Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising -anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies.

In this study, a library of phthalimide Schiff base linked to 1,4-disubstituted-1,2,3-triazoles was designed, synthesised, and characterised by different spectral analyses. All analogues have been introduced for in vitro assay of their antiviral activity against COVID-19 virus using Vero cell as incubator with different concentrations. The data revealed most of these derivatives showed potent cellular anti-COVID-19 activity and prevent viral growth by more than 90% at two different concentrations with no or weak cytotoxic effect on Vero cells. Furthermore, in vitro assay was done against this enzyme for all analogues and the results showed two of them have IC50 data by 90 µM inhibitory activity. An extensive molecular docking simulation was run to analyse their antiviral mechanism that found the proper non-covalent interaction within the Mpro protease enzyme. Finally, we profiled two reversible inhibitors, COOH and F substituted analogues that might be promising drug candidates for further development have been discovered.

Biological evaluation of novel phosphorylated pullulan-based calcium hydroxide formulations as direct pulp capping materials: An in vivo study on a rat model.

AIM: Calcium hydroxide (CH) has been considered as a direct pulp capping materials (DPC) for the last decades despite having some limitations. Phosphorylate pullulan (PPL) incorporated with CH (CHPPL) is a novel biomaterial that was introduced as a promising DPC material. Thus, the aim of the study was to evaluate the inflammatory response and mineralized tissue formation (MTF) ability of PPL-based CH formulations on rat molars after DPC. METHODOLOGY: This study consisted of six groups: CH with 1% PPL (CHPPL-1); 3% PPL (CHPPL-3); 5% PPL (CHPPL-5); Dycal and NEX MTA Cement (N-MTA) as the positive control, and no capping materials (NC). One hundred twenty maxillary first molar cavities were prepared on Wistar rats. After capping, all the cavities were restored with 4-META/MMA-TBB resin and pulpal responses were evaluated at days 1, 7, and 28. Kruskal-Wallis followed by Mann-Whitney U-test was performed with a significance level of 0.05. Immunohistochemical expression of IL-6, Nestin, and DMP-1 was observed. RESULTS: At day 1, CHPPL-1, N-MTA, and Dycal exhibited no to mild inflammation, whilst CHPPL-3, CHPPL-5, and NC showed mild to moderate inflammation, and the results were significantly different (p < .05). At day 7, mild to moderate inflammation was observed in CHPPL-1, N-MTA, and Dycal, whereas CHPPL-3, CHPPL-5, and NC exhibited moderate to severe inflammation. Significant differences were observed between CHPPL-1 and N-MTA with NC (p < .05), CHPPL-1 and CHPPL-3 with CHPPL-5 and Dycal (p < .05), and CHPPL-3 with N-MTA (p < .05). A thin layer of mineralized tissue formation (MTF) was observed in all groups. At day 28, CHPPL-1, Dycal, and N-MTA showed no to mild inflammation, whilst CHPPL-3, CHPPL-5, and NC exhibited mild to severe inflammation, and statistically significant difference was detected (p < .05). CHPPL-1, Dycal, and N-MTA exhibited continuous MTF, whilst CHPPL-3, CHPPL-5, and NC had thicker and interrupted MTF. Significant differences were observed between CHPPL-1, CHPPL-3, and N-MTA with NC group (p < .05). Variable expressions of IL-6, Nestin, and DMP-1 indicated differences in the materials' impact on odontoblast-like cell formation and tissue mineralization. CONCLUSIONS: These findings suggest that CHPPL-1 has the potential to minimize pulpal inflammation and promote MTF and had similar efficacy as MTA cement.

Tailoring MIL-100(Fe)-derived catalyst for controlled carbon dioxide conversion and product selectivity.

Here in, we are reporting the effect of the catalyst particle size on the catalytic activity and product selectivity by understanding the strength of the interaction between the active catalyst and the reactants (CO2 and H2). In this regard, two catalytic systems having different active catalyst particle sizes and support surface areas were synthesized using metal-organic frameworks (MOF) (MIL-100(Fe)) having two crystal size ranges as sacrificial templates. The active catalyst having smaller nanoparticles exhibited greater chemisorption of hydrogen (Fe-H bond), resulting in heightened selectivity for paraffin due to hydrogenation of re-adsorbed olefins. Conversely, larger nanoparticles showed enhanced chemisorption of CO2 (Fe-C bond), leading to increased selectivity for olefins (O/P = 0.15). Additionally, a reduction in particle size boosts activity from 24% to 38.7% at 340 °C/20 bar. While, higher particle size enhances the selectivity towards C5+ from 11.1 to 45.6% at (300 °C/10 bar) and 9.6 to 21.3% at (340 °C/20 bar).

