Postendodontic Pain Using Single File System with Different Irrigation Protocols in Single-visit Root Canal Treatment: A Randomized Control Trial.

AIM: To evaluate the intensity of postendodontic pain (PEP) using final irrigation with side-vented needle (SV), EndoActivator (EA), and Ultra X (UX) in single-visit endodontics (SVE) with F-One rotary files. MATERIALS AND METHODS: A total 150 patients indicated for endodontic treatment were selected. Single-visit endodontics treatment was performed under local anesthesia. For the final irrigation protocol, they were divided into three groups: group I (SV), group II (EA), and group III (UX). The severity of PEP was assessed using visual analogue scale (VAS) score after 6, 12, 24, and 48 hours. Analgesics taken by patients, for pain, were also recorded. Finally, the data were tabulated and statistically analyzed using SPSS 20.0 software at a level of significance being 0.05. RESULTS: Postendodontic pain was less in group III (UX) and group II (EA) compared with group I (SV) at 6 and 12 hours, which is statistically significant (p < 0.05). There was no statistically significant difference found after 24 hours and 48 hours. CONCLUSION: The intensity of PEP was minimum in patients treated with EndoActivator and ultrasonic along with single rotary file systems. The incidence of analgesic intake was similar in all three groups. How to cite this article: Kathiria NV, Attur K, Bagda KM, et al. Postendodontic Pain Using Single File System with Different Irrigation Protocols in Single-visit Root Canal Treatment: A Randomized Control Trial. J Contemp Dent Pract 2024;25(2):180-185.

Propensity Score-Weighted Analysis of Postoperative Infection in Patients With and Without Preoperative Urine Culture.

Importance: Although recent guidelines recommend against performance of preoperative urine culture before nongenitourinary surgery, many clinicians still order preoperative urine cultures and prescribe antibiotics for treatment of asymptomatic bacteriuria in an effort to reduce infection risk. Objective: To assess the association between preoperative urine culture testing and postoperative urinary tract infection (UTI) or surgical site infection (SSI), independent of baseline patient characteristics or type of surgery. Design, Setting, and Participants: This cohort study analyzed surgical procedures performed from January 1, 2017, to December 31, 2019, at any of 112 US Department of Veterans Affairs (VA) medical centers. The cohort comprised VA enrollees who underwent major elective noncardiac, nonurological operations. Machine learning and inverse probability of treatment weighting (IPTW) were used to balance the characteristics between those who did and did not undergo a urine culture. Data analyses were performed between January 2023 and January 2024. Exposures: Performance of urine culture within 30 days prior to surgery. Main Outcomes and Measures: The 2 main outcomes were UTI and SSI occurring within 30 days after surgery. Weighted logistic regression was used to estimate odds ratios (ORs) for postoperative infection based on treatment status. Results: A total of 250 389 VA enrollees who underwent 288 858 surgical procedures were included, with 88.9% (256 753) of surgical procedures received by males and 48.9% (141 340) received by patients 65 years or older. Baseline characteristics were well balanced among treatment groups after applying IPTW weights. Preoperative urine culture was performed for 10.5% of surgical procedures (30 384 of 288 858). The IPTW analysis found that preoperative urine culture was not associated with SSI (adjusted OR [AOR], 0.99; 95% CI, 0.90-1.10) or postoperative UTI (AOR, 1.18; 95% CI, 0.98-1.40). In analyses limited to orthopedic surgery and neurosurgery as a proxy for prosthetic implants, the adjusted risks for UTI and SSI were also not associated with preoperative urine culture performance. Conclusions and Relevance: This cohort study found no association between performance of a preoperative urine culture and lower risk of postoperative UTI or SSI. The results support the deimplementation of urine cultures and associated antibiotic treatment prior to surgery, even when using prosthetic implants.

Glutamine antagonist DRP-104 suppresses tumor growth and enhances response to checkpoint blockade in KEAP1 mutant lung cancer.

