Mechanisms of Bleomycin-induced Lung Fibrosis: A Review of Therapeutic Targets and Approaches.

Pulmonary toxicity is a serious side effect of some specific anticancer drugs. Bleomycin is a well-known anticancer drug that triggers severe reactions in the lungs. It is an approved drug that may be prescribed for the treatment of testicular cancers, Hodgkin's and non-Hodgkin's lymphomas, ovarian cancer, head and neck cancers, and cervical cancer. A large number of experimental studies and clinical findings show that bleomycin can concentrate in lung tissue, leading to massive oxidative stress, alveolar epithelial cell death, the proliferation of fibroblasts, and finally the infiltration of immune cells. Chronic release of pro-inflammatory and pro-fibrotic molecules by immune cells and fibroblasts leads to pneumonitis and fibrosis. Both fibrosis and pneumonitis are serious concerns for patients who receive bleomycin and may lead to death. Therefore, the management of lung toxicity following cancer therapy with bleomycin is a critical issue. This review explains the cellular and molecular mechanisms of pulmonary injury following treatment with bleomycin. Furthermore, we review therapeutic targets and possible promising strategies for ameliorating bleomycin-induced lung injury.

Assessing thallium phycoremediation by applying Anabaena laxa and Nostoc muscorum and exploring its effect on cellular growth, antioxidant, and metabolic profile.

Thallium (Tl), a key element in high-tech industries, is recognized as a priority pollutant by the US EPA and EC. Tl accumulation threatens aquatic ecosystems. Despite its toxicity, little is known about its impact on cyanobacteria. This study explores the biochemical mechanisms of Tl(I) toxicity in cyanobacteria, focusing on physiology, metabolism, oxidative damage, and antioxidant responses. To this end, Anabaena and Nostoc were exposed to 400 µg/L, and 800 µg/L of Tl(I) over seven days. Anabaena showed superior Tl(I) accumulation with 7.8% removal at 400 µg/L and 9.5% at 800 µg/L, while Nostoc removed 2.2% and 7.4%, respectively. Tl(I) exposure significantly reduced the photosynthesis rate and function, more than in Nostoc. It also altered primary metabolism, increasing sugar levels and led to higher amino and fatty acids levels. While Tl(I) induced cellular damage in both species, Anabaena was less affected. Both species enhanced their antioxidant defense systems, with Anabaena showing a 175.6% increase in SOD levels under a high Tl(I) dose. This suggests that Anabaena's robust biosorption and antioxidant systems could be effective for Tl(I) removal. The study improves our understanding of Tl(I) toxicity, tolerance, and phycoremediation in cyanobacteria, aiding future bioremediation strategies.

This study presents novel insights into thallium (Tl) phycoremediation using Anabaena laxa and Nostoc muscorum, crucial for addressing the increasing contamination concerns stemming from high-tech industries. Elucidating the tolerance mechanisms and physiological responses of these cyanobacterial species to Tl(I) exposure. It highlights the potential of Anabaena laxa as an effective bio-remediator, offering a sustainable solution to mitigate Tl(I) environmental impact.

Treatment of Atrophic Facial Scars Using Polydioxanone Threads: A Case Series.

The appearance of scars affects patients' aesthetic and psychological aspects, as atrophic scars can result from previous surgeries or inflammatory/infectious conditions. Recently, non-surgical techniques have been introduced to improve scar appearance and enhance patient satisfaction. To our knowledge, there has been limited published medical research evaluating the effectiveness of polydioxanone threads in managing facial scars. This report aims to present three cases where scars were managed using these materials in the facial area with a follow-up of six months post-intervention. Based on the three presented cases, it is shown that there was an improvement in the color and texture of the scar, in addition to its reduced size with no sensation of pain or itching after the procedure. These findings suggest that the materials used are promising for effectively treating facial scars.

Association Between Rhesus and ABO Blood Group Types and Their Impact on Clinical Outcomes in Critically Ill Patients with COVID-19: A Multi-Center Investigation.