Detection, characterisation and management of complex root canal configurations in the mesiobuccal roots of maxillary first molars: A case series.

This report presents the detection, characterisation, instrumentation and filling of complex canal configurations in the mesiobuccal (MB) root of maxillary first molars. Three patients were referred for root canal treatment in first maxillary molars. Medical history, age, sex and clinical findings were recorded. Intraoral periapical radiographs and cone beam computed tomography (CBCT) were used for diagnosis and pre-operative assessment. Using Ahmed et al. (2017) classification system, codes 3MaxM MB3-5-4-2 DB1-2-1 P1 (case 1), 3MaxM MB2-5-3-2 DB1 P1 (case 2) and 3MaxM MB1-4-2-1-2 DB1 P1 (case 3) were identified. Using the dental operating microscope, CBCT (if indicated) and troughing up to 3 mm allowed identification of more than three canals in the MB root of maxillary first molars. The coding system proposed by Ahmed et al. (2017) allows the classification of MB roots with highly complex canal configurations.

Assessment of the root and canal morphology in the permanent dentition of Saudi Arabian population using cone beam computed and micro-computed tomography - a systematic review.

INTRODUCTION: Root canal treatment procedures require a thorough understanding of root and canal anatomy. The purpose of this systematic review was to examine the morphological differences of teeth root and their canals assessed using cone-beam computed and micro-computed tomography in Saudi Arabian population. METHODOLOGY: An electronic search was conducted in PubMed / Medline, Scopus, Google Scholar, and Web of Science databases until January 2023 to retrieve related studies. "Root canal morphology," "Saudi Arabia," "Micro-CT," and "cone-beam computed tomography" were used as keywords. A modified version of previously published risk of bias assessment tool was used to determine the quality assessment of included studies. RESULTS: The literature search revealed 47 studies that matched the criteria for inclusion, out of which 44 studies used cone beam computed tomography (CBCT) and three were micro-computed tomography (micro-CT) studies. According to the modified version of risk of bias assessment tool, the studies were categorized as low, moderate, and high risk of bias. A total of 47,612 samples were included which comprised of either maxillary teeth (5,412), or mandibular teeth (20,572), and mixed teeth (21,327). 265 samples were used in micro-CT studies while 47,347 teeth samples were used in CBCT studies. Among the CBCT studies, except for three, all the studies were retrospective studies. Frequently used imaging machine and software were 3D Accuitomo 170 and Morita's i-Dixel 3D imaging software respectively. Minimum and maximum voxel sizes were 75 and 300 µm, Vertucci's classification was mostly used to classify the root canal morphology of the teeth. The included micro-CT studies were in-vitro studies where SkyScan 1172 X-ray scanner was the imaging machine with pixel size ranging between 13.4 and 27.4 µm. Vertucci, Ahmed et al. and Pomeranz et al. classifications were applied to classify the root canal morphology. CONCLUSION: This systematic review revealed wide variations in root and canal morphology of Saudi population using high resolution imaging techniques. Clinicians should be aware of the common and unusual root and canal anatomy before commencing root canal treatment. Future micro-CT studies are needed to provide additional qualitative and quantitative data presentations.

Arthroscopic distal clavicle resection versus conservation in patients with combined rotator cuff tears and acromioclavicular joint osteoarthritis.

