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Resistance to antibiotics is a critical growing public health problem that desires urgent action to combat. To avoid the stress on bacterial growth that evokes the resistance development, anti-virulence agents can be an attractive strategy as they do not target bacterial growth. Quorum sensing (QS) systems play main roles in controlling the production of diverse virulence factors and biofilm formation in bacteria. Thus, interfering with QS systems could result in mitigation of the bacterial virulence. Cilostazol is an antiplatelet and a vasodilator FDA approved drug. This study aimed to evaluate the anti-virulence activities of cilostazol in the light of its possible interference with QS systems in Pseudomonas aeruginosa. Additionally, the study examines cilostazol's impact on the bacterium's ability to induce infection in vivo, using sub-inhibitory concentrations to minimize the risk of resistance development. In this context, the biofilm formation, the production of virulence factors and influence on the in vivo ability to induce infection were assessed in the presence of cilostazol at sub-inhibitory concentration. Furthermore, the outcome of combination with antibiotics was evaluated. Cilostazol interfered with biofilm formation in P. aeruginosa. Moreover, swarming motility, biofilm formation and production of virulence factors were significantly diminished. Histopathological investigation revealed that liver, spleen and kidney tissues damage was abolished in mice injected with cilostazol-treated bacteria. Cilostazol exhibited a synergistic outcome when used in combination with antibiotics. At the molecular level, cilostazol downregulated the QS genes and showed considerable affinity to QS receptors. In conclusion, Cilostazol could be used as adjunct therapy with antibiotics for treating Pseudomonal infections. This research highlights cilostazol's potential to combat bacterial infections by targeting virulence mechanisms, reducing the risk of antibiotic resistance, and enhancing treatment efficacy against P. aeruginosa. These findings open avenues for repurposing existing drugs, offering new, safer, and more effective infection control strategies.
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Transarterial radioembolization (TARE), also called Selective Internal Radiation Therapy (SIRT), has emerged as an effective locoregional therapy for primary and secondary hepatic tumors, utilizing yttrium-90 (Y90) microspheres and other agents such as holmium-166 and rhenium-188. TARE has various applications in the management of HCC across different BCLC stages. Radiation segmentectomy, which involves administering high doses of Y90 (>190 Gy), can be both curative and ablative, achieving complete necrosis of the tumor. In contrast, radiation lobectomy involves administering a lower dose of Y90 (80-120 Gy) as a neoadjuvant treatment modality to improve local control and induce future liver remnant (FLR) hypertrophy in patients who are planned to undergo surgery but have insufficient FLR. Modified radiation lobectomy combines both techniques and offers several advantages over portal vein embolization (PVE). Y90 is also used in downstaging HCC patients outside liver transplantation criteria, as well as bridging those awaiting liver transplantation (LT). Multiple studies and combined analyses were described to highlight the outcomes of TARE and compare it with other treatment modalities, including TACE and sorafenib. Additionally, the review delves into the efficacy and safety of radioembolization in managing metastatic colorectal cancer and other metastatic tumors to the liver. Recent studies have emphasized the role of personalized dosimetry for improved outcomes, and thus we described the different methods used for this purpose. Pretherapy imaging, estimating lung shunt, selection of therapeutic radionuclides, adverse effects, and cost-effectiveness were all discussed as well.