Background: There is increasing evidence suggesting that ABO blood type may play a role in the immunopathogenesis of COVID-19 infection. In addition to ABO blood type, the Rhesus (Rh) factor has also been implicated in various disease processes. Therefore, our study aimed to assess the association between both ABO and Rh blood types in critically ill patients with COVID-19 and their clinical outcomes. Methods: A multicenter retrospective cohort study conducted in Saudi Arabia between March 1, 2020, and July 31, 2021, involving adult COVID-19 patients admitted to Intensive Care Units, aimed to explore potential associations between rhesus blood group types (Positive versus Negative) and clinical outcomes. The primary endpoint assessed was the hospital length of stay (LOS). Other endpoints were considered secondary. Results: After propensity score matching (3:1 ratio), 212 patients were included in the final analysis. The hospital length of stay was longer in a negative Rh blood group compared with patients in the Rh-positive group (beta coefficient 0.26 (0.02, 0.51), p = 0.03). However, neither 30-day mortality (HR 0.28; 95% CI 0.47, 1.25, p = 0.28) nor in-hospital mortality (HR 0.74; 95% CI 0.48, 1.14, p = 0.17) reached statistical significance. Additionally, among the different ABO types, the A+ blood group exhibited a higher proportion of thrombosis/infarction and in-hospital mortality (28.1% and 31.2%, respectively). Conclusion: This study highlights the potential impact of blood group type on the prognosis of critically ill patients with COVID-19. It has been observed that patients with a negative Rh blood group type tend to have a longer hospital stay, while their mortality rates and complications during ICU stay are similar to the patients with a Rh-positive group.

Patient Satisfaction Following Orthodontic Treatment: A Systematic Review.

Patient-reported outcome measures (PROMs) have become increasingly important in orthodontic treatment as they reflect patients' perceptions of treatment outcomes. Understanding patient satisfaction with orthodontic treatment is crucial for improving healthcare delivery and patient-centered care. This systematic review aimed to critically appraise the evidence regarding patient satisfaction after orthodontic treatment, exploring the effects of different treatment types, patient demographics, and other factors on satisfaction levels. Eight electronic bibliographic databases were searched without publication time or language restrictions, including PubMed®, Scopus®, the Cochrane Central Register of Controlled Trials, Web of Science™, Embase®, Google™ Scholar, Trip, and OpenGrey. A manual search was conducted on the references in the included papers. Eligibility criteria were established based on the Population, Intervention, Comparison, Outcomes, and Study (PICOS) framework. Studies were included if they reported patient satisfaction levels following orthodontic treatment using standardized questionnaires. Two reviewers independently collected and analyzed the data. The risk of bias was assessed using Cochrane's risk of bias tool (RoB2) for randomized clinical trials, and the methodologic quality for cohort and cross-sectional studies was assessed using the modified version of the Newcastle-Ottawa scale. Fourteen studies employed various questionnaires and timings to gauge post-orthodontic treatment satisfaction. Patient satisfaction levels were generally high, with most studies reporting satisfaction rates above 91%. Fixed orthodontic appliances were associated with higher satisfaction levels compared to removable appliances. While age and gender did not significantly influence satisfaction, the quality of care and doctor-patient relationships were crucial factors in patient satisfaction. This systematic review proves that patient satisfaction with orthodontic treatment is generally high, with fixed appliances and positive doctor-patient relationships contributing to higher satisfaction levels. However, the quality of the evidence was moderate to low, highlighting the need for further high-quality clinical studies in this area.

Examining the quaternary ammonium chitosan Schiff base-ZnO nanocomposite's potential as protective therapy for rats' cisplatin-induced hepatotoxicity.