PURPOSE: The most common cause of shoulder pain originating from the acromioclavicular (AC) joint is osteoarthritis, causing pain and disability. Operative Management of AC arthritis includes arthroscopic distal clavicle resection (DCR) and open clavicle resection. This study was conducted to evaluate the outcomes of isolated rotator cuff repair with conservative treatment of ACJ arthritis versus the combined resection of the distal clavicle with the repair of a rotator cuff tear, in cases with acromioclavicular arthritis. METHODS: A total of 46 patients with unilateral or bilateral combined rotator cuff tear and acromioclavicular arthritis were included, they were classified into 2 independent groups: Conservative group (23 patients), and DCR group (23 patients). All patients were subjected to full history taking, examination, pre and post-operative University of California at Los Angeles shoulder scoring scale (UCLA), Antero-Posterior and Zanca X-rays views, early and late complications. RESULTS: Mean age was (51 ± 9) years, males were predominant (56.5%). The average post-operative UCLA score was (31.1 ± 4.9), and the average time to return to work was (214 ± 22). (2.2%) of patients had early complications, (19.6%) had late complications, (32.6%) had > 24 h till 1st post-operative analgesia, and (87%) needed MgSO4 Injection. We found a highly significant increase in UCLA score measurements in the Conservative group, and a highly significant increase in UCLA score measurements in the DCR group (p < 0.01). But there was no difference between the 2 groups. CONCLUSION: Conventional conservative approach with arthroscopic rotator cuff repair and subacromial decompression has proven to be as effective as arthroscopic rotator cuff repair and subacromial decompression with DCR, in terms of efficacy and safety profiles in short term, but with more risks of potential hazards and cost with the DCR.

Microcomputed-Tomographic Analysis of the Root Canal Morphology of the Mandibular First Molars in a Malaysian Subpopulation Using Two Classification Systems / Análisis por Tomografía Microcomputada de la Morfología del Conducto Radicular de los Primeros Molares Mandibulares en una Subpoblación de Malasia Utilizando dos Sistemas de Clasificación

SUMMARY: This work investigated the morphology of the root canal system of the mandibular first molar in a Malaysian subpopulation. Using micro-computed tomography with an isotropic resolution of 22 µm, 140 mandibular first molars were scanned. MIMICS software was used for segmentation, 3-D reconstruction and analysis of the acquired images. The canal configuration was described using Vertucci [supported by the supplementary configurations proposed by Sert & Bayirli (2004)] and Ahmed et al. (2027), coding systems. The chi-square test was used to assess the association between qualitative variables. By non-considering intercanal communications, Vertucci types IV (17.1%) and I (76.4%) were the most frequently reported configurations in the mesial and distal roots, respectively. Of the reported configurations, 24.3% and 4.3% were non-classifiable by Vertucci system in the mesial and distal roots, respectively. Up to 63.6% and 9.3% of the reported configurations were non- classifiable, and type I was the most frequent when considering intercanal communications (7.1% and 76.4% in the mesial and distal roots, respectively). According to Ahmed et al., system, almost half of the sample had more than four digits (47.9%), followed by the 3-digits category (20.71%). In both systems, a significant association was found between the canal configuration and the root type (p<0.001). The mandibular first molar of this Malaysian subpopulation demonstrated a wide range of root canal morphology. When compared to the Vertucci system, the system developed by Ahmed et al., successfully classified all molars configurations despite their level of complexity. The complex canal anatomy of mandibular first molars in this subpopulation warrants special attention during root canal treatment procedures.

En este trabajo se investigó la morfología del sistema de conductos radiculares del primer molar mandibular en una subpoblación de Malasia. Utilizando tomografía microcomputada con una resolución isotrópica de 22 µm, se escanearon 140 primeros molares mandibulares. Se utilizó el software MIMICS para segmentar (enmascarar), reconstruir en 3D, visualizar y analizar las imágenes adquiridas. La configuración del canal se describió utilizando Vertucci respaldado por las configuraciones complementarias propuestas por Sert & Bayirli (2004)] y Ahmed et al. (2017, 2020), sistemas de codificación. Se utilizó la prueba de chi-cuadrado para evaluar la asociación entre variables cualitativas. Sin considerar las comunicaciones intercanales, los tipos Vertucci IV (17,1%) y I (76,4%) fueron las configuraciones reportadas con mayor frecuencia en las raíces mesiales y distales, respectivamente. De las configuraciones reportadas, el 24,3 % y el 4,3 % fueron no clasificables por el sistema de Vertucci en las raíces mesial y distal, respectivamente. Hasta el 63,6 % y el 9,3 % de las configuraciones reportadas fueron no clasificables, siendo la tipo I la más frecuente al considerar las comunicaciones intercanales (7,1 % y 76,4 % en las raíces mesiales y distales, respectivamente). Según Ahmed et al. (2017, 2020) en el sistema, casi la mitad de la muestra tenía más de cuatro dígitos (47,9 %), seguido por la categoría de 3 dígitos (20,71 %). En ambos sistemas se encontró una asociación significativa entre la configuración del canal y el tipo de raíz (p<0,001). El primer molar mandibular de esta subpoblación de Malasia demostró una amplia gama morfológica del conducto radicular. En comparación con el sistema Vertucci, el sistema desarrollado por Ahmed et al. (2017, 2020) clasificaron con éxito todas las configuraciones de los molares a pesar de su nivel de complejidad. La compleja anatomía del canal de los primeros molares mandibulares en esta subpoblación merece una atención especial durante los procedimientos de tratamiento de conducto.