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Intrahepatic cholestasis is a common clinical form of hepatobiliary injury characterized by the intrahepatic accumulation of toxic bile acids. Besides its antidiabetic activity, the dipeptidyl peptidase IV inhibitor sitagliptin (SG) has been recently assigned diverse pharmacological activities and therapeutic potential against different disorders owing to its emerging antioxidant and anti-inflammatory properties. The current study explored the potential hepatoprotective effect of SG on α-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and investigate its possible targeted signaling pathways. Mice received SG (10 and 20â¯mg/kg) for four consecutive days, two days before and after a single oral administration of ANIT (75â¯mg/kg). Our results revealed that SG administration remarkably prevented ANIT-induced histopathological lesions in the liver and maintained hepatic functions and oxidative/antioxidant balance. Ultimately, SG counteracted the inflammatory response in the liver, as indicated by the marked suppression of hepatic expression of NF-κB, TNF-α, and IL-6. Moreover, it inhibited the endoplasmic reticulum (ER) stress response in the liver. These beneï¬cial effects of SG were accompanied by upregulation of SIRT1, p-AMPK, and Nrf2 expressions while downregulating keap1 expression in the liver. In conclusion, this study is the first to demonstrate the ability of SG to protect against ANIT-induced CLI through modulating multiple signaling cascades, including SIRT1/AMPK, Nrf2/keap1, and NF-кB, which resulted in enhanced antioxidant capacity and repressed inflammatory and ER stress responses in the liver.
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1-Naftilisotiocianato , Proteínas Quinases Ativadas por AMP , Estresse do Retículo Endoplasmático , Fator 2 Relacionado a NF-E2 , NF-kappa B , Estresse Oxidativo , Sirtuína 1 , Fosfato de Sitagliptina , Animais , Sirtuína 1/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fosfato de Sitagliptina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , NF-kappa B/metabolismo , 1-Naftilisotiocianato/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Inflamação/prevenção & controle , Inflamação/metabolismo , Colestase Intra-Hepática/induzido quimicamente , Colestase Intra-Hepática/tratamento farmacológico , Colestase Intra-Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologiaRESUMO
Cholestasis is a hepatobiliary disorder characterized by the excessive accumulation of toxic bile acids in hepatocytes, leading to cholestatic liver injury (CLI) through multiple pathogenic inflammatory pathways. Currently, there are limited therapeutic options for the management of cholestasis and associated CLI; therefore, new options are urgently needed. Pirfenidone (PF), an oral bioavailable pyridone analog, is used for the treatment of idiopathic pulmonary fibrosis. PF has recently demonstrated diverse potential therapeutic activities against different pathologies. Accordingly, the present study adopted the α-naphthyl isothiocyanate (ANIT)-induced CLI model in mice to explore the potential protective impact of PF and investigate the underlying mechanisms of action. PF intervention markedly reduced the serum levels of ALT, AST, LDH, total bilirubin, and total bile acids, which was accompanied by a remarkable amelioration of histopathological lesions induced by ANIT. PF also protected the mice against ANIT-induced redox imbalance in the liver, represented by reduced MDA levels and elevated GSH and SOD activities. Mechanistically, PF inhibited ANIT-induced downregulated expressions of the farnesoid X receptor (FXR), as well as the bile salt export pump (BSEP) and the multidrug resistance-associated protein 2 (MRP2) bile acid efflux channels. PF further repressed ANIT-induced NF-κB activation and TNF-α and IL-6 production. These beneficial effects were associated with its ability to dose-dependently inhibit Wnt/GSK-3ß/ß-catenin/cyclin D1 signaling. Collectively, PF protects against ANIT-induced CLI in mice, demonstrating powerful antioxidant and anti-inflammatory activities as well as an ability to oppose BA homeostasis disorder. These protective effects are primarily mediated by modulating the interplay between FXR, NF-κB/TNF-α/IL-6, and Wnt/ß-catenin signaling pathways.