BACKGROUND: Despite cisplatin's long history as a cornerstone in cancer therapy, both acquired chemoresistance and significant impacts on healthy tissues limit its use. Hepatotoxicity is one of its side effects. Adjunct therapies have shown promise in not only attenuating liver damage caused by cisplatin but also in enhancing the efficacy of chemotherapy. In this context, a new quaternary ammonium chitosan Schiff base (QACSB) was synthesized and applied as an encapsulating agent for the in-situ synthesis of QACSB-ZnO nanocomposite. MATERIAL AND METHODS: Thirty male albino rats were classified into Group 1 (control) distilled water, Group 2 (Cisplatin-treated) (12 mg/kg, i.p), and Group 3 (QACSB-ZnO NCs/cisplatin-treated) (150 mg/kg/day QACSB-ZnO NCs, i.p) for 14 days + a single dose of cisplatin. Liver functions, tissue TNF-α, MDA, and GSH were measured as well as histopathological and immunohistochemical studies were performed. RESULTS: The QACSB-ZnO NCs significantly restore liver functions, tissue TNF-α, MDA, and GSH levels (p < 0.001). Histopathological examination showed patchy necrosis in the cisplatin-treated group versus other groups. The QACSB-ZnO NCs showed a weak TGF-ß1 (score = 4) and a moderate Bcl-2 immunohistochemistry expression (score = 6) versus the CP group. CONCLUSIONS: QACSB-ZnO NCs have been shown to protect the liver from cisplatin-induced hepatotoxicity.

Integrating Genetic and Transcriptomic Data to Identify Genes Underlying Obesity Risk Loci.

Genome-wide association studies (GWAS) have identified numerous body mass index (BMI) loci. However, most underlying mechanisms from risk locus to BMI remain unknown. Leveraging omics data through integrative analyses could provide more comprehensive views of biological pathways on BMI. We analyzed genotype and blood gene expression data in up to 5,619 samples from the Framingham Heart Study (FHS). Using 3,992 single nucleotide polymorphisms (SNPs) at 97 BMI loci and 20,692 transcripts within 1 Mb, we performed separate association analyses of transcript with BMI and SNP with transcript (PBMI and PSNP, respectively) and then a correlated meta-analysis between the full summary data sets (PMETA). We identified transcripts that met Bonferroni-corrected significance for each omic, were more significant in the correlated meta-analysis than each omic, and were at least nominally associated with BMI in FHS data. Among 308 significant SNP-transcript-BMI associations, we identified seven genes (NT5C2, GSTM3, SNAPC3, SPNS1, TMEM245, YPEL3, and ZNF646) in five association regions. Using an independent sample of blood gene expression data, we validated results for SNAPC3 and YPEL3. We tested for generalization of these associations in hypothalamus, nucleus accumbens, and liver and observed significant (PMETA<0.05 & PMETA

Influence of the Rater's Gender on Assessing Facial Beauty in Adult Patients With Vertical and Horizontal Growth Patterns.

Background The evaluation of attractiveness varies from one civilization, culture, and environment to another and between individuals. Gender can also play a role in determining the standards of attractiveness. The purpose of this study was to evaluate the effect of the rater's gender on the assessment of adult facial attractiveness with a vertical and horizontal growth pattern in patients with skeletal Class I malocclusion. Methodology The study sample comprised extraoral photos taken before the treatment of 120 patients (30 males and 30 females in each group) with skeletal Class I malocclusion and vertical and horizontal growth patterns according to the Bjork sum aged between 18 and 25 years. A panel of 30 laypersons (aged 19-25 years with an average age of 23 ± 0.53 years), including raters from both genders, were selected equally using a disproportionate stratified sampling method through a computer-generated list. The raters used the visual analog scale (VAS) to provide a score for each photograph's aesthetic quality. The most attractive group, which received the greatest aesthetic score, and the least attractive group, which received the lowest aesthetic score, were the two groups formed based on each photograph's mean aesthetic scores. Overall, 13 patients were chosen for each group. Subsequently, the average assessment score for every patient photo set was determined. Independent-sample t-tests were employed to ascertain if the raters' gender made a statistically significant difference in assessing patients with vertical and horizontal growth patterns. Results There were statistically significant differences between the gender of raters in evaluating female patients with vertical growth patterns (p < 0.001), where the average rating of the female raters was significantly greater than that of the male raters in evaluating female patients. In addition, there were statistically significant differences between the gender of raters in evaluating female patients with horizontal growth patterns (p = 0.009), where the average rating of the male raters was significantly greater than that of the female raters in evaluating female patients. Conclusions There is a limited effect of the rater's gender in evaluating facial aesthetics. However, the facial features of female patients with long faces are preferred by females more than males, and males are more critical in evaluating these patients. On the other hand, males favor the facial features of female patients with short faces more than females, and females are more critical in evaluating these patients. These results suggest considering patients' personal characteristics with vertical and horizontal growth patterns during diagnosis and treatment planning.