Loss-of-function mutations in KEAP1 frequently occur in lung cancer and are associated with poor prognosis and resistance to standard of care treatment, highlighting the need for the development of targeted therapies. We previously showed that KEAP1 mutant tumors consume glutamine to support the metabolic rewiring associated with NRF2-dependent antioxidant production. Here, using preclinical patient-derived xenograft models and antigenic orthotopic lung cancer models, we show that the glutamine antagonist prodrug DRP-104 impairs the growth of KEAP1 mutant tumors. We find that DRP-104 suppresses KEAP1 mutant tumors by inhibiting glutamine-dependent nucleotide synthesis and promoting antitumor T cell responses. Using multimodal single-cell sequencing and ex vivo functional assays, we demonstrate that DRP-104 reverses T cell exhaustion, decreases Tregs, and enhances the function of CD4 and CD8 T cells, culminating in an improved response to anti-PD1 therapy. Our preclinical findings provide compelling evidence that DRP-104, currently in clinical trials, offers a promising therapeutic approach for treating patients with KEAP1 mutant lung cancer.

Impacts of chitosan and its nanoformulations on the metabolic syndromes: a review.

A significant public health issue worldwide is metabolic syndrome, a cluster of metabolic illnesses that comprises insulin resistance, obesity, dyslipidemia, hyperglycemia, and hypertension. The creation of natural treatments and preventions for metabolic syndrome is crucial. Chitosan, along with its nanoformulations, is an oligomer of chitin, the second-most prevalent polymer in nature, which is created via deacetylation. Due to its plentiful biological actions in recent years, chitosan and its nanoformulations have drawn much interest. Recently, the chitosan nanoparticle-based delivery of CRISPR-Cas9 has been applied in treating metabolic syndromes. The benefits of chitosan and its nanoformulations on insulin resistance, obesity, diabetes mellitus, dyslipidemia, hyperglycemia, and hypertension will be outlined in the present review, highlighting potential mechanisms for the avoidance and medication of the metabolic syndromes by chitosan and its nanoformulations.

Real-World Outcomes in Patients with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec Monotherapy: Findings from the RESTORE Registry.

Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials. Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting. Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources. Results: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and at onasemnogene abeparvovec infusion was 3 (1-10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related. Conclusion: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.

Recruitment and Maintenance of CX3CR1+CD4+ T Cells during Helminth Infection.

Distinct subsets of T lymphocytes express CX3CR1 under inflammatory conditions, but little is known about CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections. In this study, we used a fate-mapping mouse model to characterize CX3CR1+CD4+ T cells during both acute Nippostrongylus brasiliensis and chronic Schistosoma mansoni murine models of helminth infections, revealing CX3CR1+CD4+ T cells to be an activated tissue-homing subset with varying capacity for cytokine production. Tracking these cells over time revealed that maintenance of CX3CR1 itself along with a TH2 phenotype conferred a survival advantage in the inflamed tissue. Single-cell RNA sequencing analysis of fate-mapped CX3CR1+CD4+ T cells from both the peripheral tissue and the spleen revealed a considerable level of diversity and identified a distinct population of BCL6+TCF-1+PD1+CD4+ T cells in the spleen during helminth infections. Conditional deletion of BCL6 in CX3CR1+ cells resulted in fewer CX3CR1+CD4+ T cells during infection, indicating a role in sustaining CD4+ T cell responses to helminth infections. Overall, our studies revealed the behavior and heterogeneity of CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections and identified BCL6 to be important in their maintenance.

Practical Guide to Education Program Evaluation Research.

This Guide to Statistics and Methods describes common methods for building evidence of validity for a program within health professional education and provides a framework for program evaluation.

Optimal eco-driving scheme for reducing energy consumption and carbon emissions on curved roads.