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1-Naftilisotiocianato , Colestase , Glicogênio Sintase Quinase 3 beta , NF-kappa B , Piridonas , Receptores Citoplasmáticos e Nucleares , Fator de Necrose Tumoral alfa , Via de Sinalização Wnt , Animais , Piridonas/farmacologia , NF-kappa B/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Masculino , 1-Naftilisotiocianato/toxicidade , Camundongos , Receptores Citoplasmáticos e Nucleares/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Colestase/induzido quimicamente , Colestase/metabolismo , Colestase/tratamento farmacológico , Colestase/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Camundongos Endogâmicos C57BL , beta Catenina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologiaRESUMO
BACKGROUND Vascular Behçet's disease (VBD) is a rare but potentially life-threatening subtype of Behçet's disease that is characterized by multisystemic vasculitis. It primarily affects males with ancestry traced back to regions along the ancient Silk Road. Both arteries and veins, regardless of size, may exhibit complications, including aneurysmal degeneration or occlusion. While venous involvement is observed in two-thirds of VBD cases, arterial complications are notably the most severe and lethal. Arterial aneurysmal degeneration is more common than occlusive complications, with larger arteries being predominantly affected in VBD. Data regarding isolated small-vessel arterial occlusive disease in VBD are limited. Given the rarity of this presentation in this patient population, it becomes mandatory to thoroughly evaluate such patients to differentiate small-vessel vasculitis from other similar diseases, such as Raynaud's phenomenon, which has a different etiology and management and generally has a more benign course. Here, we delineate the concept of isolated small-vessel vasculitis as a cause of blue toe syndrome in patients with VBD. CASE REPORT This report describes a distinctive case of vascular Behçet's disease in a 51-year-old man who initially exhibited unilateral blue toe syndrome, which swiftly progressed to dry gangrene of the toes. Despite reports of large-vessel involvement, there is a paucity of data on isolated small-vessel vasculitis-induced digital ischemia in VBD. CONCLUSIONS This atypical case underscores the necessity of clinical discernment in differentiating inflammatory microvascular occlusive disease from vasospastic Raynaud's syndrome, both of which can complicate Behçet's disease.
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Síndrome de Behçet , Síndrome do Artelho Azul , Humanos , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Masculino , Pessoa de Meia-Idade , Síndrome do Artelho Azul/etiologiaRESUMO
MOTIVATION: Molecular dynamics (MD) is a computational experiment that is crucial for understanding the structure of biological macro and micro molecules, their folding, and the inter-molecular interactions. Accurate knowledge of these structural features is the cornerstone in drug development and elucidating macromolecules functions. The open-source GROMACS biomolecular MD simulation program is recognized as a reliable and frequently used simulation program for its precision. However, the user requires expertise, and scripting skills to carrying out MD simulations. RESULTS: We have developed an end-to-end interactive MD simulation application, MolDy for Gromacs. This front-end application provides a customizable user interface integrated with the Python and Perl-based logical backend connecting the Linux shell and Gromacs software. The tool performs analysis and provides the user with simulation trajectories and graphical representations of relevant biophysical parameters. The advantages of MolDy are (i) user-friendly, does not requiring the researcher to have prior knowledge of Linux; (ii) easy installation by a single command; (iii) freely available for academic research; (iv) can run with minimum configuration of operating systems; (v) has valid default prefilled parameters for beginners, and at the same time provides scope for modifications for expert users. AVAILABILITY AND IMPLEMENTATION: MolDy is available freely as compressed source code files with user manual for installation and operation on GitHub: https://github.com/AIBResearchMolDy/Moldyv01.git and on https://aibresearch.com/innovations.
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Simulação de Dinâmica Molecular , Software , Interface Usuário-ComputadorRESUMO
Introduction: Using the Theory of Planned Behavior, this study addresses the factors that influence parental intentions to vaccinate their 12- to 17-year-old children against COVID-19. The study looked at how attitudes, subjective norms, perceived behavioral control, and fear of the COVID-19 vaccine impact these intentions. Methods: Between November and December 2021, 396 Jordanian parents completed an anonymous online survey. A multivariate logistic regression analysis was used for analyzing the relationships. Results: While 94.7% of children had received routine vaccinations, only 23.5% intended to vaccinate their children against COVID-19, indicating a vaccine acceptance gap. The analysis revealed that attitudes are the most significant positive predictor of vaccination intent, accounting for 75% of the variance. Subjective norms had a positive influence on parents' decisions, whereas fear of the COVID-19 vaccine was a significant barrier. Perceived behavioral control had a small but negative effect, indicating significant challenges to vaccination. Conclusion: The Theory of Planned Behavior (TPB) clarifies numerous factors that influence parents' decisions to immunize their children against COVID-19. Understanding these factors is critical for narrowing the gap between high rates of routine vaccinations and low rates of COVID-19 vaccinations, as well as developing effective strategies to increase vaccine acceptance among parents.
