Search Results (20)

Introduction: Successful root canal therapy relies on thorough cleaning and disinfection to eliminate microorganisms and residual pulp tissue. Advanced irrigation activation techniques, including Sonic, Ultrasonic, and Diode Laser activation, have improved cleaning efficacy, bacterial reduction, smear layer removal, and irrigant hydrodynamics. On the other hand, these irrigation activation techniques may lead to a temperature rise that may risk the surrounding periodontal tissue. Thus, this study aimed to investigate the temperature rise during different irrigation activation techniques at various time intervals and evaluate the efficacy of these techniques in removing biofilm-mimicking hydrogel BMH of a simulated root canal system in 3D-printed tooth models. Methods: Ten extracted human mandibular premolars, prepared to size 40/0.04 taper, and a hundred 3D-printed resin premolars with simulated main (0.25 mm) and lateral canals (0.15 mm at 3, 7, 11 mm from apex) were used; 50 of them were filled with biofilm-mimicking hydrogel (BMH). Five irrigation activation techniques were evaluated: Diode Laser, Ultrasonic, Sonic, XP-Finisher, and Control (n = 10). Temperature rises were measured on the extracted premolars after 30 and 60 s of activation using a thermographic camera in a controlled environment (23 ± 2 °C). Irrigant penetration, with and without BMH, was assessed in 3D-printed premolars using a 2.5% sodium hypochlorite-contrast medium mixture, visualized with a CMOS radiographic sensor. Penetration was scored (main canal: 3 points; lateral canals: 0–2 points) and analyzed with non-parametric tests. Results: Diode Laser activation technique resulted in the highest temperature rise on the external root surface, followed by the Ultrasonic, with no statistically significant difference observed among the remaining groups. In terms of efficacy, Ultrasonic and Sonic activation achieved significantly greater irrigant penetration in samples without BMH, and greater BMH removal in samples with BMH, compared to Diode Laser, XP-Finisher, and Control groups. Conclusions: In this in vitro study, Diode Laser caused the highest temperature rise, followed by Ultrasonic, with significant increases from 30 to 60 s. Temperature rise did not significantly affect penetration or BMH removal. Ultrasonic and Sonic irrigation techniques achieved the highest depth of penetration (without BMH) and biofilm-mimicking Hydrogel removal (with BMH) compared to Diode Laser, XP-Finisher, and Control. Full article

The transcription of ribosomal RNA (rRNA) by RNA Polymerase I (Pol I) is the rate-limiting step in ribosome biogenesis and a major determinant of cellular growth rates. Unlike other eukaryotes, which express identical rRNA from large tandem arrays of dozens to hundreds of identical rRNA genes in every cell, the genome of the human malaria parasite Plasmodium falciparum contains only a handful single-copy 47S rRNA loci that differ substantially from one another in length, sequence, and expression in different cell types. We found that the growth of the malaria parasite was acutely sensitive to the Pol I inhibitors 9-hydroxyellipticine and BMH-21 and demonstrated that they greatly reduce the transcription of 47S rRNAs as well as the transcription of other non-coding RNA genes. This makes P. falciparum only the second known organism where RNA Polymerase I transcribes genes other than the 47S rRNAs. We found that the various types of Pol I-transcribed genes differed by more than two orders of magnitude in their susceptibility to these inhibitors and explored the implications of these findings for the regulation of rRNA in P. falciparum. Full article