Energy consumption and emissions of a vehicle are highly influenced by road contexts and driving behavior. Especially, driving on horizontal curves often necessitates a driver to brake and accelerate, which causes additional fuel consumption and emissions. This paper proposes a novel optimal ecological (eco) driving scheme (EDS) using nonlinear model predictive control (MPC) considering various road contexts, i.e., curvatures and surface conditions. Firstly, a nonlinear optimization problem is formulated considering a suitable prediction horizon and an objective function based on factors affecting fuel consumption, emissions, and driving safety. Secondly, the EDS dynamically computes the optimal velocity trajectory for the host vehicle considering its dynamics model, the state of the preceding vehicle, and information of road contexts that reduces fuel consumption and carbon emissions. Finally, we analyze the effect of different penetration rates of the EDS on overall traffic performance. The effectiveness of the proposed scheme is demonstrated using microscopic traffic simulations under dense and mixed traffic environment, and it is found that the proposed EDS substantially reduces the fuel consumption and carbon emissions of the host vehicle compared to the traditional (human-based) driving system (TDS), while ensuring driving safety. The proposed scheme can be employed as an advanced driver assistance system (ADAS) for semi-autonomous vehicles.

Disinfection by methylthionine chloride and chitosan in combination with Photo radiation therapy on caries affected dentin nano hardness, adhesive integrity, and bond failure.

OBJECTIVE: The aim of the study was to assess the disinfection efficacy, bond integrity, and nano hardness of caries-affected dentin (CAD) surface bonded to resin cement when disinfected with chlorhexidine (CHX), Methylene blue activated by Photodynamic therapy (MB-PDT), chitosan, silver diamine fluoride (SDF), chitosan activated by PDT, and SDF-diode laser against S. mutans. MATERIALS AND METHODS: A total of 60 human mandibular molars were extracted non-traumatically and gathered using ICDAS criteria. The dentin surface was prepared, leaving CAD to receive a disinfection procedure. After inoculation with S. mutans, the CAD samples were divided into six groups and disinfected with various disinfectants (n = 10) CHX, MB-PDT, chitosan, chitosan-PDT, SDF, and SDF+ diode laser. Survival rates of S. mutans were analyzed following the restoration of samples with resin cement via the etch and rinse method to assess SBS. Also, nano hardness was analyzed. Statistical analysis was performed by using the ANOVA and the Tukey multiple test (p<0.05). The Kruskal-Wallis test was used to evaluate the change in survival rate. RESULTS: Related to the survival rates, the SDF+ diode laser displayed the highest reduction in S. mutans levels and chitosan presented the lowest level of disinfection. The intergroup comparison revealed that CHX and chitosan-PDT displayed comparable outcomes of S. mutans survival rate to that of SDF+ diode laser (p>0.05). Likewise, MB-PDT and SDF displayed a comparable survival rate of S. mutans to Chitosan disinfection (p>0.05). Considering SBS and nano hardness, the highest SBS and NH were exhibited by the SDF+ diode laser, and the lowest SBS and NH values were exhibited by MB-PDT. The intragroup comparison revealed that CAD specimens disinfected with Chitosan-PDT showed comparable SBS and NH values to the SDF+ diode laser (p>0.05). CHX, chitosan, and SDF exhibited bond values and NH comparable to MB-PDT (p<0.05). CONCLUSIONS: Synergistic use of Silver diamine fluoride with diode laser and chitosan activated by PDT can be used as an alternative to CHX for controlling S. mutans growth, promoting enhanced bond efficacy and nano hardness for bonding resin cement to the caries-affected dentin.

FolE gene expression for folic acid productivity from optimized and characterized probiotic Lactobacillus delbrueckii.