N- and s-substituted Pyrazolopyrimidines: A promising new class of potent c-Src kinase inhibitors with prominent antitumor activity.

In this work, readily achievable synthetic pathways were utilized for construction of a library of N/S analogues based on the pyrazolopyrimidine scaffold with terminal alkyl or aryl fragments. Subsequently, we evaluated the anticancer effects of these novel analogs against the proliferation of various cancer cell lines, including breast, colon, and liver lines. The results were striking, most of the tested molecules exhibited strong and selective cytotoxic activity against the MDA-MB-231 cancer cell line; IC50 1.13 µM. Structure-activity relationship (SAR) analysis revealed that N-substituted derivatives generally enhanced the cytotoxic effect, particularly with aliphatic side chains that facilitated favorable target interactions. We also investigated apoptosis, DNA fragmentation, invasion assay, and anti-migration effects, and discussed their underlying molecular mechanisms for the most active compound 7c. We demonstrated that 7c N-propyl analogue could inhibit MDA-MB-231 TNBC cell proliferation by inducing apoptosis through the regulation of vital proteins, namely c-Src, p53, and Bax. In addition, our results also revealed the potential of these compounds against tumor metastasis by downregulating the invasion and migration modes. Moreover, the in vitro inhibitory effect of active analogs against c-Src kinase was studied and proved that might be the main cause of their antiproliferative effect. Overall, these compelling results point towards the therapeutic potential of these derivatives, particularly those with N-substitution as promising candidates for the treatment of TNBC type of breast cancer.

Assessing and comparing a DDPG model and GA optimization for a heat and power virtual power plant operating in a power purchase agreement scheme.

This paper proposes a deep deterministic policy gradient (DDPG) model for the operation management of a solar power-based virtual power plant (VPP) having a PPA with the grid and supplying power and thermal energy to consumers. The VPP serves to balance the solar power intermittency, cover the demand whenever solar power is absent, and ensure an efficient supply of energy. The literature in this field has introduced optimization algorithms to determine the power plant's output power or heat on a rolling-horizon basis. Using the function approximation category, which involves reinforcement learning with neural networks, to solve the simultaneous thermal and power operation management of VPPs is still not well developed. The challenges imposed in this model are sourced from the non-linearity of the CCHP, the power and thermal balance constraints, and the consideration of continuous variables rather than discrete ones. A case study is simulated in Egypt to assess and compare the models. Compared to the genetic algorithm optimization, the proposed DDPG model achieved 3% more profit, 12% higher carbon dioxide (CO2) emissions, and 9% lower natural gas consumption. The DDPG solution was 57% faster than the GA. The results of the DDPG model proved that machine learning methods could outperform optimization in terms of optimality achievement and speed of solution. The DDPG improved the operation of energy storage units and was able to recognize the supply-demand operational pattern, ensuring the scalability of the VPP to cope with different energy demand levels.

Characterization of the root and canal anatomy of maxillary premolar teeth in an Iraqi subpopulation: a cone beam computed tomography study.