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Introduction: Candida is the primary cause of invasive fungal disease, candidiasis, especially in developed nations. The increasing resistance observed in multiple antibiotics, coupled with the prolonged process of creating new antibiotics from the ground up, emphasizes the urgent requirement for innovative methods and new compounds to combat Candida infections. Employing a treatment strategy that combines antibiotics can improve efficacy, broaden the spectrum of targeted fungal, and reduce the chances of resistance emergence. This approach shows potential in tackling the escalating problem of antibiotic resistance. The objective of this research is to explore the potential synergistic effects of combining 3-hydrazinoquinoxaline-2-thiol and thymoquinone against a variety of Candida isolates. This investigation aims to offer an understanding of the collective antimicrobial action of these compounds. Methods: Broth microdilution was utilized to assess the Minimum Inhibitory Concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol and thymoquinone for 22 clinical Candida isolates. Following this, a checkerboard assay was employed to analyze the interaction between 3-hydrazinoquinoxaline-2-thiol and thymoquinone, with a specific focus on the Fractional Inhibitory Concentration Index (FICI). Results: The MICs of thymoquinone and 3-hydrazinoquinoxaline-2-thiol were determined for 22 clinical Candida strains, with thymoquinone exhibiting MICs ranging from 64 to 8 µg/mL, and 3-hydrazinoquinoxaline-2-thiol displaying MICs varying from 64 to 8 µg/mL. Notably, the combination of 3-hydrazinoquinoxaline-2-thiol and thymoquinone resulted in a synergistic effect, leading to a significant reduction in MICs, with reductions of up to 64-fold with FICI below 0.5 against tested strains. Conclusion: The prospect of using 3-hydrazinoquinoxaline-2-thiol in combination with thymoquinone as an effective solution against Candida looks encouraging. Nevertheless, to validate its practical applicability, additional comprehensive testing and experiments are imperative.
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OBJECTIVE: The aim of this study was to compare the accuracy of panoramic radiographs (PAN) with cone-beam computed tomography (CBCT) in locating the position of the mandibular foramen (MF). PATIENTS AND METHODS: A total of 100 patients who underwent CBCT and panoramic imaging were included in the study. The location of the MF was evaluated anterior-posteriorly and superior-inferiorly on both CBCT and panoramic radiographs. Measurements were taken by two examiners, reviewed by a radiologist, and intra-examiner variability was assessed. A comparison of statistical analysis was performed using the Mann-Whitney U test, independent and paired t-test. A p-value ≤0.05 was deemed significant. RESULTS: The mean age of the patients was 35.03 years, with 51% females and 49% males. CBCT and panoramic radiographs showed comparable accuracy in locating the left (p=0.937) and right (p=0.371) MF anterior-posteriorly. In the superior-inferior dimension, the accuracy of CBCT and panoramic radiographs were comparable in locating the right (p=0.292) and left (p=0.640) MF. The gender-based accuracy of PAN and CBCT radiographs in locating the right (p=0.353) and left (p=0.985) MF was comparable. CONCLUSIONS: The study concludes that panoramic radiographs showed comparable accuracy in effectively locating MF in comparison to CBCT. The influence of gender and anatomic location (right and left sides of MF) on MF identification with panoramic radiographs was insignificant. Digital panoramic radiographs are an effective tool in accurately identifying MF location in clinical practice.
