc., Laguna Hills, California) or saline. Seven injections were made ∼ 1.0 to 1.5 cm apart (total volume 1.8 to 2.1 ml) along the circumference of the LV free wall halfway between the apex and base starting from the anteroseptal groove and ending at the posteroseptal groove. Hemodynamic and ventriculographic measurements were made before treatment (PRE) and repeated post-surgery for up to 17 weeks (POST)., Results: Compared to control, AHI significantly reduced LV end-diastolic and end-systolic volumes and improved LV sphericity. AHI treatment significantly increased EF (26 ± 0.4% at PRE to 31 ± 0.4% at POST; p < 0.05) compared to the decreased EF seen in control dogs (27 ± 0.3% at PRE to 24 ± 1.3% at POST; p < 0.05). AHI treatment was well tolerated and was not associated with increased LV diastolic stiffness., Conclusions: In HF dogs, circumferential augmentation of LV wall thickness with AHI improves LV structure and function. The results support continued development of AHI for the treatment of patients with advanced HF.

Introduction: Speed of injection may affect the solution spread in the pterygomandibular space. It was hypothesized that speed of injection will affect the anesthetic efficacy of inferior alveolar nerve block (IANB) in patients with symptomatic irreversible pulpitis., Methods: Fifty-nine adult volunteers who were actively experiencing pain participated in this prospective, randomized, single-blind study. The patients were divided into 2 groups on a random basis and received either slow or rapid IANB with 3.6 mL of 2% lidocaine with 1:200,000 epinephrine. Endodontic access preparation was initiated after 15 minutes of the initial IANB. Pain during treatment was recorded by using the Heft-Parker visual analogue scale. The primary outcome measure, and the definition of success, was the ability to undertake pulp access and canal instrumentation with no or mild pain (Heft-Parker visual analog scale score < 55 mm). Secondary outcome measure was the solution deposition pain. Statistical analysis was performed by using Mann-Whitney U test and χ(2) test., Results: Slow and rapid injections gave 43% and 51% success rates, respectively. The difference was statistically insignificant. Slow injections produced less solution deposition pain than rapid injections., Conclusions: Rate of injection has no effect on anesthetic success of IANB, but slow injections were more comfortable than rapid injections., (Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: There is a decrease in the anesthetic efficacy of inferior alveolar nerve blocks in patients with irreversible pulpitis. It was hypothesized that the increasing the volume of anesthetic solution may improve the success rates of dental pulp anesthesia in patients with pulpal pain., Methods: Fifty-five adult volunteers, actively experiencing pain, participated in this prospective, randomized, single-blind study. The patients were divided into 2 groups on a random basis and received an inferior alveolar nerve block with either 1.8 mL or 3.6 mL of 2% lidocaine with 1:200,000 epinephrine. Endodontic access preparation was initiated after 15 minutes of the initial IANB. Pain during treatment was recorded using the Heft-Parker visual analog scale (HP VAS). The primary outcome measure, and the definition of "success," was the ability to undertake pulp access and canal instrumentation with no or mild pain (HP VAS score <55 mm). Statistical analysis was performed using the chi-square test., Results: All patients included in the final analysis had profound lip anesthesia. There were no significant differences in sex, age, or preoperative pain scores of the experimental groups. IANBs of 1.8 mL lidocaine with epinephrine had a success rate of 26%, whereas the administration of 3.6 mL had a 54% success rate. The difference was statistically significant., Conclusions: Increasing the volume of 2% lidocaine to 3.6 mL improved the success rate as compared with 1.8 mL but did not give a clinical success rates of 100%., (Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Crigler-Najjar syndrome (CN) is a congenital defect in bilirubin conjugation due to complete or partial deficiency of uridine 5'-diphosphate-glucuronosyltransferase (UGT). It is of two types: CN type I and CN type II. Patients with CN type II present with indirect hyperbilirubinemia in adulthood. We report a CN type II with homozygous mutation in UGT1A1 gene. This is the first case report of mutation analysis in CN type II from India.

Introduction: The purpose of this study was to evaluate and compare the anesthetic efficacy of posterior superior alveolar (PSA) nerve blocks, buccal infiltrations, and buccal plus palatal infiltrations with 2% lidocaine with 1:200,000 epinephrine in maxillary first molars with irreversible pulpitis., Methods: Ninety-four adult patients participated in this prospective, randomized, single-blinded study. The patients were divided into 3 treatment groups on a random basis. Twenty-eight patients received a PSA nerve block, 33 patients received buccal infiltrations, and 33 patients received buccal plus palatal infiltrations with 2% lidocaine with 1:200,000 epinephrine. Endodontic access preparation was initiated 15 minutes after injection. Pain during treatment was recorded using a Heft-Parker visual analog scale. Success was recorded as "none" or "mild" pain., Results: Statistical analysis using nonparametric chi-square tests revealed that there was no statistical difference between the anesthetic success of PSA nerve blocks (64%), buccal infiltrations (54%), and buccal plus palatal infiltrations (70%)., Conclusions: None of the tested methods gave 100% anesthetic success rates in maxillary first molars with irreversible pulpitis., (Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: It was suggested that body fat distribution differs across ethnic groups, and this may be important when considering risk of disease. Previous studies have not adequately investigated differences in discrete regions of abdominal adiposity across ethnic groups., Objective: We compared the relation between abdominal adipose tissue and total body fat between persons living in Canada of Aboriginal, Chinese, and South Asian origin with persons of European origin., Design: Healthy Aboriginal, Chinese, European, and South Asian participants (n = 822) aged between 30 and 65 y were matched by sex, ethnicity, and body mass index (BMI; in kg/m(2)) range. Total abdominal adipose tissue (TAT), subcutaneous abdominal adipose tissue (SAT), visceral adipose tissue (VAT), total body fat mass, lifestyle, and demographics were assessed. Relations between BMI and total body fat, TAT, SAT, and VAT and between total body fat and TAT, SAT, and VAT were investigated., Results: BMI significantly underestimated VAT in all non-European groups. Throughout a range of total body fat mass, VAT was not significantly different between the Aboriginals and the Europeans. With total body fat >9.1 kg, Chinese participants had increasingly greater amounts of VAT than did the Europeans (P for interaction = 0.008). South Asians had less VAT with total body fat >37.4 kg but more VAT below that amount than did Europeans (P for interaction < 0.001)., Conclusion: Compared with Europeans, the Chinese and South Asian cohorts had a relatively greater amount of abdominal adipose tissue, and this difference was more pronounced with VAT. No significant differences were observed between the Aboriginals and the Europeans.