This study aims to evaluate the number of roots and root canal morphology types of maxillary premolars in relation to a patient's gender and age in an Iraqi population using two classification systems. Cone beam computed tomography (CBCT) scans of 1116 maxillary premolars from 385 patients were evaluated for the number of roots and root canal morphology types according to Vertucci's classification and Ahmed et al. classification systems. Differences in the number of roots and root canal morphology types with regard to tooth type, patients' gender and age groups were evaluated and the degree of bilateral symmetry was determined. Chi-squared test was used for statistical analysis. About 51.1% of the 1st premolars were double rooted. The majority (87.9%) of the 2nd premolars were single rooted. The three-rooted form presented in only 1.2% and 0.7% of the 1st and 2nd premolars, respectively. Vertucci Type IV (Ahmed et al. code 2MaxP B1P1) and Vertucci Type I (Ahmed et al. code 1MaxP1) were the most common canal morphology types in the 1st and 2nd premolars, respectively. Females showed a lower number of roots and a higher prevalence of Vertucci Type I configuration (P < 0.05). Younger age groups showed a higher prevalence of Vertucci Type I configuration (P < 0.05). Bilateral symmetry was seen in more than half of the maxillary premolars. There is a considerable variation in the number of roots and root canal configurations of maxillary premolars in the studied Iraqi population, with a significant difference by gender and age groups. Ahmed et al. classification provided more accurate presentation of the root and canal anatomy in maxillary premolars compared to Vertucci's classification.

The Study and Relevance of Pulp Chamber Anatomy in Endodontics - A Comprehensive Review.

With the ever-increasing understanding of tooth anatomy, there is a renewed focus on the pulp chamber as an important component of the root canal system. For example, the pulp chamber is of critical relevance during diagnostic procedures such as pulp sensibility tests, deep caries removal, vital pulp treatments, access cavity preparation, tooth whitening, tooth restoration as well as methods for examining the floor of the pulp chamber to aid the detection of root canal orifices or the presence of perforations and cracks. The more recent concept of minimal invasive endodontics has also created a need to understand better the anatomy of the pulp chamber. The purpose of this article is to discuss the research methods used to study pulp chamber anatomy and the significance of the pulp chamber in endodontic research and clinical practice. In addition, directions for future research are emphasised.

A Review of Recent Innovations in Remote Health Monitoring.

The development of remote health monitoring systems has focused on enhancing healthcare services' efficiency and quality, particularly in chronic disease management and elderly care. These systems employ a range of sensors and wearable devices to track patients' health status and offer real-time feedback to healthcare providers. This facilitates prompt interventions and reduces hospitalization rates. The aim of this study is to explore the latest developments in the realm of remote health monitoring systems. In this paper, we explore a wide range of domains, spanning antenna designs, small implantable antennas, on-body wearable solutions, and adaptable detection and imaging systems. Our research also delves into the methodological approaches used in monitoring systems, including the analysis of channel characteristics, advancements in wireless capsule endoscopy, and insightful investigations into sensing and imaging techniques. These advancements hold the potential to improve the accuracy and efficiency of monitoring, ultimately contributing to enhanced health outcomes for patients.

Implications of root, pulp chamber, and canal anatomy on pulpotomy and revitalization procedures.

OBJECTIVES: This review aims to discuss the implications of anatomy of the root, pulp chamber, and canals on pulpotomy and revitalization procedures (RPs) as treatment alternatives to root canal treatment procedures. METHODS: This narrative review was undertaken to address two main questions - why remove vital pulp tissue in teeth with complex canal anatomy when it can be preserved? And why replace the necrotic pulp in teeth with mature roots with a synthetic material when we can revitalize? This review also aims to discuss anatomical challenges with pulpotomy and revitalization procedures. RESULTS: Maintaining the vitality of the pulp via partial or full pulpotomy procedures avoids the multiple potential challenges faced by clinicians during root canal treatment. However, carrying out pulpotomy procedures requires a meticulous understanding of the pulp chamber anatomy, which varies from tooth to tooth. Literature shows an increased interest in the application of RPs in teeth with mature roots; however, to date, the relation between the complexity of the root canal system and outcomes of RPs in necrotic multi-rooted teeth with mature roots is unclear and requires further robust comparative research and long-term follow-up. CONCLUSIONS: Whenever indicated, pulpotomy procedures are viable treatment options for vital teeth with mature roots; however, comparative, adequately powered studies with long-term follow-up are needed as a priority in this area. RPs show promising outcomes for necrotic teeth with mature roots that warrant more evidence in different tooth types with long-term follow-ups.  CLINICAL RELEVANCE: Clinicians should be aware of the pulp chamber anatomy, which is subject to morphological changes by age or as a defensive mechanism against microbial irritation, before practicing partial and full pulpotomy procedures. RP is a promising treatment option for teeth with immature roots, but more evidence is needed for its applications in teeth with mature roots. A universal consensus and considerably more robust evidence are needed for the standardization of RPs in teeth with mature roots.