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Tomografia Computadorizada de Feixe Cônico , Mandíbula , Radiografia Panorâmica , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Feminino , Masculino , Mandíbula/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Adulto JovemRESUMO
Background: Fungal infections, especially those caused have emerged as a significant medical concern over the past three decades, particularly among immunocompromised patients. However, recent studies have highlighted the increasing prevalence of fungal infections resembling yeast other than Candida, such as trichosporonosis, especially among immunosuppressed individuals worldwide. Trichosporon has been identified as a significant contributor to superficial and invasive infections. Invasive trichosporonosis, primarily affecting immunocompromised patients, poses a significant threat with high mortality rates. Purpose: The current study aimed to explore the clinical epidemiology of Trichosporon spp at King Abdulaziz University Hospital (KAUH) in Saudi Arabia. Methods: This retrospective study aimed to assess the clinical epidemiology of Trichosporon spp. infections in microbiology cultures obtained from KAUH in Saudi Arabia. The study analyzed data from patients over a five-year period, focusing on demographic, clinical, and microbiological characteristics. Results: This study encompassed 21 participants, categorized into four distinct age groups. Moreover, this study indicated T. asahii as the predominant species isolated, accounting for 90.5% of infections, followed by T. mucoides (9.5%). ICU hospitalization, diabetes mellitus, taking immunosuppressive drugs, and antifungal drugs, and the use of invasive medical equipment were identified as prominent risk factors for trichosporonosis. Urinary tract infections were the most common clinical presentation, particularly among male and elderly patients. Mortality rates were high, especially among older individuals. Conclusion: This study contributes valuable epidemiological insights into trichosporonosis, highlighting the need for enhanced surveillance and preventive strategies in healthcare settings. Further research is warranted to optimize treatment approaches and infection control measures, ultimately reducing the burden of Trichosporon infections on patient outcomes.
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Multimodal biomarkers may identify former contact sports athletes with repeated concussions and at risk for dementia. Our study aims to investigate whether biomarker evidence of neurodegeneration in former professional athletes with repetitive concussions (ExPro) is associated with worse cognition and mood/behavior, brain atrophy, and altered functional connectivity. Forty-one contact sports athletes with repeated concussions were divided into neurodegenerative biomarker-positive (n = 16) and biomarker-negative (n = 25) groups based on positivity of serum neurofilament light-chain. Six healthy controls (negative for biomarkers) with no history of concussions were also analyzed. We calculated cognitive and mood/behavior composite scores from neuropsychological assessments. Gray matter volume maps and functional connectivity of the default mode, salience, and frontoparietal networks were compared between groups using ANCOVAs, controlling for age, and total intracranial volume. The association between the connectivity networks and sports characteristics was analyzed by multiple regression analysis in all ExPro. Participants presented normal-range mean performance in executive function, memory, and mood/behavior tests. The ExPro groups did not differ in professional years played, age at first participation in contact sports, and number of concussions. There were no differences in gray matter volume between groups. The neurodegenerative biomarker-positive group had lower connectivity in the default mode network (DMN) compared to the healthy controls and the neurodegenerative biomarker-negative group. DMN disconnection was associated with increased number of concussions in all ExPro. Biomarkers of neurodegeneration may be useful to detect athletes that are still cognitively normal, but with functional connectivity alterations after concussions and at risk of dementia.