Exploration of Type III effector Xanthomonas outer protein Q (XopQ) inhibitor from Picrasma quassioides as an antibacterial agent using chemoinformatics analysis.

The present study was focused on exploring the efficient inhibitors of closed state (form) of type III effector Xanthomonas outer protein Q (XopQ) (PDB: 4P5F) from the 44 phytochemicals of Picrasma quassioides using cutting-edge computational analysis. Among them, Kumudine B showed excellent binding energy (-11.0 kcal/mol), followed by Picrasamide A, Quassidine I and Quassidine J with the targeted closed state of XopQ protein compared to the reference standard drug (Streptomycin). The molecular dynamics (MD) simulations performed at 300 ns validated the stability of top lead ligands (Kumudine B, Picrasamide A, and Quassidine I)-bound XopQ protein complex with slightly lower fluctuation than Streptomycin. The MM-PBSA calculation confirmed the strong interactions of top lead ligands (Kumudine B and QuassidineI) with XopQ protein, as they offered the least binding energy. The results of absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed that Quassidine I, Kumudine B and Picrasamide A were found to qualify most of the drug-likeness rules with excellent bioavailability scores compared to Streptomycin. Results of the computational studies suggested that Kumudine B, Picrasamide A, and Quassidine I could be considered potential compounds to design novel antibacterial drugs against X. oryzae infection. Further in vitro and in vivo antibacterial activities of Kumudine B, Picrasamide A, and Quassidine I are required to confirm their therapeutic potentiality in controlling the X. oryzae infection.

Evaluation of the Best Method for Orthodontic Correction of Skeletal Deep Bites in Growing Patients: A Systematic Review.

This review aimed to evaluate the currently available evidence regarding the best method of correcting deep bites in growing patients. In September 2023, a search was conducted electronically across the following databases: PubMed®, Web of Science™, Scopus®, Embase®, Google™ Scholar, and Cochrane Library. In this systematic review, randomized control trials (RCTs), controlled clinical trials (CCTs), and cohort studies of growing patients with deep bite malocclusion who received treatment with the primary objective of treating the deep bite were included. Risk of bias of the included studies was assessed using two different tools; one tool was applied for RCTs and the other one for the CCTs and cohort studies. One RCT, one CCT, and one cohort study were included (85 patients). The flat fixed acrylic bite plane was superior in terms of duration of treatment when compared to the inclined fixed acrylic bite plane and the utility arch with posterior intermaxillary elastics. Limited evidence indicates that the inclined fixed acrylic bite plane causes a significant increase in the lower incisor inclination and a significant increase in the angle between the mandible and the anterior cranial base (SNB). However, limited evidence indicates that the utility arch with posterior intermaxillary elastics causes a significant decrease in the angle between the maxilla and the anterior cranial base (SNA). Regarding the vertical skeletal changes, it was found that the three methods were comparable; in each case, the vertical dimension of the face increased because of a significant increase in the lower first molar height. There is a need for further studies to strengthen the evidence of the treatment efficacy of the employed methods, with more RCTs to be conducted in this regard.

Design, synthesis, and anticancer evaluation of novel coumarin/thiazole congeners as potential CDK2 inhibitors with molecular dynamics.