BACKGROUND: Lactobacillus delbrueckii was one of the most common milk lactic acid bacterial strains (LAB) which characterized as probiotic with many health influencing properties. RESULTS: Among seven isolates, KH1 isolate was the best producer of folic acid with 100 µg/ml after 48 h of incubation; FolE gene expression after 24 h of incubation was in the highest value in case of KH1 with three folds. Lactose was the best carbon source for this KH1, besides the best next isolates KH80 and KH98. The selected three LAB isolates were identified through 16S rDNA as Lactobacillus delbrueckii. These three isolates have high tolerance against acidic pH 2-3; they give 45, 10, and 22 CFUs at pH 3, besides 9, 6, and 4 CFUs at pH2, respectively. They also have resistance against elevated bile salt range 0.1-0.4%. KH1 recorded 99% scavenging against 97.3% 1000 µg/ml ascorbic acid. Docking study exhibits the binding mode of folic acid which exhibited an energy binding of - 8.65 kcal/mol against DHFR. Folic acid formed four Pi-alkyl, Pi-Pi, and Pi-sigma interactions with Ala9, Ile7, Phe34, and Ile60. Additionally, folic acid interacted with Glu30 and Asn64 by three hydrogen bonds with 1.77, 1.76, and 1.96 Å. CONCLUSION: LAB isolates have probiotic properties, antioxidant activity, and desired organic natural source for folic acid supplementation that improve hemoglobin that indicated by docking study interaction.

Mouse genome rewriting and tailoring of three important disease loci.

Genetically engineered mouse models (GEMMs) help us to understand human pathologies and develop new therapies, yet faithfully recapitulating human diseases in mice is challenging. Advances in genomics have highlighted the importance of non-coding regulatory genome sequences, which control spatiotemporal gene expression patterns and splicing in many human diseases1,2. Including regulatory extensive genomic regions, which requires large-scale genome engineering, should enhance the quality of disease modelling. Existing methods set limits on the size and efficiency of DNA delivery, hampering the routine creation of highly informative models that we call genomically rewritten and tailored GEMMs (GREAT-GEMMs). Here we describe 'mammalian switching antibiotic resistance markers progressively for integration' (mSwAP-In), a method for efficient genome rewriting in mouse embryonic stem cells. We demonstrate the use of mSwAP-In for iterative genome rewriting of up to 115 kb of a tailored Trp53 locus, as well as for humanization of mice using 116 kb and 180 kb human ACE2 loci. The ACE2 model recapitulated human ACE2 expression patterns and splicing, and notably, presented milder symptoms when challenged with SARS-CoV-2 compared with the existing K18-hACE2 model, thus representing a more human-like model of infection. Finally, we demonstrated serial genome writing by humanizing mouse Tmprss2 biallelically in the ACE2 GREAT-GEMM, highlighting the versatility of mSwAP-In in genome writing.

Remote Sensing Imagery Data Analysis Using Marine Predators Algorithm with Deep Learning for Food Crop Classification.

Recently, the usage of remote sensing (RS) data attained from unmanned aerial vehicles (UAV) or satellite imagery has become increasingly popular for crop classification processes, namely soil classification, crop mapping, or yield prediction. Food crop classification using RS images (RSI) is a significant application of RS technology in agriculture. It involves the use of satellite or aerial imagery to identify and classify different types of food crops grown in a specific area. This information can be valuable for crop monitoring, yield estimation, and land management. Meeting the criteria for analyzing these data requires increasingly sophisticated methods and artificial intelligence (AI) technologies provide the necessary support. Due to the heterogeneity and fragmentation of crop planting, typical classification approaches have a lower classification performance. However, the DL technique can detect and categorize crop types effectively and has a stronger feature extraction capability. In this aspect, this study designed a new remote sensing imagery data analysis using the marine predators algorithm with deep learning for food crop classification (RSMPA-DLFCC) technique. The RSMPA-DLFCC technique mainly investigates the RS data and determines the variety of food crops. In the RSMPA-DLFCC technique, the SimAM-EfficientNet model is utilized for the feature extraction process. The MPA is applied for the optimal hyperparameter selection process in order to optimize the accuracy of SimAM-EfficientNet architecture. MPA, inspired by the foraging behaviors of marine predators, perceptively explores hyperparameter configurations to optimize the hyperparameters, thereby improving the classification accuracy and generalization capabilities. For crop type detection and classification, an extreme learning machine (ELM) model can be used. The simulation analysis of the RSMPA-DLFCC technique is performed on two benchmark datasets. The extensive analysis of the results portrayed the higher performance of the RSMPA-DLFCC approach over existing DL techniques.