Classical (MD) and ab initio (AIMD) molecular dynamics simulations were conducted to investigate the fundamental properties of solid and liquid MgO. AIMD was performed by DFT using the Strongly Conditioned and Appropriately Normed (SCAN) exchange correlation functional. The obtained pair-correlation functions of liquid MgO were used as reference data for the optimization of parameters of classical MD. For the latter, a Born–Mayer–Huggins (BMH) potential was applied, and parameters were adjusted until a best fit of both structural properties was obtained by AIMD and physical properties by experimental data. Different structural, dynamic and thermodynamic properties of solid and liquid MgO were then calculated by classical MD and compared with the literature data. Good agreement was found for the Mg-O bond length, self-diffusion coefficients, density of liquid MgO and for heat content and density of crystalline MgO. Using a void-melting approach, the melting temperature of MgO was found as 3295 ± 30 K, which is in good agreement with the recent experimental work by Ronchi et al. (3250 ± 20 K). The optimized parameters of BMH potential describe well the structural, dynamic and thermodynamic properties of solid and liquid MgO and may be combined with our previous results of a CaO-Al₂O₃-TiO₂ system to calculate the properties of a quaternary CaO-MgO-Al₂O₃-TiO₂ system. Full article

Determinants of health-seeking behavior among people living with HIV (PLHIV) are important. This study aims to develop and assess the content validity of an instrument that measures health-seeking behavior for tuberculosis among PLHIV in India. An instrument was developed using deductive methods and the Modified Andersen’s Behavioral Model of Health Services (BMHS). We identified three domains using the BMHS. Ten subject experts validated the tool between June 2022 and August 2022. Lawshe’s Content Validity Ratios (CVRs) and Scale Content Validity Indices (CVIs) were computed. The items with CVR and CVI values ≥0.62 were considered for the final tool. The health-seeking behavior among PLHIV, based on the BMHS, identified knowledge regarding TB (domain 1), healthcare accessibility and factors leading to delay in treatment-seeking behavior (domain 2), and client satisfaction regarding diagnostic and treatment-seeking behavior (domain 3). Content Validity Ratios (CVRs) of all the items related to domains 1 and 2 were ≥0.62. The Scale Content Validity Indices (for relevance), i.e., S-CVI (average) and S-CVI (proportional relevance), were ≥0.62 for all domains. The items with CVR and CVI values ≥0.62 in the domains were accepted in the final tool, which contained 69 items. Full article

Fusarium sacchari, a key pathogen of sugarcane, is responsible for the Pokkah boeng disease (PBD) in China. The 14-3-3 proteins have been implicated in critical developmental processes, including dimorphic transition, signal transduction, and carbon metabolism in various phytopathogenic fungi. However, their roles are poorly understood in F. sacchari. This study focused on the characterization of two 14-3-3 protein-encoding genes, FsBmh1 and FsBmh2, within F. sacchari. Both genes were found to be expressed during the vegetative growth stage, yet FsBmh1 was repressed at the sporulation stage in vitro. To elucidate the functions of these genes, the deletion mutants ΔFsBmh1 and ΔFsBmh2 were generated. The ΔFsBmh2 exhibited more pronounced phenotypic defects, such as impaired hyphal branching, septation, conidiation, spore germination, and colony growth, compared to the ΔFsBmh1. Notably, both knockout mutants showed a reduction in virulence, with transcriptome analysis revealing changes associated with the observed phenotypes. To further investigate the functional interplay between FsBmh1 and FsBmh2, we constructed and analyzed mutants with combined deletion and silencing (ΔFsBmh/siFsBmh) as well as overexpression (O-FsBmh). The combinations of ΔFsBmh1/siFsBmh2 or ΔFsBmh2/siFsBmh1 displayed more severe phenotypes than those with single allele deletions, suggesting a functional redundancy between the two 14-3-3 proteins. Yeast two-hybrid (Y2H) assays identified 20 proteins with pivotal roles in primary metabolism or diverse biological functions, 12 of which interacted with both FsBmh1 and FsBmh2. Three proteins were specifically associated with FsBmh1, while five interacted exclusively with FsBmh2. In summary, this research provides novel insights into the roles of FsBmh1 and FsBmh2 in F. sacchari and highlights potential targets for PBD management through the modulation of FsBmh functions. Full article

