Comparative evaluation of resin-based sealers and bioceramic sealers for postoperative pain after endodontic treatment: A systematic review.

The systematic review aimed to compare and evaluate the effect of resin-based sealers and bioceramic sealers on postoperative pain after endodontic treatment. Two reviewers independently conducted electronic search in PubMed, the Web of Science, ScienceDirect, the Wiley Online Library, SpringerLink, Google Scholar, and the Cochrane Library, employing a complete dual-review process to ensure the inclusion of all relevant studies in the review. The search was carried out until November 2021. After selecting eligible studies, the risk of bias assessment was carried out using the revised Cochrane risk-ofbias tool for randomized trials (RoB 2). A total of 1,931 studies were identified from the electronic search, and finally 10 studies were included after full-text assessment. In all our included studies, the visual analog scale (VAS) was used for recording pain scores. Most of the studies recorded pain intensity starting from 6 h to 7 days. The results showed that there was no significant difference between resin-based sealers and bioceramic sealers in terms of incidence or intensity of postoperative pain at any point in time.

Nasal Pyriform Aperture Stenosis in a Newborn: When to Operate.

Congenital nasal pyriform aperture stenosis (CNPAS) is a very rare cause of neonatal respiratory distress and is often missed because of its rarity. It arises from the overgrowth of the nasal process of the maxilla. Maxillofacial CT scan findings of pyriform aperture width <11 mm in a full-term baby, median central incisor, triangular-shaped palate, and median palatal ridge confirm the diagnosis. We describe here a case of CNPAS admitted with respiratory distress that increased further on feeding. An infant feeding tube of size 6 was not negotiable through the nostrils. Resistance was appreciated at the inlet of the nostril. Maxillofacial CT showed pyriform aperture stenosis of 3.4 mm, suggesting CNPAS. The child could not be weaned off a high-flow nasal cannula despite conservative management with decongestants, steroids spray, dilatation, and stenting for 20 days. Subsequently, surgical widening of the nasal aperture by a sublabial approach was done. The child was discharged on the 10th postoperative day on full oral feeds. It is important to suspect CNPAS in neonates with respiratory distress where other common causes have been ruled out, as it can be treated by surgery in cases refractory to conservative management.

Confinement-induced self-assembly of a diblock copolymer within a non-uniform cylindrical nanopore.

The self-assembly of a diblock copolymer melt confined within a non-uniform cylindrical nanopore is studied using the self-consistent field theory. The non-uniformity manifests in the form of a converging-diverging cylindrical nanopore. The axial variation in pore diameter presents a range of curvatures within the same confinement pore as opposed to a single curvature in a uniform-diameter cylindrical pore. The introduction of multiple curvatures leads to the formation of novel microstructures not accessible in uniform cylindrical confinement. The well-known equilibrium structures like a single helix, double helices, and concentric lamella under cylindrical confinement transition into new morphologies such as hyperboloidal phases, microstructures containing rings with a bead, rings with spheres, and a squeezed helical phase as the pore diameter varies axially. The converging-diverging geometry of the confining pore renders the helical phases seen in the cylindrical pore less favorable. A phase diagram in the parametric space of the block fraction and the ratio of the smallest and largest pore radii has been constructed to depict the order-order transition of various microstructures. The ratio of radii, a measure of the non-uniformity of the pore, along with the pore length brings out some interesting morphologies. The mechanism of these structural transitions is understood as the interplay between the variation in pore curvature attributed to the non-uniformity, the spontaneous curvature of the block copolymer interface, and the enthalpic interaction between the segregated blocks.

Determinants of outcomes and advances in CD19-directed chimeric antigen receptor therapy for B-cell acute lymphoblastic leukemia.

Relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive B-cell neoplasm associated with poor outcomes. Conventional multiagent chemotherapy and bispecific antibody therapy may induce remission; however, relapse rates remain high and overall survival is poor. Chimeric antigen receptor T-cell (CAR-T) therapy provides durable, deep complete remission, and long-term cures in relapsed and refractory B-ALL. However, with this new treatment modality, 10%-30% of patients do not achieve remission, and over 50% experience relapse after therapy. Currently, there are two approved CD19-specific CAR-T cell constructs in B-ALL, Tisagenlecleucel and Brexucabtagene Autoleucel by the United States Food and Drug Administration, and the European Medicines Agency (EMA). In this review, we discuss patients, disease, and CAR-T predictors of outcomes in B-ALL. We describe the two approved CD19-directed CAR-T cell products, review the current literature, and discuss factors associated with high risks of therapy failure and future direction in CAR-T cell therapy for B-ALL.