A series of novel coumarin-thiazoles was designed and synthesized as a possible CDK2 inhibitor with anticancer activity with low toxicity. The design relied on having hydrazine thiazole or its open-form thioamide to form H-bonds with the ATP binding site while coumarin maintained the crucial hydrophobic interactions for proper fitting. The biological evaluation revealed that the hydroxycoumarin-thiazole derivative 6c demonstrated the best inhibition with HepG2 and HCT116 IC50 2.6 and 3.5 µM, respectively. Similarly, its open thioamide chain congener 5c exhibited potent inhibition on MCF-7 and HepG2 with IC50 of 4.5 and 5.4 µM, respectively. Molecular docking simulations supported the assumption of inhibiting CDK2 by preserving the crucial interaction pattern with the hinge ATP site and the surrounding hydrophobic (HPO) side chains. Furthermore, molecular dynamics simulations of 5c and 6c established satisfactory stability and affinity within the CDK2 active site.

Rosmarinus officinalis L. essential oil enhances salt stress tolerance of durum wheat seedlings through ROS detoxification and stimulation of antioxidant defense.

Salt-induced stress poses a significant barrier to agricultural productivity by impeding crop growth. Presently, environmentalists are dedicated to safeguarding food security by enhancing agricultural yields in challenging environments. Biostimulants play a crucial role in mitigating abiotic stresses in crop production, and among these, plant essential oils (EOs) stand out as organic substances with diverse biological effects on living organisms. Among the natural promoters of plant growth, Rosmarinus officinalis L. essential oil (RoEO) has gained considerable attention. Although the manifold effects of essential oils (EOs) on plant growth have been extensively demonstrated, their impact on salt stress tolerance in durum wheat seedlings remains unexplored. This investigation was undertaken to evaluate the biostimulatory capabilities of RoEO on the durum wheat cultivar "Mahmoudi." The effects of three RoEO concentrations (1, 2.5, and 5 ppm) on seed germination, growth establishment, and the induction of salt resistance under salinity conditions (150 mM NaCl) were tested. At 5 ppm, RoEO enhanced seedlings' tolerance to salinity by improving growth and reducing membrane deterioration and oxidative stress-induced damage. The expression profile analyses of seven stress-related genes (TdNHX1, TdSOS1, TdSOD, TdCAT, TdGA20-ox1, TdNRT2.1, and TdGS) using RT-qPCR showed enhancement of several important genes in durum wheat seedlings treated with 5 ppm RoEO, even under control conditions, which may be related to salt stress tolerance. The results indicate that the application of RoEO suggests a possible alternative strategy to increase salt tolerance in durum wheat seedlings towards better growth quality, thus increasing ROS scavenging and activation of antioxidant defense.

An Evaluation of the Rate and Type of Orthodontic Tooth Movement When Injecting Platelet-Rich Plasma During Mini-Implant-Based Segmented en-Masse Retraction of Upper Anterior Teeth.

INTRODUCTION: The study aimed to determine the influence of palatal injection of platelet-rich plasma (PRP) on the rate and type of orthodontic tooth movement (OTM) during the en-masse retraction of upper anterior teeth. MATERIALS AND METHODS: Two-arm parallel-group trial, in which 30 class II division 1 adult patients (7 males and 23 females) aged 16 to 27 years were recruited. The sample was randomly divided into two groups: the experimental group, in which PRP was injected in the palatal mucosa of the maxillary six anterior teeth immediately before starting the en-masse retraction of upper anterior teeth, whereas in the control group, traditional treatment was employed. Following the first premolar extraction, space closure was accomplished using frictionless mechanics for the en-masse retraction of upper anterior teeth. In both groups, a rigid segmented arch made of stainless steel with a diameter of 0.021 x 0.025 inch and an 8-mm power arm was used for the upper anterior teeth, and mini-implants were inserted between the upper second premolar and first molar at 8 mm apical from the archwire line. NiTi coil springs were used for retraction. Measurements were recorded at the onset of space closure (T0) and every 40 days till the middle of the en-masse retraction of upper anterior teeth (T1). RESULTS: Thirty patients completed the trial, and no patients were lost to follow-up in both groups. The OTM rate in the PRP group was similar to that of the control group (P = 0.596). The upper anterior teeth in the two groups were retracted mostly by controlled tipping and partially by translation. Statistically insignificant differences were observed between the two groups regarding the rest of the cephalometric variables. No serious harms were observed in either group. CONCLUSIONS: PRP was ineffective in accelerating the OTM rate during the en-masse retraction of upper anterior teeth and it did not affect the type of tooth movement.