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Atletas , Traumatismos em Atletas , Biomarcadores , Concussão Encefálica , Imageamento por Ressonância Magnética , Humanos , Masculino , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/fisiopatologia , Concussão Encefálica/sangue , Adulto , Biomarcadores/sangue , Feminino , Traumatismos em Atletas/fisiopatologia , Traumatismos em Atletas/complicações , Traumatismos em Atletas/diagnóstico por imagem , Proteínas de Neurofilamentos/sangue , Testes Neuropsicológicos , Pessoa de Meia-Idade , Adulto Jovem , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Conectoma , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/diagnóstico , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologiaRESUMO
Pseudomonas aeruginosa belongs to the critical pathogens that represent a global public health problem due to their high rate of resistance as listed by WHO. P. aeruginosa can result in many nosocomial infections especially in individuals with compromised immune systems. Attenuating virulence factors by interference with quorum sensing (QS) systems is a promising approach to treat P. aeruginosa-resistant infections. Thymoquinone is a natural compound isolated from Nigella sativa (black seed) essential oil. In this study, the minimum inhibitory concentration of thymoquinone was detected followed by investigating the antibiofilm and antivirulence activities of the subinhibitory concentration of thymoquinone against P. aeruginosa PAO1. The effect of thymoquinone on the expression of QS genes was assessed by quantitative real-time PCR, and the protective effect of thymoquinone against the pathogenesis of PAO1 in mice was detected by the mouse survival test. Thymoquinone significantly inhibited biofilm, pyocyanin, protease activity, and swarming motility. At the molecular level, thymoquinone markedly downregulated QS genes lasI, lasR, rhlI, and rhlR. Moreover, thymoquinone could protect mice from the pathologic effects of P. aeruginosa increasing mouse survival from 20% to 100%. In conclusion, thymoquinone is a promising natural agent that can be used as an adjunct therapeutic agent with antibiotics to attenuate the pathogenicity of P. aeruginosa.
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Benzoquinonas , Biofilmes , Pseudomonas aeruginosa , Animais , Camundongos , Virulência/genética , Percepção de Quorum , Fatores de Virulência/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismoRESUMO
The current study explored the protective potential of kaempferol 3-sophoroside-7-glucoside (KSG) against acute lung injury (ALI). Pre-treatment with KSG effectively secured mice from ALI and showed similar efficaciousness to dexamethasone. KSG markedly increased the survival rate and alleviated lung pathological lesions induced by lipopolysaccharide (LPS). Furthermore, KSG attenuated differential and total cell counts in BALF (bronchoalveolar lavage fluid) and MPO (myeloperoxidase) activity. KSG counteracted the NF-κB (nuclear factor-κB) activation and significantly ameliorated the downstream inflammatory cytokine, TNF-α (tumor necrosis factor-α). Simultaneously, KSG suppressed the over-expression of NLRP3 (NOD-like receptor protein 3), caspase-1, and pro-inflammatory cytokine interleukin IL-1ß (interleukine-1ß) and prohibited the elevation of the pyroptotic parameter GSDMD-N (N-terminal domain of gasdermin D) induced by LPS challenge. In addition, KSG significantly enhanced Nrf2 (nuclear-factor erythroid-2-related factor) and HO-1 (heme-oxygenase-1) expression. Meanwhile, KSG mitigated lipid peroxidative markers (malondialdehyde, protein carbonyl and 4-hydroxynonenal) and boosted endogenous antioxidants (superoxide dismutase/reduced glutathione/catalase) in lung tissue. In silico analyses revealed that KSG disrupts Keap1-Nrf2 protein-protein interactions by binding to the KEAP1 domain, consequently activating Nrf2. Specifically, molecular docking demonstrated superior binding affinity of KSG to KEAP1 compared to the reference inhibitor, with docking scores of -9.576 and -6.633 Kcal/mol, respectively. Additionally, the MM-GBSA binding free energy of KSG (-67.25 Kcal/mol) surpassed that of the reference inhibitor (-56.36 Kcal/mol). Furthermore, MD simulation analysis revealed that the KSG-KEAP1 complex exhibits substantial and stable binding interactions with various amino acids over a duration of 100 ns. These findings showed the protective anti-inflammatory and anti-oxidative modulatory efficiencies of KSG that effectively counteracted LPS-induced ALI and encouraged future research and clinical applications of KSG as a protective strategy for ALI.