Impact of Closed System Transfer Device (CSTD) Handling Procedure for Low-Transfer-Volume Dose Preparation of Biologic Drug Products.

Many challenges have been identified for ensuring compatibility of closed system transfer devices (CSTDs) with biologic drug products. One challenge is large hold-up volumes (HUVs) of CSTD components, which can be especially problematic with early-stage biologics when low transfer volumes smaller than the nominal fill volume may be used to achieve a wide range of doses with a single drug product configuration. Here, we identified possible CSTD handling techniques during dose preparation of a drug product requiring small volume transfers during reconstitution, intermediate dilution, and dilution in an IV bag, and systematically evaluated the impact of these handling procedures on the ability to deliver an accurate dose to the next step. We show that small changes to CSTD procedures can have a major impact on dose accuracy, depending on both CSTD HUVs and drug product-specific transfer volumes. We demonstrate that it is possible to craft CSTD instructions for use to mitigate these issues, and that the dose accuracy for specific drug product/CSTD combinations can be estimated using theoretical equations. Finally, we explored potential downsides of these mitigations. Our results emphasize key factors for consideration by both drug and CSTD manufacturers when assessing compatibility and providing CSTD instructions for use with biologics requiring low transfer volumes during dose preparation.

Fungal pectinases: an insight into production, innovations and applications.

The fungal system holds morphological plasticity and metabolic versatility which makes it unique. Fungal habitat ranges from the Arctic region to the fertile mainland, including tropical rainforests, and temperate deserts. They possess a wide range of lifestyles behaving as saprophytic, parasitic, opportunistic, and obligate symbionts. These eukaryotic microbes can survive any living condition and adapt to behave as extremophiles, mesophiles, thermophiles, or even psychrophile organisms. This behaviour has been exploited to yield microbial enzymes which can survive in extreme environments. The cost-effective production, stable catalytic behaviour and ease of genetic manipulation make them prominent sources of several industrially important enzymes. Pectinases are a class of pectin-degrading enzymes that show different mechanisms and substrate specificities to release end products. The pectinase family of enzymes is produced by microbial sources such as bacteria, fungi, actinomycetes, plants, and animals. Fungal pectinases having high specificity for natural sources and higher stabilities and catalytic activities make them promising green catalysts for industrial applications. Pectinases from different microbial sources have been investigated for their industrial applications. However, their relevance in the food and textile industries is remarkable and has been extensively studied. The focus of this review is to provide comprehensive information on the current findings on fungal pectinases targeting diverse sources of fungal strains, their production by fermentation techniques, and a summary of purification strategies. Studies on pectinases regarding innovations comprising bioreactor-based production, immobilization of pectinases, in silico and expression studies, directed evolution, and omics-driven approaches specifically by fungal microbiota have been summarized.

A rare incidence and management of complex odontoma and surgical dehiscence in maxillary anterior region: A case report.

Odontoma is a benign odontogenic tumour, which is rather considered hamartoma. Hamartoma is not a true neoplasm, rather a growth of abnormal mixture of cells found in the body area they normally grows. Fully developed odontomas generally consist of enamel, dentin and pulpal tissues, in an unorganised manner. Some of them may contain cementum too. These are further grouped into compound and complex, depending on their clinical, radiographic and histologic features. Odontomas are generally asymptomatic and slow growing, but may cause bone expansion and hinderance in tooth eruption. These lesions are generally diagnosed by coincidence in radiograph. We are presenting a case and surgical management of complex odontoma and post-operative dehiscence in the anterior right maxillary region of a 38-year-old male.

Comparative analysis of reduction in pain scores after single visit root canal treatment using endodontic irrigation protocols, namely, Conventional needle irrigation, PUI, PIPS and SWEEPS: A randomized control trial.