EUS-guided Braun-type enteroenterostomy for management of an afferent limb-type obstruction in a patient with prior surgical gastrojejunostomy.

Video 1Case presentation of EUS-guided Braun-type enteroenterostomy for the management of an afferent limb-type obstruction in a patient with prior surgical gastrojejunostomy.

Contraceptives Knowledge and Perception: A Cross-Sectional Study Among Future Pharmacists in Jordan.

Background: Unintended pregnancy has huge burdens on healthcare resources and society. Contraception is essential to reduce it, and pharmacists are usually the first healthcare providers who are asked for advice about contraceptives. Therefore, the study aimed to evaluate future pharmacists' knowledge, awareness, and perceptions of contraceptive methods and assess the factors influencing their knowledge, awareness, and perceptions. Methods: This cross-sectional study was conducted among senior pharmacy students at four universities. Data was collected over three months using a structured and validated questionnaire. Both inferential (Mann-Whitney U-test and Kruskal-Wallis test) and descriptive analyses were employed. Results: A total of 310 eligible participants completed the questionnaire, and more than half of them (N=172; 55.5%) were final-year students. The Mann-Whitney U-test revealed that final-year students had significantly better knowledge (U= 14,261.5, p<0.002) and a higher level of awareness (U= 13,971.5, p<0.007) than fourth-year students. Interestingly, the Kruskal-Wallis test showed that the type of training (hospital, community, none) had a statistically significant impact on awareness scores (p<0.001). Conclusion: Final-year students had higher knowledge and were more aware of contraception than fourth-year students. Also, community pharmacy training was associated with better awareness about contraceptives . Therefore, future studies should explore the impact of incorporating more targeted contraceptive education into earlier years of pharmacy education to bridge the knowledge gap observed between final-year and fourth-year students. Additionally, research should also investigate the effectiveness of specific community pharmacy training modules on contraceptive awareness.

Correction: Microwave-assisted chemoselective synthesis and photophysical properties of 2-arylazo-biphenyl-4-carboxamides from hydrazonals.

[This corrects the article DOI: 10.1039/D3RA04558G.].

KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance.

Lung cancer treatment has benefited greatly through advancements in immunotherapies. However, immunotherapy often fails in patients with specific mutations like KEAP1, which are frequently found in lung adenocarcinoma. We established an antigenic lung cancer model and used it to explore how Keap1 mutations remodel the tumor immune microenvironment. Using single-cell technology and depletion studies, we demonstrate that Keap1-mutant tumors diminish dendritic cell and T cell responses driving immunotherapy resistance. This observation was corroborated in patient samples. CRISPR-Cas9-mediated gene targeting revealed that hyperactivation of the NRF2 antioxidant pathway is responsible for diminished immune responses in Keap1-mutant tumors. Importantly, we demonstrate that combining glutaminase inhibition with immune checkpoint blockade can reverse immunosuppression, making Keap1-mutant tumors susceptible to immunotherapy. Our study provides new insight into the role of KEAP1 mutations in immune evasion, paving the way for novel immune-based therapeutic strategies for KEAP1-mutant cancers.

PAPR reduction using SLM-PTS-CT hybrid PAPR method for optical NOMA waveform.