Effectiveness of Pre-Transplant Screening for High-Priority Multidrug-Resistant Pathogens on Pre-Engraftment Infections After Hematopoietic Stem Cell Transplantation.

Objective: Owing to the rising incidence of multidrug-resistant organisms (MDRO) and the high mortality rates associated with such bacterial infections post-hematopoietic stem cell transplantation (HSCT), we investigated the MDRO colonization rate prior to transplantation using an active surveillance approach and determined its impact on subsequent infection during the pre-engraftment period. Methods: A single-center observational study was conducted, and surveillance cultures from multiple body sites, including the rectum, nasal cavity, and groin, were performed at admission to determine MDRO colonization. Serological tests were used to detect certain viruses and toxoplasmosis before HSCT. Results: In the pre-transplant setting, 59 MDRO were recovered from the 40 HSCT recipients. Of the 59 isolates recovered from one or more body sites, 29 were positive for methicillin-resistant Staphylococcus aureus (MRSA), 7 for carbapenem-resistant Enterobacterales (CRE), and 23 were positive for extended-spectrum ß-lactamase (ESBLs). Serological assessment before HSCT revealed active or reactivation of latent infection with cytomegalovirus (7.5%), Epstein-Barr virus (EBV; 5%), and Toxoplasma gondii (2.5%) among HSCT patients. In terms of factors associated with pre-engraftment infections, the type of transplant (p=0.04) was statistically significant, whereas other factors, such as age, sex, and underlying conditions, were not. In post-transplant settings, bloodstream infections (BSIs) were documented in 2 allogeneic HSCT patients (5%), and the isolated microorganisms were ESBL-producing E. coli and non-MDR Acinetobacter baumannii. Conclusion: Active screening cultures are a helpful tool for identifying patients colonized by MDRO or relevant viruses before HSCT, and for predicting those at risk of developing subsequent pre-engraftment infections. Additionally, active screening may aid in predicting those who are likely to develop subsequent pre-engraftment infections Our findings highlight the importance of pre-transplant screening for high-priority multidrug-resistant pathogens and the application of infection control interventions after HSCT.

Retraction Note to: Anti-tumor effect of PEG-coated PLGA nanoparticles of febuxostat on A549 non-small cell lung cancer cells.

[This retracts the article DOI: 10.1007/s13205-020-2077-x.].

Patient-reported outcomes during accelerating the en-masse retraction of the upper anterior teeth using low-intensity electrical stimulation: a randomized controlled trial.

BACKGROUND: Low-intensity electrical stimulation (LIES) is considered a relatively recent technology that has received little attention in orthodontics as a method of acceleration. This study aimed to evaluate patient-reported outcome measures when LIES is used to accelerate the en-masse retraction of the upper anterior teeth. MATERIALS AND METHODS: The sample consisted of 40 patients (8 males, 32 females; mean age 21.1 ± 2.3 years), with Class II division I malocclusion who required extraction of the first premolars to retract upper anterior teeth. They were randomly assigned to the LIES group (n = 20) and the conventional en-masse retraction group (CER; n = 20). Patient responses regarding pain, discomfort, burning sensation, swelling, chewing difficulty, speech difficulty, and painkillers' consumption were recorded at these nine assessment times: 24 h (T1), 3 days (T2), and 7 days (T3) after force application, then in the second month after 24 h (T4), 3 days (T5), and 7 days (T6) of force re-activation, and finally after 24 h (T7), 3 days (T8), and 7 days (T9) of force re-activation in the third month. RESULTS: The mean values of pain perception were smaller in the LIES group than those in the CER group at all assessment times with no statistically significant differences between the two groups except during the second and third months (T5, T6, T8, and T9; P < 0.005). However, discomfort mean values were greater in the LIES group with significant differences compared to CER group during the first week of the follow-up only (T1, T2, and T3; P < 0.005). Burning sensation levels were very mild in the LIES group, with significant differences between the two groups at T1 and T2 only (P < 0.001). Speech difficulty was significantly greater in the LIES group compared to CER group at all studied times (P < 0.001). High levels of satisfaction and acceptance were reported in both groups, without any significant difference. CONCLUSION: Both the LIES-based acceleration of en-masse retraction of upper anterior teeth and the conventional retraction were accompanied by mild to moderate pain, discomfort, and chewing difficulty on the first day of retraction. These sensations gradually decreased and almost disappeared over a week after force application or re-activation. TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov, NCT05920525. Registered 17 June 2023 - retrospectively registered, http://clinicaltrials.gov/study/NCT05920525?term=NCT05920525&rank=1 .