Introduction: To assess the effects of different irrigation activation systems on postoperative pain using a Visual Analog Scale (VAS), using new laser irrigation activation system shock wave-enhanced emission photoacoustic streaming (SWEEPS), photon-induced photoacoustic streaming (PIPS), passive ultrasonic irrigation activation techniques, compared with the conventional irrigation (CI) method. Materials and Methods: Sixty patients suffering from symptomatic irreversible pulpitis in maxillary or mandibular molars were enrolled and randomly assigned to four different irrigation activation groups (n = 15) after chemomechanical root canal preparation. Preoperative and postoperative pain scores were recorded using VAS. The data were collected and subjected to statistical analysis using IBM SPSS 20.0 software at a level of significance being 0.05. Results: We observed that mean pain scores decreased with time in all patients in all groups. The decrease in pain score was found to be statistically significant (P < 0.05) among both the genders in Group 3 (PIPS) and Group 4 (SWEEPS). Postoperatively, pain scores decreased significantly using Group 4 (SWEEPS), followed by Group 3 (PIPS), Group 2 (ultrasonic activation), and Group 1 (conventional needle irrigation). No significant relation was observed statistically between pain scores and age groups among all groups, except for preoperative score in Group 3 and age groups. Conclusion: Postoperative scores were lower in laser-activated irrigation systems as compared to the other activation systems. The highest pain scores were observed in case of CI method, at pre- and post-operative periods.

Freezing process influences cake appearance of a lyophilized amorphous protein formulation with low solid content and high fill configuration.

Low solid content and high fill drug product configuration pose special challenges for achieving elegant cake appearance after lyophilization. In this study, such a configuration for a protein formulation required lyophilization within a narrow primary drying operating space to obtain elegant cakes. Freezing process optimization was explored as a solution. A Design of Experiment (DoE) approach was used to evaluate the effect of shelf cooling rate, annealing temperature, and their interaction on cake appearance. The slope of product resistance (Rp) vs. dried layer thickness (Ldry) was used as the quantitative response because elegant cake appearance correlated with a lower initial Rp and positive slope. As the Rp vs. Ldry slope can be experimentally established within the first 1/6th of the total primary drying duration, partial lyophilization runs were executed, allowing for rapid screening. The DoE model revealed that a slow cooling rate (≤0.3 °C/min) and high annealing temperature (≥-10 °C) resulted in a better cake appearance. Furthermore, X-ray micro-computed tomography showed that elegant cakes exhibited uniform porous structure and larger pores, while inelegant cakes showed dense top layers with smaller pores. With the optimized freezing process, the primary drying operating space was broadened with improved cake appearance and batch homogeneity.

The race between classical microbial fuel cells, sediment-microbial fuel cells, plant-microbial fuel cells, and constructed wetlands-microbial fuel cells: Applications and technology readiness level.

Microbial fuel cell (MFC) is an interesting technology capable of converting the chemical energy stored in organics to electricity. It has raised high hopes among researchers and end users as the world continues to face climate change, water, energy, and land crisis. This review aims to discuss the journey of continuously progressing MFC technology from the lab to the field so far. It evaluates the historical development of MFC, and the emergence of different variants of MFC or MFC-associated other technologies such as sediment-microbial fuel cell (S-MFC), plant-microbial fuel cell (P-MFC), and integrated constructed wetlands-microbial fuel cell (CW-MFC). This review has assessed primary applications and challenges to overcome existing limitations for commercialization of these technologies. In addition, it further illustrates the design and potential applications of S-MFC, P-MFC, and CW-MFC. Lastly, the maturity and readiness of MFC, S-MFC, P-MFC, and CW-MFC for real-world implementation were assessed by multicriteria-based assessment. Wastewater treatment efficiency, bioelectricity generation efficiency, energy demand, cost investment, and scale-up potential were mainly considered as key criteria. Other sustainability criteria, such as life cycle and environmental impact assessments were also evaluated.

Current Perception of Diversity in Academic Radiology: A Mixed Methods Study of Radiology Program Directors.