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OBJECTIVE: To evaluate the prevalence of bifid mandibular canals (BMC) using cone-beam computed tomography (CBCT) in the Saudi population subset. MATERIALS AND METHODS: In the study, three hundred and forty-three CBCT scans (661 sides) were evaluated for the presence of BMC, involving 162 males and 181 females. Tomographic acquisitions were performed on the device Planmeca®. The image analysis was performed on the Planmeca Romexis® software, aided by image filters associated with transverse, oblique, and panoramic reconstruction cuts for analysis of the BMC. Naitoh's classification (2009) was employed to classify mandibular canals. The prevalence of BMC was determined according to location, gender, and age of participants. The data were analyzed with Chi-square and one-way ANOVA tests at a significance level of 95%. RESULTS: The BMC was observed in 37 (12.34%) out of 343 participants, of whom 20 (54.05%) were males and 17 (45.94%) were females. There was no significant difference in the proportion of bifid canals in both genders and various age groups. The most common BMC was the retromolar canal type, with 56.75% occurrence. The dental canal type was observed in 18.91% of BMC participants. The presence of a forward canal without confluence was observed in 16.21% of participants in the BMC, whereas a forward canal with confluence was noted in 8.10% of participants. CONCLUSIONS: The prevalence of bifid mandibular canals (BMC) within a subset of the Saudi population was 12.3%. The retromolar canal was identified as the most frequently occurring type, accounting for 56.7% of cases. No significant variations in BMC prevalence were observed concerning age and gender. Consequently, it is strongly advised to conduct a thorough assessment of the mandibular canal and its potential variations using CBCT imaging before undertaking mandibular surgical procedures, in order to minimize the risk of complications.
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Tomografia Computadorizada de Feixe Cônico , Canal Mandibular , Humanos , Feminino , Masculino , Estudos Retrospectivos , Hidrolases , Processamento de Imagem Assistida por ComputadorRESUMO
Background: The growing resistance seen in various antibiotics, including those considered as last-resort options, underscores the pressing need for novel approaches and new substances to address MRSA infections. Combining antibiotics as a treatment approach can enhance effectiveness, expand the range of targeted bacteria, and minimize the likelihood of resistance emergence. This approach holds promise in addressing the escalating issue of antibiotic resistance. Purpose: This study seeks to investigate the potential synergy between 3-hydrazinoquinoxaline-2-thiol and penicillin against a diverse array of MRSA isolates, thereby providing insights into their combined antimicrobial action. Methods: Twenty-two clinical MRSA isolates subjected to broth microdilution to determine the Minimum Inhibitory Concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol and penicillin. Subsequently, a checkerboard assay was employed to evaluate the interaction between 3-hydrazinoquinoxaline-2-thiol and penicillin, focusing on the Fractional Inhibitory Concentration Index (FICI). Results: The MICs of penicillin and 3-hydrazinoquinoxaline-2-thiol were determined for 22 clinical MRSA strains. Penicillin exhibited MICs within a range of 1024 to 128 µg/mL, while 3-hydrazinoquinoxaline-2-thiol displayed MICs varying from 64 to 8 µg/mL. Remarkably, the combination of 3-hydrazinoquinoxaline-2-thiol and penicillin yielded a synergistic effect, resulting in a significant reduction of MICs by up to 64-fold. Conclusion: The potential of 3-hydrazinoquinoxaline-2-thiol in combination with penicillin as a viable solution against MRSA appears promising. However, to establish its practical utility, further extensive testing and experiments are essential.
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This journal retracts the article "Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation" [...].
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The journal retracts the article, "The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells" [...].
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BACKGROUND: Arterial stiffening is believed to contribute to the worsening of insulin resistance, and factors which are associated with needing pharmacological treatment of gestational diabetes (GDM), such as maternal obesity or advanced age, are associated with impaired cardiovascular adaptation to pregnancy. In this observational study, we aimed to investigate causal relationships between maternal haemodynamics and treatment requirement amongst women with GDM. METHODS: We assessed maternal haemodynamics in women with GDM, comparing those who remained on dietary treatment with those who required pharmacological management. Maternal haemodynamics were assessed using the Arteriograph® (TensioMed Ltd, Budapest, Hungary) and the NICOM® non-invasive bio-reactance method (Cheetah Medical, Portland, Oregon, USA). A graphical causal inference technique was used for statistical analysis. RESULTS: 120 women with GDM were included in the analysis. Maternal booking BMI was identified as having a causative influence on treatment requirement, with each unit increase in BMI increasing the odds of needing metformin and/or insulin therapy by 12% [OR 1.12 (1.02 - 1.22)]. The raw values of maternal heart rate (87.6 ± 11.7 vs. 92.9 ± 11.90 bpm, p = 0.014) and PWV (7.8 ± 1.04 vs. 8.4 ± 1.61 m/s, p = 0.029) were both significantly higher amongst the women requiring pharmacological management, though these relationships did not remain significant in causal logistic regression. CONCLUSIONS: Maternal BMI at booking has a causal, rather than simply associational, relationship on the need for pharmacological treatment of GDM. No significant causal relationships were found between maternal haemodynamics and the need for pharmacological treatment.