Temperature Changes in the Pulp Chamber During Orthodontic Bonding Using a High-Power Light-Emitting Diode Device With Two Different Exposure Times and Intensities: An In-Vitro Study.

OBJECTIVE: This study used a high-power light-emitting diode (LED) device to evaluate the effects of two exposure times and intensities on pulp chamber temperature and cooling time during bracket bonding. MATERIALS AND METHODS: Sixty upper premolars were used in the sample in this study. These premolars were split into two main groups based on the exposure time and intensity: the first group employed a traditional curing mode (TCG) for 20 seconds with an intensity of 1200 mw/cm2, whereas the second group had a quick curing mode (QCG) for 3 seconds with an intensity of 2500 mw/cm2. The pulp chamber's temperature variations and cooling times were recorded using a thermal imaging camera. The Mann-Whitney U test was used to find differences between the two-group comparison of the pulp chamber's temperature and cooling time. RESULTS: The two groups had statistically significant differences regarding the temperature increase in the pulp chamber and cooling time (p > 0.001). The mean temperature increase in the traditional curing group was 3.52°C, which is greater than that in the quick curing group (i.e., a mean value of 1.28°C). The mean cooling time in the traditional curing group was 38.83 seconds, which is greater than that in the quick curing group (9.97 seconds). CONCLUSIONS: Reducing the exposure time to 3 seconds and increasing the intensity to 2500 mw/cm2 is considered safer for the pulp chamber during and after the curing process.

Aflatoxin B1 exposure deteriorates immune abnormalities in a BTBR T+ Itpr3tf/J mouse model of autism by increasing inflammatory mediators' production in CD19-expressing cells.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficiencies in communication, repetitive and stereotyped behavioral patterns, and difficulties in reciprocal social engagement. The presence of immunological dysfunction in ASD has been well established. Aflatoxin B1 (AFB1) is a prevalent mycotoxin found in food and feed, causing immune toxicity and hepatotoxicity. AFB1 is significantly elevated in several regions around the globe. Existing research indicates that prolonged exposure to AFB1 results in neurological problems. The BTBR T+ Itpr3tf/J (BTBR) mice, which were used as an autism model, exhibit the primary behavioral traits that define ASD, such as repeated, stereotyped behaviors and impaired social interactions. The main objective of this work was to assess the toxic impact of AFB1 in BTBR mice. This work aimed to examine the effects of AFB1 on the expression of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 by CD19+ B cells in the spleen of the BTBR using flow cytometry. We also verified the impact of AFB1 exposure on the mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain of BTBR mice using real-time PCR. The findings of our study showed that the mice treated with AFB1 in the BTBR group exhibited a substantial increase in the presence of CD19+Notch-1+, CD19+IL-6+, CD19+MCP-1+, CD19+iNOS+, CD19+GM-CSF+, and CD19+NF-κB p65+ compared to the mice in the BTBR group that were treated with saline. Our findings also confirmed that administering AFB1 to BTBR mice leads to elevated mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain, in comparison to BTBR mice treated with saline. The data highlight that exposure to AFB1 worsens immunological abnormalities by increasing the expression of inflammatory mediators in BTBR mice.