OBJECTIVES: To assess the perceived state of diversity in Radiology Residency Programs in the United States and to evaluate the level of acceptance for diversity, equity, and inclusion (DEI) initiatives. METHODS: An electronic survey was conducted of the Radiology Residency Programs in the United States in December 2021 and January 2022. Respondents were recruited by email sent to the members of the Association of University Radiologists who were Radiology Residency Program Directors. Quantitative and Qualitative analyses were performed. RESULTS: Of the 198 emails sent out to the Radiology Program Directors, 53 completed surveys were returned (response rate of 27%). Although some progress has been made in increasing the number of women and Asians in Academic Radiology, there is persisting imbalance of the numbers of African American and Latinx radiologists which comprise far less than 25% of the physician workforce. Nearly half of the respondents reported having a Vice Chair of DEI. Three themes emerged from the qualitative analysis. Most respondents agreed that diversity should be considered when recruiting faculty and residents. Many noted a strong commitment to DEI but they felt there was room for improvement in formalizing efforts to aid in recruitment of underrepresented minorities. Diversity education was more likely mandatory for residents and optional for faculty. CONCLUSION: Academic Radiology programs are recognizing the value of internal DEI leadership roles. Radiologists are implementing DEI initiatives and making intentional changes in the recruitment of diverse radiologists. More concerted efforts are needed to increase the low numbers of African American and Latinx radiologists. Effective evaluation metrics for various DEI programs are needed to assess how successful these endeavors are in creating lasting changes.

Multilevel Approach to Support Diversity, Equity and Inclusion in Radiology.

Integrating diversity into healthcare systems has its challenges and advantages. Academic medicine strives to expand the diversity of the healthcare workforce. The Association of University Radiologists (AUR) put together a task force to review the concept of Diversity, Equity and Inclusion (DEI) as it pertains to Radiology and to propose strategies for better integrating DEI in Radiology. We present several measures aimed at the trainee, leadership, management and professional society levels to empower DEI in Radiology.

Dynamics and Equilibration Mechanisms in Block Copolymer Particles.

Self-assembly of block copolymers into interesting and useful nanostructures, in both solution and bulk, is a vibrant research arena. While much attention has been paid to characterization and prediction of equilibrium phases, the associated dynamic processes are far from fully understood. Here, we explore what is known and not known about the equilibration of particle phases in the bulk, and spherical micelles in solution. The presumed primary equilibration mechanisms are chain exchange, fusion, and fragmentation. These processes have been extensively studied in surfactants and lipids, where they occur on subsecond time scales. In contrast, increased chain lengths in block copolymers create much larger barriers, and time scales can become prohibitively slow. In practice, equilibration of block copolymers is achievable only in proximity to the critical micelle temperature (in solution) or the order-disorder transition (in the bulk). Detailed theories for these processes in block copolymers are few. In the bulk, the rate of chain exchange can be quantified by tracer diffusion measurements. Often the rate of equilibration, in terms of number density and aggregation number of particles, is much slower than chain exchange, and consequently observed particle phases are often metastable. This is particularly true in regions of the phase diagram where Frank-Kasper phases occur. Chain exchange in solution has been explored quantitatively by time-resolved SANS, but the results are not well captured by theory. Computer simulations, particularly via dissipative particle dynamics, are beginning to shed light on the chain escape mechanism at the molecular level. The rate of fragmentation has been quantified in a few experimental systems, and TEM images support a mechanism akin to the anaphase stage of mitosis in cells, via a thin neck that pinches off to produce two smaller micelles. Direct measurements of micelle fusion are quite rare. Suggestions for future theoretical, computational, and experimental efforts are offered.

Comparative evaluation of bioglass nanofiber, dexamethasone-coated bioglass nanofiber, and platelet-rich fibrin, as scaffolds in regenerative endodontic treatment of immature necrotic teeth: A randomized controlled trial.

Aim: The aim of this study was to evaluate and compare the regenerative endodontic potential of dexamethasone-coated bioglass nanofiber (Dex-BGnf), bioglass nanofiber (BGnf), and platelet-rich fibrin (PRF) for inducing regeneration in necrotic immature permanent teeth. Materials and Methods: A total of 36 (n = 12) immature necrotic teeth with or without evidence of periapical lesion were included in the study. Patients were randomly allocated into three groups, based on the scaffolds used: Group I (PRF), II (BGnf), and III (Dex-BGnf). The clinical (electric pulp test) and radiographic evaluations (percentage increase in apical diameter, root length, root dentin thickness, and periapical healing) were compared at 6 and 12 months after the procedure with baseline records. Statistical Analysis: One-way ANOVA, post hoc Tukey analysis, and Kruskal-Wallis test were used for evaluating the data. A 6- and 12-month improvement analysis was done using paired t-test and Friedman test. Results: Clinically, all the 36 teeth were asymptomatic, but none gave a positive response to Electric Pulp Test (EPT) in time interval of 12 months. Dex-BGnf showed a statistically significant improvement in terms of increase in root length (P = 0.020) and root dentinal thickness (P = 0.001) when compared to PRF after 12 months. Conclusion: The study has shown that Dex-BGnf yielded significantly better results than PRF for inducing apexogenesis in necrotic immature teeth.