Recently, suitably sized polymer-based nanogels containing functional groups for the binding of biologically active substances and ultimately degradable to products that can be removed by glomerular filtration have become extensively studied systems in the field of drug delivery. Herein, we designed and tailored the synthesis of hydrophilic and biodegradable poly[N-(2-hydroxypropyl) methacrylamide-co-N,N′-bis(acryloyl) cystamine-co-6-methacrylamidohexanoyl hydrazine] (PHPMA-BAC-BMH) nanogels. The facile and versatile dispersion polymerization enabled the preparation of nanogels with a diameter below 50 nm, which is the key parameter for efficient and selective passive tumor targeting. The effects of the N,N′-bis(acryloyl) cystamine crosslinker, polymerization composition, and medium including H₂O/MetCel and H₂O/EtCel on the particle size, particle size distribution, morphology, and polymerization kinetics and copolymer composition were investigated in detail. We demonstrated the formation of a 38 nm colloidally stable PHPMA-BAC-BMH nanogel with a core–shell structure that can be rapidly degraded in the presence of 10 mM glutathione solution under physiologic conditions. The nanogels were stable in an aqueous solution modeling the bloodstream; thus, these nanogels have the potential to become highly important carriers in the drug delivery of various molecules. Full article

Novel amino-substituted pyridoquinazolinone derivatives have been designed and synthesized as potential c-MYC G-quadruplex (G4) ligands, employing an efficient methodology. All the new compounds exhibited moderate to good antiproliferative activity against the human osteosarcoma U2OS cell line. NMR and docking experiments revealed that the recently synthesized compounds interact with the Pu22 G-quadruplex in the c-MYC promoter region, establishing a 2:1 complex, with each molecule positioned over the tetrads at the 3′- and 5′-ends. Full article

The reaction between the ((E)-N′-(2-hydroxy-3-methoxybenzylidene)pyrazine-2-carbohydrazide) (H₂opch) ligand and the metallo-precursor [Dy(hfac)₃]·2H₂O led to the formation of an homometallic coordination complex with the formula [Dy₂(hfac)₃(H₂O)(Hopch)₂][Dy(hfac)₄] (1). In presence of both [Dy(hfac)₃] 2H₂O and the Fe(II) salt, the heterobimetallic tetranuclear [FeDy₃(hfac)₈(H₂O)₂(opch)₂] (2) was isolated, while the addition of the co-ligand 1,2-Bis(2-hydroxy-3-methoxybenzylidene) hydrazine (H₂bmh) led to the formation of two heterobimetallic tetranuclear complexes with the formula [Fe₃Dy(hfac)₆(opch)₂(H₂bmh)] C₆H₁₄ (3) C₆H₁₄ and [Fe₂Dy₂(hfac)₇(opch)₂(H₂bmh)] 0.5C₇H₁₆ (4) 0.5C₇H₁₆. Single crystal X-ray diffraction and dc magnetic investigation demonstrated that 3 and 4 involved the iron center in the +II and +III oxidation states. Dynamic magnetic measurements highlighted the single-molecule magnet behavior of 1 and 2 in a zero applied dc field primarily due to the ferromagnetic interactions taking place in these compounds. Full article

Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in treated hospital wastewater effluents constitute a major environmental and public health concern. The aim of this study was to investigate the antibiotic resistance patterns of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolated from wastewater effluent at the Benjamin Mkapa Hospital (BMH) in Dodoma, Tanzania. These bacteria were selected to represent the most prevalent gram-negative bacteria found in hospital wastewater, and they have the potential to generate resistance and spread resistance genes to antibiotics. The wastewater BMH is treated in a Constructed Wetland (CW) planted with Typha latifolia before being released into the environment. The bacteria were isolated from wastewater effluent collected at the outlet of the CW. Isolated bacteria were analyzed for antibiotic resistance by disc diffusion method. Molecular identification of bacterial species was performed by using 16S rRNA. The results show that Klebsiella ssp. was the most common isolate detected, with a prevalence of 39.3%, followed by E. coli (27.9%) and Pseudomonas ssp. (18.0%). Klebsiella ssp. were more resistant than Pseudomonas ssp. for Tetracycline, Gentamycin, Ciprofloxacin, and Sulfamethoxazole. Pseudomonas ssp. were more resistant than Klebsiella ssp. for Ceftriaxone and Azithromycin. Klebsiella ssp. harbored more resistance genes (40%), followed by Pseudomonas ssp. (35%) and E. coli (20%). The findings of this investigation indicate that the effluent from the CW requires additional treatment to reduce discharged ARB and ARGs in the receiving water bodies. As a result, the effluent quality of the CW should be continuously monitored and assessed, and further developments for treating the final effluent are necessary. Full article