Evaluation of fortimicin antibiotic combinations against MDR Pseudomonas aeruginosa and resistome analysis of a whole genome sequenced pan-drug resistant isolate.

BACKGROUND: Multidrug-resistant (MDR) P. aeruginosa is a rising public health concern, challenging the treatment of such a ubiquitous pathogen with monotherapeutic anti-pseudomonal agents. Worryingly, its genome plasticity contributes to the emergence of P. aeruginosa expressing different resistant phenotypes and is now responsible for notable epidemics within hospital settings. Considering this, we aimed to evaluate the synergistic combination of fortimicin with other traditional anti-pseudomonal agents and to analyze the resistome of pan-drug resistant (PDR) isolate. METHODS: Standard methods were used for analyzing the antimicrobial susceptibility tests. The checkerboard technique was used for the in vitro assessment of fortimicin antibiotic combinations against 51 MDR P. aeruginosa and whole genome sequencing was used to determine the resistome of PDR isolate. RESULTS: Out of 51 MDR P. aeruginosa, the highest synergistic effect was recorded for a combination of fortimicin with ß-lactam group as meropenem, ceftazidime, and aztreonam at 71%, 59% and 43%, respectively. Of note, 56.8%, 39.2%, and 37.2% of the tested MDR isolates that had synergistic effects were also resistant to meropenem, ceftazidime, and aztreonam, respectively. The highest additive effects were recorded for combining fortimicin with amikacin (69%) and cefepime (44%) against MDR P. aeruginosa. Resistome analysis of the PDR isolate reflected its association with the antibiotic resistance phenotype. It ensured the presence of a wide variety of antibiotic-resistant genes (ß-lactamases, aminoglycosides modifying enzymes, and efflux pump), rendering the isolate resistant to all clinically relevant anti-pseudomonal agents. CONCLUSION: Fortimicin in combination with classical anti-pseudomonal agents had shown promising synergistic activity against MDR P. aeruginosa. Resistome profiling of PDR P. aeruginosa enhanced the rapid identification of antibiotic resistance genes that are likely linked to the appearance of this resistant phenotype and may pave the way to tackle antimicrobial resistance issues shortly.

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii.

Multidrug-resistant (MDR) pathogens are a rising global health worry that imposes an urgent need for the discovery of novel antibiotics particularly those of natural origin. In this context, we aimed to use the metagenomic nanopore sequence analysis of soil microbiota coupled with the conventional phenotypic screening and genomic analysis for identifying the antimicrobial metabolites produced by promising soil isolate(s). In this study, whole metagenome analysis of the soil sample(s) was performed using MinION™ (Oxford Nanopore Technologies). Aligning and analysis of sequences for probable secondary metabolite gene clusters were extracted and analyzed using the antiSMASH version 2 and DeepBGC. Results of the metagenomic analysis showed the most abundant taxa were Bifidobacterium, Burkholderia, and Nocardiaceae (99.21%, followed by Sphingomonadaceae (82.03%) and B. haynesii (34%). Phenotypic screening of the respective soil samples has resulted in a promising Bacillus isolate that exhibited broad-spectrum antibacterial activities against various MDR pathogens. It was identified using microscopical, cultural, and molecular methods as Bacillus (B.) haynesii isolate MZ922052. The secondary metabolite gene analysis revealed the conservation of seven biosynthetic gene clusters of antibacterial metabolites namely, siderophore lichenicidin VK21-A1/A2 (95% identity), lichenysin (100%), fengycin (53%), terpenes (100%), bacteriocin (100%), Lasso peptide (95%) and bacillibactin (53%). In conclusion, metagenomic nanopore sequence analysis of soil samples coupled with conventional screening helped identify B. haynesii isolate MZ922052 harboring seven biosynthetic gene clusters of promising antimicrobial metabolites. This is the first report for identifying the bacteriocin, lichenysin, and fengycin biosynthetic gene clusters in B. haynesii MZ922052.