Extramedullary Multiple Myeloma: A Patient-Focused Review of the Pathogenesis of Bone Marrow Escape.

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells, predominantly in the bone marrow. The presentation of MM in extramedullary tissue, particularly the liver, is uncommon with only a few reported cases in literature. We report a rare and unusual presentation of kappa light chain restricted MM with progression of disease to involve the liver. MM was initially diagnosed on bone marrow biopsy, initially treated with carfilzomib, lenalidomide and dexamethasone, later changed to bortezomib, daratumumab and dexamethasone. There was subsequent progression with a new biopsy-proven myelomatous liver lesion. The patient could not receive high-dose chemotherapy due to multiple co-morbidities and extent of disease and eventually succumbed to her disease rapidly. This article emphasizes the poor prognosis of extramedullary involvement in MM and the pathogenic mechanisms by which it develops. Based on a review of the literature of other cases and case series of solitary or diffuse myeloma involvement in the liver, high-dose chemotherapy in combination with proteasome inhibitors and immunomodulators has the best success rate with less relapse and progressive disease in extramedullary myeloma. Our analysis concluded that the gain of CD44, loss of CD56, loss of very late antigen-4 (VLA-4), imbalance of the chemokine receptor-4-chemokine ligand-12 (CXCR4-CXCL12) axis, metastasis-associated lung adenocarcinoma 1 (MALAT1) upregulation, RAS pathway activation as well as 13q and 17p deletions show an increased propensity of malignant plasma cells to leave the bone marrow and hone in extramedullary sites giving rise to more aggressive extramedullary diseases. Targeted therapeutics such as CD44v-directed therapy and reactivation of p53 to wild-type conformation could potentially be evaluated as treatment options in the future to improve outcomes in this aggressive form of MM, especially in patients with advanced disease and limited treatment options.

Genome mining of Fusarium reveals structural and functional diversity of pectin lyases: a bioinformatics approach.

Pectin lyase (PNL) is an important enzyme of the pectinases group which degrades pectin polymer to 4,5-unsaturated oligogalacturonides by a unique ß-elimination mechanism and is used in several industries. The existence of multigene families of pectin lyases has been investigated by mining microbial genomes. In the present study, 52 pectin lyase genes were predicted from sequenced six species of Fusarium, namely F. fujikuroi, F. graminearum, F. proliferatum, F. oxysporum, F. verticillioides and F. virguliforme. These sequences were in silico characterized for several physico-chemical, structural and functional attributes. The translated PNL proteins showed variability with 344-1142 amino acid residues, 35.44-127.41 kDa molecular weight, and pI ranging from 4.63 to 9.28. The aliphatic index ranged from 75.33 to 84.75. Multiple sequence alignment analysis showed several conserved amino acid residues and five distinct groups marked as I, II, III, IV, and V were observed in the phylogenetic tree. The Three-dimensional Structure of five of these PNLs, each representing a distinct group of phylogenetic trees was predicted using I-TASSER Server and validated. The pectin lyase proteins of Fusarium species revealed close similarity with pectin lyase of Aspergillus niger PelA(1IDJ) and PelB(1QCX). Diversity in the structural motifs was observed among Fusarium species with 2 ß-sheets, 1 ß-hairpin, 7-12 ß bulges, 18-25 strands, 6 -11 helices, 1 helix-helix interaction, 32-49 ß turns, 2-6 γ turns and 2- 3 disulfide bonds. The unique Pec_lyase domain was uniformly observed among all PNL proteins confirming its identity. The genome-wide mining of Fusarium species was attempted to provide the diversity of PNL genes, which could be explored for diverse applications after performing cloning and expression studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03333-w.