Development of Novel Class of Phenylpyrazolo[3,4-d]pyrimidine-Based Analogs with Potent Anticancer Activity and Multitarget Enzyme Inhibition Supported by Docking Studies.

Phenylpyrazolo[3,4-d]pyrimidine is considered a milestone scaffold known to possess various biological activities such as antiparasitic, antifungal, antimicrobial, and antiproliferative activities. In addition, the urgent need for selective and potent novel anticancer agents represents a major route in the drug discovery process. Herein, new aryl analogs were synthesized and evaluated for their anticancer effects on a panel of cancer cell lines: MCF-7, HCT116, and HePG-2. Some of these compounds showed potent cytotoxicity, with variable degrees of potency and cell line selectivity in antiproliferative assays with low resistance. As the analogs carry the pyrazolopyrimidine scaffold, which looks structurally very similar to tyrosine and receptor kinase inhibitors, the potent compounds were evaluated for their inhibitory effects on three essential cancer targets: EGFRWT, EGFRT790M, VGFR2, and Top-II. The data obtained revealed that most of these compounds were potent, with variable degrees of target selectivity and dual EGFR/VGFR2 inhibitors at the IC50 value range, i.e., 0.3-24 µM. Among these, compound 5i was the most potent non-selective dual EGFR/VGFR2 inhibitor, with inhibitory concentrations of 0.3 and 7.60 µM, respectively. When 5i was tested in an MCF-7 model, it effectively inhibited tumor growth, strongly induced cancer cell apoptosis, inhibited cell migration, and suppressed cell cycle progression leading to DNA fragmentation. Molecular docking studies were performed to explore the binding mode and mechanism of such compounds on protein targets and mapped with reference ligands. The results of our studies indicate that the newly discovered phenylpyrazolo[3,4-d]pyrimidine-based multitarget inhibitors have significant potential for anticancer treatment.

Critical analysis of a new system to classify root and canal morphology - A systematic review.

A novel system to classify root and canal morphology was recently introduced (Ahmed et al. 2017). This systematic review aimed to answer the following research question: Does the Ahmed et al. system provide a more accurate and practical classification of root and canal anatomy compared to other classifications? A literature search was conducted in Google Scholar, Scopus and Wiley Online Library to identify the citation counts for the article entitled 'A new system for classifying root and root canal morphology; doi.org/10.1111/iej.12685'. After removal of duplicates and unrelated articles, 15 studies were included and analysed. All studies compared the Ahmed et al. system with the Vertucci classification. Results revealed that both systems were able to classify simple canal configurations in single-rooted anterior and premolar teeth, disto-buccal and palatal roots of maxillary molars. However, the Ahmed et al. system provided more accurate and comprehensive categorisations of single-rooted teeth with complex canal anatomy, multi-rooted maxillary and mandibular premolars and the mesio-buccal root of maxillary molars. Further evidence on the utility of the Ahmed et al. system is required using other diagnostic devices especially in molars.

Introducing of novel class of pyrano[2,3-c]pyrazole-5-carbonitrile analogs with potent antimicrobial activity, DNA gyrase inhibition, and prominent pharmacokinetic and CNS toxicity profiles supported by molecular dynamic simulation.

Microbiological DNA gyrase is recognized as an exceptional microbial target for the innovative development of low-resistant and more effective antimicrobial drugs. Hence, we introduced a one-pot facile synthesis of a novel pyranopyrazole scaffold bearing different functionalities; substituted aryl ring, nitrile, and hydroxyl groups. All new analogs were characterized with full spectroscopic data. The antimicrobial screening for all analogs was assessed against standard strains of Gm + ve and Gm-ve through in vitro considers. The screened compounds displayed very promising MIC/MBC values against some of the bacterial strains with broad or selective antibacterial effects. Of these, 4j biphenyl analog showed 0.5-2/2-8 µg/mL MIC/MBC for suppression and killing of Gm + ve and Gm-ve strains. Moreover, the antimicrobial screening was assessed for the most potent analogs against certain highly resistant microbial strains. Consequently, DNA gyrase supercoiling assay was done for all analogs using ciprofloxacin as reference positive control. Obviously, the results showed a different activity profile with potent analog 4j with IC50 value 6.29 µg/mL better than reference drug 10.2 µg/mL. Additionally, CNS toxicity testing was done using the HiB5 cell line for attenuation of GABA/NMDA expression to both 4j and ciprofloxacin compounds that revealed better neurotransmitter modulation by novel scaffold. Importantly, docking and dynamic simulations were performed for the most active 4j analog to investigate its interaction with DNA binding sites, which supported the in vitro observations and compound stability with binding pocket. Finally, a novel scaffold pyranopyrazole was introduced as a DNA gyrase inhibitor with prominent antibacterial efficacy and low CNS side effect toxicity better than quinolones.Communicated by Ramaswamy H. Sarma.