In this article, we focus on optimising the SLM-PTS-CT (selective mapping, partial transmission sequence, circular transformation) hybrid method for optical non-orthogonal multiple access (O-NOMA) waveforms. The goal is to enhance the spectrum performance and practicality of O-NOMA systems while mitigating the PAPR issue through a hybrid approach. The SLM-PTS-CT hybrid method is applicable to O-NOMA waveforms, providing effective PAPR reduction. By dividing the data sequence into sub-blocks, applying phase factors, and rotating the phase of the subcarriers in such a way that the peaks of the signal are distributed more uniformly, the proposed SLM-PTS-CT achieves an optimal PAPR reduction while maintaining the benefits of O-NOMA. The efficiency of the proposed method is analysed by estimating the performance of several parameters, such as bit error rate (BER), PAPR, and power spectral density (PSD), by increasing the number of sub-blocks (S) and phase factor (P). Further, the proposed SLM-PTS-CT is compared with the conventional SLM-PTS, SLM, and PTS. The simulation results demonstrate that the proposed approach efficiently improves spectral efficiency, preserves BER performance, and reduces PAPR as compared with conventional methods.

Synthesis and Anti-Breast Cancer Potency of Mono- and Bis-(pyrazolyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine) Derivatives as EGFR/CDK-2 Target Inhibitors.

The target mono- and bis-(6-pyrazolyltriazolo-thiadiazine) derivatives 4a-c and 6a-d were synthesized using a straightforward protocol via reaction of 3-bromoacetylpyrazole 2 with 4-amino-s-triazole-3-thiols 3a-c and bis(4-amino-5-mercapto-s-triazol-3-yl)alkanes 5a-d, respectively. The bis(6-pyrazolyl-s-triazolo[3,4-b][1,3,4]thiadiazine) derivatives 8a,b and 10 were also constructed by reaction of the triazolo[3,4-b][1,3,4]thiadiazine-3-thiol 4c with the proper dibromo compounds 7a,b and 9, respectively. Structures of the new substances were determined by spectroscopic and analytical data. Compounds 4b, 4c, and 6a showed potent cytotoxicity against MCF-7 (IC50 = 3.16, 2.74, and 0.39 µM, respectively) and were safe against the MCF-10A cells. Compounds 4b, 4c, and 6a also showed promising dual EGFR and CDK-2 inhibition activities, particularly 6a was the most effective (IC50 = 19.6 and 87.9 nM, respectively), better than Erlotinib and Roscovitine. Compound 6a treatment induced EGFR and CDK-2 enzyme inhibition by 97.18% and 94.11%, respectively, at 10 µM (the highest concentration). Compound 6a notably induced cell apoptosis in MCF-7 cells, increasing the cell population by total apoptosis 43.3% compared to 1.29% for the untreated control group, increasing the cell population at the S-phase by 39.2% compared to 18.6% (control).

Combination NIPS/TIPS Synthesis of α-Fe2O3 and α/γ-Fe2O3 Doped PVDF Composite for Efficient Piezocatalytic Degradation of Rhodamine B.

Highly porous membranes based on polyvinylidene fluoride (PVDF) with the addition of nanoscale particles of non-magnetic and magnetic iron oxides were synthesized using a combined method of non-solvent induced phase separation (NIPS) and thermo-induced phase separation (TIPS) based on the technique developed by Dr. Blade. The obtained membranes were characterized using SEM, EDS, XRD, IR, diffuse reflectance spectroscopy, and fluorescent microscopy. It was shown that the membranes possessed a high fraction of electroactive phase, which increased up to a maximum of 96% with the addition of 2 wt% of α-Fe2O3 and α/γ-Fe2O3 nanoparticles. It was demonstrated that doping PVDF with nanoparticles contributed to the reduction of pore size in the membrane. All membranes exhibited piezocatalytic activity in the degradation of Rhodamine B. The degree of degradation increased from 69% when using pure PVDF membrane to 90% when using the composite membrane. The nature of the additive did not affect the piezocatalytic activity. It was determined that the main reactive species responsible for the degradation of Rhodamine B were •OH and •O2-. It was also shown that under piezocatalytic conditions, composite membranes generated a piezopotential of approximately 2.5 V.