Self-organization of a 4-miktoarm star block copolymer induced by cylindrical confinement.

Self-consistent field calculations have been carried out to reveal the self-assembly behavior of a melt of the ABCD star tetrablock copolymer confined within a cylindrical nanopore. The miktoarm star block copolymer exhibits a rich self-assembly behavior with a myriad of interesting three-dimensional ordered phases with the potential to produce advanced nanomaterials. The broad array of ordered mesophases includes helical microstructures, stack of rings/doughnuts, honeycomb structure, and perforated lamella with beads, depending on the individual block fractions and the size of the cylindrical nanopore. Such chiral motifs generated from achiral polymeric molecules are fascinating due to their superior performance in sophisticated opto-electronic devices. The study also demonstrates an interesting morphology, viz. a honeycomb structure, obtained from the self-organization of ABCD star block copolymer molecules with equal block fractions. The system exhibits order-order phase transition covering a range of ordered morphologies by changing either the block fraction or the nanopore radius. A representative phase diagram in terms of block fractions is constructed. These novel ordered microstructures, arising mainly out of structural frustration and confinement-induced entropy loss, can serve as structural scaffolds to host the spatial distribution of nanoparticles resulting into novel nanocomposites with significantly enhanced as well as controllable properties.

A comprehensive review on emerging constructed wetland coupled microbial fuel cell technology: Potential applications and challenges.

Constructed wetlands (CWs) integrated with bioelectrochemical systems (BESs) are being intensively researched with the names like constructed wetland-microbial fuel cell (CW-MFC), electro-wetlands, electroactive wetlands, and microbial electrochemical technologies-based constructed wetland since the last decade. The implantation of BES in CW facilitates the tuning of redox activities and electron flow balance in aerobic and anaerobic zones in the CW bed matrix, thereby alleviating the limitation associated with electron acceptor availability and increasing its operational controllability. The benefits of CW-MFC include high treatment efficiency, electricity generation, and recalcitrant pollutant abatement. This article presents CW-MFC technology's journey since its emergence to date, encompassing the research done so far, including the basic principle and functioning, bio-electrocatalysts as its machinery, influential factors for microbial interactions, and operational parameters controlling different processes. A few key challenges and potential applications are also discussed for the CW-MFC systems.

An algal assisted constructed wetland-microbial fuel cell integrated with sand filter for efficient wastewater treatment and electricity production.

In this study we report on a three-stage design of algal assisted constructed wetland -microbial fuel cell incorporated sand filter for efficient treatment of wastewater and bioelectricity generation, simulating a core of it. It aims for the complete removal of organic matter and other inorganic pollutants such as NO3-, NH4+ and PO43-. The conductive material equipped anode region of constructed wetland (CW) performed better for organic removal, and the system efficiently removed COD up to 96.37 ± 2.6%. The algal biomass passively aerated the cathode region and resulted in efficient removal of 85.14 ± 10.73% of NH4+ and 69.03 ± 10.14% of PO43-. The additional sand filter provided anaerobic situation favorable for removal of NO3- up to 68.41 ± 7.63%. The maximum power and current densities achieved in the system were 33.14 mW m-3 and 235.0 mA m-3, respectively.

Developability assessment for monoclonal antibody drug candidates: a case study.

Various screening approaches are used by industry to evaluate development risks associated with discovery candidates. This process has become more complicated with biological therapeutics, a class dominated by monoclonal antibodies (mAb), and, increasingly, their derivative constructs. Effective early assessment for drug-like properties (DLP) can save time and costs by allowing a more complete consideration of issues that could impact the desired end result of a stable drug product. Here we report a case study of four IgG1 mAbs, with sequence variations in the variable domain region, screened as a set of possible drug candidates. Our comprehensive, tiered approach used a battery of analytical tools to assess molecular characteristics, conformational stability, colloidal stability, and short-term storage stability. While most DLP for the four candidates were developmentally acceptable and comparable, mAb-2 was associated with adverse colloidal properties. Further investigation of mAb-2 in an expanded pH range revealed a propensity for phase separation, indicating a need for the additional product development effort. Our results support that comprehensive DLP assessments in an expanded pH range are beneficial in identifying development options for promising molecules that show challenging stability trends. This adaptable approach may be especially useful in the development of increasingly complex antibody constructs.