Chloride molten salts have become a potential heat storage material for the design of a new generation of concentrating solar power (CSP) (>700 °C) due to its abundant reserves and low cost. The difficulty of measuring the high-temperature thermal properties of chlorides can be effectively solved by using molecular dynamics simulation. However, it is challenging to get the thermophysical properties of multi-component molten salts containing CaCl₂ due to the lack of Born–Mayer–Huggins (BMH) potential parameters of CaCl₂. Through comparative analysis of the structure and thermal properties of CaCl₂, including density and thermal conductivity, a set of Born–Mayer–Huggins (BMH) potential parameters of CaCl₂ named SP2 is determined in this study. The density, specific heat capacity, and thermal conductivity of nine eutectic molten salts are simulated, including NaCl-CaCl₂, KCl-CaCl₂, NaCl-CaCl₂-MgCl₂, and NaCl-CaCl₂-KCl, and the simulation results are found to be in good agreement with the experimental results. It is also found that the SP2 parameters are able to predict the thermal properties and structure of molten multicomponent chlorides including calcium. Full article

Cancer cells require robust ribosome biogenesis to maintain rapid cell growth during tumorigenesis. Because RNA polymerase I (Pol I) transcription of the ribosomal DNA (rDNA) is the first and rate-limiting step of ribosome biogenesis, it has emerged as a promising anti-cancer target. Over the last decade, novel cancer therapeutics targeting Pol I have progressed to clinical trials. BMH-21 is a first-in-class small molecule that inhibits Pol I transcription and represses cancer cell growth. Several recent studies have uncovered key mechanisms by which BMH-21 inhibits ribosome biosynthesis but the selectivity of BMH-21 for Pol I has not been directly measured. Here, we quantify the effects of BMH-21 on Pol I, RNA polymerase II (Pol II), and RNA polymerase III (Pol III) in vitro using purified components. We found that BMH-21 directly impairs nucleotide addition by Pol I, with no or modest effect on Pols II and III, respectively. Additionally, we found that BMH-21 does not affect the stability of any of the Pols’ elongation complexes. These data demonstrate that BMH-21 directly exploits unique vulnerabilities of Pol I. Full article

Ribosome biogenesis is a cellular process critical for protein homeostasis during cell growth and multiplication. Our previous study confirmed up-regulation of ribosome biogenesis during endometriosis progression and malignant transition, thus anti-ribosome biogenesis may be effective for treating endometriosis and the associated complications. A mouse model with human endometriosis features was established and treated with three different drugs that can block ribosome biogenesis, including inhibitors against mTOR/PI3K (GSK2126458) and RNA polymerase I (CX5461 and BMH21). The average lesion numbers and disease frequencies were significantly reduced in treated mice as compared to controls treated with vehicle. Flow cytometry analyses confirmed the reduction of small peritoneal macrophage and neutrophil populations with increased large versus small macrophage ratios, suggesting inflammation suppression by drug treatments. Lesions in treated mice also showed lower nerve fiber density which can support the finding of pain-relief by behavioral studies. Our study therefore suggested ribosome biogenesis as a potential therapeutic target for treating endometriosis. Full article