Root and canal anatomy of mandibular first molars using micro-computed tomography: a systematic review.

BACKGROUND: A thorough understanding of root and canal anatomy is crucial for successful root canal treatment outcomes. This systematic review aims to explore the published micro-CT studies investigated the anatomy of root and canal system in permanent mandibular first molars. METHOD: An electronic search was performed on Web of science, PubMed, and Scopus. Micro-CT journal studies investigated the root and canal anatomy of permanent double-rooted mandibular first molars were included. Data on study characteristics, objectives of interest, specifications of the studies, and micro-CT specifications were extracted. Risk of bias assessment (ROB) of the included studies was performed using Anatomical Quality Assessment (AQUA) tool. The extracted data were presented in tables and figures to present and synthesise the results. A meta-analysis was performed for the studies related to the prevalence of Vertucci's canal configurations, middle mesial canal (MMC) configurations, and Fan's isthmus types. RESULTS: Amongst 1358 identified studies, thirty met the inclusion criteria. In terms of the objectives, the selected studies showed high anatomical variability in mandibular first molars. Twenty-two (73%), 25 (83%), and 12 (40%) of the studies reported the population/ethnicity, micro-CT specifications, and ethical approval, respectively. 28 (93%) studies did not disclose the method of sample size estimation. In only 6 (20%) of the studies, the authors had calibrated the assessment approaches. Mostly, a potential ROB was reported in domain 1 (objective(s) and subject characteristics) and domain 3 (methodology characterization). Whilst, low risk was reported in domains 2 (study design), 4 (descriptive anatomy), and 5 (reporting of results). The overall ROB was reported to be ''moderate'' in the vast majority of the studies (27/30). Meta-analysis results showed high levels of heterogeneity among the studies related to MMCs (I2 = 86%) and Fan's isthmus (I2 = 87%). As for the root canal configuration, pooled prevalence showed that Vertucci type IV and type I were the most prevalent in mesial and distal root canals, respectively. CONCLUSION: Based on moderate risk of bias level of evidence, micro-CT studies have shown wide range of qualitative and quantitative data presentations of the roots and canals in mandibular first molars. Protocol and registration. The protocol of this systematic review was prospectively registered in the Open Science Framework database ( https://osf.io ) on 2022-06-20 with the registration number 10.17605/OSF.IO/EZP7K.

Application of two systems to classify the root and canal morphology in the human dentition: A national survey in India.

PURPOSE: To assess the application and accuracy of two systems (Vertucci et al. 1974 and Ahmed et al. 2017) in classifying the root and canal morphology of human dentition among final-year undergraduates, interns, and postgraduate dental students in India. METHODS: The survey was conducted using physical and online presentation modes in two phases. Phase 1; PowerPoint presentation (PPT), describing the most used classification system (Vertucci et al. 1974) and its supplementary types and Ahmed et al. (2017) classification. A single presenter delivered the PPT to participants, using either a projector in an auditorium/seminar hall (face-to-face) or an online platform (zoom meeting software). Phase 2 involved determining the students' responses. A questionnaire was distributed amongst the participants after the lecture and collected for analysis. Fisher's exact test was used to analyze the data statistically, and the significance level was set at 0.05 (p < 0.05). RESULTS: A total of 1082 participants were involved in this survey. Overall, 93% of study participants found that Ahmed et al. classification system was more practical and accurate than Vertucci et al. system and its supplemental configurations (p < 0.001). About 97% agreed that Ahmed et al. classification system aided in understanding root and canal morphology better than Vertucci's and its additional configurations, and they recommended to include in their curriculum (p < 0.001). CONCLUSIONS: In comparison to Vertucci's classification system and supplementary types, the undergraduate and postgraduate dental students, and interns in India agreed that Ahmed et al. classification system is more practical and accurate for classifying the root and canal morphology.