This observational study is the first to examine relationships between maternal haemodynamics and treatment requirement for gestational diabetes (GDM). This is also the first study to demonstrate a causative, rather than simply associational, relationship between maternal body mass index (BMI) and the need for pharmacological treatment of GDM, with each unit increase in BMI increasing the odds of needing metformin and/or insulin therapy by 12%. Maternal heart rate and pulse wave velocity were significantly higher among women with GDM requiring pharmacological management, but this finding did not remain significant in logistic regression analysis, and no causative relationships between maternal hemodynamics and treatment requirement were identified. Our findings highlight the importance of pre- and peri-conception weight control, but do not support a role for measurement of maternal hemodynamics in the prediction of women who are likely to require pharmacological management of GDM.
Assuntos
Diabetes Gestacional , Metformina , Gravidez , Feminino , Humanos , Diabetes Gestacional/tratamento farmacológico , Metformina/uso terapêutico , Hemodinâmica , Fatores de Risco , Insulina/uso terapêuticoRESUMO
Fulminant hepatic failure (FHF) is the terminal phase of acute liver injury, which is characterized by massive hepatocyte necrosis and rapid hepatic dysfunction in patients without preexisting liver disease. There are currently no therapeutic options for such a life-threatening hepatic failure except liver transplantation; therefore, the terminal phase of the underlying acute liver injury should be avoided. Tomatidine (TOM), asteroidal alkaloid, may have different biological activities, including antioxidant and anti-inflammatory effects. Herein, the lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced FHF mouse model was established to explore the protective potential of TOM and the underlying mechanisms of action. TOM pretreatment significantly inhibited hepatocyte necrosis and decreased serum aminotransferase activities in LPS/D-GalN-stimulated mice. TOM further increased the level of different antioxidant enzymes while reducing lipid peroxidation biomarkers in the liver. These beneficial effects of TOM were shown to be associated with targeting of NF-κB signaling pathways, where TOM repressed NF-κB activation and decreased LPS/D-GalN-induced TNF-α, IL-6, IL-1ß, and iNOS production. Moreover, TOM prevented LPS/D-GalN-induced upregulation of Keap1 expression and downregulation of Nrf2 and HO-1 expression, leading to increased Nrf2-binding activity and HO-1 levels. Besides, TOM pretreatment repressed LPS/D-GalN-induced upregulation of proliferating cell nuclear antigen (PCNA) expression, which spared the hepatocytes from damage and subsequent repair following the LPS/D-GalN challenge. Collectively, our findings revealed that TOM has a protective effect on LPS/D-GalN-induced FHF in mice, showing powerful antioxidant and anti-inflammatory effects, primarily mediated via modulating Keap1/Nrf2/HO-1 and NF-κB/TNF-α/IL-6/IL-1ß/iNOS signaling pathways.
Assuntos
Falência Hepática Aguda , NF-kappa B , Tomatina/análogos & derivados , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Antioxidantes/farmacologia , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Transdução de Sinais , Fígado , Estresse Oxidativo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Necrose/metabolismo , Galactosamina/farmacologiaRESUMO
The journal retracts the article, "Development and Optimization of Luliconazole Spanlastics to Augment the Antifungal Activity against Candida albicans" [...].