The increasing rates of maternal and congenital syphilis (CS) infections are public health concerns and need further investigation in order to provide better assistance in epidemiological surveillance and new strategies for the assistance and prevention of CS. In December 2011, the Brazilian Ministry of Health (BMH) implemented ordinance number 3.242, reinforced in 2012 by ordinance number 77, aiming to improve the quality of the syphilis diagnosis system using rapid tests. Here, we evaluate the incidence, lethality, and possible factors associated with CS in Salvador, Bahia, in the pre-resolution period (2007 to 2011) and post-resolution (2012 to 2016). An observational, ecological time-series study is conducted using secondary data collected from the National Notifiable Diseases Information System (SINAN). Linear regression analysis to estimate increases or reductions in the mean incidence over time is also performed. A total of 5470 CS cases are analyzed. The incidence ranges from 2.1 cases per 1000 live births in 2007 to 17.1 cases per 1000 live births in 2019, showing a progressive increase in incidence over the years and reduction of lethality in the post-resolution period. The number of CS cases reported prior to the implementation of the ordinances (2007–2011) does not reveal a significant increase in the incidence. However, in the post-ordinances period (2012–2019), there is an average increase of the number of CS cases by three times over the years, with an average increase of 1.8 new cases annually. Our findings highlight the importance of diagnosis and support information in strategies for CS prevention. Furthermore, these data show a positive impact of resolutions on the diagnosis and evolution of the disease. Full article

Shape quality is very important in flatfish aquaculture due to the impact on commercialization. The Senegalese sole (Solea senegalensis) is a valuable flatfish with a highly elliptic body that slightly changes with age and size, and it is prone to accumulating malformations during the production cycle. The present study aims to investigate the genetic parameters of two growth traits (weight and standard length) and six shape quality predictors (ellipticity, three body heights (body height at the pectoral fin base [BHP], body maximum height [BMH] and caudal peduncle height [CPH]) and two ratios (BMH/BHP and BMH/CPH)). These traits were measured before the on-growing stage (age ~400 days (d)) and at harvest (~800 d). Phenotypic data, heritabilities and genetic and phenotypic correlations between the traits are presented and discussed. High or very high heritabilities (0.433–0.774) were found for growth traits, body heights and ellipticity and they were higher at 400 than 800 d. In contrast, the ratios of BMH/BHP and BMH/CPH were less heritable (0.144–0.306). Positive and very high (>0.95) correlations between growth traits and the three heights were found and decreased with age. In contrast, ellipticity had negative and medium-high genetic correlations with growth traits and heights, indicating fish selected for bigger size would also become rounder. The ratio of BMH/CPH showed low genetic correlations with all traits and provided complementary information to ellipticity for a better fitting to the expected lanceolate body morphology of sole. The genetic correlations for all traits at both ages were very high, indicating that selection before entering the growth-out stage in recirculation aquaculture systems is recommended to accelerate genetic gains. Full article

Exposures to phthalates, parabens, and other phenols are often correlated due to their ubiquitous use in personal care products and plastics. Examining these compounds as a complex mixture may clarify inconsistent relationships between individual chemicals and childhood adiposity. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal cohort of children in Salinas Valley, California (n = 309), we examined biomarkers of 11 phthalate metabolites and 9 phenols, including several parabens and bisphenol A, measured in maternal urine at two time points during pregnancy. We measured child height and weight at age five to calculate the body mass index (BMI) z-scores and overweight/obesity status. The association between prenatal urinary concentrations of biomarkers with the childhood BMI z-score and overweight/obesity status was analyzed using single-pollutant models and two mixture methods: Bayesian hierarchical modeling (BMH) and Bayesian kernel machine regression (BKMR). Urinary concentrations of monoethyl phthalate, monocarboxy-isononly phthalate (metabolites of diethyl phthalate and di-isodecyl phthalate, respectively), and propylparaben were consistently associated with an increased BMI z-score and overweight/obesity status across all modeling approaches. Higher prenatal exposures to the cumulative biomarker mixture also trended with greater childhood adiposity. These results, robust across two methods that control for co-pollutant confounding, suggest that prenatal exposure to certain phthalates and parabens may increase the risk for obesity in early childhood. Full article